Combination of perineural and wound infusion after above knee amputation: A randomized, controlled multicenter study.

BACKGROUND: Post-operative pain after an above-knee amputation is often severe, and in the elderly patients the adverse effects of post-operative opioids are evident. We hypothesized that continuous perineural local anesthetic infusion (CPI) combined to a wound infusion will reduce acute pain and opioid consumption compared to placebo after above knee amputation. METHODS: Ninety-three patients going through an above knee amputation were recruited for this randomized, controlled trial. Two catheters were placed, one to the sciatic nerve sheath and one under the fasciae during the amputation. After two 10 mL boluses of ropivacaine 0.75% a post-operative infusion of ropivacaine 0.2% or placebo (NaCl 0.9%) at 2 mL/h was administered for 72 hours to both catheters. The primary outcome was average stump pain during the first 5 days. RESULTS: The mean intensity of stump pain during the first five post-operative days was 1.4 (0.8) in the CPI group and 1.9 (0.9) in the placebo group on VRS, mean (SD), P = .006. The opioid consumption on first five post-operative days did not differ between the groups. CONCLUSION: A combination of continuous perineural and wound local anesthetic infusion seems to diminish the intensity of stump pain after above knee amputation.

Topical Ropivacaine in Prevention of Post-Tonsillectomy Pain in Adults.

BACKGROUND: Post-tonsillectomy pain is 1 of the most intense postoperative pain conditions. However, optimal and sufficient postoperative analgesic treatment remains unclear. We investigated the effect of topical ropivacaine for post-tonsillectomy pain in 160 adult outpatient surgery patients over 2 postoperative weeks. METHODS: At the end of tonsillectomy, 2 swabs soaked in either 1% ropivacaine or saline were packed into the tonsillar beds for 5 minutes. We used ibuprofen and a combination of acetaminophen (500 mg)-codeine (30 mg) tablets as postoperative analgesics for 2 weeks. The primary outcome was pain intensity on swallowing measured on a numeric rating scale (NRSs) during the first postoperative week expressed as area under curve (AUC). The secondary endpoints included the worst pain experienced during the 2-hour follow-up in the postanesthesia care unit, pain intensity during the second postoperative week, and the number of ibuprofen and acetaminophen-codeine tablets consumed during the 2 postoperative weeks. RESULTS: During the first postoperative week, 120 patients out of 160 (75%) provided complete results, including data on their use of analgesics according to the instructions as well as completed and returned a questionnaire daily. A total of 101 patients (63%) did the same during the second postoperative week.Median (interquartile range [IQR]) of the primary outcome NRSs (AUC) was 38 (19) for the ropivacaine group and 37 (24) for the control group during the first postoperative week (P = .77, -1.0 estimated difference; 95% confidence interval [CI] for the difference, -7.0 to 5.0); no difference was found. Median (IQR) of NRS at rest (NRSr) (AUC) was 24.5 (19) for the ropivacaine group and 24 (22) for the control group during the first postoperative week (P = .96, 0.0 estimated difference; 95% CI for the difference, -5.0 to 5.0); no difference was found. Median (IQR) of the worst pain intensity values (NRSs or NRSr) (AUC) was 5 (3) for the ropivacaine group and 5 (3) for the control group (P = .44, 0.0 estimated difference; 95% CI for the difference, -1.0 to 0.5); no difference was found. During the second postoperative week, median (IQR) of the NRSs (AUC) was 17 (13) for the ropivacaine group and 21 (23) for the control group (P = .05, -4.0 estimated difference; 95% CI for the difference, -9.0 to 0.0) and median (IQR) of the NRSr (AUC) 10.5 (10) for ropivacaine group and 11 (13) for the control group (P = .42, -1.0 estimated difference; 95% CI for the difference, -5.0 to 2.0); no difference was found.The number of rescue analgesics (acetaminophen-codeine tablets) consumed during the second postoperative week was lower in the ropivacaine group than in the control group (median [IQR] of the consumption [AUC] was 10 [12] for the ropivacaine group and 16 [12] for the control group; P = .0008, -7.0 estimated difference; 95% CI of difference, -10 to -3.0). The groups showed no differences in overall risk for post-tonsillectomy bleeding. However, bleeding requiring hemostasis under local anesthesia was more common in the ropivacaine group (18% vs 8%, P = .048, 10% estimated difference; 95% CI for the difference, 0%-21%). CONCLUSIONS: Topical ropivacaine failed to reduce pain intensity during the first postoperative week. We observed no major adverse effects.

