OBES SURG DOI 10.1007/s11695-015-1626-6
ORIGINAL CONTRIBUTIONS
Comparison of Rhabdomyolysis Markers in Patients Undergoing Bariatric Surgery with Propofol and Inhalation-based Anesthesia Amit Lehavi & Olga Sandler & Ahmad Mahajna & Abraham Weissman & Yeshayahu Shai Katz
# Springer Science+Business Media New York 2015
Abstract Background Rhabdomyolysis is a relatively uncommon, severe complication of anesthesia and surgery in the morbidly obese. As the use of propofol-based anesthesia has been associated with an increased risk of rhabdomyolysis and metabolic acidosis, this pilot study was designed to assess the effect of propofol anesthesia on the incidence of rhabdomyolysis in morbidly obese patients undergoing bariatric surgery. Methods Thirty, morbidly obese patients (body mass index 43 ±3 kg/m2) scheduled for bariatric laparoscopic sleeve gastrectomy were randomized to receive either propofol (P) or inhalational anesthetic (I)-based balanced general anesthesia. A sample of venous blood gas analysis including pH, bicarbonate concentrations, and calculated base excess was taken at the end of the operation. Creatine phosphokinase (CPK), troponin I, blood urea nitrogen, and creatinine plasma concentrations were measured at the end of the surgery and again 24 h later. Results All patients enrolled to the study completed it without significant complications. CPK, troponin I, blood urea nitrogen, and creatinine plasma concentrations at the end of the operation and at 24 h, as well as the bicarbonate concentration and the base excess at the end of the operation were not A. Lehavi (*) : O. Sandler : A. Weissman : Y. S. Katz Department of Anesthesiology, Rambam Healthcare Campus, Haifa, Israel e-mail: [email protected] A. Mahajna Department of Surgery, Rambam Healthcare Campus, Haifa, Israel Y. S. Katz Ruth and Bruce Rappaport Faculty of Medicine, Technion—Israel Institute of Technology, Haifa, Israel A. Lehavi University of Queensland School of Medicine, Brisbane, QLD, Australia
significantly different between the two study groups. A statistically significant mild respiratory acidosis was noted in the inhalational anesthetic group (pH 7.30±0.04 vs. 7.36±0.02 in the propofol group) Conclusions This small-size pilot study may suggest that propofol-based anesthesia is not related to increased incidence of rhabdomyolysis in morbidly obese patients undergoing short, uncomplicated bariatric surgery. Keywords Bariatric surgery . Rhabdomyolysis . Propofol . Propofol infusion syndrome . PRIS . Sleeve gastrectomy
Introduction Although relatively a rare phenomenon but coinciding with the major advent of special operations for the obese population, more and more publications have emerged reporting the occurrence of rhabdomyolysis with or without acute renal failure in conjugation with bariatric and obese-related surgery. In addition, a speculation on a potential role of general anesthetics has been raised regarding rhabdomyolysis during surgery in obese. No doubt that the intravenous general anesthetic propofol could theoretically be a prototypic candidate risk factor for precipitating rhabdomyolysis, since it has many years reputation as a causative of what is known as propofol infusion syndrome when administered continuously in high enough dosage and for a long time [1]. Propofol infusion syndrome is characterized by rhabdomyolysis, cardiomyopathy, metabolic acidosis, and renal failure. Thus far, only two articles describing of an association between propofol and rhabdomyolysis with regards to obesity appeared in the literature [2, 3] In the present study, the effect of propofol and of a different acting anesthetic sevoflurane administered by inhalation and thus far not incriminated as an etiological factor for
OBES SURG
rhabdomyolysis in obese patient with or without operation, on the immediate and delayed postoperative markers of muscle necrosis, cardiac injury, and kidney dysfunction were examined in patients undergoing bariatric surgery.
