Barry T. Bloom

Reported Medication Use in the Neonatal Intensive Care Unit: Data From a Large National Data Set

OBJECTIVES. The objectives were (1) to identify the drugs reported most commonly during NICU care, (2) to examine how different methods of documenting drug use could influence prioritization of drugs for future research aimed at evaluating safety and efficacy, (3) to describe the demographic differences in the population samples for some specific medications, (4) to identify which reported medications are used for patient populations with >20% mortality rates, and (5) to examine how reports of drug use change over time. METHODS. A retrospective review of a large national data set was performed. RESULTS. The 10 medications reported most commonly for the NICU were ampicillin, gentamicin, ferrous sulfate, multivitamins, cefotaxime, caffeine citrate, furosemide, vancomycin, surfactant, and metoclopramide. Medications used for patient populations with >20% mortality rates included amphotericin, clonazepam, dobutamine, epinephrine, ethacrynic acid, insulin, lidocaine, metolazone, milrinone, inhaled nitric oxide, nitroglycerin, octreotide, pancuronium, phenytoin, sodium nitroprusside, sodium polystyrene sulfonate (Kayexalate), tris-hydroxymethylaminomethane acetate buffer, and tolazoline. Several of these drugs (eg, amphotericin B and bumetanide) were used primarily for extremely premature neonates, and this usage might explain the high mortality rates for the population of neonates treated with these medications. Other medications (clonazepam, milrinone, inhaled nitric oxide, and phenytoin) were used primarily for near-term and term infants. The explanation for the high mortality rates for these neonates is less clear and may be related primarily to the severity of illness for which the medications are used. Utilization rates for several different medications (eg, cisapride, metoclopramide, and dexamethasone) changed by >50% during the past 5 years. CONCLUSIONS. Data reported here are the first from a large national data set on the use of different medications for neonates admitted for intensive care and should be helpful in establishing priority agendas for future drug studies in this population.

Empiric Use of Ampicillin and Cefotaxime, Compared With Ampicillin and Gentamicin, for Neonates at Risk for Sepsis Is Associated With an Increased Risk of Neonatal Death

BACKGROUND. We reported previously that the use of cephalosporin among premature neonates increased the risk of subsequent fungal sepsis. As a result, we recommended that ampicillin and gentamicin be used as empiric coverage for early-onset neonatal sepsis while culture results are awaited. OBJECTIVES. To describe antibiotic use during the first 3 days after birth for neonates admitted to the NICU and to evaluate the outcomes for neonates treated with 2 different antibiotic regimens. METHODS. We assembled a cohort of inborn neonates, from our deidentified administrative database, who had documented exposure to ampicillin during the first 3 days after birth. Infants treated concurrently with cefotaxime or gentamicin were evaluated, to identify the factors that were associated independently with death before discharge, with both univariate and multivariate analyses. RESULTS. There were 128914 neonates selected as the study cohort; 24111 were treated concurrently with ampicillin and cefotaxime and 104803 were treated concurrently with ampicillin and gentamicin. Logistic modeling showed that neonates treated with ampicillin/cefotaxime were more likely to die (adjusted odds ratio: 1.5; 95% confidence interval: 1.4–1.7) and were less likely to be discharged to home or foster care than were neonates treated with ampicillin/gentamicin. This observation was true across all estimated gestational ages. Other factors that were associated independently with death included immature gestational age, need for assisted ventilation on the day of admission to the NICU, indications of perinatal asphyxia or major congenital anomaly, and reported use of ampicillin/cefotaxime. CONCLUSIONS. For patients receiving ampicillin, the concurrent use of cefotaxime during the first 3 days after birth either is a surrogate for an unrecognized factor or is itself associated with an increased risk of death, compared with the concurrent use of gentamicin.

Technique for Intrapartum Administration of Surfactant without Requirement for an Endotracheal Tube

OBJECTIVE: To evaluate the feasibility and safety of administering surfactant into the nasopharynx during delivery, thus permitting the baby to aspirate the solution into the fluid-filled airway as an air–fluid interface is established. This process avoids the endotracheal intubation (ETI) and positive pressure ventilation (PPV) usually associated with prophylaxis, thus avoiding the pulmonary barotrauma associated with the conventional method of surfactant administration.STUDY DESIGN: In all, 23 neonates weighing 560 to 1804 g and born at 27 to 30 weeks had their nasopharyngeal airways suctioned and then 3.0–4.5 ml Infasurf® instilled into the nasopharynx before delivery of the shoulders. Continuous positive airway pressure (CPAP) of 10 cmH2O was administered by mask as the babies initiated breathing. Nasal CPAP at 6 cmH2O was then continued for a minimum of 48 hours.RESULTS: In all, 13 of 15 babies delivered vaginally were weaned quickly to room air and required no further surfactant or endotracheal intubation for RDS. Five of eight babies delivered by C-section required subsequent endotracheal intubation soon after birth and two received subsequent endotracheal tube surfactant.CONCLUSION: Nasopharyngeal surfactant instillation at birth appears to be relatively safe and simple to accomplish, especially for vaginal births. A large randomized clinical trial will be required to determine the efficacy of this technique when compared to prophylaxis by endotracheal intubation and to nCPAP alone.

