Low-dose ketamine infusion to facilitate opioid tapering in chronic non-cancer pain with opioid-use disorder: a historical cohort study.

BACKGROUND: Long-term opioid use is associated with pharmacological tolerance, a risk of misuse and hyperalgesia in patients with chronic pain (CP). Tapering is challenging in this context, particularly with comorbid opioid-use disorder (OUD). The antihyperalgesic effect of ketamine, through N-methyl-D-aspartate (NMDA) antagonism, could be useful. We aimed to describe the changes in the dose of opioids consumed over 1 year after a 5-day hospitalisation with ketamine infusion for CP patients with OUD. METHODS: We performed a historical cohort study using a medical chart from 1 January 2014 to 31 December 2019. Patients were long-term opioid users with OUD and CP, followed by the Pain Center of the University Hospital of Toulouse, for which outpatient progressive tapering failed. Ketamine was administered at a low dose to initiate tapering during a 5-day hospitalisation. RESULTS: 59 patients were included, with 64% of them female and a mean age of 48±10 years old. The most frequent CP aetiologies were back pain (53%) and fibromyalgia (17%). The baseline opioid daily dose was 207 mg (±128) morphine milligram equivalent (MME). It was lowered to 92±72 mg MME at discharge (p<0.001), 99±77 mg at 3 months (p<0.001) and 103±106 mg at 12 months. More than 50% tapering was achieved immediately for 40 patients (68%), with immediate cessation for seven patients (12%). 17 patients were lost to follow-up. CONCLUSIONS: A 5-day hospitalisation with a low-dose ketamine infusion appeared useful to facilitate opioid tapering in long-term opioid users with CP and OUD. Ketamine was well tolerated, and patients did not present significant withdrawal symptoms. Prospective and comparative studies are needed to confirm our findings.

Chronic pain is a risk factor for incident Alzheimer's disease: a nationwide propensity-matched cohort using administrative data.

Introduction: Chronic pain (CP) is one of the most disabling conditions in the elderly and seems to be a risk factor for the development of Alzheimer's disease and related dementias (ADRD). Only one study, using national administrative health databases, assessed and demonstrated that chronic pain (all types of pain) was a risk factor for dementia, but without assessing the impact of pain medications. Method: To assess the impact of all types of chronic pain and the long-term use of pain medications on the person-years incidence of ADRD, a retrospective nationwide healthcare administrative data study was performed using the national inter-regime health insurance information system (SNIIRAM) to the French national health data system (SNDS). Incident people >50 years old with chronic pain, defined by at least 6-months duration analgesics treatment or by a diagnosis/long-term illness of chronic pain between 2006 and 2010, were included. Chronic pain individuals were matched with non-CP individuals by a propensity score. Individuals were followed up from 9 to 13 years to identify occurrences of ADRD from 2006. Results: Among 64,496 French individuals, the incidence of ADRD was higher in the chronic pain population than control (1.13% vs. 0.95%, p <0.001). Chronic pain increases the risk of ADRD (HR = 1.23) and the incidence of ADRD was higher for women and increased significantly with age. Discussion: Our study highlights the importance of prevention, diagnosis, and management of chronic pain in elderly to reduce the risk of development and/or worsening of dementia.

Prevalence of Chronic Pain Among People with Dementia: A Nationwide Study Using French Administrative Data.

OBJECTIVE: Alzheimer's disease or Related Dementia (ADRD) is known to disturb pain perception and reduce the ability to report it, resulting in underestimation by practitioners and sub-optimal medical management. The aim of this study was to estimate the prevalence of all types of CP among people with ADRD. DESIGN: Nationwide cross-sectional study. SETTINGS: French community-dwelling and nursing home residents. PARTICIPANTS: People with ADRD, >40 years old, treated with cholinesterase inhibitors or memantine, or with a diagnosis/long-term illness of ADRD and matched with a comparison sample. SETTINGS: French community-dwelling and nursing home residents. PARTICIPANTS: People with ADRD, >40 years old, treated with cognitive stimulants (cholinesterase inhibitors and memantine) or with a diagnosis/long-term illness of ADRD and matched with a comparison sample (non-ADRD). MEASUREMENTS: The capture-recapture method was performed to provide estimates of the prevalence of CP. People treated with analgesic drugs for ≥6 months consecutively or with a medical diagnosis of CP (ICD-10 codes) or referred to a pain center were considered as having CP. RESULTS: A total of 48,288 individuals were included, of which 16,096 had ADRD and 32,192 without ADRD. The estimated prevalence of CP in people with ADRD was from 57.7% [52.9;63.3] to 57.9%[53.0;63.9], and slightly higher than the non-ADRD sample (from 49.9%[47.0;53.2] to 50.4%[47.3;53.9], p <0.001). CONCLUSIONS: The prevalence of CP among people living with ADRD was at least the same as or better than individuals without ADRD. This result should alert practitioners' attention to the need for effective pain assessment and management in this population who has difficulties to express and feel pain.

