Guilherme M. Sant'Anna

Temperature profile and outcomes of neonates undergoing whole body hypothermia for neonatal hypoxic-ischemic encephalopathy

Background: Decreases below the target temperature were noted among neonates undergoing cooling in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Trial of whole body hypothermia for neonatal hypoxic-ischemic encephalopathy. Objective: To examine the temperature profile and impact on outcome among ≥36 wk gestation neonates randomized at ⩽6 hrs of age targeting an esophageal temperature of 33.5°C for 72 hrs. Design, Setting, Patients: Infants with intermittent temperatures recorded of <32.0°C during induction and maintenance of cooling were compared to all other cooled infants, and the relationship with outcome at 18 months was evaluated. Interventions: None. Measurements and Main Results: There were no differences in the stage of encephalopathy, acidosis, or 10 min Apgar scores between infants with temperatures of <32.0°C during induction (n = 33) or maintenance (n = 10) and all other infants who were cooled (n = 58); however, birth weight was lower and the need for blood pressure support higher among infants with temperatures of <32.0°C compared to all other cooled infants. No increase in acute adverse events was noted among infants with temperatures of <32.0°C, and hours spent at <32°C was not associated with the primary outcome of death or moderate/severe disability or the Bayley II Mental Developmental Index at 18 months. Conclusions: Term infants with a lower birth weight are at risk for decreasing temperatures of <32.0°C while undergoing body cooling using a servo-controlled system. This information suggests extra caution during the application of hypothermia as these lower birth weight infants are at risk for overcooling. Our findings may assist in planning additional trials of lower target temperature for neonatal hypoxic-ischemic encephalopathy.

Weaning infants from mechanical ventilation.

Protracted mechanical ventilation is associated with increased morbidity and mortality in preterm infants and thus the earliest possible weaning from mechanical ventilation is desirable. Weaning protocols may be helpful in achieving more rapid reduction in support. There is no clear consensus regarding the level of support at which an infant is ready for extubation. An improved ability to predict when a preterm infant has a high likelihood of successful extubation is highly desirable. In this article, available evidence is reviewed and reasonable evidence-based recommendations for expeditious weaning and extubation are provided.

Thermal and respiratory control in young rats exposed to cold during postnatal development.

We questioned to what extent sustained increases in metabolic rate during the neonatal period may influence the development of thermal and respiratory control. Male rats were exposed to cold (14 degrees C) for the first 3 weeks, which increased metabolic rate with small effects on body growth. Measurements were performed at 1 month of age, when the body weight of the Cold group averaged approximately 88% of Controls. In Cold rats, the concentration of the uncoupling protein of the brown adipose tissue was increased. Acute exposures to different ambient temperatures (5, 15, 25 and 35 degrees C) provoked changes in body temperature similar in Cold and in Control rats. At these temperatures, small differences in the absolute values of oxygen consumption (Vdot;(O(2))) between the two groups could be explained by the differences in body weight. Hematocrit and lung weight of Cold rats were as in Controls, but the lung protein-DNA ratio was increased because of a drop in lung cellularity. The resting ventilation-oxygen consumption ratio (Vdot;(E)/Vdot;(O(2))) was similar between Cold and Controls. Also the changes in Vdot;(O(2)) and Vdot;(E) during acute hypoxia (10% O(2)) or hypercapnia (5% CO(2)), and the corresponding hyperventilatory responses (increases in Vdot;(E)/Vdot;(O(2))) did not significantly differ between the two groups. In conclusion, in the rat, the increased metabolic requirements caused by cold exposure during the early postnatal phases improved the thermogenic capacity, while having negligible impact on the development of respiratory control.

Prediction of extubation readiness in extreme preterm infants based on measures of cardiorespiratory variability

The majority of extreme preterm infants require endotracheal intubation and mechanical ventilation (ETT-MV) during the first days of life to survive. Unfortunately this therapy is associated with adverse clinical outcomes and consequently, it is desirable to remove ETT-MV as quickly as possible. However, about 25% of extubated infants will fail and require re-intubation which is also associated with a 5-fold increase in mortality and a longer stay in the intensive care unit. Therefore, the ultimate goal is to determine the optimal time for extubation that will minimize the duration of MV and maximize the chances of success. This paper presents a new objective predictor to assist clinicians in making this decision. The predictor uses a modern machine learning method (Support Vector Machines) to determine the combination of measures of cardiorespiratory variability, computed automatically, that best predicts extubation readiness. Our results demonstrate that this predictor accurately classified infants who would fail extubation.

Developing a neonatal unit ventilation protocol for the preterm baby.