[Treatment of postoperative pain]. / Leikkauksenjälkeisen kivun hoito.

The quality and intensity of acute postoperative pain vary according to operation and patient-specific factors, whereby pain measurement is the starting point for the treatment. The principle of multimodal pain relief should be applied in the treatment in order to be able to improve pain relief. The quality of care can be improved and costs reduced with the assistance of an acute pain management team. The future aim is to systematically identify already before the operation those patients who are susceptible to intense postoperative pain and to the progression of pain into a chronic state, as well as an individual, research evidence based pain management plan.

Antiepileptic drugs for neuropathic pain and fibromyalgia - an overview of Cochrane reviews.

BACKGROUND: Antiepileptic drugs have been used for treating different types of neuropathic pain, and sometimes fibromyalgia. Our understanding of quality standards in chronic pain trials has improved to include new sources of potential bias. Individual Cochrane reviews using these new standards have assessed individual antiepileptic drugs. An early review from this group, originally published in 1998, was titled 'Anticonvulsants for acute and chronic pain'. This overview now covers the neuropathic pain aspect of that original review, which was withdrawn in 2009. OBJECTIVES: To provide an overview of the relative analgesic efficacy of antiepileptic drugs that have been compared with placebo in neuropathic pain and fibromyalgia, and to report on adverse events associated with their use. METHODS: We included reviews published in theCochrane Database of Systematic Reviews up to August 2013 (Issue 7). We extracted information from each review on measures of efficacy and harm, and methodological details concerning the number of participants, the duration of studies, and the imputation methods used, in order to judge potential biases in available data.We analysed efficacy data for each painful condition in three tiers, according to outcome and freedom from known sources of bias. The first tier met current best standards - at least 50% pain intensity reduction over baseline (or its equivalent), without the use of last observation carried forward (LOCF) for dropouts, an intention-to-treat (ITT) analysis, in parallel group studies with at least 200 participants lasting eight weeks or more. The second tier used data from at least 200 participants where one or more of the above conditions were not met. The third tier of evidence related to data from fewer than 200 participants, or with several important methodological problems that limited interpretation. MAIN RESULTS: No studies reported top tier results.For gabapentin and pregabalin only we found reasonably good second tier evidence for efficacy in painful diabetic neuropathy and postherpetic neuralgia. In addition, for pregabalin, we found evidence of efficacy in central neuropathic pain and fibromyalgia. Point estimates of numbers needed to treat for an additional beneficial effect (NNTs) were in the range of 4 to 10 for the important outcome of pain intensity reduction over baseline of 50% or more.For other antiepileptic drugs there was no evidence (clonazepam, phenytoin), so little evidence that no sensible judgement could be made about efficacy (valproic acid), low quality evidence likely to be subject to a number of biases overestimating efficacy (carbamazepine), or reasonable quality evidence indicating little or no effect (lamotrigine, oxcarbazepine, topiramate). Lacosamide recorded such a trivial statistical superiority over placebo that it was unreliable to conclude that it had any efficacy where there was possible substantial bias.Any benefits of treatment came with a high risk of adverse events and withdrawal because of adverse events, but serious adverse events were not significantly raised, except with oxcarbazepine. AUTHORS' CONCLUSIONS: Clinical trial evidence supported the use of only gabapentin and pregabalin in some neuropathic pain conditions (painful diabetic neuropathy, postherpetic neuralgia, and central neuropathic pain) and fibromyalgia. Only a minority of people achieved acceptably good pain relief with either drug, but it is known that quality of life and function improved markedly with the outcome of at least 50% pain intensity reduction. For other antiepileptic drugs there was no evidence, insufficient evidence, or evidence of a lack of effect; this included carbamazepine. Evidence from clinical practice and experience is that some patients can achieve good results with antiepileptics other than gabapentin or pregabalin.There is no firm evidence to answer the important pragmatic questions about which patients should have which drug, and in which order the drugs should be used. There is a clinical effectiveness research agenda to provide evidence about strategies rather than interventions, to produce the overall best results in a population, in the shortest time, and at the lowest cost to healthcare providers.

