Does opioid therapy enhance quality of life in patients suffering from chronic non-malignant pain? A systematic review and meta-analysis.

Background and objective: Chronic pain is associated with a poor health-related quality of life (HRQL). Whereas the prescription rate of opioids increased during the last decades, their use in chronic non-malignant pain remains unclear. However, there is currently no clinical consensus or evidence-based guidelines that consider the long-term effects of opioid therapy on HRQL in patients with chronic non-cancer pain. This systematic review aims to address the question of whether opioid therapy improves HRQL in patients with chronic non-malignant pain and provide some guidance to practitioners. Databases and data treatment: PubMed, EMBASE and CENTRAL were searched in June 2020 for double-blind, randomized trials (RCTs), comparing opioid therapy to placebo and assessed a HRQL questionnaire. The review comprises a qualitative vote counting approach and a meta-analysis of the Short Form Health Survey (SF-36), EQ-5D questionnaire and the pain interference scale of the Brief pain inventory (BPI). Results: 35 RCTs were included, of which the majority reported a positive effect of opioids for the EQ-5D, the BPI and the physical component score (PCS) of the SF-36 compared to placebo. The meta-analysis of the PCS showed a mean difference of 1.82 [confidence interval: 1.32, 2.32], the meta-analysis of the EQ-5D proved a significant advantage of 0.06 [0.00, 0.12]. In the qualitative analysis of the mental component score (MCS) of the SF-36, no positive or negative trend was seen. No significant differences were seen in the MCS (MD: 0.65 [-0.43, 1.73]). A slightly higher premature dropout rate was found in the opioid group (risk difference: 0.04 [0.00, 0.07], p = .07). The body of evidence is graded as low to medium. Conclusion: Opioids have a statistically significant, but small and clinical not relevant effect on the physical dimensions of HRQL, whereas there is no effect on mental dimensions of HRQL in patients with chronic non-malignant pain during the initial months of treatment. In clinical practice, opioid prescriptions for chronic non-cancer pain should be individually assessed as their broad efficacy in improving quality of life is not confirmed. The duration of opioid treatment should be determined carefully, as this review primarily focuses on the initial months of therapy.

[Peripheral Regional Anesthesia Techniques - Standards in Flux?!] / Periphere Regionalanästhesieverfahren ­ Standards im Wandel?!

This review article provides an overview of current developments in peripheral regional anaesthesia (RA). The authors present a subjective compilation based on discussions at professional events and inquiries to the Working Group on Regional Anaesthesia of the German Society for Anaesthesiology and Intensive Care Medicine (DGAI). The article addresses several relevant topics, including the handling of antithrombotic medication in peripheral blockades with reference to European guidelines, the debate on the discharge timing after plexus anaesthesia, and the consideration of rebound pain as an independent pain entity following RA.Furthermore, the contentious discussion regarding the administration of peripheral nerve blockades under general anaesthesia is illuminated. The authors express no fundamental concerns in this regard but emphasize the importance of preoperative evaluation and individual patient needs. The question of mixing local anaesthetics is also addressed, with the authors critically questioning this tradition and recommending the use of individual, long-acting substances.Another focal point is the application of peripheral nerve blockades in emergency medicine, both in preclinical and emergency room settings. The authors highlight the necessity for high-quality studies and discuss the complex organizational issues associated with the preclinical application of RA techniques.

Influence of antithrombotic medication on size and neurological outcome of spinal epidural hematoma after neuraxial anesthesia: a systematic review.

INTRODUCTION: Anticoagulation guidelines were developed to reduce the potential risk of epidural bleeding following neuraxial anesthesia. However, the influence of antithrombotic medication on size of spinal epidural hematoma and neurological outcome is unclear. Therefore, our aim was to analyze whether there is a correlation. METHODS: The study was registered at Prospero (CRD42021285833). A systematic search in MEDLINE, EMBASE, CENTRAL, Web of Science and Google Scholar was conducted in August 2023 for studies reporting spinal epidural hematoma following neuraxial anesthesia. Primary endpoints were segmental extension and neurological outcome. Secondary endpoints were age, sex, body mass index, predisposition, American Society of Anesthesiologists physical status, complicated puncture, multiple punctures, bloody puncture, successful puncture, catheter usage, needle size and worst neurological deficit before treatment. Prespecified multivariate regression and propensity score matching was performed. Publications reporting on more than one patient were critically appraised. RESULTS: A total of 345 cases reported in 304 publications were included. Size of hematoma was not significantly different (antithrombotic medication: OR 0.11, 95% CI (-0.67 to 0.89), p=0.78, 'non-guideline adherent' for puncture/removal: OR 0.13, 95% CI (-0.92 to 1.18), p=0.81). Patients receiving antithrombotic medication were more likely to have persistent neurological deficit (OR 2.00, 95% CI 1.24 to 3.23), p<0.01). Significance persisted after propensity score matching (p=0.04). Patients with non-guideline adherence had a 3.42 higher chance of persistent neurological deficit (95% CI 1.71 to 6.86, p<0.001). DISCUSSION: Antithrombotic medication is not significantly associated with hematoma size; however, the use of antithrombotic medication doubled the risk for persistent neurological deficit after spinal epidural hematoma.

