Glucagon-like peptide-1 receptor agonists: a narrative review of clinical pharmacology and implications for peri-operative practice.

BACKGROUND: Glucagon-like peptide-1 receptor agonists are used increasingly in the management of patients living with type 2 diabetes mellitus and obesity. In patients using glucagon-like peptide-1 receptor agonists, a key concern in the peri-operative period is the increased risk of pulmonary aspiration due to delayed gastric emptying. This review provides an overview of the pharmacodynamic and pharmacokinetic properties of glucagon-like peptide-1 receptor agonists and the risk of delayed gastric emptying and aspiration. METHODS: We conducted searches of MEDLINE and EMBASE databases of articles published before January 2024 using the keywords and medical subject headings: incretins; glucagon-like peptide-1; GLP-1; glucagon-like peptide-1 receptor agonists; GLP-1 RA; peri-operative period; perioperative; peri-operative; stomach emptying; gastric emptying; pulmonary aspiration; aspiration; food regurgitation; and regurgitation. The evidence was analysed, synthesised and reported narratively. RESULTS: A total of 1213 articles were located after duplicates were removed. Two authors screened the titles and abstracts to identify those studies which assessed specifically the risk of delayed gastric emptying and pulmonary aspiration or regurgitation in the peri-operative period. We searched manually the reference lists of relevant studies to identify any additional case reports. Ten studies were identified. Available evidence was limited to case reports, case series and observational work. CONCLUSIONS: There is insufficient evidence to put forward definitive guidance regarding the ideal cessation period for glucagon-like peptide-1 receptor agonists before elective surgery. Precautionary practice is required until more evidence becomes available. We suggest an individualised, evidence-based approach. In patients living with type 2 diabetes mellitus, there is concern that prolonged cessation before surgery will have a detrimental effect on peri-operative glycaemic control and discussion with an endocrinologist is advised. For patients taking glucagon-like peptide-1 receptor agonists for weight management, these drugs should be withheld for at least three half-lives before an elective surgical procedure.

Association between intraoperative oliguria and postoperative acute kidney injury in non-cardiac surgical patients: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the association between intraoperative oliguria and the risk of postoperative acute kidney injury (AKI) in patients undergoing non-cardiac surgery. METHODS: The MEDLINE and EMBASE databases were searched up to August 2022 for studies in adult patients undergoing non-cardiac surgery, where the association between intraoperative urine output and the risk of postoperative AKI was assessed. Both randomised and non-randomised studies were eligible for inclusion. Study selection and risk of bias assessment were independently performed by two investigators. The risk of bias was evaluated using the Newcastle-Ottawa scale. We performed meta-analysis of the reported multivariate adjusted odds ratios for the association between intraoperative oliguria (defined as urine output < 0.5 mL/kg/hr) and the risk of postoperative AKI using the inverse-variance method with random effects models. We conducted sensitivity analyses using varying definitions of oliguria as well as by pooling unadjusted odds ratios to establish the robustness of the primary meta-analysis. We also conducted subgroup analyses according to surgery type and definition of AKI to explore potential sources of clinical or methodological heterogeneity. RESULTS: Eleven studies (total 49,252 patients from 11 observational studies including a post hoc analysis of a randomised controlled trial) met the selection criteria. Seven of these studies contributed data from a total 17,148 patients to the primary meta-analysis. Intraoperative oliguria was associated with a significantly elevated risk of postoperative AKI (pooled adjusted odds ratio [OR] 1.74; 95% confidence interval [CI] 1.36-2.23, p < 0.0001, 8 studies). Sensitivity analyses supported the robustness of the primary meta-analysis. There was no evidence of any significant subgroup differences according to surgery type or definition of AKI. CONCLUSIONS: This study demonstrated a significant association between intraoperative oliguria and the risk of postoperative AKI, regardless of the definitions of oliguria or AKI used. Further prospective and multi-centre studies using standardised definitions of intraoperative oliguria are required to define the thresholds of oliguria and establish strategies to minimise the risk of AKI.

Treatment of in-transit Merkel cell carcinoma by isolated limb infusion with cytotoxic drugs.

