Olanzapine Versus Haloperidol for Treatment of Delirium in Patients with Advanced Cancer: A Phase III Randomized Clinical Trial.

BACKGROUND: Treatment of delirium often includes haloperidol. Second-generation antipsychotics like olanzapine have emerged as an alternative with possibly fewer side effects. The aim of this multicenter, phase III, randomized clinical trial was to compare the efficacy and tolerability of olanzapine with haloperidol for the treatment of delirium in hospitalized patients with advanced cancer. MATERIALS AND METHODS: Eligible adult patients (≥18 years) with advanced cancer and delirium (Delirium Rating Scale-Revised-98 [DRS-R-98] total score ≥17.75) were randomized 1:1 to receive either haloperidol or olanzapine (age-adjusted, titratable doses). Primary endpoint was delirium response rate (DRR), defined as number of patients with DRS-R-98 severity score <15.25 and ≥4.5 points reduction. Secondary endpoints included time to response (TTR), tolerability, and delirium-related distress. RESULTS: Between January 2011 and June 2016, 98 patients were included in the intention-to-treat analysis. DRR was 45% (95% confidence interval [CI], 31-59) for olanzapine and 57% (95% CI, 43-71) for haloperidol (Δ DRR -12%; odds ratio [OR], 0.61; 95% CI, 0.2-1.4; p = .23). Mean TTR was 4.5 days (95% CI, 3.2-5.9 days) for olanzapine and 2.8 days (95% CI, 1.9-3.7 days; p = .18) for haloperidol. Grade ≥3 treatment-related adverse events occurred in 5 patients (10.2%) and 10 patients (20.4%) in the olanzapine and haloperidol arm, respectively. Distress rates were similar in both groups. The study was terminated early because of futility. CONCLUSION: Delirium treatment with olanzapine in hospitalized patients with advanced cancer did not result in improvement of DRR or TTR compared with haloperidol. Clinical trial identification number. NCT01539733. Dutch Trial Register. NTR2559. IMPLICATIONS FOR PRACTICE: Guidelines recommend that pharmacological interventions for delirium treatment in adults with cancer should be limited to patients who have distressing delirium symptoms. It was suggested that atypical antipsychotics, such as olanzapine, outperform haloperidol in efficacy and safety. However, collective data comparing the efficacy and safety of typical versus atypical antipsychotics in patients with cancer are limited. If targeted and judicious use of antipsychotics is considered for the treatment of delirium in patients with advanced cancer, this study demonstrated that there was no statistically significant difference in response to haloperidol or olanzapine. Olanzapine showed an overall better safety profile compared with haloperidol, although this difference was not statistically significant.

Accuracy of the Delirium Observational Screening Scale (DOS) as a screening tool for delirium in patients with advanced cancer.

BACKGROUND: The Delirium Observation Screening Scale (DOS) was developed to facilitate early recognition of delirium by nurses during routine clinical care. It has shown good validity in a variety of patient populations, but has not yet been validated in hospitalized patients with advanced cancer, although the DOS is commonly used in this setting in daily practice. The aim of this study was to evaluate the accuracy of the DOS in hospitalized patients with advanced cancer using the revised version of the Delirium Rating Scale (DRS-R- 98) as the gold standard. METHODS: Patients with advanced cancer admitted to the medical oncology ward were screened for delirium with the DOS and DRS-R-98. Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of the DOS were calculated, using a DOS score ≥ 3 as a cut-off for delirium. RESULTS: Ninety-five DOS negative and 98 DOS positive patients were identified. Sensitivity of the DOS, was > 99.9% (95%-CI, 95.8-100.0%), specificity was 99.5% (95%-CI 95.5-99.96%), PPV was 94.6% (95% CI 88.0-97.7), and NPV was > 99.9% (95% CI 96.1-100.0). CONCLUSIONS: The DOS is an accurate screening tool for delirium in patients with advanced cancer. Since it has the benefit of being easily implicated in daily practice, we recommend to educate caregivers to screen patients with advanced cancer by DOS analysis. By early recognition and adequate treatment of this distressing delirium syndrome the quality of life of patients with advanced cancer can be improved. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01539733 (Feb 27, 2012 - retrospectively registered), Netherlands Trial Register NTR2559 (Oct 7, 2010).