Methods Thirty morbidly obese patients scheduled for bariatric laparoscopic sleeve gastrectomy in Rambam Healthcare Campus in Haifa, Israel, a university affiliated referral hospital, were enrolled to the study and randomly assigned to receive either propofol (P) or inhalation anesthetic (I)-based anesthesia. The study was designed as a prospective, randomized, and single blinded. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. After institutional review board approval, informed consent was obtained from all individual participants included in the study; thirty morbidly obese patients scheduled for bariatric laparoscopic sleeve gastrectomy were randomly assigned to receive either propofol (P) or the inhalation anesthetic (I) sevoflurane-based anesthesia. Inclusion criteria were age between 20 and 55 years, body mass index (BMI) between 38 and 55 kg/m2. Exclusion criteria were known liver or kidney failure, previous metabolic disease, and a history of sensitivity to eggs or propofol. The duration of the procedure, as well as the rate of anesthetic and surgical complications were recorded. Each patient was laid on top of the 75-mm thick original foam mattress supplied by the operating table manufacturer (MAQUET Holding B.V. & Co. KG, Rastatt, Germany) on which an 8.4-mm soft gel cover was placed. The upper part of his body was raised 20° at reverse Trendelenburg, legs elevated 45° upward and flexed at the hips and knees (beach chair position). Anesthesia was induced using propofol 1.5– 2.5 mg/kg, fentanyl 1–2 microgram/kg, and rocuronium 0.6– 1 mg/kg. Additional doses of fentanyl were given according to the caring anesthesiologist discretion. Maintenance of anesthesia was achieved with a target controlled infusion of propofol using the Marsh model, aiming at a calculated plasma concentration of 2–5 microgram/mL in the (P) group and at an expired concentration of 1.5–3 % sevoflurane in the (I) group. Crystalloid fluid replacement was administered according to a conservative regimen (15 ml/kg). Depth of anesthesia was monitored by bispectral index (BIS), where values were kept at 40 to 60, indicating adequate hypnotic effect during general anesthesia. Standard monitors including three lead ECG, noninvasive blood pressure measurement device, and pulse oximeter were applied throughout the procedure.
A sample of venous blood gas analysis including pH, bicarbonate concentrations, and calculated base excess was taken at the end of the operation. Blood was also collected via direct phlebotomy for creatine phosphokinase (CPK) and troponin I concentrations, blood urea nitrogen and creatinine concentrations at the end of the surgery, and again 24 h later. Data was evaluated by SPSS software, version 17 (SPSS Inc. Chicago, IL, USA). All variables are presented as mean± standard deviation. The differences in demographic parameters (age, weight, and height), between (P) or (I) groups were analyzed by T test. Fisher’s exact test was used for detecting the differences in the prevalence of gender between (P) or (I). A Mann–Whitney U test was used to determine the correlation between the blood results in the two groups. P0.001). As the bicarbonate concentrations as well as the calculated base excess were normal in all patients, this cannot be regarded as metabolic acidosis. All the pH values in the (P) group were over 7.30. Whereas, values in the (I) group were under 7.35. The distribution of the PH in both study groups is presented in Chart 1.
The results of the various blood tests at the end of the operation are presented in Tables 3 and 4. In the blood sample performed 24 h after the operation, the CPK concentrations in the (P) group were 118±86 IU/L compared with 107±50 IU/L in the (I) group. Except a single patient from the (P) group, all the patients had blood CPK concentration under 200 IU/L. No significant difference was demonstrated between the two groups. The troponin I concentrations were 0.0021±0.004 microgram/L in the (P) group, compared with 0.0028±0.005 microgram/L in the (I) group. All the patients had blood troponin I concentration under 0.01 microgram/L. No significant difference was demonstrated between the two groups. The urea concentrations were 13±5 mg/dL in the (P) group compared with 10±2 mg/dL in the (I) group. All patients had normal blood urea concentrations. No significant difference was demonstrated between the two groups. The creatinine concentrations were 0.78±0.17 mg/dL in the (P) group, compared with 0.79±0.09 mg/dL in the (I) group. All patients had normal blood creatinine concentrations. No significant difference was demonstrated between the two groups.
