Remifentanil-induced PAS is not a phenomenon of intraoperative hypothermia. The higher incidence of PAS with higher doses of remifentanil probably reflects acute opioid tolerance and stimulation of N-methyl-d-aspartate receptors, similar to hyperalgesia. We conclude that patients administered high doses of remifentanil are sensitive to shivering after sudden drug withdrawal.

the elimination clearance and the volume of the central compartment. The population estimates of elimination clearance, volume of the central compartment, and steady-state volume of distribution for a reference individual were 51.0 L/h, 134 L, and 258 L, respectively. In the simulations, the values of LBM were based on the values in the study populations. The decrease in elimination clearance of oxycodone with advancing age was reflected in the elimination half-life, which increased with older age. A notable increase in the need for a 50% decrease in concentration after continuous infusion of variable length was seen in the elderly. Between the ages of 25 and 85 years, the context-sensitive half-time at steady state increased from 3.8 to 4.6 hours. Oxycodone may accumulate in the elderly compared with a young adult. Predicted peak concentrations were also much higher in older individuals.Because age was an important covariate for oxycodone pharmacokinetics, elderly patients should have a reduced dose that is carefully titrated to avoid accumulation of the drug and potential deleterious and hazardous adverse effects. Dosing in the elderly should not be based on data from healthy young volunteers. COMMENTOxycodone is an opioid synthesized from thebaine and, compared with morphine, causes less respiratory depression, sedation, pruritus, and nausea. In the current study, the authors analyzed data from 77 patients included in 4 different studies and developed a 2-compartmental model to describe oxycodone pharmacokinetics. They conclude that in the elderly there is decreased clearance of the drug so that either the dose should be reduced, or there should be an increased interval between drug doses.There are a number of general pharmacokinetic changes that occur with aging that I should like to summarize. First, there is a reduction in first-pass metabolism that is probably owing to a reduction in liver mass and blood flow. As a result, the bioavailability of drugs undergoing extensive first-pass metabolism may be substantially increased.As a consequence of changes in body composition, polar drugs that are mainly water-soluble tend to have smaller volumes of distribution (V D ) resulting in higher serum levels in older people. For example, the loading dose of digoxin needs to be reduced. Although no specific age-related changes in albumin occur, albumin levels are commonly reduced in malnutrition, which is prevalent in the elderly, so drugs that are highly protein bound may be affected. Drug clearance by the liver is illustrated by the following formula:where E is steady-state extraction ratio; Q, liver blood flow (sum of hepatic portal and hepatic arterial blood flow); [Ca], concentration of drug in portal vein and hepatic artery; [Cv], concentration of drug leaving the liver in the hepatic vein; and Cl liver = clearance by the liver. Therefore, clearance by the liver depends on both the blood flow and the extraction ratio. The latter is dependent on the metabolizing capacity of the liver, and the reduction in liver bl...

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Patients undergoing gynecological laparotomy were randomized to receive either 0.5 mg/kg ketamine at induction of anesthesia followed by an infusion of 0.3 mg/kg/h until the end of surgery (ketamine group, n = 32), or an equivalent volume of normal saline (control group, n = 32). Anesthesia was maintained with IV propofol, a fixed infusion rate of remifentanil (0.25 μg/kg/min), and epidural ropivacaine. Postanesthetic shivering (PAS) was evaluated for 30 minutes after emergence. Intraoperative temperatures were similar between the 2 groups. The incidence of PAS was less frequent in the ketamine group (n = 2, 6%) compared with the control group (n = 12, 38%, P = 0.005). We conclude that, during the early recovery phase, intraoperative ketamine reduces remifentanil-induced PAS.

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