Induction Agents Flashcards
After being drawn into a syringe, propofol should be discarded after:
12 hours
Allergy to Propofol to what components of the egg?
Most people who are allergic to eggs are allergic to egg albumin in the egg whites, whereas egg lecithin (from the yolk, answer B) is used in propofol for solubility.
Therefore, for a patient to be allergic to egg lecithin and not react to propofol, then he would have never been exposed to egg yolks before (and have no preformed antigen response to egg lecithin).
Profound hypotension after Propofol bolus contributed to …
Propofol can be thought of primarily as an afterload reducer (decreased svr), but also affects preload (decreased LVEDV) and contractility (decreased SV). Propofol affects the baroreceptor response to hypotension as well. Recall that the baroreceptors decrease their rate of firing in response to hypotension, therefore decreasing sympathetic inhibition
What factor if performed prior to induction with Propofol would most likely increase the time of apnea the longest:
A one hour infusion of propofol at 50 mcg/kg/min for sedation
Propofol is a potent respiratory depressant and its short clinical half-life after large bolus is (more) due to redistribution, not metabolism (although it IS quickly metabolized as well). Therefore, a preexisting infusion of propofol, even at levels where apnea is not produced, will still have a great effect on apnea time following large bolus since redistribution is limited. In other words, by occupying the tissues with a baseline infusion of propofol, redistribution of a large bolus is limited and apneic time may start to depend on metabolism. This is, of course, why patients can be rendered apneic for long periods of time following a total intravenous anesthetic.
Which of the following agents, when used immediately prior to surgery for pretreatment, are most likely to decrease the incidence of etomidate associated myoclonus:
Pretreatment with opioids decrease etomidate associated myoclonus, which is distinctly not a seizure.
Myoclonus and seizure can be difficult to distinguish when a history of epilepsy is present. Antiseizure medications (per se) are not useful in preventing myoclonus (Phenobarbital, Diazepam, & Phenytoin) as this is not a seizure. Lidocaine can decrease the burning pain associated with etomidate administration (due to the propylene glycol solvent). Both opioids and benzodiazepines have been shown to reduce the incidence of myoclonus, with probably equal efficacy. Diazepam (and probably the same for phenobarbital), is incorrect however, because when used as pretreatment, its onset is not fast enough to reliably prevent myoclonus, making Sufentanil the best answer.
Why Etomidate has been shown to increase mortality in critically ill patients
Etomidate has minimal effect on haemodynamics, save for mild decreases in systemic vascular resistance and mild effect on respiratory drive, seemingly making it a perfect ICU induction agent as well as sedative. Unfortunately,there seems to be a price to pay with etomidate use. With prolonged infusions etomidate has been shown rather convincingly to significantly increase mortality, likely due to adrenal suppression. Various studies have reported increased mortality with single dose etomidate for induction in patients with high ASA scores (above 3 or 4) as well as in the intensive care unit. The most convincing data is probably from severe sepsis. That being said, there are copious data to demonstrate the exact opposite, that mortality is not increased with induction doses even in sepsis. The million dollar question is, of course, what does the ABA think about this? My guess is that the ABA will not come out and say that etomidate induction increases mortality as a dogmatic statement, but may acknowledge that it has been shown in numerous studies to be associated with worse outcome.
Etomidate is an otherwise near ideal induction agent for ICU intubation because it has fewer cardiovascular effects than other drugs and one can maintain spontaneous ventilation in most cases to avoid muscle relaxation. As an aside, jaw clenching and myotonic movements can make intubation without muscle relaxation challenging and get the staff riled up (misinterpretation of seizure). Alternatives to etomidate for spontaneous ventilating intubation in the ICU include carefully titrated propofol, versed, and my favourite ketamine.
Adrenal suppression occurs with single dose of …
Transient suppression of enzymes involved in the synthesis of aldosterone and cortisol occurs predictably after a single dose of etomidate. The adrenal suppressive effects explain why etomidate drips increase mortality in the ICU.
