Cerebral Autoregulation–Guided Optimal Blood Pressure in Sepsis-Associated Encephalopathy: A Case Series

Abstract

Background: Impaired cerebral autoregulation and cerebral hypoperfusion may play a critical role in the high morbidity and mortality in patients with sepsis-associated encephalopathy (SAE). Bedside assessment of cerebral autoregulation may help individualize hemodynamic targets that optimize brain perfusion. We hypothesize that near-infrared spectroscopy (NIRS)–derived cerebral oximetry can identify blood pressure ranges that enhance autoregulation in patients with SAE and that disturbances in autoregulation are associated with severity of encephalopathy. Methods: Adult patients with acute encephalopathy directly attributable to sepsis were followed using NIRS-based multimodal monitoring for 12 consecutive hours. We used the correlation in time between regional cerebral oxygen saturation and mean arterial pressure (MAP) to determine the cerebral oximetry index (COx) as a measure of cerebral autoregulation. Autoregulation curves were constructed for each patient with averaged COx values sorted by MAP in 3 sequential 4-hour periods; the optimal pressure (MAPOPT), defined as the MAP associated with most robust autoregulation (lowest COx), was identified in each period. Severity of encephalopathy was measured with Glasgow coma scale (GCS). Results: Six patients with extracranial sepsis met the stringent criteria specified, including no pharmacological sedation or neurologic premorbidity. Optimal MAP was identified in all patients and ranged from 55 to 115 mmHg. Additionally, MAPOPT varied within individual patients over time during monitoring. Disturbed autoregulation, based on COx, was associated with worse neurologic status (GCS < 13) both with and without controlling for age and severity of sepsis (adjusted odds ratio [OR]: 2.11; 95% confidence interval [CI]: 1.77-2.52; P < .001; OR: 2.97; 95% CI: 1.63-5.43; P < .001). Conclusions: In this high-fidelity group of patients with SAE, continuous, NIRS-based monitoring can identify blood pressure ranges that improve autoregulation. This is important given the association between cerebral autoregulatory function and severity of encephalopathy. Individualizing blood pressure goals using bedside autoregulation monitoring may better preserve cerebral perfusion in SAE than current practice.

Cerebral Autoregulation in Non-Brain Injured Patients: A Systematic Review

“…Cerebral autoregulation can be also evaluated to guide optimal blood pressure. Indeed, in a study including six patients ( 18 ), pharmacological sedation free with extracranial sepsis and cerebral oximetry was measured with NIRS to identify blood pressure range, demonstrating feasibility to optimize autoregulation maintaining adequate blood pressure range. In this case series, Rosenblatt et al found an association between cerebral autoregulatory function and the development and severity of encephalopathy defined as GCS <15 but ≥ 13 (mild encephalopathy), whereas values <13 were defined as moderate or severe impairment ( 18 ).…”

“…Indeed, in a study including six patients ( 18 ), pharmacological sedation free with extracranial sepsis and cerebral oximetry was measured with NIRS to identify blood pressure range, demonstrating feasibility to optimize autoregulation maintaining adequate blood pressure range. In this case series, Rosenblatt et al found an association between cerebral autoregulatory function and the development and severity of encephalopathy defined as GCS <15 but ≥ 13 (mild encephalopathy), whereas values <13 were defined as moderate or severe impairment ( 18 ). The authors concluded that individualizing blood pressure goals by using bedside autoregulation monitoring may preserve cerebral perfusion by individualizing blood pressure range in Sepsis-associated encephalopathy (SAE) ( 18 ).…”

“…The lack of homogeneous outcomes found in the studies included can be explained by the different settings applied and makes difficult to draw any conclusion regarding the possible effects of brain monitoring on outcome. The presence of sedation during neurological evaluation, the use of different scores for neurological impairment, and CA evaluation methods can also impact on the reproducibility of the results; nevertheless, all the studies suggest that measuring CA is safe and feasible and can potentially provide important information regarding intracerebral changes during the ICU stay and possibly improve outcomes (16)(17)(18). The analyzed studies confirm the presence of frequently altered CA in sepsis or septic shock, mostly during latest phases of sepsis and altered CA is the important risk factor for cognitive dysfunction (15,17).…”

Oxidative stress and decreased tissue HSP70 are involved in the genesis of sepsis: HSP70 as a therapeutic target

“…The Glasgow Coma Scale (GCS), which verifies the level of consciousness, and electroencephalography (EEG), which checks brain electrical activity, have been tools used for the diagnosis of septic encephalopathy. ( 36 ) Oxidative stress is highlighted in the pathophysiology of neurological dysfunction in sepsis, as it is associated with acute brain inflammation, cognitive deficit and long-term neurodegeneration in rats that survive sepsis. ( 37 ) Furthermore, oxidative stress is associated with a bioenergetic imbalance, which leads to mitochondrial dysfunction and, in turn, to cell death and brain tissue damage in sepsis.…”

Current Issues and Perspectives in Patients with Possible Sepsis at Emergency Departments

“…The patients with septic shock can be identified by the association of the clinical symptoms of sepsis with persistent hypotension that requires vasopressor agents to maintain an average blood pressure of 65 mmHg, and that have serum lactate levels >18 mg/dl despite adequate volume resuscitation. If the patient shows conditions of severe hemodynamic instability, then the diuresis must be monitored (also by urinary catheterization), as well as liquids infusions and the management with amino vasopressor agents should be considered [2,10,23].…”