Showing papers in "BJA: British Journal of Anaesthesia in 2019"

Chronic pain: a review of its epidemiology and associated factors in population-based studies

Abstract: Summary Chronic pain is a common, complex, and distressing problem that has a profound impact on individuals and society. It frequently presents as a result of a disease or an injury; however, it is not merely an accompanying symptom, but rather a separate condition in its own right, with its own medical definition and taxonomy. Studying the distribution and determinants of chronic pain allows us to understand and manage the problem at the individual and population levels. Targeted and appropriate prevention and management strategies need to take into account the biological, psychological, socio-demographic, and lifestyle determinants and outcomes of pain. We present a narrative review of the current understanding of these factors.

Perioperative Quality Initiative consensus statement on preoperative blood pressure, risk and outcomes for elective surgery

Abstract: Background A multidisciplinary international working subgroup of the third Perioperative Quality Initiative consensus meeting appraised the evidence on the influence of preoperative arterial blood pressure and community cardiovascular medications on perioperative risk. Methods A modified Delphi technique was used, evaluating papers published in MEDLINE on associations between preoperative numerical arterial pressure values or cardiovascular medications and perioperative outcomes. The strength of the recommendations was graded by National Institute for Health and Care Excellence guidelines. Results Significant heterogeneity in study design, including arterial pressure measures and perioperative outcomes, hampered the comparison of studies. Nonetheless, consensus recommendations were that (i) preoperative arterial pressure measures may be used to define targets for perioperative management; (ii) elective surgery should not be cancelled based solely upon a preoperative arterial pressure value; (iii) there is insufficient evidence to support lowering arterial pressure in the immediate preoperative period to minimise perioperative risk; and (iv) there is insufficient evidence that any one measure of arterial pressure (systolic, diastolic, mean, or pulse) is better than any other for risk prediction of adverse perioperative events. Conclusions Future research should define which preoperative arterial pressure values best correlate with adverse outcomes, and whether modifying arterial pressure in the preoperative setting will change the perioperative morbidity or mortality. Additional research should define optimum strategies for continuation or discontinuation of preoperative cardiovascular medications.

Lung-protective ventilation for the surgical patient: international expert panel-based consensus recommendations.

Abstract: Summary Postoperative pulmonary complications (PPCs) occur frequently and are associated with substantial morbidity and mortality. Evidence suggests that reduction of PPCs can be accomplished by using lung-protective ventilation strategies intraoperatively, but a consensus on perioperative management has not been established. We sought to determine recommendations for lung protection for the surgical patient at an international consensus development conference. Seven experts produced 24 questions concerning preoperative assessment and intraoperative mechanical ventilation for patients at risk of developing PPCs. Six researchers assessed the literature using questions as a framework for their review. The modified Delphi method was utilised by a team of experts to produce recommendations and statements from study questions. An expert consensus was reached for 22 recommendations and four statements. The following are the highlights: (i) a dedicated score should be used for preoperative pulmonary risk evaluation; and (ii) an individualised mechanical ventilation may improve the mechanics of breathing and respiratory function, and prevent PPCs. The ventilator should initially be set to a tidal volume of 6–8 ml kg−1 predicted body weight and positive end-expiratory pressure (PEEP) 5 cm H2O. PEEP should be individualised thereafter. When recruitment manoeuvres are performed, the lowest effective pressure and shortest effective time or fewest number of breaths should be used.

Anaesthetic care of patients undergoing primary hip and knee arthroplasty: consensus recommendations from the International Consensus on Anaesthesia-Related Outcomes after Surgery group (ICAROS) based on a systematic review and meta-analysis.

Abstract: Background Evidence-based international expert consensus regarding anaesthetic practice in hip/knee arthroplasty surgery is needed for improved healthcare outcomes. Methods The International Consensus on Anaesthesia-Related Outcomes after Surgery group (ICAROS) systematic review, including randomised controlled and observational studies comparing neuraxial to general anaesthesia regarding major complications, including mortality, cardiac, pulmonary, gastrointestinal, renal, genitourinary, thromboembolic, neurological, infectious, and bleeding complications. Medline, PubMed, Embase, and Cochrane Library including Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, from 1946 to May 17, 2018 were queried. Meta-analysis and Grading of Recommendations Assessment, Development and Evaluation approach was utilised to assess evidence quality and to develop recommendations. Results The analysis of 94 studies revealed that neuraxial anaesthesia was associated with lower odds or no difference in virtually all reported complications, except for urinary retention. Excerpt of complications for neuraxial vs general anaesthesia in hip/knee arthroplasty, respectively: mortality odds ratio (OR): 0.67, 95% confidence interval (CI): 0.57–0.80/OR: 0.83, 95% CI: 0.60–1.15; pulmonary OR: 0.65, 95% CI: 0.52–0.80/OR: 0.69, 95% CI: 0.58–0.81; acute renal failure OR: 0.69, 95% CI: 0.59–0.81/OR: 0.73, 95% CI: 0.65–0.82; deep venous thrombosis OR: 0.52, 95% CI: 0.42–0.65/OR: 0.77, 95% CI: 0.64–0.93; infections OR: 0.73, 95% CI: 0.67–0.79/OR: 0.80, 95% CI: 0.76–0.85; and blood transfusion OR: 0.85, 95% CI: 0.82–0.89/OR: 0.84, 95% CI: 0.82–0.87. Conclusions Recommendation: primary neuraxial anaesthesia is preferred for knee arthroplasty, given several positive postoperative outcome benefits; evidence level: low, weak recommendation. Recommendation: neuraxial anaesthesia is recommended for hip arthroplasty given associated outcome benefits; evidence level: moderate-low, strong recommendation. Based on current evidence, the consensus group recommends neuraxial over general anaesthesia for hip/knee arthroplasty. Trial registry number PROSPERO CRD42018099935.

