Active normothermia treatment for perioperative temperature management during bedside surgery in the NICU, a case report.

Infants in the NICU setting often require emergent bedside surgical procedures, during which, they are at high risk for developing hypothermia. Reasons for hypothermia in infants include poor temperature regulation, decreased fat stores to maintain temperature, increased insensible losses. Neonatal hypothermia is associated with an increased risk of sepsis, cardiorespiratory failure (pulmonary hypertension), hypoglycemia and death. In this case series, we describe the novel use of servo-controlled water blanket system as a method to actively maintain normothermia during three surgical cases. Although water blanket systems are frequently used in the neonatal ICU to provide active hypothermia treatment, to our knowledge there have been no prior reports of this system being deployed in normal and low-birthweight infants in the perioperative period.

Clinical and vital sign changes associated with late-onset sepsis in very low birth weight infants at 3 NICUs.

BACKGROUND: In premature infants, clinical changes frequently occur due to sepsis or non-infectious conditions, and distinguishing between these is challenging. Baseline risk factors, vital signs, and clinical signs guide decisions to culture and start antibiotics. We sought to compare heart rate (HR) and oxygenation (SpO2) patterns as well as baseline variables and clinical signs prompting sepsis work-ups ultimately determined to be late-onset sepsis (LOS) and sepsis ruled out (SRO). METHODS: At three NICUs, we reviewed records of very low birth weight (VLBW) infants around their first sepsis work-up diagnosed as LOS or SRO. Clinical signs prompting the evaluation were determined from clinician documentation. HR-SpO2 data, when available, were analyzed for mean, standard deviation, skewness, kurtosis, and cross-correlation. We used LASSO and logistic regression to assess variable importance and associations with LOS compared to SRO. RESULTS: We analyzed sepsis work-ups in 408 infants (173 LOS, 235 SRO). Compared to infants with SRO, those with LOS were of lower GA and BW, and more likely to have a central catheter and mechanical ventilation. Clinical signs cited more often in LOS included hypotension, acidosis, abdominal distension, lethargy, oliguria, and abnormal CBC or CRP(p < 0.05). HR-SpO2 data were available in 266 events. Cross-correlation HR-SpO2 before the event was associated with LOS after adjusting for GA, BW, and postnatal age. A model combining baseline, clinical and HR-SpO2 variables had AUC 0.821. CONCLUSION: In VLBW infants at 3-NICUs, we describe the baseline, clinical, and HR-SpO2 variables associated with LOS versus SRO.

The effect of therapeutic hypothermia on heart rate variability.

OBJECTIVE: Heart rate variability (HRV) reflects integrity of the autonomic nervous system. However, no study has investigated the impact of therapeutic hypothermia (TH) on HRV measures in infants with hypoxic-ischemic encephalopathy (HIE). In this study, we evaluate the influence of temperature on measures of HRV for a group of infants with favorable outcomes, as compared with a control group of infants with unfavorable outcomes. STUDY DESIGN: Term-born infants with moderate-severe HIE underwent standard TH treatment and prospective electroencephalography (EEG) and electrocardiogram (ECG) recording. Infants with favorable outcome (no seizures, normal/mild EEG scores at 96 h, no magnetic resonance imaging brain injury and normal neurodevelopmental scores at 18 to 24 months) were matched on gestational age, sex and worst encephalopathy score to a group of infants with unfavorable outcomes. Time- and frequency-domain HRV measures were calculated from 60 min of ECG data obtained at three time points: 24 h (hypothermia), 48 h (hypothermia) and 96 h (normothermia). The effect of time and temperature were evaluated using repeated-measures analysis of variance. RESULTS: Sixteen infants were included (8 favorable, 8 unfavorable). For both groups of infants, an increase in the HR, RR and HF power was associated with an increase in temperature, but was not associated with any other HRV measure. In contrast, measures of HRV increased over time, as encephalopathy decreased, for infants with favorable outcomes (reflecting increased cortical-autonomic integration), but not for those with unfavorable outcomes. CONCLUSIONS: In general, the effect of hypothermia on measures of HRV is limited to changes in heart rate (bradycardia) and respiratory rate, as opposed to changes in true variability. This supports the hypothesis that persistent changes in HRV are driven by the underlying brain injury and not by the process of TH.

Impact of brain injury on functional measures of amplitude-integrated EEG at term equivalent age in premature infants.

