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Low-Dose vasopressin and renal perfusion in pediatric cardiac surgery
Kumar, A., Ghotra, G. S., Raj, S., Tiwari, N., Ramamurthy, H. R.
Annals of cardiac anaesthesia. 2023;26(3):309-317
Abstract
BACKGROUND Congenital heart surgeries are associated with post-bypass renal and cardiac dysfunctions. The use of low-dose vasopressin has been found to be beneficial in adult cardiac surgeries. OBJECTIVE To assess the hemodynamic and renal effects of patients undergoing on-pump pediatric cardiac surgery under general anesthesia (GA) with low-dose vasopressin infusion. DESIGN Prospective randomized controlled study. SETTING Operation room and ICU, tertiary care teaching hospital. PATIENTS Fifty-five pediatric cardiac patients undergoing repair for congenital heart diseases (CHD). INTERVENTIONS Low-dose vasopressin infusion in the study group and placebo in the control group. MEASUREMENTS AND MAIN RESULTS Renal near-infrared spectroscopy (NIRS), serum NGAL, and inflammatory mediators-IL6 and IL8 along with other renal and hemodynamic parameters in the perioperative period were recorded. Diastolic blood pressure (DBP) and cardiac index were significantly higher in the vasopressin group. Inflammatory markers were significantly high in the immediate postoperative period in all patients which later stabilized in the next 48 h but showed similar trends in both groups. Low-dose vasopressin infusion did not improve either renal perfusion or function. The duration of mechanical ventilation and length of hospital stay, the incidence of AKI development, and transfusion requirements were marginally lower in the vasopressin group, although not significant. CONCLUSION Low-dose vasopressin infusion improved hemodynamics and showed a decreased incidence of complications. However, it failed to show any benefit of renal function and overall outcome in pediatric cardiac surgery.
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The effect of perioperative antithrombin supplementation on blood conservation and postoperative complications after cardiopulmonary bypass surgery: A systematic review, meta-analysis and trial sequential analysis
Li, T., Bo, F., Meng, X., Wang, D., Ma, J., Dai, Z.
Heliyon. 2023;9(11):e22266
Abstract
STUDY OBJECTIVE Antithrombin (AT) activity is reduced during cardiopulmonary bypass (CPB) surgery. Guidelines has demonstrated that perioperative AT supplementation contributed to blood conservation and prevent perioperative thrombotic complications and target organ injury owing to its role in reducing thrombin generation. But these recommends is lack of support of meta-analysis in the guidelines. This meta-analysis aims to include all the relevant randomized controlled trails (RCT) on patients who experienced cardiac surgeries with CPB and investigate the effect of perioperative AT on blood conservation and complications after cardiac surgery. METHODS Standard published RCTs were searched from bibliographic databases to identify all evidence reporting perioperative AT supplementation for patients undergoing cardiovascular surgeries. The primary outcome was postoperative blood loss, the secondary outcomes were blood component transfusion (red blood cell (RBC), fresh frozen plasma (FFP), platelet and autologous blood), postoperative morbidity and in hospital mortality. The relative risk (RR) for dichotomous outcomes and the standardized mean difference (SMD) for continuous outcomes were estimated using a random-effects model. Trial sequential analysis (TSA) was performed using TSA software 0.9.5.10. RESULTS 13 RCTs with 996 participants undergoing different cardiovascular surgeries were included. Meta-analysis showed AT did not decrease postoperative blood loss (SMD -0.01, 95%CI -0.2 to 0.19). Subgroup analysis showed the effect of AT on postoperative blood loss was not associated with age, RCT type, surgery type, injection time of AT and AT deficiency. TSA further suggested that no additional studies were required for the stable result. Perioperative AT also did not reduce RBC ((SMD 0.10, 95%CI -0.66 to 0.85), (RR 0.99, 95%CI 0.83 to 1.19)), FFP ((SMD 0.11, 95%CI -0.19 to 0.41), (RR 1.30, 95%CI 0.90 to 1.87)), platelet (RR 1.10, 95%CI 0.83 to 1.46) and autologous blood (SMD 0.46, 95%CI -0.12 to 1.8504) transfusions. Perioperative AT significantly increased in hospital mortality (RR 2.53, 95%CI 1.02 to 6.28) and acute kidney injury (AKI) (RR 3.72, 95%CI 1.73 to 8.04) incidence. There was no significant difference in postoperative reexploration, thromboembolism, ECMO/IABP support, and stroke incidence between AT and non-AT group. CONCLUSIONS With the improvement of AT level and heparin sensitivity, perioperative AT has no significant effect on blood conservation. And it is noteworthy that the treatment increased in hospital mortality and the incidence of AKI after cardiac surgery.
