Comparison of fibrin sealants in peripheral vascular surgery: A systematic review and network meta-analysis
Annals of medicine and surgery (2012). 2021;61:161-168
BACKGROUND Evidence comparing fibrin sealants (FSs) in surgery are limited. This study evaluated the efficacy and safety of FSs, and manual compression in peripheral vascular surgery. METHODS A systematic review of randomized trials was conducted in Medline, Embase, and Cochrane databases within the last 15 years. Data were available to conduct a network meta-analysis (NMA) in peripheral vascular surgery. Fibrin sealant treatment arms were further broken-down and assessed by clotting time (i.e., 2-min [2C] or 1-min [1C]). The primary efficacy outcome was the proportion of patients achieving hemostasis by 4 min (T4). Treatment-related serious and non-serious adverse events (AEs) were qualitatively assessed. RESULTS Five studies (n = 693), were included in the NMA. Results predicted VISTASEAL 2C, followed by EVICEL 1C, had the highest probability of achieving T4. Compared with manual compression, significant improvements in T4 were found with VISTASEAL 2C (relative risk [RR] = 2.67, 95% CrI: 2.13-3.34), EVICEL 1C (RR = 2.58, 95% CrI: 2.04-3.23), VISTASEAL 1C (RR = 2.00, 95% CrI: 1.45-2.65), and TISSEEL 2C (RR = 1.99, 95% CrI: 1.48-2.60). TISSEEL 1C was not significantly different than manual compression (RR = 1.40, 95% CrI: 0.70-2.33). Among FSs, VISTASEAL 2C was associated with a significant improvements in T4 compared with VISTASEAL 1C (RR = 1.33, 95% CrI: 1.02-1.82), TISSEEL 2C (RR = 1.34, 95% CrI: 1.05-1.77), and TISSEEL 1C (RR = 1.90, 95% CrI: 1.18-3.74). Treatment-related serious and non-serious AE rates were typically lower than 2%. CONCLUSIONS In peripheral vascular surgeries, VISTASEAL 2C and EVICEL 1C were shown to have the highest probabilities for achieving rapid hemostasis among the treatments compared. Future studies should expand networks across surgery types as data become available.
Effects of Isovolumic Hemodilution and Platelet-Rich Plasma Separation on Platelet Activation State and Function, Complications, and Inflammation in Patients Undergoing Cardiac Surgery
Clinical laboratory. 2021;67(1)
BACKGROUND To explore the effects of isovolumic hemodilution and platelet-rich plasma separation on platelet activation state and function, complications, and inflammation in patients undergoing cardiac surgery. METHODS A total of 80 patients who needed cardiac surgery under extracorporeal circulation from February 2018 to December 2019 in our hospital were selected as research subjects and divided into observation group (n = 40) and control group (n = 40) according to the random number table method. The patients in the observation group underwent platelet-rich plasma separation, while those in control group received acute isovolumic hemodilution. Then the platelet activation state and functional indexes, hemorheological indexes, and the coagulation functional indexes were compared between the two groups of patients before operation. Next, the changes in the levels of hemoglobin and high-sensitivity C-reactive protein (hs-CRP), an inflammatory factor, during blood protection (before and at 6 hours and 12 hours after intervention) were analyzed. Moreover, the dosage of blood products during operation was compared between the two groups, and postoperative complications and recovery in the two groups were statistically assessed. RESULTS Before operation, the platelet adherence rate and aggregation rate in the observation group were significantly higher than those in control group (p < 0.05), while R and K values in thromboelastograms in the former were notably smaller than those in the latter (p < 0.05). Meanwhile, the whole blood low-shear viscosity, whole blood high-shear viscosity, and plasma viscosity in observation group were remarkably lower than those in control group (p < 0.05). In addition, the observation group exhibited shorter prothrombin time (PT), thrombin time (TT), and activated partial thromboplastin time (APTT) (p < 0.05) and a higher fibrinogen (Fib) level (p < 0.05) than the control group. At 6 hours and 12 hours after intervention and before operation, the hemoglobin level in observation group was markedly higher than that in control group (p < 0.05). In addition, the dosages of red blood cells, fresh frozen plasma, and platelets among blood products during operation in the observation group were evidently lower than those in the control group (p < 0.05), and the number of cases of hemorrhage, pulmonary infection, coagulation dysfunction, and paraplegia after operation in the former was distinctly smaller than that in the latter (p < 0.05). Furthermore, the observation group had an obviously smaller postoperative 24 hours drainage volume (p < 0.05) as well as shorter postoperative mechanical ventilation time and ICU treatment time than control group (p < 0.05). CONCLUSIONS For patients undergoing cardiac surgery under extracorporeal circulation, platelet-rich plasma separation and reinfusion technology can effectively ensure platelet activation state and function, reduce blood viscosity, ensure stable coagulation function, elevate hemoglobin level and decrease inflammatory reaction, and perioperative allogeneic blood infusion, with fewer adverse reactions in treatment, thus efficaciously facilitating the post-operative recovery of patients.
