Intravenous versus perineural dexamethasone to prolong analgesia after interscalene brachial plexus block: a systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: The efficacy of perineural vs intravenous dexamethasone as a local anaesthetic adjunct to increase duration of analgesia could be particular to specific peripheral nerve blocks because of differences in systemic absorption depending on the injection site. Given this uncertainty, we performed a systematic review with meta-analysis and trial sequential analysis comparing dexamethasone administered perineurally or intravenously combined with local anaesthetic for interscalene brachial plexus block. METHODS: Following a search of various electronic databases, we included 11 trials (1145 patients). The primary outcome was the duration of analgesia defined as the time between peripheral nerve block or onset of sensory blockade and the time to first analgesic request or initial report of pain. RESULTS: The primary outcome, duration of analgesia, was greater in the perineural dexamethasone group, with a mean difference (95% confidence interval) of 122 (62-183) min, I2=73%, P<0.0001. Trial sequential analysis indicated that firm evidence had been reached. The quality of evidence was downgraded to low, mainly because of moderate inconsistency and serious publication bias. No significant differences were present for any of the secondary outcomes, except for onset time of sensory and motor blockade and resting pain score at 12 h, but the magnitude of differences was not clinically relevant. CONCLUSIONS: There is low-quality evidence that perineural administration of dexamethasone as a local anaesthetic adjunct increases duration of analgesia by an average of 2 h compared with intravenous injection for interscalene brachial plexus block. Given the limited clinical relevance of this difference, the off-label use of perineural administration, and the risk of drug crystallisation, we recommend intravenous dexamethasone administration. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023466147).

Research priorities in regional anaesthesia: where should we focus?

Using a modified Delphi technique, an international group of regional anaesthetists generated a list of top research priorities in regional anaesthesia. The list of unanswered research questions was created from a questionnaire completed by >500 anaesthetists and distilled into 11 priorities grouped into four themes: clinical practice and efficacy, pain management, technology and equipment, and training and assessment.

Impact of spinal versus general anaesthesia on perioperative obstructive sleep apnoea severity in patients undergoing hip arthroplasty: a post hoc analysis of two randomised controlled trials.

BACKGROUND: Recommendations suggest favouring regional over general anaesthesia to reduce impact on postoperative sleep apnoea severity, but there is currently no evidence to support this. We compared the impact of general vs spinal anaesthesia on postoperative sleep apnoea severity and assessed the evolution of sleep apnoea severity up to the third postoperative night. METHODS: This post hoc analysis used pooled data from two previous randomised controlled trials in patients undergoing total hip arthroplasty under general or spinal anaesthesia (n=96), without performing a preliminary power analysis. All participants underwent respiratory polygraphy before surgery and on the first and third postoperative nights. The primary outcomes were the supine apnoea-hypopnea index on the first postoperative night and the evolution of the supine apnoea-hypopnea index up to the third postoperative night. Secondary outcomes included the oxygen desaturation index on the first and third postoperative nights. RESULTS: In the general and spinal anaesthesia groups, mean (95% confidence interval) values for the supine apnoea-hypopnoea index on the first postoperative night were 20 (16-25) and 21 (16-26) events h-1 (P=0.82), respectively; corresponding values on the third postoperative night were 34 (22-45) and 35 (20-49) events h-1 (P=0.91). The generalised estimating equations model showed a significant time effect. Secondary outcomes were similar in the two groups. CONCLUSIONS: Use of spinal anaesthesia compared with general anaesthesia was not associated with a reduction in postoperative sleep apnoea severity, which was worse on the third postoperative night. CLINICAL TRIAL REGISTRATION: NCT02717780 and NCT02566226.

Non-pulmonary complications of intrathecal morphine administration: a systematic review and meta-analysis with meta-regression.

