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End-of-Life Care in the ICU^*

Treatments Provided When Life Support Was or Was Not Withdrawn

^* From the Departments of Anesthesia (Dr. Hall) and Medicine (Dr. Rocker), Dalhousie University; Intensive Care Services, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.

Correspondence to: Richard I. Hall, MD, FCCP, Department of Anesthesia, Queen Elizabeth II Health Sciences Centre, 1796 Summer St, Halifax, Nova Scotia, Canada B3H 3A7; e-mail: rihall{at}is.dal.ca

	Abstract

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Study objective: To compare and contrast use of technology, pharmacology, and physician variability in end-of-life care of ICU patients dying with or without active life support.

Design: Retrospective cohort study.

Setting: Two medical-surgical tertiary-care ICUs in a Canadian regional referral teaching hospital.

Participants: One hundred seventy-four patients who died between July 1, 1996, and June 30, 1997.

Intervention: Data abstraction from medical records.

Results: Patients in whom life support was withheld or withdrawn (138 of 174, 79%) were older (65 ± 16 years vs 55 ± 18 years; p < 0.05 [mean ± SD]). Once the decision to withdraw life support was made, death occurred in 4.3 h (2.1 to 6.5 h; mean [95% confidence interval]). Patients who had active life support treatment until death received more support measures including inotropic agents (36 of 36 vs 21 of 138; p < 0.05), dialysis (4 of 36 vs 2 of 138; p < 0.05), and mechanical ventilation at the time of death (36 of 36 vs 81 of 138; p < 0.05). Physician differences (> 10-fold) were detected for prescribed doses of morphine and sedative agents whether or not life support was withheld or withdrawn. The median cumulative dose of morphine prescribed during the final 12 h was larger (fivefold) in patients undergoing withdrawal of life support. No documented discussion of life support withdrawal was noted in one case. In the remaining patients, the 10 staff physicians were documented to be involved in 77% (range, 54 to 94%) of the end-of-life discussions.

Conclusions: Differences were evident in technologic and pharmacologic support and in physician prescribing habits in patients for whom life support was or was not withheld or withdrawn. Substantial variability was noted in physician documentation of physician-family interactions surrounding the withdrawal of life support.

Key Words: analgesia, cardiopulmonary resuscitation • end-of-life care • intensive care • lorazepam • midazolam • morphine • propofol • sedation

	Introduction

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There is increasing public and professional interest in the care of the dying patient and the physician’s role in ensuring a comfortable and dignified death.^{1 2 3 4} To facilitate physician advocacy for quality end-of-life care in the ICU, where death is common,^{5 6} we need more data concerning modes of death, including whether mechanical ventilation or other technology is withheld or discontinued, and how medications are administered to dying patients.^{1 7 8 9 10 11 12 13 14 15 16} After the arrest of one of our colleagues and a subsequent first-degree murder charge (later dismissed),¹⁷ we reviewed all other deaths occurring in 1 year in two university-affiliated ICUs, examining the processes of end-of-life care, including variation in the use of medication for comfort by physicians and use of technology such as mechanical ventilation and dialysis within the final 12 h of life in patients from whom life support was or was not withheld or withdrawn. When life support was forgone (withheld or withdrawn), we determined the documented frequency of interactions between health-care workers with patients and families during the process of withdrawal of life support.

	Materials and Methods

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Relevant Organizational Background
This study was conducted in two adult medical-surgical ICUs at the Queen Elizabeth II Health Sciences Centre, with a total capacity of 24 beds for an 826-bed institution. The Queen Elizabeth II Health Sciences Centre serves as the only acute-care medical center for the city of Halifax, Nova Scotia (catchment population, 250,000) and serves as the tertiary and quaternary-care referral center for three Atlantic Canadian provinces (Nova Scotia, New Brunswick, and Prince Edward Island). From July 1996 to June 1997, 10 intensivists cared for patients in the ICU, providing 24-h coverage and rotating on a weekly basis. The medical house staff consisted of residents from anesthesiology, medicine, and surgery training programs on 1- to 3-month rotations. On average, three residents per month were providing care to patients in each ICU during the study period. The nursing complement consisted of 121 nurses, all of whom had postgraduate training in critical-care nursing.

