Objective: Multiorgan dysfunction in asphyxiated newborns receiving therapeutic hypothermia achieved by either selective head cooling (SHC) or whole-body cooling (WBC) has not been well characterized. The beneficial effect of SHC in organs other than the brain may potentially be limited because unlike WBC, SHC aims to achieve effective brain cooling with lesssystemic hypothermia. However, the relative effects of SHC and WBC with currently available cooling protocols on multiorgan dysfunction are unknown.The aim of this study was to compare the multiorgan dysfunction in infants receiving therapeutic hypothermia induced by either SHC or WBC.Study Design: In 59 asphyxiated newborns who received therapeutic hypothermia by either SHC (n ¼ 31) or WBC (n ¼ 28), the severity of pulmonary, hepatic and renal dysfunction and coagulopathy and electrolyte disturbances were assessed before the start of cooling (baseline), and at specific time intervals (24, 48 and 72 h) throughout cooling. Enrollment criteria, clinical monitoring and treatment during cooling, whether SHC or WBC, were similar, as reported earlier.Result: The presence of clinical respiratory distress, along with the need for ventilatory support for varying duration during cooling, was similar in both the WBC and SHC groups (100 vs 94%, P ¼ 0.49, OR 1.9, 95% CI 1.5-2.5). The use of fresh frozen plasma and platelet transfusion to treat coagulopathy and thrombocytopenia was similar (WBC 48% vs SHC 58%, P ¼ 0.59, OR 0.7, 95% CI 0.2-1.9, and WBC 41% vs SHC 32%, P ¼ 0.58, OR 1.4, 95% CI 0.5-4.2, respectively), and equivalent numbers of infants from both groups were treated with vasopressors for >24 h (WBC 59% vs SHC 55%, P ¼ 0.79, OR 1.2, 95% CI 0.4-3.4). The incidence of oliguria (urine output <0.5 ml kg -1 h -1 for >24 h after birth) and rising serum creatinine (with maximum serum creatinine >0.9 mg dl -1 ) was also similar (WBC 18% vs SHC 39%, P ¼ 0.15, OR 0.4, 95% CI 0.1-1.3, and WBC 48% vs SHC 58%, P ¼ 0.59, OR 0.7, 95% CI 0.2-1.9, respectively).Laboratory parameters to assess the differential effect of WBC versus SHC on multiorgan dysfunction during 72 h of cooling, which include serum transaminases (serum aspartate aminotransferase and alanine aminotransferase), prothrombin time, partial thromboplastin time, INR, platelet counts, serum creatinine, serum sodium, serum potassium and serum calcium, were similar between the groups at the initiation of cooling and did not differ with the method of cooling. Conclusion:Multiorgan system dysfunction in asphyxiated newborns during cooling remains similar for both cooling methods. Concerns regarding a differential effect of WBC versus SHC on multiorgan dysfunction, other than of the brain, should not be a consideration in selecting a method to produce therapeutic hypothermia.

Background:We hypothesized that acute kidney injury (AKI) in asphyxiated neonates treated with therapeutic hypothermia would be associated with hypoxic-ischemic lesions on brain magnetic resonance imaging (MRI). Methods: Medical records of 88 cooled neonates who had had brain MRI were reviewed. All neonates had serum creatinine assessed before the start of cooling; at 24, 48, and 72 h through cooling; and then on day 5 or 7 of life. A neonatal modification of the Kidney Disease: Improving Global Outcomes guidelines was used to classify AKI. MRI images were evaluated by a neuroradiologist masked to outcomes. Outcome of interest was abnormal brain MRI at 7-10 d of life. results: AKI was found in 34 (39%) of 88 neonates, with 15, 7, and 12 fulfilling criteria for stages 1, 2, and 3, respectively. Brain MRI abnormalities related to hypoxia-ischemia were present in 50 (59%) newborns. Abnormal MRI was more frequent in infants from the AKI group (AKI: 25 of 34, 73% vs. no AKI: 25 of 54, 46%; P = 0.012; odds ratio (OR) = 3.2; 95% confidence interval (CI) = 1.3-8.2). Multivariate analysis identified AKI (OR = 2.9; 95% CI = 1.1-7.6) to be independently associated with the primary outcome. conclusion: AKI is independently associated with the presence of hypoxic-ischemic lesions on postcooling brain MRI.

