A Phase 4 interventional study of Serial blood sampling and Train of four monitoring in Sepsis, Systemic Inflammatory Response Syndrome and Septic Shock, sponsored by Universidade Estadual Paulista Júlio de Mesquita Filho. Completed at 1 site in Brazil. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-01-25.
Sponsored by Universidade Estadual Paulista Júlio de Mesquita Filho · Phase 4, Interventional, and Treatment
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.
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.
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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).
Procedure: Serial blood sampling · Procedure: Train of four monitoring · Procedure: Blood testing for liver and renal function · Drug: General anesthesia · Procedure: Small to medium sized surgery under general anesthesia
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).
Procedure: Serial blood sampling · Procedure: Train of four monitoring · Procedure: Blood testing for liver and renal function · Drug: General anesthesia · Procedure: Small to medium sized surgery under general anesthesia
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).
Procedure: Serial blood sampling · Procedure: Train of four monitoring · Procedure: Blood testing for liver and renal function · Drug: General anesthesia · Procedure: Small to medium sized surgery under general anesthesia
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.
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).
Also known as: TOF
Blood testing: urea, creatinine, aspartate aminotransferase, alanine aminotransferase, albumin, glycemia
All patients were induced with individual intravenous doses of midazolam, rocuronium, fentanyl and propofol.
Also known as: Midazolam, Rocuronium, Fentanyl, Propofol
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.
Determination of AUC/dose
Determination of area under the plasma concentration versus time curve (AUC)/dose of rocuronium will be estimated for pharmacokinetic analysis.
Time frame: Up to 6h after rocuronium administration
Determination of total clearance
Determination of total clearance of rocuronium will be estimated for pharmacokinetic analysis.
Time frame: Up to 6h after rocuronium administration
Determination of volume of distribution
Determination of volume of distribution of rocuronium will be estimated for pharmacokinetic analysis.
Time frame: Up to 6h after rocuronium administration
Determination of mean residence time
Determination of mean residence time of rocuronium will be estimated for pharmacokinetic analysis.
Time frame: Up to 6h after rocuronium administration
OATP1A2 genotyping using Real Time-PCR
The single nucleotide polymorphisms of SLCO1A2 gene (404A\>T, 559G\>A, 833delA at coding sequence and -1105G\>A, -1032G\>A, -715T\>C, -361G\>A e -189_-188insA at the non-coding sequence of SLCO1A2) are being evaluated in all included patients, using Real Time PCR.
Time frame: Up to 5 minutes before rocuronium administration
Analysis of cytokine IL-1α in plasma
Plasma cytokine Interleukin-1α (IL-1α) will be evaluated in each patient.
Time frame: Up to 5 minutes before rocuronium administration; 30 and 360 minutes after rocuronium administration
Analysis of cytokine IL-1β in plasma
Plasma cytokine IL-1β will be evaluated in each patient.
Time frame: Up to 5 minutes before rocuronium administration; 30 and 360 minutes after rocuronium administration
Analysis of cytokine IL-6 in plasma
Plasma cytokine IL-6 will be evaluated in each patient.
Time frame: Up to 5 minutes before rocuronium administration; 30 and 360 minutes after rocuronium administration
Analysis of cytokine TNF-α in plasma
Plasma cytokine Tumor Necrosis Factor-α (TNF-α) will be evaluated in each patient.
Time frame: Up to 5 minutes before rocuronium administration; 30 and 360 minutes after rocuronium administration
Pharmacokinetic-Pharmacodynamic analysis: relationship between rocuronium plasma concentration and the neuromuscular blockade
The relationship between rocuronium plasma concentration and the neuromuscular blockade will be described by a sigmoid maximum effect model for each patient
Time frame: Up to 6h after rocuronium administration
This study is completed, as verified in Oct 2016. You cannot join it, but the record below documents what was studied.
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Universidade Estadual Paulista Júlio de Mesquita Filho