Perioperative medicine training resources: U5M9: Diagnosis and management of postoperative chest pain and thrombosis

Abstract
Postoperative pulmonary complications (PPCs) are common, costly, and increase patient mortality. Changes to the respiratory system occur immediately on induction of general anaesthesia: respiratory drive and muscle function are altered, lung volumes reduced, and atelectasis develops in > 75% of patients receiving a neuromuscular blocking drug. The respiratory system may take 6 weeks to return to its preoperative state after general anaesthesia for major surgery. Risk factors for PPC development are numerous, and clinicians should be aware of non-modifiable and modifiable factors in order to recognize those at risk and optimize their care. Many validated risk prediction models are described. These have been useful for improving our understanding of PPC development, but there remains inadequate consensus for them to be useful clinically. Preventative measures include preoperative optimization of co-morbidities, smoking cessation, and correction of anaemia, in addition to intraoperative protective ventilation strategies and appropriate management of neuromuscular blocking drugs. Protective ventilation includes low tidal volumes, which must be calculated according to the patient's ideal body weight. Further evidence for the most beneficial level of PEEP is required, and on-going randomized trials will hopefully provide more information. When PEEP is used, it may be useful to precede this with a recruitment manoeuvre if atelectasis is suspected. For high-risk patients, surgical time should be minimized. After surgery, nasogastric tubes should be avoided and analgesia optimized. A postoperative mobilization, chest physiotherapy, and oral hygiene bundle reduces PPCs.

Abstract
Background: Venous thromboembolism (VTE) is a common source of perioperative morbidity and mortality.

Objective: These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about preventing VTE in patients undergoing surgery.

Methods: ASH formed a multidisciplinary guideline panel balanced to minimize bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic reviews. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment.

Results: The panel agreed on 30 recommendations, including for major surgery in general (n = 8), orthopedic surgery (n = 7), major general surgery (n = 3), major neurosurgical procedures (n = 2), urological surgery (n = 4), cardiac surgery and major vascular surgery (n = 2), major trauma (n = 2), and major gynecological surgery (n = 2).

Conclusions: For patients undergoing major surgery in general, the panel made conditional recommendations for mechanical prophylaxis over no prophylaxis, for pneumatic compression prophylaxis over graduated compression stockings, and against inferior vena cava filters. In patients undergoing total hip or total knee arthroplasty, conditional recommendations included using either aspirin or anticoagulants, as well as for a direct oral anticoagulant over low-molecular-weight heparin (LMWH). For major general surgery, the panel suggested pharmacological prophylaxis over no prophylaxis, using LMWH or unfractionated heparin. For major neurosurgery, transurethral resection of the prostate, or radical prostatectomy, the panel suggested against pharmacological prophylaxis. For major trauma surgery or major gynecological surgery, the panel suggested pharmacological prophylaxis over no prophylaxis.

Abstract
Aspiration is defined as the inhalation of oropharyngeal or gastric contents into the lower respiratory tract. Upon injury, epithelial cells and alveolar macrophages secrete chemical mediators, attracting and activating neutrophils, which in turn release proteases and reactive oxygen species, degrading the alveolocapillary unit. Aspiration can lead to a range of diseases such as infectious pneumonia, chemical pneumonitis or respiratory distress syndrome with significant morbidity and mortality. It occurs in approximately 3-10 per 10 000 operations with an increased incidence in obstetric and paediatric anaesthesia. Patients are most at risk during induction of anaesthesia and extubation, in particular in emergency situations. The likelihood of significant aspiration can be reduced by fasting, pharmacological intervention and correct anaesthetic management using a rapid sequence induction. Treatment of acid aspiration is by suctioning after witnessed aspiration; antibiotics are indicated in patients with aspiration pneumonia only. Steroids are not proven to improve outcome or reduce mortality. Patients with acute lung injury requiring mechanical ventilation should be ventilated using lung protective strategies with low tidal volumes and low plateau pressure values, attempting to limit peak lung distension and end-expiratory collapse.

Abstract
Background: Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study's four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS.

Methods: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated "abnormal" laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria.

Results: An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors' diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96-5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6-41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom.

Conclusion: Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.

Abstract
Background: The aim of this study was to evaluate postoperative complications in patients having major elective surgery using oesophageal Doppler monitor-guided goal-directed haemodynamic therapy (GDHT), in which administration of fluids, inotropes, and vasopressors was guided by stroke volume, mean arterial pressure, and cardiac index.

Methods: The FEDORA trial was a prospective, multicentre, randomised, parallel-group, controlled patient- and observer-blind trial conducted in adults scheduled for major elective surgery. Randomization and allocation were carried out by a central computer system. In the control group, intraoperative fluids were given based on traditional principles. In the GDHT group, the intraoperative goals were to maintain a maximal stroke volume, with mean arterial pressure >70 mm Hg, and cardiac index ≥2.5 litres min-1 m-2. The primary outcome was percentage of patients with moderate or severe postoperative complications during the first 180 days after surgery.

Results: In total, 450 patients were randomized to the GDHT group (n=224) or control group (n=226). Data from 420 subjects were analysed. There were significantly fewer with complications in the GDHT group (8.6% vs 16.6%, P=0.018). There were also fewer complications (acute kidney disease, pulmonary oedema, respiratory distress syndrome, wound infections, etc.), and length of hospital stay was shorter in the GDHT group. There was no significant difference in mortality between groups.