Discussion A host of publications reporting rhabdomyolysis related to operations in obese and especially in bariatric surgery are found in the literature of the last decade or so. The first report of rhabdomyolysis was attributed to direct and prolonged pressure of the bed against the dorsal and gluteal muscles after bariatric surgery in three super obese patients appeared in 2003 [4]. Soon after, the fatality potential of rhabdomyolysis was demonstrated in 3 males with BMI 67 out of 100 consecutive primary uncomplicated but very prolonged bariatric surgical procedures which died due to renal failure during a 1-
Table 3 Blood markers for rhabdomyolysis, cardiac and renal injury, and acid base balance at the end of the surgery
Chart 1 pH distribution in the propofol (P) and inhalation anesthetic (I) groups at the end of the operation
Group P (n=15)
Group I (n=15)
Significancea
Creatine phosphokinase (CPK), IU/L Troponin I, microgram/L Urea, mg/dL Creatinine, mg/dL Bicarbonate, meq/L
125±94
118±59
NS
0.0025±0.005 11±3 0.65±0.10 23.2±2.0
0.0007±0.002 10±2 0.71±0.11 23.0±1.0
NS NS NS NS
Base excess, meq/L pH
−0.9±1 7.36±0.02
−2.0±2.0 7.30±0.04
NS >0.001
Values are presented as mean±SD or median a
Mann–Whitney U test
OBES SURG Table 4 Blood markers for rhabdomyolysis, cardiac and renal injury 24 h after surgery Group P (n=15)
Group I (n=15)
Significancea
Creatine phosphokinase 125±94 118±59 NS (CPK), IU/L Troponin I, microgram/L 0.0025±0.005 0.0007±0.002 NS Urea, mg/dL Creatinine, mg/dL
11±3 0.65±0.10
10±2 0.71±0.11
NS NS
Values are presented as mean±SD or median a
Mann–Whitney U test
year period [5]. A recent systematic review of the literature has found mostly reports of an isolated event or small case series and few prospective and retrospective comparative studies of rhabdomyolysis following bariatric surgery with overall 145 patients with 14 % of acute renal failure and 5 % of mortality rate [6]. However, rhabdomyolysis occurred in non-bariatric operation as well such as lumbar spine [7, 8], major urologic [9], orthopedic [10, 11], and others. Risk factors making obese patients more prone to rhabdomyolysis include male gender, American Society of Anesthesiologists (ASA) physical status III or IV, BMI >52 kg/m2, and operation time longer than 4 h and lengthened anesthesia-related immobilization [6], presence of diabetes mellitus with BMI >40 kg/m2 [12, 13], and use of statins [14]. Equal number of patients in both groups was chronically treated with statins, and our policy is not to stop taking statins before surgery. A decade ago, an advisory committee on the safety usage of statins stated that fearing the development of statin-induced myopathy during the period prior to major surgery, it would be prudent to withhold their preoperative intake [15]. Contrary to this assertion, recent publications showed improved postoperative outcome and reduced incidence of myocardial damage at the first month following surgery on continuous statins, without clinical or laboratory evidence of rhabdomyolysis [16]. It is even recommended to start statins preoperatively [17]. In this regard, this study also supports the perioperative use of statins for the obese population despite intraoperative propofol administration. In addition, we managed perioperative fluid replacement according to a conservative regimen. In a study conducted to test this issue, conservative (48 patients, 15 ml/kg) versus liberal (53 patients, 40 ml/kg) intraoperative intravenous fluid volume was administered to two groups of patients undergoing bariatric surgery. Four patients in the conservative group and three patients in the liberal group developed postoperative rhabdomyolysis, proposing that the mode of fluids administration did not affect the incidence of this complication [18] Prolonged administration of propofol in fat emulsion had long been established as promoter of propofol infusion syndrome [1]. Propofol potentially could contribute to
