Purely ropivacaine-based TEA vs single TAP block in pain management after elective laparoscopic colon surgery within an upgraded institutional ERAS program.

BACKGROUND: The aim of this study was to compare thoracic epidural analgesia (TEA) with transversus abdominis plane (TAP) block in post-operative pain management after laparoscopic colon surgery. METHODS: One hundred thirty-six patients undergoing laparoscopic colon resection randomly received either TEA or TAP with ropivacaine only. The primary endpoint was opioid requirement up to 48 h postoperatively. Intensity of pain, time to onset of bowel function, time to mobilization, postoperative complications, length of hospital stay, and patients' satisfaction with pain management were also assessed. RESULTS: We observed a significant decrease in opioid consumption on the day of surgery with TEA compared with TAP block (30 mg vs 14 mg, p < 0.001). On the first two postoperative days (POD), the balance shifted to opioid consumption being smaller in the TAP group: on POD 1 (15.2 mg vs 10.6 mg; p = 0.086) and on POD 2 (9.2 mg vs 4.6 mg; p = 0.021). There were no differences in postoperative nausea/vomiting or time to first postoperative bowel movement between the groups. No direct blockade-related complications were observed and the length of stay was similar between TEA and TAP groups. CONCLUSION: TEA is more efficient for acute postoperative pain than TAP block on day of surgery, but not on the first two PODs. No differences in pain management-related complications were detected.

S-ketamine in patient-controlled analgesia reduces opioid consumption in a dose-dependent manner after major lumbar fusion surgery: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Spinal fusion surgery causes severe pain. Strong opioids, commonly used as postoperative analgesics, may have unwanted side effects. S-ketamine may be an effective analgesic adjuvant in opioid patient-controlled analgesia (PCA). However, the optimal adjunct S-ketamine dose to reduce postoperative opioid consumption is still unknown. METHODS: We randomized 107 patients at two tertiary hospitals in a double-blinded, placebo-controlled clinical trial of adults undergoing major lumbar spinal fusion surgery. Patients were randomly allocated to four groups in order to compare the effects of three different doses of adjunct S-ketamine (0.25, 0.5, and 0.75 mg ml-1) or placebo on postoperative analgesia in oxycodone PCA. Study drugs were administered for 24 hours postoperative after which oxycodone-PCA was continued for further 48 hours. Our primary outcome was cumulative oxycodone consumption at 24 hours after surgery. RESULTS: Of the 100 patients analyzed, patients receiving 0.75 mg ml-1 S-ketamine in oxycodone PCA needed 25% less oxycodone at 24 h postoperatively (61.2 mg) compared with patients receiving 0.5 mg ml-1 (74.7 mg) or 0.25 mg ml-1 (74.1 mg) S-ketamine in oxycodone or oxycodone alone (81.9 mg) (mean difference: -20.6 mg; 95% confidence interval [CI]: -41 to -0.20; P = 0.048). A beneficial effect in mean change of pain intensity at rest was seen in the group receiving 0.75 mg ml-1 S-ketamine in oxycodone PCA compared with patients receiving lower ketamine doses or oxycodone alone (standardized effect size: 0.17, 95% CI: 0.013-0.32, P = 0.033). The occurrence of adverse events was similar among the groups. CONCLUSIONS: Oxycodone PCA containing S-ketamine as an adjunct at a ratio of 1: 0.75 decreased cumulative oxycodone consumption at 24 h after major lumbar spinal fusion surgery without additional adverse effects.

