Cardiorespiratory stability in critically ill preterm infants following dexmedetomidine initiation.

OBJECTIVE: To evaluate cardiorespiratory status in preterm infants receiving dexmedetomidine using high-resolution physiologic data. STUDY DESIGN: We analyzed preterm infants with continuous heart rate (HR) and oxygen saturation (SpO2) data for 24 hours preceding and 48 hours following dexmedetomidine initiation. Invasive arterial blood pressure (ABP), when available, was analyzed. RESULTS: In 100 infants with mean gestational age of 28 weeks and high baseline illness severity, mean HR decreased from 152 to 141 beats per minute while mean SpO2 increased from 91% to 93% in the 48 hours after dexmedetomidine initiation (p<0.01). In 57 infants with continuous ABP monitoring, mean ABP increased from 40 to 42 mmHg (p=0.01). Vasoactive-inotropic support increased before and after initiation. CONCLUSIONS: We observed cardiorespiratory changes in critically ill preterm infants following dexmedetomidine initiation; mean HR decreased and mean SpO2 increased in the 48 hours after initiation. In a subset, mean ABP increased along with vasoactive-inotropic support.

The Impact of Dexmedetomidine Initiation on Cardiovascular Status and Oxygenation in Critically ill Neonates.

Dexmedetomidine is being increasingly used as a primary or adjunctive sedative agent in neonates. There are a paucity of high-quality, high-resolution physiologic data during administration, despite significant potential cardiorespiratory effects. Term and preterm infants admitted between January 2018 and July 2020 were screened for dexmedetomidine exposure. Prospectively recorded vital signs (heart rate, oxygenation, arterial blood pressure) were cross-matched with pharmacy records to identify infants with data available 24 h before and 48 h after drug initiation. Vital sign data were processed via a standardized pipeline to (a) remove missing data, (b) obtain baseline averages of vital signs for 24 h preceding dexmedetomidine, and (c) calculate the hourly mean deviation from the baseline for the 48 h following initiation of dexmedetomidine. Infants were clustered by postmenstrual age (preterm ≤ 35 weeks; term > 35 weeks). 72 infants were identified with mean gestational age of 32 weeks and mean ± SD birth weight of 1976 ± 1341 g. Although both groups of infants experienced bradycardia, heart rate in term infants dropped faster and reached a nadir 5 beats per minute lower, before converging at a common deviation of - 10 beats per minute. No hypo- or hypertension was noted in either group. Unexpected instability of oxygenation occurred in a subset of preterm infants, requiring escalation of respiratory support. Administration of dexmedetomidine results in differential timing and magnitude of bradycardia in term and preterm infants, no major impact on blood pressure, and a surprising instability of oxygenation in preterm infants, requiring increased ventilatory support. Further investigation is warranted.

Nicardipine for the Treatment of Neonatal Hypertension During Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) is one of the primary reasons systemic hypertension is experienced in hospitalized neonates. Commonly used antihypertensive agents have resulted in significant adverse effects in neonatal and pediatric populations. Nicardipine is a desirable option because of its rapid and titratable antihypertensive properties and low incidence of adverse effects. However, data for use in neonatal ECMO are limited. We conducted a retrospective review of patients less than 44 weeks post-menstrual age who received a nicardipine infusion for first-line treatment of systemic hypertension while on ECMO at our institution between 2010 and 2016. Systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressures were evaluated for 48-h after nicardipine initiation. Eight neonates received a nicardipine infusion while on ECMO during the study period. Nicardipine was initiated at a mean dose of 0.52 ( ± 0.22) mcg/kg/min and titrated to a maximum dose of 1.1 ( ± 0.85) mcg/kg/min. The median duration of nicardipine use was 51 (range 4-227) hours. Significant decreases in SBP, DBP, and MAP occurred within one hour of initiation of nicardipine and were sustained through the majority of the 48-h evaluation period. No patients experienced hypotension. Prospective studies are warranted to evaluate the optimal dose, safety, and efficacy of nicardipine in neonates who require ECMO.

Antimicrobial Stewardship in Neonates: Challenges and Opportunities.

