General Anesthetics and Surgical Principles

General Anesthetics and Therapeutic Gases

• General anesthetics depress the central nervous system (CNS) to allow surgery
• Have low therapeutic indices, requiring careful administration
• Selection of drugs and routes depends on pharmacokinetic properties and secondary effects
• Considerations include the specific procedure, patient characteristics, and medical conditions

General Principles of Surgical Anesthesia

• Minimizing the harmful effects of anesthetics and techniques is a primary goal
• Maintaining physiological homeostasis during procedures is important, especially during blood loss, tissue ischemia, reperfusion, fluid shifts, cold exposure, and impaired coagulation
• Improving postoperative outcomes by managing the surgical stress response is crucial

Hemodynamic Effects

• General anesthesia usually decreases systemic arterial blood pressure
• Potential causes include vasodilation, myocardial depression, a blunting of baroreceptor control, and decreased central sympathetic tone
• Hypotension is exacerbated by volume depletion or preexisting heart problems

Respiratory Effects

• Most anesthetics reduce or eliminate respiratory drive and airway reflexes
• Loss of gag reflex and cough stimulus can result in regurgitation
• Endotracheal intubation is common to prevent aspiration
• Muscle relaxation facilitates airway management, achieved using neuromuscular blocking agents

Hypothermia

• Patients often develop hypothermia during surgery (body temp below 36°C)
• Causes include low ambient temperature, exposed body cavities, cold fluids, altered thermoregulation, and decreased metabolic rate
• Prevention of hypothermia is a key anesthetic goal

Nausea and Vomiting

• Nausea and vomiting are common side effects post-anesthesia
• Mechanism involves anesthetic action on the chemoreceptor trigger zone and brainstem vomiting center, regulated by neurotransmitters like serotonin, histamine, acetylcholine, dopamine, and neurokinin 1
• Antiemetic drugs like ondansetron, dolasetron, and palonosetron are effective in countering these effects

Mechanisms of Anesthesia

• The unitary theory of anesthesia, associated with anesthetic potency correlation with solubility in olive oil (Meyer-Overton rule), has been largely discarded
• Current evidence supports the theory that different anesthetic agents act on distinct molecular targets
• Intravenous anesthetics predominantly affect GABA receptors and potentially other ligand-gated channels (e.g., NMDA)
• Effects on GABA receptors increase sensitivity to GABA and enhance inhibitory neurotransmission

Parenteral Anesthetics

• Parenteral anesthetics are commonly used for induction, characterized by rapid onset and short duration of action
• They accumulate in fatty tissues

Propofol

• Widely used, rapid recovery desirable
• Lipid emulsion, associated with pain on injection and hyperlipidemia

Etomidate

• Generally reserved for patients at risk for hypotension or myocardial ischemia
• Relatively better cardiovascular stability compared to other drugs

Ketamine

• Useful for patients with hypotension risk or asthma
• Produces a distinctive dissociative anesthetic state, characterized by intact breathing and some spontaneous movement
• Provides significant analgesia, an advantage over other agents

Barbiturates

• Historically common, but reduced current use due to limited availability (e.g., thiopental not routinely sold in the US)
• High initial volume of distribution → long durations with prolonged administration
• Pharmacokinetics are context-sensitive, varying with prolonged infusions or doses
• Mechanism involves GABAA receptor agonism, leading to Cl- conduction and neuronal hyperpolarization

Inhalational Anesthetics

• Variety of gases and volatile liquids produce anesthesia
• Measured using minimum alveolar concentration (MAC) - the minimum concentration needed to prevent movement during surgical stimulation in 50% of subjects
• MAC correlates to free anesthetic concentration in the CNS
• MAC is helpful for patient monitoring, given that alveolar concentration can be continuously tracked via spectroscopy or mass spectrometry

Isoflurane

• Typically used for anesthesia maintenance after induction
• Pleasant odor, rapid onset, and recovery

Sevoflurane

• Preferred for induction due to pleasant smell, rapid onset, and lack of airway irritation

Desflurane

• Acts as a potent bronchodilator, but can irritate airways
• Minimal metabolism → quick induction and recovery

Nitrous Oxide

• Weak anesthetic, but substantial analgesic effects
• Commonly used as an adjunct
• Insoluble in blood, leading to rapid equilibration and emergence
• Can expand air-filled cavities in the body, contraindicated for certain cases

Anesthetic Adjuncts

• Enhance specific components of general anesthesia, permitting lower doses, and fewer side effects
• Benzodiazepines (e.g., midazolam, diazepam, lorazepam) are widely used for pre-operative sedation
• Alpha2-adrenergic agonists (e.g., dexmedetomidine) offer sedation and analgesia with minimal respiratory depression
• Analgesics (e.g., opioids, NSAIDs) reduce anesthetic requirements and decrease pain
• Neuromuscular blocking agents (e.g., succinylcholine, vecuronium) facilitate intubation by relaxation of airway muscles.

Monitoring of Oxygenation

• Cyanosis is not an early or reliable indicator
• Pulse oximetry quantifies hemoglobin saturation, not Po2
• Near-infrared spectroscopy assesses cerebral oxygenation

Therapeutic Uses of Oxygen

• Corrects hypoxia, which is often a symptom of underlying illness.
• Used to reduce inert gas partial pressure in various conditions（e.g., bowel obstruction, air embolism, pneumothorax）
• Hyperbaric oxygen therapy enhances oxygen availability, useful in certain conditions (e.g., trauma, burns, radiation, infections, and certain neurological conditions).

Carbon Dioxide

• Produced by metabolism and is actively exhaled
• PCO2 increase results in respiratory acidosis (less ventilation, more CO2 retained in the body)
• Central and peripheral chemoreceptors are stimulated by changes in PCO2, influencing breathing rate
• CO2 is used for certain procedures such as endoscopic surgeries and cardiac surgery

Nitric Oxide

• Cell-signaling molecule and vasodilator
• Use in treating persistent pulmonary hypertension

Helium

• Used for pulmonary function testing、respiratory obstruction treatment、laser airway surgery and diving at depths

Hydrogen Sulfide (H2S)

• Considered a toxin, but has potential therapeutic applications in limiting cell death in certain conditions