Analgesic Effect of Intraoperative Intravenous S-Ketamine in Opioid-Naïve Patients After Major Lumbar Fusion Surgery Is Temporary and Not Dose-Dependent: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: Severe pain often accompanies major spine surgery. Opioids are the cornerstone of postoperative pain management but their use can be limited by numerous side effects. Several studies claim that adjuvant treatment with intravenous (IV) ketamine reduces opioid consumption and pain after back surgery. However, the exact role of ketamine for this indication is yet to be elucidated. We compared 2 different doses of S-ketamine with placebo on postoperative analgesic consumption, pain, and adverse events in adult, opioid-naïve patients after lumbar fusion surgery. METHODS: One hundred ninety-eight opioid-naïve patients undergoing lumbar spinal fusion surgery were recruited to this double-blind trial and randomly assigned into 3 study groups: Group C (placebo) received a preincisional IV bolus of saline (sodium chloride [NaCl] 0.9%) followed by an intraoperative IV infusion of NaCl 0.9%. Both groups K2 and K10 received a preincisional IV bolus of S-ketamine (0.5 mg/kg); in group K2, this was followed by an intraoperative IV infusion of S-ketamine (0.12 mg/kg/h), while in group K10, it was followed by an intraoperative IV infusion of S-ketamine (0.6 mg/kg/h). Postoperative analgesia was achieved by an IV patient-controlled analgesia (IV PCA) device delivering oxycodone. The primary end point was cumulative oxycodone consumption at 48 hours after surgery. The secondary end points included postoperative pain up to 2 years after surgery, adverse events, and level of sedation and confusion in the immediate postoperative period. RESULTS: The median [interquartile range (IQR)] cumulative oxycodone consumption at 48 hours was 154.5 [120] mg for group K2, 160 [109] mg for group K10, and 178.5 [176] mg for group C. The estimated difference was -24 mg between group K2 and group C (97.5% confidence interval [CI], -73.8 to 31.5; P = .170) and -18.5 mg between group K10 and C (97.5% CI, 78.5-29.5; P = .458). There were no significant differences between groups.Postoperative pain scores were significantly lower in both ketamine treatment groups at the fourth postoperative hour but not later during the 2-year study period.The higher ketamine dose was associated with more sedation. Otherwise, differences in the occurrence of adverse events between study groups were nonsignificant. CONCLUSIONS: Neither a 0.12 nor a 0.6 mg/kg/h infusion of intraoperative IV S-ketamine was superior to the placebo in reducing oxycodone consumption at 48 hours after lumbar fusion surgery in an opioid-naïve adult study population. Future studies should assess ketamine's feasibility in specific study populations who most benefit from reduced opioid consumption.

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.

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.

Perioperative intravenous ketamine for acute postoperative pain in adults.

BACKGROUND: Inadequate pain management after surgery increases the risk of postoperative complications and may predispose for chronic postsurgical pain. Perioperative ketamine may enhance conventional analgesics in the acute postoperative setting. OBJECTIVES: To evaluate the efficacy and safety of perioperative intravenous ketamine in adult patients when used for the treatment or prevention of acute pain following general anaesthesia. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase to July 2018 and three trials registers (metaRegister of controlled trials, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP)) together with reference checking, citation searching and contact with study authors to identify additional studies. SELECTION CRITERIA: We sought randomised, double-blind, controlled trials of adults undergoing surgery under general anaesthesia and being treated with perioperative intravenous ketamine. Studies compared ketamine with placebo, or compared ketamine plus a basic analgesic, such as morphine or non-steroidal anti-inflammatory drug (NSAID), with a basic analgesic alone. DATA COLLECTION AND ANALYSIS: Two review authors searched for studies, extracted efficacy and adverse event data, examined issues of study quality and potential bias, and performed analyses. Primary outcomes were opioid consumption and pain intensity at rest and during movement at 24 and 48 hours postoperatively. Secondary outcomes were time to first analgesic request, assessment of postoperative hyperalgesia, central nervous system (CNS) adverse effects, and postoperative nausea and vomiting. We assessed the evidence using GRADE and created a 'Summary of findings' table. MAIN RESULTS: We included 130 studies with 8341 participants. Ketamine was given to 4588 participants and 3753 participants served as controls. Types of surgery included ear, nose or throat surgery, wisdom tooth extraction, thoracotomy, lumbar fusion surgery, microdiscectomy, hip joint replacement surgery, knee joint replacement surgery, anterior cruciate ligament repair, knee arthroscopy, mastectomy, haemorrhoidectomy, abdominal surgery, radical prostatectomy, thyroid surgery, elective caesarean section, and laparoscopic surgery. Racemic ketamine bolus doses were predominantly 0.25 mg to 1 mg, and infusions 2 to 5 µg/kg/minute; 10 studies used only S-ketamine and one only R-ketamine. Risk of bias was generally low or uncertain, except for study size; most had fewer than 50 participants per treatment arm, resulting in high heterogeneity, as expected, for most analyses. We did not stratify the main analysis by type of surgery or any other factor, such as dose or timing of ketamine administration, and used a non-stratified analysis.Perioperative intravenous ketamine reduced postoperative opioid consumption over 24 hours by 8 mg morphine equivalents (95% CI 6 to 9; 19% from 42 mg consumed by participants given placebo, moderate-quality evidence; 65 studies, 4004 participants). Over 48 hours, opioid consumption was 13 mg lower (95% CI 10 to 15; 19% from 67 mg with placebo, moderate-quality evidence; 37 studies, 2449 participants).Perioperative intravenous ketamine reduced pain at rest at 24 hours by 5/100 mm on a visual analogue scale (95% CI 4 to 7; 19% lower from 26/100 mm with placebo, high-quality evidence; 82 studies, 5004 participants), and at 48 hours by 5/100 mm (95% CI 3 to 7; 22% lower from 23/100 mm, high-quality evidence; 49 studies, 2962 participants). Pain during movement was reduced at 24 hours (6/100 mm, 14% lower from 42/100 mm, moderate-quality evidence; 29 studies, 1806 participants), and 48 hours (6/100 mm, 16% lower from 37 mm, low-quality evidence; 23 studies, 1353 participants).Results for primary outcomes were consistent when analysed by pain at rest or on movement, operation type, and timing of administration, or sensitivity to study size and pain intensity. No analysis by dose was possible. There was no difference when nitrous oxide was used. We downgraded the quality of the evidence once if numbers of participants were large but small-study effects were present, or twice if numbers were small and small-study effects likely but testing not possible.Ketamine increased the time for the first postoperative analgesic request by 54 minutes (95% CI 37 to 71 minutes), from a mean of 39 minutes with placebo (moderate-quality evidence; 31 studies, 1678 participants). Ketamine reduced the area of postoperative hyperalgesia by 7 cm² (95% CI -11.9 to -2.2), compared with placebo (very low-quality evidence; 7 studies 333 participants). We downgraded the quality of evidence because of small-study effects or because the number of participants was below 400.CNS adverse events occurred in 52 studies, while 53 studies reported of absence of CNS adverse events. Overall, 187/3614 (5%) participants receiving ketamine and 122/2924 (4%) receiving control treatment experienced an adverse event (RR 1.2, 95% CI 0.95 to 1.4; high-quality evidence; 105 studies, 6538 participants). Ketamine reduced postoperative nausea and vomiting from 27% with placebo to 23% with ketamine (RR 0.88, 95% CI 0.81 to 0.96; the number needed to treat to prevent one episode of postoperative nausea and vomiting with perioperative intravenous ketamine administration was 24 (95% CI 16 to 54; high-quality evidence; 95 studies, 5965 participants). AUTHORS' CONCLUSIONS: Perioperative intravenous ketamine probably reduces postoperative analgesic consumption and pain intensity. Results were consistent in different operation types or timing of ketamine administration, with larger and smaller studies, and by higher and lower pain intensity. CNS adverse events were little different with ketamine or control. Perioperative intravenous ketamine probably reduces postoperative nausea and vomiting by a small extent, of arguable clinical relevance.