Medication Use in the Last Days of Life in Hospital, Hospice, and Home Settings in the Netherlands.

BACKGROUND: The purpose of medication management in the last days of life is to optimize patient's comfort. Little is known about the medication use in the days before death and how this relates to the care setting. OBJECTIVE: To describe medication use in the last week of life for patients dying in hospital, hospice, and home settings in the Netherlands. DESIGN: Retrospective chart review study. SETTING: A convenience sample of patient records from the three settings in three different regions in the Netherlands that cover more than half the country. MEASUREMENTS: Information about medication use in the last week of life of patients who ultimately died an expected death was registered, including type of medication, start and if applicable stop dates, administration routes, and doses. RESULTS: One hundred seventy-nine records were analyzed. Medications most frequently used in the last week of life were analgesics (n = 168, 94.1%) and psycholeptics (n = 150, 84.7%), in particular by hospice patients. The mean number of medications used per patient was nine during day 7 before death and six on the day of dying. On the day of death, 48 (26.8%) patients used a preventive medication. This percentage was highest for patients dying in the hospital or at home. CONCLUSIONS: Patients who die an expected death receive many medications in the last week of life, part of which are preventive medications. Medication management in patients' final days of life can be improved, especially in the hospital and home setting.

Pain Pressure Threshold in the Region of the Sacroiliac Joint in Patients Diagnosed with Sacroiliac Joint Pain.

BACKGROUND: Although the prevalence of sacroiliac joint (SIJ) pain is relatively high (15 - 30%), there is no unambiguous reference standard to diagnose SIJ pain. Pressure tenderness in the SIJ region is used for diagnostic purposes, but the clinimetric properties of this procedure remain to be determined. OBJECTIVES: The aim of this study is to determine the reliability of pain pressure threshold (PPT) measurements in the SIJ region and the difference in PPTs in the SIJ region between healthy volunteers and PPTs in patients with SIJ pain. STUDY DESIGN: Prospective cohort study. SETTING: Outpatient pain clinic VU University Medical Center. METHODS: Forty-one healthy volunteers and 31 patients diagnosed with SIJ pain were included. PPTs were obtained from 5 measurement points in the region of the SIJ with a pressure pain algometer using a standardized protocol. The inter-rater reliability of this method was calculated by means of the Intraclass Correlation Coefficients (ICC) of individual assessment performed by 2 individual raters of SIJs of healthy volunteers on both sides. PPTs of healthy volunteers were compared to those of the affected side in patients with SIJ pain. RESULTS: PPT measurement showed moderate to good inter-rater reliability (ICC 0.6 - 0.82).The median PPTs of 5 points was comparable for both sides in healthy volunteers (right: 8.5 kg/cm2 [IQR 6.0 - 10.0]; left 8.3 kg/cm2 (5.8 - 10.0]). Median PPTs for the affected sides of patients with SIJ pain were significantly lower compared to the same side of healthy volunteers (right: 2.4 kg/cm2 [IQR 2.2 - 3.2, n = 15]; left: 2.5 kg/cm2 [2.3 - 3.2, n = 16]; P < 0.001 for both sides). LIMITATIONS: Only the SIJ on one side of was measured in patients with SIJ pain, where both sides would be desirable. CONCLUSIONS: Pressure pain algometry appears to be a reliable method to establish differences in PPTs between healthy volunteers and patients with SIJ pain. The diagnostic accuracy of this test should be investigated further.

Predictors of Persistent Neuropathic Pain--A Systematic Review.