Nominal logistic regression analysis of variables determining needle visibility in ultrasound images - a full factorial cadaver study.

BACKGROUND: Needle visualization is essential to avoid vascular puncture and nerve injury in ultrasound-guided regional anesthesia. Several factors that statistically influence needle visibility have been described but the dimensions of their individual impact remain unclear. This study aimed to quantify the impact of various independent factors on ultrasound needle visibility. METHODS: A total of 1500 ultrasound videos of in-plane needle insertions were obtained in embalmed cadavers with ten different commercially available echogenic and non-echogenic needles at different insertion angles and bevel orientations in a full factorial study design. The visibility of needle tip and shaft were rated as "good" or "poor" visibility. Nominal logistic regression analyses were calculated for the visibility of the needle tip and shaft. RESULTS: SonoPlex Stim Sprotte, SonoTAP Facet (needle tip and shaft) and Spinostar PencilPoint (needle tip)), insertion angle and bevel orientation were associated with good ultrasound visibility, reaching statistical significance (p < 0.05). The range of the effect on the log-odds scale for needle tip visibility was largest for the insertion angle with 6.33, followed by the tissue condition (3.76), bevel orientation (1.45) and the needle types (1.25). Regarding the needle shaft visibility, the largest effect range was observed with the insertion angle (7.36), followed by the tissue conditions with 3.96, needle type (1.86) and bevel orientation (0.95). CONCLUSION: In-plane needle visibility in ultrasound images depends mainly on the insertion angle, as expected. This is closely followed by the tissue condition, which is a factor related to the patient, thus cannot be altered to improve needle visibility. In the dimensions of the log-odds scale, the choice of a specific needle is far less important towards achieving a good visualization, whereas optimizing the bevel orientation can have a larger impact than the needle choice. Concluding from the relative dimensions of factors that determine needle visibility in this model, the importance of needles with echogenic features may be overrated.

[Perioperative pain therapy in minimally invasive thoracic surgery]. / Perioperative Schmerztherapie bei minimal-invasiver Thoraxchirurgie.

Thoracic surgery is often associated with severe postoperative pain levels. Even though these are less pronounced in thoracoscopic approaches, mechanical irritation, compression or injury of intercostal nerves and placement of chest tubes can cause pain levels, which must be treated. An adequate pain therapy in thoracic surgery is essential as insufficient inspiration due to inadequate analgesia may result in postoperative complications. Epidural anesthesia was considered the gold standard in thoracotomy for a long time. For video-assisted thoracoscopy, however, it is sometimes no longer recommended due to its benefit-risk ratio. Alternative thoracic blocks are the paravertebral block, the erector spinae plane block and the serratus anterior block, for which research has found heterogeneous results.This article summarizes the current recommendations for perioperative management of thoracoscopic surgery and gives an overview of the PROSPECT recommendations as well as the current Association of the Scientific Medical Societies in Germany (AWMF) guidelines for perioperative and postoperative pain therapy. In particular, individual regional anesthesia techniques and their current evidence are reviewed.

Rebound pain and postoperative pain profile following brachial plexus block compared to general anaesthesia-An observational study.

