Maintenance of General Anesthesia: Overview

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Maintenance of general anesthesia: Overview

Author: Sarah M Khorsand, MD
Section Editor: Girish P Joshi, MB, BS, MD, FFARCSI
Deputy Editor: Nancy A Nussmeier, MD, FAHA
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jul 2022. | This topic last updated: Jun 09, 2022.
INTRODUCTION
Immediately after induction of general anesthesia, additional agents are necessary to

maintain the anesthetic state since most induction agents have a brief duration of action.
This topic will discuss use of inhalation and intravenous (IV) agents during the
maintenance phase of general anesthesia.
Induction of general anesthesia is discussed in separate topics. (See "Induction of general

anesthesia: Overview" and "General anesthesia: Intravenous induction agents".)
Emergence from general anesthesia is also discussed separately. (See "Emergence from
general anesthesia".)
ANESTHETIC GOALS
Overall goals — The overall goals of the maintenance phase of a general anesthetic are
to maintain Stage III surgical anesthesia (ie, unconsciousness, amnesia, immobility,
unresponsive to surgical stimulation ( table 1)) at a safe anesthetic depth while also
maintaining respiratory and hemodynamic stability. Standard monitors placed prior to
induction of anesthesia are closely observed during anesthetic delivery in order to rapidly
detect and correct hemodynamic, respiratory, or temperature derangements (see "Basic
patient monitoring during anesthesia"). In addition, end-tidal inhalation anesthetic
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concentration (ETAC), raw or processed electroencephalography (EEG), or other specialized

monitors are often used to estimate anesthetic depth to aid in avoiding awareness with
recall, as discussed separately. (See "Accidental awareness after general anesthesia",
section on 'Monitoring'.)
Other topics contain details regarding management of specific aspects of anesthesia

during the maintenance phase:
● Maintenance of physiologic homeostasis including:
• Oxygenation and ventilation (see "Mechanical ventilation during anesthesia in

adults")
• Hemodynamic stability (see "Hemodynamic management during anesthesia in
adults")
• Temperature control (see "Perioperative temperature management")
● Prevention of awareness with recall (see "Accidental awareness after general

anesthesia")
● Antinociception (analgesia) during increased intensity of the degree of noxious

surgical stimulation (see "Perioperative uses of intravenous opioids in adults:
General considerations")
● Muscle relaxation to facilitate surgery and/or prevent movement as necessary for

certain surgical procedures (see "Clinical use of neuromuscular blocking agents in
anesthesia")
Anesthetic depth — Although an association has been noted between increasing

anesthetic depth (gauged by processed EEG such as the bispectral index [BIS] monitor)
and decreased postoperative survival in some observational studies, most studies did not
report blood pressure (BP) data [1]. Yet low BP due to deep anesthesia has the strongest
association with mortality in studies that did include BP data [2,3]. In a 2019 randomized
study of more than 6600 patients >60 years old who were undergoing major surgery with
a volatile inhalation anesthetic technique (see 'Inhalation anesthetic agents and
techniques' below), lighter anesthesia targeting BIS values at 50 (median 47; range 44 to
51) was compared with deeper anesthesia targeting BIS values at 35 (median 39; range 36
to 42), while appropriate BP was maintained in all patients [4]. In patients maintained with
lighter anesthesia, mean arterial BP was slightly higher (3.5 mmHg), while volatile
anesthetic use was 30 percent lower (with a minimum alveolar concentration [MAC] of
0.62; range 0.52 to 0.73 versus a MAC of 0.88; range 0.74 to 1.04). One-year mortality was
the same in both groups [4]. Although we often employ neuromonitoring techniques such
as processed EEG in selected patients (eg, those at risk for awareness (see "Accidental
awareness after general anesthesia", section on 'Brain monitoring')), we individually titrate
anesthetic agents to achieve an appropriate depth. We avoid BP significantly lower than
baseline values or frank hypotension, and we avoid excessive anesthetic depth,
particularly in older patients and those at risk for development of perioperative
neurocognitive disorders [5-7]. (See "Perioperative neurocognitive disorders in adults: Risk
factors and mitigation strategies", section on 'Avoid excessive depth during general
anesthesia'.)
SELECTION OF MAINTENANCE TECHNIQUES
Maintenance of general anesthesia may be accomplished using a primary inhalation

technique (see 'Inhalation anesthetic agents and techniques' below) or a primary
intravenous (IV) technique (see 'Total intravenous anesthesia' below). Combinations that
include one or more sedative-hypnotic agents (eg, propofol or an inhalation anesthetic)
and one or more analgesics (eg, an opioid or nonopioid analgesic agent), with or without
use of a neuromuscular blocking agent (NMBA) are often employed to achieve "balanced"
general anesthesia [8-11].
Ideal anesthetic maintenance agents have rapid onset of action, minimal cardiopulmonary
or other side effects, and are cleared from the bloodstream quickly to ensure a rapid
recovery. None of the available inhalation or IV anesthetic agents is ideal for all patients,
and all have potential adverse side effects. Balanced (ie, multimodal) anesthetic
techniques may increase the likelihood of achieving the desired goals (see 'Anesthetic
goals' above), while using less of each drug than if it were administered alone by taking
advantage of the synergism that occurs when anesthetic agents from different classes are
combined [8-12]. However, the synergistic effects of such drug combinations may result in
adverse effects such as hypotension or delayed emergence.
INHALATION ANESTHETIC AGENTS AND TECHNIQUES
All available volatile inhalation anesthetic agents (sevoflurane, desflurane, isoflurane, and
in some countries halothane) may be used for complete maintenance of general

anesthesia. An inhalation anesthetic technique may also include one gas (nitrous oxide
[N2O]) administered as a supplemental agent. (See "Inhalation anesthetic agents: Clinical
effects and uses", section on 'Maintenance of general anesthesia (all inhalation agents)'.)
Dosing considerations — Dosing of each inhalation anesthetic agent is determined by its

potency, reported as the minimum alveolar concentration (MAC) value ( table 2), with 1
MAC being the concentration of an inhaled agent in the alveoli required to prevent
movement in response to a surgical stimulus in 50 percent of patients ( table 3). MAC
values are influenced by patient age and coexisting diseases or conditions ( table 4).
(See "Inhalation anesthetic agents: Clinical effects and uses", section on 'MAC and MAC-
awake values for inhalation agents'.)
Titration of the potent inhalation anesthetic is necessary to maintain stage III surgical
anesthesia with unconsciousness, amnesia, immobility, and absence of response to
noxious stimulation. Doses of the volatile agent are decreased if N2O is also inhaled
and/or if intravenous (IV) anesthetic agent(s) are also administered [13]. (See "Inhalation
anesthetic agents: Clinical effects and uses", section on 'Influence of drug-drug
interactions'.)
Volatile inhalation agents
Advantages and disadvantages — The potent volatile inhalation anesthetic agents

share common advantages and disadvantages (see "Inhalation anesthetic agents: Clinical
effects and uses", section on 'Clinical effects'):
● Advantages:
• Ease of administration.
• Reliable blockade of responses to sensory input such as painful stimuli [14].
• Bronchodilation.
• Dose-dependent decreases in skeletal and smooth muscle tone.
• Decreased cerebral metabolic rate (CMR).
• Increased cerebral blood flow (CBF).
• Ability to monitor end-tidal anesthetic concentration (ETAC) as an indicator of

anesthetic depth; ETAC values of 0.8 to 1 MAC are typically adequate to prevent
awareness with recall. (See "Accidental awareness after general anesthesia",
section on 'End-tidal anesthetic concentration'.)
● Disadvantages:
• Dose-dependent suppression of airway reflexes.
• Dose-dependent respiratory depression.
• Dose-dependent myocardial depression and vasodilation that may cause

hypotension.
• Increased risk of postoperative nausea and vomiting (PONV) compared with most
IV anesthetic alternatives, unless prophylactic antiemetics are administered. (See
"Postoperative nausea and vomiting", section on 'Anesthetic factors'.)
• Potential to induce malignant hyperthermia in susceptible individuals. (See

"Inhalation anesthetic agents: Clinical effects and uses", section on 'Other clinical
effects'.)
Specific volatile inhalation agents — The available potent volatile agents differ in their
specific advantages and adverse effects, which affects selection for the maintenance
phase of general anesthesia. (See "Inhalation anesthetic agents: Clinical effects and uses",
section on 'Specific inhalation anesthetic agents'.)
Sevoflurane — Sevoflurane is often selected for maintenance of anesthesia during

surgical procedures lasting less than two hours due to its low blood and tissue solubilities.
Compared with older potent inhalation agents that have higher blood and tissue
solubilities (eg, isoflurane), uptake during induction, changes in anesthetic depth during
the maintenance phase of general anesthesia, and emergence are more rapid when
sevoflurane is used. (See "Inhalation anesthetic agents: Clinical effects and uses", section
on 'Advantages'.)
A disadvantage for sevoflurane use as the primary maintenance agent during longer
surgical procedures is cost, particularly when higher fresh gas flows (ie, >2 L/minute of
oxygen and/or air) are employed to deliver it. Compared with isoflurane, there is little
advantage for faster recovery after delivery of sevoflurane for more than two hours
because the blood:fat partition coefficients of these agents are similar. (See "Inhalation
anesthetic agents: Clinical effects and uses", section on 'Disadvantages and adverse
effects'.)
Further details regarding sevoflurane administration are discussed separately. (See

