- Email: [email protected]
Incidence, prevalence, risk factor and outcome of delirium in intensive care unit: a study from India
Available online at www.sciencedirect.com
General Hospital Psychiatry 34 (2012) 639 – 646
Incidence, prevalence, risk factor and outcome of delirium in intensive care unit: a study from India Akhilesh Sharma, M.D. a , Savita Malhotra, M.D., Ph.D, F.A.M.S. a , Sandeep Grover, M.D. a,⁎, Surinder Kumar Jindal, M.D. b b
a Department of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India Department of Pulmonary Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India Received 6 February 2012; accepted 14 June 2012
Abstract Objective: To evaluate the incidence, prevalence, risk factors and outcome of delirium in the respiratory intensive care unit of a tertiary care hospital. Methods: Consecutive patients admitted to an eight-bed respiratory intensive care unit were screened for presence of delirium by a psychiatrist. Patients found to have delirium were evaluated using univariate techniques for their clinical profiles, risk factors for delirium, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, duration of stay (in days) and outcome at discharge from intensive care unit besides evaluation on Delirium Rating Scale-Revised 98 version (DRS-R-98). Results: Incidence and prevalence rate of delirium were 24.4% and 53.6% respectively. Univariate analyses revealed that the prevalence of delirium was higher (64%) in mechanically ventilated patients. The predisposing risk factors identified for delirium in univariate analysis were higher age; higher Glasgow Coma Scale score; increased APACHE II score; hyperuricemia; hypoalbuminemia; presence of acidosis; abnormal alkaline transferase levels; use of mechanical ventilation; higher number of total medication received and use of sedative, steroids and insulin. Univariate analysis showed that patients who were diagnosed with delirium had significantly longer duration of intensive care unit (ICU) stay and higher mortality rates. Age, multiple organ failure, hypoactive delirium and higher DRS-R-98 scores were significant risk factors for mortality in patients with delirium. Conclusions: Delirium is highly prevalent in the ICU setting and delirium is associated with longer ICU stay and higher mortality. © 2012 Elsevier Inc. All rights reserved. Keywords: Delirium; Incidence; Intensive care; Outcome; Prevalence; Risk factors
1. Introduction With advances in psychiatry and the evolution of liaison psychiatry, over the last 15 years, there has been increased research in delirium in the context of intensive care unit admission (ICU). Studies from the West suggest that depending upon the severity of physical illness and the age of the patient, 20–83% of patients admitted to ICU develop delirium with higher rates in the mechanically ventilated elderly subjects [1–4]. Research also indicates that delirium
⁎ Corresponding author. Tel.: + 91 172 2756807; fax: +91 172 2744401/2745078. E-mail address: [email protected] (S. Grover). 0163-8343/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.genhosppsych.2012.06.009
is independently associated with significant increase in length of hospital stay, rates of admission to long term care, rate of death, cognitive decline and health care costs [5–10]. One of the important limitations of studies evaluating incidence and prevalence rates of delirium in the ICU is that the diagnosis is based exclusively on screening instruments [11–13], and in only a few studies was the diagnosis of delirium confirmed by a psychiatrist [14,15]. Conventionally, the risk factors for delirium are divided into predisposing factors and precipitating factors. In general the predisposing factors are considered to be present before admission to the ICU and are difficult to alter, whereas the precipitating factors are considered to occur during the course of illness. The precipitating factors are further subdivided into those related to the critical illness and
640
A. Sharma et al. / General Hospital Psychiatry 34 (2012) 639–646
those related to therapeutic interventions. Although the risk factors for delirium have been studied to certain extent in the non-ICU patients, studies that have evaluated the risk factors in ICU setting are small in number [16–19]. Delirium in general is considered to be associated with high mortality [20–22]. Furthermore, among the various subtypes of delirium, studies in non-ICU patients suggest that hypoactive delirium is associated with poor prognosis, and studies among ICU patients also suggest the same [23]. Although in recent times some studies from India have presented data on prevalence, phenomenology and risk factors for delirium in non-ICU units [24–35], only a few studies have evaluated delirium in the context of ICU admission. Reasons to study ICU delirium include the following: (1) life expectancy has increased with resultant increase in proportion of geriatric population requiring end of life care for various physical ailments; (2) higher rates of road traffic accidents are requiring more use of critical care beds; (3) there is also an increase in number of complex surgical/medical interventions carried out these days requiring critical care to enhance outcomes and recovery. However, despite increases in the number of ICU beds across India, the demand is far greater. Further, critical care is associated with increase health care cost and requires specialist manpower. Hence, it is very important to judiciously use the existing infrastructure and manpower. The present study aimed to study the incidence, prevalence and phenomenology of delirium in patients admitted to respiratory intensive care unit (RICU) of a tertiary care teaching hospital in India. 1.1. Methodology This study was done in the RICU of a tertiary multispeciality teaching hospital. The RICU is an eight-bed unit managed by the pulmonary and critical care specialists. This study was approved by the ethics committee of the institute, and all the patients were recruited after obtaining proxy written informed consent from the primary care takers and family members of the patients. All the cases found to have delirium were reported to the treating team and managed appropriately. The study followed a prospective cohort design and was conducted in two separate phases, each lasting for a continuous period of three months in 2008–2009 (mid October 2008 to January 2009 and March 2009 to June 2009). Patients admitted to RICU aged more than 18 years and whose relatives provided proxy informed consent were eligible for the study. Those patients who were deaf or unable to speak or understand Hindi, English or Punjabi or whose caregivers refused consent were excluded. Each patient meeting the selection criteria was assessed daily throughout the RICU stay at a fixed time of the day. Each patient meeting the selection criteria was first evaluated on the Richmond Agitation and Sedation Scale
(RASS) [36,37] within 24 hours of admission to RICU. The RASS is an instrument to assess sedation and agitation of adult ICU patients and is simple to use. It is a 10-point scale with four levels of anxiety or agitation (+ 1 to +4), one level to denote a calm and alert state (0) and 5 levels to assess the level of sedation (− 1 to − 5). A score of − 4 indicates that the patient is unresponsive to verbal stimulation and finally, culminating in unarousable states (− 5). It has good interrater reliability and validity. Those patients, who rated − 3 through +4 on RASS were screened for delirium as per the DSM-IV criteria at a fixed time of the day (between 7–9 PM) by a psychiatrist. The diagnosis of delirium was based on the information provided by the patient, caregivers, treating physician and nurses. Any patient rated as unresponsive at the first assessment was reassessed on the next day and every subsequent day through out the RICU stay to ascertain his level of sedation and agitation using RASS. If at any stage the patient was found to be arousable, then he/she was screened for delirium by the psychiatrist. All the patients (those with or without delirium at any stage during the RICU stay) were followed up throughout the RICU stay for outcome. Phenomenology of delirium was assessed on Delirium Rating Scale-Revised 98 version (DRS-R-98) [38]. It is a 16-item scale with 13 items constituting the severity scale and 3 items being of diagnostic significance. Each item is rated on 0–3 to yield a total severity score ranging 0–39, a higher score indicating greater severity. It is a well-validated instrument with high inter-rater reliability, sensitivity, and specificity [38]. Subtyping of delirium was done on the basis of RASS scores as suggested by Peterson et al. [39]. A rating of +1 to +4 during most of the period while in delirium was taken as an indicator of hyperactive delirium (those patients who frequently exhibited agitation and restlessness, attempted to remove catheters or tubes, tried to get up from the bed, required physical restrain, tried to hit or did hit the persons around, appeared hyperalert and had hallucinations and/or delusions were categorized as having hyperactive delirium). A rating of 0 to − 4 during most of the period while in delirium was taken as an indicator of hypoactive delirium (those patients who were mostly calm and quite, appeared lethargic, hardly moved spontaneously and exhibited flat affect or apathy were categorized as having hypoactive delirium). Those patients who exhibited features of both types while in delirium were considered as having mixed type of delirium. All the patients who did not have delirium at admission but were found to have delirium after the first assessment (N 24 hours of admission) were classified as new cases of delirium and were counted towards incidence rate. Whereas all the cases found to have delirium at any stage of their ICU stay (ie, within 24 hours of admission or developing delirium after that) were classified as prevalence cases. Various risk factors for delirium were also evaluated prospectively. Only those factors, present at the time of admission to the RICU [ie, age, gender, smoking, Acute
A. Sharma et al. / General Hospital Psychiatry 34 (2012) 639–646
641
2.3. Sociodemographic and clinical profile
Physiology and Chronic Health Evaluation II (APACHE II) scores, Glasgow Coma Scale score, chronic physical illnesses, anemia, smoking, history of psychiatric disorders] or those which appeared just prior to being detected to have delirium (various electrolyte imbalance, other metabolic derangements, presence of respiratory failure, treatment related variables including requirement of mechanical ventilation, medications and postoperative status) were considered. These risk factors were identified based on the review of existing literature [11,13–19]. Presence of a factor, for example, an electrolyte imbalance was considered to be present if the values of the same were either lower or higher than the normal range as specified by the hospital laboratory.
