Department of Anesthesiology and Intensive Care Medicine Department of Plastic Surgery Helsinki University Central Hospital University of Helsinki Finland
The TRAM fl ap for breast reconstruction Studies on perioperative cutaneous blood fl ow, vasoconstriction, and indices of obesity
Hanna Tuominen
Academic Dissertation
To be presented, with the permission of the Faculty of Medicine of the University of Helsinki, for public examination in Lecture Room I, Töölö Hospital, on October 31st, 2008, at 12 noon.
Helsinki 2008 Supervised by Nils Svartling, M.D., Ph.D. Department of Anesthesiology and Intensive Care Medicine and Professor Sirpa Asko-Seljavaara Department of Plastic Surgery and Professor Erkki Tukiainen Department of Plastic Surgery Helsinki University Central Hospital University of Helsinki Helsinki, Finland
Reviewed by Docent Paula Mustonen Department of Plastic Surgery Kuopio University Hospital University of Kuopio Kuopio, Finland and Docent Hannu Toivonen Department of Anesthesiology and Intensive Care Medicine Helsinki University Central Hospital University of Helsinki Helsinki, Finland
Opponent Docent Outi Kaarela Department of Plastic Surgery Oulu University Hospital University of Oulu Oulu, Finland
Hanna Tuominen M.D., Anesthesiologist Special interests: Neuroanesthesiology, Anesthesia for reconstructive plastic surgery Helsinki University Central Hospital Töölö Hospital, Topeliuksenkatu 5, 00029 HUS Helsinki, Finland hanna.tuominen@hus.fi
ISBN 978-952-92-4568-0 (paperback) ISBN 978-952-10-5021-3 (PDF) http://ethesis.helsinki.fi
Layout Lifeteam Oy • Cover Jari Salo
Helsinki University Printing House Helsinki 2008 To my family Contents
Abstract ...... 6
List of original publications ...... 8
Abbreviations ...... 9
1 Introduction ...... 10
2 Review of the literature ...... 11 2.1. Breast cancer ...... 11 2.1.1. Incidence ...... 11 2.1.2. Manifestations ...... 11 2.1.3. Treatment ...... 11 2.1.4. Prognosis ...... 13 2.2. Breast reconstruction ...... 14 2.2.1. Indications ...... 14 2.2.2. Principles of breast reconstruction ...... 14 2.2.3. Nonautologous breast reconstruction ...... 15 2.2.4. Autologous breast reconstruction ...... 16 2.2.5. The TRAM fl ap ...... 18 2.2.6. Surgical complications of the TRAM fl ap ...... 20 2.3. Blood fl ow in surgical fl aps ...... 22 2.3.1. Blood fl ow of the skin ...... 22 2.3.2. Regulation of cutaneous blood fl ow ...... 22 2.3.3. Principles of blood fl ow in fl aps ...... 23 2.3.4 Blood fl ow in the TRAM fl ap ...... 26 2.3.5. Temperature and the cutaneous blood fl ow ...... 28 2.3.6. Effect of general anesthesia on thermoregulation and cutaneous blood fl ow ....28 2.4. Monitoring of blood fl ow in fl aps ...... 29 2.4.1. Methods used to measure blood fl ow in surgical fl aps ...... 29 2.5. Endothelin ...... 32 2.5.1. Endothelin and vasoconstriction ...... 32 2.5.2. Effect of different substances on endothelin levels...... 32 2.5.3. Endothelin and surgical fl aps ...... 32 2.6. Effect of different interventions on blood fl ow in the fl ap ...... 33 2.6.1. Calcium antagonists and cutaneous blood fl ow ...... 33 2.7. Effect of overweight on fl ap blood fl ow ...... 34
4 2.7.1. Measurement of obesity ...... 34 2.7.2. Overweight and complications in TRAM fl aps ...... 35 2.7.3. Overweight and cutaneous necrosis in surgical fl aps ...... 35
3 Aims of the study ...... 37
4 Patients and methods ...... 38 4.1. Patients ...... 38 4.2. Methods ...... 38 4.2.1. Study designs ...... 38 4.2.2. Anesthetic management ...... 40 4.2.3. Surgical technique...... 41 4.2.4. Measurements...... 42 4.2.5. Statistical analyses ...... 45
5 Results ...... 46 5.1. Perioperative changes of cutaneous blood fl ow in TRAM fl aps (I, II) ...... 46 5.1.1. Cutaneous blood fl ow in pedicled TRAM fl aps (I) ...... 46 5.1.2. Cutaneous blood fl ow in free TRAM fl aps (II) ...... 47 5.2. Prediction of cutaneous necrosis in pedicled TRAM fl aps (I) ...... 49 5.3. Relation of plasma ET-1 concentrations to peripheral vasoconstriction, blood pressure, heart rate, and cutaneous or fat necrosis (III) ...... 50 5.4. Effect of felodipine on plasma ET-1 concentrations, peripheral
vasoconstriction, postoperative PtcO2, and survival of free TRAM fl aps (IV) ...... 51 5.5. Effect of indices of obesity on cutaneous or fat necrosis in pedicled TRAM fl aps (V) ...... 52
6 Discussion ...... 54 6.1. Perioperative changes of cutaneous blood fl ow in TRAM fl aps (I, II) ...... 54 6.1.1. Pedicled TRAM fl aps (I) ...... 54 6.1.2. Free TRAM fl aps (II) ...... 56 6.2. Prediction of cutaneous necrosis in pedicled TRAM fl aps (I) ...... 57 6.3. Relation of plasma ET-1 concentrations to peripheral vasoconstriction, blood pressure, heart rate, and cutaneous or fat necrosis (III) ...... 58 6.4. Effect of felodipine on plasma ET-1 concentrations, peripheral
vasoconstriction, postoperative PtcO2, and survival of free TRAM fl aps (IV) ...... 60 6.5. Effect of indices of obesity on cutaneous or fat necrosis in pedicled TRAM fl aps (V) ...... 62
7 Conclusions ...... 64
8 Acknowledgments ...... 65
9 References ...... 66
5 Abstract
In Finland breast reconstruction is performed pedicled TRAM fl aps (I), elevation of the for about – of women operated on for contralateral side of the fl ap caused an increase breast cancer. A popular method for creating a in cutaneous blood fl ow on the ipsilateral side new breast is the transverse rectus abdominis of the fl ap compared to the measurements musculocutaneous (TRAM) fl ap formed solely taken aft er induction of anesthesia. A possible of the patient’s own tissue from the lower ab- cause for the hyperemia may be opening up of dominal area. Th e fl ap can be raised as a pedi- the “choke” vessels interconnecting adjacent cled or a free fl ap. Th e pedicled TRAM fl ap, vascular areas, angiosomes. Ligation of DIEA based on its nondominant pedicle superior caused a signifi cant decrease of LDF levels on epigastric artery (SEA), is rotated to the chest the contralateral skin, lasting until the fi rst so that blood fl ow through SEA continues. postoperative day. Th e contralateral PtcO de- Th e free TRAM fl ap, based on the dominant creased from the initial ± mmHg to ± pedicle deep inferior epigastric artery (DIEA), mmHg when DIEA was cut and stayed low on is detached from the abdomen, transferred to the operation day. It increased slowly during the chest, and DIEA and vein are anastomosed the postoperative week. Th e LDF and PtcO lev- to recipient vessels on the chest. Cutaneous ne- els were lower on the contralateral than ipsilat- crosis is seen in – of the pedicled TRAM eral side of the fl ap at all measuring times. SEA fl aps and in – of free TRAM fl aps. apparently cannot perfuse the pedicled TRAM Th e aim of this study was to measure fl ap suffi ciently on the operation day. changes in cutaneous blood fl ow on the ipsilat- In ten free TRAM fl aps (II), elevation of the eral (over the rectus muscle) and contralateral contralateral side caused a similar hyperemia (opposite side) sides of the fl ap with laser Dop- as in pedicled fl aps. Interruption of blood fl ow pler fl owmetry (LDF) and transcutaneous oxy- before performing the anastomoses was seen gen tension (PtcO) at diff erent phases before, as a decrease of LDF levels. LDF levels and during and aft er breast reconstruction with the ipsilateral PtcO returned to the base line pedicled (I) and free (II) TRAM fl aps, and to levels in the recovery room, as as did the con- predict development of necrosis in pedicled tralateral PtcO on the third postoperative day. TRAM fl aps. Th e role of plasma endothelin- Compared with the pedicled fl aps in study I, (ET-), a powerful vasoconstrictor secreted the postoperative blood fl ow in the free TRAM by vascular endothelial cells, in cutaneous ne- fl ap seems generous. crosis of fl aps and the peripheral vasoconstric- Cutaneous necrosis was observed in eight tion observed aft er long operations (III), and ( ) of the pedicled TRAM fl aps (I). Th e the eff ect of felodipine, a vasodilating calcium development of cutaneous necrosis could be antagonist, on those parameters (IV) were also predicted based on intraoperative LDF measure- studied. One aim was to study the association ments. Th e contralateral LDF level decreased of cutaneous or fat necrosis and the amount of aft er ligation of the DIEA to a lower level in obesity of the patient, using body mass index fl aps developing necrosis ( + of the initial (BMI), waist-hip circumference ratio (WHCR) value) compared to fl aps healing uneventfully and thickness of subcutaneous abdominal fat ( + , p < ). Cutaneous necrosis cannot as indices of obesity (V). be predicted based on the intraoperative PtcO
Th is thesis consists of fi ve prospective stud- values. Th e contralateral PtcO was signifi cantly ies (I–V) performed in altogether women, lower in the recovery room and on the postop- ten of whom took part in studies III and V. In erative days in fl aps developing necrosis (I).
6 In study III, plasma ET- concentrations necrosis of free TRAM fl aps between the felo- were elevated preoperatively, . (.–.) dipine group (n = ) and the control group pg/ml (median, – quartiles), near pg/ (n = ) in a placebo-controlled randomized ml during the operation, and around pg/ml study. An increase of HR was seen in felodipine during the postoperative recovery room period patients. (IV). of three hours in nine patients with a pedicled Cutaneous or fat necrosis was observed in
TRAM fl ap. Temperature gradient (Tgrad, the two of the fi ve overweight patients (BMI > ), diff erence between skin temperatures of the an- in three of the six patients of ideal weight, but tebrachium and index fi nger) indicated periph- not in the one underweight patient (BMI < ). eral vasoconstriction preoperatively and post- None of the patients were obese (BMI > ). operatively. A statistically signifi cant nonlinear Four of the six patients with lower body type correlation was found in the nonparametric fat distribution (WHCR < ,), none of the Spearman rank correlation test between ET- four patients with upper body type fat distribu- and Tgrad (r = ., p < .), and ET- and mean tion and one of the two patients with WHCR arterial pressure (MAP) (r = ., p < .), but ,–, developed necrosis. Th ere were not between ET- or Tgrad and development of no diff erences in the thickness of subcutane- necrosis, and ET- and heart rate (HR). ET- ous fat in patients with and without necrosis. may play a role in postoperative peripheral va- Neither BMI nor the thickness of abdominal soconstriction aft er long operations (III). subcutaneous fat seems to be associated with Oral felodipine ( mg) administered on the the development of cutaneous or fat necrosis in preoperative evening and on the operation pedicled TRAM fl aps. An association may exist morning, caused no diff erences in periopera- between lower body type fat distribution and tive plasma ET- concentrations, Tgrad, post- development of marginal necrosis in pedicled operative PtcO, or development of cutaneous TRAM fl aps (V).
7 List of original publications
Th is thesis is based on the following original publications, referred to in the text by their Roman numerals:
I Tuominen HP, Asko-Seljavaara S, Svartling NE, Härmä MA. Cutaneous blood fl ow in the TRAM fl ap. Br J Plast Surg ; : –.
II Tuominen HP, Asko-Seljavaara S, Svartling NE. Cutaneous blood fl ow in the free TRAM fl ap. Br J Plast Surg ; : –.
III Tuominen HP, Svartling NE, Tikkanen IT, Saijonmaa O, Asko-Seljavaara S. Perioperative plasma endothelin- concentrations and vasoconstriction during prolonged plastic surgical procedures. Br J Anaesth ; : –.
IV Tuominen HP, Svartling NE, Tikkanen IT, Asko-Seljavaara S. Th e eff ect of felodipine on endothelin- levels, peripheral vasoconstriction and fl ap survival during microvascular breast reconstruction. Br J Plast Surg ; : –.
V Tuominen HP, Kinnunen J, Svartling NE, Asko-Seljavaara S. Indices of obesity and behaviour of the pedicled TRAM fl ap in breast reconstruction. Scand J Plast Reconstr Surg Hand Surg ; : –.
Th e articles have been reprinted with the kind permission of their copyright holders.
8 Abbreviations
ACE angiotensin-converting enzyme NIRS near-infrared spectroscopy
BCT breast-conserving therapy PaO arterial oxygen tension
BMI body mass index (kg /m ) PtcO transcutaneous oxygen tension
CI confi dence interval SD standard deviation
DBR delayed breast reconstruction SEA superior epigastric artery
DCIS ductal carcinoma in situ SEM standard error of mean
DIEP deep inferior epigastric perforator SIEA superfi cial inferior epigastric artery
ET endothelin Tant temperature of antebrachium skin
ET- endothelin- Tgrad temperature gradient (Tant–Tind)
GAP gluteal artery perforator Tind temperature of index fi nger
HR heart rate Tperiph peripheral temperature
IBR immediate breast reconstruction Trect rectal temperature
LCIS lobular carcinoma in situ TAP thoracodorsal artery perforator
LD latissimus dorsi TRAM transverse rectus abdominis musculocutaneous LDF laser Doppler fl owmetry WHCR waist-hip circumference ratio LDPI laser Doppler perfusion imaging WHO World Health Organization MAP mean arterial pressure
9 1 Introduction
Breast cancer is the most common cancer in To overcome the technical obstacles of women. In –, it was diagnosed an- breast reconstruction, it is of the utmost im- nually in women per in Finland, portance to understand the changes in cuta- in in women, and by the year neous blood fl ow of the fl aps during and aft er the fi gure is expected to reach (Finnish surgery. Vasoconstriction can compromise the Cancer Registry ). Despite the increasing viability of the fl ap. During operations of long incidence, the prognosis has improved during duration, imminent hypothermia results in the last couple of decades, with approximately decreased cutaneous blood fl ow. An important of the patients being alive fi ve years aft er mediator in vasoconstriction is endothelin, the diagnosis (Finnish Cancer Organizations ET-, a peptide secreted by vascular endothe- ). lial cells (Yanagisawa ). High ET- levels Chemotherapy and radiation therapy along have been measured in ischemic experimental with surgery, either conserving or radical, form fl aps (Matsuzaki ). Th e untoward eff ects the cornerstone of breast cancer treatment can be antagonized with such drugs as calcium (National Cancer Institute a). Mastectomy antagonists, which have been shown to sup- is performed in about half of patients. In pa- press ET- release (Kiowsky , Liu ) tients undergoing mastectomy, disturbances in and also to enhance the survival of experimen- body image and problems with the exogenous tal skin fl aps (Yessenow , Davis ). prosthesis can lead to a variety of psychological Overweight of the patient may pose a risk problems, physical symptoms, and diffi culties to the viability of the TRAM fl ap. Th e probable in social life. Nowadays, either immediate or underlying causes are vascular problems (Lapi- delayed breast reconstruction with an artifi cial dus ) and the stretch caused by the heavy implant or autologous tissue is off ered in many fl ap on musculocutaneous perforator vessels cases to improve the quality of life (Blamey nourishing the fl ap (Schefl an ). Conse- , Newman , Piasecki ). quently, obesity has been considered a rela- Th e disadvantages related to the prosthesis tive contraindication to breast reconstruction can be avoided, and the esthetic result is oft en by some authors (Schefl an a, Hartrampf considered better with breast reconstruction , Grotting ). However, the eff ects of using autologous tissue. Transplantation of the type of body fat distribution and the thick- either a pedicled or a free transverse rectus ness of abdominal subcutaneous fat on survival abdominis musculocutaneous (TRAM) fl ap of the fl ap skin are unknown. for breast reconstruction was introduced some Th is thesis was designed to evaluate the years ago (Robbins , Holmström , changes in cutaneous blood fl ow in the TRAM Hartrampf ). Th e breast created with the fl aps and to study the eff ects of a calcium an- TRAM fl ap is soft and natural-looking com- tagonist, felodipine, on plasma endothelin pared to other methods. Regardless of the concentrations and fl ap survival. Moreover, popularity of the TRAM fl ap, complications the eff ects of indices of obesity on TRAM fl aps related to the fl ap circulation still occur. were assessed.
10 2 Review of the literature
2.1. Breast cancer 2.1.2. Manifestations 2.1.1. Incidence Th e female breast consists of – lobules at- Breast cancer is the most common malignant tached by connective tissue and fat. Th e lobules tumor in women in Finland, accounting for are connected by small ducti (World Health of all female cancer cases. Th e incidence Organization , American Joint Com- of breast cancer has been increasing since mittee of Cancer , Finnish Current Care the s. It was diagnosed in Finland annu- Guidelines ). ally in women during –, repre- Th e most common form of breast cancer is senting per women, and in ductal carcinoma. It occurs as an invasive form women in , representing per or as ductal carcinoma in situ (DCIS). Th e women (Finnish Cancer Registry ). Th e ductal invasive carcinoma represents – incidence is at the same level in all Western of all invasive breast cancers. DCIS is an early, countries (Mäkelä ). Th e probable causes precancerous condition, where the cancer cells of the increase are trends towards obesity, have not invaded the breast tissue, but remain changes in reproductive patterns, and the use inside the ducti. DCIS usually remains lo- of postmenopausal hormone replacement cal, but may sometimes progress to invasive therapy (American Cancer Society ). cancer. Th e incidence of DCIS has increased Th anks to better diagnostics by mammog- considerably because of increased detection by raphy, more cancer cases are observed at an mammography. In USA, DCIS accounted for early stage. According to the latest trends in of all breast cancers diagnosed in and Finland, of the new cancer cases in (Page , Ernster ). Th e diagnosed in in women are expected to less common lobular carcinoma (– of be breast cancer cases (Finnish Cancer Orga- all breast cancers) originates from the lobules nizations ). and is oft en bilateral. Lobular carcinoma in situ Every tenth woman living until the age of (LCIS) also exists; it is not considered malig- years has been calculated to get breast can- nant, but is a risk factor for breast cancer. It is cer during their lifetime. Very few cases occur usually multicentric and frequently bilateral. in women younger than years. In Finland, Paget’s disease is a form of breast cancer mani- about of cases are diagnosed in the age festing as eczema of the nipple. In histological group – years, in the age group – examination, intraepidermal carcinoma cells, years, and in patients aged years or DCIS changes, and sometimes invasive growth over (Finnish Cancer Registry ). Th e inci- are observed. Th ere are also some less common dence increases with advancing age. In USA, cancer types, e.g. tubular, mucinous, papillary, in women aged – years the incidence rate scirrhous, and infl ammatory breast cancers was low, . cases per , while the cor- (National Cancer Institute a). responding rate was per in women aged – during – (American 2.1.3. Treatment Cancer Society ). Treatment of breast cancer should be tailored individually for each patient. Breast cancer is commonly treated by various combinations of surgery, radiation therapy, chemotherapy,
11 hormone therapy, and monoclonal antibody BCT, the tumor is removed by lumpectomy, therapy. It is a multidisciplinary team approach, quadrantectomy, or segmental mastectomy. involving specialists in surgery, radiology, pa- Nowadays in Finland, BCT is used in – thology, oncology, nuclear medicine, plastic of breast cancer operations. Mastectomy is per- surgery, and anesthesiology. Selection of ther- formed for – of the women, i. e. – apy may be infl uenced by the age, menopausal women yearly (Stakes ). Th e most status, general condition and opinion of the pa- important prognostic marker in breast cancer tient, stage of the disease, histologic and nuclear is the status of the axillary lymph nodes (Fisher grade of the primary tumor, estrogen-receptor , Morrow ). Th e use of sentinel node and progesterone-receptor status, measures of biopsy has decreased the need for unnecessary proliferative capacity, and HER/neu gene am- axillary evacuations, which can cause sequelae plifi cation (Finnish Current Care Guidelines for the patient (Ververs ), and scarring or , National Cancer Institute a). damage of the vessels used as recipients in mi- Th e basic objectives of the treatment are crovascular breast reconstruction. Th e lymph to remove the tumor from the breast and the node nearest the site of the primary cancer, metastases from the axilla, nowadays with the receiving the lymph drainage directly from help of sentinel node biopsy, and to minimize the tumor, is regarded as the sentinel node, the the recurrence of the cancer locally and in the most likely site of early metastases (Morton axilla. Selection of the surgical method is based ). In this procedure technetium-labeled on the pTNM classifi cation and staging of the sulfur colloid solution, vital blue dye, or both tumor (American Joint Committee of Cancer are injected around the tumor or biopsy cavity , Finnish Current Care Guidelines ). preoperatively, and the lymph node or nodes Th e operation methods used are mastectomy fi rst activated by the marker solution or the dye or breast-conserving therapy (BCT). Simple (sentinel nodes) are removed for histological or total mastectomy includes removal of the examination as a frozen section analysis. If the entire breast. In modifi ed radical mastectomy, sentinel nodes are free of cancer, the axilla is also the lymph nodes in the axilla are removed. left intact. If a metastasis is found, and in rare Radical mastectomy, including also removal cases where sentinel nodes are not found, the of the underlying chest wall muscle, is rarely axilla is evacuated in the same operation. Short used today because of proven eff ectiviness of follow-up studies have revealed hardly any the less disfi guring surgeries (Veronesi ). axillary recurrence in patients who were left Th e indications for mastectomy are shown in without axillary evacuation because of negative Table I (Finnish Current Care Guidelines , sentinel nodes (Schrenk , Chung , National Cancer Institute a). Guenther , Veronesi , Leikola ). During the last ten years, skin-sparing However, no long-term follow-up studies exist mastectomy has become popular. It involves on sentinel node biopsy since it has only been removal of the nipple/areolar complex and in use from the end of the s onwards. In preserving the breast´s skin envelope (Sim- Finland, it has been in use since . mons ). It is considered safe in selected Th e local recurrence rate is increased in T/T tumors (Toth , Cunnick ). In BCT compared with mastectomy in patients
Table I. Indications for mastectomy. 1. Tumor is large compared with the size of the breast, and neoadjuvant therapy is not planned. 2. Cases with multiple areas of cancer far from each other in the breast. 3. Infl ammatory breast cancer after chemotherapy. 4. Cases where wound margins free of cancer cannot be produced by breast conserving therapy. 5. Cases where the adjuvant therapy being planned cannot be given. 6. The patient wishes mastectomy to be performed.
