What are the physiologic effects of anesthetic drugs and techniques on the major organ systems during surgery?

Physiologic Effects of Anesthetic Drugs and Techniques on Major Organ Systems

Anesthetic agents fundamentally shift homeostatic responsibility from the patient's intrinsic regulatory mechanisms to the anesthesiologist, producing profound and predictable effects across all major organ systems that must be actively managed to prevent morbidity and mortality. 1

Cardiovascular System

Direct Myocardial Effects

• All volatile anesthetic agents (sevoflurane, desflurane, isoflurane) possess intrinsic myocardial depressant properties, reducing contractility through direct effects on cardiac muscle. 2, 3
• Volatile agents cause dose-dependent afterload reduction through peripheral vasodilation, which when combined with negative inotropy can produce significant hypotension. 3
• Despite these depressant effects, volatile anesthetics provide cardioprotection through preconditioning and postconditioning mechanisms that activate intracellular signal transduction pathways, reducing troponin release and preserving left ventricular function. 2

Hemodynamic Consequences

• The combination of reduced contractility and vasodilation creates wide hemodynamic swings that are poorly tolerated in patients with pre-existing cardiac disease. 3
• Opioid-based anesthetics provide superior cardiovascular stability compared to volatile agents alone, though high-dose opioid techniques necessitate prolonged postoperative mechanical ventilation and increase ICU length of stay. 2

Clinical Recommendation for Cardiac Risk Patients

For hemodynamically stable patients at risk for myocardial ischemia undergoing noncardiac surgery, volatile anesthetic agents should be used for maintenance of general anesthesia (ACC/AHA Class IIa recommendation). 2

• In 15 randomized trials, volatile anesthetics decreased troponin release in 6 studies, preserved early LV function in 5 studies, decreased ICU length of stay in 1 study, and decreased late cardiac events in 1 study compared to propofol or balanced techniques. 2
• Sevoflurane administered throughout surgery (not just as preconditioning) provides optimal cardioprotection with decreased troponin and reduced ICU stay. 2

Respiratory System

Pulmonary Mechanics

• All volatile agents reduce both lung and chest wall compliance, with chest wall compliance declining from ~350 ml/cmH₂O in young adults to ~136 ml/cmH₂O in elderly patients. 4
• Volatile anesthetics increase closing volume and worsen ventilation-perfusion mismatch, particularly in the supine position. 2
• Oxygen diffusion capacity declines under anesthesia, compounded by age-related changes and smoking history. 2

Airway Reactivity

• Desflurane causes significant airway irritation in pediatric patients, producing increased coughing, laryngospasm, and secretions, and is contraindicated for induction in children. 5
• Children ≤6 years with LMA maintenance using desflurane face increased risk of laryngospasm, especially during LMA removal under deep anesthesia. 5
• Patients with asthma or recent upper respiratory infection experience increased airway narrowing and resistance with volatile agents, requiring close monitoring. 5

Central Nervous System

Cerebral Blood Flow and Metabolism

• Anesthetic agents fundamentally alter cerebral autoregulation and the coupling between cerebral blood flow and metabolism, shifting responsibility for maintaining adequate cerebral perfusion to the anesthesiologist. 1
• Volatile anesthetics at standard doses increase cerebral blood flow while decreasing cerebral metabolic rate, creating a mismatch that can increase intracranial pressure. 1
• Low-dose volatile anesthetics (0.25-0.5 MAC) combined with opioids minimize cerebrovascular effects while maintaining cardioprotection. 6

Consciousness and Awareness

• Processed EEG monitoring (BIS) allows precise titration of anesthetic depth, potentially reducing recovery time and detecting intraoperative awareness. 7
• Age-adjusted MAC monitoring is essential during craniotomy procedures to prevent volatile anesthetic overdose and associated hypotension. 6

Cognitive Effects

• Elderly patients face substantially higher risk of postoperative delirium and cognitive dysfunction due to age-related cerebral and cerebrovascular decline. 4
• Depth of anesthesia monitoring using BIS or processed EEG is strongly recommended for patients >60 years at risk of postoperative delirium. 4

