Effects of Cholestatic Hepatic Disease and Chronic Renal Failure on Alfentanil Pharmacokinetics in Children

Davis, Peter J.; Stiller, Richard L.; Cook, David; Brandom, Barbara W.; Davis, Jane E.; Scierka, Annette

doi:10.1213/00000539-198905000-00006

Cited by 22 publications

(8 citation statements)

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“…In a study assessing 9 children with cholestatic liver disease and 10 children with chronic renal failure undergoing organ transplantation, no significant difference was found in alfentanil clearance or half-life 6 (Level III evidence), suggesting the drug is safe to use in these groups.…”

Section: Alfentanilmentioning

confidence: 99%

Acute Pain Management Pharmacology for the Patient with Concurrent Renal or Hepatic Disease

2005

Anaesth Intensive Care

139

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The clinical utility of most analgesic drugs is altered in the presence of patients with impaired renal or hepatic function not simply because of altered clearance of the parent drug, but also through production and accumulation of toxic or therapeutically active metabolites. Some analgesic agents may also aggravate pre-existing renal and hepatic disease. A search was performed, taking in published articles and pharmaceutical data to determine available evidence for managing acute pain effectively and safely in these two patient groups. The resulting information consisted mainly of small group pharmacokinetic studies or case reports, which included a large variation in degree of organ dysfunction. In the presence of renal impairment, those drugs which exhibit the safest pharmacological profile are alfentanil, buprenorphine, fentanyl, ketamine, paracetamol (except with compound analgesics), remifentanil and sufentanil: none of these deliver a high active metabolite load, or suffer from significantly prolonged clearance. Amitriptyline, bupivacaine, clonidine, gabapentin, hydromorphone, levobupivacaine, lignocaine, methadone, mexiletine, morphine, oxycodone and tramadol have been used in the presence of renal failure, but do require specific precautions, usually dose reduction. Aspirin, dextropropoxyphene, non-steroidal anti-inflammatory drugs and pethidine, should not be used in the presence of chronic renal failure due to the risk of significant toxicity. In the presence of hepatic impairment, most drugs are subject to significantly impaired clearance and increased oral bioavailability, but are poorly studied in the clinical setting. The agent least subject to alteration in this context is remifentanil; however the drugs' potency has other inherent dangers. Other agents must only be used with caution and close patient monitoring. Amitriptyline, carbamazepine and valproate should be avoided as the risk of fulminant hepatic failure is higher in this population, and methadone is contraindicated in the presence of severe liver disease.

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Section: Alfentanilmentioning

confidence: 99%

Acute Pain Management Pharmacology for the Patient with Concurrent Renal or Hepatic Disease

2005

Anaesth Intensive Care

139

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“…The decrease in alfentanil protein binding observed in adults with cirrhosis as well as in children with end-stage liver disease may be related to quantitative or qualitative changes in the plasma proteins or to the presence of binding inhibitors (Marshall & Williams 1978). Although we did not determine the cause for the decrease in protein binding in children with liver disease, the increase in the free or unbound fraction of a highly bound drug with a low-tointermediate extraction coefficient would account for some of alfentanil's phamacokinetic and pharmacodynamic variability (Davis et al 1989).…”

Section: Discussionmentioning

confidence: 88%

Decreased protein binding of alfentanil in plasma from children with kidney or liver failure

Davis

Stiller

McGowan

et al. 1993

Pediatric Anesthesia

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Disease states, including end-stage kidney or liver failure, can alter the protein binding of various drugs in children. The plasma protein binding of alfentanil was evaluated in blood samples from 15 children about to undergo kidney transplantation, 21 children undergoing liver transplantation, and 28 otherwise healthy children undergoing elective surgery. Compared with the heaIthy children, patients with kidney disease had a signrficant decrease in protein binding (89.2% It 5.4 v. 93.1% k 3.2), an increase in al-acid glycoprotein concentration (108.8 mg-dl-l It 44.3 v. 71.8 mgad1-l f 30.3, and no change in albumin concentration (3910 mg-dl-l f 754 v. 4555 mg-dl-' k 524);whereas patients with liver disease had a significant decrease in protein binding (85.9% f 6.2 v. 93.1% f 3.2), no change in al-acid glycoprotein concentration (65.8 mgedl-' f 31.8 v. 71.8 mg-dl k 30.3, and a decrease in albumin concentration (3045 mg-dl-' ? 1255 v. 4555 rng-dl-l k 524). Because alfentanil is highly protein bound, even small changes in the drug's free fraction could have marked pharmacodynamic effects in patients with kidney or liver failure.

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“…Dr Cook's team studied the pharmacokinetics of alfentanil in children with cholestatic liver disease during liver transplantation. They found that except for the period immediately following liver transplantation, volume of distribution, elimination half‐life, and clearance were unchanged for alfentanil and required no dose adjustments when compared to children without cholestatic liver disease . Immediately following liver transplantation, these values were found to be increased and the recommendation was that the dose may need to be decreased.…”

Section: Era Of Clinical Pharmacologymentioning

confidence: 99%

“…7 In addition to neuromuscular antagonists, Dr Cook and his team helped define the pharmacology of opioids like alfentanil in the pediatric population. [17][18][19][20][21] Alfentanil has a rapid onset of analgesia and has a shorter elimination half-life than fentanyl and sufentanil, but these parameters had not previously been defined in neonates. Dr…”

Section: During Dr Cook's Third Year Of Medical School He Was Hired mentioning

confidence: 99%

“…They found that except for the period immediately following liver transplantation, volume of distribution, elimination half-life, and clearance were unchanged for alfentanil and required no dose adjustments when compared to children without cholestatic liver disease. 17 Immediately following liver transplantation, these values were found to be increased and the recommendation was that the dose may need to be decreased. Likewise, in a piglet model, Dr Cook and his team demonstrated that increased intra-abdominal pressure (20 mm Hg) did not increase the elimination half-life of alfentanil.…”

Section: During Dr Cook's Third Year Of Medical School He Was Hired mentioning

confidence: 99%

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The advancement of pediatric anesthesia pharmacology: David Ryan Cook (scions, serendipity, and six degrees of separation)

Cladis

Christine

Yaster

et al. 2018

Pediatric Anesthesia

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Summary Dr David Ryan Cook, Professor Emeritus of Anesthesiology and Pharmacology at the University of Pittsburgh and Chief of Anesthesiology at Children's Hospital of Pittsburgh (1977‐1999), is a pioneer in the field of pediatric anesthesiology and pharmacology. Dr Cook contributed significantly to the understanding of pharmacologic differences among infants, children, and adults. His work as a clinician‐scientist, educator, and mentor defined the pharmacology of many of the anesthetic agents we continue to use today. He brought science to the art of anesthesia and enhanced the safety of pediatric perioperative care. Based on a 2017 interview with Dr Cook, this article outlines the development of his career and his contributions to the field of anesthesiology and pharmacology.

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Effects of Cholestatic Hepatic Disease and Chronic Renal Failure on Alfentanil Pharmacokinetics in Children

Cited by 22 publications

References 0 publications

Acute Pain Management Pharmacology for the Patient with Concurrent Renal or Hepatic Disease

Acute Pain Management Pharmacology for the Patient with Concurrent Renal or Hepatic Disease

Decreased protein binding of alfentanil in plasma from children with kidney or liver failure

The advancement of pediatric anesthesia pharmacology: David Ryan Cook (scions, serendipity, and six degrees of separation)

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