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Eur opean Rev iew for Med ical and Pharmacol ogical Sci ences 2017; 21: 627-634 Anesthetic management of patients with dilated for noncardiac

C.-Q. CHEN 1, X. WANG 2, J. ZHANG 1, S.-M. ZHU 1

1Department of , the First Affiliated Hospital, School of , Zhejiang University, Hangzhou, People’s Republic of China 2School of Medicine, Zhejiang University, Hang Zhou, People’s Republic of China Chao-qin Chen and Xin Wang contributed equally

Abstract. – Anesthetic management of pa - The Features of tients with dilated cardiomyopathy (DCM) is a DCM, a primary myocardial disease, is char - challenge to the anesthesiologist, due to poor acterized by left or biventricular dilation, and left systolic function, ventricular enlargement, risk of malignant arrhythmias and sudden car - systolic dysfunction, with or without congestive diac death. Therefore, preoperative assessment failure. DCM occurs in approximately and appropriate anesthetic management are 13/100000 -84/100000 people and more frequent - important in patients with DCM. This review de - ly in males. The cause of DCM is unknown, al - scribes the preoperative evaluation and anes - though it may be associated with myocarditis, thesia considerations of patients with DCM un - neuromuscular disorders, familial disease, idio - dergoing non-. Patient patho - physiology and clinical status, such as ventric - pathic causes and other possible diseases. Previ - ular function, degree of myocardial fibrosis, ously, it was thought that the largest proportion resting and high-sensitivity C-reac - of DCM was idiopathic (66%) 2. Increasing evi - tive protein can affect survival rates. Advanced dence has shown that DCM has a familial basis 3. monitoring devices, such as transesophageal Over 30 genes have been confirmed to be related and cardiac resynchroniza - 4 tion can be used to assess ventricular to DCM , and sudden cardiac death in DCM was function and myocardial fibrosis. Thoracic found to be associated with the long arm of chro - epidural blockade can improve ventricular mosome 10. Mutations in the gene encoding function. In summary, the optimal anesthetic lamin A/C were related to cardiac transplantation management of patients with dilated cardiomy - in DCM patients 5. DCM mainly manifests as re - opathy requires good preoperative assess - duced (EF) and ment, close perioperative monitoring, suitable anesthetic, optimization fluid management, and (CO). The decrease in forward blood flow leads stable hemodynamic status. to an increase in ventricular end-diastolic vol - ume, ventricular filling pressure, and eventually Key Words: leads to ventricular enlargement to maintain CO. Dilated cardiomyopathy, Non-cardiac surgery, Sys - DCM is often accompanied by arrhythmias, heart tolic dysfunction, Anesthetic management . failure, mitral or tricuspid regurgitation and sud - den death. Although the 5-year mortality rate has decreased significantly, it was still 35 -70% in Introduction children 6, and sudden death from DCM account - ed for 30% of all deaths 7. Dilated cardiomyopathy (DCM) is character - ized by left ventricular or biventricular enlarge - Preoperative Assessment ment and impairment of systolic function. Anes - The preoperative assessment is very important thetic management of patients with DCM under - in patients with DCM undergoing non -cardiac going non -cardiac surgery is challenging and is surgery. (ECG) can be used associated with high mortality 1. Unfortunately, to detect arrhythmia and evaluate the risk of sud - there is a paucity of literature to guide anesthetic den cardiac death (SCD). Left bundle branch management for these patients. To aid anesthesi - block and prolonged QRS duration (> 120 ms) ologists who care for these high-risk patients, were independent predictors of increased mortal - anesthetic management is briefly reviewed. ity and SCD in heart failure patients 8,9 . Reduction

