Patent hemostasis of radial artery: Comparison of two methods
World journal of cardiology. 2021;13(10):574-584
BACKGROUND Radial artery obstruction is the most common complication of coronary angiography performed via transradial access. Patent hemostasis can significantly reduce the risk of radial artery occlusion. Previous studies utilized sophisticated methods to evaluate radial artery patency. Simplified and easily applicable methods for successful patent hemostasis are currently lacking. AIM: To determine which method (pulse oximeter vs the traditional radial artery palpation) is better to achieve patent hemostasis. METHODS This prospective, single center study included 299 consecutive patients who underwent coronary angiography or percutaneous coronary intervention between November 2017 and July 2019. Patients less than 18 years old, with a history of radial artery disease, or no palpable artery pulse were excluded from the study. Patients were randomly assigned to two groups. In the first group, radial artery flow was assessed by palpation of the artery during hemostasis (traditional method). In the second group, radial artery patency was estimated with the use of a pulse oximeter. Two different compression devices were used for hemostasis (air chamber and pressure valve). The primary study endpoint was the achievement of successful patent hemostasis. RESULTS The two groups (pulse oximeter vs artery palpation) had no significant differences in age, sex, body mass index, risk factors, or comorbidities except for supraventricular arrhythmias. The percentage of patients with successful patent hemostasis was significantly higher in the pulse oximeter group (82.2% vs 68.1%, P = 0.005). A lower percentage of patients with spasm was recorded in the pulse oximeter group (9.9% vs 19.0%, P = 0.024). The incidence of local complications, edema, bleeding, hematoma, vagotonia, or pain did not differ between the two groups. In the multivariate analysis, the use of a pulse oximeter (OR: 2.35, 95%CI: 1.34-4.13, P = 0.003) and advanced age (OR: 1.04, 95%CI: 1.01-1.07, P = 0.006), were independently associated with an increased probability of successful patent hemostasis. The type of hemostatic device did not affect patent hemostasis (P = 0.450). CONCLUSION Patent hemostasis with the use of pulse oximeter is a simple, efficient, and safe method that is worthy of further investigation. Larger randomized studies are required to consider its clinical implications.
Bedside Allogeneic Erythrocyte Washing with a Cell Saver to Remove Cytokines, Chemokines, and Cell-derived Microvesicles
BACKGROUND Removal of cytokines, chemokines, and microvesicles from the supernatant of allogeneic erythrocytes may help mitigate adverse transfusion reactions. Blood bank-based washing procedures present logistical difficulties; therefore, we tested the hypothesis that on-demand bedside washing of allogeneic erythrocyte units is capable of removing soluble factors and is feasible in a clinical setting. METHODS There were in vitro and prospective, observation cohort components to this a priori planned substudy evaluating bedside allogeneic erythrocyte washing, with a cell saver, during cardiac surgery. Laboratory data were collected from the first 75 washed units given to a subset of patients nested in the intervention arm of a parent clinical trial. Paired pre- and postwash samples from the blood unit bags were centrifuged. The supernatant was aspirated and frozen at -70°C, then batch-tested for cell-derived microvesicles, soluble CD40 ligand, chemokine ligand 5, and neutral lipids (all previously associated with transfusion reactions) and cell-free hemoglobin (possibly increased by washing). From the entire cohort randomized to the intervention arm of the trial, bedside washing was defined as feasible if at least 75% of prescribed units were washed per protocol. RESULTS Paired data were available for 74 units. Washing reduced soluble CD40 ligand (median [interquartile range]; from 143 [1 to 338] ng/ml to zero), chemokine ligand 5 (from 1,314 [715 to 2,551] to 305 [179 to 488] ng/ml), and microvesicle numbers (from 6.90 [4.10 to 20.0] to 0.83 [0.33 to 2.80] × 106), while cell-free hemoglobin concentration increased from 72.6 (53.6 to 171.6) mg/dl to 210.5 (126.6 to 479.6) mg/dl (P < 0.0001 for each). There was no effect on neutral lipids. Bedside washing was determined as feasible for 80 of 81 patients (99%); overall, 293 of 314 (93%) units were washed per protocol. CONCLUSIONS Bedside erythrocyte washing was clinically feasible and greatly reduced concentrations of soluble factors thought to be associated with transfusion-related adverse reactions, increasing concentrations of cell-free hemoglobin while maintaining acceptable (less than 0.8%) hemolysis.
The synergistic effect of tranexamic acid and ethamsylate combination on blood loss in pediatric cardiac surgery
Annals of cardiac anaesthesia. 2021;24(1):17-23
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.
