Pain, Agitation/Sedation, Delirium, Immobility, Sleep Disruption, and Neuromuscular Blockade

Treatment of Delirium: The cause of delirium may be multifactorial, and identifying and correcting the

underlying etiology is the first step in management. Patients can also progress to alcohol withdrawal or

withdrawal from other chronic medications/substances and present with hyperactive delirium. The PADIS

guidelines suggest not using an atypical antipsychotic, haloperidol, or a statin to treat subsyndromal

delirium or delirium (N Engl J Med 2018;379:2506-16). The Modifying the Impact of the ICU-Associated

Neurological Dysfunction-USA (MIND USA) Study is a multicenter, randomized, placebo-controlled study

of 566 patients showing that haloperidol and ziprasidone did not reduce delirium, time on the ventilator, ICU

or hospital length of stay, or death compared with placebo. Arrhythmias, parkinsonism (extrapyramidal

symptoms), neuroleptic malignant syndrome, study drug discontinuation, and other safety concerns were

extremely low across all three groups. Additionally, a planned secondary analysis of the MIND USA

study showed that neither haloperidol nor ziprasidone significantly increased QTc intervals compared with

placebo. The AID-ICU trial was a multicenter, randomized, placebo-controlled trial of 963 patients with

delirium randomized to haloperidol or placebo. The mean number of days alive and out of the hospital

was 35.8 (95% CI, 32.9–38.6) in the haloperidol group and 32.9 (95% CI, 29.9–35.8) in the placebo group

with an adjusted mean difference of 2.9 days (95% CI, -1.2 to 7; p=0.22). Antipsychotics remain viable

for the short-term control of agitation (e.g., alcohol or drug withdrawal) or severe anxiety with the need

to avoid respiratory suppression (e.g., heart failure, COPD, or asthma). If an antipsychotic is initiated,

low starting doses should be considered, and daily review of drug interactions, adverse effects, dosing

titration, and need for the antipsychotic should be completed. In addition, a strategy for discontinuation

or outpatient follow-up should be documented to help avoid inadvertent continuation beyond the hospital

environment (Table 7). Serious adverse effects are associated with the use of any antipsychotic; effects

such as arrhythmias, serotonin syndrome, neuroleptic malignant syndrome, extrapyramidal symptoms, and

oversedation should be closely monitored on a daily basis. Dose ranges for atypical antipsychotics for ICU

delirium are not well described. The American Geriatrics Society 2015 Beers Criteria for medication use

in older adults includes the following recommendation: “Avoid antipsychotics for behavioral problems of

dementia or delirium unless nonpharmacological options have failed or are not possible AND the older

adult is threatening substantial harm to self or others.” If the ICU team decides to use antipsychotics in

older adults, lower starting doses should be considered, together with daily review of drug interactions

and adverse effects. The PADIS guidelines suggest using dexmedetomidine for delirium in mechanically

ventilated adults when agitation precludes weaning/extubation. The PADIS guidelines suggest not using

bright light therapy to reduce delirium in critically ill adults.

of adjunctive medications for ICU patients (e.g., antipsychotics, gabapentin, carbamazepine). Although their

use in the ICU may be appropriate, there is a potential for inadvertent continuation of these medications on

hospital discharge if a treatment plan is not clear in the medical record. This has been a well-documented

problem with other medications initiated in the ICU (e.g., histamine receptor blockers, proton pump

inhibitors), and studies have been published describing the continuation of newly prescribed antipsychotics

could lead to serious adverse effects, drug interactions, and significant drug cost as well as a presumption

of a psychiatric or neuromuscular disorder associated with these drugs. Communication to the next direct

patient care provider is crucial to appropriately direct the next steps in medication reconciliation.