Conclusions: Oesophageal Doppler monitor-guided GDHT reduced postoperative complications and hospital length of stay in low-moderate risk patients undergoing intermediate risk surgery, with no difference in mortality at 180 days.

Abstract
Background: Studies have demonstrated that high-flow nasal cannula (HFNC) prevents intubation in acute hypoxic respiratory failure when compared with conventional oxygen therapy (COT). However, the data examining routine HFNC use in the immediate postoperative period are less clear.

Research question: Is routine HFNC use superior to COT or noninvasive ventilation (NIV) use in preventing intubation in patients postoperatively?

Study design and methods: We comprehensively searched databases (PubMed, Embase, Web of Science) to identify randomized controlled trials (RCTs) that compared the effect of HFNC use with that of COT or NIV in the immediate postoperative period on reintubation, escalation of respiratory support, hospital mortality, ICU and hospital length of stay (LOS), postoperative hypoxemia, and treatment complications. We assessed individual study risk of bias (RoB) by using the revised Cochrane RoB 2 tool and rated certainty in outcomes by using the Grading of Recommendations Assessment, Development and Evaluation framework.

Results: We included 11 RCTs enrolling 2,201 patients. Ten compared HFNC with COT and one with NIV. Compared with COT use, HFNC use in the postoperative period was associated with a lower reintubation rate (relative risk [RR], 0.32; 95% CI, 0.12-0.88; absolute risk reduction [ARR], 2.9%; moderate certainty) and decreased escalation of respiratory support (RR, 0.54; 95% CI, 0.31-0.94; ARR, 5.8%; very low certainty). Post hoc subgroup analysis suggested that this effect was driven by patients who were obese and/or at high risk (subgroup differences, P = .06). We did not find differences in any of the other stated outcomes between HFNC and COT. HFNC was also no different from NIV in reintubation rate, respiratory therapy failure, or ICU LOS.

Interpretation: With evidence of moderate certainty, prophylactic HFNC reduces reintubation and escalation of respiratory support compared with COT in the immediate postoperative period after cardiothoracic surgery. This effect is likely driven by patients who are at high risk and/or obese. These findings support postoperative prophylactic HFNC use in the patients who are at high risk and/or obese undergoing cardiothoracic surgery.

Background: This project was devised to estimate the incidence of major complications of airway management during anaesthesia in the UK and to study these events.

Methods: Reports of major airway management complications during anaesthesia (death, brain damage, emergency surgical airway, unanticipated intensive care unit admission) were collected from all National Health Service hospitals for 1 yr. An expert panel assessed inclusion criteria, outcome, and airway management. A matched concurrent census estimated a denominator of 2.9 million general anaesthetics annually.

Results: Of 184 reports meeting inclusion criteria, 133 related to general anaesthesia: 46 events per million general anaesthetics [95% confidence interval (CI) 38-54] or one per 22,000 (95% CI 1 per 26-18,000). Anaesthesia events led to 16 deaths and three episodes of persistent brain damage: a mortality rate of 5.6 per million general anaesthetics (95% CI 2.8-8.3): one per 180,000 (95% CI 1 per 352-120,000). These estimates assume that all such cases were captured. Rates of death and brain damage for different airway devices (facemask, supraglottic airway, tracheal tube) varied little. Airway management was considered good in 19% of assessable anaesthesia cases. Elements of care were judged poor in three-quarters: in only three deaths was airway management considered exclusively good.

Conclusions: Although these data suggest the incidence of death and brain damage from airway management during general anaesthesia is low, statistical analysis of the distribution of reports suggests as few as 25% of relevant incidents may have been reported. It therefore provides an indication of the lower limit for incidence of such complications. The review of airway management indicates that in a majority of cases, there is 'room for improvement'.

Abstract
All perioperative patients, but especially trauma victims and those undergoing prostate or orthopedic surgery, are at increased risk of venous thromboembolism. Patients at highest risk include those with malignancy, immobility, and obesity; those who smoke; and those taking oral contraceptives, hormone replacement therapy, or antipsychotic medications. Dyspnea, anxiety, and tachypnea are the most common presenting symptoms in awake patients, and hypotension, tachycardia, hypoxemia, and decreased end-tidal CO(2) are the most common findings in patients receiving general anesthesia. The presence of shock and right ventricular failure are associated with adverse outcomes. Helical computed tomographic scanning is the preferred definitive diagnostic study, but transesophageal echocardiography may be valuable in making a presumptive diagnosis in the operating room. Early diagnosis allows supportive therapy and possible anticoagulation (in some cases, to be started before the conclusion of surgery).

_Myocardial injury after non-cardiac surgery (MINS) increases the risk of cardiovascular events and deaths, which anticoagulation therapy could prevent. Dabigatran prevents perioperative venous thromboembolism, but whether this drug can prevent a broader range of vascular complications in patients with MINS is unknown. The MANAGE trial assessed the potential of dabigatran to prevent major vascular complications among such patients.Methods_ In this international, randomised, placebo-controlled trial, we recruited patients from 84 hospitals in 19 countries. Eligible patients were aged at least 45 years, had undergone non-cardiac surgery, and were within 35 days of MINS. Patients were randomly assigned (1_1) to receive dabigatran 110 mg orally twice daily or matched placebo for a maximum of 2 years or until termination of the trial and, using a partial 2-by-2 factorial design, patients not taking a proton-pump inhibitor were also randomly assigned (1_1) to omeprazole 20 mg once daily, for which results will be reported elsewhere, or matched placebo to measure its effect on major upper gastrointestinal complications. Research personnel randomised patients through a central 24 h computerised randomisation system using block randomisation, stratified by centre. Patients, health-care providers, data collectors, and outcome adjudicators were masked to treatment allocation. The primary efficacy outcome was the occurrence of a major vascular complication, a composite of vascular mortality and non-fatal myocardial infarction, non-haemorrhagic stroke, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism. The primary safety outcome was a composite of life-threatening, major, and critical organ bleeding. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01661101.Findings_ Between Jan 10, 2013, and July 17, 2017, we randomly assigned 1754 patients to receive dabigatran (n=877) or placebo (n=877)

