Nowadays, delirium is considered a widespread problem in intensive care patients all around the globe. The incidence of ICU-acquired delirium is substantial and varies within specific subgroups, with the highest reported incidence up to 80% in mechanically ventilated patients [
This retrospective single-centre study was performed in a closed-format 20-bed mixed ICU in a tertiary teaching hospital, where all patient categories are treated except for neurosurgical patients. All patients ≥18 years with an ICU stay of >48 hours during the period 2012-2013 were included in the study. Patients admitted after cardiac arrest were excluded, since we considered postanoxic encephalopathy a different entity and hard to differentiate from delirium in the clinical setting. The study was performed in accordance with the Declaration of Helsinki, and anonymised data were used for analysis. According to applicable laws, the need for individual consent was waived by the local ethics committee.
Data were collected by the first and second author from the hospital electronic health records (Mirador®) and patient data management system (Metavision®). The following data were recorded at baseline: demographic characteristics; (psychiatric) comorbidity; use of psychoactive medication; substances of abuse; and admission type. Acute Physiology and Chronic Health Evaluation (APACHE) III and Sequential Organ Failure Assessment (SOFA) scores were calculated over the first 24 hours following ICU admission [
Drugs that were administered to treat symptoms of delirium were noted. For the most common drug (haloperidol), the number of days and the maximum given intravenous dose over 24 hours were additionally recorded. In case of enteral administration of haloperidol, the dose was divided by two to convert to an equivalent intravenous dose. Benzodiazepines were only registered when subscribed for agitation and not in case of prescription for isolated sleep disturbance.
In general, a history of psychiatric disorder is documented in the hospital electronic medical record. In case we noticed a discrepancy during ICU admission between potential psychiatric medication without a documented history of psychiatric disorder, a dedicated hospital psychiatry paramedic cross-checked the psychiatric history with the family, general practitioner, or treating psychiatric facility. Main categories of a premorbid psychiatric disorder included all forms of depressive, anxiety, psychotic, and personality disorders. Patients with dementia were not included in the study. Main categories of psychoactive drugs included sedatives, tranquilizers, antipsychotic drugs, antidepressant drugs, and mood stabilizers. Use of benzodiazepines for insomnia and tricyclic antidepressants for chronic pain was excluded. Sedation of patients was monitored by the Richmond Agitation-Sedation Scale (RASS). For every patient with RASS score >−3, the Confusion Assessment Method in the Intensive Care Unit (CAM-ICU) was performed three times a day [
The Statistical Package for Social Sciences (SPSS 24 for Windows, Chicago, IL, USA) was used for statistical analysis. Distribution of continuous data was tested with a Kolmogorov–Smirnov test. Due to the non-normal distribution, such data are presented as median (IQR). After allocation into groups (with and without psychiatric history, and with and without delirium), a sampling distribution by chi-square testing was performed. A two-sided
All 472 identified patients who fulfilled the entry criteria over a 2-year period (2012-2013) were included in the study: 93 (19.7%) with (PS group) and 379 (80.3%) without (NPS group) a premorbid psychiatric history. Psychiatric disorders in PS group included depressive disorders (
Baseline characteristics.
Psychiatric ( |
Nonpsychiatric ( |
| |
---|---|---|---|
Age (years) | 63 (56–70) | 68 (61–76) | <0.001 |
Male (%) | 47 | 67 | <0.001 |
APACHE III score | 70 (55–94) | 68 (53–87) | 0.36 |
Predicted mortality (%) | 21 (5–40) | 15 (4–36) | 0.21 |
SOFA score | 7 (5–9) | 7 (5–9) | 0.83 |
Type of admission (%) | |||
Elective surgery | 28 | 38 | |
Emergency surgery | 33 | 25 | 0.10 |
Medical | 39 | 37 | |
Reason for admission (%) | |||
Sepsis | 35 | 35 | |
Respiratory failure | 4 | 7 | |
Trauma | 1 | 3 | |
Cardiac surgery | 38 | 30 | 0.05 |
Congestive heart failure | 4 | 1 | |
Noncardiac surgery | 8 | 8 | |
Renal failure | 2 | 0 | |
Other | 8 | 16 | |
Intoxications (%) | |||
Smoking | 18 | 12 | 0.12 |
Alcohol | 6 | 15 | 0.008 |
Soft drugs | 0 | 2 | 0.04 |
Hard drugs | 0 | 2 | 0.04 |
Medication (number of drugs) | 6 (3–10) | 5 (2–8) | 0.03 |
Psychoactive drugs (%) | |||
Antipsychotics | 82 | 0 | <0.001 |
Antidepressants | 53 | 2 | <0.001 |
Sedatives | 23 | 3 | <0.001 |
Hypnotics | 20 | 8 | 0.002 |
Data are presented as median (IQR). APACHE: Acute Physiology and Chronic Health Evaluation; SOFA Sequential Organ Failure Assessment.