[Management of pain in palliative care]. / Kipu palliatiivisessa hoidossa.

Palliative pain management is usually successful, if the medication is strengthened in a stepwise manner in accordance with pain intensity, and initiation of a strong opioid is not delayed. Finding of a sufficiently effective dose of the opioid drug with simultaneous management of adverse effects requires continuous pain assessment and patient monitoring. In many cases it is possible to enhance analgesia by supplementing the medication with an antidepressant or an antiepileptic along with the opioid and paracetamol or the analgesic. Palliative radiotherapy will relieve tissue injury pain caused by bone metastases and soft tissue tumors as well as pain due to the possible nerve entrapments caused by them.

[Palliative (symptomatic) care of (imminently) dying patients]. / Kuolevan potilaan oireiden hoito.

The updated Current Care Guideline focuses on medical symptom treatment when curative treatment is no longer possible. Palliative care should be available to all dying patients at all health care levels. Pain should be treated prophylactically. Opioids are effective in cancer pain and should be chosen for moderate or severe pain in line with the WHO pain ladder. Treatment options for symptoms which call for acute interventions, such as intracranial hypertension, and options for dyspnoea, delirium, gastro-intestinal symptoms, ascites, dehydration and end-of-life treatment of elderly and demented patients are described.

Opioid trends in Finland: a register-based nationwide follow-up study.

The opioid epidemic in the U.S has gotten payers, prescribers, and policymakers alike interested in trends in opioid use. Despite no recognized opioid crisis in Europe, several countries have reported an increase in opioid-related deaths, which has further prompted discussion on the need of monitoring of opioid prescriptions. This study was conducted to offer information on opioid use during the escalation of the U.S. opioid epidemic in Finland, a Nordic country with universal tax-based health care. This is a nationwide retrospective register-based cohort study on all individuals in Finland who were dispensed opioids in 2009-2017 (n of unique patients = 1,761,584). By using the unique personal identification code assigned to every Finnish resident, we linked data from nationwide registers on dispensed drugs, medical history, and socio-demographic parameters. We report a wide set of patient demographics, dispensing trends for all opioid Anatomical Therapeutic Chemical (ATC) classes, and reasons for opioid initiation based on diagnostic coding for the most recent health care visit. For a cohort of incident opioid users with a four-year wash-out period (n = 1 370 057), we also present opioid use patterns in a three-year follow-up: the likelihood of becoming a persistent user or escalating from weak to strong opioids. A steady 7% of the Finnish population were dispensed opioids annually in 2009-2017. The mean annual quantity of dispensed opioids per opioid patient increased between 2009 and 2017 by 33%, reaching 2 583 oral morphine equivalent mg (OMEQ)/patient/year in 2017. The median quantity of dispensed opioids was lower: 315 OMEQ/year/patient. Depending on the opioid ATC class, there were either increasing or decreasing numbers of patients who had been dispensed said opioid class, and also in the mean quantity. The most common reason for opioid initiation was post-surgical pain (20%), followed by musculoskeletal pain (15%), injury (8.3%), and non-postsurgical dental pain (6.2%). 94% of new opioid initiators started with a weak opioid, i.e. codeine or tramadol. 85% of the patients who had been dispensed a weak opioid were not dispensed an opioid subsequently 3-6 months after the first one, and 95% of them had not escalated to a strong opioid in a 3-year follow-up. The number of patients dispensed opioids in Finland did not change during the escalation of the opioid epidemic in the U.S., but there were changes in the quantity of opioids dispensed per patient. Opioid therapy was typically initiated with weak opioid, the initial dispensed prescription was relatively small, and escalation to strong opioids was rare. A considerable share of patients had been prescribed opioids for chronic non-cancer pain - a type of pain where the risk-benefit ratio of opioids is controversial.

