Treatment of Persistent Pulmonary Hypertension of the Newborn: Use of Pulmonary Vasodilators in Term Neonates.

Persistent pulmonary hypertension of the newborn (PPHN) represents a challenging condition associated with significant morbidity. A successful transition from intrauterine to extrauterine life is contingent on adequate pulmonary vasodilation. Several pathophysiologies contribute to the failure of this cascade and may result in life-threatening hypoxia and acidosis in the newborn. Management includes optimal respiratory support, adequate sedation and analgesia, and support of vascular tone and cardiac function. Pulmonary vasodilation has the potential to overcome the cycle of hypoxia and acidosis, improving outcome in these infants. Oxygen and inhaled nitric oxide represent the foundation of therapy. Tertiary pulmonary vasodilators represent a greater challenge, selecting between therapies that include prostanoids, sildenafil, and milrinone. Variable levels of evidence exist for each agent. Thorough review of available data informing efficacy and adverse effects contributes to the development of an informed approach to neonates with refractory PPHN.

Assessment and Management of Delirium in the Pediatric Intensive Care Unit: A Review.

Many critically ill patients suffer from delirium which is associated with significant morbidity and mortality. There is a paucity of data about the incidence, symptoms, or treatment of delirium in the pediatric intensive care unit (PICU). Risk factors for delirium are common in the PICU including central nervous system immaturity, developmental delay, mechanical ventilation, and use of anticholinergic agents, corticosteroids, vasopressors, opioids, or benzodiazepines. Hypoactive delirium is the most common subtype in pediatric patients; however, hyperactive delirium has also been reported. Various screening tools are validated in the pediatric population, with the Cornell Assessment of Pediatric Delirium (CAPD) applicable to the largest age range and able to detect signs and symptoms consistent with both hypo- and hyperactive delirium. Treatment of delirium should always include identification and reversal of the underlying etiology, reserving pharmacologic management for those patients without symptom resolution, or with significant impact to medical care. Atypical antipsychotics (olanzapine, quetiapine, and risperidone) should be used first-line in patients requiring pharmacologic treatment owing to their apparent efficacy and low incidence of reported adverse effects. The choice of atypical antipsychotic should be based on adverse effect profile, available dosage forms, and consideration of medication interactions. Intravenous haloperidol may be a potential treatment option in patients unable to tolerate oral medications and with significant symptoms. However, given the high incidence of serious adverse effects with intravenous haloperidol, routine use should be avoided. Dexmedetomidine should be used when sedation is needed and when clinically appropriate, given the positive impact on delirium. Additional well-designed trials assessing screening and treatment of PICU delirium are needed.

Early Post-traumatic Seizure Occurrence in Pediatric Patients Receiving Levetiracetam Prophylaxis With Severe Traumatic Brain Injury.

OBJECTIVE: Although levetiracetam is used for the prevention of early Post-traumatic seizures (EPTS) after traumatic brain injury (TBI), limited data exist describing the incidence of seizures in pediatric patients receiving levetiracetam prophylaxis. The objective of this research is to evaluate the prevalence of EPTS in children given prophylactic levetiracetam after severe TBI. METHODS: This study was conducted at a Level 1 pediatric trauma center and included pediatric patients with severe TBI who received levetiracetam for EPTS prophylaxis. Demographics and clinical information were retrospectively collected and evaluated. The primary outcome was prevalence of clinical or electrographic seizures within 7 days of initial injury as noted in the EMR. RESULTS: In 4 of 44 patients (9%), seizures developed despite levetiracetam prophylaxis. Concurrent use of other medications with antiepileptic properties was common (91%). There were no differences in demographic or baseline clinical characteristics between the group of patients experiencing seizures and those who did not. However, craniotomy was significantly more common in the seizure group (75% vs. 18%, p = 0.03). CONCLUSIONS: Children receiving prophylaxis with levetiracetam after severe TBI had a lower incidence of seizures (9%) than had previously been reported in the literature (18%). Given the limited literature available supporting the use of levetiracetam for the prevention of EPTS in children experiencing severe TBI, further study is needed to support routine use.

Acetaminophen Serum Concentrations in Infants Treated Intravenously for Patent Ductus Arteriosus.