Mechanical ventilation is a resource-intensive complex medical intervention associated with high morbidity. Considerable practice style variation exists in most hospitals and is not only confusing for parents, but the lack of consistently high standard of optimal ventilation deprives some infants of the benefits of state-of-the-art care. Developing a unit protocol for mechanical ventilation requires exhaustive research, inclusion of all stake-holders, thoughtful protocol development and careful implementation after a thorough educational process, followed by monitoring. A protocol for respiratory support should be comprehensive, addressing respiratory support in the delivery room, the use of non-invasive support, intubation criteria, surfactant administration, specific ventilation modes and settings, criteria for escalating therapy, weaning protocols, extubation criteria, and post-extubation management. Evidence favors the use of non-invasive support as first line treatment, progressing to assist/control or pressure support ventilation combined with volume guarantee, if needed, and high-frequency ventilation only for specific indications. The open lung strategy is crucial to lung-protective ventilation.

Thermal and respiratory control in young rats with altered caloric intake during postnatal development.

We asked to what extent differences in caloric intake during the first postnatal weeks may modify thermal and respiratory control of 1-month old rats. Large-size (Large) and small-size (Small) rats were obtained by raising rats in, respectively, small (6 pups) and large (16 pups) litters. In Small, the rate of oxygen consumption (V(O(2))/kg) was less than in Large during the first 2-3 weeks, and higher thereafter, when the thermogenic needs to maintain body temperature (Tb) increased. At day 31, when body weight in Small was approximately 80% of Large, Small maintained Tb in the cold with higher V(O(2))/kg than Large. The total uncoupling protein of the brown adipose tissue was unchanged. Also pulmonary ventilation (VE/kg) was higher in Small, maintaining the proportionality with V(O(2)). Lung weight in Small was reduced in proportion to body weight, with higher protein-DNA ratio. The compliances of the respiratory system and lungs, normalized by body weight, and the hyperventilatory responses to hypoxia or hypercapnia, expressed as % increase in VE/V(O(2)), were similar in Small and Large. Differences between Small and Large were reduced or no longer present in a group of Small rats raised until their body weight was as in Large. We conclude that rather important developmental differences in caloric intake and metabolic level, in otherwise healthy rats, had no long-term carry over effects in the developmental processes of respiratory and thermal control, other than the effects strictly attributable to the alterations in body size.

Phenobarbital and temperature profile during hypothermia for hypoxic-ischemic encephalopathy

Data from the whole-body hypothermia trial was analyzed to examine the effects of phenobarbital administration prior to cooling (+PB) on the esophageal temperature (T e) profile, during the induction phase of hypothermia. A total of 98 infants were analyzed. At enrollment, +PB infants had a higher rate of severe hypoxic-ischemic encephalopathy and clinical seizures and lower T e and cord pH than infants that have not received phenobarbital (–PB). There was a significant effect of phenobarbital itself and an interaction between phenobarbital and time in the T e profile. Mean T e in the +PB group was lower than in the –PB group, and the differences decreased over time. In +PB infants, the time to surpass target T e of 33.5°C and to reach the minimum T e during overshoot were shorter. In conclusion, the administration of phenobarbital before cooling was associated with changes that may reflect a reduced thermogenic response associated with barbiturates.

Prospective research on infants with mild encephalopathy: the PRIME study

Objective:To determine short-term outcomes of infants with evidence of hypoxia–ischemia at birth and classified as mild neonatal encephalopathy (NE) at <6 h of age.Study Design:Prospective multicenter study. Mild NE was defined as ⩾1 abnormal category in modified Sarnat score. Primary outcome was any abnormality on early amplitude integrated electroencephalogram (aEEG) or seizures, abnormal brain magnetic resonance imaging (MRI) or neurological exam at discharge.Results:A total of 54/63 (86%) of enrolled infants had data on components of the primary outcome, which was abnormal in 28/54 (52%): discontinuous aEEG (n=4), MRI (n=9) and discharge exam (n=22). Abnormal tone and/or incomplete Moro were the most common findings. MRI abnormalities were confined to cerebral cortex but two infants had basal ganglia and/or thalamus involvement. The 18 to 24 months follow-up is ongoing.Conclusions:A larger than expected proportion of mild NE infants with abnormal outcomes was observed. Future research should evaluate safety and efficacy of neuroprotection for mild NE.

Feature selection and oversampling in analysis of clinical data for extubation readiness in extreme preterm infants

We present an approach for the analysis of clinical data from extremely preterm infants, in order to determine if they are ready to be removed from invasive endotracheal mechanical ventilation. The data includes over 100 clinical features, and the subject population is naturally quite small. To address this problem, we use feature selection, specifically mutual information, in order to choose a small subset of informative features. The other challenge we address is class imbalance, as there are many more babies that succeed extubation than those who fail. To handle this problem, we use SMOTE, an algorithm which creates synthetic examples of the minority class.

Organizational principles of cloud storage to support collaborative biomedical research

This paper describes organizational guidelines and an anonymization protocol for the management of sensitive information in interdisciplinary, multi-institutional studies with multiple collaborators. This protocol is flexible, automated, and suitable for use in cloud-based projects as well as for publication of supplementary information in journal papers. A sample implementation of the anonymization protocol is illustrated for an ongoing study dealing with Automated Prediction of EXtubation readiness (APEX).