BACKGROUND: Regional anaesthesia has the benefit of reducing the need for systemic analgesia and therefore, potentially reducing undesired side effects. With the end of the sensory nerve block however, many patients report severe pain that requires therapy with opioids and often compromise the initial opioid sparing effect. This study aimed to characterise the postoperative pain profile and the phenomenon of rebound pain after axillary brachial plexus anaesthesia (RA) compared to general anaesthesia (GA). DESIGN: Single-centre observational, stratified cohort study. SETTING: The study was conducted at University Hospital Marburg from May 2020 until September 2022. PARTICIPANTS: One hundred thirty-two patients receiving elective hand and forearm surgery were enrolled in this study. INTERVENTIONS: Group RA received ultrasound-guided brachial plexus anaesthesia via the axillary approach with 30 mL of prilocaine 1% and 10 mL ropivacaine 0.2%. Group GA received balanced or total intravenous general anaesthesia. MAIN OUTCOME MEASURES: Primary endpoint were integrated pain scores (IPS) within 24 h postoperatively. Secondary endpoints were pain scores (NRS 0-10), morphine equivalents, patient satisfaction, quality of recovery and opioid-related side effects. RESULTS: One hundred thirty-two patients were analysed of which 66 patients received brachial plexus block and 66 patients received general anaesthesia. Following RA significantly lower IPS were seen directly after surgery (p < .001) and during the post-anaesthesia care unit interval (p < .001) but equalised after 3 h at the ward. No overshoot in pain scores or increased opioid consumption could be detected. Patient satisfaction and postoperative recovery were comparable between both groups. CONCLUSION: The IPS and NRS was initially lower in the RA group, increased with fading of the block until equal to the GA group and equal thereafter. Although various definitions of rebound pain were met during this phase, the opioid sparing effect of regional anaesthesia was not counteracted by it. The incidence of episodes with uncontrolled, severe pain did not differ between groups. We found no clinical implications of rebound pain in this setting, since the RA group did not show higher pain scores than the GA group at any time point. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00021764).

Pharmacologic interventions for the therapy of postanesthetic shivering in adults: a systematic review and network meta-analysis.

INTRODUCTION: Shivering is a common side effect after general anesthesia. Risk factors are hypothermia, young age and postoperative pain. Severe complications of shivering are rare but can occur due to increased oxygen consumption. Previous systematic reviews are outdated and have summarized the evidence on the topic using only pairwise comparisons. The objective of this manuscript was a quantitative synthesis of evidence on pharmacological interventions to treat postanesthetic shivering. EVIDENCE ACQUSITION: Systematic review and frequentist network meta-analysis using the R package netmeta. Endpoints were the risk ratio (RR) of persistent shivering at one, five and 10 minutes after treatment with saline/placebo as the comparator. Data were retrieved from Medline, Embase, Central and Web of Science up to January 2022. Eligibility criteria were: randomized, controlled, and blinded trials comparing pharmacological interventions to treat shivering after general anesthesia. Studies on shivering during or after any type of regional anesthesia were excluded as well as sedated patients after cardiac surgery. EVIDENCE SYNTHESIS: Thirty-two trials were eligible for data synthesis, including 28 pharmacological interventions. The largest network included 1431 patients. The network geometry was two-centered with most comparisons linked to saline/placebo or pethidine. The best interventions were after one minute: doxapram 2 mg/kg, tramadol 2 mg/kg and nefopam 10 mg, after 5 minutes: tramadol 2 mg/kg, nefopam 10 mg and clonidine 150 µg and after 10 minutes: nefopam 10 mg, methylphenidate 20 mg and tramadol 1 mg/kg, all reaching statistical significance. Pethidine 25 mg and clonidine 75 µg also performed well and with statistical significance in all networks. CONCLUSIONS: Nefopam, tramadol, pethidine and clonidine are the most effective treatments to stop postanesthetic shivering. The efficacy of doxapram is uncertain since different doses showed contradictory effects and the evidence for methylphenidate is based on a single comparison in only one network. Furthermore, both lack data on side effects. Further studies are needed to clarify the efficacy of dexmedetomidine to treat postanesthetic shivering.

Spinal anesthesia in ambulatory surgery.

Spinal anesthesia is a safe alternative to general anesthesia but remains underrepresented in the ambulatory setting. Most concerns relate to low flexibility of spinal anesthesia duration and the management of urinary retention in the outpatient setting. This review focuses on the characterization and safety of the local anesthetics that are available to adapt spinal anesthesia very flexibly to the needs of ambulatory surgery. Furthermore, recent studies on the management of postoperative urinary retention provide evidence for safe, but report wider discharge criteria and much lower hospital admission rates. With the local anesthetics that have current approval for usage in spinal anesthesia, most requirements for ambulatory surgeries can be met. The reported evidence on local anesthetics without approval supports clinically established off-label use and can improve the results even further.

The effect of adjuvants added to local anaesthetics for single-injection upper extremity peripheral regional anaesthesia: A systematic review with network meta-analysis of randomised trials.

