Evaluation and Management of Pulmonary Hypertension in Noncardiac Surgery: A Scientific Statement From the American Heart Association.

Pulmonary hypertension, defined as an elevation in blood pressure in the pulmonary arteries, is associated with an increased risk of death. The prevalence of pulmonary hypertension is increasing, with an aging population, a rising prevalence of heart and lung disease, and improved pulmonary hypertension survival with targeted therapies. Patients with pulmonary hypertension frequently require noncardiac surgery, although pulmonary hypertension is associated with excess perioperative morbidity and death. This scientific statement provides guidance on the evaluation and management of pulmonary hypertension in patients undergoing noncardiac surgery. We advocate for a multistep process focused on (1) classification of pulmonary hypertension group to define the underlying pathology; (2) preoperative risk assessment that will guide surgical decision-making; (3) pulmonary hypertension optimization before surgery to reduce perioperative risk; (4) intraoperative management of pulmonary hypertension to avoid right ventricular dysfunction and to maintain cardiac output; and (5) postoperative management of pulmonary hypertension to ensure recovery from surgery. Last, this scientific statement highlights the paucity of evidence to support perioperative pulmonary hypertension management and identifies areas of uncertainty and opportunities for future investigation.

Inhaled Epoprostenol Compared With Nitric Oxide for Right Ventricular Support After Major Cardiac Surgery.

BACKGROUND: Right ventricular failure (RVF) is a leading driver of morbidity and death after major cardiac surgery for advanced heart failure, including orthotopic heart transplantation and left ventricular assist device implantation. Inhaled pulmonary-selective vasodilators, such as inhaled epoprostenol (iEPO) and nitric oxide (iNO), are essential therapeutics for the prevention and medical management of postoperative RVF. However, there is limited evidence from clinical trials to guide agent selection despite the significant cost considerations of iNO therapy. METHODS: In this double-blind trial, participants were stratified by assigned surgery and key preoperative prognostic features, then randomized to continuously receive either iEPO or iNO beginning at the time of separation from cardiopulmonary bypass with the continuation of treatment into the intensive care unit stay. The primary outcome was the composite RVF rate after both operations, defined after transplantation by the initiation of mechanical circulatory support for isolated RVF, and defined after left ventricular assist device implantation by moderate or severe right heart failure according to criteria from the Interagency Registry for Mechanically Assisted Circulatory Support. An equivalence margin of 15 percentage points was prespecified for between-group RVF risk difference. Secondary postoperative outcomes were assessed for treatment differences and included: mechanical ventilation duration; hospital and intensive care unit length of stay during the index hospitalization; acute kidney injury development including renal replacement therapy initiation; and death at 30 days, 90 days, and 1 year after surgery. RESULTS: Of 231 randomized participants who met eligibility at the time of surgery, 120 received iEPO, and 111 received iNO. Primary outcome occurred in 30 participants (25.0%) in the iEPO group and 25 participants (22.5%) in the iNO group, for a risk difference of 2.5 percentage points (two one-sided test 90% CI, -6.6% to 11.6%) in support of equivalence. There were no significant between-group differences for any of the measured postoperative secondary outcomes. CONCLUSIONS: Among patients undergoing major cardiac surgery for advanced heart failure, inhaled pulmonary-selective vasodilator treatment using iEPO was associated with similar risks for RVF development and development of other postoperative secondary outcomes compared with treatment using iNO. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03081052.

Trends in the Utilization of Multiorgan Support Among Adults Undergoing High-risk Cardiac Surgery in the United States.

OBJECTIVES: To examine trends in the prevalence of multiorgan dysfunction (MODS), utilization of multi-organ support (MOS), and mortality among patients undergoing cardiac surgery with MODS who received MOS in the United States. DESIGN: Retrospective cohort study. SETTING: 183 hospitals in the Premier Healthcare Database. PARTICIPANTS: Adults ≥18 years old undergoing high-risk elective or non-elective cardiac surgery. INTERVENTIONS: none. MEASUREMENTS AND MAIN RESULTS: The exposure was time (consecutive calendar quarters) January 2008 and June 2018. We analyzed hospital data using day-stamped hospital billing codes and diagnosis and procedure codes to assess MODS prevalence, MOS utilization, and mortality. Among 129,102 elective and 136,190 non-elective high-risk cardiac surgical cases across 183 hospitals, 10,001 (7.7%) and 21,556 (15.8%) of patients developed MODS, respectively. Among patients who experienced MODS, 2,181 (22%) of elective and 5,425 (25%) of non-elective cardiac surgical cases utilized MOS. From 2008-2018, MODS increased in both high-risk elective and non-elective cardiac surgical cases. Similarly, MOS increased in both high-risk elective and non-elective cardiac surgical cases. As a component of MOS, mechanical circulatory support (MCS) increased over time. Over the study period, risk-adjusted mortality, in patients who developed MODS receiving MOS, increased in high-risk non-elective cardiac surgery and decreased in high-risk elective cardiac surgery, despite increasing MODS prevalence and MOS utilization (p<0.001). CONCLUSIONS: Among patients undergoing high-risk cardiac surgery in the United States, MODS prevalence and MOS utilization (including MCS) increased over time. Risk-adjusted mortality trends differed in elective and non-elective cardiac surgery. Further research is necessary to optimize outcomes among patients undergoing high-risk cardiac surgery.