Propofol infusion syndrome: a structured literature review and analysis of published case reports.

Abstract: Summary Propofol infusion syndrome is a rare, potentially fatal condition first described in children in the 1990s and later reported in adults. We provide a narrative review of what is currently known about propofol infusion syndrome, including a structured analysis of all published case reports; child and adult cases were analysed separately as propofol is no longer used for long-term sedation in children. The review contains an update on current knowledge of the pathophysiology of this condition along with recommendations for its diagnosis, prevention, and management. We reviewed 108 publications documenting 168 cases of propofol infusion syndrome. We evaluated clinical features and analysed factors influencing mortality in child and adult cases using separate multivariate analysis models. We used separate multiple linear regression models to analyse relationships between cumulative dose of propofol and the number of features seen and organ systems involved. Lipidaemia, fever, and hepatomegaly occurred more frequently in children than in adults, whilst rhabdomyolysis and hyperkalaemia were more frequent in adults. Mortality from propofol infusion syndrome is independently associated with fever and hepatomegaly in children, and electrocardiogram changes, hypotension, hyperkalaemia, traumatic brain injury, and a mean propofol infusion rate >5 mg kg−1 h−1 in adults. The cumulative dose of propofol was associated with an increased number of clinical features and the number of organ systems involved in adult cases only. Clinicians should consider propofol infusion syndrome in cases of unexplained metabolic acidosis, ECG changes, and rhabdomyolysis. We recommend early consideration of continuous haemofiltration in the management of propofol infusion syndrome.

Influence of perioperative anaesthetic and analgesic interventions on oncological outcomes: a narrative review.

Abstract: Summary Surgery is an important treatment modality for the majority of solid organ cancers. Unfortunately, cancer recurrence following surgery of curative intent is common, and typically results in refractory disease and patient death. Surgery and other perioperative interventions induce a biological state conducive to the survival and growth of residual cancer cells released from the primary tumour intraoperatively, which may influence the risk of a subsequent metastatic disease. Evidence is accumulating that anaesthetic and analgesic interventions could affect many of these pathophysiological processes, influencing risk of cancer recurrence in either a beneficial or detrimental way. Much of this evidence is from experimental in vitro and in vivo models, with clinical evidence largely limited to retrospective observational studies or post hoc analysis of RCTs originally designed to evaluate non-cancer outcomes. This narrative review summarises the current state of evidence regarding the potential effect of perioperative anaesthetic and analgesic interventions on cancer biology and clinical outcomes. Proving a causal link will require data from prospective RCTs with oncological outcomes as primary endpoints, a number of which will report in the coming years. Until then, there is insufficient evidence to recommend any particular anaesthetic or analgesic technique for patients undergoing tumour resection surgery on the basis that it might alter the risk of recurrence or metastasis.

Pain regulation by gut microbiota: molecular mechanisms and therapeutic potential.

Abstract: Summary The relationship between gut microbiota and neurological diseases, including chronic pain, has received increasing attention. The gut microbiome is a crucial modulator of visceral pain, whereas recent evidence suggests that gut microbiota may also play a critical role in many other types of chronic pain, including inflammatory pain, headache, neuropathic pain, and opioid tolerance. We present a narrative review of the current understanding on the role of gut microbiota in pain regulation and discuss the possibility of targeting gut microbiota for the management of chronic pain. Numerous signalling molecules derived from gut microbiota, such as by-products of microbiota, metabolites, neurotransmitters, and neuromodulators, act on their receptors and remarkably regulate the peripheral and central sensitisation, which in turn mediate the development of chronic pain. Gut microbiota-derived mediators serve as critical modulators for the induction of peripheral sensitisation, directly or indirectly regulating the excitability of primary nociceptive neurones. In the central nervous system, gut microbiota-derived mediators may regulate neuroinflammation, which involves the activation of cells in the blood–brain barrier, microglia, and infiltrating immune cells, to modulate induction and maintenance of central sensitisation. Thus, we propose that gut microbiota regulates pain in the peripheral and central nervous system, and targeting gut microbiota by diet and pharmabiotic intervention may represent a new therapeutic strategy for the management of chronic pain.

