Safety and Efficacy of Spinal Vs General Anaesthesia in Bone Marrow Harvesting

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Bone Marrow Transplantation, (1998) 21, 1145–1148  1998 Stockton Press All rights reserved 0268–3369/98 $12.00 http://www.stockton-press.co.uk/bmt Safety and efﬁcacy of spinal vs general anaesthesia in bone marrow harvesting

¨ M-A Burmeister1, T Standl1, P Brauer1, K Ramsperger1, N Kroger2, A Zander2 and J Schulte am Esch1

1Department of Anaesthesiology, Bone Marrow Transplantation Unit, and 2Department of Oncology and Haematology, University Hospital Hamburg, Germany

Summary: gesia requirement have been demonstrated with RA.4 SPA may also be of interest for economical reasons. Bone marrow harvesting (BMH) can be performed with Nevertheless, SPA with the patient in the prone position either general (GA) or spinal anaesthesia (SPA). Whether is still controversial. One of the main arguments against SPA is advantageous in BMH and if this technique is safe SPA in the prone position is the difficulty in adequately for procedures performed in the prone position is still con- ventilating the patient in the event of respiratory insuf- troversial. To evaluate the safety and efficacy of both ficiency. Several reports have presented cases with cardio- anaesthetic techniques in BMH, 37 allogeneic donors (nine pulmonary arrest and resuscitation during SPA.5–7 female, 28 male; 34.3 ؎ 9 years; ASA class 1–2) received The present prospective study was designed to evaluate either spinal (group 1, n = 20) or general anaesthesia the safety and efficacy of the two different anaesthetic tech- (group 2, n = 17) according to their personal wishes. niques in healthy allogeneic donors undergoing BMH. Under standardised harvesting conditions, haematology parameters, cell counts (MNC, CD34+), haemodynamic parameters, adverse reactions and patient satisfaction Patients and methods were registered. No differences were seen between groups with respect to demographic data, harvesting time Following approval from the local ethics committee and vs 60 ؎ 16 min) and bone marrow cell counts written consent, 37 healthy (ASA class 1–2) allogeneic 17 ؎ 55) (MNC: 6.68 ؎ 2.1 vs 5.7 ؎ 1.7 ml/106). The incidence of donors (Table 1) received either spinal (group 1, n = 20) hypotension was higher in group 1 (45 vs 10.8%; or general anaesthesia (group 2, n = 17) according to their P = 0.042). Postoperative analgesic requirement and personal wishes. Randomisation of the anaesthetic tech- emesis were increased in group 2 (P Ͻ 0.04) in comparison nique was not allowed for ethical reasons in healthy allo- to group 1. In conclusion, the present study failed to show geneic bone marrow donors. All patients predonated one superiority of spinal over general anaesthesia with regard unit of autologous RBCs 4 weeks prior to the bone mar- to the quality of the harvested bone marrow. However, row harvest. the lower incidence of complaints after spinal anaesthesia On the day of BMH, patients were orally premedicated appears to offer an advantage over GA in healthy allo- with 7.5 mg midazolam 1 h before arriving at the anaes- geneic bone marrow donors. Keywords: bone marrow harvesting; anaesthesia, spinal- general; prone-position Table 1 Demographic characteristics of 37 healthy donors

