Unlicensed and Off-Label Medication Use in Pediatric and Neonatal Intensive Care Units: No Change Over a Decade.

INTRODUCTION: Many of the medications prescribed to children are off-label and/or unlicensed because pharmacologic evaluations have not been performed in this age group. METHODS: All drugs prescribed to patients admitted to the neonatal intensive care units (NICU) (n = 134) and pediatric intensive care units (PICU) (n = 56) during a 2-month observation period were recorded and classified according to patient age, drug license status, indicated use, and typical dosing, frequency and way of administration. Results were compared with prior data collected in 2002, from the same units. RESULTS: In the NICU, among the 1064 prescriptions for 49 medications, 312 (29.2%) were licensed and 63 (5.9%) unlicensed, and 693 (64.8%) were off-label use. For the neonates, 23.9% and 96.3% received at least one unlicensed medication and one off-label medication, respectively. While the difference in off-label use between the two time periods was not statistically significant, unlicensed medications were less frequently prescribed in 2016 (5.9 versus 16.6%, p = 0.001). Regarding the PICU, among the 388 prescriptions for 75 medications, 205 (52%) were licensed and 13 (3.4%) unlicensed, and 170 (43.8%) were off-label. In contrast, in 2002, none of the medications prescribed were unlicensed (p = 0.001). The number of off-label medications (41%) and number of PICU patients receiving at least one unlicensed/off-label medication in these two time periods (88.7% versus 90.5% for 2016 and 2002, respectively) were similar. CONCLUSIONS: The current study confirms the high prevalence of unlicensed and off-label drug use in a PICU and NICU setting. Compared with a similar study conducted in the same PICU in 2002, despite regulatory efforts conducted in this area, the prevalence of unlicensed medications was surprisingly higher.

Pharmacist Remote Review of Medication Prescriptions for Appropriateness in Pediatric Intensive Care Unit.

BACKGROUND: One aspect of ordering and prescribing medication is the requirement for a trained professional to review medication orders or prescriptions for appropriateness. In practice, this review process is usually performed by a clinical pharmacist. However, in many medical centers there is a shortage of staff and a pharmacist is not always available. OBJECTIVE: To determine whether remote review of medication orders by a pharmacist is a plausible method in a pediatric intensive care unit (PICU). METHODS: A pharmacist from the pharmacy department reviewed medication orders of patients admitted to our PICU over a 7-month period for appropriateness. A special form for medical orders was filled in and sent to the physician in the PICU, who replied informing whether the recommendation had been accepted. The time spent by the pharmacist for this activity was recorded. RESULTS: The review time for one medical record was 8.9 (95% CI, 6.9-10.9) min. Every additional drug prescribed increased the total review time by 0.8 (95% CI, 0.45-1.11) min. The pharmacist filled in 186 forms on 117 admissions for 109 children. The median review time was 15 (12.8-18.8) and 12 (9-15) min, respectively, for patients with psychiatric-neurologic disorders compared to those without (p = 0.032). Usually, a daily workload of 240 min was needed for the pharmacist accompanying the round in contrast to 108 min per day needed to review all the medical records in 95% of the cases. The physician accepted 51.2%, rejected 11.9%, and made no comment on 36.9% of the recommendations. CONCLUSION: Hospitals facing budget shortages can carry out focused remote reviews of prescriptions by the pharmacist.

Efficacy of oral ketamine compared to midazolam for sedation of children undergoing laceration repair: A double-blind, randomized, controlled trial.

OBJECTIVE: To assess the efficacy of oral ketamine versus oral midazolam for sedation during laceration repair at a pediatric emergency department. METHODS: Children between 1 and 10 years requiring laceration repair were randomly assigned to 2 groups, treated either with oral midazolam (0.7 mg/kg) or with oral ketamine (5 mg/kg).Main outcomes measured were level of pain during local anesthesia, as assessed by the parent on a 10-cm visual analog scale (VAS) and the number of children who required intravenous sedation. Secondary outcomes included VAS by physician, pain assessment by child, maximal sedation depth assessed by the University of Michigan Sedation Scale, time until University of Michigan Sedation Scale 2 or more, general satisfaction of a parent and treating physician, length of procedure, total sedation time, and the incidence of any adverse events. RESULTS: Sixty-eight children were recruited of which 33 were girls. Average age was 5.08 ±â€Š2.14 years. Thirty-seven children were treated with ketamine and 31 with midazolam. Parent-assessed VAS in ketamine treated patients was 5.07 ±â€Š0.75 compared with 3.68 ±â€Š0.7 in midazolam treated patients [mean difference = 1.39 95% confidence interval (CI) -0.47 to 3.26]. Twelve (32%) of the children treated with ketamine required the addition of IV sedation compared to only 2 children (6%) of the children treated with midazolam [odds ratio (adjusted for age and gender) 6.1, 95% CI: 1.2 to 30.5]. The rest of the measured variables were similar between the groups, with no statistical significance. DISCUSSION: No difference in the level of pain was found between ketamine and midazolam treated patients. Compared with oral midazolam (0.7 mg/kg), oral ketamine (5 mg/kg) was associated with higher rates of sedation failure, and thus is not recommended as a single agent for oral sedation in children requiring laceration repair.

