John Wimmer

Heat loss prevention for preterm infants in the delivery room.

OBJECTIVE:Preterm infants are prone to hypothermia immediately following birth. Among other factors, excessive evaporative heat loss and the relatively cool ambient temperature of the delivery room may be important contributors. Most infants <29 weeks gestation had temperatures <36.4°C on admission to our neonatal unit (NICU). Therefore we conducted a randomized, controlled trial to evaluate the effect of placing these infants in polyurethane bags in the delivery room to prevent heat loss and reduce the occurrence of hypothermia on admission to the NICU.METHODS:After parental consent was obtained, infants expected to be <29 weeks gestation were randomized to intervention or control groups just prior to their birth. Infants randomized to the intervention group were placed in polyurethane bags up to their necks immediately after delivery before being dried. They were then resuscitated per NRP guidelines, covered with warm blankets, and transported to the NICU, where the bags were removed and rectal temperatures were recorded. Control infants were resuscitated, covered with warm blankets, and transported without being placed in polyurethane bags. Delivery room temperatures were recorded so this potentially confounding variable could be assessed.RESULTS:Intervention patients were less likely than control patients to have temperature < 36.4°C on admission , 44 vs 70% (p<0.01) and the intervention group had a higher mean admission temperature, 36.5°C vs 36.0°C (p<0.003). This effect remained significant (p<0.0001) when delivery room temperature was controlled in analysis. Warmer delivery room temperatures (≥26°C) were associated with higher admission temperatures in both intervention and control infants, but only the subgroup of intervention patients born in warmer delivery rooms had a mean admission temperature >36.4°C.CONCLUSIONS:Placing infants <29 weeks gestation in polyurethane bags in the delivery room reduced the occurrence of hypothermia and increased their NICU admission temperatures. Maintaining warmer delivery rooms helped but was insufficient in preventing hypothermia in most of these vulnerable patients without the adjunctive use of the polyurethane bags.

Oseltamivir Dosing for Influenza Infection in Premature Neonates

Under the Emergency Use Authorization issued in April 2009, oseltamivir can be used to treat 2009 influenza A (H1N1) virus infection in children aged <1 year. No data exist on the dosing of oseltamivir in premature babies. A hospital health care worker inadvertently exposed 32 neonatal intensive care unit babies to 2009 influenza A (H1N1); a protocol was expeditiously implemented to collect samples for pharmacokinetics and dosage evaluation. Results suggest 1.0 mg/kg/dose twice daily in premature babies produces oseltamivir carboxylate exposures similar to that in older children receiving 3.0 mg/kg/dose twice daily. These results provide initial guidance on dosing oseltamivir in this vulnerable population.

Effect of routine probiotic, Lactobacillus reuteri DSM 17938, use on rates of necrotizing enterocolitis in neonates with birthweight < 1000 grams: a sequential analysis

BackgroundNecrotizing enterocolitis (NEC) is a disease in neonates, often resulting in death or serious medical or neurodevelopmental complications. The rate of NEC is highest in the smallest babies and many efforts have been tried to reduce the rate of NEC. In neonates born below 1500 grams, the rate of NEC has been significantly reduced with the use of various probiotics. This study examines the impact of routine use of a probiotic, Lactobacillus reuteri DSM 17938 (BioGaia®), on the rate of NEC in neonates at highest risk for developing NEC, those with birth weight ≤1000 grams.MethodsThis is a retrospective cohort study comparing the rates of NEC in neonates with birth weight ≤ 1000 grams. The groups are separated into those neonates born from January 2004 to June 30, 2009, before introduction of L. reuteri , and neonates born July 2009 through April 2011 who received routine L. reuteri prophylaxis. The chart review study was approved by our institutional review board and exempted from informed consent.Neonates were excluded if they died or were transferred within the first week of life. The remainder were categorized as having no NEC, medical NEC, surgical NEC, or NEC associated death. Since no major changes occurred in our NICU practice in recent years, and the introduction of L. reuteri as routine prophylaxis was abrupt, we attributed the post-probiotic changes to the introduction of this new therapy. Rates of NEC were compared using Chi square analysis with Fisher exact t-test.ResultsMedical records for 311 neonates were reviewed, 232 before- and 79 after-introduction of L. reuteri prophylaxis. The incidence of NEC was significantly lower in the neonates who received L. reuteri (2 of 79 neonates [2.5%] versus 35 of 232 untreated neonates [15.1%]). Rates of late-onset gram-negative or fungal infections (22.8 versus 31%) were not statistically different between treated and untreated groups. No adverse events related to use of L reuteri were noted.ConclusionsProphylactic initiation of L. reuteri as a probiotic for prevention of necrotizing enterocolitis resulted in a statistically significant benefit, with avoidance of 1 NEC case for every 8 patients given prophylaxis.