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.
Comparison of 4-Factor Prothrombin Complex Concentrate With Frozen Plasma for Management of Hemorrhage During and After Cardiac Surgery: A Randomized Pilot Trial
JAMA network open. 2021;4(4):e213936
IMPORTANCE Approximately 15% of patients undergoing cardiac surgery receive frozen plasma (FP) for bleeding. Four-factor prothrombin complex concentrates (PCCs) have logistical and safety advantages over FP and may be a suitable alternative. OBJECTIVES To determine the proportion of patients who received PCC and then required FP, explore hemostatic effects and safety, and assess the feasibility of study procedures. DESIGN, SETTING, AND PARTICIPANTS Parallel-group randomized pilot study conducted at 2 Canadian hospitals. Adult patients requiring coagulation factor replacement for bleeding during cardiac surgery (from September 23, 2019, to June 19, 2020; final 28-day follow-up visit, July 17, 2020). Data analysis was initiated on September 15, 2020. INTERVENTIONS Prothrombin complex concentrate (1500 IU for patients weighing ≤60 kg and 2000 IU for patients weighing >60 kg) or FP (3 U for patients weighing ≤60 kg and 4 U for patients weighing >60 kg), repeated once as needed within 24 hours (FP used for any subsequent doses in both groups). Patients and outcome assessors were blinded to treatment allocation. MAIN OUTCOMES AND MEASURES Hemostatic effectiveness (whether patients received any hemostatic therapies from 60 minutes to 4 and 24 hours after initiation of the intervention, amount of allogeneic blood components administered within 24 hours after start of surgery, and avoidance of red cell transfusions within 24 hours after start of surgery), protocol adherence, and adverse events. The analysis set comprised all randomized patients who had undergone cardiac surgery, received at least 1 dose of either treatment, and provided informed consent after surgery. RESULTS Of 169 screened patients, 131 were randomized, and 101 were treated (54 with PCC and 47 with FP), provided consent, and were included in the analysis (median age, 64 years; interquartile range [IQR], 54-73 years; 28 [28%] were female; 82 [81%] underwent complex operations). The PCC group received a median 24.9 IU/kg (IQR, 21.8-27.0 IU/kg) of PCC (2 patients [3.7%; 95% CI, 0.4%-12.7%] required FP). The FP group received a median 12.5 mL/kg (IQR, 10.0-15.0 mL/kg) of FP (4 patients [8.5%; 95% CI, 2.4%-20.4%] required >2 doses of FP). Hemostatic therapy was not required at the 4-hour time point for 43 patients (80%) in the PCC group and for 32 patients (68%) in the FP group (P = .25) nor at the 24-hour time point for 41 patients (76%) in the PCC group and for 31 patients (66%) patients in the FP group (P = .28). The median numbers of units for 24-hour cumulative allogeneic transfusions (red blood cells, platelets, and FP) were 6.0 U (IQR, 4.0-11.0 U) in the PCC group and 14.0 U (IQR, 8.0-20.0 U) in the FP group (ratio, 0.58; 95% CI, 0.45-0.77; P < .001). After exclusion of FP administered as part of the investigational medicinal product, the median numbers of units were 6.0 U (IQR, 4.0-11.0 U) in the PCC group and 10.0 U (IQR, 6.0-16.0 U) in the FP group (ratio, 0.80; 95% CI, 0.59-1.08; P = .15). For red blood cells alone, the median numbers were 1.5 U (IQR, 0.0-4.0 U) in the PCC group and 3.0 U (IQR, 1.0-5.0 U) in the FP group (ratio, 0.69; 95% CI, 0.47-0.99; P = .05). During the first 24 hours after start of surgery, 15 patients in the PCC group (28%) and 8 patients in the FP group (17%) received no red blood cells (P = .24). Adverse event profiles were similar. CONCLUSIONS AND RELEVANCE This randomized clinical trial found that the study protocols were feasible. Adequately powered randomized clinical trials are warranted to determine whether PCC is a suitable substitute for FP for mitigation of bleeding in cardiac surgery. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04114643.
Cardiac surgery patients (n= 101).
Prothrombin complex concentrate (PCC group, n= 54).
Frozen plasma (FP group, n= 47).
