thiopental and Critical-Illness

Thiopental is a thiobarbiturate given in the case of brain injuries to reduce intracranial pressure and to manage cerebral ischemia. A pharmacokinetic model has been described previously in critically ill patients with a different therapeutic strategy. New treatment options prompted us to investigate if drug-drug interactions occur. A new model is proposed describing the influence of concomitant administration of esomeprazole on the distribution of thiopental.. The study population comprised 52 critically ill patients (body weight 47.1-114 kg) aged 18-78 years who had been admitted into the critical care unit for treatment of intracranial hypertension. A total mean dose of 282.8 ± 172.7 mg/kg was given in 96 ± 72 h. Pharmacokinetic analysis was performed by using a nonlinear mixed-effect population model.. A one-compartment open model with first-order elimination identified two covariates, namely, body weight on clearance and volume of distribution, and the administration of esomeprazole on volume of distribution. The mean values (% relative standard error) for total clearance (CL) and for central volume of distribution (Vd) in patients with and without concomitant esomeprazole were 5.3 L/h (9.2 %) and 256.1 (6.4 %) and 153.2 l (19.2 %), respectively.. Based on these results, we conclude that concomitant administration of esomeprazole increases the volume of distribution and the half-live of thiopental. This drug-drug interaction should be considered when a target concentration has to be reached.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Brain Injuries; Critical Illness; Drug Interactions; Esomeprazole; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Models, Biological; Proton Pump Inhibitors; Thiopental; Young Adult

We compared the effects of single doses of etomidate and thiopentone on adrenocortical function in a randomised controlled clinical trial involving 35 critically ill patients who needed a general anaesthetic. Just before induction of anaesthesia, a baseline blood cortisol sample was taken. Twenty-four hours later we performed a short adrenocorticotrophic hormone stimulation test. No patient had a low cortisol level (< 160 nmol.l-1) at any time during the study. Baseline, pre-ACTH and post-ACTH cortisol levels were similar in the two groups. However, significantly more patients in the etomidate group had an ACTH-stimulated cortisol increment < 200 nmol.l-1. The clinical significance of these findings is not clear, but we conclude that single doses of etomidate may interfere with cortisol synthesis for at least 24 h in the critically ill.

Topics: Adolescent; Adrenal Cortex; Adrenal Cortex Function Tests; Adrenocorticotropic Hormone; Adult; Aged; Aged, 80 and over; Anesthesia, General; Anesthetics, Intravenous; Critical Care; Critical Illness; Etomidate; Female; Hospital Mortality; Humans; Hydrocortisone; Male; Middle Aged; Thiopental

Topics: COVID-19; Critical Illness; Humans; Respiration, Artificial; SARS-CoV-2; Thiopental

Topics: Anesthetics, Intravenous; Critical Illness; Emergency Medicine; Etomidate; Humans; Thiopental

To report the occurrence of life-threatening hyperkalaemia following treatment with therapeutic thiopentone coma.. The neurosurgical intensive care units of Royal North Shore Hospital and Liverpool Hospital, Sydney, Australia.. Three patients treated with theraputic thiopentone coma. One patient with raised intracranial pressure secondary to a severe traumatic brain injury and two patients with refractory vasospasm secondary to subarachnoid haemorrhage. Two of the three patients developed hypokalaemia on starting thiopentone, which was resistant to potassium supplementation. All three patients developed severe hyperkalaemia during the recovery phase of coma. This was life-threatening in all three patients and fatal in one.. Severe hypokalaemia refractory to potassium therapy may occur during therapeutic thiopentone coma. Severe rebound hyperkalaemia may occur after cessation of thiopentone infusion. Protocols for the management of patients with therapeutic barbiturate coma should recognise this potentially serious complication.

Topics: Adult; Australia; Brain Injuries; Coma; Critical Illness; Female; Glasgow Coma Scale; Humans; Hyperkalemia; Hypnotics and Sedatives; Male; Middle Aged; Subarachnoid Hemorrhage; Thiopental; Treatment Outcome

Since anesthetics are widely used in critically ill patients, this study investigates anesthetic effects on neutrophil and monocyte function concerning bacterial elimination in human whole blood.. The effects of thiopental (20 and 200 microg/ml), propofol (5 and 50 microg/ml), midazolam (0.15 and 1.5 microg/ml) and ketamine (3 and 30 microg/ml) on elimination of Escherichia (E.) coli from whole blood were investigated in vitro after incubation for 1 h in both clinical (1) (n=10) and 10-fold higher (h) (n=11) concentrations. These data were compared to neutrophil and monocyte phagocytosis (1; n=6) and burst activity (1; n=10, h; n=11), measured by flow cytometry. To enable quantification of the clearance process, a defined number of 10(5) colony forming units of E. coli were added to the blood assays and bacterial growth was determined.. All anesthetics delayed bacterial clearance from the blood in the 10-fold concentration (P<0.05). Thiopental (1+h) and propofol (h) suppressed neutrophil (59+/-3% and 38+/-6%) and monocytic (45+/-6% and 30+/-11%) oxidative burst (P<0.01). Phagocytosis was reduced even after propofol (1) in polymorphonuclear leukocytes (PMN) (34+/-9%; P<0.05) and monocytes (35+/-11%). Ketamine (h) prolonged bacterial elimination (P<0.01), which did correlate with inhibition of monocytic phagocytosis, by 26+/-14%. Midazolam application (h) resulted in an inhibition of PMN-respiratory burst by 19+/-6% (P<0.05) and impaired bacterial clearance (P<0.05).. Thiopental, propofol, midazolam and ketamine affect E. coli clearance and neutrophil and monocyte oxidative burst and phagocytosis in vitro only in high concentrations, while thiopental inhibited monocytic burst and propofol impaired PMN phagocytosis even in clinically used concentrations. These data suggest that i.v. anesthetics in concentrations recommended for general anesthesia seem to have minor influence on the investigated host defense mechanisms.

Topics: Adult; Anesthetics, Dissociative; Anesthetics, Intravenous; Bacteremia; Blood Bactericidal Activity; Colony Count, Microbial; Critical Illness; Escherichia coli; Flow Cytometry; Humans; Ketamine; Midazolam; Monocytes; Neutrophils; Phagocytosis; Propofol; Respiratory Burst; Thiopental