The Rotterdam Elderly Pain Observation Scale (REPOS) is reliable and valid for non-communicative end-of-life patients.

BACKGROUND: In palliative care, administration of opioids is often indispensable for pain treatment. Pain assessment may help recognize pain and guide treatment in non-communicative patients. In the Netherlands the Rotterdam Elderly Pain Observation Scale (REPOS) is recommended to this aim, but not yet validated. Therefore the objective of this study was to validate the REPOS in non-communicative or unconscious end-of-life patients. METHODS: In this observational study, the primary researcher applied the REPOS, while both the researcher and a nurse applied the Numeric Rating Scale (NRS). If possible, the patient in question applied the NRS as well. The NRS scores were compared with the REPOS scores to determine concurrent validity. REPOS scores obtained before and after a pain-reducing intervention were analysed to establish the scale's sensitivity to change. RESULTS: A total of 183 REPOS observations in 100 patients were analysed. Almost 90% of patients had an advanced malignancy; observations were done a median of 3 days (IQR 1 to 13) before death. Internal consistency of the REPOS was 0.73. The Pearson product moment correlation coefficient ranged from 0.64 to 0.80 between REPOS and NRS scores. REPOS scores declined with median 2 points (IQR 1 to 4) after a pain-reducing intervention (p < 0.001). Optimal sensitivity (0.81) and specificity (0.62) were found at cut-off score 3. CONCLUSIONS: This study demonstrates that the REPOS has promising psychometric properties for pain assessment in non-communicative end-of-life patients. Its application may be of additional value to relieve suffering, including pain, in palliative care.

Population pharmacodynamic modelling of midazolam induced sedation in terminally ill adult patients.

AIMS: Midazolam is the drug of choice for palliative sedation and is titrated to achieve the desired level of sedation. A previous pharmacokinetic (PK) study showed that variability between patients could be partly explained by renal function and inflammatory status. The goal of this study was to combine this PK information with pharmacodynamic (PD) data, to evaluate the variability in response to midazolam and to find clinically relevant covariates that may predict PD response. METHOD: A population PD analysis using nonlinear mixed effect models was performed with data from 43 terminally ill patients. PK profiles were predicted by a previously described PK model and depth of sedation was measured using the Ramsay sedation score. Patient and disease characteristics were evaluated as possible covariates. The final model was evaluated using a visual predictive check. RESULTS: The effect of midazolam on the sedation level was best described by a differential odds model including a baseline probability, Emax model and interindividual variability on the overall effect. The EC50 value was 68.7 µg l-1 for a Ramsay score of 3-5 and 117.1 µg l-1 for a Ramsay score of 6. Comedication with haloperidol was the only significant covariate. The visual predictive check of the final model showed good model predictability. CONCLUSION: We were able to describe the clinical response to midazolam accurately. As expected, there was large variability in response to midazolam. The use of haloperidol was associated with a lower probability of sedation. This may be a result of confounding by indication, as haloperidol was used to treat delirium, and deliria has been linked to a more difficult sedation procedure.

Hypoalbuminaemia and decreased midazolam clearance in terminally ill adult patients, an inflammatory effect?

AIMS: Midazolam is the drug of choice for palliative sedation and is titrated to achieve the desired level of sedation. Because of large inter-individual variability (IIV), however, the time it takes to achieve adequate sedation varies widely. It would therefore greatly improve clinical care if an individualized dose could be determined beforehand. To find clinically relevant parameters for dose individualization, we performed a pharmacokinetic study on midazolam, 1OH-midazolam (1-OH-M) and 1OH-midazolam-glucuronide (1-OH-MG) in terminally ill patients. METHODS: Using nonlinear mixed effects modelling (NONMEM 7.2), a population pharmacokinetic analysis was conducted with 192 samples from 45 terminally ill patients who received midazolam either orally or subcutaneously. The covariates analysed were patient characteristics, co-medication and blood chemistry levels. RESULTS: The data were accurately described by a one compartment model for midazolam, 1-OH-M and 1-OH-MG. The population mean estimates for midazolam, 1-OH-M and 1-OH-MG clearance were 8.4 l h-1 (RSE 9%, IIV 49%), 45.4 l h-1 (RSE 12%, IIV 60.5%) and 5.1 l h-1 (RSE 11%, IIV 49.9%), respectively. 1-OH-MG clearance was correlated with the estimated glomular filtration rate (eGFR) explaining 28.4% of the IIV in 1-OH-MG clearance. In addition, low albumin levels were associated with decreased midazolam clearance, explaining 18.2% of the IIV. CONCLUSION: Our study indicates albumin levels and eGFR as relevant clinical parameters to optimize midazolam dosing in terminally ill patients. The correlation between low albumin levels and decreased midazolam clearance is probably a result of inflammatory response as high CRP levels were correlated in a similar way.

