Inhalational Anesthetic Agents
Pharmacodynamics
(What the Drug Does to the Body)
Anesthetic agents produce general anesthesia by some still unclarified action on the brain.
What is "general anesthesia?"
- "an altered physiologic state characterized by reversible loss of consciousness,
analgesia of the entire body,amnesia, and some degree of muscle relaxation."
-- Lange
- "the administration of a drug or drugs which cause loss of consciousness as the result of which
the patient is unable to make meaningful responses but may still display reflex withdrawal from
a painful stimulus."
-- State of New Jersey
- and, perhaps most important and useful, our own
American Society of Anesthesioloigists (ASA) says:
"Minimal Sedation (Anxiolysis) is a drug-induced state during which patients respond normally to
verbal commands. Although cognitive function and coordination may be impaired, ventilatory and
cardiovascular functions are unaffected."
Moderate Sedation/Analgesia ('Conscious Sedation') is a drug-induced depression of consciousness
during which patients respond purposefully** to verbal commands, either alone or accompanied by
light tactile stimulation. No interventions are required to maintain a patent airway, and spontaneous
ventilation is adequate. Cardiovascular function is usually maintained."
"Deep Sedation/Analgesia is a drug-induced depression of consciousness during which patients
cannot be easily aroused but respond purposefully** following repeated or painful stimulation.
The ability to independently maintain ventilatory function may be impaired. Patients may require
assistance in maintaining a patent airway, and spontaneous ventilation may be inadequate.
Cardiovascular function is usually maintained.
**Reflex withdrawal from a painful stimulus is NOT considered a purposeful response."
And:
"General Anesthesia is a drug-induced loss of consciousness during which
patients are not arousable, even by painful stimulation. The ability to independently maintain
ventilatory function is often impaired. Patients often require assistance in maintaining a patent airway,
and positive pressure ventilation may be required because of depressed spontaneous ventilation or
drug-induced depression of neuromuscular function. Cardiovascular function may be impaired. Because sedation
is a continuum, it is not always possible to predict how an individual patient will respond. Hence,
practitioners intending to produce a given level of sedation should be able to rescue patients whose
level of sedation becomes deeper than initially intended. Individuals administering Moderate
Sedation/Analgesia ("Conscious Sedation") should be able to rescue patients who enter a state of Deep
Sedation/Analgesia, while those administering Deep Sedation/Analgesia should be able to rescue patients
who enter a state of general anesthesia."
Note that: Monitored Anesthesia Care does not describe the continuum of depth of sedation, rather it
describes "a specific anesthesia service in which an anesthesiologist has been requested to participate
in the care of a patient undergoing a diagnostic or therapeutic procedure."
So, general anesthesia is one end of a continuous spectrum. It's presence in your patient, and differentiation from
'deep sedation/analgesia' can only be confirmed by regularly observing and classifying your patient's response to
'repeated or painful stimulation.' For deep sedaton/analgesia to exist, your patient must respond purposefully; for
example, open his/her eyes on request, move requested body part, complain of pain in the operated body region, etc.
If you are not frequently testing for this responsiveness, then you do not know whether or not your patient is under
deep sedation or general anesthesia. Further, if the patient is not moving or complaining during surgical
stimulation ('repeated painful') with normal neuromuscular and CNS function (including no local anesthetics),
then deep sedation does NOT exist, rather your patient is under general anesthesia. But this state of not moving
or complaining during surgery is usually quite desirable -- it's exactly what the patient and surgeon want; so,
clearly then this latter state of general anesthesia is preferable to deep (or minimal or moderate) sedation in
terms of patient comfort and surgeon's ability to efficiently complete the procedure.
Note also that if you
paralyze your patient, you can no longer rely on patient response to repeated stimulus to confirm any degree
of depression of consciousness, let alone verify where that patient is on the general anesthetic continuum.
So, techics minimizing or avoiding muscle relaxants and allowing spontaneous ventilation are safer and easier
in this regard than technics employing paralysis when we must use inferior controlled ventilation techics and
indirect unproven estimates of sedation-anesthetic depth such as the BIS monitor. Can you ever be certain that
your paralyzed patient is not awake?
Note that fentanyl (and all narcotic analgesics) are NOT anesthetic agents because they do not reliably produce
unconsciousness or amnesia.
Finally, note that none of the definitions mention anything about endotracheal intubation. It is a common
misconception that airway instrumentation must co-exist with general anesthesia. Not so. These are two
completely different things. Patients may be intubated awake (or wake up intubated). Other patients may be induced
and maintained under general anesthesia while breathing spontaneously through their natural airway. To say that we
will induce and maintain a patient under general anesthesia says nothing at all about how we might manage that
patient's airway.
Theories of Anesthetic Action
- Agent Specific Theory
Various agents produce anesthesia by different mechanisms.
Different aspects of anesthesia may be related to different sites mechanisms of action.
In general, it seems that synaptic transmission is more sensitive to anesthetic action than neuronal conduction.
- Unitary Hypothesis
Suggests that all inhalational agents share a common mechanism of action at the molecular level.
- Meyer-Overton Rule
Potency of inhalational agents correlates directly with their lipid solubility.
- Critical Volume Hypothesis
Proposes that anesthetics expand CNS cell membranes to a critical volume, thus altering cell function.
- Fluidization and Lateral Phase Separation Theories
Suggests that anesthetic agents act by altering CNS cell membrane structure and function in.
- GABA, gamma-aminobutyric acid
- GABA is the natural CNS inhibitory neurotransmitter
- many anesthetics enhance GABA inhibition: anesthetic potency correlates with potentiation of GABA receptor
activity
- GABA receptor agonists enhance anesthesia
- GABA antagonists reverse some anesthetic effects
- NMDA, N-methyl-D-aspartate
Ketamine inhibits activation of the NMDA receptor by glutamate (excitatory CNS neurotransmitter).
Minimum Alveolar Concentration (MAC)
"The alveolar concentration of an inhaled anesthetic that prevents movement in 50% of patients in response to a standardized stimulus (eg, surgical incision)."
A measure of relative potency and standard for experimental studies.
MAC values for different agents are approximately additive. (0.7 MAC N2O + 0.6 MAC halothane = 1.3 MAC total)
"MAC awake," (when 50% of patients open their eyes on request) is approximately 0.3.
Effects that Various Physiologic Factors May Have on MAC
No change in MAC:
- duration of anesthesia
- gender
- anesthetic metabolism
- thyroid gland dysfunction
- hyperkalemia or hypokalemia
- paCO2 15-95 mmHg
- paO2 > 38 mmHg
- BP > 40 mmHg
Increases MAC:
- hyperthermia
- drugs that increase CNS catecholamines:
- monoamine oxidase inhibitors
- tricyclic antidepressants
- cocaine
- acute amphetamine ingestion
- infants
- hypernatremia
- chronic ethanol abuse (?)
Decreases MAC:
- hypothermia
- preoperative medication
- intravenous anesthetics
- neonates
- elderly
- pregnancy
- alpha-2 agonists
- clonidine
- dexmedetomindine
- acute ethanol ingestion
- lithium
- cardiopulmonary bypass
- neuraxial opioids (?)
- pO2 < 38 mmHg