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Palliative use of midazolam in acute geriatric units: a multicenter ambispective study

BMC Geriatrics volume 25, Article number: 241 (2025) Cite this article

Abstract

Introduction

End-of-life management in acute geriatric units (AGUs) is frequent but complex. Midazolam is the drug of choice for the management of refractory symptoms (particularly in the context of sedation) at the end of life. The objective of the present ambispective analysis was to investigate the frequency and modalities of midazolam use for palliative care in AGUs in France.

Methods

We conducted a prospective study in four AGUs in France, in order to identify patients having received comfort care only and having been treated with midazolam. We then retrospectively documented the modalities of midazolam use, the indications, and the level of effectiveness.

Results

Of the 210 patients identified as having received comfort care only in the AGU, 68 (32.4% (95%CI, 26.1 to 39.2%)) had received midazolam. The indication for midazolam corresponded to sedation in 67.6% of cases. The modalities of midazolam use at the end -of -life were rarely personalized, with low dose levels (less than 0.5 mg/h), mainly subcutaneous administration, and little anticipatory prescribing or dose level titration. The modalities did not appear to vary with the indication (anxiolysis vs. sedation).

Discussion

The present study is one of the first to have described the frequency and characteristics of palliative midazolam use in the AGU. Our results showed that the end-of-life use of midazolam is rarely personalized, not explicitly documented, and often not compliant with the current guidelines on palliative sedation practices.

Clinical trials registration number

NCT02949635. Registration Date: 2016-09-07.

Key message

This article describes a prospective study in acute geriatric units and shows that fewer than a third of patients identified as having received comfort care only in the acute geriatric unit were treated with midazolam at the end of their lives. Palliative care teams cared for only a third of these patients. The use of midazolam is rarely personalized, not explicitly documented, and often not compliant with the current guidelines on palliative sedation practices.

Peer Review reports

Introduction

Midazolam is often considered to be an “end-of-life (EOL) drug” associated with the limitation and withdrawal of active treatment; hence, some people may fear that the initiation of treatment with midazolam will hasten death [1, 2]. However, midazolam’s sedative effect makes it the most strongly recommended drug for the management of refractory symptoms at the EOL [3,4,5]. The European definition of sedative practices was restated by the European Association for Palliative Care (EAPC) in 2022: “palliative sedation aims to relieve refractory suffering through the monitored proportional use of medications intended to reduce consciousness in patients with life-limiting disease” [3]. There is a continuum in EOL practices, as evidenced by the name of the latest draft guidelines from the EAPC: “From anxiolysis to deep continuous sedation - development of recommendations for sedation in palliative care”. The benzodiazepine drug midazolam is used as a first-line sedative in palliative care (PC) and can also be prescribed in an anxiolytic indication [5,6,7].

EOL care is common in acute geriatric units (AGUs), and a transition to comfort care only (comfort measures only, comfort-focused care, or hospice care) is sometimes decided during the hospital stay. Comfort care only has been defined as the set of the most basic PC interventions that provide immediate relief of symptoms in a patient who is very close to death [8]. AGUs specialize in the treatment of frail older adults (generally aged 75 or over) following an acute event, such as a fall, delirium, pneumonia, another severe infection, heart failure, an acute cardiovascular event, or an adverse drug reaction. A PC team can be asked for advice or assistance by the patient’s family, nurse or physician, although this is not systematic [9,10,11]. The deployment of PC in geriatrics remains limited and faces many obstacles [12, 13]. Geriatricians may be less familiar or less comfortable with managing EOL symptoms or sedation practices. To the best of our knowledge, there are no guidelines on palliative sedation (PS) practices in the frail older adult. However, good sedation practice contributes to the quality of EOL care [14, 15].

Although midazolam prescribing has been investigated in EOL situations such as oncology and PC [16,17,18], midazolam use in AGUs has (somewhat surprisingly) not been studied previously. Hence, the objective of the present study was to evaluate the frequency and conditions of midazolam administration for palliative purposes in four AGUs in France.

Materials and methods

Study design

We performed an ambispective (prospective and retrospective) analysis of the results of the DAMAGE multicenter, prospective study (NCT02949635) of a cohort of patients aged 75 or over hospitalized in one of six AGUs in two regions of France. The inclusion period ran from September 14th, 2016, to January 29th, 2018. The DAMAGE study’s population and methodology have been described in detail elsewhere [19, 20]. In the present analysis, we retrieved retrospective data on midazolam use among DAMAGE participants having received comfort care only in the four largest AGUs for at least one day, throughout the inclusion period.

Ethical approval

The DAMAGE study was performed in compliance with the tenets of the Declaration of Helsinki and was approved by an institutional review board (CPP Nord-Ouest IV, Lille, France) on February 13th, 2015. An amendment was approved on January 21st, 2016 (reference: IDRCB 2014 A01670 47, CNIL. bxA15352514).

