- Email: [email protected]
General Anesthesia Versus Sedation for Implantation of a Biventricular Pacing Device for Cardiac Resynchronization Therapy
General Anesthesia Versus Sedation for Implantation of a Biventricular Pacing Device for Cardiac Resynchronization Therapy Paul Theron, MBChB, FRCA,* Kaushik Guha, MBBS, BSc(Hons), MRCP,† Lilian Mantziari, MD, PhD,† Salman Salahuddin, MD, DM,† Rakesh Sharma, MBBS(Hons), BSc(Hons), MRCP, PhD,† and Sian Jaggar, MBBS, BSc, FRCA, FFPMRCA, MD, CertMedEd* Objective: Heart failure carries significant risk for major noncardiac surgery. Whether this risk is transferable to minor surgery is less well-documented. Thus, the aim of this study was to assess the outcome of a contemporary cohort of heart failure patients undergoing cardiac resynchronization therapy (CRT) device insertion under general anesthesia or sedation. Design: Retrospective observational study. Setting: Tertiary cardiac specialist hospital. Participants: Heart failure patients. Interventions: CRT insertion under general anesthesia or sedation. Measurements and Main Results: Anesthesia, heart failure, and outcome data were collected on a consecutive series of patients having CRT device insertion between 2002 and 2010. A total of 242 patients were managed by the anesthesia department during the study period. After exclusion criteria were applied, data for 183 patients were analyzed. Immediate perioperative (o24 hours) mortality was zero; 30-day mortality
of 138 patients was 2.2%. One patient (0.5%) required unplanned intensive care admission. A comparison was made between the sedation (n ¼ 76) group and the general anesthesia (GA) group (n ¼ 107). When compared with the sedation group, the GA group had more intraoperative hypotension (26.2% versus 4.0%, p o 0.00001). There was no difference between the GA and sedation groups with regard to 30-day mortality (1.4% versus 3.1%, p ¼ 0.57), unplanned intensive care admission (0% versus 1.3%, p ¼ 0.42), and length of stay in days (3 versus 3, p ¼ 0.82). Conclusion: The authors found that patients with heart failure undergoing CRT insertion with concurrent general anesthesia or sedation had minimal immediate perioperative risk and that there was no difference in postoperative outcome between general anesthesia and sedation. & 2014 Elsevier Inc. All rights reserved.
H
approximately 5.8 million are affected within the United States.5,6 The condition predominantly affects the elderly, and with the trend of aging populations, there will be an increased prevalence of patients suffering from heart failure. Heart failure pharmacotherapy and device therapy have evolved over the last three decades. There is now an established evidence-based algorithm of neurohormonal antagonism and, for a subgroup of patients, device-based therapy (cardiac resynchronization therapy [CRT] and implantable cardiac defibrillators)7. The introduction of these novel treatments has improved the morbidity and mortality for patients affected by heart failure.8 Recent guidelines suggest that a patient should be considered for CRT if they have symptomatic left ventricular systolic dysfunction (a left ventricular ejection fraction o35%), a broad QRS duration, and are on optimal tolerated medical therapy. The aim of this retrospective study was to investigate whether general anesthesia or sedation could be administered safely to a cohort of patients undergoing CRT implantation and, furthermore, whether the mode of anesthesia affected outcome. Therefore, this cohort can be used as a surrogate population in which to study the effects of anesthesia in relation to severe heart failure. The endpoints of the study were the immediate (o24 hour) perioperative mortality, the 30day mortality, and unplanned intensive care unit (ICU) admission after CRT implantation.
EART FAILURE is a proven risk factor for patients undergoing major noncardiac surgery1–3 and is included in perioperative risk scoring indices. General anesthesia can result in significant hemodynamic effects, which are perceived by anesthesiologists to result in decompensation in patients with end-stage heart failure. These preconceived ideas may lead to patients with heart failure not being considered for interventional procedures or minor surgery even though it may significantly enhance the quality of their lives (albeit at some increased risk in comparison to the normal population). However, the prognosis for patients with heart failure due to left ventricular systolic dysfunction has improved over the last four decades. Hence, the calculated risk may be overestimated and patients denied the opportunity to discuss suitable interventions that may significantly enhance the quality of the life left to them. It can reasonably be expected the number of patients with heart failure requiring interventions to increase.4 The prevalence of patients with congestive heart failure is increasing throughout the Western world. Currently, approximately 15 million individuals are affected within the European Union and
From the Departments of *Anesthesia, and †Cardiology, Royal Brompton Hospital, London, United Kingdom. Dr. Mantziari is supported by grants from the European Heart Rhythm Association and the Hellenic Cardiological Society. Dr. Guha has previously received an unrestricted educational grant from Biotronik Ltd. Address reprint requests to Paul Theron, MBChB, FRCA, 103 Sandown Road, Rondebosch 7700, Cape Town, South Africa. E-mail: [email protected] © 2014 Elsevier Inc. All rights reserved. 1053-0770/2601-0001$36.00/0 http://dx.doi.org/10.1053/j.jvca.2013.07.008 280
KEY WORDS: general anesthesia, sedation, heart failure, cardiac resynchronization therapy, biventricular pacing
METHODS As this investigation formed a routine part of service development at this hospital, no ethical clearance was required.9 The data are routinely collated in departmental databases to ensure safe and effective management of all patients. A consecutive series of patients who attended the Royal Brompton Hospital, London was identified. All underwent CRT implantation in a standardized manner with concurrent
Journal of Cardiothoracic and Vascular Anesthesia, Vol 28, No 2 (April), 2014: pp 280–284
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GENERAL ANESTHESIA VERSUS SEDATION