BACKGROUND: Characterization of the prognostic variables for persistent neuropathic pain (PNP) remains incomplete despite multiple articles addressing this topic. To provide more insight into the recovery and prognosis of neuropathic pain, high-quality data are required that provide information about the predictors that contribute to the development of PNP. OBJECTIVE: To determine the methodological quality of studies about predictors for PNP and to summarize findings of predictors found in high-quality studies. STUDY DESIGN: A systematic review. SETTING: VU University Medical Center, Amsterdam, The Netherlands. METHODS: Studies were identified by searching the electronic databases PubMed, Embase, and Cochrane Library. Methodological quality of each article was independently assessed by 2 reviewers. RESULTS: Forty-six relevant studies were identified, classified into 4 different neuropathic pain (NP)-syndromes: postherpetic neuralgia (n = 35), radicular pain and sciatica (n = 3), postsurgical pain (n = 6), and other types of NP (n = 2). Seven studies were of high quality. The 3 high-quality studies found for PHN reported male gender, older age, smoking, trauma at the site of lesion, missed antiviral prescriptions, higher acute pain severity, higher rash severity, more neuropathic characteristics, shorter rash duration, and a lower health status as predictors for PNP. For persistence of radicular pain one high-quality study reported negative outcome expectancies, pain-related fear of movement, and passive pain coping as predictors for PNP. Psychological distress, acute pain, breast cancer surgery, higher body mass index, area of secondary hyperalgesia, neuropathic characteristics, hypoesthesia, and hyperesthesia were found to be predictive for postsurgical pain in 3 high-quality studies. LIMITATIONS: Some publications may have been missed during literature search. The low-quality of the studies could be the result of an incomplete description of their methods. CONCLUSIONS: High-quality studies mainly assessed factors related to disease functions and structures. Due to shortcomings in methodological quality and limited areas of predictor selection, there is a need for high-quality studies focusing on predictor measurement, statistical analysis and the use of a standardized set of predictors.

Pain in dementia: prevalence and associated factors: protocol of a multidisciplinary study.

BACKGROUND: Pain is a common problem in people with dementia, however the exact prevalence of pain in dementia subtypes, e.g. Alzheimer's Disease (AD), Vascular Dementia (VaD), Frontotemporal Dementia (FTD) and dementia with Lewy Bodies (DLB), is unknown, as is the relation between pain and the different subtypes of dementia. In this study, the prevalence of pain in people with dementia will be investigated per dementia subtype and the relationship between the various subtypes of dementia and the presence of specific types of pain (i.e. musculoskeletal pain, neuropathic pain and orofacial pain) will be examined. Secondly, associations between various types of pain, cognitive functioning, neuropsychiatric symptoms and quality of life in people with dementia will be examined. A third purpose is to study the value of the assessment of autonomic responses in assessing pain in people with dementia. Finally, the effect of feedback to the attending physician on the presence of pain, based on examination by investigators with backgrounds in neuropsychology, geriatric dentistry and elderly care medicine, will be evaluated. METHODS/DESIGN: A cross-sectional, partially longitudinal observational study in 400 participants with dementia, aged 60 years and older. Participants will be recruited from an outpatient memory clinic and dementia special care units. All participants will be examined by an elderly care medicine trainee, a dentist with experience in geriatric dentistry, and a neuropsychologist. The primary outcome is presence of pain. Secondary outcomes will include oral health, autonomic responses to pain stimulus, vital sensibility and gnostic sensibility, musculoskeletal examination, cognitive functioning, neuropsychiatric symptoms, and quality of life. DISCUSSION: This study will help to enhance our knowledge regarding the prevalence of different types of pain in different dementia subtypes i.e. AD, VaD, FTD and DLB. This study also aims to contribute to a better understanding of oral health status in people with dementia, the use of autonomic responses in the assessment of pain in people with dementia and the relationships between pain and cognitive symptoms, neuropsychiatric symptoms and quality of life in people with various dementia subtypes and in different stages of the disease.

A favorable course of palliative sedation: searching for indicators using caregivers' perspectives.

OBJECTIVE: Comparing characteristics of a favorable sedation course during palliative sedation to a less favorable course based on the reports Dutch physicians and nurses. RESULTS: Cases identified as having a favorable sedation course less often concerned a male patient (P = .019 nurses' cases), reached the intended sedation depth significantly quicker (P < .05 both nurses and physicians' cases), reached a deeper level of sedation (P = .015 physicians' cases), and had a shorter total duration of sedation compared (P < .001 physicians' cases) to patients with a less favorable sedation course. CONCLUSIONS: A favorable course during palliative sedation seems more probable when health care professionals report on a (relatively) shorter time to reach the required depth of sedation and when a deeper level of sedation can be obtained.