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3.
Prophylactic Use of Antifibrinolytics During Pediatric Cardiac Surgery With Cardiopulmonary Bypass on Postoperative Bleeding and Transfusion: A Systematic Review and Meta-Analysis
Schertz K, Karam O, Demetres M, Faraoni S, Faraoni D, Nellis ME
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2022
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Editor's Choice
Abstract
OBJECTIVES To determine the effect of intraoperative antifibrinolytics, including tranexamic acid (TXA), aminocaproic acid (EACA), or aprotinin, on bleeding in children undergoing cardiac surgery with cardiopulmonary bypass (CPB). DATA SOURCES Relevant articles were systematically searched from Ovid MEDLINE, Ovid EMBASE, CINAHL, Cochrane Library, and Web of Science to November 15, 2021. STUDY SELECTION Abstracts were screened, and full texts were reviewed using predetermined inclusion and exclusion criteria using the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. DATA EXTRACTION A standardized data extraction tool was used. DATA SYNTHESIS Sixty-eight studies including 28,735 patients were analyzed. TXA compared with placebo resulted in a mean decrease in chest tube output of 9.1 mL/kg (95% CI, 6.0-12.3 mL/kg), I2 equals to 65.2%, p value of less than 0.001, platelet requirement of 2.9 mL/kg (95% CI, 0.1-5.8 mL/kg), I2=72.5%, p value less than 0.001 and plasma requirement of 4.0 mL/kg (95% CI, 0.6-7.2 mL/kg), I2 equals to 94.5%, p value less than0.001. Aprotinin compared with placebo resulted in a mean decrease in chest tube output of 4.3 mL/kg (2.4-6.2 mL/kg), I2 equals to 66.3%, p value of less than 0.001, platelet transfusion of 4.6 mL/kg (95% CI, 0.6-8.6 mL/kg), I2 equals to 93.6%, p value of less than 0.001, and plasma transfusion of 7.7 mL/kg (95% CI, 2.1-13.2 mL/kg), I2 equals to 95.3%, p value of less than 0.001. EACA compared with placebo resulted in a mean decrease in chest tube output of 9.2 mL/kg (2.3-21.0 mL/kg), I2 equals to 96.4%, p value of less than 0.001, RBC transfusion of 7.2 mL/kg (95% CI, 2.4-12.1 mL/kg), I2 equals to 94.5%, p value equals to 0.002, and platelet transfusion of 10.7 mL/kg (95% CI, 2.9-18.5 mL/kg), I2 equals to 0%, p value of less than 0.001. No statistical difference was observed in chest tube output when TXA was compared with aprotinin. Subgroup analysis of cyanotic patients showed a significant decrease in chest tube output, platelet requirement, and plasma requirement for patients receiving aprotinin. Overall, the quality of evidence was moderate. CONCLUSIONS Antifibrinolytics are effective at decreasing blood loss and blood product requirement in children undergoing cardiac surgery with CPB although the quality of evidence is only moderate.
PICO Summary
Population
Children undergoing cardiac surgery with cardiopulmonary bypass, (68 studies, n= 28,735).
Intervention
Intraoperative antifibrinolytics, including tranexamic acid (TXA), aminocaproic acid (EACA), or aprotinin.
Comparison
Placebo.
Outcome
TXA compared with placebo resulted in a mean decrease in chest tube output of 9.1 mL/kg (95% Confidence Interval (CI): 6.0-12.3 mL/kg), platelet requirement of 2.9 mL/kg (95% CI: 0.1-5.8 mL/kg), and plasma requirement of 4.0 mL/kg (95% CI: 0.6-7.2 mL/kg). Aprotinin compared with placebo resulted in a mean decrease in chest tube output of 4.3 mL/kg (2.4-6.2 mL/kg), platelet transfusion of 4.6 mL/kg (95% CI: 0.6-8.6 mL/kg), and plasma transfusion of 7.7 mL/kg (95% CI: 2.1-13.2 mL/kg). EACA compared with placebo resulted in a mean decrease in chest tube output of 9.2 mL/kg (2.3-21.0 mL/kg), red blood cell transfusion of 7.2 mL/kg (95% CI: 2.4-12.1 mL/kg), and platelet transfusion of 10.7 mL/kg (95% CI: 2.9-18.5 mL/kg). Overall, the quality of evidence was moderate.