The mean DRS-R-98 severity score was 11.34±4.10 (range 5–21) and mean DRS-R-98 total score was 16.24±4.56 (range 7–25).
1.2. Outcome of delirium in RICU
2.5. Subtypes of delirium
Mean duration of RICU stay and death in the RICU were taken as the outcome variables. Those patients discharged from RICU or shifted out of RICU alive were considered to have survived.
As per the subtyping based on RASS, the most common subtype of delirium seen in the present study was that of hypoactive type (n= 34; 45.33%), followed by hyperactive subtype (n= 28; 37.33%) and few patients had mixed subtype of delirium (n=13; 17.33%).
The mean age of the patients who developed delirium was significantly higher. There was no difference between those who developed delirium and who did not with respect to gender, education level and past psychiatric illness. A significantly higher percentage of patients who were on mechanical ventilation developed delirium (see Table 1). 2.4. DRS-R-98 profile of patients with delirium
1.3. Statistical analysis 2.6. Risk factors for delirium Data were analyzed using the SPSS-14. Descriptive analysis was computed in terms of mean and standard deviation with range for continuous sociodemographic variables (age at assessment) and clinical variables (duration of delirium). Frequency and percentages were calculated for discontinuous sociodemographic variables (gender) and clinical variables (etiology, medications, etc.). Chi-square test, Fisher's Exact test and t test were used to compare various variables of different groups and subgroups. 2. Results 2.1. Sample Of the 178 patients eligible for the study, 19 had very short stay (b 24 h) and were transferred out, discharged or expired prior to assessment for delirium. Of the remaining 159 patients, eight patients did not meet the selection criteria (the caregivers refused consent for six patients, and two had sensory impairments). Eleven patients remained comatose throughout their RICU stay and could not be assessed. Hence, the final sample comprised 140 patients. 2.2. Incidence and prevalence of delirium Of the 140 patients screened for delirium, 54 patients were detected to have delirium at the first assessment (ie, with in 24 h of admission in RICU). Of the 86 not found to have delirium at first assessment, 21 cases developed delirium subsequently during the RICU stay. This gave an incidence rate of 24.4%. Overall, 75 patients (53.6%) out of 140 were diagnosed with delirium during their RICU stay. Of the 140 patients, 94 patients were on mechanical ventilation, of which 60 developed delirium, giving a prevalence figure of 64% for delirium in mechanically ventilated patients.
As shown in Table 1, patients who developed delirium were significantly older. Although higher percentage of them were male, had hypertension, chronic obstructive pulmonary disease, coronary artery disease, anemia, malignancy and past psychiatric illness, these differences did not reach statistical significance. With regard to precipitating factors, compared to the nondelirium group, almost all the abnormalities were more frequent in the delirium group but in univariate analysis significant differences emerged only for Glasgow Coma Scale and APACHE-II scores, hyperuricemia, hypoalbuminemia, acidosis, deranged alkaline transferase levels, mechanical ventilation, use of steroids, sedatives (ie, benzodiazepines in the form of midazolam), insulin and total number of medications received. 2.7. Risk factors in incidence cases Similar analysis was done to assess risk factors in incidence cases only (ie, those who developed delirium while in RICU) by comparing this group with non-delirious group. The variable which were found to more frequently seen in the incidence delirium group in the univariate analysis, were smoking, presence of acidosis, higher APACHE-II scores and use of sedative medications (see Table 2). 2.8. Outcome of delirium in RICU 2.8.1. Duration of stay The median duration of RICU stay of patients who developed delirium was 7.9 (interquartile range 4.8–12.9) days and those who did not develop delirium was 4.5 (interquartile range 2.9–6.2) days, and this difference between the two groups was statistically significant (Mann Whitney value=1419.5; Pb.001).
642
A. Sharma et al. / General Hospital Psychiatry 34 (2012) 639–646
Table 1 Comparison of risk factors between delirious (either incidence or prevalence cases) and non delirious subjects using univariate analysis Risk factor Predisposing factors (host factors) Age (in years) Elderly patients (≥65 years)⁎ Gender, male Smoking (have been smoking for at least 1 years regularly and currently smoking just prior to falling acutely ill) Hypertension Diabetes mellitus Chronic obstructive pulmonary disease Chronic kidney disease Coronary artery disease Anemia Hypothyroidism Malignancy Past psychiatric illness Illness related factors Glasgow Coma Scale score APACHE II score CNS infection⁎ Respiratory failure Hyponatremia (serum sodium levels b135 mEq/L) Hypernatremia (serum sodium levels N145 mEq/L) Hyperkalemia (serum potassium levels b5.0 mEq/L) Hypokalemia (serum potassium levels b3.5 mEq/L) Hyperuricemia (serum uric acid N7 mg/dl) Hypoalbuminemia (serum albumin levels b3.4 g/dl) Hyperbilirubinemia (N2 mg/dl) Urea (N100 mg/dl) Creatinine (N2 mg/dl) Deranged AST (N120 IU/l) Deranged ALT (N120 IU/l) Acidosis (pH b7.35) Alkalosis (pH N7.45) Acute renal failure Multiple organ failure Respiratory infection Sepsis Postoperative Treatment-related factors Mechanical ventilation (patient requiring assisted ventilation in the form of ventilator) Steroid medication Sedative medication Antibiotics Antipsychotics Antihypertensives Insulin Total number of medication received
Delirious subjects, n=75 (frequency)
Non-delirious subjects, n=65 (frequency)
chi-Square test/t test (significance)
49.53±19.27 23 43 20
37.43±13.94 1 29 9
4.20 (Pb.001) 19.12 (Pb.001) 2.25 (P=.13) 3.48 (0.06)
7 4 13 1 5 40 2 4 6
4 3 5 3 0 32 2 1 3
0.146 (0.702) Fisher's Exact test, P=1.00 2.89 (.089) Fisher's Exact test, P=.33 2.76 (.096) 0.23 (.62) Fisher's Exact test, P=1.00 Fisher's Exact test, P=.37 Fisher's Exact test, P=.50
6.96±2.13 19.52±5.65 6 48 30 15 21 9 28 35 3 5 6 21 25 45 22 3 13 13 31 5
5.44±2.77 14.66±6.28 1 31 20 14 16 2 12 20 4 5 3 12 12 17 18 8 8 16 32 5
3.64 (Pb.001) 4.81 (.000) 1.85 (.174) 3.76 (.056) 1.29 (.25) 0.05 (.82) 0.20 (.65) 2.69 (.10) 6.07 (.014) 3.69 (.05) Fisher's Exact test, P=.70 0.00 (1.00) 0.22 (.63) 1.75 (.18) 3.96 (.047) 16.16 (b.001) 0.04 (.83) 2.27 (0.132) 0.69 (.40) 1.12 (.28) 0.87 (.34) 0.05 (.81)
60
34
12.10 (.001)
52 27 59 14 18 38 5.97±1.33
34 13 49 7 11 17 5.46±1.16
4.733 (.030) 4.36 (.037) 0.21 (.64) 1.70 (.19) 1.06 (.30) 8.77 (.003) 2.402 (.018)
⁎ Chi-square value with Yate's correction.
2.8.2. Mortality All the 65 patients in the nondelirious group improved by the time they were shifted out of the RICU. In contrast, only 49 (65.3%) patients in the delirium group survived and 23 (30.7%) of the 75 delirious patients died during the RICU stay. Three patients of the delirium group left the RICU against the medical advice, which is often seen in India when the chances of improving are minimal. Further analysis was done to study the predictors of mortality in delirium patients,
for which the data of 23 patients who did not survive were compared with 49 patients who survived. As shown in Table 3, patients who did not survive were younger than those who were alive; more commonly had malignancy and multi-organ failure. Among the delirium variables, patients who did not survive had higher DRS-R-98 severity scores and higher DRS-R-98 total score. With regard to subtype of delirium, for comparison purposes, hyperactive and mixed subgroups were combined together and compared with
A. Sharma et al. / General Hospital Psychiatry 34 (2012) 639–646
643
Table 2 Comparison of risk factors between incidence delirium and non delirious subjects using univariate analysis Risk factor
Delirious subjects, n=21 (frequency)
Nondelirious subjects, n=65 (frequency)
chi-Square test/ t test (significance)
Smoking (have been smoking for at least 1 year regularly and currently smoking just prior to falling acutely ill) Acidosis (pH b7.35)⁎ Sedative medication
7
9
3.98 (.046)
13 10
8.93 (.003) 6.18 (.013)
APACHE II Score
18.23±5.47
17 13 Mean±S.D. 14.66±6.28
2.35 (.021)
⁎ Chi-square value with Yate's Correction.
hypoactive subtype. It was seen that hypoactive subtype was more common in patients who did not survive. As malignancy was only seen in the group which did not survive, it was not considered further in the analysis, because it is as such considered as an important predictor of mortality, irrespective of delirium.
