Management of Multifactorial Infant Delirium with Intravenous Haloperidol in the Setting of Over Sedation and Poor Enteral Absorption

Case Presentation

We present the case of an 11-month-old female with a history of prematurity, pulmonary hypoplasia, chronic respiratory failure, developmental delay, and chronic kidney disease transferred from another institution to our Pediatric Intensive Care Unit for worsening respiratory failure and consideration for extracorporeal membrane oxygenation. The patient's hospital course was complicated by poor enteral absorption and gastric prolapse from her gastrostomy site, stenotrophomonas/rhinoviral/enteroviral infections, and pulmonary hypertension. She received multiple sedating agents and neuromuscular blockade with difficulty maintaining adequate sedation for ventilation (Table 1). On hospital day 119, Psychiatry was consulted because of persistent agitation and the patient was diagnosed with delirium. Symptoms included sleep–wake cycle disturbance, lack of interactive engagement, inattention, purposeless movements, agitation, and waxing and waning alertness.

On day 136, the patient's agitation mildly improved with weaning of sedation and analgesia yet persisted at a level that interfered with adequate oxygenation and ventilation. Haloperidol was started because of delirium severity and an unreliable enteral route of administration. The patient received IV haloperidol at 0.1 mg over 15 minutes and was continued on 0.1 mg IV haloperidol twice daily (dose weight of 8.4 kg, dose of 0.024 mg/(kg·day)). The patient exhibited rapid improvement with return to baseline behavior. This improvement allowed for continued weans of midazolam, pentobarbital, methadone, and diazepam. The patient tolerated a 6-day course of haloperidol before it was discontinued. Over the following 3 days, the dexmedetomidine infusion was weaned off, while pentobarbital and methadone were discontinued the following week.

Discussion

Delirium is defined as an acute change from baseline functioning with disturbance in attention or awareness, and a fluctuating course. Delirium is prevalent in the pediatric critical care setting, yet rarely considered in the differential for altered mental status or agitation in infants (Silver et al. 2010; Turkel et al. 2013). Among children, younger age results in increased risk of delirium (Silver et al. 2010). Recognition of delirium in infancy is also impacted by diagnostic complexity (Schieveld et al. 2010; Silver et al. 2010; Turkel et al. 2013). Regulation of attention, alertness, and sleep can serve as markers for delirium development (Schieveld et al. 2010; Turkel et al. 2013). It is critical to obtain premorbid developmental history and baseline functioning, while carefully observing how the infant engages others and its environment.

Early management of delirium can reduce unnecessary use of sedation, analgesia, and other pharmacological interventions. Many commonly used agents in the critical care setting, such as benzodiazepines, opiates, barbiturates, antihistamines, and anticholinergics can precipitate or perpetuate delirium (Schieveld et al. 2010; Silver et al. 2010; Turkel et al. 2012, 2013). In cases not responsive to nonpharmacological management, the use of antipsychotics may be warranted (Silver et al. 2010; Turkel et al. 2012). It is preferred to use second-generation rather than first-generation antipsychotics, given comparable efficacy and reduced risk for side effects (Turkel et al. 2012).

In this case, the patient's delirium was related to multiple factors, including infection, respiratory insufficiency, pulmonary hypertension, and excess sedation. This was perpetuated by escalating sedation as well as severe developmental delay. Delirium was not considered in the differential initially by the intensive care team until psychiatric consultation. This highlights the critical importance of a broad differential for agitation and close collaboration between Psychiatry and the Intensive Care Unit.

During the first few weeks of delirium management, management focused on nonpharmacological approaches, as well as attempting to wean the benzodiazepine infusion, morphine infusion, barbiturate, and methadone. These attempts initially resulted in mild improvements, but were limited because of worsening patient agitation and clinical instability, including frequent severe desaturations and autonomic instability in the setting of severe agitation. Given clinical necessity, difficulty weaning sedation, and severity of underlying delirium, we transitioned to intravenous haloperidol. The patient had limited enteral intake, a prolapsed gastrostomy site, and poor enteral absorption. Haloperidol allowed for intravenous administration and the ability to make more precise titrations in dosing. Use was closely monitored with conservative dosing (less than the 0.05 mg/(kg·day)) to avoid iatrogenic injury (Schieveld et al. 2010).

The intention with pharmacological management of delirium was to eventually transition to an oral antipsychotic, preferably a second-generation antipsychotic. However, the patient had such a robust response that this allowed for improved tolerance of sedation weans and a brief course of antipsychotic medication. This case report supports previous literature suggesting the utility of haloperidol in the management of infant delirium (Schieveld et al. 2010). Although caution must be taken, intravenous haloperidol is a reasonable and effective management consideration in infants with comorbid delirium, in which alternative management strategies are unsuccessful or not feasible.