Impact of serological and PCR testing requirements on the selection of COVID-19 convalescent plasma donors
BACKGROUND Convalescent plasma is undergoing randomized trials as a potential therapeutic option for COVID-19 infection. Little empirical evidence exists regarding the determination of donor eligibility and experiences with donor selection. STUDY DESIGN AND METHODS This prospective study was conducted at a tertiary care hospital in New York to select plasma donors for a randomized, double-blind, controlled convalescent plasma trial. Clearance for donation required successful completion of an online questionnaire and an in-person screening visit, which included (a) completion of a Donor Health Questionnaire (DHQ), (b) Immunoglobulin G (IgG) antibody testing using an immunochromatographic anti- severe acute respiratory coronavirus 2 (SARS-CoV-2) test, (c) Polymerase chain reaction (PCR) testing if <28 days from symptom resolution, and (d) routine blood bank testing. RESULTS After receiving 3093 online questionnaires, 521 individuals presented for in-person screening visits, with 40.1% (n = 209) fully qualifying. Subjects (n = 312) failed to progress due to the following reasons: disqualifying answer from DHQ (n = 30, 9.6%), insufficient antibodies (n = 198, 63.5%), persistent positive PCR tests (n = 14, 4.5%), and blood donation testing labs (n = 70, 22.4%). Importantly, 24.6% and 11.1% of potential donors who reported having PCR-diagnosed infection had low or undetectable SARS-CoV-2 antibody levels, respectively. Surprisingly, 62.9% (56/89) of subjects had positive PCR tests 14-27 days after symptom resolution, with 13 individuals continuing to be PCR positive after 27 days. CONCLUSION It is feasible for a single site to fully qualify a large number of convalescent plasma donors in a short period of time. Among otherwise qualified convalescent plasma donors, we found high rates of low or undetectable antibody levels and many individuals with persistently positive PCR tests.
Randomized controlled trial of 7, 28, vs 42 day stored red blood cell transfusion on oxygen delivery (VO(2) max) and exercise duration
BACKGROUND Few studies have rigorously assessed the impact of red blood cell (RBC) transfusion on oxygen delivery. Several large trials demonstrated no clinical outcome differences between transfusion of shorter-storage vs prolonged-storage RBCs. These trials did not directly assess functional measures of oxygen delivery. Therefore, it is not clear if 42-day stored RBCs deliver oxygen as effectively as 7-day stored RBCs. STUDY DESIGN AND METHODS Leukocyte-reduced RBCs were collected by apheresis in AS-3. Thirty subjects were randomized (1:1:1) to receive 2 units of autologous RBCs at either 7, 28, or 42 days following donation. VO(2) max testing, using a standardized protocol to exhaustion, was performed 2 days before (Monday) and 2 days after (Friday) the transfusion visit (Wednesday). The primary endpoint was the percent increase in VO(2) max between Monday and Friday. The secondary endpoint was the percent change in duration of exercise for the same time points. RESULTS Hemoglobin levels decreased by 2.8 ± 1.4 g/dL after donation and increased by 2.1 ± 0.6 g/dL after transfusion. This change in hemoglobin was associated with expected decreases (then increases after transfusion) in VO(2) max and exercise duration. No differences were observed between 7-day and 42-day RBC transfusion for percent increase in median [IQR] VO(2) max (10.5 [0.2-17.3] vs 10.9 [5.7-16.8], P = .41) or for percent increase in exercise duration (5.4 [4.1-6.9] vs 4.9 [2.0-7.2], P = .91), respectively. Results were similar for 28-day RBCs and were consistent across the ITT and per-protocol analysis populations. CONCLUSION These data indicate that 42-day, 28-day, and 7-day RBCs have similar ability to deliver oxygen.
Blood donors (n= 30).
2 units of autologous red blood cells (RBCs) at 7 days following donation (n= 10).
2 units of autologous RBCs at either 28 days (n= 10), or 42 days following donation (n= 10).