OBJECTIVE: To evaluate the association between qualitative and quantitative amplitude-integrated EEG (aEEG) measures at term equivalent age (TEA) and brain injury on magnetic resonance imaging (MRI) in preterm infants. STUDY DESIGN: A cohort of premature infants born at <30 weeks of gestation and with moderate-to-severe MRI injury on a TEA MRI scan was identified. A contemporaneous group of gestational age-matched control infants also born at <30 weeks of gestation with none/mild injury on MRI was also recruited. Quantitative aEEG measures, including maximum and minimum amplitudes, bandwidth span and spectral edge frequency (SEF90), were calculated using an offline software package. The aEEG recordings were qualitatively scored using the Burdjalov system. MRI scans, performed on the same day as aEEG, occurred at a mean postmenstrual age of 38.0 (range 37 to 42) weeks and were scored for abnormality in a blinded manner using an established MRI scoring system. RESULTS: Twenty-eight (46.7%) infants had a normal MRI or mild brain abnormality, while 32 (53.3%) infants had moderate-to-severe brain abnormality. Univariate regression analysis demonstrated an association between severity of brain abnormality and quantitative measures of left and right SEF90 and bandwidth span (ß=-0.38, -0.40 and 0.30, respectively) and qualitative measures of cyclicity, continuity and total Burdjalov score (ß=-0.10, -0.14 and -0.12, respectively). After correcting for confounding variables, the relationship between MRI abnormality score and aEEG measures of SEF90, bandwidth span and Burdjalov score remained significant. CONCLUSION: Brain abnormalities on MRI at TEA in premature infants are associated with abnormalities on term aEEG measures, suggesting that anatomical brain injury may contribute to delay in functional brain maturation as assessed using aEEG.

The role of post-mortem MRI in the neonatal intensive care unit.

OBJECTIVE: Post-mortem examination can provide important information about the cause of death and play a significant role in the bereavement process. Autopsies reveal previous unknown medical problems approximately 20 to 30% of the time. A non-invasive magnetic resonance imaging-based post-mortem examination (PM-MRI) may provide an alternative for families who do not consent to an autopsy. STUDY DESIGN: This study was a prospective observational study of recently expired neonates and infants. Subjects underwent a full body MRI scan (brain, chest, abdomen and pelvis) followed by conventional autopsy if the family desired to have one. MRI results were compared with autopsy findings and the ante-mortem clinical diagnosis. A follow-up survey was conducted to investigate family perceptions of the PM-MRI process. RESULTS: Thirty-one infants underwent full PM-MRI. Of 31 infants, 19 (61%) had complete agreement between the clinician's impression and PM-MRI. Twenty-four infants also had conventional autopsy, with 14/24 (58%) infants having PM-MRI results consistent with autopsy findings. PM-MRI was superior at detection of free intraperitoneal/intrathoracic air and hepatic iron overload. Whole-body PM-MRI did not have the resolution to detect focal/microscopic injury, vascular remodeling and some forms of brain injury. Of those families who remembered the PM-MRI findings, the majority felt that the information was useful. CONCLUSIONS: PM-MRI studies may provide an important adjunct to conventional autopsy and a substitute when the latter is not possible for personal or religious reasons. Clinicians should be aware of, and communicate with the family, the resolution limits of the whole-body PM-MRI to detect certain types of injury.

Empirical estimation of the normative blood pressure in infants <28 weeks gestation using a massive data approach.

OBJECTIVE: To determine the expected systolic, mean and diastolic blood pressures at birth and respective rates of change during the first 72 h of life in infants born at <28 weeks estimated gestational age (EGA) with a favorable short-term outcome, defined as survival to 14 days with grade II or less intraventricular hemorrhage (IVH). STUDY DESIGN: Systolic, mean and diastolic blood pressures were continuously sampled at 0.5 Hz via umbilical artery catheter from birth through 72 h. The raw data were aligned by postnatal hour and underwent error correction. For each infant, the mean values of systolic, mean and diastolic blood pressure were calculated for each postnatal hour. The slope and intercept of best-fit line for each of the three blood pressure parameters was then calculated. Infants that received inotropic medications, died in the first 14 days of life, or had IVH grade III or IV were excluded. RESULT: Using 11.9 million valid data points from 35 infants (mean EGA=25.7 ± 1.5 weeks, mean birth weight=865 ± 201 g), we found independent associations of African-American race (P<0.01) and a complete course of antenatal steroids (P<0.01) with higher blood pressures at birth and a slower rate of increase. Acute chorioamnionitis was independently associated (P=0.02) with lower blood pressures at birth and a faster rate of increase. EGA and birth weight were not independently predictive of blood pressure parameters. CONCLUSION: We found that (i) the estimated mean blood pressure at birth is ~33 mmHg in a cohort of very preterm infants, (ii) blood pressure gradually increases with postnatal age, (iii) systolic blood pressure increases at a faster rate than diastolic blood pressure, (iv) race, antenatal steroid exposure and chorioamnionitis are independent modulators of blood pressure whereas EGA and birth weight are not.

Response to dopamine in prematurity: a biomarker for brain injury?

