Neuroanesthesia

Autoregulation

• Autoregulation keeps CBF constant despite changes in CPP
• There are three mechanisms:
  • Myogenic: local effect, intrinsic vascular smooth muscle response to changes in vascular transmural pressures (e.g. increased pressure → constriction)
  • Metabolic: moderate effect, local responses to CO2, O2, H+, and metabolic by-products (e.g. adenosine, lactate, prostaglandins, thromboxane)
  • Neurogenic: larger vessels, cerebral vasculature is innervated by adrenergic, cholinergic, serotonergic, and gabaminergic nerve fibers, with astrocytes playing a role in regulating ion and metabolite concentrations

Cerebral Metabolism

• Aerobic metabolism: sufficient O2, oxidative phosphorylation occurs, 1 glucose = 36 ATP
• Anaerobic metabolism: glycolysis produces only 2 ATP, pyruvate → lactic acid
• Brain has low levels of glycogen stores
• ~60% of metabolism supports ionic gradients, primarily through Na-K pumps
• ~40% supports homeostasis of neurons and glial cells, maintaining membranes and protein synthesis

Neurovascular Coupling

• CBF changes proportional to CMR changes
• CBF can parallel metabolic needs from 20-300ml/100g tissue/min
• Examples:
  • Increased neuronal activity → glutamate release → synthesis and release of NO (vasodilator)
  • CMR increased by: hyperthermia, seizures, ketamine, N2O
  • CMR decreased by: hypothermia (~6%/°C), anesthetics

CO2

• PaCO2 rapidly affects CBF in a directly proportional manner (every 1mmHg of PaCO2 affects CBF by 1mL/100g/min)
• CO2 readily crosses the blood-brain barrier, but not H+ (which causes vasodilation)
• CO2 undergoes carbonic anhydrase reaction with water in CSF and cerebral tissues to form H+ ions
• PaCO2 range of adaptation of CBF is 25-75mmHg
• PaCO2 effects on CBF are time-limited: CSF adapts to pH changes within 6-8 hours

O2

• Changes in PaO2 have minimal effect on CBF at 60-300 mmHg
• Rapid changes in CBF are seen at PaO2 < 60mmHg
• Hypoxia → ATP-dependent K+ channel activation → vasodilation
• The rostral ventrolateral medulla monitors oxygen levels in the brain and responds via neurogenic and local humoral mechanisms to affect CBF

Integrated Contemporary Model

• Not specified in the provided text

Venous Pressure

• Increases in venous pressure result in decreased venous drainage
• This increases intracranial volume → increases intracranial pressure (ICP)
• Two clinically important related concepts:
  • Highlights importance of proper positioning
  • Intrathoracic pressure (cough/PEEP) = ↑ venous pressure

Intracranial Pressure

• Intracranial contents contained within the cranial vault (~1500ml)
• Components:
  • Brain tissue (85%)
  • CSF (10%)
  • Cerebral blood volume (5%)
• Normal ICP: 5-15mmHg
• Intracranial hypertension: >20mmHg
• Crucial in calculating cerebral perfusion pressure (CPP): CPP = [MAP-CVR] - ICP
• Gold standard measurement is with intraventricular catheter
• Also measurable via subdural bolt and catheter

External Ventricular Drain

• Indications:
  • Acute symptomatic hydrocephalus
  • ICP monitoring
  • Bridge for malfunctioning/infected VP shunts
  • Cerebral "relaxation"
  • Targeted therapies (antibiotics)
• Sterile management techniques
• Flushless transducer systems, primed with preservative-free saline, gravity drain
• Leveled to external auditory meatus
• Recommendations:
  • Clamp for transport
  • Coordinate with surgeon for intraoperative management
  • Label ports and lines
  • Report and note changes in CSF color, drainage >20mL or 0/hr, line disconnections, or loss of waveform

Glial Cells

• Besides neurons, the other primary CNS cell type is glial cells
• Glial cells are more abundant (5x) and supportive in nature
• Functions:
  • Maintain ionic environment
  • Modulate action potential conduction
  • Control reuptake of neurotransmitters
  • Repair neurons
• Glial cell subtypes:
  • Astrocytes
  • Ependymal cells
  • Oligodendrocytes
  • Microglia

Blood-Brain Barrier

• The environment of the brain is kept in homeostasis via the blood-brain barrier
• Central concept of ischemic damage is the reduced energy necessary to produce adequate amounts of ATP
• Ischemia results in inefficient glycolysis rather than oxidative phosphorylation
• ATPase ion pumps begin to fail, increasing intracellular Na+, a decrease in K+, and especially Ca++ increases
• Causes neurons to depolarize and release excitatory neurotransmitters (glutamate) causing further depolarization and allowing more Ca++ to enter via NMDA receptor channels
• Calcium is the dominant factor in the ischemic damage process

