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Background: Prescribing opioids for children and adolescents should be reserved for advanced life-limiting diseases and moderate-to-severe acute pain. Pediatric codeine use is discouraged by several authorities, but the effects of these recommendations are not fully known. We investigated opioid utilization trends among 0-18-year-olds and characterized those who filled ≥1 opioid prescriptions, with emphasis on those who did so >3 times within a year.Methods: The prevalence of filled opioid prescriptions among 0-18-year-old Norwegians in 2010-2018 (N = 77,942) was measured from nationwide healthcare registries. Characteristics, healthcare utilization, and other drug use of those who newly filled 1, 2-3, or >3 opioid prescriptions in 2011-2014 were compared to 2015-2018, excluding persons with cancer.Results: From 2010 to 2018, the prevalence of opioid use decreased from 9.0 to 7.0 per 1000 persons. The largest decrease was among children <12 years, from 4.1 to 0.4 per 1000 persons, mainly due to decreasing codeine use. The proportion of those who filled >3 opioid prescriptions was 2.1% in 2011-2014 and 3.1% in 2015-2018. Those with >3 dispensations had a median of 4 contacts/year with secondary healthcare (interquartile range 2-7); the most frequent diagnoses indicated post-surgery follow-up. Most commonly dispensed other drugs were non-steroidal anti-inflammatory drugs.Conclusions: Opioid dispensations for the young have declined in recent years. Multiple opioid dispensations were rare and associated with frequent healthcare utilization. Reducing codeine is in line with recommendations, but the effects of decreased opioid use on the quality of pain management remain unknown. [ABSTRACT FROM AUTHOR]

Background: Patients are often prescribed opioids at discharge from hospital following surgery. Several studies have shown that a large number of patients do not taper off but continue to use opioids after surgery. Tapering plans and follow-up after discharge may reduce opioid consumption.Methods: This is a single-centre, investigator-initiated, randomized, controlled trial. One hundred and ten preoperative opioid users, scheduled to undergo spine surgery at Aarhus University Hospital, Denmark, are randomized into two groups: 1) an intervention group receiving an individually customized tapering plan at discharge combined with telephone counselling one week after discharge; 2) a control group receiving no tapering plan or telephone counselling. The primary outcome is number of patients exceeding their preoperative intake one month after discharge. Secondary outcomes are withdrawal symptoms during the first month after discharge, number of patients tapering off to zero three months after discharge, patient satisfaction and contacts with the health care system within the first two weeks after discharge.Conclusion: Our study is expected to provide valuable information on opioid tapering after surgery in patients with preoperative opioid use. [ABSTRACT FROM AUTHOR]

Background: Parenteral opioids are used for pain relief in labour but there are little data for oxycodone in this context. The aim of this study was to evaluate the efficacy, foetal exposure and safety of subcutaneous oxycodone in the latent phase of labour.Methods: This pragmatic trial included 76 parturients, who received subcutaneous oxycodone for pain relief in the latent phase of labour according to the hospital protocol: an initial dose 0.1 mg/kg, and a second dose, 0.05 mg/kg, could be administered four hours later. Pain intensity and pain relief were assessed using a numerical rating scale of 0-10. After delivery, blood samples from the maternal and umbilical veins were collected, and plasma concentrations of oxycodone and its main metabolites were quantified using UPLC-MS/MS. The Apgar scores and maternal and neonatal adverse effects were recorded.Results: The foetal exposure at birth was low, the median oxycodone and oxymorphone umbilical vein plasma concentrations were 1.2 ng/mL (range 0.21-7.8) and 0.14 ng/mL (0-0.26), respectively. Pain scores decreased substantially, from a median pain score of 7/10 before oxycodone to median scores of 5/10 at 30 minutes after administration, 5/10 at 60 minutes and 6/10 at 120 minutes. The median Apgar score was 9 (range 2-10) at 1 minute and 9 (6-10) at 5 minutes. Maternal adverse effects were mild, and there were no oxycodone-related neonatal adverse effects.Conclusion: Subcutaneous oxycodone provided effective analgesia during the latent phase of labour. Newborn exposure at birth was low, and oxycodone was well-tolerated. [ABSTRACT FROM AUTHOR]

Background: Patients who have limb amputation are at risk of chronic pain, including phantom limb pain that can be challenging to treat. The aim of this study was to describe the incidence of pre-operative opioid usage and the incidence and risk factors for new persistent post-operative opioid usage in opioid-naïve patients after limb amputation.Methods: A retrospective study of all patients 18 years and older underwent upper or lower extremity amputations in Landspitali University Hospital between 2005 and 2015. Patients were considered to use opioids pre-operatively if they filled an opioid prescription 1-6 months prior to amputation and were considered to have persistent opioid use if opioid prescriptions were filled between post-operative months four to twenty-four. In addition to incidence estimate, uni- and multivariate analysis was performed to identify risk factors for persistent post-operative opioid usage.Results: Of 328 total patients, 216 (66%) were opioid naïve and 112 (34%) were chronic opioid users. Of the opioid-naïve patients surviving more than 3 months 40 (20%) developed persistent post-operative opioid usage. In multivariate analysis, factors independently associated with persistent post-operative opioid usage were younger age, male gender, pre-operative use of neuropathic medications or benzodiazepines and lower (opposed to upper) extremity amputation.Conclusion: Opioid naïve patients undergoing major amputation had a 20% chance of having a persistent opioid requirement following surgery. This could represent new-onset phantom limb pain or other chronic pain. Our findings should encourage perioperative multimodal efforts to reduce the burden of chronic pain after limb amputations. [ABSTRACT FROM AUTHOR]