rhabdomyolysis and its complications in conjugation with surgery in super obese patients as presented by two recent publications reporting death after continuous propofol sedation (2, 2a). This triggered us to carry out the present study. Two interesting finding has emerged from it. First, in our group of patients, no one experienced any clinical signs of muscle disruption along with no laboratory evidence of either muscle breakdown and any cardiac, renal failure, or metabolic derangement. Second, neither propofol nor sevoflurane caused rhabdomyolysis. The results of this study would imply that anesthetic drugs (such as propofol) per se may not incriminate the primary and most important factor in precipitating rhabdomyolysis in obese patients undergoing surgery. Other causes including prolonged surgery over 4 h and a history of diabetes with BMI >40 kg/m2 are probably more contributory [6] In such cases, CK is highly recommended to be systematically measured for verifying the presence of muscle injury. Whatever the reason might be, vigilance, attention, and awareness of the anesthesiologist and the surgeon to the possibility of rhabdomyolysis in an obese surgical patient are mandatory. It should be clarified that this is indeed a pilot study, limited in scope. However, information regarding the actual incidence of rhabdomyolysis in conjugation with surgery in obese patients emerged mostly from isolated cases and small-scale studies, with an order of magnitude resembling that of our study. A recent systematic review with collected data obtained from 145 reports of rhabdomyolysis in bariatric surgery found a 60 % incidence of such phenomenon [6]. One prospective study of rhabdomyolysis after open Roux-en-Y gastric bypass conducted in 23 bariatric operations diagnosed 30 % events of elevated creatine phosphokinase (CPK) levels [12] whereas other studies found rhabdomyolysis incidence of 77 % in 22 patients [19] and 26 % in 49 patients [13]. Given these figures, we would expect to find at least ten cases of rhabdomyolysis in our study when in fact only one patient had CPK level out of the reference range. Similar low rates of rhabdomyolysis were described by others [20, 21] supporting our findings on the rarity of this complication and its clinical significance. Indeed, with an average BMI of 43 kg/m2, the patients included in this study were the obese class 3 of the World Health Organization classification which is considered the highest level range of obesity and one could expect at least 5 cases of rhabdomyolysis and 2 cases of death according to Chakravartty et al. [6]. It is unknown whether the difference between our and previous studies could be contributed to relatively short procedural time, concern for correct positioning of the patient [22], using intra-abdominal carbon dioxide insufflation pressures as low as possible, and administering neuromuscular relaxant drugs within the right dosage which prevented tissue damage and rhabdomyolysis. The major drawback of this study is that it consists of a small study group. Of course, larger scale studies will be required to provide stronger recommendation to the practicing
OBES SURG
anesthesiologists and bariatric surgeons thus further data are necessary to establish the safety of use of propofol-based total intravenous anesthesia in patients at higher BMIs, as well as its use for longer duration operations. Conflict of Interest Neither of the authors has any conflict of interest regarding this study.
References 1. Fudickar A, Bein B. Propofol infusion syndrome: update of clinical manifestation and pathophysiology. Minerva Anestesiol. 2009;75(5): 339–44. 2. Ramaiah R, Lollo L, Brannan D, et al. Propofol infusion syndrome in a super morbidly obese patient (BMI=75). Int J Crit Illn Inj Sci. 2011;1(1):84–6. doi:10.4103/2229-5151.79290. 3. Diaz JH, Roberts CA, Oliver JJ, et al. Propofol infusion syndrome or not? A case report. Ochsner J. 2014;14(3):434–7. 4. Torres-Villalobos G, Kimura E, Mosqueda JL, et al. Pressure-induced rhabdomyolysis after bariatric surgery. Obes Surg. 2003;13(2):297– 301. doi:10.1381/096089203764467252. 5. Bostanjian D, Anthone GJ, Hamoui N, et al. Rhabdomyolysis of gluteal muscles leading to renal failure: a potentially fatal complication of surgery in the morbidly obese. Obes Surg. 2003;13(2):302–5. doi:10.1381/096089203764467261. 6. Chakravartty S, Sarma DR, Patel AG. Rhabdomyolysis in bariatric surgery: a systematic review. Obes Surg. 2013;23(8):1333–40. doi: 10.1007/s11695-013-0913-3. 7. Foster MR. Rhabdomyolysis in lumbar spine surgery: a case report. Spine. 2003;28(14):E276–8. 8. Dakwar E, Rifkin SI, Volcan IJ, et al. Rhabdomyolysis and acute renal failure following minimally invasive spine surgery: report of 5 cases. J Neurosurg Spine. 2011;14(6):785–8. doi:10.3171/2011.2. SPINE10369. 9. Iser IC, Senkul T, Reddy PK. Major urologic surgery and rhabdomyolysis in two obese patients. Int J Urol: Off J Jpn Urol Assoc. 2003;10(10):558–60. 10. Karcher C, Dieterich HJ, Schroeder TH. Rhabdomyolysis in an obese patient after total knee arthroplasty. Br J Anaesth. 2006;97(6):822–4. doi:10.1093/bja/ael274.
