Cooling in neonatal hypoxic-ischemic encephalopathy: practices and opinions on minimum standards in the state of California.

OBJECTIVE: Although hospitals increasingly offer therapeutic hypothermia (TH), there is variable implementation of related services. We assessed current practices and opinions regarding what services should be required of centers providing TH in California. STUDY DESIGN: We surveyed neonatal intensive care unit physicians statewide regarding practices and opinions about services related to TH. RESULTS: Of the 50 participating centers (47% response rate), 66% offer TH. Most TH centers reported using: an evidence-based protocol (92%), neurology consultation (92%), amplitude-integrated electroencephalography (aEEG) or EEG (88%), magnetic resonance imagings (MRIs) interpreted by pediatric neuroradiologists (71%) and developmental follow-up (93%). TH centers reported treating a median of 11 patients annually (interquartile range (IQR) 4 to 24). Respondents considered it 'critical' that TH centers offer: aEEG monitoring (70%), MRI (69%), occupational and physical therapy (67%) and developmental follow-up (94%). Over 70% thought TH centers should treat a minimum volume annually (median=10, IQR 5 to 12). CONCLUSION: Physicians across practice settings in California endorsed minimum standards for TH centers to promote quality of care.

Continuous Video Electroencephalographic (EEG) Monitoring for Electrographic Seizure Diagnosis in Neonates: A Single-Center Study.

The objective of this study was to determine the diagnostic yield of continuous video electroencephalographic (EEG) monitoring in critically ill neonates in the setting of a novel, university-based Neonatal Neurocritical Care Service. Patient demographic characteristics, indication for seizure monitoring, and presence of electrographic seizures were obtained by chart review. Among 595 patients cared for by the Neonatal Neurocritical Care Service, 400 (67%) received continuous video EEG. The median duration of continuous video EEG monitoring was 49 (interquartile range = 22-87) hours. Electrographic seizures were captured in 105 of 400 (26% of monitored patients) and of those, 25 of 105 (24%) had no clinical correlate. In addition, 52 of 400 subjects (13%) were monitored due to paroxysmal events concerning for seizures, but never had electrographic seizures. Continuous video EEG monitoring helped confirm or rule out ongoing seizures in more than one-third of the cases. This finding helps to support the use of continuous video EEG in critically ill neonates.

Impact of hypothermia on predictors of poor outcome: how do we decide to redirect care?

Therapeutic hypothermia is now considered the standard of care for neonates with neonatal encephalopathy due to perinatal asphyxia. Outcomes following hypothermia treatment are favorable, as demonstrated in recent meta-analyses, but 45-50% of these neonates still suffer major disability or die due to global multi-organ injury or after redirection of care from life support due to severe brain injury. The ability to determine which patients are at highest risk of severe neurologic impairment and death and those in whom redirection of care should be considered is limited. This is especially true in the first few days after birth and in situations where the brain might be more significantly affected than other organ systems, making it difficult to discuss redirection of care. Clinical history, neurologic examination, serum biomarkers, neurophysiology [amplitude-integrated electroencephalography (aEEG) or EEG], near-infrared spectroscopy, and magnetic resonance imaging have all been studied as predictors of severe neurologic injury and poor outcome, although none is 100% predictive. Serial evaluation over time seems to be an important element to facilitate discussion regarding anticipated poor prognosis and decision-making for transition to comfort care. Thus far, brain monitoring in the form of aEEG and conventional EEG seem to be the best objective tools to identify the highest-risk patients. A delay or lack of recovery of the aEEG background during hypothermia treatment is an established important predictor of poor outcome (death or disability). This paper highlights the prognostic indicators that have been considered and focuses on aEEG as an important predictor of death or severe disability, which may facilitate conversations regarding redirection of care.

Indirect antiglobulin test-crossmatch using low-ionic-strength saline-albumin enhancement medium and reduced incubation time: effectiveness in the detection of most clinically significant antibodies and impact on blood utilization.