Merkel cell carcinoma of the skin is a rare but aggressive malignancy, which predominantly affects older adults with fair skin. Isolated limb infusion (ILI) using melphalan and actinomycin D was first developed as a minimally invasive treatment option to treat unresectable metastatic melanoma confined to the limb. We report on a 62-year-old male with in-transit metastases (ITMs) treated with ILI to highlight the ongoing role this treatment has when all other therapies have been exhausted. At presentation, the patient had widespread ITMs in the right leg. Positron emission tomography scan demonstrated recurrent disease in the thigh and pelvis, and it was decided to treat the patient with ILI. The patient progressed well in the immediate post-operative period. The patient was able to mobilize from Day 6 post-ILI and was discharged on Day 10. There was an immediate clinical response seen in the lesions, with necrosis developing in the larger lesions.

Burnout in anaesthesiology residents: A systematic review of its prevalence and stressors.

BACKGROUND: Burnout is an occupational hazard precipitated by chronic exposure to excessive work-related stress. It can have negative impacts on the health and safety of patients and clinicians. Anaesthesiologists are at a high risk of burnout; anaesthetic residents especially may experience higher levels of stress as a result of training requirements and postgraduate examinations. However, the scale of burnout among anaesthesiology residents is not well evaluated. OBJECTIVES: To determine the prevalence of burnout and identify risk factors contributing to it among anaesthesiology residents worldwide and evaluate preventive strategies at institutional and departmental levels. DESIGN: A systematic review without meta-analysis. DATA SOURCES: We searched PubMed, Embase, Scopus and PsycInfo for English language articles published up to 24 May 2021. ELIGIBILITY CRITERIA: The inclusion criteria for qualitative analysis were a reported burnout prevalence in anaesthesiology residents and the use of an assessment tool. Exclusion criteria were reviews/meta-analyses/correspondence, non-English articles, articles without anaesthesiology residents and lacking information on burnout prevalence and metrics for assessment. RESULTS: Twelve studies met the inclusion criteria; seven studies utilised the 22-item Maslach Burnout Inventory Human Services Survey (MBI-HSS) and five utilised the abbreviated Maslach Burnout Inventory (aMBI). The reported burnout prevalence among anaesthesiology residents varied between 2.7 and 67.0% (median = 24.7%). Differences in burnout criteria contributed significantly to methodological heterogeneity. Factors predisposing to burnout included long working hours, poor workplace relationships, professional examinations and adverse clinical events. Protected rest time and restricted work hours were identified as effective strategies to prevent burnout. Other preventive strategies include mindfulness and resilience courses, as well as departmental initiatives such as exercise. CONCLUSION: Burnout is common amongst anaesthesiology residents. Standardised tools and diagnostic criteria are needed to distinguish methodological heterogeneity from true heterogeneity in study populations. Interventions have been proposed to improve management strategies to minimise burnout anaesthesiology residents. PROSPERO REFERENCE: CRD42019140472.

Perioperative implications of newer generation drug-eluting coronary stents: A narrative review.

Newer generation drug-eluting stents are the most commonly inserted stent in the setting of percutaneous coronary intervention. This narrative review focuses on the evidence underpinning the perioperative management of patients with newer generation drug-eluting stents undergoing non-cardiac surgery. Six studies reported the incidence of major adverse cardiovascular events according to the time interval from percutaneous coronary intervention to non-cardiac surgery, and the comparative risks of newer and first generation drug-eluting stents. No study demonstrated an increased risk of major adverse cardiovascular events once three months had elapsed between stent implantation and non-cardiac surgery. Only one study included patients with third and fourth generation drug-eluting stents. Seven studies analysed the relationship between antiplatelet therapy, major adverse cardiovascular events and perioperative bleeding. The risks of major adverse cardiovascular events do not appear to be increased if antiplatelet therapy is ceased for less than seven days but are increased if it is discontinued for more than seven days. Most studies reported no differences in the incidence of major bleeding associated with antiplatelet therapy. The risk of perioperative major adverse cardiovascular events in non-cardiac surgery does not appear to be increased after three months following implantation with newer generation drug-eluting stents. However, the possibility of increased risk cannot be excluded as most studies were inadequately powered. The thrombotic risk is substantially reduced in patients with fourth (polymer free) generation drug-eluting stents, and urgent non-cardiac surgery can be considered one month after percutaneous coronary intervention. Larger multicentre studies are needed to define the optimal window for non-cardiac surgery after percutaneous coronary intervention and provide definitive perioperative strategies for patients presenting for non-cardiac surgery after the implantation of newer generation drug-eluting stents.