Extremely Low Birth Weight Preterm Infants Lack Vasomotor Response in Relationship to Cold Body Temperatures at Birth

Study Objective:This study evaluated peripheral vasoconstriction in extremely low birth weight (ELBW) infants when body temperature decreased during the first 12 h of life.Study Design:An exploratory, within-subjects design with 10 ELBW infants. Abdominal and foot temperatures were measured every minute. Peripheral vasoconstriction (abdominal>peripheral temperature by 2 °C) and abdominal–peripheral temperature difference were also evaluated. Results:Abdominal and peripheral temperatures were significantly correlated within each infant. One 880 g infant exhibited isolated peripheral vasoconstriction; a 960-g infant had abdominal temperatures >1 °C higher than peripheral temperatures. Eight smaller infants exhibited no peripheral vasoconstriction and spent most of their observations with peripheral greater than abdominal temperatures. In eight infants, mean temperature difference was significantly higher when abdominal temperature was <36.5 °C.Conclusion:Most ELBW infants did not exhibit peripheral vasoconstriction during their first 12 h of life, despite low temperatures. ELBW infants’ vasomotor control may be immature during this period.

Dexmedetomidine Versus Standard Therapy with Fentanyl for Sedation in Mechanically Ventilated Premature Neonates

OBJECTIVE To compare the efficacy and safety of dexmedetomidine and fentanyl for sedation in mechanically ventilated premature neonates. METHODS This was a retrospective, observational case-control study in a level III neonatal intensive care unit. Forty-eight premature neonates requiring mechanical ventilation were included. Patients received fentanyl (n=24) or dexmedetomidine (n=24) for pain or sedation. Each group also received fentanyl and lorazepam boluses as needed for agitation. The primary outcomes were efficacy and frequency of acute adverse events associated with each drug. Days on mechanical ventilation, stooling patterns, feeding tolerance, and neurologic outcomes were also evaluated. RESULTS There were no significant differences in baseline demographics between the dexmedetomidine and fentanyl patients. Patients in the dexmedetomidine group required less adjunctive sedation and had more days free of additional sedation in comparison to fentanyl (54.1% vs. 16.5%, p<0.0001). There were no differences in hemodynamic parameters between the 2 groups. Duration of mechanical ventilation was shorter in the dexmedetomidine group (14.4 vs. 28.4 days, p<0.001). Meconium passage (7.5 vs. 22.4 days, p<0.0002) and time from initiation to achievement of full enteral feeds (26.8 vs. 50.8 days, p<0.0001) were shorter in the dexmedetomidine group. Incidence of culture-positive sepsis was lower in the dexmedetomidine group (48% vs. 88%). The incidence of either severe intraventricular hemorrhage or periventricular leukomalacia was not statistically significantly reduced (2% vs. 7%). CONCLUSIONS Dexmedetomidine was safe and effective for sedation in the premature neonates included in this study. Prospective randomized-controlled trials are needed before routine use of dexmedetomidine can be recommended.

Successful Use of Dexmedetomidine for Sedation in a 24-Week Gestational Age Neonate

Objective: To describe a case of dexmedetomidine use for sedation in a 24-week gestational age premature neonate. Case Summary: A 9-day-old, 24-week gestational age male neonate on high-frequency oscillatory mechanical ventilation was experiencing severe agitation refractory to high-dose intravenous narcotics and benzodiazepines. Since the infants respiratory stability was reliant on adequate sedation, he was given dexmedetomidine after several days of suboptimal response to escalation of standard agents. Treatment prior to dexmedetomidine included continuous-infusion fentanyl 10 μg/kg/h, intravenous lorazepam 0.6 mg/kg every 4 hours, intermittent doses of both lorazepam and midazolam as needed, and a single bolus dose of phenobarbital. The patient calmed markedly during the dexmedetomidine loading dose infusion and remained adequately sedated while the drug was continued. The dexmedetomidine infusion allowed weaning of mechanical ventilation settings and eventual extubation of the infant, as well as rapid tapering of other sedative medications. The maximum dexmedetomidine infusion rate was 0.7 μg/kg/h, and total duration of therapy was 19 days. No significant adverse effects were directly attributed to dexmedetomidine use during this time. Discussion: Dexmedetomidine is a novel α2-agonist approved for short-term sedation in mechanically ventilated adults. Data describing its use in pediatric and neonatal patients continue to emerge. The prolonged use of dexmedetomidine in very-low-birth-weight neonates has not been described in the literature. Conclusions: Dexmedetomidine was an effective sedative and analgesic in a 24-week gestational age neonate treated for refractory agitation while on mechanical ventilation. Based on its documented efficacy for pain and sedation and its favorable adverse effect profile, dexmedetomidine warrants further study as first-line or adjunct therapy with narcotics for sedation in ventilated newborns.

