Factors associated with mortality in patients with COVID-19 admitted to intensive care: a systematic review and meta-analysis.

Identification of high-risk patients admitted to intensive care with COVID-19 may inform management strategies. The objective of this meta-analysis was to determine factors associated with mortality among adults with COVID-19 admitted to intensive care by searching databases for studies published between 1 January 2020 and 6 December 2020. Observational studies of COVID-19 adults admitted to critical care were included. Studies of mixed cohorts and intensive care cohorts restricted to a specific patient sub-group were excluded. Dichotomous variables were reported with pooled OR and 95%CI, and continuous variables with pooled standardised mean difference (SMD) and 95%CI. Fifty-eight studies (44,305 patients) were included in the review. Increasing age (SMD 0.65, 95%CI 0.53-0.77); smoking (OR 1.40, 95%CI 1.03-1.90); hypertension (OR 1.54, 95%CI 1.29-1.85); diabetes (OR 1.41, 95%CI 1.22-1.63); cardiovascular disease (OR 1.91, 95%CI 1.52-2.38); respiratory disease (OR 1.75, 95%CI 1.33-2.31); renal disease (OR 2.39, 95%CI 1.68-3.40); and malignancy (OR 1.81, 95%CI 1.30-2.52) were associated with mortality. A higher sequential organ failure assessment score (SMD 0.86, 95%CI 0.63-1.10) and acute physiology and chronic health evaluation-2 score (SMD 0.89, 95%CI 0.65-1.13); a lower PaO2 :FI O2 (SMD -0.44, 95%CI -0.62 to -0.26) and the need for mechanical ventilation at admission (OR 2.53, 95%CI 1.90-3.37) were associated with mortality. Higher white cell counts (SMD 0.37, 95%CI 0.22-0.51); neutrophils (SMD 0.42, 95%CI 0.19-0.64); D-dimers (SMD 0.56, 95%CI 0.43-0.69); ferritin (SMD 0.32, 95%CI 0.19-0.45); lower platelet (SMD -0.22, 95%CI -0.35 to -0.10); and lymphocyte counts (SMD -0.37, 95%CI -0.54 to -0.19) were all associated with mortality. In conclusion, increasing age, pre-existing comorbidities, severity of illness based on validated scoring systems, and the host response to the disease were associated with mortality; while male sex and increasing BMI were not. These factors have prognostic relevance for patients admitted to intensive care with COVID-19.

Priorities for peri-operative research in Africa.

Deaths following surgery are the third largest contributor to deaths globally, and in Africa are twice the global average. There is a need for a peri-operative research agenda to ensure co-ordinated, collaborative research efforts across Africa in order to decrease peri-operative mortality. The objective was to determine the top 10 research priorities for peri-operative research in Africa. A Delphi technique was used to establish consensus on the top research priorities. The top 10 research priorities identified were (1) Develop training standards for peri-operative healthcare providers (surgical, anaesthesia and nursing) in Africa; (2) Develop minimum provision of care standards for peri-operative healthcare providers (surgical, anaesthesia and nursing) in Africa; (3) Early identification and management of mothers at risk from peripartum haemorrhage in the peri-operative period; (4) The role of communication and teamwork between surgical, anaesthetic, nursing and other teams involved in peri-operative care; (5) A facility audit/African World Health Organization situational analysis tool audit to assess emergency and essential surgical care, which includes anaesthetic equipment available and level of training and knowledge of peri-operative healthcare providers (surgeons, anaesthetists and nurses); (6) Establishing evidence-based practice guidelines for peri-operative physicians in Africa; (7) Economic analysis of strategies to finance access to surgery in Africa; (8) Establishment of a minimum dataset surgical registry; (9) A quality improvement programme to improve implementation of the surgical safety checklist; and (10) Peri-operative outcomes associated with emergency surgery. These peri-operative research priorities provide the structure for an intermediate-term research agenda to improve peri-operative outcomes across Africa.

Towards high-quality peri-operative care: a global perspective.

Article 25 of the United Nations' Universal Declaration of Human Rights enshrines the right to health and well-being for every individual. However, universal access to high-quality healthcare remains the purview of a handful of wealthy nations. This is no more apparent than in peri-operative care, where an estimated five billion individuals lack access to safe, affordable and timely surgical care. Delivery of surgery and anaesthesia in low-resource environments presents unique challenges that, when unaddressed, result in limited access to low-quality care. Current peri-operative research and clinical guidance often fail to acknowledge these system-level deficits and therefore have limited applicability in low-resource settings. In this manuscript, the authors priority-set the need for equitable access to high-quality peri-operative care and analyse the system-level contributors to excess peri-operative mortality rates, a key marker of quality of care. To provide examples of how research and investment may close the equity gap, a modified Delphi method was adopted to curate and appraise interventions which may, with subsequent research and evaluation, begin to address the barriers to high-quality peri-operative care in low- and middle-income countries.

