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

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

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Hypertension, Pulmonary; Cardiac Surgery
• Intervention / Treatment: Drug: Pituitrin; Drug: normal saline

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Quan Li, doctor; Phone Number: 13964017257; Email: liquann@163.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250000
      • Qianfoshan Hospital, The First Hospital affiliated of Shandong First Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: pituitrin group; 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; 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).
PLACEBO_COMPARATOR: normal saline group; Intravenous infusion of normal saline at the same dose and speed	Drug: normal saline; Intravenous infusion of normal saline at the same dose and speed

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Qianfoshan Hospital
• Investigators: Principal Investigator: Quan Li, doctor, Qianfoshan Hospital, The First Hospital affiliated of Shandong First Medical University

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 1, 2023
• Primary Completion (ANTICIPATED): December 1, 2024
• Study Completion (ANTICIPATED): January 1, 2025

Study Registration Dates

• First Submitted: January 16, 2023
• First Submitted That Met QC Criteria: February 5, 2023
• First Posted (ESTIMATE): February 14, 2023

Study Record Updates

• Last Update Posted (ESTIMATE): February 14, 2023
• Last Update Submitted That Met QC Criteria: February 5, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: cardiac surgery; Hypertension, Pulmonary; Extracorporeal Circulation; Pituitary Hormones, Posterior
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: LM-KLC-2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No