3. Discussion This is possibly the first study from India which assessed the incidence, prevalence, risk factors and outcome delirium in ICU patients. In the present study, all the subjects admitted in RICU during the period of 6 months formed the study sample. The sample was recruited during the two time frames of 3 months each. The two study durations of 3 months were in the either half of the calendar year, taking care of the seasonal variations in the causes (especially infective causes) of admission to RICU. The major strengths of the present study include the assessment of all patients by a psychiatrist at specified times each day, which is an improvement over the previous studies [11,12,15] which just relied on the screening instruments to make the diagnosis of delirium. Further assessment at a fixed time allowed leverage for the diurnal fluctuation of symptoms and maintenance of homogeneity of assessments. Additionally, the study focused on both incidence and prevalence of delirium in ICU patients. In the present study, the prevalence rate for delirium was 53.6% and the incidence rate of delirium was 24.4%. The Table 3 Comparison of risk factors (either incidence or prevalence cases) for death during ICU stay using univariate analysis Risk factor
Deaths, n=23 Improved, n=49 chi-Square test/ (frequency) (frequency) t test (significance)
Malignancy⁎ 4 Multi-organ failure 7 Hypoactive delirium 17 Mean±SD Age (in years) 43.83±21.22 Severity of delirium 13.86±4.34 Total DRS-R-98 19.13±4.79 score
0 5 16
5.60 (.018) 4.08 (.043) 9.40 (.002)
53.13±17.20 9.86±3.36 14.60±3.62
2.08 (.041) 4.21 (b.001) 4.37 (b.001)
⁎ Chi-square value with Yate's Correction.
prevalence of delirium in mechanically ventilated patients was 64%. Previous studies have reported an incidence rate of 20–40% in ICU population [1,2,6,8,11,23,40]. Findings of the current study of incidence and prevalence fall in the range available in the literature and suggest that delirium is equally prevalent in ICU setting in developed and developing countries. Further the prevalence of delirium in mechanically ventilated subjects in the present study is also in the range reported in the literature [11,23]. The mean age of the whole sample was 45 years, similar to that reported in studies on RICU patients from our centre [41,42]. The study population in the present study was much younger than that reported in studies on medical ICU population of developed countries, where the mean age is usually more than 65 years [13,43]. These differences in age possibly reflect the kind of patients admitted in ICU in developed and developing countries. In the West ICU facilities are mostly utilized by those who are terminally ill or suffering from malignancies and infectious causes are reported less frequently [13,16,17,43,44]. Whereas in the developing countries like India, infectious causes leading to hospitalization are more frequent than the West. This age profile of the patients with delirium also similar to the age of the patients reported in other studies on delirium in non-ICU patients from our center [24,28,34]. A significantly higher percentage of elderly patients developed delirium compared to younger patients and this finding supports the notion that prevalence and incidence of delirium is higher in elderly and older age is one of the important predisposing risk factor for delirium [12,13,43,45,46]. In the present study, the hypoactive subtype was the most common subtype of delirium, followed by hyperactive subtype and mixed subtype was the least common. Hypoactive subtype being the most common subtype of delirium in the present study is line with the existing literature with respect to delirium subtypes in ICU [13,16,23,39,43–45,47]. However, the hyperactive subtype, which was the second most common subtype in the current study, is contrary to the previous reported findings, which have reported mixed subtype to be the second most common subtype [13,16,17,43,45]. Previous studies have evaluated the risk factors for delirium in intensive care unit [11,13–15,46]. The present study attempted to study the predictors of delirium in a RICU
644
A. Sharma et al. / General Hospital Psychiatry 34 (2012) 639–646
by using a prospective design. Methodologically, the present study employed a better design compared to some of the earlier studies which have employed retrospective study design to study the risk factors for delirium in ICU [46,48]. Predictors of delirium in the present study were higher Glasgow Coma Score, abnormal alkaline transferase levels, presence of acidosis, APACHE-II score; use of mechanical ventilation, steroids, sedatives and insulin and higher number of medications and smoking (only in incidence cases). Studies done in the ICU patients from west have also reported similar findings in the univariate and/or multivariate analysis [12–15,46]. Previous studies have also linked use of steroids with development of delirium [53]. Studies have also shown that use of steroids can lead to many neuropsychiatric manifestations like psychosis, depression, mania and cognitive disturbances. Hence, the possible mechanism for development of delirium may be similar to development of cognitive disturbances and psychosis, which have some overlap with delirium. In the present study use of total number of medications was an important predictor of delirium. This finding suggests that clinicians should use medications judiciously in ICU patients. A recent randomized controlled trial [54], which compared no sedation with use of sedatives in patients receiving mechanical ventilation in ICU showed that no sedation was associated with significantly more number of days without ventilation and shorter duration of stay in ICU. The present study also shows that use of sedatives is associated with development of delirium, which is a predictor of longer duration of ICU stay. Hence, it can be said that sedation should not be routinely used in all patients to induce coma, and a judicious approach in selection of patients for sedation is required. Earlier studies have reported fever, infections, anemia, azotemia, elevated hepatic enzymes, hyperbilirubinemia, hypertension, hypocalcaemia, hyponatremia, hypotension, morphine use, etc., with development of delirium in ICU patients [11,13–15,46]; however, these did not emerge as important predictors of delirium in the present study. These differences possibly reflects the differences in various types of ICU set ups studied (medical versus surgical) and patient selection practices. The present study supports the findings from other countries that delirium is associated with longer duration of ICU stay and higher ICU mortality [15,38,49–52]. This suggests that it is important to recognize delirium as early as possible and manage it appropriately so as reduce ICU morbidity and mortality. Studies have shown that physicians usually have poor knowledge about delirium, and this is often missed or expected to occur in seriously ill patients; hence, it is not given as much importance as other organ dysfunctions [55]. Hence, the first step in reducing the ICU morbidity and mortality should be to make the physician aware of these facts and help them in identifying this disorder. Another important finding of the present study is that hypoactive delirium is an important predictor of mortality. Previous studies from non-ICU set up have also reported the
same [56,57]. Studies in general have shown that many patients with hypoactive delirium are actually not referred for psychiatric consultations because these patients are not that problematic as hyperactive patients and actually these patients are missed and hypoactive delirium remains untreated. This suggests that besides increasing the awareness of the physicians about delirium and helping them to identifying delirium, having all the ICU patients routinely screened may be a worthwhile endeavor; however, a cost–benefit analysis of the same is required. The present study has many limitations like small size, restriction of assessment to a single ICU setup and single assessment of delirium per day. Furthermore, we did not assess the prevalence of dementia in the patients before the development of delirium, although some of the studies suggest that there is no difference in the phenomenology of delirium in those with and without dementia. We did not evaluate certain risk factors like hypocalcemia, noise levels, alcohol use, use of dopamine and pre-existing cognitive disturbances which have been reported to be risk factors for ICU delirium. The present study also excluded the patients with hearing and visual impairments who are considered to be at higher risk for development of delirium. Other factors like doses of sedatives and steroids were also not evaluated to understand to dosecausality/risk relationship. We also did not carry out a multivariable analysis, thus leaving open the possibility that any individual characteristic may be explained by measured or unmeasured confounders. Future studies addressing the above limitations would be useful. In our study, we also did not fix mortality time point hence this could have led to some bias introduced by discharge practices and variable length of stay. We also did not use the multivariate analysis to study the factors associated with delirium. To conclude, although being a preliminary study, the present study suggests that delirium is highly prevalent in ICU setting in developing country like India. Our study suggests that hypoactive delirium is the most common subtype of delirium in ICU patients. Older age, acidosis and use of steroids are important predictors of delirium. Delirium leads to longer ICU stay and higher mortality. Among the various predictors of mortality, hypoactive delirium is the strongest predictor of mortality. All these factors are common to ICUs across the developing and developed countries. Hence, it is important to screen all the patients admitted to ICU for delirium, judiciously use benzodiazepines and steroids and correct the associated metabolic abnormalities at the earliest. References [1] Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA 2001;286: 2703–10. [2] Bergeron N, Dubois MJ, Dumont M, et al. Intensive Care Delirium Screening Checklist: evaluation of a new screening tool. Intensive Care Med 2001;27:859–64.