anesthesia supervised by a consultant in cardiothoracic anesthesia. The standard procedure involves subclavian venous access for placement of cardiac leads and is approximately 2 hours’ duration. The study period was from 2002-2010, during which 8 cardiologists and 16 anesthesiologists were involved in performing the procedures. There was no change in the technique of implantation during this period. All patients fulfilled the appropriate guidance for CRT implantation.7,10,11 The mode of anesthesia was determined by the consultant anesthesiologist in charge of the case and was not influenced by any of the persons involved in this study. Data regarding anesthesia were entered into a secure institutionally held electronic database. All data were entered within two weeks of the procedure by a single consultant anesthesiologist (S.J.). Data included demographic, procedural, and outcome data. In particular, the mode of anesthesia and intraoperative events were recorded. The need for cardioactive agents, the occurrence of hypotension (defined as one reading of more than 25% reduction in blood pressure from baseline [first measurement on chart]), the occurrence of desaturation (of more than 10% reduction from baseline), or the need for conversion of sedation to general anesthesia also was documented. Data were recorded manually at intervals of 5 minutes on the paper anesthetic chart. The heart failure team routinely collected data for CRT implantation performed within the institution. This consisted of demographic data, including clinical, biochemical, echocardiographic, and electrophysiologic data. For the purpose of this study, subsequent outcome data were extracted from the patients’ hospital notes, electronic patient records and electronic echocardiographic system. Data also were extracted from the electronic ICU records to review the necessity for unplanned ICU admissions. The patients were divided into two groups: The general anesthesia (GA) group or the sedation group, administered by an anesthetic consultant. Because of the documentation of administered anesthesia, patients were allocated to the GA group providing they fulfilled at least one of the following criteria as absolute determinants of general anesthesia: Received nondepolarizing muscle relaxants, had an endotracheal tube or laryngeal mask airway inserted, or had received intermittent positive-pressure ventilation. All other patients were allocated to the sedation group, including those who were documented to have been converted from sedation to general anesthesia. The two groups then were compared with regard to demographics, severity of heart failure, intraoperative events, and postoperative outcomes. Exclusion criteria consisted of those patients who underwent CRT with a left ventricular ejection fraction (LVEF) of 445% or who had a documented ejection fraction of better than “severe” left ventricular dysfunction. All patients who had congenital heart disease resulting in abnormal ventricular anatomy were excluded from this analysis, as were those who had undergone prior cardiac transplantation or who underwent CRT implantation as an emergency. Statistical analysis was performed using Stata 10.1 (StataCorp, College Station, TX). Continuous variables were expressed as mean and standard deviation, and categoric variables as number and percentage. Normality was checked using the Kolmogorov-Smirnov test. For normally distributed variables, comparisons between groups used Student’s t test for continuous variables and χ2 test for categoric variables. For non-normally distributed continuous variables, comparisons between groups used Mann-Whitney U test. Logistic regression was conducted to determine whether there was an association between any analyzed variables and outcome. For all analyses, a p value of o0.05 was considered statistically significant. RESULTS
A total of 242 patients were identified. After the application of the exclusion criteria, 183 patients were used for the purpose of data analysis. The following patients were excluded: 31
patients had a LVEF 4 45%, 16 patients were not elective, 11 had complex congenital heart disease, and 1 had a previous cardiac transplant. The immediate perioperative (o24 hours) mortality was zero (0%). Thirty-day follow-up data were available for 138 patients (75%). The total mortality rate within the cohort at thirty days was n = 3 (2.2%). A solitary patient (0.5%) required an unplanned ICU admission. The median length of stay for all patients was three days. A comparison was made between patients who had sedation and GA. There were 76 patients in the sedation group and 107 in the GA group. Demographically, the groups were similar (Table 1). There was no difference between the groups with regard to the New York Heart Association functional classification or LVEF. The anesthetic techniques that were used are presented in Table 2. As the numbers are small, it is not possible to look for associations between agents and outcome. Many combinations of agents and techniques were used. In the sedation group, midazolam was used in 74% of the patients, propofol (either infusion or bolus) was used in 61% of the patients, and a remifentanil infusion was used in 46% of the patients. General anesthesia was induced most often with propofol (88%), and etomidate was used only 12% of the time. Maintenance was accomplished with either propofol TCI (48%) or inhalation anesthetics (49%). Remifentanil was used in 82% of the GA cases. Patients receiving GA were more likely to have invasive monitoring of blood pressure (97.2% versus 89.5%, p ¼ 0.05) and central venous pressure (77.6% versus 48.7%, p ¼ o0.0001). Further analysis of the cases over the period showed an increasing use of general anesthesia over sedation, as shown in Figure 1. Intraoperative events were recorded on the anesthetic database and are presented in Table 3. Intraoperative hypotension Table 1. Baseline Demographic Characteristics
Characteristic
Age (years) Sex (% male) Body mass index (kg/m2) Heart failure etiology Ischemic CM (%) Dilated CM (%) Other (%) Rhythm (%) Sinus rhythm Atrial fibrillation Paced Ejection fraction NYHA (%) III IV Creatinine (mmol/L) Diabetes (%) Hypertension (%) QRS duration (ms)
Sedation n ¼ 76
GA n ¼ 107
68 (10.6) 88.2 28.5 (5.7)
64.6 (12.9) 83.0 27.1 (4.6)
68 28 4
51 39 10
61 28 11 26.7 (8.0)
73 14 13 27.2 (7.3)
64 11 115 [90, 141] 23.6 22.5 146.1 (30.2)
64 4 107 [93, 134] 20.8 22.9 150.9 (30.5)
p Value
0.06 0.34 0.09 0.06
0.07
0.64 0.09
0.47 0.67 0.95 0.33
Values are mean (SD) and median [IQR]. Abbreviations: CM, cardiomyopathy; GA, general anesthesia; NYHA, New York Heart Association.