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Tranexamic acid reduces postoperative blood loss in Chinese pediatric patients undergoing cardiac surgery: A PRISMA-compliant systematic review and meta-analysis
Zou ZY, He LX, Yao YT
Medicine. 2022;101(9):e28966
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Abstract
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.
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Efficacy and safety of aprotinin in paediatric cardiac surgery: A systematic review and meta-analysis
Atasever AG, Eerens M, Van den Eynde R, Faraoni D, Rex S
European journal of anaesthesiology. 2021
Abstract
BACKGROUND The relicensing of aprotinin in Europe and Canada has stimulated discussions on its usefulness in paediatric cardiac surgery. OBJECTIVE To systematically evaluate the available evidence on the efficacy and safety of aprotinin in paediatric cardiac surgery. DESIGN Systematic review of all randomised and observational studies comparing aprotinin with tranexamic acid, epsilon aminocaproic acid, placebo or no drug in paediatric cardiac surgery. Meta-analyses were performed on efficacy and safety outcomes. DATA SOURCES PubMed, Cochrane Central Register of Controlled Trials, Web of Science and Embase were searched from January 2000 to March 2021. ELIGIBILITY CRITERIA Studies that enrolled children under 18 years undergoing cardiac surgery with cardiopulmonary bypass. RESULTS Thirty-two studies enrolling a total of 63 894 paediatric cardiac procedures were included. Aprotinin significantly reduced total blood loss [mean difference -4.70 ml kg-1, 95% confidence interval (CI), -7.88 to -1.53; P = 0.004], postoperative transfusion requirements and the incidence of surgical re-exploration for bleeding [odds ratio (OR) 0.74, 95% CI, 0.56 to 0.97; P = 0.03]. Aprotinin had no effects on 30-day mortality (OR 1.02, 95% CI, 0.93 to 1.11; P = 0.73) and on other safety outcomes, except for the incidence of renal replacement therapy (RRT), which was significantly increased in patients given aprotinin (OR 1.29, 95% CI, 1.08 to 1.54; P = 0.006). Findings from observational and randomised controlled trials did not largely differ. A sub-group analysis in neonates showed that aprotinin significantly reduced packed red blood cell transfusions and the incidence of postoperative surgical re-exploration for bleeding and/or tamponade. When compared with lysine analogues, aprotinin was more effective at reducing bleeding and transfusion without increasing the risk of side effects. CONCLUSION This meta-analysis suggests that aprotinin is effective and well tolerated in paediatric cardiac surgery. Given the large heterogeneity of the results and the risk of selection bias in observational studies, large randomised controlled trials are warranted.
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The synergistic effect of tranexamic acid and ethamsylate combination on blood loss in pediatric cardiac surgery
El Baser IIA, ElBendary HM, ElDerie A
Annals of cardiac anaesthesia. 2021;24(1):17-23
Abstract
BACKGROUND Pediatric patients are at risk for bleeding after cardiac surgery. Administration of antifibrinolytic agents reduces postoperative blood loss. OBJECTIVE Evaluation of the efficacy of combined administration of tranexamic acid (TXA) and ethamsylate in the reduction of postoperative blood loss in pediatric cardiac surgery. METHODS This prospective randomized study included 126 children submitted for cardiac surgery, and they were allocated into three groups: control group (n = 42); TXA group (n = 42):- received only TXA; and combined ethamsylate TXA group (n = 42):- received a combination of TXA and ethamsylate. The main collected data included sternal closure time, the needs for intraoperative transfusion of blood and its products, the total amount of blood loss, and the amount of the whole blood and its products transfused to the patients in the first 24 postoperative hours. RESULTS Blood loss volume in the first 24 postoperative hours was significantly smaller in combined group than the TXA and control groups and was significantly smaller in the TXA group than the control group. The sternal closure time was significantly shorter in the combined group than the other 2 groups and significantly shorter in TXA than the control group. The amount of whole blood transfused to patients in the combined group during surgery and in the first postoperative 24 h was significantly smaller than the other 2 groups and smaller in TXA group than the control group during surgery. CONCLUSION Combined administration of ethamsylate and TXA in pediatric cardiac surgery was more effective in reducing postoperative blood loss and whole blood transfusion requirements than the administration of TXA alone.
