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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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

▪ 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.

The validity with respect to presence or absence of CRPS I according to Veldman's criteria was assessed for measured pain, temperature, volume differences and limitations in range of motion. Evaluated were 155 assessments of 66 outpatients, initially diagnosed with CRPS I, but many of them not so on follow up visits. Pain was measured with VAS and McGill, temperature by infrared thermometry, volume differences by water displacement volumeters and limitations in range of motion by universal goniometers. Sensitivity, specificity, positive and negative predictive value of the measurement instruments at different cut-off points was calculated. Combined symptom scores were evaluated in a similar fashion. High sensitivity was found for the VAS, McGill, and range of motion. The specificity was overall lower, but highest values were obtained for volume differences. The positive predictive value was good for all measurement instruments. Negative predictive value was lower, especially for measurement of temperature and volume asymmetries. If sensitivity and specificity are equally important, VAS>3 cm, McGill>6 words, temperature difference>or=0.4 degrees C, volume difference>6.5% and ROM limitation>15% provide the best results. Using these cut off values, the highest value of sensitivity and of sensitivity and specificity combined, was found for a combination of VAS, McGill and ROM. The highest value of specificity was found for different combinations of 3, 4 and 5 instruments, all containing the VAS. We conclude that the measured pain, temperature, volume and range of motion can be used as diagnostic indicators for establishing presence or absence of CRPS I.

Objectives: To construct a single indicator on impairment level for lower extremity Complex Regional Pain syndrome type I (CRPS I). Design: The Impairment level SumScore (ISS) for upper extremity CRPS I was adapted to be used for lower extremity evaluation. Medline literature search and research findings were used to adapt the upper extremity version of the ISS, with emphasis on reliability, responsiveness and validity of measurement instruments. Where needed, additional patient data was gathered to evaluate these aspects for different measurement instruments. Setting: An outpatient clinic of a university hospital in the Netherlands. Participants: Two groups consisting of 17 and 26 healthy volunteers, and two groups of respectively 40 and 18 lower extremity CRPS I patients according to Veldman's criteria. Main outcome measures: VAS and McGill pain scores, water displacement volumeter values, and physicians' and patients' assessment of CRPS I severity. Results: A combination of measurements, incorporating pain (VAS and McGill), temperature (infrared thermometer), volume (water displacement volumeter) and active range of motion (universal goniometer), was converted in a single score ranging from 5 to 50. The reliability, as well as the responsiveness was adequate. Conclusions: The lower extremity ISS permits evaluation of the most prominent symptoms in CRPS I, and can be used to monitor changes in CRPS I.

To compare the effects of two free radical scavengers, dimethylsulfoxide 50% (DMSO) and N-acetylcysteine (NAC), for treatment of complex regional pain syndrome I (CRPS I), a randomized, double-dummy controlled, double-blind trial was conducted. Two outpatient clinics of two university hospitals in The Netherlands participated in the study and 146 patients, were included over a period of 24 months. Patients were randomized into two treatment groups, one was instructed to apply DMSO 50% five times daily to the affected extremity, the second was treated with NAC 600mg effervescent tablets three times daily, both combined with placebo. Interventions were accompanied by pain medication, occupational therapy for upper extremity CRPS I and physical therapy for lower extremity CRPS I in specific circumstances. Treatment was given for 17 weeks, with a possibility to continue or switch medication after this period, up to 1 year following the onset of treatment. An impairment level sum score was the primary outcome measure. Upper and lower extremity skills and functions, and general health status were also evaluated. Overall, no significant differences were found between NAC and DMSO after 17 and 52 weeks on impairment level and general health status. Significant differences were found for subscores of lower extremity function, in favor of DMSO-treatment. Subgroup analysis showed more favorable results for DMSO for warm CRPS I and significantly better performance of NAC for patients with a cold CRPS I. Results tended to be negatively influenced if the duration of the complaint was longer. Treatment with DMSO and NAC are generally equally effective in treatment of CRPS I. Strong indications exist for differences in effects for subgroups of patients with warm or cold CRPS I: for warm CRPS I, DMSO-treatment appears more favorable, while for cold CRPS I, NAC-treatment appears to be more effective.