"Inhalation anesthetic agents: Clinical effects and uses", section on 'Sevoflurane'.)
Desflurane — Desflurane has the lowest blood and tissue solubility of the potent
volatile inhalation agents, resulting in very rapid uptake and elimination with little
accumulation in tissues. Thus, changes in anesthetic depth and recovery during
emergence are rapid [15,16]. Use of desflurane is particularly advantageous in patients
who are older, morbidly obese, or have sleep apnea [15-17]. (See "Inhalation anesthetic
agents: Clinical effects and uses", section on 'Advantages'.)
Similar to sevoflurane, a disadvantage of desflurane is its high cost during use as the
primary maintenance agent for longer surgical procedures. Other disadvantages include
pungency with a very high incidence of airway irritation (eg, coughing, salivation, breath-
holding, laryngospasm), and sympathomimetic properties that result in tachycardia and
hypertension, particularly if higher or abruptly increased concentrations are administered.
(See "Inhalation anesthetic agents: Clinical effects and uses", section on 'Disadvantages
and adverse effects'.)
Further details regarding desflurane administration are discussed separately. (See

"Inhalation anesthetic agents: Clinical effects and uses", section on 'Desflurane'.)
Isoflurane — Isoflurane is commonly used as a primary agent to maintain general

anesthesia during longer surgical cases. It is the more potent than sevoflurane or
desflurane, inexpensive, and widely available. (See "Inhalation anesthetic agents: Clinical
effects and uses", section on 'Advantages'.)
Disadvantages of isoflurane compared with sevoflurane or desflurane include slower

onset during induction and slower recovery due to higher blood and tissue solubility.
Thus, emergence may be prolonged, particularly after a long duration of administration.
Other disadvantages include pungency with potential airway irritation during induction
and emergence. (See "Inhalation anesthetic agents: Clinical effects and uses", section on
'Disadvantages and adverse effects'.)
Further details regarding isoflurane administration are discussed separately. (See

"Inhalation anesthetic agents: Clinical effects and uses", section on 'Isoflurane'.)
Halothane — Concern about hepatotoxicity has eliminated the use of halothane in

North America; however it is still commonly used in some regions, particularly in pediatric
patients.
Halothane has the slowest onset and recovery of any of the potent inhalation agents due
to very high tissue and blood solubility. Emergence from anesthesia may be prolonged
compared with other potent volatile agents. Other disadvantages include potential
hepatotoxicity, as well as negative inotropy and chronotropy, and a high incidence of
ventricular and other dysrhythmias. (See "Inhalation anesthetic agents: Clinical effects and
uses", section on 'Disadvantages and adverse effects'.)
Advantages include its very high potency and low cost. In addition, halothane is a
bronchodilating agent with little airway irritability. (See "Inhalation anesthetic agents:
Clinical effects and uses", section on 'Advantages'.)
Further details regarding halothane administration are discussed separately. (See

"Inhalation anesthetic agents: Clinical effects and uses", section on 'Halothane'.)
Nitrous oxide gas — Nitrous oxide (N2O) is a pressurized gas that is delivered via a flow
meter on the anesthesia machine. N2O gas is often selected as a supplemental agent
during maintenance of general anesthesia with either an inhalation or IV anesthetic
technique. Its use increases anesthetic depth, resulting in decreased dose requirements
for coadministered anesthetic agents. In a review of the available evidence, the European
Society of Anaesthesiologists Task Force on Nitrous Oxide concluded that a rational
approach is targeted use of N2O considering its risk/benefit ratio in any given patient, as
with other anesthetic agents [18]. The authors routinely use N2O in the absence of
contraindications. However, N2O cannot be used as a sole agent to maintain anesthesia
because of its low potency (the MAC value is 104 percent). (See "Inhalation anesthetic
agents: Clinical effects and uses", section on 'Typical uses'.)
● Advantages – Advantages of N2O include [18,19] (see "Inhalation anesthetic agents:

Clinical effects and uses", section on 'Advantages'):
• Rapid onset and offset due to its very low blood solubility. (See "Inhalation
anesthetic agents: Properties and delivery", section on 'Partition coefficients and
potency'.)
• During the maintenance phase of general anesthesia, coadministration of N2O

with any potent volatile inhalation agent allows more rapid changes in anesthetic
depth due to a phenomenon termed the "second gas" effect. Similarly, speed of
induction and emergence are increased with coadministration of N2O due to
dilution of the alveolar concentration of the volatile anesthetic. (See "Inhalation
anesthetic agents: Properties and delivery", section on 'Second gas effect'.)
• Analgesic properties.
• Anxiolytic properties.
• Minimal hemodynamic effects.
• Cheap and wide availability.
● Disadvantages – Disadvantages include:
• Potential for diffusion into any air-filled cavity, displacing nitrogen gas. Thus,
administration is avoided in patients with possible pre-existing bowel distention,
increased middle ear pressure, pneumothorax, pneumoperitoneum,
pneumocephalus, intraocular gas, or venous air embolism. (See "Inhalation
anesthetic agents: Clinical effects and uses", section on 'Disadvantages and
adverse effects'.)
• Although visceral distension may slightly increase risk of PONV, particularly if no

antiemetic prophylactic measures are employed, this does not preclude its use in
patients without contraindications [18]. (See "Postoperative nausea and
vomiting", section on 'Anesthetic factors'.)
• Potential for transient diffusion hypoxia if N2O is discontinued at a low inspired

oxygen concentration. In this circumstance, bulk transfer of N2O gas into the
alveolus displaces oxygen, thereby decreasing alveolar oxygen concentration and
potentially inducing desaturation. Diffusion hypoxia may be prevented by delivery
of high inspired oxygen concentration for several minutes before and after
discontinuing N2O. (See "Inhalation anesthetic agents: Properties and delivery",
section on 'Second gas effect'.)
Reevaluation of available evidence suggests that the perceived drawbacks of N2O (eg,
nausea, vomiting, bowel distension) have been exaggerated or misdirected. We do not
specifically avoid N2O unless there is a contraindication for its use [18]. Further details
regarding N2O administration are discussed separately. (See "Inhalation anesthetic
agents: Clinical effects and uses", section on 'Nitrous oxide'.)
INTRAVENOUS ANESTHETIC AGENTS AND TECHNIQUES
General considerations — Appropriate doses of intravenous (IV) anesthetic agents are

titrated to maintain stage III surgical anesthesia with unconsciousness, amnesia,
immobility, and absence of response to noxious stimulation, similar to considerations for
inhalation anesthetic agents. (See 'Anesthetic goals' above and 'Dosing considerations'
above.)
When IV anesthetic drugs from different classes are combined, the hypnotic effects are
often synergistic rather than merely additive, requiring dose reductions for each agent.
Synergy is particularly common when drugs acting primarily on gamma-aminobutyric
acidA (GABAA) receptors (eg, propofol) are combined with drugs acting on other receptor
types (eg, opioids, alpha2 agonists such as dexmedetomidine) [8]. Similarly, doses of IV
agents should be reduced when an inhalation agent such as nitrous oxide (N2O) or a
potent volatile anesthetic agent is coadministered. (See "General anesthesia: Intravenous
induction agents", section on 'Dosing considerations' and "Inhalation anesthetic agents:
Clinical effects and uses", section on 'Influence of drug-drug interactions'.)
Total intravenous anesthesia — Total intravenous anesthesia (TIVA) employs a sedative-

hypnotic anesthetic (typically propofol) and an analgesic component (typically an opioid
agent). Adjuncts such as dexmedetomidine, ketamine, or lidocaine infusions may be used
for patient-specific or procedure-specific reasons to replace or minimize the total propofol
and/or total opioid doses [20]. Overall, these adjunct agents have limited benefits and
specific potential adverse effects, as noted below.
Guidelines for the safe practice of TIVA were jointly published in 2019 by the Association of
Anaesthetists, the Society for Intravenous Anesthesia in Great Britain [21]. These include:
● Infusion doses of the IV agents are adjusted based on age, frailty, and comorbid
medical conditions. Typically, a low initial infusion setting (eg, of propofol) is adjusted
by making small incremental increases.
● Drug and fluid lines should be as close to the patient as possible to minimize dead
space. Whenever possible, the IV catheter of central venous catheter through which
the infusion is being delivered should be visible throughout the anesthetic care.
● Guidelines for use of IV infusion pumps, including smart pumps, syringe pumps, and
target-controlled infusion (TCI) devices are discussed separately:
• (See "Intravenous infusion devices for perioperative use", section on 'Smart

pumps'.)
• (See "Intravenous infusion devices for perioperative use", section on 'Syringe
pumps'.)
• (See "Intravenous infusion devices for perioperative use", section on 'Target-
controlled infusion systems'.)
● Concerns include the possibility of awareness during anesthesia (see "Accidental