Corresponding Author: Sheng-mei Zhu, MD; e-mail: [email protected] 627 C.-Q. Chen, X. Wang, J. Zhang, S.-M. Zhu of resting heart rate (HR, < 80 beats/min) can re - predict survival rate in DCM 25-30 . Myocardial fi - duce the risk of life-threatening arrhythmia, slow brosis can be found in at least one -third of pa - down myocardial remodeling, improve EF and tients with DCM, and it was previously shown New York Heart Association (NYHA) classifi - that the mid-wall enhancement could predict cation 10,11 . The value of mean QT and the slope SCD in patients with DCM 31-34 . of QT end and RR intervals (QT-slope) inde - Review of the medication history of the patient pendently predict major arrhythmic events 12 . is important 35 . Many patients have been adminis - Holter ECG is a more favorable tool to detect tered -converting enzyme inhibitors arrhythmia, especially non-continuous arrhyth - (ACEI), β-adrenergic blockers and cardiotonic mia. A previous study 13 showed that the occur - drugs to reduce , slow ventricular re - rence of major arrhythmic events was the same, modeling and improve CO. β-adrenergic block - whether or not there was non-sustained ventric - ers should be used on the day of surgery to pre - ular tachycardia (nsVT). Whether heart rate vent the rebound phenomenon. Despite contro - variability and turbulence can predict arrhyth - versy, we also recommend that ACEI will be con - mic events remains controversial 14,15 . Preopera - tinued until the day of surgery, even if there is the tive echocardiography is necessary to determine possibility of intraoperative hypotension 36 . The ventricular function and to assess the degree of serum potassium level should be evaluated be - valvula r dysfunction 16 . International guidelines cause of the use of diuretics such as spironolac - considered that patients with LVEF ≤ 35% and tone. Cardiac resynchronization therapy (CRT) NYHA class I were a IIb class recommendation can reduce the morbidity and mortality of heart for ICD implantation, while NYHA class II or III failure patients 37,38 . Biventricular pacing can im - patients with LVEF ≤ 35% were a class I recom - prove left ventricular (LV) systolic function and mendation 17 . Serum levels of B-type natriuretic decrease LV size and mitral regurgitation 39-41 . peptide (BNP) have shown a correlation with left Therefore, if a patient has CRT, the function ventricular end-diastolic pressure, left ventricular needs to be evaluated preoperatively. wall stress, fibrosis and systolic dysfunction 18,19 . N-terminal (NT) pro-BNP levels over 2247 Anesthetic Management pmol/L were reported to be associated with high - The key hemodynamic features of patients er mortality rates 20 , but the utility of measuring with DCM are elevated filling pressures, myocar - NT pro-BNP levels has been questioned. Serum dial contractile dysfunction, and a marked nega - high-sensitivity CRP (hsCRP) level is also an in - tive relation between and dependent predictor of survival rates in patients afterload 42 . Therefore , the anesthetic principles with DCM 20 . Ishikawa et al 21 reported that sur - for DCM include 35,43-45 : vival rates were significantly lower in patients • Mmaintenance of , with hsCRP levels over 1 mg/L. Also, lower EF, avoiding drugs which can decrease myocardial lower serum sodium, lymphocytopenia and high - contractility, maintenance of normal diastolic er serum creatinine have been reported to be in - to ensure coronary , dependent predictors of transplantation or death maintenance of and preventing fluid in patients with DCM 22 . However, a lower EF in overload ; patients with DCM might have a normal CO. For • Prevention of increased afterload (systemic example, if a patient has 30% EF, end diastolic ), avoidance of arrhythmias volume of 250 ml, heart rate of 90 beats/min, and (i.e. tachycardia), and prevention of throm - 30% regurgitant fraction, CO will be of 6.75 boembolic events. L/min and forward CO will be 4.725 L/min. For - ward CO of 4.725 L/min may be sufficient for a Fluid Management 50 kg patient. However, if a patient presented In DCM patients, the intraoperative fluid man - with small left ventricular volume with low EF, agement should be cautiously managed. Because the patient would have reduction in CO and a of poor cardiac ejection, ventricular enlargement , poor outcome 23 . A previous study 24 suggested and elevated filling pressures, the fluid overload that there were no significant differences be - in the perioperative period could potentially lead tween the preoperative NYHA classification and to heart failure and pulmonary edema 46 . Howev - the incidence of complications. Cardiac magnetic er, the fluid restriction can reduce CO. The ade - resonance, a noninvasive imagining technique, quacy of fluid management can be judged by has been used to detect myocardial fibrosis and (CVP), ,