Potential determinants of unfavourable healthcare utilisation trajectories during the last year of life of people with incident Alzheimer Disease or Related Syndromes: a nationwide cohort study using administrative data.

BACKGROUND: people approaching the end-of-life frequently face inappropriate care. With Alzheimer Disease or Related Syndromes (ADRS), end-of-life is characterised by progressive decline, but this period remains difficult to identify. This leads to a lack of anticipation and sometimes with unfavourable healthcare utilisation trajectories (HUTs). OBJECTIVE: to quantify unfavourable HUTs during the last year of life and identify their potential determinants in both community and nursing-home settings. DESIGN: nationwide cohort study using administrative database. SETTING: French community and nursing-home residents. SUBJECTS: incident ADRS people identified in 2012, who died up to 31 December 2017. METHODS: we used multidimensional clustering to identify 15 clusters of HUTs, using 11 longitudinal healthcare dimensions during the last year of life. Clusters were qualitatively assessed by pluri-disciplinary experts as favourable or unfavourable HUTs. Individual and contextual potential determinants of unfavourable HUTs were studied by setting using logistic random-effect regression models. RESULTS: 62,243 individuals died before 31 December 2017; 46.8% faced unfavourable end-of-life HUTs: 55.2% in the community and 31.8% in nursing-homes. Individual potential determinants were identified: younger age, male gender, ADRS identification through hospitalisation, shorter survival, life-limiting comorbidities, psychiatric disorders, acute hospitalisations and polypharmacy. In the community, deprivation and autonomy were identified as potential determinants. Contextual potential determinants raised mostly in the community, such as low nurse or physiotherapist accessibilities. CONCLUSIONS: Nearly half of people with ADRS faced unfavourable HUTs during their last year of life. Individual potential determinants should help anticipate advance care planning and palliative care needs assessment. Contextual potential determinants suggest geographical disparities and health inequalities.

Monitoring the depth of palliative sedation by video-pupillometry: A case report.

BACKGROUND: Palliative sedation is sometimes interrupted by undesired arousals. Pupillometry has been used in anesthesiology to monitor pain and sedation but has never been used during palliative sedation. ACTUAL CASE: A 48 years-old patient, with multi-metastatic cancer, underwent palliative sedation to manage global suffering. On the second day, the patient experienced arousal which required medication adjustments to ensure pain relief and increased sedation. POSSIBLE COURSE OF ACTION: Depth of sedation is monitored with clinical scales, such as the Richmond Agitation-Sedation Scale. But these scales do not measure brain stem activity and are poor at predicting arousal. FORMULATION OF A PLAN: During palliative sedation, an infrared pupillometer was used to monitor pupil size and pupillary reactivity (Neurolight®, IDMed®, Marseille, France). OUTCOME: The pupillary light reflex was depressed during deep sedation. In our case, we observed a low-normal reflex along with dilated pupil before arousal. LESSONS FROM THE CASE: Our case suggests that reflex intensity and pupil size might predict arousals during palliative sedation. VIEW ON RESEARCH PROBLEMS, OBJECTIVES, OR QUESTIONS GENERATED BY THE CASE: Prospective studies are needed to confirm our findings. Pupillometry's acceptability should also be questioned from patient's, families', and caregivers' perspectives.

End of life care practice and symptom management outcomes of nursing home residents with dementia: secondary analyses of IQUARE trial.

PURPOSE: End-of-life care is a central issue in nursing homes. Poor care outcomes have been reported, especially among residents with dementia. Our aim was two-fold: to assess whether the diagnosis of dementia was associated with specific patterns of care and symptom management for residents with dementia during the last 6 months of life, and to compare these patterns of care between residents with dementia who died within 6 months and those who survived longer. METHODS: Secondary prospective analyses of the IQUARE trial (trial registration number NCT01703689). 175 nursing homes in South West France. Residents with and without dementia at baseline (May-June 2011), stratified according to their vital status at 6-month follow-up. RESULTS: Of 6275 residents enrolled in IQUARE study (including 2688 with dementia), 494 (7.9%) died within 6 months. Compared to residents without dementia (n = 254), those with dementia (n = 240) were less likely to be self-sufficient (OR = 0.08, 95% CI 0.01-0.64). They were more likely to have physical restraints (OR = 1.65, 95% CI 1.08-2.51) and less likely to be prescribed benzodiazepines (OR = 0.58, 95% CI 0.38-0.88). Among residents with dementia, those who died during the first 6 months of follow-up were more likely to be identified with a formal "end-of-life" status (OR = 5.71, 95% CI 3.48-9.37) although such identification remains low with only 15% of them. They were more likely to experience pain (OR = 1.43, 95% CI 1.04-1.97) and to be physically restrained (OR = 1.46, 95% CI 1.08-1.98). However, pain relief and psychological distress management were not improved. CONCLUSIONS: Poor quality indicators such as physical restraints are associated with end-of-life care for residents with dementia. Among symptom management outcomes, pain medication remains low even if pain complaint increased at life end.