Current Congenital Heart Surgery and Pediatric Perfusion Practices in Japan and Vietnam.

The declining birth rate and aging population are becoming increasingly serious social issues in Japan. In this report, we summarize the current congenital heart surgery and pediatric perfusion practices in Japan and Vietnam. In addition we report the rapid growth and development of congenital heart surgery in Vietnam made possible by medical education support provided by Japan over the past decade.

Review of Interleukin-6 and Cardiopulmonary Bypass-Related End-Organ Injury Along With the Potential for Mitigation With Tocilizumab.

Cardiopulmonary bypass (CPB) is essential for the conduct of open-heart procedures. While lifesaving, CPB can be associated with significant end-organ injuries believed to result from inflammatory responses triggered by the extracorporeal surfaces encountering cellular elements in the blood stream. In this review, we discuss the role of interleukin-6 (IL-6) and the potential for Tocilizumab, an anti-IL-6 receptor antibody, in mitigating these effects. We compare the inflammatory responses in CPB and cytokine storm, a clinical condition in which Tocilizumab has been effectively implemented. Finally, we examine why corticosteroids, used to reduce the morbidity of CPB, may not effectively reduce IL-6 levels.

Is extended resection for locally advanced thoracic cancer with cardiopulmonary bypass justified?

BACKGROUND: Resection of intrathoracic tumor with cardiopulmonary bypass (CPB) remains a relatively under-reported intervention in literature, and its role in managing locally advanced mediastinal and lung cancers is a topic of ongoing debate. Our aim was to review our experience and assess the role of CPB for treating locally advanced mediastinal and lung cancers. METHODS: Between 2015 and 2020, this study initially included 10 patients with primary locally advanced thoracic malignancies with apparent adjacent cardiovascular invasion demonstrated by thoracic imaging scans. Operation was performed based on a multidisciplinary tumor board consensus. Eventually, 8 patients (3 primary lung cancers and 5 mediastinal cancers) received either salvage or elective resection with CPB; two completed surgery without requiring CPB. RESULTS: Regarding the extent of adjacent structure involvement, 4 patients presented with involvement of the superior vena cava (SVC), 1 involved the right atrium (RA), 2 involved the SVC and RA, and 1 involved the SVC, the origin of main pulmonary artery, and the ascending aorta. Thirty-day mortality occurred in two of three patients receiving salvage surgery due to respiratory insufficiency. With the long-term follow-up, one patient died of recurrence 25 months postoperatively, one survived with recurrence 30 months postoperatively, and four were alive without recurrence for 35, 36, 49, and 107 months after operations. CONCLUSION: In certain patients, particularly for elective surgical candidates rather than salvage resection, CPB allows for extended resection of locally advanced thoracic cancers with acceptable perioperative safety and survival.

Unlocking the potential of deferoxamine: a systematic review on its efficacy and safety in alleviating myocardial ischemia-reperfusion injury in adult patients following cardiopulmonary bypass compared to standard care.

BACKGROUND: Reperfusion injury, characterized by oxidative stress and inflammation, poses a significant challenge in cardiac surgery with cardiopulmonary bypass (CPB). Deferoxamine, an iron-chelating compound, has shown promise in mitigating reperfusion injury by inhibiting iron-dependent lipid peroxidation and reactive oxygen species (ROS) production. OBJECTIVES: The objective of our study was to analyze and evaluate both the efficacy and safety of a new and promising intervention, that is, deferoxamine for ischemia-reperfusion injury (I/R). DESIGN: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines are used to perform the study. DATA SOURCES AND METHODS: We conducted a systematic review following PRISMA guidelines to assess the efficacy and safety of deferoxamine in reducing I/R injury following CPB. A comprehensive search of electronic databases, namely, PubMed, Scopus, and Embase, yielded relevant studies published until August 18, 2023. Included studies evaluated ROS production, lipid peroxidation, cardiac performance, and morbidity outcomes. RESULTS: (a) ROS production: Multiple studies demonstrated a statistically significant decrease in ROS production in patients treated with deferoxamine, highlighting its potential to reduce oxidative stress. (b) Lipid peroxidation: Deferoxamine was associated with decreased lipid peroxidation levels, indicating its ability to protect cardiac tissue from oxidative damage during CPB. (c) Cardiac performance: Some studies reported improvements in left ventricular ejection fraction and wall motion score index with deferoxamine. CONCLUSION: Our review shows that deferoxamine is an efficacious and safe drug that can be used to prevent myocardial I/R injury following CPB. It also highlights the need for trials on a larger scale to develop potential strategies and guidelines on the use of deferoxamine for I/R injury.

