Effect of the Central Nervous System Ischemic Response on Systemic Arterial Pressure and Intracranial Pressure Oscillations in Patients with Severe Head Injury. A Modeling Study

This work investigates the complex relationships among cerebrovascular dynamics, intracranial pressure (ICP), Cushing response, and short-term systemic regulation, during plateau waves, by means of an original mathematical model. The model incorporates the pulsating heart, the pulmonary circulation and the systemic circulation, with an accurate description of the cerebral circulation and the ICP dynamics. Various regulatory mechanisms are included: cerebral autoregulation, local blood flow control by O2/CO2 changes, sympathetic and vagal regulation of cardiovascular parameters by several reflex mechanisms (chemoreceptors, lung-stretch receptors, baroreceptors). The Cushing response has been described assuming a dramatic increase in sympathetic activity to vessels during a fall in brain oxygen delivery. With this assumption, the model is able to simulate the cardiovascular effects experimentally observed when ICP is artificially elevated and maintained at constant level (arterial pressure increase and bradicardia). According to the model, these effects arise from the interaction between the Cushing response and the baroreflex response (secondary to arterial pressure increase). Then, patients with severe head injury have been simulated by reducing intracranial compliance and cerebrospinal fluid reabsorption. With these changes. ICP oscillations with plateau waves developed. Model results indicate that the Cushing response may have both positive effects, reducing the duration of the plateau phase via an increase in cerebral perfusion pressure, and negative effects, increasing the ICP plateau level, with a risk of greater compression of the cerebral vessels. The model may be of value to assist clincians in finding the balance between clinical benefits of the Cushing response and its shortcomings.