Haemostatic therapy was not required at the 4-hour time point for 43 patients (80%) in the PCC group and for 32 patients (68%) in the FP group, nor at the 24-hour time point for 41 patients (76%) in the PCC group and for 31 patients (66%) patients in the FP group. The median numbers of units for 24-hour cumulative allogeneic transfusions (red blood cells, platelets, and FP) were 6.0 U in the PCC group and 14.0 U in the FP group. After exclusion of FP administered as part of the investigational medicinal product, the median numbers of units were 6.0 U in the PCC group and 10.0 U in the FP group. For red blood cells alone, the median numbers were 1.5 U in the PCC group and 3.0 U in the FP group. During the first 24 hours after start of surgery, 15 patients in the PCC group (28%) and 8 patients in the FP group (17%) received no red blood cells. Adverse event profiles were similar.
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.
Retrograde autologous priming method reduces plasma free hemoglobin level in aortic surgery
Annals of cardiac anaesthesia. 2021;24(4):427-433
BACKGROUND Although conventional cardiopulmonary bypass (cCPB) is still the most widely used method in open heart surgery, methods such as retrograde autologous priming (RAP) are increasingly popular in terms of limiting hemodilution. Our hypothesis is that the use of the RAP method in aortic surgery may result in a limitation of hemodilution and a decrease in fHb levels. For this purpose, plasma free hemoglobin (fHb) levels were investigated in adult open aortic arch repair with axillary artery cannulation patients using cCPB and rRAP methods. MATERIALS AND METHODS In this study, a total of 36 patients undergoing aortic surgery using rRAP and standard cCPB were investigated. Measurements were performed at five time points: After induction of anesthesia, 5(th) minute of CPB, 10(th) minute of antegrade cerebral perfusion, 30(th) minute after declamping of aorta, and at sternum closure. Besides hemodynamic variables, arterial blood gas analysis and postoperative variables, patients were assessed for fHb levels. RESULTS The rRAP group had a significantly lower increase in fHb levels in T3, T4, and T5 time points, when compared to the cCPB group (p = 0.002, 0.047, 0.009, respectively). There was no significant difference between the rRAP and cCPB groups in other intraoperative, and postoperative variables. Also, it was observed that rRAP did not make a difference in terms of blood and blood product transfusion. CONCLUSION In this study, in patients undergoing aortic surgery, a reduction in the increase of fHb was observed with the rRAP method which is a simple procedure that does not require high cost or advanced technology.
Is there a renoprotective value to leukodepletion during heart valve surgery? A randomized controlled trial (ROLO)
Journal of cardiothoracic surgery. 2021;16(1):58
BACKGROUND Acute Kidney Injury (AKI) adversely affects outcomes after cardiac surgery. A major mediator of AKI is the activation of leukocytes through exposure to the cardiopulmonary bypass circuit. We evaluate the use of leukodepletion filters throughout bypass to protect against post-operative AKI by removing activated leukocytes during cardiac surgery. METHODS This is a single-centre, double-blind, randomized controlled trial comparing the use of leukodepletion versus a standard arterial filter throughout bypass. Elective adult patients undergoing heart valve surgery with or without concomitant procedures were investigated. The primary clinical outcome measured was the development of AKI according to the KDIGO criteria. Secondary measures included biomarkers of renal tubular damage (urinary Retinol Binding Protein and Kidney Injury Molecule-1), glomerular kidney injury (urinary Micro Albumin and serum Cystatin C) and urinary Neutrophil Gelatinase Associated Lipocalin, as well as the length of hospital stay and quality of life measures through EQ-5D-5L questionnaires. RESULTS The ROLO trial randomized 64 participants with a rate of recruitment higher than anticipated (57% achieved, 40% anticipated). The incidence of AKI was greater in the leukodepletion filter group (44% versus 23%, risk difference 21, 95% CI - 2 to 44%). This clinical finding was supported by biomarker levels especially by a tendency toward glomerular insult at 48 h, demonstrated by a raised serum Cystatin C (mean difference 0.11, 95% CI 0.00 to 0.23, p = 0.068) in the leukodepleted group. There was however no clear association between the incidence or severity of AKI and length of hospital stay. On average, health related quality of life returned to pre-operative levels in both groups within 3 months of surgery. CONCLUSIONS Leukocyte depletion during cardiopulmonary bypass does not significantly reduce the incidence of AKI after valvular heart surgery. Other methods to ameliorate renal dysfunction after cardiac surgery need to be investigated. TRIAL REGISTRATION The trial was registered by the International Standard Randomized Controlled Trial Number Registry ISRCTN42121335 . Registered on the 18 February 2014. The trial was run by the Bristol Clinical Trials and Evaluation Unit. This trial was financially supported by the National Institute of Health Research (Research for Patient Benefit), award ID: PB-PG-0711-25,090.
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.