OBJECTIVE: To identify factors associated with responsiveness to dopamine therapy for hypotension and the relationship to brain injury in a cohort of preterm infants. STUDY DESIGN: The pharmacy database at St Louis Children's Hospital was retrospectively queried to identify infants who (a) were born <28 weeks gestation between 2012 and 2014, (b) received dopamine and (c) had blood pressure measurements from an umbilical arterial catheter. A control group was constructed from contemporaneous infants who did not receive dopamine. Mean arterial blood pressure (MABP) at baseline, 1 h and 3 h after initiating dopamine were obtained for each dopamine-exposed infant. MABP measurements at matched time points were obtained in the control group. RESULT: Sixty-nine dopamine-treated and 45 control infants were included. Mean ΔMABP at 3 h was 4.5±6.3 mm of Hg for treated infants vs 1±2.9 for the control. Median dopamine starting dose was 2.5 µg kg(-1) min(-1). Dopamine-treated infants were less mature and of lower birth weight while also more likely to be intubated at 72 h, diagnosed with intraventricular hemorrhage (IVH) and to die. Failure to respond to dopamine was associated with greater likelihood of developing IVH (odds ratio (OR) 5.8, 95% confidence interval (CI) 1.1-42.3), while a strong response (ΔMABP>10 mm Hg) was associated with a reduction in risk of IVH (OR 0.1, 95% CI 0.01-0.8). CONCLUSION: Low-moderate dose dopamine administration results in modest blood pressure improvements. A lack of response to dopamine is associated with a greater risk of IVH, whereas a strong response is associated with a decreased risk. Further research into underlying mechanisms and management strategies is needed.

Early hyperoxia burden detected by cerebral near-infrared spectroscopy is superior to pulse oximetry for prediction of severe retinopathy of prematurity.

OBJECTIVE: Fractional tissue oxygen extraction (FTOE) is a measure derived from cerebral near-infrared spectroscopy (NIRS) and simultaneous pulse oximetry (SpO2), capturing the proportion of oxygen delivered in arterial blood that is used by the target tissue. FTOE may provide a better proxy measurement of retinal hyperoxia than pulse oximetry alone and could provide insight into the risk for retinopathy of prematurity (ROP). In this study, we directly compared hyperoxia burden calculated from FTOE with hyperoxia burden calculated from SpO2 alone in order to assess the strength of association between hyperoxia and severe ROP. STUDY DESIGN: Infants born before <30 weeks and weighing <1500 g underwent synchronized SpO2 and FTOE recording over the first 4 days following birth. After error correction of the raw recording, hyperoxia burden was calculated as the percentage of the total SpO2 or FTOE recording with measurements exceeding defined thresholds (90/93/95% and 20/15/10%, respectively) and was compared with the outcome of severe ROP, defined as ROP requiring laser therapy, after controlling for important covariates. RESULT: A total of 63 infants were included with a mean±s.d. gestational age of 25.8±1.5 weeks and birth weight of 898.5±206.9 g; 13/63 (20%) had severe ROP. SpO2 hyperoxia burden was not associated with severe ROP at any threshold. FTOE hyperoxia burden was associated with severe ROP at the 15% (P=0.04) and 10% (P=0.03) thresholds. Infants with severe ROP spent 20% and 50% more time exceeding the 15% and 10% thresholds, respectively, as compared with those without severe ROP. CONCLUSION: In the first 96 h of life, FTOE but not SpO2 hyperoxia burden is associated with severe ROP. These preliminary results suggest that NIRS may be a viable alternative technology for targeted oxygen saturation guidelines.

Normative amplitude-integrated EEG measures in preterm infants.

OBJECTIVE: Assessing qualitative patterns of amplitude-integrated electroencephalography (aEEG) maturation of preterm infants requires personnel with training in interpretation and an investment of time. Quantitative algorithms provide a method for rapidly and reproducibly assessing an aEEG recording independent of provider skill level. Although there are several qualitative and quantitative normative data sets in the literature, this study provides the broadest array of quantitative aEEG measures in a carefully selected and followed cohort of preterm infants with mild or no visible injury on term-equivalent magnetic resonance imaging (MRI) and subsequently normal neurodevelopment at 2 and 7 years of age. STUDY DESIGN: A two-channel aEEG recording was obtained on days 4, 7, 14 and 28 of life for infants born ⩽30 weeks estimated gestational age. Measures of amplitude and continuity, spectral edge frequency, percentage of trace in interburst interval (IBI), IBI length and frequency counts of smooth delta waves, delta brushes and theta bursts were obtained. MRI was obtained at term-equivalent age and neurodevelopmental testing was conducted at 2 and 7 years of corrected age. RESULT: Correlations were found between increasing postmenstrual age (PMA) and decreasing maximum amplitude (R= -0.23, P=0.05), increasing minimum amplitude (R=0.46, P=0.002) and increasing spectral edge frequency (R=0.78, P=4.17 × 10(-14)). Negative correlations were noted between increasing PMA and counts of smooth delta waves (R= -0.39, P=0.001), delta brushes (R= -0.37, P=0.003) and theta bursts (R= -0.61, P=5.66 × 10(-8)). Increasing PMA was also associated with a decreased amount of time spent in the IBI (R= -0.38, P=0.001) and a shorter length of the maximum IBI (R= -0.27, P=0.03). CONCLUSION: This analysis supports a strong correlation between quantitatively determined aEEG measures and PMA, in a cohort of preterm infants with normal term-equivalent age neuroimaging and neurodevelopmental outcomes at 7 years of age, which is both predictable and reproducible. These 'normative' quantitative values support the pattern of maturation previously identified by qualitative analysis.