Systematic reviews and quality assessment of patient-reported outcome measures for physical function in comparative effectiveness studies regarding acute postoperative pain after total knee arthroplasty-Do we need to start all over again?

BACKGROUND AND OBJECTIVE: Recently, a consensus process specified a core outcome set (COS) of domains to be assessed in each comparative effectiveness research and clinical practice related to acute postoperative pain. Physical function (PF) was one of these domains. The aim of this review was to investigate which patient-reported outcome measures (PROMs) are used to assess PF after total knee arthroplasty (TKA) in clinical trials and if they fulfil basic requirements for a COS of PROMs based on their psychometric properties. METHODS: A systematic review of randomized controlled trials and observational studies based on a search in MEDLINE, EMBASE and CENTRAL was undertaken. PROMs and performance measures were extracted and investigated, including evaluation of psychometric properties of PROMs based on COSMIN recommendations. RESULTS: From initially 2896 identified records, 479 studies were included in the qualitative synthesis. Only 87 of these trials (18%) assessed PF using PROMs, whereas especially performance outcome measures were used in 470 studies (98%). Application of the 'COSMIN Risk-of-Bias-Box 1' to 13 of the 14 identified PROMs resulted in insufficient content validity of the included PROMs regarding the target population based on the inauguration or development articles. CONCLUSION: Our data indicate that a patient-centred postoperative assessment of PF in pain-related clinical trials early after TKA is not common, even though patient-reported assessment is widely recommended. In addition, none of the applied PROMs shows content validity based on their inauguration or development articles for the assessment of postoperative pain-related PF after TKA. SIGNIFICANCE: A systematic search for patient-reported outcome measures assessing postoperative, pain-related physical function after total knee arthroplasty in clinical trials and assessment of their content validity revealed none that fulfilled requirements based on COSMIN recommendations.

Spinal GABA transporter 1 contributes to evoked-pain related behavior but not resting pain after incision injury.

The inhibitory function of GABA at the spinal level and its central modulation in the brain are essential for pain perception. However, in post-surgical pain, the exact mechanism and modes of action of GABAergic transmission have been poorly studied. This work aimed to investigate GABA synthesis and uptake in the incisional pain model in a time-dependent manner. Here, we combined assays for mechanical and heat stimuli-induced withdrawal reflexes with video-based assessments and assays for non-evoked (NEP, guarding of affected hind paw) and movement-evoked (MEP, gait pattern) pain-related behaviors in a plantar incision model in male rats to phenotype the effects of the inhibition of the GABA transporter (GAT-1), using a specific antagonist (NO711). Further, we determined the expression profile of spinal dorsal horn GAT-1 and glutamate decarboxylase 65/67 (GAD65/67) by protein expression analyses at four time points post-incision. Four hours after incision, we detected an evoked pain phenotype (mechanical, heat and movement), which transiently ameliorated dose-dependently following spinal inhibition of GAT-1. However, the NEP-phenotype was not affected. Four hours after incision, GAT-1 expression was significantly increased, whereas GAD67 expression was significantly reduced. Our data suggest that GAT-1 plays a role in balancing spinal GABAergic signaling in the spinal dorsal horn shortly after incision, resulting in the evoked pain phenotype. Increased GAT-1 expression leads to increased GABA uptake from the synaptic cleft and reduces tonic GABAergic inhibition at the post-synapse. Inhibition of GAT-1 transiently reversed this imbalance and ameliorated the evoked pain phenotype.

Systematic Review on Pain-Related Outcome Domains After Sternotomy: A First Step Toward the Development of a Core Outcome Set.

