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129 Cards in this Set
- Front
- Back
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Drugs classified as IV anesthetics
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isopropylphenol: Propofol
barbiturates: thiopental, methohexital benzodiazepines: diazepam, midazolam, lorazepam phencyclidine: ketamine carboxylated imidazole: etomidate A two – adrenergic agonist: dexmedetomidine |
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Use of IV anesthetics
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Are widely used to facilitate rapid induction of anesthesia or to provide sedation during monitored anesthesia care and for patients in ICU settings
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What happened with the introduction of propofol?
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I've the anesthesia became more popular as a component of maintenance of anesthesia
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What is the problem with IV anesthetics?
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The currently available IV anesthetics are not ideal anesthetic drugs in the sense of producing all and only desired effects (hypnosis, amnesia, analgesia, immobility)
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With this in mind what is the technique generally used for anesthesia?
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Balanced anesthesia with multiple drugs including inhaled anesthetics, sedative hypnotics, opioids, neuromuscular blocking drugs
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What are the common characteristics of the IV anesthetics used for induction of general anesthesia?
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They are lipophilic and preferentially partition into highly perfused lipophilic tissues such as the brain and spinal cord, which accounts for their rapid onset of action
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Termination of IV anesthetics
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Regardless of the extent and speed of their metabolism, termination of the effect of a single bolus dose is the result of redistribution of the drug into less perfused and inactive tissues such as skeletal muscle and fat; thus all drugs used for induction of anesthesia have a similar duration of action for a single dose despite significant differences in the metabolism
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What is the most frequently administered drug for induction of anesthesia?
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Propofol
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When is propofol also frequently used?
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During maintenance of anesthesia and is also a common selection for sedation in the operating room, as well as in the ICU
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Drugs classified as IV anesthetics
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isopropylphenol: Propofol
barbiturates: thiopental, methohexital benzodiazepines: diazepam, midazolam, lorazepam phencyclidine: ketamine carboxylated imidazole: etomidate A two – adrenergic agonist: dexmedetomidine |
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Use of IV anesthetics
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Are widely used to facilitate rapid induction of anesthesia or to provide sedation during monitored anesthesia care and for patients in ICU settings
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What happened with the introduction of propofol?
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I've the anesthesia became more popular as a component of maintenance of anesthesia
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What is the problem with IV anesthetics?
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The currently available IV anesthetics are not ideal anesthetic drugs in the sense of producing all and only desired effects (hypnosis, amnesia, analgesia, immobility)
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With this in mind what is the technique generally used for anesthesia?
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Balanced anesthesia with multiple drugs including inhaled anesthetics, sedative hypnotics, opioids, neuromuscular blocking drugs
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What are the common characteristics of the IV anesthetics used for induction of general anesthesia?
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They are lipophilic and preferentially partition into highly perfused lipophilic tissues such as the brain and spinal cord, which accounts for their rapid onset of action
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Termination of IV anesthetics
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Regardless of the extent and speed of their metabolism, termination of the effect of a single bolus dose is the result of redistribution of the drug into less perfused and inactive tissues such as skeletal muscle and fat; thus all drugs used for induction of anesthesia have a similar duration of action for a single dose despite significant differences in the metabolism
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What is the most frequently administered drug for induction of anesthesia?
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Propofol
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When is propofol also frequently used?
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During maintenance of anesthesia and is also a common selection for sedation in the operating room, as well as in the ICU
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Physical characteristics of propofol
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2,6-diisopropylphenol; is an alkylphenol with hypnotic properties that is chemically distinct from other groups of IV anesthetics
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Propofol solubility
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Is essentially insoluble in aqueous solution and is therefore formulated as an emulsion containing 10% soybean oil, 2.25% glycerol, and 1.2% lecithin, the major component of the egg yoke fraction
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What is the problem with the available formulations of propofol?
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They support bacterial growth, so good sterile technique is important
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Ways manufacturers attempt to prevent bacterial growth and propofol
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Either ethylenediaminetetraacetic acid (0.05 mg/ml), metabisulfite (0.25 mg/ml), or benzyl alconohl (1 mg/ml) is added to the emotions to retard bacterial growth
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Timing of propofol use
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Propofol should be used at least within six hours after opening the vial
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Propofol pH and concentrations
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The solution is milky white and slightly viscous, the pH is approximately 7, and the concentration is 1% (one MG/ML)
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Caution with propofol
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Because the emulsion contains egg yolk lecithin susceptible patients may experience allergic reactions
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What is the concern about propofol formulations containing metabisulfite?
