Hemoglobin Optimization to Improve Event Free Survival and Cerebrovascular Health in Anemic Patients Undergoing Non-Cardiac Surgery
Cardiovascular and Stroke Care
Transformation: Iron restricted anemia is a global health problem and is prevalent in patients undergoing surgery. Up to 40% of patients (ACS-NSQUIP, EuSOS) undergoing elective non-cardiac surgery are anemia placing them at increased risk for morbidity (Stroke, MI) and mortality. A high proportion of these patients do not receive optimal treatment for anemia due to the lack of available resources and perceived risk of available therapies. Demonstration that readily available treatments for anemia are safe, effective and improve event free survival will help transform the care of these patients.
Adoptability: Based on a metaanalysis of published studies, we have demonstrated that a combination of erythropoietin and iron therapy is the most effective means of treating preoperative anemia and reducing the rate of blood transfusion, without evidence of increased adverse events. These treatments are readily adoptable, however, high level evidence has not demonstrated their efficacy in terms of improved patient outcome.
Outcomes: We propose to perform a blinded randomized controlled trial to determine whether erythropoietin and intravenous iron is the most effective treatment strategy for iron restricted anemia in patients undergoing non-cardiac surgery. Outcomes will include; an increase in hemoglobin concentration, reduction in red blood cell transfusion, improved brain vascular responsiveness and cognitive function, and reduction in major adverse outcomes including infection, renal failure, stroke, myocardial infarction and death.
Innovation: The innovation will be to establish an optimal anemia management program within the structure of a blinded randomized controlled trial to establish whether treatment of anemia can be demonstrated to improve overall patient outcomes, reduce severe adverse events (MI, Stroke) and maintain brain function following surgery.
Our recently conducted metaanalysis demonstrated that treatment of anemic patients with oral or intravenous (i.v.) iron and/or erythroid stimulating agents (ESAs) increases Hb concentration and reduces RBC transfusion. The combination of ESAs with iron therapy was shown to maximally reduced the risk of red blood cell (RBC) transfusion; RR 0.48 [95% CI 0.44 to 0.52], without evidence of increased adverse events or drug toxicity. Thus, there is a readily available, efficacious and safe method to treat anemia and prevent red blood cell transfusion. We propose to establish a multi-phase randomized controlled trial to assess the efficacy of anemia treatment on a number of important clincal outcomes, including measures of brain function. Our primary hypothesis is that: Preoperative optimization of hemoglobin will reduce brain dysfunction and injury associated with inadequate brain oxygen delivery in anemic patients undergoing surgery.
The innovation will be to optimize preoperative hemoglobin levels in anemic patients and then apply fMRI brain imaging methodology to: 1) Rule out the occurrence of brain injury (stroke) associated with anemia and its treatments; 2) Demonstrate potential improvement in microvascular blood vessel reactivity to carbon dioxide as a sign of vascular health after treatment of anemia; 3) Assess any changes in cognitive abilities of anemic patients before and after optimization of their hemoglobin.
These outcomes will help to determine the benefit of treating anemia prior to elective surgery an impacting health care delivery -by treating peri-operative anemia thereby improving the likelihood of event free survival after surgery.