RESUMO
OBJECTIVES: Ketamine offers a plausible mechanism with favorable kinetics in treatment of severe ethanol withdrawal. The purpose of this study is to determine if a treatment guideline using an adjunctive ketamine infusion improves outcomes in patients suffering from severe ethanol withdrawal. DESIGN: Retrospective observational cohort study. SETTING: Academic tertiary care hospital. PATIENTS: Patients admitted to the ICU and diagnosed with delirium tremens by Diagnostic and Statistical Manual of Mental Disorders V criteria. INTERVENTIONS: Pre and post guideline, all patients were treated in a symptom-triggered fashion with benzodiazepines and/or phenobarbital. Postguideline, standard symptom-triggered dosing continued as preguideline, plus, the patient was initiated on an IV ketamine infusion at 0.15-0.3 mg/kg/hr continuously until delirium resolved. Based upon withdrawal severity and degree of agitation, a ketamine bolus (0.3 mg/kg) was provided prior to continuous infusion in some patients. MEASUREMENTS AND MAIN RESULTS: A total of 63 patients were included (29 preguideline; 34 postguideline). Patients treated with ketamine were less likely to be intubated (odds ratio, 0.14; p < 0.01; 95% CI, 0.04-0.49) and had a decreased ICU stay by 2.83 days (95% CI, -5.58 to -0.089; p = 0.043). For ICU days outcome, correlation coefficients were significant for alcohol level and total benzodiazepine dosing. For hospital days outcome, correlation coefficients were significant for patient age, aspartate aminotransferase, and alanine aminotransferase level. Regression revealed the use of ketamine was associated with a nonsignificant decrease in hospital stay by 3.66 days (95% CI, -8.40 to 1.08; p = 0.13). CONCLUSIONS: Mechanistically, adjunctive therapy with ketamine may attenuate the demonstrated neuroexcitatory contribution of N-methyl-D-aspartate receptor stimulation in severe ethanol withdrawal, reduce the need for excessive gamma-aminobutyric acid agonist mediated-sedation, and limit associated morbidity. A ketamine infusion in patients with delirium tremens was associated with reduced gamma-aminobutyric acid agonist requirements, shorter ICU length of stay, lower likelihood of intubation, and a trend toward a shorter hospitalization.
Assuntos
Delirium por Abstinência Alcoólica/tratamento farmacológico , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Ketamina/uso terapêutico , Centros Médicos Acadêmicos , Adulto , Fatores Etários , Idoso , Benzodiazepinas/administração & dosagem , Quimioterapia Combinada , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Feminino , Humanos , Hipnóticos e Sedativos/uso terapêutico , Unidades de Terapia Intensiva , Ketamina/administração & dosagem , Tempo de Internação , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Functionally favorable survival remains low after out-of-hospital cardiac arrest. When initial interventions fail to achieve the return of spontaneous circulation, they are repeated with little incremental benefit. Patients without rapid return of spontaneous circulation do not typically survive with good functional outcome. Novel approaches to out-of-hospital cardiac arrest have yielded functionally favorable survival in patients for whom traditional measures had failed, but the optimal transition point from traditional measures to novel therapies is ill defined. Our objective was to estimate the dynamic probability of survival and functional recovery as a function of resuscitation effort duration to identify this transition point. METHODS AND RESULTS: Retrospective cohort study of a cardiac arrest database at a single site. We included 1014 adult (≥18 years) patients experiencing nontraumatic out-of-hospital cardiac arrest between 2005 and 2011, defined as receiving cardiopulmonary resuscitation or defibrillation from a professional provider. We stratified by functional outcome at hospital discharge (modified Rankin scale). Survival to hospital discharge was 11%, but only 6% had a modified Rankin scale of 0 to 3. Within 16.1 minutes of cardiopulmonary resuscitation, 89.7% (95% confidence interval, 80.3%-95.8%) of patients with good functional outcome had achieved return of spontaneous circulation, and the probability of good functional recovery fell to 1%. Adjusting for prehospital and inpatient covariates, cardiopulmonary resuscitation duration (minutes) is independently associated with favorable functional status at hospital discharge (odds ratio, 0.84; 95% confidence interval, 0.72-0.98; P=0.02). CONCLUSIONS: The probability of survival to hospital discharge with a modified Rankin scale of 0 to 3 declines rapidly with each minute of cardiopulmonary resuscitation. Novel strategies should be tested early after cardiac arrest rather than after the complete failure of traditional measures.