From targeting to optimizing cerebral perfusion pressure.

To the Editor: In a recent issue of Critical Care Medicine, Kumar et al (1) have completed an important clinical trial in children with CNS infections and intracranial hypertension. They examined the unsettled question of intracranial pressure (ICP) versus cerebral perfusion pressure (CPP)-targeted strategies. This is a clinical debate that has been ongoing in the field of severe traumatic brain injury (TBI). Although extrapolations from the TBI literature to other etiologies of brain injury may be pathophysiologically inappropriate, the clinical reality is one where the approach to ICP/CPP follows TBI-informed principles. On this premise, and on the basis of the physiologic concept of cerebrovascular pressure reactivity, I would like to comment on the interpretation of this trial’s results as shown in Figure 7, A and B in the article by Kumar et al (1). Pressure reactivity refers to an intrinsic mechanism of vascular smooth muscle to regulate blood flow by varying the vessel diameter in response to the arterial pressure; a pressure-reactive vascular bed constricts to an increase in blood pressure, leading to decreases in cerebral blood volume (CBV) and consequently in ICP. Contrary, in pressure-insensitive vessels, CBV and ICP follow passively variations in blood pressure. As noted by the authors, at the time of enrollment, the lack of correlation between mean arterial pressure (MAP) and ICP indicates a cohort of patients starting off with preserved pressure reactivity. As expected, in both CPP groups (survivors and nonsurvivors), ICP decreases promptly in response to therapeutic MAP augmentation. The ICP course of these two groups, however, diverges with time. Whereas the ICP remains controlled in the survivors, there is a progressive rise in the ICP of the nonsurvivor group. This progressive rise in ICP suggests that the relationship between MAP and ICP changed from an initially reactive one to a passive one. Patients who maintained pressure reactivity and were treated by CPP targeting survived; patients who became pressure passive and continued to be treated with CPP targeting developed refractory intracranial hypertension. Pressure reactivity has been shown not to be an all-or-nothing, static condition, rather it is a patient-specific and dynamic process; this has been demonstrated via monitoring of the pressure reactivity index (PRx) in TBI, aneurysmal subarachnoid hemorrhage, and intracerebral hemorrhage patients (2). In fact, Brady et al (3) found that in a pediatric TBI population, the PRx was CPP dependent with better preservation in higher CPP levels. Further evidence for this physiologic explanation is the ICP course of surviving patients in the ICP-targeted group of Kumar et al (1). These patients achieved similar CPP levels with the nonsurvivors of the CPP-targeted group, yet their ICP remained controlled because they received the pressure-passive “appropriate” regimen, that is, ICP targeting. In this respect, the findings are reminiscent of the work by Howells et al (4) who found that the outcome of two TBI groups, treated in different centers with opposing strategies, differed based on the state of pressure reactivity and the type of CPP/ICP strategy they received. When the findings by Kumar et al (1) are examined in this light, the concept of CPP optimization rather than mere targeting emerges as the one that is intuitively more sound (5). The author has disclosed that he does not have any potential conflicts of interest.