Egberts, Toine C G

Lalmohamed, Arief

Slooter, Arjen J C

van Diem-Zaal, Irene J

van Gelder, Thomas G

Utrecht University Repository

Intensive Care Med (2022) 48:762–764https://doi.org/10.1007/s00134-022-06725-xLETTERSystemic glucocorticoid use during ICU admission and symptoms of posttraumatic stress disorder in intensive care unit survivorsThomas G. van Gelder1* , Arief Lalmohamed1,2, Irene J. van Diem‑Zaal3,4, Toine C. G. Egberts1,2 and Arjen J. C. Slooter3,5© 2022 Springer‑Verlag GmbH Germany, part of Springer NatureDear Editor,Intensive care unit (ICU) survivors are at risk of develop-ing mental health problems, such as symptoms of post-traumatic stress disorder (PTSD), anxiety and depression [1–3]. Glucocorticoid use has been proposed to diminish the risk of these problems, but evidence remains conflict-ing [4, 5]. This study investigated the association between systemic glucocorticoid use during ICU admission and the incidence of PTSD symptoms in a large population of ICU survivors.This is a single-center, retrospective cohort study with 1-year follow-up using prospectively collected data. The institution’s Medical Research Ethics Committee waived the need for informed consent. Patients alive 1 year after ICU discharge, aged ≥ 18  years and admitted to the ICU > 48 h between January 2011 and February 2020 were included. The cumulative glucocorticoid dose dur-ing ICU stay was calculated per subject by (1) obtaining all glucocorticoid administrations (registered in the ICU’s Patient Data Management System), (2) converting oral doses to intravenous equivalents, (3) converting differ-ent glucocorticoids to prednisolone equivalents and (4) summing these over the period of ICU admission. The primary outcome was PTSD symptoms 1 year after ICU discharge, defined as an Impact of Event Scale (revised) score of ≥ 35 or a mean score of > 1.6, respectively. Secondary outcomes included symptoms of anxiety and depression as measured by the Hospital Anxiety and Depression Scale (sum score of ≥ 8) and Health-Related Quality of Life (HRQoL) as measured with the EuroQol-5D 1 year after discharge. Results were adjusted for age, sex, ICU length of stay, type of admission, referral by a pulmonologist (yes/no), Simplified Acute Physiology Score (SAPS) II, mechanical ventilation, delirium dur-ing ICU stay, modified Sequential Organ Failure Assess-ment (mSOFA) score on day of admission, the difference between the mSOFA score on day of admission and on day 4, cumulative midazolam dosage, cumulative propo-fol dosage and outpatient use of glucocorticoids / antide-pressants / antipsychotics / anxiolytics using a propensity score approach.In total, 1737 subjects were included of whom 690 (40%) were systemically exposed to glucocorticoids. Subjects who received glucocorticoids were more often female, had a longer ICU length of stay, were more often admitted to the ICU after acute surgery and had a higher mean SAPS II. 187 (11%) Subjects developed PTSD symptoms, 313 (18%) developed symptoms of anxi-ety and 303 (17%) developed symptoms of depression. Table  1 shows the effect of glucocorticoids on the risk of symptoms of PTSD, anxiety and depression. Adjusted logistic regression analysis showed no beneficial effect on developing PTSD symptoms (adjusted odds ratio (aOR) 0.99, 95% confidence interval (CI) 0.68–1.45) with gluco-corticoid use (n = 81; 12%) versus non-use (n = 106; 11%). Glucocorticoid use was not associated with a decreased incidence of symptoms of anxiety (aOR 0.89, 95% CI 0.65–1.21), symptoms of depression (aOR 0.81, 95% CI *Correspondence:  t.g.vangelder‑2@umcutrecht.nl 1 Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht University, PO Box 85500, 3508 GA Utrecht, The NetherlandsFull author information is available at the end of the article7630.59–1.10) or change in HRQoL (adj. linear regression; 0.027 increase in utility value, 95% CI − 0.003–0.057).Strengths of this study include the large sample size, in particular in the field of mental health disorders post ICU. Also, the mixed ICU population enhances general-izability of the results.The main limitation of this study was potential con-founding by indication, as certain diseases might call for treatment with glucocorticoids and may carry a greater risk of developing mental health problems. Also, no data were available on psychological support received by sub-jects during follow-up, which might have led to a smaller chance of finding a relationship between exposure and outcome [6].In conclusion, this study suggests no potential protec-tive effect of systemic exposure to glucocorticoids during ICU admission on the development of PTSD symptoms, nor on symptoms of anxiety and depression or lower HRQoL in ICU survivors. This study does not war-rant a randomized controlled trial on glucocorticoids to decrease PTSD symptoms in ICU survivors.Supplementary InformationThe online version contains supplementary material available at https:// doi. org/ 10. 