https://orcid.org/0000-0002-2995-5527
Figures
Abstract
Background
Antipsychotic medications are commonly prescribed to critically ill adult patients and initiation of new antipsychotic prescriptions in the intensive care unit (ICU) increases the proportion of patients discharged home on antipsychotics. Critically ill adult patients are also frequently exposed to multiple psychoactive medications during ICU admission and hospitalization including benzodiazepines and opioid medications which may increase the risk of psychoactive polypharmacy following hospital discharge. The associated impact on health resource utilization and risk of new benzodiazepine and opioid prescriptions is unknown.
Research question
What is the burden of health resource utilization and odds of new prescriptions of benzodiazepines and opioids up to 1-year post-hospital discharge in critically ill patients with new antipsychotic prescriptions at hospital discharge?
Study design & methods
We completed a multi-center, propensity-score matched retrospective cohort study of critically ill adult patients. The primary exposure was administration of ≥1 dose of an antipsychotic while the patient was admitted in the ICU and ward with continuation at hospital discharge and a filled outpatient prescription within 1-year following hospital discharge. The control group was defined as no doses of antipsychotics administered in the ICU and hospital ward and no filled outpatient prescriptions for antipsychotics within 1-year following hospital discharge. The primary outcome was health resource utilization (72-hour ICU readmission, 30-day hospital readmission, 30-day emergency room visitation, 30-day mortality). Secondary outcomes were administration of benzodiazepines and/or opioids in-hospital and following hospital discharge in patients receiving antipsychotics.
Results
1,388 propensity-score matched patients were included who did and did not receive antipsychotics in ICU and survived to hospital discharge. New antipsychotic prescriptions were not associated with increased health resource utilization or 30-day mortality following hospital discharge. There was increased odds of new prescriptions of benzodiazepines (adjusted odds ratio [aOR] 1.61 [95%CI 1.19–2.19]) and opioids (aOR 1.82 [95%CI 1.38–2.40]) up to 1-year following hospital discharge in patients continuing antipsychotics at hospital discharge.
Citation: Jaworska N, Soo A, Stelfox HT, Burry LD, Fiest KM (2023) Impacts of antipsychotic medication prescribing practices in critically ill adult patients on health resource utilization and new psychoactive medication prescriptions. PLoS ONE 18(6): e0287929. https://doi.org/10.1371/journal.pone.0287929
Editor: Ashish Sarangi, University of Missouri Columbia, UNITED STATES
Received: March 17, 2023; Accepted: June 15, 2023; Published: June 29, 2023
Copyright: © 2023 Jaworska et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: Data may only be available upon reasonable request. The custodian of the data, Alberta Health Services, limits sharing of data to ensure patient confidentiality. Alberta Health Services can be contacted at research.administration@albertahealthservices.ca to make a data request directly from the custodian to replicate the data used in the study.
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Antipsychotic medication prescribing frequently occurs among critically ill patients to manage symptoms related to delirium, anxiety, or insomnia [1]. Several large randomized control studies have shown antipsychotic medication use in critically ill adult patients does not reduce incidence and duration of delirium, leading current guidelines to recommend against the routine use of antipsychotic medication for the prevention or treatment of delirium [2–6]. Antipsychotics are also commonly continued at hospital discharge. Previous observational studies estimate 21 to 24% of antipsychotic naïve critically ill patients who receive an antipsychotic in the intensive care unit (ICU) are discharged from hospital with an ongoing antipsychotic prescription [7,8]. Patients with critical illness are exposed to a number of psychoactive medications in addition to antipsychotics during their ICU admission and may be at risk of psychoactive polypharmacy (i.e., simultaneous use of at least two classes of psychoactive medications) following hospital discharge [9–11]. Benzodiazepine and opioid use in critical illness may contribute to negative clinical outcomes following critical illness including delirium, post-traumatic stress disorder, depression, anxiety, and cognitive dysfunction [12–14]. We utilized a multi-center, propensity-score matched retrospective cohort of critically ill patients receiving antipsychotic medications in the ICU to estimate health resource utilization outcomes and 30-day mortality following hospital discharge, and to evaluate the association between antipsychotic medication prescribing and the subsequent prescriptions of benzodiazepines and opioids in-hospital and up to 1-year post-hospital discharge.
Methods
Study design
This multi-center, propensity-score matched retrospective cohort study is reported according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement [15] (S1 File).
