anesthetic drugs 2 notes

VT131: Anesthetic Drugs II - Induction and Inhalant

Terminology

• Apnea

  • Definition: The temporary absence of spontaneous breathing.

• Apneustic respiration

  • Definition: A breathing pattern characterized by a pause for several seconds at the end of the inspiratory phase, followed by a short, quick expiratory phase.

• Cataleptoid state

  • Definition: A state wherein a patient does not respond to external stimuli and exhibits muscle rigidity.

• Inotropy

  • Definition: Refers to the force of heart muscle contractions.

• Lipid soluble

  • Definition: Describes a drug’s tendency to dissolve in fats, oils, or lipids.

• Myoclonus

  • Definition: Spontaneous muscle twitching.

• Titration

  • Definition: The process of administering intravenous drugs in a series of bolus injections, discontinued when the desired depth of anesthesia is reached.

Injectable Anesthetics

• Injectable anesthetics can produce unconsciousness when administered alone, but they are typically used in conjunction with other agents to produce all desired effects of general anesthesia.

• These agents are titrated to effect, meaning the administration is done in small boluses until the desired level of anesthesia is achieved.

  • Examples of injectable anesthetics:

  • Propofol

  • Etomidate

  • Alfaxalone

  • Dissociatives

  • Barbiturates

Propofol

• Definition and Properties

  • Propofol is a substituted phenol, utilized for the induction and maintenance of general anesthesia.

  • The Drug Enforcement Administration (DEA) has proposed placing it in Schedule IV, yet it is currently not classified as a controlled substance.

  • The substance is milky white due to its formulation involving egg, lecithin, glycerin, and soybean oil.

  • It has a rapid onset and short duration of action, with high fat solubility.

  • MAIN SIDE EFFECT IS APNEA

  • if given perivascular, it can slough the skin

Central Nervous System Effects

• Propofol produces dose-dependent central nervous system (CNS) depression.

• Important note: Propofol is not an analgesic.

• Transient excitement and muscle tremors may occur during induction, particularly if the animal has not been premedicated.

Cardiovascular System Effects

• Propofol acts as a cardiac depressant, producing effects such as:

  • Bradycardia

  • Decreased cardiac output

  • Decreased vascular resistance

  • Transient hypotension

Respiratory System Effects

• Propofol is a potent respiratory depressant that can cause apnea in patients.

• Preventive measures:

  • Patients should be pre-oxygenated for 3-5 minutes prior to induction.

  • Administer propofol slowly, titrating to effect.

Other Effects and Adverse Effects

• Beneficial effects include:

  • Good muscle relaxation

  • Antiemetic effect

  • Decreased intracranial and intraocular pressure

• Potential adverse effects include pain upon IV injection.

Use of Propofol

• May be used for maintenance via small boluses every 3 to 5 minutes or as a constant rate infusion (CRI) using a syringe pump.

• Intubation and oxygen administration are advisable with this method.

• Administration of tranquilizers can reduce the required dose of propofol by as much as 75%.

Handling and Storage

• Shake the macroemulsion before use and do not utilize if the liquid appears separated, discolored, or contains large particles.

• The mixed media supports bacterial growth, posing a high risk of contamination.

• Manufacturer recommendations:

  • Discard unused propofol within 6 hours; some authorities suggest up to 24 hours of storage.

  • PropoFlo 28 (by Abbott) contains benzyl alcohol as a preservative and can be stored at room temperature for 28 days after opening.

  • Labeled for use in dogs, not advisable in cats.

Etomidate

• Definition and Properties

  • Etomidate is a noncontrolled sedative-hypnotic imidazole drug used for induction of anesthesia.

  • Characterized by minimal effects on cardiovascular and respiratory systems.

  • Due to costs and other adverse effects, it is not commonly utilized.

Central Nervous System Effects

• Causes hypnosis with minimal analgesia.

• Exhibits anticonvulsant properties.

• Considered a good choice for patients with brain trauma or undergoing brain or spinal surgery.

Cardiovascular Effects

• Exhibits minimal impact on:

  • Heart rate

  • Rhythm

  • Blood pressure

  • Cardiac output

Respiratory Effects

• Apnea may be observed after induction.

• Minimal effects on respiratory rate and tidal volume.

Other Effects and Adverse Effects

• Good muscle relaxation.

• Myoclonus may occur during induction and recovery.

• Pain may be associated with IV injection.

• Hemolysis in cats may occur after rapid injection.

• Significant decrease in cortisol levels.

• Nausea, vomiting, and excitement during induction and recovery.

Alfaxalone

• Alfaxalone (Alafaxan®) is a neurosteroid injectable anesthetic distinguished by its wide margin of safety.

