C. Lebrault

Acute Opioid Tolerance: Intraoperative Remifentanil Increases Postoperative Pain and Morphine Requirement

Background Rapid development of acute opioid tolerance is well established in animals and is more likely to occur with large doses of short-acting drugs. The authors therefore tested the hypothesis that intraoperative remifentanil administration results in acute opioid tolerance that is manifested by increased postoperative pain and opioid requirement. Methods Fifty adult patients undergoing major abdominal surgery were randomly assigned to two anesthetic regimens: (1) desflurane was kept constant at 0.5 minimum alveolar concentrations and a remifentanil infusion was titrated to autonomic responses (remifentanil group); or (2) remifentanil at 0.1 &mgr;g · kg−1 · min−1 and desflurane titrated to autonomic responses (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 also blinded to group assignment—controlled their own morphine administration. Pain scores and morphine consumption were recorded for 24 postoperative h. Results The mean remifentanil infusion rate was 0.3 ± 0.2 &mgr;g · 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 (25–75% interquartile range, 43–71) versus 32 mg (25–75% interquartile range, 19–59;P < 0.01). Conclusions Relatively large-dose intraoperative remifentanil increased postoperative pain and morphine consumption. These data suggest that remifentanil causes acute opioid tolerance and hyperalgesia.

Supplementing Desflurane-remifentanil Anesthesia with Small-dose Ketamine Reduces Perioperative Opioid Analgesic Requirements

Relative large-dose intraoperative remifentanil could lead to the need for more postoperative analgesics. Intraoperative N-methyl-d-aspartate receptor antagonists, such as ketamine, decrease postoperative opioid use. We therefore tested the hypothesis that intraoperative small-dose ketamine improves postoperative analgesia after major abdominal surgery with remifentanil-based anesthesia. Fifty patients undergoing abdominal surgery under remifentanil-based anesthesia were randomly assigned to intraoperative ketamine or saline (control) supplementation. The initial ketamine dose of 0.15 mg/kg was followed by 2 &mgr;g · kg−1 · min−1. In both groups, desflurane was kept constant at 0.5 minimum alveolar anesthetic concentration without N2O, and a remifentanil infusion was titrated to autonomic responses. All patients were given 0.15 mg/kg of morphine 30 min before the end of surgery. Pain scores and morphine consumption were recorded for 24 postoperative h. Less of the remifentanil was required in the Ketamine than in the Control group (P < 0.01). Pain scores were significantly larger in the Control group during the first 15 postoperative min but were subsequently similar in the two groups. The Ketamine patients required postoperative morphine later (P < 0.01) and received less morphine during the first 24 postoperative h: 46 mg (interquartile range, 34–58 mg) versus 69 mg (interquartile range, 41–87 mg, P < 0.01). No psychotomimetic symptoms were noted in either group. In conclusion, supplementing remifentanil-based anesthesia with small-dose ketamine decreases intraoperative remifentanil use and postoperative morphine consumption without increasing the incidence of side effects. Thus, intraoperative small-dose ketamine may be a useful adjuvant to intraoperative remifentanil.

Effect of an intubating dose of succinylcholine and atracurium on the diaphragm and the adductor pollicis muscle in humans.

This study compares the neuromuscular blocking effect of succinylcholine (0.8 mg · kg−1) and atracurium (0.6 mg · kg−1) on the diaphragm (D) and the adductor pollicis (AP) in 20 patients anesthetized with nitrous oxide, oxygen, and fentanyl. The diaphragm was monitored by measuring transdiaphragmatic pressure following bilateral phrenic nerve stimulation. After succinylcholine, the time from injection of succinylcholine to maximum depression of the single twitch response (onset time) was of 50 ± 11 s (±SD) for D compared to 80 ± 24 s for AP (P < 0.001). After succinylcholine, recovery from paralysis was earlier for D than AP. Single twitch height (TH) returned to 25% of its control value (T25) after 5 ± 2 min for D compared to 7 ± 3 min for AP (P < 0.001). Complete recovery of TH (T100) was achieved after 9 ± 4 min for D and 11 ± 5 min for AP (P < 0.01). Recovery index (T25–75) was of 2 ± 1 min for both muscles. After atracurium, the onset time for D was of 137 ± 31 s compared to 181 ± 45 s for AP (P < 0.001). The T25 was achieved after 38 ± 7 min for D compared to 63 ± 13 min for AP (P < 0.001). The TH of D returned to T100 after 60 ± 12 min compared to 87 ± 17 min for AP (P < 0.01). The train-of-four ratio returned to 1 after 64 ± 15 min for D compared to 99 ± 21 min for AP (P < 0.001). After an intubating dose of succinylcholine (0.8 mg · kg−1) or atracurium (0.6 mg · kg−1), D was always completely paralyzed, when the TH of AP was abolished and the TH of D had completely recovered when the TH of the AP had returned to 100%.

