ABSTRACT
Purpose
Intensive care unit (ICU) mortality has decreased, highlighting improved patient outcomes. However, other critical factors affect post‐ICU survival, including lasting physical, cognitive, and psychological challenges termed postintensive care syndrome (PICS), encompassing depression, anxiety, and posttraumatic stress disorder (PTSD). The prevalence of these conditions among ICU survivors is high and potentially linked to ICU treatment. This study aims to understand these factors using Taiwan's National Health Insurance Research Database (NHIRD), exploring their impact on mortality and readmission rates post‐ICU discharge.
Methods
The National Health Insurance (NHI) program in Taiwan, implemented in 1995, provides healthcare for nearly all residents. Its research arm, NHIRD, contains comprehensive medical data for nationwide studies. This research focuses on ICU patients with specific conditions from 2010 to 2018, using ICD codes for diagnosis. Statistical analyses include Cox proportional hazard models and logistic regression, aiming to assess the incidence and risks of anxiety/depression/PTSD.
Results
ICU patients showed a higher risk of anxiety/depression/PTSD compared to non‐ICU patients (adjusted HR = 1.17), with similar trends for anxiety and depression. Females, younger patients, those with higher CCI scores, on mechanical ventilators, and more extended hospital stays had increased odds of anxiety/depression/PTSD. ICU patients with anxiety/depression/PTSD faced increased risks of death and re‐admission, especially among older males with comorbidities.
Conclusion
This study discovered higher anxiety and depression rates post‐ICU compared to general ward patients, particularly among younger individuals, females, and those with longer hospital stays. Factors such as higher comorbidity scores and mechanical ventilation use were linked to lower odds. Addressing mental health postdischarge is crucial, especially for at‐risk groups.
Keywords: anxiety, depression, ICU, mortality and readmissions, PTSD
To understand post‐intensive care syndrome (PICS) using Taiwan's National Health Insurance Research Database (NHIRD).
Abbreviations
- aOR
adjusted odds ratio
- CCI
Charlson comorbidity index
- CIs
confidence intervals
- HRs
hazard ratios
- ICD‐9‐CM
International Classification of Diseases, 9th edition, Clinical Modification
- ICD‐10‐CM
International Classification of Diseases, 10th edition, Clinical Modification
- MV
mechanical ventilator
- NHI
National Health Insurance
- NHIRD
National Health Insurance Research Database
- PICS
postintensive care syndrome
- PTSD
posttraumatic stress disorder
- SD
standard deviation
1. Introduction
Mortality among intensive care unit (ICU) patients also decreased, and this decrease became more pronounced over time (Lai et al. 2018; Zimmerman et al. 2012). Reduced ICU mortality is not the only factor affecting outcomes for critically ill patients (Needham et al. 2012). The physical and mental health and long‐term outcomes of post‐ICU survivors are also important. People who survive critical illness often experience lasting physical, cognitive, and psychological challenges, usually called postintensive care syndrome (PICS) (Needham et al. 2012; Jensen et al. 2015; Brown et al. 2019).
PICS includes mental illnesses such as depression, anxiety disorders, and posttraumatic stress disorder (PTSD) (Prince et al. 2018). Depression can be a severe psychological consequence for patients admitted to the ICU and is frequently seen in survivors of critical illness receiving ICU care (Choi et al. 2016). Among critically ill survivors in 26 ICUs in the United Kingdom, the prevalence of depression is as high as 40% (Hatch et al. 2018). Previous systematic reviews have shown that significant PTSD symptoms are present in survivors of severe illness, ranging from 5% to 63%, and that these symptoms are consistently associated with lower health‐related quality of life (Jackson et al. 2007; Davydow, Gifford, et al. 2008; Wade et al. 2013; Griffiths et al. 2007). In particular, there is a potential elevation of around 30% in symptoms of depression, 40% in anxiety, and 60% in PTSD among ICU survivors. ICU treatment might be linked to the emergence of psychological disorders and associated complications (Peris et al. 2011).
The trends in most of these studies suggest that survivors who experienced ICU are at significantly increased risk for psychiatric disorders compared with the nonhospitalized general population rather than relative to other hospitalized cohorts (Sareen et al. 2020). A study in Taiwan also found that the proportion of patients discharged from ICU with mental illness was higher than that of the general population. This result was obtained by comparing patients admitted to ICU from 2000 to 2015 with matched nonhospitalized groups (Peng et al. 2022). Unfortunately, the relationship between emerging depression, anxiety, and PTSD in survivors compared with non‐ICU admissions has not been confirmed, particularly at 1‐year follow‐up after ICU discharge. Prior study methods may not have entirely excluded underlying health conditions, as individuals who were not hospitalized were compared. Depression and anxiety are recognized as factors that elevate the risk of higher mortality rates in the general population (Gilman et al. 2017; Meier et al. 2016). There were limited studies addressing the relationship between depression, anxiety, and readmission rates. One study indicated that prior depression was linked to a higher risk of hospital readmission, whereas past anxiety did not show such an association (Coppler et al. 2023).
Hence, our research aimed to explore the factors linked to depression, anxiety disorders, and PTSD among survivors of ICU treatment, precisely 12 months after their ICU admission (referred to as post‐ICU). We utilized the National Health Insurance Research Database (NHIRD) of Taiwan to assess and compare the risk of depression, anxiety, and PTSD in individuals admitted to the ICU versus those admitted to the general ward. Furthermore, our other objective is to investigate the connection between post‐ICU mental disorders (including depression, anxiety, and PTSD) and both mortality and readmission rates.
2. Material and Methods
2.1. Data Source
In 1995, the National Health Insurance (NHI) program was implemented in Taiwan to provide healthcare to nearly all residents. It aimed to improve the national health and medical care of Taiwan. The NHIRD, which contains data on the insured person's diagnosis of diseases, prescriptions, and inpatient and outpatient visits, is periodically created for nationwide research and provides general demographic and medical data in an encrypted format. The disease code in this database was based on the International Classification of Diseases, 9th and 10th editions, Clinical Modification (ICD‐9‐CM and ICD‐10‐CM). The NHIRD encrypts patient information to protect their privacy and provides researchers with anonymous identification numbers associated with relevant information, including sex, date of birth, medical services received, and prescriptions. Therefore, patient consent is not required to access the NHIRD. The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. This retrospective observational study was approved by the Research Ethics Committee of China Medical University Hospital, Taiwan (CMUH110‐REC1‐038(CR‐3)).
