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Clinical data for pharmacological delirium treatment suggest a reduction in delirium duration and severity of hyperactive agitated symptoms; however, improvements in short- or long-term patient outcomes have not been demonstrated. Antipsychotic medications should be reserved as last line agents since all can potentially confound a neurological exam and are associated with a significant adverse event profile. Efficacy of antipsychotic medications are similar when given in equivalent doses, thus the choice of an antipsychotic will depend on the ability to administer certain dosage forms and its adverse event profile. Clinical data with the use of antipsychotics in the treatment of ICU delirium is most robust with haloperidol, quetiapine, ziprasidone and olanzapine in the form of published randomized controlled trials. Typical antipsychotics (haloperidol) are considered to be the gold standard; however, it is associated with QTc prolongation and hypotension. Previously, there were concerns over its potential to lower the seizure threshold; however, current evidence suggests a fairly low incidence rate. Haloperidol is available as an oral and a parental formulation. Intravenous haloperidol can be administered in most ICU patients and is associated with less extrapyramidal side effects (EPS) (e.g., akathisia, dystonia) than its oral dosage form. In the outpatient setting, atypical antipsychotics (olanzapine, risperidone, quetiapine and ziprasidone) have demonstrated similar efficacy to haloperidol. It is unknown if atypical antipsychotics will be associated with similar or superior treatment efficacy for ICU delirium. The advantage of using atypical antipsychotics centers on the adverse drug reactions profile, which tends to be less frequent and less severe than those of haloperidol. Despite a lower incidence of extrapyramidal symptoms (EPS) compared to most typical antipsychotics, atypical antipsychotics are associated with other adverse effects. Table 2 highlights some of the major differences in the safety profile of haloperidol and the commonly used atypical antipsychotics in the ICU. QT prolongation is one adverse drug reaction where most atypical antipsychotics with the exception of ziprasidone have a clear advantage over haloperidol. It is important to recognize the degree of QTc prolongation is increased with the presence of electrolyte abnormalities, structural heart conditions, presence of certain brain injuries such as aneurysmal subarachnoid hemorrhage and coadministration of other QT prolonging medications such as fluoroquinolones and antiarrhythmics. Table 2: Comparison of pharmacokinetics and adverse drug reaction profile of commonly used antipsychotics in the critically ill patient. Category Haloperidol Olanazepine Risperidone Quetiapine Ziprasidone Dosage forms IV, IM, Enteral Enteral, SL, IM Enteral, SL Enteral Enteral, IM Half life (hours) 14 33 3-24 6 6.6 Sedation ++ ++ + ++ + EPS +++ + ++ + + QTc Prolongation +++ + + + ++ EPS= extrapyramidal symptoms IM= intramuscular, IV=intravenous, QTc= Corrected QT interval, SL= sublingual, (+) =low incidence, (++) = moderate incidence, (+++) = high incidence Since delirium is a transient and fluctuating condition, frequent re-evaluation using one of the validated delirium detection tools is necessary. Delirium treatment should be limited to the duration of delirium symptoms. Based on expert opinion, tapering and discontinuation of pharmacological therapy is generally recommended in most patients when delirium symptoms are resolved (Tomichek Critical Care 2016). Overall, there is a lack of robust clinical data for the treatment of delirium in the neuro ICU patients. There continues to be a need to further elucidate the benefits of delirium treatment in this patient population. Further validation of predisposing risk factors in the neuro ICU is also an area of need to be investigated. Both short- and long-term outcomes should be investigated in aneurysmal subarachnoid hemorrhage and traumatic brain injury patient populations and further data is necessary in the ischemic and hemorrhagic stroke patient population. 21


ezMag_277323_SmithBucklin_NCS_March_Currents_3
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