Influence of early goal-directed therapy
using arterial waveform cardiac output measurement in high-risk surgery.

The majority of complications after surgery occurs in a minority of patients. EGDT has shown to improve outcome in this patient group, which is high-risk either because of the type of surgery or due to the presence of coexisting disease. However, safety concerns and practical issues associated with advanced hemodyamic monitoring limit the introduction of EGDT in routine practice. Arterial waveform analysis (AWA) provides easy, less invasive, continuous cardiac output measurement, and could therefore guide EGDT. A number of small single-center studies investigating AWA-based EGDT in high-risk surgery showed promising results. However, a multi-center trial in a large patient sample has not been performed yet. In the presented study, we aim to determine whether EGDT, aimed at optimizing CO measured by AWA, improves outcome in high-risk, abdominal surgery. The study design is a multi-center, randomized controlled, clinical study. The study population concerns 542 patients undergoing elective, extended abdominal surgery with an increased risk of postoperative mortality and morbidity.

EGDT reduces the incidence of major complications in high-risk, abdominal surgery.

The time points for the outcome measures are indicated above.

In patients allocated to EGDT, cardiac output (CO) is continuously measured using arterial waveform analysis until discharge from the ICU or PACU, with a maximum of 24 hours. If CO decreases below a preset, age-dependent, threshold value, a therapy algorithm starts in order to increase CO above the threshold value. In this algorithm, stroke volume variation measurement and passive leg raising are used to guide the choice for fluids or vasoactive substances to increase CO.



Standard care group:

Patients assigned to standard care will be treated according to local routine, with the following conditions:

1. After induction of anesthesia and tracheal intubation, patients will be mechanically ventilated (volume control) with a fixed tidal volume of 8 ml?kg-1 (ideal body weight, IBW) throughout the procedure, adjusting respiratory rate to maintain normocapnia;

2. An arterial line, central venous line and urine catheter are placed;

3. Hypotension after induction is treated with cristalloids or colloids first, with a maximum of 500 ml. Ongoing hypotension is treated with continuous infusion of norepinephrine. Sudden, short-lasting hypotension is treated with phenylephrine, ephedrine, or cafedrine/theodrenaline, depending on local routine;

4. Transfusions will be applied according to the 4-5-6 rule.

Therapy is aimed at maintaining:

1. SpO2 >/= 95%;

2. MAP >/= 60 mmHg or 25% below baseline in case of preexisting hypertension;

3. Heart rate < 100?min-1 or 25% above baseline.