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THERON ET AL
Table 2. Anesthetic Technique as Percentage of Cases Sedation
GA
n ¼ 76
n ¼ 107
Propofol ¼ 17.1 Midazolam ¼ 73.6 Opioids only ¼ 9.2 Propofol (TCI) ¼ 31.5 Propofol bolus ¼ 27.6 Midazolam bolus ¼ 28.9 Opioid: Remifentanil ¼ 46.1 Fentanyl ¼ 3.9 Morphine ¼ 23.7 Diamorphine ¼ 25.0 Nil
Propofol ¼87.9 Midazolam ¼ 0 Etomidate ¼ 12.1 Propofol (TCI) ¼ 47.7 Sevoflurane ¼ 31.7 Isoflurane ¼ 16.8 Opioid: Remifentanil ¼ 82.2 Fentanyl ¼ 24.3 Morphine ¼ 8.4 Alfentanil ¼ 1.9 Atracurium ¼ 21.5 Rocuronium ¼ 1.9 Vecuronium ¼ 68.2 LMA ¼ 9.4 ETT ¼ 88.8 97.2 77.6
Technique
Induction agent (%)
Maintenance agent (%)
Use of neuromuscular blocking agent (%)
Airway management (%) Invasive BP monitoring (%) CVP monitoring (%)
89.5 48.7
Abbreviations: BP, blood pressure; CVP, central venous pressure; ETT, endotracheal tube; GA, general anesthesia; LMA, laryngeal mask airway; TCI, target-controlled infusion.
occurred in 26.2% of patients in the GA group versus 4.0% in the sedation group (p o 0.00001). The use of fluid boluses was higher in the GA group (17.8% versus 2.6%, p ¼ 0.002), as was the use of the vasoactive agents metaraminol and phenylephine (23.4% versus 6.6%, p ¼ 0.003). Anticholinergics also were used more commonly in the GA group (7.5% versus 0.0%, p ¼ 0.02). Inotrope use (dopamine, adrenaline, noradrenaline) was not significantly different between groups. A single patient (0.5%) experienced a desaturation episode (more than 10% from baseline). The 30-day mortality was 3.1% (2 patients) in the sedation group and 1.4% (1 patient) in the GA group (p ¼ 0.57). These three deaths occurred on days 18, 21, and 28 post-procedure (none had required ICU postprocedure). Two patients in the sedation group required conversion to GA. One was unable to tolerate the process of CRT implantation, and another had a
Fig 1.
Incidence of sedation [
clinical decompensation during the procedure and suffered significant morbidity, requiring unplanned admission to the ICU and a further month of critical care. There was no difference in the median length of stay, which was 3 days in both groups (Table 4). Multivariate logistic regression did not show any significant relationship between the 30-day mortality and any variable. There was a significant relationship between hypotension and general anesthesia. DISCUSSION
This retrospective study showed that there was minimal immediate perioperative risk to patients with heart failure undergoing CRT insertion under GA or sedation. Although the observed 30-day mortality within this cohort was 2.2%, this was independent of the mode of anesthesia. The deaths
] and general anesthesia [
] over study period on annual basis.