Risk-based targeting of adjuvant pregabalin treatment in laparoscopic cholecystectomy: a randomized, controlled trial.

Background and aims Pain is the most common reason for delayed discharge after day-case laparoscopic cholecystectomy. This study investigates a simple five-item questionnaire in evaluating the risk of postoperative pain in day-case cholecystectomy and the efficacy and safety of single-dose preoperative pregabalin on patients with multiple risk factors for pain. There are no previous studies on targeting adjuvant pain treatment based on the individual risk factors like the preoperative state of anxiety, acute or chronic pain, and the expectation of pain in day-case surgery. Methods One hundred and thirty patients scheduled for day-case laparoscopic cholecystectomy were evaluated with a five-item questionnaire assessing the risk for postoperative pain. The patients with multiple risk factors (n=60) were randomized to receive either pregabalin 150 mg or placebo, 1 h before surgery. The primary outcome was abdominal pain intensity on numerical rating scale (NRS) 1 h after surgery. Pain, analgesic consumption and adverse effects during first three postoperative days, and the length of hospital stay were also recorded. Results Pregabalin 150 mg given as an adjuvant analgesic preoperatively did not decrease postoperative abdominal pain or opioid consumption in the first hour after surgery compared to placebo in a preselected group of patients with multiple risk factors for postoperative pain (p=0.31). Preoperative anxiety assessed with a scale of 0-10 had a positive association with postoperative pain (p=0.045). Conclusions and implications This was the first trial on systematically selecting patients with a high-risk factor profile for postoperative pain as a target for a preventive adjuvant analgesic intervention. Although numerous previous studies have identified various risk factors, including those used in the current trial, it seems to be challenging to use these risk factors as predictive tools for targeting adjuvant analgesics in day-case surgery. Preoperative anxiety has a positive association with postoperative pain in day-case laparoscopic cholecystectomy, and this should be taken into account when treating these patients.

Efficacy and safety of epidural, continuous perineural infusion and adjuvant analgesics for acute postoperative pain after major limb amputation - a systematic review.

BACKGROUND AND AIMS: Treatment of pain following major limb amputations is often a clinical challenge in a patient population consisting mainly of elderly with underlying diseases. Literature on management of acute post-amputation pain is scarce. We performed a systematic review on this topic to evaluate the efficacy and safety of analgesic interventions for acute pain following major limb amputation. METHODS: A literature search was performed in PubMed, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews using the following key words: [(amputation) AND (pain OR analgesi* OR pain relief)] AND (acute OR postoperative). Randomized controlled studies (RCTs) and observational studies investigating treatment of acute pain following major amputations for any indication (peripheral vascular disease, malignant disease, trauma) were included. The review was performed according to the standards described in the PRISMA statement. The Cochrane quality assessment tool was used to evaluate the risk of bias in the RCTs. RESULTS: Nineteen studies with total of 949 patients were included. The studies were generally small and heterogeneous on outcomes, study designs and quality. There were 16 studies on epidural or continuous perineural analgesia (CPI). Based on five RCTs (n=268) and two observational studies (n=49), epidural analgesia decreased the intensity of acute stump pain as compared to systemic analgesics, during the first 24 h after the operation. Based on one study epidural analgesia caused more adverse effects like sedation, nausea and motor block than continuous perineural local anesthetic infusion. Based on one RCT (n=21) and eight observational studies (n=501) CPI seemed to decrease opioid consumption as compared to systemic analgesics only, on the first three postoperative days, and was well tolerated. Only three trials investigated systemic analgesics (oral memantine, oral gabapentine, iv ketamine). Ketamine did not decrease acute pain or opioid consumption after amputation as compared to other systemic analgesics. Gabapentin did not decrease acute pain when combined to epidural analgesia as compared to epidural analgesia and opioid treatment, and caused adverse effects. CONCLUSIONS: The main finding of this systematic review is that evidence regarding pain management after major limb amputation is very limited. Epidural analgesia may be effective, but firm evidence is lacking. Epidural causes more adverse effects than CPI. The results on efficacy of CPI are indecisive. The data on adjuvant medications combined to epidural analgesia or CPI is limited. Studies on efficacy and adverse effects of systemic analgesics for amputation pain, especially concentrating on elderly patients, are needed.

