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Published ahead of print on October 2, 2003, doi:10.1164/rccm.200303-455OC
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American Journal of Respiratory and Critical Care Medicine Vol 168. pp. 1457-1461, (2003)
© 2003 American Thoracic Society

The Long-term Psychological Effects of Daily Sedative Interruption on Critically Ill Patients

John P. Kress, Brian Gehlbach, Maureen Lacy, Neil Pliskin, Anne S. Pohlman and Jesse B. Hall

Departments of Medicine and Psychiatry, University of Chicago, Chicago, Illinois

Correspondence and requests for reprints should be addressed to John P. Kress, M.D., Section of Pulmonary and Critical Care Medicine, MC 6026, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637. E-mail: jkress{at}medicine.bsd.uchicago.edu


    ABSTRACT
 TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Critically ill patients often receive sedatives, which may delay liberation from mechanical ventilation and intensive care unit discharge. Daily interruption of sedatives alleviates these problems, but the impact of this practice on long-term psychological outcomes is unknown. We compared psychological outcomes of intensive care unit patients undergoing daily sedative interruption (intervention) with those without this protocol (control). Assessments using (1) the Revised Impact of Event Scale (evaluates signs of posttraumatic stress disorder [PTSD]), (2) the Medical Outcomes Study 36 item short-form health survey, (3) the State-Trait Anxiety Inventory, (4) the Beck Depression Inventory-2, (5) and the Psychosocial Adjustment to Illness score (overall quality of adjustment to current or residual effects of illness) were done by blinded observers. The intervention group had a better total Impact of Events score (11.2 vs. 27.3, p = 0.02), a trend toward a lower incidence of PTSD (0% vs. 32%, p = 0.06), and a trend toward a better total Psychosocial Adjustment to Illness score (46.8 vs. 54.3, p = 0.08). We conclude that daily sedative interruption does not result in adverse psychological outcomes, reduces symptoms of PTSD, and may be associated with reductions in posttraumatic stress disorder.

Key Words: sedatives • ventilation, mechanical • neuropsychological tests • outcomes research

Critically ill patients who are mechanically ventilated often require sedative drugs to ensure their comfort while in the intensive care unit (ICU). Sedative drug infusions may lead to prolonged periods of altered mental status, and many patients experience a delay in recovering consciousness after their sedatives are stopped (1). We have previously demonstrated that a routine of daily sedative interruption to allow patients to awaken to a conscious state resulted in significant reductions in duration of mechanical ventilation and ICU length of stay, as well as fewer diagnostic tests to assess changes in mental status (2).

Previous studies have reported pain and anxiety as common experiences for patients during their ICU stay, especially after invasive procedures such as arterial puncture and endotracheal suctioning (35). Some patients who recover from critical illness suffer from long-term psychological disturbances such as depression, anxiety, and other chronic stress syndromes (6, 7). Posttraumatic stress disorder (PTSD) has been described in patients who have recovered from critical illness with varying rates of occurrence depending on the population studied (8, 9). With the potential for psychological maladjustment after recovery from critical illness, a ritual of daily sedative interruption might be viewed as detrimental to the long-term psychological well being of patients who recover from critical illness (10). Alternatively, others have noted that a prolonged period of amnesia may likewise be associated with detrimental psychological effects (11, 12). Surprisingly, the impact of sedatives on long-term psychological function after critical illness has not been well studied. Furthermore, the long-term psychological impact of frequent interruption of sedative infusions during critical illness to awaken patients and follow their neurologic status is unknown. Accordingly, we sought to evaluate the psychological condition of patients requiring mechanical ventilation and continuous sedative infusions after recovery from critical illnesses. Daily sedative interruption has been shown to result in important short-term benefits in critically ill patients requiring mechanical ventilation. This investigation was focused on the long-term psychological impact of daily sedative interruption in critically ill patients. The primary research inquiry for this study was a search for evidence that daily interruption of sedation was associated with long-term psychological harm. Secondarily, we sought to look for indications that daily sedative interruption leads to improved long-term outcomes, such as decreased PTSD. Some of the results of this study have been previously reported in the form of an abstract (13).