Prevalence and Implications of Abnormal Laboratory Results in Patients in the Terminal Phase of Life.

BACKGROUND: Pathophysiological changes at the end of life may affect pharmacokinetics of drugs. However, caregivers typically do not extensively monitor patients' laboratory parameters at the end of life. OBJECTIVE: Our aim was to describe laboratory parameters of hospice patients in the week before death. METHODS: A cohort study was conducted on available laboratory results in the week before death, including clinical chemistry and hematology tests. RESULTS: Laboratory data of 125 patients in a palliative care center were included, assessed at a median of 3 days before death. Eighty percent of patients had anemia and almost all had hypoalbuminemia (97%). Elevated levels of gamma-glutamyl transferase (gGT) were found in 75%, of alkaline phosphatase (ALP) in 60%, of aspartate aminotransferase (ASAT) in 60%, and of calcium (Ca) in 68%. Alanine aminotransferase (ALAT), bilirubin, sodium (Na), and potassium (K) were abnormal in from 8.8% to 36.0% of patients. A previous unknown poor kidney function was found in 60% of patients. Thirteen patients (22%) with a regular morphine prescription and one patient treated with a non-steroidal anti-inflammatory drug (NSAID) had severe kidney failure. CONCLUSIONS: Abnormal laboratory results were expected due to the pathophysiological changes that occur during the last phase of life. Remarkably, however, electrolytes (Na and K) were balanced even shortly before death. Estimated glomerular filtration rate (eGFR), reflecting the kidney function, seems the most clinically relevant laboratory parameter, because it may guide drug choice and dosing.

Bispectral Index Monitoring in Terminally Ill Patients: A Validation Study.

CONTEXT: If regular therapies cannot relieve symptoms sufficiently in the last days of life, continuous palliative sedation may serve to reduce consciousness. Sedation level can be measured with EEG monitoring with the bispectral index (BIS) monitor. OBJECTIVES: To determine the feasibility and validity of BIS monitoring in terminally ill patients. METHODS: In this prospective study, BIS registrations were performed in unconscious end-of-life patients admitted to a palliative care center. Validated scores were used to measure level of sedation (Ramsay score), pain (Numeric Rating Scale or Rotterdam Elderly Pain Observations Scale), delirium (Delirium Observation Screening score), and overall comfort (Numeric Rating Scale). Validity and sensitivity to change of BIS values were considered, and the effects of medication and the time till death on BIS values were evaluated in a linear mixed model analysis. RESULTS: Fifty-eight patients were included for analysis. BIS monitoring was acceptable to patients, relatives, and medical staff. BIS values were moderately correlated with Ramsay scores (0.46) but were highly variable for deeply sedated patients. BIS values changed significantly before and after a midazolam dose (P < 0.001). Midazolam treatment resulted on average in a statistically significant reduction of the BIS values (-4.5, 95% CI -7.0 to -2.0), whereas morphine and haloperidol did not. CONCLUSION: This is one of the first validation studies in which BIS monitoring in end-of-life patients is described. BIS monitoring is feasible in unconscious terminally ill patients. However, based on our results, the wide range of BIS values in deeply sedated and comfortable patients seems to hamper its use in daily clinical practice.

Pharmacokinetics of Morphine, Morphine-3-Glucuronide and Morphine-6-Glucuronide in Terminally Ill Adult Patients.