Perioperative Considerations in Management of the Severely Bleeding Coagulopathic Patient.

Inherited and acquired coagulopathy are frequently associated with major bleeding in severe trauma, cardiac surgery with cardiopulmonary bypass, and postpartum hemorrhage. Perioperative management is multifactorial and includes preoperative optimization and discontinuation of anticoagulants and antiplatelet therapy in elective procedures. Prophylactic or therapeutic use of antifibrinolytic agents is strongly recommended in guidelines and has been shown to reduce bleeding and need for allogeneic blood administration. In the context of bleeding induced by anticoagulants and/or antiplatelet therapy, reversal strategies should be considered when available. Targeted goal-directed therapy using viscoelastic point-of-care monitoring is increasingly used to guide the administration of coagulation factors and allogenic blood products. In addition, damage control surgery, which includes tamponade of large wound areas, leaving surgical fields open, and other temporary maneuvers, should be considered when bleeding is refractory to hemostatic measures.

Development of New Donor-Specific and Human Leukocyte Antigen Antibodies After Transfusion in Adult Lung Transplantation.

OBJECTIVES: The development of new human leukocyte antigens (HLAs) and donor-specific antibodies (DSAs) in patients are associated with worse outcomes following lung transplantation. The authors aimed to examine the relationship between blood product transfusion in the first 72 hours after lung transplantation and the development of HLA antibodies, including DSAs. DESIGN: A retrospective observational study. SETTING: At a single academic tertiary center. PARTICIPANTS: Adult lung transplant recipients who underwent transplantation between September 2014 and June 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 380 patients were included in this study, and 87 (23%) developed de novo donor-specific antibodies in the first year after transplantation. Eighty-five patients (22%) developed new HLA antibodies that were not donor-specific, and 208 patients (55%) did not develop new HLA antibodies in the first year after transplantation. Factors associated with increased HLA and DSA development included donor pulmonary infection, non-infectious indication for transplant, increased recipient body mass index, and a preoperative calculated panel reactive antibody value above 0. Multivariate analysis identified platelet transfusion associated with an increased risk of de novo HLA antibody development compared to the negative group (odds ratio [OR; 95% CI] 1.18 [1.02-1.36]; p = 0.025). Cryoprecipitate transfusion was associated with de novo DSA development compared to the negative group (OR [95% CI] 2.21 [1.32-3.69] for 1 v 0 units; p = 0.002). CONCLUSIONS: Increased perioperative transfusion of platelets and cryoprecipitate are associated with de novo HLA and DSA development, respectively, in lung transplant recipients during the first year after transplantation.

Hydroxocobalamin or Methylene Blue for Vasoplegic Syndrome in Adult Cardiothoracic Surgery.

OBJECTIVE: 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.

The impact of race on utilization of durable left ventricular assist device therapy in patients with advanced heart failure.

BACKGROUND: Heart failure affects >6 million people in the United States alone and is most prevalent in Black patients who suffer the highest mortality risk. Yet prior studies have suggested that Black patients are less likely to receive advanced heart failure therapy. We hypothesized that Black patients would have decreased rates of durable left ventricular assist device (LVAD) implantation within our expansive heart failure program. METHODS: A retrospective single-center cohort study was conducted at a single high-volume academic medical center. Patients between 18 and 85 years admitted with a diagnosis of cardiogenic shock or congestive heart failure between 1, 2013 and 12, 2017 with a left ventricular ejection fraction < 30% and inotropic dependence or need for mechanical circulatory support were included. Patients with contraindications to durable LVAD were excluded. An adjusted logistic regression model for durable LVAD implantation within 90 days of the index admission was used to determine the effect of race on durable LVAD implantation. RESULTS: Among the 702 study patients (60.9% White, 34.1% Black), durable LVAD implantation was performed within 90 days of the index admission in 183 (26%) of the cohort. After multivariate analysis, Black patients were not found to have a statistically significant difference in durable LVAD implantation rates compared to White patients in our study (OR: 0.68 [95% confidence interval: 0.45-1.04; p: .074]). CONCLUSIONS: Black patients in our study did not have a statistically significant difference in the rate of durable LVAD implantation compared with White patients after adjustments were made for age, sex, socioeconomic, and clinical covariates. Larger prospective studies are needed to validate these findings.