Grade 3 intraventricular hemorrhage (IVH) (without parenchymal involvement) and grade 4 IVH (with parenchymal involvement) are often combined into description of a single entity, usually "severe" IVH, despite different long-term neurodevelopmental outcome. Although risk factors for severe IVH have already been well described, it is not known if these risk factors and associated short-term neonatal morbidities are different for grade 3 and grade 4 IVH, and indeed, this clustering of grade 3 and grade 4 IVH into severe IVH precludes further delineation of the potential risk and protective factors that can be altered to reduce the incidence of grade 4 IVH, which is presumably associated with worse outcome compared with grade 3 IVH. We sought to characterize and compare commonly cited risk factors and associated short-term neonatal morbidities between grade 3 and grade 4 IVH in very low-birth-weight (VLBW) infants. We performed a retrospective review of VLBW (birth weight < 1500 g) infants with severe IVH born between January 2001 and March 2007. Fifty-nine (10.5%) of 562 infants surviving beyond 3 days of age had severe IVH as recorded on routine cranial sonography during the first 7 to 10 days of life, 28 had grade 3, and 31 had grade 4 IVH. Infants with grade 4 IVH were younger [gestational age (weeks), grade 4 IVH versus grade 3 IVH: 25.5 +/- 1.7 versus 26.7 +/- 1.7, p = 0.02) and weighed less at birth [birth weight (g), grade 4 IVH versus grade 3 IVH: 860 +/- 214 versus 1007 +/- 253, p = 0.03) compared with infants with grade 3 IVH. Other commonly cited clinical factors that alter the risk for severe IVH, including mode of delivery, pregnancy-induced hypertension, premature and/or prolonged rupture of membranes, maternal fever, maternal bleeding, prenatal steroid administration, maternal magnesium sulfate therapy, 1-minute and 5-minute Apgar scores, need for delivery room resuscitation (epinephrine and chest compressions), surfactant therapy, presence of refractory hypotension, evidence of early onset culture-proven sepsis, use of high-frequency ventilation, presence of pneumothorax, and hemodynamically significant patent ductus arteriosus, were similar between infants with grade 3 and grade 4 IVH. Carbon dioxide tensions (minimum PaC (2), maximum PaCO(2), mean PaCO(2), standard deviation of PaCO(2), and coefficient of variation of PaCO (2)) in infants receiving mechanical ventilation during first 3 postnatal days were also not statistically dissimilar. To determine the variables differentiating grade 3 from grade 4 IVH in the study population, logistic regression analysis confirmed only the independent association of gestational age (odds ratio [OR] 0.6, 95% confidence interval [CI] 0.5 to 0.9, P = 0.012) and maternal magnesium sulfate therapy (OR 0.3, 95% CI 0.07 to 0.9, P = 0.04) with the development of grade 4 IVH. Short-term neonatal morbidities were also similar between infants with grade 3 and grade 4 IVH. Among VLBW infants, the risk of a grade 4 versus grade 3 IVH increases with declining gestational ag...

Background: The optimal number of blood cultures needed to document sepsis in an ill neonate has undergone little critical evaluation. Multiple site cultures may improve pathogen detection if intermittent bacteremia occurs, or if a low density of bacteria is present in the blood. We hypothesized, however, that bacterial clearance is slower and bacteremia more continuous in septic neonates, so that a single site blood culture should be sufficient to accurately document true septicemia.Objective: To determine the need for multiple site blood cultures in the evaluation of neonates for sepsis.Design/Methods: Clinical data were prospectively collected for 216 neonates who had 269 pairs of blood cultures taken from two different peripheral sites for the evaluation of possible sepsis. A minimum of 1 ml of blood was obtained from the two peripheral sites within 15-30 min of each other. Based on prior retrospective data, we determined that 203 infants would need to have two site blood cultures to demonstrate a significant improvement in pathogen detection at an alpha of 0.05 and a beta of 0.20 (80%) power.Results: A total of 186 culture pairs were taken for evaluation of earlyonset sepsis in 186 neonates, while 83 pairs were drawn for evaluation of late-onset sepsis in 43 neonates. In all, 21 neonates from the late-onset group were evaluated more than once, and 12 neonates were evaluated for both early-and late-onset sepsis. In all, 20 (9.2%) of 216 neonates had 22 episodes of culture-proven sepsis at a median age of 18 days. All neonates with positive cultures had the same organism with a similar sensitivity pattern obtained from the two different peripheral sites. The other 196 study neonates had negative blood cultures from both sites. The single episode of early-onset sepsis was caused by Listeria monocytogenes, while all remaining episodes were late-onset with the following organisms: Staphylococcus epidermidis (7), methicillin-resistant Staphylococcus aureus (MRSA) (3), combined MRSA and Candida albicans (2), Candida albicans alone (2), late-onset Group B b-hemolytic Streptococcus (GBS) (2), Klebsiella pneumoniae (2), Enterococcus fecalis (1), Escherichia coli (1), and Serratia marcescens (1). Since no infant grew organisms from only one of the two sites, the data indicate that the diagnosis of sepsis would have been made correctly in all infants with a single site culture. Conclusions:Two site blood cultures for the initial evaluation of neonatal sepsis do not have a better yield in pathogen detection. Sepsis in neonates can be detected with no loss of accuracy with a single site blood culture with blood volume of X1 ml.