BACKGROUND: Intrathecal morphine provides effective analgesia for a range of operations. However, widespread implementation into clinical practice is hampered by concerns for potential side-effects. We undertook a systematic review, meta-analysis, and meta-regression with the primary objective of determining whether a threshold dose for non-pulmonary complications could be defined and whether an association could be established between dose and complication rates when intrathecal morphine is administered for perioperative or obstetric analgesia. METHODS: We systematically searched the literature for randomised controlled trials comparing intrathecal morphine vs control in patients undergoing any type of surgery under general or spinal anaesthesia, or women in labour. Primary outcomes were rates of postoperative nausea and vomiting, pruritus, and urinary retention within the first 24 postoperative hours, analysed according to doses (1-100 µg; 101-200 µg; 201-500 µg; >500 µg), type of surgery, and anaesthetic strategy. Trials were excluded if doses were not specified. RESULTS: Our analysis included 168 trials with 9917 patients. The rates of postoperative nausea and vomiting, pruritus, and urinary retention were significantly increased in the intrathecal morphine group, with an odds ratio (95% confidence interval) of 1.52 (1.29-1.79), P<0.0001; 6.11 (5.25-7.10), P<0.0001; and 1.73 (1.17-2.56), P=0.005, respectively. Meta-regression could not establish an association between dose and rates of non-pulmonary complications. There was no subgroup difference according to surgery for any outcome. The quality of evidence was low (Grading of Recommendations Assessment, Development, and Evaluation [GRADE] system). CONCLUSIONS: Intrathecal morphine significantly increased postoperative nausea and vomiting, pruritus, and urinary retention after surgery or labour in a dose-independent manner. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023387838).

Research priorities in regional anaesthesia: an international Delphi study.

BACKGROUND: Regional anaesthesia use is growing worldwide, and there is an increasing emphasis on research in regional anaesthesia to improve patient outcomes. However, priorities for future study remain unclear. We therefore conducted an international research prioritisation exercise, setting the agenda for future investigators and funding bodies. METHODS: We invited members of specialist regional anaesthesia societies from six continents to propose research questions that they felt were unanswered. These were consolidated into representative indicative questions, and a literature review was undertaken to determine if any indicative questions were already answered by published work. Unanswered indicative questions entered a three-round modified Delphi process, whereby 29 experts in regional anaesthesia (representing all participating specialist societies) rated each indicative question for inclusion on a final high priority shortlist. If ≥75% of participants rated an indicative question as 'definitely' include in any round, it was accepted. Indicative questions rated as 'definitely' or 'probably' by <50% of participants in any round were excluded. Retained indicative questions were further ranked based on the rating score in the final Delphi round. The final research priorities were ratified by the Delphi expert group. RESULTS: There were 1318 responses from 516 people in the initial survey, from which 71 indicative questions were formed, of which 68 entered the modified Delphi process. Eleven 'highest priority' research questions were short listed, covering themes of pain management; training and assessment; clinical practice and efficacy; technology and equipment. CONCLUSIONS: We prioritised unanswered research questions in regional anaesthesia. These will inform a coordinated global research strategy for regional anaesthesia and direct investigators to address high-priority areas.

Efficacy and safety of intrathecal diamorphine: a systematic review and meta-analysis with meta-regression and trial sequential analysis.

BACKGROUND: Intrathecal diamorphine is believed to provide postoperative analgesia but is associated with adverse effects such as nausea and vomiting. There is little evidence of synthesis regarding intrathecal diamorphine in the contemporary literature. We performed a systematic review, meta-analysis with meta-regression and trial sequential analysis to determine the magnitude of intrathecal diamorphine efficacy and safety. METHODS: We systematically searched the literature for trials comparing intrathecal diamorphine with a control group in patients undergoing all types of surgery. The primary efficacy and safety outcomes were intravenous morphine consumption and incidence of postoperative nausea and vomiting at 24 h following surgery, respectively. RESULTS: Twelve trials were identified, which included data for 712 patients. Intrathecal doses of diamorphine ranged from 100 µg to 2500 µg. Intravenous morphine consumption at 24 h postoperatively was significantly reduced in the intrathecal diamorphine group, with a mean difference (95%CI) of -8 mg (-11 to -6), I2 = 93%, p < 0.001. There was a significant difference between three intrathecal diamorphine dosing subgroups but without correlation: mean differences (95%CI) -1 mg (-3-0), -26 mg (-40 to -11) and -6 mg (-15-4) in patients receiving doses of 0-200 µg, 201-400 µg and > 400 µg, respectively (p = 0.003). Intrathecal diamorphine increased postoperative nausea and vomiting with a risk ratio (95%CI) of 1.37 (1.19-1.58), I2 = 7%, p < 0.001. There were no differences in postoperative nausea and vomiting between the three intrathecal diamorphine dosing subgroups. There was no correlation observed with meta-regression of the primary efficacy and safety outcomes. The quality of evidence for all outcomes was very low. CONCLUSION: There is very low level of evidence that intrathecal diamorphine provides effective analgesia after surgery, while increasing postoperative nausea and vomiting with doses > 200 µg.