Effects of dexmedetomidine on perioperative stress, inflammation, and immune function: systematic review and meta-analysis

Abstract: Background Dexmedetomidine (DEX) is a highly selective alpha2 adrenoceptor agonist with broad pharmacological effects, including sedation, analgesia, anxiolysis, and sympathetic tone inhibition. Here we report a systematic review and meta-analysis of its effects on stress, inflammation, and immunity in surgical patients during the perioperative period. Methods We searched MEDLINE, METSTR, Embase, and Web of Science for clinical studies or trials to analyse the effects of DEX on perioperative stress, inflammation, and immune function. Results Sixty-seven studies (including randomised controlled trials and eight cohort studies) with 4842 patients were assessed, of which 2454 patients were in DEX groups and 2388 patients were in control (without DEX) groups. DEX infusion during the perioperative period inhibited release of epinephrine, norepinephrine, and cortisol; decreased blood glucose, interleukin (IL)-6, tumour necrosis factor-α, and C-reactive protein; and increased interleukin-10 in surgical patients. In addition, the numbers of natural killer cells, B cells, and CD4+ T cells, and the ratios of CD4+:CD8+ and Th1:Th2 were significantly increased; CD8+ T-cells were decreased in the DEX group when compared with the control group. Conclusions DEX, an anaesthesia adjuvant, can attenuate perioperative stress and inflammation, and protect the immune function of surgical patients, all of which may contribute to decreased postoperative complications and improved clinical outcomes.

Vasoactive-inotropic score and the prediction of morbidity and mortality after cardiac surgery

Abstract: Background The vasoactive-inotropic score (VIS) predicts mortality and morbidity after paediatric cardiac surgery. Here we examined whether VIS also predicted outcome in adults after cardiac surgery, and compared predictive capability between VIS and three widely used scoring systems. Methods This single-centre retrospective cohort study included 3213 cardiac surgery patients. Maximal VIS (VISmax) was calculated using the highest doses of vasoactive and inotropic medications administered during the first 24 h post-surgery. We established five VISmax categories: 0–5, >5–15, >15–30, >30–45, and >45 points. The predictive accuracy of VISmax was evaluated for a composite outcome, which included 30-day mortality, mediastinitis, stroke, acute kidney injury, and myocardial infarction. Results VISmax showed good prediction accuracy for the composite outcome [area under the curve (AUC), 0.72; 95% confidence interval (CI), 0.69–0.75]. The incidence of the composite outcome was 9.6% overall and 43% in the highest VISmax group (>45). VISmax predicted 30-day mortality (AUC, 0.76; 95% CI, 0.69–0.83) and 1-yr mortality (AUC, 0.70; 95% CI, 0.65–0.74). Prediction accuracy for unfavourable outcome was significantly better with VISmax than with Acute Physiology and Chronic Health Evaluation II (P=0.01) and Simplified Acute Physiological Score II (P=0.048), but not with the Sequential Organ Failure Assessment score (P=0.32). Conclusions In adults after cardiac surgery, VISmax predicted a composite of unfavourable outcomes and predicted mortality up to 1 yr after surgery.

Molecular mechanisms of action of systemic lidocaine in acute and chronic pain: a narrative review

Abstract: Systemic administration of the local anaesthetic lidocaine is antinociceptive in both acute and chronic pain states, especially in acute postoperative and chronic neuropathic pain. These effects cannot be explained by its voltage-gated sodium channel blocking properties alone, but the responsible mechanisms are still elusive. This narrative review focuses on available experimental evidence of the molecular mechanisms by which systemic lidocaine exerts its clinically documented analgesic effects. These include effects on the peripheral nervous system and CNS, where lidocaine acts via silencing ectopic discharges, suppression of inflammatory processes, and modulation of inhibitory and excitatory neurotransmission. We highlight promising objectives for future research to further unravel these antinociceptive mechanisms, which subsequently may facilitate the development of new analgesic strategies and therapies for acute and chronic pain.

Objective monitoring of nociception: a review of current commercial solutions.