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.

Ketamine in the treatment of acute pain.

Ketamine is an old anesthetic agent that relieves pain by reducing central sensitization in the central nervous system. This is advantageous for patients suffering from severe pain prior to surgery or are using a strong opioid. The S enantiomer of ketamine used for anesthesia is more powerful than racemic ketamine. The ideal dose of ketamine for pain relief is not yet known, and its adverse effects on the central nervous system, including hallucinations, sedation, and diplopia have limited its use in pain management. The significance of these effects at low doses is probably less than expected, particularly if benzodiazepines or an alpha-2 agonist, such as dexmedetomidine, are administered in addition to ketamine.

Identification and structural characterization of LytU, a unique peptidoglycan endopeptidase from the lysostaphin family.

We introduce LytU, a short member of the lysostaphin family of zinc-dependent pentaglycine endopeptidases. It is a potential antimicrobial agent for S. aureus infections and its gene transcription is highly upregulated upon antibiotic treatments along with other genes involved in cell wall synthesis. We found this enzyme to be responsible for the opening of the cell wall peptidoglycan layer during cell divisions in S. aureus. LytU is anchored in the plasma membrane with the active part residing in the periplasmic space. It has a unique Ile/Lys insertion at position 151 that resides in the catalytic site-neighbouring loop and is vital for the enzymatic activity but not affecting the overall structure common to the lysostaphin family. Purified LytU lyses S. aureus cells and cleaves pentaglycine, a reaction conveniently monitored by NMR spectroscopy. Substituting the cofactor zinc ion with a copper or cobalt ion remarkably increases the rate of pentaglycine cleavage. NMR and isothermal titration calorimetry further reveal that, uniquely for its family, LytU is able to bind a second zinc ion which is coordinated by catalytic histidines and is therefore inhibitory. The pH-dependence and high affinity of binding carry further physiological implications.

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.

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.

[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.

Does the pharmacology of oxycodone justify its increasing use as an analgesic?

Oxycodone is a semisynthetic opioid analgesic that is increasingly used for the treatment of acute, cancer, and chronic non-malignant pain. Oxycodone was synthesized in 1917 but its pharmacological properties were not thoroughly studied until recently. Oxycodone is a fairly selective µ-opioid receptor agonist, but there is a striking discrepancy between the relatively low binding potential and G protein activation by oxycodone and its analgesic efficacy. It has been claimed that this is because of active metabolites and enhanced passage to the central nervous system by active transport. We critically review studies on the basic pharmacology of oxycodone and on its pharmacokinetics and pharmacodynamics in humans. In particular, the role of pharmacogenomics and population pharmacokinetics in understanding the properties of oxycodone is discussed in detail. We compare oxycodone with morphine, the standard opioid in clinical use.

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.