Browsing by Subject "Cardiopulmonary Bypass"
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Item Open Access Activated Coagulation Time and Hepcon Protamine Titration Device to Manage Unfractionated Heparin During Cardiopulmonary Bypass in a Hemophilia A Patient on Emicizumab.(Journal of cardiothoracic and vascular anesthesia, 2021-11) Isaacs, James; Welsby, Ian J; Schroder, Jacob N; Onwuemene, Oluwatoyosi AIn the perioperative management of patients with hemophilia A, emicizumab prevents the accurate measurement of common clotting assays, including the activated clotting time (ACT), which is essential for high-dose heparin monitoring during cardiopulmonary bypass surgery. The authors describe the successful perioperative management of a hemophilia A patient on maintenance emicizumab who, following a non-ST myocardial infarction, underwent cardiopulmonary bypass grafting surgery with heparin monitoring using both the ACT and heparin levels from the Hepcon protamine titration device. Postoperatively, the patient was transitioned to recombinant factor VIII replacement therapy. In hemophilia A patients on emicizumab who require heparin titration on cardiopulmonary bypass surgery, the ACT, combined with Hepcon heparin levels, may be used to complete the surgery successfully without excessive bleeding or morbidity.Item Open Access Aprotinin improves functional outcome but not cerebral infarct size in an experimental model of stroke during cardiopulmonary bypass.(Anesthesia and analgesia, 2010-07) Homi, H Mayumi; Sheng, Huaxin; Arepally, Gowthami M; Mackensen, G Burkhard; Grocott, Hilary PBackground
Aprotinin, a nonspecific serine protease inhibitor, has been used to decrease bleeding and reduce the systemic inflammatory response after cardiopulmonary bypass (CPB). Studies have variably linked aprotinin administration with both improved as well as adverse cerebral consequences after cardiac surgery. We designed this study to determine whether an antiinflammatory dose of aprotinin could improve the histologic and functional neurologic outcome in a rat model of focal cerebral ischemia during CPB.Methods
After surgical preparation, the animals were randomized into 2 groups: an aprotinin group (60,000 kIU/kg IV) and a control group (0.9% NaCl IV). Normothermic CPB was performed for 60 minutes during which time a partial overlapping 60 minutes of right middle cerebral artery occlusion was induced. Cytokines (tumor necrosis factor-alpha, interleukin [IL]-1beta, IL-6, and IL-10) were measured at baseline, the end of CPB, then 2 and 24 hours after CPB. On postoperative day 3, the animals underwent functional neurologic testing and histologic assessment of cerebral infarct volume.Results
There was a reduction in systemic inflammation in the aprotinin group compared with the control group, demonstrated by lower levels of IL-1beta (P = 0.035) and IL-6 (P = 0.047). The aprotinin group also had a better functional neurologic performance (median [interquartile range]: aprotinin 27 [8] vs control 32 [6]; P = 0.042). However, there was no difference in cerebral infarct volume (aprotinin 306 [27] mm(3) vs control 297 [52] mm(3); P = 0.599).Conclusions
In this experimental model of stroke occurring during CPB, aprotinin decreased the systemic inflammatory response to CPB. Although there was no difference in the cerebral infarct volume, there was a small improvement in the short-term functional neurologic outcome in the aprotinin group.Item Open Access Clinical outcomes of cardiac surgery patients undergoing therapeutic plasma exchange for heparin-induced thrombocytopenia.(Vox sanguinis, 2021-02) Moreno-Duarte, Ingrid; Cooter, Mary; Onwuemene, Oluwatoyosi A; Ghadimi, Kamrouz; Welsby, Ian JBackground and objectives
Heparin-induced thrombocytopenia (HIT) is an antibody-mediated condition that leads to thrombocytopenia and possible thrombosis. Patients with HIT who require cardiac surgery pose a challenge as high doses of heparin or heparin alternatives are required to permit cardiopulmonary bypass (CPB). Intraoperative therapeutic plasma exchange (TPE) is a valuable adjunct in the management of antibody-mediated syndromes including HIT. The clinical impact of TPE on thromboembolic events, bleeding and mortality after heparin re-exposure is not well established. We hypothesized that TPE with heparin re-exposure will not lead to HIT-related thromboembolic events, bleeding or increased mortality after cardiac surgery with CPB.Materials and methods
We reviewed 330 patients who received perioperative TPE between September 2012 and September 2017.Results