• It is rapidly metabolized and non-cumulative.

• Administration follows a similar protocol to propofol, requiring cautious application.

• Rapid injection heightens the chances of apnea and vasodilation; thus IV administration should be slow.

• Patients should be preoxygenated and intubated accordingly.

• Alfaxan Multidose can be stored at room temperature for 28 days following opening.

• can be given IM

Central Nervous System Effects

• Produces dose-dependent CNS depression.

• Does not exert analgesic effects.

Cardiovascular Effects

• Minimal cardiovascular depression.

• Potential for increased heart rate and hypotension with concurrent inhalant use.

• preferred for cardiac patients

Respiratory Effects

• Respiratory depression and apnea may result from induction doses.

Other Effects

• Provides muscle relaxation and smooth inductions.

• No pain during IV injection.

• Perivascular injection does not induce tissue irritation.

• Some degree of excitement may manifest during recovery.

Dissociatives (Ketamine and Tiletamine)

• Definition and Properties

  • Ketamine is a dissociative agent frequently used in combination with tranquilizers to induce general anesthesia, sedation, immobilization, and anesthesia.

  • Tiletamine is another dissociative agent, paired with the benzodiazepine zolazepam in a formulation known as Telazol.

  • Notably, there is no reversal agent available for dissociatives.

  • Warning: Avoid use in patients with:

  • CNS signs

  • Hyperthyroidism

  • Cardiac disease

  • Pancreatic, liver, or renal disease

  • Pregnancy

  • Glaucoma

  • Penetrating eye injuries

Mode of Action and Pharmacology

• Dissociative agents inhibit NMDA receptors in the CNS responsible for pain “windup.”

Central Nervous System Effects

• Induces a cataleptoid state in which patients do not respond to external stimuli and exhibit muscle rigidity; limbs remain in the position they are placed.

• Reflexes remain intact, complicating assessments of anesthetic depth.

• Eyes typically remain open, with a centrally dilated pupil; nystagmus may develop.

• Muscle tone is either normal or increased.

• Provides limited somatic analgesia.

• Sensitivity to sensory stimuli (light or sound) is elevated.

• Patients may exhibit bizarre behavior during recovery, potentially hallucinogenic.

Cardiovascular Effects

• Increases heart rate, cardiac output, and mean arterial blood pressure.

• There is a decrease in inotropy with a slightly increased risk of arrhythmias.

Respiratory Effects

• Can induce apneustic respiration at higher doses.

• May increase salivation and respiratory secretions.

Other Effects

• Tissues may be irritated and painful upon intramuscular (IM) injection.

• Can raise intracranial and intraocular pressure.

Barbiturates

• Historically employed for anesthesia induction in dogs, cats, and horses, barbiturates are no longer favored due to difficulties in procurement and availability of safer alternatives.

Specific Barbiturates:

• Pentobarbital

  • Utilized for euthanasia; may induce anesthesia in laboratory animals.

• Phenobarbital

  • Commonly used as an anticonvulsant.

• Thiopental

  • Production ceased in 2011 in opposition to its use for lethal injections in humans; not referenced in any current textbooks and is defunct in veterinary practice.

  • An overdose of pentobarbital is employed for euthanasia.

Guaifenesin

• Definition and Properties

  • Guaifenesin (GG) serves as a muscle relaxant primarily for large animals.

  • Functions to facilitate intubation and ease induction/recovery.

  • It is not classified as an anesthetic or analgesic when used alone; it is administered alongside other agents.

  • Guaifenesin is an integral component of the “triple drip” method (GG, ketamine, and xylazine).

Effects and Adverse Effects

• Causes relaxation of skeletal muscles, including the pharyngeal and laryngeal muscles, but has minimal effects on the diaphragm.

• Cardiac and pulmonary effects are minimal.

• Adverse effects may include thrombophlebitis post-IV injection and tissue reactions from perivascular injections.

Inhalation Anesthetics

• The most frequently used halogenated compounds include:

  • Isoflurane

  • Sevoflurane

• Occasionally, desflurane and nitrous oxide may be utilized in specific practices or academic/research settings.

• Unavailable in the United States:

  • Halothane

  • Methoxyflurane

Color Codes of Inhalation Anesthetics

• Isoflurane: Color coded purple.

• Sevoflurane: Color coded yellow.

Diethyl Ether

• Diethyl ether represented the inaugural inhalant for maintaining anesthesia.

• Animals anesthetized with ether demonstrated stable cardiorespiratory metrics, blood pressure stabilization, effective muscle relaxation, and analgesia.

• Ether's downsides included significant airway side effects, protracted induction/recovery times, and frequent nausea/vomiting occurrences.