A. Sharma et al. / General Hospital Psychiatry 34 (2012) 639–646 [3] Pandharipande P, Cotton B, Shintani A, et al. Prevalence and risk factors for development of delirium in surgical and trauma intensive care unit patients. J Trauma 2008;65:34–41. [4] Lat I, McMillian W, Taylor S, et al. The impact of delirium on clinical outcomes in mechanically ventilated surgical and trauma patients. Crit Care Med 2009;37:1898–905. [5] Lin SM, Liu CY, Wang CH. The impact of delirium on the survival of mechanically ventilated patients. Crit Care Med 2004;32:2254–9. [6] Ely EW, Gautam S, Margolin R, et al. The impact of delirium in the intensive care unit on hospital length of stay. Intensive Care Med 2001;27:1892–900. [7] Ely EW, Inouye SK, Bernard GR. Delirium in mechanically ventilated patients: validity and reliability of confusion assessment methods for the intensive care unit (CAM-ICU). JAMA 2001;286:2703–10. [8] Ely EW, Margolin R, Francis J. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med 2001;29:1370–9. [9] Milbrandt EB, Deppen S, Harrison PL, et al. Costs associated with delirium in mechanically ventilated patients. Crit Care Med 2004;32:955–62. [10] Jackson JC, Gordon SM, Hart RP, et al. The association between delirium and cognitive decline: a review of the empirical literature. Neuropsychol Rev 2004;14:87–98. [11] McNicoll L, Pisani MA, Zhang Y, et al. Delirium in the intensive care unit: occurrence and clinical course in older patients. J Am Geriatr Soc 2003;51:591–8. [12] Pandharipande P, Shintani A, Peterson JF, et al. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology 2006;104:21–6. [13] Dubois MJ, Bergeron N, Dumont M, et al. Delirium in an intensive care unit: a study of risk factors. Intensive Care Med 2001;27:1297–304. [14] Aldemir M, Ozen S, Kara IH, et al. Predisposing factors for delirium in the surgical intensive care unit. Crit Care 2001;5:265–70. [15] Ouimet S, Riker R, Bergeon N, et al. Subsyndromal delirium in the ICU: evidence for a disease spectrum. Intensive Care Med 2007;33:1007–13. [16] Girard TD, Pandharipande PP, Ely EW. Delirium in the intensive care unit: review. Crit Care 2008;12(Suppl 3):S3. [17] Rompaey BV, Schuurmans MJ, Shortridge-Baggett LM, et al. Risk factors for intensive care delirium: a systematic review. Intensive Crit Care Nursing 2008;24:98–107. [18] Bruno JJ, Warren ML. Intensive care unit delirium. Crit Care Nurs Clin North Am 2010;22:161–78. [19] Mattoo SK, Grover S, Gupta N. Delirium in general practice. Indian J Med Res 2010;131:387–98. [20] Shehabi Y, Riker RR, Bokesch PM, et al. Delirium duration and mortality in lightly sedated, mechanically ventilated intensive care patients. Crit Care Med 2010;38:2311–8. [21] Inouye SK, Rushing JT, Foreman MD, et al. Does delirium contribute to poor hospital outcomes? A three-site epidemiologic study. J Gen Intern Med 1998;13:234–42. [22] Grover S, Shah R, Aarya KR. The mortality rate among patients with delirium 6 months after diagnosis by a consultation-liaison psychiatric team. Turkish J Psychiatry 2012 (in press). [23] Ely EW, Shintani A, Truman B. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004;291:1753–62. [24] Grover S, Chakrabarti S, Shah R, et al. A factor analytic study of the Delirium Rating Scale-Revised-98 in untreated patients with delirium. J Psychosom Res 2011;70:473–8. [25] Grover S, Kate N, Agarwal M, et al. Delirium in elderly: a study from a psychiatric liaison service in North India. Int Psychogeriatr 2012;24:117–27. [26] Grover S, Kumar V, Chakrabarti S. Comparative efficacy study of haloperidol, olanzapine and risperidone in delirium. J Psychosomatic Res 2011;71:277–81. [27] Grover S, Malhotra S, Bharadwaj R, et al. Delirium in children and adolescents. Int J Psychiatry Med 2009;39:179–87.
645
[28] Grover S, Subodh BN, Avasthi A, et al. Prevalence and clinical profile of delirium: a study from a tertiary-care hospital in north India. Gen Hosp Psychiatry 2009;31:25–9. [29] Jain G, Chakrabarti S, Kulhara P. Symptoms of delirium: an exploratory factor analytic study among referred patients. Gen Hosp Psychiatry 2011;33:377–85. [30] Chrispal A, Mathews KP, Surekha V. The clinical profile and association of delirium in geriatric patients with hip fractures in a tertiary care hospital in India. J Assoc Physicians India 2010;58:15–9. [31] Khurana PS, Sharma PSVN, Avasthi A. Prevalence of delirium in geriatric hospitalized general medical population. Indian J Psychiatry 2002;44:41–6. [32] Khurana PS, Sharma PSVN, Avasthi A. Risk factors in delirious geriatric general medical inpatients. Indian J Psychiatry 2002;44:266–72. [33] Khurana V, Gambhir IS, Kishore D. Evaluation of delirium in elderly: a hospital-based study. Geriatr Gerontol Int 2011;11:467–73. [34] Mattoo SK, Grover S, Chakrabarty K, et al. Symptom profile and etiology of delirium in a referral population in Northern India: factor analysis of the DRS-R98. J Neuropsychiatry Clin Neurosci 2012;24:95–101. [35] Grover S, Kate N, Malhotra S, Chakrabarti S, Mattoo SK, Avasthi A. Symptom profile of delirium in children and adolescent - Does it differs from adults and elderly? General Hospital Psychiatry 2012. http://dx.doi.org/10.1016/j.genhosppsych.2012.03.003. [36] Ely EW, Truman B, Shintani A, et al. Monitoring sedation status over time in ICU patients; reliability and validity of the Richmond agitationsedation scale (RASS). JAMA 2003;289:2983–91. [37] Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, Tesoro EP, Elswick RK. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 2002;166:1338–44. [38] Trzepacz PT, Mittal D, Torres R, et al. Validation of delirium rating scale revised-98: comparison to the delirium rating scale and cognitive test for delirium. J Neuropsychiatry Clin Neurosciences 2001;13:229–42. [39] Peterson JF, Pun BT, Dittus RS, et al. Delirium and its motoric subtypes: a study of 614 critically ill patients. J Am Geriatr Soc 2006;54:479–84. [40] Nelso JE, Tandon N, Mercado AF, et al. Brain Dysfunction: another burden for the chronically critically ill. Arch Intern Med 2006;166:1993–9. [41] Agarwal R, Gupta R, Aggarwal AN, et al. Noninvasive positive pressure ventilation in acute respiratory failure due to COPD vs other causes: Effectiveness and predictors of failure in a respiratory ICU in North India. Int J COPD 2008;3:737–74. [42] Agarwal R, Handa A, Aggarwal AN, et al. Outcomes of noninvasive ventilation in acute hypoxemic respiratory failure in a Respiratory Intensive Care Unit in North India. Respir Care 2009;54:1679–87. [43] Spronk PE, Riekerk B, Hofhuis J, et al. Occurrence of delirium is severely underestimated in the ICU during daily care: Brief Report. Intensive Care Med 2009;35:1466–8. [44] Lin SM, Huang CD, Liu CY, et al. Risk factors for the development of early-onset delirium and the subsequent clinical outcome in mechanically ventilated patients. J Crit Care 2008;23:372–9. [45] Rompaey BV, Schuurmans MJ, Shortridge-Baggett LM, et al. A comparison of the CAM-ICU and the NEECHAM Confusion Scale in intensive care delirium assessment: an observational study in nonintubated patients. Crit Care 2008;12:R16. [46] Sommer BR, Wise LC, Kraemer HC. Is dopamine administration possibly a risk factor for delirium? Crit Care Med 2002;30: 1508–11. [47] Jackson JC, Gordon SM, Hart RP, et al. The association between delirium and cognitive decline: a review of the empirical literature. Neuropsychol Rev 2004;14:87–98. [48] Chang YL, Tsai YF, Lin PJ, et al. Prevalence and risk factors for postoperative delirium in a cardiovascular intensive care unit. Am J Crit Care 2008;17:567–75.
646
A. Sharma et al. / General Hospital Psychiatry 34 (2012) 639–646
[49] Thomason JW, Shintani A, Peterson JF, et al. Intensive care unit delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-ventilated patients. Crit Care 2005;9:R375–81. [50] Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons; a predictive model and interrelationship with baseline vulnerability. JAMA 1996;275:852–7. [51] Marcantonio E, Simon S, Bergmann M, et al. Delirium symptoms in post-acute care: prevalent, persistent, and associated with poor functional recovery. J Am Geriatr Soc 2003;51:4–9. [52] Schor JD, Levkoff SE, Lipsitz LA, et al. Risk factors for delirium in hospitalized elderly. JAMA 1992;267:827–31.
[53] Vincent FM. The neuropsychiatric complications of corticosteroid therapy. Compr Ther 1995;21:524–8. [54] Ogundele O, Yende S. Pushing the envelope to reduce sedation in critically ill patients. Crit Care 2010;14:339. [55] Leentjens AF, van der Mast RC. Delirium in elderly people: an update. Curr Opin Psychiatry 2005;18:325–30. [56] Liptzin B, Levkoff SE. An empirical study of delirium subtypes. Br J Psychiatry 1992;161:843–5. [57] Kiely DK, Jones RN, Bergmann MA, Marcantonio ER. Association between psychomotor activity delirium subtypes and mortality among newly admitted post-acute facility patients. J Gerontol A Biol Sci Med Sci 2007;62:174–9.