    METHODS
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 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
We interviewed patients previously admitted to our medical ICU who were mechanically ventilated and received sedatives by continuous infusion. As a part of a previous study, patients had been prospectively randomized to undergo daily sedative interruption until awake and able to follow commands (intervention group) versus a control group awakened only at the discretion of the ICU team (2). A cohort of medical ICU patients who were intubated and receiving mechanical ventilation and deemed by the ICU team to require sedation by continuous intravenous infusion was studied. We recruited patients from a period during our original study (2) up to the time of its publication. Recruitment included patients from the original study as well as contemporaneous patients not enrolled in the original study. Patients from the original study and contemporaneous group underwent identical protocols of either daily sedative interruption or awakening at the discretion of the ICU team. Patient recruitment is outlined in Figure 1 . Long-term psychological functioning of our cohort was assessed at a minimum of 6 months after hospital discharge. Patients were initially contacted by physicians conducting the study, first by mail, followed by a phone call inviting them to participate in the study. Those who agreed to participate were interviewed by clinical psychologists who were experienced in assessing psychological adjustment of patients hospitalized for acute medical illnesses (M.L., N.P.). Participants received a financial reimbursement after the interview. This study was approved by the institutional review board at the University of Chicago, and all patients provided informed consent.



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Figure 1. Distribution of recruited patients eligible for evaluation of long-term psychological functioning.

 
Demographic data, hospital and ICU length of stay, duration of mechanical ventilation, acute physiology and chronic health evaluation II scores (14), as well as ICU admitting diagnoses were recorded for each patient. The number of new medical conditions since hospital discharge was recorded. Previous psychiatric illnesses, psychiatric treatments since hospital discharge, and time from hospital discharge to follow-up interview were recorded. Patients were also queried about recollection of ICU experiences (see online METHODS supplement for details). Each patient underwent a detailed psychological evaluation by a clinical psychologist who was blinded to patient randomization (intervention vs. control). This consisted of a structured interview, along with self-report measures. In addition, all patients were blinded to their study group assignment. The psychological evaluation included an assessment of signs of PTSD, as measured by the Impact of Events Scale (15), as well as an evaluation for the diagnosis of PTSD according to criteria established by the Diagnostic and Statistical Manual of the American Psychiatric Association, 4th edition (16). Based on a structured interview, along with self-report measures, a diagnosis of PTSD was determined by the clinical psychologist conducting the evaluation. An assessment of overall perceived health and psychological well being as measured by the Medical Outcomes Study 36 item short-form health survey (SF-36) (17, 18), as well as assessments of anxiety (State-Trait Anxiety Inventory) (19, 20), and depression (Beck Depression Inventory-2) (21, 22) was performed. Finally, an assessment of the quality of adjustment to current or residual effects of illness as measured by the Psychosocial Adjustment to Illness (PAIS) score (23) was executed. For the SF-36 score, higher values are associated with better functioning. For all other tests performed, lower values are associated with better functioning. Details of these psychological evaluations can be found in the online supplement.

Statistical Analysis
Continuous demographic data were recorded as the mean ± SD. Continuous demographic data were compared using unpaired Student's t test or Mann-Whitney U Rank Sum test as appropriate. Scores recorded on the total Impact of Events scale, the State-Trait Anxiety Inventory, the Beck Depression Inventory-2, and total PAIS scores were compared using unpaired Student's t test or Mann-Whitney U Rank Sum test as appropriate. The SF-36 survey involves multiple subgroup domains; therefore, results of this survey were compared using multivariate analysis of variance. Likewise, the subgroup Impact of Events and PAIS scores were analyzed using multivariate analysis of variance. Categorical data were assessed using chi-square analyses with Yate's correction or Fisher Exact test as appropriate. A p value of less than 0.05 was used to indicate statistical significance.


    RESULTS
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 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
A total of 105 screened patients survived to hospital discharge. The distribution of these patients is outlined in Figure 1. Of the 35 patients who we were able to contact, a total of 32 agreed to participate in the interview. Of the 105 screened patients who survived to hospital discharge, the resulting inclusion rate was 30%. As seen in Tables 1 and 2 , the patients were similar demographically. Demographic data comparing patients enrolled in the study and those screened but not enrolled showed the control group patients enrolled in the study to be younger, but otherwise, no differences were seen. Likewise, comparisons between patients screened from the original study and contemporary patients not enrolled in the original study showed no demographic differences. These data are presented in the online supplement. Similar to the results of our previous study (2), the duration of mechanical ventilation and ICU length of stay were again shorter in the intervention group, although these differences did not reach statistical significance in this smaller cohort of patients. There were no differences in baseline or current psychiatric illnesses, although a trend toward greater baseline psychiatric illnesses in the intervention group was noted. Finally, there were no differences in the incidence of new medical illnesses between the groups. The distribution of ICU admitting diagnoses was similar between the groups.


