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We compared the hemodynamic stability during carotid endarterectomy of remifentanil with that of sufentanil anesthesia. Fifty-six patients were randomly assigned into Remifentanil (n = 27) or Sufentanil (n = 29) groups. In the Remifentanil group, IV propacetamol (2 g) and morphine (0.1 mg/kg) were infused 30 min before skin closure. In the Sufentanil group, patients received 2 g propacetamol. Beat-to-beat recordings of systolic arterial blood pressure (SBP) and heart rate (HR) were stored on a computer. The maximum and minimum values of BP and HR after induction, at intubation, during the surgical procedure, and after the operation and the coefficients of variation of SBP and HR were used as indices of hemodynamic stability. The coefficients of variation of SBP and HR were similar in both groups during and after surgery. However, at intubation, maximal SBP was higher in the Sufentanil group (P < 0.05). Decreased propofol doses and isoflurane end-tidal concentrations were used in the Remifentanil group. At recovery, a similar profile of SBP and HR was found in both groups. We conclude that intra- and posthemodynamic stability was similar with remifentanil or sufentanil in patients undergoing carotid endarterectomy. However, remifentanil was more effective for blunting the increase in SBP at intubation without increasing the blood pressure-decreasing effect of induction. Intraoperative remifentanil use was associated with a decreased amount of hypnotic drug administered. IMPLICATIONS:Beat-to-beat recordings of heart rate and blood pressure in patients undergoing carotid surgery revealed that hemodynamic stability was similar with remifentanil or sufentanil anesthesia both during and after surgery. Remifentanil was more effective in limiting the increase in blood pressure associated with intubation without increasing the blood pressure-lowering effect of induction or the blood pressure response to recovery.
Vascular hyperreactivity is a common feature in patients undergoing carotid endarterectomy (CE), and the marked changes in blood pressure (BP) frequently seen during or after surgery can result in neurologic complications or in serious compromise of the myocardial oxygen balance (1,3). In addition, rapid recovery for early neurologic assessment is an important goal for the intraoperative treatment of these patients (1,2). An opioid such as remifentanil, which provides excellent BP control during surgical manipulation but can also rapidly be discontinued, should be well suited for these patients (3). In patients undergoing CE, remifentanil/isoflurane anesthesia provided rapid awakening and an early opportunity for neurologic evaluation (4). Indeed, the opioid concentration at the effect site changes faster with remifentanil than with fentanyl or sufentanil (5), and this results in more rapid variations in the level of analgesia. However, the absence of postoperative analgesia when remifentanil is used during surgery might result in an increased circulatory response to recovery. Consequently, we conducted a prospective, randomized, controlled study to compare remifentanil anesthesia with our standard practice of sufentanil anesthesia for patients undergoing carotid surgery. The global hemodynamic stability was assessed by the coefficients of variation (CV) of systolic BP (SBP) and heart rate (HR) obtained from computerized beat-to-beat recordings of SBP and HR during anesthesia and recovery. Furthermore, because acute hemodynamic changes in response to stressful perioperative stimulations are also major clinical end points in patients undergoing carotid surgery, we also focused our analysis on the time of both induction and extubation, periods associated with marked changes in HR and SBP.
This prospective study was approved by the Ethics Committee for Human Research of our hospital and was performed with written, informed consent of all patients. Fifty-six consecutive patients scheduled for CE were randomly assigned to one of the study groups (Remifentanil or Sufentanil) by a computer-generated list compiled before the start of the study. For inclusion, patients had to be scheduled for elective surgery for atheromatous lesions of the carotid artery, and CE had to be performed without another surgical procedure. Exclusion criteria included emergencies, untreated or uncontrolled hypertension, untreated or uncontrolled coronary artery disease, contraindication to propacetamol, and atrial or ventricular arrhythmias. The anesthesiologists (SM, GDW, SPG, and CB) involved in this study managed several remifentanil anesthesia cases each day for 2 mo before the start of the study. Before surgery, a detailed history was taken and a physical examination performed by a staff anesthesiologist. Three sets of SBP and HR measurements were obtained during the 24 h preceding surgery and averaged to establish baseline measurements. Troponin Ic measurement and a 12-lead electrocardiogram (ECG) recording were performed before surgery. One hour before surgery, all patients were premedicated with oral midazolam 