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Roberts: Clinical Procedures in Emergency Medicine, 4th ed.

Copyright 2004 Saunders, An Imprint of Elsevier

KETAMINE

Pharmacology.

Ketamine produces a unique state of cortical dissociation that permits painful procedures to be performed more consistently and effectively than with other PSA agents. This state of "dissociative sedation" is characterized by profound analgesia, sedation, amnesia, and immobilization ( Fig. 34-1 ), and can be rapidly and reliably produced with IV or IM administration. Ketamine has been widely used worldwide since its introduction in 1970 and has demonstrated a remarkable safety profile in a variety of settings.[4][6][92][93][94] In 1999, the JCAHO confirmed that ED ketamine administration is fully compliant with its standards when administered according to protocol.[95] Clinicians administering ketamine must be especially knowledgeable about the unique actions of this drug and the numerous contraindications to its use (see Table 34-11 ).

Figure 34-1 A child undergoing repair of a laceration while dissociated with ketamine. The blank stare is typical.

Ketamine differs from all other PSA agents in several important ways. First, it uniquely preserves cardiopulmonary stability. Upper-airway muscular tone and protective airway reflexes are maintained. Spontaneous respiration is preserved, although when administered IV, ketamine must be given slowly (over 1 to 2 minutes) to prevent respiratory depression. Second, it differs from other agents in that it lacks the characteristic dose-response continuum to progressive titration. At doses below a certain threshold, ketamine produces analgesia and sedation. However, once a critical dosage threshold (approximately 1 to 1.5 mg/kg IV or 3 to 4 mg/kg IM) is achieved, the characteristic dissociative state abruptly appears. This dissociation has no observable levels of depth, and thus the only value of ketamine "titration" is to maintain the presence of the state over time. Finally, the dissociative state is not consistent with formal definitions of moderate sedation, deep sedation, or general anesthesia (see Table 34-1 ), and therefore must be considered from a different perspective than agents that exhibit the classical sedation continuum.[13][96]

Ketamine is most effective and reliable when given IV or IM. Ketamine has a one arm-brain circulation time when given IV with onset of dissociation noted within 1 minute and effective procedural conditions lasting for about 10 to 15 minutes. When given IM, the same effect is achieved within 5 minutes, with effective procedural conditions for about 15 to 30 minutes. The typical duration from dosing until dischargeable recovery is 50 to 110 minutes when given IV, and 60 to 140 minutes when given IM.[92][97]

Like the benzodiazepines, ketamine undergoes substantial first pass hepatic metabolism. As a result, oral and rectal administration results in less predictable effectiveness and requires substantially higher doses. Clinical onset and recovery are substantially longer than when given parenterally, and thus these routes are rarely used in the ED.[61][62][98]

Ketamine can induce salivation, and is routinely coadministered with an anticholinergic. Atropine is most commonly chosen in emergency medicine due to its ready familiarity to clinicians and nurses, although glycopyrrolate is an equally acceptable but not superior alternative (see Table 34-13 ).

Adult use.

Ketamine is widely and successfully used in adults throughout the developing world for both minor and major surgery, particularly in areas lacking resources for inhalational anesthesia.[92][93][99][100] Hallucinatory so-called "emergence reactions" have been reported in up to 30% of adults receiving ketamine (although rare in children), and can be fascinating and pleasurable, or alternatively unpleasant and nightmarish.[92] Concurrent benzodiazepines are believed to blunt but not entirely eliminate such reactions in adults,[92][93][99][100] and apprehension regarding such unpleasant recoveries has limited the popularity of ketamine administration in the developed world for adults.

One study reported success administering dissociative doses (2 mg/kg IV) of ketamine with concurrent midazolam (0.07 mg/kg IV) to 77 ED adults to facilitate painful procedures (e.g., abscess incision and drainage, fracture reduction). There were no moderate or severe emergence reactions, and only five patients experienced mild reactions.[101] Furthermore, there appears to be no reason to avoid standard dissociative doses when ketamine is administered to adults. In a 1996 study using subdissociative doses (0.2 mg/kg IV) for the goal of bronchodilation in the treatment of acute asthma, three of six adults suffered dysphoric reactions.[102]

Ketamine presents potential risks to patients with coronary artery disease, as it is sympathomimetic and produces mild to moderate increases in blood pressure, heart rate, and myocardial oxygen consumption. The actual risk remains unclear due to limited experience in adults with known coronary artery disease.[99]

Given the available data, it would appear appropriate for emergency clinicians to carefully transpose their experience with ketamine into selected adult situations. Careful patient selection can help minimize potential adverse events (see Table 34-13 ).[99][101]

Pediatric use.

Ketamine is an ideal agent to facilitate short, painful procedures in children. The safety and efficacy of ketamine for this indication has been widely documented.[4][5][6][92][97] The IM route is simple and effective. Venous access is unnecessary, and atropine can be concurrently administered in the same syringe.[4] IV administration is attractive because a lower cumulative dose can be used, and recovery is faster than with the IM route. The primary caution is that with this route, ketamine must be administered slowly (each dose over 1 to 2 minutes) or respiratory depression and transient apnea can occur.[97]

Unpleasant recovery reactions are uncommon in children and teenagers, and are typically mild when they do occur.[103][104] There is no evidence of any benefit from the prophylactic administration of concurrent benzodiazepines in children,[103][104] and their role should be confined to treating unpleasant reactions if they should occur.

Adverse effects.

In the largest published ED series (1022 patients) the following adverse airway events were noted: airway malalignment (0.7%), transient laryngospasm (0.4%), and transient apnea or respiratory depression (0.3%). All were quickly identified and treated, and there were no sequelae.[4]

Vomiting was noted in 6.7% from the same series, and in most cases it occurred well into recovery.[4] The incidence was age-related, occurring in 12.1% of children aged 5 years or older, and 3.5% in those younger than 5 years.[94] There was no evidence of aspiration[4]; indeed, in 30 years of regular use there have been no documented reports of clinically significant ketamine-associated aspiration in patients without established contraindications. Delayed vomiting may occur after discharge, and patients should be advised of this possibility. Because of its unique preservation of protective airway reflexes, ketamine may be preferred over other agents for urgent or emergent procedures when fasting is not assured.[4][5][92]

Mild agitation during recovery (whimpering or crying) was noted in 17.6% of children from the same series, with more pronounced agitation in 1.6%. The incidence was age-related, with agitation occurring in 12.1% of children aged 5 or older, and 22.5% in those younger than 5.[94] Only 2 of 1022 children had reactions that treating clinicians judged severe enough to require treatment, and both children responded promptly to small doses of midazolam.[4] Another study quantified the degree of recovery agitation using a 0 to 100 mm visual analog scale; the median rating of recovery agitation was a 5, likely below the threshold of clinical importance.[103]

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