Pharmacology

• Barbiturates:
  • Decrease CMR (up to 60%) and CBF in a dose-dependent fashion
  • Decrease CMR by:
    • Reducing Ca++ influx
    • Na+ channel blockade
    • Inhibiting free radical formation
    • Potentiating GABA activity
    • Inhibiting glucose transfer across the blood-brain barrier
  • Facilitate CSF absorption, thus reducing ICP
  • Have anticonvulsant properties, reducing the potential of seizure activity
  • May have free radical scavenging properties
• Propofol:
  • Similar to barbiturates in producing a dose-dependent reduction in CBF and CMR
  • Decreases CBF and CMR up to ~50%
  • Preserves cerebral autoregulation
  • Decreases ICP > volatile anesthetics
  • Significant anticonvulsant activity
• Etomidate:
  • Near parallel CBF and CMR changes
  • ~40% reductions with CBF
  • CMR suppression is preferentially focused to the cerebral cortex
  • Myoclonic movements are not epileptic activity, but etomidate does precipitate seizure activity at lower doses
• Inhalation anesthetics:
  • Decrease CMR in a concentration-dependent manner (up to 50%)
  • Isoflurane produces the greatest decrease in CMR
  • Volatile anesthetic agents are potent cerebrovascular dilators, and increase CBF in a dose-related manner
  • Increases in CBF are greatest with halothane, and least with isoflurane and sevoflurane
  • Appears to be time-limited: 3-6 hours
• Nitrous oxide:
  • Increases CBF, CMR, and ICP
  • Increases in CBF are also noted when used in combination with volatile agents
  • Additive vasodilating effect of N2O in the presence of a volatile agent
  • Should be avoided when a closed intracranial gas space exists or intravascular air entrainment is a concern

Blood-Brain Barrier

• The blood-brain barrier consists of capillary endothelial cells connected by tight junctions and a lipid bilayer membrane that prevents the passage of polar molecules.
• Astrocytes interpose between capillaries and neurons to aid in maintenance.
• Lipid-soluble substances pass easily through the blood-brain barrier, while polar molecules require active transport.

Circumventricular Organs

• Certain areas of the blood-brain barrier are compromised by the presence of fenestrated capillaries, allowing for increased permeability.
• These areas, known as circumventricular organs, serve as points of neuroendocrine control.
• Examples of circumventricular organs include the subfornical organ, subcommissural organ, area postrema, neurohypophysis, and organum vasculosum of the lamina terminalis.

Cerebrospinal Fluid (CSF)

• CSF provides cushioning, buoyancy, and an excretory pathway for the CNS.
• CSF is found in the ventricles, cisterns, and subarachnoid space of the brain and spinal cord.
• The total volume of CSF is approximately 150ml, with a production rate of 500ml/day.
• CSF is formed primarily by active transport of Na+ by ependymal cells in the choroid plexus.

CSF Circulation

• CSF is ultimately absorbed by the arachnoid villi of the superior sagittal sinus and drains into the venous circulation.
• The complete turnover of CSF volume occurs approximately 3 times a day.

Blood-CSF Barrier

• The blood-CSF barrier is similar to the blood-brain barrier, with endothelial cells connected by tight junctions.
• Free movement of water and lipid-soluble substances occurs across the blood-CSF barrier.
• Carrier-mediated active transport is required for glucose, amino acids, and ions.

Venous Drainage

• Veins traverse the arachnoid and meningeal layers of the dura mater to flow into the nearest sinuses.
• Cerebral venous circulation is divided into 2 functional components: the superior sagittal sinus and the inferior sagittal sinus/vein of Galen.

Arterial Circulation

• The blood supply to the brain is fed by an anterior and posterior circulation.
• The anterior circulation arises from the aorta and is fed by internal carotid arteries.
• The posterior circulation arises from the subclavian artery and is fed by vertebral arteries.

Circle of Willis

• The circle of Willis is a critical structure that allows for redundancy in cerebral blood flow.
• The circle of Willis is formed by the convergence of the anterior and posterior circulations.

Neurophysiology

• The brain relies on a steady supply of oxygen and glucose, with a disproportionately high degree of blood flow.
• Gray matter has a greater requirement of blood flow than white matter.
• Cerebral blood flow is adaptive to avoid fluctuations and pauses in supply.

Regulation of Cerebral Blood Flow

• Regulation of cerebral blood flow is managed by several determinants of flow-metabolism coupling.
• These determinants include cerebral perfusion pressure, autoregulation, venous pressure, and extrinsic mechanisms such as gas tensions and temperature.

Cerebral Metabolism

• Aerobic metabolism is the primary source of energy for the brain, with anaerobic metabolism occurring in times of insufficient oxygen.
• The brain has low levels of glycogen stores and relies on a constant supply of glucose.
• Neurovascular coupling ensures that changes in cerebral metabolism are accompanied by proportional changes in cerebral blood flow.

CO2 and O2

• PaCO2 rapidly affects cerebral blood flow in a directly proportional manner.
• CO2 readily crosses the blood-brain barrier, but not H+ ions.
• Changes in PaO2 have a minimal effect on cerebral blood flow at 60-300 mmHg.

Intracranial Pressure

• Intracranial pressure is determined by the volume of intracranial contents, including brain tissue, CSF, and cerebral blood volume.
• Normal intracranial pressure is 5-15 mmHg.
• Increased intracranial pressure can result in decreased cerebral perfusion pressure.

External Ventricular Drain

• External ventricular drains are used to monitor intracranial pressure and drain CSF.
• Indications for external ventricular drains include acute symptomatic hydrocephalus, ICP monitoring, and bridge for malfunctioning/infected VP shunts.
• Sterile management techniques and flushless transducer systems are used to minimize the risk of infection.

Pharmacology

• Barbiturates decrease cerebral metabolism and cerebral blood flow in a dose-dependent fashion.
• Barbiturates may have free radical scavenging properties.
• Propofol, etomidate, and inhalation anesthetics also decrease cerebral metabolism and cerebral blood flow.
• Ketamine has a unique effect on cerebral physiology, increasing cerebral blood flow and metabolism.