Haemoglobin levels decreased by 2.8 ± 1.4 g/dL after donation and increased by 2.1 ± 0.6 g/dL after transfusion. This change in haemoglobin was associated with expected decreases (then increases after transfusion) in VO(2) max and exercise duration. No differences were observed between 7-day and 42-day RBC transfusion for percent increase in median [IQR] VO(2) max (10.5 [0.2-17.3] vs 10.9 [5.7-16.8]) or for percent increase in exercise duration (5.4 [4.1-6.9] vs 4.9 [2.0-7.2]), respectively. Results were similar for 28-day RBCs and were consistent across the ITT and per-protocol analysis populations.
Perioperative administration of buffered versus non-buffered crystalloid intravenous fluid to improve outcomes following adult surgical procedures: a Cochrane systematic review
Perioperative medicine (London, England). 2018;7:27
Background: Buffered intravenous fluid preparations contain substrates to maintain acid-base status. The objective of this systematic review was to compare the effects of buffered and non-buffered fluids administered during the perioperative period on clinical and biochemical outcomes. Methods: We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library until May 2017 and included all randomised controlled trials that evaluated buffered versus non-buffered fluids, whether crystalloid or colloid, administered to surgical patients. We assessed the selected studies for risk of bias and graded the level of evidence in accordance with Cochrane recommendations. Results: We identified 19 publications of 18 randomised controlled trials, totalling 1096 participants. Mean difference (MD) in postoperative pH was 0.05 units lower immediately following surgery in the non-buffered group (12 studies of 720 participants; 95% confidence interval (CI) 0.04 to 0.07; I (2) = 61%). This difference did not persist on postoperative day 1. Serum chloride concentration was higher in the non-buffered group at the end of surgery (10 trials of 530 participants; MD 6.77 mmol/L, 95% CI 3.38 to 10.17). This effect persisted until postoperative day 1 (5 trials of 258 participants; MD 8.48 mmol/L, 95% CI 1.08 to 15.88). Quality of this evidence was moderate. We identified variable protocols for fluid administration and total volumes of fluid administered to patients intraoperatively. Outcome data was variably reported at disparate time points and with heterogeneous patient groups. Consequently, the effect size and overall confidence interval was reduced, despite the relatively low inherent risk of bias. There was insufficient evidence on the effect of fluid composition on mortality and organ dysfunction. Confidence intervals of this outcome were wide and the quality of evidence was low (3 trials of 276 participants for mortality; odds ratio (OR) 1.85, 95% CI 0.37 to 9.33; I (2) = 0%). Conclusions: Small effect sizes for biochemical outcomes and lack of correlated clinical follow-up data mean that robust conclusions on major morbidity and mortality associated with buffered versus non-buffered perioperative fluid choices are still lacking. Buffered fluid may have biochemical benefits, including a significant reduction in postoperative hyperchloraemia and metabolic acidosis.
The impact of red blood cell storage duration on tissue oxygenation in cardiac surgery
Journal of Thoracic & Cardiovascular Surgery. , 2016 Nov 19.. 2016;153((3):):610-619 e2
OBJECTIVE Although storage alters red blood cells, several recent, randomized trials found no differences in clinical outcomes between patients transfused with red blood cells stored for shorter versus longer periods of time. The objective of this study was to see whether storage impairs the in vivo ability of erythrocytes to traverse the microcirculation and deliver oxygen at the tissue level. METHODS A subset of subjects from a clinical trial of cardiac surgery patients randomized to receive transfusions of red blood cells stored <10 days or >21 days were assessed for thenar eminence and cerebral tissue hemoglobin oxygen saturation (StO2) via the use of near-infrared spectroscopy and sublingual microvascular blood flow via side-stream darkfield videomicroscopy. RESULTS Among 55 subjects, there was little change in the primary endpoint (thenar eminence StO2 from before to after transfusion of one unit) and the change was similar in the 2 groups: +1.7% (95% confidence interval, -0.3, 3.8) for shorter-storage and +0.8% (95% confidence interval, -1.1, 2.9) for longer-storage; P = .61). Similarly, no significant differences were observed for cerebral StO2 or sublingual microvascular blood flow. These parameters also were not different from preoperatively to 1 day postoperatively, reflecting the absence of a cumulative effect of all red blood cell units transfused during this period. CONCLUSIONS There were no differences in thenar eminence or cerebral StO2, or sublingual microcirculatory blood flow, in cardiac surgery patients transfused with red blood cells stored <10 days or >21 days. These results are consistent with the clinical outcomes in the parent study, which also did not differ, indicating that storage may not impair oxygen delivery by red blood cells in this setting.Copyright Â© 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
Effects of red-cell storage duration on patients undergoing cardiac surgery
New England Journal of Medicine. 2015;372((15):):1419-29.
