Stephen M. Rupp

Effects of Perioperative Analgesic Technique on Rate of Recovery after Colon Surgery

Background Choice of perioperative analgesia may affect the rate of recovery of gastrointestinal function and thus duration and cost of hospitalization after colonic surgery.

Practice Guidelines for Central Venous Access A Report by the American Society of Anesthesiologists Task Force on Central Venous Access

P RACTICE Guidelines are systematically developed recommendations that assist the practitioner and patient in making decisions about health care. These recommendations may be adopted, modified, or rejected according to clinical needs and constraints, and are not intended to replace local institutional policies. In addition, Practice Guidelines developed by the American Society of Anesthesiologists (ASA) are not intended as standards or absolute requirements, and their use cannot guarantee any specific outcome. Practice Guidelines are subject to revision as warranted by the evolution of medical knowledge, technology, and practice. They provide basic recommendations that are supported by a synthesis and analysis of the current literature, expert and practitioner opinion, open forum commentary, and clinical feasibility data.

Elimination of atracurium in humans: contribution of Hofmann elimination and ester hydrolysis versus organ-based elimination

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 pharnacokinetic model in which hepatic and/or renal elimination occurs from the central compartment (Clorgan), and Hofmann elimination and ester hydrolysis occur from both central and peripheral compartments (Clnonorgan). To determine the in vitro rate constant for Hofmann elimination and ester hydrolysis, atracurium was added to whole blood kept at each patients 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, Cltotal, Clorgan, and Clnonorgan 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.

Vecuronium-induced Neuromuscular Blockade during Enflurane, Isoflurane, and Halothane Anesthesia in Humans

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 μg/kg, respectively. During 2.2 MAC enflurane, isoflurane, and halothane, the ED50s for vecuronium were 6.3, 9.8, and 13.8 μg/kg, respectively (P < 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 < 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 < 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).

Clinical Pharmacology of Vecuronium and Atracurium

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.

The Pharmacokinetics and Pharmacodynamics of Atracurium in Patients with and without Renal Failure

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 pharmacodynamics 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.

Pancuronium and vecuronium pharmacokinetics and pharmacodynamics in younger and elderly adults.

To evaluate the effect of aging on the distribution, metabolism, and neuromuscular junction sensitivity to pancuronium and vecuronium, the authors determined the pharmacokinetics and pharmacodynamics of these drugs in 12 healthy elderly subjects (70–84 yr) and 12 young adults (30–57 yr) during halothane-nitrous oxide anesthesia. Plasma concentrations of the muscle relaxants were determined using a selective ion-monitoring mass spectrometric technique specific for the parent compound. For vecuronium, plasma clearance (3.7 ±1.0 and 5.2 ± 0.8 ml · kg−1 · min−1, respectively), and volume of distribution at steady-state (179 ± 31 and 244 ± 38 ml · kg−1, respectively) were lower in the elderly than in young adults; values for distribution half-lives, elimination half-life, and sensitivity of the neuromuscular junction were similar for the two groups. For pancuronium, there were no statistically significant differences between groups for these pharmacokinetic or pharmacodynamic parameters. However, there was a trend toward reduced clearance (20%) and prolonged elimination half-life (16%) in the elderly as compared to the younger patients. The authors conclude that healthy elective surgical patients between the ages of 70 and 84 yr of age do not differ markedly from younger adults in their pharmacokinetic/pharmacodynamic response to vecuronium and pancuronium.

Intravenous versus epidural administration of hydromorphone : effects on analgesia and recovery after radical retropubic prostatectomy

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.

Refining the priming principle for vecuronium during rapid-sequence induction of anesthesia

Administration of a subparalyzing dose of 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 mg 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. Intubating conditions were not evaluated. The authors conclude that when vecuronium is used for rapid establishment of neuromuscular blockade during induction of anesthesia, 0.01 mg/ kg iv should be given 4 min prior to 0.1 mg/kg iv.

Nitrous oxide and epinephrine-induced arrhythmias.

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.