Remifentanil Infusion Rate Research Articles

Efficacy and safety of remifentanil in coronary artery bypass graft surgery: A randomized, double-blind dose comparison study

Objectives: To compare the efficacy and safety of 3 doses of remifentanil as part of a total intravenous anesthesia technique with low-dose propofol in patients undergoing coronary artery bypass graft (CABG) surgery. Design: Multicenter, multinational, double-blind, randomized, dose comparison study. Setting: Nine hospitals in 5 countries. Participants: One hundred forty-one patients undergoing first-time elective CABG surgery. Interventions: Patients were premedicated with a short-acting oral benzodiazepine up to 2 h before surgery and randomized to receive continuous infusions of remifentanil 1.0 μg/kg/min (n = 45), 1.5 μg/kg/min (n = 44), or 2.0 μg/kg/min (n = 43), in combination with propofol 3 mg/kg/h. Nine patients received remifentanil 1.0 μg/kg/min on an open-label basis. Three different induction sequences (IS) were used. In IS 1 (n = 31), induction was started with remifentanil infusion followed 5 minutes later by propofol 0.5 mg/kg bolus and infusion at 3 mg/kg/h. Further bolus doses of propofol (10 mg) were given if loss of consciousness (LOC) was not attained after 5 minutes; pancuronium, 0.04 to 0.1 mg/kg, was administered at LOC. In IS 2 (n = 68), a priming dose of pancuronium, 0.015 mg/kg, was administered just before starting remifentanil. In IS 3 (n = 42), bolus doses of propofol, 10 mg every 10 seconds, were given until LOC, followed by pancuronium, 0.04 to 0.1 mg/kg, and the remifentanil and propofol infusions were started. Measurements and Main Results: There were no significant differences among the remifentanil dose groups with regard to the primary outcome measure, responses to sternotomy/sternal spread/maximal sternal spread. Responses to these stimuli were recorded in 11%, 11%, and 14% of patients in the remifentanil 1.0, 1.5, and 2.0 μg/kg/min dose groups, respectively. Similarly, there were no significant differences in the responses to other surgical stimuli. There was a high incidence of muscle rigidity when remifentanil was used to induce anesthesia. Conclusions: All 3 remifentanil dose regimens provided profound suppression of responses to surgical stimuli in the majority of patients. There was no apparent advantage in starting the remifentanil infusion rate above 1.0 μg/kg/min. Remifentanil is not suitable for use as a sole induction agent. Copyright 2003, Elsevier Science (USA). All rights reserved.

Remifentanil requirements during sevoflurane administration to block somatic and cardiovascular responses to skin incision in children and adults.

The authors found no studies comparing intraoperative requirements of opioids between children and adults, so they determined the infusion rate of remifentanil to block somatic (IR50) and autonomic response (IRBAR50) to skin incision in children and adults. Forty-one adults (aged 20-60 yr) and 24 children (aged 2-10 yr) undergoing lower abdominal surgery were studied. In adults, anesthesia induction was with sevoflurane during remifentanil infusion, whereas in children remifentanil administration was started after induction with sevoflurane. After intubation, sevoflurane was administered in 100% O2 and was adjusted to an ET% of 1 MAC-awake corrected for age at least 15 min before surgery. Patients were randomized to receive remifentanil at a rate ranging from 0.05 to 0.35 microg x kg(-1) x min(-1) for at least 20 min before surgery. At the beginning of surgery, only the skin incision was performed, and the somatic and autonomic responses were observed. The somatic response was defined as positive with any gross movement of extremity, and the autonomic response was deemed positive with any increase in heart rate mean arterial pressure equal to or more than 10% of preincision values. Using logistic regression, the IR50 and IRBAR50 were determined in both groups of patients and compared with unpaired Student t test. A P value less than 0.05 was considered significant. The IR50 +/- SD was 0.10 +/- 0.02 microg x kg(-1) x min(-1) in adults and 0.22 +/- 0.03 microg x kg(-1) x min(-1) in children (P < 0.001). The IRBAR50 +/- SD was 0.11 +/- 0.02 microg x kg(-1) x min(-1) in adults and 0.27 +/- 0.06 microg x kg(-1) x min(-1) in children (P < 0.001). To block somatic and autonomic responses to surgery, children require a remifentanil infusion rate at least twofold higher than adults.