Twenty four patients received TPE for HIT before anticipated heparin use for CPB. Most patients were males (79%) scheduled for advanced heart failure therapies. Three patients (12·5%) died within 30 days after surgery but none of the deaths were considered HIT-related. Thromboembolic events (TE) occurred in 3 patients within 7 days of surgery; of those, two were possibly HIT-related.Conclusion
Therapeutic plasma exchange with heparin re-exposure was not strongly associated with HIT-related thrombosis/death after cardiac surgery with CPB.Item Open Access Conventional Ultrafiltration During Elective Cardiac Surgery and Postoperative Acute Kidney Injury.(Journal of cardiothoracic and vascular anesthesia, 2021-05) Manning, Michael W; Li, Yi-Ju; Linder, Dean; Haney, John C; Wu, Yi-Hung; Podgoreanu, Mihai V; Swaminathan, Madhav; Schroder, Jacob N; Milano, Carmelo A; Welsby, Ian J; Stafford-Smith, Mark; Ghadimi, KamrouzObjective
Conventional ultrafiltration (CUF) during cardiopulmonary bypass (CPB) serves to hemoconcentrate blood volume to avoid allogeneic blood transfusions. Previous studies have determined CUF volumes as a continuous variable are associated with postoperative acute kidney injury (AKI) after cardiac surgery, but optimal weight-indexed volumes that predict AKI have not been described.Design
Retrospective cohort.Setting
Single-center university hospital.Participants
A total of 1,641 consecutive patients who underwent elective cardiac surgery between June 2013 and December 2015.Interventions
The CUF volume was removed during CPB in all participants as part of routine practice. The authors investigated the association of dichotomized weight-indexed CUF volume removal with postoperative AKI development to provide pragmatic guidance for clinical practice at the authors' institution.Measurements and main results
Primary outcomes of postoperative AKI were defined by the Kidney Disease: Improving Global Outcomes staging criteria and dichotomized, weight-indexed CUF volumes (mL/kg) were defined by (1) extreme quartiles (Q3) and (2) Youden's criterion that best predicted AKI development. Multivariate logistic regression models were developed to test the association of these dichotomized indices with AKI status. Postoperative AKI occurred in 827 patients (50.4%). Higher CUF volumes were associated with AKI development by quartiles (CUF >Q3 = 32.6 v CUF < Q1 = 10.4 mL/kg; odds ratio [OR] = 1.68, 95% CI: 1.19-2.3) and Youden's criterion (CUF ≥ 32.9 v CUF <32.9 mL/kg; OR = 1.60, 95% CI: 1.21-2.13). Despite similar intraoperative nadir hematocrits among groups (p = 0.8), higher CUF volumes were associated with more allogeneic blood transfusions (p = 0.002) and longer lengths of stay (p < 0.001).Conclusions
Removal of weight-indexed CUF volumes > 32 mL/kg increased the risk for postoperative AKI development. Importantly, CUF volume removal of any amount did not mitigate allogeneic blood transfusion during elective cardiac surgery. Prospective studies are needed to validate these findings.Item Open Access Discordance in Grading Methods of Aortic Stenosis by Pre-Cardiopulmonary Bypass Transesophageal Echocardiography.(Anesth Analg, 2016-04) Whitener, George; McKenzie, Jeff; Akushevich, Igor; White, William D; Dhakal, Ishwori B; Nicoara, Alina; Swaminathan, MadhavBACKGROUND: Current guidelines define severe aortic valve stenosis (AS) as an aortic valve area (AVA) ≤1.0 cm by the continuity equation and mean gradient (ΔPm) ≥ 40 mm Hg. However, these measurements can be discordant when classifying AS severity. Approximately one-third of patients with normal ejection fraction and severe AS by AVA have nonsevere AS by ΔPm when measured by preoperative transthoracic echocardiography (TTE). Given the use of positive pressure ventilation and general anesthesia in the pre-cardiopulmonary bypass (pre-CPB) period, we hypothesized that discordance between ΔPm and AVA during pre-CPB transesophageal echocardiography (TEE) would be higher than previously reported by TTE. METHODS: We retrospectively examined pre-CPB TEE data for patients who had aortic valve replacement, with or without coronary artery bypass grafting, from 2000 to 2012. Patients were excluded if they had ejection fraction <55%, emergency surgery, repeat sternotomy, moderate or severe mitral regurgitation, or severe aortic regurgitation. Only patients with both pre-CPB AVA and ΔPm measurements were included. Patients were grouped according to severity (mild, moderate, and severe) by AVA or ΔPm. Discordance was defined as disagreement between severities based on either parameter. RESULTS: A total of 277 patients met inclusion criteria. There were 227 patients