Article Text

Original research
Is the process of withdrawal of life-sustaining measures in the intensive care unit different for deceased organ donors compared with other dying patients? A secondary analysis of prospectively collected data
  1. J Shahin1,2,
  2. Nathan B Scales3,
  3. F Johara2,
  4. M Hogue4,
  5. Laura Hornby5,
  6. Sam Shemie6,7,
  7. M Schmidt8,9,
  8. P Waldauf8,9,
  9. F Duska8,9,
  10. Tineke Wind10,11,
  11. W N Van Mook12,
  12. Sonny Dhanani13,14
  1. 1Division of Critical Care, Respiratory Epidemiology and Clinical Research Unit, McGill University Faculty of Medicine, Montreal, Québec, Canada
  2. 2Research Institute of the McGill University Health Centre, Montreal, Québec, Canada
  3. 3Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
  4. 4CHEO, Ottawa, Ontario, Canada
  5. 5System Development, Canadian Blood Services Organ Donation and Transplantation, Ottawa, Ontario, Canada
  6. 6Division of Critical Care, Department of Pediatrics, Montreal Childrens Hospital, Montreal, Québec, Canada
  7. 7System Development, Canadian Blood Services, Ottawa, Ontario, Canada
  8. 8Third Faculty of Medicine, Charles University, Praha, Czech Republic
  9. 9FNKV University Hospital, Prague, Czech Republic
  10. 10Maastricht University Medical Centre, Maastricht, The Netherlands
  11. 11Heart and Vascular Center, Maastricht, The Netherlands
  12. 12Deparment of Intensive Care Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands
  13. 13Critical Pediatric Critical Care Medicine, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada
  14. 14Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada
  1. Correspondence to Dr J Shahin; Jason.shahin{at}mcgill.ca

Abstract

Objective To investigate whether observable differences exist between patterns of withdrawal of life-sustaining measures (WLSM) for patients eligible for donation after circulatory death (DCD) in whom donation was attempted compared with those patients in whom no donation attempts were made.

Setting Adult intensive care units from 20 centres in Canada, the Czech Republic and the Netherlands.

Design Secondary analysis of quantitative data collected as part of a large, prospective, cohort study (the Death Prediction and Physiology after Removal of Therapy study).

Participants Patients ≥18 years of age who died after a controlled WLSM in an intensive care unit. Patients were classified as not DCD eligible, DCD eligible with DCD attempted or DCD eligible but DCD was not attempted.

Primary and secondary outcome measures The process of WLSM (timing and type and, if applicable, dosages of measures withdrawn, dosages of analgesics/sedatives) was compared between groups.

Results Of the 635 patients analysed, 85% had either cardiovascular support stopped or were extubated immediately on WLSM. Of the DCD eligible patients, more were immediately extubated at the initiation of WLSM when DCD was attempted compared with when DCD was not attempted (95% vs 61%, p<0.0001). Initiation of WLSM with the immediate cessation of cardiovascular measures or early extubation was associated with earlier time to death, even after adjusting for confounders (OR 2.94, 95% CI 1.39 to 6.23, at 30 min). Other than in a few patients who received propofol, analgesic and sedative dosing after WLSM between DCD attempted and DCD eligible but not attempted patients was not significantly different. All patients died.

Conclusions Patients in whom DCD is attempted may receive a different process of WLSM. This highlights the need for a standardised and transparent process for end-of-life care across the spectrum of critically ill patients and potential organ donors.

  • Transplant medicine
  • MEDICAL ETHICS
  • Adult palliative care
  • TRANSPLANT MEDICINE
  • Adult intensive & critical care
  • Adult anaesthesia

Data availability statement

Data are available on reasonable request. Access to the full dataset for this study is available on reasonable request.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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STRENGTHS AND LIMITATIONS OF THIS STUDY

  • Our study included a large cohort of patients enrolled from multiple sites in Canada, the Czech Republic and the Netherlands.

  • This is one of the only known studies to gather granular data on specifics of withdrawal of life-sustaining measures in dying critically ill patients, and specifically potential organ donors.

