Making a dead woman pregnant? A critique of the thought experiment of Anna Smajdor.

In a thought-provoking article - or how she herself named it, 'a thought experiment' - the philosopher-medical ethicist Anna Smajdor analyzed in this journal the idea of whole-body gestational donation (WBGD) in brain-dead female patients, as an alternative means of gestation for prospective women who cannot or prefer not to become pregnant themselves. We have serious legal, economical, medical and ethical concerns about this proposal. First, consent for eight months of ICU treatment can never be assumed to be derived from consent for post-mortem organ donation; these two are of an incomparable and entirely different medical and ethical order. Moreover, the brain-dead woman is very likely to be medically unfit for high-tech surrogacy and the brain-dead state poses a high risk for deficient embryo/fetal development. Second, from a scarcity perspective, occupying an ICU bed for eight months appears to be unjust. The costs for eight months of ICU treatment are far too high compared to the costs of surrogacy for a living, selected, and healthy woman. Neither insurance companies nor prospective parents will want to pay these exceptionally high costs for a dead woman if a living surrogate mother can be hired for a considerably lower amount. Third, there is an increased risk for harm of the child to be in WBGD. And finally, WBGD risks violating the brain-dead woman's dignity and harming the interests of her loved ones. In short, there is simply no need for brain-dead women as surrogates.

How clinicians discuss patients' donor registrations of consent and presumed consent in donor conversations in an opt-out system: a qualitative embedded multiple-case study.

BACKGROUND: The Netherlands introduced an opt-out donor system in 2020. While the default in (presumed) consent cases is donation, family involvement adds a crucial layer of influence when applying this default in clinical practice. We explored how clinicians discuss patients' donor registrations of (presumed) consent in donor conversations in the first years of the opt-out system. METHODS: A qualitative embedded multiple-case study in eight Dutch hospitals. We performed a thematic analysis based on audio recordings and direct observations of donor conversations (n = 15, 7 consent and 8 presumed consent) and interviews with the clinicians involved (n = 16). RESULTS: Clinicians' personal considerations, their prior experiences with the family and contextual factors in the clinicians' profession defined their points of departure for the conversations. Four routes to discuss patients' donor registrations were constructed. In the Consent route (A), clinicians followed patients' explicit donation wishes. With presumed consent, increased uncertainty in interpreting the donation wish appeared and prompted clinicians to refer to "the law" as a conversation starter and verify patients' wishes multiple times with the family. In the Presumed consent route (B), clinicians followed the law intending to effectuate donation, which was more easily achieved when families recognised and agreed with the registration. In the Consensus route (C), clinicians provided families some participation in decision-making, while in the Family consent route (D), families were given full decisional capacity to pursue optimal grief processing. CONCLUSION: Donor conversations in an opt-out system are a complex interplay between seemingly straightforward donor registrations and clinician-family interactions. When clinicians are left with concerns regarding patients' consent or families' coping, families are given a larger role in the decision. A strict uniform application of the opt-out system is unfeasible. We suggest incorporating the four previously described routes in clinical training, stimulating discussions across cases, and encouraging public conversations about donation.

One-year Mortality of Cancer Patients with an Unplanned ICU Admission: A Cohort Analysis Between 2008 and 2017 in the Netherlands.

Introduction: A decrease in short-term mortality of critically ill cancer patients with an unplanned intensive care unit (ICU) admission has been described. Few studies describe a change over time of 1-year mortality. Therefore, we examined the 1-year mortality of cancer patients (hematological or solid) with an unplanned ICU admission and we described whether the mortality changed over time. Methods: We used the National Intensive Care Evaluation (NICE) registry and extracted all patients with an unplanned ICU admission in the Netherlands between 2008 and 2017. The primary outcome was 1-year mortality, analyzed with a mixed-effects Cox proportional hazard regression. We compared the 1-year mortality of cancer patients to that of patients without cancer. Furthermore, we examined changes in mortality over the study period. Results: We included 470,305 patients: 10,401 with hematological cancer, 35,920 with solid cancer, and 423,984 without cancer. The 1-year mortality rates were 60.1%, 46.2%, and 28.3% respectively (P< .01). Approximately 30% of the cancer patients surviving their hospital admission died within 1 year, this was 12% in patients without cancer. In hematological patients, 1-year mortality decreased between 2008 and 2011, after which it stabilized. In solid cancer patients, inspection showed neither an increasing nor decreasing trend over the inclusion period. For patients without cancer, 1-year mortality decreased between 2008 and 2013, after which it stabilized. A clear decrease in hospital mortality was seen within all three groups. Conclusion: The 1-year mortality of cancer patients with an unplanned ICU admission (hematological and solid) was higher than that of patients without cancer. About one-third of the cancer patients surviving their hospital admission died within 1 year after ICU admission. We found a decrease in 1-year mortality until 2011 in hematology patients and no decrease in solid cancer patients. Our results suggest that for many cancer patients, an unplanned ICU admission is still a way to recover from critical illness, and it does not necessarily lead to success in long-term survival. The underlying type of malignancy is an important factor for long-term outcomes in patients recovering from critical illness.

