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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, Pharmacological interventions for the treatment of delirium in patients with cancer is controversial. This article compares olanzapine and haloperidol for the treatment of delirium in hospitalized 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). Electronic supplementary material The online version of this article (10.1186/s12885-019-5351-8) contains supplementary material, which is available to authorized users.

Item does not contain fulltext 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.

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. Key words: Neuropathic pain, persistent pain, systematic review, literature search, predictors, quality assessment, ICF-model

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 MgSO4 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 MgSO4 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 MgSO4 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 MgSO4 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 MgSO4 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.

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.

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.

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.

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.

Pain in patients with cancer can be refractory to pharmacological treatment or intolerable side effects of pharmacological treatment may seriously disturb patients' quality of life. Specific interventional pain management techniques can be an effective alternative for those patients. The appropriate application of these interventional techniques provides better pain control, allows the reduction of analgesics and hence improves quality of life. Until recently, the majority of these techniques are considered to be a fourth consecutive step following the World Health Organization's pain treatment ladder. However, in cancer patients, earlier application of interventional pain management techniques can be recommended even before considering the use of strong opioids. Epidural and intrathecal medication administration allow the reduction of the daily oral or transdermal opioid dose, while maintaining or even improving the pain relief and reducing the side effects. Cervical cordotomy may be considered for patients suffering with unilateral pain at the level below the dermatome C5. This technique should only be applied in patients with a life expectancy of less than 1 year. Plexus coeliacus block or nervus splanchnicus block are recommended for the management of upper abdominal pain due to cancer. Pelvic pain due to cancer can be managed with plexus hypogastricus block and the saddle or lower end block may be a last resort for patients suffering with perineal pain. Back pain due to vertebral compression fractures with or without pathological tumor invasion may be managed with percutaneous vertebroplasty or kyphoplasty. All these interventional techniques should be a part of multidisciplinary patient program.

brinkkemper t., klinkenberg m., deliens l., eliel m., rietjens j.a.c., zuurmond w.w.a. & perez r.s.g.m. (2011) Palliative sedation at home in the Netherlands: a nationwide survey among nurses. Journal of Advanced Nursing 67(8), 1719–1728. Abstract Aim. This paper is a report of a nationwide study conducted to assess experiences of nurses involved in palliative sedation at home after introduction of a physicians’ guideline for palliative sedation. Background. Most studies investigating the practice of palliative sedation focus on physicians’ practices and attitudes. However, little is known about experiences and attitudes of nurses. Methods. A web-based structured questionnaire was offered to 387 nurses providing medical technical care in 2007, assessing their experiences concerning decision-making, treatment policy and communication, focussing on the last patient receiving palliative sedation. Results. The questionnaire was filled out by 201 nurses (response rate 52%). The majority of respondents agreed with the indication for palliative sedation. However, 21% reported to have refused carrying out a palliative sedation in the preceding year. The general practitioner was not present at the start of palliative sedation in a third of the cases, but was available when needed. The sedation was considered insufficiently effective by 42% of the respondents. According to a third of the respondents, the level of sedation was not related to the required level of symptom relief nor were changes in dosage based on the severity of symptoms. Conclusion. Although the guideline for palliative sedation appears to be followed adequately in the majority of cases with respect to indication for palliative sedation and reportage. The survey findings revealed shortcomings in medication policy, communication, medical control over the start and continued monitoring of palliative sedation.

Complex Regional Pain Syndrome type 1 (CRPS-1) is a disabling condition characterized by sensory, autonomic, (vaso)motor and trophic disturbances, of which pain, swelling, color changes, limited mobility and change in temperature of the affected extremity are the most predominant [4,33]. CRPS-1 mainly develops after fractures, operations or a small trauma but also occasionally develops without a triggering event [26]. Different mechanisms are thought to play a role in the development of CRPS-1, providing a possible explanation for the heterogeneity seen within this patient population. One of the mechanisms proposed to be involved in the origin and maintenance of CRPS-1 is an exaggerated inflammatory response to tissue injury [2]. Scientific evidence supports the involvement of inflammatory processes in CRPS-1, whereby elevated cytokine levels [17], elevated activity of mast cells, neurogenic inflammatory reactions, [2,18] and markers of oxidative stress [6] were found. Systematic reviews addressing anti-inflammatory therapy provide limited evidence and contradictory conclusions [7,20,27]. However, in recent years additional studies have been published targeting the inflammatory component of CRPS-1. In light of the changing views about the involvement of inflammation, a comprehensive assessment of anti-inflammatory treatment approaches of CRPS-1 is warranted. The goal of the present topical review is to evaluate the effect of anti-inflammatory therapy on prevention, pain, range of motion and overall clinical improvement in CRPS-1.