Inclusion and exclusion criteria

All patients aged 75 or over, with health insurance coverage and hospitalized in an AGU were eligible for inclusion in the DAMAGE cohort. Patients hospitalized in the AGU for less than 48 h or admitted for immediate comfort care only were not included. A total of 3112 patients were included. The population was very old, with female predominance, a high prevalence of polypharmacy, and a high proportion of patients taking psychotropic medications. The prevalences of cognitive disorders (58.2%), dependency (60.9% of the patients had a 6-item Katz Index of Activities of Daily Living (ADL) score ≤ 5) and probable malnutrition (28.4%) were high. Most of the AGU admissions (79.7%) came from the emergency department [19, 20]. We next selected DAMAGE cohort members who had received comfort care only during their stay in one of the four AGUs. Patients whose medical records could not be located were subsequently excluded from the study.

Prospective data collection during the DAMAGE study

The following data were collected prospectively at several time points during the stay in the AGU. During the first 72 h in the AGU, the social, medical, and geriatric variables assessed included age, sex, living location, previous hospital admissions, the Charlson Comorbidity Index, dependency (according to the Katz activities of daily living (ADL) score), cognitive impairment, and standard laboratory parameters. After the first 72 h in the AGU, the patient’s clinical condition was assessed on a daily basis by patient’s attending physician and classified as (1) waiting for discharge, (2) an unstable clinical condition (excluding infections), (3) community-acquired infection, (4) nosocomial infection, and (5) ‘PC’ (for details, see the Supplementary Material). The DAMAGE study protocol did not feature a strict definition of PC; this was left to the geriatrician’s discretion during the stay in the AGU. A second analysis showed that the geriatrician’s designation of PC corresponded typically to a transition to comfort care only during their hospital stay, rather than the broader international definition [20]. These clinical states were mutually exclusive (i.e. only one state per day and per patient). For the present study, we included only DAMAGE cohort members with a state of comfort care only for at least one day during their stay in the AGU.

Retrospective data collection on patients receiving comfort care only in the AGU

Two reviewers (a geriatrics resident (CH) and a PC physician (CP)) reviewed each patient’s full medical records, which included all correspondence, consultation notes, hospital admissions, physicians’ and nurses’ clinical notes, prescription sheets, and official documents (advance directives, and notices of registration of a lasting power of attorney).

Midazolam administration during the stay in the AGU

Based on the medical records, all patients from the DAMAGE cohort who were classified in comfort care only at least one day during the hospital stay were classified into 2 groups: receiving or not midazolam. Midazolam administration was defined as an intravenous or sub-cutaneous perfusion of midazolam.

The indication for Midazolam

We sought to differentiate between the three main authorized indications for midazolam in geriatric PC in France: (i) proportionate sedation, (ii) continuous, deep sedation, as defined by the 2016 Claeys-Leonetti Act [21], and (iii) anxiolysis [5, 21, 22]. An anxiolytic indication corresponded to a written mention of anxiolysis or the treatment of anxious symptoms with an initial sedative effect of -1 or less on the Richmond Agitation-Sedation Scale (RASS).

The indication of continuous, deep sedation was defined in accordance with the French legislation introduced in 2016 [23]. This indication is approved in a multidisciplinary team meeting, in three situations: (i) at the patient’s request, for the relief of refractory suffering at the EOL; (ii) following a request to discontinue life-sustaining treatment, and (iii) following a decision to discontinue life-sustaining treatment in a non-communicative patient.

Proportionate sedative indications were defined as the use of midazolam in all other situations, i.e. to reduce alertness to the point of unconsciousness in a patient with intractable, unbearable symptoms. Proportionate sedation can be mild or deep and intermittent or continuous.

At the beginning of the study, 15 records were selected at random for testing the reproducibility of data extraction. The two researchers (CH and CP) extracted data independently from these 15 records. Discrepancies between the reviewers for the first 15 records were resolved by consensus, with recourse to a third reviewer (a senior geriatrician (GD)) if necessary.

Lastly, three researchers (a senior PC physician (CP) and two senior geriatricians (GD and FV)) screened all the files specifically for indications of continuous, deep sedation, as defined by the 2016 legislation.