Abstract: Nociception, in contrast to pain, is not a subjective feeling, but the physiological encoding and processing of nociceptive stimuli. However, monitoring nociception remains a challenge in attempts to lower the incidence of acute postoperative pain and the move towards a more automated approach to analgesia and anaesthesia. To date, several commercialised devices promise a more accurate reflection of nociception than the traditionally used vital signs, blood pressure and heart rate. This narrative review presents an overview of existing technologies and commercially available devices, and offers a perspective for future research. Although firm conclusions about individual methods may be premature, none currently appears to offer a sufficiently broad applicability. Furthermore, there is currently no firm evidence for any clinically relevant influence of such devices on patient outcome. However, the available monitors have significantly aided the understanding of underlying mechanisms and identification of potential pitfalls.

Association of electroencephalogram trajectories during emergence from anaesthesia with delirium in the postanaesthesia care unit: an early sign of postoperative complications.

Abstract: Background Postoperative delirium is associated with an increased risk of morbidity and mortality, especially in the elderly. Delirium in the postanaesthesia care unit (PACU) could predict adverse clinical outcomes. Methods We investigated a potential link between intraoperative EEG patterns and PACU delirium as well as an association of PACU delirium with perioperative outcomes, readmission and length of hospital stay. The risk factors for PACU delirium were also explored. Data were collected from 626 patients receiving general anaesthesia for procedures that would not interfere with frontal EEG recording. Results Of the 626 subjects enrolled, 125 tested positive for PACU delirium. Whilst age, renal failure, and pre-existing neurological disease were associated with PACU delirium in the univariable analysis, the multivariable analysis revealed the importance of information derived from the EEG, anaesthetic technique, anaesthesia duration, and history of stroke or neurodegenerative disease. The occurrence of EEG burst suppression during maintenance [odds ratio (OR)=1.86 (1.13–3.05)] and the type of EEG emergence trajectory may be predictive of PACU delirium. Specifically, EEG emergence trajectories lacking significant spindle power were strongly associated with PACU delirium, especially in cases that involved ketamine or nitrous oxide [OR=6.51 (3.00–14.12)]. Additionally, subjects with PACU delirium were at an increased risk for readmission [OR=2.17 (1.13–4.17)] and twice as likely to stay >6 days in the hospital. Conclusions Specific EEG patterns were associated with PACU delirium. These findings provide valuable information regarding how the brain reacts to surgery and anaesthesia that may lead to strategies to predict PACU delirium and identify key areas of investigation for its prevention.

Management of suspected immediate perioperative allergic reactions: an international overview and consensus recommendations.

Abstract: Suspected perioperative allergic reactions are rare but can be life-threatening. The diagnosis is difficult to make in the perioperative setting, but prompt recognition and correct treatment is necessary to ensure a good outcome. A group of 26 international experts in perioperative allergy (anaesthesiologists, allergists, and immunologists) contributed to a modified Delphi consensus process, which covered areas such as differential diagnosis, management during and after anaphylaxis, allergy investigations, and plans for a subsequent anaesthetic. They were asked to rank the appropriateness of statements related to the immediate management of suspected perioperative allergic reactions. Statements were selected to represent areas where there is a lack of consensus in existing guidelines, such as dosing of epinephrine and fluids, the management of impending cardiac arrest, and reactions refractory to standard treatment. The results of the modified Delphi consensus process have been included in the recommendations on the management of suspected perioperative allergic reactions. This paper provides anaesthetists with an overview of relevant knowledge on the immediate and postoperative management of suspected perioperative allergic reactions based on current literature and expert opinion. In addition, it provides practical advice and recommendations in areas where consensus has been lacking in existing guidelines.

State of the clinical science of perioperative brain health: report from the American Society of Anesthesiologists Brain Health Initiative Summit 2018

Abstract: Cognitive recovery after anaesthesia and surgery is a concern for older adults, their families, and caregivers. Reports of patients who were 'never the same' prompted a scientific inquiry into the nature of what patients have experienced. In June 2018, the ASA Brain Health Initiative held a summit to discuss the state of the science on perioperative cognition, and to create an implementation plan for patients and providers leveraging the current evidence. This group included representatives from the AARP (formerly the American Association of Retired Persons), American College of Surgeons, American Heart Association, and Alzheimer's Association Perioperative Cognition and Delirium Professional Interest Area. This paper summarises the state of the relevant clinical science, including risk factors, identification and diagnosis, prognosis, disparities, outcomes, and treatment of perioperative neurocognitive disorders. Finally, we discuss gaps in current knowledge with suggestions for future directions and opportunities for clinical and translational projects.

Complex regional pain syndrome: a narrative review for the practising clinician.

