Thresholds for Red Blood Cell Transfusion in Preterm Infants: Evidence to Practice.

Rapid blood loss with circulatory shock is dangerous for the preterm infant as cardiac output and oxygen-carrying capacity are simultaneously imperilled. This requires prompt restoration of circulating blood volume with emergency transfusion. It is recommended that clinicians use both clinical and laboratory responses to guide transfusion requirements in this situation. For preterm infants with anemia of prematurity, it is recommended that clinicians use a restrictive algorithm from one of two recently published clinical trials. Transfusion outside these algorithms in very preterm infants is not evidence-based and is actively discouraged.

Accuracy of Brain Natriuretic Peptide for Diagnosing Pulmonary Hypertension in Severe Bronchopulmonary Dysplasia.

BACKGROUND: Premature infants with severe bronchopulmonary dysplasia (sBPD) are at risk of pulmonary hypertension (PH). Serum brain natriuretic peptide (BNP) is used to predict disease severity in adult PH. Its diagnostic utility in sBPD-associated PH is unknown. OBJECTIVE: The aim of this paper was to determine the accuracy of BNP, against echocardiogram (echo), to diagnose PH in infants born <32 weeks' gestation with sBPD. METHODS: We conducted a retrospective cohort study of all infants with sBPD with an echo and BNP within a 24-h period, at ≥36 weeks postmenstrual age. PH was defined as: right ventricular pressure >½ systemic blood pressure estimated from tricuspid regurgitant jet or patent ductus arteriosus (PDA) velocity, bidirectional or right-to left-PDA, and/or flat/bowing ventricular septum at end-systole. Receiver-operating characteristic (ROC) curves were constructed to test the diagnostic accuracy of BNP. RESULTS: Of 128 infants, 68 (53%) had echo evidence of PH. BNP was higher among the infants with PH (median [interquartile range]: 127 pg/mL [39-290] vs. 35 [20-76], p < 0.001). The area under the ROC curve for diagnosing PH using BNP was 0.74 (95% CI 0.66-0.83). At an optimal cutpoint of 130 pg/mL, BNP correctly classified the presence or absence of PH in 70% of the infants (specificity: 92, sensitivity: 50%). CONCLUSIONS: BNP, relative to concurrent echo, demonstrated moderate accuracy for diagnosing PH in this cohort of preterm infants with sBPD. BNP may help rule in PH in this population but has low utility to rule out the disease.

Identifying and treating intrinsic PEEP in infants with severe bronchopulmonary dysplasia.

RATIONALE: Infants with severe bronchopulmonary dysplasia (sBPD) and airway obstruction may develop dynamic hyperinflation and intrinsic positive end-expiratory pressure (PEEPi ), which impairs patient/ventilator synchrony. OBJECTIVES: To determine if PEEPi is present in infants with sBPD during spontaneous breathing and if adjusting ventilator PEEP improves patient/ventilator synchrony and comfort. METHODS: Interventional study in infants with sBPD. PEEPi measured by esophageal pressure (Pes) and pneumotachometer, during pressure-supported breaths. PEEP i defined as the difference between Pes at start of the inspiratory effort minus Pes at onset of inspiratory flow. The set PEEP was adjusted to minimize PEEP i . "Best PEEP" was the setting with minimal wasted efforts (WE), an inspiratory effort seen on the Pes waveform without a corresponding ventilator breath. FiO 2 and SpO 2 measured pre- and post-PEEP adjustment. Sedation requirements evaluated 72 hours preprocedure and postprocedure. RESULTS: Twelve infants were assessed (gestational age, 24.9 ± 1.4 weeks; study age, 48.8 ± 1.5 weeks, postmenstrual age). Mean baseline ventilator PEEP was 16.4 cm H2 O (14-20 cm H 2 O). Eight infants required an increase, one, a reduction, and three, no change in the set PEEP. For the eight infants requiring an increase in set PEEP, there was an 18.9% reduction in WE and a reduction in FiO 2 (0.084 ± 0.058) requirements in the subsequent 24 hours. Conditional sedation was reduced in five infants postprocedure. No adverse events occurred during testing. CONCLUSION: PEEPi is measurable in infants with sBPD with concurrent esophageal manometry and flow-time tracings without the need for pharmacological paralysis. In those with PEEP i , increasing ventilator PEEP to offset PEEP i improves synchrony.

A Theoretical and Practical Approach to Defining "Adequate Oxygenation" in the Preterm Newborn.

