Pain management after open colorectal surgery: An update of the systematic review and procedure-specific postoperative pain management (PROSPECT) recommendations.

BACKGROUND: Open colectomy is still performed around the world and associated with significant postoperative pain. OBJECTIVES: Unpublished recommendations based on a systematic review were proposed by the PROcedure SPECific postoperative pain managemenT (PROSPECT) group in 2016. We aimed to update these recommendations by evaluating the available literature and develop recommendations for optimal pain management after open colectomy according to the PROSPECT methodology. DESIGN AND DATA SOURCES: A systematic review using the PROSPECT methodology was undertaken. Randomised controlled trials and systematic reviews published in the English language from 2016 to 2022 assessing postoperative pain after open colectomy using analgesic, anaesthetic or surgical interventions were identified. The primary outcome included postoperative pain scores. RESULTS: The previous 2016 review included data from 93 studies. Out of 842 additional eligible studies identified, 13 new studies were finally retrieved for analysis. Intra-operative and postoperative interventions that improved postoperative pain were paracetamol, epidural analgesia. When epidural is not feasible, intravenous lidocaine or bilateral TAP block or postoperative continuous pre-peritoneal infusion are recommended. Intra-operative and postoperative Cyclo-oxygenase (COX)-2 specific-inhibitors or non-steroidal anti-inflammatory drugs (NSAIDs) are recommended for colonic surgery. CONCLUSIONS: The analgesic regimen for open colectomy should include intra-operative paracetamol and COX-2 specific inhibitors or NSAIDs (restricted to colonic surgery), epidural and continued postoperatively with opioids used as rescue analgesics. If epidural is not feasible, bilateral TAP block or IV lidocaine are recommended. Safety issues should be highlighted: local anaesthetics should not be administered by two different routes at the same time. Because of the risk of toxicity, careful dosing and monitoring are necessary.

High dose glucocorticoids for treatment of postoperative pain: A systematic review of the literature and meta-analysis.

STUDY OBJECTIVE: Glucocorticoids as a component of multimodal analgesia have been studied for many years and their post-operative analgesic effects appear to be dose-dependent. We conducted a systematic review of randomized controlled trials (RCTs) to evaluate the evidence of peri-operative high dose corticosteroid therapy in comparison to placebo (placebo drug) or control group (no treatment) for improving the quality of post-operative analgesia as indicated by a reduction of 10 mm in 100 mm Visual Analogue Scale (VAS) or reduction of 1 point in a 0-10 point VAS scale, or a reduction of 1 point in an 11-point Numerical Rating Scale (NRS) score, or reduction of rescue opioid analgesia, in patients undergoing all types of surgery. DESIGN: Systematic review of RCTs with meta-analysis. SETTING: Acute postoperative pain treatment in non-obese adult population. INTERVENTIONS: Perioperative administration of high dose of Dexamethasone (≥ 0,2 mg/Kg or ≥ 15 mg), or a corresponding dose of a systemic glucocorticoid. MEASUREMENTS: Primary outcomes were postoperative pain measured in 0-100 mm VAS score at 24 h after surgery upon rest and movement. Secondary outcomes were postoperative pain 0-100 mm VAS score 48 h after surgery, postoperative rescue analgesic requirement, postoperative nausea and vomiting (PONV), relevant adverse events. MAIN RESULTS: 47 RCT's were included (3943 patients). The Mean Difference (MD) of 100 mm VAS scores for pain at rest 24 h after surgery was -6.18 mm 95% CI [-8.53, -3.83], at motion -8.86 mm 95% CI [-11.82, -5.89]. Opioid analgesic requirements evaluated in Oral Morphine Equivalents (OME) was -10.00 mg 95% CI [-13.65, -6.34]. PONV events Odds Ratio of 0.29 95%CI [0.24, 0.36]. Major adverse events OR was 0.88 95% CI [0.65, 1.19]. Minor adverse events OR 1.29 95% CI [0.86, 1.92]. CONCLUSION: High doses of glucocorticoids are one of the many possible tools available in multimodal postoperative analgesia, possibly reducing opioids consumption and recurrence of PONV but with no relevant effects in terms of reduction of postoperative VAS score. Available data show a safe therapeutic profile, without increase adverse events. PROTOCOL REGISTRATION: CRD42020137119.