No clinical evidence of acute opioid tolerance after remifentanil-based anaesthesia

We have prospectively assessed whether remifentanil-based anaesthesia is associated with clinically relevant acute opioid tolerance, expressed as greater postoperative pain scores or morphine consumption. Sixty patients undergoing elective gynaecological, non-laparoscopic, surgery were randomly assigned to receive remifentanil (group R, n=30) or sevoflurane (group S, n=30) based anaesthesia. Postoperative analgesia was provided with morphine through a patient-controlled infusion device. Mean (SD) remifentanil infusion rate in group R was 0.23 (0.10) microg kg(-1) min(-1) and mean inspired fraction of sevoflurane in group S was 1.75 (0.70)%. Mean (SD) cumulative morphine consumption during the first 24 postoperative hours was similar between groups: 28.0 (14.2) mg (group R) vs 28.6 (12.4) mg (group S). Pain scores, were also similar between groups during this period. These data do not support the development of acute opioid tolerance after remifentanil-based anaesthesia in this type of surgery.

Influence of Hypotensive and Normotensive Anesthesia on Platelet Aggregability and Hemostatic Markers in Orthognathic Surgery

This prospective randomized study investigated the influence of normotensive and hypotensive general anesthesia on platelet aggregability, intraoperative blood loss and parameters of plasmatic coagulation during extensive orthognathic surgery. A total of 30 patients were randomly allocated for either normotensive anesthesia maintained by continuous infusion of propofol and remifentanil (NORMO, n=10) or hypotensive anesthesia, whereby hypotension was induced by increasing the infusion rate of remifentanil (HYPO-R, n=10) or by administration of nitroglycerin (HYPO-N, n=10). Whole blood platelet aggregability was significantly reduced during hypotension compared to normotensive anesthesia ( P<.01, HYPO-N and HYPO-R vs. NORMO). Mean arterial blood pressure during hypotension correlated well with adenosinediphosphate- ( R=.712, P<.001) and collagen-induced platelet aggregability ( R=.685, P<.001). Within hypotensive study groups, postoperative fibrinogen levels were significantly different, whereas intraoperative platelet aggregability, postoperative platelet count, prothrombin time, activated partial thromboplastin time and antithrombin levels were not different. Normotensive anesthesia, however, caused significant decreases in platelet count (−29%), prothrombin time (−24%), fibrinogen (−41%) and antithrombin (−28%) and a significant prolongation in activated partial thromboplastin time (+21%) and thrombin time (+18%). There was a trend to reduced intraoperative blood loss in hypotensive study groups; however, differences were not significant. In conclusion, induced hypotension — independent of substances used for induction of hypotension — reduces intraoperative platelet aggregability, subsequently protecting the coagulation system against subclinical consumption coagulopathy. Induced hypotension-caused platelet dysfunction does not lead to an increased intraoperative blood loss, but quite on the contrary shows a trend to reduced intraoperative blood loss, possibly by preventing platelet-induced subclinical consumption coagulopathy.

Propofol and remifentanil pharmacodynamic interaction during orthopedic surgical procedures as measured by effects on bispectral index

Study Objective: To identify and quantify the interaction between propofol and remifentanil during surgical procedures with a bispectral index (BIS) of 50 that was chosen as a continuous surrogate measure for “adequate depth” of anesthesia. Design: Prospective, open-label study. Setting: Department of orthopedics of a university hospital. Patients: 20 patients undergoing orthopedic surgery. Interventions: Anesthesia was induced and maintained with propofol and remifentanil, both administered by target-controlled infusion (TCI). Initial target concentrations of propofol (1.5–8 μg/mL) and remifentanil (2–15 ng/mL) were chosen and alternated in order to maintain the BIS between 45 and 55. If constant target concentrations had been maintained for 20 minutes and the BIS did not depart from the desired range, blood samples were taken to determine propofol concentrations, and the BIS value was recorded. Isobolographic interaction models were fitted to the infusion rates of remifentanil and propofol, predicted target concentrations of both drugs, and measured propofol concentrations versus predicted remifentanil concentrations. Main Results: The isobole for the interaction of propofol and remifentanil in the concentration range investigated (propofol 1.5–8 μg/mL and remifentanil 1–30 ng/mL) is a concave up hyperbola ((0.15 · C prop) 3.13 · C rem = 1) with C prop = propofol plasma concentration [μg/mL] and C rem = remifentanil blood concentration [ng/mL]). Use of predicted (=TCI target) concentrations or the respective infusion rates did not alter the general shape of the interaction isobole. Conclusions: The interaction between propofol and remifentanil for maintenance of a BIS value between 45 and 55 during surgery is synergistic. This finding applies regardless of whether measured concentrations (for propofol), predicted concentrations of the infusion device, or infusion rates are used as model input. Notably, the interaction isobole of the (clinically readily available) infusion rates provides a useful dosing recommendation for the coadministration of propofol and remifentanil during maintenance of anesthesia.