John Scott Haldane recognized that the administration of supplemental oxygen required titration in the individual. Although he made this observation in adults, it is equally applicable to the preterm newborn. But how, in practice, can the oxygen requirements in the preterm newborn be determined to avoid the consequences of too little and too much oxygen? Unfortunately, the current generation of oxygen saturation trials in preterm newborns guides saturation thresholds rather than individual oxygen requirements. For this reason, we propose an alternate model for the description of oxygen sufficiency. This model considers the adequacy of oxygen delivery relative to simultaneous consumption. We describe how measuring oxygen extraction or the venous oxygen reservoir could define a physiologically based definition of adequate oxygen. This definition would provide a clinically useful reference value while making irrelevant the absolute values of both oxygen delivery and consumption. Additional trials to test adjunctive, noninvasive measurements of oxygen status in high-risk preterm newborns are needed to minimize the effects of both insufficient and excessive oxygen exposure.

Evidence, Quality, and Waste: Solving the Value Equation in Neonatology.

Rising health care costs challenge governments, payers, and providers in delivering health care services. Tremendous pressures result to deliver better quality care while simultaneously reducing costs. This has led to a wholesale re-examination of current practice methods, including explicit consideration of efficiency and waste. Traditionally, reductions in the costs of care have been considered as independent, and sometimes even antithetical, to the practice of high-quality, intensive medicine. However, it is evident that provision of evidence-based, locally relevant care can result in improved outcomes, lower resource utilization, and opportunities to reallocate resources. This is particularly relevant to the practice of neonatology. In the United States, 12% of the annual birth cohort is affected by preterm birth, and 3% is affected by congenital anomalies. Both of these conditions are associated with costly health care during, and often long after, the NICU admission. We will discuss how 3 drivers of clinical practice in neonatal care (evidence-based medicine, evidence-based economics, and quality improvement) can together optimize clinical and fiscal outcomes.

Counselling and management for anticipated extremely preterm birth.

Extremely preterm birth (birth between 22(0/7) and 25(6/7) weeks' gestational age [GA]) often requires parents to make complex choices about the care of their infant. Health professionals have a significant role in providing information, guidance and support. Parents facing the birth of an extremely preterm infant should have the chance to meet with both obstetrical and paediatric/neonatal care providers to receive accurate information about their infant's prognosis, provided with clarity and compassion. Decision making between parents and health professionals should be an informed and shared process, with documentation of all management decisions. Consultation with and transfer to tertiary perinatal centres are important for the care of both mother and fetus. As the survival of infants born before or at 22 completed weeks' GA remains uncommon, a noninterventional approach is recommended, whereas at 23, 24 and 25 weeks' GA, counselling about outcomes and decision making should be individualized for each infant and family, using factors which influence prognosis. All extremely preterm infants who are not resuscitated, or for whom resuscitation is not successful, must receive compassionate palliative care.

Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: a randomized controlled trial.

OBJECTIVE: To determine the effectiveness and safety of moderate whole-body hypothermia in newborns with hypoxic-ischemic encephalopathy born in hospitals with and without newborn intensive care facilities or complicated hypothermia equipment. DESIGN: Multicenter, international, randomized controlled trial. SETTING: Neonatal intensive care units in Australia, New Zealand, Canada, and the United States (N = 28) from February 2001 through July 2007. PARTICIPANTS: Newborns of 35 weeks' gestation or more, with indicators of peripartum hypoxia-ischemia and moderate to severe clinical encephalopathy, randomly allocated to hypothermia (n = 110) or standard care (n = 111). INTERVENTION: Whole-body hypothermia to 33.5°C for 72 hours or standard care (37°C). Infants who received hypothermia were treated at ambient environmental temperature by turning off the radiant warmer and then applying refrigerated gel packs to maintain rectal temperature at 33°C to 34°C. MAIN OUTCOME MEASURES: Death or major sensorineural disability at 2 years of age. RESULTS: Therapeutic hypothermia reduced the risk of death or major sensorineural disability at 2 years of age: 55 of 107 infants (51.4%) in the hypothermia group and 67 of 101 infants (66.3%) in the control group died or had a major sensorineural disability at 2 years (risk ratio, 0.77 [95% confidence interval, 0.62-0.98]; P = .03). The mortality rate decreased, and the survival rate free of any sensorineural disability increased. Adverse effects of hypothermia were minimal. CONCLUSIONS: Whole-body hypothermia is effective and appears to be safe when commenced within 6 hours of birth at the hospital of birth in term and near-term newborns with hypoxic-ischemic encephalopathy. This simple method of hypothermia could be used within strict protocols with appropriate training on correct diagnosis and application of hypothermia in nontertiary neonatal settings while awaiting retrieval and transport to the regional neonatal intensive care unit. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12606000036516.

Hypothermia therapy after traumatic brain injury in children.