Background: Hysterectomy is often carried out as same-day surgery. Treatment of postoperative pain is, therefore, of utmost importance to ensure timely discharge from hospital. Methadone has several desirable pharmacological features, including a long elimination half-life. Theoretically, a single intraoperative dose could provide long-lasting pain relief.Methods: This is a single-centre, investigator-initiated, randomised, double-blind study. Two-hundred and fifty women, scheduled to undergo hysterectomy at Horsens Region Hospital, Denmark, are randomized to receive methadone (0.2 mg/kg) or morphine (0.2 mg/kg) intraoperatively, 60 minutes before extubation. Primary outcomes are opioid consumption at 6 and 24 hours. Secondary outcomes include pain intensity at rest and during coughing at 1, 3, 6, 24 and 48 hours; patient satisfaction at 3 and 24 hours, postoperative nausea and vomiting at 6, 24 and 72 hours, adverse events in the postanaesthesia care unit (PACU) and time until readiness for discharge. Another outcome is persistent abdominal pain after 4 months.Conclusions: The study outlined in this protocol will provide important information about the use of methadone in same-day hysterectomy patients. The results will presumably be applicable to other types of surgery involving visceral pain. [ABSTRACT FROM AUTHOR]

Background: Life saving measures is the main focus in the initial treatment of major trauma. In surviving patients, chronic pain may be a serious problem, but the long term incidence and potential risk factors are not very well studied.Methods: All adult trauma patients included in the institutional trauma registry in 2007 were assessed for eligibility. Among exclusion criteria were: Injury Severity Score < 9, endotracheal intubation before or during admission, spinal cord lesion, known chronic drug or substance abuse, major surgery within 3 h after admission. A patient questionnaire was sent out 6 y after injury focusing on frequency and intensity of pain. A subgroup analysis was done in patients with thoracic injuries, comparing patients with epidural analgesia (EDA) and patients without.Results: Sixty-eight patients were included in the study. Sixty-nine percent reported pain 6 y after injury and 24% had severe pain. The severity of the injury was a risk factor for development of chronic pain, whereas pain during initial hospital stay was not. In patients with thoracic injuries there was no correlation between initial treatment with EDA and decreased incidence of chronic pain, however patient numbers were small. Opioids were the main analgesics used initially; no patients received non-steroidal anti-inflammatory drugs or peripheral nerve blocks during the first 24 h.Conclusion: Two thirds of the trauma patients had chronic pain 6 y after injury and one out of four had severe pain. The initial pain treatment was focused on opioids. [ABSTRACT FROM AUTHOR]

Background: Peripheral nerve blocks (PNB) are increasingly used for anaesthesia and postoperative pain control in acute orthopaedic limb surgery but rebound pain upon cessation of PNBs may challenge the benefits on the pain profile. We aimed to explore the pain profile following acute ankle fracture surgery under PNB anaesthesia and investigate if rebound pain could pose a clinical problem.Methods: Exploratory, observational study of adults scheduled for acute primary internal fixation of an ankle fracture under ultrasound-guided popliteal sciatic and saphenous ropivacaine block anaesthesia. Postoperatively, patients regularly registered pain scores while receiving a fixed analgesics regimen and patient controlled morphine on-demand. We analysed morphine consumption and depicted the detailed pain profiles as graphs allowing for visual analysis of pain courses, including rebound pain. Secondly, we compared the area under the curve and peak pain between relevant age-subgroups.Results: We included 21 patients aged 20-83. Depicted pain profiles reveal that PNB supplied effective and long lasting postoperative pain control, but cessation of the PNB led to intense rises in pain scores with six out of nine 20-60-year-olds reaching severe pain levels. The rebound was less pronounced in patients >60 years old, but nearly all reached moderate pain levels. Morphine consumption rates were high during the rebound.Conclusions: This study thoroughly analyses the post-PNB pain profile and suggests rebound pain is a clinically relevant and problematic issue with the potential to outweigh the PNB benefits, especially for younger patients. The conclusions are tentative, and a randomised study is pending. [ABSTRACT FROM AUTHOR]

Background: Safety data from long-term opioid therapy in the real world has been poorly studied in chronic non-cancer pain (CNCP). The aim was to design a pharmacovigilance data recording system and assess whether participation in this recording system improves pain management, enhancing patient's health status.Methods: A pharmacovigilance data recording system was conducted during 24 months. Data were self-reported by patients (pain, adverse events [AEs] and healthcare resources use) and physicians (morphine equivalent daily dose [MEDD] prescribed and suspected adverse drug reaction [ADRs]). Outcomes from patients with (case) or without (controls) suspected ADRs and cases follow-up were also compared with Spanish Pharmacovigilance System data.Results: A total of 753 patients were recruited in 897 visits. Fentanyl and tramadol were the most prescribed opioids, 89% with concomitant drugs, pregabalin being the one with the most potential drug interactions. Cases presented significantly higher pain intensity (VAS 67 ± 26 vs 59 ± 30 mm, P < 0.05), number of AEs (8 ± 6 vs 5 ± 3 AEs/patient, P < 0.01), polypharmacy related to pain (65% vs 34%, P < 0.01) and MEDD (139 ± 130 vs 106 ± 99 mg/d, P < 0.01) than controls. Furthermore, cases presented significant higher changes in pharmacological pain therapy due to pain, unplanned emergency visits and hospital admission than controls. Physicians notified 168 suspected ADRs mostly related to neurological or psychiatric events and 8% of them were previously unknown.Conclusions: This data recording system provided important information to achieve a better control of CNCP pharmacological pain therapy, improving patient's health status and reducing costs to the Health System. [ABSTRACT FROM AUTHOR]