The known and unknown of post-pump chorea: a case report on robust steroid responsiveness implicating occult neuroinflammation.

Post-pump chorea (PPC) is characterized by the development of choreiform movements following cardiopulmonary bypass (CPB) surgery. PPC occurs almost exclusively in children, and its pathophysiology remains unclear. Here we present an adult case of PPC after bovine aortic valve replacement (AVR) which exhibited dramatic and reproducible response to steroid, suggesting the presence of occult neuroinflammation. This observation suggests a novel underlying mechanism in certain subgroups of PPC, which is likely a heterogeneous condition to start with. Further research into the pathomechanisms of PPC could offer insights into managing this otherwise symptomatic control-only condition.

A case of the effective inhalation of nitric oxide therapy for caused severe pulmonary hypertension with protamine neutralization of systemic heparinization during totally endoscopic minimally invasive cardiac surgery.

Severe pulmonary vasoconstriction induced by protamine is a rare complication. We report a case of a 77-year-old male patient with a history of mitral valve plasty (MVP). He underwent redo MVP via right thoracotomy under the totally endoscopic procedure (MICS redo-MVP). Immediately after weaning cardiopulmonary bypass (CPB), protamine was administrated. 10 min later peak systolic pulmonary arterial pressure (sys PAP) rose to 62 mmHg, and 30 min later to 80 mmHg. Due to the negative impact of protamine administration, nitric oxide inhalation (iNO) therapy was started with a concentration of 20 ppm. 10 min after iNO therapy started, sys PAP decreased to 63 mmHg. After entering the intensive care unit (ICU), sys PAP decreased to 35 mmHg. Here, we present an effective iNO therapy case for pulmonary hypertension due to protamine and the patient had a good postoperative recovery. This study was approved by the Institutional Review Board at Kitaharima Medical Center (IRB-0602) with the waiver of informed consent.

Use of low titer O whole blood in infants and young children undergoing cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Low titer group O whole blood (LTOWB) is commonly used for severe bleeding in trauma patients. LTOWB may also benefit young children requiring cardiac surgery with cardiopulmonary bypass (CPB) at risk of severe bleeding. STUDY DESIGN AND METHODS: In this retrospective study, children <2 years old who underwent cardiac surgery with CPB were included. Comparisons were performed between those receiving component therapy (CT) versus those receiving LTOWB plus CT (LTOWB+CT). Outcomes included drainage tube (DT) output and total transfusion volumes. Optimization-based weighting was used for adjusted analyses between groups. RESULTS: There were 117 patients transfused with only CT and 127 patients transfused with LTOWB+CT. In the LTOWB+CT group, 66 were Group non-O and 61 were Group O. Total transfusion volumes given from the start of the operation until the first 24 h in the cardiac intensive care unit was a median (IQR) 41 (10, 93) mL/kg in the CT group and 48 (28, 77) mL/kg in the LTOWB+CT group, (p = .28). Median (IQR) DT output was 22 (15-32) in CT versus 22 (16-28) in LTOWB+CT groups, (p = .27). There were no differences in death, renal failure and a composite of death and renal failure between the two groups, but there were statistically fewer re-explorations for bleeding in the LTOWB+CT group (p < .001). CONCLUSIONS: The use of LTOWB appears to be safe in <2 years old undergoing cardiac surgery and may reduce re-explorations for severe bleeding. Large trials are needed to determine the efficacy and safety of LTOWB in this population with severe bleeding.