2.2. Study Population
In this study, the case (ICU) cohort consists of patients who were admitted to the ICU during any hospitalization with chronic rheumatic heart disease (ICD‐9‐CM code: 393–398; ICD‐10‐CM code: I05‐I09) or hypertension (ICD‐9‐CM code: 401–405; ICD‐10‐CM code: I10‐15, N26.2) or ischemic heart disease (ICD‐9‐CM code: 410–414; ICD‐10‐CM code: I20‐25) or disease of pulmonary circulation (ICD‐9‐CM code: 415–417; ICD‐10‐CM code: I26‐28, T80.0XXA,T81.718A, T81.72XA, T82.817A, T82.818A) or other forms of heart disease (including arrhythmias, ICD‐9‐CM code: 420–429; ICD‐10‐CM code: I23,I25,I30‐39,I40‐52, I97,R00.1) or diseases of the arteries, arterioles (ICD‐9‐CM code: 440–448; ICD‐10‐CM code I70‐79) or diseases of veins and lymphatic vessels, as well as other circulatory system diseases, and capillaries (ICD‐9‐CM code: 451–459; ICD‐10‐CM code I80‐89, I95, I97.2,I99.8,I99.9,K64,R58) or respiratory diseases (ICD‐9‐CM code: 460–519; ICD‐10‐CM code: J00‐99, M34.81, R09.1, R09.81, R09.82, R91.1, A22.1, A37.91, A48.1, B25.0, B44.0, B44.81) within 2010 and 2018. Those who didn't require admission to the ICU during hospitalization for the above conditions (non‐ICU) were matched to the case cohort by sex, age (in 5‐year intervals), the year of the index date, and measured confounders to find the control cohort. Propensity score matching was used in a 1:1 ratio. The index date of ICU patients was defined as the first date of ICU admission, and that of the controls was defined as the first date of admission. The end date of the follow‐up of ICU patients was defined as the date of the earliest date of the first occurrence of depression/anxiety/PTSD, and that of the controls was defined as death, emigration, or on December 31, 2018, or one year after the index date, whichever occurred first.
The exclusion criteria of this study included patients under 20 years old, diagnosed with depression/anxiety/PTSD before the index date, the index date didn't fall between the initial enrollment date and the end of enrollment date, the follow‐up time less than or equal to 0, and with missing data of gender and age.
2.3. Main Outcome and Covariates
Depression/anxiety/PTSD (depression: ICD‐9‐CM code 296.2, 296.3, 300.4, 309.0, 309.1, 311, ICD‐10‐CM code F32.0‐F32.5, F32.9, F33, F34.1, F43.21/Anxiety: ICD‐9‐CM code 300.0, ICD‐10‐CM code F41/PTSD: ICD‐9‐CM code 309.81, 309.1, ICD‐10‐CM code F43.1) was the primary outcome in our research, and we will also investigate the mentioned diseases separately. If the earliest date of the first occurrence of depression/anxiety/PTSD was between the index date and one year after the index date, we then considered this as having the outcome.
Covariates included age, sex, some related comorbidities, mechanical ventilation (MV), Charlson Comorbidity Index (CCI) score, and length of hospital stay. Comorbidities were as follows: diabetes (ICD‐9‐CM code 250) (ICD_10‐CM code E08‐E13), liver cirrhosis (ICD‐9‐CM code 571) (ICD_10‐CM code K70, K73, K74), COPD (ICD‐9‐CM code 490, 492, 496) (ICD_10‐CM code J41, J42, J43, J44), asthma (ICD‐9‐CM code 493) (ICD_10‐CM code J45), tuberculosis (ICD‐9‐CM code 011, 012, 018) (ICD_10‐CM code A15, A19), AIDS (ICD‐9‐CM code 042, V08) (ICD_10‐CM code B20, Z21), pneumonia (ICD‐9‐CM code 480–487) (ICD_10‐CM code A22.1, A37.91, A48.1, B25.0, B44.0, J10‐J18), stroke (ICD‐9‐CM code 430–438) (ICD_10‐CM code I60‐I69), acute respiratory failure (ICD‐9‐CM code 518.81, 518.82, 518.84) (ICD_10‐CM code J80, J960, J962, J969), septicemia (ICD‐9‐CM code 038, 041.9, 790.7) (ICD_10‐CM code A40, A41, A49.9, B96.89, R65.1, R65.20, R78.81), heart failure (ICD‐9‐CM code 428) (ICD_10‐CM code I50), urinary tract infection (ICD‐9‐CM code 599.0) (ICD_10‐CM code N39.0), shock without documentation of trauma (ICD‐9‐CM code 785.5) (ICD_10‐CM code H49.88, R57, R65.21), autoimmune diseases (ICD‐9‐CM code 710.0‐710.4, 714.0, 714.3) (ICD_10‐CM code M32‐M36), End‐Stage Renal Disease (ICD‐9‐CM code 585) (ICD_10‐CM code N18.5, N18.6), transplantation (ICD‐9‐CM code V42.0, V42.1, V42.6, V42.7, V42.84) (ICD_10‐CM code Z94.0, Z94.1, Z94.2, Z94.4, Z94.82, Z94.83), solid organ cancer (ICD‐9‐CM code 14–18, 191–195) (ICD_10‐CM code C0‐C6, C70‐C76, C7A), hematological cancer (ICD‐9‐CM code 204–208) (ICD_10‐CM code C91‐C95), and ischemic heart diseases (ICD‐9‐CM code 410–414) (ICD_10‐CM code I20‐I25). These comorbidities and MV were defined prior to the end date.
2.4. Statistical Analysis
We presented the categorical data of the study participants as numbers and percentages, and the continuous variables were demonstrated as mean and standard deviation (SD). The incidence rate is the number of events divided by person‐years. The relative risks of developing outcomes in relation to the baseline characteristics (i.e., sex, age) were analyzed and presented as hazard ratios (HRs) and 95% confidence intervals (CIs) through univariate and multivariate Cox proportional hazards models. In addition, we used logistic regression to examine the association between depression/anxiety/PTSD and clinical characteristics. Adjusted models were controlled for sex, age, comorbidities, CCI, MV, and hospital day. The Kaplan–Meier survival curve compared the cumulative incidence between case and control cohorts, and the log‐rank test examined the differences. All statistical analyses were presented using software SAS, version 9.4, and plots were plotted by software R, version 4.0. A significant level was p‐value less than 0.05.