BACKGROUND AND OBJECTIVE: Morphine dosing can be challenging in terminally ill adult patients due to the heterogeneous nature of the population and the difficulty of accurately assessing pain during sedation. To determine the pharmacokinetics of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in this population, and to find clinically relevant parameters for dose individualisation, we performed a population pharmacokinetic analysis. METHODS: Blood samples were randomly collected from 47 terminally ill patients in both the pre-terminal and terminal phases. Nonlinear mixed-effects modelling (NONMEM) was used to develop a population pharmacokinetic model and perform covariate analysis. RESULTS: The data were accurately described by a two-compartment model for morphine with two one-compartment models for both its metabolites. Typical morphine clearance was 48 L/h and fell exponentially by more than 10 L/h in the last week before death. Decreased albumin levels and a decreased estimated glomerular filtration rate (eGFR) resulted in lower metabolite clearance. Between-subject variability in clearance was 52 % (morphine), 75 % (M3G) and 79 % (M6G), and changed to 53, 29 and 34 %, respectively, after inclusion of the covariates. CONCLUSIONS: Our results show that morphine clearance decreased up to the time of death, falling by more than 10 L/h (26 %) in the last week before death, and that M3G and M6G accumulated due to decreased renal function. Further studies are warranted to determine whether dose adjustment of morphine is required in terminally ill patients.

[Palliative care for a homeless person]. / Palliatieve zorg voor een dakloze.

Homeless people have substantial health disadvantages as compared to the general population, and excessive losses in life expectancy. High proportions of psychiatric disorders, substance abuse and intellectual disability have been reported. This makes palliative care for this population extremely complex. A 55-year-old man, addicted to heroin and cocaine, was diagnosed with metastatic lung cancer. His terminal phase of life was complicated by many admissions to different care settings and problems with symptom management. Involvement of a palliative care consultation team and transfer to a homeless shelter, to which homeless people with life-threatening diseases could be admitted, gave both the patient and his family relief. This case illustrates that palliative care in homeless patients may be extremely complex due to the specific physical and psychosocial features involved. Such care should be offered proactively and on a multidisciplinary basis.

Medication use during end-of-life care in a palliative care centre.

BACKGROUND: In end-of-life care, symptoms of discomfort are mainly managed by drug therapy, the guidelines for which are mainly based on expert opinions. A few papers have inventoried drug prescriptions in palliative care settings, but none has reported the frequency of use in combination with doses and route of administration. OBJECTIVE: To describe doses and routes of administration of the most frequently used drugs at admission and at day of death. Setting Palliative care centre in the Netherlands. METHOD: In this retrospective cohort study, prescription data of deceased patients were extracted from the electronic medical records. MAIN OUTCOME MEASURE: Doses, frequency and route of administration of prescribed drugs RESULTS: All regular medication prescriptions of 208 patients, 89% of whom had advanced cancer, were reviewed. The three most prescribed drugs were morphine, midazolam and haloperidol, to 21, 11 and 23% of patients at admission, respectively. At the day of death these percentages had increased to 87, 58 and 50%, respectively. Doses of these three drugs at the day of death were statistically significantly higher than at admission. The oral route of administration was used in 89% of patients at admission versus subcutaneous in 94% at the day of death. CONCLUSIONS: Nearing the end of life, patients in this palliative care centre receive discomfort-relieving drugs mainly via the subcutaneous route. However, most of these drugs are unlicensed for this specific application and guidelines are based on low level of evidence. Thus, there is every reason for more clinical research on drug use in palliative care.

Is pain assessment feasible as a performance indicator for Dutch nursing homes? A cross-sectional approach.

Quality of care gains transparency with the help of performance indicators. For Dutch nursing homes, the current set of performance indicators does not include pain. To determine the feasibility of pain assessment as performance indicator, information about pain prevalence and analgesic prescription in one nursing home was collected. Within the time span of 3 days, pain intensity was measured in 91% of the residents (201 out of 221), either with a numeric rating scale, a verbal rating scale, or the Rotterdam Elderly Pain Observation Scale (REPOS). Numerical rating was used for 72%, verbal rating for 3%, and REPOS observation for 25% of the residents. Pain was substantial in 65 residents (32%), who received the following analgesic prescription: World Health Organization (WHO) step 1, 45%; WHO step 3, 12%; and neuroactive agents, 5%. Thirty-eight percent of these residents were in pain and received no analgesics. Residents with substantial pain significantly more often received analgesics (p = .007). Results suggest that pain assessment is feasible in a nursing home and would stimulate staff attention to pain. Further investigation is necessary to find out if a pain algorithm is feasible and will lead to improved pain treatment.