• Caution: Ether is highly flammable and explosive. Its use has been discontinued.

Halogenated Organic Compounds

• Definition: These compounds exist as liquids at room temperature and evaporate in oxygen to form gas, which is inhaled by the patient.

• The anesthetic gas quickly travels to the lungs, diffuses across the alveolar tissue, and enters the bloodstream, with high-blood-flow tissues (brain, heart, kidney) saturating more rapidly.

• Depth of anesthesia is determined by the anesthetic agent's concentration in the brain, bloodstream, and alveoli. Upon decreasing concentrations of anesthetic in the blood, the agent desorbs from the brain, resulting in patient wakefulness.

Common Characteristics of Halogenated Organic Compounds

Central Nervous System Effects

• Dose-related CNS depression.

• Hypothermia.

• Recovery phases might include paddling, excitement, and muscle fasciculations.

• Increased intracranial pressure is observed in cases of hypercapnia.

Cardiovascular Effects

• Variable impacts on heart rate.

• Effects include vasodilation, hypotension, reduced cardiac output, and diminished tissue perfusion.

Respiratory Effects

• Respiratory depression and hypoventilation.

Other Effects

• Elicit considerable muscle relaxation.

• Cross the placenta, which may lead to respiratory depression in neonates.

• Minimal hepatic or renal excretion.

• Carbon monoxide production occurs when exposed to desiccated CO2 absorbent.

Physical and Chemical Properties of Halogenated Organic Compounds

• Each halogenated compound possesses distinct physical and chemical properties, crucial for anesthesia administration.

• Significant characteristics include:

  • Vapor Pressure

  • Blood Gas Partition Coefficient

  • Minimum Alveolar Concentration (MAC)

Vapor Pressure

• Definition: Vapor pressure quantifies the tendency of a liquid anesthetic to evaporate.

• Crucial for determining the type of vaporizer required for anesthetic delivery.

• Equilibrium is defined as the state when evaporating molecules match those reentering the liquid phase.

• Vapor pressure also represents the pressure exerted by the gas phase of a substance at equilibrium.

• Agents with high vapor pressure (e.g., isoflurane, sevoflurane, desflurane, halothane) are termed volatile, indicating their propensity to evaporate and the need for precision vaporizers.

Blood Gas Partition Coefficient

• This coefficient measures the solubility of an inhalant in blood relative to alveolar gas, indicating the agent's induction and recovery speed.

• A lower blood-gas partition coefficient correlates with quicker induction/recovery and flexibility in dose adjustments.

• Isoflurane and sevoflurane exhibit low coefficients when compared with methoxyflurane, with observable differences in clinical application.

Minimum Alveolar Concentration (MAC)

• Definition: MAC is the lowest dose of an anesthetic agent at which 50% of patients do not exhibit a response to a painful stimulus.

• Serve as a measure of the anesthetic gas's potency; lower MAC indicates more potent agents.

• Dosage guidelines suggest using 1.5 times the MAC for surgical anesthesia initiation, with adjustments based on real-time assessment of patient depth.

Isoflurane

• Isoflurane is distinguished by its minimal adverse cardiovascular effects among halogenated compounds, making it the inhalation agent of preference for patients with cardiac disease.

• side effects: hypotension, respiratory depression, cardiovascular effects

Sevoflurane

• Sevoflurane is the second most utilized inhalation anesthetic for induction and general anesthesia.

• Its low blood gas partition coefficient renders it ideal for mask or chamber inductions, aided by its more pleasant odor compared to isoflurane, minimizing patient distress during mask induction.

Desflurane

• Renowned for its low blood-gas partition coefficient, desflurane facilitates rapid induction and recovery, approximately twice as quick as isoflurane.

• Commonly referred to as “one-breath anesthesia.”

• Due to its high vapor pressure and boiling point, a specialized vaporizer is mandated for administration.

• High cost and impracticality restrict usage within veterinary medicine.

Comparison of Inhalants

Nitrous Oxide

• Nitrous oxide exists as a gas at room temperature and is stored within blue-compressed gas cylinders.

• It does not require a vaporizer; instead, it is administered via a flowmeter.

• Mixed in concentrations ranging from 40% to 67% with oxygen before delivery to the patient.

Characteristics and Applications

• Primarily employed in human medicine as opposed to veterinary.

• When combined with other agents, nitrous oxide (N2O) facilitates rapid induction and recovery while providing additional analgesia.

• It additionally reduces the MAC of other anesthetics by 20% to 30%, thereby diminishing the likelihood of adverse effects.

• The advantages of nitrous oxide usage were more prominent with older agents such as methoxyflurane and halothane.