3. Result
3.1. Clinical Characteristics in Patients With and Without ICU
From January 1, 2010 to December 31, 2018, there were a total of 488,176 participants enrolled in this study, with 244,088 people in each cohort. The two groups were remarkably balanced in terms of their baseline demographics/measured confounders. Details of demographic characteristics between the two cohorts are presented in Table 1.
TABLE 1.
Clinical characteristics in patients with and without ICU.
| Variable | ICU, n (%) | p value | |
|---|---|---|---|
| No | Yes | ||
| All | 244,088 | 244,088 | |
| Sex | 0.20 | ||
| Female | 85,404 (35.0) | 85,830 (35.2) | |
| Male | 158,684 (65.0) | 158,258 (64.8) | |
| Age group (year) | 0.00 | ||
| <50 | 26,293 (10.8) | 29,441 (12.1) | |
| 50–64 | 62,809 (25.7) | 63,693 (26.1) | |
| ≥65 | 154,986 (63.5) | 150,954 (61.8) | |
| Age (year) a | 69.2 (0.03) | 68.5 (15.6) | <0.001 |
| DM | 67,310 (27.6) | 67,054 (27.5) | 0.41 |
| ESRD | 5074 (2.08) | 5193 (2.13) | 0.24 |
| Liver cirrhosis | 55,728 (22.8) | 55,906 (22.9) | 0.54 |
| COPD | 65,803 (27.0) | 65,448 (26.8) | 0.25 |
| Asthma | 28,827 (11.8) | 29,029 (11.9) | 0.37 |
| Tuberculosis | 6686 (2.74) | 6755 (2.77) | 0.55 |
| AIDS | 256 (0.10) | 252 (0.10) | 0.86 |
| Autoimmune diseases | 1695 (0.69) | 1720 (0.70) | 0.67 |
| Solid organ cancer | 40,759 (16.7) | 41,816 (17.1) | <0.001 |
| Hematological cancer | 554 (0.23) | 616 (0.25) | 0.07 |
| Transplantation | 337 (0.14) | 335 (0.14) | 0.94 |
| Ischemic heart diseases | 105,314 (43.2) | 93,933 (38.5) | <0.001 |
| Pneumonia | 81,347 (33.3) | 82,777 (33.9) | <0.001 |
| Stroke | 79,072 (32.4) | 77,253 (31.7) | <0.001 |
| Acute respiratory failure | 13,476 (5.52) | 15,669 (6.42) | <0.001 |
| Septicemia | 37,432 (15.3) | 38,820 (15.9) | <0.001 |
| Heart failure | 36,141 (14.8) | 35,997 (14.8) | 0.56 |
| Urinary tract infection | 80,054 (32.8) | 81,429 (33.4) | <0.001 |
| Shock without documentation of trauma | 12,415 (5.09) | 13,617 (5.58) | <0.001 |
| CCI | <0.001 | ||
| 0 | 51,941 (21.3) | 56,045 (23.0) | |
| 1 | 77,762 (31.9) | 72,535 (29.7) | |
| 2 | 52,821 (21.6) | 52,787 (21.6) | |
| 3+ | 61,564 (25.2) | 62,721 (25.7) | |
| Mechanical ventilator | 34,620 (14.2) | 39,487 (16.2) | <0.001 |
| Hospital day group | <0.001 | ||
| 1–3 | 55,260 (22.6) | 58,528 (24.0) | |
| 4–6 | 62,018 (25.4) | 60,258 (24.7) | |
| 7–13 | 76,762 (31.5) | 73,450 (30.1) | |
| 14+ | 50,048 (20.5) | 51,852 (21.2) | |
| Hospital day | 10.2 (25.1) | 10.1 (11.1) | 0.01 |
| Follow‐up time from ICU to mental disorders onset (year) a | 0.87 (0.29) | 0.82 (0.35) | <0.001 |
Note: Chi‐square test.
t‐test.
3.2. Risk of Depression/Anxiety/PTSD Associated With ICU
According to Table 2, we calculated the risk of depression/anxiety/PTSD associated with ICU. A total of 212,281 person‐years and 200,649 person‐years were followed up in the ICU cohort and non‐ICU cohort. It presents that participants in the non‐ICU cohort had a higher risk of depression/anxiety/PTSD (adjusted HR = 1.17, 95%CI = 1.13, 1.21) than in the ICU cohort after adjusted with age, sex, CCI score, and measured confounders. Furthermore, when we look at each outcome separately, we could see that the non‐ICU cohort also had a higher risk of anxiety and depression (anxiety: adjusted HR = 1.11, 95%CI = 1.07, 1.15; depression: adjusted HR = 1.28, 95%CI = 1.22, 1.35). As shown in Figure S1, for the ICU cohort, the cumulative incidence of the outcome, except PTSD, was significantly higher than the non‐ICU cohort.
TABLE 2.
Risk of depression/anxiety/PTSD associated with ICU.
| ICU cohort | Non‐ICU cohort | |||||||
|---|---|---|---|---|---|---|---|---|
| Variable | Event | Person‐years | IR 1000 person‐years | Event | Person‐years | IR# 1000 person‐years | Crude HR (95% CI) | Adjusted HR (95% CI) |
| Depression/anxiety/PTSD | 7727 | 212,281 | 36.40 | 8515 | 200,649 | 42.44 | 1.17 (1.13, 1.21)*** | 1.17 (1.13, 1.21)*** |
| Depression | 2747 | 12.90 | 3348 | 16.69 | 1.29 (1.23, 1.36)*** | 1.28 (1.22, 1.35)*** | ||
| PTSD | 41 | 0.19 | 44 | 0.22 | 1.14 (0.75, 1.75) | 1.04 (0.68, 1.59) | ||
| Anxiety | 5178 | 24.40 | 5391 | 26.90 | 1.11 (1.06, 1.15)*** | 1.11 (1.07, 1.15)*** | ||
Note: IR, incidence rate per 1000 person‐years; Crude HR: relative hazard ratio; Adjusted HR: multivariable analysis including age, sex, CCI score, mechanical ventilator, hospital day, and comorbidities.