Midazolam use

Data on midazolam use were then collected from all the files by one researcher (CH) and checked by a second (CP) in the event of doubt. These data included (i) the main reason for midazolam administration: a psychiatric symptom (confusion, anxiolysis, or insomnia), a somatic symptom (respiratory difficulty, pain, or bleeding) or a decision to limit or stop treatment; (ii) the involvement of a mobile PC team during the stay in the AGU; (iii) a request for midazolam by the patient, the provision of consent, and the provision of information to the patient’s relatives; (iv) treatment-related information, such as the midazolam dose level (upon initiation, during maintenance treatment and at the time of death), the presence or absence of titration, continuous or discontinuous prescribing, anticipatory prescribing, the administration route, combination with opioids or another hypnotic, and whether or not the prescription was made out of hours (i.e. at night or at the weekend); (v) evaluation of the depth of sedation and the effectiveness of treatment; (vi) explicit written documentation of the sedative or non-sedative intent of the treatment in the medical records. Based on transcriptions in the medical records of the multidisciplinary team’s assessments several times a day, the depth of sedation was rated (on the RASS) at the first assessment after the initiation of midazolam treatment or (if the midazolam treatment had already been initiated) after the last midazolam dose adjustment. Effectiveness was rated by categorizing the degree of relief as “full relief” (positive signs of comfort at all successive reassessments), “partial or delayed relief” (at least one observation of signs of discomfort after midazolam administration), and “no relief” (for all other situations).

Statistical analysis

Categorical variables were expressed as the frequency (percentage). Quantitative variables were expressed as the mean (standard deviation (SD)) or (for non-normally distributed variables) the median [interquartile range (IQR)]. The normality of distribution was assessed graphically and by applying the Shapiro-Wilk test. Patients were divided into two groups, according to the use or not of midazolam. With regard to the characteristics at baseline and the mortality in the AGU, the two groups were compared using a chi-squared test or (when the expected cell frequency was < 5) Fisher’s exact test for categorical variables and Student’s test for quantitative variables. The threshold for statistical significance was set to p < 0.05. Data were analyzed using SAS software (version 9.4, SAS Institute Inc., Cary, NC).

Results

Patient selection & Midazolam administration

In all, 214 patients (6.8% of the DAMAGE cohort) were identified as having received comfort care only during their stay in the AGU (Fig. 1). Four files were lost. Of the 210 patients included, 68 (32.4%: 95% CI, 26.1 to 39.2) received midazolam, and 127 (60.5%; 95%CI, 53.5 to 67.2) died in the AGU. Sixty-six (51.9%) of these 127 patients had not received midazolam at the end of their lives.

Fig. 1
figure 1

Flowchart

Full size image

Patient characteristics

The mean age of the study population was 87, 66% were women, and 45.6% lived in a nursing home or other institution (Table 1). Functional dependence was often severe, with a median [IQR] ADL score on admission of 0 [0;1]. PC teams cared for only 71 (34%) of the 210 patients.

The midazolam group differed significantly from the non-midazolam group in terms of the level of dependence on admission, with a lower ADL, a lower Charlson Comorbidity Index, and a higher prevalence of cognitive impairment (72.1% vs. 55.6%, respectively). The proportion of deaths during the AGU stay was significantly higher in the midazolam group (89.7%, vs. 46.5% in the non-midazolam group). The two groups did not differ significantly in terms of age, sex ratio, a history of depression or cancer, or receipt of at least one visit from the PC team.

Table 1 Patient characteristics at baseline and on discharge from hospital
Full size table

Indication for Midazolam

No indications of continuous, deep sedation as defined by the French legislation were identified (Table 2). There were 22 cases of anxiolysis (32.3%). Forty-six (67.7%) indications corresponded to proportionate sedation. Lastly, 46 of the 210 patients having received comfort care only in an AGU received sedative treatment (21.9%).

Table 2 The indication for Midazolam, according to the main symptom (for proportionate sedation only; there were no cases of continuous, deep sedation as defined in France’s 2016 Claeys-Leonetti Act)
Full size table

Midazolam treatment was initiated for a somatic symptom (mainly a respiratory symptom or prominent pain) in 43 (63.2%) cases and for a psychiatric symptom (mainly anxiety; n = 19; 27.9%) in 25 (36.8%) cases (Table 2). We did not identify any indications for the limitation or discontinuation of active treatment in the absence of refractory, distressing symptoms.

Of the 7 patients who received midazolam and did not die in the AGU (transferred either to a PC unit or at home), 6 had received the drug in an anxiolytic indication.

Modalities of Midazolam use

In 56 (82.4%) of the 68 cases, the patient’s relatives had been given information about treatment with midazolam (Table 3). Only four patients requested midazolam treatment: two in the anxiolysis group and two in the sedation group (n = 50; missing data: 18). In 50 of the 68 cases, the physician had noted whether or not the patient was able to give his/her consent to treatment initiation. In fact, 44 (88.0%) of these 50 patients were considered to be incapable of giving consent. Among the 68 patients having received midazolam, in only 27 cases (39.7%) was the indication stated clearly by the prescriber in the medical records.