awareness after general anesthesia", section on 'Brain monitoring'), or, conversely,
excessive anesthetic depth with delayed recovery (see "Perioperative neurocognitive
disorders in adults: Risk factors and mitigation strategies", section on 'Avoid
excessive depth during general anesthesia'). For this reason, raw or processed
electroencephalography (EEG) monitoring (eg, the bispectral index [BIS]) or other
neuromonitoring techniques are often used to aid intraoperative dosing ( table 5)
[21-23].
● Indications and advantages – A TIVA technique is selected in the following

circumstances:
• Patients requiring general anesthesia if there are absolute contraindications (eg,

history of malignant hyperthermia (see "Malignant hyperthermia: Diagnosis and
management of acute crisis", section on 'MH triggers')) or relative
contraindications (eg, high risk for postoperative nausea and vomiting [PONV]
(see "Postoperative nausea and vomiting", section on 'Anesthetic factors')) for
administration of volatile agents.
• Patients undergoing surgical procedures with neuromonitoring (eg, spine

surgery) because use of a sedative hypnotic (eg, propofol) and an opioid agent
has less effect on evoked potentials than potent volatile inhalation agents or N2O.
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2
In particular, motor evoked potentials (MEPs) are very sensitive to inhalation
agents, while somatosensory-evoked potentials (SSEPs) are moderately affected.
However, propofol causes a dose-dependent decrease in EEG amplitude and
frequency, ultimately producing burst suppression and electrical silence at high
doses. (See "Neuromonitoring in surgery and anesthesia", section on 'Anesthetic
effects on neuromonitoring' and "Neuromonitoring in surgery and anesthesia",
section on 'Maintenance of anesthesia'.)
● Disadvantages – Potential disadvantages of TIVA include the following:
• Blood concentrations (and therefore effect site concentration) of IV anesthetic

agents are not easily obtained. This contrasts with inhalation anesthetics, for
which the exhaled end-tidal anesthetic concentration (ETAC) of each agent can be
continuously monitored, allowing real-time dose adjustments of anesthetic
depth. Although processed or unprocessed EEG indices or other neuromonitoring
techniques are often used to titrate anesthetic agents during TIVA, such indices
do not reliably confirm that patients are not aware. However, a 2017 meta-
analysis concluded that use of processed EEG (eg, BIS) monitoring to guide TCI of
propofol dosing allows better maintenance of the target anesthetic depth
compared with manual control based on standard monitoring [22]. (See
"Accidental awareness after general anesthesia", section on 'Total intravenous
anesthesia' and "Accidental awareness after general anesthesia", section on 'Brain
monitoring'.)
• TIVA is associated with dose-dependent suppression of airway reflexes and

respiratory depression, similar to potent volatile inhalation agents.
• TIVA is also associated with dose-dependent vasodilation and myocardial

depression that may cause hypotension, similar to potent volatile inhalation
agents.
• When the limb containing the IV catheter is tucked at the patient's side table or
not continuously visible due to surgical draping, unrecognized IV infiltration and
extravasation of a continuous IV infusion into the tissue of a tucked limb can
occur, resulting in compartment syndrome. Also, unrecognized disconnection of
the IV tubing from the catheter may result in failure to administer the intended
medication. (See "Intravenous infusion devices for perioperative use", section on
'Extravasation of a continuous infusion'.)
• Possible errors in IV drug delivery via infusion devices include syringe pump or
"smart" pump setting errors that may go undetected (eg, wrong rate, wrong
dose, wrong concentration, wrong medication), failure to deliver the intended
agent, overriding soft limits with consequent overdosing, or underdosing with
possible awareness. (See "Intravenous infusion devices for perioperative use",
section on 'Risks for medication errors' and "Intravenous infusion devices for
perioperative use", section on 'Smart pumps'.)
• TIVA anesthetic techniques are typically more costly than inhalation techniques,
depending on which specific IV agents are selected [24,25]. Target-controlled
infusion (TCI) systems are not currently approved in the United States for clinical
use during TIVA techniques. (See "Intravenous infusion devices for perioperative
use", section on 'Target-controlled infusion systems'.)
Specific intravenous agents
Sedative-hypnotic agent: Propofol — Propofol is usually selected as the sedative-

hypnotic component to maintain general anesthesia during a TIVA technique.
● Dosing – Propofol is typically administered as a continuous infusion using a syringe

pump or a smart pump that requires operator programming. Although not available
in the United States, closed-loop TCI systems are used in some countries for delivery
of propofol during a TIVA technique. However, intersubject variability (eg, obesity,
underweight status) in pharmacokinetic and pharmacodynamic parameters used in
models to calculate the drug concentration of propofol at the effect site has limited
utility of TCI systems. (See "Intravenous infusion devices for perioperative use" and
"Intravenous infusion devices for perioperative use", section on 'Target-controlled
infusion systems'.)
The typical dose range for propofol is 75 to 150 mcg/kg per minute in younger and
healthier patients who can tolerate these higher doses. Propofol dosing is reduced
by factors such as older age, hypovolemia, vasodilation, myocardial dysfunction, and
coadministration of other agents, as discussed separately. (See "General anesthesia:
Intravenous induction agents", section on 'Dosing considerations'.)
Ideally, propofol dosing is titrated using EEG-based neuromonitoring, although other
technology has been used in some centers (eg, isolated forearm technique) (see
"Accidental awareness after general anesthesia", section on 'Brain monitoring'). The
infusion rate is titrated to the patient's responses to noxious surgical stimulation
when such monitoring technology is not available. In some countries, TCI systems
are used to predict the propofol concentration in the plasma and at the effect site (ie,
the brain); however, TCI systems are not available in the United States [22,26]. (See
"Intravenous infusion devices for perioperative use", section on 'Target-controlled
infusion systems'.)
● Advantages and potential adverse effects – Advantages of propofol include rapid

onset and recovery ( figure 1), and antiemetic, anticonvulsant, antipruritic, and
bronchodilatory properties. It is suitable for patients with renal and/or hepatic
insufficiency (see "General anesthesia: Intravenous induction agents", section on
'Advantages and beneficial effects'). When used as the sedative-hypnotic component
of a TIVA technique during maintenance of general anesthesia, propofol may also
have beneficial antioxidant, antiinflammatory, and immunomodulatory effects [27].
Clinically significant adverse side effects of propofol are minimal, particularly when
titrated to desired depth. However, hypotension can occur at higher doses in
susceptible patients, primarily due to venous and arterial dilation. Dose-dependent
respiratory depression is also a known side effect. (See "General anesthesia:
Intravenous induction agents", section on 'Disadvantages and adverse effects'.)
Analgesic component: Opioid agents — An opioid is usually selected to provide the

analgesic component of a TIVA technique.
● Dosing – In general, we use the lowest dose of opioid for the shortest period of time
necessary, while ensuring provision of adequate analgesia [28-30].
Protocols for enhanced recovery after surgery (ERAS) emphasize limiting the dose of
perioperative opioids because of potential adverse effects in the postoperative
period (see below). Multimodal opioid-sparing strategies in such protocols include
administration of nonopioid analgesics such as acetaminophen, nonsteroidal anti-
inflammatory drugs (NSAIDs) or cyclooxygenase (COX)-2 specific inhibitors, and
adjuvant agents with analgesic properties (eg, dexamethasone, ketamine), as well as
use of nonpharmacologic analgesic techniques such as regional blocks. Further
discussion is found in other topics:
• (See "Anesthetic management for enhanced recovery after major noncardiac

surgery (ERAS)", section on 'Pain prophylaxis' and "Anesthetic management for
enhanced recovery after major noncardiac surgery (ERAS)", section on
'Management of pain'.)
• (See "Management of acute perioperative pain in adults", section on 'Strategy for

perioperative pain control'.)
Some clinicians advocate "opioid-free" anesthesia, whereby multimodal nonopioid

analgesic agents and techniques are used rather than administering any
intraoperative (or postoperative) opioid. However, data are insufficient to
recommend patient-specific or procedure-specific indications for such complete
opioid avoidance [12,31-34]. In an individual patient, it remains essential to ensure
effective intraoperative and postoperative analgesia if opioids are minimized or
avoided [28,29,35]. (See "Perioperative uses of intravenous opioids in adults: General
considerations", section on 'Opioid-free and opioid-sparing anesthetic techniques'
and 'Adjuvant agents' below.)
● Advantages and potential adverse effects – Benefits of opioids include effective

analgesia, reduced requirements for other IV and inhalation anesthetic agents,
attenuation of autonomic responses to noxious stimuli, and blunting of cough and
gag reflexes during airway manipulation. (See "Perioperative uses of intravenous
opioids in adults: General considerations", section on 'Benefits'.)
Potential adverse effects of opioids during and after general anesthesia include (see
"Perioperative uses of intravenous opioids in adults: General considerations", section
on 'Prevention and management of adverse opioid effects'):
• Intraoperative period – Exacerbation of adverse effects of other anesthetic agents

