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 (MAP_OPT), 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, MAP_OPT 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.

Keywords: cerebral autoregulation; critical care; hemodynamics; multimodal monitoring; near-infrared spectroscopy; oximetry; sepsis; sepsis-associated encephalopathy.

Figure 1

A, B, Calculation of the cerebral oximetry index (COx) in a 71-year-old man with septic shock from disseminated Nocardia. When mean arterial pressure (MAP) was approximately 55 to 90 mm Hg, MAP and regional cerebral oxygen saturation (rScO2) measured by near-infrared spectroscopy were positively correlated. The positive correlation yielded a COx value of 0.78, indicating pressure-passive cerebral blood flow with impaired autoregulation. The linear regression line is illustrated (E[Y] = 48.1+0.16X; 95% confidence interval for slope: 0.15, 0.17; P < .001). C, D, Calculation of COx in a 69-year-old patient with septic shock from Clostridium difficile colitis. When MAP was approximately 80–100 mm Hg, MAP and rScO2 were negatively correlated. This negative correlation resulted in a COx value of ‒0.42, indicating pressure-reactive cerebral blood flow with functional autoregulation. The linear regression line is illustrated (E[Y] = 74.54–0.29X; 95% confidence interval for slope: ‒0.35, ‒0.22; P < .001).

Figure 2

Representative graph of cerebral autoregulation by near-infrared spectroscopy (NIRS)–derived cerebral oximetry (COx) monitoring during a 4-hour period. The top graph represents the time series of blood pressure, and the bottom bar-graph represents the percentage of the 4-hour monitoring time spent at each 5-mm Hg bin. Optimal mean arterial pressure (MAP_OPT) was defined as that MAP with the lowest COx. In this example, MAP_OPT is 65 mm Hg (arrow). AU indicates arbitrary unit; MAP, mean arterial pressure.

Figure 3

Cerebral oximetry monitoring for 12 hours during sepsis in 2 patients. Mean values of COx were sorted into 5-mm Hg bins of mean arterial pressure (MAP) to determine optimal mean arterial pressure (MAP_OPT) for most active autoregulation based on a valley in the graph or the lowest (nadir) COx. A, Patient 2. Cerebral autoregulation was most robust at a MAP of 75, 90, and 55 mm Hg during the first, second, and third 4-hour periods, respectively, as indicated by the valley in each bar graph (arrows). B, Patient 3. The blood pressure at which autoregulation was most functional MAP_OPT was 95, 75, and 100 mm Hg during the first, second, and third 4-hour periods, respectively (arrows). In the first 4-hour period of monitoring in patient 3, a valley in the graph was not apparent; instead, the lowest (nadir) COx indicated MAP_OPT. Error bars represent the standard error of the mean.

Figure 4

Cerebral autoregulation is significantly different in sepsis patients with moderate to severe encephalopathy and mild encephalopathy. Boxes show median (line inside boxes) and interquartile range (box limits). COx indicates cerebral oximetry index; GCS, Glasgow coma scale.

Figure 5

Cerebral oximetry index (COx) for 10 to 12 consecutive hours during sepsis grouped according to Glasgow coma scale (GCS).