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Background Choice of perioperative analgesia may affect the rate of recovery of gastrointestinal function and thus duration and cost of hospitalization after colonic surgery. Methods Fifty-four patients undergoing partial colectomy surgery were randomized into four groups. All groups received a standardized general anesthetic. Group MB received a preoperative bolus of epidural bupivacaine and morphine followed by an infusion of morphine and bupivacaine. Group M received a preoperative bolus of epidural morphine followed by an infusion of morphine. Group B received a preoperative bolus of bupivacaine followed by an infusion of bupivacaine. Group P received a preoperative bolus of intravenous morphine followed by intravenous patient-controlled morphine postoperatively. All patients participated in a standardized recovery program to minimize the influence of nonanalgesic factors on recovery of gastrointestinal function. All epidural groups were double-blinded. All patients were deemed ready for discharge according to prospectively defined criteria. Results Groups B and MB reported superior analgesia with activity (P < 0.01). Group M had a greater incidence of pruritus (P < 0.05). Group B had a greater incidence of orthostatic hypotension (P = 0.04). Groups B and MB recovered gastrointestinal function and fulfilled discharge criteria approximately 1.5 days earlier than groups M and P (P < 0.005). Conclusions Epidural analgesia with bupivacaine and morphine provided the best balance of analgesia and side effects while accelerating postoperative recovery of gastrointestinal function and time to fulfillment of discharge criteria after colon surgery in relatively healthy patients within the context of a multimodal recovery program.

Background It remains unclear whether epidural administration of hydromorphone results in spinal analgesia or clinical benefit when compared with intravenous administration. Therefore, we undertook this study to determine whether epidural administration of hydromorphone resulted in decreased opioid requirement, improved analgesia, reduced side effects, more rapid return of gastrointestinal function, or shorter duration of hospital stay than intravenous administration. Methods Sixteen patients undergoing radical retropubic prostatectomy were randomized in a double-blind manner to receive either intravenous or epidural hydromorphone via patient-controlled analgesia (PCA) for postoperative analgesia. All patients underwent a standardized combined epidural and general anesthetic and all received ketorolac for 72 h postoperatively. To decrease variability, patients were cared for according to a standardized protocol and were deemed ready for discharge according to prospectively defined criteria. Results Patients in the intravenous PCA group required approximately twice as much opioid than the epidural PCA group (P < 0.008), but there were no differences between groups in pain scores or patient satisfaction. Epidural administration resulted in a greater incidence of pruritus (P = 0.02). Gastrointestinal function recovered quickly in all patients with little variation, and there were no differences between groups. All patients were deemed ready for discharge by the third postoperative day, and removal of surgical drains was the last discharge criterion reached in all patients. Conclusions Our results indicate that epidural administration of hydromorphone results in spinally mediated analgesia. However, epidural administration did not provide significant benefits in terms of postoperative analgesia, recovery of gastrointestinal function, or duration of hospitalization. Furthermore, we suggest that radical retropubic prostatectomy no longer be used as a model to assess the effects of analgesic technique on postoperative recovery, because control of discharge criteria revealed that hospital discharge was primarily dependent on removal of surgical drains.

We asked whether the sympathomimetic effect of nitrous oxide (N2O) predisposed patients receiving N2O to arrhythmias in response to epinephrine administration. We also asked whether aging contributed to the development of arrhythmias, with or without N2O. One hundred patients having transsphenoidal hypophysectomy were randomly assigned to receive anesthesia including (n = 49) or excluding (n = 51) N2O. All patients were given an injection of epinephrine 1:200,000, with 0.5% lidocaine to produce hemostasis. Using intermittent 12-lead and continuous lead II electrocardiography, we determined the incidence of premature ventricular contraction, isorhythmic atrioventricular (AV) dissociation, and changes in T-wave morphology. Patients given N2O had a significantly higher incidence of isorhythmic AV dissociation (61.2% vs 41.2%). A trend toward a higher incidence of multiple premature ventricular contractions (16.3% vs 7.8%) was not statistically significant. Both anesthetic groups had a high incidence of postoperative changes in T-wave morphology (46.9% in the N2O group vs 50.9% in the group not given N2O). Aging alone did not affect the incidence of ventricular ectopic beats, isorhythmic AV dissociation, or changes in electrocardiographic morphology, but correlated with the development of ventricular ectopy during N2O anesthesia. We conclude that the use of N2O correlated with a higher incidence of isorhythmic AV dissociation in response to injection of epinephrine with lidocaine.

