Untitled Quiz

Inhalational Anesthetics

• Minimum Alveolar Concentration (MAC) represents the partial pressure of an inhalational anesthetic in the alveoli that causes 50% of patients to not move in response to skin incision.
• At low MAC values (0.2-0.4), formation of both implicit and explicit memory are reliably prevented.
• At 0.5 MAC, the reduction in the cerebral metabolic rate and the vasodilation caused by the anesthetic lead to a decrease in cerebral blood flow (CBF).
• At 1.0 MAC, effects are balanced, resulting in unchanged CBF.
• At 1.5 MAC, vasodilation effects exceed the reduction in cerebral metabolic rate, leading to an increase in CBF. Mild hyperventilation can offset this increase in CBF.
• Patients with increased intracranial pressure (ICP) should be monitored closely for increases in ICP due to the effects of inhalational anesthetics.
• Iso, Des, and Sevo produce initial activation of EEG at low doses, followed by slowing of electrical activity up to 1-1.5 MAC.
• At higher concentrations, EEG suppression increases to the point of electrical silence with isoflurane at 2.0-2.5 MAC.
• Isolated epileptic like patterns may be seen with Sevo between 1.0-2.0 MAC.
• Clinical seizure activity (true tonic-clonic movements) has been observed with enflurane.
• N2O alone causes fast electrical oscillations in the frontal cortex at doses associated with analgesia/depressed consciousness.

Stages of Inhalational Anesthetics

• Stage I: Analgesia (both analgesia and amnesia in late Stage I)
• Stage II: Excitement
• Stage III: Surgical Anesthesia
• Stage IV: Medullary Depression

Induction Agents

• Facilitate rapid induction of anesthesia.
• Provide sedation during monitored anesthesia care.
• Good option for maintenance of anesthesia.
• Cerebral vasoconstriction - decreased CMRO2 and CBF in parallel except for ketamine.

IV Non-Opioid Anesthetics

• Propofol: Most frequently used induction agent. Also used for maintenance of general anesthesia.
  • Alkyl phenol with hypnotic properties.
  • Poor solubility in water, requiring an emulsion of soybean oil, glycerol, and lecithin.
  • Should be used ASAP after drawing up medication, but must be used within 8 hours.
  • Requires sterile technique.
  • Metabisulfite is added to some formulations, which can cause issues with sulfite allergy and reactive airway disease.
  • MOA: Potentiates the chloride current mediated through the GABA receptor complex.
  • Short context-sensitive half-time leads to relatively prompt recovery.
  • CNS Effects:
    • Hypnotic without analgesic properties.
    • Induction may cause excitatory effects resembling seizure activity, but it is safe to use in patients with seizure disorders.
    • CBF and CMRO2 decreased, leading to decreases in ICP and IOP.
    • Potential for decreased CPP due to decreased CBF and MAP.
• Fospropofol: Water soluble prodrug of propofol.
  • Rapidly metabolized by alkaline phosphatase.
  • Produces propofol, phosphate, and formaldehyde.
  • Similar effects to propofol, but with prolonged onset and recovery.
• Barbiturates: Not commonly used anymore.
  • Thiopental: No longer available in the US.
  • Methohexital: Used for ECT. Short-acting barbiturate.
  • Combination of inhibitory and inhibition of excitatory transmission.
  • Activation of GABA receptors.
  • Dose-dependent CNS depression ranging from sedation to GA.
  • Does not provide analgesia, possible hyperalgesia.
  • Potent cerebral vasoconstrictors.
    • Decrease CBF, CBV, ICP, and CMRO2.
    • Dose-dependent suppression of EEG activity.
    • Can be used as an anticonvulsant EXCEPT for Methohexital, which activates epileptic foci.
  • Neuroprotective effects.
• Etomidate: Carboxylated imidazole derivative.
  • Poorly water soluble.
  • Hypnotic with no analgesic effects.
  • Minimal hemodynamic effects.
  • Endocrine effects limit use as a continuous infusion.
  • GABA-like effects.
  • CNS Effects:
    • Potent cerebral vasoconstrictor.
    • Decreases CBF, ICP, CMRO2.
    • No neuroprotective effects.
    • May activate seizure foci.
    • Myoclonic activity with seizure-like activity on the EEG.
• Ketamine: Partially water soluble phenylcyclidine derivative.
  • Produces significant analgesia.
  • Dissociative anesthesia.
  • MOA: Inhibition of the NMDA receptor complex.
  • Highly lipid soluble, resulting in rapid onset.
  • Metabolized in the liver and excreted in the urine.
  • Produces norketamine.
  • Low protein binding.
  • CNS Effects:
    • Cerebral vasodilator.
    • Increases CBF and CMRO2. These effects may be blunted by maintaining normocapnia.
    • Anticonvulsant properties.
    • Potential to produce myoclonic activities.
    • Used as treatment for status epilepticus when more conventional drugs are ineffective.
    • Unpleasant emergence reactions: Lower incidence and severity in children.
      • Vivid dreams, hallucinations, out-of-body experiences.
      • Increased and distorted visual, tactile, and auditory sensitivity.
      • Euphoria, high abuse potential.