Furthermore, alcohol abuse was significantly more present in the NPS group, whereas smoking did not significantly differ between groups. The overall incidence of delirium during ICU stay was 57% and did not significantly differ between groups (65% in PS group vs. 56% in the NPS group,
Main results.
Psychiatric ( |
Nonpsychiatric ( |
| |
---|---|---|---|
Delirium (%) | 65 | 56 | 0.13 |
Delirium (days) | 3 (0–6) | 1 (0–4) | 0.04 |
CAM-ICU positive (days) | 1 (0–3) | 0 (0–2) | 0.08 |
Use of midazolam (days#) | 2 (1–3) | 2 (2–3) | 0.37 |
Use of antipsychotics |
|||
Haloperidol (%) | 47 | 51 | 0.56 |
Haloperidol (days) | 0 (0–4) | 1 (0–4) | 0.65 |
Quetiapine (%) | 24 | 18 | 0.23 |
Use of sedatives |
|||
Clorazepate | 3 | 13 | <0.001 |
Propofol | 12 | 18 | 0.13 |
Others | 24 | 31 | 0.18 |
LOS ICU (days) | 7 (5–12) | 6 (4–11) | 0.07 |
LOS hospital (days) | 20 (14–32) | 16 (10–26) | 0.006 |
Mechanical ventilation (hours) | 66 (23–145) | 39 (7–130) | 0.01 |
ICU mortality (%) | 5.4 | 10.8 | 0.12 |
Hospital mortality (%) | 9.7 | 13.3 | 0.39 |
Data are presented as median (IQR). CAM-ICU: Confusion Assessment Method in the Intensive Care Unit, LOS: length of stay, ICU: intensive care unit. #For the initial sedation.
Kaplan–Meier survival analysis for patients with and without a premorbid psychiatric disorder.
In a post hoc additional analysis, we divided patients into two separate groups; one group consisted of ICU patients with delirium at any time during ICU admission (DEL,
Secondary analysis: baseline characteristics.
Delirium ( |
Nondelirium ( |
| |
---|---|---|---|
Age (years) | 68 (61–76) | 66 (56–74) | 0.007 |
Male (%) | 67 | 58 | 0.04 |
APACHE III score | 75 (58–93) | 60 (47–82) | <0.001 |
Predicted mortality (%) | 20 (7–41) | 11 (3–30) | <0.001 |
SOFA score | 7 (6–9) | 6 (4–8) | <0.001 |
Type of admission (%) | |||
Elective surgery | 40 | 34 | |
Emergency surgery | 25 | 27 | 0.33 |
Medical | 35 | 39 | |
Intoxications (%) | |||
Smoking | 14 | 12 | 0.58 |
Alcohol | 8 | 7 | 0.86 |
Soft drugs | 0.4 | 0.5 | 1 |
Hard drugs | 0.4 | 0.5 | 1 |
Medication (number of drugs) | 5 (2–8) | 5 (2–8) | 0.60 |
Psychoactive drugs (%) | |||
Antipsychotics | 3 | 4 | 0.46 |
Antidepressants | 12 | 11 | 0.77 |
Sedatives | 7 | 6 | 0.71 |
Hypnotics | 9 | 12 | 0.53 |
Continuity psychoactive drugs (%) | ( |
( |
|
No interruption | 12 | 17 | |
Restart within 4 days | 15 | 23 | 0.17 |
Restart later than 4 days | 15 | 4 | |
No restart | 58 | 56 |
Data are presented as median (IQR). APACHE: Acute Physiology and Chronic Health Evaluation; SOFA: Sequential Organ Failure Assessment.