Indirect antiglobulin test-crossmatch (IAT-XM) using enhancement media such as low-ionic-strength saline (LISS) and polyethylene glycol (PEG) usually requires 15 minutes of incubation. These methods are necessary when testing samples from blood recipients who have a higher risk of alloimmunization. In emergency situations, IAT-XM can be time-consuming and can influence presurgery routine, resulting in more red blood cell (RBC) units being tested and stored to avoid the transfusion of uncrossmatched ones. The objective of this study was to evaluate the performance of a LISS-albumin enhancer to intensify antigen-antibody reaction after 5 minutes of 37oC incubation and compare this performance with that of other enhancers, gel, and conventional tube testing. Second, the study evaluated the impact of this method's implementation in the C:T ratio (crossmatched to transfused RBC units) of a transfusion laboratory. Ninety serum samples containing alloantibodies of potential clinical significance were tested against phenotyped RBCs using four different methods: (1) tube with LISS-albumin enhancer (5 minutes of incubation), (2) tube with LISS-albumin and PEG (15 minutes of incubation), (3) gel, and (4) conventional tube method (60 minutes of incubation). In parallel, the study compared the C:T ratio of a tertiary-hospital transfusion laboratory in two different periods: 3 months before and 3 months after the implementation of the 5-minute IAT-XM protocol. The use of LISS-albumin with 5 minutes of incubation exhibited the same performance as LISS-albumin, PEG, and gel with 15 minutes of incubation. Conventional tube method results were equally comparable, but reactions were significantly less intense, except for anti-c (p = 0.406). Accuracy was 100 percent for all selected methods. After the implementation of the 5-minute IAT-XM protocol, the C:T ratio fell from 2.74 to 1.29 (p < 0.001). IAT-XM can have its incubation time reduced to 5 minutes with the use of LISS-albumin enhancement. We suggest this strategy should be used to quickly prepare RBC units for surgical patients, keeping transfusion safety without compromising blood supplies.

Every 36-h gentamicin dosing in neonates with hypoxic-ischemic encephalopathy receiving hypothermia.

OBJECTIVE: To examine the impact of a change in the empiric gentamicin dose from 5 mg kg(-1) every 24 h (Q24 h period) to 5 mg kg every 36 h (Q36 h period) on target drug concentration achievement in neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia. STUDY DESIGN: Gentamicin drug concentrations in neonates with HIE receiving therapeutic hypothermia were examined during two time periods in a retrospective chart review. During the initial treatment period (November 2007 to March 2010; n=29), neonates received Q24 h period. During the second treatment period (January 2011 to May 2012; n=23), the dose was changed to Q36 h period. Cooling criteria and protocol remained the same between treatment periods. Gentamicin drug concentrations including achievement of target trough concentrations (<2 mg l(-1)) were compared between treatment periods. Individual Bayesian estimates of gentamicin clearance were also compared. RESULT: Neonates with an elevated trough concentration >2 mg l(-1) decreased from 38 to 4% with implementation of a Q36-h dosing interval (P<0.007). The mean gentamicin trough concentration was 2.0 ± 0.8 mg l(-1) during the Q24 h period and 0.9 ± 0.4 mg l(-1) during the Q36 h period (P<0.001). Peak concentrations were minimally impacted (Q24 h 11.4 ± 2.3 mg l(-1) vs Q36 h 10.0 ± 1.9 mg l(-1); P=0.05). The change in gentamicin trough concentration could not be accounted for by differences in gentamicin clearance between treatment periods (P=0.9). CONCLUSION: A 5 mg kg(-1) every 36-h gentamicin dosing strategy in neonates with HIE receiving therapeutic hypothermia improved achievement of target trough concentration <2 mg l(-1), while still providing high peak concentration exposure.

Therapeutic hypothermia for neonatal encephalopathy results in improved microstructure and metabolism in the deep gray nuclei.

BACKGROUND AND PURPOSE: Therapeutic hypothermia has reduced morbidity and mortality and is associated with a lower burden of lesions on conventional imaging in NE. However, its effects on brain microstructure and metabolism have not been fully characterized. We hypothesized that therapeutic hypothermia improves measures of brain microstructure and metabolism. MATERIALS AND METHODS: Forty-one neonates with moderate/severe NE (29 treated with hypothermia, 12 nontreated) and 12 healthy neonates underwent MR imaging, DTI, and (1)H-MR spectroscopy. MR imaging scans were scored by the predominant pattern of brain injury: normal, watershed, and BG/thalamus. ADC, FA, Lac:NAA, and NAA:Cho values from bilateral BG and thalamus ROIs were averaged. T test and linear regression analysis were used to determine the association between hypothermia and MR imaging quantitative measures. RESULTS: Conventional MR imaging findings were normal in 41% of treated neonates; all nontreated neonates had brain injury. Values of MR imaging metrics were closer to normal in treated neonates compared with nontreated neonates: ADC was 63% higher in the BG and 116% higher in the thalamus (both P < .05), and Lac:NAA was 76% lower (P = .04) in the BG. Treated neonates with normal MR imaging findings had normal (1)H-MR spectroscopy metabolites, and ADC was higher by 35% in the thalamus (P = .03) compared with healthy neonates. CONCLUSIONS: Therapeutic hypothermia may reduce disturbances of brain metabolism and preserve its microstructure in the setting of NE, possibly by minimizing cytotoxic edema and cell death. Long-term follow-up studies are required to determine whether early post-treatment DTI and (1)H-MR spectroscopy will be useful biomarkers of treatment response.