283
GENERAL ANESTHESIA VERSUS SEDATION
Table 3. Intraoperative Events as a Percentage of Cases
Event
Hypotension 425% baseline (%) Fluid bolus required (%) Catecholamine infusions (epinephrine, norepinephrine, dopamine) (%) Vasoactive drugs (metaraminol, phenylephrine) (%) Anticholinergic (atropine, glycopyrrolate) (%)
Sedation
GA
n ¼ 76
n ¼ 107
p Values
4.0 2.6 6.6 6.6 0
26.2 17.8 3.7 23.4 7.5
o0.0001 0.002 0.49 0.003 0.02
GA, general anesthesia.
occurred after a time period of at least two weeks postprocedure, suggesting the deaths may not be attributable to anesthesia but rather to the underlying condition. None of the events followed a prolonged ICU stay. Logistic regression analysis did not show any variable to be associated with 30-day mortality, although this was most likely due to the rarity of this outcome (3 events). Hypotension was more prevalent within the group of patients receiving a GA. This was managed conservatively with a combination of intravenous fluid boluses and vasoactive agents. Requirement for inotropic agents was low and independent of the technique used. The hypotension did not result in any complication and had no effect on outcome. There is a paucity of literature in the modern era that has investigated the effect of anesthesia in a contemporary cohort of patients with heart failure. Pfau et al examined the effects of anesthesia within a population of 341 patients with heart failure and undergoing CRT implantation.12 The method of implantation was a mixture between standardized transvenous techniques and surgical placement of the epicardial LV lead, which required a thoracotomy. The majority of this group underwent general anesthesia. As in this study, intraprocedural hypotension was common and more prevalent within the patients who received general anesthesia. As with this cohort, there was zero immediate perioperative mortality. The authors agree with their opinion that the choice of anesthetic technique for minor procedures should depend more on patient variables, such as anxiety and discomfort from positioning and surgical manipulation, than on heart failure risk indices. This study included 2 patients who did not tolerate sedation, which further supported this opinion. Figure 1 shows that over the first three years, no general anesthesia was administered. However, over the latter years of the study period, there was a markedly increased use of general anesthesia, despite there being no change in the medical personnel involved. This may reflect institutional preference consequent upon any perceived lack of advantage in the sedation group and the potential disadvantage of requirement to convert unexpectedly to general anesthesia. There are numerous potential scoring systems to calculate an individual’s perioperative risk of serious complication or death.1,13 Most of the widely used risk scoring systems were conceived within the last century. They place emphasis on clinical symptoms, chest radiographic changes, and subjective grading, all of which have been demonstrated to be poor at differentiating the severity of the underlying heart failure. All current national and international guidance suggests that heart failure should be diagnosed after the use of cardiac imaging,
such as transthoracic echocardiography, and there is increasingly widespread usage of natriuretic peptide levels to further enhance diagnostic capabilities. These advances, together with the progress in management of patients with heart failure, indicate that previous risk scoring systems may need to be revised to reflect more objective measures of heart failure such as echocadiographic parameters or B-type natriuretic peptide.14 Limited observational studies such as this one may yet guide the development of larger registries and novel scoring systems, which incorporate more pertinent clinical variables. There were limitations to this study, primarily consequent upon the fact that it was retrospective in design and reflected data collected from a clinical service. It was subject to the usual limitations of such studies, with a limited number of patients, incomplete data, and no randomization. Despite the acknowledgement in principle of a control arm, there was no suitable cohort of patients within the institution. Although patient matching via propensity scoring may have been desirable, with so few outcome events this would not have been meaningful. A further limitation of the retrospective design was that individual anesthesiologist’s bias could not be excluded with regard to patient selection for GA or sedation; however, this decision was not influenced by the researchers in any way. The study setting was a tertiary/quaternary cardiology and cardiothoracic center within the United Kingdom. Therefore, the demographic characteristics of the patients within this study may not have been representative of more generalized heart failure populations. It is unlikely, however, that the population was less compromised than more general patient groups, and so safe anesthesia in this high-risk group may be comforting in less impaired groups. CRT is now firmly established as a therapeutic option; however, near the start of the 8-year study period, it may have been a novel procedure for the operator. Therefore, data collected may reflect some of the initial learning experience of cardiologists and anesthesiologists. Echocardiography data were collected from the electronic records. As per a real world clinical service, it was performed
Table 4. Clinical Outcomes of Cohort over 30-Day Period Outcome
Sedation
GA
p Values
Immediate perioperative mortality (%) 30-day mortality (%) Unplanned ICU admission (%) Length of stay in days
0 3.1 1.3 3 [1, 8]
0 1.4 0 3 [2, 6]
1.0 0.57 0.42 0.82
NOTE: Values are percentage and median [interquartile range]. Abbreviations: GA, general anesthesia; ICU, intensive care unit.
284
THERON ET AL
by the institution’s department, with no measure of intra/ interobserver variability applied. CONCLUSIONS
In conclusion, this study found that patients with heart failure undergoing elective CRT implantation, general anesthesia,
and sedation are equally safe. The occurrence of significant anesthetic-associated complications is low. The authors suggest that general anesthesia should be considered for these patients and that heart failure should not preclude surgical or procedural interventions, which may enhance quality of life for a patient.