Abstract
Introduction: Postoperative morbidity and mortality in older patients with comorbidities undergoing gastrointestinal surgery are a major burden on healthcare systems. Infections after surgery are common in such patients, prolonging hospitalisation and reducing postoperative short-term and long-term survival. Optimal management of perioperative intravenous fluids and inotropic drugs may reduce infection rates and improve outcomes from surgery. Previous small trials of cardiac-output-guided haemodynamic therapy algorithms suggested a modest reduction in postoperative morbidity. A large definitive trial is needed to confirm or refute this and inform widespread clinical practice.

Methods: The Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial is a multicentre, international, parallel group, open, randomised controlled trial. 2502 high-risk patients undergoing major elective gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intravenous fluid combined with low-dose inotrope infusion, or usual care. The trial intervention will be carried out during and for 4 hours after surgery. The primary outcome is postoperative infection of Clavien-Dindo grade II or higher within 30 days of randomisation. Participants and those delivering the intervention will not be blinded to treatment allocation; however, outcome assessors will be blinded when feasible. Participant recruitment started in January 2017 and is scheduled to last 3 years, within 50 hospitals worldwide.

Ethics/dissemination: The OPTIMISE II trial has been approved by the UK National Research Ethics Service and has been approved by responsible ethics committees in all participating countries. The findings will be disseminated through publication in a widely accessible peer-reviewed scientific journal.

Trial registration number: ISRCTN39653756.

Keywords: elective surgical procedures/adverse effects; hemodynamics/physiology; intraoperative/methods; prospective studies.

Abstract
Background: Acute cardiac events are a frequent cause of morbidity after vascular surgery. The impact of early evidence-based treatment for patients with an acute cardiac event after vascular surgery on long-term postoperative outcomes has not been extensively studied. We hypothesized that providing appropriate evidence-based treatment to patients with elevated postoperative cardiac troponin levels may limit long-term mortality.

Methods: We conducted a study of 667 consecutive major vascular surgery patients with an elevated postoperative troponin I level. We then determined which of these patients received medical therapy as per the 2007 American College of Cardiology/American Heart Association recommendations for the medical management of patients with chronic stable angina. All patients with troponin elevation were then matched with 2 control patients without postoperative troponin elevation. Matching was done using logistic regression and nearest-neighbor matching methods. The primary study end point was 12 months survival without a major cardiac event (i.e., death, myocardial infarction, coronary revascularization, or pulmonary edema requiring hospitalization).

Results: Therapy was intensified in 43 of 66 patients (65%) who suffered a troponin I elevation after surgery. Patients with a troponin I elevation not receiving intensified cardiovascular treatment had a hazard ratio (HR) of 1.77 (95% confidence interval (CI), 1.13-2.42; P = 0.004) for the primary study outcome as compared with the control group. In contrast, patients with a troponin I elevation who received intensified cardiovascular treatment had an HR of 0.63 (95% CI, 0.10-1.19; P = 0.45) for the primary outcome as compared with the control group. Patients with a troponin I elevation not receiving treatment intensification likely were at higher risk for a major cardiac event (HR, 2.80; 95% CI, 1.05-24.2; P = 0.04) compared with patients who did receive treatment intensification.

Conclusions: The main finding of this study was that in patients with elevated troponin I levels after noncardiac surgery, long-term adverse cardiac outcomes may likely be improved by following evidence-based recommendations for the medical management of acute coronary syndromes.

Abstract
Purpose: High-flow nasal cannula (HFNC) oxygen therapy is attracting increasing interest in acute medicine as an alternative to standard oxygen therapy; however, its use to prevent hypoxaemia after major abdominal surgery has not been evaluated. Our trial was designed to close this evidence gap.

Methods: A multicentre randomised controlled trial was carried out at three university hospitals in France. Adult patients at moderate to high risk of postoperative pulmonary complications who had undergone major abdominal surgery using lung-protective ventilation were randomly assigned using a computer-generated sequence to receive either HFNC oxygen therapy or standard oxygen therapy (low-flow oxygen delivered via nasal prongs or facemask) directly after extubation. The primary endpoint was absolute risk reduction (ARR) for hypoxaemia at 1 h after extubation and after treatment discontinuation. Secondary outcomes included occurrence of postoperative pulmonary complications within 7 days after surgery, the duration of hospital stay, and in-hospital mortality. The analysis was performed on data from the modified intention-to-treat population. This trial was registered with ClinicalTrials.gov (NCT01887015).

