ORIGINAL ARTICLE
Association of postoperative atrial fibrillation with higher dosing ratios of protamine-to-heparin
Yasuharu Yamada ( PhD , CCE )
1 ,* , Junzo Iemura ( MD , PhD )
2 , Atushi Kambara ( MD , PhD )
2 , Noboru Tateishi ( CCE )
3 , Yuji Kozaki ( CCE )
3 , Masako Yamada ( CCE )
4 , Junko Maruyama ( MD , PhD )
1 , and Eiichi Azuma ( MD , PhD )
1
1 Department of Clinical Engineering , Faculty of Medical Engineering , Suzuka University of Medical Science , Mie 513-8670 , Japan 2 Department of Cardiovascular Surgery , Okanami General Hospital , Mie 518-0121 , Japan 3 Division of Clinical Engineering , Okanami General Hospital , Mie 518-0121 , Japan 4 Department of Clinical Engineering , Mie University Hospital , Mie 514-0001 , Japan
Received 28 June 2022 , Accepted 29 December 2022
Abstract – Background : Postoperative atrial fibrillation ( POAF ) is defined as new-onset AF in the immediate postoperative period . The relatively high incidence of POAF after cardiac surgery is well described , but pathophysiological mechanisms underlying the initiation , maintenance , and progression of POAF may be multifactorial and have not yet been comprehensively characterized . One of the mechanisms includes altered Ca
2 + kinetics . Accumulating evidence has suggested that altered atrial cytosolic calcium handling contributes to the development of POAF , protamine reversibly modulates the calcium release channel / ryanodine receptor 2 ( RyR2 ) and voltage-dependent cardiac RyR2 . However , it is currently unknown whether such abnormalities contribute to the arrhythmogenic substrate predisposing patients to the development of POAF . Methods : We have retrospectively analyzed 147 patients who underwent cardiac surgery with cardiopulmonary bypass support . Of these , 40 patients were excluded from the analysis because of pre-existing AF . All patients received heparin followed by protamine at different dosing ratios of protamineto-heparin , depending on the periods studied . Results : The dosing ratio of protamine-to-heparin = 1.0 was compared with higher dosing ratios of protamine-to-heparin > 1.0 up to 1.7 . 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 . Statistical significance was observed in patients with higher dosing ratios of protamine-to-heparin , compared with the dosing ratio of protamine-to-heparin = 1.0 ( odds ratio = 3.890 , 95 % CI = 1.130 – 13.300 , p-value = 0.031 ). When types of diseases were analyzed in terms of higher dosing ratios of protamine-to-heparin , only valvular disorders were significantly associated with POAF ( p = 0.04 ). Conclusions : Protamine is clinically utilized to reverse heparin overdose and has been shown to display immunological and inflammatory alterations . However , its association with POAF has not been reported . Our results provide evidence that higher dosing ratios of protamine-to-heparin may increase the incidence of POAF .
Key words : Postoperative atrial fibrillation ( POAF ), Calcium , Protamine-to-heparin ratio , Cardiopulmonary bypass , Anticoagulation .
Introduction
Postoperative atrial fibrillation ( POAF ) complicates 20 – 40 % of cardiac surgical procedures [ 1 ]. Typical features include onset at 2 – 4 days postoperatively , episodes that are often fleeting , and a self-limited time course . Associated adverse consequences of POAF include hemodynamic instability , increased risk of stroke , lengthened hospital and intensive care unit stays , and greater costs [ 1 ].
* Corresponding author : yamada @ suzuka-u . ac . jp
The mechanisms of POAF are complex and incompletely defined , but include intraoperative and postoperative phenomena , such as inflammation , sympathetic activation , hypoxia , acidosis , oxidative stress , electrolyte abnormalities , and intra-atrial conduction delay that combine to trigger atrial fibrillation , often in the presence of pre-existing factors , making the atria vulnerable to atrial fibrillation induction and maintenance [ 1 , 2 ]. To prevent POAF , preoperative beta-blocker ( propranolol , carvedilol plus N-acetyl cysteine ) use is associated with a reduced incidence of postoperative AF , but not major adverse events such as death , stroke , or acute kidney injury [ 3 ]. Data for other interventions such as statins , magnesium ,
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