11. Goodman SM, Figgie M, Green D, et al. Rhabdomyolysis is a potential complication of total hip arthroplasty in the morbidly obese. HSS J: Musculoskelet J Hosp Spec Surg. 2013;9(2):200–2. doi:10.1007/ s11420-012-9310-z. 12. Youssef T, Abd-Elaal I, Zakaria G, et al. Bariatric surgery: rhabdomyolysis after open Roux-en-Y gastric bypass: a prospective study. Int J Surg. 2010;8(6):484–8. doi:10.1016/j.ijsu.2010.06.014. 13. Lagandre S, Arnalsteen L, Vallet B, et al. Predictive factors for rhabdomyolysis after bariatric surgery. Obes Surg. 2006;16(10):1365–70. doi:10.1381/096089206778663643. 14. Ettinger JE, de Souza CA, Santos-Filho PV, et al. Rhabdomyolysis: diagnosis and treatment in bariatric surgery. Obes Surg. 2007;17(4): 525–32. 15. Pasternak RC, Smith Jr SC, Bairey-Merz CN, et al. ACC/AHA/ NHLBI clinical advisory on the use and safety of statins. Circulation. 2002;106(8):1024–8. 16. Voute MT, Winkel TA, Poldermans D. Safety of fluvastatin in patients undergoing high-risk non-cardiac surgery. Expert Opin Drug Saf. 2010;9(5):793–800. doi:10.1517/14740338.2010. 499120. 17. Pereira SL, Stevermer JJ, Rowland K. Start a statin prior to vascular surgery. J Fam Pract. 2010;59(2):108–10. 18. Wool DB, Lemmens HJ, Brodsky JB, et al. Intraoperative fluid replacement and postoperative creatine phosphokinase levels in laparoscopic bariatric patients. Obes Surg. 2010;20(6):698–701. doi:10. 1007/s11695-010-0092-4. 19. de Oliveira LD, Diniz MT, de Fatima HSDM, et al. Rhabdomyolysis after bariatric surgery by Roux-en-Y gastric bypass: a prospective study. Obes Surg. 2009;19(8):1102–7. doi:10.1007/s11695-0089780-8. 20. Silecchia G, Rizzello M, Casella G, et al. Two-stage laparoscopic biliopancreatic diversion with duodenal switch as treatment of high-risk super-obese patients: analysis of complications. Surg Endosc. 2009;23(5):1032–7. doi:10.1007/s00464008-0113-8. 21. Ettinger JE, Marcilio de Souza CA, Azaro E, et al. Clinical features of rhabdomyolysis after open and laparoscopic Roux-en-Y gastric bypass. Obes Surg. 2008;18(6):635–43. doi:10.1007/s11695-0079257-1. 22. Mulier JP, Dillemans B, Van Cauwenberge S. Impact of the patient’s body position on the intraabdominal workspace during laparoscopic surgery. Surg Endosc. 2010;24(6):1398–402. doi:10.1007/s00464009-0785-8.
ORIGINAL CONTRIBUTIONS
Comparison of Rhabdomyolysis Markers in Patients Undergoing Bariatric Surgery with Propofol and Inhalation-based Anesthesia Amit Lehavi & Olga Sandler & Ahmad Mahajna & Abraham Weissman & Yeshayahu Shai Katz
# Springer Science+Business Media New York 2015
Abstract Background Rhabdomyolysis is a relatively uncommon, severe complication of anesthesia and surgery in the morbidly obese. As the use of propofol-based anesthesia has been associated with an increased risk of rhabdomyolysis and metabolic acidosis, this pilot study was designed to assess the effect of propofol anesthesia on the incidence of rhabdomyolysis in morbidly obese patients undergoing bariatric surgery. Methods Thirty, morbidly obese patients (body mass index 43 ±3 kg/m2) scheduled for bariatric laparoscopic sleeve gastrectomy were randomized to receive either propofol (P) or inhalational anesthetic (I)-based balanced general anesthesia. A sample of venous blood gas analysis including pH, bicarbonate concentrations, and calculated base excess was taken at the end of the operation. Creatine phosphokinase (CPK), troponin I, blood urea nitrogen, and creatinine plasma concentrations were measured at the end of the surgery and again 24 h later. Results All patients enrolled to the study completed it without significant complications. CPK, troponin I, blood urea nitrogen, and creatinine plasma concentrations at the end of the operation and at 24 h, as well as the bicarbonate concentration and the base excess at the end of the operation were not A. Lehavi (*) : O. Sandler : A. Weissman : Y. S. Katz Department of Anesthesiology, Rambam Healthcare Campus, Haifa, Israel e-mail: [email protected] A. Mahajna Department of Surgery, Rambam Healthcare Campus, Haifa, Israel Y. S. Katz Ruth and Bruce Rappaport Faculty of Medicine, Technion—Israel Institute of Technology, Haifa, Israel A. Lehavi University of Queensland School of Medicine, Brisbane, QLD, Australia