Anesthesia (4)

Bruno Guignard, Anne Elisabeth Bossard, Carole Coste, et al:Intraoperative remifentanil increases postoperative pain and morphine requirement. (Hôpital Ambroise Paré, Boulogne‐Billancourt, France) Anesthesiology 2000;93:409– 417.The study tested the hypothesis that intraoperative remifentanil administration results in acute opioid tolerance that is manifested by increased postoperative pain and opioid requirement. Fifty adult patients undergoing major abdominal surgery were randomly assigned to 2 anesthetic regimens: (1) the remifentanil group or (2) the desflurane group. All patients were given a bolus of 0.15 mg/kg morphine 40 min before the end of surgery. Morphine was initially titrated to need by postanesthesia care nurses blinded to group assignment. Subsequently, patients—who were blinded to group assignment—controlled their own morphine administration. Pain scores and morphine consumption were recorded for 24 postoperative h. The results indicated that the mean remifentanil infusion rate was 0.3 ± 0.2 μg · kg−1· min−1 in the remifentanil group, which was significantly greater than in the desflurane group. Intraoperative hemodynamic responses were similar in each group. Postoperative pain scores were significantly greater in the remifentanil group. These patients required morphine significantly earlier than those in the desflurane group and needed nearly twice as much morphine in the first 24 postoperative h: 59 mg (25% to 75% interquartile range, 43–71) versus 32 mg (25% to 75% interquartile range, 19–59; P&lt;0.01). Conclude that relatively large‐dose intraoperative remifentanil increased postoperative pain and morphine consumption. These data suggest that remifentanil causes acute opioid tolerance and hyperalgesia.

Remifentanil infusion facilitates early recovery for obese outpatients undergoing laparoscopic cholecystectomy.

D espite the well known adverse effects of obesity, it is still the most common nutritional disorder in the United States. Unfortunately, there is a paucity of data supporting the use of one anesthetic technique over another in obese (versus nonobese) patient populations. Prolonged emergence time from general anesthesia in obese patients can be problematic in the ambulatory setting because it can delay the early recovery process. Cork et al. (1) reported that the use of IV anesthetic and analgesic drugs does not guarantee a shorter emergence period in the obese population. Because remifentanil can reduce the required endtidal concentration of volatile anesthetics by up to 50% (2,3), we hypothesized that the use of a remifentanil infusion during a sevoflurane-based anesthetic would facilitate emergence from anesthesia in obese patients undergoing ambulatory surgery.

The Use of a Remifentanil Infusion for Hemodynamic Control During Intracranial Surgery

Remifentanil is an extremely rapid and short-acting opioid analgesic which is effective in controlling acute stress responses during surgery. During neurosurgical anesthesia, laryngoscopy and intubation, application of the head holder, scalp incision, and the craniectomy can produce significant increases in mean arterial pressure (MAP). In this dose-response study, we evaluated the efficacy of a remifentanil infusion in maintaining hemodynamic stability during intracranial surgery under desflurane anesthesia. Forty-five patients were assigned randomly to one of the three remifentanil infusion groups. All patients received a standardized anesthetic induction consisting of midazolam, 2 mg IV, lidocaine 0.75 mg/kg IV, propofol 1.0 mg/kg IV, and remifentanil 0.5 μg/kg IV. Immediately after induction of anesthesia, a remifentanil infusion was started at 0.0625 μg · kg−1 · min−1 (Group 1), 0.125 μg · kg−1 · min−1 (Group 2), or 0.250 μg · kg−1 · min−1 (Group 3) according to a double-blinded study protocol. Maintenance of anesthesia consisted of desflurane 3% (end-tidal) in air/oxygen. If the MAP exceeded 80 mm Hg, a supplemental bolus of remifentanil, 0.5 μg/kg IV was administered, and when the MAP decreased below 65 mm Hg, the remifentanil infusion was discontinued temporarily. “Rescue” cardiovascular medications consisted of nitroprusside (100 μg IV) or phenylephrine (100 μg IV). Heart rate, systolic, diastolic, and MAP values, were recorded every minute for 20 min after each specific stimulus. The overall quality of the intraoperative hemodynamic control was evaluated by the attending anesthesiologist on a scale from 1 = poor to 5 = excellent. The overall quality of the hemodynamic control was superior in Group 2 compared with Group 1 (P < 0.05). Although the total dose of remifentanil administered during the study period did not differ among the three groups, Group 1 required significantly more supplemental boluses of remifentanil (66%–80%) than Groups 2 (13%–33%) and 3 (7%–13%), and the remifentanil infusion was discontinued more often in Group 3 (80%–93%) than in Groups 1 (0%–13%) and 2 (21%–40%). In conclusion, the recommended remifentanil infusion rate for controlling acute autonomic responses during neurosurgical anesthesia is 0.125 μg · kg−1 · min−1 when administered during a desflurane-based anesthetic. Implications Compared with remifentanil 0.0625 μg · kg−1 · min−1 and 0.250 μg · kg−1 · min−1, a remifentanil infusion rate of 0.125 μg · kg−1 · min−1 provided more stable hemodynamic conditions during intracranial surgery under desflurane anesthesia.