Study setting & population
Adult patients at least 18 years of age admitted to one of four medical-surgical ICUs with electronic medical records in Calgary, Alberta, Canada (catchment population 1.5 million) from January 1, 2014 to June 30, 2016 were included in the study cohort. Patients were excluded if they had an antipsychotic medication prescription three months prior to hospital admission, length of ICU admission of <24 hours, ICU admission diagnosis of overdose, or if they died in the ICU or in hospital following ICU admission. Patients were further excluded if patient data did not link to a Discharge Abstract Database (DAD) admission or if they were non-Alberta residents. If patients had more than one admission to the ICU during the study period, only the first admission with a length of stay >24 hours was included. The primary study cohort was comprised of patients who survived to hospital discharge with follow-up on antipsychotic medication prescriptions up to 1-year following hospital discharge.
The included medical-surgical ICUs were closed units staffed by specialty accredited intensive care physicians that provide invasive mechanical ventilation, vasopressor medications, and invasive monitoring. Data for antipsychotic prescriptions were available from October 1, 2013 to June 30, 2017. Opioid and benzodiazepine prescriptions were available from January 1, 2014 to June 30, 2017.
Data sources
We used data from seven databases as sources for this study, which have previously been utilized for research purposes [16–19]. eCritical Alberta is integrated within a bedside electronic medical record (MetaVision) that collects clinical and demographic data for ICU admitted patients in Alberta [17]. The DAD collects hospital outcome and diagnosis data on all hospital patients via diagnostic codes based on the International Classification of Disease, 10th Revision, Canadian Enhancement [19]. Vital Statistics Database captures mortality data following ICU/hospital admission. The National Ambulatory Care Reporting System reports data for all emergency department visits. Sunrise Clinical Manager (SCM) is an electronic health record that captures computerized physician order entry and flowsheet documentation capturing ICU and hospital drug orders and patient drug administration [20]. The Pharmaceutical Information Network (PIN) is a web-enabled application within the Alberta Electronic Health Record that provides outpatient medication dispensing data and prescription information (i.e., quantity and compound elements) from community prescribers [21]. Data were linked deterministically via a unique provincial healthcare number. Authors did not have access to information that could identify participants during or after data collection. Included medications were identified and linked via Anatomical Therapeutic Chemical classifications.
Exposure measures
The primary exposure was the administration of ≥1 dose of antipsychotic medication while the patient was admitted in the ICU. Included antipsychotic medications were those medications that have been previously reported in the literature to be commonly administered and based on clinical experience [7,8,22,23]. Antipsychotic medications included were haloperidol, quetiapine, risperidone, olanzapine, and methotrimeprazine with all formulations considered. All other antipsychotic medications were excluded as the listed antipsychotics represent the available formulary medications at included centres and are the most common clinically utilized antipsychotics reported in the critical care literature [7,8,11,22]. Antipsychotic medication continuation at hospital discharge was defined as those patients initially admitted to ICU who survived to hospital discharge, had administration of ≥1 dose of an antipsychotic medication in the ICU and hospital ward and additionally filled an outpatient prescription for an antipsychotic medication anytime within 1-year following hospital discharge.
Outcome measures
The primary outcome was health resource utilization defined as 72-hour ICU readmission, 30-day hospital readmission, 30-day emergency room visitation, and 30-day mortality. ICU readmission was defined as readmission to ICU within 72-hours of transfer from ICU within the same hospitalization. Hospital readmission was defined as subsequent admission to hospital within 30-days of discharge from hospital for the index admission. Emergency room visitation was defined as subsequent visitation to the emergency room within 30-days following hospital discharge. Mortality was defined as death from any cause up to 30-days following hospital discharge.
Secondary outcomes included co-prescription of benzodiazepines and/or opioids during hospitalization (i.e., ICU or hospital ward) in addition to antipsychotic medication during hospitalization (i.e., ICU and hospital ward), and outpatient prescription of benzodiazepines and/or opioids up to 1-year post-hospital discharge. Prescription of a benzodiazepine and/or opioid medication in-hospital was defined as administration of ≥1 dose of any benzodiazepine and/or opioid medication during hospitalization either in the ICU or hospital ward. New outpatient prescription of psychoactive medications was defined as filling of a prescription for a pre-specified antipsychotic medication as an outpatient within 1-year following hospital discharge and an opioid or benzodiazepine medication within 1-year following hospital discharge. Included opioid drugs were hydromorphone, morphine, fentanyl, oxycodone, and codeine. Included benzodiazepine drugs were lorazepam, diazepam, temazepam, clonazepam, alprazolam, and triazolam.