  • Due to the detailed, longitudinally collected dataset, we were able to analyse cardiovascular, respiratory, analgesic and sedative data during the dying process and effectuate a clear comparison between donation after circulatory death eligible patients in whom donation was and was not attempted.

  • Our findings are drawn from a secondary analysis of existing data and are thus limited by the data already collected and thus may not be broadly generalisable.

  • This study involved an analysis of data that was collected prior to 2018; since that time, some study sites have updated their procedures and current practice may be different than what is reflected here.

Introduction

Donation after circulatory death (DCD) accounts for a significant proportion of deceased organ donation in North America and Europe. Despite its widespread uptake, practical and ethical concerns persist,1 including concerns surrounding end-of-life care received by potential organ donors. Withdrawal of life-sustaining measures (WLSM), which usually consists of removal of respiratory and/or cardiovascular support, maintains a central role in the trajectory towards DCD. The relationship between the timing and mode of WLSM and deceased organ donation is drawn even closer in the context of DCD as death must occur within specific time periods with minimal ischaemia for organ retrieval to proceed successfully.

A recent systematic review demonstrated that physicians are more likely to base decisions about the WLSM process in non-donor patients on their own experiences and preferences rather than clinical characteristics of patients.2 Thus, it is not unfounded to imagine that preferences or beliefs concerning organ donation could influence therapeutic decisions during WLSM. In order to prevent inconsistencies, physicians have been encouraged to manage WLSM practices similarly for all patients, regardless of donor eligibility.3 However, despite these recommendations, there is sparse literature examining the detailed process of WLSM in DCD donors, and it remains unknown whether DCD attempts substantially influence patterns of WLSM.

In this study, we investigated whether differences exist between WLSM for eligible DCD donors in whom donation was attempted when compared with those in whom no donation attempt was made. Specifically, we sought to (1) describe common patterns of withdrawal of respiratory and cardiovascular life-sustaining measures during the end-of-life process, (2) determine whether patterns of WLSM were associated with time to death and (3) determine whether patterns of WLSM analgesic or sedative dosing differed between patients who were eligible for DCD and who did and did not have DCD attempted.

Methods

The reporting of this study is in accordance with the STrengthening the Reporting of OBservational studies in Epidemiology statement.4

Patient and public involvement

There was no direct patient and public involvement in this secondary analysis. We intend to partner with Canadian Blood Services to enlist their help with dissemination of our findings.

Study design

We conducted a secondary analysis of quantitative data collected as part of a large, multinational sample of prospective, observational data (the Death Prediction and Physiology after Removal of Therapy (DePPaRT study)),5 on the process of WLSM in dying patients, including those eligible for DCD.

Patients

Patients in participating intensive care units (ICUs) in Canada, the Czech Republic and the Netherlands were consecutively enrolled between May 2014 and December 2018. Patients ≥18 years who died after WLSM in an ICU and had been enrolled into the DePPaRT study were included. As part of the DePPaRT protocol, patients were excluded if they had a neurological determination of death, a functional cardiac pacemaker or no arterial catheter at the time of WLSM. For this secondary analysis, patients were grouped as follows: DCD eligible and DCD not eligible; the DCD eligible group was further subdivided into DCD attempted, and DCD not attempted. Eligibility for DCD was determined using a set of standard exclusionary extended criteria that were established a priori and based on standard criteria outlined by local organ donation organisations (online supplemental figure 1). Patients were grouped as having DCD attempted if they were accepted as donors and continued down the pathway of organ donation, regardless of whether or not organ retrieval actually took place. The DCD eligible but not attempted group was defined as patients who were eligible for DCD given the above criteria but did not undergo any attempt at organ donation, for reasons that included not being in a centre that performed DCD, physician refusal for medical reasons, donor consent refusal and non-recognition of donor status.

Data collection

The following data were included: age, sex, ICU admission diagnosis (categorised into medical, neurological, surgical and trauma), severity of illness (calculated and scored using the validated Acute Physiology and Chronic Health Evaluation II (APACHE II) score6), comorbidities, analgesics/sedatives used, ventilation support, cardiovascular measures (extracorporeal membrane oxygenation, inotropes/pressors), time of initiation of WLSM and time from WLSM to death.