(eg, propofol, inhalation anesthetics) including hypotension and respiratory
depression may occur. Other potential adverse effects include bradycardia, chest
wall and skeletal muscle rigidity, and delayed emergence.
• Postoperative period – Nausea and vomiting, delirium, pruritus, urinary retention,

and potential for acute tolerance and opioid-induced hyperalgesia may occur in
the postoperative period.
● Selection of an opioid agent – Selection of a specific opioid and dosing
considerations depend on procedure-specific factors (eg, degree of analgesia

required, planned duration of surgery), patient-specific factors (eg, age,
comorbidities, tolerance to opioids), the desired speed of onset and offset, and
whether other analgesic agents are coadministered. (See "Perioperative uses of
intravenous opioids: Specific agents".)
• Continuous infusion during a TIVA anesthetic technique – Remifentanil is often

selected for continuous infusion during a TIVA technique, particularly during
shorter procedures when the intensity of noxious surgical stimulation is expected
to vary considerably. When coadministered with propofol, dose-dependent
analgesic effects of remifentanil reduce somatic movement and autonomic
nervous system ( figure 2), and these effects are more marked for painful
stimuli than for nonpainful stimuli such as calling the patient's name [14].
However, when coadministered with sevoflurane, these effects diminish with
higher remifentanil concentrations (eg, >2 ng/mL predicted effect site
concentration, which is approximately equivalent to a continuous infusion of
remifentanil at 0.1 ng/kg per minute) ( figure 2) [14].
Sufentanil may be selected as an alternative opioid infusion for longer TIVA

anesthetics due to its lower cost.
• Bolus dosing – A short-acting opioid such as fentanyl is typically selected for bolus
dosing during a TIVA anesthetic technique or to provide supplemental analgesia
during general anesthesia.
• Intraoperative dosing to provide postoperative analgesia – A long-acting opioid

(eg, morphine or hydromorphone) is typically selected, and administered
approximately 20 to 30 minutes before emergence from general anesthesia if
significant postoperative pain is anticipated.
Agent-specific uses, dosing, advantages, disadvantages, drug-drug interactions, and

pharmacokinetics for opioids employed during general anesthesia are described
separately ( table 6 and figure 3 and figure 4 and figure 5):
• Remifentanil (see "Perioperative uses of intravenous opioids: Specific agents",

section on 'Remifentanil')
• Fentanyl (see "Perioperative uses of intravenous opioids: Specific agents", section
on 'Fentanyl')
• Sufentanil (see "Perioperative uses of intravenous opioids: Specific agents",
section on 'Sufentanil')
• Alfentanil (see "Perioperative uses of intravenous opioids: Specific agents",
section on 'Alfentanil')
• Hydromorphone (see "Perioperative uses of intravenous opioids: Specific agents",
section on 'Hydromorphone')
• Morphine (see "Perioperative uses of intravenous opioids: Specific agents",
section on 'Morphine')
Adjuvant agents — Infusions of other adjuvant agents (eg, dexmedetomidine,

ketamine, lidocaine ( figure 1)) may be used to reduce or replace propofol as the
sedative-hypnotic component or an opioid as the analgesic component of a TIVA
technique. Addition of such adjuvant agents results in synergistic rather than merely
additive effects [8-10]. However, data are scant regarding specific combinations of
anesthetic agents; thus, limited knowledge exists regarding potential clinical benefits and
adverse effects of such combinations. Dose reduction of all administered agents is
appropriate when these synergistic effects result in undesirable decreases in blood
pressure.
Dexmedetomidine — Dexmedetomidine is a highly selective alpha2 agonist acting

on receptors in the brain and spinal cord. Its use as a sedative in intraoperative
interventions and intensive care unit are discussed in separate topics. (See "Monitored
anesthesia care in adults", section on 'Dexmedetomidine' and "Pain control in the critically
ill adult patient", section on 'Dexmedetomidine'.)
Dexmedetomidine is not routinely used as an adjunct to reduce dosing of sedative-

hypnotic and opioid agents during maintenance of general anesthesia. Data are limited
regarding efficacy and optimal dosing during coadministration with hypnotic intravenous
or potent inhalation anesthetic agents. In one randomized study in 80 patients
undergoing laparoscopic surgery, addition of a continuous infusion of dexmedetomidine
to a continuous infusion of propofol administered via a closed-loop anesthesia delivery
system (see "Intravenous infusion devices for perioperative use", section on 'Target-
controlled infusion systems') resulted in consistent reduction of propofol requirements
from 4.6±1.2 mg/kg per hour to 3.3±1.0 mg/kg per hour, with consistent depth of
anesthesia as measured with BIS monitoring [36]. However, in this study, addition of
dexmedetomidine increased the incidence of significant bradycardia (9 versus 41 percent)

and hypotension (6 versus 26 percent), and increased time to emergence and degree of
sedation in the early postoperative period. Similarly, other studies have demonstrated
these significant adverse effects of dexmedetomidine [23,37-40].
● Dosing – Dexmedetomidine may be selected for administration as a continuous

infusion during general anesthesia, typically at 0.1 to 0.3 mcg/kg per hour, although
higher doses up to 0.8 mcg/kg per hour are sometimes used. Dosing should be
reduced in patients with hepatic insufficiency since dexmedetomidine is heavily
protein-bound; thus, its elimination half-life may be prolonged [41]. Also, dosing is
reduced in patients with reduced hepatic blood flow such as those with low cardiac
output, and in older adults due to age-related decline in hepatic mass and function
[42,43] (see "Anesthesia for the older adult", section on 'Intravenous anesthetic and
adjuvant agents'). Clearance of dexmedetomidine is not affected by fat mass in
obese patients; thus, weight-based dosing may result in higher than necessary
plasma concentrations [44].
● Advantages and potential adverse effects – Advantages of dexmedetomidine

include its analgesic, sedative, anxiolytic, and sympatholytic properties [45]. In
particular, the analgesic effects of dexmedetomidine result in opioid-sparing effects
[46,47]. However, its overall efficacy and clinical significance in reducing
postoperative pain and opioid requirements are inconsistent [48-50].
Although dexmedetomidine reduces requirements for propofol or potent inhalation

anesthetics in a synergistic fashion [8,36], the degree of synergism remains
unknown. Assessment of dexmedetomidine-induced level of sedation is difficult [51].
Also, dexmedetomidine has a variable context-sensitive half-time that depends on
the duration of a continuous infusion (eg, four minutes after infusion for 10 minutes;
250 minutes after infusion for eight hours). This leads to difficulty in decisions
regarding optimal timing for discontinuation of dexmedetomidine in order to
prepare for emergence from general anesthesia. Thus, overdosing, delayed recovery,
and postoperative sedation may occur after coadministration of dexmedetomidine
with a sedative-hypnotic or opioid. (See "Emergence from general anesthesia",
section on 'Discontinue anesthetic agents'.)
Other adverse effects of dexmedetomidine include the potential to cause
hypotension and/or bradycardia due to its sympatholytic effects, particularly if

coadministered with other agents that also cause these effects (eg, propofol or
inhalation agents) [36,37]. Resolution occurs gradually after discontinuation of
dexmedetomidine, such that hemodynamic depression of heart rate and blood
pressure, as well as residual sedation, may persist in the early postoperative period
[36,38]. Furthermore, similar to propofol, dexmedetomidine produces dose-
dependent respiratory depression, as described elsewhere. (See "Monitored
anesthesia care in adults", section on 'Dexmedetomidine'.)
Ketamine — Ketamine is an N-methyl-d-aspartate receptor antagonist that

produces dissociative anesthesia (profound analgesia while appearing disconnected from
surroundings) [52].
● Dosing – Dosing during a TIVA technique begins with an IV bolus of 0.25 to 0.35
mg/kg, followed by infusion of less than 1 mg/kg per hour. There is no role for a
single dose of ketamine during the maintenance phase of anesthesia.
● Advantages and potential adverse effects – Ketamine has anesthetic and excellent
analgesic effects that reduce requirements for other anesthetic agents (eg, propofol,
potent inhalation anesthetics). It is often used in opioid-tolerant patients undergoing
major surgical procedures, particularly when regional analgesic techniques are not
possible [53]. Ketamine maintains airway reflexes and respiratory drive, which is
advantageous in patients who are breathing spontaneously, and also has excellent
bronchodilatory properties. (See "General anesthesia: Intravenous induction agents",
section on 'Advantages and beneficial effects'.)
In cases when neuromonitoring is necessary, a ketamine infusion may be used as an

adjuvant agent because it beneficially augments motor evoked potential (MEP) and
somatosensory evoked potential (SSEP) amplitudes [54,55]. (See "Neuromonitoring
in surgery and anesthesia", section on 'Intravenous agents'.)
Ketamine increases sympathetic tone with typical increases in blood pressure, heart
rate, and cardiac output, which may be beneficial in patients with hemodynamic
instability, but may be detrimental in patients with ischemic heart disease or
systemic hypertension. Furthermore, these sympathomimetic effects increase
pulmonary artery pressure and intracranial pressure, effects which may be
detrimental in patients with pulmonary hypertension or elevated intracranial
pressure (ICP). (See "General anesthesia: Intravenous induction agents", section on