Characteristics Group 1 Group 2 P Bone marrow harvesting (BMH) is generally performed (spinal (general under general anaesthesia (GA).1 However, regional anaes- anaesthesia) anaesthesia) n = 20 n = 17 thesia (RA) such as epidural or spinal anaesthesia (SPA) can also be used and may even have some advantages in Age (years)a 34.8 ± 8.2 33.8 ± 8.3 0.715 terms of outcome of BMH. Sex Some retrospective studies have shown a shorter har- Female 5 4 0.718 vesting time with an increased yield of nucleated cells in Male 15 13 b the harvested marrow using SPA.2,3 In addition, a reduction ASA class I 16 13 0.553 of allogeneic blood transfusions and postoperative anal- II 4 4 Height (cm)a 179.5 ± 9.0 178.2 ± 10.3 0.751 Body weight (kg)a 81.5 ± 12.0 81.6 ± 13.8 0.981 Broca index (%)a 103.1 ± 15.0 104.6 ± 13.7 0.521 Correspondence: Dr M-A Burmeister, Department of Anaesthesiology, University Hospital Eppendorf, Martinistrasse 52, D-20246 Hamburg, aMean Ϯ s.d. Germany bPreoperative risk score according to the American Society of Anesthesiol- Received 15 August 1997; accepted 9 January 1998 ogists. Spinal and general anaesthesia in bone marrow harvesting M-A Burmeister et al 1146 thetic room where they were monitored by ECG, non-invas- pared between groups. In cases of postoperative pain, ive measurement of blood pressure, pulse oximetry and a patients in both groups received a 500 mg paracetamol sup- rectal temperature probe. Patients received 500 ml of pository with a maximum of 3 g paracetamol within 24 h. Ringer’s lactate solution via a peripheral venous cannula. Patients were interviewed by an anaesthetist on days 1 In group 1, spinal anaesthesia (SPA) was administered and 4 after the harvesting procedure about problems such with the patient in the sitting position, at the L 3/4 inter- as sore throat, headache, lower backpain, shivering, nausea space. After infiltration of the skin with 5 ml lidocaine 2%, or vomiting and urinary dysfunction, using a standardized a 20-G introducer needle (Spinocan, B Braun, Melsungen, questionnaire. Germany) was inserted using the midline approach. A 26- For statistical analyses, quantitative parameters were G Quincke needle was placed in the subarachnoidal space compared with the unpaired t-test. Qualitative data were with the needle bevel parallel to the dural fibers. When free analysed using Fisher’s exact test. A P value Ͻ0.05 was flow of cerebrospinal fluid was obtained, 2.5–4.0 ml of a considered to be significant. mixture of plain bupivacaine 0.5% and hyperbaric mepivacaine 4% (Astra Chemicals, Wedel, Germany) was injected and patients were placed supine to reach a minimal anal- Results gesic level of T 12. In group 2, general anaesthesia (GA) was induced with Groups were comparable with respect to harvesting time, 0.3 mg/kg etomidate (B Braun), 0.5 ␮g/kg sufentanil total harvested volume and harvested volume per minute. (Janssen, Neuss, Germany) and 0.5 mg/kg atracurium The mononucleated cell content was slightly higher in the (Wellcome, Hamburg, Germany). Following endotracheal harvested marrow of the SPA group but the difference did intubation with a flexible spiral tube (Woodbridge, Mal- not reach significance. Total cell numbers and content of linckrodt, Ireland) and mechanical ventilation, anaesthesia CD34+ cells were virtually equal in both groups (Table 2). was maintained with 0.8–1.2 vol% isoflurane (Abbott, The perioperative decrease in haemoglobin concentration Wiesbaden, Germany) and 30% oxygen in nitrous oxide. was higher in patients receiving SPA when compared to Bradycardia (heart rate Ͻ50/min) was treated by i.v. GA (1.68 Ϯ 0.5 vs 1.1 Ϯ 0.6 g/dl; P = 0.003). However, administration of atropine 0.5–1.0 mg, hypotension (mean none of the patients required allogeneic blood transfusion. arterial blood pressure Ͼ30% below baseline) was treated Two patients of each group received their predonated auto- by i.v. injection of 1–2 ml of a mixture of 100 mg of theo- logous blood within the first 24 h because Hb levels were phylline and 5 mg of theoadrenaline (Asta Medica, Darm- below 10 g/dl. SPA patients received a mean dose of stadt, Germany). 3.15 Ϯ 0.3 ml of LA. The mean level of sensomotory For evaluation of safety, the incidence of adverse reac- blockade was at T 8 Ϯ 2 (Range: T 12–T 5). No patient tions and side-effects such as severe bradycardia (HR experienced major side-effects such as a high level of sen- Ͻ45/min) or hypotension (MAP Ͻ60 mmHg) and inadver- somotory blockade ϾT 4 or an increasing level while in tently ascending spinal anaesthesia (ϾT 4), were analysed. the prone position. Twenty minutes after subarachnoid injection of the LA Baseline values of blood pressure, heart rate, oxygen or after induction of GA, patients were moved from the saturation and rectal temperature did not differ between supine to the prone position. The level of analgesia in group groups. In the SPA group the incidence of hypotension and 1 was controlled every 5 min by pinprick. To avoid hypo- bradycardia was higher when compared to GA (45 vs thermia patients were warmed in an air warming system 10.8%, P = 0.042 and 40 vs 5.8%, P = 0.023). In the SPA (Warm Touch) to the upper body. Patients received 7 ml/kg group these episodes of haemodynamic depression had a Ringer’s lactate and 7 ml/kg hydroxyethyl starch duration of 1–3 min and were seen only 50–80 min after 70 000/0.5 (Rheohes, B. Braun, Germany) before the start subarachnoidal injection of local anaesthetics. No severe of the harvesting procedure. Equal volumes were infused bradycardia or hypotension was seen over time in both intraoperatively in both groups. SPA patients received an intranasal insufflation of 