OBJECTIVES: Pain after surgery has a major impact on acute and long-term recovery and quality of life, but its management is often insufficient. To enhance the quality of research and to allow for better comparability between studies, it is important to harmonize outcomes for assessing the efficacy and effectiveness of pain management interventions after surgery. As a first step in developing a core outcome set, this study aimed to systematically search for outcome domains assessed in research regarding acute pain management after sternotomy as an example of a typically painful surgical procedure. METHODS: A systematic literature review was performed using MEDLINE, Embase, and CENTRAL. Eligibility criteria consisted of randomized controlled trials and observational trials targeting pain management after sternotomy in adults in the acute postoperative setting (≤2 weeks). After duplicate removal and title and abstract screening by 2 independent reviewers, study characteristics and outcome domains were identified, which were extracted from full texts and summarized qualitatively. RESULTS: Of 1350 studies retrieved by database searching, 156 studies were included for full-text extraction. A total of 80 different outcome domains were identified: pain intensity, analgesic consumption, physiological function, and adverse events were the most frequent ones. Outcome domains were often not explicitly reported, and the combination of domains and assessment tools was heterogeneous. The choice of outcomes is commonly made within clinicians; patients' perspectives are not considered. CONCLUSIONS: The wide variety of commonly applied outcome domains, the nonexplicit wording, and the heterogeneous combination of the domains indicating treatment benefit demonstrate the need for harmonization of outcomes assessing perioperative pain management after surgery.

Influence of transcutaneous spinal stimulation on human LTP-like pain amplification. A randomized, double-blind study in volunteers.

OBJECTIVE: Transcutaneous spinal direct current stimulation (tsDCS) has been proven to affect nociceptive signal processing. We designed a randomized, double-blind, cross-over study to investigate whether tsDCS applied before or after inducing long-term potentiation-(LTP)-like hyperalgesia may decrease nociceptive sensitivity. METHODS: In healthy volunteers, tsDCS (2.5mA, 15min) was applied to the thoracic spine prior (n=14) or immediately following (n=12) electrical high-frequency stimulation (HFS) to the thigh, inducing hyperalgesia. Mechanical and electrical perception were assessed before HFS stimulation and at three time points following HFS stimulation (all within 90min of HFS). Subjects took part in three separate sessions to test effects of anodal, cathodal, or sham tsDCS. RESULTS: Within 60minHFS led to unilateral changes on the conditioned side: mechanical pain thresholds tended to decrease and electrical detection thresholds significantly decreased (p<0.001); pain ratings measured using the numerical rating scale (NRS) increased for electrical stimuli (p<0.01) and two categories of mechanical stimuli ("Light(8-64mN)": p=ns; "Heavy(128-512mN)": p<0.01). Irrespective of stimulation order or polarity, tsDCS could not influence nociceptive sensitivity. CONCLUSION: Hyperalgesia was adequately induced, but tsDCS had no effect on HFS-induced sensitization. SIGNIFICANCE: While tsDCS has been shown to affect pain measures, our results suggest irrespective of time of stimulation or polarity that tsDCS may be less effective in modulating pain in a sensitized state in healthy subjects.

[Survey of pain after ambulatory surgery: An internet-based instrument]. / Erhebung von Schmerzen nach ambulanten Operationen : Ein internetbasiertes Instrument.

BACKGROUND AND AIM: Pain after surgery continues to be undermanaged. Studies and initiatives aiming to improve the management of postoperative pain are growing; however, most studies focus on inpatients and pain on the first day after surgery. The management of postoperative pain after ambulatory surgery and for several days thereafter is not yet a major focus. One reason is the low return rate of the questionnaires in the ambulatory sector. This article reports the development and feasibility of a web-based electronic data collection system to examine pain and pain-related outcome on predefined postoperative days after ambulatory surgery. MATERIAL AND METHODS: In this prospective pilot study 127 patients scheduled for ambulatory surgery were asked to participate in a survey to evaluate aspects related to pain after ambulatory surgery. The data survey was divided in (1) a preoperative, intraoperative and postoperative part and (2) a postoperative internet-based electronic questionnaire which was sent via e-mail link to the patient on days 1, 3 and 7 after surgery. A software was developed using a PHP-based platform to send e-mails and retrieve the data after web-based entries via a local browser. Feasibility, internet-based hitches and compliance were assessed by an additional telephone call after day 7. RESULTS: A total of 100 patients (50 female) between 18 and 71 years (mean 39.1 ± 12.7 years) were included in the pilot study. Return rates of the electronic questionnaires were 86% (days 3 and 7) and 91% (day 1 after surgery). All 3 electronic questionnaires were answered by 82% of patients. Aspects influencing the return rate of questionnaires were work status but not age, gender, education level and preoperative pain. Telephone interviews were performed with 81 patients and revealed high operability of the internet-based survey without any major problems. CONCLUSION: The user-friendly feasibility and operability of this internet-based electronic data survey system explain the high compliance and return rate of electronic questionnaires by patients at home after ambulatory surgery. This survey tool therefore provides unique opportunities to evaluate and improve postoperative pain management after ambulatory surgery.

