Intravenous iron supplementation treats anemia and reduces blood transfusion requirements in patients undergoing coronary artery bypass grafting-A prospective randomized trial
Annals of cardiac anaesthesia. 2022;25(2):141-147
STUDY OBJECTIVE Preoperative anemia results in two- to sixfold increased incidence of perioperative blood transfusion requirements and reduced postoperative hemoglobin (Hb) level. This prospective study was designed to investigate the effect of preoperative intravenous infusion of iron on Hb levels, blood transfusion requirements, and incidence of postoperative adverse events in patients undergoing coronary artery bypass grafting. DESIGN Prospective randomized trial. SETTING Academic university hospital. PATIENTS Eighty patients (52-67 years old) underwent coronary artery bypass grafting and received either iron therapy or saline infusion preoperatively. INTERVENTIONS Patients were randomly allocated to iron or placebo groups. In the iron group, patients received a single intravenous dose of ferric carboxymaltose (1000 mg in 100 mL saline) infused slowly over 15 min 7 days before surgery. In placebo group, patients received a single intravenous dose of saline (100 mL saline) infused slowly over 15 min 7 days before surgery. MEASUREMENTS Patients were followed up with regards to incidence of anemia, Hb level on admission, preoperatively, postoperatively, 1 week and 4 weeks after discharge, aortic cross-clamp time, the number of packed red blood cells (pRBCs) units, the percentage of reticulocytes pre-postoperatively and 1 week later, hospital stay and intensive care unit (ICU) stay length, and the incidence of postoperative complications. MAIN RESULTS Iron therapy was associated with lower incidence of anemia 4 weeks after discharge (P < 0.001). Hb level was significantly higher in the iron group compared to the placebo group preoperatively and postoperatively, and 4 weeks after discharge (P < 0.001). Iron therapy resulted in shorter hospital and ICU stay (P < 0.001) and shorter aortic cross-clamp time, reduced pRBCs requirements postoperatively. Percentage of reticulocytes was significantly higher in placebo group than in iron group postoperatively and 1 week after discharge and the incidence of postoperative complications was similar to the placebo group. CONCLUSIONS Preoperative IV iron infusion is a safe and feasible way to manage preoperative anemia. Preoperative administration of IV iron is associated with a higher postoperative Hb level, shorter hospital and ICU stay, and reduced perioperative red blood cell transfusion requirements with insignificant difference in incidence of postoperative complications.
Comparison of Application Effects of Different Hemostasis Methods After Ischemic Cerebrovascular Intervention
Frontiers in surgery. 2022;9:850139
OBJECTIVE To explore the effects of two different hemostasis methods, namely, arterial compression devices and vascular closure devices, in the ischemic cerebrovascular intervention to provide a theoretical basis for clinical selection of hemostasis methods. METHODS A total of 302 patients who underwent ischemic cerebrovascular intervention in our hospital from January 2016 to December 2020 were selected as the research subjects and randomly divided into the control group (n = 151) and the observation group (n = 151). The patients in both groups underwent cerebrovascular intervention. The patients in the control group were treated with an artery compressor for hemostasis after the operation, while those in the observation group were treated with vascular closure devices for hemostasis. The hemostatic indexes and vascular parameters at the puncture site before and after the operation were compared between the two groups. The comfort level of the patients was assessed at 6, 12, and 24 h after the operation with the Kolcaba Comfort Scale score, and the postoperative complications were recorded. RESULTS There was no significant difference in the success rate of hemostasis between the two groups (p > 0.05). The hemostatic time and immobilization time of (2.69 ± 0.62) min and (4.82 ± 0.93) h in the observation group were lower than those in the control group with (16.24 ± 3.58) min and (7.94 ± 1.86) h (p < 0.05). The differences in the minimum inner diameter of the puncture site and its nearby vessels and the peak velocity of blood flow between the two groups before and after the operation were not statistically significant within or between groups (p > 0.05). The scores of the Kolcaba comfort scale in the observation group (80.16 ± 8.49) and (93.65 ± 9.26) at 6 and 12 h, respectively, after the operation, were higher than those in the control groups (72.08 ± 7.54) and (85.49 ± 8.63) (p < 0.05). The 24 h postoperative Kolcaba comfort scale score was (97.54 ± 9.86) in the observation group and (96.82 ± 9.64) in the control group, and the difference was not statistically significant (p > 0.05). In the control group, there were 7 cases of dysuria, 12 cases of low back pain, 14 cases of sleep disorder, 20 cases of mental stress, and 5 cases of wound bleeding, and the total incidence of complications was 38.41% (58/151). In the observation group, there were 4 cases of dysuria, 8 cases of low back pain, 10 cases of sleep disorder, 14 cases of mental stress, and 3 cases of wound bleeding, and the total incidence of complications was 25.83% (39/151). The total incidence of complications in the observation group was lower than that in the control group (p < 0.05). CONCLUSION For patients with ischemic cerebrovascular disease undergoing femoral artery puncture intervention, the use of vascular closure devices can stop the bleeding quickly, which can significantly shorten the bleeding time, and the postoperative braking time of patients is short, with high comfort and fewer complications.
