Reduced Mortality among COVID-19 ICU Patients after Treatment with HemoClear Convalescent Plasma in Suriname.

Convalescent plasma is a promising therapy for coronavirus disease 2019 (COVID-19), but its efficacy in intensive care unit (ICU) patients in low- and middle-income country settings such as Suriname is unknown. Bedside plasma separation using the HemoClear device made convalescent plasma therapy accessible as a treatment option in Suriname. Two hundred patients with severe SARS-CoV-2 infection requiring intensive care were recruited. Fifty eight patients (29%) received COVID-19 convalescent plasma (CCP) treatment in addition to standard of care (SOC). The CCP treatment and SOC groups were matched by age, sex, and disease severity scores. Mortality in the CCP treatment group was significantly lower than that in the SOC group (21% versus 39%; Fisher's exact test P = 0.0133). Multivariate analysis using ICU days showed that CCP treatment reduced mortality (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.18 to 0.66; P = 0.001), while complication of acute renal failure (creatinine levels, >110 mol/L; HR, 4.45; 95% CI, 2.54 to 7.80; P < 0.0001) was independently associated with death. Decrease in chest X-ray score in the CCP treatment group (median -3 points, interquartile range [IQR] -4 to -1) was significantly greater than that in the SOC group (median -1 point, IQR -3 to 1, Mann-Whitney test P = 0.0004). Improvement in the PaO2/FiO2 ratio was also significantly greater in the CCP treatment group (median 83, IQR 8 to 140) than in the SOC group (median 35, IQR -3 to 92, Mann-Whitney P = 0.0234). Further research is needed for HemoClear-produced CCP as a therapy for SARS-CoV-2 infection together with adequately powered, randomized controlled trials. IMPORTANCE This study compares mortality and other endpoints between intensive care unit COVID-19 patients treated with convalescent plasma plus standard of care (CCP), and a control group of patients hospitalized in the same medical ICU facility treated with standard of care alone (SOC) in a low- and middle-income country (LMIC) setting using bedside donor whole blood separation by gravity (HemoClear) to produce the CCP. It demonstrates a significant 65% survival improvement in HemoClear-produced CCP recipients (HR, 0.35; 95% CI, 0.19 to 0.66; P = 0.001). Although this is an exploratory study, it clearly shows the benefit of using the HemoClear-produced CCP in ICU patients in the Suriname LMIC setting. Additional studies could further substantiate our findings and their applicability for both LMICs and high-income countries and the use of CCP as a prepared readiness method to combat new viral pandemics.

Long-term outcomes and cost effectiveness of high-dose dexamethasone for cardiac surgery: a randomised trial.

Prophylactic intra-operative administration of dexamethasone may improve short-term clinical outcomes in cardiac surgical patients. The purpose of this study was to evaluate long-term clinical outcomes and cost effectiveness of dexamethasone versus placebo. Patients included in the multicentre, randomised, double-blind, placebo-controlled DExamethasone for Cardiac Surgery (DECS) trial were followed up for 12 months after their cardiac surgical procedure. In the DECS trial, patients received a single intra-operative dose of dexamethasone 1 mg.kg-1 (n = 2239) or placebo (n = 2255). The effects on the incidence of major postoperative events were evaluated. Also, overall costs for the 12-month postoperative period, and cost effectiveness, were compared between groups. Of 4494 randomised patients, 4457 patients (99%) were followed up until 12 months after surgery. There was no difference in the incidence of major postoperative events, the relative risk (95%CI) being 0.86 (0.72-1.03); p = 0.1. Treatment with dexamethasone reduced costs per patient by £921 [€1084] (95%CI £-1672 to -137; p = 0.02), mainly through reduction of postoperative respiratory failure and duration of postoperative hospital stay. The probability of dexamethasone being cost effective compared with placebo was 97% at a threshold value of £17,000 [€20,000] per quality-adjusted life year. We conclude that intra-operative high-dose dexamethasone did not have an effect on major adverse events at 12 months after cardiac surgery, but was associated with a reduction in costs. Routine dexamethasone administration is expected to be cost effective at commonly accepted threshold levels for cost effectiveness.

Clinical recognition of acute aortic dissections: insights from a large single-centre cohort study.

