Medications in this group are also referred to as sedative hypnotic agents because of the ability to sedate patients and induce sleep. Most of the agents in this class exert their effect through the GABA receptor of central nervous system neurons. Delivery of subtherapeutic doses of any agents in this class will cause disinhibition in the child and may result in agitated, uncontrolled behavior with an increased risk of laryngospasm. More of the sedative hypnotic agent will take the child through the plane of disinhibition to one of somnolence.
Barbiturates are the classic pediatric sedative agents (i.e., pentobarbital, thiopental, and methohexital). Medications in this class produce predictable sedation with variability in effects related to their lipid solubility and rate of central nervous system penetration. Thiopental production has been permanently halted (due to ethical concerns in its use in capital punishment) and has largely been replaced by etomidate as an induction agent for rapid-sequence intubation protocols. Methohexital, however, has a similar onset and dosage as propofol when administered IV, and can be used as a continuous bolus for patients needing an MRI for whom propofol is contraindicated. Both rapidly penetrate the central nervous system and induce profound sedation within 30 seconds. Respiratory depression is a prominent feature of IV administration of these drugs at standard induction doses, and apnea should be anticipated. Rectal administration of 25 to 30 mg/kg of methohexital has proved effective for sedation of children undergoing diagnostic radiology studies, with transient airway events in 4% to 10%.16,34 Absorption via this route may be rapid, and parents holding a child after administration of the drug should be closely supervised, sitting down, and positioned as if the child is already sleeping.
Pentobarbital is a rapid-acting, less-potent sedative hypnotic used primarily in sedation for very brief diagnostic studies. Administered either IV or IM, this agent produces very predictable actions, with a success rate of 97% for diagnostic studies. Pentobarbital produces better, more reliable sedation than benzodiazepines alone, but is outperformed by and has more complications than etomidate for CTs.35 “Pentobarbital rage” can occur in up to 7% of patients. Most protocols give up to 6 mg/kg in two to three rapid-push divided doses, stacking doses every 30 seconds if the preceding one does not result in sleep. Barbiturates have the advantage of not burning with administration, but may be hyperalgesic, and should be avoided in patients with known temporal lobe seizures.
Propofol is an ultrashort-acting sedative hypnotic used for both rapid sequence intubation (RSI) and PSA. Propofol's mechanism of action is unclear and may relate to both a GABA receptor effect and a direct neuronal membrane action. Propofol is a highly lipid soluble agent that produces clinical effects within 30 seconds (one arm brain circulation) with a duration of 6 to 8 minutes. Relative contraindications include severe allergies to egg or soy. For procedures such as fast CTs and lumbar punctures, recent studies use a 2 mg/kg bolus, with supplemental boluses of 1 to 2 mg/kg to maintain the sedation during the procedure.6 For prolonged sedation (i.e., MRI), a propofol bolus followed by a continuous infusion of 100 to 150 mcg/kg/min is preferable to intermittent boluses.36 ED-only studies have started with 1 mg/kg when adjunctive opioids have been used.9,37 Emergency physician administered propofol sedation has been reported in a large study of over 25,000 sedations showing a low (2.3%) rate of reversible serious adverse events.38 Propofol burns with injection, which can be mitigated by a 1 mg/kg lidocaine mini-bier block applied with tourniquet for 1 minute prior to delivery. Pain is less of an issue in older patients, particularly when an anticubital vein is used.
Airway events are the most common complications, given the profound relaxation of tone seen with propofol. The need for repositioning of the head should be expected at induction, with jaw thrusts being required 3% of the time.9,39 One study comparing methohexital and propofol in adults noted brief bag-valve-mask in 4/52 methohexital patients and 2/51 propofol patients.40 Hypotension with good perfusion is common and does not require treatment; one study found that supplemental IV fluids resulted in a mean change of systolic blood pressure of 22 mm Hg compared with 21 mm Hg in children who were not bloused.39
Supplemental oxygen seems to decrease the incidence of the most common side effect, mild hypoxia. Despite the greater frequency of airway-related events with propofol, serious adverse events are rare when deep sedation guidelines are followed and ED practitioners trained in airway management administer the drug. Given the growing ED popularity due to rapid resolution of effects and efficacy, propofol clinical practice guidelines for ED use were published in 2007.14,41
As propofol can actually act as an antiemetic, it can balance the common side effect of ketamine. Ketamine/propofol (ketofol) can be mixed 1:1 in a single syringe and titrated to effect, or given sequentially. This combination has been shown to be highly efficacious, with short recovery times, few adverse events, and high satisfaction scores.42–44 One unique side effect of propofol is the blunting of sympathetic responses, particularly cardiac.45 Patients are uniquely susceptible to vagal stimulation, resulting in rare bradycardia and deaths reported. Adjunct atropine should be readily available, though is not required for routine use in children with normal cardiac function.
Etomidate is an imidazole sedative hypnotic agent most commonly used as an induction agent for emergency intubations. It has a flat cardiovascular curve and is appropriate for hypotensive patients. Dosing at 0.3 mg/kg in a fast push brings on sedation within 30 seconds.46 In contrast to propofol, barbiturates, or opioid/benzodiazepine combinations, etomidate is associated with few airway events in children.35
Etomidate does not provide analgesia, thus, adjunct opioids are required for ED procedures such as fracture reductions. Fentanyl combined with etomidate has provided effective sedation, successful procedural completion, and rapid recovery with a median time from administration to discharge of 21 minutes in children.47 Studies evaluating its use for pediatric painful procedures have started at 0.2 to 0.3 mg/kg, with adverse events consisting of hypoxia and respiratory depression, but no reported apnea.48,49
Side effects include burning with injection and brief myoclonus up to 22% of the time. In adults, myoclonus has been reduced by pushing more rapidly, or by giving small 0.015 mg/kg doses of midazolam prior to administration.50,51 Sedation from etomidate in a single bolus wears off as or even more rapidly than with propofol, which may limit its applicability in the ED. The adrenal suppression reported with prolonged ICU use can occur transiently with even a single dose. Recent evaluation of ICU patients with meningococcemia found greater death rates in patients who were intubated with etomidate rather than other sedatives; thus, it should not be used for procedures in potentially septic or critically ill patients.52,53
Dexmedetomidine, related to clonidine, is a centrally acting α2-adrenoceptor agonist with potent sedative, analgesic, and anxiolytic actions. This drug produces minimal respiratory depression. Initial hypertension followed by hypotension and bradycardia are potential side effects diminished by loading over 10 minutes, which may limit ED utility. It does not interfere with EEG recording as compared with other sedative agents. Recovery is relatively slow, and its use has been evaluated for noninvasive prolonged studies.54 Studies in children during CT scans found a 2 μg/kg bolus over 10 minutes to be effective, with no adverse airway events in 62 children.55 Combinations of dexmedetomidine and ketamine were less satisfactory than ketamine/propofol, but buccal and intranasal routes of administration may be promising future applications for agitated children where an IV is not possible.42,56