Factor VIII inhibitor bypass activity (FEIBA) for the reduction of transfusion in cardiac surgery: a randomized, double-blind, placebo-controlled, pilot trial
Pilot and feasibility studies. 2021;7(1):137
BACKGROUND Uncontrolled bleeding after cardiac surgery can be life-threatening. Factor eight inhibitor bypassing activity (FEIBA) is a prothrombin complex concentrate empirically used as rescue therapy for correction of refractory bleeding diathesis post-cardiopulmonary bypass (CPB). FEIBA used as rescue therapy for bleeding diathesis after CPB has been associated with a low incidence of complications and a reduction in transfusion requirement and re-exploration. The feasibility and efficacy of early administration of FEIBA after the termination of CPB have not been studied in a prospective randomized trial. METHODS We designed a small randomized, double-blinded, placebo-controlled pilot trial to determine the feasibility of a larger trial testing the hypothesis that FEIBA decreases transfusion requirements after CPB. The study was designed to evaluate the feasibility of a larger pivotal trial to determine the effectiveness of FEIBA in reducing the total volume of blood products transfused perioperatively, and its safety profile. Study participants were adult patients undergoing elective major aortic cardiovascular surgery at a tertiary referral hospital, who were equally randomized to receive a single dose of either FEIBA or matched placebo intraoperatively at the end of CPB. RESULTS Twenty patients were screened and 12 were randomized and included in the analysis. Protocol adherence was high, and all patients received the study drug per intention-to-treat except one patient. There were no protocol deviations or events of unblinding, and adverse events were not different between groups. Patients in the FEIBA group were older and more likely to be female and had higher BMI, lower hematocrit, and longer hypothermic circulatory arrest. There were no differences in post-randomization blood product transfusions (difference FEIBA vs. placebo -899 mL; 95% CI -5206 to 3409) or in the administration of open-label FEIBA. CONCLUSIONS This pilot trial confirmed the adequacy of the trial design that involved the early, blinded administration of FEIBA, by demonstrating excellent protocol adherence. We conclude that a larger trial establishing the effectiveness of early prothrombin complex concentrate administration to reduce the use of blood products in the setting of high-risk cardiac surgery is feasible. TRIAL REGISTRATION ClinicalTrials.gov, NCT02577614 . Registered 16 October 2015.
Primary nursing intervention can improve the prognosis and postoperative quality of life of patients with hypertensive intracerebral hemorrhage undergoing minimally invasive surgery
American journal of translational research. 2021;13(4):2955-2961
OBJECTIVE This study aimed to explore the role of primary nursing in patients with hypertensive intracerebral hemorrhage (HICH) undergoing minimally invasive surgery. METHODS We randomly assigned 106 patients with HICH treated in our hospital to receive routine nursing (54 cases, group A) or primary nursing in addition to routine nursing (52 cases, group B). The scores of negative emotions, incidence of complications, quality of life, and prognosis of all patients were recorded. RESULTS The score of negative emotions and the incidence of complications were lower in group B than in group A (P < 0.05). The scores of quality of life and prognosis were higher in group B than in group A (P < 0.05). CONCLUSION Primary nursing intervention can improve the prognosis and postoperative quality of life of patients with HICH undergoing minimally invasive surgery.
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.