AIMS: Acute aortic dissection (AD) requires immediate treatment, but is a diagnostic challenge. We studied how often AD was missed initially, which patients were more likely to be missed and how this influenced patient management and outcomes. METHODS: A retrospective cohort study including 200 consecutive patients with AD as the final diagnosis, admitted to a tertiary hospital between 1998 and 2008. The first differential diagnosis was identified and patients with and without AD included were compared. Characteristics associated with a lower level of suspicion were identified using multivariable logistic regression, and Cox regression was used for survival analyses. Missing data were imputed. RESULTS: Mean age was 63 years, 39% were female and 76% had Stanford type A dissection. In 69% of patients, AD was included in the first differential diagnosis; this was less likely in women (adjusted relative risk [aRR]: 0.66, 95% CI: 0.44-0.99), in the absence of back pain (aRR: 0.51, 95% CI: 0.30-0.84), and in patients with extracardiac atherosclerosis (aRR: 0.64, 95% CI: 0.43-0.96). Absence of AD in the differential diagnosis was associated with the use of more imaging tests (1.8 vs. 2.3, p = 0.01) and increased time from admission to surgery (1.8 vs. 10.1 h, p < 0.01), but not with a difference in the adjusted long-term all-cause mortality (hazard ratio: 0.76, 95% CI: 0.46-1.27). CONCLUSION: Acute aortic dissection was initially not suspected in almost one-third of patients, this was more likely in women, in the absence of back pain and in patients with extracardiac atherosclerosis. Although the number of imaging tests was higher and time to surgery longer, patient outcomes were similar in both groups.

Diagnostic accuracy of stroke volume variation measured with uncalibrated arterial waveform analysis for the prediction of fluid responsiveness in patients with impaired left ventricular function: a prospective, observational study.

Uncalibrated arterial waveform analysis enables dynamic preload assessment in a minimally invasive fashion. Evidence about the validity of the technique in patients with impaired left ventricular function is scarce, while adequate cardiac preload assessment would be of great value in these patients. The aim of this study was to investigate the diagnostic accuracy of stroke volume variation (SVV) measured with the FloTrac/Vigileo™ system in patients with impaired left ventricular function. In this prospective, observational study, 22 patients with a left ventricular ejection fraction of 40 % or less undergoing elective coronary artery bypass grafting were included. Patients were considered fluid responsive if cardiac output increased with 15 % or more after volume loading (7 ml kg(-1) ideal body weight). The following variables were calculated: area under the receiver operating characteristics (ROC) curve, ideal cut-off value for SVV, sensitivity, specificity, positive and negative predictive values, and overall accuracy. In addition, SVV cut-off points to obtain 90 % true positive and 90 % true negative predictions were determined. ROC analysis revealed an area under the curve of 0.70 [0.47; 0.92]. The ideal SVV cut-off value was 10 %, with a corresponding sensitivity and specificity of 56 and 69 % respectively. Overall accuracy was 64 %, positive and negative predictive values were 69 and 56 % respectively. SVV values to obtain more than 90 % true positive and negative predictions were 16 and 6 % respectively. The ability of uncalibrated arterial waveform analysis SVV to predict fluid responsiveness in patients with impaired LVF was low.

Patient selection for cardiac surgery: Time to consider subgroups within risk categories?

BACKGROUND: Medical guidelines increasingly use risk stratification and implicitly assume that individuals classified in the same risk category form a homogeneous group, while individuals with similar, or even identical, predicted risks can still be very different. We evaluate a strategy to identify homogeneous subgroups typically comprising predicted risk categories to allow further tailoring of treatment allocation and illustrate this strategy empirically for cardiac surgery patients with high postoperative mortality risk. METHODS: Using a dataset of cardiac surgery patients (n=6517) we applied cluster analysis to identify homogenous subgroups of patients comprising the high postoperative mortality risk group (EuroSCORE ≥ 15%). Cluster analyses were performed separately within younger (<75 years) and older (≥ 75 years) patients. Validity measures were calculated to evaluate quality and robustness of the identified subgroups. RESULTS: Within younger patients two distinct and robust subgroups were identified, differing mainly in preoperative state and indication of recent myocardial infarction or unstable angina. In older patients, two distinct and robust subgroups were identified as well, differing mainly in preoperative state, presence of chronic pulmonary disease, previous cardiac surgery, neurological dysfunction disease and pulmonary hypertension. CONCLUSIONS: We illustrated a feasible method to identify homogeneous subgroups of individuals typically comprising risk categories. This allows a single treatment strategy--optimal only on average, across all individuals in a risk category--to be replaced by subgroup-specific treatment strategies, bringing us another step closer to individualized care. Discussions on allocation of cardiac surgery patients to different interventions may benefit from focusing on such specific subgroups.

