Cerebral Autoregulation

Introduction

• Cerebral autoregulation is the ability of the body to maintain a constant CBF despite changes in CPP.¹
• Cerebral autoregulation protects the brain from hypo- or hyperperfusion secondary to decreases or increases in CPP, respectively.
• Traditionally, it was believed that a constant CBF is expected in healthy adults within a mean arterial pressure (MAP) range of 60-160 mmHg, or CPP of 50-150 mmHg, assuming a normal intracranial pressure (ICP) of 10 mmHg. CPP equals MAP minus ICP or central venous pressure, whichever is higher (Figure 1).¹ The limits of cerebral autoregulation in infants and children are not known and autoregulation probably occurs at lower absolute values than in adults.

• However, recent studies question this wide range of MAP and the shape of the proposed curve. Instead, it appears that the brain adapts more easily to very slow changes and transient increases in CPP than to sudden decreases.
• The properties of cerebral autoregulation are dynamic and distinct for each individual and cannot be confidently predicted. Therefore, CBF surrogates (such as cerebral blood velocity, cerebral oximetry, and electroencephalogram [EEG]) are often closely monitored in situations where significant hemodynamic fluctuations are expected.²
• Techniques for bedside assessment of cerebral autoregulation, including transcranial Doppler (TCD), near-infrared spectroscopy (NIRS), brain tissue oxygen monitor, and ICP-derived pressure reactivity (PRx), among others, allow for individualized MAP management in critically ill patients and might lead to better outcomes.³

Mechanism

• Autoregulation of CBF involves the interaction of the myogenic, neurogenic, metabolic, and endothelial mechanisms through different physiologic and pathologic states.
• The myogenic response involves contraction of small arteries and arterioles in response to increased CPP and conversely, relaxation of the arteriolar tone with decreases in CPP.
• The neurogenic mechanism involves the release of vasoactive neurotransmitters in response to depolarization of interneurons.³
• Metabolic regulation consists of reflex vasodilation or constriction of the microvasculature secondary to changes in the local partial pressure of CO₂. Increased perfusion of a vascular bed temporarily increases blood flow, flushing out CO₂. This leads to localized reflex vasoconstriction, with a reduction of blood flow until CO₂ returns to its normal partial pressure. Conversely, decreased perfusion leads to increased CO₂, resulting in localized vasodilation and restoring blood flow to the affected vascular territory.
• The endothelial mechanism works to release nitric oxide (vasodilator), thromboxane A2, and endothelin-1 (vasoconstrictors) to help regulate CBF.
• Neurovascular coupling is the reciprocal relationship between cerebral metabolic rate for oxygen (CMRO₂) and CBF.

Other Physiologic Parameters That Affect CBF

• CO₂: When PaCO2 is within the range of 25 and 70 mmHg, it correlates with CBF. One mmHg increase in PaCO₂ will result in 1-2 mL/100g/min (or 4%) increase in CBF. Similarly, reductions in PaCO2 cause decreases in CBF. The effect of PaCO₂ changes in CBF is attenuated after 6 hours. Prolonged hyperventilation should be avoided secondary to the risk of cerebral ischemia.
• O₂: Decreases in O₂ do not influence CBF until a critical threshold of 50-60 mmHg is reached, below which there is a marked increase in CBF.⁴
• Temperature: Hypothermia results in a dose-dependent reduction in CMRO₂. For each 1°C reduction in temperature, CMRO₂ decreases by 6-7%. The reduction in CMRO₂ continues beyond the point where the EEG is completely suppressed (at 18–20°C). Hyperthermia, conversely, increases CMRO₂ up to 42°C, when the toxic effects of hyperthermia result in progressive decreases in CMRO₂.⁴
• Glucose: Severe hypoglycemia (blood glucose <2 mmol/L or 36 mg/dL) results in increased CBF.

Effects of Anesthetic Agent on CBF

• Intravenous anesthetics: Intravenous agents reduce both CMRO2 and CBF and are considered cerebral vasoconstrictors and reduce CMRO₂ and CBF in parallel, except for ketamine, which causes increases in CMRO₂ and CBF.
• Opioids: Opioids slightly decrease CMRO₂ and CBF.
• Volatile agents: Volatile agents produce a dose-dependent reduction of CMRO₂. However, due to their intrinsic vasodilatory properties (isoflurane=desflurane>sevoflurane), volatile agents uncouple CMRO₂ and CBF. Their overall effect on CBF will result in a balance between CMRO₂-related CBF reduction and intrinsic vasodilatory-related increase in CBF.
  • At 0.5 MAC, CBF is reduced.
  • At 1.0 MAC, CBF level is at baseline.
  • Above 1.0 MAC, CBF is increased.
• N₂O: N₂O administration results in increased CMRO₂ and CBF. Its effect on CBF is attenuated when administered with volatile agents and is minimal when administered with propofol.⁴

Common Pathologic States That Affect Cerebral Autoregulation

• Traumatic brain injury: Cerebral autoregulation is impaired or absent in severe traumatic brain injury. In these patients, decreases in CPP result in decreases in CBF that may reach ischemic levels and lead to secondary brain injury.¹
• Cerebral tumors: Cerebral tumors are frequently associated with disruption of the blood-brain barrier, leading to the development of vasogenic edema and increase in ICP. Cerebral autoregulation in peritumoral areas is impaired, and these areas are more susceptible to ischemia.
• Chronic hypertension: With hypertension, the cerebral autoregulation curve shifts to the right. Blood pressure management should aim to keep the MAP within 20-25% of baseline if not monitoring autoregulation specifically.⁴
• Preeclampsia: Endothelial dysfunction, alterations in cerebral blood flow, and impaired autoregulation are some of the mechanisms of cerebral edema in preeclampsia.⁵