General Hospital Psychiatry 34 (2012) 639 – 646
Incidence, prevalence, risk factor and outcome of delirium in intensive care unit: a study from India Akhilesh Sharma, M.D. a , Savita Malhotra, M.D., Ph.D, F.A.M.S. a , Sandeep Grover, M.D. a,⁎, Surinder Kumar Jindal, M.D. b b
a Department of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India Department of Pulmonary Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India Received 6 February 2012; accepted 14 June 2012
Abstract Objective: To evaluate the incidence, prevalence, risk factors and outcome of delirium in the respiratory intensive care unit of a tertiary care hospital. Methods: Consecutive patients admitted to an eight-bed respiratory intensive care unit were screened for presence of delirium by a psychiatrist. Patients found to have delirium were evaluated using univariate techniques for their clinical profiles, risk factors for delirium, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, duration of stay (in days) and outcome at discharge from intensive care unit besides evaluation on Delirium Rating Scale-Revised 98 version (DRS-R-98). Results: Incidence and prevalence rate of delirium were 24.4% and 53.6% respectively. Univariate analyses revealed that the prevalence of delirium was higher (64%) in mechanically ventilated patients. The predisposing risk factors identified for delirium in univariate analysis were higher age; higher Glasgow Coma Scale score; increased APACHE II score; hyperuricemia; hypoalbuminemia; presence of acidosis; abnormal alkaline transferase levels; use of mechanical ventilation; higher number of total medication received and use of sedative, steroids and insulin. Univariate analysis showed that patients who were diagnosed with delirium had significantly longer duration of intensive care unit (ICU) stay and higher mortality rates. Age, multiple organ failure, hypoactive delirium and higher DRS-R-98 scores were significant risk factors for mortality in patients with delirium. Conclusions: Delirium is highly prevalent in the ICU setting and delirium is associated with longer ICU stay and higher mortality. © 2012 Elsevier Inc. All rights reserved. Keywords: Delirium; Incidence; Intensive care; Outcome; Prevalence; Risk factors
1. Introduction With advances in psychiatry and the evolution of liaison psychiatry, over the last 15 years, there has been increased research in delirium in the context of intensive care unit admission (ICU). Studies from the West suggest that depending upon the severity of physical illness and the age of the patient, 20–83% of patients admitted to ICU develop delirium with higher rates in the mechanically ventilated elderly subjects [1–4]. Research also indicates that delirium
⁎ Corresponding author. Tel.: + 91 172 2756807; fax: +91 172 2744401/2745078. E-mail address: [email protected] (S. Grover). 0163-8343/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.genhosppsych.2012.06.009
is independently associated with significant increase in length of hospital stay, rates of admission to long term care, rate of death, cognitive decline and health care costs [5–10]. One of the important limitations of studies evaluating incidence and prevalence rates of delirium in the ICU is that the diagnosis is based exclusively on screening instruments [11–13], and in only a few studies was the diagnosis of delirium confirmed by a psychiatrist [14,15]. Conventionally, the risk factors for delirium are divided into predisposing factors and precipitating factors. In general the predisposing factors are considered to be present before admission to the ICU and are difficult to alter, whereas the precipitating factors are considered to occur during the course of illness. The precipitating factors are further subdivided into those related to the critical illness and
640
A. Sharma et al. / General Hospital Psychiatry 34 (2012) 639–646
those related to therapeutic interventions. Although the risk factors for delirium have been studied to certain extent in the non-ICU patients, studies that have evaluated the risk factors in ICU setting are small in number [16–19]. Delirium in general is considered to be associated with high mortality [20–22]. Furthermore, among the various subtypes of delirium, studies in non-ICU patients suggest that hypoactive delirium is associated with poor prognosis, and studies among ICU patients also suggest the same [23]. Although in recent times some studies from India have presented data on prevalence, phenomenology and risk factors for delirium in non-ICU units [24–35], only a few studies have evaluated delirium in the context of ICU admission. Reasons to study ICU delirium include the following: (1) life expectancy has increased with resultant increase in proportion of geriatric population requiring end of life care for various physical ailments; (2) higher rates of road traffic accidents are requiring more use of critical care beds; (3) there is also an increase in number of complex surgical/medical interventions carried out these days requiring critical care to enhance outcomes and recovery. However, despite increases in the number of ICU beds across India, the demand is far greater. Further, critical care is associated with increase health care cost and requires specialist manpower. Hence, it is very important to judiciously use the existing infrastructure and manpower. The present study aimed to study the incidence, prevalence and phenomenology of delirium in patients admitted to respiratory intensive care unit (RICU) of a tertiary care teaching hospital in India. 1.1. Methodology This study was done in the RICU of a tertiary multispeciality teaching hospital. The RICU is an eight-bed unit managed by the pulmonary and critical care specialists. This study was approved by the ethics committee of the institute, and all the patients were recruited after obtaining proxy written informed consent from the primary care takers and family members of the patients. All the cases found to have delirium were reported to the treating team and managed appropriately. The study followed a prospective cohort design and was conducted in two separate phases, each lasting for a continuous period of three months in 2008–2009 (mid October 2008 to January 2009 and March 2009 to June 2009). Patients admitted to RICU aged more than 18 years and whose relatives provided proxy informed consent were eligible for the study. Those patients who were deaf or unable to speak or understand Hindi, English or Punjabi or whose caregivers refused consent were excluded. Each patient meeting the selection criteria was assessed daily throughout the RICU stay at a fixed time of the day. Each patient meeting the selection criteria was first evaluated on the Richmond Agitation and Sedation Scale
(RASS) [36,37] within 24 hours of admission to RICU. The RASS is an instrument to assess sedation and agitation of adult ICU patients and is simple to use. It is a 10-point scale with four levels of anxiety or agitation (+ 1 to +4), one level to denote a calm and alert state (0) and 5 levels to assess the level of sedation (− 1 to − 5). A score of − 4 indicates that the patient is unresponsive to verbal stimulation and finally, culminating in unarousable states (− 5). It has good interrater reliability and validity. Those patients, who rated − 3 through +4 on RASS were screened for delirium as per the DSM-IV criteria at a fixed time of the day (between 7–9 PM) by a psychiatrist. The diagnosis of delirium was based on the information provided by the patient, caregivers, treating physician and nurses. Any patient rated as unresponsive at the first assessment was reassessed on the next day and every subsequent day through out the RICU stay to ascertain his level of sedation and agitation using RASS. If at any stage the patient was found to be arousable, then he/she was screened for delirium by the psychiatrist. All the patients (those with or without delirium at any stage during the RICU stay) were followed up throughout the RICU stay for outcome. Phenomenology of delirium was assessed on Delirium Rating Scale-Revised 98 version (DRS-R-98) [38]. It is a 16-item scale with 13 items constituting the severity scale and 3 items being of diagnostic significance. Each item is rated on 0–3 to yield a total severity score ranging 0–39, a higher score indicating greater severity. It is a well-validated instrument with high inter-rater reliability, sensitivity, and specificity [38]. Subtyping of delirium was done on the basis of RASS scores as suggested by Peterson et al. [39]. A rating of +1 to +4 during most of the period while in delirium was taken as an indicator of hyperactive delirium (those patients who frequently exhibited agitation and restlessness, attempted to remove catheters or tubes, tried to get up from the bed, required physical restrain, tried to hit or did hit the persons around, appeared hyperalert and had hallucinations and/or delusions were categorized as having hyperactive delirium). A rating of 0 to − 4 during most of the period while in delirium was taken as an indicator of hypoactive delirium (those patients who were mostly calm and quite, appeared lethargic, hardly moved spontaneously and exhibited flat affect or apathy were categorized as having hypoactive delirium). Those patients who exhibited features of both types while in delirium were considered as having mixed type of delirium. All the patients who did not have delirium at admission but were found to have delirium after the first assessment (N 24 hours of admission) were classified as new cases of delirium and were counted towards incidence rate. Whereas all the cases found to have delirium at any stage of their ICU stay (ie, within 24 hours of admission or developing delirium after that) were classified as prevalence cases. Various risk factors for delirium were also evaluated prospectively. Only those factors, present at the time of admission to the RICU [ie, age, gender, smoking, Acute
A. Sharma et al. / General Hospital Psychiatry 34 (2012) 639–646
641
2.3. Sociodemographic and clinical profile
Physiology and Chronic Health Evaluation II (APACHE II) scores, Glasgow Coma Scale score, chronic physical illnesses, anemia, smoking, history of psychiatric disorders] or those which appeared just prior to being detected to have delirium (various electrolyte imbalance, other metabolic derangements, presence of respiratory failure, treatment related variables including requirement of mechanical ventilation, medications and postoperative status) were considered. These risk factors were identified based on the review of existing literature [11,13–19]. Presence of a factor, for example, an electrolyte imbalance was considered to be present if the values of the same were either lower or higher than the normal range as specified by the hospital laboratory.
