Journal of the Louisiana State Medical Society
Hypothesis 1: Scheduled dosing of antipsychotic medication vs. PRN dosing reduces delirium duration The plot of the Kaplan-Meier survival estimates for Scheduled vs. PRN groups is shown in Figure 1. The ex- pected separation of curves occurred as the Scheduled group showed a greater proportion of cases moving to resolution of delirium. Formal testing between groups with the log-rank test, however, showed that duration of delirium between groups was onlymarginally significant (chi-square 3.4, df=1, p = .06). Table 2 shows the median duration of symptoms is shorter in the PRN group, but the greater proportion of patients with unresolved delirium in the PRNgroup resulted in a longer mean duration. Hypothesis 2: Timely initiation of antipsychotic medication reduces duration of delirium compared to delayed initiation In Figure 2, clear separation of the Kaplan-Meier survival estimates for duration of delirium in the Timely vs. Delayed groups is evident. The Timely group showed shorter durations of delirium compared to the Delayed group (log-rank test = 7.4, df=1, p < .05). As shown in Table 2, patients who received their first dose of antipsychotic medication within 24 hours of the onset of delirium had significantly shorter durations of delirium symptoms (me- dian 86.4 hours) compared to patients who received their first dose of antipsychotic medication more than 24 hours after the onset of delirium (median 173.8 hours). With age, sex, race (Black/African-American vs. White), or type of delirium (mixed and hypo-delirium vs. hyper- delirium) entered as covariates in separate Cox proportional hazards regression models, the effect of timely initiation of antipsychotic medication was still significant (p <.05). DISCUSSION The most important finding was that initiation of antipsychotic medication within 24 hours of the recogni- tion of delirium was associated with shorter durations of delirium compared to delayed initiation of medication. While delayed treatment of delirium has previously been addressed in the literature, 13 empirical data on this issue has been limited. This finding has at least two important clinical implications. First, this suggests that prompt recognition of delirium, which would allow more prompt treatment, has the potential to lead to improved clinical outcomes. Inpa- tients may be served well by implementation of standard- ized screening for delirium at early and regular intervals. Second, these data suggest that clinicians consider delirium as being in need of more pressing and aggressive interven- tion, as earlier intervention may interrupt a cascade of toxic metabolic processes in the central nervous system that have been shown to predict cellular death. 5 Of additional importance, was our finding that there was a trend of marginal statistical significance for the group that received scheduled doses to have shorter durations of
delirium compared to the group that received PRN doses. This is difficult to interpret in an uncontrolled, naturalistic chart review. Nevertheless, we interpret this as highly suggestive evidence that scheduled doses not only make rational sense clinically but have growing preliminary empirical support. There were qualitative findings from this chart review that are of clinical interest. There was rarely a standardized method used for screening, diagnosing, or treating delirium. In addition, it was often the nurses who made initial docu- mentation of mental status changes. Van der Boogard and colleagues [2010] showed that when the confusion assess- ment method-ICY (CAM-ICU) tool was implemented in the ICU, compliance and delirium knowledge improved in physicians and nurses, and results also indicated that more patients were treated with antipsychotic medication but with lower doses and for a shorter period of time. 14 Given this evidence, as well as our findings, implementing standardized tools to improve detection and management of delirium in this hospital setting would be a future direc- tion of our research. In addition to the limitations already mentioned, the allocations of patients to Scheduled vs. PRN groups and to Timely vs. Delayed groups were not controlled. Given the known effectiveness of antipsychotic medications for delirium and the data on the prolonged course of untreated delirium, it would be unethical to allocate subjects ran- domly to these types of groups. As imperfect as it was, this uncontrolled, naturalistic investigation appeared to be the only way to examine the relative impacts of these dosing strategies. Also, delirium diagnosis was made from clinical evaluation, without the use of standardized tools. However, descriptions of the cases in consultation and progress notes appeared consistent with delirium. There were many confounding factors that we were unable to control for without a randomized design. An in- herent difficulty in studying delirium is an inability to take into account etiologies of delirium, as the cause of delirium in many, if not most, cases of delirium is never known. However, there are few data to suggest that the course or treatment response of deliriumdiffers by etiology. Assessing how specific deliriumetiologies relate to treatment outcomes would be an area of further research. Despite these limitations, it is important to note that data on effects of delayed treatment and on dosing regi- mens are scarce. This study provides preliminary empirical information that early recognition, and perhaps scheduled dosing that is more biologically informed by the half-lives of antipsychotic medications, is important for outcomes. REFERENCES 1. Briskman I, Dubinski R, Barak Y. Treating Delirium in a General Hospital: A Descriptive Study of Prescribing Patterns and Outcomes. Int Psychogeriatr . 2010; 22: 328-331. 2. Pun BT, Ely EW. The Importance of Diagnosing and Managing ICU Delirium. Chest . 2007; 132: 624-636
246 J La State Med Soc VOL 166 November/December 2014
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