Risks to healthcare workers following tracheal intubation of patients with COVID-19: a prospective international multicentre cohort study.

Healthcare workers involved in aerosol-generating procedures, such as tracheal intubation, may be at elevated risk of acquiring COVID-19. However, the magnitude of this risk is unknown. We conducted a prospective international multicentre cohort study recruiting healthcare workers participating in tracheal intubation of patients with suspected or confirmed COVID-19. Information on tracheal intubation episodes, personal protective equipment use and subsequent provider health status was collected via self-reporting. The primary endpoint was the incidence of laboratory-confirmed COVID-19 diagnosis or new symptoms requiring self-isolation or hospitalisation after a tracheal intubation episode. Cox regression analysis examined associations between the primary endpoint and healthcare worker characteristics, procedure-related factors and personal protective equipment use. Between 23 March and 2 June 2020, 1718 healthcare workers from 503 hospitals in 17 countries reported 5148 tracheal intubation episodes. The overall incidence of the primary endpoint was 10.7% over a median (IQR [range]) follow-up of 32 (18-48 [0-116]) days. The cumulative incidence within 7, 14 and 21 days of the first tracheal intubation episode was 3.6%, 6.1% and 8.5%, respectively. The risk of the primary endpoint varied by country and was higher in women, but was not associated with other factors. Around 1 in 10 healthcare workers involved in tracheal intubation of patients with suspected or confirmed COVID-19 subsequently reported a COVID-19 outcome. This has human resource implications for institutional capacity to deliver essential healthcare services, and wider societal implications for COVID-19 transmission.

The developing world of pre-operative optimisation: a systematic review of Cochrane reviews.

Pre-operative optimisation is a heterogenous group of interventions aimed at improving peri-operative outcomes. To understand the evidence for pre-operative optimisation in the developing world, we systematically reviewed Cochrane reviews on the topic according to the Human Developmental Index (HDI) of the country where patient recruitment occurred. We used summary statistics and cartograms to describe the HDI, year of publication, timing of pre-operative intervention and risk of bias associated with each included trial. We assessed the impact of multinational trials on the risk of bias introduced by countries of differing HDI. Four-hundred and nine trials representing 51 countries and 89,389 randomly allocated participants were summarised in this review. Four-hundred and nineteen out of 451 (93%) trial populations (i.e. a group of study participants from one country) were from high and very high HDI countries. The median (IQR [range]) HDI of countries were 0.862 (0.806-0.892 [0.445-0.949]). Three of the 409 included trials were multinational, representing 32 countries and 37,736 out of 89,389 (42.2%) included participants. Africa was the least represented continent, with only 4 included trials and 566 participants, of which 62.3% were from one multinational trial. The overall risk of bias was high or unclear in 381 out of 409 (93%) trials. Inclusion of multinational trials decreased the proportion of trial populations introducing high or unclear risk of bias by 9.4% (95%CI 5.1-13.7; p < 0.0001). Half of the world's population live in low- and middle-HDI countries. This population is poorly represented in systematically reviewed evidence on pre-operative optimisation. Multinational trials increase the knowledge contribution from low- and middle-HDI countries and decrease risk of bias in systematic reviews.

Effect of aspirin in vascular surgery in patients from a randomized clinical trial (POISE-2).