Nutrition in the Neonatal Intensive Care Unit: How Do We Reduce the Incidence of Extrauterine Growth Restriction?

Extrauterine growth restriction is a major clinical problem for prematurely born neonates, especially critically ill preterm neonates, and malnutrition in the neonatal intensive-care unit remains common. There are numerous perceived risks to initiation of adequate nutritional support. How many of these factors pose a real risk to health outcomes is less clear. Current nutritional support does not prevent extrauterine growth restriction and the consequences of malnutrition are both acute and delayed. Our clinical approach to providing nutritional support impacts neonatal morbidity and long-term neuro developmental outcomes. While more and better evidence is needed to help guide best practices, this gap should not prevent neonatologists from using the observations in this review to improve their current practice. There is evidence that changes in nutritional support can have a positive influence on growth. These include early administration of intravenous amino acids and lipids, minimal enteral nutrition, and supplemented formula and human milk. Simply recognizing the degree of growth failure by monitoring weight and focusing on the accruing deficit should encourage clinicians to increase nutritional support to enhance recovery growth. Continued research is needed to define the efficiency of early feeding, more rapid advancements in nutritional support, protein needs, the optimal composition of breast-milk supplements, the etiology of necrotizing enterocolitis, and perhaps most importantly, the health consequences of extrauterine growth restriction.

Nosocomial Infection in the NICU: A Medical Complication or Unavoidable Problem?

Nosocomial sepsis is a serious problem for neonates who are admitted for intensive care. As it is associated with increases in mortality, morbidity, and prolonged length of hospital stay, both the human and fiscal costs of these infections are high. Although the rate of nosocomial sepsis increases with the degree of both prematurity and low birth weight, no specific lab test has been shown to be very useful in improving our ability to predict who has a “real” blood-stream infection and, therefore, who needs to be treated with a full course of antibiotics. As a result, antibiotic use is double the rate of “proven” sepsis and we are facilitating the growth of resistant organisms in the neonatal intensive care unit. The purpose of this article is to review the topic of nosocomial infections in neonates.

Multicenter study to assess safety and efficacy of INH-A21, a donor-selected human staphylococcal immunoglobulin, for prevention of nosocomial infections in very low birth weight infants.

Background: Prophylactic administration of intravenous immunoglobulin has been inconsistent in reducing the risk of sepsis in very low birth weight (VLBW) infants presumably because of varying titers of organism specific IgG antibodies. INH-A21 is an intravenous immunoglobulin from donors with high titers of antistaphylococcal antibodies. This dose-ranging study explored safety and preliminary activity of INH-A21 for prevention of staphylococcal sepsis in VLBW infants. Methods: This was a multicenter, double blind, group-sequential study. Infants with birth weights 500–1250 g were randomized to receive up to 4 doses of placebo, 250 mg/kg, 500 mg/kg or 750 mg/kg INH-A21. Safety and frequencies of sepsis were compared across treatment groups. Results: All treatment groups had similar mean gestational age, birth weight, Apgar score and maternal use of antibiotics. Randomizations to 250 mg/kg (N = 94) and 500 mg/kg (N = 96) doses were terminated after interim analyses demonstrated a low probability of finding a difference when compared with placebo. Infants randomized to the INH-A21 750 mg/kg group (N = 157) had fewer episodes of Staphylococcus aureus sepsis [relative risk (RR), 0.37; 95% confidence interval (CI), 0.12–1.12; P = 0.14], candidemia (RR 0.34; 95% CI 0.09–1.22; P = 0.09) and mortality (RR 0.64; 95% CI 0.25–1.61; P = 0.27) when compared with the placebo-treated cohort (N = 158). No dose-related trends were observed for adverse events or morbidities associated with prematurity. Conclusions: INH-A21 750 mg/kg demonstrated potential to reduce sepsis caused by S. aureus, candidemia and mortality in VLBW infants. Although statistical significance was not reached, based on the magnitude of the estimated differences, the efficacy and safety of INH-A21 750 mg/kg should be evaluated in an adequately powered, well-controlled study.

