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).

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.

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.

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.

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.

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.

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.

Hemodynamic changes during a combined psoas compartment-sciatic nerve block for elective orthopedic surgery.

BACKGROUND: 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. METHODS: 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)). RESULTS: 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 (P < 0.001)) 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)). CONCLUSION: 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.

Palliative sedation at home in the Netherlands: a nationwide survey among nurses.

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.

Evidence based guidelines for complex regional pain syndrome type 1.

BACKGROUND: Treatment of complex regional pain syndrome type I (CRPS-I) is subject to discussion. The purpose of this study was to develop multidisciplinary guidelines for treatment of CRPS-I. METHOD: A multidisciplinary task force graded literature evaluating treatment effects for CRPS-I according to their strength of evidence, published between 1980 to June 2005. Treatment recommendations based on the literature findings were formulated and formally approved by all Dutch professional associations involved in CRPS-I treatment. RESULTS: For pain treatment, the WHO analgesic ladder is advised with the exception of strong opioids. For neuropathic pain, anticonvulsants and tricyclic antidepressants may be considered. For inflammatory symptoms, free-radical scavengers (dimethylsulphoxide or acetylcysteine) are advised. To promote peripheral blood flow, vasodilatory medication may be considered. Percutaneous sympathetic blockades may be used to increase blood flow in case vasodilatory medication has insufficient effect. To decrease functional limitations, standardised physiotherapy and occupational therapy are advised. To prevent the occurrence of CRPS-I after wrist fractures, vitamin C is recommended. Adequate perioperative analgesia, limitation of operating time, limited use of tourniquet, and use of regional anaesthetic techniques are recommended for secondary prevention of CRPS-I. CONCLUSIONS: Based on the literature identified and the extent of evidence found for therapeutic interventions for CRPS-I, we conclude that further research is needed into each of the therapeutic modalities discussed in the guidelines.

NMDA receptor antagonists for the treatment of neuropathic pain.

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.

Possible nociceptive structures in the sacroiliac joint cartilage: An immunohistochemical study.

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.

Prescribing of pain medication in palliative care. A survey in general practice.

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 374 070 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.

Intravenous magnesium for complex regional pain syndrome type 1 (CRPS 1) patients: a pilot study.

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.

Palliative care is not yet a well-defined product within the Dutch healthcare insurance system.

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.

Reliability of a continuous pain score meter: real time pain measurement.

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.

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).

Nociceptive nerve fibers in the sacroiliac joint in humans.

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.

The efficacy of levobupivacaine, ropivacaine, and bupivacaine for combined psoas compartment-sciatic nerve block in patients undergoing total hip arthroplasty.

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.