Supernormal Oxygen Delivery for Elderly Surgical Patients

Study Overview
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Brief Summary
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Elderly patients with poor cardiopulmonary reserve tend to suffer higher risk and develop more complications following major surgery. Quite a few researches have shown the benefits of goal-directed therapy (GDT) using fluid loading or inotropic agents or both to improve outcome during major surgery. However there is concern that inotropic therapy for a supernormal oxygen delivery (DO2I) may lead to an increased incidence of myocardial ischemia. Even though the meta-analysis has stated that DO2I strategy could possibly reduce the incidence of cardiac complication than stroke volume optimization strategy, there are very few evidence available in the literature regarding the effect on myocardial ischemia in surgical patients, especially in non-cardiac surgical patients. This study is undertaken to test the hypothesis that an intraoperative DO2I optimization result in a decreased myocardial ischemia in the elderly high-risk surgical patients.

Detailed Description
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Elderly patients with poor cardiopulmonary reserve tend to suffer higher risk and develop more complications following major surgery [1]. Quite a few researches have shown the benefits of goal-directed therapy(GDT) using fluid loading or inotropic agents or both to improve outcome during major surgery [2-7]. The maintenance of adequate tissue perfusion and global oxygen delivery (DO2I) is essential to maintain adequate tissue perfusion and oxygenation in relation to increased metabolic demand during high risk surgery. However, there is concern that inotropic therapy for a supernormal oxygen delivery may lead to an increased incidence of myocardial ischemia [8]. Even though the meta-analysis has stated that DO2I optimization could possibly reduce the incidence of cardiac complication than stroke volume optimization strategy [9],there are very few evidence available in the literature regarding the effect on myocardial ischemia in surgical patients, especially in non-cardiac surgical patients. This study is undertaken to test the hypothesis that an intraoperative DO2I optimization result in a decreased myocardial ischemia in the elderly high-risk surgical patients. The investigators will conduct a prospective, randomized, controlled, double-blinded trial in seventy patients who scheduled for proximal femur surgery under General anesthesia following nerve block. Both the patients will be allocated to one of two equal groups to receive either intraoperative fluid regimen guided by SV strategy or DO2I strategy. In the control(SV) group, the patients will receive an intravenous infusion of 250 ml Ringer's lactate solution in 5 min as a fluid challenge for stroke volume maximization. In the experimental(DO2I) group, fluid and dobutamine will be given to reach a stroke volume maximization and supernormal oxygen delivery. The primary outcome is preoperative and 24h postoperative serum concentration of troponin T. Secondary outcomes include the incidence of tachycardia, arrhythmia, myocardial infarction, pneumonedema and acute heart failure, blood pressure, pulmonary infection, fluid volume, blood transfusion volume, renal function, PONV, Length of postoperative hospital stay and mortality. Data will be collected and recorded by the clinical teams who are blind to study arm allocation.

Official Title
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A Randomized Controlled Study of Supernormal Oxygen Delivery Goal-directed Therapy for Elderly Patients Undergoing Proximal Femoral Surgery.

Conditions
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Femoral Fractures

Intervention / Treatment
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* Procedure: SV maximization
* Procedure: supernormal DO2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients scheduled for proximal femur fracture (PFF) surgery at this institution American Society of Anaesthesiologists (ASA) physical status of III or VI Two or more risk factors according to risk index of Lee Exclusion Criteria: Patient age < 70 yrs Ongoing myocardial infarct or ischemia Chronic haemodialysis Inability to cooperate in the study Patient refusal

Ages Eligible for Study
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Minimum Age: 70 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: SV maximization<br>Goal-directed fluid therapy with stroke volume maximization. Device: The Volume-View system from Edwards Co. | Procedure: SV maximization<br>* When SpO2 ≥92%, mean arterial pressure (MAP) 65-100 mmHg, HR <100 bpm, Hb >8mg/dL and temperature ≥36℃, the patients will receive a 250 ml Ringer's lactate solution in 5 min as a fluid challenge for stroke volume (SV) maximization. The fluid challenge will repeat until the SV failed to increase by a factor of 10%. A reassessment on the SV maximization will be taken every 30 minutes and to restart algorithm when increased SV >10% or blood loss >250ml. Blood transfusions will be used to maintain a hemoglobin concentration over 8mg/dL.<br>* Other names: Stroke volume maximization;|
| Experimental: supernormal DO2<br>Goal-directed fluid therapy with stroke volume maximization and supernormal oxygen delivery. Device: The Volume-View system from Edwards Co. | Procedure: supernormal DO2<br>* Goal directed fluid therapy is administrated as group SV maximization. Then DO2I will be assessed. If at this stage the DO2I can not be greater than 600 mL/m2 (supernormal oxygen delivery goal), then dobutamine will be started at a dose of 2.5 μg/kg/min and increased by the same increment every 20 minutes until the described target is reached or until a maximal dose of 20 μg/kg/min is given. Dobutamine is decreased in dose or discontinued if the heart rate is above 100 beats per minute or shows signs of cardiac ischemia.<br>* Other names: Stroke volume maximization + supernormal oxygen delivery;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in concentration of troponin T at 24 hours postoperatively | Intraoperative supernormal oxygen delivery strategy will reduce the changes in concentration of troponin T at 24 hours postoperatively. | preoperative value and 24 hours postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cardiac complication up to 24 hours postoperatively | Occurrence of newly diagnosed arterial fibrilation ,severe arrhythmia,clinical signs of unstable angina, myocardial infarction,pulmonary edema or therapy-requiring cardiac failure. | up to 24 hours postoperatively | 
| blood pressure | Invasive arterial BP(mmHg) is measured through an arterial line at the arm.episode of hypotension (30% decrease in mean BP in relation to baseline values) and hypertension (30% increase in mean BP in relation to baseline values) will be recorded. | up to 24 hours postoperatively | 
| heart rate (HR) | HR(beats/min), bradycardia (HR < 50 beats/min), and tachycardia (HR > 100 beats/min) will be recorded at the same time as BP recording. | up to 24 hours postoperatively | 
| SpO2 | SpO2(%) and hypoxemia (SpO2 <90%) will be recorded at the same time as BP recording. | up to 24 hours postoperatively | 
| fluid balance | amount of fluids (ml) infused, amount of fluid losses | up to 24hours after surgery | 
| blood transfusion volume | amount of blood transfusion, amount of blood losses. | up to 24 hours postoperatively | 
| Acute Kidney Injury | perioperative and 24h postoperative urine volume, serum creatinine, blood urea nitrogen. | up to 24 hours postoperatively | 
| Postoperative Nausea and Vomiting (PONV) | Postoperative Nausea and Vomiting, The incidence of PONV will be recorded using a 4-point objective score (1 = no PONV;2 = mild nausea, no vomiting; 3 = excessive nausea or vomiting;4 = vomiting ≥2 times). | 24 hours postoperatively | 
| length of postoperative hospital stay | days from end of surgery to hospital discharge | 28 days postoperatively | 
| mortality | mortality within 28 days after surgery | 28 days postoperatively | 
| cardiac complication at 28 days postoperatively | Occurrence of newly diagnosed arterial fibrilation ,severe arrhythmia,clinical signs of unstable angina, myocardial infarction,pulmonary edema or therapy-requiring cardiac failure. | 28 days postoperatively | 
| incidence of pulmonary infection | number of patients having pulmonary infection requiring intravenous antibiotic therapy | up to 28 days postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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proximal femoral fracture, goal-directed therapy, myocardial injury, supernormal oxygen delivery, elders, stroke volume maximization