The Use of a Remifentanil Infusion for Hemodynamic Control During Intracranial Surgery

Remifentanil is an extremely rapid and short-acting opioid analgesic which is effective in controlling acute stress responses during surgery. During neurosurgical anesthesia, laryngoscopy and intubation, application of the head holder, scalp incision, and the craniectomy can produce significant increases in mean arterial pressure (MAP). In this dose-response study, we evaluated the efficacy of a remifentanil infusion in maintaining hemodynamic stability during intracranial surgery under desflurane anesthesia. Forty-five patients were assigned randomly to one of the three remifentanil infusion groups. All patients received a standardized anesthetic induction consisting of midazolam, 2 mg IV, lidocaine 0.75 mg/kg IV, propofol 1.0 mg/kg IV, and remifentanil 0.5 microg/kg IV. Immediately after induction of anesthesia, a remifentanil infusion was started at 0.0625 microg x kg(-1) x min(-1) (Group 1), 0.125 microg x kg(-1) x min(-1) (Group 2), or 0.250 microg x kg (-1) x min(-1)(Group 3) according to a double-blinded study protocol. Maintenance of anesthesia consisted of desflurane 3% (end-tidal) in air/oxygen. If the MAP exceeded 80 mm Hg, a supplemental bolus of remifentanil, 0.5 microg/kg IV was administered, and when the MAP decreased below 65 mm Hg, the remifentanil infusion was discontinued temporarily. "Rescue" cardiovascular medications consisted of nitroprusside (100 microg IV) or phenylephrine (100 microg IV). Heart rate, systolic, diastolic, and MAP values, were recorded every minute for 20 min after each specific stimulus. The overall quality of the intraoperative hemodynamic control was evaluated by the attending anesthesiologist on a scale from 1 = poor to 5 = excellent. The overall quality of the hemodynamic control was superior in Group 2 compared with Group 1 (P < 0.05). Although the total dose of remifentanil administered during the study period did not differ among the three groups, Group 1 required significantly more supplemental boluses of remifentanil (66%-80%) than Groups 2 (13%-33%) and 3 (70% 13%), and the remifentanil infusion was discontinued more often in Group 3 (80%-93%) than in Groups 1 (0%-13%) and 2 (21%-40%). In conclusion, the recommended remifentanil infusion rate for controlling acute autonomic responses during neurosurgical anesthesia is 0.125 microg x kg(-1) x min(-1) when administered during a desflurane-based anesthetic. Compared with remifentanil 0.0625 microg x kg(-1) x min(-1) and 0.250 microg x kg(-1) x min(-1), a remifentanil infusion rate of 0.125 microg x kg(-1) x min(-1) provided more stable hemodynamic conditions during intracranial surgery under desflurane anesthesia.

Inpatient experience with remifentanil.

Inpatient experience with remifentanil.

Remifentanil as an analgesic adjunct in local/regional anesthesia and in monitored anesthesia care.

Remifentanil as an analgesic adjunct in local/regional anesthesia and in monitored anesthesia care.

The Combined Effects of Sevoflurane and Remifentanil on Central Respiratory Activity and Nociceptive Cardiovascular Responses in Anesthetized Rabbits

We studied the effects of sevoflurane and remifentanil, alone and in combination, on phrenic nerve activity (PNA), resting heart rate (HR), arterial pressure (MAP), and changes in HR (Delta HR) and MAP (Delta MAP) evoked by electrical stimulation of tibial nerves in anesthetized rabbits.The 50% effective dose (95% confidence intervals) for the depressant effects of sevoflurane on Delta HR, Delta MAP, and PNA were 2.3 (1.8%-2.6%), 2.7 (2.3%-2.9%), and 3.4 (3.1%-3.7%), respectively, and for remifentanil were 0.100 (0.050-0.132), 0.850 (0.720-1.450), and 0.090 (0.080-0.145) [micro sign]g [middle dot] kg-1 [middle dot] min-1, which were reduced to 0.046 (0.021-0.065), 0.110 (0.080-0.200), and 0.030 (0.020-0.040) [micro sign]g [middle dot] kg-1 [middle dot] min-1, respectively, by 1% sevoflurane. Depression of evoked cardiovascular responses relative to PNA was greater for sevoflurane and less for remifentanil both alone and in combination with sevoflurane. Sevoflurane acted synergistically with remifentanil on PNA and Delta MAP, but not Delta HR, for which their combined effect was additive. Coadministration of 1% sevoflurane with the highest infusion rate of remifentanil (1.6 [micro sign]g [middle dot] kg-1 [middle dot] min-1) used during combined administration reduced resting HR and MAP by 25% (P < 0.05) and 41% (P < 0.05), respectively, which was greater than the predicted reductions of only 14% and 15% if their combined effects had been additive. We conclude that sevoflurane caused a relatively greater depression of nociceptive cardioaccelerator and pressor responses compared with PNA and vice versa for remifentanil. When coadministered, their combined effects on PNA, resting HR, MAP, and Delta MAP were synergistic, whereas they were merely additive for Delta HR. Implications: Although sevoflurane caused relatively greater depression of nociceptive cardiovascular responses compared with phrenic nerve activity, remifentanil either alone or combined with sevoflurane caused a much greater depression of phrenic nerve activity than cardioaccelerator and pressor responses. This could imply that, during major surgery using anesthesia combining sevoflurane and remifentanil, spontaneous ventilation is not acceptable, and depression of the resting circulation may be much greater than anticipated. (Anesth Analg 1999;89:453-61)

