Drugs to reduce bleeding and transfusion in major open vascular or endovascular surgery: a systematic review and network meta-analysis.

BACKGROUND: Vascular surgery may be followed by internal bleeding due to inadequate surgical haemostasis, abnormal clotting, or surgical complications. Bleeding ranges from minor, with no transfusion requirement, to massive, requiring multiple blood product transfusions. There are a number of drugs, given systemically or applied locally, which may reduce the need for blood transfusion. OBJECTIVES: To assess the effectiveness and safety of anti-fibrinolytic and haemostatic drugs and agents in reducing bleeding and the need for blood transfusion in people undergoing major vascular surgery or vascular procedures with a risk of moderate or severe (> 500 mL) blood loss. SEARCH METHODS: We searched: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL, and Transfusion Evidence Library. We also searched the WHO ICTRP and ClinicalTrials.gov trial registries for ongoing and unpublished trials. Searches used a combination of MeSH and free text terms from database inception to 31 March 2022, without restriction on language or publication status. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in adults of drug treatments to reduce bleeding due to major vascular surgery or vascular procedures with a risk of moderate or severe blood loss, which used placebo, usual care or another drug regimen as control. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were units of red cells transfused and all-cause mortality. Our secondary outcomes included risk of receiving an allogeneic blood product, risk of reoperation or repeat procedure due to bleeding, risk of a thromboembolic event, risk of a serious adverse event and length of hospital stay. We used GRADE to assess certainty of evidence. MAIN RESULTS: We included 22 RCTs with 3393 participants analysed, of which one RCT with 69 participants was reported only in abstract form, with no usable data. Seven RCTs evaluated systemic drug treatments (three aprotinin, two desmopressin, two tranexamic acid) and 15 RCTs evaluated topical drug treatments (drug-containing bioabsorbable dressings or glues), including fibrin, thrombin, collagen, gelatin, synthetic sealants and one investigational new agent. Most trials were conducted in high-income countries and the majority of the trials only included participants undergoing elective surgery. We also identified two ongoing RCTs. We were unable to perform the planned network meta-analysis due to the sparse reporting of outcomes relevant to this review. Systemic drug treatments We identified seven trials of three systemic drugs: aprotinin, desmopressin and tranexamic acid, all with placebo controls. The trials of aprotinin and desmopressin were small with very low-certainty evidence for all of our outcomes. Tranexamic acid versus placebo was the systemic drug comparison with the largest number of participants (2 trials; 1460 participants), both at low risk of bias. The largest of these included a total of 9535 individuals undergoing a number of different higher risk surgeries and reported limited information on the vascular subgroup (1399 participants). Neither trial reported the number of units of red cells transfused per participant up to 30 days. Three outcomes were associated with very low-certainty evidence due to the very wide confidence intervals (CIs) resulting from small study sizes and low number of events. These were: all-cause mortality up to 30 days; number of participants requiring an allogeneic blood transfusion up to 30 days; and risk of requiring a repeat procedure or operation due to bleeding. Tranexamic acid may have no effect on the risk of thromboembolic events up to 30 days (risk ratio (RR) 1.10, 95% CI 0.88 to 1.36; 1 trial, 1360 participants; low-certainty evidence due to imprecision). There is one large ongoing trial (8320 participants) comparing tranexamic acid versus placebo in people undergoing non-cardiac surgery who are at high risk of requiring a red cell transfusion. This aims to complete recruitment in April 2023. This trial has primary outcomes of proportion of participants transfused with red blood cells and incidence of venous thromboembolism (DVT or PE). Topical drug treatments Most trials of topical drug treatments were at high risk of bias due to their open-label design (compared with usual care, or liquids were compared with sponges). All of the trials were small, most were very small, and few reported clinically relevant outcomes in the postoperative period. Fibrin sealant versus usual care was the topical drug comparison with the largest number of participants (5 trials, 784 participants). The five trials that compared fibrin sealant with usual care were all at high risk of bias, due to the open-label trial design with no measures put in place to minimise reporting bias. All of the trials were funded by pharmaceutical companies. None of the five trials reported the number of red cells transfused per participant up to 30 days or the number of participants requiring an allogeneic blood transfusion up to 30 days. The other three outcomes were associated with very low-certainty evidence with wide confidence intervals due to small sample sizes and the low number of events, these were: all-cause mortality up to 30 days; risk of requiring a repeat procedure due to bleeding; and risk of thromboembolic disease up to 30 days. We identified one large trial (500 participants) comparing fibrin sealant versus usual care in participants undergoing abdominal aortic aneurysm repair, which has not yet started recruitment. This trial lists death due to arterial disease and reintervention rates as primary outcomes. AUTHORS' CONCLUSIONS: Because of a lack of data, we are uncertain whether any systemic or topical treatments used to reduce bleeding due to major vascular surgery have an effect on: all-cause mortality up to 30 days; risk of requiring a repeat procedure or operation due to bleeding; number of red cells transfused per participant up to 30 days or the number of participants requiring an allogeneic blood transfusion up to 30 days. There may be no effect of tranexamic acid on the risk of thromboembolic events up to 30 days, this is important as there has been concern that this risk may be increased. Trials with sample size targets of thousands of participants and clinically relevant outcomes are needed, and we look forward to seeing the results of the ongoing trials in the future.