628 Anesthetic management of patients with dilated cardiomyopathy for noncardiac surgery urine output , and serum lactate. A pulmonary slow sympathetic blockade 55 . Hashimoto et al 56 artery wedge pressure of 12 -15 mmHg or a CVP suggested that fentanyl (10 µg/kg) can be admin - of 8 -12 mmHg is recommended in cardiac istered intrathecally. Okutomi et al 57 showed that surgery patients 23 . However, these pressures can LVEF changed minimally after EA with bupiva - be affected by various factors 47 . The trans - caine. Intermittent boluses of bupivacaine esophageal echocardiography (TEE) may be a (0.0625%) with fentanyl (2 µg/ml) could provide more accurate tool to assess ventricular filling 48 , adequate analgesia with stable hemodynamic sta - although it is prohibited in patients with tus 58 . Previous studies 59,60 have shown that high esophageal lesions and coagulopathy. The anes - thoracic epidural sympathetic blockade can de - thesiologist should consider the amount of fluids crease left ventricular end-diastolic dimension, which have been administered preoperatively improve LVEF and NYHA classification, and re - when they determine the amount of fluid to in - duce re -hospitalization rate . fuse. A previous study 49 showed that large vol - General anesthetics chosen should have mini - umes of crystalloid fluid might cause the pul - mal inhibition on cardiovascular function accord - monary edema easier , it might reduce the tissue ing to the status of patients, and the dose admin - oxygen supply, and it might affect the wound istered. Induction of general anesthesia should be healing. Therefore, the amount of crystalloid administered with small doses, and increased should be controlled, and blood or blood prod - gradually according to the response of the pa - ucts can be infused if necessary. The furosemide tients. can be administrated to prevent the volume over - load. Intravenous Anesthetics Etomidate is often advocated as an induction Mechanical Ventilation Settings anesthetic in patients with cardiac dysfunction The mechanical ventilation may reduce ve - because it causes minimal impact on cardiovas - nous return and CO, especially in the case of in - cular function. Etomidate (0.3 mg/kg) did not sufficient capacity 50 . In contrast, large tidal vol - cause a change in in chil - ume (TV ) can reduce cardiac filling 51 ; therefore, dren with congenital heart disease 61 . Although ar - an appropriate TV (6 -8 ml/kg) can be applied. In terial pressure is maintained during etomidate patients with DCM requiring mechanical ventila - anesthesia, a previous study 62 showed that etomi - tion, the application of positive end-expiratory date anesthesia could cause increased left ven - pressure can improve CO in patients with elevat - tricular afterload, and affect myocardial function ed filling pressures, but has adverse effects on in patients with impaired LV function. Propofol CO in patients with low pulmonary capillary is a commonly used intravenous anesthesia drug. wedge pressure 52 . Propofol can reduce LV preload and afterload, induce myocardial depression, and impair early- Anesthesia Options diastolic left ventricular filling 63 , but this effect When we select the mode of anesthesia, the could be reversed by inotropic drugs. Midazolam key point is to avoid myocardial depression, is a commonly used sedative drug because it does maintain hemodynamic stability, as well as meet - not induce myocardial depression or ing the requirements of surgery. Epidural anes - 64 . Dexmedetomidine, an 2- adreno - thesia (EA) can reduce afterload and help to ceptor agonist, was selected as a sedative and maintain forward flow from the left 44 . anxiolytic drug because it has sympatholytic and Another advantage of EA is that it can provide cardio -protective effects, without respiratory de - effective postoperative analgesia. However, a pression 65 . Dexmedetomidine can increase LV large dose of local anesthesia may cause a reduc - pressure, and stroke volume 66 . However, tion in SVR and impairment of myocardial func - dexmedetomidine can slow the HR, which may tion. Therefore, slow administration of low-dose reduce CO, especially in patients where the CO of local anesthesia or slow titration have been mainly depends on HR. recommended to avoid rapid and extensive sym - pathetic nerve block 53 . Echigoya et al 54 suggested Volatile Anesthetics that mepivacaine (2 ml/kg) continuous infusion Though inhalational anesthesia has the advan - can be used in patients with DCM. EA with fen - tages of being quickly adjustable, and easily tanyl has been confirmed to reduce afterload, im - changing hemodynamic parameters, it may alter prove cardiac function, and is accompanied by ventricular function because of strong myocar -

