Abstract
Antipsychotics (APs) are commonly prescribed in critical care (CC) for the management of agitation and hyperactive delirium. However, there is a lack of consensus regarding their optimal use for the treatment of critical care delirium (CCD). In addition, differences and even disagreements were reported between AP use in practice and that recommended in guidelines and research.This programme of research set out to describe, understand and appraise CC prescribers’ rationale for initiating, optimising, and discontinuing APs when managing agitated and/or delirious CC patients in a UK teaching hospital. Four cross-sectional studies were carried out to address a range of questions. Two studies focused on AP prescribing and monitoring , the first a retrospective review of actual practice: the second a prospective review of perceived practice. Both studies were done at the same setting [GSTT CC] and within similar time frame which was the year 2016. Actual and perceived AP practice was compared to highlight key issues.
While 81% of clinicians reported prescribing APs for the management of CCD, the actual prevalence of AP prescribing for agitation and delirium was much lower (4.6%). In both studies, an atypical antipsychotic (AAP) was commonly used, with quetiapine the most frequently prescribed. The survey of perceived practice highlighted that delirium psychomotor subtypes and the presence of distressing behavioural symptoms were important factors in the decision to start or stop AP therapy. A number of interesting prescribing patterns were observed which warrant further consideration, including preferring the use of IV haloperidol, in low doses for brief duration, in elderly, nonmechanical ventilated patients and those diagnosed with agitation. Furthermore, patients supported by ECMO were commonly treated with quetiapine, at higher maximum daily doses than used in non-ECMO patients. Similar maximum daily doses of olanzapine were observed in both studies which were higher than those used in the literature, raising safety concerns. AP associated cardiovascular adverse drug reactions
(ADRs), particularly QTc prolongation, were highlighted, in both studies, as the key safety concern, with the survey demonstrating that variable criteria were used by clinicians to define QTc prolongation. Both studies reported low rates of daily delirium screening using a validated tool (CAM-ICU) and daily QTc incident monitoring using 12-lead ECG, with survey respondents overestimating the frequency of these tools application. Actual AP prescribing practice was more conservative than the perceived practice reported and should be encouraged. In comparison, monitoring for these drugs effect and safety using valid tools reported in both studies was overall poor.
The validation study incorporated a critical review to identify an appropriate tool to identify and monitor delirium in the critically ill. Six suitable tools were identified, and the DRS-R98 selected for further validation in a sample of critically ill delirious patients. The DRS-R98 demonstrated high concurrent validity and internal consistency, and moderate inter-rater reliability. These findings suggested that it could be used in research and clinical practice by trained liaison psychiatrists to assess and monitor critically ill patients with refractory or complex delirium.
The final study was a retrospective case series which explored the value of measuring serum concentrations of quetiapine and olanzapine, when prescribed to treat agitation and/or delirium in critical care. The case series identified 19 cases where serum concentrations had been requested, mainly in those with higher severity of illness or those experiencing refractory or complicated delirium. The assays had limited impact on prescribing decisions due to inappropriate sample collection time
(n=10, 52%) and delayed result return (n=18, 94%).The assays were ordered to determine if the orally administered drug was sufficiently absorbed or to determine the effect of a potential interacting drug. International guidelines were retrospectively used to interpret the serum concentrations reported and were considered to be potentially useful in interpreting assay results.
Future research should aim to describe APs effect on delirium symptoms severity, ECMO circuit impact on quetiapine serum concentration and to determine the therapeutic reference range for quetiapine when prescribed to treat CCD.
Description and in-depth analysis of AP daily prescribing practice can identify patterns which requires further evaluation or changes. These can also contribute toward the design of specific modification strategies and future research questions.
| Date of Award | 1 Aug 2021 |
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| Original language | English |
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| Supervisor | David Taylor (Supervisor) & Catherine McKenzie (Supervisor) |