The palliative performance scale applied in high-care residential hospice: a retrospective study.

BACKGROUND: The Palliative Performance Scale (PPS) is a tool that is widely used to predict end of life. In Ontario, Canada, the PPS is used to mark the terminal phase of life and eligibility for terminal care. OBJECTIVE: The aim of this retrospective study was to confirm that a PPS level of 40% can be used as a marker for the terminal phase of life. METHOD: PPS levels from 78 patients were calculated based on the intake reports made at admission to an inpatient hospice. RESULTS: Although 77 patients passed away within a period of 3 months, PPS levels at admission varied from 10% to 70%. Fifty-six percent of all patients had a PPS level of 40% or less. Regarding survival, three significant PPS profiles, consisting of two or more PPS levels could be distinguished.

Clinical evaluation of the efficacy of methylnaltrexone in resolving constipation induced by different opioid subtypes combined with laboratory analysis of immunomodulatory and antiangiogenic effects of methylnaltrexone.

BACKGROUND: Opioid-induced constipation (OIC) is one of the major symptoms in palliative care with a prevalence of 30-50%. Methylnaltrexone for the treatment of OIC is significantly more effective than placebo, but only in about fifty percent of the patients regardless of dose increase. Dose increases cause increased toxicity without additional efficacy, and are therefore not recommended. While methylnaltrexone is a µ-receptor antagonist, only a few opioids are solely µ-receptor agonists. Therefore, the response to methylnaltrexone may be determined by the receptor-profile of a specific opioid. In addition, methylnaltrexone may also affect the immune system and angiogenesis as was found in pre-clinical studies. Primary aim of this study is to determine differences in the efficacy of methylnaltrexone prescribed to resolve opioid induced constipation between three commonly used opioid subtypes: morphine sulphate, oxycodone and fentanyl. Secondary aim is to explore potential immunomodulatory and antiangiogenic effects of methylnaltrexone. METHODS: In this multi-center, prospective, parallel group trial we will evaluate the efficacy of methylnaltrexone in resolving OIC occurring as a side effect of the most common opioid subtypes: morphine, oxycodone and fentanyl. In total 195 patients with OIC despite prophylactic laxatives will receive methylnaltrexone every other day up to fourteen days. Patients will report its effect in a laxation diary. Group allocation is based on the opioid type the patient is using. At the start and end of the study period patients complete the Bowel Function Index questionnaire. A subgroup of the patients will donate blood for analysis of immunomodulatory- and anti-angiogenic effects of methylnaltrexone. DISCUSSION: In this study we aim to determine the efficacy of methylnaltrexone per opioid subtype to reduce constipation. We expect that the outcome of this study will improve the clinical use of methylnaltraxone. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov: NCT01955213 and in the Dutch trial register: NTR4272.

Continuous palliative sedation: not only a response to physical suffering.

BACKGROUND: Palliative sedation is a medical intervention aimed at relieving symptoms that can no longer be controlled by conventional treatment. Ample knowledge is available regarding the nature of such symptoms, but there is no in-depth information regarding how health care workers decide about palliative sedation. OBJECTIVE: The study objective was to investigate considerations concerning the indications for continuous palliative sedation (CPS) and issues that influence these considerations. DESIGN: The study consisted of qualitative interviews regarding patients who had recently received CPS. SETTING/SUBJECTS: The study involved physicians and nurses working in general practice, nursing homes, and hospitals. MEASUREMENT: Analyses by a multidisciplinary research team used the constant comparative method. RESULTS: Together with physical symptoms, psychological and existential suffering may combine to produce a refractory state for which other treatment options than CPS were not available or considered inappropriate. A limited life expectancy was by many considered crucial (e.g., to avoid hastening death) and by some less important (e.g., because the patient's suffering was considered to be key). Issues influencing the decision to use CPS related to patient preferences (e.g., dignity, not wanting to experience further suffering) or family issues (impact of suffering on family, family requesting CPS). CONCLUSIONS: The indication for CPS typically originates from physical symptoms and nonphysical problems producing a refractory state in which a patient suffers unbearably. In such states, preferences of patients and families and the life expectancy criterion are weighed against the severity of refractory symptoms. Therefore the use of CPS is not only a response to the physical suffering of patients in the dying phase.