Do surgical patients benefit from perioperative gabapentin/pregabalin? A systematic review of efficacy and safety.

BACKGROUND: Gabapentin and pregabalin have antiallodynic and antihyperalgesic properties useful for treating neuropathic pain. These properties may also be beneficial in acute postoperative pain. In this study we evaluated randomized, controlled trials examining the analgesic efficacy, adverse effects, and clinical value of gabapentinoids in postoperative pain. METHODS: A systematic search of Medline, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL) databases yielded 22 randomized, controlled trials on perioperative administration of gabapentinoids for postoperative pain relief. RESULTS: Pain relief was better in the gabapentin groups compared with the control groups. The opioid-sparing effect during the first 24 h after a single dose of gabapentin 300-1200 mg, administered 1-2 h preoperatively, ranged from 20% to 62%. The combined effect of a single dose of gabapentin was a reduction of opioid consumption equivalent to 30 +/- 4 mg of morphine (mean +/- 95% CI) during the first 24 h after surgery. Metaregression analysis suggested that the gabapentin-induced reduction in the 24-h opioid consumption was not significantly dependent on the gabapentin dose. Gabapentin reduced opioid-related adverse effects, such as nausea, vomiting, and urinary retention (number-needed-to-treat 25, 6, and 7, respectively). The most common adverse effects of the gabapentinoids were sedation and dizziness (number-needed-to-harm 35 and 12, respectively). CONCLUSIONS: Gabapentinoids effectively reduce postoperative pain, opioid consumption, and opioid-related adverse effects after surgery. Conclusions about the optimal dose and duration of the treatment cannot be made because of the heterogeneity of the trials. Studies are needed to determine the long-term benefits, if any, of perioperative gabapentinoids.

Spinal analgesia for severe cancer pain: A retrospective analysis of 60 patients.

BACKGROUND AND AIMS: Pain is highly prevalent in advanced cancer, and in some patients refractory to conventional opioid treatment. For these patients, invasive methods of pain relief should be considered. Spinal administration of opioids has been shown to be an effective alternative in refractory cancer pain. The aim of this retrospective study was to collect information on the use of spinal analgesia for cancer pain in Helsinki University Hospital. METHODS: A retrospective patient chart study of all cancer patients with spinal analgesia, either intrathecal or epidural, in a single academic center during a five year period (n=60). RESULTS: Forty-four patients were treated with intrathecal (IT) and sixteen with epidural (EP) technique. The most common indication for spinal analgesia was pain refractory to systemic analgesics. Good analgesia was achieved in 50% and 70% of the patients in the EP and IT groups, respectively. The median daily systemic opioid doses prior to spinal analgesia were 874.5mg and 730.5mg as oral morphine equivalents in the IT and EP groups, respectively. The systemic opioid could be discontinued or significantly reduced in 83% of the patients. Morphine was used in all IT infusions and most EP infusions, mostly combined with bupivacaine 10mg (IT) or 66mg (EP). The median starting doses of morphine were 3mg/day (IT) and 19mg/day (EP) and were increased during titration 27% to 3.8mg/day (IT) and 91% to 36.2mg/day (EP). Clonidine (median 0.015mg/day IT and 0.15mg/day EP) and/or ketamine were used as adjuvants. The average titration time to stable analgesia was 7-9 days. Numbness in lower limbs was reported by 24% of the IT group. On average, catheters were placed 98 and 61 days before death in IT and EP groups, respectively. No serious complications occurred. Catheter dislocation occurred in 27% of all sixty patients during follow-up. Treatment was discontinued in 10 patients because of catheter dislocation (n=7) or local infection (n=3). CONCLUSIONS AND IMPLICATIONS: Spinal administration of opioids is a safe and effective method of pain management in patients with severe cancer pain and can greatly reduce the need of systemic opioids. We are implementing closer collaboration with oncologists to provide spinal analgesia to more patients and earlier to reduce suffering. Catheter dislocation led to discontinuation of spinal analgesia in 17% of the patients and we are evaluating new ways to prevent catheter dislocation. The initial median spinal opioid dose was too low in both groups, and we are now using higher initial doses. A common adverse effect was numbness of the lower limbs, regardless of the relatively low doses of spinal bupivacaine. We now use lower doses and introduce the intrathecal catheter higher at L1-2 to reduce motor blockade at the level of conus. As an initial intrathecal infusions we suggest: morphine dose calculated using an oral to intrathecal ratio of 1:100 (unless the patient is elderly or already drowsy), clonidine dose 30µg/day and bupivacaine dose 7.5mg/day.

