NCT02399397

Influence of Age, Sepsis and SLCO1A2 Polymorphisms on Rocuronium Pharmacokinetics

Influence of Sepsis, Age and SLCO1A2 Genetic Polymorphisms on Rocuronium Pharmacokinetics-pharmacodynamics in ASA I-III Surgical Patients

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 36 (actual)
• Sponsor: Universidade Estadual Paulista Júlio de Mesquita Filho · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study aims to evaluate the influence of age and sepsis on in vivo activity of OATP1A2 using rocuronium (ROC) as a probe and evaluating the pharmacokinetics and pharmacodynamics in ASA I-III surgical patients. Thus, adult patients without sepsis (control group, n= 12), adult patients with sepsis (sepsis group, n= 12) and elderly patients without sepsis (elderly group, n= 12), all submitted to small to medium-sized surgeries who were induced with individual doses of rocuronium, fentanyl and propofol are being investigated.

Detailed description

Rocuronium (ROC), a neuromuscular blocking agent used in surgical procedures, is primarily eliminated by biliary excretion. Its distribution to the liver, mediated the organic anion transporting polypeptide 1A2 (OATP1A2), is a determining factor for the duration of neuromuscular blockade. Age and release of cytokines during inflammation and infection processes of sepsis can alter expression of SLCO1A2 gene, encoding OATP1A2. The objective of this study is to evaluate the influence of age and sepsis on in vivo activity of OATP1A2 using ROC as a probe and evaluating the pharmacokinetics and pharmacodynamics in ASA I-III surgical patients. Adult patients without sepsis (control group, n=12), adult patients with sepsis (sepsis group, n=12) and elderly patients without sepsis (elderly group, n=12), all submitted to small to medium-sized surgeries are being investigated. All patients are being induced with individual doses of rocuronium, fentanyl and propofol. Serial blood samples are being collected up to 360 minutes after administration of ROC. Neuromuscular blockade induced by ROC is monitored by stimulation of the adductor muscle of the thumb on the ulnar nerve through the train of four monitoring (TOF) at the same times of blood sampling. The plasma concentration of ROC will be analyzed by liquid chromatography coupled to mass spectrometry with electrospray ionization using positive ion mode.

Conditions

• Sepsis
• Systemic Inflammatory Response Syndrome
• Septic Shock

Interventions

Type	Name	Description
PROCEDURE	Serial blood sampling	Serial blood samples are being collected at times 0, 2, 5, 10, 15, 20, 30, 60, 120, 180, 240 and 360 minutes after rocuronium administration.
PROCEDURE	Train of four monitoring	Neuromuscular blockade is being evaluated at the same time of blood sampling by stimulation of the adductor muscle of the thumb on the ulnar nerve through the train of four monitoring (TOF).
PROCEDURE	Blood testing for liver and renal function	Blood testing: urea, creatinine, aspartate aminotransferase, alanine aminotransferase, albumin, glycemia
DRUG	General anesthesia	All patients were induced with individual intravenous doses of midazolam, rocuronium, fentanyl and propofol.
PROCEDURE	Small to medium sized surgery under general anesthesia	Patients classified according American Society of Anesthesiologists (ASA) as ASA I-III and submitted to small-medium sized surgery under general anesthesia were recruited for the present investigation.

Timeline

• Start date: 2014-02-01
• Primary completion: 2015-12-01
• Completion: 2015-12-01
• First posted: 2015-03-26
• Last updated: 2017-01-25

Locations

1 site across 1 country: Brazil