Covariate measures
Covariate measure were determined a priori based on clinical experience and previous studies [7,8,19,24,25]. Patient factors included age, sex, presence of each individual comorbidity from the Charlson Comorbidity Index (diabetes, chronic lung disease, chronic kidney disease, liver disease, cancer, chronic heart or peripheral vascular disease, neurological disease), illness severity upon ICU admission (SOFA score on admission), admission reason (medical, surgical, neurological, trauma), use of invasive mechanical ventilation, use of vasoactive medications, use of continuous renal replacement therapy, opioid use in ICU, benzodiazepine use in ICU, and ICU length of stay category (<3, 3 to <7, ≥7 days).
Statistical analysis
A propensity-score matched cohort of patients who received or did not receive an antipsychotic medication during hospitalization was created. Propensity-scores were based on age, sex, admission reason (medical, surgical, neurological, trauma), presence/absence of each individual Charlson comorbidity (diabetes, chronic lung disease, chronic kidney disease, liver disease, cancer, chronic heart or peripheral vascular disease, neurological disease) [26], admission APACHE II score, use of invasive mechanical ventilation (yes/no), use of non-invasive mechanical ventilation (yes/no), use of vasoactive medications (yes/no), use of continuous renal replacement therapy (yes/no), use of opioids (yes/no), use of benzodiazepines (yes/no) and ICU length of stay category (<3, 3 to <7, ≥7 days). The cohort was based on 1:1 nearest neighbor matching without replacement using the logit of the propensity-score and specified caliper width equal to 0.05 of the standard deviation of the logit of the propensity-score.
Patient characteristics were summarized using median with interquartile range (IQR) and frequency with percent, as appropriate. Primary outcomes were analyzed using mixed effects logistic regression accounting for clustering of patients within ICU sites. Among the overall cohort, mixed effects logistic regression models were adjusted for the same variables that were included in the propensity-score. Secondary outcomes were also analyzed using mixed effects logistic regression and adjusted for the same variables included in the propensity-score. A two-sided p-value of <0.05 was used to define statistical significance. Analyses were completed using R (version 4.0.0). Propensity-score matching was completed using the R package “MatchIt” (version 3.0.2) and mixed effects logistic regression models were done using the R package “lme4” (version 1.1–23) [27].
Results
Study population
There were 6,050 eligible patients admitted to one of four medical-surgical ICUs with at least one ICU admission between January 1, 2014 and June 30, 2016. After exclusion of ineligible patients, the overall study cohort for analysis consisted of 3,506 patients who survived to hospital discharge. (Fig 1) Due to missing admission reason for one patient who received antipsychotic medications and eight patients who did not receive antipsychotic medications from the overall cohort, propensity-scores were calculated for 988 patients who received antipsychotic medications in the ICU (99.9%) and 2,509 patients who did not receive antipsychotic medications in the ICU (99.7%). Of those patients with complete data, 294 patients who received antipsychotic medications in ICU and 1,815 patients who did not receive antipsychotic medications in ICU could not be matched with outcome data within the specified caliper width equal to 0.05. This resulted in 1,388 patients included in the matched cohort (Table 1). An additional 160 patients were excluded from the secondary analysis as they only received an antipsychotic medication on the hospital ward (and not in ICU). Baseline patient and hospital level characteristics of all patients admitted to the ICU during this study period can be found in S1 Table.
Baseline characteristics were balanced in the propensity-score matched cohort (Table 1). Most patients in the matched cohort were admitted via the emergency department for medical admission reasons. The median APACHE II score of those who received antipsychotic medications in the ICU was 20 [IQR 15–25] and those who did not receive antipsychotic medications was 20 [IQR 14–25]. The median age of patients in the propensity-score matched cohort in both patients who received antipsychotic medications and those who did not was 60 years [IQR 48–71], [IQR 49–69]. Median ICU length of stay was similar between those patients who did receive antipsychotic medications in ICU (7.8 days [IQR 4.9–13.2]) and those who did not receive antipsychotic medications in ICU (7.4 days [IQR 4.2–10.5]). Median length of hospital stay was similar for those patients who did receive antipsychotic medications in ICU (24.3 days [IQR 13.6–51.2]) compared to those patients who did not receive antipsychotic medications in ICU (20.5 days [IQR 10.7–46.1]).
Medication administration outcomes
The proportion of ICU patients in the overall cohort of those patients that survived their ICU and hospital stay and received at least one dose of antipsychotic medication during their ICU admission was 989 (28.2%). Among those who received antipsychotics in the matched cohort, quetiapine (542 (78.1%)), and haloperidol (291 (41.9%)) were the most common prescribed antipsychotics to patients in the ICU. Some patients prescribed antipsychotics were prescribed multiple antipsychotic types (222/694 (32.0%)). Of the ICU patients that received an antipsychotic medication in the ICU and survived to hospital discharge, 132 (21.0%) patients were prescribed an antipsychotic medication at hospital discharge. The most common antipsychotic medications continued at hospital discharge were quetiapine (91 (14.5%)) and olanzapine (32 (5.1%)) (Table 1).
