To the Editor,
About 20% of acute respiratory distress syndrome (ARDS) survivors suffer from anxiety, depression or post-traumatic stress disorder (PTSD) [1] with a negative impact on long-term quality of life [2]. Higher rates—38.8%—of psychological sequelae were described in Middle East and Severe Acute Respiratory Syndromes’ outbreaks [3]. Recent data described about 40 to 48% of COVID-19 critically ill patients with post-intensive care disorder or acute stress disorder [4, 5]. The aim of this pilot study is to assess the feasibility of an early psychological evaluation and sustained support in COVID-19 patients admitted to intensive care unit (ICU) and describe their mental health outcomes during a 6-month follow-up. Every COVID-19 survivor was evaluated by a trained clinician psychologist in ICU at invasive ventilation weaning or when conversation was feasible for patients receiving high-flow oxygen. Psychological support was performed as needed according to standard care. Clinician psychologists met the patient and identified if psychological distress symptoms were present (i.e. anxious or depressive symptoms, sleep disorder, …). They met the patient as often as required for supportive interventions (to help patients to speak about their emotions and/or fears) and also explained to the patients the care they were given while being sedated. Clinician psychologists systematically met patients or called them by phone as preferred by the patient at day 7, week 6, 12 and 24 after ICU discharge and standardized evaluation occurred at those time points with psychometric evaluation (Hospital Anxiety and Depression Scale (HADS) Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) and Insomnia Severity Index (ISI)). Univariate linear mixed regression models were used to identify predictors of mental health in follow-up. Thirty-seven patients were included (81% of men, mean age of 59 (± 11) from March to June, 2020 (Table 1). Three quarters of them (28/37) were intubated for an average length of 40 days (± 7). At discharge from hospital, 20/34 (59%) of them returned home while 14/34 (41%) went to rehabilitation centre. At day 7, 32 patients were evaluated: 5/32 (16%) had significant depression symptoms, 4/32 (13%) significant insomnia symptoms and 3/32 (9%) significant anxiety symptoms and at week 6, they were, respectively, 2/17 (12%), 3/17 (18%) and 2/17 (12%). At week 12, they were, respectively, 5/24 (21%), 3/22 (14%), 3/23 (13%), and 2/25 (8%) to have significant depression, insomnia, anxiety or PTSD symptoms and at week 24, respectively, 2/19 (11%), 2/19 (11%), 4/18 (22%), and 1/18 (6%) (Table 1). Insomnia and anxiety scores did not vary over time (Kruskal–Wallis, respectively, p = 0.76 and p = 0.95), whereas depression scores decreased at week 24 (Kruskal–Wallis, p = 0.04). Cumulative dose of midazolam, cumulative dose of clonidine and length of ICU stay were associated with insomnia in follow-up (respectively regression coefficient β: 1.14 [0.44–2.39], p = 0.007, β: 1.29 [0.24; 2.36], p = 0.02 and β: 1.02 [0.14; 1.90], p = 0.025) (Table 2). Cumulative dose of clonidine was associated with depression in follow-up (β: 0.57 [0.11; 1.03], p = 0.019). Severity of ARDS could be associated with occurrence of PTSD in follow-up despite non-statistical significance (p = 0.059) (Table 2). In conclusion, this study shows that, even in the context of a pandemic situation, it is possible to provide an early and sustained psychological support in critically ill patients. We report lower rates of post-intensive care psychological sequelae than what has previously been reported [4, 5] but the absence of control group prevent from drawing firm conclusions about the impact of psychological intervention. Nevertheless, these results strongly encourage future large randomized controlled studies to assess the efficacy of early psychological evaluation and personalized support in critically ill COVID-19 patients.
Table 1.