The Combined Effects of Sevoflurane and Remifentanil on Central Respiratory Activity and Nociceptive Cardiovascular Responses in Anesthetized Rabbits

We studied the effects of sevoflurane and remifentanil, alone and in combination, on phrenic nerve activity (PNA), resting heart rate (HR), arterial pressure (MAP), and changes in HR (delta HR) and MAP (delta MAP) evoked by electrical stimulation of tibial nerves in anesthetized rabbits. The 50% effective dose (95% confidence intervals) for the depressant effects of sevoflurane on delta HR, delta MAP, and PNA were 2.3 (1.8%-2.6%), 2.7 (2.3%-2.9%), and 3.4 (3.1%-3.7%), respectively, and for remifentanil were 0.100 (0.050-0.132), 0.850 (0.720-1.450), and 0.090 (0.080-0.145) microgram.kg-1.min-1, which were reduced to 0.046 (0.021-0.065), 0.110 (0.080-0.200), and 0.030 (0.020-0.040) microgram.kg-1.min-1, respectively, by 1% sevoflurane. Depression of evoked cardiovascular responses relative to PNA was greater for sevoflurane and less for remifentanil both alone and in combination with sevoflurane. Sevoflurane acted synergistically with remifentanil on PNA and delta MAP, but not delta HR, for which their combined effect was additive. Coadministration of 1% sevoflurane with the highest infusion rate of remifentanil (1.6 micrograms.kg-1.min-1) used during combined administration reduced resting HR and MAP by 25% (P < 0.05) and 41% (P < 0.05), respectively, which was greater than the predicted reductions of only 14% and 15% if their combined effects had been additive. We conclude that sevoflurane caused a relatively greater depression of nociceptive cardioaccelerator and pressor responses compared with PNA and vice versa for remifentanil. When coadministered, their combined effects on PNA, resting HR, MAP, and delta MAP were synergistic, whereas they were merely additive for delta HR. Although sevoflurane caused relatively greater depression of nociceptive cardiovascular responses compared with phrenic nerve activity, remifentanil either alone or combined with sevoflurane caused a much greater depression of phrenic nerve activity than cardio-accelerator and pressor responses. This could imply that, during major surgery using anesthesia combining sevoflurane and remifentanil, spontaneous ventilation is not acceptable, and depression of the resting circulation may be much greater than anticipated.

Total intravenous anesthesia with remifentanil, propofol and cisatracurium in end-stage renal failure.

To compare recovery parameters of total intravenous anesthesia (TIVA) with remifentanil and propofol, hemodynamic responses to perioperative events, and pharmacodynamic parameters of cisatracurium in 22 end-stage renal failure and 22 normal renal function patients. Anesthesia was induced with 2-3 mg x kg(-1) propofol and 1 microg x kg(-1) remifentanil and maintained with 75 microg x kg(-1) x min(-1) propofol and propofol initial infusion of 0.2 microg x kg(-1) x min(-1) propofol. Arterial pressure and heart rate were maintained by remifentanil infusion rate adjustments. The first twitch (T1) was maintained at 25% by an infusion of cisatracurium. There was no difference in the time to maintenance of adequate respiration, date of birth recollection, first analgesic administration, between the renal failure (4.8+/-2.5, 7.8+/-3.2, 12.3+/-5.3 min respectively) and the control group (5.2+/-2.8, 8.1+/-3.1, 12.7+/-5.5 min): nor were there any differences in the time to 25% T1 recovery, T1 recovery from 25% to 75%, or cisatracurium infusion rate between the renal failure group (32.1 +/-10.8 min, 18.2+/-5.5 min, 0.89+/-0.29 microg x kg(-1) min(-1) respectively) and the control group (35.9 (7.9 min, 18.4+/-3.8 min, 0.95+/-0.22 microg x kg(-1) x min(-1)). End-stage renal failure does not prolong recovery from TIVA with remifentanil and propofol, or the recovery from cisatracurium neuromuscular block.