Definitions
We used the following definitions in this study:

Withholding or Withdrawing (Forgoing) of Life Support: This was defined as removal or no further addition or escalation of major life support modalities, including inotropic agents, mechanical ventilation, dialysis, etc., with the recognition that this would likely result in the patient’s death from the underlying medical condition. We did not distinguish between withholding or withdrawal of life support, and throughout the remainder of this report, the term withdrawal should be taken to include the withholding of life support.

Comfort Measures: This was defined as the administration of drugs such as narcotics and sedatives to prevent and treat symptomatic discomfort occurring during the dying process. Nursing care, including suctioning of secretions, positioning, etc., was continued. Spiritual and emotional support were provided as requested by patients or families.

Data Abstraction
The medical records for all patients coded as dying while in the ICU were identified through the Health Records Department. For the final 12 h of life, information was collected by at least two independent data abstracters from each chart, including the following:

Patient Demographics: Patient identification number; age; sex; whether identified as primarily medical vs surgical patient at time of admission; and weight.

ICU Characteristics: Date of hospital admission; date of ICU admission; APACHE (acute physiology and chronic health evaluation) II score calculated at the time of ICU admission¹⁸ ; date and time of death; cause of death; hospital length of stay; ICU length of stay; attending intensivist at time of death; cause of death as determined by autopsy or by one of the authors on review of the record; hospital admission diagnosis; ICU admission diagnosis; date and time at which a decision was made to withdraw life support; date and time at which a Do Not Resuscitate order was written, if any; time receiving mechanical ventilation while in ICU; mechanical ventilation status at time of death; whether life support withdrawal occurred and, if so, date and time; time from the withdrawal of life support to death. For the purposes of this review, we did not specify cardiopulmonary resuscitation (CPR) as a mode of life support in the recognition that CPR may be medically inappropriate both in patients forgoing life support and for those deteriorating despite active treatment.

Treatments Received While in ICU: Mechanical ventilation, dialysis, nutritional support, presence of a tracheostomy, and fraction of inspired oxygen (FIO₂) changes.

Medication Use: All medication use for the 12 h before death if given in the ICU. Medications administered within the 12 h period before death but before arrival in ICU were not included in the analysis.

Life Support-Related Discussions: Documented discussion of the planned withdrawal of life support with the patient or substitute decision maker and a list of who was present during the discussion.

Data Analysis
The primary analysis was performed to determine differences between the group of patients for whom life support was or was not withdrawn. For demographic variables, categorical data were analyzed using ² test or Fisher’s Exact Test, and continuous data were analyzed by t test or analysis of variance. Differences in hourly morphine dose over time were analyzed by a repeated-measures analysis of variance. Differences between groups for use of life support measures were determined by ² analysis. The Mann-Whitney U test was used to determine differences in median cumulative dose of medication. An analysis of variance with Bonferroni adjustment determined differences in drug doses between physicians for medication use in patients for whom life support was and was not withdrawn. Differences were accepted as statistically significant when p < 0.05. Systat v7.0 statistical software (SPSS, Inc; Chicago, IL) was used for the analysis. Unless otherwise indicated, data results are expressed as mean and 95% confidence intervals.

	Results

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Demographics
For the 12-month period, a total of 1,327 patients were admitted to the ICUs. Of these, 1,153 survived to ICU discharge (87%), and 174 died in the ICU (13%). Life support was withdrawn in 138 patients (10.3%), resulting in a death rate related to withholding or withdrawal of life support of 79.3%. Thirty-six patients (2.7%) died despite continuation of aggressive therapy. Table 1 provides demographic data for the cohort of patients who died. Patients for whom life support was withdrawn were older (65 ± 16 years vs 55 ± 18 years [mean ± SD]; p < 0.002), but their acuity of illness was less than those for whom aggressive treatment continued (admission APACHE II score, 25 ± 9 points vs 29 ± 9 points [mean ± SD]; p < 0.02). Table 2 provides information concerning ICU characteristics. As compared with patients dying despite active therapy, patients in whom life support was withdrawn had received mechanical ventilation for a longer duration of time before death: 162 h (121 to 202) vs 46 h (22 to 71), p < 0.001; and had a longer ICU stay: 7.0 days (5.5 to 8.5) vs 2.3 days (1.5 to 3.1), p < 0.001. Hospital length of stay was not different between groups. The time from withdrawal of life support to death was similar whether or not patients were receiving mechanical ventilation: 2.8 h (1.7 to 4.5) vs 5.8 h (1.2 to 10.5); p > 0.05.