Neonatal infections result in significant morbidity and mortality. Antibiotics are vital for the treatment of infections but disrupt the neonatal microbiome, put the infant at risk for an adverse drug reaction, and may lead to the development of antibiotic resistance. Immediately after birth, clinicians must determine which infants require empiric antibiotics. Online risk stratification tools may provide a superior approach to decision trees. In infants who require empiric therapy for early-onset sepsis, ampicillin and an aminoglycoside with dosing based on recent pharmacokinetic studies represents the most appropriate first-line agents; third-generation cephalosporins should be reserved for patients with a high likelihood of Gram-negative meningitis. An antistaphylococcal penicillin and gentamicin should be utilized for suspected late-onset sepsis. Vancomycin and other broad-spectrum agents are reserved for patients with a history of resistant organisms. Antibiotic duration should be guided by understanding the clinical indications and obtaining the necessary cultures appropriately (i.e., adequate volume blood cultures). In the absence of a positive culture, antibiotic duration should often be limited. Individual institutions should leverage a multidisciplinary, interprofessional team to identify opportunities for antimicrobial stewardship. A collaborative, transparent system is required to change unit culture and generate a sustained impact on antibiotic utilization with optimal patient outcomes.

Pharmacologic Management of Neonatal Seizures.

Seizures are most often the only sign of a central nervous dysfunction in the neonate. Neonatal seizures are a symptom of a specific disease entity. The search for a cause of neonatal seizures should focus on perinatal history or acute metabolic changes in the neonate. There are four classifications of neonatal seizures: clonic, tonic, myoclonic, and subtle. Simultaneous electroencephalogram and video recording are tools to assist the practitioner in the evaluation of difficult-to-assess subtle behaviors. Although many seizures may be prevented by careful attention to metabolic changes and the neonate's overall condition, those that cannot be prevented may require pharmacologic treatment. First-generation antiepileptic drugs such as phenobarbital and phenytoin are still the first and second lines of therapy, even as questions concerning their limited clinical effectiveness and concern for potential neurotoxicity continue.

Opioid Analgesics for Sedation and Analgesia During Mechanical Ventilation.

Neonates are exposed to repetitive pain and stress during their stay in a NICU, which can lead to chronic complications related to their neurodevelopment and neurobehavior. Approximately 20 percent of all neonates in a NICU are intubated, mechanically ventilated, and require suctioning, which can cause both acute and chronic pain. Pain management in the neonate can be challenging. Nurses and other caregivers need to be well trained to assess pain in the neonate to effectively identify and provide appropriate pain management strategies. There is a lack of evidence to support routine administration of opiates in the neonate. As with any medication, the possibility of short- and long-term adverse reactions must be considered. Nonpharmacologic therapy should be used as much as possible.

Pain in the neonate: focus on nonpharmacologic interventions.

The assessment and treatment of pain in the neonate, especially preterm neonates, has been a challenge in the NICU for many years. Nurses caring for these vulnerable patients are in a key position to not only recognize when the neonate is experiencing pain but to also work collaboratively with other health care providers in determining the best method to treat and help prevent pain associated with procedures and routine caregiving activities. The American Academy of Pediatrics along with parent groups has recognized the importance of pain-prevention programs in treating pain in the neonate. Nurses, by anticipating and reducing both painful procedures and bedside interruptions, along with innovative nonpharmacologic interventions, can dramatically decrease the neonate's exposure to pain and the potential for long-term effects. An overview of nonpharmacologic interventions in the treatment of neonatal pain is provided for NICU nurses to help them effectively reduce their patient's pain and discomfort.

Gabapentin as Adjunctive Therapy in Neonatal Opioid Withdrawal Syndrome: A Case Series.