Comparison of intravenous versus perineural dexamethasone as a local anaesthetic adjunct for peripheral nerve blocks in the lower limb: A meta-analysis and systematic review.

BACKGROUND: As a local anaesthetic adjunct, the systemic absorption of perineural dexamethasone in the lower limb could be restricted because of decreased vascularity when compared with the upper limb. OBJECTIVES: To compare the pharmacodynamic characteristics of intravenous and perineural dexamethasone in the lower limb. DESIGN: Systematic review of randomised controlled trials with meta-analysis. DATA SOURCES: Systematic search of Central, Google Scholar, Ovid Embase and Ovid Medline to 18 July 2023. ELIGIBILITY CRITERIA: Randomised controlled trials, which compared the intravenous with perineural administration of dexamethasone as a local anaesthetic adjunct in peripheral nerve blocks for surgery of the lower limb. RESULTS: The most common peripheral nerve blocks were femoral, sciatic and ankle block. The local anaesthetic was long acting in all trials and the dose of dexamethasone was 8 mg in most trials. The primary outcome, the duration of analgesia, was investigated by all nine trials (n = 546 patients). Overall, compared with intravenous dexamethasone, perineural dexamethasone increased the duration of analgesia from 19.54 to 22.27 h, a mean difference [95% confidence interval (CI) of 2.73 (1.07 to 4.38) h; P = 0.001, I2 = 87]. The quality of evidence was moderate owing to serious inconsistency. However, analysis based on the location of the peripheral nerve block, the type of local anaesthetic or the use of perineural adrenaline showed no difference in duration between intravenous and perineural dexamethasone. No differences were shown for any of the secondary outcomes related to efficacy and side effects. CONCLUSION: In summary, moderate evidence supports the superiority of perineural dexamethasone over intravenous dexamethasone in prolonging the duration of analgesia. However, this difference is unlikely to be clinically relevant. Consideration of the perineural use of dexamethasone should recognise that this route of administration remains off label.

Duration of analgesia after forefoot surgery compared between an ankle and a sciatic nerve block at the popliteal crease: A randomised controlled single-blinded trial.

BACKGROUND: Forefoot surgery is associated with severe postoperative pain. Ankle and sciatic nerve blocks provide satisfactory postoperative analgesia after forefoot surgery, but little is known on their respective duration of analgesia. OBJECTIVE: This randomised controlled, single-blinded trial tested the hypothesis that after forefoot surgery in the setting of multimodal analgesia, an ankle block provides analgesia superior to that of a sciatic nerve block at the popliteal crease. DESIGN: A randomised controlled study. SETTING: A single centre study in a university hospital in Switzerland, from September 2018 to November 2022. PATIENTS: From 91 patients scheduled for forefoot surgery, 60 met the inclusion criteria of which 56 completed the protocol and their data were available for analysis. Exclusion criteria were existing sciatic nerve deficit, pre-existing peripheral neuropathy, chronic pain diagnosis, pregnancy, or identified contraindications to peripheral nerve block. INTERVENTION: Patients undergoing forefoot surgery were randomly allocated to either a multi-injection ankle block (partly under ultrasound guidance) or a sciatic nerve block at the popliteal crease (under ultrasound guidance) combined with a saphenous nerve block at the ankle. Patients in each group received a total of 30 ml of ropivacaine 0.5% and a multimodal analgesic regimen inclusive of dexamethasone, paracetamol, ketorolac then ibuprofen. MAIN OUTCOME MEASURE: The primary outcome was duration of analgesia, defined as time to first morphine request. RESULTS: Mean ±â€ŠSD duration of analgesia was 15.4 ±â€Š8.0 h in the ankle block group and 20.0 ±â€Š10.3 h in the sciatic nerve block group ( P  = 0.32). Of note, 15 of 26 (58%) and 24 of 30 (80%) patients of the ankle and sciatic nerve block groups did not request any morphine ( P  = 0.09). Other secondary outcomes were similar between groups. CONCLUSION: Compared with the ankle block, the sciatic nerve block at the popliteal crease does not provide a longer duration of analgesia in patients undergoing forefoot surgery in the setting of multimodal analgesia. TRIAL REGISTRATION: Clinicaltrials.com identifier: NCT03683342.