12 not receiving radiation therapy (Cutuli ). includes chemotherapy, hormone therapy, and Adding radiation therapy to the regimen aft er biological therapy. BCT increases long-term survival to the same Systemic treatment can be given preop- level as in patients with mastectomy (Cutuli eratively as neoadjuvant therapy in order to ). Radiation therapy is used to reduce the shrink the tumor, making the operation pos- size of the tumor or metastases before surgery sible. Neoadjuvant therapy has been found or to destroy cancer cells remaining in the to be as eff ective as postoperative therapy in breast, chest wall, or axilla aft er surgery (Early terms of survival, disease progression and dis- Breast Cancer Trialists’ Collaborative Group tant recurrence (Mauri ). Adjuvant sys- ). Most patients with DCIS can be treated temic treatment given aft er surgery as diff erent with BCT with or without radiation therapy. combinations of cytotoxic drugs has proven Tamoxifen may decrease local invasive recur- eff ective in reducing recurrence and death rence in DCIS, but it has no eff ect on survival rates, and the eff ect can last more than years (Fisher ). Th e side-eff ects of tamoxifen aft er the treatment (Hortobagyi , Early include an increased risk of thrombotic events Breast Cancer Trialists’ Collaborative Group and endometrial cancer (Fisher ). It is not ). It is given to patients with a high risk of recommended in routine therapy, but some recurrence and also to women with metastatic patient groups may benefi t from it (Finnish breast cancer when curative surgery is not pos- Current Care Guidelines , National Can- sible. Hormone therapy has been observed to cer Institute a). be eff ective in reducing recurrence and death All histologic types of invasive breast can- rates in both premenopausal and postmeno- cer may be treated with BCT and radiation pausal women with hormone receptor-positive therapy (Weiss ). In patients without dis- tumors (Early Breast Cancer Trialists’ Col- tant metastases (stages I–III A + operable III C laborative Group , ). Th e most com- patients) (American Joint Committee of Can- monly used antiestrogen drug is tamoxifen. cer ), options for surgical management of Recently, aromatase inhibitors have been ap- the primary tumor include BCT plus radiation proved for use in postmenopausal women as therapy, mastectomy plus reconstruction, and the initial hormone therapy or aft er tamoxifen mastectomy alone. Survival is equivalent with (Winer ). Th e monoclonal antibody tras- any of these options, as documented in ran- tuzumab, which targets the HER/neu protein domized prospective trials (Jacobson , of breast tumors, has been eff ective in increas- Veronesi , van Dongen , Veronesi ing survival in women with metastatic breast ). cancer (Cobleigh , Slamon , Vogel Most women with LCIS can be managed ). Data also show that women taking tras- without additional local therapy aft er biopsy. tuzumab in addition to chemotherapy have a No evidence indicates that re-excision to ob- reduced recurrence of cancer compared with tain clear margins is required. Tamoxifen has women receiving chemotherapy alone (Hamp- decreased the risk of developing breast cancer ton , Romond ). in women with LCIS (Fisher ). It is includ- ed in the therapy guidelines of LCIS patients in USA (National Cancer Institute a), but in 2.1.4. Prognosis Finland it is not routinely used in this patient group (Finnish Current Care Guidelines ). Th e majority of patients are cured perma- At present there is no curative treatment for nently. Nowadays, about of patients are disseminated breast cancer, but the quality of alive years aft er the diagnosis, aft er life can be improved and the disease-free and years, aft er years, and aft er total survival increased with systemic therapy. years (Ries ). Th e prognosis was worse Breast cancer metastases are frequently osseal, in ; in USA, of the patients whose but they are oft en found also in the liver, brain, cancer was diagnosed fi ve years earlier were lungs, and other soft tissues. Systemic therapy alive, and only ten years aft er the diag-
13 nosis. (National Cancer Institute b). Th e ), and the availability and skills of the sur- fi ve-year relative survival rate is slightly lower gical team. in the youngest age groups; of patients Breast reconstruction is considered only younger than years are alive fi ve years aft er if this is the patient’s wish. Aft er mastectomy, the diagnosis, compared with of patients many women fi nd the external prosthesis very aged – years or of those older than uncomfortable, and also experience physical years (American Cancer Society ). Th e and psychological disturbances in their body most important factor aff ecting survival is the image. Th e wish for breast reconstruction is stage of the disease. Th e risk for recurrence in strongly related to age and working status. an early stage (I) is – during ten years An estimated of mastectomized patients aft er the diagnosis and – in stage II dur- younger than years wish to have reconstruc- ing fi ve years aft er the diagnosis. Eighty-fi ve tive surgery, while the corresponding fi gure for percent of the recurrences occur within the women over years is only (Korvenoja fi rst fi ve years, but recurrence can occur even ). – years aft er the diagnosis. Today, about invasive breast can- Although the incidence of breast cancer cers are diagnosed yearly in USA, and approxi- continues to increase, mortality has been de- mately of these patients will have breast creasing, principally as a result of earlier diag- reconstruction (Jemal ). In Finland, of the nosis and improvements in adjuvant systemic women diagnosed annually with breast therapy. Th is means that increasingly more cancer, mastectomy is performed on about women with breast cancer treated years ago are – , i. e. on – women. Breast living a full life, most of them without recur- reconstruction is performed on about of rence or metastases. women younger than years. Th us, annually, some – patients undergo reconstuctive surgery aft er breast cancer in Finland (Stakes 2.2. Breast reconstruction ). Relative contraindications for the proce- 2.2.1. Indications dure are metastatic disease or severe medical Th e indications for breast reconstruction are comorbidities, e.g. massive obesity or marked loss of the breast because of surgery or absence cardiopulmonary problems. or deformity of the breast for congenital or acquired reasons. Th is thesis deals with breast reconstruction aft er mastectomy for breast 2.2.2. Principles of breast reconstruction cancer. Patients who have had or are expected to In mastectomy, varying amounts of skin, breast have considerable asymmetry of the breast tissue, and oft en the nipple-areola complex aft er tumor ablative surgery are suitable can- are removed. In traditional mastectomy, the didates for breast reconstruction. Most breast amount of skin excised is quite large, while skin reconstructions are performed on patients sparing mastectomy leaves most of the breast undergoing a mastectomy. It is recommended skin intact. Th e aim of breast reconstruction is that these patients should be counselled about to produce an optimal esthetic result by restor- reconstructive options before their tumor sur- ing the volume, shape, soft ness, contour, and gery (Blamey ). Women with locally ad- skin of the breast, using the opposite breast as a vanced disease may also be suitable candidates reference point. If the other breast is excessive- for breast reconstruction (Newman ). In ly large, its reduction may be needed. In such the preoperative evaluation, aspects taken into cases, the reductioplasty of the opposite breast account are disease status, future treatment and the breast reconstruction are performed plans, surgical history, and other health prob- during the same procedure, with the aim of lems, volume of the contralateral breast, body producing breasts as symmetric as possible. habitus, the patient´s expectations (Piasecki Breast reconstruction can be performed at
14 the time of mastectomy (immediate breast re- chological stress caused by loss of the breast construction, IBR) or at a later stage, months (Rosenqvist , Al-Ghazal ). Th e breast or years aft er mastectomy (delayed breast re- mass can be restored and the breast contour construction, DBR) (Cunningham , Feller recreated with nonautologous breast recon- , Hang-Fu ). Th e timing of the recon- struction by inserting an artifi cial implant, with struction is considered by a multidisciplinary autologous breast reconstruction using the pa- team consisting of surgeons and oncologists, tient’s own tissue to reform the breast, or with and it depends on the patient’s preferences, the a combination of these methods. Selecting the stage of the disease and the need for adjuvant type of reconstruction depends on the patient’s therapy (Curtin ). comorbidities, previous surgical history, body Breast reconstruction has traditionally been habitus, and the possibility of pregnancies in carried out as a delayed procedure, but nowa- the future. Autologous breast reconstruction days IBR has become the method of choice in is recommended for patients generally healthy many hospitals. IBR is ideal for patients with except for the breast cancer (Tachi ). If the an early disease, stages I or II. It is considered patient is a heavy smoker or has severe comor- oncologically safe in most cases, and has not bidities aff ecting the microcirculation, such as caused a delay in chemotherapy or radiothera- diabetes, cardiovascular diseases, or coagula- py according to the literature (Mustonen , tion tendency, a nonautologous reconstruction Gouy ). In Helsinki University Central or no reconstruction is oft en recommended. Hospital, IBR is recommended for patients Some characteristics of diff erent types of requiring mastectomy for diff use DCIS, for breast reconstructions are shown in Table II. patients with inherited susceptibility for breast cancer, for local recurrence aft er conservative surgery, or when mastectomy is needed be- 2.2.3. Nonautologous breast reconstruction cause of multifocality or large size of the can- cer (Jahkola ). DBR is considered a safer Th e simplest breast reconstruction technique is alternative if the patient is expected to receive to place a breast implant subcutaneously or un- oncological treatment for an invasive cancer. der the pectoralis major muscle. Th e implant is IBR could cause a delay in the start of chemo- a bag fi lled with silicone or saline, and it can be or radiotherapy when there are problems in of fi xed or adjustable volume. If the breast tu- wound healing (Jahkola , Pomahac ). mor has been operated on using a skin sparing Compared with DBR, the esthetic result of IBR technique, a prosthesis of fi xed volume can be is oft en better because the skin envelope and used. Th ere are various types of implants with the inframammary fold are maintained (Kroll diff erent forms and surfaces. Fixed volume im- ), and also the cost of the treatment is re- plants are suitable for selected patients, when duced because of one operation instead of two the desired volume of the reconstructed breast (Khoo ). Aft er successful IBR, it may be is small. Th ey are also used to give additional easier for the patient to manage with the psy- volume in connection with an autologous
Table II. Some characteristics of the main types of breast reconstructions.
Nonautologous Autologous Autologous Autologous Type of breast reconstruction (implant) (LD fl ap) (pedicled TRAM fl ap) (free TRAM fl ap) Duration of operation 1–2 hours 3–4 hours 3–6 hours 4–6 hours 1 (1 surgeon + Need of surgical teams 122 1 instrument nurse) Microsurgical experience no no sometimes yes needed Length of hospital stay 2–3 days 3–4 days 5–7 days 5–7 days
15 reconstruction, e.g. the latissimus dorsi fl ap connective tissue diseases has thus far not been (Ahmed ). Th e lengths of operation and confi rmed (Janowsky ). hospital stay are shorter in nonautologous than autologous reconstructions. Earlier, a high in- cidence of fl ap necroses, wound dehiscence, 2.2.4. Autologous breast reconstruction implant extrusions, and peri-implant contrac- tures has been reported aft er subcutaneous ap- Th e problems arising from breast reconstruc- plication of a silicone breast implant because of tions with an implant provided the motivation insuffi cient overlying skin to cover the subcu- to develop new methods for breast reconstruc- taneously placed prosthesis aft er mastectomy tion without any foreign material. Th e fi rst (Watts , Vandamme ). report of an autologous breast reconstruction Nowadays a nonautologous breast recon- was published in (De Cholnoky ). struction is performed in many centers in two Breast reconstruction with the patient’s own, phases with an expander prosthesis (Agha- autologous tissue is considered the optimal Mohammadi ). First, a tissue expander method for creating a natural-looking and is placed under the pectoralis muscle. Th is is -feeling breast. Autologous breast reconstruc- an empty silicone bag, which is gradually over tion consists of taking a fl ap of tissue from a a few weeks infl ated with saline, in an outpa- donor site and transferring it to the site of tient setting, to stretch the overlying tissue. the removed breast. Th e autologous fl aps Some months later, in a second operation, the for breast reconstruction are oft en obtained expander is removed and replaced with an from the lower abdomen or the upper back implant. Th e second operation can be avoided and sometimes the gluteal region. Tradition- by using a Becker-type expandable prosthesis, ally, the fl ap has consisted of muscle and the which has a remote injection port. When the overlying fascia, subcutis, and skin accompa- expander is fully infl ated, the injection port nied by the vessels nourishing these tissues. is removed and the prosthesis left in place Factors aff ecting the selection of the tissue for (Becker ). Th e expander technique for reconstruction include the amount of tissue breast reconstruction is suitable for women needed and the amount of tissue available at with a relative lack of skin aft er mastectomy the donor site. Th e wishes and lifestyle of the and small nonptotic breasts (Ahmed ). It patient are also considered when choosing is a good method also for young women with the fl ap (Jahkola ). Although the surgical bilateral prophylatic mastectomies, for whom procedure is complex and time-consuming, a bilateral TRAM fl ap reconstruction is not the result of a ptotic, soft , symmetrical recon- a good option because of future pregnancies structed breast is usually better than the result (Jahkola ). achieved with nonautologous reconstruction. Th e most common complication associated Moreover, the implant-related complications with breast implants is capsule contracture, are usually avoided. Autologous fl aps for breast resulting in a fi rm and spherical breast, breast reconstruction tolerate postoperative radiation asymmetry, and possible implant displacement therapy well (Zimmermann , Pomahac (Tachi ). Th e capsulated prosthesis must ). sometimes be removed and a new reconstruc- Th e fl ap can be transferred as a pedicled or tion made, causing increasing costs and incon- free fl ap or a combination of these two meth- venience for the patient. Capsular contracture ods. A pedicled fl ap is dissected from its sur- commonly develops aft er post-reconstruction roundings and turned to the recipient site so radiotherapy (Spear ). Th e safety of sili- that it remains attached to its original blood cone in breast implants has been discussed vessels. Th e use of the pedicled latissimus widely. Some leakage is thought to occur in dorsi (LD) musculocutaneous fl ap from the most implants because of degradation of the patient´s upper back was described for breast outer layer (Tachi ). Th e association be- reconstruction by Scneider with coworkers in tween silicone implants and increased risk of (Schneider ). It is a reliable fl ap with
16 a good blood supply. It is a popular method for muscles is used depends on the type of TRAM breast reconstruction for women with fairly fl ap reconstruction, the amount of tissue need- small breasts. Th e additional scars on the back ed, and the shape of the other breast (Schefl an and the usually required breast implant or ex- b, Hartrampf , Chang b, Serletti pander, with the possibility of capsular contrac- ). When the TRAM fl ap is unavailable be- ture, may limit its use (Tachi ). In , cause of extensive scars aft er lower abdominal Robbins published the original description of operations or the patient is exceptionally thin the successful use of a vertical superiorly based or very obese (Tachi , Jahkola ), the rectus abdominis musculocutaneous fl ap for pedicled fl aps used are usually the LD fl ap, the breast reconstruction in four women (Rob- thoracodorsal artery-perforator fl ap (TAP) bins ). Hartrampf and colleagues pub- (Angrigiani ), or the lateral thoracodorsal lished in anatomical and clinical studies fl ap (Holmström ). of the lower abdominal pedicled TRAM fl ap When transferring a free fl ap, the fl ap is for breast reconstruction (Hartrampf ). elevated from its original position, its pedicle Th e lower TRAM fl ap with its variations is vessels are dissected, their proximal ends are the current gold standard of autologous breast ligated, and then the pedicle vessels are cut. reconstruction (Grotting , Piasecki , Th e fl ap is then lift ed to its fi nal destination, Serletti ). Th e pedicled and free TRAM which has been prepared for the transfer, and fl aps with their subtypes are described in de- the pedicle vessels are anastomosed to the re- tail later in the text. Th e TRAM fl ap has many cipient blood vessels near the mastectomy area advantages compared with other methods for with a microsurgical technique. Th e use of a autologous breast reconstruction. Th e new soft free TRAM fl ap for breast reconstruction was and natural-looking breast can be created in fi rst reported by Holmström in (Holm- one surgical procedure, it is easier to produce ström ) and later popularised by Grotting symmetry with the other breast, the patients (Grotting ). To avoid problems caused by are usually happy to get rid of unwanted excess harvesting part of the rectus abdominis mus- abdominal fat tissue, and the scars of the opera- cle, newer modifi cations of the free TRAM fl ap tion are well concealed (Grotting , Serletti have been created, including the deep inferior ). Th e result of TRAM fl ap reconstruction epigastric perforator fl ap (DIEP) (Koshima is shown in Figure . , Allen ) and the superfi cial infe- Usually, only one of the rectus muscles is rior epigastric artery (SIEA) fl ap (Arnez ). used for unilateral breast reconstruction to Th ese fl aps consist of skin and subcutaneous limit any postoperative problems to the ab- tissue with the nourishing vessels, leaving the dominal wall. Choosing which one of the rectus rectus muscle in place. When these modifi ca- tions of the free TRAM fl ap are unavailable or unusable, the superior or inferior gluteal free fl aps (Shaw , Paletta ), the gluteal perforator free fl ap (GAP) (Blondeel ), the lateral transverse free thigh fl ap (Elliott ), the free laparoscopically harvested omental fl ap (Cothier-Savey , Jiminez ), and the Rubens fl ap (Hartrampf , Elliott ), among others may be suitable. In Finland most of the breast reconstruc- tions are performed with the LD fl ap with or without an implant, or with the TRAM fl ap and AB its modifi cations. Th e diff erent types of breast Figure 1. Result of breast reconstruction with a TRAM reconstruction performed at the Department fl ap. The same patient before (A) and after (B) the of Plastic Surgery, Helsinki University Central operation. Hospital, in are presented in Table III.
17 2.2.5. The TRAM fl ap rectus abdominis muscle is then cut above the arcuate line. At this stage, the fl ap has a double Pedicled TRAM fl ap circulation through the inferior and superior Th e technique for breast reconstruction with a epigastric vessels. Th e inferior epigastric ves- pedicled TRAM fl ap has not changed essential- sels are then cut, and the fl ap, which is now ly from the procedure described by Hartrampf perfused by the superior epigastric vessels, is and colleagues in (Hartrampf , Har- tunnelled under the upper abdominal skin and trampf , Grotting , Serletti ). Th e subcutis to the mastectomy area. Th e breast pedicled TRAM fl ap is a good option for breast is shaped by rotating the fl ap ° so that the reconstruction in patients who are generally medial side of the reconstructed breast repre- healthy nonsmokers, of normal weight or only sents the contralateral side of the fl ap. Th e dis- moderately obese, and have suitable tissue in tal portion of the contralateral side skin (zone the lower abdomen (Serletti ). IV, see Section ...) is discarded. During the Th e fl ap is formed of a transverse elliptiform operations presented in this thesis, the ab- skin island raised from the lower abdominal dominal wall was reconstructed without mesh area, mostly below the umbilicus, with the un- using nonabsorbable continuous sutures to the derlying subcutaneous fat and the rectus abdo- fascia. Nowadays, the defect in the abdominal minis muscle (whole or its medial two-thirds) fascia is usually repaired with synthetic mesh with its vessel pedicle. Usually the muscle op- (Serletti ). posite to the mastectomy side is chosen. Th e operation is performed under general anes- Free TRAM fl ap thesia. Stable hemodynamics and mild hyper- Th e use of a free TRAM fl ap for breast recon- volemic hemodilution are maintained during struction was fi rst reported by Holmström in the operation and postoperatively, and a de- (Holmström ). Aft er the studies of crease of temperature is prevented, as recom- Grotting and coworkers (Grotting ) sug- mended for microvascular operations (Robins gesting better blood fl ow in the free than the , Macdonald , Sigurdsson ). Th e pedicled TRAM fl ap, the free fl ap has gradually operation is usually performed by two micro- exceeded the pedicled fl ap in popularity (Tachi surgically experienced teams. Th e principles , Serletti ). Th e free TRAM fl ap is of this operation are outlined in Figure . Th e thought to be more reliable than the pedicled preselected skin island, about cm in width TRAM fl ap in smokers, in patients with pre- and – cm in height, is dissected from its vious abdominal scars, and in patients with surroundings. Th e distal half of the skin-sub- marked obesity, diabetes, hypertension, or cutis island, contralateral to the muscle side, is other diseases aff ecting the microcirculation fi rst elevated from the abdominal wall fascia as (Tachi , Serletti ). far as to the linea alba. Th e ipsilateral half of Th e principles of this operation are shown the skin fl ap, lying over the rectus muscle, is in Figure . Th e skin-subcutis island of the then dissected, leaving three medial centime- free TRAM fl ap is raised in the same way as ters of the anterior rectus sheath on the fl ap. with the pedicled TRAM fl ap. A small area Th e two rows of musculocutaneous perforators (length about , cm, width ,– cm) ) of the run through this strip of the rectus sheath. Th e anterior rectus fascia containing the medial
Table III. The different methods used for breast reconstructions performed after mastectomy for patients with breast cancer at the Department of Plastic Surgery, Helsinki University Central Hospital in 2007.
Other Pedicled (Pedicled) LD Free TRAM (Free) DIEP (Free) SIEA Non- autologous Total TRAM fl ap fl ap fl ap fl ap fl ap autologous free fl aps 040241735 291
18 and lateral perforators overlying the fascia is the anastomoses, the abdominal wall is closed incised. Under the fascia, a -cm portion of by nonabsorbable sutures, nowadays with the the rectus abdominis muscle extending from help of inlay mesh when needed. Th e neobreast the level below the umbilicus to the arcuate is designed, situating the former umbilical line is prepared to be taken within the fl ap. A area caudally and the contralateral side of the lateral narrow strip of the innervated rectus fl ap medially. Excessive or nonviable skin and muscle is left in place to avoid contraction of subcutis of the fl ap, especially in zone IV, is re- the muscle edges. Today, a medial strip of the moved at the closing phase. muscle is also left in place; this is believed to help maintain the abdominal muscle tonus. At Other variants of the TRAM fl ap this stage, the recipient vessels in the mastecto- Many modifi cations and refi nements have been my area are prepared. At the time of the studies made to the TRAM fl ap to ensure suffi cient in this thesis, the thoracodorsal or the scapular blood fl ow to the reconstructed breast and to circumfl ex vessels were used as recipient ves- diminish donor-site morbidity. Th e bipedicled sels in our hospital. Later on it has been stated TRAM fl ap is based on the traditional skin- that if an axillary node dissection has been or is subcutis island and both of the rectus muscles being performed the thoracodorsal vessels are with their superior epigastric pedicles. It is to be used as the recipient vessles of the fl ap. expected that blood fl ow provided by both of For patients with total mastectomy without the superior pedicles is better than blood fl ow axillary node dissection or with sentinel node through a traditional pedicled TRAM fl ap. Th e biopsy only, the internal mammary vessels are bipedicled fl ap is used when additional fl ap tis- preferred (Dupin , Serletti ). When sue is needed for creating a large neobreast for the appropriate vessels have been dissected in a woman with a limited amount of abdominal the thoracic area, the inferior epigastric vessels tissue, and for patients with lower abdominal are dissected down to their origin from the midline scarring. One of the major disadvan- external iliac vessels, part of the rectus muscle tages of a bipedicled fl ap is the increase in do- is cut at both ends, and the superior epigas- nor-site morbidity (Ishii , Wagner , tric vessels are ligated and cut. Th e inferior Simon ). epigastric vessel pedicle is then divided and One way to try to enhance the TRAM fl ap clamped, and the fl ap lift ed to the chest. Th e blood fl ow is to create an augmented or “su- pedicle vessels are anastomosed end-to-end percharged” TRAM fl ap. In this procedure the with a microsurgical technique to the recipient inferior epigastric, superfi cial epigastric, or vessels, usually the vein fi rst. Aft er completing superfi cial circumfl ex iliac vessels of the ipsi-
AB C
Figure 2. Principles of breast reconstruction. The preoperative situation is presented in Fig. 2 A, the pedicled TRAM fl ap in Fig. 2 B and the free TRAM fl ap in Fig. 2 C. The superior epigastric artery (SEA) and the deep inferior epigastric artery (DIEA) are marked in the pictures.
