Effects of combined dexamethasone and dexmedetomidine as adjuncts to peripheral nerve blocks: a systematic review with meta-analysis and trial sequential analysis.

BACKGROUND/IMPORTANCE: The effects of combining dexamethasone and dexmedetomidine on block duration are unclear. OBJECTIVE: To investigate the effects of combining dexamethasone and dexmedetomidine on block duration. EVIDENCE REVIEW: Systematic review of randomized controlled trials (RCTs) from Medline, Embase, CENTRAL, CINAHL, the Web of Science, and BIOSIS until June 8, 2023. RCTs with adults undergoing surgery with a peripheral nerve block randomized to combined dexamethasone and dexmedetomidine versus placebo or other adjuncts were eligible. Primary outcome was duration of analgesia. We performed meta-analysis, trial sequential analysis, risk of bias-2, and Grading Recommendations Assessment, Development, and Evaluation assessment. FINDINGS: We included 9 RCTs with 14 eligible comparisons. The combination of dexamethasone and dexmedetomidine was compared with placebo in three RCTs (173 participants), dexamethasone in seven (569 participants), and dexmedetomidine in four (281 participants). The duration of analgesia was likely increased with the combination versus placebo (mean difference 460 min, 95% CI 249 to 671) and versus dexmedetomidine (mean difference 388 min, 95% CI 211 to 565). The duration was likely similar with the combination versus dexamethasone (mean difference 50 min, 95% CI -140 to 239). The certainty of the evidence was moderate because most trials were at high risk of bias. CONCLUSIONS: Combined dexamethasone and dexmedetomidine likely increased the duration of analgesia when compared with placebo and dexmedetomidine. The combination likely provided a similar duration of analgesia as dexamethasone. Based on this systematic review, it seems reasonable to use dexamethasone as the sole adjunct if the goal is to increase the duration of analgesia.

Remimazolam for sedation: A protocol for a systematic review with meta-analysis, trial sequential analysis, and GRADE approach.

BACKGROUND: Procedural sedation aims to facilitate a successful diagnostic or therapeutic procedure. The pharmacokinetic properties and pharmacodynamic effects need to be taken into consideration when choosing the ideal sedative. Midazolam and propofol are frequently employed. However, they are associated with respiratory depression with increasing dosage. Also, midazolam has a potentially unpredictable pharmacodynamic response and propofol may cause hypotension and injection site pain. Remimazolam may provide a superior alternative due to its rapid pharmacodynamic profile and insignificant circulatory effects. METHODS: This protocol employs the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The review aims to assess the beneficial and harmful clinical effects of remimazolam versus placebo or other sedatives in adult patients requiring sedation in relation to a diagnostic or therapeutic procedure, or due to other circumstances. Three primary outcomes are identified: Sedation success rate, respiratory complications, and hemodynamic complications. Six secondary outcomes are identified: among these are quality of recovery and serious adverse events. All randomized trials are included. The search strategy includes six major biomedical databases. Literature screening and data extraction will be performed independently by two authors. Risk of systemic error will be assessed with Risk of Bias 2 Tool. Risk of random error will be assessed with trial sequential analysis. Heterogeneity will be evaluated by appropriate statistical tests. The certainty of the evidence will be judged using Grading of Recommendations Assessment, Development, and Evaluation. Meta-analysis will be carried out with Rstudio. A "Summary of Findings" table will be presented with our primary and secondary outcome results. DISCUSSION: The systematic review with up-to-date methodology outlined in this protocol investigates the clinical effects of remimazolam in relation to procedural sedation. The results may guide clinicians in the clinical use of remimazolam.

[Risks when applying peripheral nerve blocks].

The use of peripheral nerve blocks carries a small risk of most often temporary direct damage to the peripheral nerves. Due to lack of research and differing opinions regarding the potential of nerve blocks delaying the diagnosis of acute compartment syndrome, there is currently no consensus between anaesthetic- and orthopaedic associations regarding the use of peripheral nerve blocks in patients at risk of acute compartment syndrome. More interdisciplinary research is needed to inform and promote an evidence-based discussion of the subject, as argued in this review.

Lateral femoral cutaneous nerve block with different volumes of Ropivacaine: a randomized trial in healthy volunteers.

