Effects of Anaesthetic agents on cerebral Physiology

• Most general anaesthetics have favourable effect on the CNS by reducing electrical Activity
• Carbohydrate metabolism energy stores in the form of ATP, phosphocreatine & ADP ↑
• Effect of specific agent is complicated by concomitant administration of other drugs and

➤ Surgical stimulation
➤ Intracranial compliance
➤ BP
➤ CO2 tension
➤ Thiopental

Effect of i.v. anaerthetic agents→

• With exception of ketamine, all agents have little effect or ↓ CMR & CBF.
• Cerebral auto regulation & Co2 responsiveness is preserved with all agents.
• Parallel reduction in CMR & CBF
• Barbiturates = 4 magic actions

➤ Hypnosis
➤ ↓ CMR
➤ ↓ CBF due to ↑ in CVR
➤ Anticonvulsant action

• Thiopentone Na – Most commonly used induction agent in neuroanaestheria.
• Dose dependent ↓ in CBF & CMR until EEG becomes isoelectric correrpords to 50% ↓ in CMRO₂
• Above this ↑ ing dose do not produce reduction in CMR
• Reduce CMR,CBF uniformly throughout the brain.
• CMR is depressed more than CBF
• Reverse steal phenomenon/ robin hood phenomenon

Causes cerebral vasoconstriction in normal areas, tend to redistribute blood flow from normal to ischaemic area

• Cerebral vasculature in ischemic areas remains dilated & un affected by barbiturates because of ischemic vasomotor paralysis.
• Facilitate absorption of CSF → ↓ CSF volume
• Anticonvulsant property advantageous in neuro surgery patient who are prone to seizeres.
• Other actions of barbiturate

➤ Blockade of Na channels
➤ ↓ in intracellular ca influx
➤ Scavenging free radicals
➤ retardation of cerebral oedema.

• Studies suggest that barbiturate prophylaxis is effective in focal brain injury but not global ischemia.

Propofol→

• ↓ CBF & CMR
• ↓ in CBF doesn’t exceed CMR
• Associated with dystonic & choreiform activities
• Have significant anticonvulsant effect
• Short elimination half life is useful for neuro anaesthesia.
• Excessive hypotension & cardiac depression in eldeely or unstable pts compromise CPP.

Etomidate→

• ↓ CMR, CBF & ICP
• CMR effect is un uniform, affecting more cortex than brain stem
• ↓ CSF Production & ↑absorption
• Induction is associated with high incidence of myoclonic movements but not associated with Seizure activity on EEG
• Drug is best avoided in pts with history os epilepsy.
• Small doses can activate seizure foci in pts with epilepsy

Ketamine →

• Only I.v. anaesthetic agent that dilates cerebral vasculature & ↑ CBF 50-60% ↑
• Total CMR doesn’t change
• Selective activation of limbic & reticular system is partially offset by depresion of other areas like somatosensary & auditory.
• Seizure activity in thalamic and limbic areas is also described.
• ↓ CSF absorption with no effect on formation
• ↑ CBF, CBV & CSF volume,↑ ICP markedly with ↓ed intracranial compliance.

Opioids→

• Minimal effects on CBF, CMR & ICP, unless PaCO₂ rises secondary to respiratory depression
• Sufentanyl → ↑ in ICP with intracranial tumours
• Alfentanyly → less than sufentanyl.

mechanism– precipitous drop in BP which reflexly causes cerebral vasodilatation.

Small doses of alfentanyl <50 µg/kg activates seizure foci.

• Morphine – poor lipid soluble, slow CMS penehatin & pnalanged sedative effective.
• Meperidine → metabolise normeperidine, can induce seizers particularly in renal failure.

 Benzodiazepines→

• ↓ CBF & CMR in lesser degree than barbiturates,etomidate & Propofol
• Anticonvulsant properly
• Midazolam is of choice because of short half life.
• Midazolam induction↓ CPPin elderly & unstable pts. may prolong emergences.

 Anaesthetic Adjuncts–

IV Lignocaine →

• ↓ CMR, CBF & ICP to lesser degree.
• ↓ CBF without significant hemodynamic effects
• Risk – seizures systemic Toxicity.