[Pain medicine from intercultural and gender-related perspectives]. / Schmerzmedizin aus einer interkulturellen und geschlechterspezifischen Perspektive.

Cultural setting and sex and gender of the patient are important factors affecting the occurrence, severity, clinical course and prognosis of pain and pain-related diseases. Intercultural differences in the perception and verbal expression of symptoms and emotional function are fundamental and it is important to realize these differences in order to understand patients with a migration background. A trusting doctor-patient relationship is generally very sensitive and it is even more difficult to establish when differences in the cultural background impair mutual understanding. Regarding sex and gender there is evidence that females are more susceptible to developing chronic pain conditions, experience more severe pain and respond differently to pain therapy; however, results of recent studies indicate that females are not that different to males when comparing several modalities of experimental pain (although some differences exist). Similarly, sex and gender differences in postoperative pain seem to exist but the differences are relatively small when pain scores are compared. Other aspects, such as the response to analgesics and role of psychosocial factors should be addressed when sex and gender aspects are studied. Similarly, sex and gender differences in the prevalence of chronic pain exist but the results of some studies, e.g. those controlling for confounders, are not very clear. Research is needed to delineate the role of specific aspects affecting sex and gender differences and the underlying mechanisms (e.g. reduced inhibitory control, hormones, psychological aspects and social factors). Altogether, we need to open our minds to some intercultural and sex and gender aspects in the clinical setting. For sex and gender differences we may need a more biopsychosocial approach to understand the underlying differences and differentiate between sex and gender and sex and gender-associated aspects for acute and chronic pain.

[Postoperative pain therapy in Germany. Status quo]. / Therapie postoperativer Schmerzen in Deutschland. Aktueller Stand.

A great deal of progress has been made in the field of postoperative pain therapy in the last 20 years. Beginning from clinical trials on the effectiveness of individual procedures, such as epidural anesthesia and patient-controlled analgesia, a wide range of healthcare services research as well as basic research with human and animal experiments has been established. Whereas health services research in the 1980s and 1990s focused more on the implementation of acute pain services, outcome-oriented research approaches are nowadays the center of attention. Acute pain registries and pain certification projects initiated in Germany have to be mentioned particularly in this respect. Basic research papers from recent years increasingly address specific aspects of acute postoperative pain and have provided translational approaches that are applied around the world for studying neurobiological mechanisms of postoperative pain. At the same time, interdisciplinary cooperation in research projects has led to a better understanding of complex correlations regarding predictors and mechanisms (including psychosocial aspects) of acute and in recent times also chronic pain after surgery. In parallel, evidence-based medicine has found its way into acute pain medicine in Germany. In 2007, clinical acute pain therapy in Germany was enhanced by S3 level guidelines for the first time; however, the implementation is still incomplete. In future, questions concerning mechanism-based therapy of acute pain need to be equally in the center of attention of research, such as prevention of persisting pain after surgery and acute pain of different origins.

Transcutaneous spinal DC stimulation reduces pain sensitivity in humans.

Non-invasive approaches to pain management are needed to manage patient pain escalation and to providing sufficient pain relief. Here, we evaluate the potential of transcutaneous spinal direct current stimulation (tsDCS) to modulate pain sensitivity to electrical stimuli and mechanical pinpricks in 24 healthy subjects in a sham-controlled, single-blind study. Pain ratings to mechanical pinpricks and electrical stimuli were recorded prior to and at three time points (0, 30, and 60min) following 15min of anodal tsDCS (2.5mA, "active" electrode centered over the T11 spinous process, return electrode on the left posterior shoulder). Pain ratings to the pinpricks of the highest forces tested (128, 256, 512mN) were reduced at 30min and 60min following anodal tsDCS. These findings demonstrate that pain sensitivity in healthy subjects can be suppressed by anodal tsDCS and suggest that tsDCS may provide a non-invasive tool to manage mechanically-induced pain.

Selective prevention of mechanical hyperalgesia after incision by spinal ERK1/2 inhibition.