Diagnostic accuracy of modified transoesophageal echocardiography for pre-incision assessment of aortic atherosclerosis in cardiac surgery patients.

BACKGROUND: Epiaortic ultrasound scanning (EUS) is regarded as the reference standard for detecting atherosclerosis in the ascending aorta (AA). Combined with appropriate surgical modifications, EUS use can significantly reduce the incidence of postoperative stroke when detecting severe AA atherosclerosis. A recently introduced modification of conventional transoesophageal echocardiography (TOE), known as the A-View method, has proven capable of inspecting the distal AA. The objective of this study was to quantify the diagnostic accuracy of modified TOE in assessing atherosclerosis of the distal AA. METHODS: After approval by the institutional medical ethical committee and after obtaining written informed consent, 465 consecutive patients above 65 yr old, undergoing elective cardiac surgery with a median sternotomy, were included. The study followed a cross-sectional diagnostic design. All consecutive patients underwent modified TOE followed by EUS (reference standard) to assess the severity of distal AA atherosclerosis. We constructed contingency tables to compare the presence (and severity) of atherosclerosis, detected by the two techniques. RESULTS: The positive predictive value of modified TOE for the detection of clinically significant atherosclerosis was 67%, and the negative predictive value was 97%. The sensitivity was 95% and the specificity was 79%. One patient suffered a pulmonary haemorrhage, although he recovered without further sequelae. We did not observe any clinical significant haemodynamic or ventilatory effects. CONCLUSIONS: The high negative predictive value and sensitivity show that modified TOE yields adequate diagnostic accuracy for excluding clinically relevant aorta atherosclerosis without significant cardiopulmonary side-effects, provided that the A-View catheter is introduced carefully.

Meta-analysis of the diagnostic accuracy of transesophageal echocardiography for assessment of atherosclerosis in the ascending aorta in patients undergoing cardiac surgery.

BACKGROUND: Stroke after cardiac surgery may be caused by emboli emerging from an atherosclerotic ascending aorta (AA). Epiaortic ultrasound scanning (EUS), the current 'gold' standard for detecting AA atherosclerosis, has not gained widespread use because there is a lack of optimized ultrasound devices, it lengthens the procedure, it endangers sterility, and there is a false belief by many surgeons that palpation is as sensitive as EUS. Furthermore there is no clear evidence proving that the use of epiaortic scanning changes outcome in cardiac surgery. Various researchers investigated the ability of transesophageal echocardiography (TEE) to discriminate between the presence and absence of AA atherosclerosis. It is acknowledged that TEE has limited value in this, but it has never been supported by a meta-analysis estimating the true diagnostic accuracy of TEE based on all quantitative evidence. We aimed to do this using state-of-the-art methodology of diagnostic meta-analyses. METHODS: We searched multiple databases for studies comparing TEE vs. EUS for detection of atherosclerosis. A random-effects bivariate meta-regression model was used to obtain summary estimates of sensitivity and specificity, incorporating the correlation between sensitivity and specificity as well as covariates to explore heterogeneity across studies. RESULTS: We extracted six studies with a total of 346 patients, of whom 419 aortic segments were analyzed, including 100 segments with atherosclerosis [median prevalence 25% (range 17-62%)]. Summary estimates of sensitivity and specificity were 21% (95% CI 13-32%) and 99% (96-99%), respectively. CONCLUSIONS: Because of the low sensitivity of TEE for the detection of AA atherosclerosis, a negative test result requires verification by additional testing using epiaortic scanning. In case of a positive test result, AA atherosclerosis can be considered as present, and less manipulative strategies might be indicated.

Resolving the blind spot of transoesophageal echocardiography: a new diagnostic device for visualizing the ascending aorta in cardiac surgery.

