Protocolized Brain Oxygen Optimization in Subarachnoid Hemorrhage

Abstract

Background: Brain tissue hypoxia (P_btO₂ < 20 mmHg) is common after subarachnoid hemorrhage (SAH) and associated with poor outcome. Recent data suggest that brain oxygen optimization is feasible and reduces the time spent with P_btO₂ < 20 mmHg from 45 to 16% in patients with severe traumatic brain injury. Here, we intended to quantify the brain tissue hypoxia burden despite implementation of a protocolized treatment approach in poor-grade SAH patients and to identify the simultaneous occurrence of pathologic values potentially amenable to treatment.

Methods: We present a bi-centric observational cohort study including 100 poor-grade SAH patients admitted to two tertiary care centers who underwent multimodal brain monitoring and were managed with a P_btO₂-targeted protocolized approach. P_btO₂ optimization (≥ 20 mmHg) included a stepwise neuro-intensive care approach, aiming to prevent low cerebral perfusion pressure (CPP), and blood hemoglobin, and to keep normocapnia, normoxemia, and normothermia. Based on routine blood gas analysis, hemoglobin, PaCO_2, and PaO₂ data were matched to 2-h averaged data of continuous CPP, P_btO₂, core temperature, and to hourly cerebral microdialysis (CMD) samples over the first 11 days.

Results: Patients had a Glasgow Coma Scale of 3 (IQR 3-4) and were 58 years old (IQR 48-66). Overall incidence of brain tissue hypoxia was 25%, which was not different between both sites despite differences in the treatment approach. During brain tissue hypoxia, episodes of CPP < 70 mmHg (27%), PaCO₂ < 35 mmHg (19%), PaO₂ < 80 mmHg (14%), Hb < 9 g/dL (11%), metabolic crisis (CMD-lactate/pyruvate ratio > 40, and CMD-glucose < 0.7 mmol/L; 7%), and temperature > 38.3 °C (4%) were common.

Conclusions: Our results demonstrate that brain tissue hypoxia remains common despite implementation of a P_btO₂-targeted therapy in poor-grade SAH patients, suggesting room for further optimization.

Keywords: Aneurysmal subarachnoid hemorrhage; Brain; Critical care; Neurology.

Fig. 1

Institutional protocols to treat brain tissue hypoxia (P_btO₂ < 20 mmHg) of NICU 1 and NICU 2

Fig. 2

Mean (± SEM) P_btO₂-levels over time are shown. Percentage of anemia (Hb < 9 g/dL) increased, whereas low cerebral perfusion pressure (CPP)-levels (< 70 mmHg) decreased during episodes of brain tissue hypoxia (P_btO₂ < 20 mmHg) over the study period

Fig. 3

Bars represent the percentage of simultaneous abnormal values shown in the x-axis during the time of brain tissue hypoxia (P_btO₂ < 20 mmHg). CPP cerebral perfusion pressure, Hb hemoglobin

Fig. 4

Center-specific mean (± SEM) cerebral perfusion pressure (CPP)-levels and frequencies of brain tissue hypoxia (P_btO₂ < 20 mmHg for at least 10 min) over the study period. *p < 0.05; **p < 0.01; ***p < 0.001

Fig. 5

Brain tissue hypoxia (P_btO₂ < 20 mmHg) burden at each site based on P_btO₂ mean values of 5-min intervals. a The daily brain tissue hypoxia burden, defined as the mean (± SEM) area under the curve of brain tissue hypoxia (= sum of depth of abnormalities multiplied by the time spent in P_btO₂ < 20 mmHg normalized to monitored time) is reported in mmHg*minutes. NICU 1 is represented by the darker shades of gray, NICU 2 by the lighter shades of gray. b Time spent in brain tissue hypoxia expressed in daily mean (± SEM) minutes (normalized to monitored time). NICU 1 is represented by the darker shades of gray, NICU 2 by the lighter shades of gray. c Average depth of brain tissue hypoxia (the mean (± SEM) of the P_btO₂ values < 20 mmHg normalized to monitoring time). NICU 1 is represented by the darker shades of gray, NICU 2 by the lighter shades of gray