General Anesthetics Flashcards
The state of “general anesthesia” includes:
- Analgesia
- Amnesia
- Loss of consciousness
- Suppression of reflexes
- Skeletal muscle relaxation
Overview of balanced anesthesia?
• No single drug is capable of achieving all of the
desired goals of anesthesia.
• In balanced anesthesia, several drugs are
used in combination to produce the anesthetic
state.
• The onset of inhalational agents is not rapid:
patients are usually anesthetized with an IV
agent.
• Halogenated hydrocarbons are not good analgesics: a supplemental analgesic is
required.
• Neuromuscular blockers are used to provide
paralysis adequate for surgical access.
Types of General Anesthetics?
- INHALED ANESTHETICS
* IV ANESTHETICS
List inhaled anesthetics gases and 6 volatile halogenated hydrocarbons?
• Gases ▪N2O • Volatile halogenated hydrocarbons ▪Halothane ▪Enflurane ▪Isoflurane ▪Desflurane ▪Sevoflurane ▪Methoxyflurane
goals of IV anesthetics?
Used alone or with other drugs to: • Achieve anesthesia • As components of balanced anesthesia • Sedate patients in ICUs who must be mechanically ventilated for long periods.
IV anesthetics include(list 4)
IV anesthetics include: • Barbiturates • Propofol • Ketamine • Etomidate
inhaled anesthetic use? List 6 common features?
• Used for the maintenance of anesthesia after administration of an IV agent.
COMMON FEATURES
• Increase perfusion of brain.
• Cause bronchodilation.
• Decrease minute ventilation.
• Potency correlates with liposolubility.
• Rate of onset inversely correlates to blood
solubility.
• Recovery is due to redistribution from the brain.
MOA of inhaled anesthetics?
• The actions of inhaled anesthetics are the
consequence of direct interactions with ligand gated ion channels.
• Positive modulation of GABAA and glycine
receptors.
• Inhibition of nicotinic receptors.
Define MAC and its role in potency of anesthetics?
• Standard of comparison for potency of general
anesthetics: Minimum alveolar concentration
(MAC).
• MAC is the concentration that results in
immobility in 50% of patients when exposed to a noxious stimulus such as surgical
incision.
• MAC is expressed as % of the alveolar gas mixture.
• MAC is low for potent anesthetics and large for less potent agents.
Feature of MAC values when determining requirements?
• MAC values are additive.
• Nitrous oxide can be used as a “carrier” gas,
decreasing the anesthetic requirement of
other inhaled anesthetics.
• 0.7 MAC of isoflurane and 0.3 MAC of nitrous
oxide yield 1 MAC.
Order highest MAC to lowest MAC(not necessarily numbers)
Anesthetic MAC (%) Nitrous oxide 104 Desflurane 6 Sevoflurane 2.0 Enflurane 1.7 Isoflurane 1.4 Halothane 0.75 Methoxyflurane 0.16
Define THE MEYER–OVERTON CORRELATION
- The potency of an anesthetic can be predicted from its liposolubility.
- The oil:gas partition coefficient is a good measure of the liposolubility.
- The potency of an anesthetic increases as its solubility in oil increases.
- As λ(oil:gas) increases, the MAC decreases.
Partition coefficient definition?
• The partition coefficient is the ratio of the concentrations of a compound in one solvent to
the concentration in another solvent.
• For example, an oil:gas partition coefficient of 19
means that the concentration of anesthetic in oil
is 19-fold that present in the alveolar gas when
the partial pressure of the anesthetic is identical
at both sites.
POTENCY & LIPOSOLUBILITY relationship?
The potency of an anesthetic increases as
its liposolubility increases.
Describe anesthetic induction and 5 dependent factors?
• Anesthesia requires transfer of anesthetic from the alveolar air to the blood and then to the brain.
• The rate at which a given concentration of
anesthetic in the brain is reached depends on:
• Solubility of the anesthetic
• Its concentration in the inspired air
• Pulmonary ventilation rate
• Pulmonary blood flow
• Arteriovenous concentration gradient
Solubility of blood and onset of anesthetic? Define blood gas coefficient
• The blood:gas partition coefficient (gamma) is a useful index of solubility.
• It defines the relative solubility of an anesthetic
in the blood compared to air.
• When an anesthetic with low solubility in blood
reaches the arterial blood the arterial tension of
the anesthetic rises quickly.