Sensory block duration after spinal anaesthesia supplemented with intravenous dexamethasone: a randomised controlled double-blinded trial.

BACKGROUND: Intravenous dexamethasone prolongs duration of analgesia or sensory block after injection of local anaesthetics close to peripheral nerves by an average of 8 h. Uncertainty remains on the potential increase in the duration of sensory block after spinal anaesthesia. The objective of this randomised controlled double-blinded trial was to investigate whether dexamethasone i.v. prolongs the sensory block of spinal anaesthesia with bupivacaine when compared with a control group. METHODS: Of 50 patients undergoing lower limb osteoarticular surgery under spinal anaesthesia with isobaric bupivacaine 15 mg i.t. with morphine 100 µg i.t. were randomised to receive either dexamethasone 0.15 mg kg-1 i.v. or normal saline 3 ml i.v. The primary outcome was duration of sensory block defined as the time elapsed between injection of the local anaesthetic in the intrathecal space and the regression of sensory block by two dermatomes compared with the highest dermatome blocked. Secondary outcomes included intravenous morphine consumption, pain scores at rest and on movement, postoperative nausea and vomiting, and blood glucose at 2, 24, and 48 h. RESULTS: Median duration of sensory block was 135 (105-225) min in the dexamethasone group and 158 (135-240 min) in the control group (P=0.19). Patients in the dexamethasone group received less morphine at 24 h, had significantly less postoperative nausea and vomiting at 2 h and 24 h, and had increased blood glucose at 24 h. Other secondary outcomes were similar between groups. CONCLUSION: Intravenous dexamethasone did not prolong the sensory block of spinal anaesthesia with isobaric bupivacaine. However, it reduced morphine consumption and rate of postoperative nausea and vomiting at 24 h, at the expense of an increased blood glucose. CLINICAL TRIAL REGISTRATION: NCT03527576 (Clinicaltrials.gov).

The postoperative analgesic efficacy of liposomal bupivacaine versus long-acting local anaesthetics for peripheral nerve and field blocks: A systematic review and meta-analysis, with trial sequential analysis.

BACKGROUND: Liposomal bupivacaine is claimed by the manufacturer to provide analgesia for up to 72 h postoperatively. OBJECTIVES: To compare the postoperative analgesic efficacy of liposomal bupivacaine versus long-acting local anaesthetics for peripheral nerve or field blocks. DESIGN: A systematic review and meta-analysis with trial sequential analysis. DATA SOURCES: MEDLINE, Embase and Web of Science, among others, up to June 2022. ELIGIBILITY CRITERIA: We retrieved randomised controlled trials comparing liposomal bupivacaine versus bupivacaine, levobupivacaine or ropivacaine for peripheral nerve and field blocks after all types of surgery. Our primary endpoint was rest pain score (analogue scale 0 to 10) at 24 h. Secondary endpoints included rest pain score at 48 and 72 h, and morphine consumption at 24, 48 and 72 h. RESULTS: Twenty-seven trials including 2122 patients were identified. Rest pain scores at 24 h were significantly reduced by liposomal bupivacaine with a mean difference (95% CI) of -0.9 (-1.4 to -0.4), I2  = 87%, P  < 0.001. This reduction in pain scores persisted at 48 h and 72 h with mean differences (95% CI) of -0.7 (-1.1 to -0.3), I2  = 82%, P  = 0.001 and -0.7 (-1.1 to -0.3), I2  = 80%, P  < 0.001, respectively. There were no differences in interval morphine consumption at 24 h ( P  = 0.15), 48 h ( P  = 0.15) and 72 h ( P  = 0.07). The quality of evidence was moderate. CONCLUSIONS: There is moderate level evidence that liposomal bupivacaine reduces rest pain scores by 0.9 out of 10 units, when compared with long-acting local anaesthetics at 24 hours after surgery, and by 0.7 up to 72 hours after surgery.

Intracellular Zinc Trafficking during Crotalus atrox Venom Wound Development.