BACKGROUND: In the POISE-2 (PeriOperative ISchemic Evaluation 2) trial, perioperative aspirin did not reduce cardiovascular events, but increased major bleeding. There remains uncertainty regarding the effect of perioperative aspirin in patients undergoing vascular surgery. The aim of this substudy was to determine whether there is a subgroup effect of initiating or continuing aspirin in patients undergoing vascular surgery. METHODS: POISE-2 was a blinded, randomized trial of patients having non-cardiac surgery. Patients were assigned to perioperative aspirin or placebo. The primary outcome was a composite of death or myocardial infarction at 30 days. Secondary outcomes included: vascular occlusive complications (a composite of amputation and peripheral arterial thrombosis) and major or life-threatening bleeding. RESULTS: Of 10 010 patients in POISE-2, 603 underwent vascular surgery, 319 in the continuation and 284 in the initiation stratum. Some 272 patients had vascular surgery for occlusive disease and 265 had aneurysm surgery. The primary outcome occurred in 13·7 per cent of patients having aneurysm repair allocated to aspirin and 9·0 per cent who had placebo (hazard ratio (HR) 1·48, 95 per cent c.i. 0·71 to 3·09). Among patients who had surgery for occlusive vascular disease, 15·8 per cent allocated to aspirin and 13·6 per cent on placebo had the primary outcome (HR 1·16, 0·62 to 2·17). There was no interaction with the primary outcome for type of surgery (P = 0·294) or aspirin stratum (P = 0·623). There was no interaction for vascular occlusive complications (P = 0·413) or bleeding (P = 0·900) for vascular compared with non-vascular surgery. CONCLUSION: This study suggests that the overall POISE-2 results apply to vascular surgery. Perioperative withdrawal of chronic aspirin therapy did not increase cardiovascular or vascular occlusive complications. Registration number: NCT01082874 ( http://www.clinicaltrials.gov).

Barriers to clinical research in Africa: a quantitative and qualitative survey of clinical researchers in 27 African countries.

BACKGROUND: There is a need for high quality research to improve perioperative patient care in Africa. The aim of this study was to understand the particular barriers to clinical research in this environment. METHODS: We conducted an electronic survey of African Surgical Outcomes Study (ASOS) investigators, including 29 quantitative Likert scale questions and eight qualitative questions with subsequent thematic analysis. Protocol compliant and non-compliant countries were compared according to WHO statistics for research and development, health workforce data, and world internet statistics. RESULTS: Responses were received from 134/418 of invited researchers in 24/25 (96%) of participating countries, and three non-participating countries. Barriers included lack of a dedicated research team (47.7%), reliable internet access (32.6%), staff skilled in research (31.8%), and team commitment (23.8%). Protocol compliant countries had significantly more physicians per 1000 population (4 vs 0.9, P<0.01), internet penetration (38% vs 28%, P=0.01) and published clinical trials (1461 vs 208, P<0.01) compared with non-compliant countries. Facilitators of research included establishing a research culture (86.9%), simple data collection tools (80%), and ASOS team interaction (77.9%). Most participants are interested in future research (93.8%). Qualitative data reiterated human resource, financial resource, and regulatory barriers. However, the desire to contribute to an African collaboration producing relevant data to improve patient outcomes was expressed strongly by ASOS investigators. CONCLUSIONS: Barriers to successful participation in ASOS related to resource limitations and not motivation of the clinician investigators. Practical solutions to individual barriers may increase the success of multi-centre perioperative research in Africa.

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis.

BACKGROUND: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. METHODS: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. RESULTS: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32-0.77); P<0.01], but no difference in complication rates [OR 1.02 (0.88-1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62-0.92); P<0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61-0.88); P<0.01; I2=89%). CONCLUSIONS: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine.

The ASOS Surgical Risk Calculator: development and validation of a tool for identifying African surgical patients at risk of severe postoperative complications.

BACKGROUND: The African Surgical Outcomes Study (ASOS) showed that surgical patients in Africa have a mortality twice the global average. Existing risk assessment tools are not valid for use in this population because the pattern of risk for poor outcomes differs from high-income countries. The objective of this study was to derive and validate a simple, preoperative risk stratification tool to identify African surgical patients at risk for in-hospital postoperative mortality and severe complications. METHODS: ASOS was a 7-day prospective cohort study of adult patients undergoing surgery in Africa. The ASOS Surgical Risk Calculator was constructed with a multivariable logistic regression model for the outcome of in-hospital mortality and severe postoperative complications. The following preoperative risk factors were entered into the model; age, sex, smoking status, ASA physical status, preoperative chronic comorbid conditions, indication for surgery, urgency, severity, and type of surgery. RESULTS: The model was derived from 8799 patients from 168 African hospitals. The composite outcome of severe postoperative complications and death occurred in 423/8799 (4.8%) patients. The ASOS Surgical Risk Calculator includes the following risk factors: age, ASA physical status, indication for surgery, urgency, severity, and type of surgery. The model showed good discrimination with an area under the receiver operating characteristic curve of 0.805 and good calibration with c-statistic corrected for optimism of 0.784. CONCLUSIONS: This simple preoperative risk calculator could be used to identify high-risk surgical patients in African hospitals and facilitate increased postoperative surveillance. CLINICAL TRIAL REGISTRATION: NCT03044899.