Table 3 Modalities of Midazolam treatment, by indication: the decision-making process, administration, and patient assessment
Full size table

Midazolam was infused continuously for all patients in the sedation group and for 72.7% of the patients in the anxiolysis group. In the sedation group, five patients underwent dose level titration, three had received anticipatory prescriptions, and eight patients were prescribed midazolam out of hours. Most patients (76.1%) received a subcutaneous injection or infusion. The anxiolysis and sedation subgroups did not differ with regard to the administration modality.

On initiation, the median dose of midazolam was 0.3 mg/h. The median maintenance dose levels were similar in the anxiolysis group (5.0 mg/24 h, or approximately 0.2 mg/h) and the sedation group (7.2 mg/24 h or approximately 0.3 mg/h). At the time of death, the median [IQR] dose level was 6.1 mg/24 h [4.0; 12.0] in the anxiolysis group and 12 mg/24 h [5.0; 12.5] in the sedation group. An increase in the midazolam dose level was observed in only 26.5% of the cases. No dose decreases were observed. 91.2% of the patients receiving midazolam were also prescribed a strong opioid. None of the patients on midazolam concomitantly received an antipsychotic.

The midazolam treatment was fully effective in 33.8% of the patients– more so in the anxiolysis group than in the sedation group– and ineffective in 16.9% of patients (13.9% in the sedation group and 22.7% in the anxiolysis group).

Discussion

We described midazolam use in 210 older adults having received comfort care only after admission to the unit, although PC was not the reason for admission. Our results show that only a third of these patients received midazolam and that fewer than half the patients who died in the AGU received EOL treatment with midazolam. For the 68 patients who received midazolam, the indication for treatment was often poorly explained or not recorded at all in the medical records, consent was extremely rare, and the administration modality was often inadequate.

Midazolam is considered to be one of the four most relevant treatments at the EOL [24, 25]. The literature data on the incidence of PS are not easy to interpreted because the terms and definitions vary from study to study [15, 26]. In the studies included in a meta-analysis in 2021, the proportion of sedated patients at the EOL in PC services ranged from 2 to 28% - much as in the present study. Nevertheless, the results of some studies indicate that palliative treatments (such as opioids and benzodiazepines) are less likely to be prescribed to older adults, individuals with dementia, and patients hospitalized in geriatric medicine wards (rather than PC units) [27, 28]. In a recent Belgian, large-scale, multicenter, retrospective study of patients who died in an AGU, midazolam was prescribed on an anticipatory basis in only 51 (15%) of 338 patients [29] and was less common in patients with dementia or in those not considered to be at the EOL.

In the DAMAGE cohort, we did not find any cases of continuous, deep sedation as defined by the French legislation. This might be because the legislation had just been introduced and physicians were not yet familiar with it, as found in other studies [30]. However, geriatricians appear generally reluctant to use deep sedation because proportionality remains a fundamental principle of PS [15].

The prevalence of cognitive disorders among the study participants was high; this probably made it more difficult to obtain consent and limited a patient’s ability to express his/her EOL wishes [31, 32]. However, France has legal provisions that facilitate advance care planning (ACP) [21]. However, there was no evidence of advance directives or the nomination of a trusted support person in the 68 patient files examined. Hence, one cannot conclude that the initiation of midazolam was considered with regard to the patient’s intentions [33, 34]. Although the family physician has an important role in ACP, he/she was contacted in only 8 cases. However, this contact is often prevented by the shortness of the stay in the AGU [35].

Our analysis of the DAMAGE cohort revealed the very poor level of documentation of midazolam sedation by prescribers in AGUs: only 7.3% of midazolam prescriptions were recorded as having a sedative indication, and 67.6% of prescriptions were not accounted for. This lack of clarification has already been observed in the literature [17, 36, 37] and probably has several explanations. Firstly, definitions of sedation practice in PC continue to vary, with a continuum of practices [4, 5, 16]. It is rarely easy to differentiate between midazolam use for “symptom relief” and midazolam use for “sedation”. There may also be unease or apprehension about explicitly naming sedation practices, which are confused with euthanasia or hastening death [1, 2, 38].

Overall, the midazolam dose levels observed in the present study were lower than in the meta-analyses of use in PC services and did not differ greatly by patient or by indication [5, 16]. This might be due (at least in part) to the low therapeutic range for midazolam when used for anxiolysis only in people over 80. The lower age limit in the studies included in the meta-analysis was often 65 [16]. The low dose levels observed in the present study might also reflect practices that are not clearly defined or that seek to obtain both sedative and anxiolytic effects. Furthermore, the very low incidence of dose titration, the preferential use of subcutaneous administration, and the low incidence of anticipatory prescribing run counter to guidelines on sedative use and may reduce the treatment effectiveness [3, 7, 39, 40].