BACKGROUND: Nerve block of the lateral femoral cutaneous nerve (LFCN) is a predominantly sensory block. It reduces pain following total hip arthroplasty (THA), but the non-responder rate is high. We hypothesized, that an increased volume of ropivacaine, would result in greater coverage of incisions used for THA. METHODS: We conducted a randomized, blinded trial in 20 healthy volunteers. Participants were randomized to receive bilateral LFCN-blocks with 8 mL ropivacaine 0.75% on the left side and 16 mL ropivacaine 0.75% on the right side, or vice versa. Allocation was blinded to both participants and outcome assessors. Before nerve block performance, incision lines for posterior and lateral THA approaches were depicted with invisible ultraviolet-paint, thereby securing sufficient blinding during outcome assessment. The blocked area was mapped using temperature and mechanical discrimination tests. Quadriceps muscle strength was monitored. Primary outcome was coverage of the posterior incision line assessed by temperature discrimination test. RESULTS: We found no difference in coverage of the posterior or lateral incision lines when comparing LFCN-blocks with 8 mL versus 16 mL of ropivacaine. The blocked area was significantly larger in the 16 mL group, assessed by both temperature discrimination test (p = 0.012) and mechanical discrimination test (p = 0.034). We observed no difference between groups regarding quadriceps muscle strength (p = 1.0). CONCLUSIONS: A LFCN-block with increased volume of ropivacaine from 8 mL to 16 mL did not result in a greater coverage of posterior or lateral incision lines used for THA, but in a larger blocked sensory area. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03138668 . Registered 3rd of May 2017.

Restrictive vs liberal oxygen for trauma patients-the TRAUMOX1 pilot randomised clinical trial.

INTRODUCTION: Hyperoxaemia is commonly observed in trauma patients but has been associated with pulmonary complications and mortality in some patient populations. The objectives of this study were to evaluate whether maintenance of normoxia is feasible using a restrictive oxygen strategy in the initial phase after trauma and to evaluate the incidence of 30-day mortality and/or major pulmonary complications. METHODS: Forty-one adult trauma patients admitted to our trauma centre were randomised to 24 hours of restrictive oxygen therapy (no supplemental oxygen if the arterial oxyhaemoglobin saturation (SpO2 ) was at least 94%, n = 21) or liberal oxygen therapy (intubated patients: FiO2 1.0 in the trauma bay, 0.8-1.0 elsewhere; spontaneously breathing patients: 15 L/min via a non-rebreather mask, n = 20). Two blinded anaesthesiologists evaluated major in-hospital pulmonary complications within 30 days. RESULTS: Protocol compliance was high, as the median arterial oxygen tension was significantly lower in the restrictive group (10.8 kPa [9.7-12.0] vs 30.4 kPa [23.7-39.0], P < 0.0001). There were seven episodes of SpO2 below 90% in the restrictive group and one episode in the liberal group. Thirty-day mortality and/or major in-hospital pulmonary complications occurred in 4/20 (20%) in the restrictive group and in 6/18 (33%) in the liberal group: two patients in each group died within 30 days and the incidence of major in-hospital pulmonary complications was 2/20 (10%) in the restrictive group and 4/18 (22%) in the liberal group. CONCLUSION: Maintenance of normoxia using a restrictive oxygen strategy following trauma is feasible. This pilot study serves as the basis for a larger clinical trial.

Barriers in pain treatment in the emergency and surgical department.

INTRODUCTION: Post-operative pain is associated with poor patient satisfaction and severe complications. It is often underreported and poorly managed. The aim of this study was to investigate which factors influence and prevent optimal pain treatment according to healthcare providers. METHODS: We conducted an electronic questionnaire survey, which was distributed by e-mail to 364 doctors, nurses, dentists and social and healthcare assistants employed at the emergency and surgical departments of Zealand University Hospital, Koege, Denmark. The 15-item-questionnaire investigated which factors influenced pain treatment. RESULTS: A total of 124 of 364 (34%) healthcare providers completed the questionnaire. The four primary factors influencing pain treatment were sufficient time, inter-dis-ciplinary cooperation, patient involvement and staff edu-cation. The two primary barriers preventing optimal pain treatment were a high level of activity at the ward (40%) and a lack of knowledge (33%). CONCLUSIONS: Time, staff education, interdisciplinary cooperation and patient involvement were the primary factors influencing pain treatment. Insufficient time and limited knowledge on the part of the healthcare providers were the greatest barriers preventing good pain treatment in everyday practice. FUNDING: none. TRIAL REGISTRATION: not relevant.

Systemic dexmedetomidine is not as efficient as perineural dexmedetomidine in prolonging an ulnar nerve block.