The mean DRS-R-98 severity score was 11.34±4.10 (range 5–21) and mean DRS-R-98 total score was 16.24±4.56 (range 7–25).
1.2. Outcome of delirium in RICU
2.5. Subtypes of delirium
Mean duration of RICU stay and death in the RICU were taken as the outcome variables. Those patients discharged from RICU or shifted out of RICU alive were considered to have survived.
As per the subtyping based on RASS, the most common subtype of delirium seen in the present study was that of hypoactive type (n= 34; 45.33%), followed by hyperactive subtype (n= 28; 37.33%) and few patients had mixed subtype of delirium (n=13; 17.33%).
The mean age of the patients who developed delirium was significantly higher. There was no difference between those who developed delirium and who did not with respect to gender, education level and past psychiatric illness. A significantly higher percentage of patients who were on mechanical ventilation developed delirium (see Table 1). 2.4. DRS-R-98 profile of patients with delirium
1.3. Statistical analysis 2.6. Risk factors for delirium Data were analyzed using the SPSS-14. Descriptive analysis was computed in terms of mean and standard deviation with range for continuous sociodemographic variables (age at assessment) and clinical variables (duration of delirium). Frequency and percentages were calculated for discontinuous sociodemographic variables (gender) and clinical variables (etiology, medications, etc.). Chi-square test, Fisher's Exact test and t test were used to compare various variables of different groups and subgroups. 2. Results 2.1. Sample Of the 178 patients eligible for the study, 19 had very short stay (b 24 h) and were transferred out, discharged or expired prior to assessment for delirium. Of the remaining 159 patients, eight patients did not meet the selection criteria (the caregivers refused consent for six patients, and two had sensory impairments). Eleven patients remained comatose throughout their RICU stay and could not be assessed. Hence, the final sample comprised 140 patients. 2.2. Incidence and prevalence of delirium Of the 140 patients screened for delirium, 54 patients were detected to have delirium at the first assessment (ie, with in 24 h of admission in RICU). Of the 86 not found to have delirium at first assessment, 21 cases developed delirium subsequently during the RICU stay. This gave an incidence rate of 24.4%. Overall, 75 patients (53.6%) out of 140 were diagnosed with delirium during their RICU stay. Of the 140 patients, 94 patients were on mechanical ventilation, of which 60 developed delirium, giving a prevalence figure of 64% for delirium in mechanically ventilated patients.
As shown in Table 1, patients who developed delirium were significantly older. Although higher percentage of them were male, had hypertension, chronic obstructive pulmonary disease, coronary artery disease, anemia, malignancy and past psychiatric illness, these differences did not reach statistical significance. With regard to precipitating factors, compared to the nondelirium group, almost all the abnormalities were more frequent in the delirium group but in univariate analysis significant differences emerged only for Glasgow Coma Scale and APACHE-II scores, hyperuricemia, hypoalbuminemia, acidosis, deranged alkaline transferase levels, mechanical ventilation, use of steroids, sedatives (ie, benzodiazepines in the form of midazolam), insulin and total number of medications received. 2.7. Risk factors in incidence cases Similar analysis was done to assess risk factors in incidence cases only (ie, those who developed delirium while in RICU) by comparing this group with non-delirious group. The variable which were found to more frequently seen in the incidence delirium group in the univariate analysis, were smoking, presence of acidosis, higher APACHE-II scores and use of sedative medications (see Table 2). 2.8. Outcome of delirium in RICU 2.8.1. Duration of stay The median duration of RICU stay of patients who developed delirium was 7.9 (interquartile range 4.8–12.9) days and those who did not develop delirium was 4.5 (interquartile range 2.9–6.2) days, and this difference between the two groups was statistically significant (Mann Whitney value=1419.5; Pb.001).
642
A. Sharma et al. / General Hospital Psychiatry 34 (2012) 639–646
Table 1 Comparison of risk factors between delirious (either incidence or prevalence cases) and non delirious subjects using univariate analysis Risk factor Predisposing factors (host factors) Age (in years) Elderly patients (≥65 years)⁎ Gender, male Smoking (have been smoking for at least 1 years regularly and currently smoking just prior to falling acutely ill) Hypertension Diabetes mellitus Chronic obstructive pulmonary disease Chronic kidney disease Coronary artery disease Anemia Hypothyroidism Malignancy Past psychiatric illness Illness related factors Glasgow Coma Scale score APACHE II score CNS infection⁎ Respiratory failure Hyponatremia (serum sodium levels b135 mEq/L) Hypernatremia (serum sodium levels N145 mEq/L) Hyperkalemia (serum potassium levels b5.0 mEq/L) Hypokalemia (serum potassium levels b3.5 mEq/L) Hyperuricemia (serum uric acid N7 mg/dl) Hypoalbuminemia (serum albumin levels b3.4 g/dl) Hyperbilirubinemia (N2 mg/dl) Urea (N100 mg/dl) Creatinine (N2 mg/dl) Deranged AST (N120 IU/l) Deranged ALT (N120 IU/l) Acidosis (pH b7.35) Alkalosis (pH N7.45) Acute renal failure Multiple organ failure Respiratory infection Sepsis Postoperative Treatment-related factors Mechanical ventilation (patient requiring assisted ventilation in the form of ventilator) Steroid medication Sedative medication Antibiotics Antipsychotics Antihypertensives Insulin Total number of medication received
Delirious subjects, n=75 (frequency)
Non-delirious subjects, n=65 (frequency)
chi-Square test/t test (significance)
49.53±19.27 23 43 20
37.43±13.94 1 29 9
4.20 (Pb.001) 19.12 (Pb.001) 2.25 (P=.13) 3.48 (0.06)
7 4 13 1 5 40 2 4 6
4 3 5 3 0 32 2 1 3
0.146 (0.702) Fisher's Exact test, P=1.00 2.89 (.089) Fisher's Exact test, P=.33 2.76 (.096) 0.23 (.62) Fisher's Exact test, P=1.00 Fisher's Exact test, P=.37 Fisher's Exact test, P=.50
6.96±2.13 19.52±5.65 6 48 30 15 21 9 28 35 3 5 6 21 25 45 22 3 13 13 31 5
5.44±2.77 14.66±6.28 1 31 20 14 16 2 12 20 4 5 3 12 12 17 18 8 8 16 32 5
3.64 (Pb.001) 4.81 (.000) 1.85 (.174) 3.76 (.056) 1.29 (.25) 0.05 (.82) 0.20 (.65) 2.69 (.10) 6.07 (.014) 3.69 (.05) Fisher's Exact test, P=.70 0.00 (1.00) 0.22 (.63) 1.75 (.18) 3.96 (.047) 16.16 (b.001) 0.04 (.83) 2.27 (0.132) 0.69 (.40) 1.12 (.28) 0.87 (.34) 0.05 (.81)
60
34
12.10 (.001)
52 27 59 14 18 38 5.97±1.33
34 13 49 7 11 17 5.46±1.16
4.733 (.030) 4.36 (.037) 0.21 (.64) 1.70 (.19) 1.06 (.30) 8.77 (.003) 2.402 (.018)
⁎ Chi-square value with Yate's correction.
2.8.2. Mortality All the 65 patients in the nondelirious group improved by the time they were shifted out of the RICU. In contrast, only 49 (65.3%) patients in the delirium group survived and 23 (30.7%) of the 75 delirious patients died during the RICU stay. Three patients of the delirium group left the RICU against the medical advice, which is often seen in India when the chances of improving are minimal. Further analysis was done to study the predictors of mortality in delirium patients,
for which the data of 23 patients who did not survive were compared with 49 patients who survived. As shown in Table 3, patients who did not survive were younger than those who were alive; more commonly had malignancy and multi-organ failure. Among the delirium variables, patients who did not survive had higher DRS-R-98 severity scores and higher DRS-R-98 total score. With regard to subtype of delirium, for comparison purposes, hyperactive and mixed subgroups were combined together and compared with
A. Sharma et al. / General Hospital Psychiatry 34 (2012) 639–646
643
Table 2 Comparison of risk factors between incidence delirium and non delirious subjects using univariate analysis Risk factor
Delirious subjects, n=21 (frequency)
Nondelirious subjects, n=65 (frequency)
chi-Square test/ t test (significance)
Smoking (have been smoking for at least 1 year regularly and currently smoking just prior to falling acutely ill) Acidosis (pH b7.35)⁎ Sedative medication
7
9
3.98 (.046)
13 10
8.93 (.003) 6.18 (.013)
APACHE II Score
18.23±5.47
17 13 Mean±S.D. 14.66±6.28
2.35 (.021)
⁎ Chi-square value with Yate's Correction.
hypoactive subtype. It was seen that hypoactive subtype was more common in patients who did not survive. As malignancy was only seen in the group which did not survive, it was not considered further in the analysis, because it is as such considered as an important predictor of mortality, irrespective of delirium.