19 lateral or contralateral side of a conventional 2.2.6. Surgical complications of pedicled TRAM fl ap are anastomosed to re- the TRAM fl ap cipient vessels in the axilla (Harashina , Schefl an ). A “recharged” TRAM fl ap has Surgical complications and total fl ap loss also been developed, where the ipsilateral Postoperative infections and hematomas are (muscle side) deep inferior epigastric vessels rare in breast reconstructions with the TRAM of a pedicled TRAM fl ap are anastomosed to fl ap (Serletti ). Th e most common surgi- the deep inferior vessels of the contralateral cal complications are problems related to the side (skin-subcutis island) of the fl ap (Berrino abdominal donor site, the overlying mastec- ). Attempts to improve venous outfl low tomy skin, or the fl ap itself. Early abdominal from the pedicled TRAM fl ap have been made wall complications include seroma formation by anastomosing veins of the ipsilateral or and delayed healing of the abdominal incision, contralateral side to veins in the axillary area sometimes leading to necrosis of the umbilicus (Barnett , Yanaga ). or the abdominal skin. Th e most common late To decrease the disadvantages caused by abdominal wall complications are laxity, hernia, harvesting the rectus muscle, minimal amounts and chronic pain (Blondeel , Reece , of the rectus muscle can be included in a free Nahabedian a). To decrease abdominal TRAM fl ap, thus being called the muscle-spar- wall complications, medial and lateral portions ing free TRAM fl ap. Aft er the s, perforator of the rectus muscle can be left in place during fl aps have become popular in reconstructive pedicled and free TRAM fl ap elevations and a surgery. Th e DIEP fl ap is a free fl ap formed of synthetic mesh can be used for closure of the the same skin-subcutis island as the TRAM abdominal wound. fl ap. It is based on the perforator vessels origi- Aft er undermining, the mastectomy skin nating from the inferior epigastric vasculature area sometimes heals slowly and part of the (Koshima , Allen ). Only a small skin may be lost. Th is is considered to be due amount of the muscle and anterior rectus fas- to inadequate resection of compromised skin cia around the perforator is enclosed within during mastectomy. Th e slow healing can de- the fl ap. Th e fl ap is attached to the mastectomy lay the onset of chemotherapy aft er immediate site in the same way as the free TRAM fl ap. Th e breast reconstruction in some cases (Serletti frequency of using DIEP fl aps is on the rise, as ). surgeons become more comfortable with the Th e most important and serious complica- meticulous operation technique. tions related to the TRAM fl ap are total or par- Th e SIEA fl ap is also used as a free fl ap for tial loss of the fl ap. Total fl ap loss is the result breast reconstruction (Grotting , Arnez of irreversible cessation of blood fl ow in the ). It consists of a skin-subcutis island from fl ap, usually leading to failure of the breast re- the lower abdomen, based on the superfi cial construction. Flap ischemia can occur because inferior epigastric vessel pedicle. Th e muscle of arterial thrombosis, venous thrombosis, or and fascia remain completely intact during the the fl ap being too large for its intrinsic blood procedure, which is the main advantage of this supply (Kerrigan ). Typical rates of post- method. Th e superfi cial inferior epigastric ar- operative thrombosis lie between and tery arises from the femoral artery, about cm (Serletti ). In pedicled fl aps, thrombosis is below the inguinal ligament, and turns upward usually due to a microcirculatory low-fl ow state in front of the inguinal ligament. Th e SIEA fl ap caused by improper fl ap design, ischemia-rep- can be used only if an adequate SIEA is pres- erfusion injury, systemic factors (hypotension, ent. It is not found in about half of the patients, sepsis, vasoconstrictors or smoking), or local and in many patients the vessel caliber is too compression of the pedicle or the fl ap (Vedder small (Chevray ). ). Suffi cient reduction of venous blood fl ow can produce fl ap necrosis in spite of ad- equate arterial fl ow (Fujino ). In free fl aps, the fl ap failure is usually caused by thrombosis
20 of the pedicle artery or vein at the site of the patients, but decreased to – in the rest microvascular anastomosis. Venous occlusion of the patients, probably because of the team is more common than arterial occlusion in free getting experience on the procedure routines fl aps, leading to total fl ap loss if not treated in (Nieminen ). time (Vedder ). Venous or arterial occlu- sion is speculated to be a consequence of poor Cutaneous and fat necrosis surgical technique, leaving adventitia or media in the TRAM fl ap of the vessel exposed to blood-carrying fi brin Partial fl ap loss is observed as cutaneous or fat and platelets (Vedder ). Kinking or exter- necrosis. It is the result of locally inadequate nal compression of the artery or vein can also blood fl ow, which can be caused by, for in- be the stimulus leading to occlusion of the ves- stance, vasoconstriction of the small arterioles sel. Patients with a hypercoagulative tendency or too low perfusion pressure in the distal may be at risk for fl ap failure. It might be useful cutaneous and subcutaneous areas of the fl ap to preoperatively measure blood levels of some (Vedder ). markers for coagulation and fi brinolysis (Ols- Cutaneous necrosis of the fl ap develops son ). Flap salvage is oft en successful with early, within a few days to weeks aft er the op- immediate return to the operating room. Th e eration. It is seen clinically as dark edges of the incidence of total fl ap loss is usually less than TRAM fl ap, with no signs of local blood fl ow. It in pedicled fl aps and between and is usually treated with dressing changes and in in free fl aps (Table IV). some cases with surgical revision. Cutaneous Th e learning curve of a complex procedure necrosis oft en lengthens the hospital stay and aff ects the rate of complications. In a retrospec- costs, and exposes the patient to additional op- tive series of breast reconstructions with erations. A TRAM fl ap with cutaneous necro- free TRAM fl aps during -, the overall sis is shown in Figure . Fat necrosis is a form complication rate was among the fi rst of partial fl ap loss. It results in a fi rm mass
Table IV. Incidence of total or partial fl ap loss in pedicled and free TRAM fl aps.
Study TRAM fl ap type Number of fl aps Total fl ap loss (%) Partial fl ap loss (%) Fat necrosis (%) Hartrampf 1987 Pedicled 432 0.5 5.2 5.2 Schusterman 1992 Pedicled 48 0 17 23 Elliott 1993 Pedicled 128 0 10 N/A Kroll 1998 Pedicled 67 N/A N/A 26.9 Paige 1998 Pedicled 127 N/A 10 12.6 Clugston 2000 Pedicled 252 0 2 7.1 Garvey 2006 Pedicled 94 8.5 58.5† †
Schusterman 1994 Free 211 1 7† † Trabulsy 1994 Free 99 4 6 N/A Kroll 1998 Free 49 N/A N/A 8.2 Nieminen 1999 Free 185 1 4,3 N/A Chang 2000b Free 936 5.1 $ 6.2 N/A Kroll 2000 Free 279 0 2.2 12.9 Nahabedian 2002b Free 143 3.5 0 9.8 Scheer 2006 Free 46 4.3 6.5 9.0 N/A not reported. $ 38,5 % of patients moderately or massively overweight. † includes partial cutaneous, and fat necrosis.
21 in the subcutaneous tissue. It develops later the cutaneous blood supply and identifi ed dis- than cutaneous necrosis, generally one to six tinct skin territories, each receiving its blood months postoperatively. Th e diagnosis is made fl ow from its own source vessel (Manchot clinically or with ultrasound or mammography. ). His work formed the basis of the studies Th e fat necrosis area can be observed without of Salmon, who found that in reconstructive surgical interventions, or resected, as needed surgery a fl ap must include an arterial pedicle (Kroll ). Partial fl ap loss is seen in – (Salmon a, b). Knowledge of blood of pedicled TRAM fl aps and in – of free fl ow of skin has since remained relatively un- TRAM fl aps (Table IV). changed. Factors aff ecting the risk of partial fl ap loss Nowadays, the vasculature of the skin and in TRAM fl aps include smoking and obesity. subcutis is believed to consist of fi ve vascular Cutaneous necrosis is seen more commonly in plexuses (Figure ). Th e most superfi cial is smokers than in non-smokers (Chang a, the subepidermal plexus, beneath which run Padubidri , Selber , Booi ). In the dermal, subdermal, subcutaneous, and the addition, some studies suggest that smoking fascial plexuses. Each plexus is a horizontal increases the incidence of fat necrosis (Kroll fi ne meshwork of interconnecting vessels. Th e , Selber ), while others report no ef- plexuses have a huge capacity for distributing fect. (Alderman , Nahabedian b). Th e blood fl ow to the skin and subcutis. Th e der- role of overweight in development of cutaneous mal plexus with its muscular arteriolar vessels and fat necrosis of TRAM fl aps is described in is the main thermoregulatory system, and the Section ... subdermal plexus with its thin-walled capil- laries is the main site for nutrient exchange (Blondeel ). 2.3. Blood fl ow in surgical fl aps Th e blood fl ow to the vascular plexuses of the skin and subcutis is supplied through the 2.3.1. Blood fl ow of the skin perforator arteries, which arise from source arteries below the deep fascia (Blondeel ). Th e fi rst accurate publication of blood fl ow Th ey are described in Section ... to the skin was submitted by Harvey in (Harvey ). Tomsa subsequently described the subdermal and dermal plexuses of the skin 2.3.2. Regulation of cutaneous blood fl ow in (Tomsa ), and Spateholz the direct and indirect perforators to the skin (Spateholz Normal blood fl ow to the skin is about ml ). In , Manchot described in detail per g of tissue at rest. Th e blood fl ow to
AB Figure 3. The right breast of a patient who underwent breast reconstruction with a pedicled TRAM fl ap. Cutaneous necrosis on the fi rst (A) and seventh (B) postoperative day. The necrosis is seen at the edge of the contralateral skin of the fl ap (zone IV), now situated on the medial side of the new breast. Surgical revision was required.
22 tissues of the body is controlled by the needs A neural stimulus through the sympathetic fi - of the tissue itself (Guyton ). Several fac- bers to the α-adrenergic receptors of the vascu- tors regulate the vascular tone of skin vessels, lar smooth muscle induces constriction of the including the autonomic nervous system, precapillary sphincters and arterioles, and the cerebral functions such as emotions, ocular blood fl ow is directed, instead of to the capil- stimuli, and sounds, and other factors such as laries, through arteriovenous shunts to venules orthostatic position, nutrients, medicines, and and veins. Accordingly, sympathetic stimula- smoking. Peripheral vessels are in constant va- tion of the β-adrenergic receptors induces va- somotion, refl ected as rhythmic contractions sodilation. Th e sympathetic regulation through six to eight times per a minute (Vedder ). serotonergic receptors situated at arterio- Cutaneous blood fl ow is regulated at the lo- venous anastomoses induces vasoconstriction. cal and systemic level and by the baroreceptor Humoral regulation means regulation of blood mechanism. In the local control of cutaneous fl ow by hormones, ions, and other substances blood fl ow, the microvessels of the skin contin- of the body fl uids, stimulating the specifi c re- uously monitor the levels of oxygen, nutrients ceptors in the tissue. Th ese substances can ap- and carbon dioxide. Th ey regulate the circula- proach the tissue through the bloodstream or tion by constricting or dilating local blood ves- be secreted locally in the tissue. Norepineph- sels within seconds to minutes to provide the rine, epinephrine, angiotensin, vasopressin, se- ideal level of tissue blood fl ow needed for each rotonin, thromboxane A, and endothelin are type of activity. Hypercapnia, hypoxia, and the most important vasoconstrictors. Bradyki- acidosis cause vasodilation. Increased tissue nin, prostacyclin, and histamine are examples perfusion can induce a myogenic refl ex seen of vasodilatory substances (Guyton , Ved- as vasoconstriction and decreased blood fl ow. der ). Blood fl ow of skin decreases also as a result of elevated viscosity of the blood and local hypo- thermia (Guyton , Vedder ), 2.3.3. Principles of blood fl ow in fl aps Systemic regulation can occur neurally and humorally. Th e sympathetic vasoconstrictor In reconstructive surgery, even large tissue and vasodilator nerves modify the vessel tonus. defects can be successfully repaired with fl aps. Th e cutaneous arteriovenous anastomoses are Planning and choosing of the most suitable richly innervated by the sympathetic vasocon- fl ap for each purpose is based on knowledge of strictor nerves (Lossius , Crandall ). blood fl ow and behavior of the fl ap. Th e fl aps
Figure 4. A schematic representation of the vascular structure of the skin and subcutis. From Mathes SJ and Nahai F: Reconstructive Surgery; Principles, Anatomy & Technique. Churchill Livingstone Inc. (Elsevier), New York, USA 1997, p 15. Printed with the kind permission of the publisher.
23 can be classifi ed, based on their structure, as onow , Wang ) and in skin fl aps (Fin- muscle or fascial fl aps. If skin is included in the seth , McKee ) because of arteriolar fl ap, it is called analogously a musculocutane- vasodilation and increased capillary perfusion. ous or fasciocutaneous fl ap. Other tissues with Th e eff ect of sympathectomy on muscle blood vascular connections to the muscle or fascia fl ow has been investigated in rats. Proximal can also be included in the fl ap, e. g. bone, sympathectomy with somatic denervation tendon, bowel, or omentum. Th e known fl aps caused a triphasic dynamic response in the have a fairly constant pattern of blood fl ow peripheral microcirculation. During the fi rst through a vascular pedicle consisting of an ar- few hours there is an initial hyperadrenergic tery and vein. Th e pedicle or pedicles are called phase seen as vasoconstriction. Aft er hours, dominant if they can provide the blood fl ow a nonadrenergic phase with vasodilation can of the whole fl ap area. Minor pedicles cannot be seen. Th is can last up to two weeks, aft er guarantee the fl ap blood fl ow alone, without which a sensitized phase starts, with hyperre- the dominant pedicle (Mathes , Blondeel sponsiveness of the microvessels to vasoactive ). substances and a further increase in microcir- Th e angiosome concept developed by Taylor culation (Banbury ). and Palmer (Taylor ) lies at the founda- In animal studies, within a few hours af- tion of harvesting fl aps in modern reconstruc- ter fl ap elevation blood fl ow in the tip of the tive surgery. Th e angiosome was described as fl ap decreases markedly, while blood fl ow in a three-dimensional composite unit of tissue the proximal fl ap is preserved. Th e blood fl ow supplied by a specifi c source artery. Th e com- gradually increases to normal levels over the posite contains muscle, nerve, connective tis- next month (Vedder ). sue, bone, and overlying skin. Th e body is di- Neovascularization from the surroundings vided in angiosomes based on named source of the fl ap also increases the fl ap blood fl ow. arteries, and some angiosomes are divided into Within minutes of closing a small blood vessel, smaller territories. Th e angiosomes are usu- the nearby collaterals are dilated as a neurogen- ally interconnected with adjacent angiosomes ic or humoral phenomenon. During the next through reduced caliber choke anastomotic hours further opening of collaterals occur; the vessels or sometimes through ordinary anas- process continues for many months aft er the tomoses without caliber reduction. Th e outer operation. Hypoxia is thought to stimulate for- limit of each territory is defi ned by the position mation of local growth factors, such as VEGF, of choke vessels. Th e choke vessels can regulate fi broblast growth factor, and angiogenin, which the blood fl ow of the angiosome by dilating or in turn stimulate new vessel growth from the constricting as needed. small vasculature (Guyton ). Th e venous drainage of the body mirrors Clinical studies have found that the weight- the arterial supply in the deep tissues and in related intake of blood fl ow depends on the most areas of the skin and subcutis in the head, type of the free fl ap. Flaps with a large portion neck, and torso. Th e choke arteries are accom- of fat, like the TRAM fl ap, have a low intake panied by oscillating veins (Taylor ). Each of blood compared with fl aps containing abun- angiosome consists of matching arteriosomes dant muscle (Lorenzetti a). In free fl aps, and venosomes. the fl ap blood fl ow is believed to be dependent Th e elevation of a fl ap is followed by loss on the hemodynamic requirements of the fl ap of sympathetic innervation and spontaneous and not on the characteristics of the recipient release of vasoconstricting neurotransmit- artery (Lorenzetti b). ters. Many nutrient vessels are also cut. Th ese mechanisms lead to an acute decrease in fl ap Pedicles of muscle and fascia fl ow (Vedder ). Th e blood fl ow of muscles is based on one or In experimental studies, aft er denervation more vascular pedicles entering the muscle blood fl ow has been observed to increase in between its origin and insertion. Th e muscle skeletal muscle (Chen , Chen , Siemi- pedicle consists of an artery and paired ac-
24 companying veins, which are branches of the pedicles (for example the sartorius muscle) specifi c regional artery and vein. • and type V muscles receive their blood fl ow Th e vascular supply of muscles has been through one dominant vascular pedicle and classifi ed to fi ve types according to the pattern several secondary pedicles (e. g. the latissi- of blood fl ow by Mathes and Nahai (Mathes mus dorsi muscle). ). Th e principles of classifi cation of the Th e blood fl ow of deep fascia is based on vascular supply of muscles and fascia are vascular pedicles entering the deep surface of shown in Figure . the fascia and forming the vascular meshworks According to the classifi cation of Mathes of the subcutis and skin (see Section ..). Th e and Nahai: vascular pedicles from deep fascia to the skin • type I muscles are supplied by a single represent one of three types (Figure ): vascular pedicle (e. g. the tensor fascia lata • Type A is a direct cutaneous pedicle. It muscle), originates from the regional vessels, runs • type II muscles have one dominant pedicle closely beneath and superfi cially to the and one or more minor pedicles ( e. g. the deep fascia and gives off branches to many gracilis muscle), perforators to the skin. Th e SIEA fl ap used • type III muscles have two large vascular for breast reconstruction is based on a type pedicles arising from separate regional ves- A fasciocutaneous pedicle. sels or the pedicles are located on opposite • Type B is a septocutaneous (or intermus- sides of the muscle (e. g. the rectus abdomi- cular) pedicle running from major vessels nis muscle), between muscles up to the skin. In the ex- • type IV muscles have many segmental tremities, most perforators are of the sep-
Figure 5. The principles of classifi cation of the vascular supply of muscles and fascia based on Mathes and Nahai (1981). From the article Tukiainen E, Suominen S: Kudoskielekkeet rekonstruktiivisen plastiikkakirurgian arkea. Duodecim 2007; 123: 987-997, with kind permission of Suomalainen Lääkäriseura Duodecim. The rectus abdominis muscle of the TRAM fl ap represents type III muscle and its pedicle represents a fasciocutaneous pedicle (type C).
25 tocutaneous type. For example, the radial rest, they are microscopic. In addition to the forearm fl ap has a type B pedicle. periumbilical choke vessels, the DIEA is con- • Type C is a musculocutaneous pedicle. nected through choke vessels also inferiorly It runs from the regional vessels through with the SIEA, inferolaterally with the superfi - muscle, and then travels as a perforator cial circumfl ex iliac artery, and superolaterally through the overlying deep fascia, fi nally with the lateral cutaneous branches of the six participating in the subcutaneous and skin lowest intercostal segmental arteries (Taylor vascular networks. In the human body, , Miller ). Recently, communications musculocutaneous pedicles dominate on between the costomarginal, musculophrenic, the trunk area, seen as perforators passing and intercostal arteries have been found through fl at large muscles. Th e anterior (Marin-Gutzke ). Th e eff ect of the caliber thigh fl ap and the cutaneous part of the of choke vessels on their function has not been TRAM fl ap have musculocutaneous pedi- studied. cles (Mathes , Blondeel ). Blood fl ow to the skin and subcutis of the lower abdominal and periumbilical areas is supplied through the musculocutaneous per- 2.3.4 Blood fl ow in the TRAM fl ap forators. Th ese perforators run as branches from DIEA and SEA systems into and through Th e conventional TRAM fl ap is an asymmetric the rectus muscle to the vascular plexuses of fl ap consisting of part of one of the rectus ab- the overlying fascia and skin. Th e perforators dominis muscles, and a transverse elliptiform run in two parallel rows through the anterior area of fascia, subcutis, and skin above the rectus sheath on both sides of the linea alba, muscle. the medial row – cm laterally to the linea Th e rectus abdominis muscle is a type III alba, and the lateral row – cm medially muscle with two main vascular pedicles (see from the lateral edge of the rectus muscle. Th e Section ..). Th e two main pedicles are the highest concentration of major perforators is superior epigastric vessels and the deep infe- in the paraumbilical area. Th eir caliber varies rior epigastric vessels. Th e superior epigastric from very narrow to several millimeters (Boyd artery (SEA) usually arises from the internal , Moon ). Th e perforators from DIEA mammary artery and enters the rectus abdo- and SEA have been investigated later. In two minis muscle on its dorsal surface at the costal cadaver studies, the anatomy of DIEA perfo- margin, then running in the inferior direction. rators showed a homogenic pattern between In about of patients, the SEA arises from individuals (Nakajima , El-Mrakby ), the costomarginal artery (Milloy , Arnold while in two cadaver and ex vivo fl ap studies , Miller ). Th e deep inferior epigas- the perforators of DIEA varied markedly in tric artery (DIEA) arises from the external iliac their orientation and size (Ohjimi , Tre- artery and enters the rectus muscle on its un- gaskiss ). Th e perforators of SEA were dersurface below the arcuate line. Th e SEA and found to have a more consistent course (Tre- DIEA pedicles run inside the muscle as single-, gaskiss ). Th e branching pattern of the double-, or triple-branched arteries to the pe- DIEA has been examined recently with com- riumbilical region (Boyd , Taylor , puted tomography angiography. DIEA was ob- Moon , Watterson ), where the DIEA served to be single, bifurcating, or trifurcating. and SEA angiosomes communicate with each Th e trifurcating type had the largest amount of other through the choke vessels (see Section perforators through the rectus muscle (Rozen ..).Anatomical and radiographic studies ). have shown that the DIEA is more signifi cant In the pedicled TRAM fl ap, blood fl ow is than the SEA in supplying the skin of the ante- supplied through the SEA, which is the non- rior abdominal wall (Boyd ). dominant pedicle of the anterior abdominal Th e so-called choke vessels are of macro- skin and subcutis (Boyd ). Th e free TRAM scopic caliber in about of people; in the fl ap receives its blood supply through its domi-
26 nant pedicle DIEA, which is anastomosed to is considered zone I, and the same area on the the recipient artery in the thoracic area. contralateral side zone II. Th e skin lateral to In pedicled TRAM fl aps, blood fl ow to the the ipsilateral muscle is called zone III, and the ipsilateral skin and subcutis island, situated skin lateral to the contralateral muscle zone over the rectus muscle, comes through pa- IV. raumbilical and infraumbilical perforators, fi ll- Th e zones were initially numbered in the ing in a retrograde fashion from the superior order of assumed degree of perfusion. Cutane- epigastric system by means of the choke vessels. ous blood fl ow has been thought to be most (Boyd ). Th e contralateral skin and sub- reliable in zone I, and fairly reliable in the me- cutis island receives its blood supply through dial parts of zone III as well as in the medial anastomotic channels crossing the midline in parts of zone II. Th e distal end of zone III and the subdermal plexus (Taylor ) and by the lateral part of zone II are less reliable. Zone distinct subcutaneous arteries, mostly situated IV should be discarded routinely because it is near the umbilical area (Kaufman ). Th e prone to necrosis. When elevating a fl ap, the contralateral part of the skin-subcutis island is blood fl ow in an adjacent angiosome has been in fact a random-type fl ap. speculated to be quite reliable , becoming less In free TRAM fl aps, blood fl ow to the ip- reliable in more distant angiosomes, especially silateral skin and subcutis comes mainly from across the midline, as in zone IV in a TRAM the DIEA through the perforators. Th e contral- fl ap (Taylor ). It has been suggested that ateral island of the free TRAM fl ap is supplied zones II and III should be in reverse order in the same way as in the pedicled fl ap. because according to anatomical studies the Th e venous drainage of the TRAM fl ap skin ipsilateral perfusion is always better than the is through paraumbilical perforator veins, in a undirect perfusion to contralateral skin areas similar way as the arterial fl ow, to the deep infe- (Dinner , Moon ). rior and the deep superior epigastric veins. Mid- Hemodynamic studies on blood fl ow in line crossover runs through several branches of TRAM fl aps have not been published before the superfi cial and deep epigastric veins. In the the studies presented in this thesis. Th e stud- deep inferior epigastric pedicle, two large ve- ies published thereaft er are presented in the nae commitantes drain to the iliac circulation. Discussion. Th ese veins are larger than the ones following the SEA (Schefl an b, Watterson ). In addition, the superfi cial inferior epigastric veins add to the abundant venous outfl ow of the inferior veins. Th e deep inferior epigastric veins have valves that prevent retrograde fl ow (Costa , Taylor ). Th e periumbilical choke vessels have a bi-directional venous fl ow. When the pedicled TRAM fl ap is raised, distal venous outfl ow has to reverse from the inferior direction to the superior epigastric veins, pass- ing the venous valves through the choke ves- sels (Taylor , Moon ). To understand the diff erent types of circula- tion and to predict survival in diff erent parts of the TRAM fl ap skin, the skin of the fl ap island has been divided into four zones based on clinical experience and quality of perfusion (Hartrampf , Schefl an a and b). Th e zones are presented in Figure . Th e skin Figure 6. The four zones of the TRAM fl ap based on directly overlying the ipsilateral rectus muscle cutaneous blood fl ow.