In ICU patients that received an ongoing antipsychotic medication during their hospitalization, there was an increased odds of the co-prescription of benzodiazepines (adjusted OR 5.29 [95%CI 4.38–6.39]) as well as the co-prescription of opioids (adjusted OR 3.18 [95%CI 2.55–3.96]) during their hospitalization compared to those who did not receive antipsychotic medications during their hospitalization. (Fig 2A) Of the ICU patients that received an antipsychotic medication in the ICU that was prescribed following hospital discharge, there was an increased odds of patients receiving new concurrent prescriptions for a benzodiazepine medication (adjusted OR 1.61 [95%CI 1.19–2.19]) or an opioid medication (adjusted OR 1.82 [95%CI 1.38–2.40]) up to one-year following hospital discharge (Fig 2B).
Mixed effects logistic regression analysis of co-prescription of opioids or benzodiazepines in (A) hospitalized patientsa and (B) outpatients surviving hospital who received antipsychotic medications during ICU and on hospital ward compared to those who did not receive antipsychotic medications. *Adjusted for sex, age, presence/absence of each of the individual Charlson comorbidities (diabetes, chronic lung disease, chronic kidney disease, liver disease, cancer, chronic heart or peripheral vascular disease, neurological disease), APACHE I score on admission, admission reason (medical, surgical, neurological, trauma), invasive ventilation, non-invasive ventilation, vasoactive medications, continuous renal replacement therapy. aFor those who received antipsychotics, this includes patients who received both antipsychotic and benzodiazepine or opioid in ICU or patients who received both antipsychotic and benzodiazepine or opioid in hospital.
Health resource utilization outcomes
There was no association between ICU patients that received an antipsychotic in the ICU or the ward and 72-hour ICU readmission and 30-day emergency room visitation (Table 2). There was an increased risk of 30-day hospital readmission in the overall cohort of ICU patients that received antipsychotic medication in the ICU or ward compared to ICU patients who did not receive antipsychotic medications in the ICU or ward (adjusted OR 1.28 [95%CI 1.04–1.59). This relationship was not significant in the propensity-score matched cohort (adjusted OR 1.18 [95%CI 0.92–1.52]).
Mortality outcomes
There was no association between 30-day mortality following hospital discharge in those ICU patients who received an antipsychotic medication in ICU continued to hospital discharge compared to those ICU patients who did not receive an antipsychotic medication in ICU (adjusted OR 1.28 [95%CI 0.58–2.84]) (Table 2).
Discussion
In this multi-center propensity-matched retrospective study, we identified that one in five antipsychotic naïve ICU patients who received an antipsychotic medication in ICU were subsequently prescribed an antipsychotic medication at hospital discharge. Being prescribed an antipsychotic medication during hospitalization was associated with both an increased odds of being co-prescribed a benzodiazepine and opioid medication during hospitalization and in the 1-year following a patient’s hospital discharge.
Our results confirm and expand on previous literature describing the prescribing practices of antipsychotics during ICU admission and following hospital discharge in patients who experience critical illness [7,8,22,28,29]. Similar to previously reported results, our study found that quetiapine and olanzapine were the most common antipsychotic medications continued at hospital discharge in this ICU patient cohort [7,8]. This prescribing practice may reflect a trend toward the more common use of atypical antipsychotics for their sedating histaminergic effects for sleep and restlessness following resolution of delirium in an attempt to avoid prescribing benzodiazepines [30–32]. Additionally, benzodiazepines may be co-prescribed with opioids to help manage symptoms related to chronic pain and anxiety experienced following critical illness. A recent publication from Olafson et al. [33] examined the long-term use of ongoing psychotropic medications in a 5-year pre- and post-hospitalization period of 49,439 ICU patients compared to non-ICU hospitalized patients and identified an increased association of psychotropic medication use in the five years after ICU admission. A higher proportion of ICU patients in this cohort not only received antipsychotic medications but also antidepressants, anxiolytics, and sedative-hypnotics compared to their control group of non-ICU patients [33]. In contrast to our findings, the ICU patients in this cohort had a lower prevalence of long-term antipsychotic medication use following hospital discharge. This may be an underestimation of the association as their comparator group of non-ICU hospitalizations had a higher proportion of patients with underlying mental health disorders potentially requiring ongoing antipsychotic medications and may explain the observed differences.
