Influence of Age, Sepsis and SLCO1A2 Polymorphisms on Rocuronium Pharmacokinetics (ROCSEPSIS)

Universidade Estadual Paulista Júlio de Mesquita Filho

Status and phase: Completed; Phase 4

Conditions: Systemic Inflammatory Response Syndrome; Septic Shock; Sepsis

Treatments: Procedure: Small to medium sized surgery under general anesthesia; Procedure: Serial blood sampling; Procedure: Train of four monitoring; Procedure: Blood testing for liver and renal function; Drug: General anesthesia

Study type: Interventional

Funder types: Other

Identifiers

NCT02399397

ROC1314730-0

Details and patient eligibility

About

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.

Full 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.

Enrollment: 36 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult and elderly patients, both gender.
• Patients submitted to small to medium-sized surgeries.
• Patients who were induced with individual doses of rocuronium, fentanyl and propofol.
• Patients with normal renal function (creatinine clearance > 60 mL/min).
• Patients with normal liver function.

Exclusion criteria

• Patients who were in use of fluoxetine, carbamazepine, aminoglycoside antibiotics, OATP1A2 inhibitors.
• Patients with gastrointestinal and liver diseases, neuromuscular disorders.
• Patients who were in chronic use of drugs which alter rocuronium effect.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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36 participants in 3 patient groups

Control group

Active Comparator group

Description:

Adult patients(18-50 years old) ASA I-II without sepsis submitted to small to medium sized surgery under general anesthesia are being recruited. All patients are being induced with individualized doses of rocuronium, midazolam, propofol and fentanyl. Serial blood sampling are being collected up to 6 h after administration of the drug for pharmacokinetic study. Neuromuscular blockade is being monitored by stimulation of the adductor muscle of the thumb on the ulnar nerve through the train of four monitoring (TOF) at the same time as blood sampling. All patients are being submitted to blood testing for liver and renal function (creatinine, urea, albumin, aspartate aminotransferase and alanine aminotransferase).

Treatment:

Procedure: Small to medium sized surgery under general anesthesia

Drug: General anesthesia

Procedure: Serial blood sampling

Procedure: Blood testing for liver and renal function

Procedure: Train of four monitoring

Sepsis group

Experimental group

Description:

Adult patients (18-50 years old) ASAII and III with sepsis, systemic inflammatory response syndrome or septic shock submitted to small to medium sized surgery under general anesthesia are being recruited. All patients are being induced with individualized doses of rocuronium, midazolam, propofol and fentanyl. Serial blood sampling are being collected up to 6 h after administration of the drug for pharmacokinetic study. Neuromuscular blockade is being monitored by stimulation of the adductor muscle of the thumb on the ulnar nerve through the train of four monitoring (TOF) at the same time as blood sampling. All patients are being submitted to blood testing for liver and renal function (creatinine, urea, albumin, aspartate aminotransferase and alanine aminotransferase).

Treatment:

Procedure: Small to medium sized surgery under general anesthesia

Drug: General anesthesia

Procedure: Serial blood sampling

Procedure: Blood testing for liver and renal function

Procedure: Train of four monitoring

Elderly group

Experimental group

Description:

Elderly patients (\> 65 years old) ASA I-II without sepsis submitted to small to medium sized surgery under general anesthesia are being recruited. All patients are being induced with individualized doses of rocuronium, midazolam, propofol and fentanyl. Serial blood sampling are being collected up to 6 h after administration of the drug for pharmacokinetic study. Neuromuscular blockade is being monitored by stimulation of the adductor muscle of the thumb on the ulnar nerve through the train of four monitoring (TOF) at the same time as blood sampling. All patients are being submitted to blood testing for liver and renal function (creatinine, urea, albumin, aspartate aminotransferase and alanine aminotransferase).

Treatment:

Procedure: Small to medium sized surgery under general anesthesia

Drug: General anesthesia

Procedure: Serial blood sampling

Procedure: Blood testing for liver and renal function

Procedure: Train of four monitoring