Effect on volatile agent on CBF→

Volatile anaesthetics

• All volatile agents suppress CMRO2 in dose dependent manner as I.V anaesthetics
• Also posses intrinsic cerebral vasodilatory effects because of direct effect on vascular smooth muscles.
• Net effect → reduction in CBF caused by CMR suppression and augmentation of CBF due to vasodilatory effects.
• In dose of 0.5 MAC – CMR suppression induced reduction in CBF predominates & Net CBF decreases as compare to awake state.
• 1 MAC – CMR suppression induced CBF equalises ↑ CBF due to vasodilatation & net effect on CBF is nullified.
• > 1 MAC – cerebral vasodilatation predominates & causes ↑ CBF
• CBF/CMR ratio is altered by volatile agents
• at higher MAC levels causes greater luxury perfusion
• The vasodilatatory potency is approximately halothane >> enflurane > desflurane = isoflurane > sevofluvane.

1. CBF effects →

• Volatile agents posses intrinsic vasodilator properties, also modify cerebral auto regulation but also decreses systemic BP in dose dependent manner.
• When MAP is maintained at 80mm eg Halothane at 1.1MAC ↑ CBF by 191% & ↓ CMR By 10%
• Enflurane ↑ CBF by 45% and ↓ CMR by 15% at 1.2 MAC
• Isoflurane doesn’t increses CBF as much as halothane and enflurane
• Isoflurane CBF By 19% when syst BP is maintain within normal range CMRO₂ ↓ by 45%
• sevo & Desflurane ↓ CBF By 38% & 22% & CMR By 39 & 35% respectively
• These results suggest that isoflurane produces more cerebral vasodilatation than sevoflurane & desflurane.

2. CMR Effects →

• All agents ↓ CMRO_2, least with halothane.
• Sevoflurane effect on CMRO₂ is similar is isoflurane.
• 1 MAC doses of iso, sevo & des produces CMRO₂ by 25%, 38%, 22% respectively.
• CBF – CMR dose response relationship is alinear with volatile agents
• Distribution of CBF & CMR Charges are heterogenous with volatile agents.
• After an initial ↑ in CBF, it falls substantially with a steady state near pre anaesthetic value after 21/2-5 hrs of exposure.
• Change in CBF doesn’t predict change in cerebral blood volume accurately.
• CO₂ responsiveness is preserved by volatile agents but auto regulation is hampered.
• Enflurane is potentially epileptongenic in clinical condition.
• Hypocapnia potentiates seizure like activities of enflurane.
• Sevofluranes ability though, small to work epileptogenic activity should be kept in mind when using in epileptic patients.
• When administering with large mass lesions unstable ICP or sufficient derangement of cerebral physiology, one should keep in mind impairment of flow metabolism coupling
• Well advised to use predominantly intravenous technique until cranium and dura isopened and effect of anaesthetic technique can be directly assessed.

Nitrous Oxide (N2O) →

– Cause ↑ CBF, ↑CMR & In ICP

• May be due to synpathoadrenal activation
• N2O administered alone without i.v. anaesthetics Cause ↑ ICP & CBP
• With i. v. Anaesthetics and barbiturates, opioids & Benzodizepine, its cerebral vasodilating properties is attenuated or inhibited completely.
• With volatile agents its CBF ↑ is substantially
• With institution of hypocapnia CBF ↑ Is reduced
• Its effects on CMRO₂ is still debeted whether it ↑ is or not
• Vasodilatory action can be significant with ICP compromised patient, so better to be avoided in pts with tight brain.

Non depolarising muscle relaxants →

• Only recognised effect of non depolansing effect on ICP is two its histamine release as it ↑ CBF & ↓ syst. BP leading to ↓ CPP
• Pancuroniume though its sympathomimetic action can elevate ICP in compromised patients but no clinically significant reports
• Atracuerium metabolite, laudanosine is epileptogenic but only when produced in higher doses.
• all non depolansing NMBS can be solely used in decrese in ICP compromised patients
• They even contribute to ↓ in ICP by avoiding coughing & straining

Succhynylcholine →

• Can ↑ ICP in lightly anaesthetised humans
• No correlation between visible muscle fasciculation & ↑ in ICP.
• Need not be viewed as contraindicated if rapid assessment of paralysis is needed if administered with proper attention to CO2 retention, blood pressure, depth of anaesthesia and defasuiculation, little hazard is noted.