Abstract: Complex regional pain syndrome (CRPS) is a life-altering condition that usually affects the extremities after a trauma or nerve injury. The physiologic changes that occur as a result of the inciting injury are complex, as the name of the syndrome implies. The pain and disability associated with CRPS often lead to psychological co-morbidities that create a vicious cycle of pain, isolation, and depression. We review recent developments in the understanding of CRPS and advancements in management of this syndrome. Further research in targeting specific mechanisms involved in the pathophysiology of CRPS should lead to prevention of this condition.

Caudal epidural blocks in paediatric patients: a review and practical considerations

Abstract: Summary Caudal epidural blockade in children is one of the most widely administered techniques of regional anaesthesia. Recent clinical studies have answered major pharmacodynamic and pharmacokinetic questions, thus providing the scientific background for safe and effective blocks in daily clinical practice and demonstrating that patient selection can be expanded to range from extreme preterm births up to 50 kg of body weight. This narrative review discusses the main findings in the current literature with regard to patient selection (sub-umbilical vs mid-abdominal indications, contraindications, low-risk patients with spinal anomalies); anatomical considerations (access problems, age and body positioning, palpation for needle insertion); technical considerations (verification of needle position by ultrasound vs landmarks vs ‘whoosh' or ‘swoosh' testing); training and equipment requirements (learning curve, needle types, risk of tissue spreading); complications and safety (paediatric regional anaesthesia, caudal blocks); local anaesthetics (bupivacaine vs ropivacaine, risk of toxicity in children, management of toxic events); adjuvant drugs (clonidine, dexmedetomidine, opioids, ketamine); volume dosing (dermatomal reach, cranial rebound); caudally accessed lumbar or thoracic anaesthesia (contamination risk, verifying catheter placement); and postoperative pain. Caudal blocks are an efficient way to offer perioperative analgesia for painful sub-umbilical interventions. Performed on sedated children, they enable not only early ambulation, but also periprocedural haemodynamic stability and spontaneous breathing in patient groups at maximum risk of a difficult airway. These are important advantages over general anaesthesia, notably in preterm babies and in children with cardiopulmonary co-morbidities. Compared with other techniques of regional anaesthesia, a case for caudal blocks can still be made.

Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine initiative: patient-centred outcomes

Abstract: Background Patient-centred outcomes are increasingly used in perioperative clinical trials. The Standardised Endpoints in Perioperative Medicine (StEP) initiative aims to define which measures should be used in future research to facilitate comparison between studies and to enable robust evidence synthesis. Methods A systematic review was conducted to create a longlist of patient satisfaction, health-related quality of life, functional status, patient well-being, and life-impact measures for consideration. A three-stage Delphi consensus process involving 89 international experts was then conducted in order to refine this list into a set of recommendations. Results The literature review yielded six patient-satisfaction measures, seven generic health-related quality-of-life measures, eight patient well-being measures, five functional-status measures, and five life-impact measures for consideration. The Delphi response rates were 92%, 87%, and 100% for Rounds 1, 2, and 3, respectively. Three additional measures were added during the Delphi process as a result of contributions from the StEP group members. Firm recommendations have been made about one health-related quality-of-life measure (EuroQol 5 Dimension, five-level version with visual analogue scale), one functional-status measure (WHO Disability Assessment Schedule version 2.0, 12-question version), and one life-impact measure (days alive and out of hospital at 30 days after surgery). Recommendations with caveats have been made about the Bauer patient-satisfaction measure and two life-impact measures (days alive and out of hospital at 1 yr after surgery, and discharge destination). Conclusions Several patient-centred outcome measures have been recommended for use in future perioperative studies. We suggest that every clinical study should consider using at least one patient-centred outcome within a suite of endpoints.

Hot topics in opioid pharmacology: mixed and biased opioids

Abstract: Summary Analgesic design and evaluation have been driven by the desire to create high-affinity high-selectivity mu (μ)-opioid peptide (MOP) receptor agonists. Such ligands are the mainstay of current clinical practice, and include morphine and fentanyl. Advances in this sphere have come from designing pharmacokinetic advantage, as in rapid metabolism for remifentanil. These produce analgesia, but also the adverse-effect profile that currently defines this drug class: ventilatory depression, tolerance, and abuse liability. The MOP receptor is part of a family, and there are significant functional interactions between other members of the family (delta [δ]-opioid peptide [DOP], kappa [κ]-opioid peptide [KOP], and nociceptin/orphanin FQ receptor [NOP]). Experimentally, MOP agonism and DOP antagonism produce anti-nociception (animals) with no tolerance, and low doses of MOP and NOP ligands synergise to antinociceptive advantage. In this latter context, the lack of effect of NOP agonists on ventilation is an additional advantage. Recent development has been to move towards low-selectivity multifunctional ‘mixed ligands', such as cebranopadol, or ligand mixtures, such as Targinact®. Moreover, the observation that β-arrestin coupling underlies the side-effect profile for MOP ligands (from knockout animal studies) led to the discovery of biased (to G-protein and away from β-arrestin intracellular signalling) MOP ligands, such as oliceridine. There is sufficient excitement in the opioid field to suggest that opioid analgesics without significant side-effects may be on the horizon, and the ‘opioid Holy Grail' might be in reach.