To the best of our knowledge, our study is the first study to evaluate the independent association of continued antipsychotic prescribing in critically ill patients to hospital discharge on health resource utilization outcomes. We did not find an association between 72-hour ICU readmission, 30-day hospital readmission, 30-day emergency room visitation, and 30-day mortality in those ICU patients who received an antipsychotic medication in ICU continued to hospital discharge compared to those ICU patients who did not receive an antipsychotic medication in ICU. Our findings suggest that despite an increased association between ongoing antipsychotic medication use and benzodiazepine and opioid medication prescriptions, this does not translate into increased short-term healthcare resource utilization costs. However, these results do not account for potential increased ambulatory outpatient utilization which is known to occur in critically ill patients post-hospital discharge [34–36].
Our findings identify a novel and concerning association between antipsychotic medication use following hospital discharge in patients who experience critical illness and subsequent benzodiazepine and opioid prescription in the 1-year following hospital discharge potentially reflecting an ICU patient population at risk of long-term psychoactive polypharmacy following hospital discharge [10,11,37]. The question remains whether this increased risk of psychoactive medication prescription in the 1-year following hospital discharge further represents an association with poor patient functional and quality of life outcomes [38,39]. It is possible that patients who receive antipsychotic medications during their ICU admission may be at higher risk of frailty following hospital discharge and likewise may have worse physical and cognitive health related quality of life and greater functional dependence leading to psychoactive medication use [38–40]. Further evaluation of the association between this patient population and patient-centered functional outcomes are needed to better understand the contribution of frailty and chronic pain to these findings. This patient population may represent individuals particularly at risk of polypharmacy that may benefit from outpatient medication reconciliation by clinician experts in the post-ICU setting [38,39,41,42].
Strengths and limitations
Our retrospective study has several strengths including the large sample size with complete data on pre- and post-hospital medication prescribing up to 3-months prior to hospitalization and 1-year following hospital discharge. The use of propensity-score matched analysis controls for many patient-level and hospital-level confounders is also a strength. Previous evaluations of common demographic and clinical variables suggest good agreement between documentation in the medical record and the integrated critical care electronic medical record system, TRACER, used for data collection [43]. Despite using propensity-score matched analysis, residual confounding remains possible for factors associated with the risk of being prescribed a benzodiazepine or opioid medication that were not included as a variable such as new psychiatric diagnoses acquired because of ICU admission. Our study also has limitations. We aimed to exclude patients with appropriate clinical indications for antipsychotic medication prescriptions by excluding those patients with pre-hospital antipsychotic medication prescriptions 3-months prior to hospitalization and those patients admitted for drug overdoses as a surrogate of possible underlying mental health disorders. It is possible that evaluating antipsychotic prescriptions 3-months prior to hospitalization may not be a sufficient timeframe to exclude all patients that utilize antipsychotics for psychiatric illness clinical indications. We were unable to exclude all patients admitted for a primary psychiatric reason nor determine the proportion of patients that were appropriately prescribed antipsychotics, benzodiazepines, or opioids. Although this would potentially overrepresent the relationship between antipsychotic and benzodiazepine or opioid prescribing, the proportion of patients admitted for a primary psychiatric diagnosis missed by our exclusion criteria is expected to be small. Future studies may consider excluding patients with previous inpatient psychiatric hospitalizations or psychiatric illness diagnosis codes within their medical record as an additional strategy to identify patients that may be admitted to the ICU for a primary psychiatric diagnosis. Additionally, it was not possible to accurately discern the clinical indication for the prescription of antipsychotics, opioids, and benzodiazepines in-hospital or in the outpatient setting. Thus, there may be multifactorial indications for which these medications are being prescribed to patients during and following hospitalization. This remains an important area of future investigation to better guide clinical experts completing outpatient medication reconciliation. Our results are generalizable to an ICU patient population receiving care in a universal healthcare system with established hospital electronic medical record systems and accessible ambulatory care pathways. Generalizability may be limited in private or mixed public and private healthcare systems as well as those healthcare systems without established mechanisms for continuity of care from hospital discharge to the outpatient environment.
Conclusion
Among ICU patients surviving to hospital discharge who continue new antipsychotic medication prescriptions at hospital discharge, there was an association with new additional prescriptions of benzodiazepines and opioids in-hospital and up to 1-year following hospital discharge. There was no association between health resource utilization or 30-day mortality following hospital discharge and ongoing antipsychotic medication use at hospital discharge in this patient cohort. This ICU patient population may benefit from additional medication reconciliation prior to or following hospital discharge.