Background: The present study aimed to determine which method of anaesthesia (spinal anaesthesia or general anaesthesia) is better in reducing post-operative analgesic requirements in patients undergoing major limb amputation for lower-limb ischaemia. Another aim was to find out if anaesthesiologists use neuraxial anaesthesia in high-risk patients despite abnormal coagulation profile or use of anticoagulation.Methods: The study was a retrospective cohort study. All patients undergone above-the-knee amputation or below-the-knee amputation due to peripheral artery disease between 1996 and 2010 were reviewed to evaluate post-operative opioid consumption and complications.Results: A total of 434 amputations in 323 patients were included in the study. The number of surgical complications, the need for surgical revision and the number of intensive care unit admissions were significantly higher in the general anaesthesia group. The need for post-operative opioid medication was significantly lower in patients with above-the-knee amputation and spinal anaesthesia. The use of post-operative epidural analgesia did not reduce analgesic requirements. In the present study, there were patients who received neuraxial anaesthesia despite abnormal coagulation profile or uninterrupted warfarin or clopidogrel. There were no reported cases of spinal or epidural haematoma.Conclusion: Patients with spinal anaesthesia had a lower rate of surgical complications, re-operations and intensive care unit admissions. Patients with above-the-knee amputation and spinal anaesthesia had a lesser need for opioid medication in the post-operative period than patients with general anaesthesia. Anaesthesiologists performed neuraxial anaesthesia and/or analgesia in high-risk patients despite abnormal coagulation profile or ongoing anticoagulation, but no adverse outcomes were reported. [ABSTRACT FROM AUTHOR]

Background: Cannabinergic medications have been postulated to demonstrate efficacy in the management of pain. The aim of this systematic review was to assess the analgesic efficacy and adverse effects of cannabinoids when used for the management of acute pain.Methods: A systematic review was performed by searching the MEDLINE, EMBASE and CENTRAL databases, and the World Health Organization International Clinical Trials Registry Platform for human randomized controlled trials that assessed the analgesic efficacy of cannabinoids compared to placebo or active comparators. The reported outcomes for analgesic efficacy and adverse effects in included studies were qualitatively analysed.Results: Seven studies, including 611 patients were included in the systematic review. In five studies, cannabinoids were found to provide equivalent analgesia to placebo, in one study the analgesia provided by cannabinoids was superior to placebo, and in one study cannabinoids provided analgesia that was inferior to that provided by placebo. No synergistic or additive analgesic effect was observed when cannabinoids were used in combination with opioids. In five of the seven studies, certain adverse effects were more frequent with cannabinoid treatment than with placebo or active comparator.Conclusion: On the basis of the available randomized controlled trial evidence, cannabinoids have no role in the management of acute pain. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated a positive association between smoking and addiction to opioids in patients with chronic non-malignant pain. This could be explained by a susceptibility in some patients to develop addiction. Another explanation could be that nicotine influences both pain and the opioid system. The objective of the study was to investigate whether smoking, former smoking ± nicotine use and nicotine dependence in patients with chronic non-malignant pain were associated with opioid use and addiction to opioids.Methods: The study was a cross-sectional study carried out at a multidisciplinary Danish pain centre. All patients aged 18 or more in treatment at the pain centre on the 1st of September 2013 were invited to participate in the study.Results: A total of 98 patients (65%) participated in the study. The prevalence of current smokers was twice as high as in the general population. The prevalence of patients using opioids was 54% and the prevalence of addiction to opioids was 6%. No significant differences in addiction were found between the different smoking groups, but smokers and former smokers using nicotine tended to use opioids more frequently and at higher doses than never smokers and former smokers not using nicotine.Conclusions: The study supports previous evidence that smoking is associated with chronic pain. Our data suggest that information about use of nicotine substitution in chronic non-malignant patients are relevant both in a clinical setting, but also in future studies of the association between smoking habits, pain and opioid use. [ABSTRACT FROM AUTHOR]

Background: Chronic pain has serious consequences for individuals and society. In addition, opioid prescription for chronic non-cancer pain (CNCP) has become more frequent. This study aims to examine the trends regarding the prevalence of CNCP, dispensed opioids, and concurrent use of benzodiazepine (BZD)/BZD-related drugs in the Danish population.Methods: Data from the cross-sectional national representative Danish Health and Morbidity Surveys (2000, 2005, 2010, and 2013) were combined with The Danish National Prescription Registry at an individual level. The study populations varied between 5000 and 13,000 individuals ≥16 years (response rates: 51-63%). Respondents completed a self-administered questionnaire, which included the analyzed items on identification of chronic pain (≥6 months).Results: From 2000 to 2013, the prevalence of CNCP increased and subsequently the annual prevalence of opioid use from 4.1% to 5.7% among CNCP individuals. Higher CNCP prevalence was related to female gender, no cohabitation partner, short education, non-Western origin, and overweight/obesity. In addition, women with CNCP, especially >65 years, became more frequent users of opioids and used higher doses than men. Concurrent use of BZD/BZD-related drugs decreased (13%) from 2010 to 2013, still one-third of long-term opioid user were co-medicated with these drugs.Conclusions: The use of opioids has increased in Denmark, especially among elderly women. The concurrent use of BZD/BZD-related drugs has decreased from 2010 to 2013, but still one-third of long-term opioid users were co-medicated. [ABSTRACT FROM AUTHOR]