BACKGROUND: Atherosclerosis of the ascending aorta (AA) and stroke after cardiac surgery are related. Knowledge of the location of AA-atherosclerosis pre-sternotomy allows changes in surgical strategy to avoid manipulation of the AA. The gold-standard for assessment of AA-atherosclerosis is intraoperative epiaortic ultrasound scanning (EUS). Transoesophageal echocardiography (TOE) is unable to detect atherosclerosis in the distal AA due to the 'blind spot'. A new method [A-View (Aortic-view) method] using a fluid-filled catheter may enhance the assessment of distal AA-atherosclerosis. The aim of this study was to evaluate whether the A-View method indeed visualizes the distal AA and to assess the safety of this technology. METHODS: In a cross-sectional diagnostic study, 41 patients undergoing cardiac surgery including sternotomy underwent the same work-up including TOE, the A-View method, EUS, and routine operative monitoring. RESULTS: With the A-View method, the distal AA was visible in all (100%) patients. There were no clinical important side-effects associated with the use of the A-View catheter; however, in one patient the endotracheal tube was accidentally dislocated leading to a decrease in Sa(O2). Severity of atherosclerosis visualized with the A-View method compared with EUS results showed good agreement between the two methods [Kappa of 0.69 (0.50-0.88)]. The Bland-Altman analysis showed poor agreement in plaque-size measurements (bias 0.05 cm2, limits of agreement - 0.63 to 0.74 cm2). CONCLUSIONS: The A-View method offers a minimally invasive and safe approach to preoperatively resolving the blind spot of TOE. Compared with EUS, the A-View method yielded satisfactory results in the detection of AA-atherosclerosis. The A-View method seems a promising tool for patients undergoing cardiac surgery to direct surgical management.

Early outcome after off-pump versus on-pump coronary bypass surgery: results from a randomized study.

BACKGROUND: The use of cardiopulmonary bypass during coronary artery bypass surgery (CABG) has been associated with substantial morbidity. The recent introduction of cardiac stabilizers facilitates CABG without cardiopulmonary bypass (off-pump CABG), but it is unknown whether cardiac outcome after off-pump surgery is similar to that for the on-pump procedure. METHODS AND RESULTS: In a multicenter trial, 281 patients (mean age 61 years, SD 9 years) were randomly assigned to off-pump or on-pump CABG. In-hospital results and cardiac outcome and quality of life after 1 month are presented. Cardiac outcome was defined as survival free of stroke, myocardial infarction, and coronary reintervention. The mean numbers of distal anastomoses per patient were 2.4 (SD 1.0) and 2.6 (SD 1.1) in the off-pump and on-pump groups, respectively. Completeness of revascularization was similar in both groups. Blood products were needed during 3% of the off-pump procedures and 13% of the on-pump procedures (P<0.01). Release of creatine kinase muscle-brain isoenzyme was 41% less in the off-pump group (P<0.01). Otherwise, no differences in complications were found postoperatively. Off-pump patients were discharged 1 day earlier. At 1 month, operative mortality was zero in both groups, and quality of life had improved similarly. In both groups, 4% of the patients had recurrent angina. The proportions of patients surviving free of cardiovascular events were 93.0% in the off-pump group and 94.2% in the on-pump group (P=0.66). CONCLUSIONS: In selected patients, off-pump CABG is safe and yields a short-term cardiac outcome comparable to that of on-pump CABG.

Heart displacement during off-pump CABG: how well is it tolerated?

BACKGROUND: Heart displacement during off-pump coronary artery bypass grafting (CABG) is necessary to expose the anastomosic sites. We analyzed the hemodynamic changes in relation to the grafted arteries. METHODS: The relationship between surgical exposure and hemodynamic management was assessed in 150 consecutive patients undergoing off-pump CABG utilizing the Octopus Tissue Stabilization System (Medtronic, Minneapolis, MN). RESULTS: Surgical exposure by anterolateral thoracotomy showed no significant hemodynamic changes. Through sternotomy, stroke volume was significantly reduced by dislocation at all target sites: by 6% at the left anterior descending artery (LAD), 25% at the diagonal branch artery (D), 14% at the right coronary artery (RCA), and 21% at the obtuse marginal artery (OM). The application of head-down positioning (LAD, 56%; D, 74%; RCA, 90%; OM, 96%) increased not only surgical exposure but also preload, producing correction of ventricular filling pressures and output. In a minority of cases, dopamine (3 to 5 microg x kg(-1) x min(-1)) was added to maintain baseline hemodynamic values (LAD, 5%; D, 15%; RCA, 7%; OM, 28%). CONCLUSIONS: Revascularization during anterolateral thoracotomy was uneventful. The sternotomy approach with heart displacement induced right heart compression. Mainly fluid redistribution was sufficient to correct cardiac output. Once stabilized, systemic circulation remained unchanged during revascularization.

The Octopus Study: rationale and design of two randomized trials on medical effectiveness, safety, and cost-effectiveness of bypass surgery on the beating heart.