• Conversely, if an anesthetic has high solubility in
blood, more molecules of the anesthetic will
dissolve in blood before the partial pressure
increases significantly.
• Consequently, the arterial tension of the gas
increases less rapidly.
• Therefore there is an inverse relationship
between the blood solubility of an anesthetic and
the rate of rise of its tension in arterial blood.
• A low blood:gas partition coefficient determines a faster onset of anesthesia
Anesthetic potency and onset?
- Anesthetics with large λ(oil:gas) have large λ(blood:gas).
* High potency correlates with slow onset.
effects of ANESTHETIC CONCENTRATION
IN THE INSPIRED AIR? Ventilation?
• Increase in anesthetic concentration increases
the rate of induction.
• Increase in ventilation rate
increases rate of induction.
Effect of Pulmonary blood flow on anesthetic induction?
• An increase in pulmonary blood flow (increased
cardiac output) slows the rate of induction.
• This is because increased pulmonary blood flow
exposes a larger volume of blood to the anesthetic.
• Blood “capacity” increases and tension rises
slowly.
Arteriovenous concentration gradient effect on anesthetic induction?
• Difference between the concentration of anesthetic in arterial and venous blood.
• Reflects the solubility of the anesthetic in
the tissues.
• Uptake by tissues slows down onset and
recovery.
Describe elimination of anesthetics?
• Elimination of inhalational anesthetics is largely
the reverse process of uptake.
• For agents with low blood and tissue solubility,
recovery from anesthesia mirrors anesthetic induction, regardless of the duration of
anesthetic administration
• For agents with high blood and tissue solubility,
recovery depends on the duration of anesthetic
administration.
• This is because the anesthetic accumulates in
fat.
CV effects of inhalants?
• Most inhaled anesthetics depress normal
cardiac contractility.
• As a result, they tend to decrease mean arterial
pressure.
• Halothane and enflurane reduce MAP mainly
by myocardial depression, with little effect on
PVR.
• Isoflurane, desflurane and sevoflurane
produce vasodilation and have minimal effect on
cardiac output.
• Isoflurane, desflurane and sevoflurane may
be better choices for patients with impaired
myocardial function.
• N2O lowers blood pressure less than other
inhaled anesthetics.
• Halothane sensitizes the myocardium to
circulating catecholamines, which may lead to
ventricular arrhythmias.
• This effect is less marked for isoflurane,
sevoflurane and desflurane.
Respiratory effects of anesthetics?
- Volatile anesthetics are bronchodilators.
- Volatile anesthetics are respiratory depressants.
- Isoflurane and enflurane are the most depressant.
- N2O is the least depressant.
CNS effects of anesthetics?
- Inhaled anesthetics increase intracranial pressure.
- Undesirable in patients who already have increased intracranial pressure because of brain tumor or head injury.
- N2O increases blood flow the least.
- Enflurane at high concentrations may cause tonic clonic movements.
Consideration of N2O other effects?
• N2O exchanges with nitrogen in air-containing
cavities in the body.
• N2O enters the cavity faster than nitrogen
escapes.
• Therefore, it increases the volume and/or
pressure of the cavity.
• N2O should be avoided in the following clinical
settings:(list 7)
• N2O should be avoided in the following clinical settings: • Pneumothorax • Obstructed middle ear • Air embolus • Obstructed loop of bowel • Intraocular air bubble • Pulmonary bulla • Intracranial air
Which two organ toxicities associated with anesthetics? Which anesthetics specifically?
HEPATOTOXICITY (HALOTHANE)
• Some individuals exposed to halothane may develop a potentially severe and life-threatening hepatitis.
• There is no specific treatment
• Liver transplantation may be required.
NEPHROTOXICITY
• Methoxyflurane has nephrotoxic potential.
• Due to fluoride released during
metabolism.
Describe malignant hyperthermia in relation to anesthetics?
• Potentially fatal genetic disorder of skeletal muscle.
• Triggered in susceptible individuals by volatile
inhalation anesthetics, such as halothane, and depolarizing skeletal muscle relaxants, such as succinylcholine.
• Transmitted as an autosomal dominant trait.
• Incidence is about 1:12,000.
• Malignant hyperthermia is one of the main
causes of death due to anesthesia.