Gut Microbiome in Children with Congenital Heart Disease After Cardiopulmonary Bypass Surgery (GuMiBear Study).

The gut microbiome of infants with congenital heart disease (CHD) undergoing cardiopulmonary bypass surgery (CPB) is at risk of profound alteration. The aim of this study was to examine the gut microbiome pre- and post-bypass surgery to explore potential implications of altered gut biodiversity. A prospective cohort study involving infants with CHD who underwent CPB was performed. Faecal samples were collected from infants alongside the collection of demographic and clinical data in order to examine gut microbiome changes before and after surgery. 16S rRNA sequencing analysis was performed on DNA isolated from stool samples to determine changes in gut microbiome composition. Thirty-three patients were recruited, with samples from thirteen of these available for final analysis. Compared with healthy, matched controls, at a genus level, pre-operative samples for infants with CHD demonstrated a higher relative abundance of Escherichia-Shigella (31% vs 2-6%) and a lower relative abundance of Bifidobacterium (13% vs 40-60%). In post-operative samples, the relative abundance of Escherichia-Shigella (35%), Enterococcus (11%), Akkermansia (6%), and Staphylococcus (5%) were higher than pre-op samples. One infant developed post-operative necrotising-enterocolitis (NEC). They displayed a marked abundance of the Enterococcus (93%) genus pre-operatively. This study demonstrates that infants with CHD have an altered gut microbiome when compared with healthy controls and there might be a possible link between an abundance of virulent species and NEC.

Elevated circulating levels of neutrophil extracellular traps after cardiopulmonary bypass surgery as risk factors of postoperative atrial fibrillation and mortality.

Background: Cardiopulmonary bypass (CPB) can trigger a systemic inflammatory response during the perioperative period, which may lead to the consumption of the contact system and the production of neutrophil extracellular traps (NETs). This study attempted to determine whether the formation of NETs and contact activation are a vivid occurrence during CPB and whether they are related to post-operative atrial fibrillation (AF) and survival. Methods: A prospective observational study was conducted in 97 patients who underwent aortic valve and/or aorta replacement surgery with CPB. Circulating markers of NETs [histone-DNA complex, cell-free double stranded DNA (dsDNA), neutrophil elastase] and the contact system [prekallikrein, high molecular weight kininogen (HMWK), activated factor XII (FXIIa)] were measured at four-time points: before surgery (T0), immediately after surgery (T1), 1 day after surgery (T2), and 3 days after surgery (T3). Results: Elevated levels of circulating NETs markers were observed across post-CPB time. Significantly elevated levels of histone-DNA complex and cell-free dsDNA measured T3 were detected in patients with post-operative AF compared to those without. In logistic regression analysis, levels of histone-DNA complex and cell-free dsDNA measured at T3 were significant markers of risk for occurrence of AF. The levels of cell-free dsDNA measured T2 were significantly higher in non-survivors than in survivors. The level of cell-free dsDNA showed significant prognostic value. Conclusions: NETs markers may be useful for the assessment of risk for post-operative AF and mortality. Conduct of additional research regarding the role of NETs as clinical markers and as a therapeutic target in CPB is anticipated.

Early Impairment of Cerebral Bioenergetics After Cardiopulmonary Bypass in Neonatal Swine.