27 2.3.5. Temperature and the cutaneous the core temperature near °C (Stoen , blood fl ow Sessler ). During general anesthesia core temperature decreases in three phases (Ses- Human body temperature is controlled cen- sler , Hynson , Matsukawa a). trally by the thermoregulatory center in the During the fi rst hour the core temperature preoptic/anterior hypothalamus in the brain. decreases at least °C because of the core-to- It receives information from the core and sur- peripheral redistribution of body heat, caused face temperatures and coordinates the eff erent by anesthesia-induced inhibition of tonic va- responses regulating the temperature. During soconstriction. Aft er this, the core temperature heat stress, an increase in core or surface tem- decreases slowly, in a linear fashion when heat perature leads to loss of heat via sweating and loss exceeds metabolic heat production because cutaneous vasodilation. During cold stress, of cooling. Finally, the core temperature stabi- reduced temperatures cause refl ex decreases in lizes when thermoregulatory vasoconstriction heat dissipation by cutaneous vasoconstriction develops, reducing cutaneous heat loss and and simultaneously heat production by shiver- keeping metabolic heat in the core. General ing. During normothermia, skin blood fl ow anesthesia reduces the thresholds for vaso- averages about of cardiac output. Th e cu- constriction and shivering by approximately taneous blood fl ow varies depending on body °C (Sessler ) if the development of hy- temperature; during maximal vasoconstric- pothermia is not prevented. In reconstructive tion, as in cold stress, the absolute amount of plastic surgery, the operations usually continue blood in the skin is near to zero, and during for many hours, and thermoregulatory vaso- maximal vasodilation in heat stress the cuta- constriction, lasting for several hours postop- neous blood fl ow can consist of up to of eratively, frequently develops. Th e amount of cardiac output (Rowell , Boulant , uncovered skin during the operation also con- Kellogg ). tributes to development of hypothermia. Dur- Th e degree of thermoregulatory vasocon- ing breast reconstruction with a TRAM fl ap striction can be evaluated by the skin tempera- large areas of the patient’s skin are exposed, ture gradient (Tgrad), which is determined as because there are two surgical teams working the diff erence between fi nger and arm temper- simultaneously, one on the abdomen and the atures (Stoen ). Tgrad correlates with fi n- other on the chest. gertip blood fl ow in humans (Rubinstein , All inhaled anesthetics induce vasodilation Akata ) and is thought to indicate the state in the skin by inhibiting central thermoregu- of the arteriovenous shunts (Rubinstein ). latory control (Ozaki , Ozaki ). Iso-
Tgrad exceeding °C is generally accepted to in- fl urane has a more potent vasodilatory eff ect dicate marked vasoconstriction, and Tgrad less on skin blood fl ow than halothane (Mulhol- than °C is considered a sign of vasodilation land ). Th e thermoregulatory threshold (Stoen ). Th e concept thermoregulatory is highest for nitrous oxide and halothane, threshold is used for the level of core tempera- and lowest for sevofl urane and isofl urane; an ture at the stage when thermoregulatory vaso- inverse correlation with the anesthetic dose constriction begins (Stoen , Belani , has been found (Smith , Stoen ). Kasai , Pezawas ). Also intravenous propofol inhibits the cen- tral thermoregulatory control, thus leading to redistribution hypothermia (Leslie , 2.3.6. Effect of general anesthesia on ther- Matsukawa b). In addition, propofol moregulation and cutaneous blood fl ow produces a profound, peripheral arterial and venous dilation (Bently ), causing an Unanesthetized subjects do not become hypo- increase in skin blood fl ow. Th e agent used thermic in the ambient temperature of an op- for induction of anesthesia aff ects the degree erating room because thermoregulatory vaso- of hypothermia developing during the op- constriction with shivering usually maintains eration. Th e hypothermia is more profound
28 with intravenous propofol than with sevofl u- Temperature of the fl ap is an old method for rane inhalation as an induction agent (Ikeda monitoring fl ap blood fl ow in replanted body ). Patients developing even a short- parts and fl aps. It is considered reliable in ideal lasting propofol-induced vasodilation during circumstances (Sloan , Kaufman ) the induction of anesthesia have developed a and is still a popular method for monitoring marked hypothermia compared with patients replanted digits. However, ambient tempera- receiving inhalational induction with sevofl u- ture, core temperature, humidity, light, and rane (Ikeda ). Ketamine as an induction vasomotor responses can aff ect surface tem- agent causes considerably less hypothermia perature, which has been found to react slowly than propofol (Ikeda ), as it is an arterial when blood fl ow decreases. In buried fl aps, vasoconstrictor. Intraoperative thresholds for measuring the temperature diff erences be- thermoregulatory vasoconstriction depend on tween thermocouple probes placed proximally the size, shape, and age of the patient, depth and distally to the anastomosis is considered of anesthesia, degree of pain stimulus, and the more reliable than observing the surface tem- method of temperature management. (Sessler perature (May ). , Sessler , Washington , Kurz Several chemical techniques have been ap- , Xiong ,) plied for monitoring of fl aps. Tissue perfusion In humans anesthesia mainly aff ects cutane- can be estimated aft er an intravenous injec- ous blood fl ow, while subcutaneous blood fl ow tion of fl uorescein (Lange , McCraw , remains virtually unchanged (Saumet ). Graham ). Adequately perfused tissue fl uoresces under ultraviolet light. Th e method is useful at the time of elevation of a skin-con- 2.4. Monitoring of blood fl ow taining fl ap, but it is suitable only for a single in fl aps measurement in hours, and is thought to underestimate the amount of surviving tissue. 2.4.1. Methods used to measure blood fl ow Continuous measurements can be performed in surgical fl aps with a fi ber-optic dermofl uorometer, which Monitoring of blood fl ow in surgical fl aps is has been successfully used in monitoring essential to detect any disturbances in fl ap vi- perfusion of pedicled and free fl aps (Silver- ability. If signs of compromised blood fl ow are man , Casanova , Whitney ). observed, urgent measures are taken to reper- Indocyanine green is also a fl uorescent dye with fuse the fl ap. An ideal monitor of fl ap perfusion less side-eff ects than fl uorescein. It has given is simple, reliable, reproducible, and sensitive promising results in monitoring blood fl ow in and should give information about perfusion fl aps (Eren ). Radioactive isotopes, includ- of the whole fl ap. A selection of methods has ing technetium-m with a half-life of , been developed for monitoring blood fl ow in hours, (Aygit ), xenon- with a half-life fl aps. However, only a few methods are suitable of , days (Tsuchida ), and sodium- for continuous clinical use in superfi cial and with a half-life of , years (Harrison ), buried fl aps. Th e methods most widely used have been given to patients and the perfusion are presented in the next sections. has been monitored with scintigraphy. Th ey Th e simplest method to monitor the fl ap is can be used for monitoring perfusion in free clinical observation of fl ap color and capillary and pedicled superfi cial and buried fl aps, but refi ll aft er gentle manual pressure. A pale color they are not suitable for continuous monitor- without capillary refi ll can indicate arterial in- ing. Hydrogen gas clearance gives repeated and suffi ciency and a blueish color with a very fast quantitative measurements of tissue blood fl ow refi ll can be a sign of venous congestion. Stick- in buried and superfi cial fl aps (Aukland , ing the fl ap with a needle and observing the Glogovac ). color of blood oozing from the pinprick holes Flap blood fl ow has been assessed with can also be used as a simple monitor (Dagum methods based on the tissue metabolism. Sub- ). cutaneous and intramuscular pH measured
29 with implantable probes have decreased in is explained in detail in the next sections. In fl aps with impaired blood fl ow as a conse- conventional Doppler ultrasonography, the quence of increased anaerobic metabolism probe emits ultrasounds to a tissue up to sev- (Raskin a). Microdialysis is a technique eral centimeters in depth, and the sound waves analyzing the metabolic activity of tissue by refl ected from blood cells in large arteries and means of microdialysis catheters implanted in veins are analyzed. Th e blood fl ow in arteries the tissue. Glucose, glycerol, lactate, and pyru- and veins has a typical signal, being triphasic vate concentrations can be measured from the in arteries and lower pitched and continuous dialysate. Th e method was initially used in in veins. When blood fl ow in a vessel decreas- brain monitoring, but it has been successfully es, the signal changes. When monitoring fl ap applied in fl ap monitoring as well (Bito , pedicles, the adjacent large vessels from other Ungerstedt , Edsander-Nord , Setälä tissues may disturb the accuracy of the ultra- , Setälä ). In ischemic free fl aps, de- sound Doppler signal. Miniature implantable creased glucose concentrations and increased Doppler probes attached to a thin cuff fi tting lactate levels and lactate/pyruvate ratios have around an effl uent vein or distally to the arte- been observed (Udesen , Setälä ). rial anastomosis have been developed to over- Near-infrared spectroscopy (NIRS) is a come this problem (Swartz , Swartz , noninvasive continuous method of monitor- Kind ). ing blood fl ow of tissue. It was introduced ten Th e measurement of local partial pressure years ago to monitor circulation in surgical of oxygen is a popular way to observe blood fl aps (Hayden , Th orniley ). It mea- fl ow in fl aps. It can be measured on the surface sures the hemoglobin and oxyhemoglobin of the fl ap with a transcutaneous oxygen tension concentrations in tissue up to cm in depth. monitor (PtcO) or inside the tissue with an im-
Th e hemoglobin concentrations refl ect chang- plantable tissue oxygen tension probe. PtcO is es in blood volume, thus indirectly indicating explained in detail later in the text. Tissue oxy- the amount of perfusion. NIRS has been able gen tension monitoring has been developed to diff erentiate between arterial, venous, and since s (Hunt , Chang ), gradu- total vascular occlusion in fl aps (Irwin , ally becoming a popular monitor of local brain Th orniley ). It is considered a promising blood fl ow in neurosurgery and neurocritical tool for measuring perfusion in fl aps (Scheu- care (Dings ). It is considered a reliable fl er ). Photopletysmography estimates the method for continuous monitoring of blood fl uid volume of tissue by detecting diff erences fl ow in superfi cial and buried fl aps as well (Ma- in light absorption of the skin. Light emitted by honey , Hirigoyen ). a cutaneous diode probe is refl ected by hemo- globin in the erythrocytes of dermal capillaries Laser Doppler fl owmetry of the skin. Th e refl ected light is received by a Th e laser Doppler fl owmeter is a continuous photo detector and analyzed as light intensity monitor of microcirculation. It was introduced along a frequency spectrum, with the noise re- about years ago following the development moved. Th e method can diff erentiate between of laser technologies and fi ber-optic systems perfused and nonperfused tissue and provides (Stern , Holloway , Nilsson a, a good estimate of pedicle vessel patency (Stack Nilsson b). Th is method of measuring cu- ). Newer modifi cations have been devel- taneous blood fl ow is based on the frequency oped using a green-light emitting diode, giving shift of the laser light. A monochromatic He- an accurate estimate of possible fl ap ischemia Ne laser beam is emitted through an optical (Futran ). fi ber on the skin surface where it permeates Th e Doppler eff ect has been widely used the skin to a depth of ,– mm. Th e thickness for measuring the velocity of blood fl ow since of the epidermis, the most superfi cial layer of the s (Strandness ). Th e main modi- skin, is ,–, mm and the thickness of the fi cations are the Doppler ultrasonography and dermis below is ,– mm. Th e LDF beam is the laser Doppler fl owmetry (LDF). Th e LDF assumed to reach the dermis, and, in some cas-
30 es, the subcutaneous layer under the dermis. cepted that the variable to be monitored is the When the laser beam hits moving blood cells trend in perfusion and not the absolute value in the blood vessels, the frequency of refl ecting given by the monitor. It has been suggested laser light is spectrally broadened, while the that if the relative fl ow of a fl ap falls to frequency of light refl ected from static tissues of its initial fl ow for more than minutes, does not change. A photodetector in the LDF the fl ap should be aggressively observed, and probe receives the backscattered light beams, in cases with very low LDF readings the fl ap which are processed by the instrument, and the should be immediately explored (Heller ). result is produced as a low-noise input signal LDF is used for postoperative fl ap monitoring linearly related to the number and velocity of in many centers. moving blood cells in the measured fi eld at low Th e LDF value is infl uenced only minimally or moderate fl ow rates (Nilsson b, Ten- by wide diff erences in oxygen tensions. Th e land , Bengtsson , Svensson ). LDF level varies greatly between diff erent indi- Th e LDF output signal is presented in arbitrary viduals and also between diff erent measuring perfusion units, which is a relative value. Th e sites in one person (Tenland ), but the cu- signal can be expressed as a continuous oscil- taneous LDF values for the same donor tissues lating line in a pen-recorder. have been similar between several volunteers Initially, LDF could only be used for moni- (Goldberg ). Daily LDF variations of – toring the skin, including the capillary loops of occur frequently. A LDF value measured the dermal plexus, with a skin probe, but today continuously or repeatedly at exactly the same a variety of diff erent probes are available, in- site in a person is considered reliable (Tenland cluding implantable miniprobes for monitor- ). Th e reliability of the LDF signal is af- ing diff erent tissues, e.g. the muscle of buried fected by improper attachment or movement fl aps, and probes with diff erent fi ber separa- of the probe, location of the probe over a larger tions suitable for monitoring vascular beds at vessel, or technical problems in the apparatus diff erent depths. or the laser beam (Heden , Clinton , Th e traditional LDF measures the blood Svensson ). fl ow at a single point, and repeated measure- ments give the trend in the perfusion at this Transcutaneous oxygen tension determined site. Recently, a new development PtcO is among the oldest methods for fl ap of LDF has been made, enabling blood fl ow in monitoring (Achauer , Harrison , Se- a larger area to be measured continuously. Th e rafi n , Svedman , Smith ). PtcO laser Doppler perfusion imaging (LDPI) is a is an indirect indicator of blood fl ow, refl ecting noncontact two-dimensional system, where oxygen delivery and consumption in the skin the laser beam scans a horizontal area with the (Achauer ). Th e method measures the help of mirrors integrated in the probe system, oxygen tension of skin through a permeable and processes an image containing at least membrane. Th e probe heats the skin to a tem- measurement sites. LDPI gives quantitative perature of about . °C to induce maximal information on a specifi c region of interest vasodilation to minimize the arterial-to-skin (Essex , Wårdell ) and has proven to surface oxygen gradient. be a useful and reliable monitor of perfusion Th e probe requires calibration against an in dermatology, plastic surgery, diabetology, oxygen-free zero solution and ambient pres- and wound healing (Arnold , Fullerton sure before each measurement and a stabi- ). lization period of – minutes aft er each
LDF is generally considered a good indica- replacement. PtcO is a little lower than arte- tor of changes in blood fl ow in clinical plastic rial oxygen tension (PaO) in normal subjects surgery (Heden , Svensson a, Svens- (Brown ). son b, Yuen , Heller ), although some authors have been sceptical (Walkinshaw , Banic , Hickerson ). It is ac-
31 2.5. Endothelin striction have been suppressed by calcium an- tagonists (Kiowski , Liu , Kobayashi 2.5.1. Endothelin and vasoconstriction , Yakubu ). Th e dihydropyridine Endothelin- (ET-), described in , is one calcium channel antagonist nicardipine, and of the most potent vasoconstrictors (Yanagi- the angiotensin-converting enzyme (ACE) in- sawa ). It is a -amino acid polypeptide hibitor enalapril suppress plasma-ET- levels mainly synthesized and secreted by vascular in hypertensive patients with type diabetes endothelial cells (Yanagisawa , Remuzzi (Iwase ). Felodipine is a dihydropyridine ). Stimuli inducing the production of calcium antagonist with a powerful vasodila- endothelin include cold, thrombin, increased tory capacity. It reduces peripheral resistance transmural pressure, stretch, hypoxia, and by relaxing arterial resistance vessels with- decreased shear stress on the vascular lining out causing negative inotropic eff ects (Ljung (Yanagisawa , Yoshizumi , Gandhi ). Before the studies of this thesis, no ). Th e vasoconstrictory eff ect of ET- ap- reports of its eff ects on ET- levels had been pears to be mediated via the ET-A receptors published. situated in smooth muscle cells, while the ET-B ET- production has also been suppressed receptors are situated in vascular smooth mus- by statins, which inhibit ET- production at cle cells and endothelial cells; they also medi- the level of gene transcription (Hernández- ate the vasodilatory eff ects of ET-, depending Perera ), by ET-A-receptor antagonists on the balance between vasoconstriction and (Liu ), and by nonselective ET-A/ET-B vasodilation (Seo , Mickley ). Th e antagonists such as bosentan (Kiowski , binding of ET- to smooth muscle cells causes Sutsch ). a prolonged vasoconstriction (Remuzzi ), which is intense in arteries and even stronger in veins (Cocks ). ET--induced vasocon- 2.5.3. Endothelin and surgical fl aps striction results in an increase of blood pres- sure, but ET- does not aff ect heart rate (Re- Studies on surgical fl aps indicate that endothe- muzzi , Gandhi ). It is involved in the lin may be an important regulator of the mi- control of cardiovascular function by mainte- crocirculation and aff ect the development of nance of vascular tone in man (Remuzzi , tissue necrosis. In dogs, intra-arterial infusion Haynes ). of ET- reduced blood fl ow in skin fl aps (Sam- ET- is a local hormone and more than uelson ). Intraperitoneal injection of ET- of its secretion from the endothelium has decreased the length of skin fl ap survival in is towards the underlying muscle and not to- rats (Tane ). wards the vessel lumen. Plasma ET- concen- Th e relation of ET- levels and ischemia tration is thought to increase only when very has been investigated in experimental fl aps. high amounts of ET- are released from the Elevated plasma ET- levels have been mea- tissues (Remuzzi , Gandhi ). Plasma sured in ischemic island epigastric fl aps (Mat- ET- concentrations of .– pg/ml have been suzaki , Hjortdal , Pang ,) and detected in healthy humans (Karwatowska- increased levels of ET- have been found on Prokopczuk ). Elevated ET- levels have vascular walls of the pedicles of isolated free been observed during surgery (Hirata ) fl aps submitted to prolonged ischemia (Pang and aft er major operations (Shirakami ). ). Progressive venous stasis has induced greater production of ET- than arterial isch- emia (Menger ). 2.5.2. Effect of different substances on ET- concentration of the blood fl owing endothelin levels from the pedicle vein of free TRAM or DIEP fl aps has been evaluated in women. ET- In experimental and clinical studies, plasma concentration increased during the operation endothelin release and subsequent vasocon- in fl aps, but not in peripheral blood (Lantieri
32 ). Th e concentration of ET- in diff erent delay procedure in TRAM fl aps was suggested parts of experimental random pattern skin by Hartfampf in his initial publication (Har- fl aps has been investigated. In the early post- trampf ). Surgical delay of a fl ap has been operative hours, the highest levels of ET- shown to lead to dilation of the choke vessels have been measured in the proximal fl ap (Tane between adjacent territories. It is a permanent , Inoue ). ET- is speculated to re- and irreversible event, with a maximal eff ect strict blood fl ow by inducing vasospasm on the between and hours aft er raising the fl ap proximal parts of the fl ap (Inoue ). In one (Dhar ). Incidence of necrosis was sig- study, endogenous ET- level was highest in nifi cantly lower in pedicled TRAM fl aps with the proximal fl ap for the fi rst hours, there- ligation of the superfi cial and deep inferior aft er gradually decreasing, and increased in epigastric arteries one month before the recon- the fi rst week in the distal fl ap. Th e distal ET- struction than in fl aps without the delay proce- level correlated with the incidence of necrosis dure (Ribuff o ). (Mobley ). To fi nd a pharmacologic agent capable of In experimental fl aps, administration of an preventing or reducing fl ap ischemia, many ET-A receptor antagonist FR- (Tane substances have been investigated. A variety , Inoue ) and a combined ET-AB re- of sympatholytics, vasodilators, calcium chan- ceptor antagonist tezosentan (Erni ) has nel blockers, rheologic agents, prostaglandin improved postoperative fl ap blood fl ow and inhibitors, anticoagulants, glucocorticoids, fl ap survival. A recent study shows, however, and free radical scavengers have had little or that the increasing eff ect of ET-A antagonist no eff ect on fl ap blood fl ow or development BQ- or ET-AB antagonist PD- on of necrosis (Vedder ). Recently promis- fl ap blood fl ow is not seen until – days aft er ing results have been observed in experimen- fl ap elevation (Wettstein ). In the same tal studies where vascular endothelial growth experimental study, administration of an ET-B factor (VEGF) was given preoperatively as antagonist BQ- increased tissue survival subdermal gene therapy in experimental skin signifi cantly. An increase in fl ap blood fl ow fl aps. Th e increase in fl ap blood fl ow caused was observed on the fi rst day aft er fl ap eleva- by VEGF is thought to be mediated by nitric tion (Wettstein ). oxide (Huang ). Th e role of endothelin re- ceptor antagonists in augmenting fl ap viability is discussed in Section .. 2.6. Effect of different interven- tions on blood fl ow in the fl ap 2.6.1. Calcium antagonists and Several interventions have been attempted to cutaneous blood fl ow prevent ischemia and improve blood fl ow in fl aps, especially in high-risk patients. Th e delay Calcium channel blockers are vasoactive procedure means restricting of fl ap blood fl ow agents capable of decreasing sympathetic tone before the planned reconstruction to produce, and producing arteriolar smooth muscle relax- in the distal portions of the fl ap, moderate ation. Th ey block the adrenergically mediated ischemia, which does not cause necrosis. Th is vasoconstriction by inhibiting the fl ux of cal- method is a type of ischemic preconditioning. cium ions into vascular smooth muscle cells. Th e delay procedure is performed one to four Whether denervation changes the eff ect of weeks before the fi nal operation date by elevat- calcium channel blockers on vascular smooth ing part of the fl ap, but leaving the pedicle un- muscle, is unknown. Th e density of dihydro- cut or by ligating one of the pedicles in fl aps pyridine calcium channel blocker binding sites with more than one dominant pedicle. Selec- was decreased to almost one-third of its normal tive embolization of one of the pedicles has value aft er denervation in vas deferrens of rats also been succesfully used as a delay procedure (Jurkiewicz ), but in another study dener- in pedicled TRAM fl aps (Scheufl er ). A vation increased the eff ect of calcium channel
33 blockers nifedipine and cobolt in slow skeletal Severe obesity is defi ned as BMI greater than muscles in frogs (Vasquez ). Th is topic has the th percentile or body weight over not been investigated in humans. the ideal weight (Najjar , Choban ). Felodipine is a vascular selective dihydro- pyridine calcium channel blocker with no di- Waist-hip circumference ratio rect eff ect on cardiac contractility or conduc- Body fat distribution can be described with tion at therapeutic dosages. It dilates peripheral the waist-hip circumference ratio (WHCR) resistance arterioles, but has no eff ect on veins. (Lapidus , Soler ). WHCR is the ratio It lowers arterial blood pressure by reducing between waist circumference and hip circum- peripheral resistance without causing negative ference. Waist circumference should be mea- inotropic eff ects. Felodipine is a more power- sured with the patient standing, at the border ful vasodilator than verapamil, diltiazem, or of the lowest third of the distance between the nifedipine (Ljung ). Th e dosage used in xiphoid process and umbilicus, and hip cir- treatment of hypertension is – mg once cumference about cm below the anterior iliac daily. In healthy subjects, mg of felodipine spine (Lapidus ). causes an increase in forearm blood fl ow and a In women, upper body obesity has been as- decrease in forearm peripheral resistance (Ag- sociated with cardiovascular problems (Lapi- ner ). dus ) and increased peripheral vascular Topical nifedipine has reduced the inci- resistance (Jern ). WHCR > . is con- dence of necrosis in experimental random sidered upper body type, WHCR .–. pattern skin fl aps (Davis ). Oral dihydro- medium type and WHCR < . lower body pyridine calcium antagonists have reduced the type fat distribution (Soler ). According to incidence of necrosis in some experimental the criteria of the World Health Organization studies (Hira , Pal , Yessenow , (WHO), WHCR > . in men and > . in Bailet ), but contradictory results have women denotes abdominal obesity (National also been reported (Miller , Emery ). Institutes of Health ). Dihydropyridine calcium antagonists, e.g. amlodipine, felodipine, nisoldipine, and nife- Measurement of thickness of dipine, have been able to inhibit ET--induced fat with ultrasonography vasoconstriction in some clinical and experi- Ultrasonography is a convenient, noninvasive mental studies (Kiowski , Liu ). Th e method for imaging soft tissues without radia- eff ect of felodidipine on blood fl ow or necrosis tion exposure. It has been used for measuring in fl aps has not been reported before the stud- the thickness of subcutaneous fat (Katch , ies presented in this thesis. Ramirez , Suzuki , Orphanidou ) and muscles (Hides ). Th e thickness of subcutaneous fat of the TRAM fl ap area, and its 2.7. Effect of overweight relation to cutaneous necrosis have been inves- on fl ap blood fl ow tigated (Yano ). In that study, the average 2.7.1. Measurement of obesity subcutaneous fat thickness over the abdomen correlated with BMI. Th e subcutaneous fat Body mass index thickness could be estimated to some extent by BMI with the exception of some patients with Body mass index (BMI), calculated as weight high BMI, who had a large amount of visceral (kg) / height (m), has traditionally been con- fat but only moderatel subcutaneous fat. Ac- sidered a reliable index of relative body weight cording to the same study, abdominal fat thick- (Keys ). Th e widely used classifi cation of ness is not a risk factor for necrosis of pedicled obesity based on BMI is presented in Table V transverse rectus abdominis musculocutane- (Krotkiewski , Poirier ). Obesity is ous fl aps in patients who are thin, average, or defi ned as BMI greater than the th percentile only mildly obese (Yano ). or a body weight over ideal body weight.
