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After more than a decade of rigorous empirical work, it is increasingly accepted that long-term outcomes after critical illness are an important problem-not only clinically meaningful for patients, but scientifically fecund for understanding basic biology (1). Many-but by no means all-of our patients who survive critical illness will have important new deficits in their brain or muscle function. Many of these injuries will be new, although there will also be some acute recognition of chronic problems (2, 3). To design a randomized controlled trial of therapies to improve these long-term outcomes, we need an appropriately defined patient population, a biologically plausible intervention, and a clinically meaningful endpoint. In this issue of the Journal, Woon and colleagues (pp. 333-340) provide important and provocative new data to inform our choice of endpoint (4).
To understand why these results are so interesting, we need to make explicit the mental models of post-ICU trajectory that we usually only reference implicitly. Why could so many of us read the report by Schweickert and colleagues of a difference in hospital discharge location after early mobilization, and yet confidently use such data to justify this intervention for all patients to improve long-term outcomes (5)? I suggest that it is because those results resonated with our implicit mental model, shown in Figure 1 as the Big Hit. In a Big Hit trajectory, patients have an acute loss of function during their critical illness, from which they may gradually recover. After acute illness, it appears that peak recovery is 1-2 years after initial injury for physical functioning (6-8). Nonetheless, we expect a relatively smooth trajectory after the initial deficit. Key questions after a Big Hit are how we can reduce the depth of the initial functional loss, improve the slope of functional recovery, and minimize the residual deficits.
Woon and colleagues test the hypothesis that individual patients' cognitive function at discharge would be strongly predictive of 6-month cognitive function, as we might expect from a Big Hit trajectory. If this hypothesis were correct, the authors would thereby validate a short-term, readily obtained measure that could serve as a surrogate endpoint for a longer-term outcome. Such a validation would let us target postdischarge cognitive rehabilitation to a subset of patients, increasing cost effectiveness of any...