Perioperative diabetic ketoacidosis associated with sodium-glucose co-transporter-2 inhibitors: a systematic review

Abstract: Background Perioperative diabetic ketoacidosis (DKA) with near-normal blood glucose concentrations, termed euglycaemic ketoacidosis (EDKA), is an adverse effect associated with sodium-glucose co-transporter-2 inhibitors (SGLT2i). Guidelines are still evolving concerning the perioperative management of patients on SGLT2i. We performed a systematic review of published reports of DKA from SGLT2i in the surgical setting to understand better the clinical presentation and characteristics of SGLT2i-associated DKA. Methods We searched PubMed, Embase, and ProQuest for reports of perioperative DKA involving SGLT2i up to January 2019. Results Forty-two reports of EDKA and five cases of hyperglycaemic diabetic ketoacidosis (HDKA) were identified from 33 publications. Canagliflozin was implicated in 26 cases. Presentation time varied from a few hours up to 6 weeks after operation. Precipitating factors may include diabetes medication changes, diet modifications, and intercurrent illnesses. There were 13 cases (12 EDKA and one HDKA) of bariatric surgery, 10 of them noted very-low-calorie diet regimes as a precipitating factor. No precise association between interruption of SGLT2i and the occurrence of DKA could be identified. Seven patients required mechanical ventilation, and acute kidney injury was noted in five. Five cases needed imaging to rule out anastomotic leak and pulmonary embolism, all of them revealed negative findings. Outcome data were available in 32 cases, all of them recovered completely. Conclusions EDKA is likely to be under-recognised because of its atypical presentation and may delay the diagnosis. Understanding this clinical entity, vigilance towards monitoring plasma/capillary ketones helps in early identification and assists in the management.

The prescription opioid crisis: role of the anaesthesiologist in reducing opioid use and misuse

Abstract: Summary Reports of strategies to prevent and treat the opioid epidemic are growing. Significant attention has been paid to the benefits of opioid addiction research, clinical prescribing, and public policy initiatives in curbing the epidemic. However, the role of the anaesthesiologist in minimising opioid use and misuse remains underexplored. For many patients with an opioid use disorder, the perioperative period represents the source of initial exposure. As perioperative physicians, anaesthesiologists are in the unique position to manage pain effectively while simultaneously decreasing opioid consumption. Multiple opportunities exist for anaesthesiologists to minimise opioid exposure and prevent subsequent persistent opioid use. We present a global strategy for decreasing perioperative opioid use and misuse among surgical patients. A historical perspective of the opioid epidemic is presented, together with an analysis of opioid supply and demand forces. We then present specific temporal strategies for opioid use reduction in the perioperative period. We emphasise the importance of preoperative identification of patients at risk for long-term opioid use and misuse, review the evidence supporting the opioid sparing capacity of individual multimodal analgesic agents, and discuss the benefits of regional anaesthesia for minimising opioid consumption. We describe postoperative and post-discharge tools, including effective multimodal analgesia and the role of a transitional pain service. Finally, we offer general institutional strategies that can be led by anaesthesiologists, identify gaps in knowledge, and offer directions for future research.

Comparative epidemiology of suspected perioperative hypersensitivity reactions.

Abstract: Summary Suspected perioperative hypersensitivity reactions are rare but contribute significantly to the morbidity and mortality of surgical procedures. Recent publications have highlighted the differences between countries concerning the respective risk of different drugs, and changes in patterns of causal agents and the emergence of new allergens. This review summarises recent information on the epidemiology of perioperative hypersensitivity reactions, with specific consideration of differences between geographic areas for the most frequently involved offending agents.

Clinical impact of peripherally inserted central catheters vs implanted port catheters in patients with cancer: an open-label, randomised, two-centre trial

Abstract: Background Centrally inserted totally implanted vascular access ports (PORTs) and peripherally inserted central catheters (PICCs) are widely used for the administration of chemotherapy. Our aim was to study the incidence of catheter-related deep venous thrombosis in patients with cancer receiving chemotherapy through either a PICC or a PORT. Methods Adults with non-haematological cancer (mainly breast and colorectal) from two Swedish oncology centres were included and followed for up to 1 yr. Patients were randomly assigned to receive a single-lumen PICC or PORT. The primary end point was the occurrence of a clinically significant catheter-related deep venous thrombosis, and the secondary end point was a composite of adverse events related to the catheter: insertion complication, thrombosis, occlusion, infection, and mechanical problems. Results The trial recruited 399 participants (PICC, n=201; PORT, n=198) between March 2013 and February 2017. The PICCs were associated with 16 (8%) deep venous thromboses compared with two (1%) in the PORT group (HR=10.2; 95% confidence interval, 2.3–44.6; P=0.002). The overall incidence of composite adverse events was higher for patients with a PICC compared with those with a PORT (HR=2.7; 95% confidence interval, 1.6–4.6; P Conclusions PICCs are associated with higher risk for catheter-related deep venous thrombosis and other adverse events when compared with PORTs. This increased risk should be considered when choosing a vascular access device for chemotherapy, especially in patients with solid malignancy. Clinical trial registration NCT01971021.