Results: Between 6 November 2013 and 1 March 2015, 220 patients were randomly assigned to receive either HFNC (n = 108) or standard oxygen therapy (n = 112); all of these patients completed follow-up. The median duration of the allocated treatment was 16 h (interquartile range 14-18 h) with standard oxygen therapy and 15 h (interquartile range 12-18) with HFNC therapy. Twenty-three (21 %) of the 108 patients treated with HFNC 1 h after extubation and 29 (27 %) of the 108 patients after treatment discontinuation had postextubation hypoxaemia, compared with 27 (24 %) and 34 (30 %) of the 112 patients treated with standard oxygen (ARR 4, 95 % CI -8 to 15 %; p = 0.57; adjusted relative risk [RR] 0.87, 95 % CI 0.53-1.43; p = 0.58). Over the 7-day postoperative follow-up period, there was no statistically significant difference between the groups in the proportion of patients who remained free of any pulmonary complication (ARR 7, 95 % CI -6 to 20 %; p = 0.40). Other secondary outcomes also did not differ significantly between the two groups.

Conclusions: Among patients undergoing major abdominal surgery, early preventive application of high-flow nasal cannula oxygen therapy after extubation did not result in improved pulmonary outcomes compared with standard oxygen therapy.

Keywords: High-risk surgery; Oxygen therapy; Perioperative medicine; Postoperative hypoxaemia; Postoperative pulmonary complications.

Abstract
Background: VTE is a common cause of preventable death in surgical patients.

Methods: We developed recommendations for thromboprophylaxis in nonorthopedic surgical patients by using systematic methods as described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.

Results: We describe several alternatives for stratifying the risk of VTE in general and abdominal-pelvic surgical patients. When the risk for VTE is very low (< 0.5%), we recommend that no specific pharmacologic (Grade 1B) or mechanical (Grade 2C) prophylaxis be used other than early ambulation. For patients at low risk for VTE (∼1.5%), we suggest mechanical prophylaxis, preferably with intermittent pneumatic compression (IPC), over no prophylaxis (Grade 2C). For patients at moderate risk for VTE (∼3%) who are not at high risk for major bleeding complications, we suggest low-molecular-weight heparin (LMWH) (Grade 2B), low-dose unfractionated heparin (Grade 2B), or mechanical prophylaxis with IPC (Grade 2C) over no prophylaxis. For patients at high risk for VTE (∼6%) who are not at high risk for major bleeding complications, we recommend pharmacologic prophylaxis with LMWH (Grade 1B) or low-dose unfractionated heparin (Grade 1B) over no prophylaxis. In these patients, we suggest adding mechanical prophylaxis with elastic stockings or IPC to pharmacologic prophylaxis (Grade 2C). For patients at high risk for VTE undergoing abdominal or pelvic surgery for cancer, we recommend extended-duration, postoperative, pharmacologic prophylaxis (4 weeks) with LMWH over limited-duration prophylaxis (Grade 1B). For patients at moderate to high risk for VTE who are at high risk for major bleeding complications or those in whom the consequences of bleeding are believed to be particularly severe, we suggest use of mechanical prophylaxis, preferably with IPC, over no prophylaxis until the risk of bleeding diminishes and pharmacologic prophylaxis may be initiated (Grade 2C). For patients in all risk groups, we suggest that an inferior vena cava filter not be used for primary VTE prevention (Grade 2C) and that surveillance with venous compression ultrasonography should not be performed (Grade 2C). We developed similar recommendations for other nonorthopedic surgical populations.

Conclusions: Optimal thromboprophylaxis in nonorthopedic surgical patients will consider the risks of VTE and bleeding complications as well as the values and preferences of individual patients.

Abstract
There is a need for large trials that test the clinical effectiveness of interventions in the field of perioperative medicine. Clinical outcome measures used in such trials must be robust, clearly defined and patient-relevant. Our objective was to develop standards for the use of clinical outcome measures to strengthen the methodological quality of perioperative medicine research. A literature search was conducted using PubMed and opinion leaders worldwide were invited to nominate papers that they believed the group should consider. The full texts of relevant articles were reviewed by the taskforce members and then discussed to reach a consensus on the required standards. The report was then circulated to opinion leaders for comment and review. This report describes definitions for 22 individual adverse events with a system of severity grading for each. In addition, four composite outcome measures were identified, which were designed to evaluate postoperative outcomes. The group also agreed on standards for four outcome measures for the evaluation of healthcare resource use and quality of life. Guidance for use of these outcome measures is provided, with particular emphasis on appropriate duration of follow-up. This report provides clearly defined and patient-relevant outcome measures for large clinical trials in perioperative medicine. These outcome measures may also be of use in clinical audit. This report is intended to complement and not replace other related work to improve assessment of clinical outcomes following specific surgical procedures.

No abstract available

Abstract
The development of pulmonary atelectasis is common in the surgical patient. Pulmonary atelectasis can cause various degrees of gas exchange and respiratory mechanics impairment during and after surgery. In its most serious presentations, lung collapse could contribute to postoperative respiratory insufficiency, pneumonia, and worse overall clinical outcomes. A specific risk assessment is critical to allow clinicians to optimally choose the anesthetic technique, prepare appropriate monitoring, adapt the perioperative plan, and ensure the patient's safety. Bedside diagnosis and management have benefited from recent imaging advancements such as lung ultrasound and electrical impedance tomography, and monitoring such as esophageal manometry. Therapeutic management includes a broad range of interventions aimed at promoting lung recruitment. During general anesthesia, these strategies have consistently demonstrated their effectiveness in improving intraoperative oxygenation and respiratory compliance. Yet these same intraoperative strategies may fail to affect additional postoperative pulmonary outcomes. Specific attention to the postoperative period may be key for such outcome impact of lung expansion. Interventions such as noninvasive positive pressure ventilatory support may be beneficial in specific patients at high risk for pulmonary atelectasis (e.g., obese) or those with clinical presentations consistent with lung collapse (e.g., postoperative hypoxemia after abdominal and cardiothoracic surgeries). Preoperative interventions may open new opportunities to minimize perioperative lung collapse and prevent pulmonary complications. Knowledge of pathophysiologic mechanisms of atelectasis and their consequences in the healthy and diseased lung should provide the basis for current practice and help to stratify and match the intensity of selected interventions to clinical conditions.