Furthermore, the homogeneity of EOL prescriptions did not guarantee effectiveness, which was often only partial: the depth of sedation (according to the RASS) was moderate in half the cases. Few situations involved deep sedation. In the present study, the effectiveness of midazolam treatment was assessment by physicians and nurses and noted in the patient’s medical records. However, serial assessments were rare, and a standardized evaluation was hardly ever used. The units did not apply techniques designed to quantify the level of sedation, such as the measurements of parasympathetic nervous system activity used in anesthesiology [41, 42]. In most cases, the physician subjectively assessed the patient’s overall comfort. Once again, the lack of a clear indication for midazolam can undermine the ability to assess treatment effectiveness in a meaningful way and thus to adjust the dose level as appropriate.

This finding suggests that geriatricians are not sufficiently well trained in sedation practice. Training and collaboration with PC teams needs to be strengthened, in order to improve EOL practices and develop guidelines on PS tailored to the needs of older people.

Limitations and strengths

Firstly, this study was one of the largest to assess midazolam use for EOL in the AGU. Secondly, the ambispective design made it possible to include participants without biasing the units’ medical practice; the study therefore reflected real-life PS in the AGU. Thirdly, the multidisciplinary investigation by geriatricians and PC physicians enabled a more detailed interpretation of the retrospective data. The comparison of several points of view prompted discussion and dialogue, notably with regard to the observed lack of continuous, deep sedation until death.

The study’s main limitations are related to the retrospective extraction of the data on midazolam use. The prescriber’s true intention was difficult to establish with certainty, due to the low level of documentations in the medical records. Hence, the indication was often not explicitly stated. Even though the records were reviewed twice, some indications might have been wrongly classified. In the field of sedation in geriatrics, prospective studies appear to be more appropriate for assessing the prescriber’s intention [43]. A second limitation relates to the subjective evaluation of midazolam’s effectiveness and the lack of use of validated clinical assessment scales. Thirdly, the patient’s general state prior to death was not always well documented, and a loss of vigilance might have been unrelated to the drug treatment in some cases [44]. Fourthly, we included only patients known to have received comfort care only after admission to the AGUs and thus excluded patients who died before an EOL situation could be noted and those specifically admitted to the unit for EOL care. Fifthly, the DAMAGE study protocol did not feature a strict definition of PC; this was left to the geriatrician’s discretion during the stay in the AGU and probably often corresponded to comfort care [20]. However, this approach is probably similar to real-life practice in hospitals. In a 2024 audit of 177 demented patients who died in hospital in Australia, only 106 out of 177 (60%) were identified as having received EOL care a very short before death (median: 2 days), and only 37 out of 177 (21%) had had a PC consultation during their hospital stay (a median of 3 days before death) [45]. It is also possible that geriatricians’ sedative practices have changed as a result of the COVID-19 pandemic because (i) respiratory distress requiring PS was more frequent, (ii) there was more systematic coordination with PC teams, which disseminated protocols for good sedation practice. However, these protocols were specific for COVID-19, and little attention was paid to improving PC skills. Although the need for training during the COVID-19 epidemic has been highlighted [46], it is not known whether this need has been met. A study of social workers suggested that only a few PC-related skills had improved moderately after the first wave of COVID-19 [47].

Lastly, the study population was drawn from four AGUs in university medical centers. It is therefore possible that the practices described here are not representative of those in France as a whole. However, we do not believe that this weakens our conclusions. University medical centers generally receive more resources and have more highly trained staff. It is therefore unlikely that other hospitals have profoundly different practices or more extensive training.

Conclusion

Our present results showed that (i) fewer than a third of patients identified as having received comfort care only in the AGU were treated with midazolam at the end of their lives, and (ii) more than half of the patients who died in the AGU and were identified as having received comfort care only did not receive midazolam. Moreover, midazolam prescriptions were rarely documented as sedation by the attending geriatricians. Midazolam prescribing could be improved by avoiding low dosages and increasing anticipatory prescribing and dose level titration. Lastly, our results highlighted the importance of studying PC and the need for better training in sedation practices in geriatric medicine.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Lucchi E, Milder M, Dardenne A, Bouleuc C. Could palliative sedation be seen as unnamed euthanasia? A survey among healthcare professionals in oncology. BMC Palliat Care. 2023;22:97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. den Hartogh G. Continuous deep sedation and homicide: an unsolved problem in law and professional morality. Med Health Care Philos. 2016;19:285–97.

    Article  Google Scholar 

  3. Surges SM, Garralda E, Jaspers B, Brunsch H, Rijpstra M, Hasselaar J, et al. Review of European guidelines on palliative sedation: A foundation for the updating of the European association for palliative care framework. J Palliat Med. 2022;25:1721–31.

    Article  PubMed  Google Scholar 

  4. de Graeff A, Dean M. Palliative sedation therapy in the last weeks of life: a literature review and recommendations for standards. J Palliat Med. 2007;10:67–85.