A systematic literature review was conducted to determine the diagnostic validity of the criteria for sacroiliac (SI) joint pain as proposed by the International Association for the Study of Pain (IASP). Databases were searched up to September 2007. Quality of the studies was assessed using a Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Sensitivity, specificity, and diagnostic odds ratios (DOR) were calculated together with 95% confidence intervals (0). Statistical pooling was conducted for results of provocative tests. Eighteen studies were included. Five studies examined the pattern of SI joint pain, whereas another 5 examined stressing test specific for SI joint pain. None of the studies evaluated the diagnostic validity of the SI joint infiltration or the diagnostic validity of the IASP criteria set as a whole. in all studies, the SI joint selective infiltration was used as a gold standard; however, the technique, medications, and required pain relief after the infiltration varied considerably between the studies. Taking the double infiltration technique as reference test, the pooled data of the thigh thrust test (DOR, 18.461; Cl, 5.82 to 58.53), compression test (DOR, 3.88; Cl, 1.7 to 8.9), and 3 or more positive stressing tests (DOR, 17.16; Cl, 7.6 to 39) showed discriminative power for diagnosing SI joint pain. Perspective: This review of clinical studies focused on the diagnostic validity of the IASP criteria for diagnosing SI joint pain. A meta-analysis showed that the thigh thrust test, the compression test, and 3 or more positive stressing tests have discriminative power for diagnosing SI joint pain. Because a gold standard for SI joint pain diagnosis is lacking, the diagnostic validity of tests related to the IASP criteria for SI joint pain should be regarded with care. (C) 2009 by the American Pain Society

Purpose To examine what pain and adjuvant medication is prescribed in palliative care patients at home in The Netherlands. Methods In a nationwide, representative, prospective study in general practice in The Netherlands, prescribed medication was registered in 95 general practices with a listed population of 374070 patients. The GPs identified those who received palliative care in a retrospective survey of the 2169 patients who died within the 1-year study period. We analysed the analgesics, laxatives and anti-emetics that were prescribed during the last 3 months of life for these patients. Results The response rate of the survey was 74%. 425 patients received palliative care and 73% of them were prescribed pain medication: 55% a non-opioid analgesic (paracetamol, NSAIDs), 21% a weak opioid (tramadol, codeine), and 51% a strong opioid. Relatively more younger than older patients were prescribed strong opioids, and more cancer than non-cancer patients were prescribed an analgesic. During the last 3 months of life, the proportion of patients prescribed a non-opioid or a weak opioid increased gradually. The proportion of patients prescribed a strong opioid increased considerably nearing the patient's death. About one third of the non-cancer patients were prescribed strong opioids, mostly commencing in the last 2 weeks before death. In 48% of all patients with an opioid prescription, the GP did not prescribe a laxative. Conclusions Weak opioids and laxatives are frequently omitted from pain regimens in palliative care at home in The Netherlands. Copyright (C) 2008 John Wiley & Sons, Ltd

We present a newly developed continuous pain score meter (CPSM). The CPSM is based on the principles of the visual analog score (VAS), and electronically measures pain score in a continuous, instead of a single, manner. In this study, we determine the test-retest reliability of this meter. Thirty-two healthy volunteers received a reproducible pain stimulus on the right thumbnail and forearm. After a 1-minute interval the procedure was repeated. During the stimulus, pain was continuously measured with the CPSM, providing values of peak continuous pain score (CPS) and area under the CPS curve (AUC CPS). The intra-class correlation coefficient (ICC) and the 95% limits of agreement were used to assess the agreement between measurements. ICC of peak CPS (0.89 and 0.83) and AUC CPS (0.79 and 0.86) for nail and arm showed a good reproducibility. This study has successfully established the test-retest reliability of the CPSM. The real-time continuous pain measurement may provide more detailed information on a subjects' pain perception compared to a single VAS, in particular during an interval of pain stimuli.

Collins S, van Hilten JJ, Marinus J, Zuurmond WW, de Lange JJ, Perez RS. Development of a symptoms questionnaire for complex regional pain syndrome and potentially related illnesses: the Trauma Related Neuronal Dysfunction Symptoms Inventory. Objective To develop a questionnaire to evaluate symptoms of complex regional pain syndrome type I (CRPS-I), fibromyalgia, and repetitive strain injury to determine the test-retest reliability and investigate concurrence in the clinical manifestations of CRPS-I and fibromyalgia. Design The Trauma Related Neuronal Dysfunction Symptoms Inventory (TSI) was developed by determining the content validity and the practical use of the questionnaire. Furthermore, the test-retest reliability was assessed on 2 identical questionnaires filled out within a 7-day interval by CRPS-I and fibromyalgia patients. Setting Outpatient pain clinic of a Dutch medical center. Participants CRPS-I (n=26; mean age, 54y) and fibromyalgia patients (n=42; mean age, 45.4y). Interventions Not applicable. Main Outcome Measure Test-retest reliability calculated with intraclass correlation (ICC). Results Reliability scores were good for the whole questionnaire, its categories, and domains (ICC>.75) for both CRPS-I and fibromyalgia patients. Sensory complaints (except for change in cold perception), motor complaints, and visceral complaints (diarrhea and incontinence) were reported by both CRPS-I and fibromyalgia patients. A change in cold perception, discoloration, change in skin temperature, change in sweating behavior, change in the severity of edema during exercise, and trophic changes of skin were reported significantly more often by CRPS-I patients, whereas complaints of the (upper and lower) back, constipation, urine retention, and experiencing a dry mouth were reported significantly more often by fibromyalgia patients. Conclusions The TSI is a reliable instrument with good content validity, which can be used in the evaluation of similarities and differences between CRPS-I and fibromyalgia. The systematic evaluation of symptoms of CRPS-I and potentially related illnesses may provide a better basis for future research into the underlying mechanism(s).