REFERENCES 1. Lee TH, Marcantonio ER, Mangione CM, et al: Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation 100:1043-1049, 1999 2. Boersma E, Kertai MD, Schouten O, et al: Perioperative cardiovascular mortality in noncardiac surgery: Validation of the Lee cardiac risk index. Am J Med 118:1134-1141, 2005 3. Hammill BG, Curtis LH, Bennett-Guerrero E, et al: Impact of heart failure on patients undergoing major noncardiac surgery. Anesthesiology 108:559-567, 2008 4. Heidenreich PA, Trogdon JG, Khavjou OA, et al: Forecasting the future of cardiovascular disease in the United States: A policy statement from the American Heart Association. Circulation 123:933-944, 2011 5. Braunschweig F, Cowie MR, Auricchio A: What are the costs of heart failure? Europace 13:ii13-ii17, 2011 (suppl) 6. Roger VL, Go AS, Lloyd-Jones DM, et al: Heart disease and stroke statistics—2011 update: A report from the American Heart Association. Circulation 123:e18-e209, 2011 7. Dickstein K, Cohen-Solal A, Filippatos G, et al: ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 29:2388-2442, 2008 8. Albouaini K, Egred M, Rao A, Alahmar A, et al: Cardiac resynchronisation therapy: Evidence based benefits and patient selection. Eur J Intern Med 19:165-172, 2008 9. National Patient Safety Agency: National Research Ethics Service. Defining Research. https://www.immunology.org/Document.Doc?id= 491. Published December 2009
10. Barnett D, Phillips S, Longson C: Cardiac resynchronisation therapy for the treatment of heart failure: NICE technology appraisal guidance. Heart 93:1134-1135, 2007 11. Dickstein K, Vardas PE, Auricchio A, et al: 2010 Focused Update of ESC Guidelines on device therapy in heart failure: an update of the 2008 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure and the 2007 ESC guidelines for cardiac and resynchronization therapy. Developed with the special contribution of the Heart Failure Association and the European Heart Rhythm Association. Eur Heart J 31:2677-2687, 2010 12. Pfau G, Schilling T, Kozian A, et al: Outcome after implantation of cardiac resynchronization/defibrillation systems in patients with congestive heart failure and left bundle-branch block. J Cardiothorac Vasc Anesth 24:30-36, 2010 13. Fleisher LA, Beckman JA, Brown KA, et al: ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery) developed in collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. J Am Coll Cardiol 50: e159-e241, 2007 14. Rodseth RN, Lurati Buse GA, Bolliger D, et al: The predictive ability of pre-operative B-type natriuretic peptide in vascular patients for major adverse cardiac events: An individual patient data metaanalysis. J Am Coll Cardiol 58:522-529, 2011
of 138 patients was 2.2%. One patient (0.5%) required unplanned intensive care admission. A comparison was made between the sedation (n ¼ 76) group and the general anesthesia (GA) group (n ¼ 107). When compared with the sedation group, the GA group had more intraoperative hypotension (26.2% versus 4.0%, p o 0.00001). There was no difference between the GA and sedation groups with regard to 30-day mortality (1.4% versus 3.1%, p ¼ 0.57), unplanned intensive care admission (0% versus 1.3%, p ¼ 0.42), and length of stay in days (3 versus 3, p ¼ 0.82). Conclusion: The authors found that patients with heart failure undergoing CRT insertion with concurrent general anesthesia or sedation had minimal immediate perioperative risk and that there was no difference in postoperative outcome between general anesthesia and sedation. & 2014 Elsevier Inc. All rights reserved.
H
approximately 5.8 million are affected within the United States.5,6 The condition predominantly affects the elderly, and with the trend of aging populations, there will be an increased prevalence of patients suffering from heart failure. Heart failure pharmacotherapy and device therapy have evolved over the last three decades. There is now an established evidence-based algorithm of neurohormonal antagonism and, for a subgroup of patients, device-based therapy (cardiac resynchronization therapy [CRT] and implantable cardiac defibrillators)7. The introduction of these novel treatments has improved the morbidity and mortality for patients affected by heart failure.8 Recent guidelines suggest that a patient should be considered for CRT if they have symptomatic left ventricular systolic dysfunction (a left ventricular ejection fraction o35%), a broad QRS duration, and are on optimal tolerated medical therapy. The aim of this retrospective study was to investigate whether general anesthesia or sedation could be administered safely to a cohort of patients undergoing CRT implantation and, furthermore, whether the mode of anesthesia affected outcome. Therefore, this cohort can be used as a surrogate population in which to study the effects of anesthesia in relation to severe heart failure. The endpoints of the study were the immediate (o24 hour) perioperative mortality, the 30day mortality, and unplanned intensive care unit (ICU) admission after CRT implantation.