In a univariate analysis, the presence of delirium at any time during ICU admission was significantly associated with prolonged mechanical ventilation and prolonged ICU and hospital stay, but not with mortality (Table
Secondary analysis: main results.
Delirium ( |
Nondelirium ( |
| |
---|---|---|---|
Use of midazolam (days#) | 2 (1–3) | 2 (1–3) | 0.56 |
Use of antipsychotics |
|||
Haloperidol (%) | 81 | 8 | <0.001 |
Quetiapine (%) | 31 | 3 | <0.001 |
Use of sedatives |
|||
Clorazepate | 8 | 1 | <0.001 |
Propofol | 63 | 0 | <0.001 |
Others | 41 | 4 | <0.001 |
LOS ICU (days) | 8 (6–15) | 5 (4–7) | <0.001 |
LOS hospital (days) | 20 (13–34) | 13 (9–19) | <0.001 |
Mechanical ventilation (hours) | 78 (23–186) | 23 (4–64) | <0.001 |
ICU mortality (%) | 9.9 | 9.9 | 1 |
Hospital mortality (%) | 13.6 | 11.4 | 0.58 |
Data are presented as median (IQR). CAM-ICU: Confusion Assessment Method in the Intensive Care Unit, LOS: length of stay, ICU: intensive care unit. #For the initial sedation
Kaplan–Meier survival analysis for patients with and without delirium during ICU stay.
Binary multiple regression analysis.
|
Exp ( |
95% CI Exp ( | ||
---|---|---|---|---|
Lower | Upper | |||
Male sex | 0.010 | 0.590 | 0.392 | 0.886 |
Age | 0.011 | 1.021 | 1.005 | 1.037 |
APACHE III score | 0.042 | 1.258 | 1.008 | 1.571 |
Psychiatric disorder | 0.019 | 1.815 | 1.103 | 2.987 |
Dependent variable: presence of delirium. Hosmer and Lemeshow
In this single-centre retrospective study, the incidence of a premorbid psychiatric disorder in long-stay ICU patients was 19.7%, with anxiety disorders as the main representative. In patients with a premorbid psychiatric disorder, the incidence of delirium was not significantly higher, but the duration of delirium was longer in comparison with controls.
The observed overall incidence of delirium of 57% in this population of long-stay ICU patients is in line with the reported range within and between previous publications. In a point-prevalence study among 104 ICUs worldwide, the reported prevalence in nonselected ICU patients was 32% [
Clearly our study has limitations. The retrospective design does not allow for strict definitions a priori, and the single-centre setting includes local protocols and treatment behaviour. Premorbid psychiatric disorders may not always be reported at the time of ICU admission, and patients may even suffer from psychiatric diseases without previous recognition. However, our long-term follow-up, cross-check with (potential) psychiatric medication, and the availability of medical correspondence in the hospital electronic health records allowed us to minimize the potential bias of missing premorbid psychiatric disorders. Similarly, the assessment of delirium remains a challenge. Although in our setting both ICU nurses and doctors screen for delirium multiple times each day, the incidence may still be underreported. CAM-ICU in general has good specificity but lacks sensitivity for the nonagitated forms of delirium [
In this selected group of ICU patients with a length of stay >48 hours and a premorbid psychiatric disorder, the incidence of delirium was not significantly higher in comparison with patients without a premorbid psychiatric disorder. However, there was a significant increase in duration of delirium in patients with a premorbid psychiatric disorder. A premorbid psychiatric disorder was not associated with 5-year all-cause mortality. In a multivariate analysis, the incidence of delirium per se was independently associated with male sex, age, APACHE III score, and a premorbid psychiatric disorder. However, delirium per se was not associated with a significant increase in long-term all-cause mortality.
The data that support the findings of this study are available from the Medical Centre Leeuwarden, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are, however, available from the authors upon reasonable request and with permission of the Medical Centre Leeuwarden.
The authors declare that there are no conflicts of interest regarding the publication of this paper.
Anna van der Kuur and Carina Bethlehem contributed equally to this work.