Reducing Acquired Infections in the NICU: Observing and Implementing Meaningful Differences in Process Between High and Low Acquired Infection Rate Centers

BACKGROUND: Acquired infection is one of the most prevalent sources of concern in neonatal intensive care units (NICUs). Center-to-center variation has been noted by both the National Nosocomial Infection Surveillance System and the Vermont Oxford Network suggesting that site of care influences outcomes including acquired infection.OBJECTIVE: To reduce the acquired infection rate by isolating and then implementing meaningful process differences between high and low infection rate centers.DESIGN/METHOD: A multistaged observation and intervention study. The primary outcome measure was defined as a positive blood culture, collected more than 3 days after birth. Hospital patient days along with infection episodes were collected for all NICU admissions in the network during the baseline and postimplementation periods. A detailed observation guide was used during site visits to high and low infection rate centers. The observations recorded in the guide allowed the team to isolate meaningful differences, which were shared with the network. Individual NICUs decided which of the meaningful differences, if any, to implement. To estimate the impact on costs, additional data were gathered in a case-matched series of infants in one demonstration site.RESULTS: In all, 15 meaningful differences were isolated and shared with the network. The network rate for acquired infection dropped from 3.8 to 2.9 episodes per 1000 patient days. In the demonstration site, the infection rate dropped from 7.4 to 4.0 per 1000 patient days.CONCLUSION: Isolation of process level differences between high and low performing centers followed by implementation of these meaningful differences may reduce acquired infections. Other targeted areas of care may benefit from this quality improvement methodology.

Prevention and Treatment of Nosocomial Sepsis in the NICU

Nosocomial sepsis is a serious problem for neonates who are admitted for intensive care. It is associated with an increase in mortality, morbidity, and prolonged length of hospital stay. Thus, both the human and fiscal costs of these infections are high. Although the rate of nosocomial sepsis increases with the degree of both prematurity and low birth weight, no specific lab test has been shown to be very useful in improving our ability to predict who has a “real” blood-stream infection and, therefore, who needs to be treated with a full course of antibiotics. As a result, antibiotic use is double the rate of “proven” sepsis and we are facilitating the growth of resistant organisms in the neonatal intensive care unit. The purpose of this article is to describe simple changes in process, which when implemented, can reduce nosocomial infection rates in neonates and improve outcomes.

Site of care influences breastmilk feedings at NICU discharge.

OBJECTIVE: To determine if site of care influences rates of breastmilk use in neonatal intensive care units (NICUs).STUDY DESIGN: Subjects included all admissions to 124 NICUs between 1/1/1999 and 12/31/2000 who were subsequently discharged home. We reviewed discharge feeding data collected during the routine provision of care, and used stepwise logistic regression analysis to identify which factors were independently associated with a neonate being discharged on some breastmilk versus none.RESULTS: We studied 42,891 neonates; 21,327 (49.7%) were sent home receiving some breastmilk and 21,564 (50.3%) were not. The significant variables associated with being discharged on breastmilk were more mature gestational age, white race, maternal age, parents being married, and site of care. Site of care remained significant even when adjusted for other variables.CONCLUSION: Neonates admitted to NICUs are often discharged on feedings that do not include breastmilk. Beyond previously identified risk factors, site of care significantly influences this occurrence.

A paradigm shift in the prevention of retinopathy of prematurity.

For more than 50 years it has been known that oxygen therapy can lead to retinopathy of prematurity (ROP). Recent clinical research has led many neonatologists to lower the target oxygen saturation alarm limits to 85–93% and to titrate the inspired oxygen in small increments. Despite efforts to optimize oxygen therapy, the number of cases of severe ROP remains high as more extremely low birth weight infants survive. Based on new insights into the pathogenesis of ROP, there are multiple interventions, in addition to optimizing oxygen therapy that may help decrease severe ROP. Interventions that have the potential to prevent phase I ROP (birth to ≤32 weeks PMA) include increasing retinal erythropoietin (exogenous rHuEPO) and serum IGF-1 (breast milk and/or exogenous IGF-1), maintaining serum glucose below 120 mg, and providing omega-3 supplements. Interventions with potential to prevent proliferative ROP in phase II (infants >32–34 weeks PMA) include treating anemia with a liberal policy of transfusion in premature infants with stage III ROP, photopic adaptation, vitamin E supplements (>34 weeks PMA), and omega-3 supplements. The WINROP algorithm has shown promise as a biomarker in the early identification of extremely low birth weight infants at high risk for proliferative ROP. As there is interplay of multiple factors in the causation of ROP, we suggest that the simultaneous application of some combination of multiple interventions, mentioned above, may reduce the burden of ROP in the most vulnerable infants. These conceptsneed study in well-designed randomized clinical trials before being incorporated into clinical practice.