Abstract
Postoperative pulmonary complications are common and cause increased mortality and hospital stay. Smoking and respiratory diseases including asthma, chronic obstructive pulmonary disease and obstructive sleep apnoea are associated with developing postoperative pulmonary complications. Independent risk factors for such complications also include low pre-operative oxygen saturation, or a recent respiratory infection. Postponing surgery in patients who have respiratory infections or inadequately treated respiratory disease, until these can be fully treated, should, therefore, reduce postoperative pulmonary complications. There is evidence from several studies that pre-operative smoking cessation reduces such complications, with no agreed duration at which the benefits become significant; the longer the abstinence, the greater the benefit. Intensive smoking cessation programmes are more effective, and there are long-term benefits, as many patients become permanent non-smokers following their surgery. Supervised exercise programmes normally last 6-8 weeks, and although they reduce overall complications, the evidence of benefit for postoperative pulmonary complications is mixed. High-intensity interval training can improve fitness in just 2 weeks, and so may be more useful for surgical patients. Specific respiratory pre-operative interventions, such as deep breathing exercises and incentive spirometry, can help when used as components of a package of respiratory care. Pre-operative inspiratory muscle training programmes that involve inspiration against a predetermined respiratory load may also reduce some postoperative pulmonary complications. Pre-operative exercise programmes are recommended for patients having major surgery, or in those where pre-operative testing has shown low levels of cardiorespiratory fitness; interval training or respiratory interventions are more feasible as these reduce complications after a shorter pre-operative intervention.

Abstract
The occurrence of postoperative pulmonary complications (PPCs) is frequently observed and has been linked to elevated levels of morbidity and mortality, which have adverse effects on both clinical and financial outcomes in healthcare settings. This systematic review aims to present the evidence that supports our comprehension of PPCs and emphasize the circumstances that necessitate the use of postoperative noninvasive ventilation (PNIV) or re-intubation with postoperative mechanical ventilation (POMV). A search was conducted on the National Library of Medicine's Pubmed database and Cochrane Library until November 29, 2020, to find published reports of randomized control trials (RCTs) that assessed postoperative pulmonary complications. Data related to the prevalence of PPCs and the use of PNIV, POMV, and length of hospital stay were extracted from all the studies. For the analysis, a total of 13 studies involving 6,609 patients were included, and out of these, four RCTs reported statistically significant results. The use of protective lung ventilation (PLV) with low tidal volume and positive end-expiratory pressure (PEEP) during intraoperative ventilation, along with pressure-controlled (PCV) ventilation, as well as the postoperative ventilation strategy of continuous positive airway pressure (CPAP) combined with standard oxygen therapy were the only techniques that demonstrated a clear reduction in the incidence of PPCs. Furthermore, the use of PLV with low tidal volume and PEEP and intraoperative mechanical ventilation with a vital capacity maneuver followed by 10 cm H2O of PEEP were found to decrease the requirement for postoperative noninvasive ventilation. CPAP with standard oxygen therapy was the only intervention that reduced the need for reintubation. Various ventilation strategies are available for both intraoperative and postoperative periods with the goal of decreasing the need for postoperative noninvasive ventilation (PNIV) or re-intubation with postoperative mechanical ventilation (POMV).

Abstract
Objective: To evaluate the effect of high-flow nasal cannula oxygen (HFNO) therapy on hospital length of stay (LOS) and postoperative pulmonary complications (PPCs) in adult postoperative patients.

Data sources: PubMed, Embase, the Cochrane Library, Web of Science of Studies, China National Knowledge Index, and Wan Fang databases were searched until July 2018.

Study selection: Randomized controlled trials (RCTs) comparing HFNO with conventional oxygen therapy or noninvasive mechanical ventilation in adult postoperative patients were included. The primary outcomes were hospital LOS and PPCs; short-term mortality (defined as intensive care unit, hospital, or 28-day mortality) and intubation rate were the secondary outcomes.

Data extraction: Demographic variables, high-flow oxygen therapy application, effects, and side effects were retrieved. Data were analyzed by the methods recommended by the Cochrane Collaboration. The strength of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation. Random errors were evaluated with trial sequential analysis.

Data synthesis: Fourteen studies (2568 patients) met the inclusion criteria and were included. Compared to the control group, the pooled effect showed that HFNO was significantly associated with a shorter hospital stay (mean difference: -0.81; 95% confidence interval [CI]: -1.34 to -0.29, P = .002), but not mortality (risk ratio [RR]: 1.0, 95% CI: 0.63 to 1.59, P = 1.0). Weak evidence of a reduction in reintubation rate (RR: 0.76, 95% CI: 0.57-1.01, P = .06) and PPC rate (RR: 0.89, 95% CI: 0.75-1.06, P = .18) with HFNO versus control group was recorded.

Conclusions: The available RCTs suggest that, among the adult postoperative patients, HFNO therapy compared to the control group significantly reduces hospital LOS.