BACKGROUND: Activation of extracellular signal-regulated kinases (ERK1/2) has been shown to play an important role in several pain states. Here we investigated the ERK1/2 contribution to non-evoked and evoked pain-like behaviour in rats after surgical incision. METHODS: Spinal phosphorylation of ERK1 and ERK2 was assessed 15 min, 4 h, 24 h and 5 days after plantar incision and sham incision. The effect of PD98059, a specific inhibitor of ERK1/2 activation, administered intrathecally (IT) 1 h before or 2 h after incision on spinal ERK1 and ERK2 phosphorylation was assessed. In behavioural experiments, the effect of PD98059 administered 1 h before or after incision on non-evoked pain behaviour and mechanical and heat hyperalgesia was assessed. RESULTS: Phosphorylated ERK1 and ERK2 were rapidly increased in the ipsilateral dorsal horn from rats after incision post-operatively. This increased ERK1 and ERK2 phosphorylation were blocked by PD98059 administered before incision. In congruence, IT administration of PD98059 before incision delayed mechanical hyperalgesia after incision; however, administration after incision had only a modest effect on mechanical hyperalgesia. In addition, PD98059 did not affect non-evoked pain behaviour or heat hyperalgesia after incision. CONCLUSION: The results suggest that spinal ERK1 and ERK2 are involved in regulation of pain after incision differentially with regard to the pain modality. Furthermore, blockade of ERK1/2 activation was most effective in a preventive manner, a condition which is rare after incision. Spinal ERK1/2 inhibition could therefore be a very useful tool to manage selectively movement-evoked pain after surgery in the future.

[Differences of analgesic efficacy and complication rates between ultrasound and nervestimulator guided peripheral nerve catheters : Database analysis on patient-relevant target parameters]. / Vergleich der Analgesiequalität und Komplikationen von ultraschall- und nervenstimulatorgesteuerten peripheren Nervenkathetern : Datenbankanalyse zu patientenrelevanten Zielparametern.

BACKGROUND: Peripheral nerve catheters (PNC) play an important role in postoperative pain treatment following major extremity surgery. There are several trials reported in the literature which investigated the efficacy and safety of ultrasound (US) and nerve stimulator (NS) guided PNC placement; however, most of these trials were only small and focused mainly on anesthesiologist-related indicators of block success (e.g. block onset time and procedure time) but not primarily on patient-related outcome data including postoperative pain during movement. AIM: This retrospective analysis compared the analgesic efficacy and safety of US versus NS guided peripheral nerve catheters (PNC) for postoperative pain therapy in a large cohort of patients. MATERIAL AND METHODS: Data of patients (June 2006-December 2010) treated with US (nus = 368 June 2008-December 2010) and NS (nns = 574, June 2006-May 2008) guided PNC were systematically analyzed. Apart from demographic data, postoperative pain scores [numeric rating scale (NRS): 0-10] on each treatment day, the number of patients with need for additional opioids, cumulative local anesthetic consumption and catheter-related complications were compared. RESULTS: On the day of surgery patients treated with US-guided PNC reported lower NRS at rest (p = 0.034) and during movement (p < 0.001). Additionally, the number of patients requiring additional opioids on the day of surgery was lower in the US group (absolute difference 12.4 %, p = 0.001). Furthermore, the number of multiple puncture attempts (absolute difference 5.6 %, p < 0.001) and failed catheter placements (absolute difference 3.4 %, p = 0.06) were lower in the US group. There were no patients in both groups with long-lasting neurological impairment. CONCLUSION: This database analysis demonstrated that patients treated with US-guided PNC reported significantly lower postoperative pain scores and the number of patients requiring additional opioids was significantly lower on the day of surgery. The numbers of multiple punctures and failed catheter placements were reduced in the US group, which might be seen as an advantage of US-guided regional anaesthesia.

[Perioperative pain management for abdominal and thoracic surgery]. / Perioperative Schmerztherapie bei abdominellen und thorakalen Operationen.