Background: Although persons with chronic pain are frequent users of the health care system, they report poor satisfaction with health care services. Participants with persistent opioid use in Nord-Trøndelag Health Study (HUNT)3 report severe pain in spite of treatment. The aim of the study was to test the hypothesis that subjects with persistent opioid use have both a higher consumption of health care services and a poorer satisfaction than the remaining subjects reporting chronic pain.Methods: This cross-sectional study was based on linkage of self-reported data from the substudy (10,238 were invited, 6927 met the inclusion criteria) of health care use in HUNT3; a population-based health survey during the years 2006-2008 and the complete national registers of the Norwegian Prescription Database and the Cancer Registry of Norway. Patients with chronic pain are stratified according to the level of opioid use as persistent users of opioids, intermittent users, and persons not using opioids.Results: Persons with chronic non-malignant pain reported a higher consumption of all health care services compared to the control group. Consumption of health care services increased with increasing level of opioid use. Persons with persistent opioid use were highly satisfied with all health care services, although less satisfied than persons without chronic pain.Conclusions: Combined with previous findings of high levels of pain in spite of opioid treatment, the present findings indicate that symptomatic relief is not a prerequisite for patient satisfaction. The study shows higher patient satisfaction compared to previous studies. [ABSTRACT FROM AUTHOR]

Background: Renal impairment and the risk of toxicity caused by accumulation of opioids and/or active metabolites is an under-investigated issue. This study aimed at analysing if symptoms/adverse effects in opioid-treated patients with cancer were associated with renal function. Methods: Cross-sectional multicentre study (European Pharmacogenetic Opioid Study, 2005-2008), in which 1147 adult patients treated exclusively with only one of the most frequently reported opioids (morphine/oxycodone/fentanyl) for at least 3 days were analysed. Fatigue, nausea/vomiting, pain, loss of appetite, constipation and cognitive dysfunction were assessed (EORTC QLQ-C30). Glomerular filtration rate (GFR) was estimated using Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI Creatinine) equations. Results: Mild to severe low GFR was observed among 40-54% of patients. CG equation showed that patients with mild and moderate/severe low GFR on morphine treatment had higher odds of having severe constipation (P < 0.01) than patients with normal GFR. In addition, patients with moderate/severe low GFR on morphine treatment were more likely to have loss of appetite (P = 0.04). No other significant associations were found. Conclusion: Only severe constipation and loss of appetite were associated with low GFR in patients treated with morphine. Oxycodone and fentanyl, in relation to the symptoms studied, seem to be safe as used and titrated in routine cancer pain care. [ABSTRACT FROM AUTHOR]

Background: Lumiracoxib is a novel selective cyclooxygenase-2 (COX-2) inhibitor in development for the treatment of chronic and acute pain.Methods: This randomized, double-blind multicentre study enrolled 180 patients (aged 18-80 years) with moderate-to-severe pain (>or=2 on a 4-point categorical scale) within 48 h of unilateral total knee or total hip arthroplasty. Patients were randomized to receive lumiracoxib 400 mg once daily (n = 60), placebo (n = 60) or naproxen 500 mg twice daily (n = 60). The study consisted of a 12-h single-dose phase followed by a multiple-dose phase (up to 96 h or until discontinuation). The primary efficacy measure was the summed (time-weighted) pain intensity difference over 0-8 h after the first dose (SPID-8).Results: Lumiracoxib and naproxen were comparable and both treatments were superior to placebo for the primary efficacy measure, SPID-8. Both treatments were generally similar and also superior to placebo for the secondary efficacy measures during both the single- and multiple-dose phases for up to 96 h. Both active treatments were well tolerated.Conclusion: Lumiracoxib is an effective alternative to traditional non-selective non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of post-operative pain. [ABSTRACT FROM AUTHOR]

Background: Pre-incisional treatment with either N-methyl-D-aspartate (NMDA) receptor antagonists or non-steroidal anti-inflammatory drugs (NSAIDs) improves postoperative pain relief. This study examines the effect on postlaparoscopic cholecystectomy (LC) pain of a combination of dextromethorphan (DM), a NMDA-receptor antagonist, and tenoxicam, a NSAID, given preoperatively.Methods: Eighty-eight ASA I or II patients scheduled for LC were entered into a randomized, double-blind study and randomly allocated to one of four groups. Controls received 20 mg (4 ml) of chlorpheniramine maleate (CPM) IM and 4 ml of normal saline (N/S) IV. Group DM received 40 mg of DM (containing 20 mg of CPM) IM and 4 ml of N/S IV. Group T were given CPM 20 mg IM, and tenoxicam 40 mg (4 ml) IV. Group DM + T were given DM 40 mg (containing 20 mg of CPM) IM, and tenoxicam 40 mg IV. All treatments were given 30 min before skin incision. Analgesic effects were evaluated by Visual Analog Scale (VAS) pain scores at rest and during coughing, at 1, 2, 4, 12, 24 and 48 h after surgery. The time to the first request for meperidine for pain relief, and total meperidine consumption, were recorded for 48 h after surgery.Results: Compared to controls, patients given DM and DM + T first requested meperidine significantly later, had lower meperidine consumption, made fewer requests for meperidine, and had lower pain scores. There were significant differences between the DM + T and T groups at 2 and 4 h in both resting and incident VAS pain scores, the incidence of meperidine requests and the time to first meperidine injection. There were significant differences between groups DM and T at 1 h for resting pain and at 2 and 4 h for incident pain. Except for a significant difference in the incident pain score 1 h after surgery, there were no other differences in pain scores between the DM and DM + T groups. Neither synergistic nor antagonistic interaction was observed between DM and tenoxicam.Conclusions: The results suggest that pretreatment with DM, but not tenoxicam, provides significant pre-emptive analgesia for postoperative pain management in patients after LC surgery. Combining DM and tenoxicam also gives good pain relief. [ABSTRACT FROM AUTHOR]