The relationship between pre-operative hypertension and intra-operative haemodynamic changes known to be associated with postoperative morbidity.

Hypertension is not consistently associated with postoperative cardiovascular morbidity and is therefore not considered a major peri-operative risk factor. However, hypertension may predispose to peri-operative haemodynamic changes known to be associated with peri-operative morbidity and mortality, such as intra-operative hypotension and tachycardia. The objective of this study was to determine whether pre-operative hypertension was independently associated with haemodynamic changes known to be associated with adverse peri-operative outcomes. We performed a five-day multicentre, prospective, observational cohort study which included all adult inpatients undergoing elective, non-cardiac, non-obstetric surgery. We recruited 343 patients of whom 164 (47.8%) were hypertensive. An intra-operative mean arterial pressure of < 55 mmHg occurred in 59 (18.2%) patients, of which 25 (42.4%) were hypertensive. Intra-operative tachycardia (heart rate> 100 beats.min-1 ) occurred in 126 (38.9%) patients, of whom 61 (48.4%) were hypertensive. Multivariable logistic regression did not show an independent association between the stage of hypertension and either clinically significant hypotension or tachycardia, when controlled for ASA physical status, functional status, major surgery, duration of surgery or blood transfusion. There was no association between pre-operative hypertension and peri-operative haemodynamic changes known to be associated with major morbidity and mortality. These data, therefore, support the recommendation of the Joint Guidelines of the Association of Anaesthetists of Great Britain and Ireland (AAGBI) and the British Hypertension Society to proceed with elective surgery if a patient's blood pressure is < 180/110 mmHg.

Optimising perioperative care for hip and knee arthroplasty in South Africa: a Delphi consensus study.

BACKGROUND: A structured approach to perioperative patient management based on an enhanced recovery pathway protocol facilitates early recovery and reduces morbidity in high income countries. However, in low- and middle-income countries (LMICs), the feasibility of implementing enhanced recovery pathways and its influence on patient outcomes is scarcely investigated. To inform similar practice in LMICs for total hip and knee arthroplasty, it is necessary to identify potential factors for inclusion in such a programme, appropriate for LMICs. METHODS: Applying a Delphi method, 33 stakeholders (13 arthroplasty surgeons, 12 anaesthetists and 8 physiotherapists) from 10 state hospitals representing 4 South African provinces identified and prioritised i) risk factors associated with poor outcomes, ii) perioperative interventions to improve outcomes and iii) patient and clinical outcomes necessary to benchmark practice for patients scheduled for primary elective unilateral total hip and knee arthroplasty. RESULTS: Thirty of the thirty-three stakeholders completed the 3 months Delphi study. The first round yielded i) 36 suggestions to preoperative risk factors, ii) 14 (preoperative), 18 (intraoperative) and 23 (postoperative) suggestions to best practices for perioperative interventions to improve outcomes and iii) 25 suggestions to important postsurgical outcomes. These items were prioritised by the group in the consecutive rounds and consensus was reached for the top ten priorities for each category. CONCLUSION: The consensus derived risk factors, perioperative interventions and important outcomes will inform the development of a structured, perioperative multidisciplinary enhanced patient care protocol for total hip and knee arthroplasty. It is anticipated that this study will provide the construct necessary for developing pragmatic enhanced care pathways aimed at improving patient outcomes after arthroplasty in LMICs.

HIV, vascular surgery and cardiovascular outcomes: a South African cohort study.

Risk factors for peri-operative cardiac morbidity are poorly described in HIV-positive patients. This prospective observational study describes cardiovascular risk factors in a cohort of vascular surgical patients of known HIV status. We recruited 225 patients with 73 (32%) being HIV-positive. When compared with HIV-negative patients, the HIV-positive patients were younger (mean (SD) 56.4 (13.3) vs 40.5 (10.4) years, respectively, p < 0.01). They had fewer Revised Cardiac Risk Index cardiovascular risk factors (median (range [IQR]) 1 (0-5 [0-2]) vs 0 (0-2 [0-0]), respectively, p < 0.001), with the exception of congestive cardiac failure (p = 0.23) and renal dysfunction (p = 0.32), and so were of a significantly lower Revised Cardiac Risk Index risk category (p < 0.01). HIV-positive and -negative patients had similar outcomes in: 30-day mortality (p = 0.78); three-day postoperative troponin leak (p = 0.66); and a composite outcome of mortality and troponin release (p = 0.69). We conclude that although HIV-positive patients have fewer cardiovascular risk factors, they have similar peri-operative major adverse cardiac events to HIV-negative patients. Research should focus on why this is the case, and if alternative clinical risk predictors can be developed for HIV patients.