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TABLE 1. Baseline characteristics of control and intervention groups

 

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TABLE 2. Primary intensive care unit admission diagnoses

 
The majority of patients recalled being present in the ICU during their hospital stay (68.4% control vs. 69.2% intervention, p = 1.0); however, very few patients in either group actually recalled the experience of awakening in the ICU at the time of this follow-up interview. Indeed, there was a trend toward more patients in the control group recalling awakening in the ICU when queried in this long-term follow-up evaluation (5 of 19 [26.3%] control vs. 0 of 13 [0%] intervention, p = 0.06). Interestingly, no patient in the intervention group recalled awakening in the ICU, despite daily attempts to awaken them.

Patients in the intervention group fared significantly better with regard to signs of PTSD. The average Total Impact of Events score was 11.2 ± 14.9 in the intervention group versus 27.3 ± 19.2 in the control group (difference, 16.1; 95% confidence interval, 3.0 to 29.2; p = 0.02). Likewise, the intervention group had lower Avoidance Subscale scores (7.8 ± 9.2 vs. 15.7 ± 10.5) as well as lower Intrusive Thoughts Subscale scores (5.6 ± 7.3 vs. 13.8 ± 9.7). By multivariate analysis of variance, comparison of individual Impact of Events subscales scores demonstrated a p value of 0.055. Impact of Events Score data are summarized in Table 3 . Overall, a total of six patients—all in the control group—were diagnosed with PTSD, based on Diagnostic and Statistical Manual of the American Psychiatric Association, 4th edition criteria (6 of 19 vs. 0 of 13, p = 0.06).


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TABLE 3. Impact of events scores

 
By multivariate analysis of variance, there were no differences in SF-36 scores between the two groups. As seen in Table 4 , patients in the intervention group had higher scores than the control group in five of eight categories of the SF-36 test, although there was no overall statistical difference between the groups.


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TABLE 4. Medical outcomes study 36 item short-form health survey transformed scores

 
Chronic anxiety was commonly observed in this cohort of patients. Anxiety levels tended to be higher in the control group, although these differences did not reach statistical significance. For trait (chronic) anxiety, 12 of 19 (63.2%) control subjects and 6 of 13 (46.2%) intervention patients had scores greater than 84%, a level consistent with a clinical state of chronic anxiety (p = 0.56). Acute states of anxiety were not excessively high in either group. For state (acute) anxiety, 4 of 19 (21.1%) control subjects and 4 of 13 (30.8%) intervention patients had scores greater than 84%, a level consistent with a clinical state of acute anxiety (p = 0.68). These results are summarized in Table 5 .


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TABLE 5. State-trait anxiety percentile scores

 
Mild depression was noted in both groups, with the control group having a higher average Beck Depression Index score (control 17.2 ± 10.6 vs. sedative interruption 13.7 ± 9.7; difference, 3.5; 95% confidence interval, -4.2 to 11.3; p = 0.36), although the difference did not reach statistical significance. These average scores correlated with borderline clinical depression (score 17–20) in the control group and mild mood disturbance (score 11–16) in the intervention group. Figure 14e in the online supplement illustrates Beck Depression Index scores by category.

The quality of patients' adjustments to the current or residual effects of their illnesses, as measured by the PAIS Score, showed better (lower) scores in the intervention group in six of the seven domains. The total PAIS T-score (sum of seven domains, reflecting overall quality of adjustment to current or residual effects of illness) showed a trend toward a better (lower) score in the intervention group (46.8 vs. 54.3; difference, 7.5; 95% confidence interval, -1.0 to 16.0; p = 0.08). Multivariate analysis of variance comparing the seven domains likewise showed an overall trend favoring the intervention group (p = 0.10). The results of the PAIS scores are summarized in Table 6 .


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TABLE 6. Psychosocial adjustment to illness scores

 

    DISCUSSION
 TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Sedation of critically ill patients requiring intubation and mechanical ventilation is a common practice. The distress—both physical and psychological—accompanying critical illness may be substantial in some situations (4, 5, 2427). Recognition of the potential for such distress has led to routine, presumptive administration of sedatives in many circumstances, often to a point of drug-induced coma (28). Intuitively, this may seem to be the most humane approach to managing sick patients; however, there is little evidence that such an approach improves outcome in any regard (10). Indeed, some studies suggest that the inability to recall real memories of the ICU experience may lead to psychological distress after recovery (11, 12). Others have previously expressed concern that sedative interruption might be psychologically harmful to patients, wondering "whether patients would perceive a daily lurch into drug-free dysphoria followed by a slide back into sedative-induced torpor as worse than the few extra days of mechanical ventilation that may be necessary when sedation is not interrupted" (10). Clearly, our results do not support the notion that daily awakening from sedation is psychologically harmful to patients.

