Outcomes and Adverse Effects With Peramivir for the Treatment of Influenza H1N1 in Critically Ill Pediatric Patients.

OBJECTIVES: Influenza is an environmental pathogen and infection presents as a range from asymptomatic to fulminant illness. Though treatment is supportive, antiviral agents have a role in the management of infection. Pediatric use of peramivir is largely based on reports and extrapolations of pharmacokinetic data. We seek to describe efficacy and safety of peramivir in critically ill pediatric patients. METHODS: This is a retrospective, institutional review board-approved chart review of all patients under 21 years of age, admitted to the PICU, and treated with peramivir for influenza H1N1 infection between January 1, 2016, and March 31, 2016, at a single-center, 12-bed PICU. The primary outcome was time to sustained resolution of fever; secondary outcomes included dose, duration, and adverse effects of peramivir therapy. RESULTS: Seven patients were included with median age of 3.7 years. Median time to sustained resolution of fever was 49.3 hours, median duration of mechanical ventilation was 14.2 days, median ICU LOS was 18.7 days, and hospital LOS was 24.7 days. No patients suffered mortality. Three patients experienced leukopenia, one of which experienced a concurrent neutropenia. Three patients experienced hyperglycemia, 2 experienced hypertension, 1 experienced increased aspartate aminotransferase and increased alanine aminotransferase, and 1 experienced diarrhea. All adverse events assessed were classified as possible using published adverse event causality assessments. CONCLUSIONS: Peramivir has been shown to be an effective therapy for the treatment of influenza H1N1 in critically ill pediatric patients. In our experience with 7 pediatric patients, peramivir was well tolerated at typical durations of therapy; however, increased vigilance is warranted during prolonged courses or in patients with reasons for altered pharmacokinetics and pharmacodynamics.

Successful Phenobarbital Desensitization After DRESS Reaction in the Management of Refractory Status Epilepticus.

PURPOSE: Drug reaction with eosinophilia and systemic symptoms (DRESS) is associated with antiepileptic drug use and is a rare but life-threatening side effect. We present a case of phenobarbital-induced DRESS in a patient who subsequently required phenobarbital and was successfully desensitized. SUMMARY: A 5-year-old male presented with medically refractory status epilepticus (SE). He had been trialed on several antiepileptic medications without achieving burst suppression. Burst suppression was achieved with a pentobarbital infusion, and thus, phenobarbital was initiated as the pentobarbital was weaned. After five days of phenobarbital, the patient developed signs and symptoms concerning for DRESS; a punch biopsy confirmed the drug reaction. Two months later, he again developed SE unresponsive to antiepileptic infusions. Burst suppression was achieved with pentobarbital, and it was decided to transition the patient to phenobarbital. Due to concerns of phenobarbital-induced DRESS, the patient underwent a phenobarbital desensitization consisting of 6 doses sequentially administered in 10-fold increasing concentrations before achieving therapeutic dosing. Three days later, the patient achieved therapeutic phenobarbital levels, was weaned off of pentobarbital, and remained seizure-free without recurrence of DRESS. CONCLUSIONS: Graded desensitization may be an option to minimize recurrence of DRESS in patients where avoidance of the offending agent is not possible.

Adverse drug reactions in therapeutic hypothermia after cardiac arrest.

BACKGROUND: Therapeutic hypothermia (TH) improves survival and neurologic function in comatose survivors of cardiac arrest. Many medications used to support TH have altered pharmacokinetics and pharmacodynamics during this treatment. It is unknown if or at what frequency the medications used during TH cause adverse drug reactions (ADRs). METHODS: A retrospective chart review was conducted for patients admitted to an intensive care unit (ICU) after cardiac arrest and treated with TH from January 2009 to June 2012 at two urban, university-affiliated, tertiary-care medical centres. Medications commonly used during TH were screened for association with significant ADRs (grade 3 or greater per Common Terminology Criteria for Adverse Events) using three published ADR detection instruments. RESULTS: A total of 229 patients were included, the majority being males with median age of 62 presenting with an out-of-hospital cardiac arrest in pulseless electrical activity or asystole. The most common comorbidities were hypertension, coronary artery disease, and diabetes mellitus. There were 670 possible ADRs and 69 probable ADRs identified. Of the 670 possible ADRs, propofol, fentanyl, and acetaminophen were the most common drugs associated with ADRs. Whereas fentanyl, insulin, and propofol were the most common drugs associated with a probable ADR. Patients were managed with TH for a median of 22 hours, with 38% of patients surviving to hospital discharge. CONCLUSIONS: Patients undergoing TH after cardiac arrest frequently experience possible adverse reactions associated with medications and the corresponding laboratory abnormalities are significant. There is a need for judicious use and close monitoring of drugs in the setting of TH until recommendations for dose adjustments are available to help prevent ADRs.

Pharmacokinetics of Peramivir in an Adolescent Patient Receiving Continuous Venovenous Hemodiafiltration.