Supporting information
S1 Table. Patient and hospital characteristics among all patients admitted to ICU during study period.
https://doi.org/10.1371/journal.pone.0287929.s001
(DOCX)
S1 File. STROBE Statement for cohort studies.
https://doi.org/10.1371/journal.pone.0287929.s002
(DOCX)
References
- 1. Devlin JW, Smithburger P, Kane JM, Fraser GL, Skrobik Y. Intended and Unintended Consequences of Constraining Clinician Prescribing: The Case of Antipsychotics. Crit Care Med. 2016;44(10):1805–7. Epub 2016/09/17. pmid:27635480.
- 2. Girard TD, Exline MC, Carson SS, Hough CL, Rock P, Gong MN, et al. Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness. N Engl J Med. 2018;379(26):2506–16. Epub 2018/10/23. pmid:30346242; PubMed Central PMCID: PMC6364999.
- 3. van den Boogaard M, Slooter AJC, Bruggemann RJM, Schoonhoven L, Beishuizen A, Vermeijden JW, et al. Effect of Haloperidol on Survival Among Critically Ill Adults With a High Risk of Delirium: The REDUCE Randomized Clinical Trial. JAMA. 2018;319(7):680–90. Epub 2018/02/22. pmid:29466591; PubMed Central PMCID: PMC5839284.
- 4. Page VJ, Ely EW, Gates S, Zhao XB, Alce T, Shintani A, et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial. The Lancet Respiratory Medicine. 2013;1(7):515–23. pmid:24461612
- 5. Burry L, Hutton B, Williamson DR, Mehta S, Adhikari NK, Cheng W, et al. Pharmacological interventions for the treatment of delirium in critically ill adults. Cochrane Database Syst Rev. 2019;9:CD011749. Epub 2019/09/04. pmid:31479532; PubMed Central PMCID: PMC6719921.
- 6. Devlin JW, Skrobik Y, Gelinas C, Needham DM, Slooter AJC, Pandharipande PP, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018;46(9):e825–e73. Epub 2018/08/17. pmid:30113379.
- 7. Marshall J, Herzig SJ, Howell MD, Le SH, Mathew C, Kats JS, et al. Antipsychotic utilization in the intensive care unit and in transitions of care. J Crit Care. 2016;33:119–24. Epub 2016/01/29. pmid:26818629; PubMed Central PMCID: PMC4842336.
- 8. Tomichek JE, Stollings JL, Pandharipande PP, Chandrasekhar R, Ely EW, Girard TD. Antipsychotic prescribing patterns during and after critical illness: a prospective cohort study. Crit Care. 2016;20(1):378. Epub 2016/11/25. pmid:27881149; PubMed Central PMCID: PMC5122157.
- 9. Skrobik Y. Insights into Critical Care and Post-ICU Opiate Administration. American Journal of Respiratory and Critical Care Medicine. 2020;202(4):484–6. pmid:32464072
- 10. Loggia G, Attoh-Mensah E, Pothier K, Morello R, Lescure P, Bocca ML, et al. Psychotropic Polypharmacy in Adults 55 Years or Older: A Risk for Impaired Global Cognition, Executive Function, and Mobility. Front Pharmacol. 2019;10:1659. Epub 2020/02/23. pmid:32082159; PubMed Central PMCID: PMC7002919.
- 11. Boncyk CS, Farrin E, Stollings JL, Rumbaugh K, Wilson JE, Marshall M, et al. Pharmacologic Management of Intensive Care Unit Delirium: Clinical Prescribing Practices and Outcomes in More Than 8500 Patient Encounters. Anesth Analg. 2021;133(3):713–22. Epub 2021/01/13. pmid:33433117.
- 12. Kok L, Slooter AJ, Hillegers MH, van Dijk D, Veldhuijzen DS. Benzodiazepine Use and Neuropsychiatric Outcomes in the ICU: A Systematic Review. Crit Care Med. 2018;46(10):1673–80. Epub 2018/07/10. pmid:29985215.
- 13. Pisani MA, Murphy TE, Araujo KL, Slattum P, Van Ness PH, Inouye SK. Benzodiazepine and opioid use and the duration of intensive care unit delirium in an older population. Crit Care Med. 2009;37(1):177–83. Epub 2008/12/04. pmid:19050611; PubMed Central PMCID: PMC2700732.
- 14. Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369(14):1306–16. Epub 2013/10/04. pmid:24088092; PubMed Central PMCID: PMC3922401.
