Argipressin 20units/1ml solution for injection ampoules

Introduction Liver resection carries a high risk for extensive bleeding and need for blood transfusions, which is associated with significant negative impact on outcome. In malignant disease, the most common indication for surgery, it also includes increased risk for recurrence of cancer. Argipressin decreases liver and portal blood flow and may have the potential to reduce bleeding during liver surgery, although this has not been explored. Method and analysis ARG-01 is a prospective, randomised, placebo-controlled, double-blinded study on 248 patients undergoing liver resection at Sahlgrenska University Hospital, Sweden. Patients will be randomised to one of two parallel groups, infusion of argipressin or normal saline administered peroperatively. The primary endpoint is peroperative blood loss. Secondary outcomes include need for blood transfusion, perioperative variables, length of hospital stay, the inflammatory response, organ damage markers and complications at 30 days. Ethics and dissemination The study is enrolling patients since March 2022. The trial is approved by the Swedish Ethical Review Authority (Dnr 2021-03557) and the Swedish Medical Product Agency (Dnr 5.1-2021-90115). Results will be announced at scientific meetings and in international peer-reviewed journals. Trial registration number ClinicalTrials.gov, NCT05293041 and EudraCT, 2021-001806-32

Abstract licence: CC BY 4.0

Introduction Cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC) is a treatment for peritonitis carcinomatosa. These procedures often involve significant blood and fluid loss, leading to hyperdynamic circulation and vasodilation, necessitating intraoperative fluids and vasoconstrictors such as catecholamines. Excessive fluid administration to counteract vasodilation can cause intraoperative fluid overload, which is linked to increased postoperative complications. Vasopressin has emerged as a potential alternative to catecholamines, restoring vascular tone via non-adrenergic pathways and supporting perfusion pressure, potentially reducing the need for compensatory fluids solely administered to compensate for vasodilation. We hypothesise that compared with norepinephrine, vasopressin reduces cumulative intraoperative fluid administration during CRS-HIPEC within a goal-directed fluid therapy (GDFT) protocol, ultimately leading to a lowering of postoperative complications.Methods and analysis HiPress is a two-centre, two-arm randomised clinical trial with blinding of both patients and outcome assessors. A total of 70 adult patients undergoing CRS-HIPEC will be included. Patients will be randomised to receive either continuous low-dose argipressin or continuous low-dose norepinephrine. Both groups will receive standardised GDFT during the procedure. The primary endpoint is cumulative intraoperative fluid administration (mL). Secondary endpoints include direct fluid-related outcomes (eg, cumulative intraoperative fluid (ml/kg/hour), postoperative fluid balance until day five and ultrasound-assessed pulmonary oedema and venous congestion) and indirect fluid-associated outcomes (eg, quality of recovery, surgical and abdominal complications, acute kidney injury (AKI), pulmonary complications, length of ICU and hospital stay and 30-day mortality).Ethics and dissemination The study is enrolling patients since February 2025. The trial is approved by the Medical Research Ethics Committee (hereinafter: MREC) NedMec, The Netherlands (Ref: D-25-500202). Results of the trial will be published in an international peer-reviewed journal and announced at national and international scientific meetings.Trial registration number Clinical Trials Information System (CTIS): European Union clinical trials register (EUCT) number: 2024–5 13 598-33-00

Abstract licence: CC BY-NC 4.0

IntroductionThe hemodynamic management of septic patients involves initial fluid therapy, followed by the use of vasoconstrictors in case of treatment failure. The latest Surviving Sepsis Campaign guidelines suggest the synergistic use of argipressin in addition to norepinephrine when hemodynamic optimization is not achieved with norepinephrine alone.MethodsIn our single-center retrospective observational study, the primary endpoint is the safety of initial norepinephrine-argipressin association treatment, assessed through a reduction in Resistance Index. Our secondary endpoint includes the efficacy of this combination, measured by an increase in Mean Arterial Pressure and a reduction in Resistance Index as an indicator of organ perfusion. The Resistance Index (RI) is evaluated through Power Doppler ultrasound. RI is crucial for assessing multi-district vascular tone and multiorgan perfusion. Patients were categorized into three groups based on their treatment. In Group 1, we analyzed patients treated with norepinephrine alone in incremental doses; in Group 2, we analyzed patients receiving the initial norepinephrine-argipressin association treatment (norepinephrine 0.05 mcg/kg/min-argipressin 0.03 IU/min); in the third group (Group 3), we analyzed patients given argipressin (0.03 IU/min) after norepinephrine (<0.10–0.25≥ mcg/kg/min) to stabilize their hemodynamics (MAP > 65 mmHg). RI measurements were taken in the Renal Artery (ARE), Radial Artery (AR), Central Retinal Artery (CRA), and Superior Mesenteric Artery (AMS) at four different time points: T0 before vasopressor therapy, T1 at 1 h, T2 at 24 h, and T3 at 48 h after vasopressor infusion.ResultsA total of 48 patients were divided into three groups: 17 patients in Group 1, 16 in Group 2, and 15 in Group 3. In Group 1, an increase in Mean Arterial Pressure (MAP) was observed, but there was an increase in RIs in the right CRI and left ARE. In Group 2, there was an improvement in MAP and a reduction in RIs in the right/left CRI, left ARE, AMS, and right AR. In Group 3, there was an increase in MAP and a reduction in RIs in the right/left CRI, left ARE, AMS, and right AR.ConclusionEarly norepinephrine-argipressin association treatment appears to be a valid strategy for hemodynamic optimization in this patient population.

Abstract licence: CC BY 4.0

Infusion of Argipressin during hepatic resection surgery may reduce blood loss. It may also reduce transfusion requirements, and mitigate the perioperative inflammatory response compared to placebo. Subjects will be randomized to infusion of Argipressin or placebo during surgery. Blood loss, transfusion requirements, surgical data including length of stay in hsopital, inflammatory markers and markers of renal- intestinal- and cardiac injury will be assessed. Two sub-studies has been added; one for evaluation of coagulation function, and one for assessment of pain scores and morphine consumption. Conditions: Colon Cancer Liver Metastasis, Inflammatory Response, Vasopressin Causing Adverse Effects in Therapeutic Use. Interventions: Argipressin, Placebo.

Source: ClinicalTrials.gov (public domain)