EART FAILURE is a proven risk factor for patients undergoing major noncardiac surgery1–3 and is included in perioperative risk scoring indices. General anesthesia can result in significant hemodynamic effects, which are perceived by anesthesiologists to result in decompensation in patients with end-stage heart failure. These preconceived ideas may lead to patients with heart failure not being considered for interventional procedures or minor surgery even though it may significantly enhance the quality of their lives (albeit at some increased risk in comparison to the normal population). However, the prognosis for patients with heart failure due to left ventricular systolic dysfunction has improved over the last four decades. Hence, the calculated risk may be overestimated and patients denied the opportunity to discuss suitable interventions that may significantly enhance the quality of the life left to them. It can reasonably be expected the number of patients with heart failure requiring interventions to increase.4 The prevalence of patients with congestive heart failure is increasing throughout the Western world. Currently, approximately 15 million individuals are affected within the European Union and
From the Departments of *Anesthesia, and †Cardiology, Royal Brompton Hospital, London, United Kingdom. Dr. Mantziari is supported by grants from the European Heart Rhythm Association and the Hellenic Cardiological Society. Dr. Guha has previously received an unrestricted educational grant from Biotronik Ltd. Address reprint requests to Paul Theron, MBChB, FRCA, 103 Sandown Road, Rondebosch 7700, Cape Town, South Africa. E-mail: [email protected] © 2014 Elsevier Inc. All rights reserved. 1053-0770/2601-0001$36.00/0 http://dx.doi.org/10.1053/j.jvca.2013.07.008 280
KEY WORDS: general anesthesia, sedation, heart failure, cardiac resynchronization therapy, biventricular pacing
METHODS As this investigation formed a routine part of service development at this hospital, no ethical clearance was required.9 The data are routinely collated in departmental databases to ensure safe and effective management of all patients. A consecutive series of patients who attended the Royal Brompton Hospital, London was identified. All underwent CRT implantation in a standardized manner with concurrent
Journal of Cardiothoracic and Vascular Anesthesia, Vol 28, No 2 (April), 2014: pp 280–284
281
GENERAL ANESTHESIA VERSUS SEDATION
anesthesia supervised by a consultant in cardiothoracic anesthesia. The standard procedure involves subclavian venous access for placement of cardiac leads and is approximately 2 hours’ duration. The study period was from 2002-2010, during which 8 cardiologists and 16 anesthesiologists were involved in performing the procedures. There was no change in the technique of implantation during this period. All patients fulfilled the appropriate guidance for CRT implantation.7,10,11 The mode of anesthesia was determined by the consultant anesthesiologist in charge of the case and was not influenced by any of the persons involved in this study. Data regarding anesthesia were entered into a secure institutionally held electronic database. All data were entered within two weeks of the procedure by a single consultant anesthesiologist (S.J.). Data included demographic, procedural, and outcome data. In particular, the mode of anesthesia and intraoperative events were recorded. The need for cardioactive agents, the occurrence of hypotension (defined as one reading of more than 25% reduction in blood pressure from baseline [first measurement on chart]), the occurrence of desaturation (of more than 10% reduction from baseline), or the need for conversion of sedation to general anesthesia also was documented. Data were recorded manually at intervals of 5 minutes on the paper anesthetic chart. The heart failure team routinely collected data for CRT implantation performed within the institution. This consisted of demographic data, including clinical, biochemical, echocardiographic, and electrophysiologic data. For the purpose of this study, subsequent outcome data were extracted from the patients’ hospital notes, electronic patient records and electronic echocardiographic system. Data also were extracted from the electronic ICU records to review the necessity for unplanned ICU admissions. The patients were divided into two groups: The general anesthesia (GA) group or the sedation group, administered by an anesthetic consultant. Because of the documentation of administered anesthesia, patients were allocated to the GA group providing they fulfilled at least one of the following criteria as absolute determinants of general anesthesia: Received nondepolarizing muscle relaxants, had an endotracheal tube or laryngeal mask airway inserted, or had received intermittent positive-pressure ventilation. All other patients were allocated to the sedation group, including those who were documented to have been converted from sedation to general anesthesia. The two groups then were compared with regard to demographics, severity of heart failure, intraoperative events, and postoperative outcomes. Exclusion criteria consisted of those patients who underwent CRT with a left ventricular ejection fraction (LVEF) of 445% or who had a documented ejection fraction of better than “severe” left ventricular dysfunction. All patients who had congenital heart disease resulting in abnormal ventricular anatomy were excluded from this analysis, as were those who had undergone prior cardiac transplantation or who underwent CRT implantation as an emergency. Statistical analysis was performed using Stata 10.1 (StataCorp, College Station, TX). Continuous variables were expressed as mean and standard deviation, and categoric variables as number and percentage. Normality was checked using the Kolmogorov-Smirnov test. For normally distributed variables, comparisons between groups used Student’s t test for continuous variables and χ2 test for categoric variables. For non-normally distributed continuous variables, comparisons between groups used Mann-Whitney U test. Logistic regression was conducted to determine whether there was an association between any analyzed variables and outcome. For all analyses, a p value of o0.05 was considered statistically significant. RESULTS