PTSD is a concerning problem for some patients who recover from critical illness (9). Although there is no evidence that the use of sedative drugs modifies this response, the widespread use of sedatives in the ICU suggests that clinicians may administer these agents hoping to prevent consolidation of the experience of critical illness into permanent memory. Perhaps intuitive to this practice is the notion that this might prevent the subsequent development of problems such as PTSD. In contrast to this perception, we noted that patients in the intervention group fared significantly better than control patients with regard to signs of PTSD. Indeed, no patient in the intervention group suffered from PTSD, whereas six patients in the control group were given this diagnosis, a difference with a strong trend (p = 0.06) favoring the intervention group.

Our findings support those of Jones and colleagues, who recently reported their experience interviewing patients after an ICU admission that required mechanical ventilation (12). They noted that patients with delusional memories of their ICU experience were more likely to have PTSD-related symptoms than those with factual memories. The notion of maintaining even fragmented factual memories is particularly germane to our study, as no patient in the intervention group was able to remember the daily ritual of waking up during this follow-up evaluation. This is in contrast to the control group, where 26% recalled awakening at some point during their ICU stay.

Our study found no differences between the two groups with regard to anxiety or depression, suggesting that daily sedative interruption is not harmful with regard to these important areas. Likewise, the similar SF-36 scores in the two groups suggest that daily sedative interruption does not adversely impact overall perceived health and psychological well being.

Patients' quality of adjustment to current or residual effects of their critical illness reflected by the total PAIS score demonstrated a trend toward a better outcome in the intervention group. The PAIS subgroup domains showed better scores in the intervention group in virtually every domain. These data suggest that a protocol of daily sedative interruption is not associated with harmful outcomes with regard to patients' quality of adjustment to the current or residual effects of illness.

The intervention group had a shorter duration of mechanical ventilation and ICU length of stay compared with the control group, although this difference was not statistically significant in this small cohort. Whether the reductions in ventilator time and ICU stay impacted psychological outcomes is not clear. Certainly it is reasonable to speculate that shortening these endpoints would be beneficial from a psychological standpoint; however, more studies are needed to confirm this hypothesis. Whether prolonged immobility and/or resulting weakness, specific drugs used for sedation, inadequate treatment of depression, or other unrecognized issues may be contributing to psychological maladjustment requires further study. Regardless of the reason(s), we were able to demonstrate that daily interruption of sedative infusions did not lead to harmful outcomes in this cohort. In contrast, significantly improved outcomes with regard to signs of PTSD were seen. The trends favoring daily sedative interruption in other areas suggest the possibility of benefit, although the study was not powered to answer all of these questions.

An important limitation is the small number of patients enrolled in this single center study. After the publication of our previous work on short-term benefits of daily sedative interruption (2), randomization of patients to sedative interruption versus control groups was difficult at our institution because of perception of the benefits of daily sedative interruption. Another limitation is our recruitment of patients from our original study as well as contemporaneous patients not enrolled in the study. This could potentially introduce bias because our cohort was not randomized. We believe this is unlikely because all patients were recruited during a similar time interval (from the beginning of the original study of daily sedative interruption until publication of results) and there were no differences in demographics or the sedation strategies (intervention or control) between screened patients in the original study and contemporaries. The high number of patients who died after hospital discharge or were lost to follow-up is a potential confounder and an additional limitation. Although it is not possible to exclude this definitely, the similarities in demographic data between those who dropped out and those enrolled speak against this. Unfortunately, patient dropout is a common problem in long-term follow-up studies of critically ill patients, particularly in urban and/or socioeconomically disadvantaged settings. Clearly, more studies in the area of psychological impact of ICU sedative practices are needed.

In conclusion, we have shown that patients recovering from critical illness who have received continuous sedative infusions rarely recall awakening from sedation, even when such awakening occurs on a daily basis. Signs of PTSD occurred significantly less commonly in those undergoing daily sedative interruption. Based on these results, we can conclude that daily interruption of sedative infusions is not detrimental to the long-term psychological well being of critically ill patients. In contrast, it may result in improved psychological functioning in a number of important areas.


    Acknowledgments
 
J.P.K. has participated as a speaker in scientific meetings or courses organized and financed by Astra Zeneca; B.G. has no declared conflict of interest; M.L. has no declared conflict of interest; N.P. has no declared conflict of interest; A.S.P. has participated as a speaker in scientific meetings or courses organized and financed by Astra Zeneca; J.B.H. has no declared conflict of interest.


    FOOTNOTES
 
Supported by the National Institutes of Health/National Institute of General Medical Sciences grant K23 GM63906.

This article has an online supplement, which is accessible from this issue's table of contents online at www.atsjournals.org

Received in original form March 30, 2003; accepted in final form September 29, 2003


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