ADJUVANT AGENTS — Adjuvant intravenous (IV) agents are often used to supplement the

effects of the primary anesthetic induction agent. The most common adjuvants are an
opioid, lidocaine, and/or a benzodiazepine (usually midazolam) (table 3).

Many patients receive more than one adjuvant agent during induction, particularly if
endotracheal intubation is planned, in order to reduce the dose of sedative-hypnotic as well
as blunt airway reflexes and the sympathetic stress response to laryngoscopy and tracheal
intubation. There is no evidence from randomized trials to support use of a particular drug
combination. Choices and doses of agents are determined by patient-specific factors,
including age and comorbidities.

Administration of adjuvant agents is usually reduced or eliminated in older patients and in

those with impaired renal and/or hepatic function, as well as in those with actual or potential
hemodynamic instability. (See 'Dosing considerations' above.)

Opioids — Opioids are the most commonly used adjuvant agents during induction of
general anesthesia (table 3). Although opioids bind to specific receptors in the brain, spinal
cord, and peripheral neurons, the agents used during induction of anesthesia bind primarily
to mu receptors. (See "Perioperative uses of intravenous opioids in adults".)

●Advantages during induction

•Suppression of airway reflexes that result in coughing and/or bronchospasm

during laryngoscopy and intubation [102].

•Attenuation of the stress response to laryngoscopy and endotracheal intubation

that would otherwise result in tachycardia and hypertension [103-105].

•Reduction of pain caused by IV injection of propofol, etomidate, or muscle

relaxants [23-27], although reduction may be optimally achieved with lidocaineor a
combination of lidocaine plus an opioid [26].

•Supplementation of sedation to reduce the dose requirement of the selected

sedative-hypnotic induction agent [106-110].

●Adverse effects

•Exacerbation of the hypotensive effects of sedative-hypnotic induction agents.

•Respiratory depression and/or apnea, a side effect of all commonly used opioids.

If laryngeal mask insertion with subsequent spontaneous ventilation is planned,
some clinicians will omit opioid administration during the induction sequence to
avoid a period of postinduction apnea.

•Other adverse effects may become evident in the postoperative period when large
or additional opioid doses are administered, including nausea and vomiting, ileus,
constipation, urinary retention, pruritus, delirium, acute tolerance, and
 hyperalgesia. These effects are discussed separately. (See "General anesthesia:
Maintenance", section on 'Opioid agents'.)

●Dosing – Opioid medications produce analgesia and sedation in a dose-dependent

manner. Dose reduction is prudent in selected patients:

•Older adults, since potency may be increased by age-related changes in

pharmacokinetics and pharmacodynamics. (See "Anesthesia for the older adult",
section on 'Opioids'.)

•Coadministration with agents from different classes because of synergistic effects

of these combinations (eg, sedative-hypnotics such as propofol, benzodiazepines
such as midazolam, or volatile inhalation anesthetic agent) [1].

•Patients with actual or potential hemodynamic instability, since opioids may

exacerbate hypotension or bradycardia.

Typical doses of the opioid agents commonly used during induction of general
anesthesia (eg, fentanyl, sufentanil) are noted in the table (table 3).

Remifentanil may be used in selected cases requiring rapid sequence intubation

if succinylcholine is contraindicated and the prolonged duration of a nondepolarizing
neuromuscular blocking agent (NMBA) is undesirable. The remifentanil intubation
technique is described separately. (See "Rapid sequence induction and intubation
(RSII) for anesthesia", section on 'Remifentanil intubation'.)

Lidocaine — Lidocaine 0.5 to 1.5 mg/kg is often administered to suppress airway reflexes,

reduce the pain of injection of other induction agents, and supplement anesthetic effects
(table 3).

●Advantages during induction

•Suppresses the cough reflex during laryngoscopy and intubation [111-120].

•Reduces incidence of bronchospasm by reducing airway responsiveness to

noxious stimuli and to drugs that cause bronchospasm, despite causing an
increase in airway tone [121-123]. (See "Anesthesia for adult patients with
asthma", section on 'Intravenous agents'.)

•Reduces pain caused by IV injection of agents, such as propofol or muscle

relaxants, when administered into the same vein at a low dose (approximately 40
mg) [28]. Lidocaine is more effective than opioids in mitigating injection pain
because of its local anesthetic effect [22-27].

•Supplements sedation to reduce the dose requirement of the selected IV

sedative-hypnotic induction agent [124].

●Adverse effects

•Accentuates the hypotensive effects of sedative-hypnotic induction agents.

 •May increase the ventricular rate in patients with atrial fibrillation.

●Dosing – Dose is based on the indication:

•For reduction of pain on injection due to propofol or another agent, 20 to 30 mg is

administered into the same vein.

•For attenuation of airway responses to laryngoscopy and endotracheal intubation,

1 to 1.5 mg/kg is administered as a bolus.

-Dose is reduced to 0.5 to 1 mg/kg in older adults.

-Dose is reduced to ≤0.5 mg/kg or eliminated in patients with hemodynamic

instability.

Midazolam — Midazolam is often used shortly before (within 30 to 60 minutes) induction as

a premedicant or during induction as an adjuvant agent, especially in anxious, fully awake
patients. The primary mechanism of action is activation of the gamma-aminobutyric
acidA (GABAA) receptor, thereby inhibiting neurotransmission [125].

●Advantages before and during induction – Midazolam has dose-dependent

properties that include (table 3) [126]:

•Anxiolysis

•Amnesia

•Anticonvulsant properties

•Sedation, which supplements and reduces dose requirement of the selected IV

sedative-hypnotic induction agent [108]

●Adverse effects

•Mild systemic vasodilation and decreased cardiac output (CO), with consequent
decrease in blood pressure (BP). This may be pronounced in patients with
preexisting hypovolemia or vasodilation [126].

•Dose-dependent respiratory depression, which may be problematic if an opioid is

concurrently administered. Minute ventilation and the ventilatory response to
carbon dioxide (CO2) decrease; apnea may occur with higher doses
(≥0.15 mg/kg) [126,127].

●Dosing – A typical dose for younger, anxious adults is 1 to 4 mg administered in 1-mg

increments.

•Dose is eliminated or reduced to 0.5 to 2 mg in older adults, administered in 0.5-

mg increments.

•Dose is eliminated or reduced to 0.5 to 1 mg in patients with actual or potential

hemodynamic instability.
 •Dose is eliminated for some enhanced recovery after surgery (ERAS) protocols.

SELECTION OF INDUCTION AGENTS — Induction of general anesthesia may be

accomplished using either an intravenous (IV) or inhalational technique, although
combinations of agents are common. The selection of an induction technique for general
anesthesia is discussed separately. (See "General anesthesia: Induction", section on
'Selection of induction technique'.)

The choice of an induction agent for rapid sequence intubation in the operating room and
elsewhere is discussed separately. (See "Rapid sequence induction and intubation (RSII) for
anesthesia", section on 'Induction agents' and "Induction agents for rapid sequence
intubation in adults outside the operating room", section on 'Choice of induction agent'.)