Background: Comparative postoperative non-steroidal anti-inflammatory drug (NSAID) studies in orthopedic patients have usually been restricted in time to the first postoperative day. The opioid-sparing effect of NSAIDs may be beneficial postoperatively as long as pain otherwise restricts ambulation and rehabilitation. We therefore compared the analgesic efficacy of the maximum recommended doses of diclofenac and ketoprofen for 3 days after knee arthroplasty.Methods: We studied 64 knee arthroplasty patients, operated on under spinal anesthesia. In a randomized, double-blind and placebo-controlled fashion, the patients received either i.v. diclofenac 75 mg (n = 24), ketoprofen 100 mg (n = 24) or saline (n = 16) in the recovery room, followed by oral diclofenac 150 mg/day, ketoprofen 300 mg/day or placebo, respectively, for 3 days, supplemented by patient-controlled analgesia (PCA) with i.v. oxycodone.Results: The mean consumption of oxycodone during the first, second and third study days was 45.3, 22.3 and 15.2 mg in the diclofenac group, 43.5, 37.5 and 21.8 mg in the ketoprofen group, and 61.2, 45.9 and 36.1 mg, respectively, in the placebo group. Oxycodone consumption was significantly lower (P < 0.05) in the ketoprofen group than in the placebo group in the postoperative period 13-24 h and 61-72 h. Diclofenac was superior to placebo in the postoperative period 25-48 h (P < 0.01), 49-60 h (P < 0.05) and to ketoprofen at 49-60 h (P < 0.05). During administration of diclofenac on days 1-3 and ketoprofen on day 2, the mean pain scores (VAS) were lower than in the placebo group (P < 0.05). Six patients had difficulties in operating the PCA device. There were no differences in blood loss.Conclusion: We conclude that in the first day after knee arthroplasty (13-24 h), ketoprofen exerted an opioid-sparing effect. After day 1 (25-60 h), with the doses used, diclofenac proved to be better than placebo, whereas ketoprofen was not. [ABSTRACT FROM AUTHOR]

Background: The usefulness of intravenous patient-controlled analgesia (PCA) with opioids for postoperative analgesia is not well defined.Methods: We systematically searched (MEDLINE, EMBASE, Cochrane Library, bibliographies, any language, to January 2000) for randomised trials comparing opioid-based PCA with the same opioid given intramuscularly, intravenously, or subcutaneously. Weighted mean differences (WMD) for continuous data, relative risks (RR) and numbers-needed-to-treat (NNT) for dichotomous data were calculated with 95% confidence intervals (CI) using fixed and random effects models.Results: Data from 32 trials were analysed: 22 (1139 patients) were with morphine, five (682) with pethidine, three (184) with piritramide, one (47) with nalbuphine and one (20) with tramadol. In three morphine and one pethidine trial (352 patients), more patients preferred PCA (89.7% vs. 65.8%, RR 1.41 (95%CI 1.11 to 1.80), NNT 4.2). Combined dichotomous data on pain intensity and relief, and the need for rescue analgesics from eight morphine, one pethidine, one piritramide, and one nalbuphine trial (691 patients), were in favour of PCA (RR 1.22 (1.00 to 1.50), NNT 8). In two morphine trials (152), pulmonary complications were more frequently prevented with PCA (100% vs. 93.3%, RR 1.07 (1.01 to 1.14), NNT 15). There was equivalence for cumulative opioid consumption, pain scores, duration of hospital stay, and opioid-related adverse effects.Conclusion: These trials provide some evidence that in the postoperative pain setting, PCA with opioids, compared with conventional opioid treatment, improve analgesia and decrease the risk of pulmonary complications, and that patients prefer them. [ABSTRACT FROM AUTHOR]

Background: Administration of bupivacaine caudally has been used for postoperative analgesia after urogenital, rectal and lower abdominal surgery in children. Caudal opioids may offer analgesic advantages over bupivacaine alone but have been associated with side effects such as respiratory depression. Tramadol is an analgesic assumed to lack a respiratory depressant effect and has been shown to provide effective, long-lasting analgesia after epidural administration in adults and children. The aim of this study was to determine whether the addition of tramadol to bupivacaine caudally prolongs the duration of analgesia compared with bupivacaine alone, with respect to side effects, and whether caudal tramadol alone provides satisfactory analgesia.Methods: Sixty boys, aged 12-84 months, undergoing unilateral herniorrhaphy, were allocated randomly to three groups. Children in group B received 0.25% plain bupivacaine 1 ml kg(-1), group BT received an identical local anesthetic dose mixed with tramadol 1.5 mg kg(-1) and group T received caudal tramadol 1.5 mg kg(-1) in 0.9% sodium chloride in the same total volume (1 ml kg(-1)). Pain and demeanour assessments were made 1, 2, 3, 4, 6, 12 and 24 h after recovery from anesthesia with reference to a three-point scale.Results: Analgesia time (time between caudal injection and first administration of analgesic) in group BT (13.5+/-2.2 h) was significantly longer than in the other two groups (P<0.05). In group T, more patients required additional analgesia after surgery than in the other two groups (P<0.05). Pain scores in the three groups were similar up to 4 h after operation but the mean score in group T was higher than groups B and BT 4 and 6 h after operation (P<0.05). Significantly more patients who had received caudal bupivacaine alone or with tramadol had lower pain and demeanour scores during the first 24 h after operation compared with those in the tramadol group.Conclusion: Caudal administration of bupivacaine with the addition of tramadol resulted in superior analgesia with a longer period without demand for additional analgesics compared with caudal bupivacaine and tramadol alone without an increase of side effects. [ABSTRACT FROM AUTHOR]