'Disadvantages and adverse effects'.)
Potential adverse effects of ketamine include psychotomimetic effects that may

cause hallucinations, nightmares, and vivid dreams during and shortly after
emergence from anesthesia. Even single low doses of ketamine used for induction of
anesthesia (0.5 mg to 1 mg/kg) can induce such negative experiences [56]. Thus,
ketamine is typically reserved for opioid-tolerant patients who are undergoing
painful surgery in order to avoid or limit opioid dosing [53]. (See "Delayed
emergence and emergence delirium in adults", section on 'Evaluation and
treatment'.)
Lidocaine — Lidocaine is a local anesthetic agent that is often used during IV

induction of general anesthesia to suppress airway reflexes, reduce the pain of injection of
other induction agents, and supplement their anesthetic effects. Lidocaine infusion is
occasionally used during maintenance of general anesthesia as a component of a
multimodal analgesia technique. (See "General anesthesia: Intravenous induction agents",
section on 'Lidocaine'.)
● Dosing – When used during the maintenance phase, lidocaine is administered as a 1

to 1.5 mg/kg bolus, followed by continuous infusion of 1 to 1.5 mg/kg per hour (or 2
mg/minute in some studies) [57-59]. Notably, calculated doses should be based on
lean or adjusted body weight, rather than on actual body weight (calculator 1 and
calculator 2) [59].
● Advantages and potential adverse effects – Some studies have reported that
infusion of lidocaine reduces opioid and sedative-hypnotic requirements and
improves postoperative pain control after open or laparoscopic abdominal surgery,
particularly if regional anesthetic techniques cannot be employed, and lidocaine may
also improve pain control and reduce airway reactivity in patients undergoing head
and neck procedures [57-60].
However, the overall role of lidocaine infusion as an analgesic adjunct is questionable. A

2018 meta-analysis concluded that lidocaine infusion does not have any beneficial effects
on postoperative pain scores, opioid consumption, opioid-related adverse effects, or
gastrointestinal recovery compared with placebo or no treatment [61]. Notably, few
studies have assessed adverse effects of administering a continuous IV infusion of
lidocaine [61]. However, lidocaine has the potential to cause hypotension [62,63].
NEUROMUSCULAR BLOCKING AGENTS
General considerations — A neuromuscular blocking agent (NMBA) may be employed to

improve surgical conditions in selected cases.
Two classes of NMBAs exist: depolarizing (succinylcholine [SCh]) and nondepolarizing

agents (eg, rocuronium, vecuronium, pancuronium, atracurium, cisatracurium,
mivacurium) ( table 7). All nondepolarizing NMBAs have a slower onset and longer
duration than SCh. A nondepolarizing NMBA is typically selected during the maintenance
phase unless the surgical procedure is expected to last only a few minutes. (See "Clinical
use of neuromuscular blocking agents in anesthesia", section on 'Classification of
neuromuscular blocking agents'.)
Intraoperative monitoring of the intensity of neuromuscular blockade is necessary

throughout the maintenance phase of general anesthesia when a NMBA is administered
[64-66]. (See "Monitoring neuromuscular blockade".)
Advantages and disadvantages
● Advantages:
• Muscle relaxation in the surgical field and/or complete absence of movement

facilitates safety and technical performance in many surgical procedures, and
may allow lower insufflation pressures during laparoscopy. (See "Clinical use of
neuromuscular blocking agents in anesthesia", section on 'Facilitation of
surgery'.)
• Use of an NMBA may reduce total administered doses of anesthetic agents. (See
"Accidental awareness after general anesthesia", section on 'Neuromuscular
blockade'.)
● Disadvantages:
• Risk of awareness is potentially increased since use of an NMBA may reduce the
total administered doses of anesthetic agents, particularly when complete
paralysis eliminates all purposeful movement. (See "Accidental awareness after
general anesthesia", section on 'Neuromuscular blockade'.)
• Residual neuromuscular block after administration of NMBAs is an important risk

factor for anesthesia-related morbidity and mortality. Strategies to avoid residual
block are discussed in detail in a separate topic. (See "Clinical use of
neuromuscular blocking agents in anesthesia", section on 'Avoidance of residual
neuromuscular blockade'.)
• NMBAs, particularly rocuronium and SCh, have a relatively high incidence of

anaphylaxis compared with other agents employed during general anesthesia.
Anaphylaxis is more common in some countries (eg, Australia, New Zealand,
France, and Norway), possibly due to immunologic cross-reactivity with
pholcodine (an over-the-counter cough suppressant available in those countries).
(See "Perioperative anaphylaxis: Clinical manifestations, etiology, and
management", section on 'Neuromuscular-blocking agents'.)
Specific neuromuscular blocking agents — Selection of a specific NMBA is based on the

planned duration of the surgical procedure, presence of severe renal or hepatic
dysfunction, the NMBA that was administered during anesthetic induction, whether the
surgical procedure requires peripheral nerve stimulation or motor-evoked potential (MEP)
monitoring, and availability and cost of each agent within an individual institution or
country ( table 7).
Further details regarding use of NMBAs are discussed separately. (See "Clinical use of
neuromuscular blocking agents in anesthesia".)
TRANSITION TO THE EMERGENCE PHASE
Emergence is the return of consciousness after discontinuing administration of anesthetic

and adjuvant agents at the end of the surgical procedure. Most patients transition
smoothly from a surgical anesthetic state (Stage III) to an awake state (Stage I)
( table 1). Preparations for emergence are discussed in a separate topic. (See
"Emergence from general anesthesia", section on 'Preparations for emergence'.)
SUMMARY AND RECOMMENDATIONS
● Goals – Overall goals during the maintenance phase of a general anesthetic include
maintaining Stage III surgical anesthesia (ie, unconsciousness, amnesia, immobility,
and unresponsiveness to surgical stimulation ( table 1)) at a safe anesthetic depth,
while also maintaining respiratory and hemodynamic stability. (See 'Anesthetic goals'
above.)
● Techniques – Maintenance of general anesthesia may be accomplished by

employing a primary inhalation technique, a primary intravenous (IV) technique, or a
combination of inhalation and IV agents. Coadministration of agents from different
classes takes advantage of their synergistic effects, increasing the likelihood of
achieving the desired anesthetic goals while using less of each drug than if it were
administered alone. (See 'Selection of maintenance techniques' above.)
● Inhalation anesthetic agents
• Potent volatile inhalation agents – Specific advantages, disadvantages, and

adverse effects differ among these agents, as described separately:
- Sevoflurane (see "Inhalation anesthetic agents: Clinical effects and uses",

section on 'Sevoflurane')
- Desflurane (see "Inhalation anesthetic agents: Clinical effects and uses",

section on 'Desflurane')
- Isoflurane (see "Inhalation anesthetic agents: Clinical effects and uses",

section on 'Isoflurane')
- Halothane (see "Inhalation anesthetic agents: Clinical effects and uses",

section on 'Halothane')
- Dosing considerations – Dose titration of potent volatile inhalation agents is

necessary to maintain stage III surgical anesthesia. Each inhalation
anesthetic agent's potency is reported as a minimum alveolar concentration
(MAC) value ( table 3 and table 2), which is influenced by patient age and
coexisting diseases or conditions ( table 4). Dosing is decreased with
concomitant administration of nitrous oxide (N2O) and/or if IV anesthetic
agents. (See 'Volatile inhalation agents' above.)
- Advantages – General advantages of the potent volatile inhalation agents

(eg, sevoflurane, desflurane, isoflurane, halothane) include ease of titration,
dose-dependent decreases in skeletal muscle tone, cerebral metabolic rate,
and bronchodilation (except desflurane), and ability to use end-tidal
anesthetic concentration (ETAC) values to titrate anesthetic depth. ETAC
values of 0.8 to 1 MAC are typically adequate to prevent awareness with
recall.
- Disadvantages – General disadvantages include dose-dependent systemic

vasodilation (with decreased blood pressure) and respiratory depression, and
increased risk of postoperative nausea and vomiting (PONV) compared with
most IV anesthetic alternatives, unless prophylactic antiemetics are
administered. The volatile inhalation anesthetics also have the potential to
precipitate malignant hyperthermia. (See 'Volatile inhalation agents' above.)
● Nitrous oxide – Nitrous oxide (N2O) is a pressurized anesthetic gas delivered via a
flow meter on the anesthesia machine. We routinely use N2O unless there is a
contraindication. Advantages include rapid onset and offset of anesthetic effect that
allows decreased dosing of other anesthetic agents, as well as analgesia and
anxiolysis. N2O is always avoided in patients with pre-existing bowel distention,
increased middle ear pressure, pneumothorax, pneumoperitoneum,
pneumocephalus, intraocular gas, or venous air embolism. (See 'Nitrous oxide gas'
above.)
● Total intravenous anesthesia (TIVA) – TIVA employs an IV sedative-hypnotic

anesthetic (typically propofol) and an analgesic agent (typically an opioid). (See 'Total
intravenous anesthesia' above.)
• Propofol – Propofol is most commonly selected as the sedative-hypnotic

component of a TIVA technique because of its rapid onset and recovery; beneficial
antiemetic, bronchodilatory, and anticonvulsant properties; and relatively benign
adverse side effects ( table 8). Propofol is infused at 75 to 150 mcg/kg per
minute, with titration according to individual requirements, the degree of noxious
surgical stimulation, and coadministration of other anesthetic agents. (See
'Sedative-hypnotic agent: Propofol' above.)
• Opioids – An opioid is most commonly employed as the analgesic component of
a TIVA technique. Potential adverse effects include exacerbation of hypotensive

