Comparative Pharmacokinetics of Fentanyl and Alfentanil

Bower, S.; Hull, C.J.

doi:10.1093/bja/54.8.871

Cited by 179 publications

(77 citation statements)

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“…However, since traditional opioids accumulate in the body over time, the optimal use of opioids in these techniques is often limited by side-effects, such as delayed or recurrent ventilatory depression, which can delay postoperative recovery [2,3]. Moreover, since traditional opioids are metabolised by the liver, they must be used with caution in patients with hepatic insufficiency [4,5].…”

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confidence: 99%

A comparison of remifentanil and alfentanil in patients undergoing major abdominal surgery

et al. 1997

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SummaryThe efficacy and safety of remifentanil and alfentanil for patients undergoing major abdominal surgery were compared. Premedicated patients received a loading dose of remifentanil (1.0 mg.kg ¹1 ; n ¼ 116) and a continuous infusion of 0.5 mg.kg ¹1 .min ¹1 , or a loading dose of alfentanil (25 mg.kg ¹1 ; n ¼ 118) and a continuous infusion of 1.0 mg.kg ¹1 .min ¹1 . Propofol was administered (10 mg every 10 s) until loss of consciousness. Patients' lungs were ventilated with 66% nitrous oxide and 0.5% (end-tidal) isoflurane in oxygen. The study drug infusion rate was reduced by 50% 5 min after intubation. Alfentanil was discontinued 15 min before the end of surgery, whereas remifentanil was continued in the immediate postoperative period at a reduced dose. Responses to intubation (28%) and skin incision (17%) occurred approximately twice as often in the alfentanil group (15% and 8%; p ¼ 0.014 and p ¼ 0.037, respectively). More patients receiving alfentanil had one or more responses to surgery (72% vs. 57%; p ¼ 0.016). The time to spontaneous respiration, adequate respiration, response to verbal command and time to recovery room discharge were similar. However, owing to decreased variability, the time to extubation was shorter with remifentanil than with alfentanil (p ¼ 0.048). There was a similar overall incidence of adverse events in both groups, 82% and 75% of patients, respectively. Adverse events associated with remifentanil were rapidly controlled by dose reductions. The incidence of intra-operative hypotension and bradycardia was higher in the remifentanil group (p Յ 0.033). An initial remifentanil infusion rate of 0.1 mg.kg ¹1 .min ¹1 titrated to individual need provided postoperative pain relief in the presence of adequate respiration in 71% of patients. When using remifentanil in the immediate postoperative setting, rapid administration of bolus doses and infusion rate increases resulted in a relatively high incidence of muscle rigidity, respiratory depression and apnoea. Changing the postoperative regimen to avoid rapid changes in remifentanil blood concentration resulted in more effective analgesia and dramatically reduced the incidence of adverse events during this period. In patients undergoing major abdominal surgery, remifentanil appears to offer superior intra-operative haemodynamic stability during stressful surgical events compared with alfentanil without compromising recovery from anaesthesia. Remifentanil can be administered as a postoperative analgesic agent at a starting dose of 0.1 mg.kg ¹1 .min ¹1 ; however, it should only be used in the presence of adequate supervision and monitoring of the patient. Administration of bolus doses is not recommended in this setting.

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confidence: 99%

A comparison of remifentanil and alfentanil in patients undergoing major abdominal surgery

et al. 1997

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“…As médias das concentrações plasmáticas residuais de fentanil variaram entre 1,7 e 1,1 ng.ml 1º PO: primeiro dia de pós-operatório, 2º PO: segundo dia de pós-operatório, IC95%: intervalo de confiança 95%; * significância estatística, teste de Wilcoxon, p < 0, 05 A dor (mediana) mensurada pela escala numérica verbal variou de 1,9 a 3 no primeiro dia e de 3,7 a 2,1 no segundo dia de pós-operatório, sem significância estatística (teste de Wilcoxon, p < 0,05) conforme ilustra a figura 1 e tabela II. Correlacionou-se a intensidade da dor com a concentração plasmática residual de fentanil através da curva de Efeito versus Concentração no período pós-operatório, obtendo coeficientes de correlação de 0,04 para o primeiro dia e 0,0002 para o segundo dia de pós-operatório conforme a figura 2.…”

Section: Resultsunclassified

Efeito analgésico residual do fentanil em pacientes submetidos a revascularização do miocárdio com circulação extracorpórea

Issy

Espada

Sakata

et al. 2002

Rev. Bras. Anestesiol.

