Online Letters to the Editor
Withdrawal on ICU: When Is the Point of Cardiac Death? To the Editor:
W
e applaud the efforts of Dhanani et al (1) in broaching this complex ethical and clinical question. Although in our practice as a group of British anesthetic trainees (2) we largely witness donation after brainstem death, we are becoming increasingly involved in donation after circulatory death (DCD) and therefore welcome this article as an example of well-designed and managed research into patients at the end of life with the potential for organ donation. We are, however, disappointed that the article focuses more on secondary outcomes of the study, seemingly at the expense of the arguably more valuable primary objective, feasibility of running such a study, and we question the applicability of some of the results to clinical practice. Regarding this assessment of feasibility of research into the dying process following withdrawal of treatment in the intensive care setting, a comprehensive and thorough description of the research methodology is provided. It was concerning, however, that 27% of enrolled patients were excluded from analysis due to study violations. We also find it confusing that although the authors advocate the need for standardized criteria for diagnosing death in potential DCD patients, the study design itself did not standardize this process across the sites involved. This creates a heterogeneous dataset from which it is difficult to draw conclusions of the relevance of the recorded data in relation to the definition of death. With further reference to study design, the use of a questionnaire to gain feedback from clinical staff, the high rates of study enrollment, and the process of consent for the study are all highly commendable, but these results were somewhat underplayed. Looking specifically at the feedback questionnaire, staff perceptions are essential when trying to develop further research with regard to complex and sensitive areas of medicine, none more so than the dying process. Given that 7% of respondents felt that the study impacted on their ability to perform their duties, and 3% felt it negatively impacted patient care, further exploration is warranted to ensure future studies are more acceptable. Undue weight was given to the clinical recordings in the authors’ report of the study and is concerned by the authors’ focus on the phenomenon of “autoresuscitation,” which has never been documented in the absence of cardiopulmonary resuscitation (3), and is sufficiently rare that a sample size of 45 is unlikely to detect such an event. What was however important is highlighting that continued electrocardiogram monitoring is unlikely to be of value in declaration of death in a potential donor and may in fact lead to undue concern for relatives and allied health professionals. We also question the applicability and ethical relevance of the electroencephalographic results in this study as this was not a core recording as described in the study protocol. We would be grateful if the authors could clarify the reasons why this was not universally
Critical Care Medicine
used if it was felt to be significant as when applied to such a small subset of patients it adds little to our understanding of neurological processes during death. Overall, this article adds greatly to the process of designing research into this evidently poorly understood and rapidly developing field. We hope that the authors share in more detail their pearls and pitfalls resulting from this process. We look forward to increasing clarity, biologically and ethically, on the nature and definition of death in patients who are potential DCD donors, thus allowing a reduction in warm ischemic time and hopefully therefore greater utilization of potentially lifesaving organs (4). The authors have disclosed that they do not have any potential conflicts of interest. Nicholas R. Plummer, MA, MSci, MB, BChir, Phillippa Shorrock, FRCA, Matthew Leech, BSc, Matthew Jackson, FFICM, Thomas Heaton, Salman Razzaki, MSc, John Gilbey, MRPharmS, Victoria McCormack, FRCA, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, Lancashire, United Kingdom; on behalf of the North West Research and Audit Group
REFERENCES
1. Dhanani S, Hornby L, Ward R, et al; Canadian Critical Care Trials Group and in collaboration with the Bertram Loeb Chair and Research Consortium in Organ and Tissue Donation: Vital Signs After Cardiac Arrest Following Withdrawal of Life-Sustaining Therapy: A Multicenter Prospective Observational Study. Crit Care Med 2014; 42:2358–2369 2. North West Research and Audit Group: 2014. Available at: http:// www.NWRAG.org. Accessed December 16, 2014 3. Hornby K, Hornby L, Shemie SD: A systematic review of autoresuscitation after cardiac arrest. Crit Care Med 2010; 38:1246–1253 4. Wind J, Snoeijs MG, Brugman CA, et al: Prediction of time of death after withdrawal of life-sustaining treatment in potential donors after cardiac death. Crit Care Med 2012; 40:766–769 DOI: 10.1097/CCM.0000000000000850