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Its use in patients with reactive airways, asthma, or sulfite allergies
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Propofol metabolism and excretion
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Propofol is rapidly metabolized in the liver and the resulting water – soluble compounds are presumed to be an active and excreted through the kidneys; however plasma clearance is high and exceeds hepatic blood flow, thus indicating the importance of extra hepatic metabolism
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How has the importance of extra hepatic metabolism of propofol been confirmed?
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During the anhepatic phase of liver transplantation
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What other organs thought to play a major role in the extra hepatic metabolism propofol, and what percent of the elimination is thought to account for?
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The lungs are thought to play a major role, and may account for the elimination of up to 30% of the lead a bolus dose of propofol
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What does the high plasma clearance of propofol help explain?
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The more complete recovery from propofol with less hangover than observed with thiopental
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Even with the metabolism of propofol, what is the termination of drug effect after a single bolus dose mainly the result of?
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As with other IV drugs, transfer of propofol from the central plasma compartment and the associated termination of drug effect after a single bolus dose are mainly the result of redistribution from highly perfused, brain, to poorly perfused, skeletal muscle, compartments
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How long does it typically take to wake up after induction dose of propofol?
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8 to 10 min., as evident from the time course of the decline in plasma concentration after a single bolus dose
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What properties make propofol suitable for use as a continuous IV infusion?
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Rapid metabolism resulting in efficient plasma clearance in conjunction with slow redistribution from poorly perfused compartments back into the central compartment makes it suitable
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What does the context – sensitive half – time describe?
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The elimination half – time after a continuous infusion as a function of the duration of the infusion
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Context – sensitive half – time of propofol
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Is brief, even after prolonged infusion, and recovery remains relatively from
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How are the kinetics of propofol, and of other IV anesthetics, after a single bolus and after continuous infusion best described?
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By a three – component model, a mathematical model used as the basis for the development of systems for target – controlled infusions
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What is the presumed mechanism of action of propofol?
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Potentiation of the chloride current mediated through the gamma – amino butyric acid type A (GABA a) receptor complex
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What does propofol primarily due in the central nervous system?
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It primarily at as a hypnotic and does not have any analgesic properties
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What is the effect of propofol pons cerebral blood flow and pressure?
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It produces a decrease in cerebral blood flow and the cerebral metabolic rate for oxygen (CMRO2), which results in decreases in intracranial pressure (ICP) and intraocular pressure; the magnitude of these changes is comparable to those produced by thiopental
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What is the negative effect of this?
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The reduced cerebral blood flow combined with the reduced mean arterial pressure caused by peripheral vasodilation can critically decrease cerebral perfusion pressure
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What do animal studies suggest about propofol?
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That it is neuroprotective during focal ischemia to the same extent as thiopental or isoflurane
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What does propofol do when administered in large doses?
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Produces burst suppression in the EEG, an end point that has been used for the administration of IV anesthetics for neuro protection during neurosurgical procedures
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What can occasionally be observed during induction with propofol?
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Excitatory effects such as twitching or spontaneous movement, although these effects may resemble seizure activity most studies and reports support an anticonvulsant effect of propofol, and it may safely be administered to patients with seizure disorders
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What is unique about propofol when compared with similar doses of other induction drugs?
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Propofol produces the most pronounced decrease in systemic blood pressure, an effect which may be attributed to profound vasodilation, whereas a direct myocardial depressant effect is controversial
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Vasodilation with propofol
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Occurs in both the arterial and venous circulation and leads to reductions in preload and after load
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When is the effect on systemic blood pressure more pronounced?
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With increased age, inpatients with reduced intravascular volume, and with rapid injection
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What else about propofol exacerbates its hypotensive effect?
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Propofol markedly inhibit the normal baroreceptor response and produces only a small increase in heart rate, thus exacerbating hypotension; profound bradycardia and asystole after propofol administration have been described in healthy adults despite prophylactic anticholinergics
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effects of propofol on the respiratory system
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-is a potent respiratory depressant, causing apnea after an induction dose, and causing decreased minute ventilation with a maintenance infusion through a decrease in tidal volume and respiratoy rate, with the decreased VT being the more pronounced of the two
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what else does propofol change in terms of ventilation?
