No single drug is capable of achieving all of the desired goals of anesthesia. So a method termed balanced anesthesia, several inhaled and/or IV drugs are used in combo to produce the anesthetic state.
- Anesthetic partial pressure for an inhalational agent in the brain is not attained rapidly, therefore patients are usually anesthetized with an IV agent
- Halogenated hydrocarbons inhaled general anesthetics often exhibit inadequate degree of analgesia, therefore supplemental analgesic is required
- Neuromuscular blocking agents must be used to provide paralysis adequate for surgical access
- Anesthetic plan is designed to minimize any undesirable CVS and resp responses to these drugs
Anesthesia protocols vary depending on the type of intervention, whether it is diagnostic, therapeutic, surgical. What is the protocol for minor procedures?
Monitored anesthesia care or conscious sedation
–profound analgesia but with retention of the patients ability to maintain a patent airway and respond to verbal commands
What is the protocol for extensive surgical procedures?
Induction of anesthesia with IV thiopental or propofol
Maintenance of anesthesia with a combo of inhaled and IV anesthetic drugs
Neuromuscular blocking drugs
Inhaled anesthetics can be divided into two classes based on their physical properties. What are these two classes?
Nitrous Oxide is a gas at ambient temp
All other inhaled anesthetics are halogenated hydrocarbons
–examples: halothane, enflurane, isoflurane, desflurane, sevoflurane, and methoxyflurane
IV anesthetics are used both as adjuncts to inhaled anesthetics and as part of techniques that do not include any inhaled anesthetics. What do they include?
What is induction of anesthesia?
It is the time from administration of anesthetic to the development of surgical anesthesia
–general anesthesia is normally induced with an IV anesthetic such as thiopental
Additionally IV skeletal muscle relaxant can be given to facilitate intubation and relaxation
What is the maintenance phase of anesthesia?
It is the period during which the patient is surgically anesthetized
–anesthesia is maintained by administration of inhaled anesthetics.
What is the recovery phase of anesthesia?
Time from discontinuation of administration of anesthesia until consciousness is regained
Traditionally, anesthetic effects are divided into 4 stages of increasing depth of CNS depression, what are these four stages?
Stage I: Analgesia, Amnesia
Stage II: Excitement, delirium. resp is irregular, vomiting. to avoid this stage, thiopental is given
Stage III: Surgical anesthesia and unconsciousness
Stage IV: medullary depression, no eye movement and resp and cardio failure
–the most reliable indications that stage III has been achieved are loss of the eyelash reflex and establishment of a respiratory pattern that is regular in rate and depth.
Inhaled gases are primarily used for the maintenance of anesthesia after administration of an IV agent. The depth of anesthesia can be rapidly altered by rapidly changing concentration of inhaled anesthetic. what are some common features?
- Decreased cerebrovascular resistance, resulting in increased perfusion of brain
- Cause bronchodilation and decrease minute ventilation
- Potency correlates with liposolubility
- Rate of onset is inversely correlated to blood solubility
- Recovery from their effects is due to redistribution from the brain
What are the pharmacodynamics for inhaled anesthetics?
Direct interactions with ligand gated ion channels
- -GABA receptor inhibition (inhibits the inhibitory synaptic transmission)
- -inhibit nicotinic receptors
- -glycine receptor is another ligand gated ion channel that may function as a target for inhaled anesthetics.
A standard of comparison for potency of general anesthetics is the minimum alveolar concentration: MAC. explain this
- of an anesthetic is defined as the concentration (the percentage of the alveolar gas mixture, or partial pressure of the anesthetic as a percentage of 760mm Hg) that results in immobility in 50% of patients when exposed to a noxious stimulus such as surgical incision
- -is expressed as percent of gas in a mixture required to achieve the effect
- -represents the ED50 on a quantal dose response curve
Numerically, MAC is low and large for what?
Low for potent anesthetics such as halothane
Large for less potent agents such as nitrous oxide
–therefore 1/MAC is an index of potency of the anesthetic
MAC gives no information about the slope of the dose response curve. In general however, what are the slopes for anesthetics?
The slopes of the dose response curves for inhalational anesthetics are steep
–MAC, 95% of patients may fail to respond to stimulation at 1.1 MAC
What are some important points at MAC?
- Higher in infants and lower in elderly
- Sex, height, and weight dont affect MAC
- Adjunct drugs such as opioid analgesics or sedative hypnotics, MAC is decreased, which means that the inspired concentration of anesthetic should be decreased
- Hypothermia, hypothyroidism and pregnancy decrease MAC
- Anxiety and thyrotoxicosis increase MAC
- MAC values are additive. (NO can be used as a carrier gas decreasing the anesthetic requirement of other anesthetics)
The most reliable predictor of anesthetic potency is the anesthetic’s liposolubility called the meyer-overton correlation, what is this?