The authors reply:
W
e thank Plummer et al (1) for acknowledging the importance of our pilot study (2) observing vital signs after cardiac arrest. We are grateful for the opportunity to respond to several key points. Plummer et al (1) were “disappointed that the article [focused] more on secondary outcomes.” We would like to reemphasize, as was clearly stated in the article, that the primary objective of this pilot study was feasibility. We described in detail the primary outcomes of recruitment, consent, and data acquisition. To the latter, the objectives included the ability to be able to describe the circulatory and neurologic observational data. We agree that the limited data from this pilot study on circulatory autoresuscitation and cessation of electroencephalogram activity should be viewed with extreme caution and that no firm conclusions should be made. Our current prospective study of 500 patients will include circulatory and neurologic recordings to better document the natural history www.ccmjournal.org
e119
Online Letters to the Editor
of cessation of circulatory and neurologic function after withdrawal of life-sustaining therapies (WLST) in the ICU. We thank Plummer et al (1) for acknowledging that the description of our methods was comprehensive. To this, we intend to further publish a more detailed account of the consent development and implementation process. Most of the protocol violations were related to technical aspects of waveform data acquisition. The purpose of the pilot study was to identify opportunities for improving methods for subsequent work. The current large prospective study has moved to an electronic waveform data capture, which will enhance vital sign interpretation and reduce protocol violations. Comments were also made regarding the need to standardize the declaration of death for the study. We agree that is an important issue in improving the practice of donation after circulatory death (DCD). The pilot study was strictly observational in nature, which was instrumental for its success. We chose, after much consultation, to refrain from instructing practice. However, the purpose of these studies is to provide better evidence to inform death determination practices and health policy in this regard. Finally, Plummer et al (1) reflect on the underplaying of the satisfaction questionnaire. We regret that we did not take the opportunity to enhance this part of the pilot study. The richness of these data would have been interesting. For our current larger study, we have included a qualitative interview that will help describe the experience of substitute decision makers concerning DCD, WLST, and research at the end-of-life in the ICU. In summary, we attempted to describe the key points of feasibility as the primary objective for the pilot study and also included descriptions of the novel waveform data acquired. We feel strongly, as does Plummer et al (1), that it is irresponsible to overinterpret limited observational waveform data. As expected with pilot studies, many things were learned and have led to protocol improvements. Our subsequent study of 500 patients will include circulatory and neurologic recordings with electronic waveform data acquisition in order to better document the natural history of circulatory and neurologic death after WLST in the ICU. Design and implementation of the study and manuscript development were coordinated at the Children’s Hospital of Eastern Ontario. Supported, in part, by grants from the Children’s Hospital of Eastern Ontario Research Institute, Physician’s Services Incorporated, and Canadian Institute for Health Research. Dr. Dhanani consulted for Trillium Gift of Life Network (chief medical officer). Ms. Hornby served as a research consultant for Canadian Blood Services and received grant support as the project manager for CIHR-funded research in organ donation. Dr. Shemie is a medical advisor for deceased donation to Canadian Blood Services. Sonny Dhanani, MD, Pediatric Critical Care, Children’s Hospital of Eastern Ontario, Ottawa Children’s Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada, and Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Laura Hornby, MSc, Children's Hospital of Eastern e120
www.ccmjournal.org
Ontario Research Institute, Ottawa, ON, Canada; and Canadian Blood Services, Ottawa, ON, Canada; Sam D. Shemie, MD, Pediatric Critical Care, Montreal Children’s Hospital, McGill University Health Centre, McGill University, Montreal, QC, Canada
REFERENCES
1. Plummer NR, Shorrock P, Leech M, et al; on behalf of the North West Research and Audit Group: Withdrawal on ICU: When Is the Point of Cardiac Death? Crit Care Med 2015; 43:e119 2. Dhanani S, Hornby L, Ward R, et al; Canadian Critical Care Trials Group and in collaboration with the Bertram Loeb Chair and Research Consortium in Organ and Tissue Donation: Vital signs after cardiac arrest following withdrawal of life-sustaining therapy: A multicenter prospective observational study. Crit Care Med 2014; 42:2358–2369 DOI: 10.1097/CCM.0000000000000888