Intravenous magnesium for chronic complex regional pain syndrome type 1 (CRPS-1).

OBJECTIVE: To assess the effects of intravenous administration of magnesium on complex regional pain syndrome type 1 (CRPS-1), a randomized double-blind placebo-controlled trial was performed. METHODS: Fifty-six patients with CRPS-1 (International Association for the Study of Pain Orlando criteria) received MgSO(4) 70 mg/kg or placebo (NaCl 0.9%) in 4 hours over 5 consecutive days. Pain (BOX-11 and McGill), the level of impairment (Impairment level Sum Score [ISS]), functional limitations (Radboud Skills Questionnaire, Walking Skills Questionnaire/questionnaire rising and sitting down), participation (Impact on Participation and Autonomy [IPA]), and quality of life (Short Form-36, EuroQol, IPA) were evaluated at baseline and at 1, 3, 6, and 12 weeks. RESULTS: No significant differences were found between MgSO(4) and placebo on the BOX-11 and ISS at different time points during the trial on intention-to-treat and per-protocol analysis. A significant improvement on the BOX-11 was found after the first week of the trial in both groups (mean 0.7; standard deviation 1.1). For the MgSO(4) group, a clinically relevant and statistically significant improvement on the ISS at 1 week (median 5, interquartile range [IQR] -1 to 8) and a significant improvement on the McGill up to 6 weeks (median 2 words, IQR 0-4.5) were found compared with baseline, which were not found in the placebo group. Significant improvement in perceived job participation was found for the MgSO(4) group at 12 weeks (median improvement 1.44-1.17; P = 0.01). ISS improved significantly more in patients with a low Hospital Anxiety and Depression Scale (HADS) score (≤10) in the MgSO(4) group (mean 4.4 vs mean -3.1; P = 0.02). CONCLUSION: Administration of the physiological competitive N-methyl-D-aspartate receptor antagonist magnesium in chronic CRPS provides insufficient benefit over placebo. Future research should focus on patients with acute CRPS and early signs and symptoms of central sensitization.

Oxidative stress in Complex Regional Pain Syndrome (CRPS): no systemically elevated levels of malondialdehyde, F2-isoprostanes and 8OHdG in a selected sample of patients.

Exaggerated inflammation and oxidative stress are involved in the pathogenesis of Complex Regional Pain Syndrome (CRPS). However, studies assessing markers for oxidative stress in CRPS patients are limited. In this study, markers for lipid peroxidation (malondialdehyde and F2-isoprostanes) and DNA damage (8-hydroxy-2-deoxyguanosine) were measured in nine patients (mean age 50.1 ± 17.1 years) with short term CRPS-1 (median 3 months) and nine age and sex matched healthy volunteers (mean age 49.3 ± 16.8 years) to assess and compare the level of oxidative stress. No differences were found in plasma between CRPS patients and healthy volunteers for malondialdehyde (5.2 ± 0.9 µmol/L vs. 5.4 ± 0.5 µmol/L) F2-isoprostanes (83.9 ± 18.7 pg/mL vs. 80.5 ± 12.3 pg/mL) and 8-hydroxy-2-deoxyguanosine (92.6 ± 25.5 pmol/L vs. 86.9 ± 19.0 pmol/L). Likewise, in urine, no differences were observed between CRPS patients and healthy volunteers for F2-isoprostanes (117 ng/mmol, IQR 54.5-124.3 vs. 85 ng/mmol, IQR 55.5-110) and 8-hydroxy-2-deoxyguanosine (1.4 ± 0.7 nmol/mmol vs. 1.4 ± 0.5 nmol/mmol). Our data show no elevation of systemic markers of oxidative stress in CRPS patients compared to matched healthy volunteers. Future research should focus on local sampling methods of oxidative stress with adequate patient selection based on CRPS phenotype and lifestyle.