OBJECTIVE: Although acetaminophen has emerged as a therapeutic option for treating hemodynamically significant patent ductus arteriosus (PDA) in preterm infants, limited data exist on pharmacodynamics. The objective of this research is to report serum acetaminophen concentrations at steady state in infants treated with intravenous acetaminophen for PDA and to examine associations with clinical outcomes. METHODS: This retrospective study evaluated all infants admitted during the study period who received intravenous acetaminophen for the treatment of PDA. Acetaminophen dosing was 15 mg/kg every 6 hours. A serum acetaminophen concentration was obtained 4 hours after the eighth dose. Associations between serum concentrations and efficacy, assessed by ductal constriction on echocardiogram, and safety, assessed by serum creatinine and hepatic transaminases, were explored using simple linear regression. RESULTS: A total of 36 infants were included, with a median birth weight of 720 g (IQR 585-895 g) and a median gestational age of 25 weeks (IQR 24-26 weeks). The median acetaminophen concentration in the cohort was 12.3 mg/L (IQR 6.7-16.5 mg/L; range, 1.1-29.0 mg/L). Serum acetaminophen concentrations did not correlate with infant demographics, hepatic transaminases during treatment, or duct size at treatment completion. We observed ductal closure across a wide range of serum acetaminophen concentrations. CONCLUSIONS: We did not identify an association between acetaminophen serum concentrations following intravenous therapy and ductal response or hepatic toxicity.

Pain Management in Pediatric Chronic Kidney Disease.

Pain is a common problem in children with chronic kidney disease (CKD); however, limited data exist regarding its management. Although most pain is managed pharmacologically, in some instances non-pharmacologic management can aid in safely ameliorating discomfort. Because of the accumulation of toxic metabolites, many common pain medications have adverse effects on kidney function or altered pharmacokinetics in the setting of CKD. Decreased clearance impacts safe dosing of analgesics. The pain management of patients on renal replacement therapy requires an understanding of drug clearance due to the different modalities of dialysis. This educational review highlights pain medications that are safe, albeit often with adjusted dosing, as well as drugs best avoided in the management of pediatric kidney disease. Acetaminophen should be used as a first-line therapy for pain management in children with CKD. Opioids may be added to control moderate to severe pain. Although data are currently lacking, buprenorphine holds promise as a potentially useful drug for the treatment of pain in pediatric patients with CKD. The addition of adjuvant pain medications and non-pharmacologic therapies maybe also be helpful. Despite these options, pain often remains difficult to treat in children with CKD.

Acetaminophen for Patent Ductus Arteriosus in Extremely Low-Birth-Weight Neonates.

OBJECTIVE: Although non-steroidal anti-inflammatory drugs (NSAIDs) are the current standard therapy for the treatment of patent ductus arteriosus (PDA), many neonates have contraindications to receiving or may fail NSAID therapy. To avoid surgical ligation, these patients may benefit from an alternative therapy. The objective of this research is to report the efficacy and safety of acetaminophen for the treatment of PDA in a cohort of premature neonates. METHODS: Demographics and clinical course were retrospectively evaluated for all neonates admitted during the study period who received acetaminophen for the treatment of PDA. Initial acetaminophen dosing was 15 mg/kg every 6 hours (88% intravenous). Efficacy was analyzed from ductal constriction on echocardiogram as well as need for further PDA treatment. Markers of hepatic and renal function as well as respiratory support and neonatal morbidities were evaluated to describe the safety of acetaminophen. RESULTS: Forty-one neonates were identified with a median birth weight of 760 g (IQR 614-948 g) and median gestational age of 25 weeks (IQR 24-27 weeks). Treatment was initiated at a median postnatal age of 15 days (IQR 8-19 days) for a median duration of 7 days (IQR 6-10 days). Twenty-seven neonates (66%) required no further PDA treatment, with echocardiographic PDA closure documented in 10 neonates (24%) and reduced ductal size in 15 neonates (37%). No clinically significant adverse effects attributable to acetaminophen therapy were detected. CONCLUSIONS: Most patients in this study responded to acetaminophen treatment for PDA, indicating that this therapy may be an option for extremely low-birth-weight neonates in order to avoid surgical ligation.