Abstract
Aim: Thrombolytic therapy induces faster clot dissolution than anticoagulation in patients with acute pulmonary embolism (PE) but is associated with an increased risk of haemorrhage. We reviewed the risks and benefits of thrombolytic therapy in the management of patients with acute PE.

Methods and results: We systematically reviewed randomized controlled studies comparing systemic thrombolytic therapy plus anticoagulation with anticoagulation alone in patients with acute PE. Fifteen trials involving 2057 patients were included in our meta-analysis. Compared with heparin, thrombolytic therapy was associated with a significant reduction of overall mortality (OR; 0.59, 95% CI: 0.36-0.96). This reduction was not statistically significant after exclusion of studies including high-risk PE (OR; 0.64, 95% CI: 0.35-1.17). Thrombolytic therapy was associated with a significant reduction in the combined endpoint of death or treatment escalation (OR: 0.34, 95% CI: 0.22-0.53), PE-related mortality (OR: 0.29; 95% CI: 0.14-0.60) and PE recurrence (OR: 0.50; 95% CI: 0.27-0.94). Major haemorrhage (OR; 2.91, 95% CI: 1.95-4.36) and fatal or intracranial bleeding (OR: 3.18, 95% CI: 1.25-8.11) were significantly more frequent among patients receiving thrombolysis.

Conclusions: Thrombolytic therapy reduces total mortality, PE recurrence, and PE-related mortality in patients with acute PE. The decrease in overall mortality is, however, not significant in haemodynamically stable patients with acute PE. Thrombolytic therapy is associated with an increase of major and fatal or intracranial haemorrhage.

Abstract
Objective: To identify, appraise, and synthesise the best available evidence on the efficacy of perioperative interventions to reduce postoperative pulmonary complications (PPCs) in adult patients undergoing non-cardiac surgery.

Design: Systematic review and meta-analysis of randomised controlled trials.

Data sources: Medline, Embase, CINHAL, and CENTRAL from January 1990 to December 2017.

Eligibility criteria: Randomised controlled trials investigating short term, protocolised medical interventions conducted before, during, or after non-cardiac surgery were included. Trials with clinical diagnostic criteria for PPC outcomes were included. Studies of surgical technique or physiological or biochemical outcomes were excluded.

Data extraction and synthesis: Reviewers independently identified studies, extracted data, and assessed the quality of evidence. Meta-analyses were conducted to calculate risk ratios with 95% confidence intervals. Quality of evidence was summarised in accordance with GRADE methods. The primary outcome was the incidence of PPCs. Secondary outcomes were respiratory infection, atelectasis, length of hospital stay, and mortality. Trial sequential analysis was used to investigate the reliability and conclusiveness of available evidence. Adverse effects of interventions were not measured or compared.

Results: 117 trials enrolled 21 940 participants, investigating 11 categories of intervention. 95 randomised controlled trials enrolling 18 062 participants were included in meta-analysis; 22 trials were excluded from meta-analysis because the interventions were not sufficiently similar to be pooled. No high quality evidence was found for interventions to reduce the primary outcome (incidence of PPCs). Seven interventions had low or moderate quality evidence with confidence intervals indicating a probable reduction in PPCs: enhanced recovery pathways (risk ratio 0.35, 95% confidence interval 0.21 to 0.58), prophylactic mucolytics (0.40, 0.23 to 0.67), postoperative continuous positive airway pressure ventilation (0.49, 0.24 to 0.99), lung protective intraoperative ventilation (0.52, 0.30 to 0.88), prophylactic respiratory physiotherapy (0.55, 0.32 to 0.93), epidural analgesia (0.77, 0.65 to 0.92), and goal directed haemodynamic therapy (0.87, 0.77 to 0.98). Moderate quality evidence showed no benefit for incentive spirometry in preventing PPCs. Trial sequential analysis adjustment confidently supported a relative risk reduction of 25% in PPCs for prophylactic respiratory physiotherapy, epidural analgesia, enhanced recovery pathways, and goal directed haemodynamic therapies. Insufficient data were available to support or refute equivalent relative risk reductions for other interventions.

Conclusions: Predominantly low quality evidence favours multiple perioperative PPC reduction strategies. Clinicians may choose to reassess their perioperative care pathways, but the results indicate that new trials with a low risk of bias are needed to obtain conclusive evidence of efficacy for many of these interventions.

Study registration: Prospero CRD42016035662.

Abstract
Coronary artery disease is a leading cause of mortality worldwide, and patients with obstructive coronary artery disease require optimal cardiovascular medical therapy along with lifestyle modification for secondary prevention of future cardiac events. Optimal medical therapy includes antiplatelet agents, high-intensity statins, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, aldosterone antagonists, and calcium channel blockers. There are differences in the medical therapy guidelines of the American Heart Association/American College of Cardiology and the European Society of Cardiology. In addition, there are emerging medical therapies that may be added to future guidelines with additional cardiovascular outcome benefits.

Pulmonary aspiration complicates between 1 in 900 to 1 in 10 000 general anaesthetics,1 dependent on risk factors. All novice anaesthetists in the UK are taught to consider the risk of aspiration and to modify their anaesthetic technique accordingly. The prevention of aspiration remains a cornerstone of anaesthetic practice.

The recent Royal College of Anaesthetists 4th National Audit Project2 (NAP4) collected data on the incidence and causes of major airway complications in the UK. Over 50% of airway-related deaths in anaesthesia were as a consequence of aspiration, outweighing the much feared can't intubate can't ventilate (CICV) scenario. In addition, 23% of all cases reported to NAP4 involved aspiration as either the primary or secondary event. Cases not resulting in death commonly resulted in significant morbidity and prolonged stay on intensive care.