An overview of predictors for persistent neuropathic pain.

Neuropathic pain (NP) is a pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. A variety of factors associated with the development of persistent NP have been suggested. The goal of the present article is to provide an overview of current knowledge about prognostic factors for persistent NP. The International Classification of Functioning, Disability and Health model is used as a framework to categorize these predictors. Most reported predictors in the literature were found in the International Classification of Functioning, Disability and Health-category of personal factors, especially age and psychological factors, functions and structure, including sensory signs and symptoms. Predictors in the category of environmental factors, activities and participation were less frequently described.

Breakthrough cancer pain: an observational study of 1000 European oncology patients.

CONTEXT: Breakthrough pain is common in patients with cancer and is a significant cause of morbidity in this group of patients. OBJECTIVES: The aim of this study was to characterize breakthrough pain in a diverse population of cancer patients. METHODS: The study involved 1000 cancer patients from 13 European countries. Patients were screened for breakthrough pain using a recommended diagnostic algorithm and then questioned about the characteristics and management of their pain. RESULTS: Of the 1000 patients, 44% reported incident pain, 41.5% spontaneous pain, and 14.5% a combination. The median number of episodes was three a day. The median time to peak intensity was 10 minutes, with the median for patients with incident pain being five minutes (P < 0.001). The median duration of untreated episodes was 60 minutes, with the median for patients with incident pain being 45 minutes (P = 0.001). Eight hundred six patients stated that pain stopped them doing something, 66 that it sometimes stopped them doing something, and only 107 that it did not interfere with their activities. Patients with incident pain reported more interference with walking ability and normal work, whereas patients with spontaneous pain reported more interference with mood and sleep. As well, 65.5% of patients could identify an intervention that improved their pain (29.5%, pharmacological; 23%, nonpharmacological; 12%, combination). Regarding medications, 980 patients were receiving an opioid to treat their pain, although only 191 patients were receiving a transmucosal fentanyl product licensed for the treatment of breakthrough pain. CONCLUSION: Breakthrough cancer pain is an extremely heterogeneous condition.

The use of observational scales to monitor symptom control and depth of sedation in patients requiring palliative sedation: a systematic review.

BACKGROUND: Palliative sedation is the intentional lowering of consciousness of a patient in the last phase of life to relieve suffering from refractory symptoms such as pain, delirium and dyspnoea. AIM: In this systematic review, we evaluated the use of monitoring scales to assess the degree of control of refractory symptoms and/or the depth of the sedation. DESIGN: A database search of PubMed and Embase was performed up to January 2010 using the search terms 'palliative sedation' OR 'terminal sedation'. DATA SOURCES: Retro- and prospective studies as well as reviews and guidelines containing information about monitoring of palliative sedation, written in the English, German or Dutch language were included. RESULTS: The search yielded 264 articles of which 30 were considered relevant. Most studies focused on monitoring refractory symptoms (pain, fatigue or delirium) or the level of awareness to control the level of sedation. Four prospective and one retrospective study used scales validated in other settings: the Numeric Pain Rating Scale, the Visual Analogue Scale, the Memorial Delirium Assessment Scale, the Communication Capacity Scale and Agitation Distress Scale. Only the Community Capacity Scale was partially validated for use in a palliative sedation setting. One guideline described the use of a scale validated in another setting. CONCLUSIONS: A minority of studies reported the use of observational scales to monitor the effect of palliative sedation. Future studies should be focused on establishing proper instruments, most adequate frequency and timing of assessment, and interdisciplinary evaluation of sedation depth and symptom control for palliative sedation.

Palliative sedation: reliability and validity of sedation scales.