BACKGROUND: We tested the joint hypotheses that both perineural and systemic dexmedetomidine prolong the duration of an ulnar nerve block (UNB) compared with ropivacaine alone and that systemic dexmedetomidine is noninferior compared with perineural dexmedetomidine in block prolongation. METHODS: We performed bilateral UNBs in 22 healthy volunteers on two separate days. On the first day, each arm was randomized to either 4 mL ropivacaine 5 mg/mL+1 mL dexmedetomidine 100 µg/mL (Perineural) or 4 mL ropivacaine 5 mg/mL+1 mL saline (Systemic). On the subsequent treatment day, each arm was randomized to 1 mL of saline plus 4 mL of ropivacaine at either 7.5 mg/mL(HiRopi) or 5 mg/mL (NoDex). The primary outcome measure was the duration of sensory block assessed by mechanical discrimination. RESULTS: Mean sensory block duration was longer in both the Perineural (14.4 hours, 95% CI 13.1 to 15.6) and Systemic treatments (9.2 hours, 95% CI 8.6 to 9.8) compared with the NoDex treatment (7.1 hours, 95% CI 6.6 to 7.6) (p<0.0001 for both). Systemic dexmedetomidine was inferior (not noninferior) compared with perineural dexmedetomidine, as the 95% CI of the difference (mean difference 5.2 hour, 95% CI 4.2 to 6.1) exceeded the noninferiority limit of 3.6 hour. Onset time did not differ among the groups. The other test modalities demonstrated similar block durations as the primary outcome. CONCLUSIONS: Adding dexmedetomidine perineurally to ropivacaine doubles the duration of an UNB. Systemic dexmedetomidine also prolongs the duration of UNB, but has less of an effect compared with the perineural route. TRIAL REGISTRATION NUMBER: NCT03222323.

Clonidine used as a perineural adjuvant to ropivacaine, does not prolong the duration of sensory block when controlling for systemic effects: A paired, blinded, randomized trial in healthy volunteers.

BACKGROUND: Clonidine used as an adjuvant to ropivacaine have been shown to prolong the duration of peripheral nerve blocks. The mechanism of action remains unclear. We hypothesized, that clonidine used as an adjuvant to ropivacaine extends the duration of an adductor canal block (ACB) by a peripheral mechanism, compared to ropivacaine alone when controlling for systemic effects. METHODS: We conducted a paired, blinded, randomized trial in healthy volunteers. Participants received bilateral ACBs containing 20 ml ropivacaine 0.5% + 1 ml clonidine 150µg/ml in one leg and 20 ml ropivacaine 0.5% + 1 ml saline in the other leg. The primary outcome measure was duration of sensory block assessed by temperature sensation (alcohol swab). Secondary outcome measures were duration of sensory block assessed by: pinprick, maximum pain during tonic heat stimulation, warmth detection threshold and heat pain detection threshold. RESULTS: We enrolled 21 volunteers and all completed the trial. There was no difference in duration of sensory block assessed with an alcohol swab: Mean duration in the leg receiving ropivacaine + clonidine was 19.4h (SD 2.7) compared to 19.3h (SD 2.4) in the leg receiving ropivacaine + placebo with a mean difference of 0.1h (95% CI: -1.0 to 1.3), P = 0.83. No differences in block duration were detected when assessed by: Pinprick, mean difference 0.0 h (95% CI: -1.3 to 1.3), maximum pain during tonic heat stimulation, mean difference -0.7 h (95% CI: -2.1 to 0.8), warmth detection threshold, mean difference -0.1 h (95% CI: -1.8 to 1.6) or heat pain detection threshold, mean difference -0.2 h (95% CI: -1.7 to 1.4). CONCLUSIONS: Administering clonidine perineurally as an adjuvant to ropivacaine in an ACB did not prolong the duration of sensory block in a setup controlling for systemic effects of clonidine.

Anaesthesia for awake craniotomy is safe and well-tolerated.

INTRODUCTION: Awake craniotomy for tumour resection has been performed at Glostrup Hospital since 2004. We describe and discuss the various anaesthetic approaches for such surgery and retrospectively analyse the 44 planned awake craniotomies performed at Glostrup Hospital. The surgery falls into four phases: craniotomy, mapping, tumour resection and closing. Three methods are being used: monitored anaesthetic care, asleep-awake-asleep and asleep-awake (AA). MATERIAL AND METHODS: Anaesthesia is induced and maintained with propofol and remifentanil. A laryngeal mask (LM) is used as an airway during the craniotomy phase. In the AA method, patients are mapped and the tumour is resected while the patient is awake. RESULTS: A total of 41 of 44 planned AA craniotomies were performed. Three had to be converted into general anaesthesia (GA) due to tight brain, leaking LM and tumour haemorrhage, respectively. The following complications were observed: bradycardia 10%, leaking LM 5%, nausea 10%, vomiting 5%, focal seizures 28%, generalized seizures 10%, hypoxia 2%, hypotension 5% and hypertension 2%. CONCLUSION: Our results comply well with the international literature in terms of complications related to haemodynamics, respiration, seizures, vomiting and nausea and in terms of patient satisfaction. Awake craniotomy is a well-tolerated procedure with potential benefits. More prospective randomized studies are required.