Despite the awareness among anaesthetists of the need to minimize the risks of aspiration and advances in anaesthetic practices, NAP4 provided evidence that aspiration often occurred as a consequence of incomplete assessment of aspiration risk or a failure to modify anaesthetic technique. This review aims to highlight the key findings from NAP4 with regard to aspiration and evaluates the literature on aspiration risk assessment and decision-making.

Abstract
Myocardial injury after noncardiac surgery (MINS) differs from myocardial infarction in being defined by troponin elevation apparently from cardiac ischemia with or without signs and symptoms. Such myocardial injury is common, silent, and strongly associated with mortality. MINS is usually asymptomatic and only detected by routine troponin monitoring. There is currently no known safe and effective prophylaxis for perioperative myocardial injury. However, appropriate preoperative screening may help guide proactive postoperative preventative actions. Intraoperative hypotension is associated with myocardial injury, acute kidney injury, and death. Hypotension is common and largely undetected in the postoperative general care floor setting, and independently associated with myocardial injury and mortality. Critical care patients are especially sensitive to hypotension, and the risk appears to be present at blood pressures previously regarded as normal. Tachycardia appears to be less important. Available information suggests that clinicians would be prudent to avoid perioperative hypotension.

Abstract
Myocardial injury after noncardiac surgery is defined by elevated postoperative cardiac troponin concentrations that exceed the 99th percentile of the upper reference limit of the assay and are attributable to a presumed ischemic mechanism, with or without concomitant symptoms or signs. Myocardial injury after noncardiac surgery occurs in ≈20% of patients who have major inpatient surgery, and most are asymptomatic. Myocardial injury after noncardiac surgery is independently and strongly associated with both short-term and long-term mortality, even in the absence of clinical symptoms, electrocardiographic changes, or imaging evidence of myocardial ischemia consistent with myocardial infarction. Consequently, surveillance of myocardial injury after noncardiac surgery is warranted in patients at high risk for perioperative cardiovascular complications. This scientific statement provides diagnostic criteria and reviews the epidemiology, pathophysiology, and prognosis of myocardial injury after noncardiac surgery. This scientific statement also presents surveillance strategies and treatment approaches.

Abstract
Study objective: Chest pain is relatively common postoperatively. Myocardial infarction (MI) is one cause of chest pain after surgery, but chest pain also results from less severe conditions. Because of its potential severity, chest pain usually prompts the activation of Rapid Response Systems (RRS). While chest pain is a cardinal symptom of myocardial ischemia in the non-surgical setting, the significance and relevance of chest pain after noncardiac surgery remains unclear.

Design: We conducted a retrospective analysis of noncardiac surgical inpatients for whom postoperative chest pain triggered our multidisciplinary RRS.

Setting: Surgical wards at Cleveland Clinic, Cleveland, OH.

Patients: Postsurgical patients after noncardiac surgery in whom the RSS system was activated for chest pain.

Interventions: RRS specified interventions like ECG readings, troponin measurements, transfer to ICU.

Measurements: Our primary outcome was MI. Secondary outcomes included the proportion of patients who had an ECG performed, troponin measurements, echocardiography, cardiac catheterization, and were admitted to the Intensive Care Unit (ICU).

Main results: 5850 surgical patients experienced postoperative chest pain and triggered an RRS activation between 2009 and 2019. A total of 3110 patients had troponin T measured within 6 h after RRS activation, and 538 of them (17%) had elevated troponin, meeting the Fourth Universal Definition criteria for MI. Additionally, 2 patients had ST-segment elevation infarction (STEMI) without troponin measurement. Among the 540 patients with MI, only 19 (3.5%) were diagnosed with a STEMI by ECG, 388 (72%) had echocardiography, 43 patients (8%) had cardiac catheterization, 8 patients (1.5%) required emergent cardiac surgery, and 424 (79%) were admitted to an ICU.

Conclusion: Chest pain is a serious clinical sign, often indicating a postoperative myocardial infarction, and therefore should be taken seriously. Troponin screening should be routinely considered in postsurgical patients who report chest pain.

Abstract
Background: Intraoperative hypotension may contribute to postoperative acute kidney injury (AKI) and myocardial injury, but what blood pressures are unsafe is unclear. The authors evaluated the association between the intraoperative mean arterial pressure (MAP) and the risk of AKI and myocardial injury.

Methods: The authors obtained perioperative data for 33,330 noncardiac surgeries at the Cleveland Clinic, Ohio. The authors evaluated the association between intraoperative MAP from less than 55 to 75 mmHg and postoperative AKI and myocardial injury to determine the threshold of MAP where risk is increased. The authors then evaluated the association between the duration below this threshold and their outcomes adjusting for potential confounding variables.

Results: AKI and myocardial injury developed in 2,478 (7.4%) and 770 (2.3%) surgeries, respectively. The MAP threshold where the risk for both outcomes increased was less than 55 mmHg. Compared with never developing a MAP less than 55 mmHg, those with a MAP less than 55 mmHg for 1-5, 6-10, 11-20, and more than 20 min had graded increases in their risk of the two outcomes (AKI: 1.18 [95% CI, 1.06-1.31], 1.19 [1.03-1.39], 1.32 [1.11-1.56], and 1.51 [1.24-1.84], respectively; myocardial injury 1.30 [1.06-1.5], 1.47 [1.13-1.93], 1.79 [1.33-2.39], and 1.82 [1.31-2.55], respectively].