Outcome of cancer patients considered for intensive care unit admission in two university hospitals in the Netherlands: the danger of delayed ICU admissions and off-hour triage decisions.

BACKGROUND: Very few studies assessed the association between Intensive Care Unit (ICU) triage decisions and mortality. The aim of this study was to assess whether an association could be found between 30-day mortality, and ICU admission consultation conditions and triage decisions. METHODS: We conducted a retrospective cohort study in two large referral university hospitals in the Netherlands. We identified all adult cancer patients for whom ICU admission was requested from 2016 to 2019. Via a multivariable logistic regression analysis, we assessed the association between 30-day mortality, and ICU admission consultation conditions and triage decisions. RESULTS: Of the 780 cancer patients for whom ICU admission was requested, 332 patients (42.6%) were considered 'too well to benefit' from ICU admission, 382 (49%) patients were immediately admitted to the ICU and 66 patients (8.4%) were considered 'too sick to benefit' according to the consulting intensivist(s). The 30-day mortality in these subgroups was 30.1%, 36.9% and 81.8%, respectively. In the patient group considered 'too well to benefit', 258 patients were never admitted to the ICU and 74 patients (9.5% of the overall study population, 22.3% of the patients 'too well to benefit') were admitted to the ICU after a second ICU admission request (delayed ICU admission). Thirty-day mortality in these groups was 25.6% and 45.9%. After adjustment for confounders, ICU consultations during off-hours (OR 1.61, 95% CI 1.09-2.38, p-value 0.02) and delayed ICU admission (OR 1.83, 95% CI 1.00-3.33, p-value 0.048 compared to "ICU admission") were independently associated with 30-day mortality. CONCLUSION: The ICU denial rate in our study was high (51%). Sixty percent of the ICU triage decisions in cancer patients were made during off-hours, and 22.3% of the patients initially considered "too well to benefit" from ICU admission were subsequently admitted to the ICU. Both decisions during off-hours and a delayed ICU admission were associated with an increased risk of death at 30 days. Our study suggests that in cancer patients, ICU triage decisions should be discussed during on-hours, and ICU admission policy should be broadened, with a lower admission threshold for critically ill cancer patients.

Assessment of mortality and performance status in critically ill cancer patients: A retrospective cohort study.

INTRODUCTION: Given clinicians' frequent concerns about unfavourable outcomes, Intensive Care Unit (ICU) triage decisions in acutely ill cancer patients can be difficult, as clinicians may have doubts about the appropriateness of an ICU admission. To aid to this decision making, we studied the survival and performance status of cancer patients 2 years following an unplanned ICU admission. MATERIALS AND METHODS: This was a retrospective cohort study in a large tertiary referral university hospital in the Netherlands. We categorized all adult patients with an unplanned ICU admission in 2017 into two groups: patients with or without an active malignancy. Descriptive statistics, Pearson's Chi-square tests and the Mann-Whitney U tests were used to evaluate the primary objective 2-year mortality and performance status. A good performance status was defined as ECOG performance status 0 (fully active) or 1 (restricted in physically strenuous activity but ambulatory and able to carry out light work). A multivariable binary logistic regression analysis was used to identify factors associated with 2-year mortality within cancer patients. RESULTS: Of the 1046 unplanned ICU admissions, 125 (12%) patients had cancer. The 2-year mortality in patients with cancer was significantly higher than in patients without cancer (72% and 42.5%, P <0.001). The median performance status at 2 years in cancer patients was 1 (IQR 0-2). Only an ECOG performance status of 2 (OR 8.94; 95% CI 1.21-65.89) was independently associated with 2-year mortality. CONCLUSIONS: In our study, the majority of the survivors have a good performance status 2 years after ICU admission. However, at that point, three-quarter of these cancer patients had died, and mortality in cancer patients was significantly higher than in patients without cancer. ICU admission decisions in acutely ill cancer patients should be based on performance status, severity of illness and long-term prognosis, and this should be communicated in the shared decision making. An ICU admission decision should not solely be based on the presence of a malignancy.