    Article  PubMed  Google Scholar 

  5. Tomczyk M, Jaques C, Jox RJ. Clinical practice guidelines on palliative sedation around the world: A systematic review. J Palliat Care. 2022;:082585972211386.

  6. Beller EM, van Driel ML, McGregor L, Truong S, Mitchell G. Palliative Pharmacological sedation for terminally ill adults. Cochrane Database Syst Rev. 2015;1:CD010206.

    PubMed  Google Scholar 

  7. Ostgathe C, Bausewein C, Schildmann E, Bazata J, Handtke V, Heckel M, et al. Expert-approved best practice recommendations on the use of sedative drugs and intentional sedation in specialist palliative care (SedPall). BMC Palliat Care. 2023;22:126.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Blinderman CD, Billings JA. Comfort care for patients dying in the hospital. N Engl J Med. 2015;373:2549–61.

    Article  CAS  PubMed  Google Scholar 

  9. Lazris A. Geriatric palliative care. Prim Care Clin Off Pract. 2019;46:447–59.

    Article  Google Scholar 

  10. Kapo J, Morrison LJ, Liao S. Palliative care for the older adult. J Palliat Med. 2007;10:185–209.

    Article  PubMed  Google Scholar 

  11. Oliver DJ, Borasio GD, Caraceni A, de Visser M, Grisold W, Lorenzl S, et al. A consensus review on the development of palliative care for patients with chronic and progressive neurological disease. Eur J Neurol. 2016;23:30–8.

    Article  CAS  PubMed  Google Scholar 

  12. Visser R, Borgstrom E, Holti R. The overlap between geriatric medicine and palliative care: A scoping literature review. J Appl Gerontol Off J South Gerontol Soc. 2021;40:355–64.

    Article  Google Scholar 

  13. Voumard R, Rubli Truchard E, Benaroyo L, Borasio GD, Büla C, Jox RJ. Geriatric palliative care: a view of its concept, challenges and strategies. BMC Geriatr. 2018;18:220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Cherny NI, Radbruch L, Board of the European Association for Palliative Care. European association for palliative care (EAPC) recommended framework for the use of sedation in palliative care. Palliat Med. 2009;23:581–93.

    Article  PubMed  Google Scholar 

  15. Twycross R. Reflections on palliative sedation. Palliat Care. 2019;12:1178224218823511.

    PubMed  PubMed Central  Google Scholar 

  16. Arantzamendi M, Belar A, Payne S, Rijpstra M, Preston N, Menten J, et al. Clinical aspects of palliative sedation in prospective studies. A systematic review. J Pain Symptom Manage. 2021;61:831–e84410.

    Article  PubMed  Google Scholar 

  17. Gamblin V, Berry V, Tresch-Bruneel E, Reich M, Da Silva A, Villet S, et al. Midazolam sedation in palliative medicine: retrospective study in a French center for cancer control. BMC Palliat Care. 2020;19:85.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Giroud M, Sellier E, Laval G. [Use of Midazolam in hospitalized patients: analysis of medical practice]. Bull Cancer (Paris). 2013;100:811–7.

    Article  PubMed  Google Scholar 

  19. Deschasse G, Bloch F, Drumez E, Charpentier A, Visade F, Delecluse C, et al. Development of a predictive score for mortality at 3 and 12 months after discharge from an acute geriatric unit as a trigger for advanced care planning. J Gerontol Biol Sci Med Sci. 2022;77:1665–72.

    Article  Google Scholar 

  20. Deschasse G, Charpentier A, Prod’homme C, Genin M, Delecluse C, Gaxatte C, et al. Transition to comfort care only and End-of-Life trajectories in an acute geriatric unit: A secondary analysis of the DAMAGE cohort. J Am Med Dir Assoc. 2022;23:1492–8.

    Article  PubMed  Google Scholar 

  21. LOI n°. 2016-87 du 2 février 2016 créant de nouveaux droits en faveur des malades et des personnes en fin de vie. 2016.

  22. Imai K, Morita T, Yokomichi N, Mori M, Naito AS, Tsukuura H, et al. Efficacy of two types of palliative sedation therapy defined using intervention protocols: proportional vs. deep sedation. Support Care Cancer Off J Multinatl Assoc Support Care Cancer. 2018;26:1763–71.

    Google Scholar 

  23. Aubry R. [Principles and challenges of law N° 2016-87 of 2 February 2016 creating new rights for the sick and the end-of-life]. Rev Prat. 2017;67:1131–3.

    PubMed  Google Scholar 

  24. Lindqvist O, Lundquist G, Dickman A, Bükki J, Lunder U, Hagelin CL, et al. Four essential drugs needed for quality care of the dying: a Delphi-study based international expert consensus opinion. J Palliat Med. 2013;16:38–43.