Study protocol for multicentre randomized controlled trial of HeLP (Heat Loss Prevention) in the delivery room

INTRODUCTION Immediate postnatal hypothermia is an independent risk factor for death in premature newborns. Three randomized controlled trials (RCTs) and five historical controlled trials show statistically significant differences in admission temperature between infants wrapped in occlusive skin wrap and unwrapped infants. This paper presents a study protocol for The Vermont Oxford Network (VON) Heat Loss Prevention (HeLP) Trial, a multicentre RCT of two interventions (standard of care vs. occlusive wrap) that investigates the effect of polyethylene occlusive wrap applied immediately after birth on mortality in infants born 24 + 0/7 to 27 + 6/7 week gestation. METHODS Inclusion criteria include: infants 24 + 0/7 to 27 + 6/7 weeks gestational age and a firm decision prior to birth to provide full resuscitative measures. Exclusion criteria comprise infants born with blistering skin conditions or congenital anomalies that are not covered by skin. The primary outcome measure is all-cause mortality until discharge from the hospital or at six months corrected gestational age. The secondary outcome measures include baseline and post-stabilization axillary temperatures, acidosis, hypotension, hypoglycaemia, seizures in the first 12h, patent ductus arteriosus, and respiratory distress syndrome. Long-term follow-up at 18 to 24 months corrected age will be assessed with the combined risk of death and major neurosensory disability as the primary outcome. DISCUSSION Key covariates and protocol deviations are addressed and steps to monitor these are described. Wrapping may prove an inexpensive and easy method to benefit premature newborns in level I and II nurseries, in both developed and developing countries, as well as large tertiary care centres. REB APPROVAL Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada-355-2003 University of Alberta, Edmonton, Alberta, Canada-Pro00003810 Vermont Oxford Network, Burlington, Vermont, USA-CHRMS: M04-295.

Low-dose aminophylline for the treatment of neonatal non-oliguric renal failure-case series and review of the literature.

OBJECTIVE Aminophylline is a methylxanthine with multiple physiologic actions. At low doses, aminophylline can antagonize adenosine and improve renal function via increased glomerular filtration rate. Despite its clinical use, little data exists in neonates for this indication. Therefore, the objective of this report is to describe the impact of aminophylline on renal function indices in a series of neonates with acute renal failure. MATERIALS AND METHODS This was a retrospective chart review of 13 neonates with acute renal failure who received aminophylline during a 15-month study period. Aminophylline was administered at 1 mg/kg intravenously or orally every twelve hours. Forty-six percent (n = 6) of the patients received a 5 mg/kg loading dose before initiation of maintenance therapy. Most patients had already received other treatments for renal failure, including diuretics and dopamine. RESULTS Resolution of acute renal failure (with normalization of serum creatinine and blood urea nitrogen) was documented in 10 patients (77%). Four of the thirteen patients died from complications due to their prematurity. Failure of low-dose aminophylline was observed in 3 of the 4 patients who died. CONCLUSIONS Low-dose aminophylline in neonates with acute renal failure is associated with an improvement in renal function indices.

Effect of Routine Lactobacillus reuteri DSM 17938 use on Rates of Late-onset infection in Extremely-low-birth-weight Infants

Background: Preterm infants are at high risk for late-onset infections due to gram-negative or fungal organisms. Evidence supports that a common source for these organisms may be the gastrointestinal tract. One theoretical way to change the infection rate is to alter the bacterial flora inhabiting the newborn gastrointestinal tract using probiotics. This study examines the impact of routine use of a probiotic, Lactobacillus reuteri DSM 17938 (BioGaia®), on the rate of late-onset gram-negative and fungal infection in neonates with birth weight ≤ 1000 grams. Methods: This is a retrospective cohort study comparing the rates of gram-negative bacterial and fungal infections in neonates with birth weight ≤ 1000 grams. The groups are separated into those neonates born from January 2004 to June 30, 2009, before introduction of L. reuteri, and neonates born July 2009 through July 2012 who received routine L. reuteri prophylaxis. Neonates were excluded if they died or were transferred within the fi rst week of life. The remainder were included in the study and recorded as either having late onset infection related to gram negative organisms or fungi, or not having late onset infection. Since no major changes occurred in our NICU practice in recent years, and the introduction of L. reuteri as routine prophylaxis was abrupt, we attributed the post-probiotic changes to the introduction of this new therapy. Rates of infection were compared using Chi square analysis with Fisher exact t-test. Results: Medical records for 354 neonates were reviewed, 232 before- and 122 after-introduction of L. reuteri prophylaxis. Despite a marked reduction in necrotizing enterocolitis and mortality, the incidence of late-onset infection varied from year-to-year, but was not signifi cantly altered by the introduction of routine L. reuteri. No adverse events related to use of L. reuteri were noted. Conclusions: Prophylactic initiation of L. reuteri as a probiotic does not decrease late-onset infection.

Pharmacoeconomic impact of use of the probiotic Lactobacillus reuteri DSM 17938 for prevention of necrotizing enterocolitis in extremely low-birth-weight infants

Mary Ann VT Dimaguila1,2 Peter Gal1,3,4 Tiffany Wilson1 John E Wimmer Jr1,2 McCrae Smith1,2 Rita Q Carlos1,2 Christie C Davanzo1,2 J Laurence Ransom1,2 1Women’s Hospital of Greensboro, Cone Health, Greensboro, NC, USA; 2Piedmont Neonatology, Greensboro, NC, USA; 3Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 4Greensboro Area Health Education Center, Greensboro, NC, USA