935361 research-article2020 PMJ0010.1177/0269216320935361Palliative MedicineJackson et al. Short Report End-of-life care in COVID-19: An audit of pharmacological management in hospital inpatients Palliative Medicine 1­–6 © The Author(s) 2020 Article reuse guidelines: sagepub.com/journals-permissions https://doi.org/10.1177/0269216320935361 DOI: 10.1177/0269216320935361 journals.sagepub.com/home/pmj Timothy Jackson , Katie Hobson, Hannah Clare, Daniel Weegmann, Catherine Moloughney and Sally McManus Abstract Background: Hospital clinicians have had to rapidly develop expertise in managing the clinical manifestations of COVID-19 including symptoms common at the end of life, such as breathlessness and agitation. There is limited evidence exploring whether end-of-life symptom control in this group requires new or adapted guidance. Aim: To review whether prescribing for symptom control in patients dying with COVID-19 adhered to existing local guidance or whether there was deviation which may represent a need for revised guidance or specialist support in particular patient groups. Design/setting: A retrospective review of the electronic patient record of 61 hospital inpatients referred to the specialist palliative care team with swab-confirmed COVID-19 who subsequently died over a 1-month period. Intubated patients were excluded. Results: In all, 83% (40/48) of patients were prescribed opioids at a starting dose consistent with existing local guidelines. In seven of eight patients where higher doses were prescribed, this was on specialist palliative care team advice. Mean total opioid dose required in the last 24 h of life was 14 mg morphine subcutaneous equivalent, and mean total midazolam dose was 9.5 mg. For three patients in whom non-invasive ventilation was in place higher doses were used. Conclusion: Prescription of end-of-life symptom control drugs for COVID-19 fell within the existing guidance when supported by specialist palliative care advice. While some patients may require increased doses, routine prescription of higher starting opioid and benzodiazepine doses beyond existing local guidance was not observed. Keywords COVID-19, symptom control, end-of-life care What is already known about the topic? •• Previous work has examined symptom control in the last days of life more broadly, including previous national audit data (most recently NACEL 2019). •• There has been very limited other work examining pharmacological management of symptoms in patients dying with COVID-19 given the quickly emerging nature of the pandemic, which focused more on symptoms experienced and patterns of decline. What this paper adds •• More detailed analysis of pharmacological symptom management in a hospital inpatient cohort than has been undertaken to date. •• Analysis of whether prescribing adheres to the existing symptom control guidance. •• Examination of the role of specialist palliative care services supporting generalist clinicians in symptom management of COVID-19. Salford Royal NHS Foundation Trust, Salford, UK Corresponding author: Timothy Jackson, Salford Royal NHS Foundation Trust, Stott Lane, Greater Manchester, Salford M6 8HD, UK. Email: firstname.lastname@example.org 2 Palliative Medicine 00(0) Implications for practice, theory or policy •• Routine use of higher opioid or benzodiazepine doses for symptom control in patients dying with COVID-19 was not observed and it is suggested that existing guidance should form the basis of symptom management. •• It is proposed that where prescribing beyond suggested starting doses for end-of-life symptom control is required for COVID-19, a responsive and accessible specialist palliative care service has a key role in supporting generalist clinicians. •• Further research is suggested incorporating validated outcome measures for symptom control alongside prescription at the end of life in COVID-19. Background The COVID-19 pandemic has placed unprecedented demands on healthcare services across all sectors, with significant excess mortality being recognised internationally.1 In the acute setting, providing effective symptom management for patients dying with COVID-19 has been a key role for hospital clinicians, supported by specialist palliative care team advice where needed. Access to specialist palliative care across settings has been highlighted as an important consideration in response to the COVID-19 pandemic.2 Breathlessness and agitation have been identified as frequent symptoms in this group and these patients have the potential to deteriorate rapidly.3,4 New guidance for symptom control in