A double-blind, randomised, placebo-controlled trial of oral midazolam plus oral ketamine for sedation of children during laceration repair.

OBJECTIVES: To compare the efficacy of oral midazolam alone with a combination of oral midazolam and ketamine in children requiring laceration repair. DESIGN: A randomised, double-blind, placebo-controlled study. SETTING: Paediatric emergency department. PARTICIPANTS: Children 1-10 years of age with lacerations requiring sedation. INTERVENTIONS: Using a computer-generated sequence, children were randomly assigned in blocks of four to one of two groups: oral midazolam (0.5 mg/kg) plus oral placebo and oral midazolam (0.5 mg/kg) plus oral ketamine (5 mg/kg). The allocation sequence was kept by the pharmacy staff, and the investigators were blinded to randomisation until statistical analysis of the study was completed. MAIN OUTCOME MEASURES: Visual Analogue Scale (VAS) assessment by a parent and Sedation Score assessment by an investigator. RESULTS: 60 children were recruited; 29 were assigned for treatment with midazolam and 31 for the combination of midazolam and ketamine. There were no differences in basic demographics and wound characteristics between the groups. VAS assessment by a parent was 4.5±3.3 mm in the midazolam+ketamine group versus 4.4±2.7 mm in the midazolam alone group (mean difference 0.1, CI -1.9 to 1.71). Sedation Score during procedure was lower in the midazolam+ketamine group (mean difference 1.14, 95% CI 0.67 to 1.6). Intravenous sedation was required in two (6%) of the children in the midazolam+ketamine group, and in eight (27%) in the midazolam alone group. p=0.039. No clinically significant adverse effects were documented in either group. CONCLUSIONS: No difference was found in pain assessment during local anaesthetic injection between the group treated with midazolam and ketamine, and the group treated with midazolam alone. The combination of oral midazolam and ketamine led to deeper sedation than midazolam alone, with less children requiring intravenous sedation. CLINICAL TRIAL REGISTRATION: The trial was registered in www.clinicaltrials.gov as NCT01470157.

Hepcidin in acute iron toxicity.

BACKGROUND: Hepcidin regulates extracellular iron concentration by inhibiting iron release from macrophages and preventing iron absorption in the intestine. Our objective was to evaluate the expression of hepcidin in the liver in acute iron poisoning in a rat model. METHODS: Male Wistar rats were assigned to group 1, who received 750 mg/kg elemental iron (LD(50)) by gavage, and group 2 (control), who received distilled water. Iron concentrations and liver transaminases were measured in the serum. Hepcidin messenger RNA levels were measured in the liver. RESULTS: Mean serum iron levels, aspartate aminotransferase, alanine aminotransferase, and uric acid were significantly higher in group 1 compared to group 2 (P < .0001, P = .01, P < .0001, and P = 0.0001, respectively). Hepcidin messenger RNA levels in the liver were significantly higher in the study group (P = .005). CONCLUSIONS: In acute iron intoxication, hepcidin expression in the liver significantly increased. Further studies are needed to determine whether hepcidin levels correlate with the severity of the intoxication.

Acute paralysis following recreational MDMA (Ecstasy) use.

Methylenedioxymethamphetamine (MDMA), commonly known as Ecstasy, is a hallucinogenic compound structurally related to amphetamine. Ecstasy's severe neurological toxicity includes seizures, subarachnoidal hemorrhage, cerebral infarction, intracranial bleeding and cerebral venous thrombosis. We describe the first case of spinal cord damage presenting as acute quadriplegia and respiratory insufficiency in a healthy adolescent following Ecstasy recreational usage.

Neuroleptic malignant syndrome in a child treated with an atypical antipsychotic.

Neuroleptic malignant syndrome (NMS) is an uncommon potentially fatal side effect of neuroleptic drugs, characterized by movement disorder, altered mental status and autonomic instability. A single dose of clotiapine was administered to an 11-year old male with acute psychosis. The previously healthy child had signs consistent with NMS including hyperthermia, hypertension, motor and mental changes. Repeat examination performed two weeks later, demonstrated that while his hyperthermia subsided, his mental status deteriorated. Olanzapine was administered, after which the child had hyperthermia, dystonia and more pronounced restlessness, once again consistent with NMS. He developed respiratory failure and was intubated and mechanically ventilated. Lorazepam, dantrolene and bromocriptine were administered as treatment of possible NMS. His mental condition, movement disorder and autonomic dysfunction improved significantly. Two weeks later, the patient was discharged in good general condition without the need for any ongoing medical treatment. There are only few case reports of NMS in children treated with olanzapine, an atypical antipsychotic. In children, caution must be exercised when prescribing antipsychotics, particularly atypical antipsychotics as these drugs may cause NMS. Because of the low incidence of NMS, a high index of suspicion is needed to identify cases so prompt treatment can be undertaken.