Constipation is one of the most common problems in patients receiving palliative care and can cause extreme suffering and discomfort. The aims of this study are to raise awareness of constipation in palliative care, provide clear, practical guidance on management and encourage further research in the area. A pan-European working group of physicians and nurses with significant experience in the management of constipation in palliative care met to evaluate the published evidence and produce these clinical practice recommendations. Four potentially relevant publications were identified, highlighting a lack of clear, practical guidance on the assessment, diagnosis and management of constipation in palliative care patients. Given the limited data available, our recommendations are based on expert clinical opinion, relevant research findings from other settings and best practice from the countries represented. Palliative care patients are at a high risk of constipation, and while general principles of prevention should be followed, pharmacological treatment is often necessary. The combination of a softener and stimulant laxative is generally recommended, and the choice of laxatives should be made on an individual basis. The current evidence base is poor and further research is required on many aspects of the assessment, diagnosis and management of constipation in palliative care. Palliative Medicine (2008); 22: 796–807

To assess the effects of intravenous administration of the free radical scavenger mannitol 10% on complaints associated with complex regional pain syndrome Type I (CRPS I), a randomized, placebo-controlled, double-blinded trial was performed. Forty-one CRPS I patients according to the Bruehl et al diagnostic criteria, were included in 2 outpatient pain clinics of 2 university medical centers and randomly assigned to receive either 10% mannitol iv in 1 L 0.9% NaCL in 4 hours for 5 consecutive days or equal volumes of 0.9% NaCL (placebo). Patients in both groups received physical therapy according to protocol and rescue pain medication if required. Complaints on impairment and disability level and quality of life were assessed up to 9 weeks after baseline, with primary measurement points at 2, 6, and 9 weeks. Monitoring of pain using the visual analogue scale took place continuously during the course of the trial. Except for a significant improvement on a subscale of the Jebsen-Taylor hand function test, no significant differences were found between mannitol and placebo treatment. Changes in both groups in the course of the trial were small and clinically irrelevant on all measurement indices. We conclude that intravenous administration of 10% mannitol is not more effective than placebo in reducing complaints for CRPS I patients and provides no addition to already-established interventions for CRPS I. Whether 10% mannitol can provide beneficial effects for subgroups of CRPS I patients with a pathophysiological profile more closely fitting the presumed mode of action for this intervention remains to be established. Perspective This article addresses the efficacy of the intravenous administration of the free radical scavenger mannitol for treatment of CRPS type 1. This intervention is not more effective than placebo in reducing complaints for CRPS I patients and provides no addition to already-established interventions for CRPS I.

Psoas compartment block (PCB) is a potentially useful but controversial technique for lower limb surgery. We have conducted a systematic review of the efficacy and safety of PCB for anaesthesia and postoperative analgesia for hip and knee surgery. Relevant studies were identified within PubMed, EMBASE, and the Cochrane Library. The main outcome measure for anaesthesia was anaesthetic efficacy. For postoperative analgesia, the severity of postoperative pain was compared. The data were subjected to meta-analysis using relative risks with 95% confidence intervals (95% CI) for dichotomous variables and weighted mean differences with 95% CI for continuous variables. Thirty publications were included. PCB is an effective intervention for analgesia after hip and knee surgery. It appears superior to opioids for pain relief after hip surgery. This analgesic benefit may be extended beyond 8 h by the use of a catheter technique. Compared with Winnie's 3-in-1 block, PCB is associated with more consistent block of the obturator nerve. PCB may be an alternative to postoperative neuraxial block. Although PCB combined with sciatic nerve block and sedation is an effective technique for minor knee surgery, there is currently insufficient data to recommend the use of this approach for hip and major knee surgery. PCB is a safe and effective alternative for analgesia after hip and knee surgery. More research is required to define its role in the intraoperative setting and confirm potentially beneficial effects on variables such as perioperative haemodynamics and blood loss.

BackgroundPain 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/DesignA 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.DiscussionThis 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.

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.

Pain measurement in the nursing home is important, because when adequate actions are taken, it can improve the quality of life and prevent morbidity.The VDS and VAS, allthough they are unidimentional instruments, the most widely used measurement instruments. The MCGill Pain questionaire is the obvious instrument for non-malignant pain, the BPI for malignant pain. For patients with hampered communication skills the most obvious are DOLOPLUS2 or the PACSALC.