Information on life-sustaining measures at the time of withdrawal was retrieved from the DePPaRT database and consisted of pharmacological, respiratory and cardiovascular support measures for which data were collected from the hour prior to WLSM until determination of death. Other pharmacological therapies consisted of analgesic and sedative type and dosages administered throughout the WLSM period.

Respiratory support measures recorded changes to the parameters of invasive and non-invasive modes of oxygen delivery as well as concentration of inhaled oxygen, while cardiovascular support measures included dosages and type of vasopressors, inotropes and/or cardiac assist devices. Respiratory support and cardiovascular support measures were categorised to reflect different practice patterns of either stopping life-sustaining measures immediately at the outset of the withdrawal process or performing a staggered weaning during the dying process. Withdrawal of respiratory support/cardiovascular support measures were classified, both individually and combined, as: (1) terminal extubation/cessation, if the patient was extubated and cardiovascular measures were stopped within 15 min of the start of WLSM; (2) terminal weaning, if the endotracheal tube and cardiovascular support measures remained in place but with staggered reduction of support parameters or dosing changes or (3) unchanged if no changes to respiratory/cardiovascular support measures were made during WLSM. The initiation of WLSM was marked by the first documented change in any respiratory or cardiovascular therapy. Any respiratory or cardiovascular support that was stopped within a 15 min window surrounding the therapy documented as the first to be removed was considered also to be a terminal extubation or cardiovascular support cessation. This reflects the pragmatic reality that stopping multiple measures simultaneously can take time in a busy intensive care setting and does not necessarily occur at the exact same time.

Statistical analysis

Patient characteristics and patterns of WLSM

We used R (V.4.0.5, R Foundation for Statistical Computing, https://www.R-project.org/) and Python (V.3.7, Python Software Foundation, www.python.org) to complete a descriptive analysis of the study cohort. Continuous variables were analysed using the Student’s t-test or Wilcoxon rank-sum test as appropriate. Categorical variables were analysed by using χ2 tests or two-tailed Fisher’s exact tests.

Time to death

Time-to-death analyses were performed using a multivariate logistic regression model, adjusted for covariates (including APACHE II score, age, sex and admission diagnosis), which was fitted with generalised estimating equations and robust SEs to adjust for clustering of outcomes. Covariates were chosen both a priori and through statistical selection using bivariable analysis. Statistically significant covariates with a p<0.05 were selected for inclusion into the regression model. Time to death was divided into death within 30 min, 1 hour or 2 hours from initiation of WLSM to reflect common temporal cut-off criteria for organ retrieval in DCD. These three cut-off points reflect real-life commonly used time points that transplant physicians use to assess organ viability at time to death during the DCD process. Survival curves for attempted DCD status were adjusted for age, gender, APACHE II score, admission diagnosis and country. Survival curves for cardiovascular support and extubation were adjusted for the same variables, as well as each other. Schoenfeld plots were used to test for time varying variables. After identifying features that had time varying effects, survival analyses were performed for two groups; the first group was censored at 1 hour after WLSM, while the second group consisted of all patients who were still alive at 1 hour (censoring at 24 hours). Schoenfeld plots were used to confirm there were no time-varying effects after data splitting.

Comparison of analgesic and sedative dosing

Analgesic and sedative dosing received up to 2 hours after the start of WLSM were stratified by time to death and by DCD attempted status, using either the hour prior to WLSM, or three different time windows after WLSM (0–30 min, 0–60 min or 60–120 min). For each window after WLSM, only patients who survived the window of interest were considered. Analgesic doses of morphine, hydromorphone, fentanyl, piritramide and sufentanil, were converted into morphine equivalents using pharmacological conversion factor guidelines.7 Sedative dosing considered all doses of midazolam and propofol separately. The total amount of each drug in each time window was determined by summing the amount of drug infused over the specified period as well as any boluses applied during that period. To compare drug dosing between DCD eligible but not attempted versus DCD attempted patients, the total doses applied during the time window of interest were compared, with p values calculated using a two-tailed Wilcoxon rank-sum test, with corrections for tied values. Thirteen patients with morphine equivalent doses larger than 65 mg (even after site queries) were considered potentially erroneous and excluded from the dosing analysis (five of which were DCD attempted patients, three were DCD eligible but not attempted).