    Article  PubMed  Google Scholar 

  25. De Schreye R, Smets T, Deliens L, Annemans L, Gielen B, Cohen J. Appropriateness of End-of-Life Care in People Dying With Dementia: Applying Quality Indicators on Linked Administrative Databases. J Am Med Dir Assoc. 2020;21:1093–e11011.

    Article  PubMed  Google Scholar 

  26. Deschepper R, Laureys S, Hachimi-Idrissi S, Poelaert J, Distelmans W, Bilsen J. Palliative sedation: why we should be more concerned about the risks that patients experience an uncomfortable death. Pain. 2013;154:1505–8.

    Article  PubMed  Google Scholar 

  27. Steindal SA, Bredal IS, Ranhoff AH, Sørbye LW, Lerdal A. The last three days of life: a comparison of pain management in the young old and the oldest old hospitalised patients using the Resident Assessment Instrument for Palliative Care. Int J Older People Nurs. 2015;10:263–72.

    Article  PubMed  Google Scholar 

  28. Janssens WH, Van Den Noortgate NJ, Piers RD. Pharmacological treatment in the dying geriatric patient: describing use and dosage of opioids in the acute geriatric wards and palliative care units of three hospitals. Eur Geriatr Med. 2021;12:545–50.

    Article  PubMed  Google Scholar 

  29. Van Den Noortgate NJ, Verhofstede R, Cohen J, Piers RD, Deliens L, Smets T. Prescription and Deprescription of Medication During the Last 48 Hours of Life: Multicenter Study in 23 Acute Geriatric Wards in Flanders, Belgium. J Pain Symptom Manage. 2016;51:1020–6.

    Article  PubMed  Google Scholar 

  30. Mesnage V, Bretonniere S, Goncalves T, Begue A, Bernardin G, Brette M-D, et al. Enquête du centre national des soins palliatifs et de la fin de vie sur la sédation profonde et continue jusqu’au décès (SPCJD) à 3 ans de la loi Claeys-Leonetti. Presse Médicale Form. 2020;1:134–40.

    Article  Google Scholar 

  31. Weisbrod N. Primary Palliative Care in Dementia. Neurother J Am Soc Exp Neurother. 2022;19:143–51.

    Google Scholar 

  32. Baztán JJ, Suárez-García FM, López-Arrieta J, Rodríguez-Mañas L, Rodríguez-Artalejo F. Effectiveness of acute geriatric units on functional decline, living at home, and case fatality among older patients admitted to hospital for acute medical disorders: meta-analysis. BMJ. 2009;338:b50.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Piers R, Albers G, Gilissen J, De Lepeleire J, Steyaert J, Van Mechelen W, et al. Advance care planning in dementia: recommendations for healthcare professionals. BMC Palliat Care. 2018;17:88.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Wendrich-van Dael A, Bunn F, Lynch J, Pivodic L, Van den Block L, Goodman C. Advance care planning for people living with dementia: An umbrella review of effectiveness and experiences. Int J Nurs Stud. 2020;107:103576.

    Article  PubMed  Google Scholar 

  35. Bally KW, Krones T, Jox RJ. Advance Care Planning for People with Dementia: The Role of General Practitioners. Gerontology. 2020;66:40–6.

    Article  PubMed  Google Scholar 

  36. Claessens P, Menten J, Schotsmans P, Broeckaert B. Palliative sedation: a review of the research literature. J Pain Symptom Manage. 2008;36:310–33.

    Article  PubMed  Google Scholar 

  37. Stone P, Phillips C, Spruyt O, Waight C. A comparison of the use of sedatives in a hospital support team and in a hospice. Palliat Med. 1997;11:140–4.

    Article  CAS  PubMed  Google Scholar 

  38. Maeda I, Morita T, Yamaguchi T, Inoue S, Ikenaga M, Matsumoto Y, et al. Effect of continuous deep sedation on survival in patients with advanced cancer (J-Proval): a propensity score-weighted analysis of a prospective cohort study. Lancet Oncol. 2016;17:115–22.

    Article  PubMed  Google Scholar 

  39. van Deijck RHPD, Hasselaar JGJ, Verhagen SCAHHVM, Vissers KCP, Koopmans RTCM. Level of Discomfort Decreases After the Administration of Continuous Palliative Sedation: A Prospective Multicenter Study in Hospices and Palliative Care Units. J Pain Symptom Manage. 2016;52:361–9.

    Article  PubMed  Google Scholar 

  40. Surges SM, Brunsch H, Jaspers B, Apostolidis K, Cardone A, Centeno C, et al. Revised European Association for Palliative Care (EAPC) recommended framework on palliative sedation: An international Delphi study. Palliat Med. 2024;38:213–28.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Six S, Laureys S, Poelaert J, Maîresse O, Theuns P, Bilsen J, et al. Neurophysiological Assessments During Continuous Sedation Until Death Put Validity of Observational Assessments Into Question: A Prospective Observational Study. Pain Ther. 2021;10:377–90.