Intravenous iron supplement for iron deficiency in cardiac transplant recipients (IronIC): A randomized clinical trial
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2021
AIMS: Heart transplant recipients have reduced exercise capacity despite preserved graft function. The IronIC trial was designed to test the hypothesis that intravenous iron therapy would improve peak oxygen consumption in these patients. METHODS AND RESULTS This randomized, placebo-controlled, double-blind trial was performed at our national center for heart transplantation. One hundred and 2 heart transplant recipients with a serum ferritin <100 µg/liter or 100 to 300 µg/liter, in combination with transferrin saturation of <20%, and hemoglobin level >100 g/liter were enrolled ≥1 year after transplantation. A cardiopulmonary exercise test was performed before administration of the study drug and at 6 months follow-up. The primary endpoint was peak oxygen consumption. Key secondary outcomes included iron status, handgrip strength, quality of life, and safety. Fifty-two patients were randomized to receive ferric derisomaltose 20 mg/kg, and 50 to placebo. The between-group difference in baseline-adjusted peak oxygen consumption was 0.3 ml/kg/min (95% confidence interval -0.9 to 1.4, p = 0.66). In patients with a baseline ferritin <30 µg/liter, peak oxygen consumption was significantly higher in the ferric derisomaltose arm. At 6 months, iron stores were restored in 86% of the patients receiving ferric derisomaltose vs 20% in patients receiving placebo (p < 0.001). Quality of life was significantly better in patients receiving ferric derisomaltose. Twenty-seven adverse events occurred in the intravenous iron group vs 30 in the placebo group (p = 0.39). CONCLUSION Intravenous iron treatment did not improve peak oxygen consumption in heart transplant recipients with ferritin <100 µg/liter or 100 to 300 µg/liter in combination with transferrin saturation <20%. TRIAL REGISTRATION NUMBER http//www.clinicaltrials.gov identifier NCT03662789.
Randomized trial comparing radial hemostasis techniques; catechol conjugated chitosan pad (InnoSEAL) versus pneumatic compression band
Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions. 2021
OBJECTIVES Primary objectives: to compare radial artery occlusion rate (RAO) after cardiac catheterization between catecholamine-chitosan pad (InnoSEAL) and pneumatic compression device (PCD) and to compare difference in hemostasis time and radial monitoring termination time between two arms. Secondary objectives: to compare radial site bleeding and ease of use of two methods by cath-lab technicians. BACKGROUND Hemostatic pads may be an effective alternative to PCD with lesser chance of access site complications with advantage of shortened compression time. METHODS Patients (N = 606) undergoing trans-radial, diagnostic or interventional procedures were randomized to either InnoSEAL arm or PCD. RAO was assessed using US Duplex; performed 6-24 hr posthemostatic device removal. Time to hemostasis was recorded as per defined protocols. Ease of use among cath-lab technicians was assessed through 5 point Likert scale. RESULTS Data of 597 patients was analyzed (299 InnoSEAL, 298 PCD). RAO rate was 8.5% in InnoSEAL and 9.4% in PCD arm (p value >.05). The pooled median hemostasis time and time to termination of radial monitoring was 42 versus 225 min and 50 versus 240 min in InnoSEAL and PCD arms, respectively (p value: <.01). There was no difference in Grade I/II hematoma (InnoSEAL: 1.3% vs. PCD: 3.4%). InnoSEAL was marginally acceptable compared to PCD by technicians. CONCLUSION Hemostasis time is significantly shorter in InnoSEAL arm with reasonable acceptability to its usage among cath lab staff. RAO and bleeding complications are comparable between the arms. Based on our findings, it seems feasible to include Chitosan based hemostasis pad routinely in cath lab.
Bleeding in the Elderly: Risk Factors and Impact on Clinical Outcomes After an Acute Coronary Syndrome, a Sub-study of the Randomized ANTARCTIC Trial
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2021
BACKGROUND Elderly patients are at high-risk of bleeding, but are under-represented in clinical trials. OBJECTIVES The aims were to determine the incidence and the predictive factors of bleeding and to assess the impact of bleeding on further ischemic outcomes in elderly patients after acute coronary syndrome (ACS) treated with percutaneous coronary intervention. METHODS From the 877 patients aged ≥ 75 years included in the ANTARCTIC randomized trial, data on Bleeding Academic Research Consortium (BARC) bleeding complications and major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, myocardial infarction, and stroke, were collected over 1 year. RESULTS Clinically relevant bleeding events (BARC types 2, 3, or 5) were observed in 20.6% of patients (n = 181) at 1 year, of which, one third occurred in the first month. Anemia (adjusted hazard ratio [adj.HR] 3.98, 95% confidence interval [CI] 1.41-11.22; p = 0.009), severe chronic renal failure (adj.HR 1.83, 95% CI 1.12-2.98; p = 0.015), and femoral access (adj.HR 2.54, 95% CI 1.71-3.77; p < 0.001) were independently associated with clinically relevant bleeding events, while age > 85 years (adj.HR 2.22, 95% CI 1.14-4.30; p = 0.018) was independently associated with major bleeding events (BARC types 3 or 5). Patients with a clinically relevant bleeding event had a higher rate of MACE at 1 year (adj.HR 2.04, 95% CI 1.24-3.38; p = 0.005), with a particularly strong effect on stroke (adj.HR 5.55, 95% CI 2.04-15.06; p < 0.001). CONCLUSIONS Clinically relevant bleeding events were observed in one out of five elderly patients undergoing stenting for an ACS and were strongly associated with further stroke occurrence. Rather than the antiplatelet therapy, comorbidities and an age > 85 years predicted bleeding outcomes in this elderly population. CLINICAL TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT01538446. https://www.clinicaltrials.gov .