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it reduces the ventilatory response to hypoxia and hypercarbia
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how does propofol compare to thiopental in terms of the respiratory system?
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-it causes a greater reduction in upper airway reflexes than thiopental does, making it better suited for airway instrumentation such as LMA placement
-also due to this, it decreases the incidence of wheezing after induction of anesthesia and tracheal intubation in healthy and asthmatic patients |
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what is a desired SE of propofol?
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its antiemetic effects
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does propofol potentiate neuromuscular blockade?
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no, like thiopental it does not, even though it has been shown to give good intubating conditions after an induction dose without muscle blockers
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what should you think about with unexplained tachycardia during propofol anesthesia?
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-should look for lab evidence of metabolic acidosis caused by propofol infusion syndrome
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what is the common complaint with propofol?
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pain on injection
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how can this be improved?
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-by premedication with opioid, coadministration with lidocaine, or using larger veins or diluting the propofol
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what is propofol most commonly used for?
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induction of anesthesia
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induction dose of propofol
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1-3 mg/kg IV
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what things reduce the required induction dose? increase it?
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-it is reduced in the elderly, those with decreased cardiovascular reserve, and those premedicated with benzos or opiates
-kids need a higher dose (2.5-3.5 mg/kg IV) |
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propofol for maintenance
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-can be done as part of a balanced technique with agnets, N2O, sedative-hypnotics, and opioids, or as TIVA, usually combined with opioids
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what therapeutic plasma concentrations are needed for maintenance?
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3-8 ug/mL, which typically requires an infusion of 100-200 ug/kg/min when combined with N2O and opiates
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plasma concentration of propofol necessary for sedation?
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1-2 ug/ml, which usually necessitates an infusion between 25-75 ug/kg/min
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what is the caveat with sedating patients with propofol?
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due to its narrow therapeutic range and potent respiratory depressant effects, it should only be given by those trained in airway management
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using propofol to treat nausea/vomiting
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can use subanesthetic bolus or infusion doses:
-bolus 10-20 mg IV -infusion 10 ug/kg/min |
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ketamine
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a phencyclidine derivative (PCP) introduced in 1965
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difference between ketamine and other IV anesthetics
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-it produces significant analgesia
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state produiced by an induction dose of ketamine
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-produces "dissociative anesthesia", a characteristic cataleptic state where the patient's eyes stay open with a slow nystagmic gaze
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ketamine physical characteristics
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-a partially water-soluble and highly lipid-soluble derivative of PCP
-it is 5-10x more lipid soluble than thiopental |
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stereoisomers of ketamine
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-of the two the S-(+) form is more potent than the R-(-)
-only the racemic mixture is available in the US |
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ketamine use pros and cons
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-is limited by the unpleasant psychomimetic side effects
-however, its unique features such as potent analgesia with minimal respiratory depression, make it desirable in many settings -it is frequently now used at subanesthetic doses as an adjunt to reduce opioid needs |
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what does ketamine's high lipid solubility mean?
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means it has rapid onset of effect
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termination of ketamine induction bolus
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like the other IV nesthetics, it is terminated by redistribution to inactive tissue sites
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ketamine metabolism and metabolities
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-is metabolized primarily by the liver and involves N-demethylation by the CYP450
-the primary active metabolite is norketamine, which is 1/3 to 1/5 as potent as ketamine -norketamine is then hydroxylated and conjugated to water-soluble inactive metabolites which are then excreted in the urine |
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what is another unique thing about ketamine among IV anestheitcs?
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its the only IV anesthetic with low protein binding (12%)
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mechanism of action of ketamine
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-is complex, but is likely mainly due to inhibition of the N-methyl-D-aspartate receptor complex (NMDA)
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ketamine and benzos
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-if ketamine is given alone the amnesia is not as complete as when given with a benzo
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ketamine and reflexes
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-reflexes are preserved, but it cant be assumed patients are able to protect their upper airway
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other effects of ketamine
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lacrimation and salivation can increase, so may need to premedicate with an anticholinergic drug
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what is the main factor limiting the use of ketamine?
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unpleasant emergence reactions
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emergence reactions with ketamine
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-include vivid colorful dreams, unpleasant hallucinations, out of body experiences, and increased or distorted visual, tactile, and auditory sensations
-these can be associated with fear and confusion -may also be associated with a euphoric state, explaining its potential for abuse -children have a lower incidence of these reactions, and they can be mitigated with combining the drug with a benzo |
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in what neurologic way is ketamine different from the other IV anesthetics?