Background: The additive effect of non-steroidal anti-inflammatory drugs administered with propacetamol after major orthopaedic surgery has not been studied. Thus, we performed a prospective, placebo-controlled study to assess the analgesic effects of ketoprofen in patients undergoing spinal fusion surgery and receiving propacetamol.Methods: Fifty patients undergoing spinal fusion surgery received either 100 mg of ketoprofen every 8 h or a placebo, postoperatively. All patients received propacetamol and morphine (intravenous titration followed by patient-controlled analgesia (PCA) over 24 h). Pain was assessed using a visual analogue pain scale (VASpi). Data are mean+/-SD.Results: During morphine titration, ketoprofen did not significantly reduce the dose of morphine (8+/-6 vs 11+/-4 mg, NS) whereas it significantly decreased VASpi (P<0.001). During PCA, ketoprofen significantly reduced morphine consumption (25+/-17 vs 38+/-20 mg, P=0.04) and VASpi (P=0.002). The total postoperative morphine consumption was significantly (33%) reduced with ketoprofen.Conclusion: Ketoprofen reduced morphine requirements and improved postoperative analgesia in patients undergoing major spinal surgery and receiving propacetamol. [ABSTRACT FROM AUTHOR]

Background: We designed this study to compare the postoperative analgesic effects of intrathecal morphine and nalbuphine, the endpoints being onset and offset of action.Methods: Geriatric patients scheduled for elective total hip replacement under continuous spinal anaesthesia were randomized to two double-blinded groups in the recovery room as soon as they experienced a pain score higher than 3 cm on the visual analogue scale (VAS, 0-10 cm). Either 160 microg morphine or 400 microg nalbuphine in 4 ml normal saline were administered intrathecally. Pain scores on VAS, rescue analgesia (diclofenac and morphine, not allowed during the first 60 min), and the adverse effects (respiratory depression, postoperative nausea and vomiting, itching) were recorded for 24 h after surgery.Results: The study was stopped after inclusion of 2 x 12 patients due to slow onset of analgesia in the morphine patients. In the nalbuphine group, when compared to the morphine group, the time to a pain score <3 cm (8+/-6 vs. 31+/-32 min, P<0.001), the time to the lowest pain score (18+/-11 vs. 66+/-75 min, P<0.001) and the time to the first systemic analgesic intervention for a pain score >3 cm (218+/-256 vs. 1076+/-440 min, P<0.05) were significantly shorter. The analgesic requirements during the first 24 h were significantly lower in the morphine group (P<0.001).Conclusion: We conclude that after total hip replacement, administration of intrathecal nalbuphine resulted in a significantly faster onset of pain relief and shorter duration of analgesia than intrathecal morphine. [ABSTRACT FROM AUTHOR]

Background: There is often no satisfactory treatment for chronic pain after spinal cord injury. We have previously reported that intrathecal (i.t.) administration of the adenosine A1-receptor agonist R-phenylisopropyl-adenosine (R-PIA) or the opioid morphine has anti-allodynic effects in a model of presumed chronic central pain after photochemically induced spinal cord injury in rats. In the present study, we set out to investigate the possible interaction between i.t. R-PIA and morphine in spinally injured rats.Methods: Sprague-Dawley rats displaying allodynia-like behaviors to mechanical and cold stimuli after photochemically induced spinal cord injury with minor motor deficits were used. R-PIA and morphine, either alone or in combination, were administered i.t. through an implanted catheter to lumbar spinal cord.Results: Cumulative doses of R-PIA or morphine dose-dependently reduced the mechanical allodynia-like behavior, with a threshold of 1 nmol and 1.5 nmol, respectively. When co-administrated, R-PIA and morphine produced marked suppression of mechanical allodynia at doses of 5 pmol and 7.5 pmol, respectively. The effect of i.t. co-administration of R-PIA and morphine on cold allodynia was comparable to i.t. R-PIA alone. The combination of R-PIA and morphine did not increase adverse effects such as motor deficits in comparison to either drug alone.Conclusion: These results demonstrate a supra-additive interaction between the adenosine A1-receptor agonist R-PIA and morphine to reduce mechanical allodynia-like behavior in rats with chronic spinal cord injury. The combination of R-PIA and morphine administered spinally may be superior to R-PIA or morphine alone for treating such pain. [ABSTRACT FROM AUTHOR]

Background: The study was aimed to evaluate the analgesic efficacy, postoperative comfort, recovery characteristics and side effects of three different analgesic agents administered prophylactically.Methods: Eighty patients undergoing day-case minor operative laparoscopy were randomly allocated into four groups to receive tenoxicam 20 mg i.v. (Group T), fentanyl 100 microg i.v. (Group F), 5 ml of bupivacaine 2.5 mg/ml for infiltration of trocar sites (Group B), 30, 10 and 5 min before incision respectively. Bupivacaine, 35 ml, 2.5 mg/ml was also administered into the pelvic cavity in Group B. Group P received only placebo. Postoperative pain, analgesic requirements, first response to verbal stimulus, first analgesic requirement, ability to walk without help, to drink and to void, blood pressures, SpO2 and respiration rates were recorded in the PACU. Postoperative pain was evaluated by verbal rating scale. Pain scores, analgesic requirements and side effects were evaluated by telephone calls until the 48th postoperative hour.Results: Postoperative pain scores were lower and time to requirement of rescue analgesics was longer in groups F and B compared to Group P. In the PACU, analgesic requirements were lower in Group B, compared to Group P. Nausea and vomiting were increased in Group F.Conclusion: Tenoxicam 20 mg i.v. was found to be ineffective whereas bupivacaine was superior to other groups in reducing pain and analgesic requirements. Bupivacaine also increased time to first analgesics and obtained better recovery characteristics, underlining its value in prophylactic pain management compared to the other two agents. [ABSTRACT FROM AUTHOR]

