Pediatric Procedural Sedation with Ketamine

Ketamine for procedural sedation can be given intravenously or intramuscularly. The dose of ketamine to produce profound dissociation is:

• 1 to 1.5 mg/kg IV – This is given over 1-2 minutes, is effective within 1-2 minutes, results in effective sedation lasting 10-20 minutes, and if inadequate a further 0.5 mg/kg dose may be given
  or
• 4 to 5 mg/kg IM – This is effective within 2 to 5 minutes, results in effective sedation lasting 15-30 minutes and a repeat IM dose (2-4 mg/kg) can be given after 10 to 15 minutes if the initial effect is inadequate

The IM route is useful when IV access is problematic, but the downsides include:

• a longer recovery time (mean of 120 minutes for IM vs. 80 minutes for IV)
• vomiting is more likely (usually occurs during emergence)
• sedation doses are less easily titrated

Higher doses, or even a continuous infusion, may be required in small children due to their relatively higher volume of distribution.

Atropine (0.02 mg/kg, up to maximum of 0.6mg) or glycopyrrolate are often administered as a co-medication to reduce the hypersalivation caused by ketamine.
The weight of evidence at this time, based on meta-analyses of controlled trials, suggests that anticholinergics should not be routinely used:

• glycopyrrolate appears to increase airway complications.
• atropine confers no benefit.

However, atropine may be beneficial for certain procedures where having dry oral mucosae may be beneficial to the proceduralist rather than the sedationist, e.g. repair of tongue lacerations.

Emergence phenomena include recovery agitation, dreams, hallucinations and depersonalisation.They are less common in children than adults:

• adults: 10-20% (as high as 30% in some studies), with 1-2% clinically significant.
• children: 7.6%, with 1.4% clinically significant.

Benzodiazepines are useful for treating emergency reactions, but they do not decreased the likelihood of an emergence reaction occurring. Furthermore, co-administration of midazolam increases the risk of respiratory complications, although emesis is reduced.

In one study, involving adult patients in a non-emergency department setting, no emergence phenomena occurred if ketamine was adminstered in the following circumstances:

• patients were interviewed in the preoperative area:
• they were assured that the medication was safe and would provide complete analgesia during the procedure.
• they were told that the anesthetic medication would allow them to dream about a topic of their choice
• they were instructed to concentrate on that pleasant thought/dream during induction of anesthesia.
• they were  encouraged to share their thoughts and feelings before undergoing ketamine sedation.
• ambient operating room and recovery room stimuli were  minimized (e.g. noise and lighting).

Studies performed in non-emergency department settings suggest that ketamine (0.5 to 1 mg/kg IV) followed by propofol (1mg/kg IV) results in more rapid recovery times (time from administration to discharge is halved in some studies) with no increase in clinically significant adverse effects.Although ‘ketafol’ (sometimes mixed in the same syringe) is being used in emergency departments, there are currently no RCTs in an emergency department setting to support this practice.

Ketamine can cause hypertonia and semi-purposeful movements that may interfere with imaging if the patient is required to lie still.

Ketamine is traditionally contra-indicated in situations where raised intra-cranial or intra-ocular pressure may be harmful or poorly tolerated.These contra-indications are largely based on data from the 1970s. More recent studies in animals and ICU patients have undermined the belief that ketamine causes clinically significant increases in either intra-cranial or intra-ocular pressures. Indeed, some believe ketamine may be neuroprotective as a result of maintaining a stable ICP but with increased cerebral blood flow.

At present, it is probably best to choose an agent other than ketamine in these settings, unless other agents are less suitable for other reasons.

The dissociative state is a lack of response to external stimuli due to ‘disconnection’ of the thalamoneocortical system from the limbic system, as a result of non-competitive antagonism at NMDA receptors.Above a dose of about 1mg/kg IV the dissociative effects of ketamine  do not exhibit dose-responsive effects. Once a patient is fully dissociated, higher doses do not result in a deeper level of sedation.

‘Sub-dissociative’ doses (<1mg/kg IV or <2 mg/kg IM) of ketamine provide potent analgesia, due to agonism of mu, delta, and kappa opioid receptors.

Airway effects:

• maintenance of airway reflexes
• risk of laryngospasm — rare (~0.4%)
• excessive salivation

Respiratory effects:

• no suppression of respiratory drive
• bronchodilation

Most guidelines state that patients should be fasted for 4-6 hours prior to procedural sedation. However, no relationship between adverse respiratory events and fasting times has been found in any studies thus far.Fasting time should be tailored to the risks of aspiration versus the benefit of an early procedure. Fasting times should not be an issue in true emergencies (e.g. neurovascular compromise due to a displaced fracture).

For two main reasons:

• increased rates of respiratory complications
• animal studies implicate NMDA antagonists as a cause of apoptosis and neurodegeneration in developing brains.

Ketamine is also absolutely contra-indicated in patients with a history of overt psychosis.

• Weingart S. Delayed Sequence Intubation (DSI). EMcrit
• Nickson C. Ketamine sedation and laryngospasm. LITFL
• Strayer E. Taming the Ketamine Tiger. EMupdates
• Guideline: Ketamine use in the emergency department. RCH Melbourne
• Larson PC. Laryngospasm-The Best Treatment. Anesthesiology, 89 (5), 1293-1294 PMID: 9822036