- 15. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453–7. Epub 2007/12/08. pmid:18064739.
- 16. Chiasson TC, Manns BJ, Stelfox HT. An economic evaluation of venous thromboembolism prophylaxis strategies in critically ill trauma patients at risk of bleeding. PLoS Med. 2009;6(6):e1000098. Epub 2009/06/26. pmid:19554085; PubMed Central PMCID: PMC2695771.
- 17. Brundin-Mather R, Soo A, Zuege DJ, Niven DJ, Fiest K, Doig CJ, et al. Secondary EMR data for quality improvement and research: A comparison of manual and electronic data collection from an integrated critical care electronic medical record system. Journal of Critical Care. 2018;47:295–301. pmid:30099330
- 18. Stelfox HT, Soo A, Niven DJ, Fiest KM, Wunsch H, Rowan KM, et al. Assessment of the Safety of Discharging Select Patients Directly Home From the Intensive Care Unit: A Multicenter Population-Based Cohort Study. JAMA Intern Med. 2018;178(10):1390–9. Epub 2018/08/22. pmid:30128550; PubMed Central PMCID: PMC6584269.
- 19. Fiest KM, Soo A, Hee Lee C, Niven DJ, Ely EW, Doig CJ, et al. Long-Term Outcomes in ICU Patients with Delirium: A Population-based Cohort Study. Am J Respir Crit Care Med. 2021;204(4):412–20. Epub 2021/04/07. pmid:33823122.
- 20. Lee S, Xu Y, AG DAS, Martin EA, Doktorchik C, Zhang Z, et al. Unlocking the Potential of Electronic Health Records for Health Research. Int J Popul Data Sci. 2020;5(1):1123. Epub 2020/09/17. pmid:32935049; PubMed Central PMCID: PMC7473254 relevant to this article.
- 21. Garies S, Youngson E, Soos B, Forst B, Duerksen K, Manca D, et al. Primary care EMR and administrative data linkage in Alberta, Canada: describing the suitability for hypertension surveillance. BMJ Health Care Inform. 2020;27(3). Epub 2020/08/25. pmid:32830109; PubMed Central PMCID: PMC7445345.
- 22. Levine AR, Lemieux SM, D’Aquino D, Tenney A, Pisani M, Ali S. Risk Factors for Continuation of Atypical Antipsychotics at Hospital Discharge in Two Intensive Care Unit Cohorts. Clinical Medicine Insights: Psychiatry. 2019;10:1179557319863813.
- 23. Burry LD, Williamson DR, Mehta S, Perreault MM, Mantas I, Mallick R, et al. Delirium and exposure to psychoactive medications in critically ill adults: A multi-centre observational study. J Crit Care. 2017;42:268–74. Epub 2017/08/15. pmid:28806561.
- 24. Quach S, Hennessy DA, Faris P, Fong A, Quan H, Doig C. A comparison between the APACHE II and Charlson Index Score for predicting hospital mortality in critically ill patients. BMC Health Serv Res. 2009;9:129. Epub 2009/08/01. pmid:19643010; PubMed Central PMCID: PMC2731744.
- 25. Soo A, Zuege DJ, Fick GH, Niven DJ, Berthiaume LR, Stelfox HT, et al. Describing organ dysfunction in the intensive care unit: a cohort study of 20,000 patients. Crit Care. 2019;23(1):186. Epub 2019/05/28. pmid:31122276; PubMed Central PMCID: PMC6533687.
- 26.
Charlson Me Fau—Pompei P, Pompei P Fau—Ales KL, Ales Kl Fau—MacKenzie CR, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. (0021–9681 (Print)).
- 27. Ho D, Imai K, King G, Stuart EA. MatchIt: Nonparametric Preprocessing for Parametric Causal Inference. 2011. 2011;42(8):28. Epub 2011-06-14.
- 28. Jasiak KD, Middleton EA, Camamo JM, Erstad BL, Snyder LS, Huckleberry YC. Evaluation of discontinuation of atypical antipsychotics prescribed for ICU delirium. J Pharm Pract. 2013;26(3):253–6. Epub 2012/11/28. pmid:23184410.
- 29. Lambert J, Vermassen J, Fierens J, Peperstraete H, Petrovic M, Colpaert K. Discharge from hospital with newly administered antipsychotics after intensive care unit delirium—Incidence and contributing factors. J Crit Care. 2021;61:162–7. Epub 2020/11/11. pmid:33171333.