Regional anaesthesia for ambulatory surgery.

Regional anaesthesia (RA) has an important and ever-expanding role in ambulatory surgery. Specific practices vary depending on the preferences and resources of the anaesthesia team and hospital setting. It is used for various purposes, including as primary anaesthetic technique for surgery but also as postoperative analgesic modality. The limited duration of action of currently available local anaesthetics limits their application in postoperative pain control and enhanced recovery. The search for the holy grail of regional anaesthetics continues. Current evidence suggests that a peripheral nerve block performed with long-acting local anaesthetics in combination with intravenous or perineural dexamethasone gives the longest and most optimal sensory block. In this review, we outline some possible blocks for ambulatory surgery and additives to perform RA. Moreover, we give an update on local anaesthesia drugs and adjuvants, paediatric RA in ambulatory care and discuss the impact of RA by COVID-19.

Remimazolam and serious adverse events: A scoping review.

Remimazolam is anticipated to be an interesting anaesthetic and sedative. It combines the pharmacodynamic properties of midazolam with pharmacokinetic properties similar to remifentanil. However, worrisome case reports of anaphylaxis, delayed emergence and re-sedation have emerged recently and necessitate further investigation.PubMed (including MEDLINE) and EMBASE were searched for all studies reporting serious adverse events where remimazolam was administered for sedation or anaesthesia.Thirty-six case reports and 73 trials were identified, involving a total of 6740 patients who received remimazolam. Hypotension was reported in 911 cases, delayed emergence in 68 cases, anaphylaxis in 10 cases and re-sedation in 8 cases. The incidence of hypotension seems to be lower compared with other anaesthetics, even in high-risk patients.Delayed emergence might be related to the metabolism of remimazolam through carboxylesterase 1 (CES1), a tissue esterase predominant in the liver. There is significant interindividual variation, and it is inhibited by flavonoids, fatty acids and alcohol. Individual benzodiazepine sensitivity has also been reported. A higher BMI, older age and low plasma albumin concentration are risk factors for delayed emergence. Anaphylaxis might be related to a non-IgE-mediated effect of the excipient dextran-40 or a partially IgE-mediated reaction to remimazolam itself. Resedation has been reported after flumazenil reversal and is explained by the specific pharmacokinetic properties of flumazenil and remimazolam. Reversal by flumazenil should be reserved for and used carefully in patients with delayed emergence. VISUAL ABSTRACT: http://links.lww.com/EJA/A864 .

Pain management after cardiac surgery via median sternotomy: A systematic review with procedure-specific postoperative pain management (PROSPECT) recommendations.

BACKGROUND: Pain after cardiac surgery via median sternotomy can be difficult to treat, and if inadequately managed can lead to respiratory complications, prolonged hospital stays and chronic pain. OBJECTIVES: To evaluate available literature and develop recommendations for optimal pain management after cardiac surgery via median sternotomy. DESIGN: A systematic review using PROcedure-SPECific Pain Management (PROSPECT) methodology. ELIGIBILITY CRITERIA: Randomised controlled trials and systematic reviews published in the English language until November 2020 assessing postoperative pain after cardiac surgery via median sternotomy using analgesic, anaesthetic or surgical interventions. DATA SOURCES: PubMed, Embase and Cochrane Databases. RESULTS: Of 319 eligible studies, 209 randomised controlled trials and three systematic reviews were included in the final analysis. Pre-operative, intra-operative and postoperative interventions that reduced postoperative pain included paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), intravenous magnesium, intravenous dexmedetomidine and parasternal block/infiltration. CONCLUSIONS: The analgesic regimen for cardiac surgery via sternotomy should include paracetamol and NSAIDs, unless contraindicated, administered intra-operatively and continued postoperatively. Intra-operative magnesium and dexmedetomidine infusions may be considered as adjuncts particularly when basic analgesics are not administered. It is not clear if combining dexmedetomidine and magnesium would provide superior pain relief compared with either drug alone. Parasternal block/surgical site infiltration is also recommended. However, no basic analgesics were used in the studies assessing these interventions. Opioids should be reserved for rescue analgesia. Other interventions, including cyclo-oxygenase-2 specific inhibitors, are not recommended because there was insufficient, inconsistent or no evidence to support their use and/or due to safety concerns.

