Advantages and disadvantages of etomidate use for intubation of patients with sepsis.

Etomidate is a potent imidazole hypnotic used widely in single doses in the rapid sequence intubation of critically ill patients with sepsis due to its presumed hemodynamic safety, fast onset, and short duration of action. However, the literature is conflicting regarding the hemodynamic advantages of etomidate over other induction agents, and its safety in this population is a matter of strong debate in the critical care community as the drug is associated with suppression of adrenal steroidogenesis, which can last up to 72 hours after a single dose, primarily through potent inhibition of the 11ß-hydroxylase enzyme. However, the clinical impact of this adrenal suppressive effect is not certain. The use of continuous-infusion etomidate in critically ill patients was abandoned more than 20 years ago due to reports of increased mortality. Nevertheless, mortality data of single-dose etomidate are still controversial, with no strong evidence of benefit over other agents and a tendency toward harm (keeping in mind the limitations of the available literature). Proponents of single-dose etomidate use in patients with sepsis suggest that the increased mortality associated with etomidate is merely a reflection of the patients' severity of illness and not related to the drug itself, whereas others believe that the drug causes true harm and increases mortality in this population. In view of the lack of a clear clinical advantage of etomidate over other agents used in rapid sequence intubation, it would be prudent to favor other agents until further conclusive evidence of etomidate safety is available in critically ill patients with sepsis.

Etomidate and mortality in cirrhotic patients with septic shock.

BACKGROUND: Clinical effects and outcomes of a single dose etomidate prior to intubation in the intensive care setting is controversial. The aim of this study is to evaluate the association of a single dose effect of etomidate prior to intubation on the mortality of septic cirrhotic patients and the impact of the subsequent use of low dose hydrocortisone. METHODS: This is a nested-cohort study within a randomized double blind placebo controlled study evaluating the use of low dose hydrocortisone in cirrhotic septic patients. Cirrhotic septic patients ≥ 18 years were included in the study. Patients who received etomidate prior to intubation were compared to those who did not receive etomidate for all cause 28-day mortality as a primary outcome. RESULTS: Sixty two intubated patients out of the 75 patients randomized in the initial trial were eligible for this study. Twenty three of the 62 intubated patients received etomidate dose prior to intubation. Etomidate use was not associated with all cause 28-day mortality or hospital mortality but was associated with significantly higher ICU mortality (91% vs. 64% for etomidate and controls groups, respectively; p = 0.02). Etomidate patients who received subsequent doses of hydrocortisone required lower doses of vasopressors and had more vasopressor-free days but no improvement in mortality. CONCLUSIONS: In this group of septic cirrhotic patients with very high mortality, etomidate increased ICU mortality. Subsequent use of hydrocortisone appears to have no benefit beyond decreasing vasopressor requirements. The lowest mortality was observed in patients who did not receive etomidate but received hydrocortisone.

Clinical experience with alteplase in the management of intracardiac and major cardiac vessels thrombosis in pediatrics: a case series.

BACKGROUND AND OBJECTIVES: Experience with alteplase in pediatric patients is limited and recommendations are extrapolated from adult data. Comprehensive guidelines on the management of thromboembolic events in this group are lacking. We assessed the efficacy and safety of alteplase (recombinant tissue plasminogen activator) in the management of intracardiac and major cardiac vessel thrombosis in pediatric patients. METHODS: All pediatric patients, 14 years of age and younger, with intracardiac or major cardiac vessel thrombus who were treated with alteplase from 1997 to 2004 at our tertiary care institute were identified through the pharmacy database. Patient data were retrospectively evaluated for the efficacy and safety of altepase. RESULTS: Five cases were eligible out of nineteen who received alteplase. Patient ages ranged from 40 days to 13 years. The initial dose of alteplase ranged from 0.3 to 0.6 mg/kg followed by a continuous infusion in three patients with a dosage range between 0.05 and 0.5 mg/kg/hr, while intermittent infusion was used in the other two patients. The duration of therapy ranged from 2 to 4 days. By the end of the treatment, two patients had complete resolution of thrombus and one had partial resolution. Two patients failed to respond and had "old" thrombus. Major bleeding events were reported in three patients. The rest had minor bleeding events. CONCLUSION: Alteplase may effectively dissolve intracardiac thrombi, particularly when freshly formed. Continuous infusion for a long duration appears to be associated with an increased risk of major bleeding. Optimal dose and duration of infusion are still unknown.