A total of 242 patients were identified. After the application of the exclusion criteria, 183 patients were used for the purpose of data analysis. The following patients were excluded: 31
patients had a LVEF 4 45%, 16 patients were not elective, 11 had complex congenital heart disease, and 1 had a previous cardiac transplant. The immediate perioperative (o24 hours) mortality was zero (0%). Thirty-day follow-up data were available for 138 patients (75%). The total mortality rate within the cohort at thirty days was n = 3 (2.2%). A solitary patient (0.5%) required an unplanned ICU admission. The median length of stay for all patients was three days. A comparison was made between patients who had sedation and GA. There were 76 patients in the sedation group and 107 in the GA group. Demographically, the groups were similar (Table 1). There was no difference between the groups with regard to the New York Heart Association functional classification or LVEF. The anesthetic techniques that were used are presented in Table 2. As the numbers are small, it is not possible to look for associations between agents and outcome. Many combinations of agents and techniques were used. In the sedation group, midazolam was used in 74% of the patients, propofol (either infusion or bolus) was used in 61% of the patients, and a remifentanil infusion was used in 46% of the patients. General anesthesia was induced most often with propofol (88%), and etomidate was used only 12% of the time. Maintenance was accomplished with either propofol TCI (48%) or inhalation anesthetics (49%). Remifentanil was used in 82% of the GA cases. Patients receiving GA were more likely to have invasive monitoring of blood pressure (97.2% versus 89.5%, p ¼ 0.05) and central venous pressure (77.6% versus 48.7%, p ¼ o0.0001). Further analysis of the cases over the period showed an increasing use of general anesthesia over sedation, as shown in Figure 1. Intraoperative events were recorded on the anesthetic database and are presented in Table 3. Intraoperative hypotension Table 1. Baseline Demographic Characteristics
Characteristic
Age (years) Sex (% male) Body mass index (kg/m2) Heart failure etiology Ischemic CM (%) Dilated CM (%) Other (%) Rhythm (%) Sinus rhythm Atrial fibrillation Paced Ejection fraction NYHA (%) III IV Creatinine (mmol/L) Diabetes (%) Hypertension (%) QRS duration (ms)
Sedation n ¼ 76
GA n ¼ 107
68 (10.6) 88.2 28.5 (5.7)
64.6 (12.9) 83.0 27.1 (4.6)
68 28 4
51 39 10
61 28 11 26.7 (8.0)
73 14 13 27.2 (7.3)
64 11 115 [90, 141] 23.6 22.5 146.1 (30.2)
64 4 107 [93, 134] 20.8 22.9 150.9 (30.5)
p Value
0.06 0.34 0.09 0.06
0.07
0.64 0.09
0.47 0.67 0.95 0.33
Values are mean (SD) and median [IQR]. Abbreviations: CM, cardiomyopathy; GA, general anesthesia; NYHA, New York Heart Association.
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Table 2. Anesthetic Technique as Percentage of Cases Sedation
GA
n ¼ 76
n ¼ 107
Propofol ¼ 17.1 Midazolam ¼ 73.6 Opioids only ¼ 9.2 Propofol (TCI) ¼ 31.5 Propofol bolus ¼ 27.6 Midazolam bolus ¼ 28.9 Opioid: Remifentanil ¼ 46.1 Fentanyl ¼ 3.9 Morphine ¼ 23.7 Diamorphine ¼ 25.0 Nil
Propofol ¼87.9 Midazolam ¼ 0 Etomidate ¼ 12.1 Propofol (TCI) ¼ 47.7 Sevoflurane ¼ 31.7 Isoflurane ¼ 16.8 Opioid: Remifentanil ¼ 82.2 Fentanyl ¼ 24.3 Morphine ¼ 8.4 Alfentanil ¼ 1.9 Atracurium ¼ 21.5 Rocuronium ¼ 1.9 Vecuronium ¼ 68.2 LMA ¼ 9.4 ETT ¼ 88.8 97.2 77.6
Technique
Induction agent (%)
Maintenance agent (%)
Use of neuromuscular blocking agent (%)
Airway management (%) Invasive BP monitoring (%) CVP monitoring (%)
89.5 48.7
Abbreviations: BP, blood pressure; CVP, central venous pressure; ETT, endotracheal tube; GA, general anesthesia; LMA, laryngeal mask airway; TCI, target-controlled infusion.
occurred in 26.2% of patients in the GA group versus 4.0% in the sedation group (p o 0.00001). The use of fluid boluses was higher in the GA group (17.8% versus 2.6%, p ¼ 0.002), as was the use of the vasoactive agents metaraminol and phenylephine (23.4% versus 6.6%, p ¼ 0.003). Anticholinergics also were used more commonly in the GA group (7.5% versus 0.0%, p ¼ 0.02). Inotrope use (dopamine, adrenaline, noradrenaline) was not significantly different between groups. A single patient (0.5%) experienced a desaturation episode (more than 10% from baseline). The 30-day mortality was 3.1% (2 patients) in the sedation group and 1.4% (1 patient) in the GA group (p ¼ 0.57). These three deaths occurred on days 18, 21, and 28 post-procedure (none had required ICU postprocedure). Two patients in the sedation group required conversion to GA. One was unable to tolerate the process of CRT implantation, and another had a
Fig 1.
Incidence of sedation [
clinical decompensation during the procedure and suffered significant morbidity, requiring unplanned admission to the ICU and a further month of critical care. There was no difference in the median length of stay, which was 3 days in both groups (Table 4). Multivariate logistic regression did not show any significant relationship between the 30-day mortality and any variable. There was a significant relationship between hypotension and general anesthesia. DISCUSSION
This retrospective study showed that there was minimal immediate perioperative risk to patients with heart failure undergoing CRT insertion under GA or sedation. Although the observed 30-day mortality within this cohort was 2.2%, this was independent of the mode of anesthesia. The deaths
] and general anesthesia [
] over study period on annual basis.
