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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.

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.

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

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 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.

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)

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.

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.

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 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.

In this noninterventional study, the implementation of 'modern' pain management in clinical practice was investigated by recording the regular prescription, administration and efficacy of analgesic drugs. This resulted in a reproducible and superficial quality control design for hospitals. One hundred and fifty surgical patients were followed during 5 days postoperatively. For every patient, pain, mood and sedation were measured using visual analogue and verbal descriptive scores; the prescription of analgesics at set times and administered doses of analgesics were also recorded. Only paracodeine and naproxen were administered regularly as prescribed, unlike paracetamol and morphine. The prescribed daily dose of morphine was only received by 4.2% of all patients. Although the postoperative pain treatment pathway was considered to be improved after better education and communication, in fact the opposite was found. This is probably caused by traditional thinking, lack of control and time pressure on the hospital staff and the subservient attitude of the patient.

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.

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.