Yoshinobu Nakayama

Thromboelastometry-guided intraoperative haemostatic management reduces bleeding and red cell transfusion after paediatric cardiac surgery

BACKGROUND Thromboelastometric evaluation of coagulation might be useful for prediction and management of bleeding after paediatric cardiac surgery. We tested the hypothesis that the use of a thromboelastometry-guided algorithm for blood product management reduces blood loss and transfusion requirements. METHODS We studied 78 patients undergoing paediatric cardiac surgery with cardiopulmonary bypass (CPB) for the initial 12 h after operation. Stepwise multiple linear regression was used to develop an algorithm to guide blood product transfusions. Thereafter, we randomly assigned 100 patients to conventional or algorithm-guided blood product management, and assessed bleeding and red cell transfusion requirements. RESULTS CPB time, post-bypass rotational thromboelastometry (ROTEM(®)) EXTEM amplitude at 10 min (A10), and FIBTEM-A10 were independently associated with chest tube drainage volume during the initial 12 h after operation. Discriminative analysis determined cut-off values of 30 mm for EXTEM-A10 and 5 mm for FIBTEM-A10, and estimated optimal intraoperative fresh-frozen plasma and platelet concentrate transfusion volumes. Thromboelastometry-guided post-bypass blood product management significantly reduced postoperative bleeding (9 vs 16 ml kg(-1), P<0.001) and packed red cell transfusion requirement (11 vs 23 ml kg(-1), P=0.005) at 12 h after surgery, and duration of critical care stay (60 vs 71 h, P=0.014). CONCLUSIONS Rotational thromboelastometry-guided early haemostatic intervention by rapid intraoperative correction of EXTEM-A10 and FIBTEM-A10 reduced blood loss and red cell transfusion requirements after CPB, and reduced critical care duration in paediatric cardiac surgical patients. CLINICAL TRIAL REGISTRATION UMIN Clinical Trials Registry UMIN000006832 (December 4, 2011).

Fibrinogen Measurements in Plasma and Whole Blood: A Performance Evaluation Study of the Dry-Hematology System

BACKGROUND:An accurate and rapid determination of fibrinogen level is important during hemorrhage to establish a timely hemostatic intervention. The accuracy of fibrinogen measurements may be affected by the specific methodology for its determination, fluid therapies, and anticoagulant agents. The dry-hematology method (DRIHEMATO®) is a novel approach to determine fibrinogen levels in plasma and whole blood based on thrombin-activated coagulation time. We hypothesized that plasma or whole blood fibrinogen level using the dry-hematology method would be similar to those measured with conventional plasma fibrinogen assays. METHODS:Acquired hypofibrinogenemia was modeled by serial dilutions of blood samples obtained from 12 healthy volunteers. Citrated whole blood samples were diluted with either normal saline, 5% human albumin, or 6% hydroxyethyl starch to achieve 25%, 50%, and 75% volume replacement. The dry-hematology method, the Clauss method, the prothrombin time (PT)-derived method, determination of antigen levels, and thromboelastometric fibrin formation were compared in plasma or whole blood samples. The effect of heparin on each assay was examined (0 to 6 IU/mL). Comparisons of dry-hematology and other methods were also conducted using ex vivo samples obtained from cardiac surgical patients (n = 60). RESULTS:In plasma samples, there were no significant differences between dry-hematology and the Clauss method, while dry-hematology showed lower fibrinogen levels compared with PT-derived and antigen level methods. The dry-hematology method yielded acceptable concordance correlation coefficients (Pc) with the Clauss method, the PT-derived method, and fibrinogen antigen levels (Pc = 0.91–0.99). The type of diluents and heparin affected the results of the PT-derived method and thromboelastometric assay, but not the dry-hematology method. In cardiac surgical patients, the overall correlation in fibrinogen levels between dry-hematology and the other methods was comparable to the results from in vitro dilution experiments. The dry-hematology reported higher fibrinogen values in whole blood compared with those measured in plasma samples, but hematocrit adjustment decreased the bias between whole blood and plasma samples from 73 mg/dL (95% prediction interval: 40, 106) to −13 mg/dL (95% prediction interval: −35, 8.5). CONCLUSIONS:This study demonstrated that fibrinogen levels can be accurately assessed by the dry-hematology method in plasma and the results are not affected by heparin or colloids. For whole blood fibrinogen measurements by dry-hematology, hematocrit adjustment is necessary to compensate for dynamic changes in hematocrit in perioperative bleeding settings.