34 2.7.2. Overweight and complications obese patients were treated succesfully. Th e au- in TRAM fl aps thors state that the surgeon and patient must be aware of the possible association between Overweight is associated with an increased obesity and complications. According to this risk of comorbidities (Poirier ) and com- study, morbidly obese (BMI > ) patients plications related to surgical procedures (Ab- should avoid any type of TRAM fl ap breast re- del-Moneim , Choban ). Obesity of constructions (Chang b). the patient may cause several complications at Th e outcomes of pedicled and free TRAM the donor site and in the fl ap itself, probably fl aps in relation to weight were compared in because of cardiovascular problems (Lapidus a retrospective study. Of the patients, ). were obese (BMI > ,). Th e overall compli- High rates of fl ap and donor-site morbidity cation rate was similar in pedicled and free have been observed in obese patients who un- TRAM fl aps. An increased complication rate derwent breast reconstruction with a pedicled was observed in free TRAM fl aps of severely TRAM fl ap (Holmström , Hartrampf , obese (BMI ≥ ,) women and in pedicled Kroll , Berrino , Watterson , fl aps of obese (BMI ,–) smokers. Th e Spear ). Th ese complications include total overall complication rate correlated with BMI fl ap loss, fl ap hematoma, fl ap seroma, mastec- in free but not in pedicled TRAM fl aps. Th is tomy skin fl ap necrosis, donor-site infection, study indicates that both the pedicled and free donor-site seroma, and abdominal hernia. TRAM fl aps can be used successfully in obese Many authors have considered obesity a rela- patients, bearing in mind the possibility of tive contraindication to breast reconstruction complications (Moran ). with a pedicled TRAM fl ap (Schefl an a, Hartrampf ). Th e free TRAM fl ap has been recommend- 2.7.3. Overweight and cutaneous necrosis ed instead of the pedicled TRAM fl ap for obese in surgical fl aps patients and other high-risk patients such as heavy smokers (Watterson , Paige , Obesity of the patient may pose a risk to the Chang a). Obesity has, however, also been viability of the TRAM fl ap. Th e probable un- associated with increased complication rates in derlying causes are vascular problems (Lapidus free fl aps, and is suggested to be a relative con- ) and the stretch caused by the heavy fl ap traindication to free TRAM fl ap reconstruc- on musculocutaneous perforator vessels nour- tion as well (Grotting , Schusterman , ishing the fl ap (Schefl an ). Consequently, Grotting , Kroll , Schusterman , obesity has been considered a relative con- Schusterman , Selber ). traindication to breast reconstruction by some In a retrospective review of free TRAM authors (Schefl an a, Hartrampf , fl ap breast reconstructions, overweight (BMI Grotting ). –,) and obese (BMI –,) patients In pedicled TRAM fl aps, obesity has in- had signifi cantly more fl ap and donor-site com- creased the risk of cutaneous necrosis in several plications than patients with an ideal weight. studies (Berrino , Moran , Ducic , However, the majority of overweight and even Spear ), but some authors have reported
Table V. Classifi cation of obesity based on body mass index (BMI) (weight (kg) / height (m)2).
Slightly Slightly Obesity Obesity Obesity Study Ideal weight Overweight underweight overweight grade 1 grade 2 grade 3 Krotkiewski 1983 < 19 19–24 25–27 28–30 Obesity > 30 Poirier 2006 < 18.5 18.5–24.9 Overweight 25–29.9 30–34.9 35–39.9 > 40
35 no eff ect (Kroll ). Fat necrosis has been ob- cutaneous necrosis was not increased in over- served in pedicled fl aps of obese patients more weight and obese patients (Chang b). In a oft en than in fl aps of patients with ideal weight retrospective comparison of outcomes of (Berrino ). In free TRAM fl aps, the risk of pedicled and free TRAM fl aps in patients with cutaneous necrosis increased in some studies BMI > ., cutaneous necrosis was more com- (Selber ), while other studies found no ef- mon in pedicled fl aps than in free fl aps. Th e fect (Chang b, Moran ). average BMI was in patients with pedicled In a retrospective study of pedicled fl aps and in those with free fl aps. Th e in- TRAM fl aps, obese patients (BMI > ) had an cidence of fat necrosis was equal for both fl ap increased risk for cutaneous necrosis compared types (Moran ). Prospective studies on the with patients with normal weight or over- eff ect of obesity on fat or cutaneous necrosis in weight (Spear ). In a retrospective survey TRAM fl aps, except for Study V in this thesis, of free TRAM fl aps, the incidence of fat or have not been reported.
36 3 Aims of the study
Th e purpose of this study was to obtain new knowledge about microcircula- tion and the TRAM fl ap during breast reconstruction.
Th e study focused on the following questions:
. What kind of perioperative changes are measured with LDF and PtcO in the cutaneous blood fl ow of pedicled and free TRAM fl aps for breast reconstruction (I, II)?
. Can postoperative development of cutaneous necrosis be predicted in
pedicled TRAM fl aps with perioperative LDF or PtcO measurements (I)?
. What kind of changes occur in the plasma concentrations of ET- during and aft er prolonged plastic surgical operations (TRAM fl ap being used as an example)? Can any association be found between the ET- concentrations and peripheral vasoconstriction, changes in blood pressure and heart rate, and development of cutaneous or fat necrosis (III)?
. Can preoperatively administered felodipine, a vasodilating calcium antagonist, cause changes in plasma ET- release and degree of vasoconstriction perioperatively, or cutaneous blood fl ow and development of cutaneous necrosis in a free TRAM fl ap postoperatively (IV)?
. Is there any association between the indices of obesity and the postoperative development of skin or fat necrosis in pedicled TRAM fl aps (V)?
37 4 Patients and methods
4.1. Patients 4.2. Methods 4.2.1. Study designs Th is clinical investigation was performed on women undergoing a breast reconstruction Study I with a TRAM fl ap at the Department of Plastic Surgery, Helsinki University Central Hospital, Fift een consecutive females scheduled for in –. Th e purpose and nature of the breast reconstruction were enrolled in this study were explained to the patients before prospective study. obtaining their informed consent. Th e study Changes in the cutaneous blood fl ow of a protocols of all investigations were approved pedicled TRAM fl ap were investigated with by the Ethics Committee of Töölö Hospital and LDF and PtcO at ten predetermined times pe- the protocol of Study IV also by the Finnish rioperatively and on the fi rst, third, and seventh National Agency for Medicines. Th e work con- postoperative days (Table VII). Th e patients sisted of fi ve studies (I–V). Th e characteristics were observed for development of cutaneous of the patients are shown in Table VI. necrosis during the one-week hospital stay. During Study II four patients with breast reconstruction using a “supercharged” TRAM Study II fl ap, i. e. a pedicled TRAM fl ap with an addi- In this prospective study, the cutaneous blood tional anastomosis to the vessels in the thora- fl ow of a free TRAM fl ap was evaluated in cal area, were also evaluated. women with breast reconstruction. Th e skin
In Study I two patients had hypertension re- blood fl ow was measured with LDF and PtcO quiring medication, and one also had hypothy- at the same preoperative and intraoperative reosis. In Study II, one patient took medication predetermined times as in Study I, and on the for hypertension and one for hypothyreosis. third postoperative day. In Study V, one patient took aspirin and gold Measurements were also taken from the for rheumatoid arthritis with mild symptoms. four women with a pedicled TRAM fl ap with Otherwise, all the patients were considered an additional microvascular anastomosis of healthy, except for the breast cancer treated the inferior epigastric vessels. earlier. Wound healing was observed clinically and
Table VI. Characteristics of patients in Studies I–V.
Study I II III IV V Number of patients 15 11 10 1 20 12 1 Age, years 46 (31–61) 46 (32–59) 47 (31–60) 46 (34–59) 9 (31–60) Weight, kg 64 (52–76) 66 (52–85) 65 (47–74) 64 (50–85) 63 (47–74) Height, cm 163(158–173) 165 (160–175) 164 (147–171) 164 (156–169) 163 (147–171) Time from mastectomy, years 4.8(1,5–7) 6.2(2–19) 4.2 (2,5–11) N/A 3.7(2,5–11) Duration of operation, minutes. 284(225–330) 396(312–510) 282 (230–360) 291(225–460) 280(230–360) Smokers 1/15 0/11 2/10 7/20 1/12
1 Nine of the patients were the same in Studies III and V. N/A Not reported. The data are represented as arithmetic means (range).
38 an ultrasound investigation was performed on values of MAP and HR were measured, and the reconstructed breast during the hospital a blood sample was drawn for plasma ET- stay in order to detect any signs of fat necrosis. determination on the preoperative day on the
ward. Tgrad, MAP, and HR were measured and Study III blood for ET- determination was sampled on Ten women undergoing a pedicled TRAM fl ap the operation day at the same measuring times reconstruction were investigated in a prospec- as in Study III (Table VIII). Postoperatively, on tive manner in order to determine whether the ward, blood was sampled for plasma ET- plasma ET- concentration has any role in the determinations on the fi rst, second, and sixth vasoconstriction that develops during long- postoperative days. To assess cutaneous blood lasting operations. Plasma ET- concentra- fl ow of the TRAM fl ap area, PtcO was mea- tions, forearm-fi nger temperature gradient sured on the fl ap marked on the abdominal
(Tgrad), rectal temperature (Trect), mean arte- skin preoperatively and one hour aft er arrival rial pressure (MAP,) and heart rate (HR) were in the recovery room, on the fi rst, second, and measured at nine predetermined times before, sixth postoperative days on the fl ap at its fi nal during, and aft er the operation (Table VIII). site. All measurements were performed on the Wound healing was observed in the same way ipsilateral (the side with the rectus muscle) and as in Study II. contralateral sides of the vertical skin area of the fl ap. Wound healing was observed clini- Study IV cally. Th e eff ect of felodipine on plasma ET- levels, peripheral vasoconstriction, and fl ap survival Study V was examined in a randomized, double-blind, Th e association of degree and type of obesity and prospective setting in women sched- with outcome of the pedicled TRAM fl aps for uled for breast reconstruction with a free breast reconstruction was evaluated in TRAM fl ap. Th e patients were randomly allo- women. Th e study was planned to be per- cated to receive either felodipine (Plendil® As- formed partly on the same patients as in Study tra Zeneca, Sweden) mg or a placebo tablet III. One of the ten patients in Study III refused perorally on the preoperative evening and in to take part in Study V, and so nine patients the morning before the operation. Th e baseline were the same in Studies III and V.
Table VII. The Laser Doppler fl owmetry (LDF) and PtcO2 measuring times in Studies I and II.
LDF LDF P O P O Phase Measuring time tc 2 tc 2 ipsilaterally contralaterally ipsilaterally. contralaterally 1 On preoperative day I, II I, II 2 Patient anesthetized, before incision I, II I, II I, II I, II 3 Contralateral side of fl ap elvated I, II I, II I, II 4 Whole fl ap elevated and rectus muscle cut I, II I, II I, II Inferior epigastric artery ligated (I) or superior 5 I, II I, II I, II pedicle ligated (II) Inferior epigastric vein ligated (I) or fl ap on 6 I, II I, II I, II the chest, before anastomosis (II) 7 Recovery room I, II I, II I, II I, II On fi rst postoperative day (I) I I I I 8 On third postoperative day (II) II II II II 9 On third postoperative day IIII 10 On seventh postoperative day IIII
39 On the preoperative day, weight was esti- tered to facilitate tracheal intubation. Anesthe- mated by measuring body mass index (BMI), sia was maintained with inhaled nitrous and type of body fat distribution by waist-hip- oxide and .– isofl urane in oxygen. Th e circumference ratio (WHCR). Th ickness of the aim was to maintain systolic blood pressure at abdominal fat over the rectus muscle was mea- – mmHg during dissection of the fl ap sured by ultrasonography on the preoperative and at about mmHg aft er the fl ap had been day and at one week, six weeks, three months, transferred to the mastectomy wound and/ and nine months postoperatively. or the anastomoses were fi nished. Th e lungs Survival of the TRAM fl aps was evaluated were ventilated mechanically to normocapnia clinically during the hospital stay and at the (exhaled end-tidal carbon dioxide concentra- outpatient visits at the same time-points as the tion at about ) with a Servo ventilator ultrasonography measurements were made. (Siemens-Elema, Sweden). Neuromuscular Signs of fat necrosis were noted during the ul- block was produced with pancuronium – mg trasonography investigations. as needed aft er a bolus of . mg/kg. Fentanyl was given in doses of .–. mg. At the end of the operation, neuromuscular block was an- 4.2.2. Anesthetic management tagonized with neostigmine . mg and glyco- pyrronium . mg. Isofl urane and nitrous oxide Th e patients were operated on under general inhalation were discontinued aft er the wounds anesthesia as recommended for microvascu- had been bandaged. Th e trachea was extubated lar and fl ap surgery at the time of Studies I–V when spontaneous ventilation was adequate. (Robins , Macdonald ). Th e patients Hydroxyethyl starch (Plasmafusin, were premedicated with mg of diazepam Leiras-Kabi Infusion Oy, Vantaa, Finland) ( approximately minutes before induction ml) was given aft er induction, and Ringer’s ac- of anesthesia. Aft er intravenous boluses of etate was infused to maintain a stable hemo- fentanyl . mg, glycopyrronium . mg, and dynamic state and mild hypervolemic hemodi- precurarization with pancuronium mg, an- lution. Hematocrit (packed cell volume) was esthesia was induced with thiopentone mg/ kept at .–., and transfusion was given kg. Suxamethonium –. mg/kg was adminis- as needed. Dextran ( ml) (Rheomacro-
Table VIII. The measuring times in Studies III and IV.
Phase Measuring time ET-1 T T MAP HR P O (Study III) grad rect tc 2 On preoperative day IV IV IV IV 1 Before induction of anesthesia III, IV III, IV III, IV III, IV 2 1 hour after induction of anesthesia III, IV III, IV III, IV III, IV III, IV 3 3 hours after induction of anesthesia III, IV III, IV III, IV III, IV III, IV 4 At end of operation III, IV III, IV III, IV III, IV III, IV 5 10 minutes after arrival in recovery room III, IV III, IV III, IV III, IV III, IV 6 30 minutes after arrival in recovery room III, IV III, IV III, IV III, IV III, IV 7 1 hour after arrival in recovery room III, IV III, IV III, IV III, IV III, IV IV 8 2 hours after arrival in recovery room III, IV III, IV III, IV III, IV III, IV 9 3 hours after arrival in recovery room III, IV III, IV III, IV III, IV III, IV On fi rst postoperative day IV IV On second postoperative day IV IV On sixth postoperative day IV IV
40 dex, Kabi Infusion A/S, Norway) was infused the umbilicus and the lower border above the aft er the operation until the next morning. All suprapubic area. A schematic representation of infusions were given via venous cannulas in the surgical procedures is provided in Figure the upper extremity on the side opposite the at the Review of the Literature section. operative side. Intraoperative heat loss was prevented by Pedicled TRAM fl aps (I, III, V) warming the infusion bags in water at °C Th e rectus muscle and pedicle on the opposite before the infusion started. Ambient tem- side to the mastectomy area were used. Th e half perature was maintained at approximately – of the fl ap situated contralaterally to the rectus °C during the operation and in the recovery abdominis muscle and mainly below the um- room. Skin-surface warming devices were not bilicus was fi rst elevated as far as the linea alba. used during operation, except for a water-fi lled Th e ipsilateral (over the rectus muscle) side warming mattress intraoperatively. of the TRAM fl ap was then dissected, leaving In the recovery room, the patients breathed three centimetres of the anterior rectus sheath room air during the measurements in Studies I on the fl ap. Th e rectus abdominis muscle was and II. At all other times the patients breathed cut above the arcuate line. At this stage, the oxygen via a face mask in the recovery fl ap had a double circulation through the in- room. Oxycodone in intravenous doses of . ferior and the superior epigastric vessels. Next, mg/kg was given for pain relief. Th e need for the DIEA was ligated and then the vein. Th e pain medication was assessed by experienced fl ap was tunnelled under the upper abdomi- anesthesia nurses. No other medication was nal skin to the mastectomy wound. Th e breast given in the recovery room. On the ward pre- was shaped by rotating the fl ap °C so that operatively and postoperatively, the patients the medial side of the breast represented the breathed room air. Analgesics were given as random side of the fl ap. Th e distal portion of needed on the postoperative days. the random side (zone IV) was discarded. Th e Electrocardiogram, heart rate, intra-arte- abdominal wall was reconstructed without for- rial pressure, pulse oximetry, urinary output, eign material using nonabsorbable continuous end-tidal carbon dioxide concentration, and sutures to the fascia. inspiratory oxygen concentration were moni- tored continuously throughout the anesthesia. Free TRAM fl aps (II, IV) Neuromuscular block was monitored with a Th e rectus muscle and pedicle on the opposite nerve stimulator. A cannula was inserted in the side to the mastectomy area were used. Th e radial artery of the arm with the infusion can- contralateral side of the fl ap was fi rst elevated nula for continuous blood pressure monitoring to the linea alba. Th e ipsilateral side (situated and for taking blood samples. over the rectus muscle) of the TRAM fl ap was then dissected. Next, . cm of the anterior rectus sheath and cm of the rectus muscle 4.2.3. Surgical technique were taken above the arcuate line to the fl ap. A lateral strip (. cm in width) of the rectus Th e same surgeon (SAS), as the head of the muscle was left in place to avoid contraction team, elevated all the fl aps using a standardized of the muscle edges. Th e rectus muscle was cut technique and performed all the anastomoses below the deep inferior epigastric pedicle. Th e in free fl aps. Th e fl ap was designed and drawn rectus muscle was then cut at a level below the on the skin surface on the preoperative day. All umbilicus, and the superior epigastric pedicle TRAM fl aps were formed of the rectus muscle was ligated. Th e DIEA was dissected down to and vessels opposite to the mastectomy side and the external iliac vessels. Th e pedicle was about a symmetric elliptic area of skin and subcutis cm long. Th e deep inferior epigastric vessels around and below the umbilicus. Th e height of were then ligated, and the fl ap was without the skin island varied from to cm, the perfusion. Th e abdominal wall was closed by upper border of the fl ap being slightly above nonabsorbable sutures. Th e assistant dissected
41 the scar at the chest wall and the skin to the and with PtcO in Studies I, II, and IV. Th e in- inframammary fold. spired oxygen concentration was during
Th e recipient vessels in the axilla were ex- the pre- and postoperative LDF and PtcO mea- posed. Th e deep inferior epigastric pedicle was surements, intraoperatively, and anastomosed end-to-end either to the thora- during an oxygen stimulation test in Study I. codorsal vessels or to the scapular circumfl ex Sterility of the LDF and PtcO probes was main- vessels. Th e free TRAM fl ap was placed on the tained during the operation. chest wall, the umbilicus caudally and the con- tralateral side of the fl ap side medially. Exces- LDF (I, II) sive skin and subcutis were removed, and the Th e LDF values were measured with a laser breast was shaped. Doppler fl owmeter (Perifl ux B, Perimed, Stockholm, Sweden) at times shown in Table Pedicled TRAM fl aps with the additional VII. A standard probe was used. One probe microvascular anastomosis (II) holder was attached with a double-sided Th ese four pedicled TRAM fl aps were elevated sticker on the axial (ipsilateral) side and one in the same way as the regular pedicled TRAM on the random (contralateral) side of the fl ap fl aps, and the deep inferior epigastric pedicle skin, both the same distance from midline, ap- was dissected and ligated (phase a). Th e fl ap proximately – cm depending on the form of was pulled to the thoracic wall (phase ). Th e the fl ap (Fig. ). Each measurement lasted for inferior epigastric vessels were anastomosed at least minutes. end-to-end to the thoracodorsal vessels ( cas- Th e measurements were made at the prede- es) or the scapular circumfl ex vessels ( case) termined times shown in Table VII. Th e fi rst in the axilla. measurement was performed aft er the patient had been anesthetized. Th e probe holders were 4.2.4. Measurements then detached during skin disinfection and later attached at exactly the same sites. Aft er Cutaneous blood fl ow this the probe holders remained attached at the Th e cutaneous blood fl ow of the TRAM fl ap sites until the last measurement on the third was monitored with LDF in Studies I and II (II) or the seventh (I) postoperative day.