Anaesthetic considerations for strabismus surgery in children and adults.

Strabismus correction surgery is the most common eye operation in children. Adults have approximately a 4% lifetime risk of developing strabismus. Current treatment options include pharmacological injection of botulinum toxin or bupivacaine, conventional corrective surgery, adjustable suture surgery and minimally invasive surgery. Repeated surgery is common as each operation has a 60%-80% chance of successful correction. The benefits of early surgical correction in large-angle strabismus in children outweigh the risks of anaesthesia. General anaesthesia is suitable for patients of all age groups, for complicated or repeated surgery, and bilateral eye procedures. Regional ophthalmic block reduces the incidence of oculocardiac reflex and emergence agitation, and provides postoperative analgesia, but requires a cooperative patient as many experience discomfort. Topical anaesthesia has been used in pharmacological injection, minimally invasive surgery, uncomplicated conventional strabismus surgery and some adjustable suture strabismus surgery. Its use, however, is only limited to cooperative adult patients. Prophylactic antiemesis with both ondansetron and dexamethasone is recommended, especially for children. A multimodal analgesia approach, including paracetamol, intravenous non-steroidal anti-inflammatory drugs, topical local anaesthetic and minimal opioid usage, is recommended for postoperative analgesia, while a supplementary regional ophthalmic block is at the discretion of the team.

Anesthesia guidelines for COVID-19 patients: a narrative review and appraisal.

The coronavirus disease 2019 (COVID-19) pandemic has challenged health systems globally and prompted the publication of several guidelines. The experiences of our international colleagues should be utilized to protect patients and healthcare workers. The primary aim of this article is to appraise national guidelines for the perioperative anesthetic management of patients with COVID-19 so that they can be enhanced for the management of any resurgence of the epidemic. PubMed and EMBASE databases were systematically searched for guidelines related to SARS-CoV and SARS-CoV-2. Additionally, the World Federation Society of Anesthesiologists COVID-19 resource webpage was searched for national guidelines; the search was expanded to include countries with a high incidence of SARS-CoV. The guidelines were evaluated using the Appraisal of Guidelines for Research and Evaluation II tool. Guidelines from Australia, Canada, China, India, Italy, South Africa, South Korea, Taiwan, the United Kingdom, and the United States of America were evaluated. All the guidelines focused predominantly on intubation and infection control. The scope and purpose of guidelines from China were the most comprehensive. The UK and South Africa provided the best clarity. Editorial independence, the rigor of development, and applicability scored poorly. Heterogeneity and gaps pertaining to preoperative screening, anesthesia technique, subspecialty anesthesia, and the lack of auditing of guidelines were identified. Evidence supporting the recommendations was weak. Early guidelines for the anesthetic management of COVID-19 patients lacked quality and a robust reporting framework. As new evidence emerges, national guidelines should be updated to enhance rigor, clarity, and applicability.

Neuroimmune mechanisms of pain: Basic science and potential therapeutic modulators.

This narrative review aims to describe the role of peripheral and central immune responses to tissue and nerve damage in animal models, and to discuss the use of immunomodulatory agents in clinical practice and their perioperative implications. Animal models of pain have demonstrated that nerve injury activates immune signalling pathways that drive aberrant sensory processes, resulting in neuropathic and chronic pain. This response involves the innate immune system. T lymphocytes are also recruited. Glial cells surrounding the damaged nerves release cytokines and proinflammatory mediators that activate resident immune cells and recruit circulatory immune cells. Toll-like receptors on the glial cells play a crucial role in the pathogenesis of chronic pain. Animal models indicate an immune mechanism of neuropathic pain. Analgesic drugs and anaesthetic agents have varied effects on the neuroimmune interface. Evidence of a neuroimmune interaction is mainly from animal studies. Human studies are required to evaluate the clinical implications of this neuroimmune interaction.

Adding low concentrations of clonidine to ropivacaine for transversus abdominis plane blocks does not reduce plasma ropivacaine levels, suggesting a lack of vasoconstrictor effect.