When ketamine is absolute contraindicated
CHF
Ketamine activates the sympathetic nervous system leading to increased heart rate, cardiac output, stroke volume, etc in most patients. This is because the up-regulation of the sympathetic nervous system masks the direct myocardial depression associated with large doses of ketamine. With severe CHF the sympathetic nervous system is often already nearly fully ramped up, especially with compounded stress (bowel obstruction with associated dehydration). In these cases the small increase in sympathetic activation possible is far outweighed by the direct myocardial depression, as was this case. Tachycardia is seen with ketamine, not bradycardia or heart block. Ventilatory drive is well preserved with ketamine. Also note than pretty much the only patients in heart failure that have cardiovascular collapse to ketamine exist only on the boards…so read between the lines for my opinion as far as how “dangerous” the direct myocardial depressant effects are.
Premedication with …. can prevent recall nightmares induced by ketamine
BDZ
Ketamine is associated with psychotomimetic effects, especially during the recovery phase. During ketamine anesthesia patients are disassociated, meaning that patients are not conscious or aware of sensory impulses. Likely, the process where the dissociative state starts fading (and the patient associates sensory information with their consciousness), the nightmares occur. During ketamine anesthesia, patients often appear aware, with eye opening, nystagmus, swallowing, and movements. Benzodiazepines, fairly reliably, prevent recall of nightmares. Droperidol, a butyrophenone somewhat similar to haloperidol can tranquilize the patient into a cooperative and sedated state with associated fear and anxiety that they are unable to express (this used to be a hot boards subject, but has faded). This is distinctly different than the dissociative state seen with ketamine. Fentanyl, clonidine and diphenhydramine can be sedating but neither would be expected to prevent recall of the psychotomimetic effects of ketamine.
Propofol is incomplete anesthetics because it lacks ….
Analgesic effect
Propofol’s cardiovascular effects are most notably hypotension through vasodilation (both venous/preload and arterial/afterload). Compensatory increases in heart rate are prevented by baroreflex blunting. Direct myocardial depression is controversial. Respiratory wise it has a narrow window for causing hypnosis without apnea. It is fairly effective at blunting airway reflexes as well. Neurologically, a strong hypnotic effect is achieved through its activity at the GABA-A receptor. Any analgesic properties of propofol are weak if present at all (again controversial). Pain on injection can be decreased by pretreating with lidocaine (or even ondansetron as well as other medications) or using a larger vein. Dilution with saline or lidocaine can also decrease pain on injection.
Propofol metabolized through…
Emergence following a bolus dose of propofol is mostly due to redistribution from the central compartment to (vessel rich) peripheral compartments as well as a contribution of hepatic metabolism. Lung metabolism of propofol is the largest extrahepatic site of elimination
Methohixtal
- unavailable in the US (due to its use for death penalty)
- intraarterial injection cause spasm with prolonged vasoconstriction which can ultimately lead to limb loss. The treatment is classically stellate ganglion block.
- There is also a component of crystallization and physical capillary obstruction with barbiturates as well.
- That being said, a portion of the administered drug will invariably make it to the central circulation and cause the normal effects. One effect is vasodilation (without significant baroreceptor blunting) with a decrease in blood pressure.
- Barbiturates cause respiratory depression and apnea as well.
- Neurologically, barbiturates are the gold standard for decreasing brain oxygen consumption (CMRO2), cerebral blood flow (CBF), and intracranial pressure (ICP).
- A classic board worthy piece of dogma is that barbiturates decrease the tolerance to pain (antianalgesic properties), which in real life is questionable.
Metabolites of Versed
Midazolam is metabolized to alpha-1 hydroxymidazolam (which is biologically active.
Midazolam’s termination of effect (from single bolus) is primarily redistribution, not metabolism.
Morphine metabolites is …
Morphine is metabolized to morphine-6-gluconoride (you need to know this one) and is a major contributor to mu-receptor mediated respiratory depression
Meperidine metabolites is ..
Meperidine is metabolized to normeperidine, which in the setting of high levels (secondary to renal failure for example) can lead to seizures and CNS stimulation.