COVID-19 critically ill patients’ socio-demographic, comorbidities and care characteristics
| Variables | n (%) | Mean ± SD | Median [IQR] |
|---|---|---|---|
|
Gender Women Men |
37 (100.0%) 7 (18.9%) 30 (81.1%) |
||
| Age | 37 (100.0%) | 58.8 ± 11.3 | 59.4 [53.4–63.7] |
|
History of: Sleep disorders Psychiatric consultations On-going depression Past trauma or PTSD Past depression Drug addiction (cannabis) History of: Tobacco use COPD Asthma Chronic hypertension Diabetes Chronic heart condition Chronic coronary disease Chronic kidney disease Pharmacological treatment ACEi Diuretics Proton pump inhibitor Beta-blockers Statins Metformin Fibrates Benzodiazepine Serotonin reuptake inhibitor ARB Aspirin Lithium Anticoagulant Cordarone None |
33 (89.9%) 6 (18.2%) 5 (14.7%) 4 (12.2%) 4 (12.2%) 2 (6.1%) 1 (3.0%) 37 (100.0%) 13 (35.1%) 6 (16.2%) 3 (8.1%) 22 (59.5%) 8 (21.6%) 6 (16.2%) 5 (13.5%) 2 (5.4%) 37 (100.0%) 12 (32.4%) 11 (29.7%) 11 (29.7%) 9 (24.3%) 7 (18.1%) 6 (16.2%) 5 (13.5%) 5 (13.5%) 4 (10.8%) 3 (8.1%) 3 (8.1%) 2 (5.4%) 2 (5.4%) 1 (2.7) 7 (18.1%) |
||
| Duration of symptoms before admission to ICU (days) | 37 (100.0%) | 8.0 ± 2.6 | 8 [7–9] |
|
Clinical respiratory distress: Yes No |
32 (86.5%) 5 (15.6%) 27 (84.4%) |
||
|
Thromboembolic event: Yes No |
37 (100.0%) 9 (24.3%) 28 (75.7%) |
||
|
Acute respiratory distress syndrome Mild Moderate Severe |
37 (100.0%) 11 (29.7%) 17 (50.0%) 9 (24.3%) |
||
|
Neutrophils/lymphocytes ratio Less than 3.7 More than 3.7 |
37 (100.0%) 6 (16.2%) 31 (83.8%) |
||
|
C-reactive protein (mg/L) Ferritin (µg/L) Lactate Dehydrogenase (UI/L) Albumin (g/L) Fibrinogen (g/L) D-dimers (mg/L) |
37 (100.0%) 33 (89.9%) 32 (86.5%) 35 (94.6%) 33 (89.9%) 32 (86.5%) |
152 ± 105 2,206 ± 2,043 468 ± 165 20 ± 5 8.5 ± 1.3 5,535 ± 10,478 |
140 [66–202] 1,470 [941–3,258] 450 [367–537] 21 [16–24] [7.3–9.8] 1,554 [802–5,084] |
|
Oro-tracheal intubation: Yes No |
37 (100.0%) 28 (75.7%) 9 (24.3%) |
||
| Duration of intubation (days) | 28 (100.0%) | 39.9 ± 6.6 | 39 [38–40] |
| Duration of sedation (days) | 28 (100.0%) | 19.0 ± 15.2 | 14 [9–22] |
| Cumulative dose of midazolam (mg) | 24 (85.7%) | 1731 ± 2115 | 889 [364–2.188] |
| Cumulative dose of propofol (mg) | 22 (78.6%) | 23.560 ± 27.083 | 12.392 [5.060–34.264] |
| Cumulative dose of morphine (mg) | 22 (78.6%) | 1459 ± 2491 | 882 [230– 1.463] |
| Cumulative dose of clonidine (mg) | 22 (78.6%) | 2.44 ± 2.18 | 1.81 [0.85–3.2] |
| Cumulative dose of levomepromazine (mg) | 13 (46.4%) | 267 ± 350 | 173 [0–287] |
|
Use of prone positioning Yes No |
28 (100%) 17 (60.7%) 11 (39.3%) |
||
|
Use of nitrogen monoxide Yes No |
37 (100.0%) 3 (8.1%) 24 (91.9%) |
||
|
Use of norepinephrine Yes No |
37 (100.0%) 26 (70.3%) 11 (29.7%) |
||
| Maximal dose of norepinephrine (µg/kg/min) | 22 (84.6%) | 0.30 ± 0.31 | 0.17 [0.11–0.41] |
| Cumulative dose of norepinephrine (mg) | 23 (88.5%) | 85.9 ± 143.4 | 28.0 [9.5–94.5] |
|
Place of follow-up Home Rehabilitation center |
34 (91.9%) 20 (58.8%) 14 (41.2%) |
||
|
Psychometric evaluation at day 7 Significant depression Significant insomnia Significant anxiety |
32 (86.5%) 5 (15.6%) 4 (12.5%) 3 (9.4%) |
||
|
Psychometric evaluation at week 6 Significant depression Significant insomnia Significant anxiety |
17 (45.9%) 2 (11.8%) 3 (17.7%) 2 (11.8%) |
||
|
Psychometric evaluation at week 12 Significant depression Significant insomnia Significant anxiety Significant PTSD symptoms |
24 (64.9%) 5 (20.8%) 22 (59.5%) 3 (13.6%) 23 (62.2%) 3 (13.0%) 25 (67.6%) 2 (8.0%) |
||
|
Psychometric evaluation at week 24 Significant depression Significant insomnia Significant anxiety Significant PTSD symptoms |
19 (51.4%) 2 (10.5%) 2 (10.5%) 18 (48.6%) 4 (22.2%) 1 (5.6%) |
ACEi angiotensin-converting enzyme inhibitor, ARB angiotensin II receptor blocker, COPD chronic obstructive pulmonary disease, ICU intensive care unit PTSD post-traumatic stress disorder
Table 2.
