Limited short-term prognostic utility of cerebral NIRS during neonatal therapeutic hypothermia

Objective: We evaluated the utility of amplitude-integrated EEG (aEEG) and regional oxygen saturation (rSO(2)) measured using near-infrared spectroscopy (NIRS) for short-term outcome prediction in neonates with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia. Methods: Neonates with HIE were monitored with dual-channel aEEG, bilateral cerebral NIRS, and systemic NIRS throughout cooling and rewarming. The short-term outcome measure was a composite of neurologic examination and brain MRI scores at 7 to 10 days. Multiple regression models were developed to assess NIRS and aEEG recorded during the 6 hours before rewarming and the 6-hour rewarming period as predictors of short-term outcome. Results: Twenty-one infants, mean gestational age 38.8 +/- 1.6 weeks, median 10-minute Apgar score 4 (range 0-8), and mean initial pH 6.92 +/- 0.19, were enrolled. Before rewarming, the most parsimonious model included 4 parameters (adjusted R-2 = 0.59; p = 0.006): lower values of systemic rSO(2) variability (p = 0.004), aEEG bandwidth variability (p = 0.019), and mean aEEG upper margin (p = 0.006), combined with higher mean aEEG bandwidth (worse discontinuity; p = 0.013), predicted worse short-term outcome. During rewarming, lower systemic rSO(2) variability (p = 0.007) and depressed aEEG lower margin (p = 0.034) were associated with worse outcome (model-adjusted R-2 = 0.49; p = 0.005). Cerebral NIRS data did not contribute to either model. Conclusions: During day 3 of cooling and during rewarming, loss of physiologic variability (by systemic NIRS) and invariant, discontinuous aEEG patterns predict poor short-term outcome in neonates with HIE. These parameters, but not cerebral NIRS, may be useful to identify infants suitable for studies of adjuvant neuroprotective therapies or modification of the duration of cooling and/or rewarming.