Objective To assess the validity of physician's judgements of symptoms associated with Complex Regional Pain Syndrome Type 1. Methods The validity of physicians' judgments was assessed using measurements with regard to presence and severity of pain, temperature and volume asymmetry, and reduction in active range of motion in 66 Complex Regional Pain Syndrome Type 1 outpatients. Measurements were performed using Visual Analog Scales and McGill (number of words chosen total) for pain, infrared thermography for temperature differences, water displacement volumeters for volume differences, and hand-held goniometers for active range of motion. Physicians were blind to the outcomes of the measurements. Results In general, physicians were capable of determining presence or absence of measured symptoms and indicate the direction of the symptom asymmetry. Establishing presence of temperature and volume asymmetries was, however, inadequate. Poor to moderate correspondence was found for the severity of individual symptoms between physicians' judgments and measurements. For the total number of assessments, correlation coefficients ranged from 0.39 for Volume to 0.68 for Pain. In general, lower correlations and percentages of association for Volume and Temperature were found. Monitoring changes between consecutive patient assessments showed poor correspondence between both assessment methods, with correlation coefficients ranging from 0.25 for Volume to 0.37 for Pain. Conclusions We conclude that establishing the presence of Complex Regional Pain Syndrome Type 1 symptoms, except for temperature and volume asymmetries, and monitoring of disease progression based on these symptoms can be performed by clinical judgment. The severity of the individual symptoms evaluated in this study should be measured with reliable and valid measurement instruments.

Objective: To determine the cost effectiveness and cost utility of acetylcysteine versus dimethyl sulfoxide (DMSO) for patients with reflex sympathetic dystrophy (RSD), from a societal viewpoint. Design: An economic evaluation was conducted alongside a double-dummy, double-blind, randomised, controlled trial. Patients were followed for 1 year. The primary outcome measure was the Impairment-level Sum Score (ISS). Utilities were determined by the EuroQOL instrument (EQ-5D). Both cost-effectiveness and cost-utility analyses were performed. Differences in mean direct, indirect and total costs were estimated. Corresponding 95% confidence intervals were calculated by bootstrapping techniques. Results: Both groups (DMSO, n = 64; acetylcysteine, n = 67) showed relevant improvement; no differences in effects were found. Only the total direct costs were significantly lower in the DMSO group for the period of 0-52 weeks. The incremental cost-effectiveness ratios showed that, in general, DMSO generated fewer costs and more effects compared with acetylcysteine. Post-hoc subgroup analyses on cost effectiveness suggested that patients with warm RSD could be best treated with DMSO and patients with cold RSD with acetylcysteine. These results were based on small subsamples. Conclusion: In general, DMSO is the preferred treatment for patients with RSD.

Pancreatic cancer has a very poor prognosis resulting in the death of 98% of patients. Pain may be severe and difficult to treat. Management of pain includes chemotherapy, radiotherapy, pharmacologic treatment, and neurolytic celiac plexus block. Recent reviews of the efficacy of neurolytic celiac plexus block however, have reached conflicting conclusions. In this paper, we present two patients with severe pancreatic cancer pain resistant to pharmacologic treatment. Analgesic effect following repeated neurolytic celiac plexus blocks with alcohol was limited in time. Post-mortem neurohistopathologic examination of the celiac plexus revealed an abnormal celiac architecture with a combination of abnormal neurons with vacuolization and normal looking neuronal structures (ganglionic structures and nerve fibers) embedded in fibrotic hyalinized tissue. Our results show that a neurolytic celiac plexus block with alcohol is capable of partially destroying the celiac plexus. These findings may explain the significant but short-lasting analgesic effect following neurolytic celiac plexus block with alcohol.

Background: Diagnosis of complex regional pain syndrome type I (CRPS I) is based on clinical observation of symptoms. As little information is available on the reliability of CRPS I diagnosis, we evaluated the agreement between therapists with regard to the presence and severity of CRPS I and its symptoms. Methods: The interrater reliability was evaluated in 37 presumed CRPS I patients by three observers; one consultant anesthesiologist and two resident anesthesiologists. Patients were assessed on the basis of Veldman's CRPS criteria. Results: The interrater reliability for diagnosing CRPS I was good for the majority of observer combinations. The percentage of agreement for the absence or presence of CRPS I was good (88%-100%). Cohen's Kappa's ranged from 0.60 to 0.86. The agreement for the mean symptom score ranged from 70.2% to 88.6%; Kappa's were lower and showed more variation. Interrater reliability for assessment of the severity of CRPS I and its symptoms was poor. Factors influencing the interrater reliability were symptom type, individual observers and sample population. Conclusion: Diagnosing CRPS I can be performed on the basis of clinical observation. Further assessment of severity of CRPS I and its symptoms should be performed with reliable and valid measurement instruments.

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.