5 mg and their usual cardiovascular medication, except angiotensin-converting enzyme inhibitors. Monitoring included a five-lead ECG with ST segment trends on leads V4, V5, and II; invasive arterial BP (TRAM, Marquette Electronics, Inc., Loves Park, IL); and pulse oxygen saturation (SpO2), end-tidal CO2, and inspiratory and end-tidal anesthetic concentrations.). After placement of an IV catheter and 10 mL/kg crystalloid infusion, the patients received either an initial loading dose of 1 µg/kg of remifentanil in 30 s followed by a continuous infusion of 0.5 µg · kg-1 · min-1 or 0.5 µg/kg sufentanil in 30 s, with an additional bolus, if required. Propofol was administered until loss of consciousness. After a 0.5 mg/kg atracurium infusion and tracheal intubation, the remifentanil infusion rate was changed or a bolus of sufentanil was given as required by the surgical stress. Ventilation (10 mL/kg, 12/min) was controlled to maintain an ETCO2 between 30 and 35 mm Hg. Isoflurane was administered for maintenance of anesthesia with a fresh gas flow of 2 L/min (50% N2O/50% oxygen). As usual in the vascular surgery unit, no specialized monitoring for cerebral ischemia or arterial shunting was used during the study. During the procedure, the anesthesiologist was required to maintain SBP and HR within ±30% of baseline values. In both groups, fluid administration and vasoconstrictor (ephedrine or phenylephrine) administration were based on hemodynamic monitoring. In the two groups, 2 g propacetamol (a nonopioid analgesic) was infused IV 3045 min before the end of surgery. In addition, patients in the Remifentanil group received 0.1 mg/kg morphine IV at the same time. Isoflurane was stopped at the beginning of skin closure. Remifentanil infusion was stopped at the last surgical suture. All patients were tracheally extubated in the surgical room.
All the patients were admitted after surgery to the recovery room for at least 2 h. Postoperative care, including hemodynamic monitoring and treatments and standardized nursing care, was under the supervision of the attending anesthesiologist of the recovery room. The pain score, by using a visual analog scale (VAS) (6), and the sedation score, by using the Ramsay scale, were evaluated every 10 min after extubation for 40 min and at 1, 1.5, and 2 h after extubation. Morphine titration was used to obtain a VAS value of A 12-lead ECG recording was performed at the end of the surgery and compared with the preoperative ECG. ECG was repeated daily on the three postoperative days. Troponin Ic levels were measured at the induction, 1 h after surgery, and on the three postoperative days. These measurements were repeated if any abnormal value was detected. The SBP and HR signals obtained from the monitor (TRAM) were acquired at 200 samples per second and stored on a personal computer hard drive by using an analog-to-digital convertor data acquisition system (MP30; Biopac, Santa Barbara, CA). After reviewing for removal of artifacts and arterial catheter flushings, each complete arterial pressure tracing was scanned for a beat-to-beat analysis. Values of SBP and HR were stored in Excel 5.0 (Microsoft, Redmond, WA) files for each patient. All Excel files were scanned again to determine whether the hemodynamic abnormalities were artifacts or real events. The positive and negative CVs of SBP and HR [(SD of the mean/mean) x 100] were calculated for the period lasting from the induction of anesthesia to 5 min after extubation and for the recovery period until discharge. In addition, the highest and the lowest SBP and the highest and lowest HR of these two periods were recorded. The total volume of fluid infusion, the time spent at each isoflurane concentration, and the total doses of anesthetic drugs, ephedrine, phenylephrine, ß-adrenergic blockers, and calcium channel blockers were recorded for both groups. The same analysis was performed for the period lasting from induction to 5 min after intubation (inductionintubation period) and for the period lasting from 5 min before extubation to 5 min after extubation (extubation). In addition, the highest and the lowest SBP and the highest and lowest HR were recorded for each phase. Hemodynamic events were defined as 1) hypotension (i.e., an SBP value less than 80 mm Hg or <30% of baseline value) lasting more than 1 min; 2) hypertension lasting more than 1 min (i.e., an SBP value more than 170 mm Hg or >30% of baseline value); 3) tachycardia lasting more than 1 min (i.e., an HR value more than 90 bpm or >30% of baseline value); and 4) bradycardia lasting more than 1 min (i.e., an HR value less than 40 bpm or <30% of baseline value). The total duration and the number of patients experiencing these events were calculated for each patient of both groups. Recovery times were recorded from discontinuation of isoflurane to spontaneous ventilation, eye opening (assessed every minute), and extubation. Adverse events were defined as the appearance of transient ischemic attack, nonreversible neurologic deficits and myocardial infarction, death, and postoperative nausea and vomiting.
