TABLE 114 Drugs Used for Induction of Anesthesiax

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SODIUM THIOPENTAL Sodium thiopental is the most commonly employed drug for induction of anesthesia and has been in use for some five decades. It is very inexpensive and provides reliable induction of anesthesia within 1 min. It causes significant venodilation and moderate direct myocardial suppression, which result in decreases in blood pressure and cardiac output in spite of an increase in heart rate mediated by a minimally suppressed baroreceptor reflex. It lowers intracranial and intraocular pressures and has long been the drug of choice where elevations of these pressures are a concern. Only barbiturates, of all the pharmacologic interventions studied, have been shown to provide cerebroprotection in acute brain injury, leading to the preference for this drug in the setting of intracranial mass lesions or head trauma. Its side effects include histamine release, which may manifest as flushing, exaggerated hypotension, and wheezing in patients with reactive airways. Neuroexcitatory effects during induction, such as twitching, cough, and hiccups, are relatively common. It can cause extensive tissue necrosis if extravasated.

PROPOFOL Since its release in the United States in 1989, this drug has enjoyed increasing popularity, particularly in elective settings. Its onset of action is similar to that of thiopental, and it produces comparable decreases in blood pressure and cardiac output. Unlike thiopental, there is no reflex increase in heart rate. Propofol appears to be superior to thiopental at suppressing pharyngeal and laryngeal reflexes and for this reason is usually chosen for insertion of an LMA without paralysis. Like thiopental, it lowers intracranial and intraocular pressures, and, while experience with propofol is less extensive, it is probably as good a choice as thiopental in similar settings. It does not cause histamine release or stimulate bronchospasm, and extravasation has not been reported to cause significant tissue injury. It is notorious for causing pain on injection, which may be markedly attenuated by preadministration of a small dose of lidocaine. It is significantly more expensive than thiopental, and, given the overall similarity of their profiles, propofol has not been widely adopted for use in RSI due to this factor. Because it is prepared as an emulsion that readily supports bacterial growth, propofol must either be administered on discarded within 6 h of opening its container.

KETAMINE Unlike any of the other induction agents, ketamine tends to increase heart rate, blood pressure, and cardiac output. These effects appear to be mediated through central sympathetic stimulation, since ketamine appears to be a weak myocardial depressant in isolated heart preparations. Such effects enhance its attractiveness in settings such as trauma with hypovolemia. It is also a bronchodilator with no suppression of ventilatory drive, making it an excellent choice for patients with known reactive airway disease. In addition, it has significant analgesic and amnestic properties. It can be given intramuscularly in a dose of 4 to 6 mg/kg with onset of anesthesia within 5 min. This may be desirable in the combative patient in whom intravenous access has not been secured. Unfortunately, it also carries a number of undesirable side effects. Despite the bronchodilatation, there are marked increases in upper airway secretions, which can occur briskly and complicate airway management. It increases cerebral blood flow, intracranial pressure, and intraocular pressure and should not be used in patients in whom these effects are a concern. Finally, it is associated with a significant incidence of emergence hallucinations, particularly in patients with a known history of psychosis, although this reaction is less common in children than in adults. This response can be attenuated by coadministration of benzodiazepines.

MIDAZOLAM Of the benzodiazepines, midazolam is the most popular for induction of anesthesia due to its rapid onset time and lack of venous irritation. The doses required for induction are much larger than those used for sedation. The onset of action is still somewhat slower than with the other induction agents discussed here. As a consequence of the large dose, the time to recovery is prolonged compared to that for the other induction agents. Unlike the other induction agents, however, midazolam can be reversed by the benzodiazepine antagonist flumazenil, although this should be done with caution due to the risk of seizures. Remarkably little hemodynamic perturbation occurs with an induction dose, although significant hypotension may occur in a hypovolemic or critically ill patient. Apnea is common, and coadministration of opioids markedly potentiates respiratory suppression. Amnesia is most reliably accomplished with this induction agent. While expensive compared to thiopental, it is commonly used in the emergency department due to its stable hemodynamic profile.

ETOMIDATE Etomidate is worthy of discussion due to its stable hemodynamic profile. An induction dose results in almost no change in heart rate, blood pressure, or cardiac output, since it appears to affect neither vascular tone nor baroreceptor reflex. It has little effect on ventilatory drive and none on airway smooth muscle. It lowers cerebral blood flow, intracranial pressure, and intraocular pressure much to the same degree as do thiopental and propofol. It completely lacks any analgesic properties and may require a low (2- to 4-pg/kg) dose of fentanyl to fully suppress the response to intubation. Side effects include pain on injection, myoclonic movements on induction, and a high incidence of subsequent nausea and vomiting. Reports suggesting adrenal suppression occurring with only an induction dose of the drug decreased its popularity, but evidence of the clinical significance of this observation has not been reported.

CHOICE OF AGENTS The choice of agent should be dictated by the specifics of the patient's physiologic status as well as by the experience of the emergency physician. Factors such as cost and convenience of storage and administration affect a department's choice of options. Specific scenarios for which pharmacologic management may be tailored are discussed below.

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