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“…Studies were included if they contained relevant PK parameters or models, established routes of administration, and patients younger than 18 years of age. Identified studies and case reports were reviewed so that only those Table 1 Overview of pharmacological properties of fentanyl and its derivatives [3,4,14,15,52,112,[173][174][175][176][177][178][179][180] 1.7 ± 0.2 (2.5-3.0)…”

Section: Comprehensive Reviewmentioning

confidence: 99%

“…A rebound phenomenon was described in half of the patients owing to tissue redistribution. Furthermore, half-life was prolonged in neonates with markedly increased intraabdominal pressure (1.5-3 times the population mean of 317 min), which may have compromised the blood flow in the splanchnic Table 2 continued N Age Weight (kg) Dose (lg/kg) Route CL (mL/ min/kg) Results were switched by mistake in the publication Table 4 Pharmacokinetic information on alfentanil in children [13, 131, 132, 134-137, 142-144, 148, 149, 188, 190, 191] [148] veins to the portal vein [30] impacting fentanyl metabolism [4,31]. In neonates and infants during non-cardiac surgery, CL increased with age, with the most rapid increase at a postnatal age of 2 weeks, whereas V d and half-life did not change after a bolus of 54.1 ± 2.3 lg/kg [32].…”

Section: Intravenous Fentanylmentioning

confidence: 99%

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Correction to: Pharmacokinetics of Fentanyl and Its Derivatives in Children: A Comprehensive Review

et al. 2017

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Fentanyl and its derivatives sufentanil, alfentanil, and remifentanil are potent opioids. A comprehensive review of the use of fentanyl and its derivatives in the pediatric population was performed using the National Library of Medicine PubMed. Studies were included if they contained original pharmacokinetic parameters or models using established routes of administration in patients younger than 18 years of age. Of 372 retrieved articles, 44 eligible pharmacokinetic studies contained data of 821 patients younger than 18 years of age, including more than 46 preterm infants, 64 full-term neonates, 115 infants/toddlers, 188 children, and 28 adolescents. Underlying diagnoses included congenital heart and pulmonary disease and abdominal disorders. Routes of drug administration were intravenous, epidural, oral-transmucosal, intranasal, and transdermal. Despite extensive use in daily clinical practice, few studies have been performed. Preterm and term infants have lower clearance and protein binding. Pharmacokinetics was not altered by chronic renal or hepatic disease. Analyses of the pooled individual patients' data revealed that clearance maturation relating to body weight could be best described by the Hill function for sufentanil (R 2 = 0.71, B max 876 mL/min, K 50 16.3 kg) and alfentanil (R 2 = 0.70, B max (fixed) 420 mL/min, K 50 28 kg). The allometric exponent for estimation of clearance of sufentanil was 0.99 and 0.75 for alfentanil clearance. Maturation of remifentanil clearance was described by linear regression to bodyweight (R 2 = 0.69). The allometric exponent for estimation of remifentanil clearance was 0.76. For fentanyl, linear regression showed only a weak correlation between clearance and bodyweight in preterm and term neonates (R 2 = 0.22) owing to a lack of data in older age groups. A large heterogeneity regarding study design, clinical setting, drug administration, laboratory assays, and pharmacokinetic estimation was observed between studies introducing bias into the analyses performed in this review. A limitation of this review is that pharmacokinetic data, based on different modes of administration, dosing schemes, and parameter estimation methods, were combined.The online version of the original article can be found under

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Comparative Pharmacokinetics of Fentanyl and Alfentanil

Cited by 179 publications

References 4 publications

A comparison of remifentanil and alfentanil in patients undergoing major abdominal surgery

A comparison of remifentanil and alfentanil in patients undergoing major abdominal surgery

Efeito analgésico residual do fentanil em pacientes submetidos a revascularização do miocárdio com circulação extracorpórea

Correction to: Pharmacokinetics of Fentanyl and Its Derivatives in Children: A Comprehensive Review

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