New approach for treatment of prolonged postoperative pain: APS Out-Patient Clinic.

BACKGROUND AND AIMS: Persistent postoperative pain (PPP) is a significant clinical problem. Several patient-related risk factors for PPP have been identified, including a previous chronic pain problem, young age, female gender and psychological vulnerability. Intra- and postoperative risk factors include surgical complications such as infections, haematoma, nerve damage and repeated surgery. As the length of hospital stay has been shortened, some patients may be discharged despite ongoing pain and insufficient analgesic medication. The challenge is to identify patients at high risk of developing PPP and to create a targeted care pathway to ensure effective and safe pain treatment especially in the subacute postoperative phase at home. This observational study describes the first two years of the Acute Pain Service Out-Patient Clinic (APS-OPC) at the Helsinki University Hospital. METHODS: Patient characteristics, known risk factors, and details of treatment of PPP for the first 200 patients referred to our APS-OPC were retrospectively collected from the medical records. The APS-OPC clinic functions in close collaboration with the Multidisciplinary Pain Clinic (MPC), and the number of patients in need of physiotherapist, psychologist or psychiatrist counselling was recorded, as well as the number of patients referred to the MPC for further PPP management. RESULTS: Patients were referred to the APS-OPC from different surgical specialities, the two most common being thoracic and orthopaedic surgery. Seventy per cent of the patients (139/200) presented symptoms indicating neuropathic postsurgical pain. The patients had, on average, five risk factors for PPP. The median time from surgery to the first contact to the APS-OPC was two months, and the median duration of follow-up was 2.8 months (0-16 months). The median number of contacts with APS-OPC was 3 (range 1-14). Every fourth patient needed only one contact to the APS-OPC. Nineteen per cent of the patients had an appointment with the physiotherapist and 20% with a psychologist or psychiatrist. At discharge after surgery, 54% of the patients were using weak opioids, 32% strong opioids and 71% gabapentinoids; at discharge from the APS-OPC, these numbers were 20%, 6% and 43%, respectively. Twenty-two per cent of the patients were referred to the MPC for further pain management. CONCLUSIONS: The APS-OPC provides a fluent fast-track method of ensuring effective multimodal analgesia in the subacute recovery phase after surgery. Even strong opioids can be safely used after discharge and then tapered off in close supervision of the APS-OPC anaesthesiologist. As the APS-OPC was implemented in close collaboration with the MPC, the multidisciplinary resources are easily available during the course of the APS-OPC treatment. IMPLICATIONS: The first two years of the APS-OPC have shown that a significant number of surgical patients benefit from continuing active pain management after discharge from hospital. This fast-track service provides physician-supervised titration of analgesics to improve pain relief in the subacute phase. An important task of the APS-OPC is to ensure that strong opioids are not inappropriately continued after recovery. Another goal of the APS-OPC is to identify patients in need of multidisciplinary pain management services to prevent chronification.

Systematic review on analgesics given for pain following tonsillectomy in children.

In this systematic review effectiveness of analgesics for pain after tonsillectomy in children was evaluated and trial methodology of the included studies explored. Databases were searched for randomised, controlled studies on systemic paracetamol, NSAIDs and opioids. Eighty-four studies were evaluated for inclusion. Thirty-six studies were included and 48 excluded. Only in two studies investigated analgesics were given postoperatively for pain. All other studies investigated prophylactic administration of analgesics. Only five studies were truly placebo controlled. Trial methodology of the included studies varied greatly in respect to analgesics and doses used, duration of follow-up periods, methods of pain measurement, rescue analgesics and criteria for administrating rescue analgesia used. Sensitivity of studies was often unclear. Only 16 out of 36 studies were considered to be sensitive. Because of highly variable methodology and lack of sensitivity only limited conclusions on clinical efficacy of analgesics investigated can be drawn. No analgesic in single prophylactic dose provided analgesia for day of operation. Further studies are needed to find the optimal analgesic(s) for pain after tonsillectomy in children.

