The Effect of Pituitrin on the Patients With Pulmonary Hypertension Undergoing Cardiac Surgery

Study Overview
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Brief Summary
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This study is a parallel group, single blind, randomized controlled trial. Patients with pulmonary hypertension who met the inclusion criteria and planned to undergo elective cardiac surgery under cardiopulmonary bypass from July 1, 2022 to December 1, 2024 in the Department of cardiac surgery of the First Affiliated Hospital of Shandong First Medical University were selected. After removing the aortic blocking forceps, the experimental group immediately injected the test drug (pituitrin 0.04u/ (kg · h)) intravenously, The control group was immediately injected with the corresponding dose of normal saline by intravenous pump. The main outcome was the composite endpoint of all-cause mortality 30 days after operation or common complications after cardiac surgery (stroke, requiring mechanical ventilation for more than 48 hours, deep sternal wound infection, cardiac reoperation, extracorporeal membrane oxygenation, atrial fibrillation or acute renal injury).

Detailed Description
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Cardiac surgery is the most important treatment for serious coronary heart disease, valvular heart disease, congenital heart disease and other heart diseases. Its postoperative mortality and serious complications have also been widely concerned, especially in patients with pulmonary hypertension. The persistent pulmonary hypertension and systemic vascular paralysis during the perioperative period are the main causes of early postoperative death and serious complications such as organ failure.Catecholamine vasoactive drugs commonly used in cardiac surgery may aggravate the condition of pulmonary hypertension, while the use of drugs to reduce pulmonary hypertension, such as nitric oxide, prostaglandins and phosphodiesterase inhibitors, may worsen the state of systemic vascular paralysis. Vasopressin and oxytocin are two effective components in pituitrin, and vasopressin is the main component that exerts strong vasoconstrictive effect.Vasopressin binds to receptors distributed in vascular smooth muscle, pituitary and kidney, and exerts its effects by regulating adenosine triphosphate sensitive K+ channel function, nitric oxide production and enhancing vascular response to catecholamine.In addition, oxytocin can also bind to the receptors distributed in the heart and vascular endothelium, and play a role by releasing atrial natriuretic peptide and nitric oxide.Therefore, pituitrin can not only constrict systemic circulation vessels and increase systemic circulation pressure, reduce pulmonary artery pressure and pulmonary vascular resistance, but also protect the heart and kidney. Therefore, this study intends to explore whether pituitrin has an impact on the prognosis of patients with pulmonary hypertension after cardiac surgery, so as to provide reference for its clinical application.

Official Title
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The Effect of Pituitrin on Postoperative Outcomes in Patients With Pulmonary Hypertension Undergoing Cardiac Surgery: a Randomized Controlled Study

Conditions
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Cardiac Surgery, Hypertension, Pulmonary