BACKGROUND Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoing cardiac surgery may be especially vulnerable to the adverse effects of transfusion.METHODS We conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12 years of age or older who were undergoing complex cardiac surgery and were likely to undergo transfusion of red cells were randomly assigned to receive leukocyte-reduced red cells stored for 10 days or less (shorter-term storage group) or for 21 days or more (longer-term storage group) for all intraoperative and postoperative transfusions. The primary outcome was the change in Multiple Organ Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more severe organ dysfunction) from the preoperative score to the highest composite score through day 7 or the time of death or discharge.RESULTS The median storage time of red-cell units provided to the 1098 participants who received red-cell transfusion was 7 days in the shorter-term storage group and 28 days in the longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7 points, respectively (95% confidence interval for the difference, -0.6 to 0.3; P=0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0% in the longer-term storage group (P=0.43); 28-day mortality was 4.4% and 5.3%, respectively (P=0.57). Adverse events did not differ significantly between groups except that hyperbilirubinemia was more common in the longer-term storage group.CONCLUSIONS The duration of red-cell storage was not associated with significant differences in the change in MODS. We did not find that the transfusion of red cells stored for 10 days or less was superior to the transfusion of red cells stored for 21 days or more among patients 12 years of age or older who were undergoing complex cardiac surgery. (Funded by the National Heart, Lung, and Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341.).
A prospective, double-blind, randomized clinical feasibility trial of controlling the storage age of red blood cells for transfusion in cardiac surgical patients
BACKGROUND Recent evidence demonstrates an association between duration of storage of red blood cells (RBC) and morbidity and mortality after cardiac surgery. We studied the feasibility of two different schemes for categorizing and randomizing age of RBC units transfused in cardiac surgical patients. STUDY DESIGN AND METHODS In Phase 1, 20 subjects were randomly assigned to standard of care (SOC) versus no RBCs with more than 21 days' storage duration. In Phase 2, 23 subjects were randomized to RBCs of 7 +/- 4 versus 21 +/- 4 days' storage duration. The age of study RBC units was masked. RESULTS In Phase 1, no patients received RBCs 31 days or older in SOC, and there was overlap in storage age shared in both arms so the predefined feasibility criteria were not met. In Phase 2, it was feasible to deliver specified age RBCs to the 7-day arm (achieved in 100% of subjects), but feasibility was not demonstrated for the 21-day arm (only 50% of subjects transfused with target age RBCs). Significant differences, however, were observed between the 7 +/- 4- and 21 +/- 4-day arms with respect to age of all RBC units (6 +/- 2 vs. 18 +/- 7, p = 0. 0002) and maximum age (7 +/- 2 vs. 20 +/- 7, p < 0. 0001). CONCLUSION Given the current storage age distribution of available RBC inventory, use of a SOC arm in future studies is unlikely to result in a large exposure to oldblood. It is feasible to randomize patients to youngerRBCs (3-11 days) but design strategies are needed to provide intermediate-agedor oldblood as a comparator.
Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline
Annals of Thoracic Surgery. 2007;83((5 Suppl):):S27-86.