629 C.-Q. Chen, X. Wang, J. Zhang, S.-M. Zhu dial depression and preload reduction 67 . Isoflu - used. All of those agents can improve the stroke rane has been shown to reduce SVR in NYHA volume, can increase the HR, and can decrease class II and III patients with coronary artery dis - the filing pressure, while at the same time they ease 68,69 . However, another study 70 suggested that can increase the cardiac work and the oxygen 1.1 -1.5 MAC isoflurane reduced CO and mean consumption 78,79 . Due to myocardial degenera - arterial pressure, and did not have beneficial ef - tion and fibrosis, digoxin should be administrated fects on LV afterload in the presence of LV dys - in small doses for poor tolerance. β-adrenergic function. Sevoflurane (8%) has been found to agonists are the optimal vasoactive agent for cause a second degree atrioventricular block 71 . DCM. Several anesthesiologists recommend Ibrahim 72 reported that the induction of anesthe - pump infusion of dopamine before induction of sia with 3% sevoflurane and a bolus (1 µg/kg) of anesthesia, to shorten the time of hypotension af - remifentanil in a child with DCM caused severe ter induction. cardiovascular collapse. Adequate anesthetic depth is important to prevent the overload of af - Postoperative Analgesia terload. Inhalational anesthesia at a low concen - Good postoperative must tration (0.5 -1.0 MAC) with a small dose (2 -3 maintain postoperative hemodynamic stability, µg/kg) of fentanyl may be safely used because it avoid cardiac depression, and avoid increasing did not decrease myocardial contractility 73 . Rylo - SVR and HR. Combined application of local va et al 74 reported on a successful case of xenon anesthetics, nonsteroidal anti-inflammatory drugs anesthesia use in a patient with DCM, but further and opioids are often used for postoperative anal - research on xenon anesthesia is required. gesia 80 . Epidural analgesia may be the best method for effective analgesia, with few adverse Opioids events 81,82 . Previous studies 83-85 have demonstrat - Opioids (fentanyl and sufentanil) have mini - ed that postoperative thoracic epidural analgesia mal side effects on cardiac function 75 . Adequate can improve heart function in patients with heart HR and preload are necessary to maintain CO in failure and reduce perioperative adverse cardiac patients with DCM. Remifentanil can cause events. Epidural with fentanyl may be able to bradycardia, especially in patients with anesthe - provide rapid analgesia. sia, on pure oxygen inhalational and using β- adrenergic blockade 76 . Morphine may cause de - creasing preload and/or systemic vascular resis - Conclusions tance (SVR ). Application of large doses of all opioids must be carefully monitored. This review focused on the preoperative evalu - ation and anesthesia considerations of patients Intraoperative Monitoring and with DCM. The optimal anesthetic management Vasoactive Drugs must assess the patient’s pathophysiology and Suitable monitoring is needed to maintain an clinical status, select an appropriate method of appropriate hemodynamics state. Invasive arterial anesthesia based on the kind of surgery and the monitoring, central venous pressure monitoring, degree of cardiac function, strengthen periopera - pressure monitoring, TEE, tive monitoring, select suitable anesthetics, and pacemakers, defibrillators, and bispectral index maintain management of optimization fluid and can be used during surgery according to the state stable hemodynamic status. of the patient. If a patient has an acute circulatory failure during surgery, appropriate vasoactive agents and fluid should be administered. Norepi - ––––––––––––––––– –– nephrine, epinephrine, or phenylephrine can in - Acknowledgements crease mean arterial pressure. We would like to thank Yue-ying Zheng for her suggestions can increase coronary perfusion by increasing di - with the study. astolic blood pressure, while cardiac toxicity can be induced if the infusion is prolonged. Phenyle - –––––––––––––––– ––– phrine can worsen right ventricular function in Sources of Funding 77 patients with pulmonary . If in - This work was supported by the Department of Anesthesiol - otropic agents are required, milrinone, dobuta - ogy, the First Affiliated Hospital, School of Medicine, Zhe - mine, dopamine and low dose epinephrine can be jiang University, Hang Zhou, China.

630 Anesthetic management of patients with dilated cardiomyopathy for noncardiac surgery

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