Objective: To assess the test–retest reliability of two questionnaires for measuring activity limitations in patients with Complex Regional Pain Syndrome type 1 (CRPS I) of the lower extremity. Design: Patients filled out the Walking Stairs Questionnaire and the Questionnaire Rising and Sitting Down twice during a one-week period. Setting: Outpatient pain clinic of a university hospital. Patients: Twenty-one outpatients with CRPS I of the lower extremity. Results: The Walking Stairs Questionnaire and the Questionnaire Rising and Sitting Down were reliable in terms of test–retest reliability as expressed by Spearman's r (range 0.79–0.90 and 0.85–0.89 respectively) and the ICC (range 0.78–0.84 and 0.84–0.87 respectively). Conclusion: Both questionnaires form a reliable tool for measuring activity limitations of patients with CRPS I of a lower extremity.

Background and Objectives Neuropathic cancer pain due to tumor growth near the brachial plexus is often treated with a combination of nonsteroidal anti-inflammatory drugs, tricyclic antidepressants, anticonvulsants, and oral or transdermal opioids. We propose placement of a catheter along the brachial plexus using a posterior approach for patients not responding to the above-mentioned treatment. Case Report We describe 2 patients with neuropathic cancer pain in the arm and shoulder despite treatment with dexamethasone, amitriptyline, gabapentin, opioids, and, in 1 patient, oral ketamine. An increase in daily opioid dosage did not relieve the pain but caused unacceptable side effects of nausea, vomiting, and sedation. Continuous administration of local anesthetics via a brachial plexus catheter inserted at the cervical level using a posterior approach resulted in a markedly improved analgesia and decreased opioid requirement. Conclusion Continuous brachial plexus block should be considered in patients with severe neuropathic cancer pain in the arm and shoulder. To achieve sufficient pain relief for prolonged periods of time, a catheter was inserted to block the brachial plexus using a posterior approach. This technique may be a valuable alternative to the interscalene approach because of the improved fixation of the catheter in the muscle sheet of the trapezius, splenius cervicus, and levator scapulae muscles, and the decreased likelihood of catheter dislodgment during neck movements.

We examined changes in the cardiorespiratory system of small children during surgical correction of strabismus with a laryngeal mask airway and spontaneous respiration with sevoflurane or halothane inhaled anesthesia. Fifty-one children, 1-7 yr old, having outpatient strabismus correction were randomized to sevoflurane (S) or halothane (H) in 66% nitrous oxide at 1.3 minimum alveolar concentration. Children breathed spontaneously through a laryngeal mask airway and were not pretreated with anticholinergics. The oculocardiac reflex (OCR), defined as a 20% decrease in heart rate (HR) from baseline, dysrhythmias, or sinoatrial arrest concomitant with ocular muscle traction occurred less frequently with sevoflurane than with halothane (S 38%, H79%, P = 0.009). The baseline HR was higher with sevoflurane (S 114 +/- 13 bpm, H 101 +/- 15 bpm, P = 0.002). The lowest HR occurred with halothane (S 95 +/- 22 bpm, H 73 +/- 19 bpm, P = 0.001). The incidence of dysrhythmias was higher in the halothane group (S 4%, H 42%, P = 0.004). Reductions in minute ventilation and PETCO(2) accompanied OCRs. Airway irritability was present with halothane only (S 0, H 3). Eleven children, of whom the majority had received halothane, required measures to correct SpO(2)95% or PETCO(2)60 mm Hg during maintenance anesthesia (S 11%, H 32%). Sevoflurane may be a more suitable anesthetic than halothane for operations involving traction on the ocular muscles with spontaneous respiration in children because of reduced incidence of OCR, airway irritability, and ventilatory disturbances.Some children experience a sudden slowing of the heart and impaired breathing when the surgeon pulls on the eye muscles during squint operations under anesthesia. Sevoflurane, a recently developed anesthetic vapor, may reduce this problem when compared with the established vapor halothane.

