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Organ-protective Features of Halogenated Anesthetics

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

80th Clinical and Scientific Congress of the International Anesthesia Research Society

San Francisco, California / March 24-28, 2006

In an era when fast-tracking techniques have an expanding role in cardiac surgery, volatile anesthetics with a short emergence profile can play a major role, noted Dr. Thomas M. Hemmerling, CHUM-Hôtel-Dieu, and Associate Clinical Professor of Anesthesiology, Université de Montréal, Quebec. Both sevoflurane and desflurane would appear to have ideal characteristics in this setting, as both agents provide rapid emergence after surgery. However, few studies have compared the two anesthetics with respect to their cardiac profile. Some of the available data suggest that sevoflurane has a proclivity for induction of bradycardia, and other data indicate desflurane may confer a tachyarrhythmic effect in some patients.

“Arrhythmias can be an issue in some patients and usually occur on the second or third day after surgery,” stated Dr. Hemmerling. “The occurrence varies a lot, but can be as high as 30 to 35% and does not seem to be any less with off-pump coronary artery bypass [OPCAB] than with pump surgery. In our own experience, we have a rate of about 15% in OPCAB procedures using sevoflurane.”

Arrhythmia Findings

Two halogenated anesthetics were analyzed in a randomized clinical trial involving 40 patients undergoing OPCAB. Anesthesia was maintained with either 1 minimum alveolar concentration (MAC) of sevoflurane or 1 MAC of desflurane. Continuous ECG monitoring was performed during and for as long as 72 hours after surgery. Other parameters assessed included troponin-T, CK-MB, regional wall motion, ejection fraction, time to extubation, respiratory function and hemodynamic stability.

The two patient groups had similar demographic and clinical characteristics at baseline. Duration of surgery (150 to 160 minutes), number of bypass grafts (three), ischemic time (20 to 21 minutes) and extubation time (11 to 12 minutes) also did not differ. Results of laboratory and functional assessments were similar.

Significantly more patients randomized to desflurane developed atrial fibrillation and supraventricular tachycardia (SVT) compared to those administered sevoflurane (P<0.05 for both comparisons). Atrial fibrillation occurred in five desflurane patients and one sevoflurane patient. SVT also occurred in five desflurane patients but in no sevoflurane patients. Bradycardia occurred in four sevoflurane patients and in three of the desflurane group (Table 1).

Table 1. Different Types of Arrhythmia Observed


Dr. Hemmerling observed that the arrythmia findings are consistent with those previously reported from a retrospective analysis of patients undergoing OPCAB surgery (Acta Anaesthesiol Belg 2005;56(2):147-54). The results demonstrated that in the OPCAB setting, sevoflurane led to significantly less atrial fibrillation and SVT than desflurane while allowing equally rapid extubation. “At this point, we would not recommend desflurane as the volatile anesthetic of choice in fast-tracking and ultrafast-tracking cardiac surgery patients,” Dr. Hemmerling stated.

Another study reported at the meeting compared sevoflurane and isoflurane in patients undergoing OPCAB. The study involved 117 patients enrolled at two participating centres. The patients were randomized to either agent for maintenance anesthesia without nitrous oxide, explained Dr. Ellise Delphin, Professor and Chair of Anesthesiology, University of Medicine and Dentistry of New Jersey, Newark. Patients in both groups were anesthetized with etomidate, and an intermediate-acting muscle relaxant was used to facilitate intubation and maintain intraoperative neuromuscular blockade. Intraoperative fentanyl was limited to a dose of 5 mg/kg.

The Mini-Mental State Examination (MMSE) and Memory Recall Test (MRT) were carried out preoperatively, a few minutes after extubation, and 90 minutes later. Pain was evaluated every 15 minutes after extubation for 90 minutes. Sixteen patients were excluded because of incomplete data, leaving 101 patients for comparison.

Patients in the two groups did not differ with respect to baseline characteristics, nor were there differences in hemodynamic and cardioprotective effects or length of intensive care unit or total hospital stay. Cardiac enzyme levels (troponin, CK-MB, CPK) were assessed in a subgroup of patients receiving sevoflurane or isoflurane. Levels were not statistically different on the day of surgery, 24 hours afterward nor 48 hours later.

Reduced Extubation Time

A significant reduction in the time to extubation was associated with sevoflurane with a mean time to extubation of 2 hours 56 minutes vs. 4 hours 17 minutes with isoflurane (P<0.05). The mean change in MMSE score (on a scale of 0 to 30) was -8.1 at extubation and -4.8 after 90 minutes in the sevoflurane patients, which did not differ from isoflurane values at the same times (-9.2, -6.2). The MRT results (based on a scale of 0 to 8) were decreased by an average of 1.8 at extubation and 90 minutes later in the sevoflurane patients vs. -1.7 and -1.3 in the isoflurane group.

Table 2. Co
Preoperative Baseline

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The MMSE scores of women did not recover as quickly as did those of men after 24 hours (P<0.006). Dr. Delphin remarked she and colleagues had no clear explanation for the gender difference. Pain scores did differ significantly 90 minutes after extubation. The pain score (on a scale of 0 to 10) averaged 7.2 at extubation with sevoflurane vs. 7.6 with isoflurane; at 90 minutes, the mean pain score was 5.7 and 4.3, respectively (P<0.05). Dr. Delphin commented that the difference was not surprising, given the earlier extubation in patients receiving sevoflurane. “We conclude that both isoflurane and sevoflurane provide a means of delivering hemodynamically stable and safe anesthesia in OPCAB cases without the use of high-dose narcotics,” stated Dr. Delphin. “Females may have delayed recovery of cognitive function at 24 hours. Sevoflurane permitted patients to be extubated more quickly and to recover cognitive function more quickly compared to isoflurane. Pain control was an issue in both groups.”