Neurologic Assessment of Comatose Survivors of Cardiac Arrest: The Details Matter To the Editor:
I
n a recent issue of Critical Care Medicine, Mulder et al (1) recently reported their experience with time to awakening and withdrawal of life-sustaining treatment (WLST) in cardiac arrest survivors treated with therapeutic hypothermia (TH). They emphasize that current American Academy of Neurology (AAN) guidelines recommend prognostication at 72 hours post arrest, and they state that the aim of their study was to “test the hypothesis that treatment of comatose out-ofhospital cardiopulmonary arrest survivors with TH may result in awakening beyond 72 hours” (1). In this observational study of 154 patients, Mulder et al (1) noted that all patients who were not treated with TH and who awoke did so before 72 hours, whereas 17% of patients treated with TH awoke beyond 72 hours and had good outcomes. From this, they conclude that these results suggest that an observation period of only 72 hours after cardiac arrest might not be adequate (1). It is important to recognize, however, that neither the current AAN guidelines (2) nor Levy et al (3) in their seminal article intended the 72-hour mark to become a magic deadline at which a patient’s fate is determined. The AAN guidelines—which occasionally are misinterpreted—do not state that patients who have good outcomes are expected to awaken within 72 hours. Rather, the guidelines emphasize that certain findings at 72 hours—after confounders to the examination have been excluded—can reliably predict a poor outcome. Unfortunately, determining accurate predictors of a good outcome has proven elusive, and the prognosis for many of these patients at 72 hours is classified as “indeterminate,” a finding that will not surprise clinicians who see these patients frequently. Thus, the fact that many patients will require observation beyond 72 hours after cardiac arrest is consistent with current guidelines, particularly at institutions in which the sedoanalgesia practice is more aggressive (4) or in patients with kidney, liver, or respiratory failure. “Delayed” awakenings can April 2015 • Volume 43 • Number 4
Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Withdrawal on ICU: When Is the Point of Cardiac Death? To the Editor:
W
e applaud the efforts of Dhanani et al (1) in broaching this complex ethical and clinical question. Although in our practice as a group of British anesthetic trainees (2) we largely witness donation after brainstem death, we are becoming increasingly involved in donation after circulatory death (DCD) and therefore welcome this article as an example of well-designed and managed research into patients at the end of life with the potential for organ donation. We are, however, disappointed that the article focuses more on secondary outcomes of the study, seemingly at the expense of the arguably more valuable primary objective, feasibility of running such a study, and we question the applicability of some of the results to clinical practice. Regarding this assessment of feasibility of research into the dying process following withdrawal of treatment in the intensive care setting, a comprehensive and thorough description of the research methodology is provided. It was concerning, however, that 27% of enrolled patients were excluded from analysis due to study violations. We also find it confusing that although the authors advocate the need for standardized criteria for diagnosing death in potential DCD patients, the study design itself did not standardize this process across the sites involved. This creates a heterogeneous dataset from which it is difficult to draw conclusions of the relevance of the recorded data in relation to the definition of death. With further reference to study design, the use of a questionnaire to gain feedback from clinical staff, the high rates of study enrollment, and the process of consent for the study are all highly commendable, but these results were somewhat underplayed. Looking specifically at the feedback questionnaire, staff perceptions are essential when trying to develop further research with regard to complex and sensitive areas of medicine, none more so than the dying process. Given that 7% of respondents felt that the study impacted on their ability to perform their duties, and 3% felt it negatively impacted patient care, further exploration is warranted to ensure future studies are more acceptable. Undue weight was given to the clinical recordings in the authors’ report of the study and is concerned by the authors’ focus on the phenomenon of “autoresuscitation,” which has never been documented in the absence of cardiopulmonary resuscitation (3), and is sufficiently rare that a sample size of 45 is unlikely to detect such an event. What was however important is highlighting that continued electrocardiogram monitoring is unlikely to be of value in declaration of death in a potential donor and may in fact lead to undue concern for relatives and allied health professionals. We also question the applicability and ethical relevance of the electroencephalographic results in this study as this was not a core recording as described in the study protocol. We would be grateful if the authors could clarify the reasons why this was not universally