Comparison of Remifentanil in Combination with Isoflurane or Propofol for Short-Stay Surgical Procedures

There are few data in the literature that describe the use of remifentanil when administered as a component of an inhalation or total i.v. anaesthetic (TIVA) technique. We studied 251 male and female patients, aged 18-75 years, ASA I-II, undergoing inguinal hernia repair, arthroscopic knee surgery or varicose vein surgery of at least 30 min duration without premedication. Patients were randomized to receive a remifentanil loading dose of 1.0 microgram kg-1 followed by a continuous infusion of 0.5 microgram kg-1 min-1 in combination with isoflurane (end-tidal concentration 0.6%), (Group I, n = 115) or propofol (initial infusion rate 9 mg kg-1 h-1 reduced to 6 mg kg-1 h-1 after 10 min), (Group P, n = 118). The remifentanil infusion rate was reduced by 50%, 5 min after tracheal intubation. Intraoperative stresses were treated with a remifentanil bolus (1 microgram kg-1) followed by an increase in the remifentanil infusion rate. At the insertion of the last suture, the remifentanil infusion and concomitant anaesthetic were switched off simultaneously. Times to spontaneous respiration, adequate respiration and tracheal extubation were significantly shorter in group I compared with group P (6.4 min vs 7.6 min, P < 0.01; 7.6 min vs 9.3, P < 0.003; 7.8 min vs 9.5 min, P < 0.015). Overall mean systolic blood pressures during surgery were greater in group P compared with group I (P < 0.05) but the absolute differences were clinically insignificant (4-5 mm Hg).

VARYING THE OPIOID ANALGESIC VS THE VOLATILE ANESTHETIC

S32 INTRODUCTION: It is a common clinical practice to maintain hemodynamic stability during surgery by varying the inspired concentration of the volatile anesthetic. Alternatively, the anesthesiologist may choose to utilize intravenous adjuvants (e.g., opioid analgesics) to maintain hemodynamic stability during the maintenance period. In this study, the effect of using a variable-rate infusion of remifentanil was compared to varying the inspired concentration of sevoflurane in outpatients undergoing laparoscopic procedures with respect to the early recovery and side effect profiles. METHODS: 46 healthy consenting women undergoing outpatient laparoscopic cholecystectomy were enrolled in this IRB-approved study. After premedication with midazolam, 2 mg iv, anesthesia was induced with remifentanil (REMI), 1 [micro sign]g/kg iv, propofol, 1.5 mg/kg iv and rocuronium 0.6 mg/kg iv. Following tracheal intubation, patients were randomly assigned to either a variable REMI or sevoflurane (SEVO) group. Anesthesia was maintained with a REMI infusion, SEVO and N2 O 65% in oxygen. In the REMI group, the REMI infusion rate was varied from 0.05 to 0.3 [micro sign]g/kg/min in combination with SEVO 0.7% [end tidal (ET)]. In the SEVO group, the inspired concentration was varied from 1 to 4% while the REMI infusion rate was maintained at 0.05 [micro sign]g/kg/min. The objective was to maintain the MAP value within +/- 15% of the preanesthetic baseline values. Rocuronium, 0.15 mg/kg iv, boluses were administered to maintain adequate muscle relaxation. At the end of the procedure, all patients received ketorolac, 60mg iv/im and droperidol, 0.625 mg iv. In addition, bupivacaine 0.25% was injected at the fascial level of the surgical portals. Recovery times from discontinuation of the maintenance anesthetic drugs to awakening, orientation and home-readiness were recorded. The incidence of nausea and vomiting, as well as requests for "rescue" medication were recorded during the first 24 h after surgery. These data were analyzed using ANOVA for continuous variables and Chi-square test for discrete variables, with p-values <0.05 considered statistically significant (*) (mean values +/- SD). RESULTS: The two treatment groups were similar with respect to demographic data and anesthesia times (Table 1). Compared to the SEVO group, the REMI group had significantly lower HR values. Although the REMI group had a faster emergence from anesthesia, the orientation and discharge times were not significantly different. In addition, patients in the REMI group tended to have a high incidence of postoperative vomiting. However, there were no differences between the two groups with respect to the requirements for rescue antiemetic and analgesic medications.Table 1DISCUSSION: Emergence was more rapid when a variable remifentanil infusion was used to control acute autonomic responses during surgery; however, it failed to improve the overall recovery profile compared to simply varying the inspired concentration of the volatile agent.