AB
Figure 7. LDF and PtcO2 measurement sites on the TRAM fl aps, with the fl ap at its original site (A) and on the chest (B). The black circles represent the sites of the LDF probes and the white circles the sites of the PtcO2 probes. The measuring sites were the same in free and in pedicled (in this picture) TRAM fl aps.
42 PtcO2 (I, II, IV) was inserted about – cm and taped in place. In Studies I and II, the peripheral tem-
PtcO of the TRAM fl ap skin was measured with perature (Tperiph) was measured from the index a transcutaneous oximeter (Transcom , fi nger of the mastectomy side. In studies III Novametrix Medical Systems, Inc., CT, USA). and IV, probes for skin temperature measure- Th e measurement sites were on the ipsilateral ments were attached on the radial side of the side, over the rectus muscle of the TRAM fl ap, middle third of the antebrachium (Tant) and and on the contralateral side of the fl ap, about on the tip of the index fi nger (Tind) of the arm cm cranially to the LDF measurement sites on the mastectomy side. No intravenous fl uids on both sides of the fl aps (Fig. ). were infused in the arm with the peripheral Th e measurements were made using one temperature probes. probe, which was moved to the other mea- Th e baseline values of Trect were recorded suring sites according to the study protocol. immediately aft er the induction of anesthesia, Before the fi rst measurement and before each and the baseline values of the peripheral tem- replacement, the PtcO probe was calibrated peratures (Tperiph, Tant and Tind) before the induc- against an oxygen-free zero solution and ambi- tion of anesthesia. ent pressure. Th e temperature of the probe was In Studies I and II, Trect and Tperiph were . °C. Th e skin seemed to tolerate the heat- measured continuously during the operation. ing well since no burn injuries were observed Th e values at phases and and at the end of on the skin under the probe. the operation were included in the study. In
In Studies I and II, the PtcO measurements Studies III and IV, the thermoregulatory vaso- were performed at the times shown in Table constriction was evaluated as the temperature
VII. On the operation day, the ipsilateral and gradient (Tgrad) between Tant and Tind (Tant–Tind) contralateral values were obtained aft er the (Stoen ). Tgrad was measured continuously patient was anesthetized (phase ) and in the during the operation, and the perioperative recovery room. Between phases and , the values were included in the studies as shown in
PtcO probe was left on the contralateral side Table VIII. Tgrad exceeding °C was considered and kept in place. Th e ipsilateral values were signifi cant degree of vasoconstriction. not measured from phase to phase due to Th e arm on the mastectomy side was cov- the time-consuming calibration needed before ered with a cotton sheet during the operation. each replacement of the probe. Aft er the op- Th e rest of the patient was covered with dou- eration, the PtcO values were taken from both ble-thickness cotton drapes. In the recovery sides of the fl ap. room, the arm with the measurement probes
In Study IV, PtcO was measured from the was exposed; otherwise, the patient was cov- ipsilateral and contralateral sides of the TRAM ered with a hospital blanket and a sheet. fl ap at the times shown in Table VIII. An oxygen stimulation test was performed Plasma ET-1 determinations (III, IV) in Study I aft er each postoperative measure- In Studies III and IV, blood samples for ET- ment, with the patient breathing oxygen determinations were taken at the times shown for minutes. A minimum rise of in the in Table VIII. In Study III, before induction of
PtcO value was considered a positive result in anesthesia, a G venous cannula was inserted the oxygen test. without local anesthesia into a cubital vein of the arm on the side of the removed breast to Temperature measurements (I–IV) obtain blood for the plasma ET- determina- Rectal and peripheral temperatures were tions. Th e cannula was closed with an obtura- measured with thermocouple probes (Exacon tor while not in use. In Study IV, on the preop- MC , Exacon, Copenhagen, Denmark). erative day on the ward, a venous blood sample Th e patients had received laxatives to empty was drawn from the cubital vein for plasma the rectum for the surgery. Aft er induction of ET- determination before the blood pressure anesthesia, the rectal temperature (Trect) probe measurement. In the perioperative period, ar-
43 terial blood samples for ET- determinations were obtained from the indwelling catheter in were collected at the times shown in Table VIII. the radial artery. In Study IV, samples for the ET- determina- Blood was sampled for arterial oxygen ten- tions were obtained from venous blood on the sion (PaO) determinations in Study I at phase postoperative days. , three hours aft er the induction of anesthesia, Ten milliliters of blood was drawn into ice- in the recovery room, and during the oxygen chilled tubes containing mM (fi nal concen- stimulation test. In Study II, PaO was deter- tration) NaEDTA and carried immediately to mined at phases and . In Study III, arterial the laboratory. Plasma was separated by cen- samples for PaO determinations were taken trifugation at °C and stored at – °C until one and three hours aft er induction of anesthe- assayed for ET-. sia and minutes aft er arrival in the recovery Radioimmunoassay of ET- was performed room, and in Study IV three hours aft er induc- as described earlier (Fyhrquist ) using tion and minutes and two hours aft er arrival ET- and ET- antiserum generated in rabbits. in the recovery room. Th e antiserum showed cross-reaction Blood for hematocrit determinations was with ET- and ET- and < . cross-reaction sampled in all studies as needed to maintain with the –, –, and – sequences the desired level of hemodilution. In Study III, of preproendothelin and with big ET-, se- the hematocrit values determined at the same quences – and –. times as PaO, and in Study IV the values ob- Before ET- radioimmunoassay, plasma tained preoperatively and two hours aft er ar- samples were purifi ed using Bondelut C- rival in the recovery room were included in the OH analytical columns. One milliliter of study. plasma was acidifi ed with acetic acid and applied on a column. Aft er the samples had Assessment of weight (V) been washed with distilled water, the absorbed On the preoperative day, the weight and the peptide was eluted with ethanol and type of body fat distribution was estimated by acetic acid. Th e eluted fraction was lyophilized measuring BMI and WHCR. BMI is calculated and dissolved into assay buff er, mM buff er as weight (kg) / height (m). WHCR is the ratio pH ., containing mM NaEDTA, . nM between waist circumference and hip circum- cystine, . merthiolate, . bovine se- ference. Waist circumference was measured rum albumin, and . triton x-. Radio- with the patient standing, with a tape measure, immunoassay was performed using sequential at the border of the lowest third of the distance incubation by adding I-labelled ET- on the between the xiphoid process and umbilicus, third day. Bound ligands were separated on and hip circumference was measured about the fourth day using the second antibody tech- cm below the anterior iliac spine (Lapidus nique. Th e sensitivity of the assay was . pg / ). tube, and the recovery of ET- added to plasma Th ickness of the abdominal fat and the was . For external control, in each ET- rectus abdominis muscle of the fl ap area were radioimmunoassay three samples of pooled measured by ultrasonography. All ultasonog- normal human plasma containing , , or raphy measurements were made by the same pg of human ET- were measured. radiologist. Aloka SSD ultrasonography equipment (Aloka Co. Ltd., Japan) with a . Hemodynamic measurements and MHz surface probe was used for the measure- other blood samples (I–IV) ments. Th e margins of the TRAM fl ap were HR and MAP values registered at the times drawn on the abdominal skin on the preop- shown in Table VIII were included in Stud- erative day. Th e ipsilateral side of the fl ap was ies III and IV. On the preoperative day on the divided into fi ve equally long segments on its ward, blood pressure (noninvasive blood pres- long axis, and the thickness of the subcutane- sure monitor) and HR were measured with the ous fat was measured at these four points. Th e patient seated. Th e perioperative MAP values maximal thickness of the underlying rectus
44 abdominis muscle on the ipsilateral side was Study III measured at three points: on the top and bot- tom margins of the fl ap and at the midpoint Parametric data are given as mean ± SD and between them. Postoperatively, the same mea- nonparametric data as median (– surements were made at one week, six weeks, quartiles). Th e statistical analysis for diff er- three months, and nine months, at the same ences between the measuring times was per- sites of the fl ap, and the patients were inter- formed with the Wilcoxon-Pratt test. Nonlin- viewed and examined. Possible complications ear correlation between measured parameters were also analyzed. A clearly increased signal was tested with the Spearman rank test. intensity of the fat tissue in ultrasonography was regarded as a sign of fat necrosis. Study IV Th e data are given as means ( confi dence intervals (CI)). Characteristics of the patients 4.2.5. Statistical analyses are given as means (range). For comparison between the groups at each measuring time, Studies I and II diff erences of means ( CIs) were calculat- Th e LDF values were obtained in arbitrary ed. Statistical signifi cance was tested with the units. Because of the wide variation between pooled variance t-test. LDF values measured from diff erent persons and diff erent sites of the same person (Tenland Study V ), the LDF values taken at each site are Patients were divided into groups depending presented as a percentage of the reference val- on the BMI and WHCR as follows: BMI < ue of that measuring site. Th e values measured = slightly underweight; BMI – = ideal at phase (I, II) are regarded as the reference weight; BMI – = slightly overweight; and values of the LDF and PtcO measurements. BMI – = moderately overweight (Krot- Th e measured values are expressed as kiewski ), and WHCR < . = lower body mean ± SEM (I) or mean ± SD (II). Th e statisti- type; WHCR .–. = medium type; and cal signifi cance of diff erences between means WHCR > . = upper body type fat distribu- was tested using Student’s t-test for dependent tion (Soler ). and independent series (I). Th e statistical diff er- Abdominal fat thickness of each patient ences between the measuring times within one at every measuring time was calculated as a group were analyzed with the nonparametric mean of the four measurements taken. Th e Wilcoxon-Pratt test. Diff erences between the signifi cance of diff erences between the groups free TRAM fl aps and the pedicled TRAM fl aps was tested with the Chi-square test. Statistical with additional anastomosis were tested with analysis of diff erences in the measured vari- a two-sample rank-sum test (Mann-Whitney ables between the measurement times was test) (II). made with the Wilcoxon-Pratt test and for dif- ferences between the patients with and without necrosis with the Mann-Whitney test. P values of less than . were considered signifi cant.
45 5 Results
5.1. Perioperative changes of cutane- line level (phase ). When the whole fl ap was ous blood fl ow in TRAM fl aps (I, II) elevated and the inferior part of the rectus muscle cut (phase ), the blood fl ow returned One patient was excluded from Study I because to baseline level on both sides. Aft er ligation of technical problems in her LDF measure- of the inferior epigastric artery (phase ), the ments. Th us, the measurements of patients contralateral LDF value decreased signifi cantly are presented in this study. In Study II, there to ± (p < .) and the ipsilateral value were technical problems in the LDF measure- to ± of baseline level. Ligation of the ments of one patient and her LDF measure- vein (phase ) did not cause a change from ments were therefore excluded from the study. phase in LDF values. In the recovery room Other measurements in Study II are from all (phase ), the LDF values were contralaterally the patients. low, ± (p < .) of the reference value, and ipsilaterally near baseline level. On the fi rst (phase ), third (phase ), and seventh 5.1.1. Cutaneous blood fl ow (phase ) postoperative day, the LDF values in pedicled TRAM fl aps (I) were near baseline level on contralateral and ipsilateral sides of the fl ap. LDF values
Th e changes in LDF values at the contralateral PtcO2 values and ipsilateral measurement sites of the pedi- Th e PtcO values at the contralateral and ipsilat- cled TRAM fl aps are shown in Figure . eral measurement sites of the pedicled TRAM Elevation of the contralateral side of the fl aps are shown in Figure .
TRAM fl ap (phase ) caused a signifi cant On the preoperative day (phase ), PtcO increase in the ipsilateral value from base- was ± mmHg on the contralateral and
Figure 8. LDF values as a percentage of the initial value (phase 2) on the ipsilateral and contralateral sides of the 14 pedicled TRAM fl aps. ** represents p < 0.01 and *** p < 0.001 for difference from the initial value on each side of the fl ap. Measuring times as in Table VII. Values represent mean ± SEM.
46 ± mmHg on the ipsilateral side the fl ap. at ± mmHg. In the recovery room (phase
When the patient was anesthetized (phase ), ), the contralateral PtcO was ± mmHg
PtcO increased signifi cantly contralaterally and ipsilateral PtcO ± mmHg. On the fi rst and ipsilaterally. PtcO was measured only con- (phase ), third (phase ), and seventh (phase tralaterally between phases and . When the ) postoperative day, the contralateral and contralateral side of the fl ap was elevated, the ipsilateral PtcO values were low, but increased contralateral PtcO returned to ± mmHg. slowly towards the end of the study period. It decreased signifi cantly compared with the During phases , , , and the ipsilateral baseline to ± mmHg when the whole fl ap PtcO values were signifi cantly higher than the was elevated and the rectus muscle cut (phase contralateral values. All values measured dur- ). When the pedicle artery (phase ) and vein ing phases – diff ered signifi cantly from the
(phase ) were cut, contralateral PtcO stayed initial contralateral and ipsilateral values. Stable oxygenation of the patients was
maintained throughout the operation. PaO was ± mmHg one hour aft er induction of anesthesia, ± mmHg three hours aft er the induction, ± mmHg in the recovery room with the patient breathing room air, and ± mmHg in the recovery room during the oxygen stimulation test.
5.1.2. Cutaneous blood fl ow Figure 9. Changes in transcutaneous oxygen in free TRAM fl aps (II) tension (PtcO2) at the ipsilateral and contralateral measurement sites of the 14 pedicled TRAM fl aps. LDF values ** represents p < 0.01 and *** p < 0.001 for difference from the initial value (phase 1) on each side of the Changes in LDF values on the contralateral fl ap. § represents p < 0.01 for differences between the and ipsilateral measurement sites of the free ipsilateral and contralateral sides at each measuring TRAM fl aps are shown in Figure . time. Measuring times as in Table VII. Values represent Elevation of the contralateral side of the mean ± SEM. TRAM fl ap (phase ) caused an increase in the
Figure 10. LDF values as a percentage of the initial value (phase 2) at the ipsilateral and contralateral measuring sites of 10 free TRAM fl aps. * represents p < 0.05 for differences from the initial value on each side of the fl ap. Measuring times are as in Table VII. Values are given as mean ± SD.
47 contralateral and ipsilateral LDF levels. When the LDF values had increased further, contral- the whole fl ap was elevated and the inferior aterally to ± and ipsilaterally signifi - part of the rectus muscle cut (phase ), the cantly to ± (p < .). blood fl ow decreased contralaterally signifi - cantly compared with phase to ± of PtcO2 values
the initial value (p < .) and remained ip- Th e PtcO values at the contralateral and ipsi- silaterally at ± . Aft er ligation of the lateral measurement sites of the free TRAM superior epigastric pedicle (phase ), the LDF fl aps are shown in Figure .
values remained stable. When the inferior Th e preoperative PtcO was contralaterally pedicle was also cut and the fl ap was without ± mmHg and ipsi laterally ± mmHg circulation and lift ed to the chest (phase ), the (phase ). Aft er induction of anesthesia (phase
LDF value decreased contralaterally signifi - ), PtcO increased signifi cantly both contra- cantly to ± (p < .) and ipsilaterally laterally and ipsilaterally. Aft er elevation of to ± . In the recovery room (phase ), the contralateral side of the fl ap (phase ), the
the LDF values had returned to the baseline contralateral PtcO fell to the initial level. Th e
level. On the third (phase ) postoperative day, ipsilateral PtcO was not measured in phases
–. Th e contralateral PtcO decreased to ± mmHg when the whole fl ap was dis- sected and both pedicles were intact (phase ). When the fl ap was without perfusion in phase
, the contralateral PtcO fell to ± mmHg (p < .). In the recovery room (phase ),
the contralateral PtcO was ± mmHg (p
< .) and the ipsilateral PtcO ± mmHg. On the third postoperative day the contralat-
eral and ipsilateral PtcO was still low compared with the baseline values. Th e LDF and P O values of the four pa- Figure 11. Transcutaneous oxygen tension (P O ) at tc tc 2 tients with the pedicled TRAM fl ap and an the ipsilateral and contralateral measuring sites of 11 additional microvascular anastomosis in Study free TRAM fl aps. * represents p < 0.05 for differences from the initial value on each side of the fl ap. II are given in Table IX. Th ere were too few pa- Measuring times are as in Table VII. Values are given tients for us to be able to draw any statistical as mean ± SD. conclusions.
Table IX. Contralateral and ipsilateral LDF and PtcO2 values of the patients with a pedicled TRAM fl ap with an additional microvascular anastomosis (n = 4). Values are given as mean ± SD.
LDF (% of initial value) PtcO2 (mmHg) contra ipsi contra ipsi Phase 1 51 ± 6 45 ± 1 Phase 2 100 100 64 ± 26 42 ± 24 Phase 3 260 ± 255 163 ± 47 47 ± 37 Phase 4 77 ± 56 83 ± 21 14 ± 16 Phase 5a 54 ± 30 73 ± 30 10 ± 18 Phase 6 77 ± 59 76 ± 17 0 ± 0 Phase 7 236 ± 258 93 ± 36 20 ± 18 23 ± 13 Phase 8 145 ± 70 158 ± 56 19 ± 13 32 ± 4
48 5.2. Prediction of cutaneous tension values. Th e only patient who smoked necrosis in pedicled TRAM fl aps (I) did not develop necrosis.
During the hospital stay eight of the patients LDF values with pedicled TRAM fl aps developed cutane- Th e LDF values in the patients with and with- ous necrosis, which was diagnosed clinically. out necrosis are shown in Figure . Th e width of the necrosis varied between and Th e contralateral LDF values were signifi - mm. Th e two patients with a -mm-wide cantly lower in the TRAM fl aps with necrosis skin necrosis had other complications. One than in the fl aps healing without complications had a postoperative deep vein thrombosis, and in phase ( ± vs. ± , respectively, p liver metastases were detected later by ultra- < .), phase ( ± vs. ± , p < .) sonography. Th e other patient had received and phase ( ± vs. ± , p < .). radiotherapy for spinal metastases three years Th e contralateral LDF values were lower in the earlier. On the postoperative days, she had necrosis group than in the non-necrosis group marked postoperative atelectasis. Both of these also during phases , , , , and , but the patients were taking tamoxifen preoperatively. changes were not statistically signifi cant. Th ree of the eight patients with skin necrosis Th e ipsilateral LDF values were signifi cantly needed a surgical revision. Th e smaller areas lower in the necrosis group than in the patients of necrosis healed spontaneously. No signifi - without necrosis during phase ( ± vs. cant diff erences existed between the patients ± , respectively, p < .) and phase with and without necrosis with regard to age, ( ± vs. ± , p < .). No statis- weight, height, duration of operation, transfu- tically signifi cant changes occurred during sions needed, or hemoglobin or arterial oxygen phases , , , , , and .
AB Figure 12. LDF levels as a percentage of the initial value (phase 2) at the contralateral (A) and ipsilateral (B) measuring sites of the 14 pedicled TRAM fl aps in patients with and without necrosis.* represents p < 0.05 and ** p < 0.01 for difference between the patients with and without necrosis at each measuring time. Measuring times as in Table VII. Values are given as mean ± SEM.
AB
Figure 13. Changes in PtcO2 at the contralateral (A) and ipsilateral (B) measuring sites of the 14 pedicled TRAM fl aps in patients with and without cutaneous necrosis. * represents p < 0.05, ** p < 0.01, and *** p < 0.001 for difference between the patients with and without necrosis at each measuring time. Measuring times as in Table VII. Values are given as mean ± SEM.
49 PtcO2 values 5.3. Relation of plasma ET-1 con- centrations to peripheral vasocon- Th e P O values in the patients with and with- tc striction, blood pressure, heart rate, out necrosis are shown in Figure . and cutaneous or fat necrosis (III) Th e contralateral PtcO values were near zero aft er ligation of the artery (phase ) in Plasma ET-1 concentrations the fl aps with necrosis and at a slightly higher level in fl aps without necrosis. Th e PtcO val- In one of the ten patients in Study III, the plas- ues in the necrosis group were signifi cantly ma ET- levels were exceptionally high at the lower than in the necrosis group during phase three measurement times. Her highest ET- ( ± mmHg vs. ± mmHg, respectively) concentration was pg/ml, – standard and phase ( ± mmHg vs. ± mmHg) deviations above the mean of the plasma ET- (Fig. A). levels of the other patients. A technical error in
Th e ipsilateral PtcO values were signifi cantly handling her ET- samples was suspected, and lower in the necrosis group than in the patients thus all data for this patient were excluded. Th e without necrosis during phase ( ± mmHg patient was a nonsmoker who had had a mas- vs. ± mmHg, respectively), phase ( ± tectomy three years earlier and had received mmHg vs. ± mmHg), and phase ( ± postoperative radiotherapy. Her fl ap healed mmHg vs. ± mmHg (Fig. B). without necrosis. Data of nine patients were Th e oxygen challenge test was done at phas- included in the fi nal evaluation. es –. Th e oxygen test was more oft en nega- Th e preoperative plasma ET- concentra- tive on the contralateral side of fl aps develop- tions were . (.–.) pg/ml (median, ing cutaneous necrosis than in fl aps without – quartiles). At one and three hours aft er necrosis, but the diff erence was not statistically induction of anesthesia (phases and ) and at signifi cant. In the two patients with a -mm- the end of operation (phase ), they were sig- wide necrosis, the oxygen test was negative on nifi cantly lower, near pg/ml on average. Ten both sides of the fl ap in all but one measure- minutes aft er the patients’ arrival in the recov- ment. ery room, plasma ET- concentrations were signifi cantly higher than at the end of opera-
Figure 14. Perioperative changes in forearm-fi nger Figure 15. Perioperative changes in mean arterial temperature gradients (Tgrad) (difference between the pressure (MAP, white squares) and heart rate (HR, skin temperatures of the antebrachium and index black squares). Values are given as mean ± SD. * fi nger of the same arm). Values are given as median represents p < 0.05 compared with values measured and 25–75 % percentiles. * represents p < 0.05 before induction and † p < 0.05 compared with compared with values measured before induction and values at the end of the operation. Measurement † p < 0.01 compared with values at the end of the times as in Table VIII. operation. Measurement times as in Table VIII.