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-its a cerebral vasodilator, which increases CBF and CMRO2
-so its not used for pts with intracranial pathology, esp increased ICP |
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how might these undesirable CBF effects be blunted?
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by maintenance of normocapnea
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ketamine and seizures
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-despite its ability to cause myoclonus, it is an anticonvulsant and can be used to treat status epilepticus if other drugs fail
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ketamine effects on the CV system
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-causes significant but transient increases in BP, HR, and CO, presumably through sympathetic stimulation
-might not be desirable effects as they increase cardiac work and myocardial oxygen consumption, so these effects can be blunted by coadministration of an opiate, benzo, or inhaled anesthetic |
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ketamine and the myocardium
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-its controversial, but it is considered a direct myocardial depressant, which is usually masked by the sympathetic stimulation, but can be unmasked in sick patients who dont have the ability to increase sympathetic activity
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ketamine and ventilation
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-does not produce respiratory depression
--keeps the respiratory response to hypercapnea in tact, and keeps blood gases stable -can rarely cause transient hypoventilation after rapid large IV doses for induction |
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ketamine and airway reflexes
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-while upper airway reflexes remain intact, you cant assume the patient can protect their airway
-the increased salivation, esp in children, can cause an increased risk of laryngospasm if not pretreated with an anticholinergic |
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ketamine and the lungs
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-relaxes bronchial smooth muscle and can be used in pts with reactive airway disease or in bronchoconstriction
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ketamine routes of administration
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-can be given IV, IM, oral, rectal, or epidural, making it usual for premedication of uncooperative patients
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induction of anesthesia with ketamine
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can be done with 1-2 mg/kg IV, or 4-6 mg/kg IM
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maintenance with ketamine
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-though not normally done, can be useful due to its short context-sensitive half-time
-can achieve general anesthesia with ketamine infusion 15-45 ug/kg/min, plus 50-70% N2O, or with 30-90 ug/kg/min ketamine alone |
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analgesia with ketamine
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-provides effect analgesia without loss of airway reflexes
-small doses of 0.2-0.8 mg/kg IV may be useful during regional when you need additional analgesia (such as a C-section under neuraxial anesthesia with inadequate block) -can laso infuse subanalgesic doses, 3-5 ug/kg/min) during general and early postop to reduce opiate tolerance |
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etomidate
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-IV anesthetic with hypnotic properties, with no analgesic effects, and with minimal hemodynamic effects
-its pharmacokinetics make it suitable for a continuous infusion, but its endocrine side effects mean it is rarely used for this |
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physiochemical proerties of etomidate
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-a carboxylated imidazole derivative with 2 optical isomers
-the preparation only contains the D-(+) isomer, which has hypnotic properties |
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other physical proteries of etomidate
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-is poorly soluvble in water, and so comes in a 2 mg/mL solution in 35% propylene glycol
-this solution has apH 6.9, so dont have to worry about precipitation like with thiopental |
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induction dose of etomidate
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-produces rapid onset of anesthesia, with recovery depending on redistribution to inactive tissue sites, comparable with thiopental and propofol
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etomidate metabolism
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-is primarily through ester hydrolysis to inactive metabolites, which are excrete 78% in the urine, 22% bile
-<3% of the drug is excreted unchanged in the urine |
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clearance of etomidate
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-is 5x that for thiopental, as reflected by the shorter elimination half-time (11 for thiopental, 3-5 for etomidate)
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duration of action of etomidate based on dose given
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-the duration of action is linearly related to the dose
-for every 0.1 mg/kg etomidate, get 100 seconds of unconsciousness |
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why can you give larg, repeated doses of etomidate, and run continuous infusions?