Recrudescence of Opioid Effects After Intraoperative Remifentanil Infusion Complicated by Infiltration of the Intravenous Catheter

To the Editor: We describe a case in which recrudescence of opioid effects occurred shortly after the emergence. A 77-yr-old woman (5[prime]6[prime], 65 kg) underwent microscopic direct laryngoscopy and laser excision of a supraglottic cyst. General anesthesia was induced with a remifentanil infusion of 0.5 [micro sign]g [center dot] kg-1 [center dot] min-1 and a propofol bolus of 1.0 mg/kg; succinylcholine 1.5 mg/kg was given to facilitate laryngoscopy and endotracheal intubation. Anesthesia was maintained with remifentanil, nitrous oxide 70% in oxygen, and isoflurane 0.2%. The remifentanil infusion rate was decreased to 0.25 [micro sign]g [center dot] kg-1 [center dot] min-1 1 min after intubation and to 0.125 [micro sign]g [center dot] kg (-1) [center dot] min-1 10 min thereafter. The succinylcholine infusion was titrated using a nerve stimulator. Thirty minutes into the procedure, the antecubital IV line had infiltrated. Approximately 162.5 [micro sign]g (0.125 [micro sign]g [center dot] kg-1 [center dot] min-1 x 65 kg x 20 min) of remifentanil had been infused. A second IV catheter was promptly inserted, and the succinylcholine and remifentanil infusions were restarted within 6 min. Fifteen minutes later, the succinylcholine infusion was stopped. Five minutes later, the surgery ended, and the nitrous oxide, isoflurane, and remifentanil were discontinued simultaneously. The IV tubing was flushed. Within 10 min, the patient was breathing regularly at a rate of 12 breaths/min; she seemed appropriate, responded to verbal commands, and demonstrated a 5-s head lift. She was tracheally extubated and transported to the recovery room. One minute after her arrival in the postanesthesia care unit, the patient's respiratory rate was 4 breaths/min, her heart rate was 40-45 bpm, and her SpO2 was 88%-92%. She did not respond to a vigorous painful stimulus (jaw thrust). We unsuccessfully attempted to ventilate the patient using a bag-valve-mask apparatus. After the administration of naloxone 40 [micro sign]g IV, her respiratory rate was 12 breaths/min, and her SpO2 improved. A repeat naloxone dose was given, and the patient responded appropriately to verbal stimuli. The patient's subsequent postoperative recovery was uneventful. Why did opioid effects recrudesce in this patient? We postulate that the interstitial remifentanil accumulation provided a sequestered repository from which remifentanil gradually diffused back into the circulation. We caution that remifentanil may have prolonged opioid effects when infused interstitially rather than directly into the circulation. Giovanni Cucchiaro, MD Richard A. Beers, MD Department of Anesthesiology; SUNY Health Science Center; Syracuse, NY 13210

Comparison of remifentanil in combination with isoflurane or propofol for short-stay surgical procedures

There are few data in the literature that describe the use of remifentanil when administered as a component of an inhalation or total i.v. anaesthetic (TIVA) technique. We studied 251 male and female patients, aged 18-75 years, ASA I-II, undergoing inguinal hernia repair, arthroscopic knee surgery or varicose vein surgery of at least 30 min duration without premedication. Patients were randomized to receive a remifentanil loading dose of 1.0 microgram kg-1 followed by a continuous infusion of 0.5 microgram kg-1 min-1 in combination with isoflurane (end-tidal concentration 0.6%), (Group I, n = 115) or propofol (initial infusion rate 9 mg kg-1 h-1 reduced to 6 mg kg-1 h-1 after 10 min), (Group P, n = 118). The remifentanil infusion rate was reduced by 50%, 5 min after tracheal intubation. Intraoperative stresses were treated with a remifentanil bolus (1 microgram kg-1) followed by an increase in the remifentanil infusion rate. At the insertion of the last suture, the remifentanil infusion and concomitant anaesthetic were switched off simultaneously. Times to spontaneous respiration, adequate respiration and tracheal extubation were significantly shorter in group I compared with group P (6.4 min vs 7.6 min, P < 0.01; 7.6 min vs 9.3, P < 0.003; 7.8 min vs 9.5 min, P < 0.015). Overall mean systolic blood pressures during surgery were greater in group P compared with group I (P < 0.05) but the absolute differences were clinically insignificant (4-5 mm Hg).