Treatment Limitation Decisions in Critically Ill Patients With a Malignancy on the Intensive Care Unit.

BACKGROUND: Treatment limitation decisions (TLDs) on the ICU can be challenging, especially in patients with a malignancy. Up-to-date literature regarding TLDs in critically ill patients with a malignancy admitted to the ICU is scarce. The aim was to compare the incidence of written TLDs between patients with an active malignancy, patients with a malignancy in their medical history (complete remission, CR) and patients without a malignancy admitted unplanned to the ICU. METHODS: We conducted a retrospective cohort study in a large university hospital in the Netherlands. We identified all unplanned admissions to the ICU in 2017 and categorized the patients in 3 groups: patients with an active malignancy (study population), with CR and without a malignancy. A TLD was defined as a written instruction not to perform life-saving treatments, such as CPR in case of cardiac arrest. A multivariate binary logistic regression analysis was used to identify whether having a malignancy was associated with TLDs. RESULTS: Of the 1046 unplanned admissions, 125 patients (12%) had an active malignancy and 76 (7.3%) patients had CR. The incidence of written TLDs in these subgroups were 37 (29.6%) and 20 (26.3%). Age (OR 1.03; 95% CI 1.01 -1.04), SOFA score at ICU admission (OR 1.11; 95% CI 1.05 -1.18) and having an active malignancy (OR 1.75; 95% CI 1.04-2.96) compared to no malignancy were independently associated with written TLDs. SOFA scores on the day of the TLD were not significantly different in patients with and without a malignancy. CONCLUSIONS: This study shows that the presence of an underlying malignancy is independently associated with written TLDs during ICU stay. Patients with CR were not at risk of more written TLDs. Whether this higher incidence of TLDs in patients with a malignancy is justified, is at least questionable and should be evaluated in future research.

Determining the impact of timing and of clinical factors during end-of-life decision-making in potential controlled donation after circulatory death donors.

Controlled donation after circulatory death (cDCD) occurs after a decision to withdraw life-sustaining treatment and subsequent family approach and approval for donation. We currently lack data on factors that impact the decision-making process on withdraw life-sustaining treatment and whether time from admission to family approach, influences family consent rates. Such insights could be important in improving the clinical practice of potential cDCD donors. In a prospective multicenter observational study, we evaluated the impact of timing and of the clinical factors during the end-of-life decision-making process in potential cDCD donors. Characteristics and medication use of 409 potential cDCD donors admitted to the intensive care units (ICUs) were assessed. End-of-life decision-making was made after a mean time of 97 hours after ICU admission and mostly during the day. Intracranial hemorrhage or ischemic stroke and a high APACHE IV score were associated with a short decision-making process. Preserved brainstem reflexes, high Glasgow Coma Scale scores, or cerebral infections were associated with longer time to decision-making. Our data also suggest that the organ donation request could be made shortly after the decision to stop active treatment and consent rates were not influenced by daytime or nighttime or by the duration of the ICU stay.

End-of-life practices in traumatic brain injury patients: Report of a questionnaire from the CENTER-TBI study.

PURPOSE: We aimed to study variation regarding specific end-of-life (EoL) practices in the intensive care unit (ICU) in traumatic brain injury (TBI) patients. MATERIALS AND METHODS: Respondents from 67 hospitals participating in The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study completed several questionnaires on management of TBI patients. RESULTS: In 60% of the centers, ≤50% of all patients with severe neurological damage dying in the ICU, die after withdrawal of life-sustaining measures (LSM). The decision to withhold/withdraw LSM was made following multidisciplinary consensus in every center. Legal representatives/relatives played a role in the decision-making process in 81% of the centers. In 82% of the centers, age played a role in the decision to withhold/withdraw LSM. Furthermore, palliative therapy was initiated in 79% of the centers after the decision to withdraw LSM was made. Last, withholding/withdrawing LSM was, generally, more often considered after more time had passed, in a patient with TBI, who remained in a very poor prognostic condition. CONCLUSION: We found variation regarding EoL practices in TBI patients. These results provide insight into variability regarding important issues pertaining to EoL practices in TBI, which can be useful to stimulate discussions on EoL practices, comparative effectiveness research, and, ultimately, development of recommendations.

