The Journal of ExtraCorporeal Technology Issue 55-1 | Page 33

Y . Yamada et al .: J Extra Corpor Technol 2023 , 55 , 23 – 29 25

Table 1 . Patient demographics and drug effects on POAF .

POAF , postoperative atrial fibrillation ; BMI , body mass index .

documented AF ( n = 40 ), who received anticoagulant therapy within 6 months before the open heart surgery or during the follow-up period , could not survive the open-heart procedures , and could not receive regular follow-up at the out-patient clinics were all excluded from the analysis . The definition of POAF was new-onset AF , which is sustained for over 30 s , and detected by either continuous telemetry in the intensive care unit , standard 12-lead electrocardiogram , or implanted devices . All medical records were followed until their last clinical visit , repeat cardiac surgery or death . The index date of outcomes was defined as the date of diagnosis .

Statistical analysis . All statistical analyses were performed using EZR software ( available free of charge at the website of Saitama Medical Center , Jichi Medical University , Saitama , Japan ) [ 11 ], which is a graphical user interface for the program R ( The R Foundation for Statistical Computing , Vienna , Austria ). The software is a modified version of R commander software ( version 2.4-0 ) that contains additional statistical functions frequently used in biostatistics . Results were expressed as odds ratios ( ORs ) with 95 % confidence intervals ( CIs ) from logistic regressions . Fischer ’ s exact test and chi-square test were used to analyze frequency distributions . The t-test was used to determine whether differences in the means of two sets of samples were significant . A P-value less than 0.05 was considered significant .

Results

A total of 147 patients received cardiac surgery between February 1 , 2004 , to December 13 , 2021 , of which 40 patients were excluded because of pre-existing AF . After excluding patients with pre-existing AF , a total of 107 patients were enrolled in this cohort . Table 1 reports odds ratios ( ORs ) and 95 % confidence intervals from logistic regression analysis of POAF incidence . As shown in Table 1 , statistical significance in patients with POAF was not observed in age ( 67.7 ± 12.3 vs . 69.2 ± 7.3 , p = 0.848 ), gender ( 67.4 vs . 66.7 %, p = 0.717 ), BMI ( 23.0 ± 3.8 vs . 23.2 ± 4.5 , p = 0.908 ), hypertension ( 45.7 vs . 46.7 %, p = 0.136 ), and diabetes ( 25.0 vs . 40.0 %, p = 0.426 ) in this cohort . The chances of taking antiarrhythmic agents such as beta-blockers were similar in both groups ( 42.4 vs . 46.7 %, p = 0.79 ). POAF developed in 15 patients ( 15 / 107 = 14 %), of these , 5 out of 57 patients

( 33.3 %) in the dosing ratio of protamine-to-heparin = 1.0 and 10 out of 35 patients ( 66.7 %) in the higher dosing ratios of protamine-to-heparin . Compared to individuals using dosing ratios of protamine-to-heparin > 1.0 ( up to 1.7 ), dosing ratios of protamine-to-heparin = 1.0 was associated with reduced risk of POAF ( OR = 3.890 , CI : 1.130 – 13.300 , p = 0.031 ). As shown in Table 2 , when types of diseases ( surgeries ) were analyzed in terms of higher dosing ratios of protamine-to-heparin , only valvular disorders were significantly associated with POAF ( p = 0.04 ).

Discussion

In this study , we investigated retrospectively the development of POAF after cardiac surgery , based on the recent reports concerning altered Ca ^{2 +} kinetics in POAF . As for risk factors of POAF , Yamashita et al . recently performed a systematic review and meta-analysis and identified that older age and a history of heart failure were significant risk factors for POAF whether the included studies were prospective or retrospective data sets [ 12 ]. Our clinical data suggested that higher dosing ratios of protamine-to-heparin also increased the incidence of POAF .

The advantages of unfractionated heparin are its rapid onset of action , clinical efficacy , rapid neutralization by protamine , safety , and low cost . The dose of heparin used to prevent blood clotting during cardiopulmonary bypass ( CPB ) is 300 – 400 U / kg plus additional doses to achieve and maintain an ACT of greater than 480 s [ 13 ]. Historically , an ACT target of 480 s has been considered adequate , although due to the varying measurement methods , there is often a poor correlation between different devices [ 14 ]. The individual response to a fixed dose of heparin may vary . Higher doses of heparin may result in better thrombin inhibition , thereby preserving coagulation factors on CPB . Reversing heparin with protamine should be done after separation from CPB . The appropriate dose in relation to the amount of heparin administered is critically important . A common error is to administer additional protamine with ongoing microvascular oozing in the surgical field , despite an absence of evidence that coagulopathy is related to residual heparin [ 10 , 13 ]. Furthermore , additional protamine can itself have an anticoagulant effect by impairing thrombin generation and potentiating fibrinolysis . The impact of the high protamine-to-heparin ratio on coagulation time was studied by