Critical Care Medicine
used if it was felt to be significant as when applied to such a small subset of patients it adds little to our understanding of neurological processes during death. Overall, this article adds greatly to the process of designing research into this evidently poorly understood and rapidly developing field. We hope that the authors share in more detail their pearls and pitfalls resulting from this process. We look forward to increasing clarity, biologically and ethically, on the nature and definition of death in patients who are potential DCD donors, thus allowing a reduction in warm ischemic time and hopefully therefore greater utilization of potentially lifesaving organs (4). The authors have disclosed that they do not have any potential conflicts of interest. Nicholas R. Plummer, MA, MSci, MB, BChir, Phillippa Shorrock, FRCA, Matthew Leech, BSc, Matthew Jackson, FFICM, Thomas Heaton, Salman Razzaki, MSc, John Gilbey, MRPharmS, Victoria McCormack, FRCA, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, Lancashire, United Kingdom; on behalf of the North West Research and Audit Group
REFERENCES
1. Dhanani S, Hornby L, Ward R, et al; Canadian Critical Care Trials Group and in collaboration with the Bertram Loeb Chair and Research Consortium in Organ and Tissue Donation: Vital Signs After Cardiac Arrest Following Withdrawal of Life-Sustaining Therapy: A Multicenter Prospective Observational Study. Crit Care Med 2014; 42:2358–2369 2. North West Research and Audit Group: 2014. Available at: http:// www.NWRAG.org. Accessed December 16, 2014 3. Hornby K, Hornby L, Shemie SD: A systematic review of autoresuscitation after cardiac arrest. Crit Care Med 2010; 38:1246–1253 4. Wind J, Snoeijs MG, Brugman CA, et al: Prediction of time of death after withdrawal of life-sustaining treatment in potential donors after cardiac death. Crit Care Med 2012; 40:766–769 DOI: 10.1097/CCM.0000000000000850
The authors reply:
W
e thank Plummer et al (1) for acknowledging the importance of our pilot study (2) observing vital signs after cardiac arrest. We are grateful for the opportunity to respond to several key points. Plummer et al (1) were “disappointed that the article [focused] more on secondary outcomes.” We would like to reemphasize, as was clearly stated in the article, that the primary objective of this pilot study was feasibility. We described in detail the primary outcomes of recruitment, consent, and data acquisition. To the latter, the objectives included the ability to be able to describe the circulatory and neurologic observational data. We agree that the limited data from this pilot study on circulatory autoresuscitation and cessation of electroencephalogram activity should be viewed with extreme caution and that no firm conclusions should be made. Our current prospective study of 500 patients will include circulatory and neurologic recordings to better document the natural history www.ccmjournal.org
e119
Online Letters to the Editor
of cessation of circulatory and neurologic function after withdrawal of life-sustaining therapies (WLST) in the ICU. We thank Plummer et al (1) for acknowledging that the description of our methods was comprehensive. To this, we intend to further publish a more detailed account of the consent development and implementation process. Most of the protocol violations were related to technical aspects of waveform data acquisition. The purpose of the pilot study was to identify opportunities for improving methods for subsequent work. The current large prospective study has moved to an electronic waveform data capture, which will enhance vital sign interpretation and reduce protocol violations. Comments were also made regarding the need to standardize the declaration of death for the study. We agree that is an important issue in improving the practice of donation after circulatory death (DCD). The pilot study was strictly observational in nature, which was instrumental for its success. We chose, after much consultation, to refrain from instructing practice. However, the purpose of these studies is to provide better evidence to inform death determination practices and health policy in this regard. Finally, Plummer et al (1) reflect on the underplaying of the satisfaction questionnaire. We