with AVA ≤ 1.0 cm. The proportion of these patients with a ΔPm < 40 mm Hg was 54% (95% confidence interval, 47%-61%). The rate of discordance was significantly higher than the rate (37%; P < 0.001) found in previously reported analyses using TTE. Of the patients with a ΔPm ≥ 40 mm Hg, only 8% (n = 9/113) had a discordant AVA. In contrast, of the patients with ΔPm < 40 mm Hg, 80% (n = 131/164) had a discordant AVA. CONCLUSIONS: We confirmed our hypothesis that grading AS by ΔPm and AVA during pre-CPB TEE exhibits higher discordance than reported for TTE by others. It remains unclear whether these discrepancies reflect the effect of general anesthesia, imaging modality (TTE versus TEE) differences, inaccuracies in AS grading cutoffs when applied to pre-CPB TEE, or selection bias of the surgical population.Item Open Access Hydroxocobalamin or Methylene Blue for Vasoplegic Syndrome in Adult Cardiothoracic Surgery.(Journal of cardiothoracic and vascular anesthesia, 2022-02) Kram, Shawn J; Kram, Bridgette L; Cook, Jennifer C; Ohman, Kelsey L; Ghadimi, KamrouzObjective
To compare hydroxocobalamin and methylene blue for the treatment of vasopressor-refractory vasoplegic syndrome (VS) after adult cardiac surgery with cardiopulmonary bypass (CPB).Design
A retrospective, propensity-matched, cohort study was performed. The primary endpoints were the percentage change in vasopressor use at 30, 60, and 120 minutes, characterized as both norepinephrine equivalents and vasoactive inotropic score. Eligible patients who received methylene blue were matched 3:1 with patients who received hydroxocobalamin based on sequential organ failure assessment score, preoperative mechanical circulatory support, CPB duration, and use of pre-CPB vasopressors, angiotensin-converting enzyme inhibitors, or beta-blockers.Setting
A quaternary care academic medical center.Participants
Adult patients who underwent cardiac surgery with CPB from July 2013 to June 2019.Interventions
Patients were included who received either hydroxocobalamin (5,000 mg) or methylene blue (median 1.2 mg/kg) for VS in the operating room during the index surgery or in the intensive care unit up to 24 hours after CPB separation.Measurements and main results
Of the 142 included patients, 120 received methylene blue and 22 received hydroxocobalamin. After matching, 66 patients in the methylene blue group were included in the analysis. Baseline demographics, surgical characteristics, and vasoactive medications were similar between groups. There were no significant between-group differences in percentage change in norepinephrine equivalents or vasoactive inotropic score at each timepoint.Conclusions
In adult patients undergoing cardiothoracic surgery using CPB with VS, the ability to reduce vasopressor use was similar with hydroxocobalamin compared with methylene blue.Item Open Access Invited commentary.(Ann Thorac Surg, 2013-07) Jr, FJCItem Open Access Minimally Invasive Pulmonary Fibroelastoma Resection.(Innovations (Philadelphia, Pa.), 2019-11-19) Nellis, Joseph R; Wojnarski, Charles M; Fitch, Zachary W; Andersen, Nicholas A; Turek, Joseph WPulmonary fibroelastomas are a rare primary cardiac tumor with less than 50 cases reported in the literature to date. We performed a minimally invasive valve-sparing tumor resection through a left anterior mini-incision (LAMI). The procedure was performed without cardiac arrest or aortic cross clamp, expediting postoperative recovery and allowing for an uncomplicated discharge on postoperative day 5. LAMI is a safe and reliable alternative to median sternotomy for patients requiring interventions on the right ventricular outflow tract and main pulmonary artery, including pulmonary fibroelastoma resection and pulmonary valve replacement when needed.Item Open Access Modulation of Heparin Therapy by RNA Aptamers and Andexanet Alfa(2021) Chabata, Charlene VongaiUnfractionated heparin (UFH) is the primary anticoagulant for highly procoagulant indications including cardiopulmonary bypass (CPB) and more recently, severe COVID-19. UFH, however, is unable to fully inhibit thrombin generation leading to continuous activation of both coagulation and inflammatory cascades, increasing the risk for thrombo-inflammatory adverse events. The widespread use of UFH makes it important to improve on its action by addressing its incomplete inhibition of thrombin generation. Additionally, there is a need to better understand how to effectively administer UFH in relation to other therapeutics to avoid counter interactions that leave patients vulnerable to life threatening complications. Known limitations of unfractionated