Clonidine has been used successfully to prolong the duration of action of local anaesthetics in peripheral nerve blocks, but its mechanism of action in this setting remains unclear. Some studies suggest that clonidine exerts a vasoconstrictor effect, limiting the washout of local anaesthetic from its site of deposition. We investigated this potential vasoconstrictor effect, using plasma ropivacaine concentrations as a surrogate measure of vasoconstriction, in patients who received transversus abdominis plane (TAP) blocks with and without clonidine. Eighty women undergoing laparoscopic gynaecological surgery were randomly assigned to receive one of four TAP block solutions: 0.2% ropivacaine (control), ropivacaine with clonidine 2 µg/kg (clonidine), ropivacaine with 1:400,000 adrenaline (adrenaline) or ropivacaine and a subcutaneous injection of clonidine 2 µg/kg (SC clonidine). The primary outcome was total venous plasma ropivacaine concentrations up to 6 h after the block. There were no significant differences in plasma ropivacaine concentrations between the control group and the clonidine group at any timepoint in the study, nor were there differences in either the mean maximum ropivacaine concentration ( Cmax) (1.99 µg/mL versus 2.05 µg/mL, P = 0.712) or the time to maximum concentration ( Tmax) (51.0 min versus 56.0 min, P = 0.537). The SC clonidine group also did not differ significantly from the controls ( Cmax 2.13 µg/mL versus 1.99 µg/mL, P = 0.424; Tmax 43.5 min versus 51.0 min, P = 0.201). Plasma ropivacaine concentrations in the adrenaline group were significantly lower than the controls from 10 to 90 min ( P < 0.003 for each comparison), and the Cmax was less than that of the control group (1.36 µg/mL versus 1.99 µg/mL, P < 0.001) with a longer Tmax (103.5 min versus 51.0 min, P = 0.001). These findings indicate that clonidine at a concentration of 1.35 µg/mL added to ropivacaine for TAP blocks did not produce a reduction in plasma ropivacaine concentrations. This suggests a lack of vasoconstrictor effect during TAP blocks. Further studies should evaluate whether vasoconstriction occurs when clonidine is used at higher concentrations or for other blocks.

Correlation and agreement between the TEG® 5000 and the TEG® 6s during liver transplant surgery.

The TEG® 5000 and novel TEG® 6s measure the viscoelasticity of whole blood during in vitro clot formation. The two devices measure similar coagulation variables but utilize distinctly different technologies. This study aimed to determine the correlation and agreement between the thrombelastographic parameters obtained by the two devices during liver transplant surgery. We obtained blood samples at six predefined intervals during the surgery of 10 consecutive patients. Two operators proficient in the use of the TEG® 6s and TEG® 5000 systems performed thrombelastographic measurements on each sample: non-citrated TEG® 5000, citrated TEG® 5000 and citrated TEG® 6s. Agreement and correlation were assessed using Bland Altman plots and Lin's concordance correlation. There was considerable inter-device variability for the different parameters measured by the TEG® 5000 and TEG® 6s devices. Acceptable agreement was observed when results were within the normal reference ranges. However, with increasing coagulopathy, agreement was poor and results could not be considered interchangeable. Although each of the three tests appeared reliable for qualitative detection of abnormalities of clot formation during liver transplant surgery, we found their quantitative results were not interchangeable.

The role of prehabilitation in frail surgical patients: A systematic review.

INTRODUCTION: Increasing emphasis is being placed on the detection of frailty in the pre-operative setting given its association with surgical morbidity and mortality. Prehabilitation seeks to increase the physiological reserve of frail patients, attenuating the risk of irreversible functional decline following surgery. AIM/HYPOTHESIS: This systematic review appraises the evidence available for prehabilitation in frail surgical patients. We proposed that exercise prehabilitation would especially benefit frail patients, with improvements in pre-operative functional capacity, and reductions in complications and length of hospital stay. METHODS: A literature search was conducted in MEDLINE, PubMed and CINAHL databases. Studies were included if they consisted of a prehabilitation intervention in frail patients undergoing surgery and specified a frailty model/index. Eight studies were included for analysis, 2 of which are ongoing studies. RESULTS: In 3 studies, prehabilitation consisted of an exercise intervention alone. There was a high feasibility of prehabilitation and a trend to improved pre-operative function, however, no evidence of improved post-operative functional recovery was there. In 2 studies, prehabilitation consisted of both exercise and nutritional interventions. Reductions in mortality and duration of hospital stay were reported, but the quality of evidence was judged to be very low. There was a lack of evidence of improved outcomes following pre-operative inspiratory muscle training in frail patients. DISCUSSION: This systematic review focuses on prehabilitation in frail surgical patients and reports that evidence supporting any outcome is limited, despite high feasibility and acceptability. There is a need for large randomised controlled trials to better establish the effects of prehabilitation in frail patients.