Background Six patients with severe neuropathic pain caused by a Pancoast tumor were treated with the continuous administration of local anesthetics. These patients had not responded to any other treatment, including nonsteroidal anti-inflammatory drugs, opioids, dexamethasone, tricyclic antidepressants, anticonvulsants, ketamine, and transcutaneous electric nerve stimulation. Interventions An axillary catheter was placed in the brachial plexus using a posterior approach that has not been described previously. A continuous infusion system of local anesthetics was delivered via a catheter. In two patients, the main purpose was to evaluate the technical possibilities and implications of this new approach. In all patients, the visual analogue scale score was evaluated until the patient died. In four additional patients, the quality of life and performance skills were recorded. Results In all patients, there was a significant reduction in the visual analog scale score, and there was an increase in performance skills and quality of life in four patients. No side effects occurred from this technique or from the continuous administration of local anesthetics. Conclusions We conclude that neuropathic pain may be treated by local anesthetics administered through an axillary catheter placed in the brachial plexus. This technique is reversible and is preferable to destructive procedures such as cordotomy.

Acute Reflex Sympathetic Dystrophy (acute RSD) was defined using a reproducible classification. Elevated temperature of the affected extremity ("calor"), measured by the dorsal side of the observer's hand and mentioned by the patient, pain ("dolor") measured by the Visual Analogue Scale (VAS), redness ("rubor"), edema ("tumor") and limited active range of motion ("functio laesa"), all contributed to the classification system. Patients scoring 4 to 5 positive symptoms were considered to have acute RSD. A prospective, randomized and double blind study was performed in 32 patients, all suffering from acute RSD. In all of these patients the primary injury was the result of a previous accident. One patient was taken out of the study because of his surgery. The study involved treatment with a fatty cream with 50% dimethyl sulfoxide (DMSO, group A), or without DMSO (placebo, group B), both for 2 months. All patients received physiotherapy applied within pain limits. Application of the creams resulted in both groups in an improvement of RSD-scores and VAS-scores after 2 months. However, the improvement of the RSD score in patients of group A (DMSO-group) was significantly (P < 0.01) better compared to group B. The results suggest a certain activity of DMSO 50% cream in patients suffering from RSD and is, therefore, recommendable.

This study was designed to compare the influence of epidural and spinal anesthesia on blood viscosity. We studied 22 patients, ASA classification I, who underwent elective knee or ankle arthroscopy and received epidural (n = 11) or spinal (n = 11) anesthesia with plain bupivacaine, and 10 control volunteers, who did not undergo surgery or receive anesthesia. There were significant decreases in hematocrit, plasma viscosity, and whole-blood viscosity at high (70 s-1), medium (0.5 s-1), and low (0.05 s-1) shear rates. The magnitude of changes was similar in all groups but occurred earlier in the control group (between 10 and 30 min) and after spinal administration (between 10 and 30 min) rather than after epidural administration (between 30 and 60 min) of bupivacaine. Only spinal anesthesia was associated with a decrease in erythrocyte deformability. The observed rheologic changes are attributed to hemodilution from the intravenous administration of fluids and the redistribution of fluid in the intravascular and extravascular compartments after sympathetic blockade and to postural changes rather than the effect of bupivacaine on blood elements.

Whole-lung lavage under hyperbaric oxygen conditions was performed in two patients suffering from severe respiratory insufficiency in pulmonary alveolar proteinosis. Under these conditions, gas exchange was maintained and the mixed venous partial pressure of oxygen and oxygen saturation showed increases to acceptable levels. This enabled us to limit the FIo 2 in order to extend the oxygen tolerance and to perform lavage procedures more effectively. Both patients showed a very significant improvement of their clinical course, and we conclude that elective use of hyperbaric oxygen in unilateral lung lavages should be considered in these severe cases.

Fourteen patients undergoing hip replacement surgery under psoas compartment block combined with general anaesthesia were studied. Group 1 (n = 7) received plain and Group 2 (n = 7) received 0.25% bupivacaine with adrenaline. The mean maximum peak concentrations were 1.93 (SEM 0.46) micrograms/ml and 1.04 (SEM 0.19) micrograms/ml at 10 minutes in groups 1 and 2 respectively. Bupivacaine concentrations were higher at all times in the group which received plain than the group receiving solution containing adrenaline. These differences were statistically significant at 10, 15 (p less than 0.05) and 30 minutes (p less than 0.025). The highest recorded plasma bupivacaine concentration was 4.54 micrograms/ml in one patient receiving plain bupivacaine. No patient developed any signs of toxic symptoms. The duration of analgesia was longer (p less than 0.005) in the group receiving bupivacaine with adrenaline. Bupivacaine 0.25% with adrenaline 1:200 000 is safe for psoas compartment block, and is recommended for hip surgery.