significantly different between the two study groups. A statistically significant mild respiratory acidosis was noted in the inhalational anesthetic group (pH 7.30±0.04 vs. 7.36±0.02 in the propofol group) Conclusions This small-size pilot study may suggest that propofol-based anesthesia is not related to increased incidence of rhabdomyolysis in morbidly obese patients undergoing short, uncomplicated bariatric surgery. Keywords Bariatric surgery . Rhabdomyolysis . Propofol . Propofol infusion syndrome . PRIS . Sleeve gastrectomy
Introduction Although relatively a rare phenomenon but coinciding with the major advent of special operations for the obese population, more and more publications have emerged reporting the occurrence of rhabdomyolysis with or without acute renal failure in conjugation with bariatric and obese-related surgery. In addition, a speculation on a potential role of general anesthetics has been raised regarding rhabdomyolysis during surgery in obese. No doubt that the intravenous general anesthetic propofol could theoretically be a prototypic candidate risk factor for precipitating rhabdomyolysis, since it has many years reputation as a causative of what is known as propofol infusion syndrome when administered continuously in high enough dosage and for a long time [1]. Propofol infusion syndrome is characterized by rhabdomyolysis, cardiomyopathy, metabolic acidosis, and renal failure. Thus far, only two articles describing of an association between propofol and rhabdomyolysis with regards to obesity appeared in the literature [2, 3] In the present study, the effect of propofol and of a different acting anesthetic sevoflurane administered by inhalation and thus far not incriminated as an etiological factor for
OBES SURG
rhabdomyolysis in obese patient with or without operation, on the immediate and delayed postoperative markers of muscle necrosis, cardiac injury, and kidney dysfunction were examined in patients undergoing bariatric surgery.
Methods Thirty morbidly obese patients scheduled for bariatric laparoscopic sleeve gastrectomy in Rambam Healthcare Campus in Haifa, Israel, a university affiliated referral hospital, were enrolled to the study and randomly assigned to receive either propofol (P) or inhalation anesthetic (I)-based anesthesia. The study was designed as a prospective, randomized, and single blinded. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. After institutional review board approval, informed consent was obtained from all individual participants included in the study; thirty morbidly obese patients scheduled for bariatric laparoscopic sleeve gastrectomy were randomly assigned to receive either propofol (P) or the inhalation anesthetic (I) sevoflurane-based anesthesia. Inclusion criteria were age between 20 and 55 years, body mass index (BMI) between 38 and 55 kg/m2. Exclusion criteria were known liver or kidney failure, previous metabolic disease, and a history of sensitivity to eggs or propofol. The duration of the procedure, as well as the rate of anesthetic and surgical complications were recorded. Each patient was laid on top of the 75-mm thick original foam mattress supplied by the operating table manufacturer (MAQUET Holding B.V. & Co. KG, Rastatt, Germany) on which an 8.4-mm soft gel cover was placed. The upper part of his body was raised 20° at reverse Trendelenburg, legs elevated 45° upward and flexed at the hips and knees (beach chair position). Anesthesia was induced using propofol 1.5– 2.5 mg/kg, fentanyl 1–2 microgram/kg, and rocuronium 0.6– 1 mg/kg. Additional doses of fentanyl were given according to the caring anesthesiologist discretion. Maintenance of anesthesia was achieved with a target controlled infusion of propofol using the Marsh model, aiming at a calculated plasma concentration of 2–5 microgram/mL in the (P) group and at an expired concentration of 1.5–3 % sevoflurane in the (I) group. Crystalloid fluid replacement was administered according to a conservative regimen (15 ml/kg). Depth of anesthesia was monitored by bispectral index (BIS), where values were kept at 40 to 60, indicating adequate hypnotic effect during general anesthesia. Standard monitors including three lead ECG, noninvasive blood pressure measurement device, and pulse oximeter were applied throughout the procedure.