View larger version (21K): [in this window] [in a new window] [Download PPT slide]   Figure 1.. Mean (± SD) dose of morphine administered to patients for whom life support was forgone (withdrawal; n = 108) vs those for whom acute care was continued (no withdrawal; n = 17) over the final 12 h of life. Note the increase in dose in the final 4 h of life in the withdrawal group.

Personnel Involved in the Process of Withdrawal of Life Support
Staff physician participation in documented discussions of life support withdrawal ranged from a low of 54% of relevant discussions to a high of 94% (group mean, 77%). In one case, no documented discussion concerning withdrawal of life support was recorded at any time on the medical record. Data for presence of individuals during documented discussions of the withdrawal of life support are provided in Table 6 . Patients were able to participate directly in decisions to withdraw life support in 13 cases (9.4%).

	Discussion

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We recognize there are several limitations to our study. The data represent the experience in a single large tertiary-care center in Canada. As such, the experience reported here may not be reflective of practice in community hospitals¹⁵ or reflect practice elsewhere. However, it is in keeping with some of the data reported from another tertiary-care center in Canada,⁹ and similar rates of withdrawal of life support have been reported from some American ICUs.^{5 6} The drug doses we report are similar to those reported from other North American ICUs.^{9 12 14} Our study extends these observations by including: information on use of sedative and neuromuscular blocking agents; provision of therapies such as dialysis, nutrition, inotropic agents at the time of death; physician variability in drug dosing for patients actively treated or for whom life support was withdrawn; and documented presence of physicians during discussions related to the withdrawal of life support.

Our review is retrospective in nature and suffers from the difficulties of reports of this nature, eg, a failure to document drug dosing or to record the presence of all participants during an interview with the patient or family. Strengths of our review were that each chart was reviewed independently at least twice for data abstraction, which limits the chance that data present were missed.

Several observations concerning our findings are noteworthy. In keeping with other recent studies, the majority of deaths in our ICU (79%) occurred in the setting of withholding or withdrawal of life support.^{1 5 9 13 15} The time from the initiation of the withdrawal of life support until death occurred was short (4 h) and similar to that reported by Keenan et al¹⁵ (6.5 h). This is likely to reflect the severity of illness of critically ill patients approaching the end of life when therapeutic options are exhausted and intervention serves only to prolong the dying process. Once the decision to withdraw life support was made, most active measures to sustain life were rapidly discontinued, which may explain the difference in time to death of our patients (4 h) from those reported by Wood and Martin¹³ (32.5 h), from whom measures were withdrawn in a graded fashion.

The short interval between discontinuation of therapy and death may also be an explanation for the type and degree of medication use in the final 12 h of life (Table 4) . Active care was provided up to the point at which the decision to withdraw life support was made, and in the majority of cases involved substantial pharmacologic and technical support. As life support was withdrawn, caregivers may have perceived or anticipated distress on behalf of the patient and intervened to prevent associated discomfort. Support for this hypothesis is provided by examination of Figure 1 , which shows that increases in morphine administration are most evident in the final 4 h before death—a time frame consistent with the average time from withdrawal of life support to death (Table 1) .

Differences existed in the proximate causes of death for patients from whom life support was or was not withdrawn. Patients from whom life support was withdrawn were older, had a more protracted course, and died of sepsis and organ failure or neurologic injury, whereas patients for whom active care continued died of more acute medical catastrophes, eg, pulmonary embolism or acute myocardial infarction. The relative proportion of elderly patients is increasing, and our data show patients for whom life support is withdrawn are more likely to be elderly with multisystem disease. It appears that rather than dying at home, as may have occurred in the past, an increasing proportion of ICU deaths occur in the sick elderly population, and death has become more technical in nature. These demographic observations are similar to those reported by other investigators.^{1 9 19}