A novel method for ultrasound-guided radial arterial catheterization in pediatric patients.

BACKGROUND:Radial arterial catheterization in pediatric patients is occasionally difficult despite ultrasound guidance. We therefore assessed the factors affecting catheterization and tested an intervention designed to improve its success. METHODS:For initial assessment, we performed multiple logistic regression analyses using 102 pediatric patients. Dependent variables included first-attempt and overall success or failure; independent variables were systolic blood pressure, weight, ASA physical status, trisomy 21, arterial diameter, and subcutaneous depth of the radial artery (<2, 2–4, ≥4 mm). The effect of subcutaneous arterial depth on cannulation success was assessed using Kaplan-Meier curves with log-rank and Dunn tests. We then assessed catheterization success in 60 patients who were randomized to no treatment or subcutaneous saline injection, as necessary, to increase the subcutaneous arterial depth from <2 to 2 to 4 mm. RESULTS:Subcutaneous arterial depth of 2 to 4 mm was derived as a significant independent predictor of initial and overall success from the multiple logistic regression analyses. The 2 to 4 mm group had a significantly shorter catheterization time compared with the other 2 groups in the log-rank test (2–4 vs <2 mm group; P = 0.01, 2–4 vs ≥4 mm group; P < 0.001), and higher success rate in the first attempt (<2 [43.8%] vs 2–4 mm [76.9%], P = 0.02; 2–4 [76.9%] vs ≥4.0 mm [19.4%], P < 0.001), and the overall attempt (<2 [62.5%] vs 2–4 mm [89.7%], P = 0.04; 2–4 [89.7%] vs ≥4.0 mm [51.6%], P = 0.002). Injecting subcutaneous saline to bring arterial depth from <2 mm to 2 to 4 mm significantly shortened catheterization time (P = 0.002), and improved the success rate in the first-attempt (saline injection [85.0%] vs <2 mm [30.0%], P < 0.001), and the overall attempt (saline injection [90.0%] vs <2 mm [55.0%], P = 0.02). CONCLUSIONS:Ultrasound-guided radial artery catheterization in pediatric patients was fastest and most reliable when the artery was 2 to 4 mm below the skin surface. For arteries located <2 mm below the skin surface, increasing the depth to 2 to 4 mm by subcutaneous saline injection reduced catheterization time and improved the success rate.

Anomalous Origin of Left Coronary Artery from Aortic Arch Associated with HLHS

Anomalous origin of the coronary artery from the aortic arch associated with hypoplastic left heart syndrome is an extremely rare anomaly. Coronary anomalies can significantly deteriorate the clinical outcomes of hypoplastic left heart syndrome. We describe the case of a newborn with concomitant hypoplastic left heart syndrome and abnormal origin of the left coronary artery arising from the distal aortic arch.

Potential contribution of erythrocyte microRNA to secondary erythrocytosis and thrombocytopenia in congenital heart disease