the Neuromuscular Blocking Effect of Vecuronium on the Human Diaphragm

This study compares the neuromuscular blocking effect of vecuronium (0.1 mg/kg) on the diaphragm and the adductor pollicis in nine anesthetized patients. Monitoring of the diaphragm consisted of measurement of the transdiaphragmatic pressure after bilateral phrenic nerve stimulation. Onset time for

Pharmacokinetics of alfentanil in chronic renal failure.

The pharmacokinetics of alfentanil were studied during general anesthesia in nine patients with renal failure and in ten patients with normal renal function. All patients received 0.05 mg/kg alfentanil as an intravenous bolus injection. Plasma concentrations were measured at intervals up to 8 hr, using a specific radioimmunoassay technique. Protein binding was measured by equilibrium dialysis. Elimination half-life and plasma clearance were similar in both groups. The volume of distribution at steady state was greater (P < 0.02) in patients with renal failure (405 ± 86 ml/kg) than in patients with normal renal function (281 ± 97 ml/kg). Patients with renal failure had a higher (P < 0.01) alfentanil plasma free fraction (0.19 ± 0.06) than patients with normal renal function (0.11 ± 0.03). When kinetic parameters were corrected for protein binding, the unbound volume of distribution and the free drug clearance were unchanged in patients with renal failure. These results suggest that the modification of alfentanil free fraction in renal failure does not induce any change in elimination but may influence the distribution of alfentanil.

Equivalence of postoperative analgesia with patient-controlled intravenous or epidural alfentanil.

The analgesia and the frequency and severity of oxyhemoglobin desaturation related to alfentanil administration were compared in 32 patients randomly selected to receive patient-controlled analgesia (PCA) by either the epidural (EPI) or intravenous (i.v.) route for a mean period of 16 h after major abdominal surgery. Bolus increments of 250 micrograms of alfentanil with a lockout interval of 5 min for i.v. and of 10 min for EPI route were administered by a programmable pump. Oxygen saturation (SpO2) was monitored for 16 h, using a pulse oximeter; data were collected continuously and stored every 30 s via an interface connected to a computer. For the purpose of analysis, SpO2 was divided into six categories: 95%-100%, 90%-94%, 85%-89%, 80%-84%, 75%-79%, and 70%-74%. Both routes provided similar degrees of analgesia at rest and on coughing. Maximum pain relief was obtained earlier in the i.v. group (P < 0.01). The total consumption of alfentanil was 13,141 +/- 3471 micrograms (mean +/- SD) in the i.v. group and 8000 +/- 4213 micrograms in the EPI group (P < 0.001). The effects on SpO2 were not statistically different between the two groups. Cumulative time spent in each saturation category was similar for the EPI and i.v. groups. Severe desaturation episodes, defined as SpO2 < or = 85% for at least 60 s, occurred in 69% of patients in the EPI group and 56% in the i.v. group.(ABSTRACT TRUNCATED AT 250 WORDS)

NEUROMUSCULAR BLOCKING EFFECT OF VECURONIUM ON HUMAN DIAPHRAGM

This study compares the neuromuscular blocking effect of vecuronium (0.1 mg/kg) on the diaphragm and the adductor pollicis in nine anesthetized patients. Monitoring of the diaphragm consisted of measurement of the transdiaphragmatic pressure after bilateral phrenic nerve stimulation. Onset time for neuromuscular blockade of the diaphragm was 1.6 +/- 0.3 min (+/-SD) compared to 2.5 +/- 0.3 min in the adductor pollicis (P less than 0.001). The diaphragm recovered earlier and more rapidly than the adductor pollicis. The twitch height (TH) returned to 25% of its control value after 27 +/- 8 min for the diaphragm, compared to 41 +/- 11 min for the adductor pollicis (P less than 0.01). Complete TH recovery was achieved after 49 +/- 14 min for the diaphragm and after 74 +/- 22 min for the adductor pollicis (P less than 0.01). The recovery index of 12 +/- 4 min for the diaphragm was significantly shorter (P less than 0.05) than for the adductor pollicis (20 +/- 9 min.) We conclude that monitoring of peripheral muscles in anesthetized patients given vecuronium provides adequate information about the degree of paralysis of the diaphragm.