Patients from whom life support was withdrawn had significantly fewer interventions than patients from whom active care, including drug therapy and dialysis, was continued (Table 4) . Decisions to forgo life-sustaining therapy occurred late in the course of care (Table 1) . Once the decision to withdraw life support is made and the goals of therapy change from attempted cure to the provision of comfort measures, the use of aggressive modalities of treatment, including dialysis, nutrition, inotropic support, and perhaps mechanical ventilation, would need to be justified in terms of provision of comfort. If the treatment goal is to provide comfort as death occurs, arguably these modalities may prolong death unnecessarily.²⁰ However, a legitimate goal of therapy for one caregiver may not necessarily be perceived the same way by another caregiver, and our data suggest that variability in decision making at the end of life exists in practice as well as in theory.^{7 8 21 22 23}

We found substantial variability surrounding use of medications for end-of-life care—both within and between staff physicians. Patients for whom active care was continued received less sedation and analgesia than patients receiving palliative care after the decision to forgo life support (Fig 1 and Table 5 ). Reasons why this might be so are speculative, but patients in the palliative care group may have been perceived as showing more signs of suffering or discomfort than in the active care groups and hence have received more medication, particularly morphine. Alternatively, the suddenness of death in the acute care group may have precluded graduated increases in medications designed to promote comfort.

We noted a progressive increase in drug dose over time for patients in whom life support was withdrawn (eg, morphine increased from 1.6 to 11.4 mg/h). In the context of providing comfort, this is not difficult to explain and is not unique to our situation; reported doses of morphine administered during the withdrawal of life support include a range from 0.7 to 350 mg/h (mean, 21 ± 33 mg/h),⁹ 0 to 80 mg/h (mean of 0.4 ± 0.7 mg/h),¹⁴ and 5.7 ± 1.7 mg/h before withdrawal to 14.8 ± 4.5 mg/h during withdrawal.¹²

For sedation, a much larger variability in agents used was noted, with proportionate use of diazepam, midazolam, and propofol. Doses administered were also variable and, at least for propofol, exceeded any recognized dosing recommendations²⁴ in at least some cases (Table 5) . This may represent the development of tolerance to the agent in the time interval before the last 12 h of life. It may also represent a lack of familiarity with any of these agents, leading to a potential for inappropriate use.

The process of the withdrawal of life support frequently involves numerous discussions with family as treatment goals are reestablished and the likelihood of survival declines. In this study, however, there was variability in these discussions concerning the documented presence of an attending physician (54 to 94% of cases). Some physicians may be more uncomfortable breaking bad news to patients and families and may delegate this to other members of the health-care team (Table 6) or alternatively may not feel documentation of these discussions is necessary. From our experience with a murder investigation and based on our subsequent practice review, we strongly recommend that physicians be involved in discussions surrounding withdrawal of life support and to document these discussions appropriately. We have modified our own local practices accordingly.

The high incidence of ICU deaths related to withdrawal of life support and the rapidity with which death occurs after withdrawal of life support has implications for the provision of effective palliative care. The time frame within which patients and their families must approach impending death is short, and how families cope with the acute illness and death in this setting is, to our knowledge, not well explored. Our data suggest there is a place for considering palliative care training as part of ICU educational programs, and support the developing trend toward integration of palliative care precepts and research into the ICU.

In this study, we have demonstrated variability in the process of withdrawal of life support during the final 12 h of life in the ICU. Although guidelines or position statements help in decision making regarding withdrawal of life support,^{25 26 27 28 29 30 31} there is little available information concerning practice issues and the actual process of the withdrawal of life support. This may reflect a reluctance on behalf of practitioners to disclose such information for fear of public and peer scrutiny, approbation, and possible medicolegal implications. We too have had anxieties regarding the presentation of such data in the public forum. Nevertheless, open dialogue and debate surrounding palliative care in the ICU is integral to the development of optimum care for all of our patients. We hope the presentation of these data will contribute to the required dialogue.

	Acknowledgements

 
The authors acknowledge the assistance of Joyce Norris and members of the Quality Assurance Department of the Queen Elizabeth II Health Sciences Centre for their help with data abstraction.

	Footnotes

 
Abbreviations: APACHE = acute physiology and chronic health evaluation; CPR = cardiopulmonary resuscitation; FIO₂ = fraction of inspired oxygen

Presented in part at the October 1998 Annual Meeting of the American College of Chest Physicians (Toronto, Ontario), and the May 1999 Canadian Anesthesiologists’ Society Annual Meeting (Calgary, Alberta).

Received for publication December 8, 1999. Accepted for publication April 13, 2000.

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