Comparison of the Effects of Ringer's Lactate and 6% Hydroxyethyl Starch 130/0.4 on Blood Loss and Need for Blood Transfusion After Off-Pump Coronary Artery Bypass Graft Cardiac Surgery
Background Infusion of crystalloids fluid replacement therapy tends to cause a greater expansion of intravascular volume. However, colloids can affect blood coagulation leading to greater blood loss and transfusion requirements. This study compared the intraoperative and postoperative blood loss with Ringer's lactate (RL) versus 6% hydroxyethyl starch (HES) 130/0.4 as infusion fluid during cardiac surgery. Methods Eighty adult male and female patients undergoing elective cardiac surgery were randomly assigned to receive either RL or 6% HES 130/0.4 20 ml/kg during off-pump coronary artery bypass graft (OP-CABG) surgery. Intraoperative blood loss and 24 hours postoperative chest tube drainage were the primary outcomes. Simultaneously, blood transfusions, thromboelastometry variables, total fluid requirement, renal function, and intensive care unit (ICU) stay were assessed. Results The intraoperative blood loss was similar (p > 0.05) with HES (716 ml) and RL (658 ml). Postoperative chest tube drainage was higher (p < 0.05) with HES (513 ml) as against RL (449 ml). The total fluid requirement was higher in the RL group. Alteration of thromboelastometry variables, renal function, and ICU stay was comparable between the two groups. Postoperative chest tube drainage was less with the use of RL during cardiac surgery. A lesser total fluid requirement in the HES group did not lead to any improvement in renal function and the length of ICU stay. Conclusions Crystalloids (RL) provide similar outcomes to HES and can be used as substitutes to colloids during cardiac surgery. However, further large-scale multicenter studies with varied indications can be suggested to substantiate the equivalence of crystalloids to colloids in perioperative management.
The effect of intravenous ferric carboxymaltose on cardiac reverse remodelling following cardiac resynchronization therapy-the IRON-CRT trial
European heart journal. 2021
AIMS: Iron deficiency is common in heart failure with reduced ejection fraction (HFrEF) and negatively affects cardiac function and structure. The study the effect of ferric carboxymaltose (FCM) on cardiac reverse remodelling and contractile status in HFrEF. METHODS AND RESULTS Symptomatic HFrEF patients with iron deficiency and a persistently reduced left ventricular ejection fraction (LVEF <45%) at least 6 months after cardiac resynchronization therapy (CRT) implant were prospectively randomized to FCM or standard of care (SOC) in a double-blind manner. The primary endpoint was the change in LVEF from baseline to 3-month follow-up assessed by three-dimensional echocardiography. Secondary endpoints included the change in left ventricular end-systolic (LVESV) and end-diastolic volume (LVEDV) from baseline to 3-month follow-up. Cardiac performance was evaluated by the force-frequency relationship as assessed by the slope change of the cardiac contractility index (CCI = systolic blood pressure/LVESV index) at 70, 90, and 110 beats of biventricular pacing. A total of 75 patients were randomized to FCM (n = 37) or SOC (n = 38). At baseline, both treatment groups were well matched including baseline LVEF (34 ± 7 vs. 33 ± 8, P = 0.411). After 3 months, the change in LVEF was significantly higher in the FMC group [+4.22%, 95% confidence interval (CI) +3.05%; +5.38%] than in the SOC group (-0.23%, 95% CI -1.44%; +0.97%; P < 0.001). Similarly, LVESV (-9.72 mL, 95% CI -13.5 mL; -5.93 mL vs. -1.83 mL, 95% CI -5.7 mL; 2.1 mL; P = 0.001), but not LVEDV (P = 0.748), improved in the FCM vs. the SOC group. At baseline, both treatment groups demonstrated a negative force-frequency relationship, as defined by a decrease in CCI at higher heart rates (negative slope). FCM resulted in an improvement in the CCI slope during incremental biventricular pacing, with a positive force-frequency relationship at 3 months. Functional status and exercise capacity, as measured by the Kansas City Cardiomyopathy Questionnaire and peak oxygen consumption, were improved by FCM. CONCLUSIONS Treatment with FCM in HFrEF patients with iron deficiency and persistently reduced LVEF after CRT results in an improvement of cardiac function measured by LVEF, LVESV, and cardiac force-frequency relationship.