EFFECTS OF HEMOCONCENTRATOR IN THE CPB CIRCUIT ON REMIFENTANIL REQUIREMENTS

S79 Introduction: Remifentanil is an ultrashort acting opioid. It allows for precise control of hemodynamic parameters, and therefore is a valuable drug in cardiac surgery. Our initial experience with remifentanil in patients undergoing cardiopulmonary bypass (CPB) with a hemoconcentrator (HC) in the CPB circuit demonstrated increased remifentanil requirements. We hypothesized that the HC (Minntech, Minneapolis) removes temifentanil from the CPB circuit. This study was designed to evaluate this observation. Methods: Thirty patients undergoing cardiac surgery and placed on CPB were included in this study. A continuous infusion of remifentanil was started at the induction of anesthesia. This infusion was maintained throughout the procedure and during CPB to maintain the mean arterial pressure (MAP) between 60 and 80 mmHg. CPB blood flow rates were adjusted to maintain a cardiac index (C.I.) of 2.4 to 2.6 L/min/m2. Our hypothesis was then tested by adjusting the circuitry to administer the remifentanil on either the arterial or venous side of the CPB circuit (i.e. distal or proximal to the HC). Remifentanil was administered proximal (n=10) or distal (n=10) to the HC, as well as without the use of a HC (n=10). Remifentanil infusion rates were recorded during CPB before (baseline), during and after use of the HC. Results: There were no significant differences between groups in age, height, weight and preoperative C.I. Without a HC in the CPB circuit, remifentanil infusion rate did not require adjustment. There was an 82% increase in remifentanil infusion rate when administered on the venous side of the concentrator, compared to baseline (p<0.05). When given on the arterial side of the HC, the infusion rate did not need to be adjusted (p>0.05 when compared to baseline) (Table 1)Table 1: Remifentanil Infusion Rate (mcg/kg/min, mean +/- SD)Discussion: These results suggest that remifentanil is removed in the hemoconcentrating process. The HC filters molecules smaller than 65000 daltons. Remifentanil has a molecular weight of 412.9 daltons. [1] Conclusion: We therefore recommend the administration of remifentanil on the arterial side of the hemoconcentrator to obtain maximal efficacy of the drug during cardiopulmonary bypass.

EMERGENCE AND RECOVERY FROM BIS-GUIDED ADMINISTRATION OF ANESTHESIA

S499 INTRODUCTION: Remifentanil, a short-acting opioid has been shown to reduce the amount of co-administered hypnotic required. [1] Bispectral index (BIS), a processed EEG variable, correlates with the level of hypnosis during anesthesia. [2,3] BIS levels under 60 are required to obtain adequate hypnosis during surgical procedures. [4,5] This study compares emergence and recovery from BIS-guided anesthesia with remifentanil with either isoflurane or propofol. METHODS: After HIC approval, 76 consenting patients were randomized to two groups, one receiving remifentanil and isoflurane (ISO), the other remifentanil and propofol (PRO). In both groups, anesthesia was induced with propofol and remifentanil. Hemodynamic responses were used to titrate remifentanil infusion rates, maintaining MAP and heart rate within a 20% range compared with awake baseline. BIS was used to titrate ISO/PRO, maintaining BIS between 45 and 60. Thirty minutes before end of surgery 0.15 mg/kg morphine was administered for postoperative pain control. 15 min. before end of surgery anesthetics were reduced to keep BIS between 60 and 75. At the end of surgery, remifentanil and anesthetic agents were discontinued. Patients were observed for return of spontaneous and adequate respiration, return of consciousness and extubation. Postanesthetic assessment was performed using a modified Aldrete-score (0-10). [6] A score of 9 was needed for discharge. Statistical analysis was performed using Chi square and repeated t-testing (Bonferoni-Holms adjusted). RESULTS: Demographic data showed no significant differences between the groups (Table 1). Surgical duration was significantly shorter with isoflurane (94 +/- 40 min) than with propofol (121 +/- 53 min).Table 1: Demographic dataRecovery data were calculated from end of drugs' administration to return of spontaneous respiration (spont resp), adequate respiration (adeq resp), consciousness (ROC), extubation (EXT) and and full recovery (REC). (Table 2)Table 2: Recovery times (min)Mean remifentanil infusion rate was significantly lower (p<0.001) with ISO (0.18 +/- 0.06 [micro sign]g/kg/min) than with PRO (0.31 +/- 0.20 [micro sign]g/kg/min). Average isoflurane endtidal concentration was 0.66 +/- 0.13 %, propofol infusion rate 123 +/- 48 [micro sign]g/kg/min. CONCLUSIONS: BIS-guided anesthesia with remifentanil in combination with both isoflurane or propofol has comparably short recovery times. At comparable hypnotic levels, controlled by BIS, hemodynamic control requires higher doses of remifentanil with propofol, than with isoflurane.