An Observational Study on a Protocol for Withdrawal of Life-Sustaining Measures on Two Non-Academic Intensive Care Units in The Netherlands: Few Signs of Distress, No Suffering?

CONTEXT: Because anticipation of death is common within the intensive care unit, attention must be paid to the prevention of distressing signs and symptoms, enabling the patient to die peacefully. In the relevant studies on this subject, there has been a lack of focus on measuring determinants of comfort in this population. OBJECTIVES: To evaluate whether dying without distressing signs after the withdrawal of life-sustaining measures is possible using a newly introduced protocol and to analyze the potential influence of opioids and sedatives on time till death. METHODS: This was a prospective observational study, in two nonacademic Dutch intensive care units after the introduction of a national protocol for end-of-life care. The study lasted two years and included adult patients in whom mechanical ventilation and/or vasoactive medication was withdrawn. Exclusion criteria included all other causes of death. RESULTS: During the study period, 450 patients died; of these, 305 patients were eligible, and 241 were included. Ninety percent of patients were well sedated before and after withdrawal. Severe terminal restlessness, death rattle, or stridor was seen in less than 6%. Dosages of opioids and sedatives increased significantly after withdrawal, but did not contribute to a shorter time till death according the regression analysis. CONCLUSION: The end-of-life protocol seems effective in realizing adequate patient comfort. Most patients in whom life-sustaining measures are withdrawn are well sedated and show few signs of distress. Dosages of opioids and sedatives increase significantly during treatment withdrawal but do not contribute to time until death. Dying with a minimum of distressing signs is thus practically possible and ethically feasible.

[Determination of brain death in organ donation: is EEG required?]. / Vaststellen van hersendood bij orgaandonatie: is een eeg noodzakelijk?

The determination of brain death is a prerequisite of multiple organ donation in ventilated patients in the ICU. The criteria for brain death differ internationally. In some countries, brain stem death is equivalent to brain death. In others, including the Netherlands, in addition to the determination of brain stem death, an EEG must also be carried out to rule out cortex activity according to the criteria of "whole brain death". However, this does not prove that there is complete failure of all brain functions; indeed, EEG does not examine the subcortical brain. The Dutch Health Board has established that brain death is ruled out by rest activity in the cortex, but not by persistent subcortical activity. This is conceptually incorrect. The criteria for brain stem death fit better in practice than the criteria for whole brain death. Taking an EEG should therefore no longer be an obligation in establishing brain death, as is the case in many other countries.

Withdrawal of life-sustaining treatment in a mixed intensive care unit: most common in patients with catastropic brain injury.

OBJECTIVE: To determine the incidence of withdrawal of life-sustaining treatment in various groups of patients in a mixed intensive care unit (ICU). DESIGN: Observational retrospective. SETTING: University hospital mixed medical, neurological, neurosurgical and surgical ICU. PATIENTS: All patients admitted to the ICU between 1 November 2006, and 31 October 2007. RESULTS: 1,353 Patients were admitted to our ICU between 1 November 2006, and 31 October 2007. During this period, 218 (16.1%) patients died in the ICU, 10 of which were excluded for further analysis. In 174 (83.7%) of the remaining 208 patients, life-sustaining treatment was withdrawn. Severe CNS injury was in 86 patients (49.4%) being the reason for withdrawal of treatment, followed by MODS in 67 patients (38.5%). Notably, treatment was withdrawn in almost all patients (95%) who died of CNS failure. Patients who died in the ICU were significantly older, more often admitted for medical than surgical reasons, and had higher SOFA and APACHE II scores compared with those who survived their ICU stay. Also, SOFA scores before discharge/death were significantly different from admission scores. Of the 1,135 patients who survived their ICU stay, only 51 patients (4.5%) died within 28 days after ICU discharge. CONCLUSIONS: In 83, 7% of patients who die in the mixed ICU life-sustaining treatment is withdrawn. Severe cerebral damage was the leading reason to withdraw life-sustaining treatment.

The use of opioids and sedatives and time until death after withdrawing mechanical ventilation and vasoactive drugs in a dutch intensive care unit.