3. Discussion This is possibly the first study from India which assessed the incidence, prevalence, risk factors and outcome delirium in ICU patients. In the present study, all the subjects admitted in RICU during the period of 6 months formed the study sample. The sample was recruited during the two time frames of 3 months each. The two study durations of 3 months were in the either half of the calendar year, taking care of the seasonal variations in the causes (especially infective causes) of admission to RICU. The major strengths of the present study include the assessment of all patients by a psychiatrist at specified times each day, which is an improvement over the previous studies [11,12,15] which just relied on the screening instruments to make the diagnosis of delirium. Further assessment at a fixed time allowed leverage for the diurnal fluctuation of symptoms and maintenance of homogeneity of assessments. Additionally, the study focused on both incidence and prevalence of delirium in ICU patients. In the present study, the prevalence rate for delirium was 53.6% and the incidence rate of delirium was 24.4%. The Table 3 Comparison of risk factors (either incidence or prevalence cases) for death during ICU stay using univariate analysis Risk factor
Deaths, n=23 Improved, n=49 chi-Square test/ (frequency) (frequency) t test (significance)
Malignancy⁎ 4 Multi-organ failure 7 Hypoactive delirium 17 Mean±SD Age (in years) 43.83±21.22 Severity of delirium 13.86±4.34 Total DRS-R-98 19.13±4.79 score
0 5 16
5.60 (.018) 4.08 (.043) 9.40 (.002)
53.13±17.20 9.86±3.36 14.60±3.62
2.08 (.041) 4.21 (b.001) 4.37 (b.001)
⁎ Chi-square value with Yate's Correction.
prevalence of delirium in mechanically ventilated patients was 64%. Previous studies have reported an incidence rate of 20–40% in ICU population [1,2,6,8,11,23,40]. Findings of the current study of incidence and prevalence fall in the range available in the literature and suggest that delirium is equally prevalent in ICU setting in developed and developing countries. Further the prevalence of delirium in mechanically ventilated subjects in the present study is also in the range reported in the literature [11,23]. The mean age of the whole sample was 45 years, similar to that reported in studies on RICU patients from our centre [41,42]. The study population in the present study was much younger than that reported in studies on medical ICU population of developed countries, where the mean age is usually more than 65 years [13,43]. These differences in age possibly reflect the kind of patients admitted in ICU in developed and developing countries. In the West ICU facilities are mostly utilized by those who are terminally ill or suffering from malignancies and infectious causes are reported less frequently [13,16,17,43,44]. Whereas in the developing countries like India, infectious causes leading to hospitalization are more frequent than the West. This age profile of the patients with delirium also similar to the age of the patients reported in other studies on delirium in non-ICU patients from our center [24,28,34]. A significantly higher percentage of elderly patients developed delirium compared to younger patients and this finding supports the notion that prevalence and incidence of delirium is higher in elderly and older age is one of the important predisposing risk factor for delirium [12,13,43,45,46]. In the present study, the hypoactive subtype was the most common subtype of delirium, followed by hyperactive subtype and mixed subtype was the least common. Hypoactive subtype being the most common subtype of delirium in the present study is line with the existing literature with respect to delirium subtypes in ICU [13,16,23,39,43–45,47]. However, the hyperactive subtype, which was the second most common subtype in the current study, is contrary to the previous reported findings, which have reported mixed subtype to be the second most common subtype [13,16,17,43,45]. Previous studies have evaluated the risk factors for delirium in intensive care unit [11,13–15,46]. The present study attempted to study the predictors of delirium in a RICU
644
A. Sharma et al. / General Hospital Psychiatry 34 (2012) 639–646
by using a prospective design. Methodologically, the present study employed a better design compared to some of the earlier studies which have employed retrospective study design to study the risk factors for delirium in ICU [46,48]. Predictors of delirium in the present study were higher Glasgow Coma Score, abnormal alkaline transferase levels, presence of acidosis, APACHE-II score; use of mechanical ventilation, steroids, sedatives and insulin and higher number of medications and smoking (only in incidence cases). Studies done in the ICU patients from west have also reported similar findings in the univariate and/or multivariate analysis [12–15,46]. Previous studies have also linked use of steroids with development of delirium [53]. Studies have also shown that use of steroids can lead to many neuropsychiatric manifestations like psychosis, depression, mania and cognitive disturbances. Hence, the possible mechanism for development of delirium may be similar to development of cognitive disturbances and psychosis, which have some overlap with delirium. In the present study use of total number of medications was an important predictor of delirium. This finding suggests that clinicians should use medications judiciously in ICU patients. A recent randomized controlled trial [54], which compared no sedation with use of sedatives in patients receiving mechanical ventilation in ICU showed that no sedation was associated with significantly more number of days without ventilation and shorter duration of stay in ICU. The present study also shows that use of sedatives is associated with development of delirium, which is a predictor of longer duration of ICU stay. Hence, it can be said that sedation should not be routinely used in all patients to induce coma, and a judicious approach in selection of patients for sedation is required. Earlier studies have reported fever, infections, anemia, azotemia, elevated hepatic enzymes, hyperbilirubinemia, hypertension, hypocalcaemia, hyponatremia, hypotension, morphine use, etc., with development of delirium in ICU patients [11,13–15,46]; however, these did not emerge as important predictors of delirium in the present study. These differences possibly reflects the differences in various types of ICU set ups studied (medical versus surgical) and patient selection practices. The present study supports the findings from other countries that delirium is associated with longer duration of ICU stay and higher ICU mortality [15,38,49–52]. This suggests that it is important to recognize delirium as early as possible and manage it appropriately so as reduce ICU morbidity and mortality. Studies have shown that physicians usually have poor knowledge about delirium, and this is often missed or expected to occur in seriously ill patients; hence, it is not given as much importance as other organ dysfunctions [55]. Hence, the first step in reducing the ICU morbidity and mortality should be to make the physician aware of these facts and help them in identifying this disorder. Another important finding of the present study is that hypoactive delirium is an important predictor of mortality. Previous studies from non-ICU set up have also reported the
same [56,57]. Studies in general have shown that many patients with hypoactive delirium are actually not referred for psychiatric consultations because these patients are not that problematic as hyperactive patients and actually these patients are missed and hypoactive delirium remains untreated. This suggests that besides increasing the awareness of the physicians about delirium and helping them to identifying delirium, having all the ICU patients routinely screened may be a worthwhile endeavor; however, a cost–benefit analysis of the same is required. The present study has many limitations like small size, restriction of assessment to a single ICU setup and single assessment of delirium per day. Furthermore, we did not assess the prevalence of dementia in the patients before the development of delirium, although some of the studies suggest that there is no difference in the phenomenology of delirium in those with and without dementia. We did not evaluate certain risk factors like hypocalcemia, noise levels, alcohol use, use of dopamine and pre-existing cognitive disturbances which have been reported to be risk factors for ICU delirium. The present study also excluded the patients with hearing and visual impairments who are considered to be at higher risk for development of delirium. Other factors like doses of sedatives and steroids were also not evaluated to understand to dosecausality/risk relationship. We also did not carry out a multivariable analysis, thus leaving open the possibility that any individual characteristic may be explained by measured or unmeasured confounders. Future studies addressing the above limitations would be useful. In our study, we also did not fix mortality time point hence this could have led to some bias introduced by discharge practices and variable length of stay. We also did not use the multivariate analysis to study the factors associated with delirium. To conclude, although being a preliminary study, the present study suggests that delirium is highly prevalent in ICU setting in developing country like India. Our study suggests that hypoactive delirium is the most common subtype of delirium in ICU patients. Older age, acidosis and use of steroids are important predictors of delirium. Delirium leads to longer ICU stay and higher mortality. Among the various predictors of mortality, hypoactive delirium is the strongest predictor of mortality. All these factors are common to ICUs across the developing and developed countries. Hence, it is important to screen all the patients admitted to ICU for delirium, judiciously use benzodiazepines and steroids and correct the associated metabolic abnormalities at the earliest. References [1] Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA 2001;286: 2703–10. [2] Bergeron N, Dubois MJ, Dumont M, et al. Intensive Care Delirium Screening Checklist: evaluation of a new screening tool. Intensive Care Med 2001;27:859–64.