Vecuronium and atracurium provide addition flexibility to the clinician using neuromuscular blocking drugs. The shorter duration of action, lack of significant cardiovascular effects, and the lack of dependence on the kidney for elimination provide clinical advantages over, or alternatives to, currently available nondepolarizing neuromuscular blocking drugs.

To determine the effect of the commonly used volatile anesthetics on a vecuronium-induced neuromuscular blockade, the authors studied 54 patients anesthetized with 1.2 MAC or 2.2 MAC enflurane, isoflurane, or halothane (MAC value includes contribution from 60% nitrous oxide). During 1.2 MAC enflurane, isoflurane, and halothane, the ED50S (the doses depressing twitch tension 50%) for vecuronium were 12.8, 14.7, and 16.9 micrograms/kg, respectively. During 2.2 MAC enflurane, isoflurane, and halothane, the ED50S for vecuronium were 6.3, 9.8, and 13.8 micrograms/kg, respectively (P less than 0.05). Time from injection to peak effect was the same for each anesthetic group (6.5 +/- 0.5 min, mean +/- SD), except for the group given 2.2 MAC enflurane (9.7 +/- 0.6 min) (P less than 0.05). The duration of a 50% block from injection to 90% recovery was the same for each group (mean 20 +/- 4 min), except for the group given 2.2 MAC enflurane (46.5 min) (P less than 0.05). The authors conclude that enflurane is the most potent volatile anesthetic, followed by isoflurane and then halothane, in augmenting a vecuronium-induced neuromuscular blockade. Increasing the concentration of volatile anesthetic has less effect on a neuromuscular blockade produced by vecuronium than on one produced by other nondepolarizing relaxants (e.g., pancuronium and d-tubucurarine).

To determine what effect the addition of epinephrine has on bupivacaine toxicity, toxic doses of bupivacaine were administered to awake spontaneously breathing pigs. Twenty animals were randomized to one of two groups. One group received an infusion of bupivacaine with epinephrine (5 micrograms/ml) at a rate of 2 mg.kg-1.min-1; the other received an infusion of plain bupivacaine at the same rate. Bupivacaine infusion was continued until cardiovascular collapse. Following cardiovascular collapse we attempted to resuscitate the animals via open chest cardiac massage and a standardized resuscitation protocol. The addition of epinephrine to bupivacaine significantly increased blood pressure and systemic vascular resistance but not heart rate or cardiac output early in the bupivacaine infusion. Epinephrine had no effect on the dose of bupivacaine that caused cardiovascular collapse (P = 0.1), on the plasma concentration of bupivacaine at collapse (P = 0.9), or on the ability to resuscitate animals following cardiovascular collapse. The addition of epinephrine decreased the dose of bupivacaine required to initiate cardiac dysrhythmias (P = 0.003). The first dysrhythmia experienced by the epinephrine group was second degree heart block, which contrasts with the premature ventricular and atrial dysrhythmias experienced by the plain group. The dose of bupivacaine that produced seizures was also reduced by the addition of epinephrine (P = 0.006). The addition of epinephrine to bupivacaine did not alter the dose of bupivacaine that caused cardiovascular collapse in awake spontaneously breathing pigs but did decrease the dose of bupivacaine that caused seizures and dysrhythmias.

To compare the effect of halothane and enflurane on an atracurium-induced neuromuscular blockade, the authors studied 40 patients during elective surgery. During 1.25 MAC enflurane-nitrous oxide (n = 20) or halothane-nitrous oxide (n = 20) (MAC value includes contribution from 60% nitrous oxide), the doses depressing twitch tension 50% (ED50S) for atracurium were 70 and 77 micrograms/kg, respectively. The difference was not significant. Time from injection to peak effect did not differ between groups. However, the duration of action of atracurium (expressed as duration 50 or the duration of a 50% blockade) was longer during enflurane-nitrous oxide anesthesia (34.2 min) than during halothane-nitrous oxide anesthesia (25.5 min) (P less than 0.05). The authors conclude that the potency of atracurium does not differ during halothane-nitrous oxide and enflurane-nitrous oxide anesthesia. Combining the results of this study with a previous study (atracurium ED50 = 68 micrograms/kg and 83 micrograms/kg during isoflurane-nitrous oxide and fentanyl-nitrous oxide anesthesia respectively), the potency of atracurium does not differ by more than 20% among the four anesthetic techniques studied. The background anesthetic appears to have less effect on an atracurium-induced neuromuscular blockade than on one produced by other longer-acting nondepolarizing muscle relaxants (e.g., pancuronium and d-tubocurarine).