Pain management after elective craniotomy: A systematic review with procedure-specific postoperative pain management (PROSPECT) recommendations.

BACKGROUND: Pain after craniotomy can be intense and its management is often suboptimal. OBJECTIVES: We aimed to evaluate the available literature and develop recommendations for optimal pain management after craniotomy. DESIGN: A systematic review using procedure-specific postoperative pain management (PROSPECT) methodology was undertaken. DATA SOURCES: Randomised controlled trials and systematic reviews published in English from 1 January 2010 to 30 June 2021 assessing pain after craniotomy using analgesic, anaesthetic or surgical interventions were identified from MEDLINE, Embase and Cochrane Databases. ELIGIBILITY CRITERIA: Each randomised controlled trial (RCT) and systematic review was critically evaluated and included only if met the PROSPECT requirements. Included studies were evaluated for clinically relevant differences in pain scores, use of nonopioid analgesics, such as paracetamol and NSAIDs, and current clinical relevance. RESULTS: Out of 126 eligible studies identified, 53 RCTs and seven systematic review or meta-analyses met the inclusion criteria. Pre-operative and intra-operative interventions that improved postoperative pain were paracetamol, NSAIDs, intravenous dexmedetomidine infusion, regional analgesia techniques, including incision-site infiltration, scalp nerve block and acupuncture. Limited evidence was found for flupirtine, intra-operative magnesium sulphate infusion, intra-operative lidocaine infusion, infiltration adjuvants (hyaluronidase, dexamethasone and α-adrenergic agonist added to local anaesthetic solution). No evidence was found for metamizole, postoperative subcutaneous sumatriptan, pre-operative oral vitamin D, bilateral maxillary block or superficial cervical plexus block. CONCLUSIONS: The analgesic regimen for craniotomy should include paracetamol, NSAIDs, intravenous dexmedetomidine infusion and a regional analgesic technique (either incision-site infiltration or scalp nerve block), with opioids as rescue analgesics. Further RCTs are required to confirm the influence of the recommended analgesic regimen on postoperative pain relief.

Spinal anaesthesia in obstetrics.

This article provides a comprehensive review of the technique, drugs of choice, and potential side effects and complications associated with the drugs used and the single-shot spinal anaesthesia (SSS) technique for caesarean delivery. Although neuraxial analgesia and anaesthesia are generally considered safe, all interventions come with potential adverse effects. As such, the practice of obstetric anaesthesia has evolved to minimize such risks. This review highlights the safety and efficacy of SSS for caesarean delivery while also discussing potential complications such as hypotension, postdural puncture headache, and nerve injury. In addition, drug selection and dosages are examined as well, emphasizing the importance of individualized treatment plans and close monitoring for optimal outcomes.

Current status of the combined spinal-epidural technique in obstetrics and surgery.

