General Anesthesia

The speed of inhalational induction depends on how quickly the partial pressure of the anesthetic rises in the alveolus and then equilibrates with the brain. Several pharmacokinetic factors determine this rate.

The blood:gas partition coefficient is the most important pharmacokinetic property of an inhalational anesthetic. It describes how readily the drug dissolves in blood relative to the alveolar gas. A high coefficient means the drug is highly soluble in blood — blood acts as a large reservoir that must be filled before alveolar partial pressure can rise, producing a slow induction. A low coefficient means the drug is poorly soluble — alveolar partial pressure rises quickly, the brain equilibrates rapidly, and induction is fast.

Desflurane and nitrous oxide have the lowest blood:gas coefficients (approximately 0.42 and 0.47, respectively) and the fastest inductions. Sevoflurane (approximately 0.65) is intermediate and widely used for pediatric inhalational induction. Isoflurane (approximately 1.4) and halothane (approximately 2.4) are more soluble and have slower inductions. The same principle governs emergence: agents with low solubility wash out rapidly, producing fast awakening.

Increasing alveolar ventilation speeds induction by delivering more anesthetic to the alveolus faster, raising alveolar partial pressure. This effect is most pronounced for highly soluble agents, where blood uptake continuously drains the alveolus. Hyperventilation accelerates induction; hypoventilation delays it.

High cardiac output means more blood flows through the pulmonary capillaries per minute, removing more anesthetic from the alveolus and slowing the rise in alveolar partial pressure — thus slowing induction. Conversely, low cardiac output (as in hemorrhagic shock) reduces pulmonary blood flow, allows alveolar partial pressure to rise more rapidly, and can produce an unexpectedly fast induction with cardiovascular depression in an already compromised patient. This is an important clinical paradox: the sickest patients are at greatest risk of anesthetic overdose during inhalational induction.

When a highly concentrated inspired mixture is used, alveolar partial pressure rises faster than simple diffusion alone would predict — this is the concentration effect. The second gas effect is an extension of this principle: when nitrous oxide is given simultaneously with a second volatile agent, the rapid absorption of the large volume of nitrous oxide augments delivery of the co-administered agent, accelerating its alveolar partial pressure rise. Both effects are most relevant when nitrous oxide is part of the induction mixture.

Diffusional hypoxia (also called the Fink effect) occurs at the end of nitrous oxide anesthesia. When nitrous oxide administration is discontinued, the large amount of nitrous oxide dissolved in blood rapidly diffuses back into the alveoli. This outflux of nitrous oxide dilutes alveolar oxygen and carbon dioxide, transiently reducing the alveolar partial pressure of oxygen to levels that can cause clinically significant hypoxemia.

The effect is greatest in the first five to ten minutes following cessation of nitrous oxide and is reliably prevented by administering 100% oxygen for several minutes at the end of the anesthetic before allowing the patient to breathe room air. Failure to do so is a preventable cause of post-anesthetic oxygen desaturation. The mechanism is the reverse of the second gas effect: just as rapid nitrous oxide uptake concentrates other alveolar gases during induction, rapid nitrous oxide efflux dilutes them during emergence.

Preanesthetic medication serves several simultaneous goals: reduction of anxiety and facilitation of smooth induction, provision of baseline analgesia, reduction of postoperative nausea and vomiting risk, modification of autonomic reflexes, and reduction of gastric volume and acidity. No single agent accomplishes all these goals; contemporary premedication regimens are multimodal and patient-specific.

Benzodiazepines are the most widely used preanesthetic sedatives. Midazolam is the standard perioperative agent because of its rapid onset, short duration, reliable anterograde amnesia, and minimal cardiovascular effects at standard doses. In addition to anxiolysis and amnesia, midazolam reduces the minimum alveolar concentration of volatile agents, contributing to a smoother induction and lower maintenance requirements. Dexmedetomidine is increasingly used as an alternative premedication in patients for whom benzodiazepines are undesirable, such as those with obstructive sleep apnea or those at elevated risk for postoperative delirium.

Opioids given before induction provide baseline analgesia and blunt the hemodynamic response to laryngoscopy and endotracheal intubation — the most stimulating part of the anesthetic induction sequence. Fentanyl administered intravenously in the pre-induction period is most commonly used because of its rapid onset and short duration. The main risks are respiratory depression and increased postoperative nausea and vomiting.

Postoperative nausea and vomiting risk is stratified using the Apfel score, which assigns one point each for: female sex, non-smoker status, history of postoperative nausea and vomiting or motion sickness, and anticipated postoperative opioid use. Patients with three or four risk factors have a high risk of postoperative nausea and vomiting and warrant multimodal prophylaxis targeting multiple receptor systems.

Anticholinergic agents serve two distinct perioperative roles. Glycopyrrolate is used as an antisialagogue (drying agent for secretions) before airway procedures. Unlike atropine and scopolamine — which are tertiary amines and cross the blood-brain barrier, producing central nervous system effects including sedation and confusion — glycopyrrolate is a quaternary ammonium compound that does not cross the blood-brain barrier and is therefore free of central anticholinergic effects. Atropine is used to treat or prevent bradycardia, including the bradycardia that can occur following succinylcholine administration in pediatric patients. Scopolamine, applied as a transdermal patch, provides prolonged cholinergic blockade of the vomiting center and is particularly effective for postoperative nausea and vomiting prophylaxis in high-risk patients.

Pulmonary aspiration of gastric contents causes chemical pneumonitis (Mendelson syndrome). The risk is determined by two independent factors: gastric volume and gastric acidity. Three classes of drugs address these factors pharmacologically.

Proton pump inhibitors (such as pantoprazole or omeprazole) and H2 receptor antagonists (such as famotidine) both reduce gastric acid production and raise gastric pH, but proton pump inhibitors provide more sustained and complete acid suppression. Sodium citrate given orally immediately before induction acts as a rapid buffer, directly neutralizing existing gastric acid; because it is non-particulate, it does not itself cause lung injury if aspirated. Metoclopramide accelerates gastric emptying and raises lower esophageal sphincter tone through dopamine D2 antagonism and serotonin 5-hydroxytryptamine type 4 receptor agonism in the gastrointestinal tract, reducing gastric volume in patients at risk of aspiration.