A large 60 year old man developed septic shock and multiorgan failure secondary to a severe community acquired pneumonia. On the twelfth night of his ICU admission he became increasingly agitated and pulled out his vascath, NG tube and dislodged his tracheostomy. The resulting loss of airway led to a severe desaturation event before he was anaesthetised and reintubated, with loss of around 500ml blood from the haemofiltration circuit and vascath wound haemorrhage. He was commenced on regular haloperidol, but his CAM-ICU remained positive for 48 hours. Haloperidol was continued for 4 days, and he had a prolonged respiratory wean.
How is delirium best managed on the intensive care unit?
Delirium is an acute fluctuating disorder of consciousness and cognition. It has a high prevalence in ICU patients varying from 20% to 80% but despite this is under-recognised by clinicians. There are three main commonly recognised subtypes: hypoactive delirium, characterised by withdrawal and apathy; hyperactive delirium, characterised by agitation and restlessness; and a mixed form. Hypoactive and mixed forms are the most common, and may explain why the condition may be under-diagnosed due to a lack of recognition of delirium in a seemingly settled patient (1).
Developing delirium can have major adverse consequences for the ICU patient including accidental self-extubation, inadvertent removal of catheters and lines, prolongation of mechanical ventilation, ICU and hospital length of stay, and increased mortality. Delirium is also associated with a measurable long term cognitive decline (1).
Managing the problems of delirium on the ICU involve preventing, recognising and treating it when found. Preventing delirium involves identifying and minimising the impact of risk factors. Predisposing (host) factors are usually not modifiable but should be recognised in order to identify at risk patients. Precipitating factors should be identified and targeted, particularly those that are iatrogenic in nature. These include factors such as immobilisation, sleep disturbance and medications, particularly sedatives and opioids (2).
Recognising and diagnosing delirium can present a significant challenge on the ICU. Compared to other hospital patients, ICU patients are often sedated, mechanically ventilated and unable to speak. Several sedation scoring systems have been validated in ICU patients (Sedation Agitation Scale (SAS), the Richmond Agitation Sedation Scale (RASS), and the Motor Activity Assessment Scale (MAAS)) to allow titration of sedation to an appropriate level. An over-sedated patient cannot be assessed for delirium. Several delirium assessment instruments have been validated for use in ICU patients (Intensive Care Delirium Screening Checklist (ICDSC), the Delirium Detection Score (DDS) and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU)) and regular screening for the presence of delirium should be part of routine daily ICU care (2).
Treating delirium involves detecting, minimising or treating organic and iatrogenic causes. Multicomponent strategies must be implemented to reduce the incidence of delirium. Interventions include repeated reorientation to time and day; minimising sleep disturbance; provision of spectacles, hearing aids and dentures, early mobilisation. Maintaining hydration status; maintaining electrolyte homeostasis and minimising exposure to sedative drugs where possible (1-2).
Pharmacotherapy usually aims to target the excess dopaminergic activity or the dearth of muscarinic activity in the brain which are thought to be the major neuropathophysiological mechanisms causing delirium. Haloperidol is the initial agent of choice in treating delirium. It has a relatively wide therapeutic window, can be given intravenously, and has relatively few significant side effects, of which prolongation of the QT interval is most significant. However, there is actually relatively little evidence for its efficacy. However, the recently published HOPE-ICU randomised control trial found no evidence that haloperidol modified the duration of delirium in critically ill patients compared to the control group (3). The negative outcomes from this trial will likely further stimulate the search for an effective treatment for delirium.
Enteral olanzapine is an atypical antipsychotic agent and is often a second choice for delirium treatment in the critically ill. A single centre randomised control trial compared olanzapine to haloperidol in treating ICU patients with delirium. Both were found to be similarly effective in reducing delirium symptoms with no excess side effects observed in the olazapine group (4).
Choice of sedative agent has an impact on delirium. Benzodiazepines are associated with the development of delirium and should generally be avoided except in where the patient displays dangerous motor activity or specific delirium syndromes such as alcohol withdrawal. Dexmedetomidine is associated with less delirium than benzodiazepines. It does not reduce the incidence of delirium, but may reduce the duration of delirium (5). Morphine, fentanyl, codeine and pethidine are all deliriogenic.
Delirium is a major, common problem in ICU patients. Prevention is undoubtedly more desirable than treating established dementia, and care ‘bundles’ may be required which incorporate several interventions to reduce the incidence of delirium. There are several recommended protocols for the pharmacotherapy of delirium, but with recent evidence failing to demonstrate a benefit for haloperidol there is room for further work to be done on the optimal strategy for managing the acutely hyperactively delirious patient.
1. Girard TD, Pandharipande PP, Ely EW. Review: Delirium in the Intensive Care Unit. Critical Care 2008, 12(Suppl 3): S3
2. Borthwick M, Bourne R, Craig M, Egan A, Oxley J. Detection, UKCPA: Prevention and Treatment of Delirium in Critically Ill Patients. Intensive Care Society Guideline 2006
3. Page V et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind placebo-controlled trial. Lancet Resp Med 2013; Vol 1 (7):515-523
4. Skrobik Y, Bergeron N, Dumont M, Gottfried S Olanzapine vs Haloperidol: treating delirium in a critical care setting. Intensive Care Med 2004; 30:444-449
5. Jakob SM, Ruokonen E, Grounds R, et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. J Am Med Assoc. 2012;307:1151–1160