BACKGROUND: Peripheral regional anaesthesia is frequently used for upper extremity surgery. To prolong the duration of analgesia, adjuvants can be added to single-injection local anaesthetics. Despite attempts to compare several adjuvants in pairwise meta-analyses, a comprehensive comparison is still missing. OBJECTIVE: The objective of this network meta-analysis was to determine the effectiveness of adjuvants in upper extremity peripheral nerve blocks. DESIGN: A systematic review of randomised controlled trials with network meta-analyses. DATA SOURCES: A literature search in Embase, CENTRAL, MEDLINE and Web of Science was performed up to March 2023. ELIGIBILITY CRITERIA: Randomised trials comparing different adjuvants injected perineurally in peripheral upper extremity nerve blocks were eligible. Frequentist network meta-analysis was conducted using a random effects model with physiological saline as the comparator. The primary endpoint was the ratio of means (ROM) of the duration of analgesia. RESULTS: The review included 242 randomised controlled trials with a total of 17 391 patients. Twenty-eight adjuvants were compared in the largest networks. Most network estimations consisted of a high proportion of direct evidence. Fourteen adjuvants increased the duration of analgesia significantly by the following factors, ROM [95% confidence interval (CI)]: dexamethasone 1.95 (1.79 to 2.13), buprenorphine 1.83 (1.51 to 2.24), butorphanol 1.84 (1.41 to 2.39), potassium chloride 1.89 (1.15 to 3.11), dexmedetomidine 1.70 (1.59 to 1.81), sufentanil 1.70 (1.27 to 2.29), ketorolac 1.68 (1.24 to 2.27), midazolam 1.55 (1.24 to 1.94), tramadol 1.52 (1.32 to 1.75), nalbuphine 1.50 (1.30 to 1.72), morphine 1.43 (1.09 to 1.88), magnesium sulfate 1.42 (1.20 to 1.67), clonidine 1.36 (1.24 to 1.50) and fentanyl 1.23 (1.08 to 1.40). Inconsistency in network meta-analysis was substantial. Overall side effect rates were low with all adjuvants. CONCLUSION: The best interventions to prolong the duration of analgesia were dexamethasone, followed by dexmedetomidine, opioids, electrolytes, ketorolac and midazolam. There are general concerns about the quality of underlying studies and the risk of publication bias. TRIAL REGISTRATION: PROSPERO 2018 CRD42018115722.

Risk factors and protective factors of acute postoperative pain: an observational study at a German university hospital with cross-sectional and longitudinal inpatient data.

OBJECTIVES: Surgical fear is one of the most important psychological risk factors for postoperative pain, but less is known about the contribution of protective factors. This study investigated somatic and psychological risk and resilience factors of postoperative pain and validated the German version of the Surgical Fear Questionnaire (SFQ). SETTING: University Hospital of Marburg, Germany. DESIGN: Single-centre observational study and cross-sectional validation study. PARTICIPANTS: Data for validating the SFQ were obtained from a cross-sectional observational study (N=198, mean age 43.6 years, 58.8% female) with persons undergoing different kinds of elective surgery. A sample of N=196 (mean age 43.0 years, 45.4% female) undergoing elective (orthopaedic) surgery was analysed to investigate somatic and psychological predictors of relevant acute postsurgical pain (APSP). OUTCOME MEASURES: Participants completed preoperative and postoperative assessments at postoperative days 1, 2 and 7. Presurgical pain, age, gender, pain expectation, surgical setting, physical status, anaesthesia, surgical fear, pain catastrophising, depression, optimism and self-efficacy were examined as predictors. RESULTS: Confirmatory factor analysis confirmed the original two-factor structure of the SFQ. Correlation analyses indicated good convergent and divergent validity. Internal consistency (Cronbach's α) was between 0.85 and 0.89. Blockwise logistic regression analyses for the risk of APSP revealed outpatient setting, higher preoperative pain, younger age, more surgical fear and low dispositional optimism as significant predictors. CONCLUSIONS: The German SFQ is a valid, reliable and economical instrument with which the important psychological predictor surgical fear can be assessed. Modifiable factors that increase the risk of postoperative pain were higher pain intensity before surgery and being fearful about negative consequences of the surgery whereas positive expectations seem to buffer against postsurgical pain. TRIAL REGISTRATION NUMBERS: DRKS00021764 and DRKS00021766.

Efficacy of Adjuvants in Ophthalmic Regional Anesthesia: A Systematic Review and Network Meta-analysis.