Abdominal and thoracic surgical procedures can result in significant acute postoperative pain. Present evidence shows that postoperative pain management remains inadequate especially after "minor" surgical procedures. Various therapeutic options including regional anesthesia techniques and systemic pharmacotherapy are available for effective treatment of postoperative pain. This work summarizes the pathophysiological background of postoperative pain after abdominal and thoracic surgery and discusses the indication, effectiveness, risks, and benefits of the different therapeutic options. Special focus is given to the controversial debate about the indication for epidural analgesia, as well as various alternative therapeutic options, including transversus abdominis plane (TAP) block, paravertebral block (PVB), wound infiltration with local anesthetics, and intravenous lidocaine. In additional, indications and contraindications of nonopioid analgesics after abdominal and thoracic surgery are discussed and recommendations based on scientific evidence and individual risk and benefit analysis are made. All therapeutic options discussed are eligible for clinical use and may contribute to improve postoperative pain outcome after abdominal and thoracic surgical procedures.

Ultrasound compared with nerve stimulation guidance for peripheral nerve catheter placement: a meta-analysis of randomized controlled trials.

BACKGROUND: The aim of this meta-analysis was to compare the efficacy and safety of ultrasound (US) vs nerve stimulation (NS) guidance for peripheral nerve catheter placement. METHODS: This meta-analysis was performed according to the PRISMA statement and the recommendations of the Cochrane Collaboration. For dichotomous outcomes relative risks [RRs; 95% confidence intervals (CIs)] were calculated, while for continuous outcomes, mean differences (MDs; 95% CI) were calculated. All statistical analyses were performed using the Revman® statistical software (Version 5.1). RESULTS: Fifteen randomized controlled trials including 977 patients satisfied the inclusion criteria. Peripheral nerve catheters placed under US guidance showed a higher RR of 1.14 (95% CI: 1.02-1.27; P=0.02) for an overall successful block in comparison with NS. However, postoperative pain scales at movement (numeric rating scale: 0-10) were comparable between US- vs NS-guided peripheral nerve catheters 24 (MD: 0.08; 95% CI: -0.77 to 0.94; P=0.85) and 48 (MD: 1.0; 95% CI: -0.3 to 2.3; P=0.13) h after surgery. Patients receiving a US-guided peripheral nerve catheter had a lower RR of 0.13 (95% CI: 0.04-0.38; P=0.0002) for an accidental vascular puncture. CONCLUSIONS: There is evidence that US-guided peripheral nerve catheters show a higher success rate and a lower risk for an accidental vascular puncture compared with NS guidance. However, this difference resulted only in marginally lower postoperative pain scores at rest. Nevertheless, these results were influenced by heterogeneity and should be interpreted with caution.

Is intraoperative dexmedetomidine a new option for postoperative pain treatment? A meta-analysis of randomized controlled trials.

In the present meta-analysis, we assessed the efficacy and safety of intravenous administration of dexmedetomidine (DEX) compared with placebo or opioids for acute postoperative pain treatment in adults undergoing surgery. The meta-analysis was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement and the recommendations of the Cochrane Collaboration. Randomized controlled trials investigating perioperative administration of DEX were included. For dichotomous outcomes relative risks (RR; 95% confidence intervals [CI]) and for continuous outcomes mean differences (MD; 95% CI) were calculated. Twenty-eight randomized controlled trials including 1420 patients were finally included. Patients treated with DEX reported lower postoperative pain intensity (MD1h postoperatively: -1.59U (numeric rating scale: 0 to 10) 95% CI: -2.37 to -0.82; P=.000001) and showed a lower postoperative opioid consumption (MD24h postoperatively: -17.24mg; 95% CI: -24.38 to -10.10; P=.00001) compared with placebo. Additionally, the DEX group showed a lower RR for opioid-related adverse events (e.g. RRNausea (postanesthesia care unit): 0.66; 95% CI: 0.43 to 1.02; P=.06). The most common adverse event in patients treated with DEX was intraoperative bradycardia with a RR of 2.66 (RR: 2.66; 95% CI: 1.54 to 4.58; P=.0004) compared with placebo. There is evidence that DEX administration leads to lower postoperative pain, reduced opioid consumption, and a lower risk for opioid-related adverse events. The comparison of DEX vs opioids for postoperative pain treatment is less clear due to limited data. The most common adverse event was intraoperative bradycardia after DEX administration. Therefore cautions in patients at risk are warranted, and large trials focusing on long-term outcomes after intraoperative DEX use are needed.