Critically ill patients requiring renal replacement therapy commonly experience pharmacokinetic alterations. This case report describes the pharmacokinetics of peramivir (Rapivab, BioCryst Pharmaceuticals, Inc, Durham, NC), the first US Food and Drug Administration-approved intravenous neuraminidase inhibitor for the treatment of influenza, in an adolescent patient receiving continuous renal replacement therapy (CRRT). A 49.5-kg, 17-year-old Caucasian female presented with fever, cough, and persistent hypoxia. She quickly progressed to acute respiratory and renal failure in the setting of viral septic shock as a result of a severe influenza H1N1 infection. On hospital day 3, therapy was switched from oseltamivir (Tamiflu, Roche Laboratories Inc, Nutley, NJ) to peramivir owing to the concern for inadequate enteral absorption. On the third day of peramivir treatment, at a dose of 200 mg daily, peramivir serum concentrations revealed a smaller peak concentration, larger volumes of distribution, similar 24-hour area under the curve, and a shorter half-life as compared to adult patients with normal renal function. This illustrated the significant differences in pharmacokinetics when administered in the setting of CRRT. The patient had resolution of viral infection as evidenced by negative respiratory viral panel polymerase chain reaction at hospital day 14 and was eventually discharged at her baseline.

Evaluation of the Safety of Quetiapine in Treating Delirium in Critically Ill Children: A Retrospective Review.

OBJECTIVE: Quetiapine is an atypical antipsychotic that has been used off-label for the treatment of intensive care unit (ICU) delirium in the adult population, with studies demonstrating both efficacy and a favorable safety profile. Although there is a potential role for quetiapine in the treatment of pediatric ICU delirium, there has been no systematic reporting to date of safety in this patient population. METHODS: Pharmacy records were used to identify 55 consecutive pediatric ICU patients who were diagnosed with delirium and received quetiapine. A comprehensive retrospective medical chart review was performed to collect data on demographics, dosing, and side effects. RESULTS: Fifty patients treated between January 2013 and November 2014 were included, and five patients were excluded from the study. Subjects ranged in age from 2 months to 20 years. Median daily dose was 1.3 mg/kg/day, and median duration of treatment was 12 days. There were three episodes of QTc prolongation that were clinically nonsignificant with no associated dysrhythmia: Two resolved over time without intervention, and one resolved with decrease in quetiapine dosage. There were no episodes of extrapyramidal symptoms or neuroleptic malignant syndrome. CONCLUSIONS: In this population of critically ill youth, short-term use of quetiapine as treatment for delirium appears to be safe, without serious adverse events. Further research is required to assess efficacy and evaluate for long-term effects. A prospective, randomized, placebo-controlled study of quetiapine in managing pediatric delirium is necessary.

Effect of early mobilization on sedation practices in the neurosciences intensive care unit: a preimplementation and postimplementation evaluation.

INTRODUCTION: The use of sedation and analgesia protocols, daily interruption of sedation, and early mobilization (EM) have been shown to decrease duration of mechanical ventilation and hospital length of stay (LOS). METHODS: A retrospective chart review was conducted during a 6-month premobilization (pre-EM) and 6-month postmobilization (post-EM) period. Patients older than 18 years who were admitted to the neurosciences intensive care unit (ICU) and mechanically ventilated for at least 24 hours without documentation of withdrawal of life support or brain death were included. RESULTS: Thirty-one pre-EM and 37 post-EM patients were included. Baseline demographics were similar with the exception of more ischemic stroke patients in the pre-EM group (P < .05). In the pre-EM and post-EM groups, patients received similar cumulative doses of propofol, dexmedetomidine, and benzodiazepines but higher median (interquartile range) doses of opioids (50.0 [13.8-165.0] vs 173.3 [41.2-463.2] µg of fentanyl equivalents [P < .05]) in the post-EM group. Neurosciences ICU LOS was 10 (6-19) and 13 (8-18) days, respectively (P = .188). CONCLUSIONS: After implementation of an EM program, an increase in opioid use and no significant change in other sedatives were observed. Despite an increase in the amount of physical therapy and occupational therapy provided to patients, there was no change in hospital and ICU LOS or duration of mechanical ventilation.

Quetiapine as treatment for delirium in critically ill children: A case series.

Delirium occurs in a substantial number of critically ill children and may contribute to increased hospital length of stay, and short- and long-term morbidity. Children with delirium may benefit from early pharmacologic treatment. In this case series, we describe four critically ill children, ranging from eight months to 14 years of age, who were prescribed quetiapine as treatment for delirium. In all four patients, delirium improved within 24 hours of initiation of quetiapine. With proven efficacy in adults with delirium, an established track record in children for indications other than delirium, and a favorable safety profile, quetiapine may be a therapeutic option in treating delirium in critically ill children. The time has come for a prospective, blinded study of quetiapine as treatment for pediatric delirium.