2 l oxygen per minute. The bone marrow was harvested under standardised con- Table 2 Bone marrow harvest characteristics ditions with respect to the staff and material used. Multiple punctures were made to both posterior iliac crests with a 3 Characteristics Group 1 Group 2 P mm needle followed by aspirations to a limit of 10 ml per (spinal (general aspiration. The harvesting time, total harvested volume, anaesthesia) anaesthesia) = = harvested volume per minute, total nucleated and CD34+ n 20 n 17 cell content, were evaluated. Harvest time (min)a,b 55 ± 17 61 ± 16 0.279 To estimate the percentage of mononucleated cells visual BM volume harvested (ml)a 1301.9 ± 85.9 1336.0 ± 117.8 0.315 counting of a sample of unmanipulated marrow was perfor- BM volume harvested per min 26.4 ± 11.3 23.6 ± 6.8 0.370 med. For assessment of total cell counts and content of (ml)a CD34+ cells the microcell counter Sysmex F 300, and the Total cell numbers (1010)a 2.27 ± 0.5 2.30 ± 0.5 0.856 7 a ± ± laserflow cytometry device Facscan (Becton Dickinson, Total cell numbers (ml/10 ) 1.75 0.39 1.73 0.39 0.953 Mononucleated cells (ml/106)a 6.68 ± 2.13 5.70 ± 1.72 0.137 Frankfurt, Germany) were used, respectively. CD34+ cell count (ml/104)a 12.30 ± 8.5 12.69 ± 6.82 0.908 Perioperative changes in haemoglobin concentration, leu- cocyte and platelet counts, haemodynamics, rectal tempera- aMean Ϯ s.d. ture and postoperative analgesic requirement were com- bTime from first to last puncture. Spinal and general anaesthesia in bone marrow harvesting M-A Burmeister et al 1147 groups. However, the mean arterial pressure (MAP) was the room temperature and consecutively the patient’s tem- higher in the SPA group during BMH due to a higher mean perature during bone marrow collection. This effect can be use of vasoconstrictors (0.66 Ϯ 0.49 ml vs 0.23 Ϯ 0.36 ml, explained by thermoreactive vasodilatation within the vas- P = 0.006). Postoperatively, the MAP was higher in the GA cular bed of the bone marrow. group (Figure 1). No episodes of oxygen desaturation of A recent study from Knudsen et al2 showed decreased more than 3% below baseline were seen in either group. harvesting time and better quality of harvested bone mar- The intraoperative rectal temperatures of donors was vir- row in 10 patients undergoing spinal anaesthesia when tually equal between groups (36.3 Ϯ 0.4°C vs compared to a retrospective control group receiving gen- 36.2 Ϯ 0.4°C, P = 0.45). eral anaesthesia. Postoperative requirements of analgesics and the inci- These results are in accordance with data from Mich- dence of postoperative emesis were increased in patients elsen9 and Stein et al10 who examined the influence of cat- after general anaesthesia when compared to spinal anaes- echolamines on the circulation within the bone marrow of = = thesia (40 vs 5%, P 0.02; and 5 vs 29%, P 0.033). rabbits and dogs. These authors demonstrated that epineph- No difference was seen in terms of frequency of head- rine and norepinephrine cause a decrease in intramedullary ache or lower backpain between groups (group 1 vs 2: 15 venous and tissue pressures, presumably by vasoconstric- = = vs 11.8%; P 0.678 and 15 vs 23.5%; P 0.207). Urinary tion of intramedullary arteries and arterioles. The same dysfunction and shivering were not seen in either group. effects were found in the intramedullary tissue of cats after As expected, the incidence of sore throat was higher in stimulation of the sympathetic nerves.11 Therefore, sym- group 2 (35%) than in group 1 (0%). pathetic blockade as a result of spinal or epidural anaesthesia probably increases intramedullary filling pressure and may facilitate aspiration of intramedullary cells during Discussion bone marrow harvesting. In the present study we examined the influence of anaes- High yield, and good quality harvested bone marrow are essential requirements for successful outcome of either allo- thesia on the yield and quality of marrow collected. We geneic or autologous bone marrow transplantation. In showed a slightly increased yield of nucleated cells under addition, the harvesting procedure has to fulfil high safety spinal anaesthesia, with comparable harvesting times, using standards and should be as comfortable as possible, either technique. A positive effect of the sympathetic block- especially for allogeneic donors. As a consequence, anaes- ade yielded by spinal anaesthesia on the yield of nucleated thetic technique as one of the main factors having influence cells or harvest time could not be demonstrated in this clini- on perioperative conditions and convenience in BMH, was cal setting. evaluated in this study. In contrast, the incidence of hypotension and bradycardia It is also possible that haemodynamic parameters such was higher in patients receiving spinal anaesthesia. This as blood pressure, peripheral vascular resistance, filling fact is well known after SPA5–7,12 but it is of greater impor- pressures or cardiac output which are mediated by anaes- tance in procedures performed in the prone position such thesia may have an impact on ease of bone marrow har- as BMH. Cardiocirculatory depression in this situation must vesting. be avoided. Therefore early detection of hypotension by Only a few clinical investigations concerning exogenous continuous monitoring and immediate therapy with vaso- influences such as anaesthesia during bone marrow har- constrictors is essential under such circumstances. The rea- vesting have been performed. Zeller et al8 found an son for the late onset of hypotension and bradycardia in increased yield of harvested bone marrow cells by raising spinal anaesthesia patients seems to be due to decreasing