effects of propofol, respiratory depression, bradycardia, PONV, ileus, constipation,
delirium, pruritus, and potential for acute tolerance. Choice of a specific opioid is
dependent upon patient- and procedure-specific factors ( table 6).
• Other adjuvant agents – Infusions of other IV agents (eg, dexmedetomidine,

ketamine, lidocaine) may be used for patient-specific or procedure-specific
reasons to reduce or replace propofol as the sedative-hypnotic component or an
opioid as the analgesic component of a TIVA technique. Overall, these adjunct
agents have limited benefits and specific potential adverse effects, as noted
above. (See 'Adjuvant agents' above.)
● Neuromuscular blocking agents (NMBAs) – A nondepolarizing NMBA is typically

employed if profound muscle relaxation in the surgical field and/or absence of
movement are necessary ( table 7). Disadvantages of neuromuscular blockade
include intraoperative elimination of purposeful movement as a sign of awareness,
and the potential for residual postoperative neuromuscular weakness, which may
lead to respiratory complications. (See 'Neuromuscular blocking agents' above.)
ACKNOWLEDGMENTS
The UpToDate editorial staff acknowledges Liza M Weavind, MBBCh, FCCM, MMHC and
Adam King, MD, who contributed to an earlier version of this topic review.
Use of UpToDate is subject to the Terms of Use.
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Topic 96308 Version 36.0
GRAPHICS
Stages of anesthetic depth
Stage I Analgesia state: Patient is conscious and rational, with decreased

perception of pain.
Stage II Delirium stage: Patient is unconscious; body responds reflexively; irregular

breathing pattern with breathholding.
Stage III Surgical anesthesia: Increasing degrees of muscle relaxation; unable to

protect airway.
Stage IV Medullary depression: There is depression of cardiovascular and respiratory

centers.
Adapted from: Hewer CL. The stages and signs of general anesthesia. Br Med J 1937; 2:274.
Graphic 107796 Version 2.0
Minimum alveolar concentration (MAC) values for inhalation agents: 1

MAC
Minimum alveolar concentration

Inhalation anesthetic agent
(MAC) value (1 MAC)*
Nitrous oxide 104
Desflurane 6.6
Sevoflurane 1.8
Isoflurane 1.17
Halothane 0.75
The minimum alveolar concentration (MAC) value is the concentration of an inhalation

anesthetic agent in the lung alveoli required to prevent movement in response to a surgical
stimulus in 50% of patients.
* These MAC values are for a 40-year-old person.
Definition of minimum alveolar concentration (MAC) values
MAC level Effect
0.3 MAC MAC awake (MAC value below this will allow the patient to become
conscious)
1 MAC End-tidal concentration of anesthetic agent necessary to prevent movement

in response to a surgical stimulus in 50% of patients
1.5 MAC MAC value where 90% of patients will not move in response to a surgical
stimulus
2.0 MAC MAC-BAR (MAC value required to block autonomic responses to a surgical
stimulus in 50% of patients)
MAC: minimum alveolar concentration; a value of 1.0 MAC is the concentration of an

inhalation anesthetic agent in the alveoli required to prevent movement to a surgical stimulus
in 50% of patients.
Factors that influence minimum alveolar concentration (MAC) values of

inhalation anesthetic agents
Factors that increase MAC Factors that decrease MAC
Chronic alcohol use Acute alcohol use

Infancy (highest MAC at 6 months) Older age
Hypernatremia Hyponatremia
Hyperthermia Hypothermia
Amphetamines Anemia (Hgb <5 g/dL)
Cocaine Hypercarbia
Ephedrine Hypoxia
Metabolic acidosis
Pregnancy
Nitrous oxide
Opioids
Benzodiazepines
Propofol
Alpha 2 agonists
Intravenous lidocaine
Factors that increase or decrease the minimum alveolar concentration (MAC) value, defined as
the concentration of an inhalation anesthetic agent in the alveoli required to prevent
movement in response to a surgical stimulus in 50 percent of patients.
MAC: minimum alveolar concentration; Hgb: hemoglobin.
Adapted from:
1. McKay RE. Inhaled anesthetics. In: Basics of Anesthesia, 6th ed, Miller RD, Pardo, Jr., MC (Eds), Elsevier,
Philadelphia 2011.
2. Bartunek AE, Minimum alveolar concentration. In: Faust's Anesthesiology Review, 4th ed, Murray MJ, Harrison
BA, Mueller JT, et al (Eds), Elsevier, Philadelphia 2015.
3. Miller's Anesthesia, 8th ed, Miller RD, Cohen NH, Eriksson LI, et al (Eds), Elsevier, Philadelphia 2015.
Processed EEG brain monitors
Monitoring
Monitor* Manufacturer ¶ Parameters Notes
range
Unprocessed Non-proprietary Alpha, beta, No specific Advantages: Ra

electroencephalogram (EEG) gamma, delta, index response time,
theta waves, cheap, non-
Permutation
sleep spindles; K proprietary.
entropy can
complexes,
be derived Disadvantages
spectral edge
index or value,
frequency, burst
requires attent
suppression;
requires trainin
isoelectricity.
High Wakefulness
frequency, common.
low
amplitude
(gamma and
beta
dominance)
Alpha Drowsiness/se
oscillations common.
Spindles, K Explicit recall r

complexes,
some delta
waves
Slow delta Surgical anesth

waves, common.
spectral edge
<12
Burst Deep anesthes

suppression common.
and
isoelectricity
Bispectral index (BIS) Covidien Medical Bispectral index 0 to 100 Raw EEG and
(proprietary parameters su
algorithm) based spectral edge
upon beta power, frequency can
bispectral should be disp
coherence Advantages: In
(synchfastslow), value can be u
and burst guide anesthes
suppression ratio. May improve
outcomes.
Disadvantages
response time,
costly, propriet
80 to 100 Wakefulness
common.
60 to 80 Drowsiness/se
common.
50 to 60 Explicit recall r
30 to 50 Surgical anesth
common.
0 to 30 Deep anesthes
common.
Entropy GE Healthcare State entropy (SE) SE: (0 to 100) SE of EEG signa

and response calculated up t
RE: (0 to 91)
entropy (RE) Hz. RE includes
indices; burst additional
suppression ratio; frequencies up
entropy of EEG Hz. SE is alway
signal decreases Raw EEG can a
with sleep and should be disp
anesthesia.
common.
Sudden drop May be associa

in entropy with loss of
responsivenes
40 to 60 Explicit recall r
Surgical anesth
common.
Sudden rise May indicate p

in RE muscle activity
Lower Deep anesthes

entropy common.
numbers and
burst
suppression
A-line Danmeter a/s Middle latency 0 to 100 Full range.

auditory evoked
AEP Monitor/2 60 to 100 Wakefulness
potentials
(Adds EEG parameters) common.
(MLAEPs); ARX
Auditory Index 40 to 60 Drowsiness/se
(AAI); middle common.
latency (20 to 80
25 to 40 Light anesthes
msec); Composite
common.
AAI Index
(Proprietary - 15 to 25 Surgical anesth
combines EEG common.
and MLAEP 0 to 15 Deep anesthes
information). common.
Cerebral State Danmeter a/s Cerebral State 0 to 100 Full range.

Index (CSI)
Hand-held device 90 to 100 Wakefulness
(Proprietary);
common.
Wireless connection to burst suppression
anesthesia monitor electromyography 80 to 90 Drowsiness
and signal quality common.
are indicated;
60 to 80 Light anesthes
index derived common.
mainly from alpha
and beta EEG 40 to 60 Surgical anesth
ratios, burst common.
suppression. 10 to 40 Deep anesthes
common.
0 to 10 Burst suppress
isoelectric EEG
Narcotrend MT Cerebrogram A to F Full range.

MonitorTechnik (Proprietary); Raw
A Wakefulness
GmbH & Co. KG EEG waveform
common.
displayed; median
and spectral edge B Drowsiness
frequencies; common.
power in EEG C Light anesthes
frequency bands
common.
is shown.
D Surgical anesth
common.
E Deep anesthes
common.
F Burst suppress
isoelectric EEG
NeuroSense monitor NeuroWave The index is 1 to 100 Conceptualized

systems Inc. calculated via use in closed-lo
analysis of the anesthesia.
EEG signals in the
Promoted as h
gamma frequency
a rapid respon
band; uses
time.
bilateral frontal
EEG channels for
derivation of
index.
qCON 2000 monitor Quantum Medical The qCON index 0 to 99 Theoretically

(proprietary) is a provides
measure of information on
hypnosis that is hypnosis and
derived from nociception.
spectral analysis
Promoted as h
and burst
a rapid respon
suppression rate.
time.
The qNOX
reference scale
(proprietary) is
derived through
EEG signals in
patients moving
in response to
nailbed pressure,
and is the
component
designed for
noxiousness. The
proprietary
algorithm of this
device, based on
"Adaptive Neuro
Fuzzy Inference
System"
(proprietary),
assumes that the
EEG signal
contains
dissociable
information on
hypnosis and
nociception.
SEDline Hospira Patient state 0 to 100 Full range.

index (PSI)
(proprietary); raw
common.
EEG waveform
displayed; density 50 to 90 Drowsiness/se
spectral array common.
(DSA) shown;
converts EEG
common.
acquired from
four active, 10 to 25 Deep anesthes
ground and common.
reference 0 to 10 Burst suppress
electrodes into a isoelectric EEG
proprietary index;
anteriorization of
EEG power; loss
of coherence.
SNAP II Stryker SNAP index 0 to 100 Full range.