Compared with whole body cooling (WBC), selective head cooling (SHC) of asphyxiated newborns presumably allows effective brain cooling with less systemic hypothermia and potentially fewer systemic adverse effects. It is not known if pulmonary dysfunction, one of the potential adverse systemic effects of therapeutic hypothermic neuroprotection, differs with the method of cooling. We sought to investigate if pulmonary mechanics and gas exchange during therapeutic hypothermia differ between WBC and SHC. The severity of pulmonary dysfunction was determined in 59 asphyxiated newborns receiving therapeutic hypothermic neuroprotection by either SHC (n ¼ 31) or WBC (n ¼ 28). Ventilatory parameters and simultaneous alveolar-arterial oxygen gradient (A-a DO 2 ) and partial pressure of carbon dioxide, arterial (PaCO 2 ) were measured before the start of cooling (baseline), and at 4, 8, 12, 24, 48, and 72 hours of cooling. The diagnosis of persistent pulmonary hypertension of the newborn (PPHN) was established by echocardiography. Clinical monitoring and treatment during cooling, whether SHC or WBC, were similar. All (96%) but two infants (from the SHC group) required mechanical ventilation of varying duration during cooling, and nine infants (15%) developed PPHN. The baseline ventilator pressures requirement, and A-a DO 2 were similar among the 48 ventilated infants without PPHN (WBC 23, SHC 25) at the start of cooling. Ventilatory requirements remained modest and did not differ with the method of cooling. Similar numbers of infants without PPHN were able to be extubated after improvement in respiratory status while being cooled (WBC 42.8% versus SHC 37.9%, p ¼ 0.79, odds ratio [OR] 1.2, 95% confidence interval [CI] 0.4 to 3.5). Nine infants (WBC 5, SHC 4) developed PPHN. Six of the nine (WBC 4, SHC 2) required inhaled nitric oxide therapy, and one infant from the WBC group subsequently required extracorporeal membrane oxygenation. The incidence of PPHN was similar in both the WBC and SHC groups (17.8% versus 12.9%, p ¼ 0.72, OR 1.5, 95% CI 0.3 to 6.1). Pulmonary dysfunction is common but not severe in asphyxiated infants during therapeutic hypothermia. Pulmonary mechanics and gas exchange do not differ with the method of achieving hypothermia.

Of the selected precooling variables, only the 10 min Apgar score is independently associated with death despite therapeutic cooling in infants with HIE. Infants who remain asystolic at 10 min and beyond are unlikely to survive despite cooling, and the rare survivor is likely to have severe disability.

Hypoxic-ischaemic lesions on brain MRI following therapeutic cooling were more frequent and more severe with SHC compared with WBC.

Objective: To determine whether phenobarbital (PB) given before therapeutic hypothermia to infants with hypoxic-ischemic encephalopathy (HIE) augments the neuroprotective efficacy of hypothermia.Study Design: Records of 68 asphyxiated infants of X36 weeks' gestation, who received hypothermia for moderate or severe HIE were reviewed. Some of these infants received PB prophylactically or for clinical seizures. All surviving infants had later brain magnetic resonance imaging (MRI). The composite primary outcome of neonatal death related to HIE with worsening multiorgan dysfunction despite maximal treatment, and the presence of post-hypothermia brain MRI abnormalities consistent with hypoxic-ischemic brain injury, were compared between the infants who received PB before initiation of hypothermia (PB group, n ¼ 36) and the infants who did not receive PB before or during hypothermia (No PB group, n ¼ 32). Forward logistic regression analysis determined which of the pre-hypothermia clinical and laboratory variables predict the primary outcome.Result: The two groups were similar for severity of asphyxia as assessed by Apgar scores, initial blood pH and base deficit, early neurologic examination, and presence of an intrapartum sentinel event. The composite primary outcome was more frequent in infants from the PB group (PB 78% versus No PB 44%, P ¼ 0.006, odds ratio 4.5, 95% confidence interval 1.6 to 12.8). Multivariate analysis identified only the PB receipt before initiation of hypothermia (P ¼ 0.002, odds ratio 9.5, 95% confidence interval 2.3 to 39.5), and placental abruption to be independently associated with a worse primary outcome.Conclusion: PB treatment before cooling did not improve the composite outcome of neonatal death or the presence of an abnormal post-hypothermia brain MRI, but the long-term outcomes have not yet been evaluated.