In a preliminary study performed during CE, we found a mean value for CV of SBP of 15.5% ± 4% with sufentanil/isoflurane anesthesia. Thus, we calculated that 52 patients would be necessary for the assessment of a 20% reduction of the mean of CV of SBP with
Patients clinical characteristics are shown in Table 1. The mean values of SBP and HR and the positive and negative CVs of SBP and HR were not significantly different between groups (Tables 2 and 3). No significant difference was found in the mean and the lowest value of SBP or in the mean and the lowest or highest values of HR (Table 3). At intubation, the maximal value of SBP was higher in the Sufentanil group (Table 3). The rates of hypertension, hypotension, or tachycardia and the durations of these events were similar in the two groups (Table 3). One patient in the Remifentanil group experienced bradycardia lasting 1.5 min during this period.
During surgery, the mean values of SBP were higher in the Sufentanil group (Table 4). The positive and negative CVs of SBP were not different between groups (Table 2). No significant difference was found between groups in the duration of hypertension, hypotension, tachycardia, bradycardia, or the number of patients experiencing these hemodynamic events (Table 4). The highest and the lowest values of SBP and HR were similar in both groups (Table 4). More patients experienced bradycardia in the Sufentanil group (Table 4).
The dose of propofol used for the induction of anesthesia was smaller in the Remifentanil group (Table 5). The maximal end-tidal isoflurane concentration required to blunt hemodynamic response to surgical stress was smaller in the Remifentanil group (0.7% ± 0.3% vs 1% ± 0.4%; P < 0.01). In the Remifentanil group, the small concentrations of isoflurane were administered longer than in the Sufentanil group (Fig. 1; P < 0.01). No significant difference was found between groups in the volume loading, total doses of ephedrine or phenylephrine, number of patients receiving channel blockers or ß-adrenergic blockers, or the total doses of calcium channel blockers or ß-adrenergic blockers (Table 5).
In the extubation period, the mean values of SBP and HR were 157 ± 18 and 150 ± 18 mm Hg (nonsignificant) and 89 ± 16 and 83 ± 15 bpm (nonsignificant) for the Remifentanil and Sufentanil groups, respectively. The positive and negative CVs of SBP and HR were not significantly different between groups (Table 1). All patients in both groups received ß-adrenergic blockers (esmolol) or calcium channel blockers (nicardipine) at extubation. The time interval until eye opening was shorter in the Remifentanil group (8 ± 3 vs 11 ± 5 min; P < 0.05), whereas the times until spontaneous ventilation (Remifentanil, 8 ± 4 min; Sufentanil, 6 ± 4 min) or extubation (Remifentanil, 10 ± 4 min; Sufentanil, 12 ± 5 min) were similar. During the recovery period, the mean values of SBP and the positive and negative CVs of SBP and HR were not significantly different between groups (Tables 1 and 6). The total duration of episodes of hypertension and tachycardia and the highest value and the lowest value of SBP and HR were similar in both groups (Table 6). No patient experienced bradycardia or hypotension. No significant difference was found between groups in the total doses of esmolol or nicardipine.
IV doses of morphine used for titration in the recovery period were 6 ± 4 and 5 ± 5 mg for the Remifentanil and Sufentanil groups, respectively (nonsignificant). Higher levels of VAS were found in the Remifentanil group (Fig. 2), but the peak level did not exceeded 42 mm. No difference was found in Ramsay scores between study groups. No significant change in postoperative troponin Ic levels was found in the study groups during the recovery room period.
There were no deaths in the study population. One postoperative myocardial infarction was observed in the Remifentanil group on the first postoperative day, with ECG ST depression and troponin Ic levels at 2.7 ng/mL (normal level, <0.5 ng/mL). One complete atrial-ventricular block was observed in the Sufentanil group on the first postoperative day without Ic troponin increase. One postoperative transient ischemic attack occurred in each group. Seven patients in the Remifentanil group and six patients in the Sufentanil group had postoperative nausea or vomiting. All were treated successfully with 10 mg metoclopramide.
Our study demonstrates that remifentanil is more effective than sufentanil for blunting BP response to a noxious intraoperative stimulation such as intubation without increasing the blood pressure-decreasing effect of anesthesia. It is interesting that remifentanil anesthesia was not associated with an increased BP and HR response to recovery, and this is important because HR control is essential after vascular surgery to limit the risk of myocardial ischemia (7).
