Optimising the dose of clonidine to achieve sedation in intensive care unit patients with population pharmacokinetics.

AIMS: The aim of this study was to investigate the population pharmacokinetics (PK) of clonidine in intensive care unit (ICU) patients in order to develop a dosing regimen for sedation. METHODS: We included 24 adult mechanically ventilated, sedated patients from a mixed medical and surgical ICU. Intravenous clonidine was added to standard sedation in doses of 600, 1200 or 1800 µg/d. Within each treatment group, 4 patients received a loading dose of half the daily dose administered in 4 hours. Patients gave an average of 12 samples per individual. In total, 286 samples were available for analysis. Model development was conducted with NONMEM and various covariates were tested. After modelling, doses to achieve a target steady-state plasma concentration of >1.5 µg/L were explored using stochastic Monte Carlo simulations for 1000 virtual patients. RESULTS: A 2-compartment model was the best fit for the concentration-time data. Clearance (CL) increased linearly with 0.213%/h; using allometric scaling, body weight was a significant covariate on the central volume of distribution (V1). Population PK parameters were: CL 17.1 (L/h), V1 124 (L/70 kg), intercompartmental CL 83.7 (L/h), and peripheral volume of distribution 178 (L), with 33.3% CV interindividual variability on CL and 66.8% CV interindividual variability on V1. Simulations revealed that a maintenance dose of 1200 µg/d provides target sedation concentrations of >1.5 µg/L in 95% of the patients. CONCLUSION: A population PK model for clonidine was developed in an adult ICU. A dosing regimen of 1200 µg/d provided a target sedation concentration of >1.5 µg/L.

In vivo Elimination of Clonidine by Continuous Venovenous Hemofiltration in Critically Ill Patients.

BACKGROUND: Clonidine is an α2-agonist that is commonly used for sedation in the intensive care unit. When patients are on continuous venovenous hemofiltration (CVVH) in the presence of kidney dysfunction, the sieving coefficient of clonidine is required to estimate how much drug is removed by CVVH. In the present study, we measured the sieving coefficient of clonidine in critically ill, ventilated patients receiving CVVH. METHODS: A total of 20 samples of plasma and ultrafiltrate of 3 patients on CVVH, using a standard 1.5 m2 polyacrylonitrile AN69 membrane, during continuous clonidine infusion were collected. After correction for the effect of predilution, we calculated the sieving coefficient for clonidine. RESULTS: The mean sieving coefficient of clonidine was 0.52 (SD 0.097). CONCLUSION: Using a polyacrylonitrile AN69 membrane in a CVVH machine, the in vivo sieving coefficient of clonidine was 0.52.

[Strychnine poisoning: uncommon, but does still happen]. / Strychnine-intoxicatie: zeldzaam maar niet verdwenen.

BACKGROUND: Acute strychnine poisoning is an uncommon form of intoxication, characterized by severe tonic clonic seizures and tetanus-like contractions while the patient is fully conscious. It can result in respiratory failure, leading to death. CASE DESCRIPTION: A 47-year-old man was admitted to the casualty department 2 hours after self-poisoning with strychnine. The clinical picture consisted of persistent seizures, which were treated with midazolam and propofol. The patient went into respiratory failure and asystole, so intubation and cardiac massage were initiated. Other complications were severe metabolic acidosis, hyperthermia and rhabdomyolysis with renal failure. The treatment consisted of cooling, hyperhydration and intravenous administration of sodium bicarbonate. He was discharged to a mental care institution with no persistent symptoms 11 days later. CONCLUSION: Early aggressive treatment of a strychnine intoxication can be life-saving. Knowledge of the clinical picture and the right treatment is important. Treatment is primarily focussed on stopping the convulsions and securing the airway.