CONTEXT: Observer-based sedation scales have been used to provide a measurable estimate of the comfort of nonalert patients in palliative sedation. However, their usefulness and appropriateness in this setting has not been demonstrated. OBJECTIVES: To study the reliability and validity of observer-based sedation scales in palliative sedation. METHODS: A prospective evaluation of 54 patients under intermittent or continuous sedation with four sedation scales was performed by 52 nurses. Included scales were the Minnesota Sedation Assessment Tool (MSAT), Richmond Agitation-Sedation Scale (RASS), Vancouver Interaction and Calmness Scale (VICS), and a sedation score proposed in the Guideline for Palliative Sedation of the Royal Dutch Medical Association (KNMG). Inter-rater reliability was tested with the intraclass correlation coefficient (ICC) and Cohen's kappa coefficient. Correlations between the scales using Spearman's rho tested concurrent validity. We also examined construct, discriminative, and evaluative validity. In addition, nurses completed a user-friendliness survey. RESULTS: Overall moderate to high inter-rater reliability was found for the VICS interaction subscale (ICC = 0.85), RASS (ICC = 0.73), and KNMG (ICC = 0.71). The largest correlation between scales was found for the RASS and KNMG (rho = 0.836). All scales showed discriminative and evaluative validity, except for the MSAT motor subscale and VICS calmness subscale. Finally, the RASS was less time consuming, clearer, and easier to use than the MSAT and VICS. CONCLUSION: The RASS and KNMG scales stand as the most reliable and valid among the evaluated scales. In addition, the RASS was less time consuming, clearer, and easier to use than the MSAT and VICS. Further research is needed to evaluate the impact of the scales on better symptom control and patient comfort.

Pressure during decision making of continuous sedation in end-of-life situations in Dutch general practice.

BACKGROUND: Little is known about pressure from patients or relatives on physician's decision making of continuous palliative sedation. We aim to describe experienced pressure by general practitioners (GPs) in cases of continuous sedation after the introduction of the Dutch practice guideline, using a questionnaire survey. METHODS: A sample of 918 Dutch GPs were invited to fill out a questionnaire about their last patient under continuous sedation. Cases in which GPs experienced pressure from the patient, relatives or other persons were compared to those without pressure. RESULTS: 399 of 918 invite GPs (43%) returned the questionnaire and 250 provided detailed information about their most recent case of continuous sedation. Forty-one GPs (16%) indicated to have experienced pressure from the patient, relatives or colleagues. In GPs younger than 50, guideline knowledge was not related to experienced pressure, whereas in older GPs, 15% with and 36% without guideline knowledge reported pressure. GPs experienced pressure more often when patients had psychological symptoms (compared to physical symptoms only) and when patients had a longer estimated life expectancy. A euthanasia request of the patient coincided with a higher prevalence of pressure for GPs without, but not for GPs with previous experience with euthanasia. GPs who experienced pressure had consulted a palliative consultation team more often than GPs who did not experience pressure. CONCLUSION: One in six GPs felt pressure from patients or relatives to start sedation. This pressure was related to guideline knowledge, especially in older GPs, longer life expectancy and the presence of a euthanasia request, especially for GPs without previous experience of euthanasia.

Considerations of physicians about the depth of palliative sedation at the end of life.

BACKGROUND: Although guidelines advise titration of palliative sedation at the end of life, in practice the depth of sedation can range from mild to deep. We investigated physicians' considerations about the depth of continuous sedation. METHODS: We performed a qualitative study in which 54 physicians underwent semistructured interviewing about the last patient for whom they had been responsible for providing continuous palliative sedation. We also asked about their practices and general attitudes toward sedation. RESULTS: We found two approaches toward the depth of continuous sedation: starting with mild sedation and only increasing the depth if necessary, and deep sedation right from the start. Physicians described similar determinants for both approaches, including titration of sedatives to the relief of refractory symptoms, patient preferences, wishes of relatives, expert advice and esthetic consequences of the sedation. However, physicians who preferred starting with mild sedation emphasized being guided by the patient's condition and response, and physicians who preferred starting with deep sedation emphasized ensuring that relief of suffering would be maintained. Physicians who preferred each approach also expressed different perspectives about whether patient communication was important and whether waking up after sedation is started was problematic. INTERPRETATION: Physicians who choose either mild or deep sedation appear to be guided by the same objective of delivering sedation in proportion to the relief of refractory symptoms, as well as other needs of patients and their families. This suggests that proportionality should be seen as a multidimensional notion that can result in different approaches toward the depth of sedation.