Safety in General Surgery

Investigators led by Dr. Neera Sah, Magee-Womens Hospital, Pittsburgh, Pennsylvania, explored potential differences between desflurane and sevoflurane in a population of patients undergoing noncardiac surgery, specifically laparoscopic gastroplasty for morbid obesity. Morbid obesity poses a risk for post-operative respiratory complications and delays emergence from general anesthesia, noted Dr. Sah. Because of their low blood/gas partition coefficients, the two volatile anesthetics allow for rapid emergence, which has the potential to reduce the risk of post-operative respiratory complications.

She indicated that a previous study demonstrated a faster recovery time with desflurane in patients undergoing laparotomy (Ebert and Schmid. In: Barash et al., eds. Clinical Anesthesia, 4th ed. Philadelphia, PA. Lippincott, Williams and Wilkins; 2001: 377-417).

The study involved 70 patients whose body mass index (BMI) exceeded 35. All the patients were scheduled for laparoscopic gastroplasty involving general anesthesia. The patients were randomized to either anesthetic. Intraoperative observations were time from turning off anesthetic agent to eye opening and extubation. Post-operative observations were oxygen saturation, blood pressure, heart rate, pain, nausea visual analogue scale (VAS) scores, emesis, modified Aldrete score, and MMSE measured at entry to post-anesthesia care unit (PACU) and then at 15-minute intervals until discharge.

The two patient groups did not differ with respect to baseline characteristics, including gender, age and BMI. Duration of surgery (approximately 151 minutes) was also the same in both groups.

Time to eye opening ranged between 4.5 and 5.5 minutes, mean time to extubation was about 8 to 9 minutes, and time spent in the PACU was 144 minutes with sevoflurane and 160 minutes with desflurane, a difference th
atistical significance (P=0.08) (Table 3).

Table 3. PACU Values

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“Our study showed no real differences between desflurane and sevoflurane in these patients,” concluded Dr. Sah. “Other studies have shown a difference favouring desflurane, but most of those earlier studies involved open gastroplasty, so the duration of surgery was much longer. The fact that the surgery lasted less than 2.5 hours in all patients was probably the reason we didn’t see any difference between the two anesthetics. Basically, we have shown that either sevoflurane or desflurane works just as well if the duration of surgery is less than 2.5 hours.”

Deep Anesthesia

Deep anesthesia poses additional issues regarding the safety and efficacy of halogenated anesthetic agents. Presentations at the IARS shed more light on the issues in different clinical circumstances.

Inhalation of a high concentration of a halogenated anesthetic permits rapid and smooth induction of general anesthesia with minimal impact on systemic hemodynamics (Anesth Analg 2001; 93:1185-7). The technique is useful for ambulatory anesthesia of short duration. However, induction time may vary according to patient age, vital capacity (VC) and cardiac output. Investigators at Kanazawa Medical University, Uchinada, Japan, evaluated the influence of preoperative respiratory and cardiac function on sevoflurane induction time.

The study involved 27 patients scheduled for elective surgery requiring general anesthesia. Spirometry and body plethysmography were performed several days before surgery. VC and functional residual capacity (FRC) were compared with age- and sex-predicted reference values and expressed as a percentage of predicted values. Bispectral (BIS) monitoring also was performed.

Patients were instructed through an earphone to inhale, grasp a rubber ball connected to a pressure transducer, exhale and grasp the ball again. The instructions were repeated every 12 seconds. Anesthesia was induced with age-corrected 2.5 MAC sevoflurane and oxygen. The investigators measured the time from the beginning of anesthetic inhalation to loss of eyelash reflex, inability to grasp the ball, and decrease in BIS value to less than 60.

Loss of eyelash reflex occurred at 42 seconds, followed by inability to grasp the ball (66 seconds) and decrease in BIS value to less than 60 (99 seconds). No preoperative characteristic correlated with the loss of eyelash reflex. Time to inability to grasp the ball did correlate positively with age (P=0.02) and negatively with residual volume (P=0.015) and FRC (P=0.042). Only age correlated positively with time to BIS value less than 60 (P=0.004).

The investigators concluded that age is the most reliable predictor of induction time with 2.5 MAC sevoflurane. The results suggested that per cent residual volume, per cent FRC and preoperative cardiac index are unlikely to cause prolongation of induction time with MAC 2.5 of the anesthetic.

Deep anesthesia can cause hypoperfusion and end-organ ischemia, raising questions about its safety, according to Dr. Helen Li, University of Texas Medical Branch, Galveston, and colleagues. The safety of deep anesthesia for burst suppression therapy (BST) was examined in a group of patients with severe, refractory unipolar and bipolar depression.

The patients had a cumulative total of 197 treatments with sevoflurane BST, each producing at least two consecutive minutes of electrocerebral silence. Patients were intubated after induction and maintained with 8% sevoflurane until experiencing electrocerebral silence for two minutes. ASA standard monitoring parameters were employed, as well as five-lead EEG.

The end-tidal MAC of the agent ranged between 2.4 and 3.5, and exposure to deep anesthesia (defined as intubation to cessation of sevoflurane) ranged between 21 and 42 minutes. All patients received fluid therapy with lactated Ringer’s solution for hypotension, and some also received ephedrine or phenylephrine. No patient experienced a myocardial infarction, stroke or clinically significant ischemia during the procedure.

Dr. Li and colleagues concluded that sevoflurane BST could be carried out without serious complications with careful pre- and intraoperative anesthetic management.

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