Hypoxia and Outcome Prediction in Early Stage Coma: Towards an Improvement of Clinical and Electrophysiological Predictors

HOPE conducts a 2.5-year multicenter prospective cohort study in Germany on outcome prediction in the early stages of coma caused by cerebral hypoxia-ischemia.

The main features of the project are:

• Control for a self-fulfilling prophecy
• Long-term follow-up (12 months) covering acute and neurorehabilitation phases
• Use of sensitive measures of level of consciousness
• Further in-depth and systematic examination of the predictive value of somato-sensory evoked potentials (SSEP)

Using as a reference existing guidelines and previous research, we consider the following factors to be predictors of a negative outcome with a high specificity of > 90% with small 95% confidence intervals: loss of cortical N20 SEP potentials, loss of more than one brain stem reflex, non-reactive EEG, or a NSE above 33 mcg/L. We refer to the presence of any of these specific unfavourable test results during the ICU treatment as a "negative predictor". Therefore, our null hypothesis is that the probability of a favourable outcome, despite the presence of a negative predictor, is < 10%. We will use Simon's two-stage design. The null hypothesis will be tested against a one-sided alternative. In the first stage, we will accrue 72 patients. If there are 8 or fewer good outcomes in these 72 patients, the study will be discontinued because the null hypothesis could not be rejected. Otherwise, we will recruit 100 additional patients to gather a total of 172. The null hypothesis will be rejected if 28 or more favourable outcomes are observed in these 172 patients. This design yields a type I error rate of 0.05 and power of 80% if the true response rate is 25%, i.e. if indeed 25% or more patients have a favourable outcome despite a negative predictor. This calculation is based on the assumption that 25% of the enrolled patients have at least one negative predictor.

HOPE has seven data entry points (i.e. study visits).The primary endpoints are completion of the follow-up period or patient death. HOPE collects clinical and demographic data in accordance to Utstein-style recommendations. The most crucial part of the study is determining the current level of consciousness by means of the revised version of the Coma Recovery Scale (CRS-R). The CRS-R allows a precise categorization of the current level of consciousness based on a structured and systematic clinical examination of auditory, visual, motor, oromotor, communication and arousal functions. Other assessment instruments employed yield information about functional outcome/ADL, neuropsychological performance, and health-related quality of life.