Efficacy of fibrinogen concentrate compared with cryoprecipitate for reversal of the antiplatelet effect of clopidogrel in an in vitro model, as assessed by multiple electrode platelet aggregometry, thromboelastometry, and modified thromboelastography.

OBJECTIVES: The management of dual-antiplatelet therapy when patients present for surgical revascularization is a clinical challenge. Whether increasing fibrinogen levels can restore hemostasis in this context is not established but may represent increased platelet glycoprotein fibrinogen binding, altered adenosine diphosphate (ADP)-dependent platelet activation, or an increase in formation of soluble fibrin as a component of whole blood clot. DESIGN: The study hypothesis was that fibrinogen concentrate would normalize in vitro hemostatic parameters after clopidogrel loading. The effect was compared with cryoprecipitate. SETTING: University Hospital PARTICIPANTS: Elective coronary catheter studies INTERVENTIONS: Assessment of platelet aggregation was made using whole blood platelet impedance. Viscoelastic assessment also was made using whole blood rotational thromboelastometry and modified thromboelastography. Twenty patients presenting for cardiac catheterization on dual-antiplatelet therapy were studied. Whole blood was titrated with increasing amounts of cryoprecipitate and fibrinogen concentrate. Samples then were diluted 40% with normal saline and further titrated. MEASUREMENT AND MAIN RESULTS: The principal finding of the study was that fibrinogen supplementation primarily improved assays of fibrin formation. Improvement in platelet aggregation response to ADP and TRAP was not observed. Neither cryoprecipitate nor fibrinogen concentrate, at the concentrations used, were able to improve the amplitude at 30 minutes (A30) in the modified TEG-ADP assay. Furthermore, they produced comparable amplitudes at 30 minutes despite a twofold difference in fibrinogen supplementation. CONCLUSIONS: Fibrinogen supplementation may play a role in the hemostatic resuscitation of patients on dual-antiplatelet therapy, but there is no evidence in this in vitro study that there is a specific platelet effect involved that would allow for platelet substitution.

Isolated limb infusion with melphalan and actinomycin D for melanoma: a systematic review.

Isolated limb infusion (ILI) was developed as a simplified and minimally invasive alternative to isolated limb perfusion (ILP) to treat unresectable limb melanoma. A number of centers around the world have reported their results using this procedure. In this study a systematic review of reported ILI experiences was undertaken. A literature search was conducted according to the guidelines for systematic reviews in order to select eligible papers reporting limb toxicity and response rates following ILI using melphalan and actinomycin D to treat limb melanoma. A total of 576 patients from seven publications were included. Regional toxicity following ILI was low: no visible effect of the treatment or slight erythema or edema was observed in 79% of the patients, while considerable erythema and/or edema with blistering was experienced by 19%. In 2% there was a threatened or actual compartment syndrome. No procedure-related amputation was reported. Complete response occurred in 33% of the patients and partial response in 40%, an overall response rate of 73%. Stable disease and progressive disease were achieved in 14% and 13% of the patients, respectively. This first systematic review of ILI procedures using melphalan and actinomycin D indicates that regional toxicity was generally low, with satisfactory response rates. When comparing ILI and ILP, it must be borne in mind that ILI is often performed in significantly older patients and in patients with higher stages of disease, which decreases the likelihood of a favorable response.

Isolated limb infusion: technical aspects.

OBJECTIVE: To describe the technique of isolated limb infusion (ILI) for regional high dose chemotherapy in patients with advanced malignancies confined to a limb, as currently practiced at Melanoma Institute Australia (MIA). BACKGROUND: ILI is progressively being used around the world but to date the reported response rates are generally lower than those reported by MIA. DISCUSSION: This description of the ILI protocol at MIA provides details that may allow other surgeons to improve results.