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because of its minimal CV side effects, and short context sensitive half-time
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etomidate protein binding
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-like other drugs, is highly protein bound (77%), primarily to albumin
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mechanism of action of etomidate
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-primarily works through potentiation of GABAA-mediated chloride channels, like most other IV anesthetics
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etomidate effect on the brain
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-is a potent cerebral vasoconstrictor, decreaseing CBF and ICP, and CMRO2
-these are similar to comparable doses of thiopental |
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etomidate and neuroprotection
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-despite lowering CMRO2, has not been shown in animal studies to be neuroprotective, while human studies are lacking
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etomidate and the EEG
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-etomidate causes greater frequency of excitatory spikes than thiopental
-similar to methohexital it can activate seizure foci, manifested as fast activity on the EEG -also, it causes myoclonus in >50% of patients, which may be associated with myoclonic activity on the EEG |
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CV effects of etomidate
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-has the desired feature of CV stability after bolus injection
-BP decreases are nonexistent or modest, and if happen reflect decreased SVR, and therefore any BP lowering effects will be exaggerated by hypovolemia, and optimizing fluid status can prevent them -causes minimal changes on HR, CO, and myocardial contractility |
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etomidate effects on respirations
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-ventilatory depression is less pronounced than with barbiturates, though apnea can follow rapid IV injection of the drug
-this depression of ventilation will be exaggerated when adding inhaled anesthetics or opioids |
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endocrine effects of etomidate
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-causes adrenocortical suppression by producing a dose-dependent inhibition of 11B-hydroxylase, which is necessary to convert cholesterol to cortisol
-this lasts 4 to 8 hours after an induction dose -no outcome studies have demonstrated an adverse effect on outcomes using etomidate for induction |
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induction dose of etomidate
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0.2-0.3 mg/kg IV
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induction with etomidate
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-unconsciousness onset is comparable to propofol and thiopental
-involuntary myoclonus is common, but can be masked by muscle relaxants -can get pain during injection, and venous irritation afterward is common -awakening after a single dose is rapid, with little residual depressant effects |
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etomidate and analgesia
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does not produce analgesia
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etomidate and PONV
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-may be more common than with propofol or thiopental
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principal limiting factor to the use of etomidate
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-transient adrenocortical supression, which theoretically may be desired to provide stress-free anesthesia, but may but undesirable if it prevents protective stress responses during the perioperative period
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dexmeditomidine
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-highly selective a2-adrenergic agonist
-a2-agonists were recognized as being useful due to observations of the decreased anesthetic requirments for patients on chronic clonidine -of course, a2-antagonists can antagonize its effects |
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physiochemical properties of dexmeditomidine
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-is the active S-enantiomer of medetomidine, which is a highly selective a2-agonist and imidazole derivative used in veterinary medicine
-is water-soluble and available as a parenteral formulation |
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dexmedetomidine metabolism
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-undergoes rapid hepatic metabolism involving conjugation, N-methylation, and hydroxylation, follwed by conjugation
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dexmedetomidine excretion
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-metabolites are excreted through the urine and bile
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how can the clearance of dexmedetomidine by described?
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as high
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how about the elimination half-life?
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as short
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dexmedetomidine context-sensitive half-time
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-is significant
-after a 10 minute infusion is 4 minutes, but after an 8 hour infusion is 250 minutes |
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pharmacodynamics of dexmedetomidine
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-selectively activates a2 receptors in the CNS
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hynosis from dexmedetomidine
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-likely results from activation of a2 receptors in the locus ceruleus
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analgesia from dex
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-originates at the level of the spinal cord
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how does the sedation produced by dex differ from that produced by other IV anesthetics?
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-it more resembles a natural sleep state due to activation of natural sleep pathways
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dex and cerebraovasculature
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-it produces a decrease in CBF with no effect on ICP or CMRO2
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what does dex have the potential for?
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tolerance and dependence
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dex and the CV system
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-decreases HR and SVR, and consequently BP
-a bolus may cause an increase in BP and pronounced dec in HR, likely due to activation of peripheral a2-receptors; the bradycardia may be so pronounced it needs to be treated -in addition to severe bradycardia, heart block and asystole have been observed, likely due to unopposed vagal stimulation; the effect of anticholinergics remains unchanged |
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dexmedetomidine effect of respiratory system
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-small decrease in tidal volume, with no change in respiratory rate
-also no change in the ventilatory response to CO2 -as with any sedation, can lead to upper airway obstruction -has a synergistic effect when combined with other sedative-hypnotics |
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dexmedetomidine uses
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-for short-term sedation of ventilated ICU patients
-in the OR, used as an adjunct to general or as sedation for awake fiberoptic or regional -as part of general, decreases the requirments of inhaled and IV agents |
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dexmedetomidine dose
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0.5-1 ug/kg loading dose over 10-15 min, followed by an infusion of 0.2-0.7 ug/kg/hr
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