In this study, we examined zinc trafficking in human umbilical vein endothelial cells (HUVEC) stimulated with Crotalus atrox (CA venom) snake venom. We utilized MTS cytotoxicity assays to monitor the cytotoxic range of CA venom. HUVEC monolayers stimulated with 10 µg/mL CA venom for 3 h displayed cellular retraction, which coincided with 53.0 ± 6.5 percent viability. In contrast, venom concentrations of 100 µg/mL produced a complete disruption of cellular adherence and viability decreased to 36.6 ± 1.0. The zinc probe Fluozin-3AM was used to detect intracellular zinc in non-stimulated controls, HUVEC stimulated with 10 µg/mL CA venom or HUVEC preincubated with TPEN for 2 h then stimulated with 10 µg/mL CA venom. Fluorescent intensity analysis returned values of 1434.3 ± 197.4 for CA venom demonstrating an increase of about two orders of magnitude in labile zinc compared to non-stimulated controls. Endothelial response to CA venom induced a 96.1 ± 3.0- and 4.4 ± 0.41-fold increase in metallothionein 1X (MT1X) and metallothionein 2A (MT2A) gene expression. Zinc chelation during CA venom stimulation significantly increased cell viability, suggesting that the maintenance of zinc homeostasis during envenomation injury improves cell survival.

Regional anesthesia in the emergency department outside the operating theatre.

PURPOSE OF REVIEW: Moderate to severe pain is common and remains a significant problem in the emergency department and regional anesthesia provides optimal and safe pain relief. This review aims to discuss the benefits, indications of the most common ultrasound-guided regional anesthesia techniques that can be provided by clinicians in the emergency department as part of multimodal analgesia. We will also comment on the education and training for effective and safe ultrasound-guided regional anesthesia in the emergency department. RECENT FINDINGS: The emergence of multiple new fascial plane blocks that provide easier to learn alternatives, yet effective analgesia for specific patient groups can now safely be taught and utilized in the emergency department. SUMMARY: Emergency physicians are perfectly placed to utilize the advantages of ultrasound-guided regional anesthesia. Various techniques can now be employed to cover most of the painful injuries presenting to the emergency department, thus modifying the morbidity and outcomes of emergency patients. Some of the new techniques require minimal training, provide safe and effective pain relief with low risk of complications. Ultrasound-guided regional anesthetic techniques should form an integral part of the curriculum of emergency department physicians.

Local anaesthetic adjuncts for peripheral nerve blockade.

PURPOSE OF REVIEW: Moderate-to-severe pain is common and remains a significant problem. Compared with opioid analgesia alone, single-shot peripheral nerve blockade has been associated with improved pain relief and the potential of decreased side effects. Single-shot nerve blockade, however, is limited by its relatively short duration of action. In this review, we aim to summarize the evidence related to local anaesthetic adjuncts for peripheral nerve blockade. RECENT FINDINGS: Dexamethasone and dexmedetomidine exhibit characteristics that most closely resemble the ideal local anaesthetic adjunct. In upper limb block, dexamethasone has been demonstrated to be superior to dexmedetomidine regardless of administration route for the duration of sensory and motor blockade as well as the duration of analgesia. No clinically significant differences between intravenous and perineural dexamethasone were found. Perineural and intravenous dexamethasone have the potential to prolong sensory blockade to a greater extent than motor blockade. The evidence indicates that the mechanism of action of perineural dexamethasone in upper limb block is systemic in nature. Unlike perineural dexmedetomidine, intravenous dexmedetomidine has not been shown to result in differences in the characteristics of regional blockade compared with local anaesthetic alone. SUMMARY: Intravenous dexamethasone is the local anaesthetic adjunct of choice, increasing the duration of sensory and motor blockade as well as the duration of analgesia by 477, 289 and 478 min, respectively. In view of this, we recommend consideration of the intravenous administration of dexamethasone at a dose of 0.1-0.2 mg/kg for all patients undergoing surgery whatever the level of postoperative pain, mild, moderate or severe. Further research should focus on the potential synergism of action between intravenous dexamethasone and perineural dexmedetomidine.

Crotalus atrox venom-induced cellular toxicity: Early wound progression involves reactive oxygen species.