Background: Epidural opioid analgesia has become more popular for postoperative pain treatment in children. Epidural opioids are associated with adverse effects such as respiratory depression, excessive sedation, protracted vomiting, urinary retention and pruritus. Following minor surgery, ketoprofen has a synergistic effect with opioids, resulting in an improved analgesia without increase in incidence of adverse effects. To see whether this is also true following major surgery, we compared the effect of i.v. ketoprofen and placebo as an adjuvant to epidural sufentanil analgesia.Methods: A prospective, randomised, double-blind, placebo-controlled, parallel-group study design was used in 58 children, aged 1-15 years, receiving a standardised combined spinal-epidural anaesthesia. Intravenous ketoprofen or saline was provided as a bolus and a continuous infusion in addition to epidural sufentanil infusion, which was adjusted as clinically required. Epidural bupivacaine was used for rescue analgesia. The study drug infusion was discontinued when pain scores were <3 on a 0-10 scale for 6 h with an epidural sufentanil infusion rate of 0.03 microg kg(-1) h(-1).Results: Children in the ketoprofen group received less rescue analgesia (none/29 vs. 8/29 children in the placebo group). In the ketoprofen group, criteria to discontinue epidural sufentanil were achieved more often (14 vs. 6 children) before the end of the 72 h study period. Less children in the ketoprofen group suffered pruritus (13 vs. 4). The incidence of nausea/retching and vomiting was similar (11 vs. 12) in both groups.Conclusion: In this study, ketoprofen as a background analgesic to epidural sufentanil provided improved postoperative analgesia and reduced incidence of adverse effects of the epidural opioid. [ABSTRACT FROM AUTHOR]

Background: Postoperative respiratory disturbances may be the result either of depression of respiratory drive, or alteration of respiratory pattern.Methods: Using an inductance plethysmograph, we continuously recorded the breathing in 52 patients for 4 h after major thoracic, abdominal, and body surface surgery. The ventilatory response to hypercapnia was measured preoperatively, and at the start and end of the observation period.Results: From a variety of statistical measures of respiratory depression, it was found that the occurrence of apnoeas (breath times >10 s), did not correlate with measures of respiratory drive, or with dose or route of administration of opioid, site of surgery, pain, or drowsiness. Instead, the incidence of apnoeas correlated most closely with measures of respiratory pattern (standard deviation of breath times (r=0.72), the mean breath time (r=0.63), approximate entropy of the breath times (r= -0.32)). Twenty-nine percent of patients had some breath times (Ttot) longer than 20 s.Conclusion: We would conclude that changes in respiratory pattern are not closely correlated with changes in traditional measures of respiratory drive. [ABSTRACT FROM AUTHOR]

Background: Epidural infusion of morphine, usually with bupivacaine, for postoperative pain relief has proved to be safe and effective. Lidocaine with its short duration of action and low toxicity may be an alternative to bupivacaine. The clinical importance of the choice of local anaesthetic drug on mobilisation after lower abdominal surgery has not been studied previously. Methods: A total of 52 patients was randomised to epidural infusion of morphine (1.6–4.4 μg · kg-1 · h-1) with either lidocaine (0.44–0.98 mg · kg-1 · h-1) or bupivacaine (0.10–0.28 mg · kg-1 · h-1) in a double-blind fashion. The time to mobilisation, degree of pain relief, blood pressure, respiration and motor function were recorded at regular intervals postoperatively for 40 h. Serum concentrations of lidocaine, its main metabolite monoethylglycinexylidide (MEGX) and bupivacaine were measured at 3, 15 and 40 h. Results: There were no significant differences in the clinical characteristics between the two patient groups. There were no significant differences in the time from the end of surgery to the time the patients were able to stand without support (bupivacaine: median 24 h (interquartile range (IQR): 22–31), lidocaine: median 28 h (IQR 23–40), P=0.15) or were able to walk without support (bupivacaine: median 46 h (IQR 28–62), lidocaine: median 48 h (IQR 35–54), P=0.78). No significant differences between the groups were recorded with respect to pain relief, blood pressure, respiration, sedation score and motor function. The plasma concentration of lidocaine and bupivacaine increased significantly during the treatment period (P<0.01 for both drugs), but not the concentration of MEGX. The highest venous lidocaine concentration was 17.5 μmol/l and the highest bupivacaine concentration was 18.8 μmol/l. There was a significant correlation between the concentration of both lidocaine and bupivacaine and the concentration of α1-acid glycoprotein (AAG) (lidocaine: r=0.77, P<0.001, bupivacaine: r=0.60, P<0.001), suggesting that the free fraction of the drugs did not increase. No patients showed serious signs of toxicity. The epidural infusion rates remained stable in both groups during the study period. Conclusion: There were no clinically or statistically significant differences in the postoperative course after lower abdominal surgery in patients who received an epidural infusion of morphine combined with bupivacaine as compared to patients who received morphine with lidocaine. Further clinical studies to establish the place of lidocaine in postoperative epidural analgesia should be performed. [ABSTRACT FROM AUTHOR]

Background: Moderate to severe pain occurs after craniotomy in 60% of patients. We evaluated the feasibility and safety of patient-controlled analgesia (PCA) with oxycodone in neurosurgical patients, and compared the efficacy of paracetamol with ketoprofen.Methods: In the study there were 45 patients, who received either paracetamol 1000 mg or ketoprofen 100 mg three times a day. Oxycodone-boluses 0.03 mg/kg were given by PCA-device maximally three times an hour, lock-out time 10 min. The amount of oxycodone used, pain scores and side-effects were recorded.Results: The ketoprofen group required less oxycodone than the paracetamol group (medians 37.1 mg vs 19.6 mg, P < 0.05). The VAS scores were comparable between the groups at the beginning of the study, during the first postoperative evening and the next morning, but the paracetamol group had a higher score at the conclusion of the study (P < 0.05). The patients in both groups were equally satisfied with the pain relief. There were no differences in side-effects between the groups.Conclusions: PCA with oxycodone is a suitable method for pain control after craniotomy. No progressive hypoventilation, desaturation or excessive sedation were encountered. Ketoprofen appeared to be more effective than paracetamol. [ABSTRACT FROM AUTHOR]