PURPOSE: This network meta-analysis aims to determine the differences between adjuvants that are used in combination with local anesthetics for ophthalmic regional anesthesia. DESIGN: Systematic review and network meta-analysis. METHODS: A systematic literature search for randomized controlled trials, comparing the impact of adjuvants in ophthalmic regional anesthesia, in Embase, CENTRAL, MEDLINE and Web of Science was performed. Risk of bias was evaluated using the Cochrane risk of bias tool. Frequentist network meta-analysis was performed using a random effects model with saline as the comparator. Primary endpoints were the onset and the duration of sensory block and globe akinesia, as well as the duration of analgesia. Summary measure was the ratio of means (ROM). Secondary endpoints were the rates of side effects and adverse events. RESULTS: A total of 39 trials were identified as eligible for network meta-analysis, including 3046 patients. In all, 17 adjuvants were compared in the most extensive network (onset of globe akinesia). The addition of fentanyl (F), clonidine (C), or dexmedetomidine (D) showed the best overall results. Onset of sensory block was as follows: F 0.58 (CI = 0.47-0.72), C 0.75 (0.63-0.88), D 0.71 (0.61-0.84); onset of globe akinesia: F 0.71 (0.61-0.82), C 0.70 (0.61-0.82), D 0.81 (0.71-0.92); duration of sensory block: F 1.20 (1.14-1.26), C 1.22 (1.18-1.27), D 1.44 (1.34-1.55); duration of globe akinesia: F 1.38 (1.22-1.57), C 1.45 (1.26-1.67), D 1.41 (1.24-1.59); and duration of analgesia: F 1.46 (1.33-1.60), C 1.78 (1.63-1.96), D 1.41 (1.28-1.56). CONCLUSIONS: The addition of fentanyl, clonidine, or dexmedetomidine showed beneficial effects regarding onset and duration of sensory block and globe akinesia.

[Pain Management in Palliative Care]. / Schmerztherapie in der Palliativmedizin.

Patients in the palliative phase of a disease often suffer from pain, which leads to a significant reduction in quality of life. Since in most cases there is a progression rather than an improvement of the disease over time, pain therapy must also be dynamically adapted. Due to accompanying symptoms and the physical burden of the disease, treatment of pain is often difficult. In the palliative situation, pain should not only be understood as an excitation of nociceptors but is rather also an expression of mental stress. In this article, we would like to give an overview of the available drugs, application methods and alternative treatment options. Specifically, the article is divided into the following subsections: non-opioid analgesics, opioids, co-analgesics, patient-controlled analgesia procedures, neuraxial and peripheral regional anesthesia procedures, neurolysis, supportive therapies and palliative sedation. Thus, when treating palliative patients, the focus should not only be on the one symptom of pain, but, in the sense of the bio-psycho-social model, a multimodal oriented treatment of the patient with all his symptoms, also including his relatives, must be carried out.

Measures to prolong duration of sensory block after regional anaesthesia.

PURPOSE OF REVIEW: The duration of single-injection regional anaesthesia is limited due to the inherent pharmacological properties of local anaesthetics. The ideal duration of a regional anaesthesia block lasting for the first 24 h postoperatively can be stated, while a residual analgesic effect thereafter is desirable.The aim of this review is to present current options to prolong the duration of action of single-injection peripheral regional anaesthesia in the ambulatory setting. Secondly, this review outlines and discusses the latest evidence regarding the clinical use of adjuvants and sustained-release local anaesthetics. RECENT FINDINGS: Extended-release formulations of local anaesthetics such as liposomal bupivacaine have been developed to prolong regional anaesthesia up to 96 h. Recent studies, however, show that the actual effects remain far behind expectations and that the efficacy is only marginally better than bupivacaine hydrochloride.Adjuvants to local anaesthetics have been studied extensively with heterogenous results. Dexamethasone and alpha-2 agonists range among the most effective measures to prolong single-injection nerve blocks.Continuous nerve blocks and catheter techniques may prolong regional anaesthesia very effectively, but are less cost-effective regarding block procedure, postoperative care and handling logistical issues especially in ambulatory surgery. SUMMARY: In conclusion, adjuvants are the recommended measure to prolong regional anaesthesia where needed. With good evidence supporting it, dexamethasone is the most effective adjuvant, followed by dexmedetomidine. Both have few side effects and a favourable safety profile. However, a preferable duration of analgesia lasting for the first 24 h postoperatively is still not reliably achievable.

Equianalgesic potency ratios of opioids used in patient-controlled analgesia: A network meta-analysis.