heparin (UFH) have encouraged the evaluation of anticoagulant aptamers as alternatives to UFH in highly procoagulant settings such as cardiopulmonary bypass (CPB). Despite progress, these efforts have not been totally successful. In the first part of this work, we take a different approach and explore whether properties of an anticoagulant aptamer can complement UFH, rather than replace it, to address shortcomings with UFH use. Combining RNA aptamer 11F7t, which targets Factor X/Xa, with UFH (or Low Molecular Weight Heparin) yields a significantly enhanced anticoagulant cocktail effective in normal and COVID-19 patient blood. In these studies we determined that this aptamer-UFH combination a.) supports continuous circulation of human blood through an ex vivo membrane oxygenation circuit, as is required for patients undergoing CPB and COVID-19 patients requiring extracorporeal membrane oxygenation, b.) allows for a reduced level of UFH to be employed c.) more effectively limits thrombin generation compared to UFH alone and d.) is rapidly reversed by the administration of protamine sulfate, the standard treatment for reversing UFH clinically following CPB. Thus, the combination of Factor X/Xa aptamer and UFH has significantly improved anticoagulant properties compared to UFH alone and underscores the potential of RNA aptamers to improve medical management of acute care patients requiring potent yet rapidly reversible anticoagulation. In the second part of this work, we focused on understanding the interactions between Andexanet alfa (AnXa), a reversal agent for FXa targeted direct oral anticoagulants (DOACs), and UFH. While AnXa was designed to control bleeding associated with the use of DOACs, no studies on its effect on subsequent UFH anticoagulation prior to surgery were carried out. Following FDA approval of AnXa in 2018, several cases have been reported where prior AnXa administration cause heparin resistance during CPB. In our studies, we established that the concomitant presence of AnXa and UFH in whole human blood diminishes the anticoagulant effect of heparin. Furthermore, AnXa addition to ex vivo membrane oxygenation circuit, where UFH anticoagulated blood was being circulated led to the formation of macroscopic and microscopic clots within the circuit. Further studies established potential countermeasures to alleviate heparin resistance in this context through administration of antithrombin (AT) and excess UFH. These results give insight into the interaction of AnXa and UFH during extracorporeal oxygenation and how to circumvent the thrombotic sequalae associated with this interaction. We believe this work will greatly inform and improve patient outcomes. We hope it will also encourage issuance of a warning against concurrent or sequential administration of indirect inhibitors of FXa (UFH, LMWH and Fondaparinux) and AnXa.
Item Open Access Prevalence and repair of intraoperatively diagnosed patent foramen ovale and association with perioperative outcomes and long-term survival.(JAMA, 2009-07) Krasuski, Richard A; Hart, Stephen A; Allen, Drew; Qureshi, Athar; Pettersson, Gosta; Houghtaling, Penny L; Batizy, Lillian H; Blackstone, EugeneContext
A recent survey suggested that cardiothoracic surgeons may alter planned procedures to repair incidentally discovered patent foramen ovale (PFO). How frequently this occurs and the impact on outcomes remain unknown.Objective
To measure the frequency of incidentally discovered PFO closure during cardiothoracic surgery and determine its perioperative and long-term impact.Design, setting, and patients
We reviewed the intraoperative transesophageal echocardiograms of 13,092 patients without prior diagnosis of PFO or atrial septal defect undergoing surgery at the Cleveland Clinic, Cleveland, Ohio, from 1995 through 2006. Postoperative outcomes were prospectively collected until discharge.Main outcome measures
All-cause hospital mortality and stroke were predetermined primary outcomes; length of hospital stay, length of intensive care unit stay, and time on cardiopulmonary bypass were secondary outcomes.Results
Intraoperative PFO was diagnosed in 2277 patients in the study population (17%), and risk factors for stroke were similar in patients with and without PFO. After propensity matching was performed with the comparator groups, patients with PFO demonstrated similar rates of in-hospital death (3.4% vs 2.6%, P = .11) and postoperative stroke (2.3% vs 2.3%, P = .84). Surgical closure was performed in 639 PFO patients (28%), and surgeons were more likely to close defects in patients who were younger (mean [SD] age, 61.1 [14] vs 64.4 [13] years; P < .001), were undergoing mitral or tricuspid valve surgery (51% vs 32%, P < .001), or had history of transient ischemic attack or stroke (16% vs 10%, P < .001). Patients with repaired PFO demonstrated a 2.47-times greater odds (95% confidence interval, 1.02-6.00) of having a postoperative stroke compared with those with unrepaired PFO (2.8% vs 1.2%, P = .04). Long-term analysis demonstrated that PFO repair was associated with no survival difference (P = .12).Conclusions