A Meta-Analysis of Using Protamine for Reducing the Risk of Hemorrhage During Carotid Recanalization: Direct Comparisons of Post-operative Complications
Frontiers in pharmacology. 2022;13:796329
Background: Protamine can decrease the risk of hemorrhage during carotid recanalization. However, it may cause severe side effects. There is no consensus on the safety and efficacy of protamine during surgery. Thus, we conduct a comprehensive review and meta-analysis to compare the differences between the protamine and the no-protamine group. Method: We systematically obtained literature from Medline, Google Scholar, Cochrane Library, and PubMed electronic databases. All four databases were scanned from 1937 when protamine was first adopted as a heparin antagonist until February 2021. The reference lists of identified studies were manually checked to determine other eligible studies that qualify. The articles were included in this meta-analysis as long as they met the criteria of PICOS; conference or commentary articles, letters, case report or series, and animal observation were excluded from this study. The Newcastle-Ottawa Quality Assessment Scale and Cochrane Collaboration's tool are used to assess the risk of bias of each included observational study and RCT, respectively. Stata version 12.0 statistical software (StataCorp LP, College Station, Texas) was adopted as statistical software. When I (2) < 50%, we consider that the data have no obvious heterogeneity, and we conduct a meta-analysis using the fixed-effect model. Otherwise, the random-effect model was performed. Result: A total of 11 studies, consisting of 94,618 participants, are included in this study. Our analysis found that the rate of wound hematoma had a significant difference among protamine and no-protamine patients (OR = 0.268, 95% CI = 0.093 to 0.774, p = 0.015). Furthermore, the incidence of hematoma requiring re-operation (0.7%) was significantly lower than that of patients without protamine (1.8%). However, there was no significant difference in the incidence of stroke, wound hematoma with hypertension, transient ischemic attacks (TIA), myocardial infarction (MI), and death. Conclusion: Among included participants undergoing recanalization, the use of protamine is effective in reducing hematoma without increasing the risk of having other complications. Besides, more evidence-based performance is needed to supplement this opinion due to inherent limitations.
Comparison of post-operative bleeding incidence in laser hemorrhoidoplasty with and without hemorrhoidal artery ligation: a double-blinded randomized controlled trial
BMC surgery. 2022;22(1):146
INTRODUCTION The effectiveness of hemorrhoidal artery ligation supplementation in reducing the incidence of post laser hemorrhoidoplasty bleeding has not been investigated. METHODS This was a double-blind, randomized controlled trial comparing post-operative bleeding incidence in patients undergoing laser hemorrhoidoplasty (LHP) only versus LHP with hemorrhoidal artery ligation (HAL). Outcome measures included post-operative bleeding and its severity (i.e. verbal rating scale and Clavien-Dindo classification), presence of perianal swelling and pain score (visual analog score) at 1-day, 1-week and 6-weeks post-operatively. Statistical tests were performed and a value of P < 0.05 was considered significant. RESULTS Seventy-six patients were randomized. There was no difference in median operating time. The bleeding incidence was highest at 1-week post-operatively (17.1%), and decreased to 1.3% at 6-weeks. There was no significant difference in bleeding incidence between both groups at any of the measured timepoints (P > 0.05). Severity of bleeding and incidence of post-operative perianal swelling were similar in both groups (P > 0.05). There was no difference in median pain scores. CONCLUSION Supplementation of HAL to LHP does not reduce the post-operative bleeding incidence. LHP is sufficient as a stand-alone procedure for treating haemorrhoids. TRIAL REGISTRATION National Registration Number is NMRR-15-1112-24065 (IIR). The trial start date was 1st January 2015 with the ClinicalTrials.gov identifier and registration number as NCT04667169.