OBJECTIVE: To determine equianalgesic potency ratios for opioids with an -evidence-based approach without the use of pre-existing potency tables. DESIGN: Frequentist network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing opioids in patient-controlled analgesia (PCA). SETTING: A systematic review. DATA SOURCES: A systematic search of MEDLINE, EMBASE, the Cochrane Library (CENTRAL), and Web of Science identified relevant RCTs from start of recording to 2019. ELIGIBILITY CRITERIA: RCTs comparing opioids via intravenous PCA in acute pain, with comparable resulting pain scores and identical treatment with coanalgesics at study level. The quality of studies was assessed using the Cochrane risk of bias tool with six items. RESULTS: 52 RCTs were identified with data for 16 opioids. Primary endpoint was the inverted ratio of means of the total consumption administered via PCA, which resembles the analgesic potency. The calculated analgesic potencies were sufentanil 423 [95 percent CI 334.99; 532.96], fentanyl 58 [48.22; 68.60], buprenorphine 37 [26.66; 50.81], remifentanil 13 [9.37; 19.13], alfentanil 7 [4.02; 11.01], hydromorphone 6 [4.96; 8.43], oxymorphone 6 [4.46; 8.84], butorphanol 4.5 [3.05; 6.73], diamorphine 2.2 [1.16; 4.10], morphine 1, oxycodone 0.9 [0.65; 1.34], piritramide 0.9 [0.55; 1.56], nalbuphine 0.7 [0.54; 0.95], pethidine 0.12 [0.10; 0.15], meptazinol 0.08 [0.03; 0.20], and tramadol 0.08 [0.07; 0.10]. CONCLUSIONS: The results in part contradict the values from the literature, which have been criticized for their imprecision. From clinical experience however, our findings seem very plausible. Short-acting opioids are less potent compared to longer acting drugs, eg, morphine, probably due to shorter intervals for -readministration.

[Rebound pain-From definition to treatment]. / "Rebound pain" ­ von der Definition bis zur Therapie.

BACKGROUND: Rebound pain as a side effect of regional anaesthesia is an excessive sensation of pain after the effect of local anaesthesia has subsided. This sensation goes well beyond the normal wound pain following a surgical intervention. This phenomenon has entered focus of research in the past 10 years now, but the specific causes are so far unclear and there are still no targeted treatment recommendations. OBJECTIVE: This review article is intended to give the readership an overview of the current state of research about rebound pain. The theories of pathophysiology are presented and prophylaxis as well as treatment strategies are explained. MATERIAL AND METHODS: For this review article, the publications about rebound pain that appeared from 2005 up to May 2021 in PubMed were reviewed and the authors' definitions of rebound pain as well as the assumptions on pathophysiology and treatment recommendations were summarized. RESULTS AND DISCUSSION: A total of 22 original papers from the years 2005-2021 were evaluated regarding the differences between the definitions of rebound pain, the assumption of its occurrence as well as possible treatment options. It turns out that there is no uniform definition by the professional societies, the pathophysiology has not yet been clearly identified and no clear recommendations for prophylaxis or treatment can be given to date; however, early administration of pain medication (e.g. NSAIDs) before the end of the nerve block has proven to be helpful. Likewise, dexamethasone as an adjuvant to regional anaesthesia shows positive effects regarding the occurrence of rebound pain. In any case, it makes sense to provide patients with comprehensive information about this special side effect of regional anaesthesia so that those affected can correctly classify the excessive pain reaction. Targeted studies to avoid severe pain after regional anaesthesia, e.g. through the addition of adjuvants, are necessary in order to keep side effects as low as possible and thereby improve patient comfort and the acceptance of regional anaesthesia.

[Liposomal bupivacaine-No breakthrough in postoperative pain management]. / Liposomales Bupivacain ­ kein Durchbruch in der postoperativen Schmerztherapie.