Clinical outcomes of cardiac surgery patients undergoing therapeutic plasma exchange for heparin-induced thrombocytopenia.

BACKGROUND 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.

Conventional Ultrafiltration During Elective Cardiac Surgery and Postoperative Acute Kidney Injury.

OBJECTIVE: 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.

Using Plasma and Prothrombin Complex Concentrates.

Surgical patients, following procedural interventions or traumatic injury, often bleed due to ongoing blood loss or coagulopathy. Volume resuscitation and transfusion management are critical for the massively bleeding patient. While transfusions may correct coagulopathy, they carry multiple risks including circulatory overload and transfusion-related acute lung injury. Factor concentrates, specifically prothrombin complex concentrates (PCCs), are often used as part of multimodal therapy for bleeding along with laboratory testing to rapidly assess underlying coagulopathy. Although they are commonly used as part of management algorithms, studies evaluating their efficacy against fresh frozen plasma (FFP) or other potential therapies are needed. Further, PCCs are indicated to treat the coagulopathy associated with non-vitamin K oral anticoagulants in the perioperative setting. The focus of this commentary will be the perioperative use of PCCs, plasma, and FFP.

Percutaneous Intervention for Left Ventricular Assist Device Outflow Obstruction.

Left ventricular assist devices (LVADs) are used to support patients with advanced systolic heart failure (HF). These patients might develop LVAD dysfunction and consequent HF symptoms. Occasionally, outflow graft obstruction is responsible for LVAD dysfunction. Here, we describe percutaneous techniques to repair the outflow graft and avoid re-sternotomy.

Three-factor prothrombin complex concentrates for refractory bleeding after cardiovascular surgery within an algorithmic approach to haemostasis.

BACKGROUND/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.

Frailty in the End-Stage Lung Disease or Heart Failure Patient: Implications for the Perioperative Transplant Clinician.

The syndrome of frailty for patients undergoing heart or lung transplantation has been a recent focus for perioperative clinicians because of its association with postoperative complications and poor outcomes. Patients with end-stage cardiac or pulmonary failure may be under consideration for heart or lung transplantation along with bridging therapies such as ventricular assist device implantation or venovenous extracorporeal membrane oxygenation, respectively. Early identification of frail patients in an attempt to modify the risk of postoperative morbidity and mortality has become an important area of study over the last decade. Many quantification tools and risk prediction models for frailty have been developed but have not been evaluated extensively or standardized in the cardiothoracic transplant candidate population. Heightened awareness of frailty, coupled with a better understanding of distinct cellular mechanisms and biomarkers apart from end-stage organ disease, may play an important role in potentially reversing frailty related to organ failure. Furthermore, the clinical management of these critically ill patients may be enhanced by waitlist and postoperative physical rehabilitation and nutritional optimization.

Heparin-Induced Thrombocytopenia: A Review for Cardiac Anesthesiologists and Intensivists.

Patients undergoing cardiovascular surgery may be exposed to heparin before surgery, during cardiopulmonary bypass (CPB), or in the immediate postoperative period. For this reason, cardiovascular surgery patients are at increased risk for heparin-induced thrombocytopenia (HIT), occurring in 1 to 3% of patients. The diagnosis of HIT can be difficult, if based solely on the development of thrombocytopenia, because cardiac surgical patients have multiple reasons to be thrombocytopenic. Several clinical scoring systems have been developed to reduce unnecessary testing and better define the pretest probability of HIT, which we will review in detail with a diagnostic algorithm. In addition, we will cover the prevention and treatment HIT.

Aortic Regurgitation in Acute Type-A Aortic Dissection: A Clinical Classification for the Perioperative Echocardiographer in the Era of the Functional Aortic Annulus.

The functional aortic annulus offers a clinical approach for the perioperative echocardiographer to classify the mechanisms of aortic regurgitation in acute type-A dissection. Comprehensive examination of the functional aortic annulus in this setting using transesophageal echocardiography can guide surgical therapy for the aortic root by considering the following important aspects: severity and mechanism of aortic regurgitation, extent of root dissection, and the pattern of coronary artery involvement. The final choice of surgical therapy also should take into account factors, such as patient presentation and surgical experience, to limit mortality and morbidity from this challenging acute aortic syndrome. This review explores these concepts in detail within the framework of the functional aortic annulus, detailed anatomic considerations, and the latest literature.

Intraoperative vasoplegia: methylene blue to the rescue!