***p < 0.001.
3.3. Risk of Depression/Anxiety/PTSD Associated With Clinical Characteristics in Post‐ICU Patients
Table 3 illustrates the association between depression/anxiety/PTSD and clinical characteristics in post‐ICU patients. Compared to males, females had higher odds of developing depression/anxiety/PTSD. The adjusted odds ratio (aOR) was 1.33 (95%CI = 1.27, 1.40). Depression/anxiety/PTSD events were associated with increased odds of younger patients when we compared to older patients (<50 years: aOR = 1.18, 95%CI = 1.10, 1.27; 50–64 years: aOR = 1.18, 95%CI = 1.12, 1.25). The association was also significant when looking into the CCI score, when “CCI score equal to zero” was the reference, the aORs were as follows: (1) aOR = 0.89, 95%CI = 0.83, 0.94; (2) aOR = 0.86, 95%CI = 0.80, 0.93; (3) aOR = 0.81, 95%CI = 0.75, 0.88. In the same way, patients using MV were 0.77 times (95%CI = 0.72, 0.83) more likely to have depression/anxiety/PTSD than people without taking MVs. Furthermore, patients with longer hospital stays had higher odds of developing depression/anxiety/PTSD compared to patients with shorter hospital stays (4–6 days: aOR = 1.10, 95%CI = 1.03, 1.17; 7–13 days: aOR = 1.30, 95%CI = 1.22, 1.39; ≥14 days: aOR = 1.67, 95%CI = 1.55, 1.80).
TABLE 3.
Risk of depression/anxiety/PTSD associated with clinical characteristics in post‐ICU patients.
| depression/anxiety/PTSD, n (%) | ||||
|---|---|---|---|---|
| Variable | No | Yes | Crude OR (95% CI) | Adjusted OR (95% CI) |
| Sex | ||||
| Female | 82,367 (35.0) | 3463 (40.7) | 1.28 (1.22, 1.33)*** | 1.33 (1.27, 1.40)*** |
| Male | 153,206 (65.0) | 5052 (59.3) | 1 (Reference) | 1 (Reference) |
| Age group (year) | ||||
| <50 | 28,324 (12.0) | 1117 (13.1) | 1.16 (1.08, 1.23)*** | 1.18 (1.10, 1.27)*** |
| 50–64 | 61,281 (26.0) | 2412 (28.3) | 1.15 (1.10, 1.21)*** | 1.18 (1.12, 1.25)*** |
| ≥65 | 145,968 (62.0) | 4986 (58.6) | 1 (Reference) | 1 (Reference) |
| Comorbidity | ||||
| DM | 65,106 (27.6) | 1948 (22.9) | 0.78 (0.74, 0.82)*** | 0.80 (0.76, 0.85)*** |
| ESRD | 5026 (2.13) | 167 (1.96) | 0.92 (0.79, 1.07) | 1.07 (0.91, 1.26) |
| Liver cirrhosis | 53,900 (22.9) | 2006 (23.6) | 1.04 (0.99, 1.09) | 1.12 (1.06,1.18)*** |
| COPD | 63,232 (26.8) | 2216 (26.0) | 0.96 (0.91, 1.01) | 1.07 (1.01, 1.13)*** |
| Asthma | 28,932 (11.9) | 1097 (12.9) | 1.10 (1.03, 1.17)** | 1.16 (1.08, 1.24)*** |
| Tuberculosis | 6573 (2.79) | 182 (2.14) | 0.76 (0.66, 0.88)*** | 0.89 (0.76, 1.03) |
| AIDS | 244 (0.10) | 8 (0.09) | 0.91 (0.45, 1.84) | 1.11 (0.55, 2.26) |
| Autoimmune diseases | 1666 (0.71) | 54 (0.63) | 0.90 (0.68, 1.18) | 0.86 (0.65, 1.13) |
| Solid organ cancer | 40,660 (17.3) | 1156 (13.6) | 0.75 (0.71, 0.80)*** | 0.84 (0.78, 0.91)*** |
| Hematological cancer | 600 (0.25) | 16 (0.19) | 0.74 (0.45, 1.21) | 0.90 (0.54, 1.48) |
| Transplantation | 326 (0.14) | 9 (0.11) | 0.76 (0.39, 1.48) | 0.79 (0.40, 1.54) |
| Ischemic heart diseases | 90,586 (38.5) | 3347 (39.3) | 1.04 (0.99, 1.08) | 1.15 (1.09, 1.21)*** |
| Pneumonia | 80,232 (34.1) | 2545 (29.9) | 0.83 (0.79, 0.87)*** | 0.90 (0.86, 0.95)*** |
| Stroke | 74,014 (31.4) | 3239 (38.0) | 1.34 (1.28, 1.40)*** | 1.36 (1.29, 1.42)*** |
| Acute respiratory failure | 15,461 (6.56) | 208 (2.44) | 0.36 (0.31, 0.41)*** | 0.46 (0.40, 0.54)*** |
| Septicemia | 37,936 (16.1) | 884 (10.4) | 0.60 (0.56, 0.65)*** | 0.69 (0.64, 0.75)*** |
| Heart failure | 34,877 (14.8) | 1120 (13.2) | 0.87 (0.82, 0.93)*** | 0.90 (0.84, 0.96)** |
| Urinary tract infection | 78,621 (33.4) | 2808 (33.0) | 0.98 (0.94, 1.03) | 0.99 (0.94, 1.04) |
| Shock without documentation of trauma | 13,352 (5.67) | 265 (3.11) | 0.54 (0.47, 0.61)*** | 0.74 (0.65, 0.84)*** |
| CCI | ||||
| 0 | 53,864 (22.9) | 2181 (25.6) | 1 (Reference) | 1 (Reference) |
| 1 | 69,841 (29.7) | 2694 (31.6) | 0.95 (0.90, 1.01) | 0.89 (0.83, 0.94)*** |
| 2 | 51,037 (21.7) | 1750 (20.6) | 0.85 (0.79, 0.90)*** | 0.86 (0.80, 0.93)*** |
| 3+ | 60,831 (25.8) | 1890 (22.2) | 0.77 (0.72, 0.82)*** | 0.81 (0.75, 0.88)*** |
| Mechanical ventilator | 38,438 (16.3) | 1049 (12.3) | 0.72 (0.68, 0.77)*** | 0.77 (0.72, 0.83)*** |
| Hospital day | ||||
| 1–3 | 56,788 (24.1) | 1740 (20.4) | 1 (Reference) | 1 (Reference) |
| 4–6 | 58,293 (24.8) | 1965 (23.1) | 1.10 (1.03, 1.18)** | 1.10 (1.03, 1.17)** |
| 7–13 | 70,773 (30.0) | 2677 (31.4) | 1.23 (1.16, 1.31)*** | 1.30 (1.22, 1.39)*** |
| 14+ | 49,719 (21.1) | 2133 (25.1) | 1.40 (1.31, 1.49)*** | 1.67 (1.55, 1.80)*** |
Note: Crude OR: relative odds ratio; Adjusted OR: multivariable analysis including age, sex, CCI score, mechanical ventilator, hospital day, and comorbidities.