A systematic review of trial methodology, using the placebo groups of randomized controlled trials in paediatric postoperative pain.

Trial methodology was evaluated in paediatric analgesic studies. Databases were searched for randomised, placebo controlled studies of systemic paracetamol, NSAIDs and opioids administered for acute postoperative pain in children. Eighty-three studies met the inclusion criteria and 40 were included for the analysis. Analgesics were administered for established postoperative pain in two studies only. In all other studies they were administered in a prophylactic manner. As study design and sensitivity are particularly demanding in studies using pre-emptive dosing of analgesics, the placebo groups were analysed for issues of study sensitivity. Postoperative pain outcomes included pain scores in 34, rescue analgesia in 36, time to first rescue analgesia in 15, pain on activity in eight, number of patients with pain in six, pain relief in three, global efficacy rating in two and analgesic consumption via PCA in four studies. Twenty of 36 studies reported criteria for rescue analgesia that varied from 20 to 77% of the maximum pain intensity. Need of rescue analgesia showed more often differences between study groups than time to first rescue analgesia or pain intensity. Rescue analgesia was administered to 21-100% of the patients in the placebo groups where no other analgesics were given perioperatively. Most patients in the placebo groups had pain that was greater than 30% of the maximum. In conclusion, analysis of the methodology showed several aspects of trial design that can be improved in future studies. Placebo control groups can be used in paediatric analgesic studies to demonstrate internal sensitivity.

The effect of paracetamol and tropisetron on pain: experimental studies and a review of published data.

Experimental studies suggest that paracetamol-induced analgesia is mediated via central serotonergic pathways and attenuated by 5-HT3-antagonists. However, clinical studies do not support this, and 5-HT3-antagonists are expected to reduce pain by blocking the descending pronociceptive pathway. The current project tested whether tropisetron attenuates analgesia by paracetamol. Two randomized, double-blind, crossover studies with 18 healthy male volunteers in each were performed. Pain stimuli were cold water immersion (cold pressor test), contact heat pain (study 1) and electrical stimulation (study 2). In both studies, tropisetron 5 mg i.v. or saline was administered, followed by paracetamol 2 g i.v. 30 min. later. Individual changes in heat and cold pain intensity, cold pain tolerance and unpleasantness were recorded. The same thresholds were also expressed as scores (% of the individual score at baseline). Additionally, previously published findings on the effects of paracetamol and its interaction with 5HT3-antagonists in human experimental pain models were reviewed. After calculation of the sensory and pain scores (%), tropisetron seemed to amplify the analgesic action of paracetamol. Paracetamol 2 g i.v. did not show any statistically significant analgesia in thermal tests (study 1), or differences in sensory, pain detection or moderate pain thresholds of the electrical stimulus (study 2). As paracetamol did not have a measurable analgesic effect in these tests, no conclusions can be drawn about the interaction between paracetamol and tropisetron. However, tropisetron may have an analgesic effect of its own. Clinicians should not avoid using these drugs together, unless larger clinical studies indicate otherwise.

Parenteral opioids in emergency medicine - A systematic review of efficacy and safety.