Understanding the mechanisms that produce cellular cytotoxicity is fundamental in the field of toxicology. Cytotoxic stimuli can include organic toxins such as hemorrhagic snake venom, which can lead to secondary complications such as the development of necrotic tissue and profuse scarring. These clinical manifestations mimic cytotoxic responses induce by other organic compounds such as organic acids. We used hemorrhagic snake venom and human embryonic kidney cells (HEK 293T) as a model system to better understand the cellular responses involved in venom induced cytotoxicity. Cells stimulated with Crotalus atrox (CA) (western diamondback) venom for 4 or 10 h demonstrated significant cytotoxicity. Results from 2',7'-Dichlorodihydrofluorescein diacetate (H2 DCF-DA) assays determine CA venom stimulation induces a robust production of reactive oxygen species (ROS) over a 3-h time course. In contrast, pretreatment with polyethylene glycol (PEG)-catalase or N-acetyl cysteine (NAC) prior to CA venom stimulation significantly blunted H2 DCFDA fluorescence fold changes and showed greater cytoprotective effects than cells stimulated with CA venom alone. Pre- incubating HEK293T cells with the NADPH oxidase (NOX) pan-inhibitor VAS2870 prior venom stimulation significantly minimized the venom-induced oxidative burst at early timepoints (≤2 h). Collectively, our experiments show that pre-application of antioxidants reduces CA venom induce cellular toxicity. This result highlights the importance of ROS in the early stages of cytotoxicity and suggests muting ROS production in noxious injuries may increase positive clinical outcomes.

The analgesic efficacy of transversus abdominis plane block vs. wound infiltration after inguinal and infra-umbilical hernia repairs: A systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Both transversus abdominis plane (TAP) block and wound infiltration with local anaesthetic have been used to relieve pain after inguinal or infra-umbilical hernia repair. OBJECTIVES: To determine whether TAP block or local anaesthetic infiltration is the best analgesic option after inguinal or infra-umbilical hernia repair. DESIGN: Systematic review and meta-analysis with trial sequential analysis. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Clinical Trials, Web of Science, up to June, 2020. ELIGIBILITY CRITERIA: We retrieved randomised controlled trials comparing TAP block with wound infiltration after inguinal or infra-umbilical hernia repair. Primary outcome was rest pain score (analogue scale 0 to 10) at 2 postoperative hours. Secondary pain-related outcomes included rest pain score at 12 and 24 h, and intravenous morphine consumption at 2, 12 and 24 h. Other secondary outcomes sought were block-related complications such as rates of postoperative infection, haematoma, visceral injury and systemic toxicity of local anaesthetic. RESULTS: Seven trials including 420 patients were identified. There was a significant difference in rest pain score at 2 postoperative hours in favour of TAP block compared with wound infiltration, with a mean (95% confidence interval) difference of -0.8 (-1.3 to -0.2); I2  = 85%; P   =  0.01. Most secondary pain-related outcomes were also significantly improved following TAP block. No complication was reported. The overall quality of evidence was moderate. CONCLUSION: There is moderate level evidence that TAP block provides superior analgesia compared with wound infiltration following inguinal or infra-umbilical hernia repair. TRIAL REGISTRY NUMBER: PROSPERO CRD42020208053.

Transversus abdominis plane block versus local anaesthetic wound infiltration for analgesia after caesarean section: A systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Transversus abdominis plane (TAP) block and local anaesthetic wound infiltration are used to relieve pain after caesarean section. OBJECTIVES: To determine whether TAP block or local anaesthetic wound infiltration is the better analgesic option after caesarean section. DESIGN: Systematic review and meta-analysis with trial sequential analysis. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Clinical Trials, Web of Science up to June 2020. ELIGIBILITY CRITERIA: We retrieved randomised controlled trials comparing TAP block with wound infiltration after caesarean section. Primary outcome was pain score during rest (analogue scale, 0 to 10) at 2 h postoperatively, analysed according to the TAP block technique (ultrasound-guided/landmark-guided), anaesthetic strategy (spinal/general), intrathecal fentanyl (yes/no) and multimodal analgesia (yes/no). Secondary pain-related outcomes included pain scores during rest at 12 and 24 h, and total intravenous morphine consumption at 2, 12 and 24 h. We sought rates of block complications, including postoperative infection, haematoma, visceral injury and local anaesthetic systemic toxicity. RESULTS: Seven trials, totalling 475 patients, were identified. There was no difference in pain score during rest at 2 h between groups. Subgroup analyses revealed no differences related to TAP block technique (P = 0.64), anaesthetic strategy (P = 0.53), administration of intrathecal fentanyl (P = 0.59) or presence of multimodal analgesia (P = 0.57). Pain score during rest at 12 h and intravenous morphine consumption at 2 and 12 h were identical in both groups. Data were insufficient to compare block complications. Overall quality of evidence was moderate. CONCLUSION: There is moderate level evidence that TAP block and wound infiltration provide similar postoperative analgesia after caesarean section. TRIAL REGISTRY NUMBER: PROSPERO CRD42020208046.