OxVent: Design and evaluation of a rapidly-manufactured Covid-19 ventilator.

BACKGROUND: The manufacturing of any standard mechanical ventilator cannot rapidly be upscaled to several thousand units per week, largely due to supply chain limitations. The aim of this study was to design, verify and perform a pre-clinical evaluation of a mechanical ventilator based on components not required for standard ventilators, and that met the specifications provided by the Medicines and Healthcare Products Regulatory Agency (MHRA) for rapidly-manufactured ventilator systems (RMVS). METHODS: The design utilises closed-loop negative feedback control, with real-time monitoring and alarms. Using a standard test lung, we determined the difference between delivered and target tidal volume (VT) at respiratory rates between 20 and 29 breaths per minute, and the ventilator's ability to deliver consistent VT during continuous operation for >14 days (RMVS specification). Additionally, four anaesthetised domestic pigs (3 male-1 female) were studied before and after lung injury to provide evidence of the ventilator's functionality, and ability to support spontaneous breathing. FINDINGS: Continuous operation lasted 23 days, when the greatest difference between delivered and target VT was 10% at inspiratory flow rates >825 mL/s. In the pre-clinical evaluation, the VT difference was -1 (-90 to 88) mL [mean (LoA)], and positive end-expiratory pressure (PEEP) difference was -2 (-8 to 4) cmH2O. VT delivery being triggered by pressures below PEEP demonstrated spontaneous ventilation support. INTERPRETATION: The mechanical ventilator presented meets the MHRA therapy standards for RMVS and, being based on largely available components, can be manufactured at scale. FUNDING: Work supported by Wellcome/EPSRC Centre for Medical Engineering,King's Together Fund and Oxford University.

Leading Causes of Anesthesia-Related Liability Claims in Ambulatory Surgery Centers.

OBJECTIVE: We present a contemporary analysis of patient injury, allegations, and contributing factors of anesthesia-related closed claims, which involved cases that specifically occurred in free-standing ambulatory surgery centers (ASCs). METHODS: We examined ASC-closed claims data between 2007 and 2014 from The Doctors Company, a medical malpractice insurer. Findings were coded using the Comprehensive Risk Intelligence Tool developed by CRICO Strategies. We compared coded data from ASC claims with hospital operating room (HOR) claims, in terms of injury severity category, nature of injury, nature of allegation, contributing factors identified, and contributing comorbidities and claim value. RESULTS: Ambulatory surgery center claims were more likely to be classified as medium severity than HOR claims, more likely to involve dental damage or pain than HOR claims, but less likely to involve death or respiratory or cardiac arrest. Technical performance was the most common contributing factor: 47% of ASCs and 48% of HORs. Only 7% of allegations relating to technical performance were judged to be a direct result of poor technical performance. The most common anesthesia procedures resulting in ASC claims were injection of anesthesia into a peripheral nerve (34%) and intubation (29%). Obesity was the most common contributing comorbidity in both settings. Mean closed claim value was significantly lower for ASC than HOR claims, averaging US $87,888 versus $107,325. CONCLUSIONS: Analysis of ASC and HOR claims demonstrates significant differences and several common sources of liability. These include improving strategies for thorough screening, preoperative assessment and risk stratifying of patients, incorporating routine dental and airway assessment and documentation, diagnosing and treating perioperative pain adequately, and improving the efficacy of communication between patients and care providers.

Essential Elements of Multimodal Analgesia in Enhanced Recovery After Surgery (ERAS) Guidelines.

Perioperative multimodal analgesia uses combinations of analgesic medications that act on different sites and pathways in an additive or synergistic manner to achieve pain relief with minimal or no opiate consumption. Although all medications have side effects, opiates have particularly concerning, multisystemic, long-term, and short-term side effects, which increase morbidity and prolong admissions. Enhanced recovery is a systematic process addressing each aspect affecting recovery. This article outlines the evidence base forming the current multimodal analgesia recommendations made by the Enhanced Recovery After Surgery Society (ERAS). We describe current evidence and important future directions for effective perioperative multimodal analgesia in enhanced recovery pathways.