(Proprietary);
spectral analysis
common.
of low (0 to 18 Hz)
and high (>80 Hz) 65 to 90 Drowsiness/se
frequency EEG common.
components; PDA
portable device;
common.
raw EEG
waveform 0 to 50 Deep anesthes
displayed. common.
* All brain monitors are not specific for the anesthetic state. Patient morbidity, drugs and even
natural sleep can confound anesthetic depth monitoring.
¶ Specific manufacturer guidelines for use may vary.
The context-sensitive half-time of several intravenous anesthetic agents
Reproduced from: Robert RC, Patel CM. Anesthetic Pump Techniques Versus the Intermittent Bolus: What the Oral Surgeon
Needs to Know. Oral Maxillofac Surg Clin North Am 2018; 30:227. Illustration used with the permission of Elsevier Inc. All rights
reserved.
Effect of remifentanil at different concentrations of propofol and sevoflurane
Effect of addition of remifentanil to probability of response to noxious stimulus, at different concentrations

and sevoflurane (B).
TOTS: tolerance to tetanic stimulation; vol%: end-tidal sevoflurane concentration
From: Kuizenga MH, Colin PJ, Reyntjens KM, et al. Population Pharmacodynamics of Propofol and Sevoﬂurane in Healthy Volunteers
Score and the Patient State Index: A Crossover Study. Anesthesiology 2019; 131:1223. DOI: 10.1097/ALN.0000000000002966. Copyri
American Society of Anesthesiologists. Reproduced with permission from Wolters Kluwer Health. Unauthorized reproduction of this m
prohibited.
Perioperative uses and doses of intravenous opioid agents*
Manageme
Induction Maintenance Monitored
of acute
Drug of general of general anesthesia Comments
postoperat
anesthesia anesthesia care (MAC)
pain
Fentanyl Bolus Bolus dose(s): Bolus doses: High-dose Bolus doses: 2

dose(s): 25 to 25 to 50 mcg as 25 to 50 mcg. fentanyl is not to 50 mcg eve
100 mcg or needed. commonly used five minutes
0.5 to 1 for anesthetic until patient i
Maintenance
mcg/kg; may induction, but comfortable.
infusion to
be may be selected
supplement
administered for patients
TIVA: 1 to 2
in divided with severe
mcg/kg per
doses. myocardial
hour. ¶
dysfunction.
High-dose
opioid Continuous
induction (ie, infusions are
"cardiac not commonly
induction"): used if
10 to 25 extubation is
mcg/kg. planned at the
end of the
procedure
because
emergence may
be delayed due
to a long
context-
sensitive half
time.
Remifentanil Remifentanil Maintenance Before A different

intubation infusion to placement of opioid or
technique supplement regional another
without an inhalation block: analgesic agent
NMBA: 3 to 5 anesthesia or 90 or technique
mcg/kg TIVA: 0.05 to 0.3 seconds should be
administered mcg/kg per before: initiated before
with an minute. 1 the remifentanil
induction (Some clinicians mcg/kg. infusion is
dose of administer a 5 discontinued to

propofol and loading dose, minutes ensure
ephedrine 10 typically 0.5 to 1 before: adequate
mg. mcg/kg over 60 0.5 postoperative
to 90 seconds.) mcg/kg analgesia.
per
minute.
Maintenance
dose: Infusion
at 0.05 to 0.3
mcg/kg per
minute.
Sufentanil Bolus Bolus dose(s): 5 Infusion is

dose(s): 0.05 to 10 mcg as typically
to 0.1 needed. discontinued 30
mcg/kg in to 45 minutes
Maintenance
divided prior to end of
infusion to
doses. surgery for a
supplement
predictable
High-dose TIVA: 0.05 to
decline in
opioid 0.15 mcg/kg per
concentration.
induction (ie, hour (or 0.0008
"cardiac to 0.0025
induction"): 1 mcg/kg per
to 3 mcg/kg. minute).
Alfentanil Bolus Bolus dose(s): Infusion is

dose(s): 500 500 mcg as typically
mcg (which needed. discontinued 30
may be to 45 minutes
Maintenance
repeated), or prior to end of
infusion to
50 to 100 surgery for a
supplement
mcg/kg predictable
TIVA: 0.5 to 1.5
administered decline in
mcg/kg per
in divided concentration.
minute.
doses.
Maintenance:
0.5 to 1.5
mcg/kg per
minute.
Hydromorphone Bolus doses: 0.2 It is ideal to use Initial bolus

to 0.5 mg as hydromorphone doses of 0.2 t
needed. towards the end 0.5 mg every

of surgery minutes until
(rather than pain is relieve
during surgery) or unwanted
in order to side effects
provide pain become evide
relief in the
After initial pa
PACU and
control, typica
beyond.
doses are 0.2
0.5 mg every
three to four
hours.
Morphine Bolus doses: 1 It is ideal to use Initial bolus

to 2 mg as morphine doses of 1 to
needed. towards the end mg every five
of surgery minutes until
(rather than pain is relieve
during surgery) or unwanted
in order to side effects
provide pain become evide
relief in the
After initial pa
PACU and
control, typica
beyond.
doses are 2 to
Typically, 1 to 2
mg IV every
mg increments
three hours.
to a total of
approximately
0.05 to 0.2
mg/kg IBW are
administered
about 20
minutes prior to
the expected
time of
extubation.
Methadone 0.1 to 0.2 A single post- Repeat dosing

mg/kg (ideal induction dose not
body weight) has been shown recommende
IV up to 20 to have overall as redistribut
mg, given opioid-sparing half-life is
post- effects relatively shor
induction. throughout the (approximate
perioperative minute), but

period in once exceede
various surgical the eliminatio
populations. half-life is mu
Evidence is longer
equivocal (approximate
regarding 30 hours).
whether a
single post-
induction dose
results in
clinically
significant
respiratory
depression.
Data is lacking
on the effect of
a single dose of
methadone on
QTc. Consider
other options
for patients
with underlying
prolonged QTc.
TIVA: total intravenous anesthesia; NMBA: neuromuscular blocking agents; PACU: post-
anesthesia care unit; IBW: ideal body weight; IV: intravenous.
* Opioids are used as adjuvant agents during induction and maintenance of general
anesthesia and during monitored anesthesia care (MAC).
¶ Fentanyl infusion is not commonly used if extubation is planned at the end of the procedure.
Rapid attainment of steady state with remifentanil
Simulation demonstrating plasma concentrations after

administration of a bolus dose of remifentanil followed by an
infusion, showing the rapid attainment of steady state when a bolus
is used.
Ce: Effect site concentration.
Reproduced from: Ogura T, Egan TD. Opioid Agonists and Antagonists. In:
Pharmacologyand Physiology for Anesthesia: Foundations and Clinical Application,
Hemmings HC, Egan TD (Eds), Philadelphia, PA, Elsevier, 2013. Illustration used with
the permission of Elsevier Inc. All rights reserved.
Context-sensitive half time for opioids
Context-sensitive half time, or time in minutes to a 50 percent decrease in effect-site

concentration (Ce) after an infusion is stopped.
Reproduced from: Ogura T, Egan TD. Opioid Agonists and Antagonists. In: Pharmacologyand Physiology for
Anesthesia: Foundations and Clinical Application, Hemmings HC, Egan TD (Eds), Philadelphia, PA, Elsevier, 2013.
Illustration used with the permission of Elsevier Inc. All rights reserved.
Bolus front-end and back-end pharmacokinetics of opioids
Percent of peak effect-site concentration (Ce) after bolus dosing of different opioids.
Reproduced from: Ogura T, Egan TD. Opioid Agonists and Antagonists. In: Pharmacology and Physiology for
Anesthesia: Foundations and Clinical Application, Hemmings HC, Egan TD (Eds), Philadelphia, PA, Elsevier, 2013.
Illustration used with the permission of Elsevier Inc. All rights reserved.
Properties of neuromuscular blocking agents
Agent* Vecuronium Rocuronium Pancuronium Mivacurium
Type (structure) Non- Non- Non- Non-depolarizing

depolarizing depolarizing depolarizing
Type (duration) Intermediate Intermediate Long Short
Potency - ED 95 0.04 0.30 0.07 0.08

(mg/kg)
Intubating dose 0.10 to 0.20 0.60 to 1.00 0.08 to 0.12 0.20

(mg/kg) (1.20 with RSII
dose)
Onset time (min) 3 to 4 1 to 2 2 to 3 3 to 4
Time to 25% 20 to 35 30 to 50 (60 to 60 to 120 15 to 20

recovery (min) 80 with RSII
dose)
Elimination half-life (min)
Normal organ 50 to 60 60 to 100 100 to 130 2 to 2.5

function
Renal Mild increase 100 to 300 Increased x2 3 to 4

impairment
Hepatic Significant 120 to 400 Increased x2 3 to 6

impairment increase
Maintenance 0.01 0.10 0.02 0.10

dose (mg/kg)
Infusion dose 1 to 2 5 to 12 Not 5 to 8

(mcg/kg/min) recommended
Elimination Renal 10 to Renal 30%; Renal 40 to 70%; Plasma

route/metabolism 50%; hepatic 70% hepatic 20% cholinesterase (70%
hepatic 30 to of succinylcholine
50% rate)
Active 3-desacetyl- 17-desacetyl- 3-OH- No active metabolites

metabolites vecuronium rocuronium pancuronium;
(minimal) 17-OH-
pancuronium
Side effects Vagal blockade Minimal Vagal block Histamine release
with large (tachycardia),

doses catecholamine
release
Contraindications None None Short surgical Pseudocholinesterase