Tranexamic acid reduces postoperative blood loss in Chinese pediatric patients undergoing cardiac surgery: A PRISMA-compliant systematic review and meta-analysis
BACKGROUND Tranexamic acid has been increasingly used for blood conservation in cardiac surgery. However, the evidence supporting the routine use of tranexamic acid in Chinese pediatric patients undergoing cardiac surgery remains weak. This meta-analysis aimed to systematically review the efficacy of tranexamic acid when applying to Chinese pediatric patients undergoing cardiac surgery. PARTICIPANTS Chinese pediatric patients undergoing cardiac surgery. INTERVENTIONS Tranexamic acid or control drugs (saline/blank). METHODS PUBMED, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP Data till May 4, 2021, database search was updated on August 1. Primary outcomes of interest included postoperative bleeding, allogeneic transfusion, and reoperation for bleeding. Secondary outcomes of interest included postoperative recovery. For continuous/dichotomous variables, treatment effects were calculated as weighted mean difference (WMD)/odds ratio and 95% confidence interval. RESULTS A database search yielded 15 randomized controlled trials including 1641 patients, where 8 studies were allocated into non-cyanotic congenital group, 5 were allocated into cyanotic congenital group, and the other 2 were allocated into combined cyanotic/non-cyanotic group. This meta-analysis demonstrate that tranexamic acid administration can reduce the postoperative 24 hours blood loss in non-cyanotic, cyanotic, and combined cyanotic/non-cyanotic patients, the red blood cell transfusion in non-cyanotic and cyanotic patients, and the fresh frozen plasma transfusion in non-cyanotic and combined cyanotic/non-cyanotic patients. CONCLUSION This meta-analysis demonstrates that tranexamic acid is highly effective in reducing the blood loss in Chinese pediatric cardiac surgery, but it behaves poorly when it comes to the transfusion requirement. To further confirm this, more well-designed and adequately-powered randomized trials are needed.
Effects of perioperative erythropoietin administration on acute kidney injury and red blood cell transfusion in patients undergoing cardiac surgery: A systematic review and meta-analysis
BACKGROUND The renoprotective effects of erythropoietin (EPO) are well-known; however, the optimal timing of EPO administration remains controversial. Red blood cell (RBC) transfusion is an independent risk factor for cardiac surgery-associated acute kidney injury (CSA-AKI). We aimed to evaluate the efficacy of EPO on CSA-AKI and RBC transfusion according to the timing of administration. METHODS We searched the Cochrane Library, EMBASE, and MEDLINE databases for randomized controlled trials. The primary outcome was the incidence of CSA-AKI following perioperative EPO administration, and the secondary outcomes were changes in serum creatinine, S-cystatin C, S-neutrophil gelatinase-associated lipocalin, urinary neutrophil gelatinase-associated lipocalin, length of hospital and intensive care unit (ICU) stay, volume of RBC transfusion, and mortality. The subgroup analysis was stratified according to the timing of EPO administration in relation to surgery. RESULTS Eight randomized controlled trials with 610 patients were included in the study. EPO administration significantly decreased the incidence of CSA-AKI (odds ratio: 0.60, 95% confidence interval [CI]: 0.43-0.85, P = .004; I2 = 52%; P for heterogeneity = .04), intra-operative RBC transfusion (standardized mean difference: -0.30, 95% CI: -0.55 to -0.05, P = .02; I2 = 15%, P for heterogeneity = .31), and hospital length of stay (mean difference: -1.54 days, 95% CI: -2.70 to -0.39, P = .009; I2 = 75%, P for heterogeneity = .001) compared with control groups. Subgroup analyses revealed that pre-operative EPO treatment significantly reduced the incidence of CSA-AKI, intra-operative RBC transfusion, serum creatinine, and length of hospital and ICU stay. CONCLUSION Pre-operative administration of EPO may reduce the incidence of CSA-AKI and RBC transfusion, but not in patients administered EPO during the intra-operative or postoperative period. Therefore, pre-operative EPO treatment can be considered to improve postoperative outcomes by decreasing the length of hospital and ICU stay in patients undergoing cardiac surgery.
Patients undergoing cardiac surgery (8 studies, n= 610).
Perioperative erythropoietin (EPO).
EPO administration significantly decreased the incidence of cardiac surgery-associated acute kidney injury (CSA-AKI), intra-operative red blood cell transfusion (standardized mean difference: -0.30), and hospital length of stay (mean difference: -1.54 days) compared with control groups. Subgroup analyses revealed that pre-operative EPO treatment significantly reduced the incidence of CSA-AKI, intra-operative red blood cell transfusion, serum creatinine, and length of hospital and intensive care unit stay.