Comparison of Postoperative Outcomes in Elderly Patients With a Do-Not-Resuscitate Order Undergoing Elective and Nonelective Hip Surgery.

PURPOSE: Emergency hip surgery generally has worse outcomes than elective hip surgery, even when adjusted for patient and surgical factors. Do-not-resuscitate (DNR) status patients are typically at higher perioperative risk and undergo a narrow range of surgical procedures. We aimed to compare the outcomes after hip surgery of differing degrees of urgency in this cohort. MATERIALS AND METHODS: Using National Surgical Quality Improvement Program (NSQIP) data, we conducted univariate and multivariate analyses comparing outcomes of DNR status patients after emergency and nonemergency hip surgery (2007-2013). We conducted a subanalysis of mortality in elective versus nonelective cases (elective variable introduced from 2011). RESULTS: Of 668 hip surgery cases in DNR status patients, 210 (31.4%) were emergency and 458 (68.8%) were nonemergency. There were no significant associations between emergency and nonemergency surgery regarding patient demographics, comorbidities, functional capacity, anesthesia type, or operative duration. There was no significant difference in the 30-day postoperative mortality between emergency (21.4%) and nonemergency (16.4%) or between elective (19.6%) and nonelective (18.3%) hip fracture surgeries performed in patients with preexisting DNR status. Morbidity patterns in emergency vs nonemergency cases demonstrated no significant differences, with the commonest 3 complications being transfusion (21.0% and 21.4%, respectively), urinary tract infection (9.5% and 7.9%, respectively), and pneumonia (both at 5.2%). The 30-day home discharge rates were low at 4.7% and 5.6%, respectively. Multivariate analysis demonstrated no significant associations between emergency and nonemergency surgery for mortality, discharge destination, length of stay or complications, except perioperative myocardial infarction (3.7% vs 1.3%, P < .04). CONCLUSION: For patients with DNR status, both emergent and non-emergent hip surgery carries high mortality, greatly exceeding rates predicted for that patient by American College of Surgeons NSQIP risk calculators. Morbidity rates and patterns for patients with DNR status are also similar in emergency and nonemergency groups. These data may be useful in discussing risk and obtaining adequately informed consent in DNR patients undergoing hip surgery.

SCAMPs for Multimodal Post-Operative Analgesia: A Concept to Standardize and Individualize Care.

PURPOSE OF REVIEW: We discuss the challenges and strategies in delivering post-operative pain relief that is both standardized and individualized as appropriate. Post-operative pain remains under-treated and is frequently complicated by side effects. Guidelines for multimodal analgesia report varying strengths of evidence. Additionally, there are particular evidence gaps in establishing how individual and population subgroups responses vary, due to pharmacogenetic, metabolic, and psychological variation. RECENT FINDINGS: In cases where evidence is scarce or low quality, Standardized Clinical Assessment and Management Plans (SCAMPs) are an innovative method for healthcare practitioners to integrate available evidence resources and avoid unplanned variations in the quality of care delivered. Implementation of SCAMPs can be facilitated by the sheer volume of relevant information for drug prescribing and monitoring, drug-drug interactions, laboratory tests of organ function, drug metabolism and excretion data, electronic medical record data, and individual pharmacogenetic profile data. Standardization of care using algorithms or computer-assisted prescribing is emerging as a useful tool to raise compliance where guidance does exist. Individualizing care may require computational analysis of vast quantities of individual and population data to support or lead clinician decision-making. Such technology is used widely across diverse fields ranging from meteorology and commerce to agriculture and gene sequencing, but there are particular applications and challenges within medicine. To maximize benefit and reduce harm from post-operative analgesia, standardization and individualization, such as SCAMPs must be balanced and employed as appropriate.

Do-Not-Resuscitate status as an independent risk factor for patients undergoing surgery for hip fracture.

