Pharmacologic Principles of Sedation and Analgesia
Sedation and analgesia may be provided by a variety of drugs, which differ
significantly in their pharmacologic classification and effects. The most
widely used include the benzodiazepines and narcotics.
Benzodiazepines are often used for sedation and analgesia. They are considered
to be sedatives/hypnotics or tranquilizers. They are used for anxiolysis,
sedation and amnesia. The most widely used for sedation include diazepam
(Valium), midazolam (Versed) and lorazepam (Ativan). Midazolam use has
overtaken that of diazepam, due to a shorter duration of action and water
solubility that helps to decrease the pain associated with injection.
The benzodiazepines produce a spectrum of effects, depending upon the dose.
They range from tranquility and drowsiness to sedation, and ultimately,
unconsciousness. Anterograde amnesia is associated with benzodiazepines.
The most significant side effect of any of the benzodiazepines is severe
respiratory depression, particularly when used in combination with other
CNS depressants. Benzodiazepines cause minimal cardiac depression when
used alone. However, when combined with other anesthetic agents, including
narcotics, which by themselves are cardio stable drugs, cardiovascular
depression may occur. A sedating dose of diazepam is 0.05-0.1 mg per kilo
IV (see Hospital Conscious Sedation Policy). For midazolam, an initial
dose of 0.01 mg per kilogram IV may be used. Lorazepam has a much longer
clinical duration and is most useful as a premedication, given IM at a
dose of .05 mg per kilo. These agents should be administered slowly due
to the widely varied response from patient to patient. The dose should
be lowered in the elderly or debilitated patient. The patient must be
monitored by qualified personnel after administration of these agents.
Flumazenil (Romazicon), a benzodiazepine antagonist, can reverse the effects
of the agents above. It should be used cautiously because it can precipitate
acute withdrawal in patients who are chronically dependent on benzodiazepines.
When given IV, the dose is 0.2 mg repeated at 1-minute intervals to a
maximum of 1 mg (see Hospital Conscious Sedation Policy). The onset of
action is usually within 2 minutes. While flumazenil reliably antagonizes
the sedative effects of benzodiazepines, its antagonism of respiratory
depression is not as reliable and should not be depended upon. Respiratory
depression should be initially treated with supplemental oxygen, and if
needed, positive pressure ventilation by a bag/valve/mask system. Furthermore,
the duration of action of the benzodiazepine used may exceed that of flumazenil.
Continued monitoring is essential even after flumazenil use.
Narcotics, which are routinely used for sedation and analgesia, act at
a variety of different receptor sites. The use of narcotics serves to
produce analgesia. In combination with the benzodiazepine, this provides
sedation, anxiolysis and analgesia, which is the goal. In addition, a
local anesthetic injection or topical anesthetic may also be used to provide
anesthesia for a specific indication or site.
The narcotics can be divided into several classes. They include naturally
occurring opioids, semisynthetic opioids and synthetic opioids. The potency
and duration of action among these different classes vary considerably.
For analgesia, a mu receptor agonist is ideal. It acts centrally in pain
suppressing areas of the brain and spinal cord. While narcotics may render
a patient apneic and completely unresponsive to noxious stimulation, the
patient may retain enough residual awareness to later recall the procedural
events. For this reason, a narcotic is often given in combination with
a benzodiazepine, which produces more reliable amnesia.
Widely used mu agonists include morphine sulphate, methadone, meperidine
(Demerol), and fentanyl. Agonist-antagonist opioids are also used. They
have different actions at different receptor sites, resulting in diverse
pharmacologic effects. They may also precipitate withdrawal in narcotic
addicted patients. Agents in this class include butorphanol (Stadol) and
The most common narcotic antagonist utilized is naloxone. Naloxone is a
pure antagonist of all opioid effects and is used primarily to antagonize
respiratory depression and acute opioid overdose. The duration of action
of naloxone is about 20-30 minutes. It is important to recognize that
the opioid-analgesia is antagonized like the respiratory depression. This
antagonism can precipitate acute withdrawal in opioid-addicted patients.
Rare, but potentially fatal, reactions to naloxone include pulmonary edema,
seizures, hypertension, arrhythmias, and cardiovascular collapse. Careful
titration (see Hospital Conscious Sedation Policy) and close monitoring
are essential. Naloxone is administered in a dose of 2 to 5 micrograms
per kilogram IV every 2 to 3 minutes up to a total of 10 micrograms per
kilogram, or ¼ amp IV every 2 to 3 minutes up to 1 amp.