Atracurium, a nondepolarizing muscle relaxant, is eliminated through several pathways, including Hofmann elimination (spontaneous degradation in plasma and tissue at normal body pH and temperature) and ester hydrolysis (catalysis by nonspecific esterases). Because elimination of atracurium occurs in both tissue and plasma, traditional pharmacokinetic models assuming elimination from a single central compartment are inaccurate for atracurium. The authors developed a two-compartment pharmacokinetic model in which hepatic and/or renal elimination occurs from the central compartment (Cl organ), and Hofmann elimination and ester hydrolysis occur from both central and peripheral compartments (Cl nonorgan). To determine the in vitro rate constant for Hofmann elimination and ester hydrolysis, atracurium was added to whole blood kept at each patient's pH and temperature. The values for this rate constant ranged from 0.0193 to 0.0238 per min. When these values were applied to the pharmacokinetic model, Cl total, Cl organ, and Cl nonorgan were 4.8 +/- 1.1, 3.0 +/- 0.9, and 1.9 +/- 0.6 ml . kg-1 . min-1, respectively. The authors conclude that more than one-half of the clearance of atracurium occurs via pathways other than Hofmann elimination and ester hydrolysis.

To determine the influence of renal function on the pharmacology of atracurium, 10 patients with normal renal function and 10 with renal failure (scheduled for cadaver kidney transplant) were anesthetized with nitrous oxide and halothane. Atracurium besylate, 0.5 mg . kg-1, was given as an iv bolus and plasma samples were collected over a 4-h period. These samples were assayed for atracurium (all patients) and laudanosine, one of the principal metabolites (eight of the normal group), using an ion-exchange liquid chromatographic assay. The plasma concentrations of atracurium for each patient were fitted to a two-compartment pharmacokinetic model. The onset time, duration of action, and recovery time of atracurium neuromuscular blockade were measured. There were no differences found in the pharmacokinetics or pharmaco-dynamics of atracurium between patients with normal renal function and those with renal failure. There were measurable levels of laudanosine following atracurium administration with peak levels of 199 +/- 31 ng . ml-1 at 2 min. The authors conclude that the pharmacokinetics and pharmacodynamics of atracurium are not altered by renal failure.

The blood pressure (BP) response to cerebellar retraction during microvascular decompression of the fifth cranial nerve was investigated in 26 ASA physical status 2 or 3 patients with trigeminal neuralgia. One surgeon performed all operations. To determine the effect of three anesthetic techniques on the BP response, patients were randomly assigned to receive halothane, isoflurane, or sufentanil in sufficient doses with 60% nitrous oxide to achieve a precerebellar retraction systolic BP that was 10-20% below the average ward systolic BP (as per standard clinical practice). The resultant doses were halothane 1.65 +/- 0.27 (mean +/- SD) MAC, isoflurane 1.56 +/- 0.17 MAC (P greater than 0.05), and sufentanil 2.7 micrograms/kg (MAC values include 0.6 MAC contribution from 60% nitrous oxide). In all patients BP increased during the cerebellar retractor placement period compared with the preretractor placement period (P less than 0.05). The peak increase in systolic BP in response to cerebellar retraction was 17 +/- 6 mmHg for halothane, 38 +/- 20 mmHg for isoflurane, and 26 +/- 19 mmHg for sufentanil. The difference between halothane and isoflurane was significant (P less than 0.05). Mean and diastolic BP showed similar significant differences. The authors conclude that halothane attenuates the hypertensive response to cerebellar retraction more than isoflurane when administered in approximately 1.6 MAC concentrations (MAC value includes contribution from nitrous oxide).

