Feb 162014

Delirium -- sudden, severe confusion that occurs with acute illness -- is very common in ICU patients. As a group, patients experiencing delirium in the ICU tend to have worse outcomes than patients without delirium, all other things being equal (as far as that equality can be determined). But no one knows if it is delirium itself that worsens outcomes from critical illness, or if delirium is simply a marker of worse illness or vulnerability in the patient (i.e., an unmeasured, confounding variable -- the whole correlation-is-not-causation thing). In particular, no one has shown how to effectively prevent or treat ICU delirium, or that efforts to reduce delirium per se improve outcomes after critical illness.

Well, that's about it; you're up to date on delirium in the ICU. You wanted more?

OK, as long as we acknowledge that writing more, or publishing a significant review article in the NEJM from which this summary is largely taken, or including delirium checks and interventions in guidelines from critical care societies, each imply that there is more knowledge and certainty here than may be the case, and that interventions for it are helpful. None of which is clear, today. Accordingly, we'll move forward skeptically, interrogating the original texts along the way.

What We Don't Know About Delirium in the ICU

Delirium in the ICU is very difficult to study. From the excellent 2014 NEJM review by Reade and Finfer:

Estimates for the incidence of delirium in the ICU range from 16% to 89%, with the reported incidence affected
both by the characteristics of the population being studied and by the diagnostic criteria used ... Separating the effects of delirium status from those of illness severity with respect to the risk of death is difficult, since patients with more serious illnesses are at increased risk for both delirium and death. Association studies typically adjust for illness severity on admission to the ICU rather than at the time that delirium is diagnosed.

PulmCCM translation: Considered as a whole, the existing body of literature on delirium is difficult to interpret, due to its heterogeneity and the inherent challenges in studying delirium in the ICU.

The pathophysiology of delirium that is associated with critical illness remains largely uncharacterized and may vary depending on the cause. GABAergic and cholinergic neurotransmitter systems [may] play a contributory role ... central cholinergic deficiency may be a final common pathway. Alternative hypotheses include excess dopaminergic activity and direct neurotoxic effects of inflammatory cytokines. Currently, these hypotheses are unproven, making pharmacologic management strategies largely empirical.

PulmCCM translation: No one really knows what the pathophysiology of delirium is -- not even which receptor-family ballpark we should best be playing in.

There is very little evidence to guide the management of established delirium, and most existing trials were categorized by the investigators as pilot studies. Only one small placebo-controlled trial [of quetiapine] supports the efficacy of a drug treatment for established delirium in patients in the ICU.

PulmCCM translation: There are no established effective treatments for delirium in the ICU.

What We Kind-Of Know About Delirium in the ICU

How to define delirium. Delirium (per the DSM-IV) is a disturbance of consciousness, with change in cognition, development over a short period, and fluctuation over time (the "4 domains" of delirium). Inattention is considered by many to be the primary sign of delirium. Delirium may occur with (hyperactive) or without agitation (hypoactive).

Who tends to get delirious. Risk factors for delirium include older age, having more than one condition associated with coma, recent sedation, neurologic conditions including dementia, and severe critical illness. Although delirium is common in the ICU, no one knows exactly how common. Probably > 50%. Maybe 80% of mechanically ventilated patients. Benzodiazepine use might be a risk factor for delirium in ICU patients.

We don't usually notice delirium. Delirium usually goes unrecognized by people who are not looking for it (25% detection rate in routine practice; 64% by actively-screening research nurses; gold-standard: trained MDs). Two scales, the Confusion Assessment Method (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) are in use. CAM-ICU requires a 10-point test of attention to voice or pictures; the ICDSC seems more amenable to integration with the clinical exam and gestalt. One group found CAM-ICU better predicted outcomes from critical illness than did ICDSC. It has not been established that use of these scales results in superior detection of delirium compared to trained nurses using informal testing (gestalt).

Delirium seems bad. Each day of delirium is associated with about a 10% increase in the relative risk of death within one year in older patients (so if someone had an a priori 20% risk of death, 3 days of delirium would make it 26%). "Catching" delirium also increases the risk for long-term cognitive dysfunction, which is common in ICU patients. See above correlation-vs-causation conundrum.

Delirium has been prevented outside the ICU using verbal orientation strategies, ensuring patients can hear and see, giving them water to drink, and encouraging them to walk as soon as possible. Antipsychotics (Haldol, Risperdal) as prophylaxis around the time of surgery prevented some delirium in several studies. The SCCM suggests not using antipsychotics to prevent ICU delirium.

In the ICU, dexmedetomidine (Precedex) has resulted in less delirium than midazolam, propofol or both, at equal sedation depths, in various randomized trials (JAMA 2012, 2009, and 2007). This protective effect seemed to end after the infusions were stopped (patients had equal rates of delirium afterward).

There is no known effective treatment for established delirium in the ICU. All we have to go on today is a randomized trial showing that quetiapine (Seroquel) improved the rate of discharge to home or rehabilitation in a whopping 36 critically ill, delirious adults.

There is a black-box FDA warning against using antipsychotics for dementia-related psychosis, because it seems to have caused some deaths. This proscription mainly applied to using these drugs for "sundowning" but could easily be construed to include some ICU delirium.

What The SCCM Says About Delirium in the ICU

In its 2013 clinical practice guidelines for the management of pain, agitation and delirium, the Society of Critical Care Medicine has taken all this uncertainty in stride. They advise us to presume that identifying delirium and trying to reduce it will help ICU patients, and that we act accordingly. Specifically:

  • We should screen for and monitor delirium in all ICU patients (Grade 1B: strong recommendation based on moderate quality evidence) with either the CAM-ICU or ICDSC scales. Why the strong recommendation, and what's the moderate quality evidence, when no one has shown that identifying delirium or reducing it improves outcomes? After reading the rationale section, it's based on a leap of faith -- "high-quality cohort data relating delirium to critical outcomes shows high delirium 'miss rates' in the absence of monitoring" -- since we don't know that identifying their delirium would have helped those patients. Authors also point out that "informed patients at moderate to high risk want to be monitored for delirium" based on surveys, that this may result in reorientation and reduced fear, and that formalized delirium screening on every ICU patient is not that hard.
  • Patients in the ICU should be "mobilized" as soon as they are able (early mobilization). Ideally this means walking (while intubated is the new vogue), or bed and chair exercises if patients cannot yet walk (Grade 1B: above)
  • Don't use antipsychotics to prevent delirium in the ICU (Grade 2C; suggestion from low quality evidence).
  • SCCM has no comment on giving antipsychotics for established ICU delirium. Don't give them to people with prolonged QTc intervals at baseline, taking QTc-prolonging medications, or who have had torsades de pointes (Grade 2C).
  • For patients with established ICU delirium who need continuous sedation, they suggest using dexmedetomidine (Precedex) rather than benzodiazepines, unless alcohol or benzodiazepine withdrawal is present (Grade 2B, suggestion from moderate-strength evidence).

Michael C. Reade and Simon Finfer. Sedation and Delirium in the Intensive Care Unit. N Engl J Med 2014; 370:444-454.

Barr J et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med 2013 Jan;41(1):263-306. doi: 10.1097/CCM.0b013e3182783b72.

Sedation and Analgesia in the ICU -- PulmCCM Review

Sedation and Analgesia in Mechanically Ventilated Patients -- PulmCCM Review

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Delirium in the ICU (Review)