A useful measure of liposolubility is the oil:gas partition coefficient (oil:gas)
-the potency of an anesthetic increases as its liposolubility increases. In other words, as (oil:gas) increases, the MAC decreases
Achievement of a brain concentration of an anesthetic adequate to cause anesthetic requires transfer of the anesthetic from the alveolar air to blood and then to the brain. The rate at which a given concentration of anesthetic in the brain is reached depends on what?
Solubility properties of the anesthetic, its concentration in the inspired air, pulmonary ventilation rate, pulmonary blood flow, and the concentration gradient of the anesthetic between arterial and mixed venous blood
Solubility is one of the most important factors influencing the transfer of an anesthetic from the lungs to the arterial blood. What is a measure of solubility?
The blood:gas partition coefficient
–defines the relative solubility of an anesthetic for the blood compared to air
Blood: Gas partition coefficients for Desflurane, NO, and sevoflurane – which are not very soluble in blood, are low.
Methoxyflurane value is greater than 10
What is the relationship between blood solubility and arterial blood concentration?
An inverse relationship between blood solubility of an anesthetic and the rate of rise of its tension in arterial blood
–therefore a low blood:gas partition coefficient determines a faster onset of anesthesia
Additionally if we look at the oil:gas and the blood:gas together we can see a trend
–anesthetics with larger oil:gas tend to have larger blood:gas
Therefore the more potent inhaled anesthetics tend to have slower onsets.
What are some MAC values, oil:gas partition coefficient and blood:gas coefficient for various drugs?
NO: 104% ; 1.4 ; 0.47 — rapid onset and recovery
Desflurane: 6% ; 19 ; 0.42 – rapid onset and recovery
Sevoflurane: 2.0% ; 51 ; 0.69 — rapid onset and recovery
Enflurane: 1.7% ; 98 ; 1.8 – Medium rate of onset and recovery
Isoflurane: 1.4% ; 98 ; 1.4 – Medium rate of onset and recovery
Halothane: 0.75% ; 224 ; 2.3 – Medium rate of onset and recovery
Methoxyflurane: 0.16% ; 960 ; 12 – Very slow onset and recovery
The rate of rise of anesthetic gas tension in arterial blood is directly dependent on both the rate and depth of ventilation. An increase in pulmonary ventilation therefore causes what?
Will cause only a slight increase in arterial tension if the anesthetic has low blood solubility
–but can significantly increase tension of anesthetics with moderate or high blood solubility
An increase in pulmonary blood (increased cardiac output) causes what?
Slows the rate of rise in arterial tension
–particularly for those anesthetics with moderate to high blood solubility.
Therefore a decrease in pulmonary blood flow has the opposite effect
The arteriovenous concentration gradient is the difference between the concentration of gas in arterial and venous blood. It therefore reflects what?
Solubility of the gas in tissues
–an anesthetic which is highly soluble in tissues will have a high arteriovenous gradient and thus a slow onset of action and recovery.
Moving on to elimination. The time to recovery from inhalation anesthesia depends on the rate of elimination of anesthetics from the brain. What is the rate of elimination?
For agents with low blood and tissue solubility
–recovery from anesthesia should mirror anesthetic induction, regardless of the duration of administration
For agents with high blood and tissue solubility, recovery will be a function of the duration of anesthetic administration (because accumulated anesthetic in the fat acts as a reservoir)
The rate of recovery from anesthesia is faster for agents with low blood:gas partition coefficients. Therefore what drugs are these?
Nitrous Oxide, desflurane and sevoflurane
–display recovery times that are significantly shorter than halothane or isoflurane
What are routes of elimination from the body?
Clearance by the lungs into the expired air
–major route of elimination
The washout of halothane during recovery is more rapid then that of enflurane, why is that?
Over 40% of inspired halothane is metabolized during an average anesthetic procedure, while less than 10% of enflurane is metabolized over the same period.
Oxidative metabolism of halothane results from what?
In the formation of trifluoroacetic acid and release of bromide and chloride ions
–halothane is metabolized to the chlorotrifluoroethyl free radical
What is the metabolism of isoflurane and desflurane?
Least metabolized of the fluorinated anesthetics
–only traces appear in the urine
Metabolism of enflurane and sevoflurane results in what?
Formation of Fluoride
Over 70% of absorbed methoxyflurane is metabolized by what?
The liver with the release of fluoride at concentrations that can be nephrotoxic
Nitrous Oxide is not metabolized by human tissue. Give a summary of metabolism of inhaled anesthetics?
In descending order
Methoxyflurane , halothane , enflurane , sevoflurane, isoflurance, desflurane, and NO