Renal System

• Renal function significantly affects pharmacokinetics and pharmacodynamics of anesthetic drugs, necessitating routine preoperative assessment. 2
• Age-related renal decline is accelerated by nephrotoxic comorbidities (hypertension, diabetes) and drugs (NSAIDs, ACE inhibitors), requiring dose adjustments. 2, 4

Hepatobiliary System

• Halogenated anesthetics can cause hepatic dysfunction, icterus, and fatal liver necrosis through hypersensitivity reactions. 5
• Desflurane is contraindicated in patients with history of moderate to severe hepatic dysfunction following previous halogenated agent exposure. 5

Metabolic and Endocrine Effects

Stress Response

• Volatile anesthesia produces more pronounced surgery-induced inflammatory response and altered cell-mediated immunity compared to total intravenous anesthesia, attributed to enhanced stress hormone release. 2
• Major surgery triggers characteristic pituitary and sympathetic activation, leading to hyperglycemia, protein catabolism, and insulin resistance. 2

Glucose Homeostasis

• Volatile anesthetics (sevoflurane, isoflurane) produce hyperglycemic responses through both impaired glucose clearance and increased glucose production. 2
• Blood glucose levels are higher with sevoflurane/fentanyl compared to propofol/fentanyl combinations. 2

Immune System

• Volatile anesthetics modulate both innate and adaptive immunity through effects on neutrophils, macrophages, natural killer cells, T cells, and B cells. 2
• Isoflurane, sevoflurane, and desflurane can induce B cell damage through calcium release from endoplasmic reticulum. 2
• "Immunosenescence" in elderly patients reduces infection-fighting capacity and impairs wound healing, compounded by anesthetic effects. 4

Critical Cardiac Arrhythmia Risk

• QTc prolongation with risk of torsade de pointes has been reported with desflurane, requiring careful cardiac rhythm monitoring in susceptible patients (those with congenital Long QT Syndrome or taking QT-prolonging drugs). 5

Perioperative Hyperkalemia

• Volatile anesthetics are associated with rare but fatal increases in serum potassium causing cardiac arrhythmias and death in pediatric patients, particularly those with latent neuromuscular disease (especially Duchenne muscular dystrophy). 5
• Concomitant succinylcholine use is associated with most cases, though not all. 5

Carbon Monoxide Production

• Desflurane reacts with desiccated CO₂ absorbents to produce carbon monoxide, potentially causing elevated carboxyhemoglobin levels. 5
• Replace suspected desiccated CO₂ absorbent before desflurane administration, particularly when fresh gases have passed through canisters at high flow rates for extended periods. 5

Age-Related Physiologic Considerations

Cardiovascular Reserve in Elderly

• Elderly patients exhibit "effective beta-blockade" from reduced β-receptor responsiveness, markedly limiting cardiac output increases and compensation for fluid losses. 2, 4
• Baroreceptor dysfunction and reduced angiotensin II responsiveness severely compromise hypovolemia compensation. 2, 4
• Decreased cardiac compliance further restricts stress response capacity, compounded by atherosclerotic disease and cardiac polypharmacy. 2, 4

Dosing Adjustments

• Induction doses of anesthetic agents must be reduced by 30-50% in elderly patients compared to standard adult dosing to account for physiological decline. 4
• Inadequate titration can precipitate circulatory collapse due to limited compensatory mechanisms in elderly patients. 4

Neuraxial Techniques

• Spinal and epidural anesthesia produce sympathetic blockade, resulting in decreased preload and afterload. 2
• High dermatomal levels during abdominal procedures can cause significant hypotension if preload becomes compromised or cardioaccelerator blockade occurs. 2
• Seven randomized trials in vascular surgery showed no outcome differences between regional and general anesthesia techniques. 2
• Thoracic epidural analgesia decreases postoperative pulmonary complications but does not influence MI incidence or overall mortality after coronary artery bypass surgery. 2