Temperature dysregulation during therapeutic hypothermia predicts long-term outcome in neonates with HIE.

Few reliable or easily obtainable biomarkers to predict long-term outcome in infants with hypoxic-ischemic encephalopathy (HIE) have been identified. We previously showed that mattress temperature (MT), as proxy for disturbed temperature regulation during therapeutic hypothermia (TH), predicts injury on early MRI and holds promise as physiologic biomarker. To determine whether MT in neonates treated with TH for moderate-severe HIE is associated with long-term outcome at 18-22 months, we performed a secondary analysis of the Optimizing Cooling trial using MT data from 167 infants treated at a core temperature of 33.5°C. Median MTs from four time-epochs (0-6 h, 6-24 h, 24-48 h, and 48-72 h of TH) were used to predict death or moderate-severe neurodevelopmental impairment (NDI), using epoch-specific derived and validated MT cutoffs. Median MT of infants who died or survived with NDI was consistently 1.5-3.0°C higher throughout TH. Infants requiring a median MT above the derived cut-offs had a significantly increased odds of death or NDI, most notably at 0-6 h (aOR 17.0, 95%CI 4.3-67.4). By contrast, infants who remained below cut-offs across all epochs had 100% NDI-free survival. MTs in neonates with moderate-severe HIE during TH are highly predictive of long-term outcome and can be used as physiologic biomarker.

Optical Detection of Intracranial Pressure and Perfusion Changes in Neonates With Hydrocephalus.

OBJECTIVE: To demonstrate that a novel noninvasive index of intracranial pressure (ICP) derived from diffuse optics-based techniques is associated with intracranial hypertension. STUDY DESIGN: We compared noninvasive and invasive ICP measurements in infants with hydrocephalus. Infants born term and preterm were eligible for inclusion if clinically determined to require cerebrospinal fluid (CSF) diversion. Ventricular size was assessed preoperatively via ultrasound measurement of the fronto-occipital (FOR) and frontotemporal (FTHR) horn ratios. Invasive ICP was obtained at the time of surgical intervention with a manometer. Intracranial hypertension was defined as invasive ICP ≥15 mmHg. Diffuse optical measurements of cerebral perfusion, oxygen extraction, and noninvasive ICP were performed preoperatively, intraoperatively, and postoperatively. Optical and ultrasound measures were compared with invasive ICP measurements, and their change in values after CSF diversion were obtained. RESULTS: We included 39 infants, 23 with intracranial hypertension. No group difference in ventricular size was found by FOR (P = .93) or FTHR (P = .76). Infants with intracranial hypertension had significantly higher noninvasive ICP (P = .02) and oxygen extraction fraction (OEF) (P = .01) compared with infants without intracranial hypertension. Increased cerebral blood flow (P = .005) and improved OEF (P < .001) after CSF diversion were observed only in infants with intracranial hypertension. CONCLUSIONS: Noninvasive diffuse optical measures (including a noninvasive ICP index) were associated with intracranial hypertension. The findings suggest that impaired perfusion from intracranial hypertension was independent of ventricular size. Hemodynamic evidence of the benefits of CSF diversion was seen in infants with intracranial hypertension. Noninvasive optical techniques hold promise for aiding the assessment of CSF diversion timing.

Standardizing treatment of preterm infants with post-hemorrhagic hydrocephalus at a single institution with a multidisciplinary team.

BACKGROUND: Preterm infants with post-hemorrhagic hydrocephalus (PHH) are often treated with temporizing measures such as ventricular access devices (VADs) in order to drain cerebrospinal fluid (CSF) prior to permanent diversion with ventriculoperitoneal shunt (VPS) placement. LOCAL PROBLEM: There is little consensus on the timing and management of VADs and VPSs. This leads to marked practice variations among treating services that can adversely affect patient outcomes. METHODS: This is a quality improvement study evaluating practices from February 2011 to September 2017 including infants with PHH in a single level IV NICU. INTERVENTIONS: A multidisciplinary team created a local clinical pathway modified from the Hydrocephalus Clinical Research Network's Shunting Outcomes in Post-Hemorrhagic Hydrocephalus protocol to manage infants with PHH. Methods of CSF diversion and shunt timing were based on weight. Neonatal care providers performed VAD aspiration; timing was guided by imaging and clinical exam criteria. Surgical procedures were performed in the NICU. RESULTS: There were 78 patients eligible for the study. Prior to pathway implementation, infections occurred in 4% of VAD and 3% of VPS patients. There have been no infections since inception of the pathway. With pathway implementation, treatment compliance improved from 55 to 86% while conversion compliance rate improved from 89 to 100%. CONCLUSIONS: Standardization of care for PHH infants leads to improvement in patient outcomes such as a decrease in time to VAD placement. Reservoir aspirations by the neonatology team did not result in an increase in infection rate.

Oxygen sensing neurons and neuropeptides regulate survival after anoxia in developing C. elegans.

Hypoxic brain injury remains a major source of neurodevelopmental impairment for both term and preterm infants. The perinatal period is a time of rapid transition in oxygen environments and developmental resetting of oxygen sensing. The relationship between neural oxygen sensing ability and hypoxic injury has not been studied. The oxygen sensing circuitry in the model organism C. elegans is well understood. We leveraged this information to investigate the effects of impairments in oxygen sensing on survival after anoxia. There was a significant survival advantage in developing worms specifically unable to sense oxygen shifts below their preferred physiologic range via genetic ablation of BAG neurons, which appear important for conferring sensitivity to anoxia. Oxygen sensing that is mediated through guanylate cyclases (gcy-31, 33, 35) is unlikely to be involved in conferring this sensitivity. Additionally, animals unable to process or elaborate neuropeptides displayed a survival advantage after anoxia. Based on these data, we hypothesized that elaboration of neuropeptides by BAG neurons sensitized animals to anoxia, but further experiments indicate that this is unlikely to be true. Instead, it seems that neuropeptides and signaling from oxygen sensing neurons operate through independent mechanisms, each conferring sensitivity to anoxia in wild type animals.

Continuous antibiotic prophylaxis and cerebral spinal fluid infection in patients with intracranial pressure monitors.

INTRODUCTION: Inconsistencies in the recommendation of prophylactic antibiotics for patients with intracranial pressure monitors compelled us to assess the effect of our standard regimen of continuous antibiotic prophylaxis on cerebrospinal fluid infection. We examined the rate, possible risk factors, causative organisms, and characteristics of infection. METHODS: Three hundred eleven patients admitted between September 1998 and February 2001 with an intracranial pressure monitoring device in place were included. Two hundred eleven patients received a ventriculostomy, 95 an intraparenchymal fiber optic intracranial pressure monitor (ICPM), and 5 both an ICPM and a ventriculostomy. RESULTS: The overall infection rate was 5.5% (17/311). No patient with an ICPM developed CSF infection. The infection rate among ventriculostomy patients was 8.1% (17/211). The majority of infections (82%) were caused by Gram-positive species. Younger age (OR=1.04 for each year, 95% CI=1.01-1.08, p=0.03) and increasing duration of ventriculostomy insertion (OR=1.2 for each day of catheter insertion, 95% CI=1.1-1.3, p<0.001) were risk factors for CSF infection in multivariate analysis. Infected patients experienced longer lengths of stay in the NICU (p<0.001) and hospital (p<0.001); however, infection did not impact clinical outcome, as measured by mortality and discharge GCS. CONCLUSION: ICP monitors have a low overall infection rate. When infection occurs, gram positive organisms predominate. For patients with ventriculostomy, duration of catheter insertion strongly predicts infection, but did not alter in-hospital mortality.