Video-EEG monitoring in newborns with hypoxic-ischemic encephalopathy treated with hypothermia.

BACKGROUND: Therapeutic hypothermia (TH) is becoming standard of care in newborns with hypoxic-ischemic encephalopathy (HIE). The prognostic value of the EEG and the incidence of seizures during TH are uncertain. OBJECTIVE: To describe evolution of EEG background and incidence of seizures during TH, and to identify EEG patterns predictive for MRI brain injury. METHODS: A total of 41 newborns with HIE underwent TH. Continuous video-EEG was performed during hypothermia and rewarming. EEG background and seizures were reported in a standardized manner. Newborns underwent MRI after rewarming. Sensitivity and specificity of EEG background for moderate to severe MRI brain injury was assessed at 6-hour intervals during TH and rewarming. RESULTS: EEG background improved in 49%, remained the same in 38%, and worsened in 13%. A normal EEG had a specificity of 100% upon initiation of monitoring and 93% at later time points. Burst suppression and extremely low voltage patterns held the greatest prognostic value only after 24 hours of monitoring, with a specificity of 81% at the beginning of cooling and 100% at later time points. A discontinuous pattern was not associated with adverse outcome in most patients (73%). Electrographic seizures occurred in 34% (14/41), and 10% (4/41) developed status epilepticus. Seizures had a clinical correlate in 57% (8/14) and were subclinical in 43% (6/14). CONCLUSIONS: Continuous video-EEG monitoring in newborns with HIE undergoing TH provides prognostic information about early MRI outcome and accurately identifies electrographic seizures, nearly half of which are subclinical.

Comparison of conventional tube test technique and gel microcolumn assay for direct antiglobulin test: a large study.

Gel microcolumn assay (GMA) is a modified serological technique that has been used for ABO and Rh typing, direct antiglobulin test (DAT), detecting alloantibodies, red cell phenotyping, and other applications. However, for DAT, the role of GMA is controversial. The purpose of this large study was to compare the performance of the conventional tube test (CTT) to GMA for detecting potentially significant antibodies coating red blood cells in vivo. From January 1996 to May 2002, we performed DATs by GMA and CTT on 9,862 blood samples submitted to our reference laboratory, using LISS/Coombs cards (DiaMed-Latino America, Lagoa Santa-MG, Brazil) for GMA and polyspecific and monospecific anti-IgG reagents for CTT. Acid eluates were prepared from all positive DAT samples. The specificity of eluates was determined by GMA. We detected nonconcordant results in 2,079 out of 3,163 positive DATs (65.7%). All of these tests were only positive in GMA. Sensitivity and specificity for DATs was 100% and 83.0% for gel, and 50.7% and 97.8% for tube, respectively. Based on this study GMA showed to be more sensitive than CTT for detecting potentially significant antibodies coating red blood cells in vivo.

Comparison of conventional tube test with diamed gel microcolumn assay for anti-D titration.

Anti-D titration is the first step in the evaluation of the RhD-sensitized patient. Traditionally, anti-D titration has been performed by tube agglutination. Gel microcolumn assay is a method that has gained widespread usage throughout the world, mainly for ABO/Rh typing, unexpected antibody screening and direct antiglobulin tests. As gel assay has become widely used as a routine method to detect red blood cell alloantibodies, a critical anti-D titer needs to be established. Seventy-nine known blood samples with anti-D (titers 1-32) were titrated simultaneously by the conventional tube test and the gel microcolumn assay. Red blood cells (R0r phenotype) were used, with a final concentration of 3% for tube and 0.8% for gel. Serial twofold dilutions (2-2.048) were prepared for each technique, followed by reading in antiglobulin phase. Anti-D titration in the gel microcolumn assay showed significantly higher titers (mean 3.4-fold) than the conventional tube test in all samples studied. Based on these data, it was not possible to determine a critical titer for anti-D titration by the gel microcolumn assay.