Introduction and aim Pain is a frequent symptom in emergency patients and opioids are commonly used to treat it at emergency departments and at pre-hospital settings. The aim of this systematic review is to examine the efficacy and safety of parenteral opioids used for acute pain in emergency medicine. Method Qualitative review of randomized controlled trials (RCTs) on parenteral opioids for acute pain in adult emergency patients. Main outcome measures were: type and dose of the opioid, analgesic efficacy as compared to either placebo or another opioid and adverse effects. Results Twenty double-blind RCTs with results on 2322 patients were included. Seven studies were placebo controlled. Majority of studies were performed in the emergency department. Only five studies were in prehospital setting. Prehospital studies Four studies were on mainly trauma-related pain, one ischemic chest pain. One study compared two different doses of morphine in mainly trauma pain showing faster analgesia with the larger dose but no difference at 30 min postdrug. Three other studies on the same pain model showed equal analgesic effects with morphine and other opioids. Alfentanil was more effective than morphine in ischemic chest pain. Emergency department studies Pain models used were acute abdominal pain seven, renal colic four, mixed (mainly abdominal pain) three and trauma pain one study. Five studies compared morphine to placebo in acute abdominal pain and in all studies morphine was more effective than placebo. In four out of five studies on acute abdominal pain morphine did not change diagnostic accuracy, clinical or radiological findings. Most commonly used morphine dose in the emergency department was 0.1 mg/kg (five studies). Other opioids showed analgesic effect comparable to morphine. Adverse effects Recording and reporting of adverse effects was very variable. Vital signs were recorded in 15 of the 20 studies (including all prehospital studies). Incidence of adverse effects in the opioid groups was 5-38% of the patients in the prehospital setting and 4-46% of the patients in the emergency department. Nausea or vomiting was reported in 11-25% of the patients given opioids. Study drug was discontinued because of adverse effects five patients (one placebo, two sufentanil, two morphine). Eight studies commented on administration of naloxone for reversal of opioid effects. One patient out of 1266 was given naloxone for drowsiness. Ventilatory depression defined by variable criteria occurred in occurred in 7 out of 756 emergency department patients. Conclusion Evidence for selection of optimal opioid and dose is scarce. Opioids, especially morphine, are effective in relieving acute pain also in emergency medicine patients. Studies so far are small and reporting of adverse effects is very variable. Therefore the safety of different opioids and doses remains to be studied. Also the optimal titration regimens need to be evaluated in future studies. The prevention and treatment of opioid-induced nausea and vomiting is an important clinical consideration that requires further clinical and scientific attention in this patient group.

Trends in opioid consumption in the Nordic countries 2002-2006.

OBJECTIVE: The purpose of the study was to examine the trends in opioid consumption in the five Nordic countries between 2002 and 2006 and to explore possible explanations for changes in the quality and quantity of opioids consumed. METHODS: Data on opioid consumption were extracted from the databases of the respective national authorities. Six strong and four weak opioids were included in the analysis. Data were presented as DDDs/1000 inhabitants/day. In addition, information on the reimbursement system and opioid prescription regulations in respective countries was obtained. Also, the cost of analgesic medication in the Nordic countries was compared as equipotent doses of CR morphine, CR oxycodone and transdermal fentanyl. RESULTS: During the five year period examined the total use of opioids showed some increase in all countries except Sweden. In Finland and Norway the increase in the total consumption was mainly due to an increase in the consumption of strong opioids while in Denmark the rise was due to increased consumption of weak opioids. The consumption of morphine was stabile or decreased slightly in all countries while the use of transdermal fentanyl increased in Denmark, Finland and Sweden and oxycodone in all countries except Iceland. The consumption of dextropropoxyphene decreased in all countries. Reimbursement policies or prescription regulations do not seem to explain the kind/type of opioids consumed or changes in their consumption. CONCLUSIONS: Consumption of opioid analgesics in the Nordic countries showed changes over the five year period that cannot be explained by pharmacology, price, reimbursement or prescription regulations. Marketing has most likely significantly influenced the type and amount of opioids consumed.

Interpretation of the large red-and-white visual analog scale by children compared with adults.

The red-and-white visual analog scale (VAS) is a modification of the traditional VAS. The purpose of this study was to compare how children of various ages and adults rate their anticipatory pain intensity on the red-and-white VAS. One hundred children were interviewed as part of the anesthesiologist's preoperative visit before elective eye surgery. For comparison, 50 healthy adults were interviewed in a similar manner. The medians and ranges describing mild, moderate, and severe pain, or pain intensity at which medicine would be requested, did not differ between preschool children, young schoolchildren, and adolescents or between children and adults. The median score of anticipated need for pain medication was 50% of the maximum for children.