Epidural and spinal blocks are well-accepted neuraxial techniques but both have several disadvantages. Combined spinal-epidural (CSE) can combine the best features of both techniques and reduce or eliminate these disadvantages. It provides the rapidity, density, and reliability of subarachnoid block with the flexibility of catheter epidural technique to extend the duration of anesthesia/analgesia (and to improve spinal block). It is an excellent technique for determining minimum intrathecal drug doses. Although most commonly employed in obstetric practice, CSE is also used in a wide variety of non-obstetric surgical procedures including orthopedic, vascular, gynecological, urological, and general surgical procedures. The needle-through-needle technique remains the most commonly used method to perform CSE. Several technical variations including Sequential CSE and Epidural Volume Extention (EVE) are commonly used particularly in obstetric and high-risk patients such as those with cardiac disease where a slower onset of sympathetic block is desirable. The risks of complications such as epidural catheter migration through the dural hole, neurological complications, and subarachnoid spread of epidurally administered drugs are possible but have not been a clinically relevant problem in the 40+ years of their existence. In obstetrics, CSE is used for labor pain because it produces rapid-onset analgesia with reduced local anesthetic consumption and less motor block. The epidural catheter placed as part of a CSE is more reliable than a catheter placed as part of a conventional epidural. Less breakthrough pain throughout labor is noted and fewer catheters require replacing. Side effects of CSE include greater potential for hypotension and more fetal heart rate abnormalities. CSE is also used for cesarean delivery. The main purpose is to decrease the spinal dose so that spinal-induced hypotension can be reduced. However, reducing the spinal dose requires an epidural catheter to avoid intra-operative pain when surgery is prolonged.

Preclinical evidence for anaesthesia-induced neurotoxicity.

Preclinical research concerning anaesthesia-induced neurotoxicity was initiated in 1999. A decade later, the earliest clinical observational data showed mixed results in neurodevelopmental outcomes following anaesthesia exposure at a young age. Hence to date, preclinical studies remain the cornerstone of research in this field, primarily because of the vulnerability of clinical observational studies to confounding bias. This review summarises current preclinical evidence. Most studies used rodent models, although non-human primates have also been employed. Across all gestational and postnatal ages, there is evidence that all commonly used general anaesthetics induce neuronal injury (e.g. apoptosis) and cause neurobehavioural impairment (e.g. learning and memory deficits). These deficits were more pronounced when animals were subjected to either repeated exposure, prolonged durations of exposure or higher doses of anaesthesia. To interpret these results in the clinical context, the strengths and limitations of each model and experiment should be carefully considered, as these preclinical studies were often biased by supraclinical durations and a lack of control with regard to physiological homeostasis.

Introduction and history of anaesthesia-induced neurotoxicity and overview of animal models.

Brain development is initiated at around 3 weeks of gestation. The peak velocity of brain weight gain occurs around birth, with the neural circuitry subsequently being refined until at least 20 years of age. Antenatal and postnatal general anaesthesia suppresses neuronal firing during this critical period and may therefore impair brain development, referred to as "anaesthesia-induced neurotoxicity". Whilst up to 1% of children are exposed to general anaesthesia antenatally (e.g., as an innocent bystander to maternal laparoscopic appendectomy), 15% of children under 3 years of age undergo general anaesthesia postnatally (e.g., otorhinolaryngologic surgery). In this article, the history of preclinical and clinical research in anaesthesia-induced neurotoxicity will be reviewed, starting from the pioneering preclinical study in 1999 until the most recent systematic reviews. The mechanisms of anaesthesia-induced neurotoxicity are introduced. Finally, an overview of the methods used in preclinical studies will be provided, with a comparison of the different animal models that have been employed to investigate this phenomenon.

Additive or synergistic analgesic effect of metamizole on standard pain treatment at home after arthroscopic shoulder surgery: A randomised controlled superiority trial.