patients with COVID-19 has been proposed by some groups, drawing on emerging experience.5,6 This audit reviews whether prescribing by clinicians in an acute hospital setting for patients dying with COVID-19 adhered to existing local palliative care symptom control guidance. Where there was deviation from prescribing guidance, we sought to review why this had taken place, and whether this represented a need for revised guidance with higher drug starting doses, further education or other change in practice. We also sought to identify, if possible, any clinical sub-group where higher doses of symptom management drugs were administered. Aims •• For patients dying with COVID-19, to review whether prescribing for end-of-life symptom control for breathlessness, pain and agitation adhered to current standards based on regional symptom control guidelines. •• If prescribing deviated from current guidance, to establish why this was necessary and whether different guidance for starting doses of symptom control drugs may be required. Audit standards 1. A subcutaneous (SC) opioid should be prescribed for anticipatory management of pain and breathlessness as needed (PRN) in the last days of life.7 2. 3. For opioid naïve patients, an initial PRN opioid dose equivalent of no more than 5 mg morphine SC should be prescribed for symptom control in the last days of life.7 Patients should be prescribed midazolam at an initial dose of no more than 5 mg PRN SC for agitation in the last days of life.7 Method We examined the prescribing at a large acute NHS Hospital Trust in North West England, using the existing local symptom control guidance for non-specialists as a baseline standard. The hospital specialist palliative care team is an advisory service within the hospital, providing 7-day support across all clinical areas but without dedicated palliative care beds. A retrospective review of the electronic patient record was undertaken for patients referred to the palliative care team who were confirmed by swab as positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and died during a 1-month period in March/April 2020. Sixty-one inpatients were included with COVID-19 either as the primary reason for admission or identified during inpatient stay. Prescribing by any clinician in the last days of life was evaluated through examination of the electronic Prescribing record. End-of-life symptom control prescriptions for breathlessness, pain, agitation and respiratory secretions were examined in detail by clinicians from the specialist palliative care team. Prescribing for nausea, which was not felt to be a prominent feature within this patient group, was not examined.1 Data were collected on patient characteristics that may affect prescribing decisions, such as renal function and body mass index. Data were also collected on comorbidities, age, frailty (clinical frailty score, where recorded)8 and oxygen requirement at the point of identification of dying. We also recorded primary reason for referral to the specialist palliative care team and frequency of palliative care visits. Data were entered directly onto a database and stored securely. The audit was registered with the hospital audit department. Jackson et al. 3 Test confirmed hospital in-paents with COVID-19 referred to specialist palliave care (n=61) Died before review (n=5) Dying phase not idenfied prior to death (n=3) Supported by invasive venlaon on crical care unit (n=5) In-paents with COVID-19 in audit (n=48) Figure 1. In-patients with test confirmed COVID-19 included in audit. Results Patient characteristics A total of 61 patients with SARS-CoV-2 RNA positive swabs were referred to the hospital specialist palliative care team and died during the audit period. Patients where the dying phase was not identified, or those who died prior to any review or remote advice being given by the specialist palliative care team were excluded from further analysis, as were patients who were supported by invasive ventilation on the critical care unit at the time of referral – see Figure 1. All patients included and known to the specialist palliative care team had at least one underlying comorbidity and most patients had comorbidities in two or more groups. Compared with all specialist palliative care referrals from March/April 2019, fewer patients in the 2020 COVID-19 positive cohort had cancer (33% vs 55%) and there were a higher number with cardiovascular (60% vs 27%) comorbidities. Further characteristics of the 48 patients known to the specialist palliative care team, identified as dying and not mechanically