One of the main limitations concerning the use of local anesthetics is due to their restricted duration of action. In recent years, liposomal formulations with prolonged release kinetics have been developed to extend the pharmacological duration of action of the 1­stage peripheral regional anesthesia (single-shot procedure) and thus bring about a longer duration of action. The focus here is particularly on achieving postoperative freedom from pain for at least 24 h (or even better 48 h) and thus early mobilization of patients using on-demand medication causing (at most) minor local sensory blockade without causing motor impairments (at least that is the ideal). Therefore, methods of utilizing slow-release drugs as seen in liposomal carrier systems have experienced increasing scientific attention in the last few years. A common modern pharmacological example with a theoretically significantly longer duration of action is liposomal bupivacaine, an amide local anesthetic. Due to a multivesicular liposome structure, the retarded release of the active component bupivacaine HCl leads to a theoretical pharmacological effectiveness of up to 72 h. Previous studies consistently showed a safety profile comparable to conventional bupivacaine HCl. Liposomal bupivacaine has been approved by the U.S. Food and Drug Administration (FDA) under the trade name Exparel© (Pacira Pharmaceuticals, Parsippany, NJ, USA) since 2011; however, its use is currently limited to local wound infiltration, transverse abdominis plane (TAP) blocks, and interscalene nerve blocks of the brachial plexus. In 2020, the European Medicines Agency (EMA) also approved the use of liposomal bupivacaine for blockade of the brachial plexus or the femoral nerve and as a field block or for wound infiltration to treat postoperative pain. So far, studies on the clinical effectiveness of liposomal bupivacaine have been very heterogeneous and there have been no conclusive meta-analyses with sufficient rigor or significance. Recent systematic reviews and meta-analyses, combining the results of clinical studies regarding the analgesic efficiency of liposomal bupivacaine in different fields of application, consistently refuted any benefit of clinical relevance provided by the liposomal formulation. There is currently sufficient evidence to now end the ongoing debate around liposomal bupivacaine. The aim of this work is to give the reader a current, evidence-based overview of this substance.

Comparison of left double lumen tube and y-shaped and double-ended bronchial blocker for one lung ventilation in thoracic surgery-a randomised controlled clinical trial.

BACKGROUND: Double lumen tube (DLT) intubation is the most commonly used technique for one lung ventilation. Bronchial blockers (BB) are an alternative, especially for difficult airways. The EZ-bronchial blocker (EZB) is an innovative y-shaped and double-ended device of the BB family. METHODS: A randomised, controlled trial was conducted in 80 patients undergoing elective thoracic surgery using DLT or EZB for one lung ventilation (German Clinical Trial Register DRKS00014816). The objective of the study was to compare the clinical performance of EZB with DLT. Primary endpoint was total time to obtain successful one lung ventilation. Secondary endpoints were time subsections, quality of lung collapse, difficulty of intubation, any complications during the procedure, incidence of objective trauma of the oropharynx and supraglottic space and intubation-related subjective symptoms. RESULTS: 74 patients were included, DLT group (n = 38), EZB group (n = 36). Median total time to obtain one lung ventilation [IQR] in the DLT group was 234 s [207 to 294] versus 298 s [243 to 369] in the EZB group (P = 0.007). Median total time was relevantly influenced by different preparation times. Quality of lung collapse was equal in both groups, DLT group 89.5% were excellent vs. 83.3% in the EZB group (P = 0.444). Inadequate lung collapse in five patients of the EZB group resulted in unsuccessful repositioning attempts and secondary DLT placement. Endoscopic examinations revealed significantly more carina trauma (P = 0.047) and subglottic haemorrhage (P = 0.047) in the DLT group. Postoperative subjective symptoms (sore throat, hoarseness) were more common in the DLT group, as were speech problems. CONCLUSIONS: Using EZB prima facie results in prolonged time to obtain one lung ventilation with equal quality of lung collapse for the thoracic surgeon. If preparation times are omitted in the analysis, the time difference is statistically and clinically not relevant. Our data showed only little evidence for reducing objective airway trauma as well as subjective complaints. In summary both procedures were comparable in terms of times and clinical applicability. Therefore decisions for DLT or EZB should depend more on individual experience, in-house equipment and the individual patient, than on any times that are neither clinically significant nor relevant. TRIAL REGISTRATION: German Clinical Trial Register DRKS00014816 , prospectively registered on 07.06.2018.

The analgesic efficacy of liposomal bupivacaine compared with bupivacaine hydrochloride for the prevention of postoperative pain: a systematic review and meta-analysis with trial sequential analysis.