To determine the effect of benzodiazepine premedication on central nervous system and cardiovascular effects of bupivacaine, the authors administered toxic doses of bupivacaine to awake spontaneously breathing pigs after intravenous premedication with midazolam (0.06 mg/kg), diazepam (0.15 mg/kg), or saline. Five minutes after administration of one of these solutions, they began an infusion of bupivacaine at 2 mg.kg-1.min-1. The bupivacaine infusion was continued until cardiovascular collapse. They then attempted to resuscitate the animals via open chest cardiac massage and a standard resuscitation protocol. Premedication with midazolam or diazepam significantly delayed the onset of ventricular dysrhythmias (P less than 0.05), decreased the incidence of seizures (P less than 0.05), and prevented the increase in blood pressure and heart rate following bupivacaine infusion (P less than 0.05). Benzodiazepine premedication did not affect the dose of bupivacaine or the blood concentration required to produce cardiovascular collapse. The ability to resuscitate animals premedicated with midazolam did not differ from control; however, significantly fewer animals premedicated with diazepam were resuscitated (P less than 0.05). A clinically relevant observation was that almost all animals premedicated with a benzodiazepine progressed directly to cardiovascular collapse without first manifesting seizures.

Administration of a subparalyzing dose of a nondepolarizing muscle relaxant (priming dose) prior to its intubating dose hastens the onset time (time from muscle relaxant administration to 100% depression of twitch tension) of neuromuscular blockade. This study was undertaken to determine the optimal priming and intubating doses and time interval between these doses (priming interval) of vecuronium during rapid-sequence induction of anesthesia. The authors measured single-twitch tension in 79 healthy, awake, premedicated (fentanyl, 50-150 mu iv, and/or diazepam, 5-10 mg iv) patients. In Part A of the study, the priming dose was varied (0.0, 0.005, 0.01, 0.0015, or 0.02 mg/kg iv). Decrement of twitch tension and symptoms were recorded 3 min later. Four minutes after the priming dose, thiopental, 4-6 mg/kg iv, and vecuronium, 0.1 mg/kg iv, were given. Onset times for the 0.01, 0.015, and 0.02 mg/kg groups were significantly shorter than for 0.005 and 0.0 mg/kg groups. No breathing difficulties were encountered in any of the groups. Decrement of twitch tension greater than 25% of control only occurred in the 0.02 mg/kg group (4 of 11 patients). In Part B, the priming interval was varied (2, 4, or 6 min) after giving the optimal priming dose (0.01 mg/kg). Anesthesia was induced as in Part A. Onset times for the 4-min group were significantly faster than the 2- or 6-min groups. In Part C, the intubating dose was varied (0.07, 0.1, or 0.15 mg/kg iv) after the optimal priming dose and optimal priming interval (4 min). Onset times for the 0.1 mg/kg and 0.15 mg/kg groups were significantly faster than the 0.07 mg/kg group.(ABSTRACT TRUNCATED AT 250 WORDS)

To compare the time course of neostigmine and edrophonium antagonism of varying intensity neuromuscular blockade induced by atracurium, pancuronium, or vecuronium, the authors studied 98 patients anesthetized with nitrous oxide (60%) and halothane or enflurane. Neuromuscular blockade, as monitored by single stimulus-induced twitch tension (TT), was antagonized at varying degrees of spontaneous recovery (2-80% of control TT). Time to antagonism (time from injection of neostigmine or edrophonium to 90% recovery of control TT) was not different between edrophonium, 0.5 mg/kg, and neostigmine, 0.04 mg/kg, when spontaneous recovery had been allowed to occur to at least 11% of control TT prior to antagonist administration (P greater than 0.05). For profound neuromuscular blockade (TT less than or equal to 10% of control) induced by pancuronium or vecuronium, time (mean +/- SD) to antagonism with neostigmine, 0.04 mg/kg, was 7.0 +/- 2.2 min and 5.6 +/- 1.7 min, respectively, while the same for edrophonium, 0.5 mg/kg, was 20.0 +/- 8.0 min and 15.0 +/- 12.5 min, respectively (P less than 0.05). Time to antagonism of profound atracurium-induced neuromuscular blockade was 8.5 +/- 3.3 min for neostigmine, 0.04 mg/kg, and 9.8 +/- 7.0 min for edrophonium, 0.5 mg/kg, (P less than 0.05). For profound vecuronium-and pancuronium-induced neuromuscular blockade, time to antagonism by edrophonium, 1.0 mg/kg, was 4.6 +/- 3.0 min and 3.9 +/- 1.6 min respectively. The authors conclude that neostigmine, 0.04 mg/kg, antagonizes neuromuscular blockade within 12 min when TT is greater than 2% of control at time of reversal. When TT is greater than 10% of control, edrophonium, 0.5 mg/kg, produces similar time to antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)