- As plasma concentration falls, some drug
leaves the highly perfused organs to maintain equilibrium. This
redistribution from the vessel-rich group is responsible for termination
of effect of many anesthetic drugs. For example, awakening from
the effects of thiopental is not due to metabolism or excretion
but rather to redistribution of the drug from brain to
- Non–protein-bound drugs freely cross
from plasma into the glomerular filtrate. The nonionized fraction
of drug is reabsorbed in the renal tubules, whereas the ionized
portion is excreted in urine.
- Elimination half-life of a drug is proportional
to the volume of distribution and inversely proportional to the
rate of clearance.
- The plasma concentration of a drug with long
half-lives may still fall rapidly if distribution accounts for the
vast majority of the decline and elimination is a relatively insignificant
contributor. Therefore, the rate of clinical recovery from a drug
cannot be predicted by its half-lives alone.
- Repetitive administration of barbiturates saturates
the peripheral compartments, so that redistribution cannot occur
and the duration of action becomes more dependent on elimination.
- Barbiturates constrict the cerebral vasculature.
This effect may protect the brain from transient episodes of focal
ischemia (eg, cerebral embolism) but probably not from global ischemia
(eg, cardiac arrest).
- Although apnea may be less common after benzodiazepine
induction than after barbiturate induction, even small intravenous
doses of diazepam and midazolam have resulted in respiratory arrest. Ventilation
must be monitored in all patients receiving intravenous benzodiazepines,
and resuscitation equipment must be immediately available.
- The accumulation of morphine metabolites (morphine
3-glucuronide and morphine 6-glucuronide) in patients with renal
failure has been associated with narcosis and ventilatory depression lasting
- Opioids (particularly fentanyl, sufentanil, and
alfentanil) can induce chest wall rigidity severe enough to prevent
- The stress response to surgical stimulation
is measured in terms of the secretion of specific hormones, including
catecholamines, antidiuretic hormone, and cortisol. Opioids block
the release of these hormones more completely than volatile anesthetics.
- In sharp contrast to other anesthetic agents,
ketamine increases arterial blood pressure, heart rate, and cardiac
output. These indirect cardiovascular effects are due to central
stimulation of the sympathetic nervous system and inhibition of
the reuptake of norepinephrine.
- Induction doses of etomidate transiently inhibit
enzymes involved in cortisol and aldosterone synthesis. Long-term
infusions lead to adrenocortical suppression that may be associated
with an increased mortality rate in critically ill patients.
- Propofol formulations can support the growth
of bacteria, so good sterile technique must be observed in preparation
and handling. Sepsis and death have been linked to contaminated
- Droperidol is a potent antiemetic; however,
delayed awakening limits its intraoperative use to low doses (0.05
mg/kg, to a maximum of 2.5 mg). The antidopaminergic activity
of droperidol rarely precipitates extrapyramidal reactions (eg,
oculogyric crises, torticollis, agitation), which can be treated
with diphenhydramine. Nonetheless, droperidol should be avoided
in patients with Parkinson disease.
General anesthesia is not limited to the use of inhalation agents.
Numerous drugs that are administered orally, intramuscularly, ...