Continuous palliative sedation for cancer and noncancer patients.

CONTEXT: Palliative care is often focused on cancer patients. Palliative sedation at the end of life is an intervention to address severe suffering in the last stage of life. OBJECTIVES: To study the practice of continuous palliative sedation for both cancer and noncancer patients. METHODS: In 2008, a structured questionnaire was sent to 1580 physicians regarding their last patient receiving continuous sedation until death. RESULTS: A total of 606 physicians (38%) filled out the questionnaire, of whom 370 (61%) reported on their last case of continuous sedation (cancer patients: n=282 [76%] and noncancer patients: n=88 [24%]). More often, noncancer patients were older, female, and not fully competent. Dyspnea (odds ratio [OR]=2.13; 95% confidence interval [CI]: 1.22, 3.72) and psychological exhaustion (OR=2.64; 95% CI: 1.26, 5.55) were more often a decisive indication for continuous sedation for these patients. A palliative care team was consulted less often for noncancer patients (OR=0.45; 95% CI: 0.21, 0.96). Also, preceding sedation, euthanasia was discussed less often with noncancer patients (OR=0.42; 95% CI: 0.24, 0.73), whereas their relatives more often initiated discussion about euthanasia than relatives of cancer patients (OR=3.75; 95% CI: 1.26, 11.20). CONCLUSION: The practice of continuous palliative sedation in patients dying of cancer differs from patients dying of other diseases. These differences seem to be related to the less predictable course of noncancer diseases, which may reduce physicians' awareness of the imminence of death. Increased attention to noncancer diseases in palliative care practice and research is, therefore, crucial as is more attention to the potential benefits of palliative care consultation.

Predictors for persistent neuropathic pain--a Delphi survey.

BACKGROUND: Chronic neuropathic pain has a major effect on quality of life. In order to prevent neuropathic pain from becoming chronic and improve neuropathic pain care, it is important to identify predictors associated with the persistence of neuropathic pain. OBJECTIVE: To identify potential predictors associated with the persistence of neuropathic pain. STUDY DESIGN: A 2-round Delphi study. SETTING: University Medical Center and Pain Management Research Center. METHODS: A 2-round Delphi study was conducted among 17 experts in the field of neuropathic pain. Selection of the panel was based on the citation index ranking for neuropathic pain-related research and/or membership in the neuropathic pain special interest group of the International Association for the Study of Pain (IASP), complemented with experts with demonstrated field knowledge.Potential predictors were categorized according to the International Classification of Functioning, Disability and Health model. Participants were asked to identify important predictors, suggest new predictors, and grade the importance on a 0-10 scale. For the second round, predictors were considered important if the median score was ≥ 7 and the interquartile range (IQR) ≤ 3. RESULTS: In the first round, 20 predictors were selected and 58 were added by the experts (patient characteristics [15], environmental factors [25], functions & structure [4], participation & health related quality of life [14]). In the second round, 12 predictors were considered important (patient characteristics [4; e.g., depression, pain catastrophizing], environmental factors [surgery as treatment for neuropathic pain], functions & structure [6; e.g., allodynia, duration of the complaints], participation & trait anxiety/depression as a part of health related quality of life). Presence of depression and pain catastrophizing were considered the most important predictors for chronic neuropathic pain (median ≥ 8; IQR ≤ 2). LIMITATIONS: The study design did not include plenary discussion among the experts. The meaning of the individual topics used in this study could have been subject to interpretation bias. CONCLUSIONS: Overall, psychological factors and factors related to sensory disturbances were considered important predictors for persistence of neuropathic pain. Activity related factors and previously received paramedical and alternative treatment were considered to be less important. The list of possible predictors obtained by this study may serve as a basis for development of a clinical prediction rule for chronic neuropathic pain.