**p < 0.01, ***p < 0.001.
3.4. Risk of Death Associated With Depression/Anxiety/PTSD and Clinical Characteristics in Post‐ICU Patients
As Table 4 demonstrates, a total of 50,723 patients died after ICU. Patients with depression/anxiety/PTSD had a higher risk of death than patients without (adjusted HR = 1.07, 95%CI = 1.03, 1.11). Males had a higher risk of death than females (adjusted HR = 1.12, 95%CI = 1.03, 1.11). Also, the older the age, the higher the risk of death (50–64: adjusted HR = 1.43, 95%CI = 1.36, 1.50; ≥65: adjusted HR = 3.82, 95%CI = 3.65, 3.99). Besides, among patients diagnosed with comorbidities like heart failure, stroke, and COPD, the risk of death was higher than those without being diagnosed with comorbidities. Furthermore, as the CCI score increased or the length of hospital stay increased, the higher the risk of death.
TABLE 4.
Risk of death associated with depression/anxiety/PTSD and clinical characteristics in post‐ICU patients.
| Variable | Event N = 50,723 | Person‐years | IR 100 person‐years | Crude HR (95% CI) | Adjusted HR (95% CI) |
|---|---|---|---|---|---|
| Depression/anxiety/PTSD | |||||
| No | 47,959 | 714,615 | 67.10 | 1 (Reference) | 1 (Reference) |
| Yes | 2764 | 37,994 | 72.80 | 1.09 (1.05, 1.13)*** | 1.07 (1.03, 1.11)*** |
| Sex | |||||
| Female | 19,447 | 256,624 | 75.80 | 1 (Reference) | 1 (Reference) |
| Male | 31,276 | 495,986 | 63.10 | 0.83 (0.82, 0.85)*** | 1.12 (1.10, 1.14)*** |
| Age group (year) | |||||
| <50 | 2197 | 118,714 | 18.50 | 1 (Reference) | 1 (Reference) |
| 50–64 | 7161 | 238,268 | 30.10 | 1.63 (1.55, 1.71)*** | 1.43 (1.36, 1.50)*** |
| ≥65 | 41,365 | 395,627 | 104.60 | 5.67 (5.43, 5.92)*** | 3.82 (3.65, 3.99)*** |
| DM | 17,163 | 202,894 | 84.60 | 1.38 (1.36, 1.41)*** | 0.94 (0.92, 0.96)*** |
| ESRD | 2003 | 12,893 | 155.40 | 2.35 (2.25, 4.46)*** | 1.48 (1.41, 1.55)*** |
| Liver cirrhosis | 11,385 | 158,998 | 71.60 | 1.08 (1.06, 1.10)*** | 1.01 (0.99, 1.03) |
| COPD | 17,722 | 164,726 | 107.60 | 1.91 (1.88, 1.95)*** | 1.21 (1.19, 1.23)*** |
| Asthma | 7198 | 81,713 | 88.10 | 1.36 (1.32, 1.39)*** | 0.86 (0.83, 0.88)*** |
| Tuberculosis | 1799 | 14,757 | 121.90 | 1.83 (1.75, 1.92)*** | 1.18 (1.13, 1.24)*** |
| AIDS | 26 | 693 | 37.50 | 0.56 (0.38, 0.82)*** | 0.53 (0.36, 0.79)** |
| Autoimmune diseases | 407 | 4911 | 82.90 | 1.23 (1.12, 1.36)*** | 0.99 (0.90, 1.09) |
| Solid organ cancer | 11,062 | 81,445 | 135.80 | 2.29 (2.25, 2.34)*** | 1.27 (1.24, 1.30)*** |
| Hematological cancer | 121 | 931 | 130.00 | 1.93 (1.61, 2.30)*** | 1.51 (1.26, 1.80)*** |
| Transplantation | 46 | 1193 | 38.60 | 0.58 (0.43, 0.77)*** | 0.70 (0.10, 5.03) |
| Ischemic heart diseases | 18,760 | 337,049 | 55.70 | 0.73 (0.71, 0.74)*** | 0.82 (0.80, 0.83)*** |
| Pneumonia | 20,615 | 192,024 | 107.40 | 2.00 (1.96, 2.03)*** | 1.38 (1.36, 1.41)*** |
| Stroke | 20,382 | 222,371 | 91.70 | 1.60 (1.57, 1.63)*** | 1.10 (1.08, 1.12)*** |
| Acute respiratory failure | 1795 | 13,606 | 131.90 | 1.99 (1.90, 2.08)*** | 1.43 (1.36, 1.50)*** |
| Septicemia | 9929 | 70,834 | 140.17 | 2.34 (2.29, 2.39)*** | 1.42 (1.38, 1.45)*** |
| Heart failure | 11,599 | 93,368 | 124.20 | 2.09 (2.05, 2.13)*** | 1.53 (1.50, 1.56)*** |
| Urinary tract infection | 21,195 | 201,971 | 104.90 | 1.96 (1.92, 1.99)*** | 1.27 (1.24, 1.29)*** |
| Shock without documentation of trauma | |||||
| CCI | |||||
| 0 | 6598 | 204,143 | 32.30 | 1 (Reference) | 1 (Reference) |
| 1 | 12,565 | 260,113 | 48.30 | 1.50 (1.45, 1.54)*** | 1.36 (1.32, 1.40)*** |
| 2 | 12,594 | 156,618 | 80.40 | 2.49 (2.42, 2.57)*** | 1.82 (1.76, 1.88)*** |
| 3+ | 18,966 | 131,736 | 144.00 | 4.48 (4.35, 4.60)*** | 2.63 (2.54, 2.73)*** |
| Mechanical ventilator | 6744 | 87,088 | 77.40 | 1.17 (1.14, 1.20)*** | 1.00 (0.97, 1.03) |
| Hospital days | |||||
| 1–3 | 7061 | 188,931 | 37.37 | 1 (Reference) | 1 (Reference) |
| 4–6 | 11,696 | 202,232 | 57.83 | 1.55 (1.50, 1.59)*** | 1.24 (1.21, 1.28)*** |
| 7–13 | 18,096 | 228,212 | 79.30 | 2.12 (2.06, 2.18)*** | 1.44 (1.39, 1.48)*** |
| 14+ | 13,870 | 133,233 | 104.10 | 2.78 (2.70, 2.86)*** | 1.65 (1.59, 1.70)*** |
Note: IR, incidence rate per 1000 person‐years; Crude HR: relative hazard ratio; Adjusted HR: multivariable analysis including age, sex, CCI score, mechanical ventilator, hospital day, and comorbidities.
