Therapeutic hypothermia: quantification of the transition of core body temperature using the flexible mixture bent-cable model for longitudinal data

Abstract

By reducing core body temperature, T_c, induced hypothermia is a therapeutic tool to prevent brain damage resulting from physical trauma. However, all physiological systems begin to slow down due to hypothermia that in turn can result in increased risk of mortality. Therefore, quantification of the transition of T_c to early hypothermia is of great clinical interest. Conceptually, T_c may exhibit an either gradual or abrupt transition. Bent-cable regression is an appealing statistical tool to model such data due to the model's flexibility and greatly interpretable regression coefficients. It handles more flexibly models that traditionally have been handled by low-order polynomial models (for gradual transition) or piecewise linear changepoint models (for abrupt change). We consider a rat model for humans to quantify the temporal trend of T_c to primarily address the question: What is the critical time point associated with a breakdown in the compensatory mechanisms following the start of hypothermia therapy? To this end, we develop a Bayesian modelling framework for bent-cable regression of longitudinal data to simultaneously account for gradual and abrupt transitions. Our analysis reveals that: (a) about 39% of rats exhibit a gradual transition in T_c; (b) the critical time point is approximately the same regardless of transition type; (c) both transition types show a significant increase of T_c followed by a significant decrease.