Sensitivity analysis

A sensitivity analysis was performed by only including the patients from Canadian sites and repeating the analysis to determine if there were major international differences that could skew the study outcomes. To quantify any potential between country differences in the frequency of extubation for the three study cohorts, a post hoc analysis, using a Bayesian approach, was performed to estimate the probability of extubation given DCD status, country of origin and intubation status. We calculated this probability over 5000 bootstrap iterations, using sampling with replacement and maintaining the original sample size in each iteration.

Results

We included 635 adult patients who died following WLSM in 20 ICUs across Canada, the Czech Republic and the Netherlands (online supplemental table 1). DCD was attempted in 85 patients and organs were procured from 59 of these patients.

Patient characteristics

Compared with the 314 patients who were not eligible for DCD, the 321 DCD eligible patients were more likely to be younger, admitted with a neurological or trauma diagnosis, be mechanically ventilated while in the ICU and suffer from less comorbidities (table 1).

Table 1

Demographics and life-sustaining therapies prior to WLSM

The 85 DCD-eligible patients in whom organ donation was attempted were also younger, had less comorbidities, slightly lower APACHE II scores and less likely to be receiving cardiovascular support prior to WLSM compared with the DCD-eligible patients who did not have DCD attempted.

Patterns of WLSM

Eighty-five per cent of patients (534/626) were either extubated or had cardiovascular support stopped within 15 min of the start of WLSM. Nine patients were not intubated or not on any cardiovascular support at the start of WLSM. This indicates that most patients, regardless of DCD eligibility classification, had at least one support therapy completely stopped within 15 min of WLSM. In the DCD attempted group, 83/85 (98%) of patients had either all respiratory and/or all cardiovascular support withdrawn within 15 min of WLSM, compared with 200/232 (86%, p=0.004) of the DCD eligible but not attempted group (table 2).

Table 2

Patterns of withdrawal of life support measures by subgroup of DCD eligibility and DCD attempted

Clinically significant differences were observed in the management of respiratory support measures during the withdrawal process. More patients were extubated within 15 min of WLSM when DCD was attempted compared with DCD eligible patients in whom DCD was not attempted (95% (81/85) vs 61% (142/231, p<0.0001)). Ventilator parameters remained unchanged or were weaned within 15 min of WLSM for 4/85 (5%) of eligible patients in whom DCD was attempted and 89/231 (39%) of DCD eligible patients in whom no attempt for DCD was made.

Time to death

The time from initiation of WLSM to death was similar for DCD eligible patients and patients not eligible for DCD, with more than half of all patients dying within 2 hours (59% (188/321) and 67% (210/314), respectively (table 1). Within the group of patients eligible for DCD, a greater proportion of patients with DCD attempted died within each tested time window, with 71% (60/85) dying within 2 hours of initiation of WLSM as compared with 54% (128/236) of eligible patients who did not have DCD attempted. An initial survival analysis uncovered time varying effects for extubation status and admission diagnosis (online supplemental figure 2). The analysis was, therefore, divided into one group with death censored at 1 hour, and a second group that survived the first hour. The survival probability in patients for whom DCD was attempted was reduced in the first hour (HR 1.49, 95% CI 1.01 to 2.18, p=0.043, figure 1A) compared with DCD eligible patients where DCD was not attempted, even after adjusting for differences in baseline covariates and country. Specifically, the adjusted median survival of DCD attempted patients was 0.47 hours (95% CI 0.35 to >1 hour), while for not attempted patients, it was 0.75 hours (95% CI 0.5 to >1 hour). When considering the association between patterns of WLSM and time to death for all patients, the terminal cessation of cardiovascular measures was consistently more strongly associated with a shorter time to death when compared with terminal extubation at each time point tested, even after adjusting for confounders (table 3, figure 1B,C).