A. Sharma et al. / General Hospital Psychiatry 34 (2012) 639–646 [3] Pandharipande P, Cotton B, Shintani A, et al. Prevalence and risk factors for development of delirium in surgical and trauma intensive care unit patients. J Trauma 2008;65:34–41. [4] Lat I, McMillian W, Taylor S, et al. The impact of delirium on clinical outcomes in mechanically ventilated surgical and trauma patients. Crit Care Med 2009;37:1898–905. [5] Lin SM, Liu CY, Wang CH. The impact of delirium on the survival of mechanically ventilated patients. Crit Care Med 2004;32:2254–9. [6] Ely EW, Gautam S, Margolin R, et al. The impact of delirium in the intensive care unit on hospital length of stay. Intensive Care Med 2001;27:1892–900. [7] Ely EW, Inouye SK, Bernard GR. Delirium in mechanically ventilated patients: validity and reliability of confusion assessment methods for the intensive care unit (CAM-ICU). JAMA 2001;286:2703–10. [8] Ely EW, Margolin R, Francis J. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med 2001;29:1370–9. [9] Milbrandt EB, Deppen S, Harrison PL, et al. Costs associated with delirium in mechanically ventilated patients. Crit Care Med 2004;32:955–62. [10] Jackson JC, Gordon SM, Hart RP, et al. The association between delirium and cognitive decline: a review of the empirical literature. Neuropsychol Rev 2004;14:87–98. [11] McNicoll L, Pisani MA, Zhang Y, et al. Delirium in the intensive care unit: occurrence and clinical course in older patients. J Am Geriatr Soc 2003;51:591–8. [12] Pandharipande P, Shintani A, Peterson JF, et al. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology 2006;104:21–6. [13] Dubois MJ, Bergeron N, Dumont M, et al. Delirium in an intensive care unit: a study of risk factors. Intensive Care Med 2001;27:1297–304. [14] Aldemir M, Ozen S, Kara IH, et al. Predisposing factors for delirium in the surgical intensive care unit. Crit Care 2001;5:265–70. [15] Ouimet S, Riker R, Bergeon N, et al. Subsyndromal delirium in the ICU: evidence for a disease spectrum. Intensive Care Med 2007;33:1007–13. [16] Girard TD, Pandharipande PP, Ely EW. Delirium in the intensive care unit: review. Crit Care 2008;12(Suppl 3):S3. [17] Rompaey BV, Schuurmans MJ, Shortridge-Baggett LM, et al. Risk factors for intensive care delirium: a systematic review. Intensive Crit Care Nursing 2008;24:98–107. [18] Bruno JJ, Warren ML. Intensive care unit delirium. Crit Care Nurs Clin North Am 2010;22:161–78. [19] Mattoo SK, Grover S, Gupta N. Delirium in general practice. Indian J Med Res 2010;131:387–98. [20] Shehabi Y, Riker RR, Bokesch PM, et al. Delirium duration and mortality in lightly sedated, mechanically ventilated intensive care patients. Crit Care Med 2010;38:2311–8. [21] Inouye SK, Rushing JT, Foreman MD, et al. Does delirium contribute to poor hospital outcomes? A three-site epidemiologic study. J Gen Intern Med 1998;13:234–42. [22] Grover S, Shah R, Aarya KR. The mortality rate among patients with delirium 6 months after diagnosis by a consultation-liaison psychiatric team. Turkish J Psychiatry 2012 (in press). [23] Ely EW, Shintani A, Truman B. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004;291:1753–62. [24] Grover S, Chakrabarti S, Shah R, et al. A factor analytic study of the Delirium Rating Scale-Revised-98 in untreated patients with delirium. J Psychosom Res 2011;70:473–8. [25] Grover S, Kate N, Agarwal M, et al. Delirium in elderly: a study from a psychiatric liaison service in North India. Int Psychogeriatr 2012;24:117–27. [26] Grover S, Kumar V, Chakrabarti S. Comparative efficacy study of haloperidol, olanzapine and risperidone in delirium. J Psychosomatic Res 2011;71:277–81. [27] Grover S, Malhotra S, Bharadwaj R, et al. Delirium in children and adolescents. Int J Psychiatry Med 2009;39:179–87.
645
[28] Grover S, Subodh BN, Avasthi A, et al. Prevalence and clinical profile of delirium: a study from a tertiary-care hospital in north India. Gen Hosp Psychiatry 2009;31:25–9. [29] Jain G, Chakrabarti S, Kulhara P. Symptoms of delirium: an exploratory factor analytic study among referred patients. Gen Hosp Psychiatry 2011;33:377–85. [30] Chrispal A, Mathews KP, Surekha V. The clinical profile and association of delirium in geriatric patients with hip fractures in a tertiary care hospital in India. J Assoc Physicians India 2010;58:15–9. [31] Khurana PS, Sharma PSVN, Avasthi A. Prevalence of delirium in geriatric hospitalized general medical population. Indian J Psychiatry 2002;44:41–6. [32] Khurana PS, Sharma PSVN, Avasthi A. Risk factors in delirious geriatric general medical inpatients. Indian J Psychiatry 2002;44:266–72. [33] Khurana V, Gambhir IS, Kishore D. Evaluation of delirium in elderly: a hospital-based study. Geriatr Gerontol Int 2011;11:467–73. [34] Mattoo SK, Grover S, Chakrabarty K, et al. Symptom profile and etiology of delirium in a referral population in Northern India: factor analysis of the DRS-R98. J Neuropsychiatry Clin Neurosci 2012;24:95–101. [35] Grover S, Kate N, Malhotra S, Chakrabarti S, Mattoo SK, Avasthi A. Symptom profile of delirium in children and adolescent - Does it differs from adults and elderly? General Hospital Psychiatry 2012. http://dx.doi.org/10.1016/j.genhosppsych.2012.03.003. [36] Ely EW, Truman B, Shintani A, et al. Monitoring sedation status over time in ICU patients; reliability and validity of the Richmond agitationsedation scale (RASS). JAMA 2003;289:2983–91. [37] Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, Tesoro EP, Elswick RK. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 2002;166:1338–44. [38] Trzepacz PT, Mittal D, Torres R, et al. Validation of delirium rating scale revised-98: comparison to the delirium rating scale and cognitive test for delirium. J Neuropsychiatry Clin Neurosciences 2001;13:229–42. [39] Peterson JF, Pun BT, Dittus RS, et al. Delirium and its motoric subtypes: a study of 614 critically ill patients. J Am Geriatr Soc 2006;54:479–84. [40] Nelso JE, Tandon N, Mercado AF, et al. Brain Dysfunction: another burden for the chronically critically ill. Arch Intern Med 2006;166:1993–9. [41] Agarwal R, Gupta R, Aggarwal AN, et al. Noninvasive positive pressure ventilation in acute respiratory failure due to COPD vs other causes: Effectiveness and predictors of failure in a respiratory ICU in North India. Int J COPD 2008;3:737–74. [42] Agarwal R, Handa A, Aggarwal AN, et al. Outcomes of noninvasive ventilation in acute hypoxemic respiratory failure in a Respiratory Intensive Care Unit in North India. Respir Care 2009;54:1679–87. [43] Spronk PE, Riekerk B, Hofhuis J, et al. Occurrence of delirium is severely underestimated in the ICU during daily care: Brief Report. Intensive Care Med 2009;35:1466–8. [44] Lin SM, Huang CD, Liu CY, et al. Risk factors for the development of early-onset delirium and the subsequent clinical outcome in mechanically ventilated patients. J Crit Care 2008;23:372–9. [45] Rompaey BV, Schuurmans MJ, Shortridge-Baggett LM, et al. A comparison of the CAM-ICU and the NEECHAM Confusion Scale in intensive care delirium assessment: an observational study in nonintubated patients. Crit Care 2008;12:R16. [46] Sommer BR, Wise LC, Kraemer HC. Is dopamine administration possibly a risk factor for delirium? Crit Care Med 2002;30: 1508–11. [47] Jackson JC, Gordon SM, Hart RP, et al. The association between delirium and cognitive decline: a review of the empirical literature. Neuropsychol Rev 2004;14:87–98. [48] Chang YL, Tsai YF, Lin PJ, et al. Prevalence and risk factors for postoperative delirium in a cardiovascular intensive care unit. Am J Crit Care 2008;17:567–75.
646
A. Sharma et al. / General Hospital Psychiatry 34 (2012) 639–646
[49] Thomason JW, Shintani A, Peterson JF, et al. Intensive care unit delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-ventilated patients. Crit Care 2005;9:R375–81. [50] Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons; a predictive model and interrelationship with baseline vulnerability. JAMA 1996;275:852–7. [51] Marcantonio E, Simon S, Bergmann M, et al. Delirium symptoms in post-acute care: prevalent, persistent, and associated with poor functional recovery. J Am Geriatr Soc 2003;51:4–9. [52] Schor JD, Levkoff SE, Lipsitz LA, et al. Risk factors for delirium in hospitalized elderly. JAMA 1992;267:827–31.
[53] Vincent FM. The neuropsychiatric complications of corticosteroid therapy. Compr Ther 1995;21:524–8. [54] Ogundele O, Yende S. Pushing the envelope to reduce sedation in critically ill patients. Crit Care 2010;14:339. [55] Leentjens AF, van der Mast RC. Delirium in elderly people: an update. Curr Opin Psychiatry 2005;18:325–30. [56] Liptzin B, Levkoff SE. An empirical study of delirium subtypes. Br J Psychiatry 1992;161:843–5. [57] Kiely DK, Jones RN, Bergmann MA, Marcantonio ER. Association between psychomotor activity delirium subtypes and mortality among newly admitted post-acute facility patients. J Gerontol A Biol Sci Med Sci 2007;62:174–9.