Other IV Anesthetics

• Dexmedetomidine: Highly selective, water soluble alpha-2 adrenergic agonist.
  • Effects can be antagonized with alpha-2 antagonist drugs.
  • Metabolites are excreted in the urine and bile, resulting in a short elimination half-time.
  • Context-sensitive half-time increases with longer infusions, leading to the potential development of tolerance and dependence.
  • CNS Effects:
    • Selective alpha adrenergic effects through activation of CNS alpha-2 receptors.
    • Hypnosis through stimulation of alpha-2 receptors.
    • Analgesic effect originates at the level of the spinal cord.
    • Sedative effects resemble a physiologic sleep state. Allows spontaneous breathing, decreasing the risk for hypercapnia.
    • Decrease in CBF without significant changes in ICP and CMRO2.
• Opioids (Phenylpiperidines): Produce analgesia without hypnotic effects.
  • Can be used in combination with benzodiazepines as an induction agent.
  • Slight decrease in CMRO2 and CBF.
  • Large doses of potent opioids can induce chest wall and laryngeal rigidity, especially with remifentanil.
  • Opioid agonists interact fully with opioid receptors.
    • Mu: Analgesia, euphoria, sedation, dependence, respiratory depression, miosis, marked constipation, urinary retention, bradycardia, pruritus, muscle rigidity, biliary spasm.
    • Kappa: Analgesia, dysphoria, sedation, miosis, anti-shivering.
    • Delta: Analgesia, dependence, mild constipation, urinary retention.
  • Opioid receptors are a group of inhibitory G-protein coupled receptors.
  • CNS Effects of Opioids:
    • Analgesia: Inhibits ascending transmission of nociceptive transmission from the spinal cord. Activates pain control pathways from the midbrain.
    • Sedation and Euphoria: Receptor dependent; not an anesthetic.
    • ICP changes result from hypercarbia.
  • Full Agonists:
    • Fentanyl: 100x more potent than morphine.
      • Produces profound dose-dependent effects.
      • Termination by redistribution.
      • Highly lipid soluble, resulting in rapid onset and short DOA.
      • Undergoes significant first-pass effect in the lungs.
      • Continuous infusion or high bolus doses result in a change in the termination of effect.
      • Clearance is dependent on liver blood flow.
      • Inactive metabolites.
      • Affected by redistribution unless given in high doses.
    • Remifentanil: Rapid and ultra-short acting.
      • Has an ester group that allows for easy and rapid metabolism by blood and tissue esterases.
      • Increased risk for muscle rigidity, limiting bolus dosing. Most commonly used as a drip in neuroanesthesia.
      • Concerns with post-op analgesia. Use a long-acting pain medication if post-op pain control is required.
      • Should not be given epidurally or intrathecally.
      • Not for use for post-op pain.
    • Sufentanil: Most potent of all phenylpiperidines.
      • Highly lipophilic.
      • Shorter half-life than fentanyl.
      • Excreted unchanged in the urine.
      • Profound respiratory depression. Not ideal for neuro patients or those with high ICP.
    • Alfentanil: More rapid onset and shorter DOA than fentanyl.
      • Highly non-ionized.
      • High variability in patient response.
      • High potential for post-op nausea.
      • Peak respiratory depression in less than 2 minutes.
  • Partial Agonists:
    • Buprenorphine:
      • Synthetic opioid derivative.
      • Very potent and slow to dissociate.
      • High affinity to the mu receptor (50x greater than morphine).
      • Exhibits a ceiling effect.
      • Antagonistic effects due to its ability to displace opioid agonists from their receptors (kappa).
    • Nalbuphine:
      • Partial agonist related to the opioid antagonist naloxone.
      • Agonist at the kappa receptor and weak antagonist at the mu receptor.
      • Potent analgesic.
      • Respiratory depression exhibits a ceiling effect.
      • Can be used to treat post-op shivering (kappa).
      • Very slow to dissociate from the opioid receptor.
      • May be used for withdrawal effects.
      • Equal in analgesic potency to morphine.
      • Less potent antagonist than naloxone.
      • Does not impact the CV system.
      • Can cause dysphoria.
      • Consider rescue options if using agonist/antagonist as a primary analgesic.
  • Opioid Antagonists:
    • Naloxone: Non-selective opioid antagonist at all receptors.
      • Used to treat: opioid-induced respiratory depression, pruritus (regional block), and suspected drug overload.
      • Shorter duration of action than most opioids (half-life is one hour).
      • Administer in low and incremental doses.
      • Can cause pulmonary edema.
    • Naltrexone:
      • Not addictive.
      • Similar actions to naloxone: blocks euphoric and sedative effects of opioids, reduces/suppresses opioid cravings.
      • Exhibits a longer duration of action than naloxone.
      • Often given as a part of a treatment protocol for those recovering from SUD (Vivitrol extended-release).
    • Nalmefene:
      • Alcohol abuse treatment.
      • Similar to naltrexone, but not the same drug.
      • Improved opioid receptor binding, bioavailability, and less hepatotoxicity.