BACKGROUND/IMPORTANCE: Liposomal bupivacaine (LB) is a prolonged release formulation of conventional bupivacaine designed for prolonging local or peripheral regional single injection anesthesia. To this day, the benefit of the new substance on relevant end points is discussed controversial. OBJECTIVE: The objective was to determine whether there is a difference in postoperative pain scores and morphine consumption between patients treated with LB and bupivacaine hydrochloride in a systematic review and meta-analysis. EVIDENCE REVIEW: Randomized controlled trials (RCT) were identified in Embase, CENTRAL, MEDLINE and Web of Science up to May 2020. Risk of bias was assessed using Cochrane methodology. Primary end points were the mean pain score difference and the relative morphine equivalent (MEQ) consumption expressed as the ratio of means (ROM) 24 and 72 hours postoperatively. FINDINGS: 23 RCTs including 1867 patients were eligible for meta-analysis. The mean pain score difference at 24 hours postoperatively was significantly lower in the LB group, at -0.37 (95% CI -0.56 to -0.19). The relative MEQ consumption after 24 hours was also significantly lower in the LB group, at 0.85 (0.82 to 0.89). At 72 hours, the pain score difference was not significant at -0.25 (-0.71 to 0.20) and the MEQ ratio was 0.85 (0.77 to 0.95). CONCLUSION: The beneficial effect on pain scores and opioid consumption was small but not clinically relevant, despite statistical significance. The effect was stable among all studies, indicating that it is independent of the application modality.

Videolaryngoscopy versus direct laryngoscopy for double-lumen endotracheal tube intubation in thoracic surgery - a randomised controlled clinical trial.

BACKGROUND: Double-lumen tube (DLT) intubation is necessary for thoracic surgery and other operations with the need for lung separation. However, DLT insertion is complex and might result in airway trauma. A new videolaryngoscopy (GVL) with a thin blade might improve the intubation time and reduce complexity as well as iatrogenic airway complications compared to conventional direct laryngoscopy (DL) for DLT intubation. METHODS: A randomised, controlled trial was conducted in 70 patients undergoing elective thoracic surgery using DLT for lung separation. Primary endpoint was time to successful intubation. The secondary endpoints of this study were number of intubation attempts, the assessment of difficulty, any complications during DLT intubation and the incidence of objective trauma of the oropharynx and supraglottic space and intubation-related subjective symptoms. RESULTS: 65 patients were included (DL group [n  =  31], GVL group [n  =  34]). Median intubation time (25th-75th percentiles) in GVL group was 93 s (63-160) versus 74 (58-94) in DL group [p = 0.044]. GVL resulted in significantly improved visualisation of the larynx (Cormack and Lehane grade of 1 in GVL group was 97% vs. 74% in DL Group [p = 0.008]). Endoscopic examinations revealed significant differences in GVL group compared to DL group showing less red-blooded vocal cord [p = 0.004], vocal cord haematoma [p = 0.022] and vocal cord haemorrhage [p = 0.002]. No significant differences regarding the postoperative subjective symptoms of airway were found. CONCLUSIONS: Videolaryngoscopy using the GlideScope®-Titanium shortly prolongs DLT intubation duration compared to direct laryngoscopy but improves the view. Objective intubation trauma but not subjective complaints are reduced. TRIAL REGISTRATION: German Clinical Trial Register DRKS00020978, retrospectively registered on 09. March 2020.

Effect of bupivacaine and adjuvant drugs on skeletal muscle tissue oximetry and blood flow: an experimental study.

BACKGROUND: Skeletal muscle microvascular blood flow plays a critical role in many myopathologies. The influence of bupivacaine and adjuvants on skeletal muscle microvascular perfusion and tissue oximetry is poorly understood but might be a relevant risk factor for myopathies after local anesthetic administration. The aim of this experimental study was to determine the effects of bupivacaine alone or in combination with epinephrine or clonidine on skeletal muscle perfusion and tissue oximetry. METHODS: Combined tissue spectrophotometry and Laser-Doppler flowmetry and tissue oximetry were used to assess local muscle blood flow in anesthetized pigs after topical administration of test solutions (bupivacaine, bupivacaine with epinephrine or clonidine, saline). Measurements were performed for up to 60 mins. RESULTS: The application of bupivacaine alone did not alter relative muscle blood flow significantly, whereas the addition of epinephrine or clonidine to bupivacaine resulted in a significant reduction of relative muscle blood flow at T30 and T60. However, bupivacaine resulted in a significant decrease of tissue oximetry values when compared to saline control group at T30 and T60. The application of bupivacaine combined with clonidine or epinephrine resulted in no significant reduction of tissue oximetry when compared to bupivacaine alone. CONCLUSION: Bupivacaine alone results in a significant decrease of tissue oximetry in skeletal muscle which is not increased by the addition of epinephrine or clonidine despite further reductions of microcirculatory perfusion. Overall, bupivacaine alone or with adjuvants does produce local muscle ischemia for which pathological consequences need to be addressed in further studies.