Table 3

Crude and adjusted estimates of the association between method of WLSM and time to death in a cohort of 635 patients undergoing WLSM

Figure 1

Survival analysis demonstrating adjusted time to death for DCD eligible cohort survival probability over time for the DCD eligible cohort, as calculated using an adjusted Cox analysis using either patients with death censored after the first hour after WLSM (top row) or patients who survived the first hour (censored at 24 hours, bottom row). (A), (D) DCD attempted versus DCD eligible but not attempted. (B), (E) Extubated versus not extubated. (C), (F) Cardiovascular support (CV) stopped versus not stopped. All analyses have been adjusted for age, gender, APACHE II score, admission diagnosis and country. The extubation analysis and cardiovascular support analysis each additionally adjusted for the other factor. The shaded regions depict the 95% CIs. Note that the survival probabilities shown in the group that survived the first hour are conditional on surviving the first hour. DCD, donation after circulatory death; WLSM, withdrawal of life-sustaining measures.

Analgesic use

Eighty-six per cent (545/635) of patients in the total cohort received some form of analgesia within 2 hours after the start of WLSM. Eighty per cent (509/635) received analgesics by continuous intravenous infusion, 21% (133/635) received analgesic boluses, while 65% (413/635) and 6% (36/635) received analgesic infusions or boluses only, respectively. Within the group of 321 patients eligible for DCD, 89% (76/85) of DCD attempted were given analgesics after WLSM, compared with 82% (198/236) of the DCD eligible but not attempted group (p=0.28, table 2). Of patients given analgesia prior to WLSM, cumulative morphine equivalent doses tended to be higher in the DCD attempted group (median dose of 5 mg vs 4 mg, p=0.03). Of those patients given analgesics after WLSM, the cumulative morphine equivalent dose varied slightly by donor status (DCD attempted vs not attempted) and time from WLSM (figure 2A). Patients in whom DCD was attempted tended to have slightly higher analgesic drug doses applied in the first 30 min and the first hour after WLSM compared with patients eligible for DCD but for whom donation was not attempted, but the difference was not statistically significant (median dose of 6 mg vs 5 mg, p=0.122, for hour one, figure 2A). There was no apparent difference in dosing between donor status during the second hour after WLSM (5 mg for DCD attempted and not attempted groups, p=0.40, for hour 2). The median dose of approximately 5 mg/hour remained constant for the DCD not attempted but eligible group across all three time periods. Of note, the differences in the mean (rather than median) dosing varied between donor status in the 30 min and 60 min period, reflecting differences in outliers (11.4 mg for DCD attempted vs 6.0 mg for DCD eligible but not attempted, 60 min after WLSM) (figure 2A, red triangles).

Figure 2

Analgesic and sedative doses administered after WLSM. (A) Morphine equivalent analgesic doses and (B) midazolam doses, administered within the hour before WLSM, or the first 30 min, 1 hour or between 1 and 2 hours after WLSM, for patients who received analgesic or midazolam doses, either before WLSM (first column), or after WLSM and survived these same time periods, for DCD attempted versus DCD eligible but not attempted patients. Individual doses are overlayed on top of the box plot in grey. The median dose and number of patients are displayed for each group. The red triangles indicate the mean dose for each group. DCD, donation after circulatory death; WLSM, withdrawal of life-sustaining measures.

Sedative use

Sixty-five per cent (412/635) of patients in the total cohort received either midazolam or propofol within 2 hours after WLSM; 60% received infusions, 16% received boluses, with 49% and 4% receiving only infusions or only boluses only, respectively. Within the group of 321 patients eligible for DCD, DCD attempted patients were more likely to receive sedation, before and after WLSM, with 68% (58/85, 95% CI 58% to 77%) and 24% (20/85, 95% CI 16% to 34%) given midazolam and/or propofol after WLSM, respectively, compared with 50% (117/236, 95% CI 43% to 56%, p=0.003) and 11% (25/236, 95% CI 7% to 15%, p=0.006) of the DCD eligible but not attempted group (table 2 and online supplemental table 2).

For patients who received midazolam prior to WLSM, DCD attempted patients tended to receive higher doses than patients who did not have DCD attempted (median doses of 3.93 vs 3.0 mg, p=0.046). For patients who received sedatives after WLSM, there did not appear to be any difference between DCD attempted and not attempted groups for midazolam dosing (median doses of 2 mg vs 2.5 mg within 30 min after WLSM, p=0.96, figure 2B). Doses of propofol were not different between groups prior to WLSM; within 30 and 60 min after WLSM, doses were higher in DCD attempted patients (median doses of 131 mg vs 55 mg for 30 min, p=0.047, (online supplemental figure 2A,B), however, there were few patients receiving propofol available for comparison between groups.