A sample of venous blood gas analysis including pH, bicarbonate concentrations, and calculated base excess was taken at the end of the operation. Blood was also collected via direct phlebotomy for creatine phosphokinase (CPK) and troponin I concentrations, blood urea nitrogen and creatinine concentrations at the end of the surgery, and again 24 h later. Data was evaluated by SPSS software, version 17 (SPSS Inc. Chicago, IL, USA). All variables are presented as mean± standard deviation. The differences in demographic parameters (age, weight, and height), between (P) or (I) groups were analyzed by T test. Fisher’s exact test was used for detecting the differences in the prevalence of gender between (P) or (I). A Mann–Whitney U test was used to determine the correlation between the blood results in the two groups. P0.001). As the bicarbonate concentrations as well as the calculated base excess were normal in all patients, this cannot be regarded as metabolic acidosis. All the pH values in the (P) group were over 7.30. Whereas, values in the (I) group were under 7.35. The distribution of the PH in both study groups is presented in Chart 1.
The results of the various blood tests at the end of the operation are presented in Tables 3 and 4. In the blood sample performed 24 h after the operation, the CPK concentrations in the (P) group were 118±86 IU/L compared with 107±50 IU/L in the (I) group. Except a single patient from the (P) group, all the patients had blood CPK concentration under 200 IU/L. No significant difference was demonstrated between the two groups. The troponin I concentrations were 0.0021±0.004 microgram/L in the (P) group, compared with 0.0028±0.005 microgram/L in the (I) group. All the patients had blood troponin I concentration under 0.01 microgram/L. No significant difference was demonstrated between the two groups. The urea concentrations were 13±5 mg/dL in the (P) group compared with 10±2 mg/dL in the (I) group. All patients had normal blood urea concentrations. No significant difference was demonstrated between the two groups. The creatinine concentrations were 0.78±0.17 mg/dL in the (P) group, compared with 0.79±0.09 mg/dL in the (I) group. All patients had normal blood creatinine concentrations. No significant difference was demonstrated between the two groups.
Discussion A host of publications reporting rhabdomyolysis related to operations in obese and especially in bariatric surgery are found in the literature of the last decade or so. The first report of rhabdomyolysis was attributed to direct and prolonged pressure of the bed against the dorsal and gluteal muscles after bariatric surgery in three super obese patients appeared in 2003 [4]. Soon after, the fatality potential of rhabdomyolysis was demonstrated in 3 males with BMI 67 out of 100 consecutive primary uncomplicated but very prolonged bariatric surgical procedures which died due to renal failure during a 1-
Table 3 Blood markers for rhabdomyolysis, cardiac and renal injury, and acid base balance at the end of the surgery
Chart 1 pH distribution in the propofol (P) and inhalation anesthetic (I) groups at the end of the operation
Group P (n=15)
Group I (n=15)
Significancea
Creatine phosphokinase (CPK), IU/L Troponin I, microgram/L Urea, mg/dL Creatinine, mg/dL Bicarbonate, meq/L
125±94
118±59
NS
0.0025±0.005 11±3 0.65±0.10 23.2±2.0
0.0007±0.002 10±2 0.71±0.11 23.0±1.0
NS NS NS NS
Base excess, meq/L pH
−0.9±1 7.36±0.02
−2.0±2.0 7.30±0.04
NS >0.001
Values are presented as mean±SD or median a
Mann–Whitney U test
OBES SURG Table 4 Blood markers for rhabdomyolysis, cardiac and renal injury 24 h after surgery Group P (n=15)
Group I (n=15)
Significancea
Creatine phosphokinase 125±94 118±59 NS (CPK), IU/L Troponin I, microgram/L 0.0025±0.005 0.0007±0.002 NS Urea, mg/dL Creatinine, mg/dL
11±3 0.65±0.10
10±2 0.71±0.11
NS NS
Values are presented as mean±SD or median a
Mann–Whitney U test
year period [5]. A recent systematic review of the literature has found mostly reports of an isolated event or small case series and few prospective and retrospective comparative studies of rhabdomyolysis following bariatric surgery with overall 145 patients with 14 % of acute renal failure and 5 % of mortality rate [6]. However, rhabdomyolysis occurred in non-bariatric operation as well such as lumbar spine [7, 8], major urologic [9], orthopedic [10, 11], and others. Risk factors making obese patients more prone to rhabdomyolysis include male gender, American Society of Anesthesiologists (ASA) physical status III or IV, BMI >52 kg/m2, and operation time longer than 4 h and lengthened anesthesia-related immobilization [6], presence of diabetes mellitus with BMI >40 kg/m2 [12, 13], and use of statins [14]. Equal number of patients in both groups was chronically treated with statins, and our policy is not to stop taking statins before surgery. A decade ago, an advisory committee on the safety