**p < 0.01, ***p < 0.001.
3.5. Risk of Re‐Admission Associated With Depression/Anxiety/PTSD and Clinical Characteristics in Post‐ICU Patients
In Table 5, a total of 117,631 patients were re‐admitted after ICU. Patients with depression/anxiety/PTSD had a higher risk of re‐admission than patients without (adjusted HR = 1.40, 95%CI = 1.36, 1.43). Males had a higher risk of re‐admission than females (adjusted HR = 1.09, 95%CI = 1.07, 1.10). Also, the older the age, the higher the risk of re‐admission (50–64: adjusted HR = 1.15, 95%CI = 1.13, 1.18; ≥65: adjusted HR = 1.62, 95%CI = 1.59, 1.65). Among patients diagnosed with comorbidities like heart failure, stroke, and COPD, the risk of re‐admission was higher than without diagnosed with comorbidities. Furthermore, as the CCI score increased or the length of hospital stay increased, the higher the risk of re‐admission.
TABLE 5.
Risk of re‐admission associated with depression/anxiety/PTSD and clinical characteristics in post‐ICU patients.
| Variable | Event N = 117,631 | Person‐years | IR 100 person‐years | Crude HR (95% CI) | Adjusted HR (95% CI) |
|---|---|---|---|---|---|
| Depression/anxiety/PTSD | |||||
| No | 111,367 | 425,070 | 26.20 | 1 (Reference) | 1 (Reference) |
| Yes | 6264 | 17,477 | 35.80 | 1.38 (1.35, 1.42)*** | 1.40 (1.36, 1.43)*** |
| Sex | |||||
| Female | 41,648 | 149,371 | 27.90 | 1 (Reference) | 1 (Reference) |
| Male | 75,983 | 293,175 | 25.90 | 0.94 (0.93, 0.95)*** | 1.09 (1.07, 1.10)*** |
| Age group (year) | |||||
| <50 | 11,920 | 79,741 | 15.00 | 1 (Reference) | 1 (Reference) |
| 50–64 | 29,636 | 148,441 | 20.00 | 1.30 (1.28, 1.33)*** | 1.15 (1.13, 1.18)*** |
| ≥65 | 76,075 | 214,364 | 35.50 | 2.17 (2.13, 2.21)*** | 1.62 (1.59, 1.65)*** |
| DM | 36,566 | 108,061 | 33.80 | 1.34 (1.33, 1.36)*** | 1.04 (1.03, 1.06)*** |
| ESRD | 3286 | 5569 | 59.00 | 1.99 (1.92, 2.06)*** | 1.41 (1.36, 1.47)*** |
| Liver cirrhosis | 27,710 | 88,619 | 31.30 | 1.19 (1.17, 1.21)*** | 1.11 (1.09, 1.12)*** |
| COPD | 33,379 | 86,596 | 38.60 | 1.52 (1.50, 1.54)*** | 1.16 (1.14, 1.17)*** |
| Asthma | 15,429 | 42,869 | 36.00 | 1.33 (1.31, 1.36)*** | 1.02 (1.00, 1.04)* |
| Tuberculosis | 3110 | 7771 | 40.00 | 1.43 (1.38, 1.48)*** | 1.10 (1.06, 1.14)*** |
| AIDS | 88 | 445 | 19.80 | 0.76 (0.61, 0.93)** | 0.64 (0.52, 0.79)*** |
| Autoimmune diseases | 950 | 2424 | 39.20 | 1.40 (1.31, 1.49)*** | 1.23 (1.15, 1.31)*** |
| Solid organ cancer | 18,833 | 42,395 | 44.40 | 1.68 (1.66, 1.71)*** | 1.17 (1.15, 1.19)*** |
| Hematological cancer | 213 | 467 | 45.60 | 1.66 (1.45, 1.89)*** | 1.34 (1.17, 1.54)*** |
| Transplantation | 212 | 507 | 41.80 | 1.51 (1.32, 1.73)*** | 1.14 (0.99, 1.31) |
| Ischemic heart diseases | 51,860 | 189,663 | 27.30 | 1.04 (1.03, 1.06)*** | 1.09 (1.08, 1.11)*** |
| Pneumonia | 38,252 | 104,044 | 36.80 | 1.48 (1.46, 1.50)*** | 1.25 (1.23, 1.27)*** |
| Stroke | 39,298 | 125,242 | 31.40 | 1.24 (1.22, 1.25)*** | 1.06 (1.04, 1.07)*** |
| Acute respiratory failure | 2673 | 7594 | 35.20 | 1.29 (1.24, 1.34)*** | 1.13 (1.09, 1.18)*** |
| Septicemia | 16,008 | 36,001 | 44.50 | 1.66 (1.63, 1.69)*** | 1.30 (1.27, 1.32)*** |
| Heart failure | 19,690 | 47,505 | 41.50 | 1.56 (1.54, 1.59)*** | 1.24 (1.22, 1.26)*** |
| Urinary tract infection | 40,166 | 108,616 | 37.00 | 1.49 (1.47, 1.51)*** | 1.21 (1.19, 1.23)*** |
| Shock without documentation of trauma | 4425 | 13,071 | 33.90 | 1.25 (1.21, 1.29)*** | 1.06 (1.03, 1.10)*** |
| CCI | |||||
| 0 | 23,480 | 133,739 | 17.60 | 1 (Reference) | 1 (Reference) |
| 1 | 35,289 | 159,262 | 22.20 | 1.24 (1.22, 1.26)*** | 1.14 (1.12, 1.16)*** |
| 2 | 27,149 | 85,941 | 31.60 | 1.70 (1.67, 1.73)*** | 1.38 (1.35, 1.41)*** |
| 3+ | 31,713 | 63,605 | 49.90 | 2.52 (2.47, 2.56)*** | 1.78 (1.74, 1.82)*** |
| Mechanical ventilator | 13,910 | 52,840 | 26.30 | 0.99 (0.98, 1.01) | 1.01 (0.99, 1.03) |
| Hospital days | |||||
| 1–3 | 25,454 | 112,055 | 22.70 | 1 (Reference) | 1 (Reference) |
| 4–6 | 30,401 | 119,404 | 25.50 | 1.11 (1.09, 1.13)*** | 1.02 (1.00, 1.04)* |
| 7–13 | 37,356 | 135,391 | 27.60 | 1.19 (1.18, 1.21)*** | 1.05 (1.04, 1.07)*** |
| 14+ | 24,420 | 75,697 | 32.30 | 1.38 (1.36, 1.41)*** | 1.13 (1.11, 1.16)*** |
Note: IR, incidence rate per 1000 person‐years; Crude HR: relative hazard ratio; Adjusted HR: multivariable analysis including age, sex, CCI score, mechanical ventilator, hospital day, and comorbidities.