[Oral therapy algorithm for the treatment of postoperative pain. A prospective observational study]. / Oraler Therapiealgorithmus bei akuten postoperativen Schmerzen. Eine prospektive Beobachtungsstudie.

BACKGROUND: Postoperative pain continues to be undermanaged, at least in part, due to inadequate organization and lack of use of opioids. Especially patients who do not receive consultation from an acute pain service and are therefore not eligible to receive regional anesthesia techniques or patient-controlled devices suffer from severe pain after surgery. The aim of the present prospective observational study was to assess the efficacy and feasibility of an analgesia algorithm for this subgroup of patients. METHODS: An oral opioid concept including controlled-release (cr) oxycodone, immediate-release (ir) hydromorphone and a non-opioid analgesic was implemented at three different departments at the University Clinic of Muenster, Germany. Briefly, cr-oxycodon was administered preoperatively to patients undergoing ear nose and throat (ENT), general or elective trauma surgery on the day of surgery and every 12 h for a maximum of 4 days postoperatively. Inadequately managed pain above 3 on a visual analog scale (VAS 0-10) at rest and above 5 during movement was treated with ir-hydromorphone on patient request. After written informed consent, patients were assessed prospectively for up to 5 days perioperatively using a standardized questionnaire preoperatively, for 4 days postoperatively as well as 6 and 12 months after surgery. RESULTS: A total of 275 patients were included in the present prospective observational study: (ENT surgery: 163, trauma surgery 82 and general surgery 30). Median resting and evoked numeric rating scale (NRS) pain scores were equal or less than 3 and 5, respectively. Less patients received cr-oxycodone after ENT and general surgery compared to trauma surgery (p < 0.001). Constipation was more frequent after general and trauma surgery compared to ENT surgery. Vomiting decreased from 20 %-30 % on the day of surgery to 10 % or less regardless of the type of operation. No severe adverse events were observed. Additionally, patients with an increased depression score before surgery reported greater immediate postoperative pain than non-depressed patients. Of the patients 11 (15.7 %) and 7 (14.9 %) complained about persistent postoperative pain 6 and 12 months after surgery, respectively and these patients had increased acute pain ratings during the first postoperative days. CONCLUSIONS: The present study has demonstrated that the implementation of an oral opioid algorithm for patients without patient-controlled intravenous or regional analgesia is effective and feasible on surgical wards. Patients who underwent trauma surgery needed more cr-oxycodone. Side effects were similar regardless of the operation with the exception of obstipation which was more frequent after trauma and general surgery compared to ENT surgery.

[Spinal and epidural anesthesia in patients with hemorrhagic diathesis : decisions on the brink of minimum evidence?]. / Rückenmarknahe Regionalanästhesie bei Patienten mit hämorrhagischen Diathesen : Entscheidungen am Rande des Evidenzminimums?

Neuraxial anesthesia is an established and safe procedure in perioperative pain therapy which can help to minimize complications and to improve perioperative outcome. In patients with acquired bleeding disorders by comorbidities or concomitant antithrombotic medication an individual decision should be made based on risks and benefits. A large number of literature references and guidelines help making a decision, for example the recently updated evidence-based guidelines of the American Society of Regional Anesthesia and Pain Medicine for patients receiving antithrombotic or thrombolytic therapy. However, no explicit recommendations or guidelines exist for patients with hemorrhagic diatheses, such as von Willebrand disease (vWD), hemophilia A and B and idiopathic thrombocytopenic purpura (ITP). Published data regarding the safety of neuraxial techniques in these patients is scarce. Neuraxial anesthesia in patients with vWD is only acceptable when coagulation is optimized (substitution of factor concentrates or hemostatic agents depending on the type of vWD) and monitored frequently during the procedure. The only exception might be obstetric patients with vWD type I as coagulation frequently normalizes at the end of pregnancy. In these patients neuraxial anesthesia can often be performed without supplementation of clotting factors.Neuraxial techniques in patients with hemophilia A or B are usually contraindicated. The procedure may only be acceptable if serious reasons exist against general anesthesia. Supplementation of the missing factor to normal levels and monitoring during procedure is essential if neuraxial block is performed.Patients with ITP often present with low platelet counts. Normally, spinal or epidural anesthesia is considered safe if the platelet count is over 80,000/µl. However, the consistently low platelet counts in ITP seem to be less problematic than rapidly falling values due to other diseases, because this is often accompanied by platelet dysfunction or coagulopathy. In several studies neuraxial anesthesia was successfully performed with platelet counts between 50,000 and 80,000/µl. Nevertheless, the minimum safe platelet count for neuraxial blockade remains undefined in these patients.Evidence-based recommendations for neuraxial anaesthesia in patients with hemophilia, vWD or ITP cannot be offered. Each patient has to be treated individually with appropriate caution. This overview is intended to assist in the decision for or against neuraxial anesthesia in these patients, with emphasis on the pathophysiological background, blood investigations and case reports from the literature.