BackgroundChildren with cyanotic heart disease develop secondary erythrocytosis and thrombocytopenia via unknown mechanisms. Mature erythrocyte microRNAs may reflect clinical pathologies and cell differentiation processes pre-enucleation. This study evaluated erythrocyte microRNAs in children with cyanotic heart disease.MethodsErythrocyte microRNAs from children with cyanotic and acyanotic heart disease and without cardiac disease were quantified with Ion PGM System (n=10 per group). Differential expression was confirmed by quantitative PCR (qPCR; n=20 per group).ResultsMir-486-3p, mir-486-5p, and mir-155-5p increased in patients with cyanotic heart disease compared with those without heart disease: fold differences (95% confidence interval): mir-486-3p: 1.92 (1.14–3.23), P=0.011; mir-486-5p: 2.27 (1.41–3.65), P<0.001; and mir-155-5p: 1.44 (1.03–2.03), P=0.028. Mir-486-5p was increased, and let-7e-5p and mir-1260a were decreased in patients with acyanotic heart disease compared with those without heart disease: mir-486-5p: 1.66 (1.03–2.66), P=0.035; let-7e-5p: 0.66 (0.44–0.99), P=0.049; and mir-1260a: 0.53 (0.29–0.99), P=0.045.ConclusionSeveral microRNA levels changed in children with cyanotic and acyanotic heart disease. Mir-486-3p and -5p are associated with hematopoietic differentiation. Mir-486-3p regulates the erythroid vs. megakaryocyte lineage fate decision. Mir-155 is a hypoxia-inducible microRNA, whose overexpression inhibits megakaryocyte differentiation. Erythrocyte microRNA expression changes may contribute to erythrocytosis and thrombocytopenia in children with cyanotic heart disease.

A Comparative Study of Point-of-Care Prothrombin Time in Cardiopulmonary Bypass Surgery

OBJECTIVE Point-of-care (POC) devices allow for prothrombin time/international normalized ratio (PT/INR) testing in whole blood (WB) and timely administration of plasma or prothrombin complex concentrate during cardiopulmonary bypass surgery. This study evaluated the sensitivities of a new POC PT test, a dry-hematology method with heparin neutralization technology (DRIHEMATO PT-S [DRI PT-S]; A&T Corporation, Kanagawa, Japan), and compared it with other POC tests currently available. DESIGN Prospective, observational study. SETTING University hospital, single center. PARTICIPANTS Healthy volunteers and warfarin-treated and cardiac surgical patients. MEASUREMENT AND MAIN RESULTS In WB samples obtained from 6 healthy volunteers, PT-INR results of DRI PT-S were not affected by an in vitro addition of heparin <6.0 U/mL. In warfarin-treated samples (n = 88, PT/INR 0.98-3.87), PT-INR with DRI PT-S showed acceptable correlation with the laboratory method (r2 = 0.85, p < 0.001). In blood samples obtained from cardiac surgical patients (n = 72), heparin prolonged the PT/INR with the laboratory assay, dry-hematology method with non heparin neutralization technology (DRI PT), Coaguchek XS (Roche Diagnostics, Basel, Switzerland), and Hemochron Jr. (Accriva Diagnostics, Edison, NJ), but DRI PT-S was not affected by heparin anticoagulation. In nonheparinized samples, different methods between DRI PT-S and the laboratory method yielded acceptable correlations (r2 = 0.76, p < 0.0001). There was a moderate correlation between factor levels and the PT-INR with DRI PT-S (factor [F]II: r2 = 0.63, FVII: r2 = 0.47, FX: r2 = 0.67; p < 0.0001). CONCLUSIONS This study demonstrated that PT/INR can be accurately assessed using the dry-hematology method in WB under therapeutic heparin levels. Currently available other POC PT/INR tests are affected by heparin, and thus they are not recommended for coagulation monitoring during cardiopulmonary bypass.

Difficult tracheal intubation and post-extubation airway stenosis in an 11-month-old patient with unrecognized subglottic stenosis: a case report

BackgroundSubglottic stenosis can lead to life-threatening difficult tracheal intubation during general anesthesia. We report a case of difficult tracheal intubation in an 11-month-old female who had unrecognized subglottic stenosis.Case presentationThe patient was scheduled for elective correction of a right accessory auricle. She was suspected of having first and second branchial arch syndrome. Preoperative physical examination was normal. Anesthesia was induced uneventfully using sevoflurane. It was not possible to pass size 4.0, 3.5, or 3.0 cuffed endotracheal tubes due to an advanced subglottic lesion. Subsequent successful intubation was achieved using a 3.0 uncuffed tube. Stridor was audible after extubation, and the patient required several days’ treatment with dexamethasone to address respiratory distress.ConclusionsWe encountered unrecognized subglottic stenosis that led to difficult tracheal intubation and post-extubation airway stenosis.