BACKGROUND: There is growing evidence that the analgesic effect of metamizole is mediated at least partly by central mechanisms, including the endocannabinoid/endovanilloid system. Consequently, metamizole may have additive or even synergistic analgesic effects with paracetamol and nonsteroidal anti-inflammatory drugs (NSAID). OBJECTIVE: This study aimed to assess if triple therapy with metamizole, ibuprofen and paracetamol (MIP) is superior to double therapy with ibuprofen and paracetamol (i.p.) in treating pain at home after ambulatory arthroscopic shoulder surgery. DESIGN/SETTING/PATIENTS/INTERVENTION: In this double-blind, controlled, high-volume single centre, superiority trial, 110 patients undergoing elective ambulatory arthroscopic shoulder surgery were randomised to receive either MIP ( n  = 55) or i.p. ( n  = 55) orally for 4 days between December 2019 and November 2021. Pain intensity at movement and rest, using a numeric rating scale (NRS), perceived pain relief, use of rescue medication and adverse effects of study medication were recorded at the post-anaesthesia care unit (PACU) and on postoperative day (POD) 1 to 4 and 7. Quality of Recovery (QoR) and satisfaction with study medication were measured at POD 7 with telephone follow-up. MAIN OUTCOME MEASURE: The primary outcome measure was postoperative pain intensity on movement measured by an 11-point NRS (where 0 = no pain and 10 = worst pain imaginable) on POD 1. RESULTS: For the primary outcome, superiority of MIP in reducing postoperative pain at movement on POD 1 was not confirmed: mean difference NRS [95% confidence interval (CI), -0.08 (-1.00 to 0.84)]. For pain on movement and at rest, no significant differences were found between groups in the PACU nor on POD 1 to 4 or day 7. Nausea was reported significantly more frequently in the metamizole group (22.6 vs. 58.5; P  < 0.001). Other adverse effects of study medication, rescue opioid consumption, perceived pain relief, QoR at POD 7, and overall patient satisfaction were similar in both groups. CONCLUSION: Clinically, triple oral treatment with metamizole, paracetamol and ibuprofen is not superior to oral paracetamol and ibuprofen in multimodal pain treatment at home after ambulatory arthroscopic shoulder surgery. TRIAL REGISTRATION: European Union Clinical Trials Register 2019-002801-23 and Clinicaltrials.gov NCT04082728.

Effects of cumulative duration of repeated anaesthesia exposure on foetal brain development in the ovine model.

OBJECTIVE: Anaesthesia is required in 0.4-1% of pregnant women, and prolonged and repeated exposures to anaesthesia may be required. It is unknown whether these exposures may result in foetal neurotoxicity in humans. As sheep have a gestation comparable to that of humans, the objective of this study was to analyse the neurodevelopmental outcome of ovine foetuses that had been exposed in utero to repeated and prolonged anaesthesia. DESIGN: Randomized controlled preclinical study. SETTING: Anaesthesia for non-obstetric surgery during pregnancy. ANIMALS: Twenty-four healthy pregnant Swifter ewes. INTERVENTIONS: The ewes were randomized to no anaesthesia exposure (control-group), single exposure (at gestational age 68-70 days), or repeated exposure (at gestational age 68-70 days and 96-98 days) to 2.5 h of sevoflurane anaesthesia and maternal laparotomy. All lambs were delivered at approximately term gestation (gestational age: 140-143 days). MEASUREMENTS: The primary outcome was neuron density in the frontal cortex 24 h after birth for the control-group versus the repeated-exposure-group. Key secondary outcome was the time needed to achieve the milestone of standing. Secondary outcomes included other neurobehavioural assessments (e.g., motoric milestones) and histological parameters quantified in multiple brain regions (neuron density, total cell density, proliferation, inflammation, synaptogenesis, astrocytes and myelination). MAIN RESULTS: Neuron density in the frontal cortex did not differ between groups (mean ±â€¯standard deviation: control-group: 403 ±â€¯39, single-exposure group: 436 ±â€¯23 and repeated-exposure-group: 403 ±â€¯40 neurons/mm2, control-group versus repeated-exposure-group: p = 0.986, control-group versus single-exposure-group: p = 0.097). No significant difference was observed for the time needed to achieve the milestone of standing. Only very limited differences were observed for other histological outcome parameters and neurobehavioural assessments. CONCLUSIONS: There is no evidence for foetal neuronal injury or neurobehavioural impairments after a cumulative duration of 5 h repetitive prenatal anaesthesia in sheep.