Intervention / Treatment
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* Drug: Pituitrin
* Drug: normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥18 years and ≤80 years; scheduled for elective cardiopulmonary bypass heart surgery (adult congenital heart disease surgery, coronary artery bypass grafting, valve replacement, valvuloplasty, heart transplantation and aortic surgery); Patients who had pulmonary hypertension (Mean pulmonary artery pressure at rest ≥ 25mmhg or pulmonary artery systolic pressure (PASP) ≥ 40mmhg as shown by echocardiography); sign informed consent. Exclusion Criteria: use pituitrin or vasopressin before operation; Patients who had acute coronary syndrome; preoperative use of left ventricular assist devices other than intra aortic balloon - pump (IABP); Patients who had liver, thyroid and adrenal diseases, severe lung diseases, diabetes; Patients who had preoperative renal insufficiency (The increase of serum creatinine (SCR) within 48 h ≥ 0.3mg/dl (or ≥ 26.5 μ mol/L)； Or it is known or speculated that the increase of SCR in the past 7 days is more than 1.5 times of the basic value; Or 0.5ml/kg urine volume per hour for 6H); Patients who had severe carotid artery stenosis, preoperative stroke, mental disorder and other difficult to communicate and cooperate; Patients who had peripheral vascular disease, allergy to vasopressin or pituitrin, severe hyponatremia (na+ < 130 mmol/l), acute mesenteric ischemia, pregnancy, malignant tumors, required ECMO and underwent emergency surgery or reoperation; Patients who had participated in other clinical studies in recent 3 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pituitrin group<br>The specification of posterior pituitary injection is 1ml/6U, diluted with normal saline to 0.5u/ml, and injected by intravenous pump at the rate of 0.04u/ (kg · h). | Drug: Pituitrin<br>* The specification of posterior pituitary injection is 1ml/6U, diluted with normal saline to 0.5u/ml, and injected by intravenous pump at the rate of 0.04u/ (kg · h).<br>|
| Placebo Comparator: normal saline group<br>Intravenous infusion of normal saline at the same dose and speed | Drug: normal saline<br>* Intravenous infusion of normal saline at the same dose and speed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| a composite endpoint of mortality or severe postoperative complications | severe complications after cardiac surgery, including stroke, requirement of mechanical ventilation for longer than 48h, deep sternal wound infection, reoperation, or acute renal failure | Within 30 days after cardiac surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of postoperative infection | The patient appears infection after surgery. | Within 30 days after cardiac surgery | 
| septic shock | Septic shock was defined as the septic syndrome with shock caused by microorganisms and their toxins. | Within 30 days after cardiac surgery | 
| duration of mechanical ventilation | Total duration of mechanical ventilation during or after surgery. | Time from the beginning of mechanical ventilation to the end of mechanical ventilation up to 30 days after cardiac surgery. | 
| postoperative pulmonary complications | This is a composite endpoint indicator, includs atelectasis, pleural effusion, diaphragmatic dysfunction, prolonged mechanical ventilation, pneumonia, pneumothorax, acute respiratory distress syndrome, etc.The occurrence of any of the above pulmonary complications is considered as a positive outcome. | Within 30 days after cardiac surgery | 
| time to achieve hemodynamic stability | From hemodynamic change to hemodynamic stability. | Within 30 days after cardiac surgery | 
| use of dobutamine or other vasoactive drugs | The patients use dobutamine or other vasoactive drugs. | Within 30 days after cardiac surgery | 
| incidence of digital ischemia | Digital ischemia is a symptom caused by insufficient blood supply to the fingers. | Within 30 days after cardiac surgery | 
| acute mesenteric ischemia | Acute mesenteric ischemia includes arterial and venous thrombosis, thrombosis, and vasoconstriction secondary to low blood flow. Arterial lesions mainly included superior mesenteric artery embolism, superior mesenteric artery thrombosis and non occlusive mesenteric ischemia. The main venous lesions were mesenteric venous thrombosis. | Within 30 days after cardiac surgery | 
| gastrointestinal complications | Including dyspepsia, abdominal distension, constipation, postoperative stress ulcer, gastrointestinal bleeding, etc. | Within 30 days after cardiac surgery | 
| incidence of acute myocardial infarction | Acute myocardial infarction is myocardial necrosis caused by acute and persistent ischemia and hypoxia of coronary artery. | Within 30 days after cardiac surgery | 
| new onset tachyarrhythmia | Tachyarrhythmia includes premature beat, tachycardia, atrial fibrillation and ventricular fibrillation, etc. | Within 30 days after cardiac surgery | 
| water poisoning | Water poisoning refers to that when the total amount of water ingested by the body greatly exceeds the amount of water discharged, so that water is retained in the body, resulting in the decrease of plasma osmotic pressure and the increase of circulating blood volume. | Within 30 days after cardiac surgery | 
| vasodilative shock | Vasodilative shock is caused by vasodilation, increased vascular bed volume and relatively insufficient intravascular blood volume, including septic shock, anaphylactic shock and neurogenic shock. | Within 30 days after cardiac surgery | 
| incidence of pulmonary embolism | Pulmonary embolismwas defined as clinical pathophysiological syndrome of pulmonary circulatory dysfunction caused by pulmonary artery and its branches blocked by various emboli falling off of systemic circulation. | Within 30 days after cardiac surgery | 
| low cardiac output syndrome | Low cardiac output syndrome refers to the complex pathophysiological changes of insufficient perfusion of multiple organs and tissue hypoxia due to the decrease of cardiac output. | Within 30 days after cardiac surgery | 
| acute respiratory distress syndrome | Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by refractory hypoxemia, which is caused by intrapulmonary and / or extrapulmonary causes. | Within 30 days after cardiac surgery | 
| delirium | Delirium refers to a group of syndromes, also known as acute brain syndrome. It is manifested as consciousness disorder, disorganized behavior, no purpose and unable to concentrate. | Within 30 days after cardiac surgery | 
| need for renal replacement therapy (RRT) | Replacement therapy usually includes hemodialysis, peritoneal dialysis and kidney transplantation. | Within 30 days after cardiac surgery | 
| need for hemodialysis | Hemodialysis (hd) is one of the renal replacement therapies for patients with acute and chronic renal failure. | Within 30 days after cardiac surgery | 
| incidence of readmission to ICU | The patients re-enters ICU. | Within 30 days after cardiac surgery | 
| length of ICU stay | From the day of surgery to the time the patient leaves the ICU. | Within 30 days after cardiac surgery | 
| length of stay | From the day of surgery to the time the patient leaves the hospital. | Within 30 days after cardiac surgery | 
| levels of serum antidiuretic hormone in patients | T1-T4 were defined as entering the operating room, 4, 12 and 24 hour postoperatively, respectively. | at entering the operating room(T1), 4 hour(T2), 12 hour(T3) and 24 hour(T4) postoperatively | 
| levels of copeptin in patients | T1-T4 were defined as entering the operating room, 4, 12 and 24 hour postoperatively, respectively. | at entering the operating room(T1), 4 hour(T2), 12 hour(T3) and 24 hour(T4) postoperatively | 
| secondary endotracheal intubation | Secondary endotracheal intubation refers to the second endotracheal intubation after the patient's postoperative endotracheal intubation is removed. | Within 30 days after cardiac surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiac surgery, Hypertension, Pulmonary, Pituitary Hormones, Posterior, Extracorporeal Circulation