induction harvesting recovery room 110

100 * * * 90

MAP (mmHg) * 60 * * 50 123456789 Measurepoints (MP) 1-9 spinal anaesthesia general anaesthesia

Figure 1 Comparison of the perioperative mean arterial blood pressure (MAP) between group 1 (spinal anaesthesia) and group 2 (general anaesthesia). MP 1, pre induction; MP 2, 15 min after induction; MP 3, after turning into prone position; MP 4, start of harvesting; MP 5, 600 ml harvesting volume; MP 6, end of harvesting; MP 7, 5 min recovery room; MP 8, 60 min recovery room; MP 9, 120 min recovery room. Values expressed as mean Ϯ sd. *P Ͻ 0.05 vs group 2 (GA). Spinal and general anaesthesia in bone marrow harvesting M-A Burmeister et al 1148 sympathictone secondary to decreased anxiety during the References harvesting procedure. Respiratory complications with the patient in the prone position are more complicated compared to those seen with 1 Filshie J, Pollock AN, Hughes RG et al. Forum. The anaes- patients in supine position. Respiratory insufficiency during thetic management of bone marrow harvest for transplantation. spinal anaesthesia is commonly a consequence of high lev- Anaesthesia 1984; 39: 480–484. Ͼ 2 Knudsen LM, Johnsen HE, Gaasdal E, Jensen L. Spinal versus els ( T 4) of sensomotory block. Treatment of respiratory general anaesthesia for bone marrow transplantation (letter). insufficiency by endotracheal intubation and mechanical Bone Marrow Transplant 1995; 15: 486–487. ventilation is virtually impossible when patients are in the 3 Gallerani E, Gentili E, Arena M. Peridural anesthesia in the prone position. Brain’s Laryngeal Mask Airway is a poss- harvesting of bone marrow: review of a case series from July ible method of securing the airway, although insertion of 1990 to June 1991 at the Bone Marrow Transplantation Center the LMA is difficult with the patient in the prone position. of Florence. Minerva Anesthesiol 1991; 57: 464–465. As a consequence, the anaesthetic level must be accurately 4 Lavi A, Efrat R, Feigin E, Kadari A. Regional versus general assessed and found to be constant before the patient is anesthesia for bone marrow harvesting. J Clin Anesth 1993; 5: 204–206. moved into the prone position. The hyperbaric local anaes- 5 Dobson PM, Caldicott LD, Gerrish SP. Delayed asystole dur- thetic mixture used in this study provides a reliable spread ing spinal anaesthesia for transurethral resection of the pros- and a stable level of sensomotory blockade within 10 min.13 tate. Eur J Anaesthesiol 1993; 10: 41–43. Shah14 has demonstrated that the epidural pressure is lower 6 Nishikawa T, Anzai Y, Namiki A. Asystole during spinal in the prone when compared to the supine position. There- anaesthesia after change from Trendelenburg to horizontal fore, an increasing level of anaesthesia in the prone position position. Can J Anaesth 1988; 35: 406–408. as a consequence of dural compression is unlikely. Con- 7 McConachie I. Vasovagal asystole during spinal anaesthesia. Anaesthesia 1991; 46: 281–282. ¨ firming this theoretical view, anaesthetic level was not al- 8 Zeller W, Hesse I, Durken M et al. Increasing the yield of tered by position in our patients when they were turned to harvested bone marrow cells by raising the room temperature the prone position 20 min after injection of LA. during marrow collection. Exp Hematol 1995; 23: 1527–1529. To date, the standard anaesthesia technique in the prone 9 Michelsen K. Hemodynamics of the bone marrow circulation. position is general anaesthesia with intubation and con- Acta Physiol Scand 1968; 73: 264–280. trolled ventilation. Nevertheless, there are studies reporting 10 Stein AH Jr, Morgan HC, Porras RF. The effect of pressor surgical procedures in the prone position using regional and depressor drugs on intramedullary bone marrow pressure. anaesthesia without severe complications. Riegel and J Bone Joint Surg 1958; 40: 1103–1110. 