The neurocognitive outcomes of hemodilution in adult patients undergoing coronary artery bypass grafting using cardiopulmonary bypass
Annals of cardiac anaesthesia. 2022;25(2):133-140
OBJECTIVE The study aimed to evaluate the effect of mild and moderate hemodilution during CPB on the neurocognitive dysfunction in patients undergoing coronary artery bypass grafting. DESIGN A randomized clinical study. SETTING Cardiac center. PATIENTS 186 patients scheduled for cardiac surgery with cardiopulmonary bypass. INTERVENTION The patients were classified into 2 groups (each = 93), Mild hemodilution group: The hematocrit value was maintained >25% by transfusion of packed-red blood cells plus hemofiltration during CPB. Moderate hemodilution group: the hematocrit value was maintained within the range of 21-25%. MEASUREMENTS The monitors included the hemofiltrated volume, number of transfused packed red blood cells, and the incidence of postoperative cognitive dysfunction. MAIN RESULTS The hemofiltrated volume during CPB was too much higher with mild hemodilution compared to the moderate hemodilution (p = 0.001). The number of the transfused packed red blood cells during CPB was higher with mild hemodilution compared to the moderate hemodilution (p = 0.001), but after CPB, the number of the transfused packed red blood cells was lower with the mild hemodilution group than the moderate hemodilution (p = 0.001). The incidence of total postoperative neurological complications was significantly lower with the mild hemodilution group than moderate hemodilution (p = 0.033). The incidence of neurocognitive dysfunction was significantly lower with mild hemodilution group than moderate hemodilution (p = 0.042). CONCLUSIONS The mild hemodilution was associated with a significant decrease in the incidence of neurocognitive dysfunction compared to moderate hemodilution in patients undergoing coronary artery bypass grafting. Also, the transfused packed red blood cells increased during CPB and decreased after CPB with the mild hemodilution than moderate hemodilution.
Optimal protamine dosing after cardiopulmonary bypass: The PRODOSE adaptive randomised controlled trial
PLoS medicine. 2021;18(6):e1003658
BACKGROUND The dose of protamine required following cardiopulmonary bypass (CPB) is often determined by the dose of heparin required pre-CPB, expressed as a fixed ratio. Dosing based on mathematical models of heparin clearance is postulated to improve protamine dosing precision and coagulation. We hypothesised that protamine dosing based on a 2-compartment model would improve thromboelastography (TEG) parameters and reduce the dose of protamine administered, relative to a fixed ratio. METHODS AND FINDINGS We undertook a 2-stage, adaptive randomised controlled trial, allocating 228 participants to receive protamine dosed according to a mathematical model of heparin clearance or a fixed ratio of 1 mg of protamine for every 100 IU of heparin required to establish anticoagulation pre-CPB. A planned, blinded interim analysis was undertaken after the recruitment of 50% of the study cohort. Following this, the randomisation ratio was adapted from 1:1 to 1:1.33 to increase recruitment to the superior arm while maintaining study power. At the conclusion of trial recruitment, we had randomised 121 patients to the intervention arm and 107 patients to the control arm. The primary endpoint was kaolin TEG r-time measured 3 minutes after protamine administration at the end of CPB. Secondary endpoints included ratio of kaolin TEG r-time pre-CPB to the same metric following protamine administration, requirement for allogeneic red cell transfusion, intercostal catheter drainage at 4 hours postoperatively, and the requirement for reoperation due to bleeding. The trial was listed on a clinical trial registry (ClinicalTrials.gov Identifier: NCT03532594). Participants were recruited between April 2018 and August 2019. Those in the intervention/model group had a shorter mean kaolin r-time (6.58 [SD 2.50] vs. 8.08 [SD 3.98] minutes; p = 0.0016) post-CPB. The post-protamine thromboelastogram of the model group was closer to pre-CPB parameters (median pre-CPB to post-protamine kaolin r-time ratio 0.96 [IQR 0.78-1.14] vs. 0.75 [IQR 0.57-0.99]; p < 0.001). We found no evidence of a difference in median mediastinal/pleural drainage at 4 hours postoperatively (140 [IQR 75-245] vs. 135 [IQR 94-222] mL; p = 0.85) or requirement (as a binary outcome) for packed red blood cell transfusion at 24 hours postoperatively (19 [15.8%] vs. 14 [13.1%] p = 0.69). Those in the model group had a lower median protamine dose (180 [IQR 160-210] vs. 280 [IQR 250-300] mg; p < 0.001). Important limitations of this study include an unblinded design and lack of generalisability to certain populations deliberately excluded from the study (specifically children, patients with a total body weight >120 kg, and patients requiring therapeutic hypothermia to <28°C). CONCLUSIONS Using a mathematical model to guide protamine dosing in patients following CPB improved TEG r-time and reduced the dose administered relative to a fixed ratio. No differences were detected in postoperative mediastinal/pleural drainage or red blood cell transfusion requirement in our cohort of low-risk patients. TRIAL REGISTRATION ClinicalTrials.gov Unique identifier NCT03532594.