BACKGROUND A minority of patients having cardiac procedures (15% to 20%) consume more than 80% of the blood products transfused at operation. Blood must be viewed as a scarce resource that carries risks and benefits. A careful review of available evidence can provide guidelines to allocate this valuable resource and improve patient outcomes. METHODS We reviewed all available published evidence related to blood conservation during cardiac operations, including randomized controlled trials, published observational information, and case reports. Conventional methods identified the level of evidence available for each of the blood conservation interventions. After considering the level of evidence, recommendations were made regarding each intervention using the American Heart Association/American College of Cardiology classification scheme. RESULTS Review of published reports identified a high-risk profile associated with increased postoperative blood transfusion. Six variables stand out as important indicators of risk: (1) advanced age, (2) low preoperative red blood cell volume (preoperative anemia or small body size), (3) preoperative antiplatelet or antithrombotic drugs, (4) reoperative or complex procedures, (5) emergency operations, and (6) noncardiac patient comorbidities. Careful review revealed preoperative and perioperative interventions that are likely to reduce bleeding and postoperative blood transfusion. Preoperative interventions that are likely to reduce blood transfusion include identification of high-risk patients who should receive all available preoperative and perioperative blood conservation interventions and limitation of antithrombotic drugs. Perioperative blood conservation interventions include use of antifibrinolytic drugs, selective use of off-pump coronary artery bypass graft surgery, routine use of a cell-saving device, and implementation of appropriate transfusion indications. An important intervention is application of a multimodality blood conservation program that is institution based, accepted by all health care providers, and that involves well thought out transfusion algorithms to guide transfusion decisions. CONCLUSIONS Based on available evidence, institution-specific protocols should screen for high-risk patients, as blood conservation interventions are likely to be most productive for this high-risk subset. Available evidence-based blood conservation techniques include (1) drugs that increase preoperative blood volume (eg, erythropoietin) or decrease postoperative bleeding (eg, antifibrinolytics), (2) devices that conserve blood (eg, intraoperative blood salvage and blood sparing interventions), (3) interventions that protect the patient's own blood from the stress of operation (eg, autologous predonation and normovolemic hemodilution), (4) consensus, institution-specific blood transfusion algorithms supplemented with point-of-care testing, and most importantly, (5) a multimodality approach to blood conservation combining all of the above.
Cost-benefit and efficacy of aprotinin compared with epsilon-aminocaproic acid in patients having repeated cardiac operations: a randomized, blinded clinical trial
BACKGROUND Aprotinin and epsilon-aminocaproic acid are routinely used to reduce bleeding during cardiac surgery. The marked difference in average wholesale cost between these two drug therapies (aprotinin, $1,080 vs. epsilon-aminocaproic acid, $11) has generated significant controversy regarding their relative efficacies and costs. METHODS In a multicenter, randomized, prospective, blinded trial, patients having repeated cardiac surgery received either a high-dose regimen of aprotinin (total dose, 6 x 10(6) kallikrein inactivator units) or epsilon-aminocaproic acid (total dose, 270 mg/kg). RESULTS Two hundred four patients were studied. Overall (data are median [25th-75th percentiles]), aprotinin-treated patients had less postoperative thoracic drainage (511 ml [383-805 ml] vs. 655 ml [464-1,045 ml]; P = 0.016) and received fewer platelet transfusions (0 [range, 0-1] vs. 1 [range, 0-2]; P = 0.036). The surgical field was more likely to be considered free of bleeding in aprotinin-treated patients (44% vs. 26%; P = 0.012). No differences, however, were seen in allogeneic erythrocyte transfusions or in the time required for chest closure. Overall, direct and indirect bleeding-related costs were greater in aprotinin- than in epsilon-aminocaproic acid-treated patients ($1,813 [$1,476-2,605] vs. $1,088 [range, $511-2,057]; P = 0.0001). This difference in cost per case varied in magnitude among sites but not in direction. CONCLUSIONS Aprotinin was more effective than epsilon-aminocaproic acid at decreasing bleeding and platelet transfusions. Epsilon-aminocaproic acid, however, was the more cost-effective therapy over a broad range of estimates for bleeding-related costs in patients undergoing repeated cardiac surgery. A cost-benefit analysis using the lower cost of half-dose aprotinin ($540) still resulted in a significant cost advantage using epsilon-aminocaproic therapy (P = 0.022).