Sensitivity analysis

A sensitivity analysis with the 360 patients from Canadian ICUs showed similar results to the whole cohort (online supplemental table 3 and figure 4). Differences in respiratory support management remained significant with more patients extubated in the DCD attempted group compared with the DCD eligible but not attempted (95% vs 69%, p<0.0001, online supplemental table 3). Canadian patients were also more likely to receive sedation if DCD was attempted, but no difference in analgesic or sedative dosing between DCD eligible patients who did and did not have DCD attempted was found (online supplemental figure 5A,B). Bootstrap analysis demonstrated differences in extubation rate by country between DCD attempted and DCD eligible but not attempted groups (online supplemental figure 6). While the probability of being extubated (given intubation) was similar for the DCD attempted patients across countries (95% or greater), the probability varied for the DCD eligible but not attempted patients. The mean probability of being extubated for the DCD eligible but not attempted group, given the patient was intubated, was 69% for Canadian patients and 38% for Czech patients. All DCD eligible patients (attempted or not) from the Netherlands were extubated.

Discussion

This study compared the process of WLSM in the largest cohort to date of dying critically ill patients across three countries, including patients eligible for DCD. Patients eligible for DCD in whom donation was attempted were more likely to be extubated and to die within 2 hours of the start of WLSM than DCD eligible patients in whom no attempt at donation was made. There was a significant difference in time to death between groups of DCD eligible patients in whom donation was and was not attempted which persisted despite adjustment for potential confounders. Further, the methods of WLSM were associated with time to death, regardless of DCD status, with immediate cessation of cardiovascular support having the strongest association with a faster time to death.

The strengths of this study lie mainly in the fact that this is one of the only known studies to gather granular data on specifics of WLSM in dying critically ill patients, and specifically potential organ donors. Moreover, appropriate comparative analyses were possible as patients included in the study were not limited to organ donors; this provided for a natural comparative population of DCD eligible patients who did not proceed to organ donation. Due to the detailed, longitudinally collected dataset, we were able to analyse cardiovascular, respiratory, analgesic and sedative data during the dying process and effectuate a clear comparison between DCD eligible patients in whom donation was and was not attempted. To our knowledge, there is no other study comparing these two groups of patients.

We faced several important limitations in this work. First, our findings are drawn from a secondary analysis of existing data and are thus limited by the data already collected. We tried to adjust for the most significant confounding variables, but it is possible that additional variables not collected could have explained differences in the process of WLSM between groups. Second, a large proportion of patients came from the Czech Republic which may have had a different approach in terms of ICU admission criteria or even WLSM practice. Our results may only reflect specific practices in the Czech Republic and Canada and thus may not be generalisable. Third, this study involved an analysis of data that was collected prior to 2018; since that time, some study sites have updated their procedures and current practice may be different than what is reflected here.

Our results demonstrate differences in methods of WLSM between patients who had DCD attempted and DCD eligible patients without DCD attempted, as well as non-DCD eligible groups. The majority of existing data in the literature are on the DCD attempted group. For example, a recent study looking at developing a predictive tool for estimating time to death looked at a cohort of Dutch patients.8 They found no variation in withdrawal practice whereby supportive care was withdrawn simultaneously in all patients, but that study did not consider DCD eligible patients who did not proceed to donation. There is no clear indication why differences in WLSM practices may differ between DCD attempted and not attempted groups of patients. One reason may be due to the pressures associated with DCD and organ donation. For example, ICU physicians may have a greater presence at the bedside which may increase the responsiveness to symptom control. In addition, the bedside presence of families, motivated to have a successful organ donation process transpire, could have an impact on the physician’s end-of-life treatment plan. More likely, it is possible that observable differences in the WLSM processes between attempted and non-attempted donors were simply due to differences in patient characteristics between groups. DCD attempted patients may have been more symptomatic requiring more intervention after WLSM. Finally, variation in WLSM practice may be a function of physician practice regardless of DCD, perhaps reflecting different patients’ needs among the three cohorts that are indeed different at the baseline. Previous studies have documented variation in WLSM practice among different Canadian centres in non-DCD populations.9 10