Efficacy and adverse effects of ketamine as an additive for paediatric caudal anaesthesia: a quantitative systematic review of randomized controlled trials.

BACKGROUND: The aim of this quantitative systematic review was to assess the efficacy and adverse effects of ketamine added to caudal local anaesthetics in comparison with local anaesthetics alone in children undergoing urological, lower abdominal, or lower limb surgery. METHODS: The systematic search, data extraction, critical appraisal, and pooled data analysis were performed according to the PRISMA statement. All randomized controlled trials (RCTs) were included in this meta-analysis and relative risk (RR), mean difference (MD), and the corresponding 95% confidence intervals (CIs) were calculated using the Revman(®) statistical software for dichotomous and continuous outcomes. RESULTS: Thirteen RCTs (published between 1991 and 2008) including 584 patients met the inclusion criteria. There was a significant longer time to first analgesic requirements in patients receiving ketamine in addition to a local anaesthetic compared with a local anaesthetic alone (MD: 5.60 h; 95% CI: 5.45-5.76; P<0.00001). There was a lower RR for the need of rescue analgesia in children receiving a caudal regional anaesthesia with ketamine in addition to local anaesthetics (RR: 0.71; 95% CI: 0.44-1.15; P=0.16). CONCLUSIONS: Caudally administered ketamine, in addition to a local anaesthetic, provides prolonged postoperative analgesia with few adverse effects compared with local anaesthetics alone. There is a clear benefit of caudal ketamine, but the uncertainties about neurotoxicity relating to the dose of ketamine, single vs repeated doses and the child's age, still need to be clarified for use in clinical practice.

Efficacy and safety of paravertebral blocks in breast surgery: a meta-analysis of randomized controlled trials.

BACKGROUND: Thoracic paravertebral blocks (PVBs) are successfully performed for pain management after breast surgery. The aim of the present quantitative systematic review was to assess the efficacy and adverse events of PVB in women undergoing breast surgery. METHODS: The systematic search, data extraction, critical appraisal, and pooled analysis were performed according to the PRISMA statement. The relative risk (RR), mean difference (MD), and their corresponding 95% confidence intervals (CIs) were calculated using the RevMan statistical software for dichotomous and continuous outcomes, respectively. Pain scores were converted to a scale ranging from 0 (no pain) to 10 (worst pain). RESULTS: Fifteen randomized controlled trials (published between 1999 and 2009) including 877 patients met the inclusion criteria. There was a significant difference in worst postoperative pain scores between PVB and general anaesthesia (GA) at <2 h (MD: -2.68; 95% CI: -3.33 to -2.02; P<0.00001), 2-24 h (MD: -2.34; 95% CI: -2.42 to -1.12; P<0.00001), and 24-48 h (MD: -1.75; 95% CI: -3.19 to 0.31; P=0.02). Accordingly, lower pain scores were observed for combined PVB with GA compared with GA alone for <2 h (MD: -1.87; 95% CI: -2.53 to -1.21; P<0.00001), 2-24 h (MD: -2.21; 95% CI: -3.07 to -1.35; P<0.00001), and 24-48 h (MD: -1.80; 95% CI: -2.92 to 0.68; P=0.002). The RR for the reported adverse events (e.g. pneumothorax) was low. CONCLUSIONS: There is considerable evidence that PVB in addition to GA or alone provide a better postoperative pain control with little adverse effects compared with other analgesic treatment strategies.