283
GENERAL ANESTHESIA VERSUS SEDATION
Table 3. Intraoperative Events as a Percentage of Cases
Event
Hypotension 425% baseline (%) Fluid bolus required (%) Catecholamine infusions (epinephrine, norepinephrine, dopamine) (%) Vasoactive drugs (metaraminol, phenylephrine) (%) Anticholinergic (atropine, glycopyrrolate) (%)
Sedation
GA
n ¼ 76
n ¼ 107
p Values
4.0 2.6 6.6 6.6 0
26.2 17.8 3.7 23.4 7.5
o0.0001 0.002 0.49 0.003 0.02
GA, general anesthesia.
occurred after a time period of at least two weeks postprocedure, suggesting the deaths may not be attributable to anesthesia but rather to the underlying condition. None of the events followed a prolonged ICU stay. Logistic regression analysis did not show any variable to be associated with 30-day mortality, although this was most likely due to the rarity of this outcome (3 events). Hypotension was more prevalent within the group of patients receiving a GA. This was managed conservatively with a combination of intravenous fluid boluses and vasoactive agents. Requirement for inotropic agents was low and independent of the technique used. The hypotension did not result in any complication and had no effect on outcome. There is a paucity of literature in the modern era that has investigated the effect of anesthesia in a contemporary cohort of patients with heart failure. Pfau et al examined the effects of anesthesia within a population of 341 patients with heart failure and undergoing CRT implantation.12 The method of implantation was a mixture between standardized transvenous techniques and surgical placement of the epicardial LV lead, which required a thoracotomy. The majority of this group underwent general anesthesia. As in this study, intraprocedural hypotension was common and more prevalent within the patients who received general anesthesia. As with this cohort, there was zero immediate perioperative mortality. The authors agree with their opinion that the choice of anesthetic technique for minor procedures should depend more on patient variables, such as anxiety and discomfort from positioning and surgical manipulation, than on heart failure risk indices. This study included 2 patients who did not tolerate sedation, which further supported this opinion. Figure 1 shows that over the first three years, no general anesthesia was administered. However, over the latter years of the study period, there was a markedly increased use of general anesthesia, despite there being no change in the medical personnel involved. This may reflect institutional preference consequent upon any perceived lack of advantage in the sedation group and the potential disadvantage of requirement to convert unexpectedly to general anesthesia. There are numerous potential scoring systems to calculate an individual’s perioperative risk of serious complication or death.1,13 Most of the widely used risk scoring systems were conceived within the last century. They place emphasis on clinical symptoms, chest radiographic changes, and subjective grading, all of which have been demonstrated to be poor at differentiating the severity of the underlying heart failure. All current national and international guidance suggests that heart failure should be diagnosed after the use of cardiac imaging,
such as transthoracic echocardiography, and there is increasingly widespread usage of natriuretic peptide levels to further enhance diagnostic capabilities. These advances, together with the progress in management of patients with heart failure, indicate that previous risk scoring systems may need to be revised to reflect more objective measures of heart failure such as echocadiographic parameters or B-type natriuretic peptide.14 Limited observational studies such as this one may yet guide the development of larger registries and novel scoring systems, which incorporate more pertinent clinical variables. There were limitations to this study, primarily consequent upon the fact that it was retrospective in design and reflected data collected from a clinical service. It was subject to the usual limitations of such studies, with a limited number of patients, incomplete data, and no randomization. Despite the acknowledgement in principle of a control arm, there was no suitable cohort of patients within the institution. Although patient matching via propensity scoring may have been desirable, with so few outcome events this would not have been meaningful. A further limitation of the retrospective design was that individual anesthesiologist’s bias could not be excluded with regard to patient selection for GA or sedation; however, this decision was not influenced by the researchers in any way. The study setting was a tertiary/quaternary cardiology and cardiothoracic center within the United Kingdom. Therefore, the demographic characteristics of the patients within this study may not have been representative of more generalized heart failure populations. It is unlikely, however, that the population was less compromised than more general patient groups, and so safe anesthesia in this high-risk group may be comforting in less impaired groups. CRT is now firmly established as a therapeutic option; however, near the start of the 8-year study period, it may have been a novel procedure for the operator. Therefore, data collected may reflect some of the initial learning experience of cardiologists and anesthesiologists. Echocardiography data were collected from the electronic records. As per a real world clinical service, it was performed
Table 4. Clinical Outcomes of Cohort over 30-Day Period Outcome
Sedation
GA
p Values
Immediate perioperative mortality (%) 30-day mortality (%) Unplanned ICU admission (%) Length of stay in days
0 3.1 1.3 3 [1, 8]
0 1.4 0 3 [2, 6]
1.0 0.57 0.42 0.82
NOTE: Values are percentage and median [interquartile range]. Abbreviations: GA, general anesthesia; ICU, intensive care unit.
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by the institution’s department, with no measure of intra/ interobserver variability applied. CONCLUSIONS
In conclusion, this study found that patients with heart failure undergoing elective CRT implantation, general anesthesia,
and sedation are equally safe. The occurrence of significant anesthetic-associated complications is low. The authors suggest that general anesthesia should be considered for these patients and that heart failure should not preclude surgical or procedural interventions, which may enhance quality of life for a patient.
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