Assessment of pain: can caregivers or relatives rate pain in nursing home residents?

Aim. To compare pain reports of nursing home residents to ratings by proxies. Background. It is not easy to assess pain in cognitively impaired residents. For residents who are unable to report pain intensity themselves, proxies (i.e. relatives or caregivers) might serve as sources of information. The utility of these proxies in assessing residents' pain is not clear however. Design. A multicenter cross-sectional study. Methods. Pain intensity was rated on a Numeric Rating Scale; proxies were asked how certain they were about their observations. Agreements on ratings were computed by means of intra class correlation (ICC) coefficients for continuous variables and multiple linear regression analyses were performed with the level of pain intensity by proxies as the dependent variable. Results. The sample consisted of 174 residents (median age 82 years), of whom 124 were cognitively impaired and 50 intact, and 293 proxies: 171 caregivers and 122 relatives. All three parties reported median pain intensity during the preceding week as 6.0. Data were consistent with low-to-moderate correlation coefficients between residents and caregivers (ICC = -0.12 to 0.25), residents and relatives (ICC = -0.51 to 0.48) and caregivers and relatives (ICC = 0.03 to 0.31). Residents themselves judged pain intensity at rest significantly higher than did proxies (p = 0.05). Caregivers scored significantly higher ratings for residents on analgesics (p = 0.001) and significantly lower pain ratings if they were more satisfied with the prescribed analgesics (p = 0.01). Conclusions. Proxy report of relatives and caregivers on presence and intensity of pain is unreliable, especially for cognitively impaired persons. The use of a standardised pain observation scale could be helpful. Relevance to clinical practice. Pain management in nursing home residents could be improved by educating caregivers about assessment and treatment of chronic pain. Relatives should be informed about chronic pain and learn how to alleviate pain through non-pharmacological interventions.

Pain management in Dutch nursing homes leaves much to be desired.

This cross-sectional multicenter study describes several aspects of pain, pain intensity, and pain treatment in a Dutch nursing home population. A standardized pain questionnaire, including the Numeric Rating Scale (NRS), was used to measure aspects of pain and intensity of present pain, pain experienced in the previous week, and tolerable pain. The eligible sample comprised 320 residents (median age 79 years), of whom 233 residents completed the questionnaire. Sixty-six percent (n = 153) experienced (mostly chronic) pain, either in the previous week (median NRS 6) or at present (median NRS 5). Intolerable pain was recorded in 41% of 100 residents. The higher the pain scores, the more interference with activities of daily living was reported. Of the 153 residents with pain, about one-fourth did not receive any pain medication, and 65 (43%) received step 1, 13 (9%) step 2, and 16 (11%) step 3 analgesics. Most residents (60%) were satisfied with pain treatment, and 21% were not. Considering the high prevalences and intensities of pain, pain management in Dutch nursing homes leaves much to be desired. Apparently, residents do not seem to expect effective pain management. Awareness and knowledge about pain assessment and treatment, however, needs to be raised. Pain measurement tools and treatment protocols should be implemented in daily practice.

Observation scales for pain assessment in older adults with cognitive impairments or communication difficulties.

BACKGROUND: Several pain observation scales have been developed to accurately assess and manage pain in older adults with severe cognitive impairments, communication difficulties, or both. OBJECTIVE: To review relevant pain observation scales and the psychometric qualities of these scales. METHODS: The literature was searched for articles reporting the use of a pain observation scale in an empirical study and describing psychometric properties in older adults with cognitive impairments, communication difficulties, or both. RESULTS: Thirteen pain observation scales were included. Scales differed in numbers of items, types of categories, and psychometric properties. Facial expression, vocalization, motor behavior, and social behavior or mood are categories present in most of the scales. In terms of reliability and validity, however, most studies are too limited or incomplete to allow definite conclusions to be drawn about usefulness in daily practice. DISCUSSION: As different methods of evaluating reliability and validity were used, and different aims (e.g., type of pain) were pursued, the available scales cannot be compared easily. Nevertheless, a few are promising, given preliminary results. These should be examined further on psychometric properties and usefulness in different populations because optimal pain assessment is necessary for efficient and effective pain treatment.