Challenging authority and speaking up in the operating room environment: a narrative synthesis

Abstract: Multidisciplinary care teams exist throughout healthcare systems. In the operating room (OR), effective communication between teams is essential, especially during crisis situations where patient safety can be in acute danger. An often-neglected skillset in educational curriculums is challenging authority. This narrative synthesis aims to explore the literature on challenging authority in the OR environment. A systematic search of Medline, EBM reviews and PsycINFO was conducted using terms related to challenging authority, speaking up, communication, patient safety, gradients and hierarchy. The initial search identified 4822 publications, out of which 31 studies were included. The data synthesis of the included studies was grouped into three distinct categories following a meta-aggregative approach: discussion and review articles, observational or qualitative studies, and studies identifying the role of specific barriers or investigating the effect of educational interventions. Themes emerging from expert beliefs, what reality tells us and what we test are consistent. Hierarchy, organisational culture and education are the most frequently observed and tested themes. Simulation research has been successful in eliciting and confirming the role of specific barriers to speaking up. Barriers and enablers are largely modifiable within institutions however, education regarding the importance of speaking up will need to accompany these modifications for any significant changes to occur.

Effectiveness of 80% vs 30–35% fraction of inspired oxygen in patients undergoing surgery: an updated systematic review and meta-analysis

Abstract: Background In 2016, the World Health Organization (WHO) strongly recommended the use of a high fraction of inspired oxygen (FiO2) in adult patients undergoing general anaesthesia to reduce the risk of surgical site infection (SSI). Since then, further trials have been published, trials included previously have come under scrutiny, and one article was retracted. We updated the systematic review on which the recommendation was based. Methods We performed a systematic literature search from January 1990 to April 2018 for RCTs comparing the effect of high (80%) vs standard (30–35%) FiO2 on the incidence of SSI. Studies retracted or under investigation were excluded. A random effects model was used for meta-analyses; the sources of heterogeneity were explored using meta-regression. Results Of 21 RCTs included, six were newly identified since the publication of the WHO guideline review; 17 could be included in the final analyses. Overall, no evidence for a reduction of SSI after the use of high FiO2 was found [relative risk (RR): 0.89; 95% confidence interval (CI): 0.73–1.07]. There was evidence that high FiO2 was beneficial in intubated patients [RR: 0.80 (95% CI: 0.64–0.99)], but not in non-intubated patients [RR: 1.20 (95% CI: 0.91–1.58); test of interaction; P=0.048]. Conclusions The WHO updated analyses did not show definite beneficial effect of the use of high perioperative FiO2, overall, but there was evidence of effect of reducing the SSI risk in surgical patients under general anaesthesia with tracheal intubation. However, the evidence for this beneficial effect has become weaker and the strength of the recommendation needs to be reconsidered.

Pain, placebo, and test of treatment efficacy: a narrative review

Abstract: Summary Over the past decade, the mechanisms underlying placebo effects have begun to be identified. At the same time, the placebo response appears to have increased in pharmacological trials and marked placebo effects are found in neurostimulation and surgical trials, thereby posing the question whether non-pharmacological interventions should be placebo-controlled to a greater extent. In this narrative review we discuss how the knowledge of placebo mechanisms may help to improve placebo control in pharmacological and non-pharmacological trials. We review the psychological, neurobiological, and genetic mechanisms underlying placebo analgesia and outline the current problems and potential solutions to the challenges with placebo control in trials on pharmacological, neurostimulation, and surgical interventions. We particularly focus on how patients' perception of the therapeutic intervention, and their expectations towards treatment efficacy may help develop more precise placebo controls and blinding procedures and account for the contribution of placebo factors to the efficacy of active treatments. Finally, we discuss how systematic investigations into placebo mechanisms across various pain conditions and types of treatment are needed in order to ‘personalise' the placebo control to the specific pathophysiology and interventions, which may ultimately lead to identification of more effective treatment for pain patients. In conclusion this review shows that it is important to understand how patients' perception and expectations influence the efficacy of active and placebo treatments in order to improve the test of new treatments. Importantly, this applies not only to assessment of drug efficacy but also to non-pharmacological trials on surgeries and stimulation procedures.