Dexamethasone for the treatment of established postoperative nausea and vomiting: A randomised dose finding trial.

BACKGROUND: Dexamethasone is widely used for the prevention of postoperative nausea and vomiting (PONV) but little is known about its efficacy for the treatment of established PONV. OBJECTIVE: To test the antiemetic efficacy of intravenous dexamethasone for the treatment of established PONV in adults undergoing surgery under general anaesthesia and to determine whether there is dose-responsiveness. DESIGN: The DexPonv trial is a multicentre, placebo-controlled, randomised, double-blind, dose-finding study. Inclusion of patients was between September 2012 and November 2017. Follow-up for PONV symptoms was for 24 h. Thirty days postoperatively, patients were contacted by study nurses for any information on postoperative bleeding and infection. SETTING: Four public hospitals in Switzerland. PATIENTS: A total of 803 adults scheduled for elective surgery without any antiemetic prophylaxis signed the consent form; 714 were included. Among those, 319 had PONV and 281 patients were eventually randomised (intention to treat population and safety set). The per protocol set consisted of 260 patients. INTERVENTIONS: Patients with PONV symptoms (including retching) were randomised to a single intravenous dose of dexamethasone 3, 6 or 12 mg or matching placebo. MAIN OUTCOME MEASURES: The primary endpoint was the absence of further nausea or vomiting (including retching), within 24 h after administration of the study drug. RESULTS: Dexamethasone was ineffective during the first 24 h, whatever the dosage, compared to placebo, even when the model was adjusted for known risk factors (P = 0.170). There were no differences in the time to treatment failure or the quality of sleep during the first night. There was a positive correlation between the dose of dexamethasone and blood glucose concentrations (P < 0.001), but not with bleeding risk, wound infections or other adverse effects. CONCLUSION: This randomised trial failed to show anti-emetic efficacy of any of the tested intravenous regimens of dexamethasone for the treatment of established PONV in adults undergoing surgery under general anaesthesia. TRIAL REGISTRATION: clinicaltrials.gov (NCT01975727).

Rapid Sequence Induction With a Standard Intubation Dose of Rocuronium After Magnesium Pretreatment Compared With Succinylcholine: A Randomized Clinical Trial.

BACKGROUND: Succinylcholine remains the muscle relaxant of choice for rapid sequence induction (RSI) but has many adverse effects. High-dose rocuronium bromide may be an alternative to succinylcholine for RSI but recovery times are nearly doubled compared with a standard intubating dose of rocuronium. Magnesium sulfate significantly shortens the onset time of a standard intubating dose of rocuronium. We set out to investigate whether intravenous (IV) pretreatment with MgSO4 followed by a standard intubating dose of rocuronium achieved superior intubation conditions compared with succinylcholine. METHODS: Adults were randomized to receive a 15-minute IV infusion of MgSO4 (60 mg·kg-1) immediately before RSI with propofol 2 mg·kg-1, sufentanil 0.2 µg·kg-1 and rocuronium 0.6 mg·kg-1, or a matching 15-minute IV infusion of saline immediately before an identical RSI, but with succinylcholine 1 mg·kg-1. Primary end point was the rate of excellent intubating conditions 60 seconds after administration of the neuromuscular blocking agent and compared between groups using multivariable log-binomial regression model. Secondary end points were blood pressure and heart rate before induction, before and after intubation, and adverse events up to 24 hours postoperatively. RESULTS: Among 280 randomized patients, intubating conditions could be analyzed in 259 (133 MgSO4-rocuronium and 126 saline-succinylcholine). The rate of excellent intubating conditions was 46% with MgSO4-rocuronium and 45% with saline-succinylcholine. The analysis adjusted for gender and center showed no superiority of MgSO4-rocuronium compared with saline-succinylcholine (relative risk [RR] 1.06, 95% confidence interval [CI], 0.81-1.39, P = .659). The rate of excellent intubating conditions was higher in women (54% [70 of 130]) compared with men (37% [48 of 129]; adjusted RR 1.42, 95% CI, 1.07-1.91, P = .017). No significant difference between groups was observed for systolic and diastolic blood pressures. Mean heart rate was significantly higher in the MgSO4-rocuronium group. The percentage of patients with at least 1 adverse event was lower with MgSO4-rocuronium (11%) compared with saline-succinylcholine (28%) (RR 0.38, 95% CI, 0.22-0.66, P < .001). With saline-succinylcholine, adverse events consisted mainly of postoperative muscle pain (n = 26 [19%]) and signs of histamine release (n = 13 [9%]). With MgSO4-rocuronium, few patients had pain on injection, nausea and vomiting, or skin rash during the MgSO4-infusion (n = 5 [4%]). CONCLUSIONS: IV pretreatment with MgSO4 followed by a standard intubating dose of rocuronium did not provide superior intubation conditions to succinylcholine but had fewer adverse effects.