usage of statins stated that fearing the development of statin-induced myopathy during the period prior to major surgery, it would be prudent to withhold their preoperative intake [15]. Contrary to this assertion, recent publications showed improved postoperative outcome and reduced incidence of myocardial damage at the first month following surgery on continuous statins, without clinical or laboratory evidence of rhabdomyolysis [16]. It is even recommended to start statins preoperatively [17]. In this regard, this study also supports the perioperative use of statins for the obese population despite intraoperative propofol administration. In addition, we managed perioperative fluid replacement according to a conservative regimen. In a study conducted to test this issue, conservative (48 patients, 15 ml/kg) versus liberal (53 patients, 40 ml/kg) intraoperative intravenous fluid volume was administered to two groups of patients undergoing bariatric surgery. Four patients in the conservative group and three patients in the liberal group developed postoperative rhabdomyolysis, proposing that the mode of fluids administration did not affect the incidence of this complication [18] Prolonged administration of propofol in fat emulsion had long been established as promoter of propofol infusion syndrome [1]. Propofol potentially could contribute to
rhabdomyolysis and its complications in conjugation with surgery in super obese patients as presented by two recent publications reporting death after continuous propofol sedation (2, 2a). This triggered us to carry out the present study. Two interesting finding has emerged from it. First, in our group of patients, no one experienced any clinical signs of muscle disruption along with no laboratory evidence of either muscle breakdown and any cardiac, renal failure, or metabolic derangement. Second, neither propofol nor sevoflurane caused rhabdomyolysis. The results of this study would imply that anesthetic drugs (such as propofol) per se may not incriminate the primary and most important factor in precipitating rhabdomyolysis in obese patients undergoing surgery. Other causes including prolonged surgery over 4 h and a history of diabetes with BMI >40 kg/m2 are probably more contributory [6] In such cases, CK is highly recommended to be systematically measured for verifying the presence of muscle injury. Whatever the reason might be, vigilance, attention, and awareness of the anesthesiologist and the surgeon to the possibility of rhabdomyolysis in an obese surgical patient are mandatory. It should be clarified that this is indeed a pilot study, limited in scope. However, information regarding the actual incidence of rhabdomyolysis in conjugation with surgery in obese patients emerged mostly from isolated cases and small-scale studies, with an order of magnitude resembling that of our study. A recent systematic review with collected data obtained from 145 reports of rhabdomyolysis in bariatric surgery found a 60 % incidence of such phenomenon [6]. One prospective study of rhabdomyolysis after open Roux-en-Y gastric bypass conducted in 23 bariatric operations diagnosed 30 % events of elevated creatine phosphokinase (CPK) levels [12] whereas other studies found rhabdomyolysis incidence of 77 % in 22 patients [19] and 26 % in 49 patients [13]. Given these figures, we would expect to find at least ten cases of rhabdomyolysis in our study when in fact only one patient had CPK level out of the reference range. Similar low rates of rhabdomyolysis were described by others [20, 21] supporting our findings on the rarity of this complication and its clinical significance. Indeed, with an average BMI of 43 kg/m2, the patients included in this study were the obese class 3 of the World Health Organization classification which is considered the highest level range of obesity and one could expect at least 5 cases of rhabdomyolysis and 2 cases of death according to Chakravartty et al. [6]. It is unknown whether the difference between our and previous studies could be contributed to relatively short procedural time, concern for correct positioning of the patient [22], using intra-abdominal carbon dioxide insufflation pressures as low as possible, and administering neuromuscular relaxant drugs within the right dosage which prevented tissue damage and rhabdomyolysis. The major drawback of this study is that it consists of a small study group. Of course, larger scale studies will be required to provide stronger recommendation to the practicing
OBES SURG
anesthesiologists and bariatric surgeons thus further data are necessary to establish the safety of use of propofol-based total intravenous anesthesia in patients at higher BMIs, as well as its use for longer duration operations. Conflict of Interest Neither of the authors has any conflict of interest regarding this study.
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