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.

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.

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.

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.

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.

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.

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.

Interscalene versus supraclavicular plexus block for the prevention of postoperative pain after shoulder surgery: A systematic review and meta-analysis.

BACKGROUND: Interscalene brachial plexus blockade is the most common regional anaesthesia technique for alleviating pain after shoulder surgery, but complications occur, including ipsilateral hemidiaphragmatic paresis, Horner's syndrome and hoarseness. The supraclavicular approach might be an effective alternative with fewer adverse effects. OBJECTIVES: The aim of this study was to determine whether there is a difference in postoperative pain scores and morphine equivalents between interscalene and supraclavicular brachial plexus blocks. Secondary endpoints were serious adverse events. DESIGN: A systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: A comprehensive literature search of Embase, CENTRAL, MEDLINE and Web of Science was performed from the earliest record to December 2018. ELIGIBILITY CRITERIA: Prospective randomised controlled trials that compare interscalene and supraclavicular brachial plexus blocks in patients undergoing shoulder surgery were eligible for inclusion. Only studies that reported their methods transparently and comprehensibly were included. Conference abstracts or meeting abstracts were not excluded a priori. Risk of bias was assessed using Cochrane methodology. RESULTS: Twelve studies were eligible for meta-analysis. The supraclavicular approach showed overall comparable 24-h pain scores (mean difference -0.34; 95% CI -0.75 to 0.07, P = 0.11) and comparable morphine equivalent consumption (mean difference 1.84 mg per 24 h; 95% CI -0.00 to 3.69, P = 0.05). Secondary endpoint analysis revealed a significantly lower rate of hemidiaphragmatic paresis (risk ratio 0.56; 95% CI 0.39 to 0.82, P = 0.003) and Horner's syndrome (risk ratio 0.29; 95% CI 0.19 to 0.44, P < 0.00001) for the supraclavicular approach. There was no significant difference in hoarseness (risk ratio 0.73; 95% CI 0.48 to 1.13, P = 0.16). CONCLUSION: After 24 postoperative hours, pain scores and consumption of morphine equivalents were comparable. Adverse effects were less common with the supraclavicular approach. The supraclavicular approach might be an efficient alternative to the interscalene approach for shoulder surgery. However, the available evidence is inadequate and prevents a firm conclusion.