Modified ultrafiltration reduces postoperative blood loss and transfusions in adult cardiac surgery: a meta-analysis of randomized controlled trials
Interactive cardiovascular and thoracic surgery. 2021
OBJECTIVES Cardiopulmonary bypass in cardiac surgery has been associated with several deleterious effects including haemodilution and systemic inflammation. Modified ultrafiltration (MUF) has been well established in paediatric cardiac surgery in counteracting postperfusion syndrome. However, MUF is less commonly used in adult cardiac surgery. In this meta-analysis, we compared clinical outcomes in adult patients who underwent cardiopulmonary bypass with and without MUF. METHODS Electronic searches were performed using Pubmed, Ovid Medline, EMBASE and the Cochrane Library until April 2020. Selection criteria were randomized studies of adult cardiac surgery patients comparing MUF versus no MUF. Primary outcomes were postoperative mortality, haematocrit, blood transfusion, chest tube drainage, duration of intensive care unit (ICU) stay and duration of mechanical ventilation. RESULTS Thirteen randomized controlled trials were included, comprising 626 patients in the MUF group, and 610 patients in the control (no-MUF) group. There was a significantly improved postoperative haematocrit [mean difference 2.70, 95% confidence interval (CI) 0.68-4.73, P = 0.009], lower chest tube drainage (mean difference -105 ml, 95% CI -202 to -7 ml, P = 0.032), lower postoperative blood transfusion rate (mean difference -0.73 units, 95% CI -0.98 to -0.47 units, P < 0.0001) and shorter duration of ICU stay (mean difference -0.13 days, 95% CI -0.27 to -0.00 days, P = 0.048) in the MUF group. There was no difference in ventilation time (mean difference -0.47 h, 95% CI -2.05 to 1.12 h, P = 0.56) or mortality rates (odds ratio 0.62, 95% CI 0.28-1.33, P = 0.22). There were no reported complications associated with MUF. CONCLUSIONS MUF is a safe and feasible option in adult cardiac patients, with significant benefits including improved postoperative haematocrit, as well as reduced postoperative chest tube bleeding, transfusion requirements and duration of ICU stay.
Comparison of the in-vivo effect of two tranexamic acid doses on fibrinolysis parameters in adults undergoing valvular cardiac surgery with cardiopulmonary bypass - a pilot investigation
BMC anesthesiology. 2021;21(1):33
BACKGROUND The blood saving efficacy of TXA in cardiac surgery has been proved in several studies, but TXA dosing regimens were varied in those studies. Therefore, we performed this study to investigate if there is a dose dependent in-vivo effect of TXA on fibrinolysis parameters by measurement of fibrinolysis markers in adults undergoing cardiac surgery with CPB. METHODS A double-blind, randomized, controlled prospective trial was conducted from February 11, 2017 to May 05, 2017. Thirty patients undergoing cardiac valve surgery were identified and randomly divided into a placebo group, low-dose group and high-dose group by 1: 1: 1. Fibrinolysis parameters were measured by plasma levels of D-Dimers, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), plasmin-antiplasmin complex (PAP), tissue plasminogen activator (tPA) and thrombomodulin (TM). Those proteins were measured at five different sample times: preoperatively before the TXA injection (T(1)), 5 min after the TXA bolus (T(2)), 5 min after the initiation of CPB (T(3)), 5 min before the end of CPB (T(4)) and 5 min after the protamine administration (T(5)). A Thrombelastography (TEG) and standard coagulation test were also performed. RESULTS Compared with the control group, the level of the D-Dimers decreased in the low-dose and high-dose groups when the patients arrived at the ICU and on the first postoperative morning. Over time, the concentrations of PAI-1, TAFI, and TM, but not PAP and tPA, showed significant differences between the three groups (P < 0.05). Compared with the placebo group, the plasma concentrations of PAI-1 and TAFI decreased significantly at the T3 and T4 (P < 0.05); TAFI concentrations also decreased at the T5 in low-dose group (P < 0.05). Compared with the low-dose group, the concentration of TM increased significantly at the T4 in high-dose group. CONCLUSIONS The in-vivo effect of low dose TXA is equivalent to high dose TXA on fibrinolysis parameters in adults with a low bleeding risk undergoing valvular cardiac surgery with cardiopulmonary bypass, and a low dose TXA regimen might be equivalent to high dose TXA for those patients. TRIAL REGISTRATION ChiCTR-IPR-17010303 , Principal investigator: Zhen-feng ZHOU, Date of registration: January 1, 2017.