Objectives: We previously demonstrated cerebral mitochondrial dysfunction in neonatal swine immediately following a period of full-flow cardiopulmonary bypass (CPB). The extent to which this dysfunction persists in the postoperative period and its correlation with other markers of cerebral bioenergetic failure and injury is unknown. We utilized a neonatal swine model to investigate the early evolution of mitochondrial function and cerebral bioenergetic failure after CPB. Methods: Twenty piglets (mean weight 4.4 ± 0.5 kg) underwent 3 h of CPB at 34 °C via cervical cannulation and were followed for 8, 12, 18, or 24 h (n = 5 per group). Markers of brain tissue damage (glycerol) and bioenergetic dysfunction (lactate to pyruvate ratio) were continuously measured in cerebral microdialysate samples. Control animals (n = 3, mean weight 4.1 ± 1.2 kg) did not undergo cannulation or CPB. Brain tissue was extracted immediately after euthanasia to obtain ex-vivo cortical mitochondrial respiration and frequency of cortical microglial nodules (indicative of cerebral microinfarctions) via neuropathology. Results: Both the lactate to pyruvate ratio (P < .0001) and glycerol levels (P = .01) increased in cerebral microdialysate within 8 h after CPB. At 24 h post-CPB, cortical mitochondrial respiration was significantly decreased compared with controls (P = .046). The presence of microglial nodules increased throughout the study period (24 h) (P = .01, R2 = 0.9). Conclusion: CPB results in impaired cerebral bioenergetics that persist for at least 24 h. During this period of bioenergetic impairment, there may be increased susceptibility to secondary injury related to alterations in metabolic delivery or demand, such as hypoglycemia, seizures, and decreased cerebral blood flow.

Application of extracorporeal membrane oxygenation in the remote transport of a patient with a ruptured sinus of Valsalva aneurysm: a case report.

Background: A ruptured sinus of Valsalva aneurysm can lead to rapid heart failure and sudden cardiac death. Management of patients who develop severe heart failure and need to be transferred to a specialized hospital for surgical treatment can be challenging. In patients with severe shock due to a ruptured sinus of Valsalva aneurysm into the right atrium, extracorporeal membrane oxygenation (ECMO) transport is an effective means to ensure patient safety, but increases the right cardiac load. We report the experience of veno-arterial (VA) ECMO transport in the treatment of acute cardiogenic shock caused by rupture of a congenital sinus of Valsalva aneurysm. Case presentation: We describe the case of an 18-year-old male who began having acute episodes of chest pain, shortness of breath, palpitations, and dizziness 18 h before presenting to the emergency department. An echocardiogram revealed an acute ruptured sinus of Valsalva aneurysm and a shunt to the right atrium. The patient presented with severe shock. VA-ECMO was administered to ensure safe transport to the cardiac center. The outcome of emergency surgical repair was good. The patient was on ECMO for 8 h. He returned to the general ward after 7 days and was successfully discharged after 40 days. He had good exercise tolerance 2 years after surgery and no evidence of heart failure. Conclusion: Although ECMO transport can increase right cardiac load, it is an effective and safe method to move patients with severe shock caused by a ruptured sinus of Valsalva aneurysm into the right atrium. Methods to decrease right cardiac load, such as decreasing ECMO flow combined with cardiotonic drugs, should be adopted. Successful treatment involves rapid establishment of cardiopulmonary bypass and urgent repair of the ruptured sinus of Valsalva aneurysm.

Cerebral protection in acute type A aortic dissection surgery: a systematic review and meta-analysis.

Background: Acute type A aortic dissection (ATAAD) still challenges physicians and warrants emergent surgical management. Two main methods to reduce cerebrovascular events in ATAAD surgeries are antegrade cerebral perfusion (ACP) and retrograde cerebral perfusion (RCP). We conducted a systematic review and meta-analysis to compare the outcomes of ACP and RCP methods during the ATAAD surgery. Methods: In this study, we searched the databases until March 29th, 2023. Studies that reported the data for comparison of different types of brain perfusion protection during aortic surgery in patients with ATAAD were included. Results: Twenty-six studies met the eligibility criteria. All studies had a low risk of bias as they were evaluated by the Joanna Briggs Institute (JBI) critical appraisal tool. Eventually, we included 26 studies in the current meta-analysis, and a total of 13,039 patients were evaluated. The calculated risk ratio (RR) for permanent neurologic dysfunction (PND) in ACP and RCP comparison was RR =1.23, 95% confidence interval (CI): (0.84, 1.80) (P value =0.2662), and in unilateral ACP (uACP) and bilateral ACP (bACP) was RR =1.2786, 95% CI: (0.7931, 2.0615) (P value =0.3132). When comparing the ACP-RCP and uACP-bACP groups, significant differences were found between ACP-RCP the groups in terms of circulatory arrest time (P value =0.0017 and P value =0.1995, respectively), cardiopulmonary bypass time (P value =0.5312 and P value =0.7460, respectively), intensive care unit (ICU)-stay time (P value =0.2654 and P value =0.0099), crossclamp time (P value =0.6228 and P value =0.2625), and operative mortality (P value =0.9368 and P value =0.2398, respectively), and when comparing the u-ACP and b-ACP groups for transient neurologic deficit (TND), an RR of 1.32, 95% CI: (1.05, 1.67) (P value =0.0199). The results showed high heterogeneity and no publication bias. Conclusions: This study demonstrated that the ACP and RCP are both safe and acceptable techniques to use in emergent settings. The uACP technique is equivalent to bACP in terms of PND and mortality, however, uACP is preferred over bACP in terms of TND.