50 tion, but did not diff er signifi cantly from the 5.4. Effect of felodipine on plasma concentrations before induction. Th ey stayed ET-1 concentrations, peripheral va- around pg/ml until the end of the study. soconstriction, postoperative PtcO2, Peripheral vasoconstriction and survival of free TRAM fl aps (IV)
Tgrad of . (.–.) °C indicating vasocon- striction was observed preoperatively. During Th e characteristics of the patients and opera- the operation, Tgrad was negative, indicating va- tions were comparable within the groups. In sodilation. Aft er the operation, vasoconstric- the control group, one patient developed a tion developed again, Tgrad being at its highest postoperative hematoma necessitating surgical one and two hours aft er the patients arrived in evacuation, one patient suff ered from pneu- the recovery room (phases and ). Th ereaft er, monia, and one patient had a postoperative peripheral cutaneous vasoconstriction dimin- pulmonary embolism. ished, but some vasoconstriction was still ob- served at the end of the study (Figure ). Plasma ET-1 concentrations Th e preoperative plasma ET- concentrations Blood pressure and heart rate were . (.–.) pg/ml (means, CIs) in During anesthesia, MAP was signifi cantly the felodipine group and . (.–.) pg/ml lower than before induction. Postoperatively, in the control group. No statistically signifi cant it diff ered from the pre-induction level only at diff erences were present in ET- concentrations two hours aft er arrival in the recovery room. between the study groups at any measurement All MAP values measured in the recovery room time (Figure ). were signifi cantly higher than those measured at the end of the operation. HR remained at the Temperature pre-induction level during the operation. At all Before induction of anesthesia, Tgrad was . measurement times in the recovery room, it (.–.) °C in the felodipine group and . was signifi cantly higher than the level before (.–.) °C in the control group. Th ere were induction and also the level at the end of the no statistically signifi cant diff erences in Tgrad operation (Figure ). between the study groups during the study
period (Figure ). In both groups, Trect de- Healing of fl aps creased during the fi rst hour of anesthesia and Four of the nine TRAM fl aps healed unevent- was at it lowest three hours aft er induction, fully. Th ere was minor skin necrosis in three fl aps and fat necrosis in two fl aps. Th e three fl aps with skin necrosis needed surgical revision. Th e fi nal result in all fl aps was satisfactory.
Correlation of ET-1 with measured parameters In the nonparametric Spearman rank correla- tion test, a statistically signifi cant nonlinear correlation existed between ET- and Tgrad (r = ., p < .) and between ET- and MAP (r = ., p < .), but not between ET- and HR. A statistically signifi cant nonlinear correlation was present between the preoperative Tgrad and development of necrosis (r= ., p < .). No Figure 16. Perioperative changes in plasma ET-1 levels statistically signifi cant correlation was found in the felodipine and control groups. Values are given between development of necrosis and intra- as means (95 % CIs). The black squares represent the felodipine group and white squares the control group. and postoperative Tgrad values or ET- levels.
51 . (.–.) °C in the felodipine group did not diff er statistically with regard to PtcO and . (.–.) °C in the control group. at any measurement time. In both groups, two It increased again in the recovery room, peak- of ten patients developed a minor cutaneous ing three hours aft er the operation to . necrosis of the contralateral fl ap edge, which (.–.) °C in the felodipine group and healed without surgical revision. In these pa-
. (.–.) °C in the control group. No tients, the contralateral PtcO was near zero in statistically signifi cant diff erences were ob- the recovery room and during the fi rst days served in Trect between the two study groups at on the ward. In the felodipine group, a statisti- any measurement time. cally signifi cant diff erence was present in the
contralateral PtcO between the patients with Blood pressure and heart rate and without necrosis in the recovery room (p Th roughout the study period, HR was higher < .). in the felodipine group than in the control group. Th e diff erence was statistically signifi - cant before induction [. (.–.) beats 5.5. Effect of indices of obesity per min (bpm) in the felodipine group and on cutaneous or fat necrosis in . (.–.) bpm in the control group, dif- pedicled TRAM fl aps (V) ference of means . (.–.), p < .] and minutes aft er arrival to the recovery room Six of the patients had ideal relative body [. (.–.) in the felodipine group and weight (BMI –), one was slightly under- . (.–.) in the control group, diff er- weight (BMI < ), three were slightly over- ence of means . (.–.), p < .]. weight (BMI –), and two were moderately Th e preoperative MAP was . (.– overweight (BMI –). No patients in this .) mmHg in the felodipine group and study were obese (BMI > ). At the time of the . (.–.) mmHg in the control group. study, marked obesity was considered a con- Th roughout the study period, no statistically traindication for TRAM fl ap breast reconstruc- signifi cant diff erences in MAP were observed tion in Helsinki University Central Hospital. between the groups. Based on WHCR, four patients had an upper type, two a medium type, and six a lower type Healing of fl aps body fat distribution.
Th e ipsilateral and contralateral PtcO de- Th ickness of the subcutaneous fat on the creased in both groups from the initial ipsilateral side of the pedicled TRAM fl ap was mmHg to a lower level during the postopera- preoperatively . mm (mean) (range .– tive period. Th e felodipine and control groups .). One week aft er the operation, it had in- creased signifi cantly to . mm (–.) (p < . compared with the preoperative level), remaining at this level for the remainder of the study period. Of the patients, four developed minor cutaneous necrosis on the edge of the contral- ateral side of the TRAM fl ap and one developed fat necrosis seen on ultrasonography. Th ree of the patients with cutaneous necrosis needed surgical revision. Th ere were no signifi cant dif- ferences in fat thickness between the patients with and without cutaneous or fat necrosis at any measurement time. No statistically signifi cant diff erences were Figure 17. The perioperative changes in Tgrad in the felodipine and control groups. Values are given as present in development of necrosis between the means (95 % CIs). groups based on BMI. Necrosis was more com-
52 mon in patients with a WHCR of less than ., type fat distribution. In patients with a WHCR i. e. in patients with a lower body type body fat of more than ., there were no cases of ne- distribution (four of six developed necrosis), crosis. Th ese diff erences were not, however, than in patients with an upper or medium body statistically signifi cant (Table X a and b).
Table X. Presence of cutaneous or fat necrosis in patients grouped (A) by body mass index (BMI) and (B) by waits-hip circumference ratio (WHCR). AB
BMI (kg/m2) Necrosis (n = 5) No necrosis (n=7) WHCR Necrosis (n = 5) No necrosis (n = 7) <19 0 1 < 0,80 4 2 19–24 3 3 0,80–0,84 1 1 25–27 2 1 >0,84 0 4 28–30 0 2
53 6 Discussion
6.1. Perioperative changes of cutane- urdsson ). Our patients were kept mildly ous blood fl ow in TRAM fl aps (I, II) hypervolemic and hemodiluted in all studies, as recommended for microvascular surgery Breast reconstruction with the TRAM fl ap (Robins , Macdonald , Sigurdsson is performed on tens of thousands of women ). worldwide each year. Th e fairly common dis- turbances in the fl ap’s cutaneous blood fl ow may lengthen the treatment, increase costs, 6.1.1. Pedicled TRAM fl aps (I) and sometimes spoil the result of the opera- tion. Before the studies presented in this thesis, Th e results of Study I show that the elevation the behavior of the cutaneous blood fl ow in of the contralateral side of the pedicled TRAM diff erent phases of the TRAM fl ap operation fl ap caused an increase in cutaneous blood was unknown. fl ow, more clearly on the ipsilateral side of the Th e temperature of the patient can aff ect fl ap. Before the operation, blood supply to the cutaneous blood fl ow (Rowell , Boulant skin and subcutis of the TRAM fl ap area origi- , Kellogg ). Temperature and fl ap nated from the DIEA, whose branches run as blood fl ow are also connected to each other. paraumbilical and infraumbilical perforators In an experimental study on dogs, fl ap blood through the rectus muscles to the vascular fl ow varied directly with temperature (Awwad plexuses near the surface of the skin (Boyd ). Moreover, hypothermia decreased blood , Moon ). When the contralateral fl ow in the rat epigastric fl ap (Kinnunen ). side of the TRAM fl ap is elevated, the perfora- Th e changes measured in cutaneous blood fl ow tors rising from the underlying rectus muscle in the studies of this thesis can be assumed not are ligated, and the natural route for cutane- to have resulted from changes in the patient’s ous blood fl ow is lost. One would expect then temperature, because during these studies the a decrease in the cutaneous blood fl ow because patients remained fairly normothermic due to aft er its elevation the contralateral skin and the high ambient temperature ( °C), the use subcutis island receive blood only indirectly of a warming mattress, and warmed infusion from the ipsilateral side through anastomotic fl uids. channels in the subdermal plexus (Taylor Anesthesia aff ects mainly cutaneous, not the ) and distinct subcutaneous periumbili- subcutaneous blood fl ow in humans (Saumet cal arteries (Kaufman ). However, in this ). All inhaled anesthetics induce vasodila- study, hyperemia was observed with LDF when tion in the skin (Ozaki , Ozaki ). Th e the contralateral part of the fl ap was elevated vasodilatory eff ect of isofl urane is more potent in pedicled TRAM fl aps. Th e signifi cant in- than that of halothane (Mulholland ). In crease in LDF level on the ipsilateral side could the present studies, the patients were anesthe- be caused by opening up of the choke vessels tized with isofl urane. Th e decrease in LDF level between adjacent vascular angiosomes, leading aft er ligation of DIEA was likely not caused to increased blood fl ow from the SEA system by the anesthesia itself. It has been observed (Taylor ). Opening of the arteriovenous experimentally that blood fl ow measured by shunts has been found aft er elevation of a LDF is maintained well during normovolemic myocutaneous rectus abdominis island fl ap in conditions in musculocutaneous fl aps both pigs (Hjortdal ). Our fi ndings suggest that with halothane and isofl urane anesthesia (Sig- the same phenomenon may occur in humans.
54 Some degree of hyperemia was also measured published their report. Th ey demonstrated in on the contralateral side of the fl ap. Th is might an intraoperative investigation of pedicled be the result of opening up of the para- and TRAM fl aps that occlusion of the SEA at the infraumbilical reduced-caliber choke vessels upper level of the skin fl ap caused a decrease (Taylor ). Th e opening of the choke vessel in DIEA blood fl ow measured by ultrasound. may be stimulated by hypoxia caused by eleva- Th ey assumed that survival of all lower TRAM tion of the contralateral side. fl ap tissues requires reversal of the direction of A similar hyperemia was observed aft er el- blood fl ow to the fl ap (Harris ), in accor- evation of musculocutaneous fl aps in dogs by dance with our opinion.
Gottrup and coworkers (Gottrup ). Boyd In this study, the contralateral PtcO fell to and colleagues observed in a controlled experi- a very low level aft er the whole fl ap was ele- mental study that a delay procedure, preopera- veated and the DIEA was ligated. It remained tive ligation of SEA in TRAM fl aps, resulted near zero untill the seventh postoperative day, in a postoperative increase in the amount of when the measurements ceased. Very low PtcO viable fl ap skin. Th e authors speculated that values have been found in surviving fl aps post- transient hypoxia resulting from ligation of operatively (Achauer , Svedman , SEA may play a role in triggering DIEA to Gottrup ). In , Raskin and his group take over some of the territory previously and later Hjortdal and coworkers concluded perfused by SEA (Boyd ). Later, the delay that low PtcO levels measured aft er elevation procedure was found to lead to dilation of the of island fl aps were caused by decreased blood choke vessels between adjacent territories and fl ow in the subdermal plexus. Th ey speculated not to ingrowth of new vessels (Dhar ). that sympathetic denervation would stimulate Ribuff o and coworkers used the study setting opening up of the arteriovenous shunts and and protocol originally presented in Study I a decrease in blood fl ow in the most superfi - and measured blood fl ow with LDF and echo cial cutaneous layers (Raskin b, Hjortdal color-fl ow in pedicled TRAM fl aps. Th ey con- ). Th is could explain the very low PtcO fi rmed our results, showing hyperemia when values measured aft er DIEA ligation and dur- the contralateral side of the pedicled TRAM ing the postoperative period in Study I. PtcO fl ap is elevated (Ribuff o ). has been postulated to refl ect oxygen delivery In Study I, ligation of the DIEA caused a and consumption in the skin, and low oxygen signifi cant decrease in LDF value on the con- tension may be an indirect measure of in- tralateral side. Skin blood fl ow on the con- creased metabolic rate in the skin (Achauer tralateral side of the fl ap did not return to the ). Low postoperative PtcO levels in these baseline until the fi rst postoperative day. Th e patients might also be a sign of increased con- ipsilateral cutaneous blood fl ow remained near sumption of oxygen. Th e slow increase in PtcO the baseline level at all postoperative measur- during the postoperative week could indicate ing times. Based on these results, the SEA ap- that a few days aft er the operation SEA is grad- parently cannot provide adequate perfusion to ually able to maintain blood fl ow also in the the contralateral skin paddle immediately aft er most superfi cial cutaneous layers. ligation of the DIEA, which is the dominant ar- Th e postoperative PtcO levels were con- tery of the TRAM fl ap (Boyd , Hendricks stantly lower on the contralateral side of the ). Th e return of LDF levels to the baseline fl ap than on the ipsilateral side. Th is is prob- on the postoperative days could be speculated ably caused for anatomical reasons, as the con- to be a sign of SEA being able to increase blood tralateral side is postoperatively less perfused fl ow in the fl ap gradually aft er the operation than the ipsilateral side due to cutting of the by keeping the choke vessels open. Th e origin perforators during fl ap elevation. of microvascular blood fl ow, previously from Aft er this work, other studies have been DIEA, must be reversed if the whole fl ap is to conducted on the hemodynamics of pedicled survive aft er the operation. TRAM fl aps. Codner and colleagues measured Soon aft er Study I Harris and coworkers intravascular blood pressure of DIEA and the
55 corresponding vein before and aft er bipedicled and II confi rm the clinical observations of the TRAM fl ap breast reconstructions in patients free TRAM fl ap demonstrating very few cir- with and without delay. Th ey observed an in- culatory complications. In Study II, only one crease in DIEA and vein blood pressure aft er of patients developed a minor skin necrosis transfer of the fl ap to the chest, indicating an and one a fat necrosis, compared with Study I, increase in fl ap blood fl ow. Postoperatively, where eight of pedicled TRAM fl aps showed they observed a decrease in TRAM fl ap per- signs of minor cutaneous necrosis. Th e more fusion pressure in fl aps without delay and an reliable cutaneous blood fl ow in free fl aps has increase in fl aps with delay (Codner ). not been demonstated with hemodynamic Ribuff o and coworkers noted a similar decrease measurements earlier in the literature. Nowa- as in the present study in the contralateral LDF days the majority of TRAM fl ap breast recon- level of pedicled TRAM fl aps when the DIEA structions are performed in Finland with a free was ligated. Th ey also thought that this is due TRAM fl ap and newer modifi cations such as to blood fl ow inversion (Ribuff o ). In the the DIEP or SIEA fl ap. Pedicled TRAM fl aps studies of Clugston and coworkers, DIEA and are used in selected cases, especially outside the concomitant vein were cannulated. Th eir microsurgical units. measurements showed that the venous pres- In free TRAM fl aps, the ipsilateral and con- sure increased and the perfusion pressure de- tralateral LDF values increased, as in pedicled creased when the fl ap was rotated to the chest fl aps in Study I, during the elevation of the (Clugston ). However, unlike in our study, contralateral fl ap island and decreased to or they did not measure cutaneous blood fl ow. below the initial level when the whole fl ap was Scheufl er et al have demonstrated by angiog- elevated and the rectus muscle cut. Because raphy the opening of choke arteries between the elevation procedures are rather similar in the superior and the deep inferior epigastric pedicled and free fl aps, no diff erences were systems (Scheufl er ). In another recent expected. study of pedicled TRAM fl aps Scheufl er and When the DIEA and vein were cut and the associates found an increase in the systolic peak free fl aps were positioned on the chest, a sig- fl ow of the SEA early aft er surgery. Consistent nifi cant decrease in the contralateral PtcO and with our view, they speculated that hypoxia in LDF levels was observed in free fl aps as a sign the fl ap tissue could lead to opening of choke of reduction of blood fl ow. Th e LDF levels in arteries between the superior and deep inferior the free fl aps did not decrease to zero, although epigastric arteries (Scheufl er ). the fl ap was without blood fl ow. LDF is unable to distinguish between nutrient and non-nu- trient blood fl ow, and thus LDF seems to mis- 6.1.2. Free TRAM fl aps (II) interpret the non-nutrient random movement of cells in a nonperfused tissue as blood fl ow Cutaneous blood fl ow between pedicled and (Marks ). free TRAM fl aps was not compared in the In the recovery room, when the anastomo- same study. However, some conclusions be- ses were functioning, ipsilateral and contralat- tween the pedicled fl aps in Study I and the eral LDF levels returned to baseline levels in free fl aps in Study II can be drawn, because the the free fl aps. Th is result diff ers from the pedi- patients, operating conditions, anesthesia, and cled fl aps, where the contralateral LDF levels in measurements were similar. the recovery room were still signifi cantly lower On an anatomical basis, one might expect than at the beginning of the operation. In the that cutaneous blood fl ow would be better in recovery room, the contralateral PtcO was low free than in pedicled TRAM fl aps since the free compared with the initial level in free fl aps, but fl ap is supplied by the dominant pedicle of the had increased markedly compared with the TRAM fl ap, the DIEA (Boyd , Hendricks values measured before the anasto moses were
), and the pedicled fl ap by the nondomi- formed. Th e ipsilateral PtcO had increased to nant pedicle, the SEA. Th e results of Studies I the preoperative level in the recovery room,
56 and on the third postoperative day it was near gradually exceeded the pedicled TRAM fl ap in the initial level on both sides of the free fl aps. popularity as a breast reconstruction method, Th ese fi ndings diff er clearly from the pedicled despite the procedure being more demanding.
TRAM fl aps (Study I) where the PtcO levels Breast reconstruction with a pedicled TRAM were very low throughout the postoperative fl ap can be performed with less microsurgical period. Th e SEA apparently cannot perfuse experience. If the pedicled TRAM fl aps prone the pedicled fl ap adequately on the fi rst days to cutaneous necrosis could be identifi ed dur- aft er the operation. Th ese results indicate that ing or immediately aft er surgery, some surgical the postoperative blood fl ow in the free TRAM or pharmacological interventions could be at- fl ap, measured by PtcO and LDF is more gen- tempted to enhance blood fl ow in the fl ap, and erous than in the pedicled fl ap. Th is phenom- thus to increase the success rate. enon likely results mainly from the free fl ap In Study I, cutaneous necrosis was observed being supplied by the dominant pedicle of the during the study period on the contralateral TRAM fl ap, the DIEA, while the nondominant side of eight of the the pedicled TRAM fl aps pedicle SEA supplies the blood fl ow of the ( ), which is comparable with the indicence pedicled TRAM fl ap. rates given in the literature (Hartrampf ,
Th e contralateral LDF and PtcO levels were Schusterman , Elliott , Kroll , constantly lower than the ipsilateral values at Paige , Clugston , Garvey ). Fac- each measuring time in pedicled as well as in tors known to increase the risk of cutaneous free TRAM fl aps. Th is result agrees with the necrosis in pedicled TRAM fl aps are smoking anatomical fi ndings suggesting that the ipsi- (Chang a, Padubidri , Selber , lateral cutaneous perfusion is superior to the Booi ) and obesity (Berrino , Moran contralateral blood fl ow (Dinner , Moon , Ducic , Spear ). However, in
). Th e LDF and PtcO were measured at Study I, only one patient smoked and her fl ap zones I and III; these zones are numbered ac- healed without complications. Th e weight of cording to the original classifi cation of skin the patients did not diff er between the patients zones of the TRAM fl ap, where perfusion is with and without cutaneous necrosis of the best in zone I and worst in zone IV (Hartrampf fl ap. , Schefl an a and b). Hallock has Based on the results of Study I, intraop- later investigated cutaneous blood fl ow intra- erative LDF measurements appear to be able operatively in free TRAM fl aps with LDF (Hal- to predict cutaneous necrosis of the pedicled lock ). Th ey confi rmed the fi ndings of the TRAM fl ap. Th e contralateral LDF value aft er present studies, showing that LDF levels were ligation of the DIEA decreased more in fl aps at all times higher on the ipsilateral than on the developing cutaneous necrosis than in fl aps contralateral side of the TRAM fl ap skin. Th ey healing uneventfully. Th e diff erence between also revealed that the DIEA is the dominant the fl aps with and without necrosis remained source vessel of the TRAM fl ap compared with signifi cant until the fi rst postoperative day. the SEA, as has been assumed based on ana- Th e contralateral LDF level decreased aft er tomical studies (Boyd , Hendricks ). ligation of the DIEA to ± of the initial Hallock and coworkers stated that a relative value in the fl aps developing cutaneous necro- ischemia exists contralaterally even in free sis. Based on this fi nding, the pedicled TRAM TRAM fl aps (Hallock ). fl aps prone to cutaneous necrosis can be iden- tifi ed with intraoperative LDF measurements. It is important to be able to identify the fl aps 6.2. Prediction of cutaneous susceptible to cutaneous necrosis during the necrosis in pedicled TRAM fl aps (I) operation because the surgical plan can still be changed from the pedicled fl ap to one with a According to clinical studies, cutaneous necro- more secure blood fl ow. sis is more common in pedicled than free TRAM Later, in a retrospective study of free fl aps, which is why the free TRAM fl ap has fl aps, postoperative LDF identifi ed developing
57 complications before they were clinically vis- lower than in the free fl aps of Study II. Th e ible. If LDF level decreased to less than of number of patients is too low for drawing any the baseline for minutes or longer, aggressive conclusions. Various pharmacological agents, exploration was considered necessary (Heller such as VEGF and endothelin antagonists ). In a recent study of muscle-sparing free (Tane , Inoue , Erni , Wettstein TRAM fl aps, a lower blood fl ow was observed ) have been applied to enhance fl ap blood with LDF in zone IV of patients with fl ap com- fl ow, but usually these must be administered plications compared with patients without fl ap before the operation. An ideal agent could be complications (Booi ). Th eir results are in administered to the patient at the moment that accordance with ours. the risk for decreased fl ap fl ow is observed.