Univariate mixed model with random intercept of factors associated with the occurrence of psychological sequelae during follow-up
| β | [95%] CI | p value | |
|---|---|---|---|
| Predicting insomnia in follow-up | |||
| History of sleep disorders | 4.24 | [− 0.54;9.08] | 0.082 |
| Acute respiratory distress syndrome | 0.099 | ||
| Mild | Reference | Reference | |
| Moderate | 1.32 | [− 2.46;5.09] | |
| Severe | 4.87 | [0.35;9.34] | |
| Cumulative dose of morphine (for 1000 units) | 0.74 | [− 0.06;1.53] | 0.069 |
| Cumulative dose of midazolam (for 100 units) | 1.41 | [0.44;2.39] | 0.007 |
| Cumulative dose of clonidine (for 1 unit) | 1.29 | [0.24;2.36] | 0.020 |
| Maximal dose of norepinephrine | − 2.78 | [− 11.5;5.98] | 0.520 |
| Length of ICU stay (for 10 days) | 1.02 | [0.14;1.90] | 0.025 |
| Predicting anxiety in follow-up | |||
| History of sleep disorders | 0.98 | [− 1.87;3.78] | 0.488 |
| Acute respiratory distress syndrome | 0.206 | ||
| Mild | Reference | Reference | |
| Moderate | 0.75 | [− 1.39;2.94] | |
| Severe | 2.36 | [− 0.30;4.97] | |
| Cumulative dose of morphine (for 1000 units) | 0.15 | [− 0.45;0.76] | 0.612 |
| Cumulative dose of midazolam (for 100 units) | 0.02 | [− 0.12;0.07] | 0.537 |
| Cumulative dose of clonidine (for 1 unit) | 0.43 | [− 0.12;0.98] | 0.118 |
| Maximal dose of norepinephrine | − 2.61 | [− 7.64;2.44] | 0.301 |
| Length of ICU stay (for 10 days) | 0.46 | [− 0.07;0.99] | 0.091 |
| Predicting depression in follow-up | |||
| History of sleep disorders | 1.19 | [− 2.09;4.41] | 0.464 |
| Acute respiratory distress syndrome | 0.823 | ||
| Mild | Reference | Reference | |
| Moderate | 0.75 | [− 1.89;3.42] | |
| Severe | 0.81 | [− 2.43;3.99] | |
| Cumulative dose of morphine (for 1000 units) | 0.05 | [− 0.60;0.69] | 0.883 |
| Cumulative dose of midazolam (for 100 units) | 0.02 | [− 0.05;0.09] | 0.588 |
| Cumulative dose of clonidine (for 1 unit) | 0.57 | [0.11;1.03] | 0.019 |
| Maximal dose of norepinephrine | − 2.82 | [− 8.11;2.54] | 0.292 |
| Length of ICU stay (for 10 days) | 0.39 | [− 0.23;1.01] | 0.208 |
| Predicting post-traumatic stress disorder in follow-up | |||
| History of sleep disorders | 8.36 | [− 1.60;18.4] | 0.100 |
| Acute respiratory distress syndrome | 0.059 | ||
| Mild | Reference | Reference | |
| Moderate | 0.55 | [− 7.13;8.17] | |
| Severe | 9.81 | [1.06;18.5] | |
| Cumulative dose of morphine (for 1000 units) | 0.21 | [− 1.77;2.17] | 0.826 |
| Cumulative dose of midazolam (for 100 units) | 0.16 | [− 0.04;0.35] | 0.103 |
| Cumulative dose of clonidine (for 1 unit) | 0.93 | [− 1.14;3.01] | 0.363 |
| Maximal dose of norepinephrine | 5.71 | [− 9.65;21.0] | 0.449 |
| Length of ICU stay (for 10 days) | 1.54 | [− 0.37;3.42] | 0.109 |
Bold values indicate statistically significant association
β: regression coefficient of the linear mixed model with random intercept
CI confidence interval, ICU intensive care unit
Acknowledgements
We would like to thank Audrey Fontaine, Aurélie Mollar, Anouk Chignac, Sarah Gimenez and Flore Mathias for their participation in psychological support and evaluation. We also thank also Cécile Klochendler, Cedric Valtat, Muriel Bascarisse, Aurélien Boiseau for research organization, data collection and monitoring.
Abbreviations
- ARDS
Acute respiratory distress syndrome
- HADS
Hospital Anxiety and Depression Scale
- ICU
Intensive care unit
- ISI
Insomnia Severity Index
- PCL-5
Posttraumatic Stress Disorder Checklist for DSM-5
- PTSD
Post-traumatic stress disorder
Authors' contributions
RP, DG, SB designed the study and wrote the manuscript. AO collected patients’ data. JC performed statistical analysis. All authors read and approved the final manuscript.
Funding
No funding.
Availability of data and materials
The datasets analysed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
Informed consent for each patient was obtained as required by French ethics law and research was performed according to The Code of Ethics of the World Medical Association (Declaration of Helsinki).
Consent for publication
Not applicable.
Competing interests
On behalf of all authors, the corresponding author states that there is no competing interests.
Footnotes
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References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets analysed during the current study are available from the corresponding author on reasonable request.