Video assisted thorascopic assisted correction of left partial anomalous pulmonary venous connection: one case report.

INTRODUCTION: The left partial anomalous pulmonary vein connection is a rare congenital heart disease, especially with intact atrial septum. Now we reported a case of the left superior pulmonary vein drainage to left innominate vein through a vertical vein, and corrected with video assisted thoracoscopy. CASE PRESENTATION: A-59-years old man diagnosed left anomalous partial pulmonary vein connection with presentation of short breathiness and palpation, and diagnosed with computer tomography pulmonary angiography. The operation was carried out under video assisted thoracoscopy with one manipulation incision and one observational incision, the vertical vein was dissected and anastomosis with left atrial appendage. The patients recovered smoothly and postoperative CTPA showed anastomosis ostium was unobstructed. CONCLUSION: The left lateral thoracotomy and video assisted thoracoscopic surgery is a feasible for correction of left PAPVC with intact interatrial septum without using CPB.

Fifth-time redo mitral valve replacement via right thoracotomy under systemic hyperkalemia cardiopulmonary bypass without aortic cross-clamp.

The surgical management of prosthetic valvular endocarditis (PVE) can be challenging. We report a case of a 46-year-old female patient who had a history of four cardiac operations. We chose a mitral valve replacement via right thoracotomy to enable optimal exposure of the mitral valve (MV). Because of multi-reoperations, we employed systemic hyperkalemia for cardiac arrest to protect the heart during cardiopulmonary bypass (CPB) without aortic cross-clamping. Here, we present a complex operation that performed management of CPB under hyperkalemia and the patient had a good postoperative recovery.

The role of CD38 in ischemia reperfusion injury in cardiopulmonary bypass and thoracic transplantation: a narrative review.

Background and Objective: Ischemia reperfusion injury (IRI) is often the underlying cause of endothelium breakdown and damage in cardiac or transplantation operations, which can lead to disastrous post-operative consequences. Recent studies of cluster of differentiation 38 (CD38) have identified its critical role in IRI. Our objective is to provide a comprehensive overview of CD38-mediated axis, pathways, and potential CD38 translational therapies for reducing inflammation associated with cardiopulmonary bypass (CPB) or thoracic transplantation and IRI. Methods: We conducted a review of the literature by performing a search of the PubMed database on 2 April 2023. To find relevant publications on CD38, we utilized the MeSH terms: "CD38" AND "Ischemia" OR "CD38" AND "Transplant" OR "CD38" AND "Heart" from 1990-2023. Additional papers were included if they were felt to be relevant but were not captured in the MeSH terms. We found 160 papers that met this criterion, and following screening, exclusion and consensus a total of 36 papers were included. Key Content and Findings: CD38 is most notably a nicotine adenine dinucleotide (NAD)+ glycohydrolase (NADase), and a generator of Ca2+ signaling secondary messengers. Ultimately, the release of these secondary messengers leads to the activation of important mediators of cellular death. In the heart and during thoracic transplantation, this pathway is intimately involved in a wide variety of injuries; namely the endothelium. In the heart, activation generally results in vasoconstriction, poor myocardial perfusion, and ultimately poor cardiac function. CD38 activation also prevents the accumulation of atherosclerotic disease. During transplantation, intracellular activation leads to infiltration of recipient innate immune cells, tissue edema, and ultimately primary graft dysfunction (PGD). Specifically, in heart transplantation, extracellular activation could be protective and improve allograft survival. Conclusions: The knowledge gap in understanding the molecular basis of IRI has prevented further development of novel therapies and treatments. The possible interaction of CD38 with CD39 in the endothelium, and the modulation of the CD38 axis may be a pathway to improve cardiovascular outcomes, heart and lung donor organ quality, and overall longevity.