regret that we did not take the opportunity to enhance this part of the pilot study. The richness of these data would have been interesting. For our current larger study, we have included a qualitative interview that will help describe the experience of substitute decision makers concerning DCD, WLST, and research at the end-of-life in the ICU. In summary, we attempted to describe the key points of feasibility as the primary objective for the pilot study and also included descriptions of the novel waveform data acquired. We feel strongly, as does Plummer et al (1), that it is irresponsible to overinterpret limited observational waveform data. As expected with pilot studies, many things were learned and have led to protocol improvements. Our subsequent study of 500 patients will include circulatory and neurologic recordings with electronic waveform data acquisition in order to better document the natural history of circulatory and neurologic death after WLST in the ICU. Design and implementation of the study and manuscript development were coordinated at the Children’s Hospital of Eastern Ontario. Supported, in part, by grants from the Children’s Hospital of Eastern Ontario Research Institute, Physician’s Services Incorporated, and Canadian Institute for Health Research. Dr. Dhanani consulted for Trillium Gift of Life Network (chief medical officer). Ms. Hornby served as a research consultant for Canadian Blood Services and received grant support as the project manager for CIHR-funded research in organ donation. Dr. Shemie is a medical advisor for deceased donation to Canadian Blood Services. Sonny Dhanani, MD, Pediatric Critical Care, Children’s Hospital of Eastern Ontario, Ottawa Children’s Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada, and Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Laura Hornby, MSc, Children's Hospital of Eastern e120
www.ccmjournal.org
Ontario Research Institute, Ottawa, ON, Canada; and Canadian Blood Services, Ottawa, ON, Canada; Sam D. Shemie, MD, Pediatric Critical Care, Montreal Children’s Hospital, McGill University Health Centre, McGill University, Montreal, QC, Canada
REFERENCES
1. Plummer NR, Shorrock P, Leech M, et al; on behalf of the North West Research and Audit Group: Withdrawal on ICU: When Is the Point of Cardiac Death? Crit Care Med 2015; 43:e119 2. Dhanani S, Hornby L, Ward R, et al; Canadian Critical Care Trials Group and in collaboration with the Bertram Loeb Chair and Research Consortium in Organ and Tissue Donation: Vital signs after cardiac arrest following withdrawal of life-sustaining therapy: A multicenter prospective observational study. Crit Care Med 2014; 42:2358–2369 DOI: 10.1097/CCM.0000000000000888
Neurologic Assessment of Comatose Survivors of Cardiac Arrest: The Details Matter To the Editor:
I
n a recent issue of Critical Care Medicine, Mulder et al (1) recently reported their experience with time to awakening and withdrawal of life-sustaining treatment (WLST) in cardiac arrest survivors treated with therapeutic hypothermia (TH). They emphasize that current American Academy of Neurology (AAN) guidelines recommend prognostication at 72 hours post arrest, and they state that the aim of their study was to “test the hypothesis that treatment of comatose out-ofhospital cardiopulmonary arrest survivors with TH may result in awakening beyond 72 hours” (1). In this observational study of 154 patients, Mulder et al (1) noted that all patients who were not treated with TH and who awoke did so before 72 hours, whereas 17% of patients treated with TH awoke beyond 72 hours and had good outcomes. From this, they conclude that these results suggest that an observation period of only 72 hours after cardiac arrest might not be adequate (1). It is important to recognize, however, that neither the current AAN guidelines (2) nor Levy et al (3) in their seminal article intended the 72-hour mark to become a magic deadline at which a patient’s fate is determined. The AAN guidelines—which occasionally are misinterpreted—do not state that patients who have good outcomes are expected to awaken within 72 hours. Rather, the guidelines emphasize that certain findings at 72 hours—after confounders to the examination have been excluded—can reliably predict a poor outcome. Unfortunately, determining accurate predictors of a good outcome has proven elusive, and the prognosis for many of these patients at 72 hours is classified as “indeterminate,” a finding that will not surprise clinicians who see these patients frequently. Thus, the fact that many patients will require observation beyond 72 hours after cardiac arrest is consistent with current guidelines, particularly at institutions in which the sedoanalgesia practice is more aggressive (4) or in patients with kidney, liver, or respiratory failure. “Delayed” awakenings can April 2015 • Volume 43 • Number 4
Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