Intrathecal morphine and sleep apnoea severity in patients undergoing hip arthroplasty: a randomised, controlled, triple-blinded trial.

BACKGROUND: Intrathecal morphine prolongs analgesia after surgery, but has been implicated in postoperative respiratory depression or apnoeic episodes. However, this has not been investigated in a prospective trial using respiratory polygraphy. This randomised controlled triple-blinded trial tested the hypothesis that intrathecal morphine increases sleep apnoea severity, measured using respiratory polygraphy. METHODS: Sixty subjects undergoing hip arthroplasty under spinal anaesthesia received either 15 mg isobaric bupivacaine 0.5% with 0.5 ml normal saline 0.9% (control group) or 15 mg isobaric bupivacaine 0.5% with 0.5 ml intrathecal morphine 100 µg (intrathecal morphine group). Respiratory polygraphy was performed before surgery and on the first and third postoperative nights. The primary outcome was the apnoea-hypopnoea index in the supine position (supine AHI) on the first postoperative night. Secondary outcomes included supine AHI on the third postoperative night, oxygen desaturation index (ODI), and ventilatory frequency during the first and third postoperative nights. RESULTS: On the first postoperative night, mean (95% confidence interval) values for supine AHI were 20.6 (13.9-27.3) and 21.2 (12.4-30.0) events h-1 in the control and intrathecal morphine groups, respectively (P=0.90). There were no significant between-group differences for any of the secondary outcomes, except for a significantly higher central and mixed apnoea index preoperatively and significantly lower mean SpO2 on the third postoperative night in the control group. CONCLUSIONS: Intrathecal morphine did not increase sleep apnoea severity when measured using respiratory polygraphy. Of note, all patients had an increased number of apnoeic episodes on the third postoperative night. CLINICAL TRIAL REGISTRATION: NCT02566226.

Low- versus high-dose intraoperative opioids: A systematic review with meta-analyses and trial sequential analyses.

BACKGROUND: Opioid-induced hyperalgesia is a state of nociceptive sensitisation secondary to opioid administration. The objective of this meta-analysis was to test the hypothesis that high-dose intraoperative opioids contribute to increased post-operative pain and hyperalgesia when compared with a low-dose regimen in patients under general anaesthesia. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines and rated the certainty of evidence with the Grading of Recommendations, Assessment, Development and Evaluation system. Only trials investigating pain outcomes and comparing two different dosages of the same intraoperative opioid in patients under general anaesthesia were included. The primary outcome was pain score (analogue scale, 0-10) at 24 post-operative hours. Secondary outcomes included pain score and cumulative intravenous morphine equivalents (mg) consumed at 2 post-operative hours, together with mechanical pain threshold (g·mm-2 ). RESULTS: Twenty-seven randomised controlled trials, including 1630 patients, were identified. Pain score at rest at 24 post-operative hours was increased in the high-dose group (mean difference [95% CI]: -0.2 [-0.4, -0.1]; trial sequential analysis-adjusted CI: -0.4, -0.02; low certainty of evidence). Similarly, at 2 post-operative hours, both pain score (mean difference [95% CI]: -0.4 [-0.6, -0.2]; low certainty of evidence) and cumulative intravenous morphine equivalents consumed (mean difference [95% CI]: -1.6 mg [-2.6, -0.7]; low certainty of evidence) were significantly higher in the high-dose group. Finally, the threshold for mechanical pain was significantly lower in the high-dose group (mean difference to pressure [95% CI]: 3.8 g·mm-2 [1.8, 5.8]; low certainty of evidence). CONCLUSIONS: There is low certainty of evidence that high-dose intraoperative opioid administration increases pain scores in the post-operative period, when compared with a low-dose regimen.