A blinded meta analysis was performed on randomized clinical trials (RCT) on the medicinal treatment of reflex sympathetic dystrophy (complex regional pain syndrome type I) to assess the methodological quality and quantify the analgesic effect of treatments by calculating individual and summary effect sizes. The internal validity of 21 RCTs was investigated and the quality weighted summary effect size was calculated using a fixed effect model (Glass Δ). The methodological quality ranged from moderate to good (average 46%). Differences were found between the trials in inclusion/exclusion criteria, treatment methods, duration of treatments and trials, and measurement instruments. Statistical analysis was possible for four subgroups; one evaluating the analgesic effects of sympathetic suppressors in general (n = 12), one subgroup concerning the analgesic effects of guanethidine (n = 6), one investigating the analgesic effect of intravenous regional sympathetic blocks (n = 9), and one subgroup (n = 5) evaluating the analgesic effect of calcitonin. Except for the calcitonin subgroup (P = 0.002), the quality-weighted summary effect size of these subgroups were not significant. No significant analgesic effect by sympathetic suppressing agents could be established. Calcitonin seems to provide effective pain relief in reflex sympathetic dystrophy patients. The results of the present study show that weighting methodological quality influences the magnitude of the effect sizes of specific treatment methods. Future studies should control for methodological quality.

In terminally ill cancer patients with refractory pain, long-term spinal opioid therapy may provide a profound analgesia with minimal side effects. The reversibility of the technique and its efficacy throughout the body and for different types of pain are important advantages. For epidural administration, it is preferable to use lipid soluble opioids (sufentanil). For intrathecal administration, morphine is the best choice. The advantages of intrathecal administration over epidural administration are the need for lower doses because of a more direct administration at the receptor site, the easy positioning of the catheter, and less risk for migration of the catheter. In severe refractory pain which does not respond to spinal opioids, the use of non-opioids (e.g., a local anesthetic or an alpha-2 adrenoreceptor agonist) as coanalgesics may be recommended for improving pain relief. Long-term spinal opioid therapy at home has been made possible by technical and organizational development. In home care, only one physician should be the manager for the patient. Coordination should be optimized among patient, family, general practitioner, oncologist, anesthesiologist, home nurse, technician, and pharmacist.

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.

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 Conclusion Breakthrough cancer pain is an extremely heterogeneous condition.

Terminally ill patients suffering from intractable cancer pain are treated in our hospital on an outpatient basis with a percutaneous intrathecal (i.t.) catheter and a portable pump delivering morphine continuously. In a patient showing an increased demand of morphine the dose was raised from 1.5 to 2 mg/h, but pain intensity did not decrease. Subsequently a 1.5 ml dose of 5% lidocaine was administered; however, no motor or sensory block was observed. After controlling the catheter position and passage through the catheter, a sample of cerebrospinal fluid (CSF) was taken and the pH was measured. It was found to be outside the physiological range of 7.19 (normal range: 7.27-7.37), possibly explaining the decreased activity of the local anesthetic. The purpose of this study was to determine the influence of morphine, with or without sodium metabisulfite, on pH in vitro, using artificial CSF (ACSF) and on pH in vivo during i.t. administration of morphine. An in vitro model was used to measure pH changes by adding a morphine solution (concentrations of 0.5, 2, 5 and 10 mg/ml) with and without sodium metabisulfite to ACSF solutions (Elliott B). Fourteen patients were consecutively selected for continuous administration of morphine. An i.t. catheter was inserted, tunnelled and connected with an external pump (Provider 5500, Abbott, Chicago, IL). CSF was aspirated and pH was measured with a blood-gas system (Ciba-Corning 288, Medfield, USA). In vitro, morphine solutions with or without sodium metabisulfite added to an Elliott B solution (pH = 7.47, 37 degrees C) caused a concentration-related decrease in pH.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

Item does not contain fulltext Pain in patients with cancer can be refractory to pharmacological treatment or intolerable side effects of pharmacological treatment may seriously disturb patients' quality of life. Specific interventional pain management techniques can be an effective alternative for those patients. The appropriate application of these interventional techniques provides better pain control, allows the reduction of analgesics and hence improves quality of life. Until recently, the majority of these techniques are considered to be a fourth consecutive step following the World Health Organization's pain treatment ladder. However, in cancer patients, earlier application of interventional pain management techniques can be recommended even before considering the use of strong opioids. Epidural and intrathecal medication administration allow the reduction of the daily oral or transdermal opioid dose, while maintaining or even improving the pain relief and reducing the side effects. Cervical cordotomy may be considered for patients suffering with unilateral pain at the level below the dermatome C5. This technique should only be applied in patients with a life expectancy of less than 1 year. Plexus coeliacus block or nervus splanchnicus block are recommended for the management of upper abdominal pain due to cancer. Pelvic pain due to cancer can be managed with plexus hypogastricus block and the saddle or lower end block may be a last resort for patients suffering with perineal pain. Back pain due to vertebral compression fractures with or without pathological tumor invasion may be managed with percutaneous vertebroplasty or kyphoplasty. All these interventional techniques should be a part of multidisciplinary patient program.