BACKGROUND: We studied the frequency of withdrawal of mechanical ventilation (MV) and/or vasoactive agents (VAs), the time until death, and dosages of opioids and sedatives in a Dutch academic intensive care unit (ICU), and compared these practices with international observations in this field. METHODS: Retrospective data were collected from the electronic and paper files of all patients who died after withdrawal of treatment in a Dutch ICU between October 2006 and February 2007. RESULTS: In this period, 471 patients were admitted to the ICU, of whom 88 died (18%). In 60 of these patients (68%), MV and/or VAs were withdrawn. This group represented 13% of the total ICU population. Of the 60 patients for whom MV and/or VAs were withdrawn, 54 (90%) died after withdrawal of MV (with or without VAs). Six (10%) died after withdrawal of VAs only, 33 (55%) after withdrawal of MV in combination with VAs, and 21 (35%) after withdrawal of MV only. Death occurred after withdrawal of MV in combination with VAs after a median of 30 minutes (interquartile range [IQR], 10-195 minutes). When only MV was discontinued, the median time until death was 50 minutes (IQR, 15-530 minutes). When only VAs were withdrawn, patients died after a median of 45 minutes (IQR, 20-715 minutes). Ten patients (17%) did not receive opioids or sedatives in their last hours. Fifty patients received opioids in their last hours. Fentanyl, with a median dosage at time of death of 100 µg/h, was the most frequently used opioid. Forty (80%) of the 50 patients mentioned above received some kind of sedative until death. In the MV withdrawal group, 34 of the 54 patients (63%) received sedatives in the last hours of their lives: 16 (27%) received midazolam (median, 10 mg/h), 12 (22%) propofol (median, 160 mg/h), and 6 (11%) lorazepam (2.0 mg/h). Sedatives were administered to all patients in whom only VAs were withdrawn. CONCLUSIONS: Dutch patients who die in the ICU, or die after discharge from the ICU, die after MV and/or VAs are withdrawn. When treatments are withdrawn, death follows within 1 hour in most patients, which is a reflection of the severity of illnesses. At least 80% of patients receive opioids, and 67% receive sedatives until death. Fentanyl is the most used opioid, whereas midazolam is the most used sedative. Dosages of opioids and sedatives did not significantly exceed the ranges described as usual in the international literature.

Accidental methanol ingestion: case report.

BACKGROUND: The incidence of methanol (CH3OH) intoxication differs enormously from country to country. Methanol intoxication is extremely rare in the Dutch population. Even a low dose can already be potentially lethal. Patients are conventionally treated with hemodialysis. Therefore we'd like to present a report of a foreign sailor in Rotterdam who accidentally caused himself severe methanol intoxication, with a maximum measured concentration of 4.4 g/L. CASE PRESENTATION: The patient presented with hemodynamic instability and severe metabolic acidosis with pH 6.69. The anion gap was 39 mmol/L and the osmol gap 73 mosmol/kg. Treatment with ethanol and continuous venovenous hemodiafiltration (CVVH-DF) was initiated. Despite the hemodynamic instability it is was possible to achieve rapid correction of pH and methanol concentration with CVVH-DF while maintaining a stable and therapeutic ethanol serum concentration. Despite hemodynamic and acid-base improvement, our patient developed massive cerebral edema leading to brain death. Permission for organ donation was unfortunately not ascertained. CONCLUSIONS: We conclude that in a hemodynamic instable situation high methanol concentrations and methanol-induced derangements of homeostasis are safely and effectively treated with CVVH-DF and that severe cerebral edema is another possible cause of death rather than the classical bleeding in the putamen area.

Progressive multifocal leukoencephalopathy, a review and an extended report of five patients with different immune compromised states.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the brain caused by the JC-virus. Both a decreased cellular or humoral immune response can increase the susceptibility for JC-virus induced PML. Not only HIV infected people are at risk, a wide range of otherwise immune compromised patients are a potential target for this virus. This report of five PML patients shows the importance of a clinician's familiarity with this disease and it's presenting symptoms. The presenting symptoms of PML can sometimes mimic worsening of the underlying disease. Although different therapeutic strategies have been tried, the outcomes remain very poor. In this series, treatment with cidofovir appears not to be effective in treating PML, neither in HIV positive nor HIV negative patients. Experimental therapy with leflunomide, after tapering of the immunosuppressive medication, did change the natural course of PML in one patient.