AIM: To determine morbidity and mortality in hip fracture patients and also to assess for any independent associations between Do-Not-Resuscitate (DNR) status and increased post-operative morbidity and mortality in patients undergoing surgical repair of hip fractures. METHODS: We conducted a propensity score matched retrospective analysis using de-identified data from the American College of Surgeons' National Surgical Quality Improvement Project (ACS NSQIP) for all patients undergoing hip fracture surgery over a 7 year period in hospitals across the United States enrolled in the ACS NSQIP with and without DNR status. We measured patient demographics including DNR status, co-morbidities, frailty and functional baseline, surgical and anaesthetic procedure data, post-operative morbidity/complications, length of stay, discharge destination and mortality. RESULTS: Of 9218 patients meeting the inclusion criteria, 13.6% had a DNR status, 86.4% did not. Mortality was higher in the DNR compared to the non-DNR group, at 15.3% vs 8.1% and propensity score matched multivariable analysis demonstrated that DNR status was independently associated with mortality (OR = 2.04, 95%CI: 1.46-2.86, P < 0.001). Additionally, analysis of the propensity score matched cohort demonstrated that DNR status was associated with a significant, but very small increased likelihood of post-operative complications (0.53 vs 0.43 complications per episode; OR = 1.21; 95%CI: 1.04-1.41, P = 0.004). Cardiopulmonary resuscitation and unplanned reintubation were significantly less likely in patients with DNR status. CONCLUSION: While DNR status patients had higher rates of post-operative complications and mortality, DNR status itself was not otherwise associated with increased morbidity. DNR status appears to increase 30-d mortality via ceilings of care in keeping with a DNR status, including withholding reintubation and cardiopulmonary resuscitation.

Patterns of intra-arterial blood pressure monitoring for patients undergoing total shoulder arthroplasty under general anesthesia: a retrospective analysis of 23,073 patients.

Total shoulder arthroplasty (TSA) is typically performed in the beach-chair position. Maintenance of adequate mean arterial pressure is required to provide appropriate cerebral perfusion pressure and prevent cerebral ischemia. Placement of an arterial line to facilitate invasive monitoring is discretionary, based on clinical judgment. We aimed to describe patient, surgical and institutional factors associated with the current use of blood pressure monitoring via an arterial line for TSA. We used de-identified patient data from the National Anesthesia Clinical Outcomes Registry between 2010 and 2015 to identify patients undergoing TSA under general anesthesia. We conducted a multivariable logistic regression model to demonstrate factors significantly associated with arterial line placement. We report results as odds ratios (OR) with their associated 95 % confidence intervals (CI). Of 23,073 patients undergoing TSA under general anesthesia, 443 (1.92 %) had intra-arterial blood pressure monitoring. Patient age over 65 years old (OR 1.74, CI 1.37-2.21), congestive heart failure (OR 7.09, CI 2.63-19.14) and surgery lasting at least 180 min (OR 4.10, CI 3.33-5.05) were all associated with increased odds for arterial line placement. Compared to university hospitals, arterial line placement was more likely in attached or freestanding surgical centers (OR 2.01, CI 1.37-2.96) and less likely in medium sized community hospitals (OR 0.62, CI 0.42-0.93), small community hospitals (OR 0.11, CI 0.03-0.34) and facilities performing less than 100 TSAs per year (OR 0.19, CI 0.12-0.31). Utilization of arterial line monitoring for TSA has associations with both institutional and patient factors. This study demonstrates the national patterns for the use of arterial lines for TSA and may serve as a resource to aid in clinical judgment.

Unplanned Reintubation Following Cardiac Surgery: Incidence, Timing, Risk Factors, and Outcomes.

OBJECTIVES: To determine the incidence, timing, risk factors for, and outcomes after unplanned reintubation following cardiac surgery in adults. DESIGN: Retrospective analysis of admission data from the American College of Surgeons National Surgical Quality Improvement Project Database, 2007-2013, inclusive. Univariate and multivariate analyses of risk factors and outcomes. PARTICIPANTS: A total of 18,571 patients, over 18 years of age, undergoing cardiac surgery. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Reintubation incidence was 4.0%. Risk factors included older age, preoperative partial or total dependence, dyspnea at rest or on exertion, chronic kidney disease, chronic obstructive pulmonary disease, previous cardiac surgery, congestive heart failure, emergency surgery, longer duration of surgery, and mitral and tricuspid valve surgery. Patients requiring reintubation after surgery had 7.5 times higher mortality (21.9% v 2.9%), longer hospital admissions (22.2 v 7.8 days), and were less likely to be discharged home within 30 days (35% v 80%). Multivariate analysis demonstrated increased risk of failure to wean from the ventilator, pneumonia, sepsis, pulmonary embolism, deep vein thrombosis, and discharge to skilled care, rehabilitation, or other care. CONCLUSIONS: Patients reintubated after cardiac surgery had significantly higher mortality, complication rates, and length of stay. Novel risk factors identified could be used to tailor extubation timing and strategy appropriately. Compared to noncardiac surgery, some risk factors for reintubation differed and risk continued beyond the immediate postoperative period to a greater degree.