BACKGROUND: Hypothermia therapy improves survival and the neurologic outcome in animal models of traumatic brain injury. However, the effect of hypothermia therapy on the neurologic outcome and mortality among children who have severe traumatic brain injury is unknown. METHODS: In a multicenter, international trial, we randomly assigned children with severe traumatic brain injury to either hypothermia therapy (32.5 degrees C for 24 hours) initiated within 8 hours after injury or to normothermia (37.0 degrees C). The primary outcome was the proportion of children who had an unfavorable outcome (i.e., severe disability, persistent vegetative state, or death), as assessed on the basis of the Pediatric Cerebral Performance Category score at 6 months. RESULTS: A total of 225 children were randomly assigned to the hypothermia group or the normothermia group; the mean temperatures achieved in the two groups were 33.1+/-1.2 degrees C and 36.9+/-0.5 degrees C, respectively. At 6 months, 31% of the patients in the hypothermia group, as compared with 22% of the patients in the normothermia group, had an unfavorable outcome (relative risk, 1.41; 95% confidence interval [CI], 0.89 to 2.22; P=0.14). There were 23 deaths (21%) in the hypothermia group and 14 deaths (12%) in the normothermia group (relative risk, 1.40; 95% CI, 0.90 to 2.27; P=0.06). There was more hypotension (P=0.047) and more vasoactive agents were administered (P<0.001) in the hypothermia group during the rewarming period than in the normothermia group. Lengths of stay in the intensive care unit and in the hospital and other adverse events were similar in the two groups. CONCLUSIONS: In children with severe traumatic brain injury, hypothermia therapy that is initiated within 8 hours after injury and continued for 24 hours does not improve the neurologic outcome and may increase mortality. (Current Controlled Trials number, ISRCTN77393684 [controlled-trials.com].).

Indomethacin prophylaxis, patent ductus arteriosus, and the risk of bronchopulmonary dysplasia: further analyses from the Trial of Indomethacin Prophylaxis in Preterms (TIPP).

OBJECTIVES: To determine the risk of bronchopulmonary dysplasia (BPD) in subgroups of infants with and without patent ductus arteriosus (PDA) who were randomized to indomethacin prophylaxis or placebo, and to examine whether adverse drug effects on edema formation and oxygenation may explain why indomethacin prophylaxis does not reduce BPD. STUDY DESIGN: We studied 999 extremely low birth weight infants who participated in the Trial of Indomethacin Prophylaxis in Preterms (TIPP) and who survived to a postmenstrual age of 36 weeks. RESULTS: The incidence of BPD in the 2 subgroups of infants with PDA was 52% (55/105) after indomethacin prophylaxis and 56% (137/246) after placebo. In contrast, rates of BPD in the 2 subgroups without a PDA were 43% (170/391) after indomethacin prophylaxis and 30% (78/257) after placebo (P [interaction] = .015). Logistic regression analysis with adjustment for prognostic baseline factors showed that adverse and independent effects of indomethacin prophylaxis on the need for supplemental oxygen and on weight loss by the end of the first week of life may increase the risk of BPD in infants without PDA. CONCLUSIONS: Harmful side effects on oxygenation and edema formation may explain why indomethacin prophylaxis does not prevent BPD even though it reduces PDA.

Positive end-expiratory pressure above lower inflection point minimizes influx of activated neutrophils into lung.

OBJECTIVES: To compare the effects of low vs. high tidal volume (Vt) with three positive end-expiratory pressure (PEEP) strategies on activated neutrophil influx into the lung. DESIGN: Prospective, randomized controlled animal study. SETTING: Animal laboratory in a university hospital. SUBJECTS: Newborn piglets. INTERVENTIONS: Surfactant-depleted piglets were randomized in littermate pairs; to PEEP of either 0 (zero end-expiratory pressure [ZEEP]; n = 6), 8 cm H2O (PEEP 8; n = 5), or 1 cm H2O above the lower inflection point (LIP) (PEEP>LIP; n = 6). Within each pair piglets were randomized to a low VT (5-7 mL/kg) or high VT strategy (17-19 mL/kg). After 4 hrs of mechanical ventilation, 18-fluorodeoxyglucose (18FDG) was injected and positron emission tomography scanning was performed. MEASUREMENTS AND MAIN RESULTS: VT and PEEP changes on influx constants of 18FDG were assessed by analysis of variance. A within-litter comparison of Vt was nonsignificant (p = .50). A between-litter comparison, ordered in linear trend rank, from ZEEP, to PEEP 8, to PEEP>LIP, showed a strong effect of PEEP on influx constant (p = .019). CONCLUSIONS: PEEP set above the LIP on the inspiratory limb of the pressure-volume curve affords a stronger lung protection than VT strategy.