Changes in platelet Bax levels contribute to impaired platelet response to thrombin after cardiopulmonary bypass: Prospective observational clinical and laboratory investigations

Background Anucleate platelets can undergo apoptosis in response to various stimuli, as do nucleated cells. Cardiopulmonary bypass (CPB) causes platelet dysfunction and can also activate platelet apoptotic pathways. We therefore evaluated time-dependent changes in blood platelet Bax (a pro-apoptotic molecule) levels and platelet dysfunction after cardiac surgery. Methods We assessed blood samples obtained from subjects having on-pump or off-pump coronary artery bypass graft surgery ( n =20 each). We also evaluated the in vitro effects of platelet Bax increase in eight healthy volunteers. Results Thrombin-induced platelet calcium mobilisation and platelet-surface glycoprotein Ib (GPIb) expression were lowest at weaning from CPB and did not recover on postoperative day one. On-pump surgery increased platelet expression of Bax, especially the oligomerised form, along with translocation of Bax from the cytosol to mitochondria and platelet-surface tumour necrosis factor-alpha (TNF-α)-converting enzyme (TACE) expression. In contrast, mitochondrial cytochrome c expression was reduced. While similar in direction, the magnitude of the observed changes was smaller in patients having off-pump surgery. In vitro , a cell-permeable Bax peptide increased platelet Bax expression to the same extent seen during bypass and produced similar platelet changes. These apoptotic-like changes were largely reversed by Bcl-xL pre-administration, and were completely reversed by combined application of inhibitors that stabilise outer mitochondrial membrane permeability and TACE. Conclusions CPB increases platelet Bax expression, which contributes to reduced platelet-surface GPIb expression and thrombin-induced platelet calcium changes. These changes in platelet apoptotic signalling might contribute to platelet dysfunction after CPB. Clinical trial registration UMIN Clinical Trials Registry (number UMIN000006033).

Management of Anesthesia under Extracorporeal Cardiopulmonary Support in an Infant with Severe Subglottic Stenosis.

A 4-month-old female infant who weighed 3.57 kg with severe subglottic stenosis underwent tracheostomy under extracorporeal cardiopulmonary support. First, we set up extracorporeal cardiopulmonary support to the infant and then successfully intubated an endotracheal tube with a 2.5 mm inner diameter before tracheostomy by otolaryngologists. Extracorporeal cardiopulmonary support is an alternative for maintenance of oxygenation in difficult airway management in infants.

A Practical Training Program for Peripheral Radial Artery Catheterization in Adult Patients: A Prospective, Randomized Controlled Trial.

Background:The main cause of unsuccessful peripheral radial artery catheterization using traditional palpation is imprecisely locating the arterial center. The authors evaluated factors causing disparities between the arterial centers determined by palpation versus ultrasound. The authors applied them to create and test a novel catheterization training program. Methods:The arterial central axis was determined by ultrasound and palpation in 350 adults. Potential independent predictors of disparity included sex, body mass index, pulse pressure, transverse arterial diameter, subcutaneous arterial depth, chronic hypertension, and experience as an anesthesiologist (less than 3 vs. greater than or equal to 3 yr). Using the results, the authors developed a radial artery catheterization training program. It was tested by enrolling 20 first-year interns, randomized to a training or control group. The time to successful insertion was the primary outcome measure. The success rate and time required for catheterization by palpation were evaluated in 100 adult patients per group. Results:Independent predictors of central axis disparity were pulse pressure, subcutaneous radial artery depth, years of experience, and chronic hypertension. Training improved the catheterization time (training group 56 ± 2 s vs. control group 109 ± 2 s; difference –53 ± 3 s; 95% CI, –70 to –36 s; P < 0.0001) and total success rate (training group 83 of 100 attempts, 83%; 95% CI, 75 to 90 vs. control group 57 of 100, 57%; 95% CI, 47 to 66; odds ratio, 3.7; 95% CI, 2.7 to 5.1). Conclusions:Misjudging the central axis position of the radial artery is common with a weak pulse and/or deep artery. The authors’ program, which focused on both these issues, shortened the time for palpation-guided catheterization and improved success.