1007/ s00134‑ 022‑ 06725‑x.Author details1 Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht University, PO Box 85500, 3508 GA Utrecht, The Netherlands. 2 Division of Phar‑macoepidemiology and Clinical Pharmacology, Utrecht Institute for Phar‑maceutical Sciences, Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands. 3 Department of Intensive Care Medicine and UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, PO Box 85500, 3508 GA Utrecht, The Netherlands. 4 Department of Intensive Care Medicine, Radboud Institute of Health Science, Radboud University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands. 5 Department of Neurology, UZ Brussel and Vrije Universiteit Brussel, Brussels, Belgium. Author contributionsTGVG Methodology, Formal analysis, Data Curation, Writing—Original Draft, Visualization. AL Methodology, Writing—Review and Editing, Supervision. IJVDZ Methodology, Writing—Review and Editing, Supervision. TCGE Concep‑tualization, Writing—Review and Editing, Supervision. AJCS Conceptualization, Resources, Writing—Review and Editing, Supervision.FundingThis research did not receive any specific grant from funding agencies in the public, commercial, or not‑for‑profit sectors.DeclarationsTable 1 Primary and secondary endpointsResults after multiple imputationPTSD posttraumatic stress disorder, OR odds ratio, CI confidence interval, IQR interquartile rangea Missing for 95 patients (5%)b Missing for 49 patients (3%)c Missing for 42 patients (2%)d Missing for 67 patients (4%)e Adjusted for age, sex, Intensive Care Unit (ICU) length of stay, type of admission, referral by a pulmonologist (yes/no), Simplified Acute Physiology Score II, mechanical ventilation, delirium during ICU stay, modified Sequential Organ Failure Assessment (mSOFA) score on day of admission, difference between mSOFA on day of admission and on day 4, cumulative midazolam dosage, cumulative propofol dosage and outpatient use of glucocorticoids / antidepressants / antipsychotics / anxiolyticsPTSD symptoms, n (%)aCrude OR (95% CI) Adjusted OR (95% CI)eGlucocorticoid use 81 (12) 1.17 (0.86–1.60) 0.99 (0.68–1.45)No glucocorticoid use 106 (11)Symptoms of anxiety,  n (%)bCrude OR (95% CI) Adj. OR (95% CI)eGlucocorticoid use 121 (18) 0.95 (0.74–1.23) 0.89 (0.65–1.21)No glucocorticoid use 192 (19)Symptoms of depression, n (%)cCrude OR (95% CI) Adj. OR (95% CI)eGlucocorticoid use 106 (16) 0.79 (0.61–1.03) 0.81 (0.59–1.10)No glucocorticoid use 197 (19)EQ-5D Utility score,  median (IQR)dChange in utility value (crude) Change in utility value (adjusted)eGlucocorticoid use 0.811 (0.687–1) − 0.003 (− 0.028–0.022) 0.027 (− 0.003–0.057)No glucocorticoid use 0.811 (0.687–1)764Conflicts of interestNone.Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims in pub‑lished maps and institutional affiliations.Accepted: 2 May 2022Published: 13 May 2022References 1. Parker AM, Sricharoenchai T, Raparla S, Schneck KW, Bienvenu OJ, Need‑ham DM (2015) Posttraumatic stress disorder in critical illness survivors: a meta analysis. Crit Care Med 43(5):1121–1129 2. Nikayin S, Rabiee A, Hashem MD, Huang M, Bienvenu OJ, Turnbull AE et al (2016) Anxiety symptoms in survivors of critical illness: a systematic review and meta‑analysis. Gen Hosp Psychiatry 43:23–29 3. Rabiee A, Nikayin S, Hashem MD, Huang M, Dinglas VD, Bienvenu OJ et al (2016) Depressive symptoms after critical illness: a systematic review and meta‑analysis. Crit Care Med 44(9):1744–1753 4. Schelling G, Roozendaal B, Quervain DJ‑F (2004) Can posttraumatic stress disorder be prevented with glucocorticoids? Ann N Y Acad Sci 1032(1):158–166 5. Kok L, Hillegers MH, Veldhuijzen DS, Cornelisse S, Nierich AP, van der Maaten JM et al (2016) The effect of dexamethasone on symptoms of posttraumatic stress disorder and depression after cardiac surgery and intensive care admission. Crit Care Med 44(3):512–520 6. 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Systemic glucocorticoid use during ICU admission and symptoms of posttraumatic stress disorder in intensive care unit survivors

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