Cerebral Blood Flow Deviations in Critically Ill Patients: Potential Insult Contributing to Ischemic and Hyperemic Injury

Abstract

Background: Ischemic and hyperemic injury have emerged as biologic mechanisms that contribute to cognitive impairment in critically ill patients. Spontaneous deviations in cerebral blood flow (CBF) beyond ischemic and hyperemic thresholds may represent an insult that contributes to this brain injury, especially if they accumulate over time and coincide with impaired autoregulation.Methods: We used transcranial Doppler to measure the proportion of time that CBF velocity (CBFv) deviated beyond previously reported ischemic and hyperemic thresholds in a cohort of critically ill patients with respiratory failure and/or shock within 48 h of ICU admission. We also assessed whether these CBFv deviations were more common during periods of impaired dynamic autoregulation, and whether they are explained by concurrent variations in mean arterial pressure (MAP) and end-tidal PCO2 (PetCO2).Results: We enrolled 12 consecutive patients (three females) who were monitored for a mean duration of 462.6 ± 39.8 min. Across patients, CBFv deviated by more than 20–30% from its baseline for 17–24% of the analysis time. These CBFv deviations occurred equally during periods of preserved and impaired autoregulation, while concurrent variations in MAP and PetCO2 explained only 13–21% of these CBFv deviations.Conclusion: CBFv deviations beyond ischemic and hyperemic thresholds are common in critically ill patients with respiratory failure or shock. These deviations occur irrespective of the state of dynamic autoregulation and are not explained by changes in MAP and CO2. Future studies should explore mechanisms responsible for these CBFv deviations and establish whether their cumulative burden predicts poor neurocognitive outcomes.

Perspective: Drawing on Findings From Critical Illness to Explain Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…Probable drivers of distortions in the structure and function of endothelial lining (i.e., glycocalyx) are cytokines ( 31 ), inflammation, exposure to oxidative stress ( 28 , 32 ) and/or sympatho-adrenal hyperactivation ( 33 ). Crucially, endothelial dysfunction during critical illness has been associated with altered cerebral blood flow ( 34 , 35 ) and increased blood–brain barrier (BBB) permeability resulting in long-term cognitive impairment ( 36 , 37 ). A leaky BBB could also contribute to increased intracranial pressure ( 38 , 39 ).…”

The Relationship between Cerebrovascular Reactivity and Cerebral Oxygenation during Hemodialysis

“…32 Cerebral autoregulation response can vary in patients with traumatic brain injury and critical illness, and, in some circumstances, intact cerebral autoregulation may not reduce risk of change in CBF. [33][34][35] The cerebral vascular response is complex and, in our study, including BP and fluid removal explain only a portion of the DScO 2 during HD. Additional explanatory factors that could affect DScO 2 during HD include factors that affect vasodilation, such as change in serum bicarbonate levels and hematocrit that can occur during HD; factors that may affect intracranial pressure, including fluid, electrolyte, and osmotic shifts during HD; markers of cerebral metabolism; and the severity of vascular disease risk factors, such as degree of BP, glycemic, and serum phosphate level control, that may affect vascular stiffness.…”

“…Similar to CVR, cerebral autoregulation may also fluctuate during HD due to cerebral fluid and osmotic shifts that can affect intracranial pressure and subsequently affect cerebral prefusion pressure 32 . Cerebral autoregulation response can vary in patients with traumatic brain injury and critical illness, and, in some circumstances, intact cerebral autoregulation may not reduce risk of change in CBF 33 – 35 . The cerebral vascular response is complex and, in our study, including BP and fluid removal explain only a portion of the Δ ScO 2 during HD.…”

Spectroscopy detects skeletal muscle microvascular dysfunction during onset of sepsis in a rat fecal peritonitis model

“…Septic patients may develop acute brain dysfunction, referred to as sepsis-associated encephalopathy, which is linked to greater mortality 56 , and sepsis survivors are at risk of long-term cognitive impairment 57 . The mechanisms that drive septic brain injury are not completely understood, and inflammation 58 , 59 , oxidative stress 60 , MVD 61 , and dynamic variability in MAP and arterial CO 2 levels 62 are suspected. Animal studies attempted to dissect the key inflammatory players in septic brains, with microglial activation as an important driver 63 , which has also been suggested in septic patients 59 .…”