A posterior lumbar plexus block or psoas compartment block (PCB) is an effective locoregional anesthetic technique for analgesia and anesthesia of the entire lower extremity including the hip. Since the first description in the early seventies, this technique has been modified based on advanced knowledge of the anatomical localization of the lumbar plexus and the improvement of technical equipment. This paper provides an overview of the history, clinical efficacy, and risk profile of the PCB focused on hip surgery. Current status and future expectations are discussed.

Hemodynamic variables can theoretically be influenced by a combined psoas compartment-sciatic nerve block (CPCSNB) owing to a relatively high systemic absorption of local anesthetics and extended vasodilatation in the anesthetized limb (hemisympatectomy). In this study we assessed and documented hemodynamic changes during CPCSNB for elective orthopedic surgery.Twenty consecutive patients scheduled for a total hip arthroplasty revision surgery were subjected to a CPCSNB with 150 mg bupivacaine (with epinephrine 1:200.000) 90 minutes before surgery (2 separate single-injection blocks: 30 mg bupivacaine for the sciatic nerve block and 120 mg bupivacaine for the psoas compartment block). Cardiac index, invasive arterial blood pressure, and heart rate were measured at baseline and 60 minutes after puncture using a minimally invasive cardiac output monitoring device (FloTrac/Vigileo™ system (Edwards Lifesciences, Irvine, CA)).Cardiac index did not change after a CPCSNB (preblock cardiac index 2.98 ± 0.54 l · min(-1) · m(-2) versus postblock cardiac index 2.99 ± 0.60 l · min(-1) · m(-2)). There was a significant reduction in mean arterial blood pressure (108 ± 16 mm|Hg vs. 99 ± 16 mm|Hg (P0.001)) and diastolic blood pressure (75 ± 9 mm|Hg vs. 68 ± 10 mm|Hg (P = 0.001)). Heart rate increased significantly (68 ± 9 beats · min(-1) vs. 73 ± 10 beats · min(-1) (P = 0.001)).CPCSNB did not affect cardiac index. Changes in arterial blood pressure and heart rate, although statistically significant, remained within an acceptable clinical range (10% variation). CPCSNB does not appear to induce clinically significant hemodynamic changes in this group of patients.

To determine the intrarater-reliability, interrater-reliability and normal reference scores of the Semmes Weinstein Monofilament test (SWM) of the feet of healthy subjects. In addition, the stability of the SWM for prospective use was assessed by determining systematic changes in sensory thresholds.Interrater-reliability was assessed on five locations of the plantar side of both feet using monofilaments 1.65, 2.36, 2.44, 2.83, 3.22, 3.61, 3.84, 4.08, 4.31, 5.56, 6.65 in 60 healthy subjects by two or three investigators (test day 1). Intrarater-reliability and systematic changes in sensory thresholds were assessed 3 weeks later (test day 22) by one investigator.Median interrater-reliability for the five test locations for both feet was poor to moderate. Median intrarater-reliability was good for the left foot and poor to moderate for the right foot. Significantly lower median sensory thresholds were found for the first SWM measurement at test day 22 compared to the first and second measurement of test day 1. Given the observed reliability of the SWM, a normal sensory score for the feet was situated between monofilament 3.22 and 4.08.The SWM are reliable when measured by one researcher. Systematic changes in sensory thresholds were observed; therefore, the stability of the SWM for use in prospective studies could not be verified.

Objective. The N-methyl-D-Aspartate (NMDA) receptor has been proposed as a primary target for the treatment of neuropathic pain. The aim of the present study was to perform a meta-analysis evaluating the effects of (individual) NMDA receptor antagonists on neuropathic pain, and the response (sensitivity) of individual neuropathic pain disorders to NMDA receptor antagonist therapy. Design. PubMed (including MEDLINE), EMBASE and CENTRAL were searched up to October 26, 2009 for randomized placebo controlled trials (RCTs) on neuropathic pain. The methodological quality of the included trials was independently assessed by two authors using the Delphi list. Fixed or random effects model were used to calculate the summary effect size using Hedges' g. Setting. NA. Patients. The patients used for the study were neuropathic pain patients. Interventions. The interventions used were NMDA receptor antagonists. Outcome measurements. The outcome of measurements was the reduction of spontaneous pain. Results. Twenty-eight studies were included, meeting the inclusion criteria. Summary effect sizes were calculated for subgroups of studies evaluating ketamine IV in complex regional pain syndrome (CRPS), oral memantine in postherptic neuralgia and, respectively, ketamine IV, and oral memantine in postamputation pain. Treatment with ketamine significantly reduced pain in postamputation pain (pooled summary effect size: −1.18 [confidence interval (CI) 95% −1.98, −0.37], P = 0.004). No significant effect on pain reduction could be established for ketamine IV in CRPS (−0.65 [CI 95% −1.47, 0.16], P = 0.11) oral memantine in postherptic neuralgia (0.03 [CI 95% −0.51, 0.56], P = 0.92) and for oral memantine in postamputation pain (0.38 [CI 95% −0.21, 0.98], P = 0.21). Conclusions. Based on this systematic review, no conclusions can yet be made about the efficacy of NMDA receptor antagonists on neuropathic pain. Additional RCTs in homogenous groups of pain patients are needed to explore the therapeutic potential of NMDA receptor antagonists in neuropathic pain.