Incidental PFO is common in patients undergoing cardiothoracic surgery but is not associated with increased perioperative morbidity or mortality. Surgical closure appears unrelated to long-term survival and may increase postoperative stroke risk.Item Open Access Robotic Mitral Valve Repair in Older Individuals: An Analysis of The Society of Thoracic Surgeons Database.(The Annals of thoracic surgery, 2018-11) Wang, Alice; Brennan, J Matthew; Zhang, Shuaiqi; Jung, Sin-Ho; Yerokun, Babatunde; Cox, Morgan L; Jacobs, Jeffrey P; Badhwar, Vinay; Suri, Rakesh M; Thourani, Vinod; Halkos, Michael E; Gammie, James S; Gillinov, A Marc; Smith, Peter K; Glower, DonaldBackground
National outcomes of robotic mitral valve repair (rMVr) compared with sternotomy (sMVr) in older patients are currently unknown.Methods
From 2011 to 2014, all patients aged 65 years and older undergoing MVr in The Society of Thoracic Surgeons Adult Cardiac Surgery Database linked to Medicare claims data were identified. Patients who underwent rMVr were propensity matched to patients who underwent sMVr. Standard differences and falsification outcome of baseline characteristics were tested to ensure a balanced match. Cox models were used to calculate 3-year mortality, heart failure readmission, and mitral valve reintervention, adjusting for competing risks where appropriate.Results
After matching, 503 rMVr patients from 65 centers and 503 sMVr from 251 centers were included. There were no significant differences in comorbidities or falsification outcome. Cardiopulmonary bypass and cross-clamp times were longer with rMVr versus sMVr at 125 versus 102 minutes (p < 0.0001) and 85 versus 75 minutes (p < 0.0001), respectively. The rMVr patients had shorter intensive care unit (27 vs 47 hours, p < 0.0001) and hospital stay (5 vs 6 days, p < 0.0001), less frequent transfusion (21% vs 35%, p < 0.0001), and less atrial fibrillation (28% vs 40%, p < 0.0001). Three-year mortality (hazard ratio, 1.21; 95% confidence interval, 0.68 to 2.16; p = 0.52), heart failure readmission (hazard ratio, 1.42; 95% confidence interval, 0.80 to 2.52, p = 0.10), and mitral valve reintervention (hazard ratio, 0.42; 95% confidence interval, 0.15 to 1.18; p = 0.22) did not differ between the groups.Conclusions
The rMVr procedure was associated with less atrial fibrillation, less frequent transfusion requirement, and shorter intensive care unit and hospital stay, without a significant difference in 3-year mortality, heart failure readmission, or mitral valve reintervention. In older patients, rMVr confers short-term advantages without a detriment to midterm outcomes.Item Open Access The effect of blood pressure on cerebral outcome in a rat model of cerebral air embolism during cardiopulmonary bypass.(The Journal of thoracic and cardiovascular surgery, 2011-08) Qing, M; Shim, JK; Grocott, HP; Sheng, H; Mathew, JP; Mackensen, GBObjective
Higher mean arterial pressure during cardiopulmonary bypass may improve cerebral outcome associated with cerebral air embolism by increasing emboli clearance and collateral flow to salvage the ischemic penumbra. However, this may come at the expense of increased delivery of embolic load. This study was designed to investigate the influence of mean arterial pressures on cerebral functional and histologic outcome after cerebral air embolism during cardiopulmonary bypass in an established rat model.Methods
Male Sprague-Dawley rats were exposed to 90 minutes of normothermic cardiopulmonary bypass with 10 cerebral air embolisms (0.3 μL/bolus) injected repetitively. Rats were randomized to 3 groups (n = 10, each) that differed in mean arterial pressure management during cardiopulmonary bypass: 50 mm Hg (low mean arterial pressure), 60 to 70 mm Hg (standard mean arterial pressure), and 80 mm Hg (high mean arterial pressure). Neurologic score was assessed on postoperative days 3 and 7 when cerebral infarct volumes were determined. Cognitive function was determined with the Morris water maze test beginning on postoperative day 3 and continuing to postoperative day 7.Results