(other than procedures (<60 deficiency
specific allergy) min); not
recommended
for continuous
infusion
Comments Not for Pain on Significant Reversal by

prolonged ICU injection; accumulation, cholinesterase
administration easily prone to inhibitors; mixture of
(myopathy); reversible by residual block 3 isomers (cis-cis
reversible by sugammadex; (3-OH minimal);
sugammadex; elimination metabolite has edrophonium for
elimination half-life 50% activity of antagonism more
half-life halved prolonged in pancuronium) effective during deep
in late ICU patient; block
pregnancy; 3- 17-desacetyl
desacetyl metabolite has
metabolite has 20% activity
60% of the
parent
compound
potency
NA: data not available; ED 95 : effective dose to achieve 95% depression of baseline muscle
contraction; NMBA: neuromuscular blocking agents; RSII: rapid sequence induction and
intubation; K + : potassium; MH: malignant hyperthermia; ST: single twitch; ICU: intensive care
unit.
* The data are averages obtained from published literature and do not account for other
influences such as volatile anesthetics, muscle temperature, etc.
Adapted from: Brull SJ. Neuromuscular blocking agents. In: Clinical Anesthesia, 8th ed, Barash PG, Cullen BF,
Stoelting RK, et al (Eds), Wolters Kluwer, Philadelphia 2017.
Intravenous anesthetic induction agents
Suggested Potential adverse

Drug Uses Advantages
induction dose* effects
Propofol Induction agent 1 to 2.5 mg/kg Rapid onset Dose-dependent

of choice for Older age: 1 to and offset hypotension
most patients 1.5 mg/kg Antiemetic Dose-dependent
Hypovolemia or properties respiratory depressio
hemodynamic Antipruritic Pain during injection
compromise: ≤1 properties Microbial
mg/kg Bronchodilation contamination risk
Anticonvulsant Rare anaphylaxis in
properties patients with allergy t
Decreases its soybean oil emulsio
CMRO 2 , CBF, with egg phosphatide
and ICP
Etomidate May be selected 0.15 to 0.3 Rapid onset High incidence of PON
in patients with mg/kg and offset Pain during injection
hemodynamic Presence of Hemodynamic Involuntary myocloni
instability due to profound stability with no movements
any cause hypotension: 0.1 changes in BP, Absence of analgesic
to 0.15 mg/kg HR, or CO effects
Anticonvulsant Transient acute
properties adrenocortical
Decreases suppression
CMRO 2 , CBF,
and ICP
Ketamine May be selected 1 to 2 mg/kg Rapid onset Cardiovascular effects

in hypotensive Chronic use of Increases BP, Increases myocardial
patients or those tricyclic HR, and CO in oxygen demand due
likely to develop antidepressants: most patients increases in HR, BP, a
hypotension (eg, 1 mg/kg Profound CO
hypovolemia, Presence of analgesic Increases pulmonary
hemorrhage, profound properties arterial pressure (PAP
sepsis, severe hypotension: 0.5 Bronchodilation Potentiates
cardiovascular to 1 mg/kg Maintains cardiovascular toxicit
compromise)
Intramuscular airway reflexes of cocaine or tricyclic
dose: 4 to 6 and respiratory antidepressants
mg/kg drive Exacerbates

Intramuscular hypertension,
route available tachycardia, and
if IV access lost arrhythmias in
pheochromocytoma
Direct mild myocardia
depressant effects
Neurologic effects
Psychotomimetic
effects (hallucinations
nightmares, vivid
dreams)
Increases CBF and ICP
may increase CMRO
Unique EEG effects m
result in
misinterpretation of B
and other processed
EEG values
Other effects
Increases salivation
Methohexital Induction for 1.5 mg/kg Lowers seizure Limited availability

electroconvulsive threshold, Dose-
therapy (ECT) facilitating ECT dependent hypotensi
because it Decreases Dose-dependent
activates seizure CMRO 2 , CBF, respiratory depressio
foci and ICP Involuntary myocloni
movements
Pain during injection
Contraindicated in
patients with porphyr
CMRO 2 : cerebral metabolic oxygen requirement; CBF: cerebral blood flow; ICP: intracranial
pressure; BP: blood pressure; HR: heart rate; CO: cardiac output; PONV: postoperative nausea
and vomiting; EEG:electroencephalographic; ECT: electroconvulsive therapy.
* Use adjusted body weight or estimated lean body weight for anesthetic drug dosing.
Contributor Disclosures
Sarah M Khorsand, MD No relevant financial relationship(s) with ineligible companies to
disclose. Girish P Joshi, MB, BS, MD, FFARCSI Consultant/Advisory Boards: Baxter [anesthesia]. All of
the relevant financial relationships listed have been mitigated. Nancy A Nussmeier, MD, FAHA No
relevant financial relationship(s) with ineligible companies to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

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Maintenance of general anesthesia: Overview - UpToDate 23/08/2022 15:21

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Immediately after induction of general anesthesia, additional agents are necessary to

Induction of general anesthesia is discussed in separate topics. (See "Induction of general

concentration (ETAC), raw or processed electroencephalography (EEG), or other specialized

Other topics contain details regarding management of specific aspects of anesthesia

● Maintenance of physiologic homeostasis including:

• Oxygenation and ventilation (see "Mechanical ventilation during anesthesia in

● Prevention of awareness with recall (see "Accidental awareness after general

● Antinociception (analgesia) during increased intensity of the degree of noxious

● Muscle relaxation to facilitate surgery and/or prevent movement as necessary for

Anesthetic depth — Although an association has been noted between increasing

SELECTION OF MAINTENANCE TECHNIQUES

Maintenance of general anesthesia may be accomplished using a primary inhalation

INHALATION ANESTHETIC AGENTS AND TECHNIQUES

in some countries halothane) may be used for complete maintenance of general

Dosing considerations — Dosing of each inhalation anesthetic agent is determined by its

Volatile inhalation agents

Advantages and disadvantages — The potent volatile inhalation anesthetic agents

• Reliable blockade of responses to sensory input such as painful stimuli [14].

• Dose-dependent decreases in skeletal and smooth muscle tone.

• Decreased cerebral metabolic rate (CMR).

• Increased cerebral blood flow (CBF).

• Ability to monitor end-tidal anesthetic concentration (ETAC) as an indicator of

• Dose-dependent suppression of airway reflexes.

• Dose-dependent respiratory depression.

• Dose-dependent myocardial depression and vasodilation that may cause

• Potential to induce malignant hyperthermia in susceptible individuals. (See

Sevoflurane — Sevoflurane is often selected for maintenance of anesthesia during

Further details regarding sevoflurane administration are discussed separately. (See

Further details regarding desflurane administration are discussed separately. (See

Isoflurane — Isoflurane is commonly used as a primary agent to maintain general

Disadvantages of isoflurane compared with sevoflurane or desflurane include slower

Further details regarding isoflurane administration are discussed separately. (See

Halothane — Concern about hepatotoxicity has eliminated the use of halothane in

Further details regarding halothane administration are discussed separately. (See

● Advantages – Advantages of N2O include [18,19] (see "Inhalation anesthetic agents:

• During the maintenance phase of general anesthesia, coadministration of N2O

• Minimal hemodynamic effects.

• Cheap and wide availability.

● Disadvantages – Disadvantages include:

• Although visceral distension may slightly increase risk of PONV, particularly if no

• Potential for transient diffusion hypoxia if N2O is discontinued at a low inspired

INTRAVENOUS ANESTHETIC AGENTS AND TECHNIQUES

General considerations — Appropriate doses of intravenous (IV) anesthetic agents are

Total intravenous anesthesia — Total intravenous anesthesia (TIVA) employs a sedative-

by making small incremental increases.

• (See "Intravenous infusion devices for perioperative use", section on 'Smart

● Concerns include the possibility of awareness during anesthesia (see "Accidental

● Indications and advantages – A TIVA technique is selected in the following

• Patients requiring general anesthesia if there are absolute contraindications (eg,

• Patients undergoing surgical procedures with neuromonitoring (eg, spine

● Disadvantages – Potential disadvantages of TIVA include the following:

• Blood concentrations (and therefore effect site concentration) of IV anesthetic

• TIVA is associated with dose-dependent suppression of airway reflexes and

• TIVA is also associated with dose-dependent vasodilation and myocardial

'Extravasation of a continuous infusion'.)

Specific intravenous agents

Sedative-hypnotic agent: Propofol — Propofol is usually selected as the sedative-

● Dosing – Propofol is typically administered as a continuous infusion using a syringe

Ideally, propofol dosing is titrated using EEG-based neuromonitoring, although other

● Advantages and potential adverse effects – Advantages of propofol include rapid