Individualized Perioperative Hemodynamic Goal-directed Therapy in Major Abdominal Surgery (iPEGASUS-trial) - A Multi-center, Prospective, Randomized Trial
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Hemodynamic Instability
- Sponsor
- Universitätsklinikum Hamburg-Eppendorf
- Enrollment
- 380
- Locations
- 7
- Primary Endpoint
- Composite of morbidity and mortality on day 28
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
To evaluate the impact of perioperative, algorithm driven, hemodynamic therapy based on individualized fluid and cardiac output optimization on postoperative moderate and severe complications in patients undergoing major abdominal surgery including visceral, urological, and gynecological operations.
In the proposed study, hemodynamic therapy is tailored individually to each patient, based on individual preload optimization by the functional parameter "pulse pressure variation (PPV)" and based on an individually titrated goal of cardiac index. The proposed study therefore further develops the concept of hemodynamic goal-directed therapy to individually set goals and is designed to assess its impact on morbidity and mortality.
Detailed Description
Postoperative mortality in patients undergoing surgery is on average still 4% in Europe as evaluated recently in a cohort study across 28 European countries and is considered to be even higher in high risk surgery. But besides this significant risk of death, in particular moderate and severe postoperative complications, affecting up to 40% of patients after major surgery, frequently lead to severe reductions of quality of life and cause high healthcare costs in western nations. Perioperative hemodynamic goal-directed optimization is believed to be an integral part to reduce in particular postoperative morbidity significantly and possibly also mortality. Algorithm driven optimization of macrocirculation aiming on best possible oxygen and substrate delivery to end organs and tissues is thought to be the theoretical mechanism of this therapy. A recent large multi-center trial based on such a pragmatic, non-individualized protocol failed to reduce composite morbidity underlining this weak point of this approach. The reason for failing statistically significant improvement of clinical outcome first of all has to be seen in not taking into account individual hemodynamic needs of each single patient. Every patient was hemodynamically treated according to a "one size fits all of maximizing stroke volume" approach. In contrast, a first mono-center trial gave evidence that individualized early goal-directed therapy based on an individually optimized volumetric cardiac preload parameter (global end-diastolic volume) reduces complications and ICU length of stay after cardiac surgery. Further, and even more important, a first multi-center pilot study using a goal-directed algorithm aiming to optimize blood flow oriented on individual cardiac capacities (individualized optimal cardiac index) in major abdominal surgery demonstrated feasibility and a reduction in postoperative complications. This finding needs to be confirmed in a multi-center study that is adequately powered to detect changes in specific complications and in mortality before clinical practice can be changed accordingly. Therefore, the hypothesis of this proposed prospective two arm randomized study is that algorithm driven individualized hemodynamic goal-directed therapy reduces moderate and severe postoperative complications being a massive burden on quality of life and health care costs. The proposed study develops the concept of hemodynamic goal-directed therapy to individually set goals and is designed to assess its impact on morbidity and mortality.
Investigators
Eligibility Criteria
Inclusion Criteria
- •To provide high generalizability and representativeness the high number of patients with laparotomy and major surgical trauma is included into this study. - Therefore, open visceral, urological, and gynecological surgery is covered by this study.
- •Expected duration of surgery must be ≥ 120 minutes and requirement of volume therapy needs to be expected ≥ 2 liters.
- •Risk for any postoperative complications needs to be ≥10% assessed by the ACS (American College of Surgery)- NSQUIP (National Surgical Quality Improvement Program) risk calculator.
Exclusion Criteria
- •Patients \<18 years,
- •laparoscopic approach,
- •patients not having sinus rhythm,
- •patients having highly impaired left ventricular function (ejection fraction \<30%) or severe aortic valve stenosis (aortic valve area \<1 cm2, mean gradient \>40 mmHg),
- •pregnant women,
- •emergency surgeries (surgery required within 24 hours),
- •primarily vascular surgery,
- •patients suffering from septic shock,
- •patients having phaeochromocytoma,
- •patients suffering from non-cardiac chest pain,
Outcomes
Primary Outcomes
Composite of morbidity and mortality on day 28
Time Frame: 28 days
Considering the high relevance for the individual patient and the society, postoperative outcome is most appropriately reflected by a combination of morbidity and mortality. Therefore, the primary endpoint is a composite comprising rate of patients with one or more moderate or severe postoperative complications or death within 28 days post surgery. Moderate and severe postoperative complications are defined on the basis of a consensus statement of an ESA (European Society of Anesthesiology)- ESICM (European Society of Intensive Care Medicine) joint task force on perioperative outcome measures.
Secondary Outcomes
- Mortality(Day 180)
- Quality of life after 6 months(Time point of enrolment and on day180)
- Morbidity(Day 1,3,5,7 and 180)