ventilated, are detailed in Table 1. Review of prescribing All patients were prescribed a SC opioid in the last days of life, and only eight were prescribed these at a dose exceeding 5 mg SC morphine equivalent PRN. In seven of these eight cases, the opioids were given based on the advice of the specialist palliative care team for clinical reasons (e.g. three of the eight patients were previously on a regular opioid). In only four of the eight patients prescribed >5 mg PRN SC morphine equivalent was it actually administered in the last 24 h of life (Table 2). Dose requirements in the last 24 h of life Patients on a background opioid prior to identification of the dying phase were excluded from this analysis (remaining n = 42). Data reviewed would suggest that prescribed frequency and doses of end-of-life symptom control medications were within the parameters of existing symptom control guidance. No patients in our cohort were administered levomepromazine or haloperidol for control of agitation. A syringe pump was in place in the last 24 h of life for 33 of 48 patients (Table 3). Patients who were, at the time of specialist palliative care referral, supported by non-invasive ventilation (n = 3) required higher doses of SC morphine equivalent (mean: 41 mg, range: 35–55 mg vs mean: 14.0 mg) and midazolam (mean: 22.5 mg, range: 15–30 mg vs mean: 9.5 mg). Of note however, one patient in this group was already on a background opioid. This may reflect an increased symptom burden during the process of withdrawing such measures when they are no longer felt effective; though limited conclusions can be drawn from this small sample and we are unable to present validated outcome data on overall effectiveness of symptom management in this group. Specialist palliative care support Table 4 details specialist palliative care support to patients. Patients were most often referred for endof-life care or symptom control, and were reviewed face to face by a member of the team on a mean of 2.9 occasions following referral. In addition to face to face reviews, the specialist palliative care team supported ward teams with remote reviews and advice and had a key role in communication with relatives (telephone contact). Of the 48 patients, 23 died within 24 h of the dying phase being recognised, and 34 within 48 h. Limitations Not all patient deaths with COVID-19 were reviewed. It is possible that those who were not referred to the specialist palliative care team either deteriorated more quickly (dying not recognised) or were not felt to require specialist advice. We were not able to objectively assess whether symptom control was fully achieved. Conclusion For 83% of patients dying with COVID-19, prescribing was in accordance with the existing local end-of-life symptom control guidance, and in all but one patient where this was not the case, advice from the specialist palliative care team was followed. This suggests that in patients with COVID-19, routine prescription of higher starting PRN opioid/benzodiazepine doses or adaptation of current endof-life symptom control guidance was not required. It also supports international calls for accessible specialist palliative care advice.2 4 Palliative Medicine 00(0) Table 1. Characteristics of patients with test-confirmed COVID-19, known to the palliative care team. Characteristic Value Age (n = 48) Mean: 75.4 (range: 35–96) Median: 77 M = 27 F = 21 Mean: 5.5 (range: 3–9) Median: 5.5 0 (n = 18) 1 (n = 14) 2 ( n = 4) 3 (n = 1) 4+ (n = 11) 1 (n = 7) 2 (n = 19) 3 (n = 16) 4+ (n = 6) Cardiovascular (n = 29) Respiratory (n = 13) Cancer (n = 16) Neurological (n = 13) Diabetes (n = 9) Renal (n = 7) Gastroenterological (n = 7) Dementia (n = 6) Frailty (n = 5) Hepatic (n = 1) Other (n = 11) Overweight/obese (n = 25) Mean: 45.8 (range: 1–316.5) Median: 27.8 Mean: 10.6 (range: 0–15) Median: 15 Median: 67 Range: 14 − ⩾90 Mean: 11.5 days, median: 6.5, range: 0–80d Sex (n = 48) Clinical Frailty Score (n = 28) Previous hospital admissions in last 1 year (n = 47) Number of co-morbid conditions (n = 48) Comorbid conditionsa Body mass index (n = 42) Hours from recognition of dying to death (n = 48) Supplementary O2 (L/min) at time dying was recognised (n = 45)b eGFRc (n = 47) Total time in hospital prior to death (n = 48) NIV: non-invasive ventilation; CPAP: continuous positive airway pressure; eGFR: estimated glomerular filtration rate. aMore than one co-morbid condition for many patients, so n > 48. bPatients supported by NIV/CPAP where higher flow rates may be used were excluded, n = 3. cMean was unable to be calculated as reporting