PtcO levels were signifi cantly lower in fl aps Nitric oxide precursors administered during developing necrosis than in fl aps without the operation have yielded promising results necrosis contralaterally on the third and sev- in preventing ischemia-reperfusion injury in enth postoperative days and ipsilaterally at all myocutaneous fl aps of pigs (Cordeiro ). postoperative measuring times. Development of necrosis could not, however, be predicted based on the intraoperative PtcO values. 6.3. Relation of plasma ET-1 An oxygen challenge test, a response of concentrations to peripheral P O to increased inspired oxygen concentra- tc vasoconstriction, blood pressure, tion, has been claimed to be a sign of intact circulation and fl ap survival (Achauer ). heart rate, and cutaneous or fat In the present study, a negative oxygen test was necrosis (III) observed in the two patients with the broadest ( mm) necrotic areas. In the other six pa- A long-lasting vasoconstriction is com- tients with smaller necrotic areas, the oxygen mon during and aft er prolonged operations test gave contradictory results. A possible ex- such as reconstructive procedures. Cutaneous planation for this is that the PtcO probes were vasoconstriction is known to depend on body not exactly over the contralateral edge (zone temperature (Rowell , Boulant , Kel- IV), where the necrosis developed, but were logg ). Th e role of ET-, a powerful vaso- placed a little more centrally in the fl ap. constrictory peptide secreted from endothelial If the fl aps at risk of developing cutaneous cells, in development of intra- and postopera- necrosis could be identifi ed intraoperatively tive vasoconstriction remains obscure. In ex- with LDF, PtcO, or other monitoring methods, perimental studies, administration of ET- has some approaches augmenting fl ap blood fl ow reduced blood fl ow in skin fl aps (Samuelson could be tried during the same operation. A , Inoue ) and decreased fl ap survival new promising monitoring method is intra- (Tane ). operative ICG fl uorescence video angiography, A relationship between plasma ET- con- which has been used to visualize the individual centrations and peripheral vasoconstriction perfusion map in pedicled TRAM fl aps. It might was observed in this study. Th e increase of be useful for showing the area that should be plasma ET- levels and Tgrad coinincided pre- discarded because of poor perfusion (Yamagu- operatively and postoperatively. Elevated plas- chi ). One attempt to improve fl ap blood ma ET- concentrations have been measured fl ow has been to add a microsurgical anasto- during severe hemodynamic stress, myocar- mosis to a pedicled TRAM fl ap (Harashina dial ischemia, sepsis, and trauma (Cernacek , Schefl an ). In Study II, we measured , Koller , Pittet ). Elevated ET- skin blood fl ow in four pedicled TRAM fl aps levels have also been observed during surgery with an additional microvascular an astomosis (Hirata ). In Study III, slightly elevated in the axilla. In these four patients, the postop- plasma ET- levels were measured preopera- erative PtcO and LDF levels were higher than tively and postoperatively. Th e highest values the levels in the pedicled fl aps in Study I, but were noted before induction. Th e cause for the
58 increased preoperative ET- levels is unclear. ), but probably not by releasing nitric ox- ET- is known to be released as a result of hy- ide (Brendel , Johns ). Th e isofl urane- poxia, stretch, increased intramural pressure, induced vasodilation may have exceeded the and cold (Gandhi ). Systemic hypoxia can vasoconstrictory eff ect of ET- during anes- be assumed not to be the cause for elevated thesia. Moreover, if the initial ET- release was ET- levels in Study III. Before induction, the transient, it could have caused vasodilation by patients’ peripheral oxygen saturation was stimulating nitric oxide or prostacyclin release normal, and the intra- and postoperative PaO (Johns ). levels were also within normal limits. A Tgrad of Postoperatively, an increase in the plasma . °C, indicating peripheral vasoconstriction, ET- concentrations was measured ten min- was observed preoperatively. Possibly, adren- utes aft er arrival in the recovery room. Th e ergic stimulation following anxiety, despite ET- levels in the recovery room remained benzodiazepine premedication, resulted in slightly elevated, around pg/ml, compared peripheral vasoconstriction, which could have with the intraoperative levels. Elevated plasma induced peripheral hypoxia and hypothermia, ET- levels have been measured during the fi rst leading to ET- release. Th e increase in the postoperative hours in several studies (Itoh preoperative plasma ET- concentration could , Miyaguchi , Sato ). In another also have arisen from the pain due to insertion study, increased ET- levels were observed of the antecubital venous cannula, since local postoperatively in patients receiving a knee ar- anesthesia was not used for the cannulation. throplasty. Th e maximal plasma ET- concen- Whether minor pain causes changes in ET- tration was measured . hours aft er the end levels, is unknown. of surgery, when ET- concentrations were . During the operation the ET- levels were times the preoperative value (Matziolis ). within normal limits in Study III, around pg/ In a study of elderly patients undergoing ma- ml. In the study of Shirakami and coworkers jor surgical procedures, the plasma ET- con- plasma ET- levels remained near preoperative centrations were elevated preoperatively and values during minor surgery, including total postoperatively in patients with hypertension knee replacement, cholecystectomy, or hys- compared with patients with normal blood terectomy. During major operations, such as pressure (Nelson ). ET- was not mea- gastrectomy, esophagectomy, hepatectomy or sured intraoperatively in that study. heart surgery, ET- levels were higher than be- An increase in Tgrad as a sign of vasocon- fore the operation (Shirakami ). In Study striction was measured as soon as the patients III, the breast reconstruction with a pedicled were transferred to the recovery room. Th e TRAM fl ap could be assumed to be compa- vasoconstriction disappeared by the end of rable with the minor surgical procedures in the recovery room period. At the same time, which the ET- levels were not elevated in Shi- plasma ET- concentrations were higher than rakami’s study. during the operation. Th e postoperatively el- Peripheral vasoconstriction was not ob- evated plasma ET- concentrations appear to served one hour aft er the induction of anesthe- be associated with peripheral hypothermia. sia. On the contrary, Tgrad was reduced, indicat- Th e peripheral vasoconstriction manifesting ing vasodilation, which lasted throughout the during the immediate postoperative hours may operation. Th e vasoconstrictive eff ect of the cause release of ET- from the peripheral parts high pre-induction level of plasma ET- on the of the body. Alternatively, surgical stress and microvessels may have been prevented with manipulation of tissues have been suggested to the use of isofl urane during anesthesia. Like all induce increased ET- release aft er operations inhaled anesthetics, isofl urane inhibits central (Onizuka , Onizuka , Shirakami thermoregulatory control (Ozaki , Ozaki ) and may have caused the peripheral va- ). Th e vasodilatatory eff ect of isofl urane soconstriction. is mediated by stimulating the β-adrenergic A statistically signifi cant correlation ex- receptors of vascular smooth muscle (Philbin isted between plasma ET- concentrations
59 and MAP. Th e elevated ET- values pre- and Circulating ET- levels are thought to greatly postoperatively were accompanied by rather underestimate local concentrations (Wagner high MAP levels. Th is result is in accordance ). Th e circulating half-life of ET- is only with earlier fi ndings showing that ET--in- . minutes (Vierhapper ). Very small in- duced vasoconstriction leads to an increase in travenous doses of synthetic ET- cause an in- blood pressure but does not aff ect heart rate crease in forearm blood fl ow in humans. When (Remuzzi , Gandhi ). Elevated ET- the ET- dose increases, blood fl ow decreases levels have been measured in several disease as a result of an intense vasoconstriction of the states with disturbed vascular control, e.g. small arteries and arterioles with a duration Raynaud´s phenomenon, pulmonary hyper- of at least two hours (Remuzzi , Gandhi tension, and subarachnoid hemorrhage (Miller ). Vasoconstriction develops slowly, in , Remuzzi , Gandhi ). Th ere may – minutes, in segments of human mesen- be several mechanisms underlying develop- teric arteries (Miyauchi ). Fast pulmonary ment of high blood pressure pre- and postop- clearance for ET- has been observed in some eratively, and endothelin may be one of them. animal models, but this has been questioned in ET- antagonists are in clinical use in the treat- humans (Gandhi ). ment of pulmonary hypertension and in phase Th e cause for the high ET- levels of the III testing for the treatment of vasospasm aft er patient who was excluded remains obscure. subarachnoid hemorrhage. Incorrectly high ET- values can be seen aft er In this study, no statistical connection be- incomplete lyophilization, which is unlikely in tween ET- concentrations and development this case, since dozens of samples were handled of cutaneous necrosis was found. Flap blood simultaneously in the radioimmunoassay. He- fl ow was not measured in Study III, but the de- moglobin remaining in the sample may also velopment of necrosis was observed clinically. lead to very high ET- values; however the One of the many factors causing cutaneous method used of extraction removes all hemo- necrosis is intense vasoconstriction of the fl ap globin from the sample. vessels, leading to decreased fl ap microcircula- tion (Khouri ). ET- may be an important regulator of the fl ap blood fl ow, aff ecting the development of necrosis (Menger , Samu- 6.4. Effect of felodipine on plasma elson , Tane , Inoue , Pang , ET-1 concentrations, peripheral va- Mobley ). Studies on the eff ect of ET an- soconstriction, postoperative P O , tagonists on fl ap blood fl ow and development tc 2 of necrosis have recently yielded promising re- and survival of free TRAM fl aps (IV) sults (Tane , Inoue , Erni , Wet- tstein ). In our study, the small size of the Administration of calcium antagonists has patient group may have masked the connection suppressed ET- release and subsequent va- between ET- and cutaneous necrosis. Future soconstriction in experimental and clinical studies are needed to determine the relation of studies (Kiowski , Liu , Kobayashi ET-, cutaneous blood fl ow, and development , Yakubu ). Calcium antagonists have of necrosis in surgical fl aps. also reduced the incidence of necrosis of fl aps Th e blood samples for plasma ET- deter- in some experimental studies (Hira , Pal minations were drawn from the limb on which , Yessenow , Bailet ), while having
Tind and Tant probes were positioned. Th e el- no eff ect in others (Miller , Emery ). evated ET- levels observed before induction Felodipine is a vasodilatory dihydropyridine could be assumed to refl ect a considerable lo- calcium antagonist capable of relaxing arterial cal release of ET- from the same limb. ET- is resistance vessels (Ljung ). Th eoretically, it a local hormone. Most of its release from the might be able to decrease perioperative ET- vascular endothelium is directed to the muscle levels and vasoconstriction and increase cuta- layer of the vessel and not to the bloodstream. neous blood fl ow in a fl ap. However, felodipine
60 had no eff ect on plasma ET- concentrations, increase in ET- concentration in the venous
Tgrad, or postoperative PtcO of free TRAM fl aps blood from the fl ap, but not in peripheral ve- in this prospective, double-blind, and random- nous blood, aft er opening of the arterial anas- ized study (IV). tomosis. Th ey speculated that increased ET- In Study IV, the plasma ET- levels on the level could be an explanation for the vasospasm preoperative and postoperative days were quite seen in free fl aps (Lantieri ). high compared with levels in healthy humans at Tgrad has been shown to correlate well with rest (,– pg/ml) (Karwatowska-Prokopczuk volume plethysmography as a sign of peripheral ). Elevated ET- levels have been measured blood fl ow (Rubinstein ). Th e degree of va- during major operations, e.g. heart surgery or sodilation judged by Tgrad was similar in the two gastrectomy (Shirakami ). Endothelin study groups, although Tgrad tended to be lower may play a role in the no-refl ow phenomenon in the felodipine group during the fi rst hour seen in free fl aps and replanted digits (Lantieri aft er the operation. A larger dose of felodipine ). Breast reconstruction with a free TRAM possibly could have had a clearer vasodilatory fl ap is a time-consuming operation with a fairly eff ect. Th e dosage of oral felodipine, mg at long ischemia in the fl ap and extensive manip- : hours and mg eight hours later, was ulation of vessels during the preparation and chosen based on the daily doses used for treat- performing of anastomoses. Stretch and isch- ment of hypertension (.– mg once daily). In emia are among factors increasing ET- release unanesthetized healthy subjects, mg of felo- (Gandhi ). Th e stretch and manipulation dipine causes an increase in forearm blood fl ow of the recipient and fl ap vessels and ischemia of and a decrease in forearm peripheral resistance the fl ap before the anastomoses are completed (Agner ). However, a dose of felodipine might have induced marked local ET- release, larger than the one used to treat of hypertension seen as relatively high plasma ET- concentra- increases the risk of excessive tachycardia and tions in Study IV. hypotension. Despite its powerful vasodilatory In Study IV, the intraoperative and postop- capacity, felodipine may be no more eff ective erative ET- concentrations were determined than other calcium antagonists in preventing from arterial plasma. However, venous plasma vasoconstriction under clinical circumstances ET- concentrations refl ect the actual levels in resembling the ones of this study. the tissues more accurately than arterial con- Th e given dose of felodipine was clinically centrations since ET- is released locally (Wag- eff ective based on the pre-induction HR, which ner ) and the pulmonary clearance of ET- was signifi cantly higher in the felodipine group from plasma is very rapid (Gandhi ). Th e than in the control group. Felodipine, with its venous ET- concentrations have been found vasodilating properties, caused a decrease in to be higher than arterial concentrations in systemic vascular resistance in this study, based healthy humans (Wagner ). Th e arterial on the increase of HR and no changes in MAP. ET- concentrations were measured in Study Felodipine had no eff ect on the pre-induction IV on the operation day because the aim was to or on intraoperative MAP values. In healthy determine out the ET- level in the blood fl ow- subjects, a single dose of felodipine increases ing to the fl ap. An eff ect of felodipine on ET- resting HR (Agner , Carruthers ). concentrations might have been observerd, if In this study, HR during and aft er anesthesia the ET- levels had been measured from the stayed at a higher level in the felodipine group vein of the fl ap pedicle. Venous ET- concen- than in control patients, showing that the eff ect trations would have given a clearer image of the of felodipine continued up to the postoperative actual amount of ET- release in the fl ap. Re- period. Th e highest MAP levels in both groups cently, Lantieri and coworkers measured ET- were measured minutes and one hour aft er concentrations from peripheral venous plasma the patients had arrived in the recovery room. and the venous blood running from the fl ap in In healthy subjects, felodipine has no eff ect or patients during breast reconstructions with only causes a minor decrease in mean resting free TRAM or DIEP fl aps. Th ey observed an blood pressure (Agner , Carruthers ).
61 Th e postoperative rise of blood pressure is part m). Based on our results, BMI and cutaneous of the stress response induced by surgery (Hal- or fat necrosis do not seem to be associated. ter ). According to this study, felodipine Th e small size of the patient group is, however, has a minor decreasing eff ect on postoperative a limitation of the study. No patients had BMI blood pressure, probably because of its vasodi- > . Five of the women were overweight latory capacity. (BMI ≥ ), and cutaneous of fat necrosis was Felodipine and control groups did not diff er observed in two of their fl aps. In a Finnish with regard to PtcO values or development of population study, . of women aged to necrosis of the fl ap. Th is is in contrast to some years and . of women aged years or experimental studies, where the incidence of more had BMI > in – (Aromaa necrosis was reduced by calcium antagonists ). Had our study group been larger, more (Hira , Pal , Yessenow , Bailet patients likely would have been obese, and a ). In both groups of Study IV, two of the connection might have emerged between BMI ten patients developed a minor cutaneous ne- and cutaneous necrosis. crosis on the contralateral side of the fl ap. Th is Th e eff ect of the type of body fat distribu- in consistent with the incidence of cutaneous tion on development of cutaneous necrosis necrosis reported in studies on free TRAM has not been investigated earlier in TRAM fl aps (Schusterman , Trabulsy , fl aps. In this study, fi ve of patients devel- Chang , Kroll , Nahabedian b). oped marginal cutaneous or fat necrosis on Th e incidence of cutaneous necrosis is much the contralateral side of pedicled TRAM fl aps. higher in pedicled than free TRAM fl aps (Har- Th ere were no fl aps with necrosis in the pa- trampf , Schusterman , Elliott , tients with upper body type fat distribution Kroll , Paige , Clugston , Garvey (WHCR > .). Upper body type (male type) ). Th e eff ect of felodipine might have been obesity has been associated with cardiovascu- clearer had the study groups consisted of pa- lar problems (Lapidus , Björntorp , tients with pedicled instead of free TRAM Kannel ) and increased peripheral vascu- fl aps. lar resistance (Jern ) in women. Increased peripheral resistance may be one contributing factor in development of partial necrosis in 6.5. Effect of indices of obesity pedicled fl aps, so one would expect necrosis to on cutaneous or fat necrosis in be more common in patients with upper body pedicled TRAM fl aps (V) type fat distribution. However, the results of this study contradict this hypothesis, instead Cutaneous necrosis is a common complication suggesting an association between lower body in pedicled TRAM fl aps. It usually develops type (female type) fat distribution and de- in the most distal contralateral part of the fl ap velopment of marginal necrosis in pedicled (zone IV). Surgical revisions are oft en needed TRAM fl aps. to treat the necrotic area. Th ey increase costs, In pedicled TRAM fl aps, peripheral vascu- lengthen hospital stay, and cause physical and lar resistance might not play a major role in emotional distress to the patient. Overweight development of marginal cutaneous or fat ne- and obesity increase the risk of cutaneous ne- crosis. In women with lower body type fat dis- crosis in pedicled TRAM fl aps according to tribution, the relative overweight in the lower several studies (Berrino , Moran , abdomen likely stretches the perforators run- Ducic , Spear ), but one earlier study ning through the rectus muscles, as suggested reported that obesity had no eff ect on inci- by Schefl an (Schefl an ). In such cases, the dence of cutaneous necrosis (Kroll ). Fat SEA cannot provide suffi cient blood supply to necrosis has been observed in pedicled fl aps of the entire fl ap. One can also speculate that the obese patients more oft en than in patients with fl ap area is too large to be perfused suffi ciently ideal weight (Berrino ). Obesity has been in women with lower body type fat distribution. determined in those studies as BMI ≥ (kg/ Th e exact size of the skin island of the TRAM
62 fl ap was not measured in this study, but the size during the fi rst week aft er the operation. It of the TRAM fl ap was chosen to achieve the then stayed fairly unchanged throughout the best possible symmetry with the other breast. nine-month study period. Th e initial increase Another explanation might be that the supe- of thickness probably resulted from edema in rior epigastric vessels are smaller in women the immediate postoperative period and re- with lower type body fat distribution. If this modeling of the fl ap. Based on these fi ndings, hypothesis proves to be correct, a free TRAM the thickness of abdominal fat does not seem fl ap might be more suitable than a pedicled to be associated with cutaneous necrosis of fl ap for breast reconstruction in women with pedicled TRAM fl aps. Recently, Yano and co- lower body type obesity. Th e caliber of the su- workers measured the thickness of abdominal perior epigastric vessels could be established subcutaneous fat preoperatively in pedicled preoperatively with computed tomography TRAM fl aps. Th ree of their patients developed angiography or intraoperatively with ICG an- cutaneous necrosis and six fat necrosis of the giography, and in the case of very thin vessels, fl ap. Th eir results showed that abdominal fat the operation plan could be changed e.g. to a thickness is not a risk factor for necrosis in free TRAM fl ap pedicled TRAM fl aps in patients who are thin, Th e amount of obesity can be estimated average, or mildly obese. Th eir fi ndings are in also by measuring the thickness of subcutane- accordance with ours. Th ey also observed a ous fat with ultrasound (Katch , Ramirez close correlation between BMI and thickness , Suzuki , Orphanidou ). Here, of subcutaneous fat in the abdominal area the mean thickness of abdominal fat increased (Yano ).
63 7 Conclusions
. During breast reconstruction with a pedicled TRAM fl ap, elevation of the contralateral side of the fl ap causes an increase in cutaneous blood fl ow of the fl ap. When the DIEA is ligated, a decrease in cutaneous blood
fl ow is observed with LDF and PtcO on the contralateral side of the fl ap,
continuing on the postoperative days. Th e LDF and PtcO levels are lower on the contralateral side than on the ipsilateral side of the fl ap at all measuring times (I).
In a free TRAM fl ap, the intraoperative changes in cutaneous blood fl ow are similar to those in a pedicled fl ap. Th e postoperative blood fl ow in a
free TRAM fl ap measured by PtcO and LDF is more generous than in a pedicled fl ap (II).
. Development of cutaneous necrosis of a pedicled TRAM fl ap can be predicted based on intraoperative LDF measurements. Th e contralateral LDF value decreases to ± of the initial value aft er ligation of the DIEA in fl aps developing cutaneous necrosis during the next week. Cutaneous
necrosis cannot be predicted based on intraoperative PtcO values (I).
. A correlation exists between the perioperative plasma ET- concentrations and the peripheral vasoconstriction, as well as between plasma ET- concentrations and MAP during and aft er a long plastic surgical operation. ET- levels are elevated in the recovery room. No association is present between ET- concentrations in systemic blood and development of cutaneous necrosis or HR in pedicled TRAM fl aps (III).
. Felodipine, a vasodilating calcium channel blocker, has no eff ect on plasma
ET- concentrations, peripheral vasoconstriction, postoperative PtcO, or development of cutaneous necrosis in free TRAM fl aps. Felodipine has a minor decreasing eff ect on postoperative blood pressure (IV).
. Neither BMI nor thickness of abdominal fat seems to be associated with the development of cutaneous or fat necrosis in pedicled TRAM fl aps. However, this study included no patients with BMI >. An association may exist between lower body type fat distribution and development of marginal necrosis in pedicled TRAM fl aps (V).
64 8 Acknowledgments
Th ese studies were carried out at the Depart- his contribution to the radiological aspects, ment of Anesthesiology and Intensive Care and Docent Markku Härmä for his invaluable Medicine, the Department of Plastic Surgery, advice with statistics. the Department of Medicine, and the Depart- Carol Ann Pelli of the University Language ment of Radiology at Helsinki University Cen- Services Offi ce for expert language revision of tral Hospital, and at the Minerva Institute for this manuscript. Medical Research. Jari Salo for designing the thesis cover. My warmest gratitude is owed to the follow- Jukka Alstela for the photography. ing persons: Jari Simonen for the thesis layout. Professor Emeritus Tapani Tammisto and My former and present colleagues at Töölö Professor Per Rosenberg of the Department of Hospital for their support and help over these Anesthesiology and Intensive Care for providing years. Th e nursing staff at the Department of excellent facilities for clinical and scientifi c work Plastic Surgery, especially the dedicated anes- and for taking an active interest in this thesis. thesiology nurses, who helped with the mea- My supervisors, Professor Sirpa Asko-Sel- surements during the evenings. My former col- javaara, Dr. Nils Svartling, and Professor Erkki leagues and the nursing staff at Diacor Hospital Tukiainen, for generous guidance and support. for their encouragement to fi nish this work. Sirpa is also thanked for placing the facilities All of the patients who kindly participated of the Department of Plastic Surgery at my dis- in these studies. posal, and, together with Nisse for suggesting My friends and relatives for keeping me oc- the topic of this thesis. I am indebted to them cupied with other aspects of life. Special thanks for their never-ending enthusiasm about sci- to Marja Hynninen, Aino Hakonen, Päivi ence and for introducing me to the fascinating Marttila, and my horse-riding companions. world of microvascular fl aps. Erkki is warmly My late parents Anni and Osmo Tuominen, acknowledged for friendly guidance during the whose love and encouragement have been cru- last years of this work, aft er Sirpa’s retirement. cial for me. My dear brothers Olli and Juha, Docent Tarja Randell for helping me to together with their families, for being an im- wrap up the long process of this thesis. With- portant part of my life. out her positive attitude and constant interest And last, but certainly not least, Jarmo for in my work, this project would never have been understanding and support during the long fi nished. process of fi nishing this thesis, and our daugh- Docents Ulla Karhunen, Tarja Randell, Olli ter Silja for being the light of my life. Kirvelä and Pekka Tarkkila, who, as heads of Financial support from grants from the the Department of Anesthesiology of Töölö Association of Development and Education Hospital, provided me with the facilities for in Plastic Surgery and Burn Treatment in Fin- clinical and research work. land, Chirurgi Plasticae Fenniae, the Finnish Docents Paula Mustonen and Hannu Medical Foundation, the Karin and Einar Stro- Toivonen, the offi cial reviewers of this thesis, ems Foundation, Suomen Astra, and Helsinki for their thorough review and for constructive University Central Hospital Research Funds is criticism. gratefully acknowledged. My coworkers Docents Ilkka Tikkanen and Helsinki, October Outi Saijonmaa for their expertise in the fi eld of endothelins, Docent Jaakko Kinnunen for
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