The Octopus Study consists of two multicenter randomized clinical trials in which coronary artery bypass grafting on the beating heart (off-pump CABG) using the Utrecht Octopus Method is compared to intracoronary stent implantation and conventional CABG. The primary endpoint in the comparison of off-pump CABG versus stent implantation (OctoStent Trial) is medical effectiveness (i.e., absence of reintervention and major adverse cardiac and cerebrovascular events at 1 year after treatment). The primary endpoint in the comparison of off-pump CABG versus conventional CABG (OctoPump Trial) is cerebral safety (i.e., absence of cognitive deficits and cerebrovascular events at 3 months after treatment). Secondary endpoints in both trials include presence and severity of angina, quality of life, exercise capacity, and cost-effectiveness. A total of 560 patients will be enrolled. A random sample of 210 patients will undergo repeat angiography at 1 year to assess angiographic restenosis rate and graft patency. Including 1-year follow-up, the study will last for 3 years. Control Clin Trials 2000;21:595-609

When and how to shunt the coronary circulation in off-pump coronary artery bypass grafting.

OBJECTIVE: To assess the sequelae of temporary coronary artery occlusion in off-pump, beating heart CABG, i.e. ischemia, hemodynamic instability and the need for conversion to cardiopulmonary bypass. METHODS: In 200 patients (150 male), mean age 60 (range 35-81) years, 365 distal anastomoses were performed, i.e. 1.8 anastomoses per patient through limited and full access. One hundred seventy six LAD, 61 diagonal, 71 RCA, 7 RPD and 50 circumflex branches were grafted. Patients were pretreated with calcium antagonists, long-acting beta-blockade and had thoracic epidural blockade. The anastomosis was constructed using two microvascular clamps, preceded by ischemic preconditioning in non-occlusive disease. Myocardial ischemia was defined as > 1 mm S-T segment elevation. A simple aorto-coronary shunt, consisting of two intravenous catheters and a 10 cm connecting tube (flow > 20 ml/min), was used in critical ischemia. RESULTS: Ischemia occurred during 35 (10%) temporary coronary artery occlusions. Fifteen of these (43%) were RCA. In five of these 15 patients, all with non-occlusive disease, critical ischemia occurred with bradycardia, third-degree heart block and subsequently severe hypotension, which normally requires conversion to cardio-pulmonary bypass. Following introduction of the shunt (4 patients) electrocardiographic and hemodynamic parameters normalized within 30 s. The off-pump procedures could be continued uneventfully. There were no peri-operative infarctions. CONCLUSION: Temporary segmental occlusion is an effective method for anastomosis suturing in off-pump, beating heart CABG. Critical ischemia was observed rarely, only in the RCA and in non-occlusive disease. Temporary aorto-coronary shunting could avoid conversion to cardiopulmonary bypass and myocardial infarction.

Embracing the heart: perioperative management of patients undergoing off-pump coronary artery bypass grafting using the octopus tissue stabilizer.

OBJECTIVE: To describe hemodynamic alterations during coronary artery bypass grafting (CABG) without extracorporeal circulation using the Octopus Tissue Stabilizer, and to describe the two anesthetic management protocols based on either general anesthesia with opioids (34 patients) or general anesthesia with high thoracic epidural anesthesia (TEA; 66 patients). DESIGN: A prospective observational report. SETTING: An academic university heart center. PARTICIPANTS: First 100 patients undergoing CABG using the Octopus Tissue Stabilizer. INTERVENTIONS: None. MAIN RESULTS: Current management provided satisfactory results in preventing hypoperfusion of the heart and inadequate systemic circulation without the use of major pharmacologic interventions. Movement of the heart to reach the target site of anastomosis caused hemodynamic alterations. These could easily be corrected by anesthetic interventions, such as fluid load and low doses of inotropes. High TEA allows earlier extubation compared with the opioid anesthesia technique (0.9 v 4.5 hours). Perioperative management and the incidence of postoperative complications did not differ between anesthetic techniques. Major complications, such as death, intraoperative myocardial infarction, and stroke, did not occur. CONCLUSION: Both anesthetic protocols are safe and effective in handling these patients. Off-pump CABG surgery requires anesthetic interventions because hemodynamic alterations are caused by the presentation of the heart to the surgeon. The complication rate is low but needs to be evaluated, compared with conventional CABG, in a prospective randomized study. High thoracic epidural anesthesia allows early recovery, but improved outcome could not be proved in this patient group.