Background: Although patient-controlled analgesia (PCA) with morphine provides a high degree of satisfactory postoperative analgesia in children, it is often associated with a high incidence of postoperative nausea and vomiting (PONV). Our aim in this study was to evaluate the prophylactic effect of dixyrazine, a phenothiazine with proven anti-emetic properties.Methods: The incidence of nausea and vomiting was studied in 60 children using PCA after major surgery. The patients were randomised to receive either dixyrazine 0.25 mg kg-1 or placebo on the induction of anaesthesia in a double-blind, placebo-controlled design. The anaesthetic technique was standardised. The PCA pump was programmed to deliver bolus doses of morphine of 20 micrograms kg-1 with a continuous background infusion of 8-10 micrograms kg-1 h-1. Nausea, vomiting, sedation and pain scores were noted every 3 h for a period of 24 h.Results: The morphine consumption of morphine was the same in both groups. During the stay in the recovery room the incidence of vomiting was 3% in the dixyrazine group compared to 30% in the placebo group (P < 0.05). On the ward, 57% versus 83% of the children vomited (P < 0.05). Rescue antiemetics were significantly lower, 30%, in the dixyrazine group compared to 60% in the placebo group (P < 0.05). Higher sedation scores were recorded for the dixyrazine group in the recovery room. No other adverse effects were found.Conclusion: A significant number of children using PCA with morphine after major surgery experience PONV. Although prophylactic dixyrazine reduces the incidence and severity of vomiting, the incidence still remains high. [ABSTRACT FROM AUTHOR]

Background: Opioids given as adjuncts to balanced inhalational anaesthesia augment postoperative nausea and vomiting (PONV). Tramadol, equipotent to pethidine, does not depress respiration, but can cause an increase in blood pressure and headache via its monoaminergic actions. Nalbuphine, ten times as potent as pethidine, has a ceiling respiratory depressant and ceiling analgesic effect at >0.3 mg · kg-1. We compared the effects of equipotent doses of tramadol and nalbuphine (3.0 and 0.3 mg · kg-1, respectively) given as analgesic with induction of anaesthesia on emesis during recovery from anaesthesia and on PONV and headache until 24 h after ENT surgery, using saline (0.2 ml · kg-1) and an equipotent dose of pethidine (1.5 mg · kg-1) as controls. Method: The study population (N=281) comprised 4 comparable subgroubs (N=69 to 71 each). Anaesthetic medications were standardised. Emesis during recovery from anaesthesia and nausea, vomiting, retching, headache and administrations of antiemetic and analgesics until 24 h after surgery were recorded. Results: Emesis and antiemetic requirements during recovery from anaesthesia were similar and infrequent in each group, as were the incidences of nausea alone (3 to 5%), vomiting alone (17 to 31%), and nausea with vomiting (10 to 22%) during the first 24 h after surgery. However, any complaint of PONV was least frequent in the saline and pethidine groups (32% and 37%, respectively) and most frequent in the tramadol and nalbuphine groups (49% and 52%, respectively; P<0.05 versus saline, both comparisons; P=NS versus pethidine, both comparisons). The times to onset and severity of PONV were similar in each group, but patients given nalbuphine most frequently (P<0.025) needed rescue antiemetic to treat PONV. Headache occurred with similar frequency in each group. Conclusion: It is concluded that tramadol, nalbuphine and pethidine have similar emetic effect in the doses and manner used, and that tramadol does not increase the incidence of postoperative headache when used as peroperative analgesic. [ABSTRACT FROM AUTHOR]

We report a case of severe low back pain during pregnancy in a woman with incomplete tetraplegia due to viral myelitis. The pain was interpreted as a radiculopathy in the presence of multiple herniated discs. Surgical intervention was not indicated and physiotherapy failed; therefore, a symptomatic drug treatment with oral analgesics was initiated. To minimise the total daily opioid dosage and the potential risk of a neonatal withdrawal syndrome due to opioids, the route of administration was changed from oral to epidural. Adequate pain relief was maintained with this regimen until caesarean section was necessary. The neonatal withdrawal symptoms after delivery were mild. Residual pain slowly diminished after delivery and the patient was able to discontinue opioid therapy. The aetiology of low back pain remains unclear and may be multifactorial. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Consumption of and satisfaction with health care among opioid users with chronic non-malignant pain" by A. B. Hansen, S. Skurtveit and colleagues in the June 2015 issue.

A response from the author of the article "Consumption of and satisfaction with health care among opioid users with chronic non-malignant pain" in the previous issue is presented.

Discusses the association of optimal intraoperative isoflurane concentration with reduced postoperative morphine needs in morbidly obese patients. Analysis of brain waves recorded during surgery; Post-operative morphine requirements of the patients; Use of an electroencephalogram variable called spectral edge frequency.

Background: We have compared the effects of pethidine, pentazocine and placebo in the treatment of post-anesthetic shivering.Methods: Forty-five patients who shivered after routine surgery were allocated randomly to receive normal saline (n=15), pentazocine 7.5 mg (n=15) or pethidine 17.5 mg (n=15).Results: After 10 min, 13 patients had stopped shivering in the pethidine group, which was significantly more than the incidence in the two other groups (placebo=2; pentazocine=4) (P<0.01). Pentazocine was not significantly different from normal saline in affecting shivering.Conclusion: We conclude that pentazocine 7.5 mg was not effective in the treatment of post-anesthetic shivering. [ABSTRACT FROM AUTHOR]