Objectives. To explore the feasibility of intravenous magnesium administration as a potential candidate intervention for a large size trial in Complex Regional Pain Syndrome Type 1 (CRPS 1). Design. Randomized clinical trial. Setting. Outpatient pain clinic. Patients. Ten CRPS 1 patients. Interventions. Eight patients received 70 mg/kg magnesium sulphate infusions in 4 hours for 5 days. For blinding purposes, 2 patients received equal amount NaCl 0.9% solutions (data not analyzed or presented). Interventions were accompanied by standardized physical therapy. Outcome Measures. Pain was assessed using an 11-point Box scale (three times daily for a week) and the McGill Pain Questionnaire. Skin sensitivity was measured with the Semmes Weinstein Monofilaments, (other) impairments with the Impairment Level Sumscore. In addition, functional limitations (Radboud Skills Questionnaire, questionnaire rising and sitting down) and quality of life (Short Form-36 [SF-36], EuroQol) were evaluated. Assessments were performed at baseline, 1, 3, 6, and 12 weeks after intervention. Results. Mild systemic side effects were experienced and the infusions were locally well tolerated. Pain was significantly reduced at all follow up compared with baseline (T1: P = 0.01, T3: P = 0.04, T6: P = 0.02, T12: P = 0.02). McGill sensory subscale improved significantly at T1 (number of words chosen: P = 0.03 and pain rating index: P = 0.03). Impairment level ( P = 0.03) and quality of life (EuroQol P = 0.04, SF-36 physical P = 0.01) were significantly improved at T12. No improvement was found for skin sensitivity and functional limitations. Conclusion. Intravenous magnesium significantly improved pain, impairment and quality of life and was well tolerated. The results of this pilot study are encouraging and suggest that magnesium IV as a treatment in CRPS 1 should be further explored in a large size formal trial design.

Item does not contain fulltext In the Netherlands, the quality and availability of palliative care has improved markedly within the last decade. However, many open questions remain concerning the position of palliative care as an insurable product on the Dutch healthcare market. Therefore, we analysed the policies of all private Dutch healthcare insurance companies as well as the public insurance policy for extraordinary medical costs. We studied how and which parts of palliative care were reimbursed in 2007. We observed a huge variability in costs and reimbursement regulations reflecting a rapid turnover of products for palliative care due to various new developments on this specific field of medical care. We conclude that a better definition of the product 'palliative care' is necessary for patients, health care providers and insurance companies.

The sacroiliac joint (SI joint) is a known source of low back pain. In the absence of validated physical signs and imaging studies, the diagnosis of SI joint pain can be secured by positive response to SI joint intra-articular infiltration with local anesthetics. The current anatomical and histological knowledge concerning intra-articular structures of the sacroiliac joint is insufficient to explain the efficacy of this infiltration. Consequently, this study was undertaken to detect the intra-articular presence of substance P and calcitonin gene-related peptide (CGRP) positive nerve fibers, providing indirect evidence of nociceptive innervation of the SI joint. Free-floating sections, obtained from iliac and sacral cartilage and subchondral bone of the SI joint and adjacent ligamentous tissue, of 10 human cadavers were studied immunohistochemically. Tissue of nine human cadavers showed the presence of substance P and CGRP immunoreactivity in the superficial layer of sacral and iliac cartilage, and the surrounding ligamentous structures. Subchondral bone reacted weakly to the antisera used. These findings support the view that the SI joint may be capable of intra-articular nociception and may explain the positive response to the intra-articular deposition of local anesthetic.

PURPOSE OF REVIEW: We will evaluate the usefulness of the new intrathecal analgesic ziconotide in palliative care medicine. We will also examine the place and efficacy of neurolytic celiac plexus blockade in patients suffering from malignancy in the upper abdomen, after introducing better localization methods of the celiac plexus. RECENT FINDINGS: The analgesic effects of intrathecally administered ziconotide have been studied in patients suffering from pain due to AIDS or cancer. The results show a moderate to complete pain relief, significantly better than in placebo groups. However, safety studies show a high incidence of side effects. The technique of neurolytic celiac plexus blocks is refined by endoscopic ultrasound techniques. SUMMARY: The place of ziconotide in palliative care is doubtful due to unpredictable and sometimes long-lasting side effects. Real evidence on the efficacy and duration of neurolytic celiac plexus blocks for relief of pancreatic cancer pain is still not available. Future studies will need to be performed applying validated measurement instruments and assessing the patient's impression of the procedure's demands in terms of physical and mental tolerance.