- 30. Cohrs S, Rodenbeck A, Guan Z, Pohlmann K, Jordan W, Meier A, et al. Sleep-promoting properties of quetiapine in healthy subjects. Psychopharmacology (Berl). 2004;174(3):421–9. Epub 2004/03/19. pmid:15029469.
- 31. Pisani MA, Friese RS, Gehlbach BK, Schwab RJ, Weinhouse GL, Jones SF. Sleep in the intensive care unit. Am J Respir Crit Care Med. 2015;191(7):731–8. Epub 2015/01/17. pmid:25594808; PubMed Central PMCID: PMC5447310.
- 32. Hamidi A, Roberts RJ, Weinhouse GL, Szumita PM, Degrado JR, Dube KM, et al. Characterization of Nocturnal Neuroactive Medication Use and Related Sleep Documentation in Critically Ill Adults. Crit Care Explor. 2021;3(3):e0367. Epub 2021/04/01. pmid:33786443; PubMed Central PMCID: PMC7994043.
- 33. Olafson K, Marrie RA, Bolton JM, Bernstein CN, Bienvenu OJ, Kredentser MS, et al. The 5-year pre- and post-hospitalization treated prevalence of mental disorders and psychotropic medication use in critically ill patients: a Canadian population-based study. Intensive Care Med. 2021. Epub 2021/09/09. pmid:34495357.
- 34. Hirshberg EL, Wilson EL, Stanfield V, Kuttler KG, Majercik S, Beesley SJ, et al. Impact of Critical Illness on Resource Utilization: A Comparison of Use in the Year Before and After ICU Admission. Crit Care Med. 2019;47(11):1497–504. Epub 2019/09/14. pmid:31517693; PubMed Central PMCID: PMC6798747.
- 35. Brandstetter S, Dodoo-Schittko F, Brandl M, Blecha S, Bein T, Apfelbacher C, et al. Ambulatory and stationary healthcare use in survivors of ARDS during the first year after discharge from ICU: findings from the DACAPO cohort. Ann Intensive Care. 2019;9(1):70. Epub 2019/06/16. pmid:31201576; PubMed Central PMCID: PMC6570725.
- 36. Jouan Y, Grammatico-Guillon L, Teixera N, Hassen-Khodja C, Gaborit C, Salmon-Gandonniere C, et al. Healthcare trajectories before and after critical illness: population-based insight on diverse patients clusters. Ann Intensive Care. 2019;9(1):126. Epub 2019/11/11. pmid:31707487; PubMed Central PMCID: PMC6842359.
- 37. Morandi A, Vasilevskis E, Pandharipande PP, Girard TD, Solberg LM, Neal EB, et al. Inappropriate medication prescriptions in elderly adults surviving an intensive care unit hospitalization. J Am Geriatr Soc. 2013;61(7):1128–34. Epub 2013/07/17. pmid:23855843; PubMed Central PMCID: PMC3713508.
- 38. Brummel NE, Bell SP, Girard TD, Pandharipande PP, Jackson JC, Morandi A, et al. Frailty and Subsequent Disability and Mortality among Patients with Critical Illness. Am J Respir Crit Care Med. 2017;196(1):64–72. Epub 2016/12/07. pmid:27922747; PubMed Central PMCID: PMC5519959.
- 39. Bagshaw SM, Stelfox HT, Johnson JA, McDermid RC, Rolfson DB, Tsuyuki RT, et al. Long-term association between frailty and health-related quality of life among survivors of critical illness: a prospective multicenter cohort study. Crit Care Med. 2015;43(5):973–82. Epub 2015/02/11. pmid:25668751.
- 40. Geen O, Rochwerg B, Wang XM. Optimizing care for critically ill older adults. CMAJ. 2021;193(39):E1525–E33. Epub 2021/10/06. pmid:34607846.
- 41. Battle CE, Lovett S, Hutchings H. Chronic pain in survivors of critical illness: a retrospective analysis of incidence and risk factors. Critical care (London, England). 2013;17(3):R101-R. pmid:23718685.
- 42. Stollings JL, Bloom SL, Wang L, Ely EW, Jackson JC, Sevin CM. Critical Care Pharmacists and Medication Management in an ICU Recovery Center. Ann Pharmacother. 2018;52(8):713–23. Epub 2018/02/18. pmid:29457491.
- 43. Brundin-Mather R, Soo A, Zuege DJ, Niven DJ, Fiest K, Doig CJ, et al. Secondary EMR data for quality improvement and research: A comparison of manual and electronic data collection from an integrated critical care electronic medical record system. J Crit Care. 2018;47:295–301. Epub 20180722. pmid:30099330.