*p < 0.05, **p < 0.01, ***p < 0.001.
4. Discussion
Our investigation revealed that patients admitted to the ICU had a significantly higher incidence and risk of developing depression and anxiety compared to those with the same conditions treated in general wards. However, it remains uncertain whether the observed effects are due to ICU admission itself or the underlying medical condition that necessitated ICU care. To address this, we employed a study design aimed at tackling the issue. Specifically, we compared patients admitted to the ICU with those who had similar medical conditions but were not admitted to the ICU. This approach helps to isolate the effects of different diseases.
Although we cannot eliminate the influence of disease severity, we applied statistical matching methods. Patients who did not require ICU admission during hospitalization for the specified conditions (non‐ICU group) were matched to the ICU cohort based on sex, age (in 5‐year intervals), the year of the index date, and measured confounders. This matching ensured comparability between the ICU and non‐ICU groups in terms of underlying medical conditions and severity. To further account for disease severity, we included variables such as the severity of the underlying medical condition, comorbidities, length of hospital stay, CCI, and MV use in our statistical models. This approach allowed us to control these factors when assessing the independent effect of ICU admission.
In addition, to minimize the potential influence of preexisting psychiatric disorders (e.g., depression, anxiety, or posttraumatic stress disorder), we excluded patients with these conditions prior to the index date. This enabled us to conduct a longitudinal follow‐up study to monitor changes in psychiatric symptoms over time following ICU admission. Our results reflect experiencing a sudden or severe instance of a potentially life‐threatening illness, coupled with potentially traumatic experiences in the ICU, may contribute to the development of treatable psychological problems, such as posttraumatic stress, anxiety, and depression (Girard et al. 2007; Desai et al. 2011). Although our findings are consistent with the increased susceptibility to depression and anxiety observed in ICU survivors, our findings do not suggest a higher incidence of PTSD. Furthermore, research shows that PTSD often coexists with other conditions, such as depression and various anxiety disorders (Brady et al. 2000). Our study suggests potential underdiagnosis of PTSD due to symptom overlap with depression and anxiety disorders. Diagnosis challenges arise from compatible criteria use, leading to missed PTSD cases when trauma history is not explored. In addition to PTSD, mental disorders might be undiagnosed, either. Therefore, long‐term psychological sequelae and interventions are necessary.
Previous studies indicate that younger adults and females in ICU have a higher susceptibility to mental disorders (Desai et al. 2011). In Taiwan, our research highlighted younger age and female gender as notable risk factors for depression, anxiety, and PTSD among ICU patients. Female gender, specifically, showed an independent link with increased psychological distress levels (McKinley et al. 2012). Several theories have been suggested to explain this age‐related finding, with many highlighting the overlooked risk of depression in older adults (Kessler et al. 2010). Younger individuals often have better survival rates and easier access to mental health services. However, they face unique challenges like academic pressures, uncertain careers, and complex relationships, leading to higher stress and depression. Further research is needed to uncover additional contributing factors.
Chronic medical illness is associated with depression and anxiety disorders (Fiest et al. 2011). In our findings, we found that ICU patients with liver cirrhosis, chronic obstructive pulmonary disease, asthma, ischemia heart disease, and stroke were at higher risk of developing depression, anxiety, and PTSD, and the findings align with the survey among those patients (Hernaez et al. 2022; Long et al. 2020; Plank et al. 2023; Johnson et al. 2020; Chun et al. 2022). However, conditions like diabetes, solid organ tumors, pneumonia, sepsis, heart failure, and shock are associated with a lower risk of developing these disorders, prompting the need for more investigation.
Our research found that a higher CCI was associated with a lower likelihood of developing depression, anxiety, or PTSD after ICU treatment. Patients with more comorbidities were less prone to these disorders post‐ICU. However, our study didn't include patients with pre‐existing mental disorders, which may have influenced our results and requires consideration.
The need for MV could be identified as a vulnerability factor contributing to the occurrence of mental disorders. A study offers crucial insights into the prevalence of psychiatric disorders in patients needing MV during critical illness, along with the risks associated with psychiatric diagnoses and psychiatric medication use post‐ICU discharge (Wunsch et al. 2014). However, our findings were not congruent with the above report. The factors contributing to this phenomenon may include a heightened probability of mortality and complications (He et al. 2021). In cases involving severe physical conditions, there is a tendency to overlook underlying mental disorders.
While some studies have not discovered a correlation between the duration of hospital or ICU stay and an elevated risk of anxiety and depression (Nikayin et al. 2016; Battle et al. 2015), it is essential to note the variability in findings across different research investigations. Studies of survivors of acute lung injury or acute respiratory distress syndrome have identified prolonged ICU length of stay prolonged sedation, and prolonged MV as potential risk factors for post‐ICU psychopathology (Davydow, Desai, et al. 2008). While our data did not include information on ICU length of stay, our study found that longer overall hospitalization was associated with an increased risk of developing mental disorders. Further clinical research is needed to identify potential contributing factors.