▪ Abstract Background and Objectives: The aim of our study was to compare postoperative analgesic efficacy, and the extent of sensory and motor blockade of levobupivacaine, ropivacaine, and bupivacaine administered in a combined psoas compartment–sciatic nerve block (PCSNB) for total hip arthroplasty. Methods: Forty-five patients undergoing total hip arthroplasty under general anesthesia combined with PCSNB, were randomly assigned to receive either 50 mL levobupivacaine 3 mg/mL, 50 mL ropivacaine 4.5 mg/mL or 50 mL bupivacaine 3 mg/mL with epinephrine. Postoperative, the pain intensity at rest, the degree of motor block (Modified Bromage Scale) and the extent of sensory block (pin prick test) were recorded at 4, 8, 12, 24, and 48 hours following initial injection in a double blind fashion. Results: The postoperative pain intensity was low and did not differ between groups, except for a significantly lower pain intensity in group ropivacaine compared with group levobupivacaine at 4 hours. Five patients (11%), equally divided over three groups, needed parenteral rescue opiates postoperatively. The extent of sensory block was not different between the three groups. In each group the majority of patients showed no sensory block in dermatome L1. Group levobupivacaine initially showed the least motor impairment. Motor impairment was found to be significantly higher in bupivacaine group compared with both ropivacaine and levobupivacaine groups at 12 (P = 0.012) and 48 hours (P = 0.003). Conclusions: Levobupivacaine, bupivacaine and ropivacaine are equally effective for PCSNB in patients undergoing total hip arthroplasty. Residual pain may be due to the lack of sensory block in dermatome L1, suggesting that modification of this technique should be considered for this type of surgery. ▪

Background and Objectives A positive response to sacroiliac joint intra-articular infiltration with local anesthetics is used to confirm sacroiliac joint pain. However, current anatomical and histological knowledge concerning the anatomy of pain perception within the sacroiliac joint intra- and peri-articular structures is insufficient to explain the efficacy of this infiltration, because of the use of unspecific histochemical visualization techniques. Methods In this study, immunohistochemistry for calcitonin gene-related peptide (CGRP) and substance P was used to trace nociceptive fibers and receptors in the anterior and interosseous sacroiliac ligaments obtained from 5 human cadavers without history of sacroiliac joint pain. Results Microscopic analysis of stained slides showed presence of CGRP and substance P immunoreactive fibers. Thick, wavy, formed bundles were observed in dense and loose connective tissue, whereas single, beaded nerve fibers, occasionally ramified, were observed more frequently in the dense connective tissue and next to blood vessels. Based on their morphologic features, these immunoreactive structures were classified as receptors type IV. Additionally, receptors type II were found in anterior and interosseous ligaments, which contained CGRP or substance P immunoreactive free nerve endings. Conclusions We conclude that the presence of CGRP and substance P immunoreactive fibers in the normal anterior capsular ligament and interosseous ligament provides a morphological and physiological base for pain signals originating from these ligaments. Therefore, diagnostic infiltration techniques for sacroiliac joint pain should consider extra- as well as intra-articular approaches.

Complex Regional Pain Syndrome type I (CRPS I) is an illness which usually occurs due to major or minor tissue injury to the extremities. Because a unique pathophysiological mechanism for CRPS I has not yet been established, the diagnosis is based on observation and measurement of clinical symptoms and signs. In this study, a comparison was made between three sets of diagnostic criteria (the IASP, Bruehl et al. and Veldman et al.) based on patient reports and physicians' assessments of signs and symptoms associated with CRPS I, in 372 outpatients suspected of having CRPS I. Agreement between CRPS I diagnosis among the three sets was poor (κ-range: 0.29-0.42), leading to positive CRPS I diagnoses according to Veldman et al.'s criteria in 218 cases (59%), according to the IASP in 268 cases (72%), and according to Bruehl et al. in 129 cases (35%). Significant differences in patient profiles were found between the diagnostic sets for the number of patients reporting continuing disproportionate pain, larger area affected than the initial trauma (both p < 0.001), increase of symptoms due to exercise (p = 0.009), edema (p = 0.015), temperature asymmetry (p = 0.015), hyperesthesia, allodynia (both p < 0.001) and hyperalgesia (p = 0.036). Similarly, significant differences emerged for physicians' observations of hyperesthesia and allodynia (both p < 0.001). Highest combined values of sensitivity (SE) and specificity (SP) for the strongest cases of presence (n = 108) or absence (n = 62) of CRPS I were found for reported hyperesthesia (SE + SP:165%), allodynia (160%), observed color asymmetry (162%), hyperesthesia (157%), temperature asymmetry (154%) and edema (152%). The lack of agreement between the different diagnostic sets for CRPS I and the different clinical profiles that result from it may lead to different therapeutic and study populations, hampering adequate treatment and scientific development for this illness. We propose explicit reference to diagnostic criteria used in studies, and registration in trials of a broad variety of CRPS I features, as used in this study, to make subgroup phenotyping and post hoc analyses based on different diagnostic criteria possible.