SYSTEMIC EFFECTS OF INHALATIONAL AGENTS

• CO best maintained with isoflurane.
• Isoflurane – Most cardiostable inhalational agent & agent of choice for cardiovascular surgery.
• Due to reflex tachycardia acting as protective baroreceptor reflex is minimally inhibited by isoflurane. 

CO decreasing drugs:

• All inhalational agents decrease CO, except ether & cyclopropane.
• Cardiovascular stability in decreasing order:Isoflurane (most stable) > desflurane > Sevoflurane > Halothane > Enflurane. 

Baroreceptor reflex:

• Halothane – Only agent suppressing baroreceptor reflex –> causes tachycardia.

Myocardial contractility:

• All inhalational agents cause directly depress contractility. 
• Isoflurane, desflurane & sevoflurane cause minimum depression to similar level.

Sympathetic stimulation:

• Cyclopropane & Ether -> maintain CO & not decrease SVR.
• (Note: Other inhalational agents cause those effects).

Effect on liver:

Hepatotoxicity:

• Mild toxicity – All inhalational agents.
• By decreasing hepatic blood flow.
• Direct hepatotoxicity (hepatitis, hepatic necrosis)
• Halothane, chloroform, trilene & methoxyflurane.

DOC in liver disease: 

• Isoflurane – Due to least effect on hepatic blood flow.

Effect on kidney:

Renal function depression:

• All inhalational agents.
• By decreasing renal blood flow. 

Nephrotoxic agent:

• Most nephrotoxic – Methoxyflurane causes high output (polyuric) renal failure.
• Sevoflurane & enflurane – No renal toxicity in normal person; contraindicated in renal patients.
• By producing nephrotoxic compound A.
• Desflurane has no nephrotoxicity.

Note: 

• Direct toxicity caused by fluorinated compounds due to inorganic fluoride (F-) production.
• Renal threshold beyond which fluoride levels are toxic is 50 mm. 

Effect on Brain:

Increasing ICT:

• All inhalational agents.
• By increasing cerebral blood flow –> ICT.
• Provide cerebral protection by decreasing cerebral metabolic rate.
• Maximum cerebral protection – Isoflurane.
• Inhalational DOC for neurosurgery.
• Enflurane – Provokes seizure.
• Contraindicated in epilepsy.

Neurotoxicity:

• Dichloroacetylene involving most commonly 5th CN.

Effect on hematopoietic system:

• Bone marrow depression (aplastic anemia) & Vit B₁₂ deficiency – By nitrous oxide.
• Vit B₁₂ deficiency causes megaloblastic anemia & subacute degeneration of spinal cord.

Effect on muscle relaxation & analgesia:

Muscle relaxation:

• All inhalational agents except N₂O. 
• By neuro-muscular blockade.
• Maximum relaxation – By ether (unused), desflurane.

Analgesic action:

• All inhalational agents except halothane.
• Maximum – Trilene, N₂O & ether. 
• No analgesic action – Halothane.

Effect on uterine relaxation:

• All fluorinated anesthetics.
• Halothane (maximum), isoflurane, desflurane, sevoflurane, enflurane.

Halothane:

• DOC for assisting external or internal version during late pregnancy.
• Contraindicated during labor 4 – Due to post-partum hemorrhage.

Effect on Inflammability & reaction with sodaline:

Inflammable agents:

• Ether, Cyclopropane, ethylene oxide, ethyl chloride.
• Cautery should not be used in vicinity (up to 25 cms).

Inducing inflammability:

• Agents can be made non-inflammable by adding fluorine atoms.
• Trichloroethylene (Trilene) & sevoflurane reacts with soda lime -> Not be used in closed (circle) system.

Effect on metabolism:

• Most inhaled anesthetics are eliminated from lung.
• Hepatic metabolism also occurs in order:
• Methoxyflurane (> 50%) > Halothane (20%)> Ether (10 -15%) > enflurane (3-5%) > sevoflurane (3%) > isoflurane (0.2%) > desflurane (< 0.1%) > N₂0 (0%). 
• N₂0 does not have any metabolism in body.
• Some agent cause hyperglycemia; chloroform (most profound), ether cyclopropane.

Effects on anesthetic circuit:

• Corroding metals & vaporizing in breathing circuit – Halothane.
• Halothane & methoxyflurane – Absorbed by rubber of anesthetic circuit & polyvinylchloride of ET tube.
• Can be used only on replacing plastic tubing.