Benzodiazepines

• Anxiolysis and anterograde pre-op medications.
• Highly lipid soluble; rapidly enter the CNS.
• Rapid onset, redistribution to inactive tissue sites, and subsequent termination of effects.
• Acts on glycine and GABA receptors.
• Midazolam: Shortest context-sensitive half-time.
  • Can be used for continuous infusion.
  • Decreases CMRO2 and CBF, but less than propofol and barbiturates.
    • Ceiling effect for decreased CMRO2.
  • Little to no change in ICP in patients with decreased intracranial compliance.
  • Potent anticonvulsant.
  • Can be terminated by flumazenil.
• Diazepam and Lorazepam are also benzodiazepines.

Neuromuscular Blocking Agents

• Depolarizers: Act on receptors at the motor end plate, making the end plate refractory to ACh.
  • Succinylcholine: Has a single linear structure.
    • MOA: Agonist at nicotinic receptors at the NMJ.
    • DOA: < 10 minutes.
    • Considerations: Fasciculations (can cause transient increases in ICP), Hyperkalemia in patients with burns, nerve damage, neuromuscular disease, closed head injury, etc.

Cerebral Blood Flow (CBF) Autoregulation

• MAP range of 50/60 to 150/160 mmHg: CBF remains relatively constant due to myogenic activity and autoregulation.
• Myogenic activity: Smooth muscle in blood vessels contracts (vasoconstriction) in response to increased blood pressure (BP) or mean arterial pressure (MAP), reducing blood flow. Conversely, it relaxes (vasodilation) in response to decreased BP/MAP, increasing blood flow.
• MAP above 150/160 mmHg: CBF becomes directly proportional to MAP, creating a linear relationship.
• Hyperemia (excessive blood flow) can occur at MAPs above 160 mmHg: This can increase intracranial pressure (ICP), potentially leading to compression and damage of brain tissue, disruption of the blood-brain barrier (BBB), and cerebral edema.
• MAP below 60 mmHg: CBF is directly proportional to MAP and CBF decreases linearly with decreasing MAP. This can lead to cerebral ischemia.

Neurological Assessment in Coma

• Glasgow Coma Scale (GCS): Used to assess level of consciousness. A score of 3 indicates the most severe impairment.
• Posturing:
  • Decorticate posturing (flexor posturing): Arms flexed, hands clenched, legs extended, feet turned inward. Occurs with damage to cerebral hemispheres, internal capsule, thalamus, or midbrain.
  • Decerebrate posturing (extensor posturing): Head arched back, arms extended and rotated internally, legs extended and internally rotated. Indicates brainstem damage, common in Pontine strokes.
  • Progression from decorticate to decerebrate posturing: Often indicates uncal (transtentorial) or tonsillar brain herniation.
• Reflexes:
  • Oculocephalic (Doll's Eyes) Reflex: Eyes move opposite to head movement. Absence or asymmetry indicates brainstem dysfunction.
  • Oculovestibular (Caloric) Reflex: Cold water injected into ear induces nystagmus (involuntary eye movement) in the direction of the non-injected ear.

Neurologic Testing in Coma Patients

• Pupillary Response: Tests Cranial Nerves 2 and 3.
• Extraocular Muscle Testing: Tests Cranial Nerves 3, 4, and 6. Assesses eye movement reflexes.
• Oculocephalic (Doll's Eyes) Reflex: Tests Cranial Nerves 3, 4, 5, 6, and 8. Assesses reflexes for eye stabilization during head movement.
• Oculovestibular (Caloric) Reflex: Tests Cranial Nerves 3, 4, 6, and 8. Assesses eye response to cold water injection.
• Other Cranial Nerve Testing:
  • Cranial Nerve 3: Light response.
  • Cranial Nerve 5: Corneal reflex.
  • Cranial Nerve 7: Facial grimacing in response to noxious stimuli.
  • Cranial Nerves 9 and 10: Gag reflex.

Effects of Anesthesia Agents on CBF

• Inhaled Anesthetics:
  • Volatiles: Isoflurane, Desflurane, and Sevoflurane.
  • Gaseous Anesthetics: Nitrous Oxide (N2O) and Xenon.
  • N2O increases cerebral metabolic rate of oxygen (CMRO2) and CBF, potentially increasing ICP. These effects may be mitigated by combining N2O with other agents, IV anesthetics, or hyperventilation.
  • Cerebral effects: Anesthetics decrease brain metabolic activity and CMRO2. They also have intrinsic vasodilatory properties, which can increase CBF. The net effect on CBF depends on the concentration of the agent delivered.

Key Considerations

• Cerebral blood flow (CBF) autoregulation: Crucial for maintaining stable blood supply to the brain.
• Hyperventilation: Can decrease CBF in patients with increased intracranial pressure (ICP) but can also contribute to cerebral ischemia, especially in patients with low MAPs.
• Neurological posturing: Can indicate serious brain damage, especially when progressing from decorticate to decerebrate posturing.
• Anesthesia agents can have varying effects on CBF: Carefully consider the effects of specific agents on the individual patient.