Severe noncardiogenic pulmonary edema after cardiopulmonary bypass: Case report.

Lung injury is a common complication after cardiopulmonary bypass (CPB). However, cases of noncardiogenic pulmonary edema in which the patient ultimately requires extracorporeal membrane oxygenation (ECMO) support are uncommon. A 54-year-old man was admitted to the hospital with shortness of breath after activity and paroxysmal dyspnoea at night for 3 months. Infective endocarditis and acute heart failure were diagnosed. The patient underwent emergency surgery including aortic valve replacement, mitral valve replacement, tricuspid valve repair, and ventricular septal defect correction. It's noteworthy that the patient experienced significant pulmonary edema during the surgery and within 8 hours postoperatively, with over 3000 mL of yellow-clear fluid aspirated from the trachea and bronchi. The patient eventually recovered through ECMO V-V mode treatment. Inflammatory markers were markedly elevated during the perioperative period, and blood smear revealed Gram-positive bacterial infection. Blood NGS testing detected Streptococcus pneumoniae infection. Despite various factors contributing to the patient's pulmonary edema, it is hypothesized that the edema is related to uncontrolled inflammatory response and cytokine storm. Therefore, when significant pulmonary edema occurs during surgery, swift and decisive actions are necessary to avoid missing the optimal rescue window. If required, the use of ECMO is an effective final treatment option.

Difficulty Weaning From Cardiopulmonary Bypass Following an Aortic Valve Replacement.

Aortic valve replacement (AVR) remains the treatment of choice for severe aortic stenosis. Despite the growing number of transcatheter AVR (TAVR) in younger and intermediate-to-low-risk patients, surgical AVR (SAVR) is widely used and retains low operative mortality, low rate of complications, and predictable long-term valve durability. Although it is a straightforward procedure, on some occasions, a surgeon could face challenging situations, such as compromised coronary flow and an inability to wean the patient from cardiopulmonary bypass (CPB). Our patient required concomitant coronary artery bypass grafting to overcome biventricular failure and facilitate successful weaning from CPB.

Harlequin syndrome during peripheral cardiopulmonary bypass in a patient with an obstructing tracheal schwannoma: A case report.

Surgical resection of obstructive tracheal tumors can be challenging to cardiothoracic surgeons and anesthesiologists. It is often difficult in these cases to maintain oxygenation by face mask ventilation during induction of general anesthesia. Also, the extent and location of these tracheal tumors can preclude conventional induction of general anesthesia and subsequent successful endotracheal intubation. Peripheral cardiopulmonary bypass (CPB) under local anesthesia and mild intravenous sedation may be safe to support the patient until securing a definitive airway. We describe a case of a 19-year-old female with a tracheal schwannoma, who developed differential hypoxemia (Harlequin, or North-South, syndrome) after institution of awake peripheral femorofemoral venoarterial (VA) partial CBP.

Symptomatic uterine leiomyomatosis with intracaval and intracardiac invasion: Video case report.

