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Abstract

Correspondence: Des Breen, des.breen@btinternet.com R21 CL cr = creatinine clearance; HR = heart rate; ICU = intensive care unit; MAP = mean arterial pressure; PI = Pain Intensity (scale); RR = respiratory rate; SAE = serious adverse event; SAPS = Simplified Acute Physiology Score; SAS = Sedation-Agitation Scale; SDT = scheduled down-titration. AbstractIntroduction This open label, multicentre study was conducted to assess the times to offset of the pharmacodynamic effects and the safety of remifentanil in patients with varying degrees of renal impairment requiring intensive care. Methods A total of 40 patients, who were aged 18 years or older and had normal/mildly impaired renal function (estimated creatinine clearance ≥ 50 ml/min; n = 10) or moderate/severe renal impairment (estimated creatinine clearance < 50 ml/min; n = 30), were entered into the study. Remifentanil was infused for up to 72 hours (initial rate 6-9 µg/kg per hour), with propofol administered if required, to achieve a target Sedation-Agitation Scale score of 2-4, with no or mild pain. Results There was no evidence of increased offset time with increased duration of exposure to remifentanil in either group. The time to offset of the effects of remifentanil (at 8, 24, 48 and 72 hours during scheduled down-titrations of the infusion) were more variable and were statistically significantly longer in the moderate/severe group than in the normal/mild group at 24 hours and 72 hours. These observed differences were not clinically significant (the difference in mean offset at 72 hours was only 16.5 min). Propofol consumption was lower with the remifentanil based technique than with hypnotic based sedative techniques. There were no statistically significant differences between the renal function groups in the incidence of adverse events, and no deaths were attributable to remifentanil use. Conclusion Remifentanil was well tolerated, and the offset of pharmacodynamic effects was not prolonged either as a result of renal dysfunction or prolonged infusion up to 72 hours.

Could remifentanil reduce duration of mechanical ventilation in comparison with other opioids for mechanically ventilated patients? A systematic review and meta-analysis

“…Similar to fentanyl, alfentanil, and sufentanil, remifentanil is a potent, selective 4-anilidopiperidine μ-opioid analgesic. However, unlike fentanyl and other opioids, remifentanil is completely metabolized by unspecific esterases in a manner that is independent of liver or renal function [ 5 , 6 ]. Since unspecific esterases have been found to be widely distributed in living human cells, there are no ICU disease states or types of organ failure that would lead to reduced breakdown of remifentanil.…”

“…Since unspecific esterases have been found to be widely distributed in living human cells, there are no ICU disease states or types of organ failure that would lead to reduced breakdown of remifentanil. The major breakdown product of remifentanil is remifentanil acid (RA), which has a potency of only 1/300 to 1/4600 that of remifentanil, has poor brain penetration and is unlikely to cause respiratory failure [ 6 , 7 ]. Remifentanil has a highly predictable onset and offset effect, a terminal half-life of approximately 10 to 20 minutes, and a context-sensitive half-life of 3 to 4 minutes [ 6 , 8 ].…”

“…The major breakdown product of remifentanil is remifentanil acid (RA), which has a potency of only 1/300 to 1/4600 that of remifentanil, has poor brain penetration and is unlikely to cause respiratory failure [ 6 , 7 ]. Remifentanil has a highly predictable onset and offset effect, a terminal half-life of approximately 10 to 20 minutes, and a context-sensitive half-life of 3 to 4 minutes [ 6 , 8 ]. The unique pharmacokinetics of remifentanil may lead to reductions in time to weaning and extubation and, accordingly, may be associated with reductions in mechanical ventilation time, length of ICU stay (ICU-LOS), and costs.…”

Remifentanil up2date – Teil 2

“…Der relevante Remifentanilstabilisator Glyzin steigt wie der Ammoniakspiegel unter Remifentanilgabe nicht an [36]. Viele Autoren [34,37,38] sowie die Fachinformationen [15] bewerten den Einsatz als sicher und empfehlen keine Dosisanpassung. Einzelne Untersuchungen ermittelten sogar einen renoprotektiven Effekt [39].…”

Effect of Dexmedetomidine and Remifentanil on Renal Function in Patients Undergoing Bariatric Surgery

“…Following this principle, remifentanil, with its characteristic extrahepatic metabolism (plasma and tissue esterases), which guarantees rapid recovery, even after prolonged infusion, and has an elimination half-life of 9 to 10 minutes, has a good indication for anesthesia in patients obese [3] [4] [5]. Breen et al [6] studied the effect of remifentanil infused over 72 hours in patients with renal failure, admitted to the intensive care unit, with no increase in the incidence of adverse effects and prolonged pharmacodynamic effects of the drug.…”