Conclusions: Even short durations of an intraoperative MAP less than 55 mmHg are associated with AKI and myocardial injury. Randomized trials are required to determine whether outcomes improve with interventions that maintain an intraoperative MAP of at least 55 mmHg.

Abstract
Venous thromboembolism (VTE) is a common condition that can lead to complications such as postphlebitic syndrome, chronic pulmonary artery hypertension, and death. The approach to the diagnosis of has evolved over the years and an algorithm strategy combining pretest probability, D-dimer testing, and diagnostic imaging now allows for safe, convenient, and cost-effective investigation of patients. Patients with low pretest probability and a negative D-dimer can have VTE excluded without the need for imaging. The mainstay of treatment of VTE is anticoagulation, whereas interventions such as thrombolysis and inferior vena cava filters are reserved for special situations. Low-molecular-weight heparin has allowed for outpatient management of most patients with deep vein thrombosis at a considerable cost savings to the health care system. Patients with malignancy-associated VTE benefit from decreased recurrent rates if treated with long-term low-molecular-weight heparin. The development of new oral anticoagulants further simplifies treatment. The duration of anticoagulation is primarily influenced by underlying cause of the VTE (whether provoked or not) and consideration of the risk for major hemorrhage. Testing for genetic and acquired thrombophilia may provide insight as to the cause of a first idiopathic deep vein thrombosis, but the evidence linking most thrombophilias to an increased risk of recurrent thrombosis is limited.

Abstract
Importance: Little is known about the relationship between perioperative high-sensitivity troponin T (hsTnT) measurements and 30-day mortality and myocardial injury after noncardiac surgery (MINS).

Objective: To determine the association between perioperative hsTnT measurements and 30-day mortality and potential diagnostic criteria for MINS (ie, myocardial injury due to ischemia associated with 30-day mortality).

Design, setting, and participants: Prospective cohort study of patients aged 45 years or older who underwent inpatient noncardiac surgery and had a postoperative hsTnT measurement. Starting in October 2008, participants were recruited at 23 centers in 13 countries; follow-up finished in December 2013.

Exposures: Patients had hsTnT measurements 6 to 12 hours after surgery and daily for 3 days; 40.4% had a preoperative hsTnT measurement.

Main outcomes and measures: A modified Mazumdar approach (an iterative process) was used to determine if there were hsTnT thresholds associated with risk of death and had an adjusted hazard ratio (HR) of 3.0 or higher and a risk of 30-day mortality of 3% or higher. To determine potential diagnostic criteria for MINS, regression analyses ascertained if postoperative hsTnT elevations required an ischemic feature (eg, ischemic symptom or electrocardiography finding) to be associated with 30-day mortality.

Results: Among 21 842 participants, the mean age was 63.1 (SD, 10.7) years and 49.1% were female. Death within 30 days after surgery occurred in 266 patients (1.2%; 95% CI, 1.1%-1.4%). Multivariable analysis demonstrated that compared with the reference group (peak hsTnT <5 ng/L), peak postoperative hsTnT levels of 20 to less than 65 ng/L, 65 to less than 1000 ng/L, and 1000 ng/L or higher had 30-day mortality rates of 3.0% (123/4049; 95% CI, 2.6%-3.6%), 9.1% (102/1118; 95% CI, 7.6%-11.0%), and 29.6% (16/54; 95% CI, 19.1%-42.8%), with corresponding adjusted HRs of 23.63 (95% CI, 10.32-54.09), 70.34 (95% CI, 30.60-161.71), and 227.01 (95% CI, 87.35-589.92), respectively. An absolute hsTnT change of 5 ng/L or higher was associated with an increased risk of 30-day mortality (adjusted HR, 4.69; 95% CI, 3.52-6.25). An elevated postoperative hsTnT (ie, 20 to <65 ng/L with an absolute change ≥5 ng/L or hsTnT ≥65 ng/L) without an ischemic feature was associated with 30-day mortality (adjusted HR, 3.20; 95% CI, 2.37-4.32). Among the 3904 patients (17.9%; 95% CI, 17.4%-18.4%) with MINS, 3633 (93.1%; 95% CI, 92.2%-93.8%) did not experience an ischemic symptom.

Conclusions and relevance: Among patients undergoing noncardiac surgery, peak postoperative hsTnT during the first 3 days after surgery was significantly associated with 30-day mortality. Elevated postoperative hsTnT without an ischemic feature was also associated with 30-day mortality.

Abstract
Pulmonary atelectasis is common in the perioperative period. Physiologically, it is produced when collapsing forces derived from positive pleural pressure and surface tension overcome expanding forces from alveolar pressure and parenchymal tethering. Atelectasis impairs blood oxygenation and reduces lung compliance. It is increasingly recognized that it can also induce local tissue biologic responses, such as inflammation, local immune dysfunction, and damage of the alveolar-capillary barrier, with potential loss of lung fluid clearance, increased lung protein permeability, and susceptibility to infection, factors that can initiate or exaggerate lung injury. Mechanical ventilation of a heterogeneously aerated lung (e.g., in the presence of atelectatic lung tissue) involves biomechanical processes that may precipitate further lung damage: concentration of mechanical forces, propagation of gas-liquid interfaces, and remote overdistension. Knowledge of such pathophysiologic mechanisms of atelectasis and their consequences in the healthy and diseased lung should guide optimal clinical management.