    Article  PubMed  Google Scholar 

  42. Bauschert L, Prod’homme C, Pierrat M, Chevalier L, Lesaffre H, Touzet L. End-of-life Comfort Evaluation, is Clinic Enough? A Retrospective Cohort Study of Combined Comfort Evaluation with Analgesia/Nociception Index and Clinic in non-Communicative Patients. J Palliat Care. 2021;:8258597211063687.

  43. Rijpstra M, Vissers K, Centeno C, Menten J, Radbruch L, Mercadante S, et al. Monitoring the clinical practice of palliative sedation (PALSED) in patients with advanced cancer: an international, multicentre, non-experimental prospective observational study protocol. BMC Palliat Care. 2023;22:8.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Belar A, Arantzamendi M, Payne S, Preston N, Rijpstra M, Hasselaar J, et al. How to measure the effects and potential adverse events of palliative sedation? An integrative review. Palliat Med. 2021;35:295–314.

    Article  PubMed  Google Scholar 

  45. Triandafilidis Z, Carr S, Davis D, Chiu S, Leigh L, Jeong S, et al. What care do people with dementia receive at the end of life? Lessons from a retrospective clinical audit of deaths in hospital and other settings. BMC Geriatr. 2024;24:40.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Bovero A, Tosi C. Hospice palliative care professionals’ opinions, emotions, skills and ethical reflections during the first phase of the COVID-19 pandemic. Int J Palliat Nurs. 2022;28:4–14.

    Article  PubMed  Google Scholar 

  47. Pelleg A, Chai E, Morrison RS, Farquhar DW, Berglund K, Gelfman LP. Expanding the Palliative Care Workforce during the COVID-19 Pandemic: An Evaluation of Core Palliative Care Skills in Health Social Workers. J Palliat Med. 2021;24:1705–9.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank all the physicians who helped to recruit study participants at the investigating centers. We also thank the members of the clinical research support team at Lille University Hospital for their assistance and logistic support throughout the study. Lastly, we thank David Fraser PhD (Biotech Communication SARL, Ploudalmézeau, France) for copy-editing assistance.

Funding

This work was funded by the French government’s interregional hospital-based clinical research program (grant reference: PHRC I 13–097). The funding body did not have any role in designing the study, collecting, analyzing and/or interpreting the data, or drafting the manuscript.

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Authors and Affiliations

  1. Palliative care unit, Univ. Lille, ULR 2694 METRICS, CHU Lille, Lille, F-59000, France

    Chloé Prod’homme

  2. University Lille, CHU Lille, ULR 2694-METRICS: Évaluation des Technologies de Santé et des Pratiques Médicales, Lille, France

    Guillaume Deschasse, Fabien Visade, François Puisieux & Jean-Baptiste Beuscart

  3. Department of Geriatrics, CHU Amiens-Picardie, Amiens, France

    Guillaume Deschasse & Frederic Bloch

  4. Department of Geriatrics, Lille Catholic Hospitals, Lille, France

    Fabien Visade & Celine Delecluse

  5. Department of Geriatrics, CHU Lille, Lille, France

    Camille Hennion, Anne Charpentier, Cedric Gaxatte, François Puisieux & Jean-Baptiste Beuscart

Authors
  1. Chloé Prod’homme
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  2. Guillaume Deschasse
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Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Chloé Prod’homme.

Ethics declarations

Ethics approval and consent to participate

The DAMAGE study was performed in compliance with the tenets of the Declaration of Helsinki and was approved by an institutional review board (CPP Nord-Ouest IV, Lille, France) on February 13th, 2015. An amendment was approved on January 21st, 2016 (reference: IDRCB 2014 A01670 47, CNIL. bxA15352514). The patients and their primary family caregivers or legal representatives were given detailed verbal and written information about the study, in order to ensure that the patients fully understood the potential risks and benefits of participation. In accordance with the French legislation on observational, non-interventional studies of routine clinical care, written consent was not required. The patients were informed that they could refuse to participate in the study and that refusal would not have any impact on their treatment in the AGU. If the patient was unable to refuse to participate in the DAMAGE study (notably because of severe neurocognitive disorders), the next of kin or legal representative could refuse participation. All participants were free to withdraw from the study at any time. This withdrawal had no impact on the care received.

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Not applicable.

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The authors declare no competing interests.

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Prod’homme, C., Deschasse, G., Visade, F. et al. Palliative use of midazolam in acute geriatric units: a multicenter ambispective study. BMC Geriatr 25, 241 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12877-025-05860-6

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Keywords

BMC Geriatrics

ISSN: 1471-2318

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