Pharmacokinetics Anesthesiologists, and Pharmacodynamics of Remifentanil in Persons with Renal Failure Compared with Healthy Volunteers

Hoke, Frank; Shlugman, D.; Dershwitz, Mark; Michałowski, Piotr; Malthouse-Dufore, Sherry; Connors, Patricia M.; Martel, David; Rosow, Carl E.; Muir, Keith T.; Rubin, Nina; Glass, Peter S. A.

doi:10.1097/00000542-199709000-00012

Cited by 141 publications

(18 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…20,21 Studies suggest that these potency ratios are sufficiently large to avoid a pharmacologically significant impact of the metabolite (GR90291 for remifentanil and ASL-8123 for esmolol) even when its elimination is slowed by renal failure. 22,23 …”

Section: Discussionmentioning

confidence: 99%

Distinct Hypnotic Recoveries After Infusions of Methoxycarbonyl Etomidate and Cyclopropyl Methoxycarbonyl Metomidate

Pejo

Liu²,

Lin³

et al. 2016

Anesthesia &Amp; Analgesia

View full text Add to dashboard Cite

Background Methoxycarbonyl etomidate (MOC-etomidate) and cyclopropyl methoxycarbonyl metomidate (CPMM) are rapidly metabolized “soft” etomidate analogues. CPMM’s duration of hypnotic effect is context-insensitive whereas MOC-etomidate’s is not. In the current study, we tested the hypothesis that CPMM’s effect is context-insensitive because, unlike MOC-etomidate, its metabolite fails to reach physiologically important concentrations in vivo even with prolonged continuous infusion. Methods We compared the potencies with which MOC-etomidate and CPMM activate α1(L264T)β3γ2 gamma-aminobutyric acid type A receptors and induce loss-of-righting reflexes (i.e. produce hypnosis) in tadpoles with those of their metabolites (MOC-ECA and CPMM-CA, respectively). We measured metabolite concentrations in blood and cerebrospinal fluid of Sprague Dawley rats upon CPMM infusion and compared them to those achieved with MOC-etomidate infusion. We measured the rates with which brain tissue from Sprague Dawley rats metabolize MOC-etomidate and CPMM. Results Both analogues and their metabolites enhanced gamma-aminobutyric acid type A receptor function and induced loss-of-righting reflexes in a concentration-dependent manner. However in these 2 assays, CPMM-CA’s potency relative to its parent hypnotic was approximately 1:4,900 and 1:1,900, respectively, whereas MOC-ECA’s was only approximately 1:415 and 1:390, respectively. With 2-hr CPMM infusions, CPMM-CA reached respective concentrations in the blood and cerebrospinal fluid that were 2 and >3 orders of magnitude lower than that which produced hypnosis. CPMM was metabolized by brain tissue at a rate that is approximately 1/15th that of MOC-etomidate. Conclusions Hypnotic recovery after CPMM administration is context-insensitive because its metabolite does not accumulate to hypnotic levels in the central nervous system. This reflects the very large potency ratio between CPMM and its carboxylic acid metabolite CPMM-CA and the resistance of CPMM to metabolism by esterases present in the brain.

show abstract

Section: Discussionmentioning

confidence: 99%

Distinct Hypnotic Recoveries After Infusions of Methoxycarbonyl Etomidate and Cyclopropyl Methoxycarbonyl Metomidate

Pejo

Liu²,

Lin³

et al. 2016

Anesthesia &Amp; Analgesia

View full text Add to dashboard Cite

show abstract

“…Also important to note is that Remifentanil is not a substrate for pseudocholinesterase and, therefore, is not influenced by pseudocholinesterase deficiency [23]. Furthermore, renal and hepatic function has been shown not to influence duration of its clinical action [24, 25]. However, hypothermia has been shown to decrease enzymatic function of plasma esterases by about 20% potentially leading to accumulation of Remifentanil [26].…”

Section: Discussionmentioning

confidence: 99%

Accidental Subcutaneous Remifentanil Infusion as a Cause of Delayed Awakening after Craniotomy

Wolfson

Swamidoss

2011

Case Reports in Anesthesiology

View full text Add to dashboard Cite

show abstract

“…Moreover, fentanyl is not cleared by HD. Remifentanil clearance is clinically independent of renal function, but its metabolite, remifentanil acid, results in renal failure without a toxic effect [77]. …”

Section: Ckd/eskd Patients Admitted In the Icumentioning

confidence: 99%

Management of Chronic Kidney Disease Patients in the Intensive Care Unit: Mixing Acute and Chronic Illness

Rosa

Samoni²,

Villa³

et al. 2017

Blood Purif

3,608

View full text Add to dashboard Cite

Patients with chronic kidney disease (CKD) are at high risk for developing critical illness and for admission to intensive care units (ICU). ‘Critically ill CKD patients' frequently develop an acute worsening of renal function (i.e. acute-on-chronic, AoC) that contributes to long-term kidney dysfunction, potentially leading to end-stage kidney disease (ESKD). An integrated multidisciplinary effort is thus necessary to adequately manage the multi-organ damage of those kidney patients and contemporaneously reduce the progression of kidney dysfunction when they are critically ill. The aim of this review is to describe (1) the pathophysiological mechanisms underlying the development of AoC kidney dysfunction and its role in the progression toward ESKD; (2) the most common clinical presentations of critical illness among CKD/ESKD patients; and (3) the continuum of care for CKD/ESKD patients from maintenance hemodialysis/peritoneal dialysis to acute renal replacement therapy performed in ICU and, vice-versa, for AoC patients who develop ESKD.

show abstract

Pharmacokinetics Anesthesiologists, and Pharmacodynamics of Remifentanil in Persons with Renal Failure Compared with Healthy Volunteers

Cited by 141 publications

References 14 publications

Distinct Hypnotic Recoveries After Infusions of Methoxycarbonyl Etomidate and Cyclopropyl Methoxycarbonyl Metomidate

Distinct Hypnotic Recoveries After Infusions of Methoxycarbonyl Etomidate and Cyclopropyl Methoxycarbonyl Metomidate

Accidental Subcutaneous Remifentanil Infusion as a Cause of Delayed Awakening after Craniotomy

Management of Chronic Kidney Disease Patients in the Intensive Care Unit: Mixing Acute and Chronic Illness

Contact Info

Product

Resources

About