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Antifibrinolytic Drugs for the Prevention of Bleeding in Pediatric Cardiac Surgery on Cardiopulmonary Bypass: A Systematic Review and Meta-analysis
Siemens K, Sangaran DP, Hunt BJ, Murdoch IA, Tibby SM
Anesthesia and analgesia. 2021
Abstract
BACKGROUND Bleeding is one of the commonest complications affecting children undergoing cardiac surgery on cardiopulmonary bypass. Antifibrinolytic drugs are part of a multifaceted approach aimed at reducing bleeding, though sufficiently sized pediatric studies are sparse, and dosing algorithms are heterogeneous. Our objective was to evaluate the efficacy and safety of antifibrinolytic agents as well as the effectiveness of different dosing regimens in pediatric cardiac surgery using cardiopulmonary bypass. METHODS We performed a systematic review and meta-analysis evaluating randomized controlled trials published between 1980 and 2019, identified by searching the databases MEDLINE, EMBASE, PubMed, and CENTRAL. All studies investigating patients <18 years of age without underlying hematological disorders were included. The primary outcome was postoperative bleeding; secondary end points included blood product transfusion, mortality, and safety (thromboses, anaphylaxis, renal or neurological dysfunction, and seizures). Different dosing regimens were compared. Studies were dual appraised, outcomes were reported descriptively and, if appropriate, quantitatively using the Review Manager 5 (REVMAN 5) software (The Cochrane Collaboration). RESULTS Thirty of 209 articles were included, evaluating the following drugs versus control: aprotinin n = 14, tranexamic acid (TXA) n = 12, and epsilon-aminocaproic acid (EACA) n = 4. The number of participants per intervention group ranged from 11 to 100 (median, 25; interquartile range [IQR], 20.5) with a wide age span (mean, 13 days to 5.8 years) and weight range (mean, 3.1-26.3 kg). Methodological quality was low to moderate.All agents reduced mean 24-hour blood loss compared to control: aprotinin by 6.0 mL/kg (95% confidence interval [CI], -9.1 to -3.0; P = .0001), TXA by 9.0 mL/kg (95% CI, -11.3 to -6.8; P < .00001), and EACA by 10.5 mL/kg (95% CI, -21.1 to 0.0; P = .05). Heterogeneity was low for TXA (I2 = 29%; P = .19), moderate for aprotinin (I2 = 41%; P = .11), and high for EACA (I2 = 95%; P = <.00001). All agents also reduced 24-hour blood product transfusion. There was no clear dose-response effect for TXA nor aprotinin. Studies were underpowered to detect significant differences in mortality, thromboses, anaphylaxis, and renal or neurological dysfunction. CONCLUSIONS The available data demonstrate efficacy for all 3 antifibrinolytic drugs. Therefore, the agent with the most favorable safety profile should be used. As sufficient data are lacking, large comparative trials are warranted to assess the relative safety and appropriate dosing regimens in pediatrics.