It has been suggested that a conflict of interest may exist within the system of deceased organ donation where the possibility exists that life support measures might be withdrawn prematurely for the purpose of organ procurement.11 Our findings documented some variability in the withdrawal process for DCD patients as compared with non-DCD patients. This variability could, but not necessarily, support the contention by some ethical analyses that a potential conflict of interest does exist. Crucially, it should be noted that given that all patients died, the patterns of end-of-life care may influence time to death specifically and eligibility for organ retrieval, rather than survivability after WLSM. Extubation and the terminal cessation of cardiovascular measures were more strongly associated with a shorter time to death. This process of WLSM for DCD specifically may be worth considering as recommendations in future WLSM guidelines to optimise patient and family wishes to have their loved ones donate organs in that it would be more likely to ensure adequate time to death within the allowable time for DCD to occur.12 Further investigation into family perceptions regarding time to death and donation is needed. We also identified variability in WLSM practice between countries, with the Netherlands and Canadian centres giving more sedation and more likely to extubate. Further standardisation of WLSM procedures during DCD may be necessary. Our findings support the need for ongoing collaboration and consultation with stakeholders to monitor and improve the quality of end-of-life care during organ donation and in all dying critically-ill patients.

Observable differences in patterns of WLSM between DCD attempted and eligible but not attempted patients suggest that ‘usual practice’ of WLSM, as dictated by most DCD guidelines, may not occur in the same way when there is the potential for organ donation. Further qualitative research is needed to understand if physicians may be consciously or subconsciously working to fulfil the consented aspirations for organ donation of patients and their families. Importantly, further investigation of family perspectives on WLSM practice and impact on potential for donation will be imperative. Finally, it remains to be determined to what extent variation from usual practice is ethically justifiable in DCD donors, in whom such an alteration facilitates fulfilment of their wish to donate organs.

Conclusions

ICU patients for whom DCD is attempted may undergo a different process of WLSM, with higher extubation rates, complete cessation of circulatory support and a shorter time to death following WLSM when compared with eligible patients in whom no attempt for organ donation is made. Our findings support the need for ongoing collaboration and consultation with stakeholders to improve and monitor the quality of end-of-life care during organ donation and in all dying patients.13

Data availability statement

Data are available on reasonable request. Access to the full dataset for this study is available on reasonable request.

Ethics statements

Patient consent for publication

Ethics approval

The original research protocol was approved by the institutional review board or ethics committee at each participating site (coordinating site: Children’s Hospital of Eastern Ontario Research Ethics Board, No. 14/08E, see online supplemental file for full list). All patients’ surrogate decision -makers provided written informed consent for participation in the study. Consent for organ donation was obtained independently from this study, according to local practice. This secondary analysis of data was approved by the Children’s Hospital of Eastern Ontario Research Ethics Board.

References

Supplementary materials

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Footnotes

  • Contributors JS, NBS, LH, SS and SD contributed to the conception, planning and design of the study. FJ, MH and FD contributed to the design of the study. MH, MS, PW and TW were responsible for data acquisition. JS, FJ and NBS conducted analyses and reported results. JS, NS, LH, SDS, FD, JTW, WNKAvM and SD contributed to interpret the data. JS, NBS, LH and SD drafted the manuscript. All authors critically reviewed the manuscript. All authors read and approved the manuscript for submission. JS is responsible for the overall content as guarantor. JS accepts full responsibility for the finished work and/or the conduct of the study, had access to the data and controlled the decision to publish.

  • Funding This work has been supported by Canadian Blood Services and the Canadian Donation and Transplantation Research Program. Support was also provided by an institutional grant from Cooperatio Intensive Care Medicine, Charles University, Prague, Czech Republic.

  • Disclaimer These funders had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; nor in the decision to submit the article for publication. In addition, the authors confirm our independence from funders, other than as previously disclosed, and that all authors had full access to all of the data (including statistical reports and tables) in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

  • Competing interests LH is a paid consultant for Canadian Blood Services. SD is a paid Hospital Donation Physician for Ontario Health.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.