Maresin 1 attenuates neuroinflammation in a mouse model of perioperative neurocognitive disorders

Abstract: Background Resolution of inflammation is an active and dynamic process after surgery. Maresin 1 (MaR1) is one of a growing number of specialised pro-resolving lipids biosynthesised by macrophages that regulates acute inflammation. We investigated the effects of MaR1 on postoperative neuroinflammation, macrophage activity, and cognitive function in mice. Methods Adult male C57BL/6 (n=111) and Ccr2RFP/+Cx3cr1GFP/+ (n=54) mice were treated with MaR1 before undergoing anaesthesia and orthopaedic surgery. Systemic inflammatory changes, bone healing, neuroinflammation, and cognition were assessed at different time points. MaR1 protective effects were also evaluated using bone marrow derived macrophage cultures. Results MaR1 exerted potent systemic anti-inflammatory effects without impairing fracture healing. Prophylaxis with MaR1 prevented surgery-induced glial activation and opening of the blood–brain barrier. In Ccr2RFP/+Cx3cr1GFP/+ mice, fewer infiltrating macrophages were detected in the hippocampus after surgery with MaR1 prophylaxis, which resulted in improved memory function. MaR1 treatment also reduced expression of pro-inflammatory cell surface markers and cytokines by in vitro cultured macrophages. MaR1 was detectable in the cerebrospinal fluid of older adults before and after surgery. Conclusions MaR1 exerts distinct anti-inflammatory and pro-resolving effects through regulation of macrophage infiltration, NF-κB signalling, and cytokine release after surgery. Future studies on the use of pro-resolving lipid mediators may inform novel approaches to treat neuroinflammation and postoperative neurocognitive disorders.

Post-discharge impact and cost-consequence analysis of prehabilitation in high-risk patients undergoing major abdominal surgery: secondary results from a randomised controlled trial.

Abstract: Background Prehabilitation may reduce postoperative complications, but sustainability of its health benefits and impact on costs needs further evaluation. Our aim was to assess the midterm clinical impact and costs from a hospital perspective of an endurance-exercise-training-based prehabilitation programme in high-risk patients undergoing major digestive surgery. Methods A cost-consequence analysis was performed using secondary data from a randomised, blinded clinical trial. The main outcomes assessed were (i) 30-day hospital readmissions, (ii) endurance time (ET) during an exercise testing, and (iii) physical activity by the Yale Physical Activity Survey (YPAS). Healthcare use for the cost analysis included costs of the prehabilitation programme, hospitalisation, and 30-day emergency room visits and hospital readmissions. Results We included 125 patients in an intention-to-treat analysis. Prehabilitation showed a protective effect for 30-day hospital readmissions (relative risk: 6.4; 95% confidence interval [CI]: 1.4–30.0). Prehabilitation-induced enhancement of ET and YPAS remained statistically significant between groups at the end of the 3 and 6 month follow-up periods, respectively (ΔET 205 [151] s; P=0.048) (ΔYPAS 7 [2]; P=0.016). The mean cost of the programme was €389 per patient and did not increment the total costs of the surgical process (€812; CI: 95% –878 – 2642; P=0.365). Conclusions Prehabilitation may result in health value generation. Moreover, it appears to be a protective intervention for 30-day hospital readmissions, and its effects on aerobic capacity and physical activity may show sustainability at midterm. Clinical trial registration NCT02024776.

Organophosphorus nerve agent poisoning: managing the poisoned patient

Abstract: Summary Organophosphorus (OP) nerve agent poisoning made the headlines in 2018 with the nerve agent ‘Novichok' poisonings in Salisbury, England. This event highlighted a gap in the knowledge of most clinicians in the UK. In response, this special article aims to enlighten and signpost anaesthetists and intensivists towards the general management of OP nerve agent poisoned patients. Drawing on a broad range of sources, we will discuss what OP nerve agents are, how they work, and how to recognise and treat OP nerve agent poisoning. OP nerve agents primarily act by inhibiting the enzyme acetylcholinesterase, causing an acute cholinergic crisis; death usually occurs through respiratory failure. The antimuscarinic agent atropine, oximes (to reactivate acetylcholinesterase), neuroprotective drugs, and critical care remain the mainstays of treatment. The risk to medical staff from OP poisoned patients appears low, especially if there is a thorough decontamination of the poisoned patient and staff wear appropriate personal protective equipment. The events in Salisbury in the past year were shocking, and the staff at Salisbury District General Hospital performed admirably in treating those affected by Novichok nerve agent poisoning. We eagerly anticipate their future clinical publications so that the medical community might learn from their valuable experiences.