• The malignant hyperthermia syndrome includes: (list 6)
- Tachycardia
- Hypertension
- Severe muscle rigidity
- Hyperthermia
- Hyperkalemia
- Acidosis
Basis of Malignant hyperthermia?
• Malignant hyperthermia results from altered control of Ca2+ release from the SR.
• In most cases, the syndrome is caused by a
defect in the ryanodine receptor gene (RYR1).
• Abnormal RYR receptors trigger unregulated
release of calcium from the SR, which may lead
to an acute malignant hyperthermia crisis.
Mechanism and consequence of malignant hyperthermia?
• The increased Ca2+ concentration causes
increased muscle contraction which generates
heat.
• Increased levels of aerobic metabolism produce
CO2 and deplete O2 and ATP.
• A switch to anaerobic metabolism worsens
acidosis with the production of lactate.
• Energy stores get depleted.
• Muscle fibers die leading to hyperkalemia and
myoglobinuria.
MALIGNANT HYPERTHERMIA: TREATMENT?
• Dantrolene: blocks Ca2+ release from the
sarcoplasmic reticulum.
• Measures to reduce body temperature and
restore electrolyte and acid-base balance.
THE CAFFEINE-HALOTHANE MUSCLE CONTRACTURE TEST?
• The most reliable test to establish susceptibility
to malignant hyperthermia.
• A muscle sample is removed from the thigh.
• The response to halothane and caffeine is
assessed.
Consequence of prolonged N2O exposure?
Hematotoxicity
• Prolonged exposure to N2O decreases methionine synthase activity and causes
megaloblastic anemia.
• Potential occupational hazard for staff working in poorly ventilated dental
operating suites.
List 4 IV anesthetics?
▪ Barbiturates
▪ Propofol
▪ Ketamine
▪ Etomidate
Describe Ultra short acting barbiturates?
Thiopental and Methohexital
• Used for induction of anesthesia and for short surgical procedures.
• Their anesthetic effects are terminated by redistribution from the brain to other tissues, but hepatic metabolism is required for their elimination from the body.
• VRG: brain, liver, kidneys
• MG: muscle, skin
• FG: fat
• They decrease intracranial pressure.
• They do not produce analgesia.
• They may cause hyperalgesia.
• May cause apnea, coughing, chest wall spasm,
laryngospasm and bronchospasm: a concern for
asthmatic patients.
Overview of propofol?
- Postoperative vomiting is uncommon. Antiemetic.
- Used for induction and maintenance of anesthesia.
- Produces no analgesia.
- Rapidly metabolized in the liver.
- Potent respiratory depressant.
- Reduces intracranial pressure.
- Causes hypotension through decreased PVR.
- Fospropofol: prodrug converted to propofol in vivo.
Overview of Etomidate?
- Primarily used for anesthetic induction of patients at risk for hypotension.
- Causes minimal CV and respiratory depression.
- No analgesic effects.
- Reduces intracranial pressure.
- Associated with nausea and vomiting.
Overview of Ketamine?
• Produces dissociative anesthesia, characterized by catatonia, amnesia and
analgesia, with or without loss of consciousness.
• Mechanism of action may involve blockade of NMDA receptors.
• Only IV anesthetic that possesses both analgesic properties and the ability to produce CV stimulation.
• Increases intracranial pressure.
• Causes sensory and perceptual illusions, and
vivid dreams (‘emergence phenomena’).
• Diazepam, midazolam, or propofol reduce the
incidence of these phenomena.
Overview of Neuroleptic-Opioid Combinations
Neuroleptic-Opioid Combinations
• When a potent opioid analgesic, such as
fentanyl, is combined with a neuroleptic such as
droperidol, neurolept analgesia is established.
• Neurolept analgesia can be converted to neurolept anesthesia by the concurrent administration of 65% N2O in O2
.
adjuncts to anesthetics?
• Adjuvant drugs provide additional effects that
are desirable during surgery but are not necessarily provided by the general anesthetics.
• Benzodiazepines. For their anxiolytic and anterograde amnesic properties.
• Opioids. For analgesia.
• Neuromuscular blockers. To achieve muscle relaxation.
• Antiemetics, eg ondansetron. To prevent
possible aspiration of stomach contents.
• Antimuscarinics, eg scopolamine
• For its amnesic effects
• To prevent salivation and bronchial secretions
• To protect the heart from bradycardia caused by inhalation agents and neuromuscular blockers.