Our study discovered an association between post‐ICU depression, anxiety, and PTSD and increased mortality for 12 months following ICU discharge. The association persists when adjusted for age, sex, illness severity (CCI), the length of hospital stays, and the presence of other psychopathological issues. A large UK study also showed depression had higher mortality following ICU discharge (Hatch et al. 2018). For comparison, a large US study in a general veterans’ population estimates that diagnosed depression is associated with a 17% greater hazard of all‐cause mortality at 3 years (Zivin et al. 2015).
The link between depression, anxiety, PTSD, and mortality among post‐ICU individuals may be influenced by chronic illness severity and pre‐ and postdischarge factors not addressed here. Detecting and managing depression symptoms post‐ICU discharge is crucial, highlighting the need for vigilance in ICU follow‐up care. Moreover, these mental health issues also heightened readmission risks.
4.1. Strengths and Limitations
This study's strength lies in its sizable patient sample, representing nationwide ICU admissions for high external validity. Unlike prior studies, it compares ICU patients with non‐ICU controls, accounting for hospitalization effects. We focused on cardiopulmonary disease cases to mitigate confounding factors. Individuals with pre‐existing psychopathological conditions are at risk of exacerbation post‐ICU treatment. A specific phenotype suggests those with depression, anxiety, or PTSD are prone to critical illness (Hatch et al. 2018). We excluded participants with prior psychiatric diagnoses to reduce confounding. This approach enhances the study's credibility and contributes to a more accurate understanding of psychiatric risks in post‐ICU care.
This study has several notable limitations. First, due to inherent confounding factors in LHID claims, detailed critical illness characteristics and relevant data like habits, biomarkers, and psychosocial factors were unavailable, affecting our ability to thoroughly assess ICU admission‐mental disorder risk associations. We lacked data on potential mediators specific to the ICU stay, such as delirium, sedation practices, sleep disruption, or traumatic experiences (e.g., invasive procedures, isolation). In addition, we did not have information on the length of ICU stay and regarding the length of MV. The disease severity at admission (e.g., using APACHE II scores) was also not provided. Furthermore, we were unable to explore biological factors (e.g., systemic inflammation, neurohormonal stress responses) or environmental factors (e.g., ICU trauma, prolonged immobility) to distinguish the physical effects of illness from the psychological impacts of ICU care. Further clinical investigations with comprehensive data collection are needed to clarify this relationship. For example, a subgroup analysis based on ICU stay duration (e.g., < 48 h, 2–7 days, > 7 days) could be conducted to examine whether psychiatric outcomes vary across these groups. In addition, disease severity, MV duration, and other ICU‐related factors (e.g., sedation and use of restraints) should be included in multivariate models. Second, as an observational study using international disease codes, mental disorders might be underdiagnosed, particularly in individuals not seeking medical attention. Lastly, the administrative dataset's diagnosis of mental disorders lacks validation, posing challenges and potentially overrepresenting subclinical cases in Taiwan's health insurance system. Medical expenditure structures, emphasizing diagnosis codes for billing, impact disease recording accuracy (Edwards et al. 2020). Future studies on post‐ICU survivors and psychiatric disorders should address these concerns for a more comprehensive understanding.
5. Conclusion
This study noted higher rates of anxiety and depression 12 months post‐ICU compared to general ward patients, especially among younger individuals, females, and those with longer hospital stays. Interestingly, higher CCI and MV use was linked to lower rates of these mental health issues. However, residual confounders require further investigation to clarify these associations. In addition, post‐ICU depression, anxiety, and PTSD were tied to increased mortality and readmission. Clinicians should prioritize mental health support postdischarge, especially for at‐risk groups like women, younger patients, and those with multiple comorbidities.
Author Contributions
Chen‐Shu Chang: writing–original draft, writing–review and editing, conceptualization, methodology. Fuu‐Jen Tsai: conceptualization, writing–review and editing, data curation, formal analysis. Chun‐Hui Liao: conceptualization, writing–review and editing, writing–original draft, methodology, project administration, supervision.
Ethics Statement
The authors also thank the Hospital of China Medical University Institutional Review Board for approving the study (CMUH110‐REC1‐038(CR‐3)).
Conflicts of Interest
The authors declare no conflicts of interest.
Peer Review
The peer review history for this article is available at https://publons.com/publon/10.1002/brb3.70319
Supporting information
Supplemental Figure S1 The cumulative incidence of depression, anxiety, and PTSD
Acknowledgments
This study is supported in part by the National Science and Technology Council (NSTC 112‐2321‐B‐039‐006) and China Medical University Hospital (DMR‐109‐106; DMR‐HHC‐109‐14; DMR‐111‐130). We are grateful to the Health Data Science Center, China Medical University Hospital for providing administrative, technical, and funding support. The funders had no role in the study design, data collection and analysis, the decision to, or the preparation of the manuscript. No additional external funding was received for this study.
Funding: The authors received no specific funding for this work.
Data Availability Statement
The dataset utilized in this study is maintained by the Taiwan Ministry of Health and Welfare (MOHW). Access to the current data requires approval from the MOHW. Researchers interested in obtaining access to this dataset can submit an application form to the MOHW at the following email address: stcarolwu@mohw.gov.tw. The Taiwan Ministry of Health and Welfare is located at No.488, Sec. 6, Zhongxiao E. Rd., Nangang Dist., Taipei City 115, Taiwan (R.O.C.). For inquiries, please contact them via phone at +886‐2‐8590‐6848. All pertinent data are included in the paper.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supplemental Figure S1 The cumulative incidence of depression, anxiety, and PTSD
Data Availability Statement
The dataset utilized in this study is maintained by the Taiwan Ministry of Health and Welfare (MOHW). Access to the current data requires approval from the MOHW. Researchers interested in obtaining access to this dataset can submit an application form to the MOHW at the following email address: stcarolwu@mohw.gov.tw. The Taiwan Ministry of Health and Welfare is located at No.488, Sec. 6, Zhongxiao E. Rd., Nangang Dist., Taipei City 115, Taiwan (R.O.C.). For inquiries, please contact them via phone at +886‐2‐8590‐6848. All pertinent data are included in the paper.