Hematocrit Level Linked to Cardiac Events After Noncardiac Surgery

PROVIDENCE, R.I., June 12-- Even mild preoperative anemia or polycythemia were associated with an increased risk of death and serious cardiac events in older veterans having major noncardiac surgery, researchers here reported.

Thirty-day mortality and cardiac events increased with either positive or negative deviations from normal hematocrits, reported Wen-Chih Wu, M.D., of the Providence VA Medical Center, and colleagues, in the June 13 issue of the Journal of the American Medical Association.

Despite nearly universal measurement of hematocrit values prior to major surgery, the prognostic implications of preoperative anemia or polycythemia are incompletely understood for this high-risk population, and many reports differ on the hematocrit values that can be harmful, Dr. Wu said.

The findings emerged from a retrospective cohort study that used the VA National Surgical Quality Improvement Program database to study 310,311 veterans 65 older. The veterans had major noncardiac surgery from 1997 through 2004 in 132 VA medical centers across the U.S.

On the basis of preoperative hematocrit levels, patients, mainly men (97.7%), were stratified into standard categories of anemia (hematocrit < 39.0%), normal hematocrit (39.0%-53.9%), and polycythemia (hematocrit ? 54%).

Measured by conventional definitions, 42.8% of the cohort had pre-op anemia, 0.2% had polycythemia, and the remaining 56.9% had normal levels.

The crude 30-day post-op mortality rate was 3.9% and the cardiac event rate was 1.8% for the entire study population.

Thirty-day mortality and cardiac event rates increased incrementally, with either positive or negative deviations from normal hematocrit levels, the researchers reported.

A 1.6% (95% confidence interval, 1.1%-2.2%) increase in 30-day postoperative mortality was associated with every percentage-point increase or decrease in the hematocrit value from the normal range.

Compared with a normal hematocrit, a patient with a pre-operative hematocrit of 30.0 % had a 14.4% increased risk of 30-day post-op mortality, and a patient with a pre-op hematocrit of 24 % had a 24.0% increase risk of post-op mortality, the researchers said.

Additional analyses suggest that the adjusted risk of 30-day postoperative mortality and cardiac morbidity begins to rise when hematocrit levels decrease to less than 39% or exceed 51%, the researchers said.

Other than death, major cardiac events included cardiac arrest or Q-wave MI with symptoms or abnormally high levels of cardiac enzymes within 30 days of the index surgery.

Major noncardiac surgeries were defined as procedures done in an operating room requiring general, spinal, or epidural anesthesia.

Operations included prostatectomy, hernia repair, rechanneling of artery, total knee or hip replacement, partial removal of colon, cystoscopy or resection of small bladder tumors, in addition to a long list of other common procedures.

The large cohort with anemia had the most female and nonwhite patients, and the highest rate of diabetes, cardiac disease, neurologic disorders, renal disease, infected surgical wounds, cancer, and pre-op blood transfusions, to name just a few disorders. The group also tended to be older.

Patients with polycythemia were more likely to be smokers, to consume more than two drinks of alcohol a day, and to undergo general, otolaryngoloic, or emergency surgery than patients without polycythemia.

Among study limitations, the researchers cited the fact that about 21% of the preoperative hematocrits were obtained more than four weeks prior to surgery and may not have accurately reflected levels at the time of surgery.

Second, they said, the conclusions for polycythemia may not have been as robust as those for anemia due to a much smaller sample size.

Third, given the observational nature of this study, it was not possible to determine the causal relationship between hematocrit values and the risk of postoperative adverse events.

They also noted that they could not relate the etiology and chronicity of the abnormal hematocrit values with outcomes. If these changes reflect underlying conditions, then a low hematocrit value may be a marker of risk and not a modifiable risk factor.

The results of this study, the investigators said, suggest that in older patients, even minimal degrees of anemia or polycythemia are a risk for those undergoing noncardiac surgery.

Further studies are needed, they wrote, to examine the value of blood restoration strategies, ranging from adding iron, erythropoietin, or red blood cell products for most major elective surgeries.

As for polycythemia, if it is a modifiable risk factor, and not just a marker of conditions that confer risk, the restoration of the intravascular volume may help improve the risk profile of patients with high hematocrit values, they said.

Future studies, Dr. Wu and colleagues said, should determine whether these findings are reproducible in other populations and whether treatment of these two preoperative conditions can improve the postoperative outcomes for this vulnerable population.

In an accompanying editorial, Farhood Farjah, M.D., and David R. Flum, M.D., (a JAMA contributing editor), both of the University of Washington in Seattle questioned the risks of attempting to treat these two conditions.

"Assuming the relationship of hematocrit and outcome is real and generalizes to other cohorts, the central issue to be determined is whether modifying hematocrit improves outcome."

The theory linking preoperative anemia and postoperative events, they said, is that the stress of an operation combined with the limited ability of the heart to compensate in older anemic individuals may lead to cardiac ischemia and death.

Interventions correcting anemia aimed at preventing cardiac stress might be expected to save lives, but expectation and reality are often at odds, they said.

Several randomized trials have compared blood transfusion for moderate anemia compared with more severe degrees of the condition in cardiac surgery and critically ill patients. None of these studies identified important differences in clinical outcomes attributable to transfusion for hematocrit levels that were in the moderate anemia range specified as problematic in the VA study.

Since no intervention is without risk, clinicians should avoid using the findings reported by Dr.Wu and colleagues to justify interventions-transfusion, erythropoietic agents, iron supplementation-outside the research setting, Drs. Farjah and Flum cautioned.

In other clinical arenas involving patients with anemia, such as those with renal failure and cancer, clinicians may have prematurely

embraced use of erythropoietic agents to boost red blood cell counts, only to learn later that despite their best intentions, they may have been causing more harm than benefit.

"The community of clinicians caring for patients preoperatively should learn from these experiences and resist the urge to 'not just stand there-but do something,' " Drs Farjah and Flum said.