Background: Fibroid is the most prevalent benign tumor of the female genital tract. Intravenous and intracardiac leiomyomatosis (IVL and ICLM, respectively) are rare complications that present with symptoms of pulmonary thromboembolism and heart failure and whose etiology, despite controversial, is a direct vascular invasion by a primary uterine leiomyoma. Case presentation: We present the case of a 31-year-old female patient with a previous history of pelvic pain and dysmenorrhea, whose ultrasound showed an enlarged and heterogeneous uterus. Complete hysterectomy was performed, and the anatomopathological examination showed leiomyomas without evidence of malignancy. One month later, the patient manifested dyspnea and chest pain. A neoplastic thrombus was identified, extending from the inferior vena cava to the right atrium, for which we proceeded with cavo-atrial thrombectomy under Normothermic Cardiopulmonary Bypass (CPB) with Warm Blood Cardioplegia (WBC). A metastatic lung injury of non-malignant histology was also detected. Discussion: Uterine leiomyoma is a very common benign tumor of the female genital tract. IVL with ICLM are rare and difficult-to-treat complications, whose etiology is a direct vascular invasion by a primary uterine leiomyoma, although it is still controversial. The incidence of ICLM is 10 to 30% of IVL cases. The main symptoms of ICLM are dyspnea, syncope, edema of the lower extremities and palpitations. Treatment is based on complete surgical removal of the tumor thrombus. Studies demonstrated that the one-stage procedure is safer from the patient's perspective and that CPB with WBC reduced intraoperative blood loss and total operative time, ensuring a less traumatic postoperative. Conclusions: Most patients with uterine leiomyoma are asymptomatic and acute complications are rare. In ICLM clinical manifestations are related to heart failure and flow obstruction. Because of the severity of the condition and the curative potential of treatment, surgery is morbid but highly recommended. The use of CPB with WBC improved the postoperative period and increased the patient's quality of life.

H1 and H2 antihistamines pretreatment for attenuation of protamine reactions after cardiopulmonary bypass: a randomized-controlled study.

BACKGROUND: Protamine administration post-cardiopulmonary bypass (CPB) can potentially cause hemodynamic instability. Histamine released from mast cells is believed to be responsible for hypotension after protamine administration. The aim of this study was to examine the effects of pretreatment with H1 and H2 antihistamines on changes in systemic arterial pressure following protamine administration. METHODS: This study was a randomized, triple-blinded, placebo-controlled study, conducted at a university hospital. Forty adult patients undergoing elective coronary artery bypass grafting (CABG) or single valve surgery were included. The patients were randomly allocated (20 patients in each group) to receive a single dose of combined chlorpheniramine 10 mg and ranitidine 50 mg or normal saline intravenously immediately after separation from CPB prior to protamine administration. Trajectory changes in systolic blood pressure (SBP), mean arterial pressure (MAP), and vasoactive-inotropic score (VIS) from baseline until 35 minutes following protamine administration (24-time points) were compared between the two groups. Serial serum tryptase levels were also obtained at baseline, 30 and 60 minutes after protamine was given. RESULTS: Forty patients were included in the analysis. Demographic and baseline blood pressure were similar between the two groups. At 30 minutes after protamine administration, there were no significant differences in both crude SBP [mean difference: -7.1 mmHg, 95% confidence interval (CI), -1.1 to 15.3 mmHg, P=0.09] and SBP after adjustment for the European System for Cardiac Operative Risk Evaluation (EuroSCORE II), CPB time, and VIS (mean difference: -3.9 mmHg, 95% CI, -11.9 to 4.0 mmHg, P=0.33). There were also no significant differences in crude MAP (mean difference: -2.1 mmHg, 95% CI, -6.9 to 2.7 mmHg, P=0.39) and adjusted MAP (mean difference: -0.7 mmHg, -5.9 to 4.4 mmHg, P=0.78) between the two groups. None of the patients in both groups had a significant increase in serum tryptase from baseline. No differences in median serum tryptase levels at baseline, 30 and 60 minutes were demonstrated between the two groups. CONCLUSIONS: Pretreatment with H1 and H2 antihistamines does not attenuate blood pressure responses to protamine administration in patients after CPB. Mechanisms other than histamine release from mast cells might be responsible for protamine-induced cardiovascular changes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03583567.