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Randomized Pilot Trial of Acute Normovolemic Hemodilution in Pediatric Cardiac Surgery Patients
Harris WM, Treggiari MM, LeBlanc A, Giacomuzzi C, You JJ, Muralidaran A, Shen I
World J Pediatr Congenit Heart Surg. 2020;11(4):452-458
Abstract
BACKGROUND Due to the substantial improvement in survival among pediatric patients undergoing congenital heart surgery, reducing early and long-term morbidity is becoming the major focus of care. Blood transfusion is associated with worse postoperative outcomes after cardiac surgery. Acute normovolemic hemodilution (ANH) is a blood conservation strategy that aims to reduce allogenic blood transfusion during cardiac surgery. However, there are scant data regarding its efficacy for pediatric cardiac surgery patients. METHODS We designed a single-center, controlled, randomized, pilot trial in patients between 6 and 36 months old undergoing pediatric heart surgery. Patients were equally assigned to undergo ANH prior to initiation of cardiopulmonary bypass or to be managed per usual care. The primary end point was the amount of blood product transfused perioperatively. Secondary end points were markers of morbidity: postoperative bleeding, hematocrit, inotropic agents use, intensive care unit, and hospital stay. The analysis was by intention-to-treat. Estimates of differences between groups are presented with 95% CIs. RESULTS Twelve pediatric heart surgery patients were randomized to each group, ANH and usual care. Baseline characteristics were similar between groups. Acute normovolemic hemodilution implementation did not result in a reduction in the administration of blood product transfused (difference between ANH and usual care among patients transfused = -1.4 mL [-29.4 to 26.6], P = .92). Secondary end points were not different between groups. CONCLUSIONS In this small trial of pediatric cardiac surgery patients, ANH as a strategy to reduce blood component therapy was safe; however, the study failed to show a reduction in perioperative transfusion or other postoperative outcomes.
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Zero-balance ultrafiltration of the priming blood modifies the priming components and improves the clinical outcome in infants undergoing cardiopulmonary bypass: A randomized controlled trial
Gholampour Dehaki, M., Niknam, S., Bakhshandeh, H., Azarfarin, R.
Artificial Organs. 2020;44(3):288-295
Abstract
Cardiopulmonary bypass (CPB) requirement in infants presents a unique challenge because of the large prime volume-to-blood volume ratio. Packed red blood cells (PRBCs) tend to deteriorate with long-term storage owing to their unphysiological composition and osmolality. Given that blood priming is inevitable in neonates, it is suggested that the metabolic load and osmolality are diminished before CPB initiation. We conducted the present study to test the hypothesis that the zero-balance ultrafiltration (Z-BUF) of the priming blood with 0.45% saline might be sufficient for modifying the metabolic load and osmolality and, thus, achieving a physiological state. Sixty infants with a weight below 10 kg undergoing CPB were randomly assigned either to a control group or to a Z-BUF group and the Z-BUF of the priming blood was performed in the latter group. Electrolytes and osmolality were measured in the priming blood. The bleeding volume, the blood transfusion rate, the length of mechanical ventilation, the length of stay in the intensive care unit (ICU), the body temperature, and renal biomarkers were compared between the 2 groups. The osmolality and the levels of potassium, sodium, glucose, chloride, and lactate in the priming blood were significantly decreased after Z-BUF (P < .01). The Z-BUF group showed significant reductions in postoperative blood loss; postoperative blood transfusion; time to extubation; the length of stay in the ICU; the levels of lactate, sodium, and blood urea nitrogen at 24 hours postoperatively and the body temperature at 18 hours postoperatively (P < .05). However, no statistically significant differences were found between the 2 groups regarding the body temperature and the levels of serum creatinine and blood urea nitrogen after admission to the ICU. The results of the present study demonstrated that the Z-BUF of the priming blood could be a useful strategy in infants undergoing CPB insofar as it significantly modified the composition of the priming blood and improved the clinical outcome among our patients.
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Topical versus low-dose systemic tranexamic acid in pediatric cardiac surgery: A randomized clinical study
Hatami F, Valizadeh N, Salehi F, Hosseinzadeh Maleki M
Journal of cardiac surgery. 2020
Abstract
OBJECTIVES The current study aimed to compare the benefits of topical and low-dose systemic tranexamic acid administration in pediatric cardiac surgery. METHODS A total of 117 children undergoing cardiac surgery for congenital heart disease were assigned into three groups. Patients in the systemic group received 20 mg/kg(-1) tranexamic acid through the cardiopulmonary bypass followed by another dose of 20 mg/kg(-1) after cardiopulmonary bypass separation. Patients in the topical group were administered with 50 mg/kg(-1) tranexamic acid poured into the pericardium, while the control group received no antifibrinolytics. The outcome measures of bleeding and blood products transfusion were recorded over the first 48 h postoperatively. RESULTS Chest tube drainage was significantly lower in both topical and systemic groups than the control group, but it did not differ between the case groups. Blood products requirement did not show a difference between groups. Neurological or thromboembolic events did not variate among the groups, and no deaths occurred in this study. CONCLUSION Topical or systemic tranexamic acid administration reduced postoperative blood loss effectively without adding an extra risk.