Remifentanil reduced

Drug withdrawal A withdrawal syndrome has been described after the use of remifenta-nil by infusion in intensive care units [166 ]. Within 10 minutes of withdrawal, patients experienced tachycardia, hypertension, sweating, mydriasis, and myoclonus. These symptoms persisted despite the use of morphine and clonidine and only resolved on readministration of remifentanil. Gradual tapering of remifentanil reduces the incidence of withdrawal symptoms. 

Figure 7.6 Structure of remifentanil and its major metabolite formed by ester hydrolysis. contrast, alfentanil has an intermediate hepatic extraction (0.3-0.5) and alfentanil clearance will be sensitive to changes in both liver blood flow and reduced enzyme capacity in patients with liver disease. Although the kidneys play a minor role in the elimination of most opioids, renal disease can influence their pharmacokinetic profile, secondary to alterations in plasma proteins and intra- and extravascular volumes. Neither the pharmacokinetics nor the pharmacodynamics of remifentanil is significantly altered in patients with liver or renal disease.

Mixtures of remifentanil and sevoflurane have been used in two prospective, open, randomized studies (5,6), which showed that adding remifentanil results in a reduced requirement for sevoflurane for maintenance of anesthesia, leading to faster and easier recovery. 

In a prospective randomized comparison of combined sevoflurane plus remifentanil with combined fentanyl plus etomidate for induction of anesthesia in 10 patients with ischemic heart disease, 3 of the 20 patients given sevoflurane plus remifentanil developed severe bradycardia (heart rate less than 40) and one developed asystole, but the difference between the two groups did not reach statistical significance (20). Therefore, in patients with ischemic heart disease remifentanil should be used with caution, and concurrent administration of glycopyr-rolate 0.2 mg is advisable to reduce the incidence of bradycardia, hypotension, or both, without increasing the heart rate. 

In a prospective study in 12 men undergoing elective coronary artery bypass grafting, remifentanil 0.5 and 2.0 micrograms/kg/minute combined with propofol preserved hemodynamic stability and reduced myocardial blood flow and metabolism to a similar extent (24). Asystole has been attributed to remifentanil (25). 

Drug withdrawal Acute withdrawal syndrome has been reported as a significant occurrence after remifentanil withdrawal the incidence was reduced by gradual reduction of the rate of infusion [168 ]. 

Remifentanil is rapidly and extensively metabolized by nonspecific blood and tissue esterases (but not plasma cholinesterase) to a carboxylic acid derivative that is 4600 times less active than the parent compound [2]. Approximately 95% of remifentanil is excreted in the urine as this metabolite. It follows that the pharmacokinetics of remifentanil are not significantly changed in patients with renal impairment. The clearance of the carboxylic acid metabolite is reduced with renal dysfunction however, there is no demonstrated clinical relevance of the accumulated metabolite. The pharmacokinetics are also unchanged in patients with severe hepatic impairment (even those awaiting liver transplant. 

Cost remifentanil costs about ten times as much as fentanyl. If operating-room time or ICU stay is reduced, this cost may be offset. This has not been demonstrated conclusively. 

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