Cardiac biomarkers in the prediction of risk in the non-cardiac surgery setting.

B-Type natriuretic peptides and troponin measurements have potential in predicting risk in patients undergoing non-cardiac surgery. Using the American Heart Association framework for the evaluation of novel biomarkers, we review the current evidence supporting the peri-operative use of these two biomarkers. In patients having major non-cardiac surgery who are risk stratified using clinical risk scores, the measurement of natriuretic peptides and troponin, both before and after surgery, significantly improves risk stratification. However, only pre- and postoperative natriuretic peptide measurement and postoperative troponin measurement have shown clinical utility. It is now important for trials to be conducted to determine whether integrating pre- and postoperative natriuretic peptide and postoperative troponin measurement into clinical practice is able to improve clinical outcomes in patients undergoing non-cardiac surgery.

The efficacy of peri-operative interventions to decrease postoperative delirium in non-cardiac surgery: a systematic review and meta-analysis.

The purpose of this meta-analysis was to determine the efficacy of peri-operative interventions in decreasing the incidence of postoperative delirium. An electronic search of four databases was conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adhered to. We included randomised controlled trials of non-cardiac surgery with a peri-operative intervention and that reported postoperative delirium, and identified 29 trials. Meta-analysis revealed that peri-operative geriatric consultation (OR 0.46, 95% CI 0.32-0.67) and lighter anaesthesia (OR 2.66, 95% CI 1.27-5.56) were associated with a decreased incidence of postoperative delirium. For the other interventions, the point estimate suggested possible protection with prophylactic haloperidol (OR 0.62, 95% CI 0.36-1.05), bright light therapy (OR 0.20, 95% CI 0.03-1.19) and general as opposed to regional anaesthesia (OR 0.76, 95% CI 0.47-1.23). This meta-analysis has shown that peri-operative geriatric consultations with multicomponent interventions and lighter anaesthesia are potentially effective in decreasing the incidence of postoperative delirium.

What is the best pre-operative risk stratification tool for major adverse cardiac events following elective vascular surgery? A prospective observational cohort study evaluating pre-operative myocardial ischaemia monitoring and biomarker analysis.

Although brain natriuretic peptide has been shown to be superior to the revised cardiac risk index for risk stratification of vascular surgical patients, it remains unknown whether it is superior to alternative dynamic risk predictors, such as other pre-operative biomarkers (C-reactive protein and troponins) or myocardial ischaemia monitoring. The aim of this prospective observational study was to determine the relative clinical utility of these risk predictors for the prediction of postoperative cardiac events in elective vascular surgical patients. Only pre-operative troponin elevation (OR 56.8, 95% CI 6.5-496.0, p < 0.001) and brain natriuretic peptide above the optimal discriminatory point (OR 6.0, 95% CI 2.7-12.9, p < 0.001) were independently associated with cardiac events. Both brain natriuretic peptide and troponin risk stratification significantly improved overall net reclassification (74.6% (95% CI 51.6%-97.5%) and 38.5% (95% CI 22.4-54.6%, respectively)); however, troponin stratification decreased the correct classification of patients with cardiac complications (-59%, p < 0.001). Pre-operative brain natriuretic peptide evaluation was the only clinically useful predictor of postoperative cardiac complications.

The influence of clinical risk factors on pre-operative B-type natriuretic peptide risk stratification of vascular surgical patients.

The role of the revised cardiac risk index in risk stratification has recently been challenged by studies reporting on the superior predictive ability of pre-operative B-type natriuretic peptides. We found that in 850 vascular surgical patients initially risk stratified using B-type natriuretic peptides, reclassification with the number of revised cardiac risk index risk factors worsened risk stratification (p < 0.05 for > 0, > 2, > 3 and > 4 risk factors, and p = 0.23 for > 1 risk factor). When evaluated with pre-operative B-type natriuretic peptides, none of the revised cardiac risk index risk factors were independent predictors of major adverse cardiac events in vascular patients. The only independent predictor was B-type natriuretic peptide stratification (OR 5.1, 95% CI 1.8-15 for the intermediate class, and OR 25, 95% CI 8.7-70 for the high-risk class). The clinical risk factors in the revised cardiac risk index cannot improve a risk stratification model based on B-type natriuretic peptides.