15,16 11 Herzig E, Root WS. Relation of sympathetic nervous system Becq report a series of more than 1850 spinal anaest- to blood pressure of bone marrow. Am J Physiol 1959; 196: hetics performed for lumbar disc surgery using the prone 1053–1056. position without severe complications. 12 Fox MAL, Webb RK, Singleton R et al. The Australian Inci- Tolksdorf et al17 have used SPA in 30 older patients for dent Monitoring Study. Problems with regional anaesthesia: translumbar aortography. They showed that only 10 an analysis of 2000 incident reports. Anaesth Intens Care patients with supplementary intravenous sedation had 1993; 21: 646–649. 13 Eckert S, Standl T. A comparison of a 0.5% isobaric bupiva- increasing paCO2 and decreasing paO2. To avoid changes in sensomotory block by moving caine–4% hyperbaric mepivacaine mixture and 0.5% hyper- patients from the supine to the prone position, injection of baric bupivacaine for single-dose spinal anaesthesia. Anaesth- esist 1997; 46: 121–125. local anaesthetic for SPA can be performed with the patient 14 Shah JL. Effect of posture on extradural pressure. Br J Anaes- 18,19 already in the prone position, using hypobaric drugs. thesia 1984; 56: 1373–1377. Lavi et al4 presented a retrospective comparison between 15 Becq MC, Verdin M, Riegel B et al. Hemodynamic effects general and epidural anaesthesia for bone marrow har- of genupectoral position during the surgery of lumbar disk vesting. Patients with RA required less RBC units and post- herniation: spinal anesthesia versus general anesthesia. Agres- operative analgesics. sologie 1994; 34: 49–50. These results are consistent with our data of less post- 16 Riegel B, Alibert F, Becq MC et al. Lumbar disk herniation operative complaints such as emesis and less analgesia with surgical option: general versus local anesthesia. Round table. Agressologie 1994; 34: 33–37. requirements in patients receiving spinal anaesthesia when 17 Tolksdorf W, Rohowsky R, Eberwein S. The effects of fluni- compared to patients undergoing general anaesthesia. This tracepam and benzoctamine on the blood gases during trans- is also well recognised from a study in orthopaedic lumbar aortography in spinal anaesthesia. AINS 1980; 15: patients.20 407–411. In conclusion, the present study failed to show superior- 18 Maroof M, Khan RM, Siddique M, Tarip M. Hypobaric spinal ity of spinal over general anaesthesia with respect to quality anaesthesia with bupivacaine (0.1%) gives selective sensory of harvested bone marrow or the harvesting time. Using block for ano-rectal surgery. Can J Anaesth 1995; 42: 691– continuous monitoring of cardiorespiratory functions and 694. LA with fast onset and reliable fixation times, SPA appears 19 Larsen JR. Emergency spinal anaesthesia in the prone position. Acta Anaesthesiol Scand 1997; 41: 790–791. to be safe for this procedure using the prone position. The 20 Standl T, Eckert S, Schulte am Esch J. Postoperative com- lower incidence of postoperative complaints after spinal plaints after spinal and thiopentone-isoflorane anaesthesia in anaesthesia may offer an advantage over general anaes- patients undergoing orthopaedic surgery. Spinal versus general thesia in healthy allogeneic bone marrow donors. anaesthesia. Acta Anaesthesiol Scand 1996; 40: 222–226.