PURPOSE OF REVIEW: To evaluate the efficacy, dosing, and safety of methylene blue (MTB) in perioperative vasoplegic syndrome (VS). RECENT FINDINGS: Vasoplegic syndrome is a state of persistent hypotension with elevated cardiac output, low filling pressures, and low systemic vascular resistance (SVR). It occurs in up to 25% of patients undergoing cardiac surgery with cardiopulmonary bypass, can last up to 72 h, and is associated with a high mortality rate. MTB has been found to increase SVR and decrease vasopressor requirements in vasoplegic syndrome by inhibiting nitric oxide synthase, thus limiting the generation of nitric oxide, while inhibiting activation of soluble guanylyl cyclase and preventing vasodilation. MTB has been used in postgraft reperfusion during liver transplantation and anaphylaxis in a limited number of cases. Additionally, this medication has been used in septic shock with promising results, but similar to the cardiac surgical population, the effects of MTB administration on clinical outcomes has yet to be elucidated. SUMMARY: MTB should be considered during vasoplegic syndrome in cardiac surgery with cardiopulmonary bypass and usage may be more effective in an early critical window, prior to end-organ hypoperfusion. Other perioperative scenarios of MTB use show promise, but additional studies are required to develop formative conclusions.

Assessment of Paravalvular Leak After Transcatheter Aortic Valve Replacement: Transesophageal Echocardiography Compared With Transthoracic Echocardiography.

OBJECTIVES: Determine whether moderate or greater paravalvular leak (PVL) after transcatheter aortic valve replacement quantified using intraoperative transesophageal echocardiography (TEE) is associated with mortality and investigate the correlation between PVL grading using intraoperative TEE and postoperative transthoracic echocardiography (TTE). DESIGN: Retrospective, observational study. SETTING: Single academic institution. PARTICIPANTS: The study comprised adult patients undergoing elective transcatheter aortic valve replacement between April 2011 and February 2014. INTERVENTIONS: Patients were grouped by amount of PVL on intraoperative TEE into "significant" (moderate or greater) and "nonsignificant" (no, trivial, or mild) PVL groups. Demographics and patient characteristics were compared. Continuous variables were assessed with t-tests or Wilcoxon rank sum tests and categorical variables with the chi-square or Fisher exact test. A Cox proportional hazards model adjusted for EuroSCORE was used to test the independent association of PVL with late mortality, and covariate-adjusted survival curves were constructed. A Fleiss-Cohen-weighted kappa value was used to assess agreement between PVL grading using intraoperative TEE and postoperative TTE. MEASUREMENTS AND MAIN RESULTS: One hundred ninety-six patients were grouped into the "significant" (n = 22) or "nonsignificant" (n = 174) PVL group. Twenty patients (10%) died during the follow-up period. Significant PVL on either TTE (p = 0.62, hazard ratio 1.68, 95% confidence interval [CI] 0.22-12.85) or TEE (p = 0.49, hazard ratio 0.49; 95% CI 0.06-3.68) was not associated with a survival difference. Modest agreement was found between PVL on intraoperative TEE and postoperative TTE (kappa = 0.47, CI 0.37-0.57, p < 0.0001). CONCLUSIONS: Larger studies are needed to evaluate the association of PVL graded on intraoperative TEE with survival. There is modest agreement between the degree of PVL found on TEE and TTE.

Prothrombin Complex Concentrates for Bleeding in the Perioperative Setting.

Prothrombin complex concentrates (PCCs) contain vitamin K-dependent clotting factors (II, VII, IX, and X) and are marketed as 3 or 4 factor-PCC formulations depending on the concentrations of factor VII. PCCs rapidly restore deficient coagulation factor concentrations to achieve hemostasis, but like with all procoagulants, the effect is balanced against thromboembolic risk. The latter is dependent on both the dose of PCCs and the individual patient prothrombotic predisposition. PCCs are approved by the US Food and Drug Administration for the reversal of vitamin K antagonists in the setting of coagulopathy or bleeding and, therefore, can be administered when urgent surgery is required in patients taking warfarin. However, there is growing experience with the off-label use of PCCs to treat patients with surgical coagulopathic bleeding. Despite their increasing use, there are limited prospective data related to the safety, efficacy, and dosing of PCCs for this indication. PCC administration in the perioperative setting may be tailored to the individual patient based on the laboratory and clinical variables, including point-of-care coagulation testing, to balance hemostatic benefits while minimizing the prothrombotic risk. Importantly, in patients with perioperative bleeding, other considerations should include treating additional sources of coagulopathy such as hypofibrinogenemia, thrombocytopenia, and platelet disorders or surgical sources of bleeding. Thromboembolic risk from excessive PCC dosing may be present well into the postoperative period after hemostasis is achieved owing to the relatively long half-life of prothrombin (factor II, 60-72 hours). The integration of PCCs into comprehensive perioperative coagulation treatment algorithms for refractory bleeding is increasingly reported, but further studies are needed to better evaluate the safe and effective administration of these factor concentrates.