To accurately evaluate BP stability, we used a continuous beat-to-beat computerized recording of BP. This contrasts with other studies performed in cardiac and noncardiac surgery, in which the evaluation of BP stability was often based on arterial BPs obtained in steady state, on intraoperative highest or lowest BPs, or on arterial BPs more or less than predefined values during stressful periods such as induction, intubation, skin incision, or extubation (811). The durations of these periods are short compared with the total duration of the anesthesia (see Tables 4 and 5). Consequently, a main part of the anesthesia is not considered in the analysis. In most studies, the failure to record BP continuously is a significant limitation because the absolute amount of change in BP that could have occurred during intermittent measurement intervals would not have been accurately detected. Thus, more potent tools are required for evaluation of hemodynamic stability during anesthesia. In a multicenter study, a 96-hour monitoring of SBP and HR every 10 seconds was used to evaluate the effects of the A global analysis of SBP and HR variations showed that the positive and negative CVs of SBP and HR were not different in the two groups during anesthesia; this suggests a similar intraoperative hemodynamic stability with remifentanil or sufentanil anesthesia during CE. A smaller dose of propofol was used for induction in the Remifentanil group. More patients in the Sufentanil group underwent at least one episode of bradycardia, whereas the incidence of hypertension, hypotension, and tachycardia was similar in the two groups. During the induction/intubation phase, the hemodynamic stability assessed by the CVs of SBP and HR was similar with remifentanil or sufentanil anesthesia. However, we found a higher peak value of SBP in the Sufentanil group, whereas the lowest value of SBP was similar in the two groups. Such results did not influence the global CV of SBP because hypertension during intubation lasted only three to four minutes, i.e., 2%3% of the total duration of the anesthesia (Table 5). Nevertheless, this confirms that remifentanil infusion during this period was more potent for limiting the increase in SBP during laryngoscopy and intubation. It is important to note that this beneficial effect was not associated with an increase in the BP-reducing effect of induction; this contrasts with the findings of previous reports (10,18). Our study protocol, which imposed slow infusion of remifentanil and propofol administration based on loss of consciousness, probably played a role in this result (19). In patients undergoing CE, a remifentanil/volatile anesthetic technique provided rapid awakening and an early opportunity for neurologic examination (4).Our results indicate that these beneficial effects can be obtained without any increased risk for intraoperative hypotension or for postoperative hypertension or tachycardia. These results are of particular interest in patients undergoing CE, which carries the risk of substantial complications related to intra- and postoperative hemodynamic disturbances. For our study, which investigated the use of a short-acting opioid for CE to have meaningful clinical implications, our control group followed a course that conformed to routine clinical practice (20). Because the level of analgesia may influence the stability of anesthesia, the equipotency of our opioid regimen is a major determinant of the hemodynamic stability during the maintenance of anesthesia. By using STANPUMP software (Bovill model), we ensured that our opioid regimens resulted in equipotent concentrations of sufentanil and remifentanil during maintenance. The remifentanil concentration at steady-state reached 17 ng/mL both in plasma and at the effect site, and sufentanil concentrations were close to 1.60 ng/mL in plasma and 1.80 ng/mL at the effect site. Assuming a ratio in sufentanil/remifentanil potency of 10 (21), the opioid infusions resulted in grossly equipotent concentrations. However, isoflurane was used at smaller concentrations in the Remifentanil group (Fig. 1). Yet a similar hemodynamic pattern was obtained at equipotent concentrations of sufentanil and remifentanil, with a smaller isoflurane concentration in the Remifentanil group. Because opioid concentrations were grossly equipotent, these results could be caused by the mode of administration (continuous versus bolus) or to the pharmacodynamic properties of remifentanils interacting with isoflurane (21). We did not find any differences in the CVs of SBP or HR between the two groups during the recovery period. The similar hemodynamic response to recovery in both groups shows that the intraoperative stability noted with remifentanil is not associated with an increased circulatory response to recovery, which might have resulted from its pharmacokinetic properties. It should be noted that with IV administration of propacetamol and morphine before skin closure, no difference was found in the global hemodynamic stability or the requirement of ß-adrenergic blockers or calcium channel blockers between the two groups during extubation and the recovery period, because all patients in this study received antihypertensive treatments. The pain level was slightly but significantly increased in the Remifentanil group during the recovery period but reached a similar level in the two groups at the time of discharge from the recovery room (22 and 25 mm in the Remifentanil and Sufentanil groups, respectively). However, these different levels of postoperative pain did not result in more marked postoperative hemodynamic changes in the Remifentanil group. In conclusion, a similar global hemodynamic stability was observed during and after CE in patients receiving remifentanil or sufentanil during surgery. Remifentanil was more effective in limiting the increase in BP associated with intubation without increasing the BP-reducing effect of induction. The circulatory response to recovery was not increased in patients who received intraoperative remifentanil. On the basis of these results and the pharmacokinetic properties of remifentanil, this short-acting opioid seems to be a useful alternative to sufentanil in patients undergoing carotid surgery.
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