limit was above 90 (⩾90). dPatients who were inpatients prior to diagnosis of COVID-19. Table 2. Review of prescribing. Element of prescribing reviewed Value Prescribed a PRN subcutaneous opioid in last days of life (audit standard 1). Prescribed a PRN subcutaneous opioid at an equivalent subcutaneous morphine dose of 5 mg or less (audit standard 2). Prescribed a PRN subcutaneous opioid at an equivalent subcutaneous morphine dose of >5 mg during last 24 h of life. Administered one or more PRN subcutaneous opioid doses at an equivalent subcutaneous morphine dose of >5 mg during last 24 h of life. Prescribed midazolam PRN subcutaneous for agitation in last days of life. Prescribed PRN subcutaneous midazolam at a dose of 5 mg or less (audit standard 3). Prescribed PRN subcutaneous midazolam at a dose of >5 mg during last 24 h of life. Administered one or more PRN subcutaneous midazolam doses of >5 mg during last 24 h of life. N = 48 N = 40 N=8 N=4 Patients were administered a median total of 14.0 mg of SC morphine equivalent and 9.5 mg of midazolam SC in the last 24 h of life, and 69% had a syringe pump in place, N = 48 N = 47 N=1 N=0 which is comparable with limited other evidence in this area.3,4 However, patients in whom non-invasive ventilation was withdrawn were administered higher doses, and Jackson et al. 5 Table 3. Doses of drugs administered in the last 24 h of life. Drug Route Number of patients (from 42a) Number of PRN doses Dose requirements (total) Opioids PRN SC opioidb 28 Syringe pumpc 26 Mean: 2.5 (range: 1–7) Median: 2.5 NA All routes combinedd 42 PRN SC midazolamb 27 Syringe pump 20 All routes combined 42 PRN SC glycopyrronium 19 Mean: 9.4 mg (range: 2–35 mg) Median: 8.75 mg Mean: 11.9 mg (range: 5–45 mg) Median: 10 mg Mean: 14 mg (range: 0–55 mg) Median: 11.25 Mean: 7.0 mg (range: 2.5–25 mg) Median: 5 mg Mean: 10.5 mg (range: 5–25 mg) Median: 10 mg Mean: 9.5 mg (range: 0–35 mg) Median: 8.75 mg Mean: 242 µg (range: 200–400 µg) Median: 200 µg Mean: 600 µg (range: 600 µg) Median: 600 µg Mean: 196 µg (range: 0–1000 µg) Median: 0 Midazolam Glycopyrronium Syringe pump All routes combined Mean: 1.7 (range: 0–7) Median: 1 Mean: 2.1 (range: 1–6) Median: 2 NA Mean: 1.4 (range: 0–6) Median: 1 Mean: 1.2 (range: 0–2) Median: 1 NA 8 42 Mean: 0.5 (range: 0–2) Median: 0 SC: subcutaneous. aPatients on a background opioid prior to identification of dying phase and those mechanically ventilated in critical care were excluded. bAny patient who was administered a PRN dose for any indication. cMorphine SC equivalent/24 h dose in syringe pump for any indication. dTotal dose requirements (morphine SC equivalent) in the last 24 h of life, including cumulative PRN doses, were administered subcutaneously through a syringe pump for any indication. Table 4. Specialist palliative care support during final illness. Reason for referral to specialist palliative care team (n = 48) Reviewed by specialist palliative care team or advice given within 24 h of referral (n = 48) Number of times patient reviewed face to face by specialist palliative care team in final admission (n = 26) Number of times in final illness patient reviewed remotely (n = 34) Care supported by an individualised last days of life care plan (n = 48) aOne End-of-life care (n = 26) Pain/symptom control (n = 17) Emotional/psychological support (carer) (n = 4) Emotional/psychological support (patient) (n = 1) N = 47a Mean: 2.9, median: 2, range: 1–13 Mean: 1.32, median: 1, range: 0–3 45 patient seen >24 h after referral was referred prior to COVID-19 pandemic period and triaged appropriately. it may be necessary to consider using higher doses or second-line drug options in this group. While it is suggested that no immediate changes to local, non-specialist guidance on end-of-life symptom control drug starting doses is required for patients with COVID-19, research is necessary to assess symptom response and identify any specific groups where higher doses or second-line drug options may be needed. This work reinforces the importance of timely, 7-day access to specialist palliative care advice. 6 Palliative Medicine 00(0) Declaration of conflicting interests The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article. 4. 5. Funding The author(s) received no financial support for the research, authorship and/or publication of this article. 6. ORCID iD Timothy Jackson https://orcid.org/0000-0003-1829-9728 References 1. 2. 3. Verity R, Okell LC, Dorigatti I, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis 2020; 20: 669–677. 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