Neurologic score was better in high and standard mean arterial pressure groups versus low mean arterial pressure groups. High mean arterial pressure resulted in shorter water maze latencies compared with standard and low mean arterial pressure on postoperative days 6 and 7. Total infarct volume and number of infarct areas were not different among groups.Conclusions
The use of higher mean arterial pressure during cardiopulmonary bypass in a rat model of cerebral air embolism conveyed beneficial effects on functional cerebral outcome with no apparent disadvantage of increased delivery of embolic load. Maintaining higher perfusion pressures in situations of increased cerebral embolic load may be considered as a collateral therapeutic strategy.Item Open Access Three-factor prothrombin complex concentrates for refractory bleeding after cardiovascular surgery within an algorithmic approach to haemostasis.(Vox sanguinis, 2019-05) Hashmi, Nazish K; Ghadimi, Kamrouz; Srinivasan, Amudan J; Li, Yi-Ju; Raiff, Robert D; Gaca, Jeffrey G; Root, Adam G; Barac, Yaron D; Ortel, Thomas L; Levy, Jerrold H; Welsby, Ian JBACKGROUND/OBJECTIVES:Prothrombin complex concentrates (PCC) are increasingly administered off-label in the United States to treat bleeding in cardiovascular surgical patients and carry the potential risk for acquired thromboembolic side-effects after surgery. Therefore, we hypothesized that the use of low-dose 3-factor (3F) PCC (20-30 IU/kg), as part of a transfusion algorithm, reduces bleeding without increasing postoperative thrombotic/thromboembolic complications. MATERIALS/METHODS:After IRB approval, we retrospectively analysed 114 consecutive, complex cardiovascular surgical patients (age > 18 years), between February 2014 and June 2015, that received low-dose 3F-PCC (Profilnine® ), of which seven patients met established exclusion criteria. PCC was dosed according to an institutional perioperative algorithm. Allogeneic transfusions were recorded before and after PCC administration (n = 107). The incidence of postoperative thromboembolic events was determined within 30 days of surgery, and Factor II levels were measured in a subset of patients (n = 20) as a quality control measure to avoid excessive PCC dosing. RESULTS:Total allogeneic blood product transfusion reached a mean of 12·4 ± 9·9 units before PCC and 5·0 ± 6·3 units after PCC administration (P < 0·001). The mean PCC dose was 15·8 ± 7·1 IU/kg. Four patients (3·8%) each experienced an ischaemic stroke on postoperative day 1, 2, 4 and 27. Seven patients (6·5%) had acquired venous thromboembolic disease within 10 days of surgery. Median factor II level after transfusion algorithm adherence and PCC administration was 87%. CONCLUSIONS:3F-PCC use for refractory bleeding after cardiovascular surgery resulted in reduced transfusion of allogeneic blood and blood products. Adherence to this algorithmic approach was associated with an acceptable incidence of postoperative thrombotic/thromboembolic complications.Item Open Access What's fishy about protamine? Clinical use, adverse reactions, and potential alternatives.(Journal of thrombosis and haemostasis : JTH, 2023-07) Levy, Jerrold H; Ghadimi, Kamrouz; Kizhakkedathu, Jayachandran N; Iba, ToshiakiProtamine, a highly basic protein isolated from salmon sperm, is the only clinically available agent to reverse the anticoagulation of unfractionated heparin. Following intravenous administration, protamine binds to heparin in a nonspecific electrostatic interaction to reverse its anticoagulant effects. In clinical use, protamine is routinely administered to reverse high-dose heparin anticoagulation in cardiovascular procedures, including cardiac surgery with cardiopulmonary bypass. Despite the lack of supportive evidence regarding protamine's effectiveness to reverse low-molecular-weight heparin, it is recommended in guidelines with low-quality evidence. Different dosing strategies have been reported for reversing heparin in cardiac surgical patients based on empiric dosing, pharmacokinetics, or point-of-care measurements of heparin levels. Protamine administration is associated with a spectrum of adverse reactions that range from vasodilation to life-threatening cardiopulmonary dysfunction and shock. The life-threatening responses appear to be hypersensitivity reactions due to immunoglobulin E and/or immunoglobulin G antibodies. However, protamine and heparin-protamine complexes can activate complement inflammatory pathways and inhibit other coagulation factors. Although alternative agents for reversing heparin are not currently available for clinical use, additional research continues evaluating novel therapeutic approaches.