OBJECTIVE: We describe a single center experience with gabapentin as adjunctive therapy in infants with neonatal opioid withdrawal syndrome (NOWS). METHODS: We performed a retrospective chart review of infants receiving gabapentin for NOWS. Data points collected included patient's sex, gestational age, maternal opioid exposure, NOWS medication dosing and length of therapy, number of failed wean attempts, time to successful morphine wean and duration of morphine wean, length of stay in the neonatal intensive care unit (NICU), and NOWS medications at discharge. RESULTS: Six infants received gabapentin as adjunctive treatment for NOWS. All infants failed 2-4 morphine weans before initiation of gabapentin despite the addition of clonidine. All infants that received gabapentin were successfully weaned off morphine. The time to wean off morphine after gabapentin initiation varied from 4-35 days. Maximum gabapentin doses ranged from 15 - 42.7 mg/kg/day. Five infants were discharged from the NICU on gabapentin. CONCLUSIONS: Gabapentin appeared to facilitate successful morphine weans in six patients with NOWS who were previously unable to wean despite the initiation of clonidine.

Respiratory effects of prolonged prednisolone use in infants with evolving and established Bronchopulmonary dysplasia.

BACKGROUND: Current literature focuses on systemic corticosteroids for prevention of bronchopulmonary dysplasia (BPD) in preterm infants with limited data on use for pulmonary disease after the first month of life. Prednisolone may be a reasonable option for late treatment given its desirable pharmacologic properties and use in other pediatric disease states. AIMS: To characterize a premature population that received an extended prednisolone course and determine the effect on respiratory and anthropometric outcomes over time. STUDY DESIGN: Single-center, retrospective study. SUBJECTS: Preterm infants who received ≥30 days of prednisolone or methylprednisolone for treatment of respiratory complications following preterm birth. OUTCOMES MEASURES: Assessment of pulmonary severity score (PSS), weight, length, and occipital frontal circumference weekly during the first 4 weeks of prednisolone and after discontinuation. RESULTS: Thirty-four infants with a mean gestational age of 26.5 ± 2.5 weeks and birth weight of 846 ± 353 g were identified. Nine patients were on invasive mechanical ventilation and 25 patients were on non-invasive respiratory support at prednisolone initiation. Prednisolone was initiated at a mean post-menstrual age of 41.7 ± 5 weeks and a mean dose of 1.7 ± 0.6 mg/kg/day. A significant decrease in PSS was seen over time (p < 0.001) without rebound following discontinuation. Eleven patients decreased the mode of respiratory support during prednisolone treatment. No significant impact in anthropometric outcomes were identified. CONCLUSION: Prolonged prednisolone use was associated with a sustained decrease in PSS without adverse effects on growth measurements. These results suggest potential benefit of prednisolone on respiratory outcomes in a subset of preterm infants.

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.

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.

Minoxidil-associated anorexia in an infant with refractory hypertension.

Minoxidil is a potent antihypertensive used as an adjunctive agent in refractory hypertension. It exerts an antihypertensive effect through two mechanisms: selective arterial vasodilation by activation of potassium channels in the vascular smooth muscle and stimulation of carotid and aortic baroreceptors, leading to downstream release of renin and norepinephrine. Although frequently cited in reviews of antihypertensive agents, limited data about the use of minoxidil in neonates are available. We describe an infant girl, born at 35 weeks of gestation, who was diagnosed with idiopathic hypertension after extensive diagnostic evaluation. Adequate blood pressure control was not achieved with captopril, amlodipine, and clonidine. Oliguria secondary to captopril and rapid-onset congestive heart failure due to persistent hypertension led to the introduction of intravenous agents labetalol and nitroprusside. Although adequate blood pressure control was achieved, attempts to transition back to oral agents were unsuccessful, prompting the use of minoxidil as an alternative agent. Although good blood pressure control was achieved, the infant's oral intake plummeted from 210 to 63 ml/kg/day. The anorexia quickly resolved after stopping minoxidil, and she was discharged home at 5 months of age receiving propranolol, amlodipine, and doxazosin. Use of the Naranjo adverse drug reaction probability scale indicated a definite relationship (score of 10) between the patient's development of anorexia and minoxidil therapy. To our knowledge, there have been no previous reports of minoxidil-associated anorexia in preterm or term infants. Clinicians should be aware that anorexia is a possible adverse effect of minoxidil in this patient population when initiating the drug in similar patients.