Anemia and end-organ dysfunction in critically ill medical and surgical ICU patients

Author list Sarah Hemauer Adam J. Kingeter Xue Han Matthew S. Shotwell Pratik P. Pandharipande Liza M. Weavind

Department of Anesthesiology and Biostatistics, Vanderbilt University Medical center, Nashville, TN

Background: Anemia is associated with increased morbidity and mortality, however, transfusion of packed red blood cell (PRBC) is also an independent predictor of worse clinical outcomes. Recent data have supported the safety of restrictive transfusion strategies with a resultant decrease in PRBC use and acceptance of anemia, yet little is known about the impact of this anemia on the daily risk of individual organ dysfunctions in medical and surgical ICU patients.

Methods: We performed a post-hoc analysis of prospectively collected data from the BRAIN- ICU observational cohort study of medical and surgical ICU patients admitted with respiratory failure or shock. Baseline demographic data as well as detailed in-ICU and hospital data, including daily hemoglobin levels, were collected in the study up to hospital Day 30. Patients were evaluated daily for brain dysfunction (delirium) using the CAM-ICU, for cardiac dysfunction (ischemia) using troponin levels, for renal dysfunction using the renal SOFA score (based on creatinine and urinary output) and for respiratory dysfunction using the respiratory SOFA score (based on the PaO2/FiO2 ratio) or need for mechanical ventilation. We also collected data on in-hospital mortality and calculated time to death. The adjustedindependent associations between the current daydaily hemoglobin level and organ dysfunction the following day daily organ dysfunction outcomes were assessed using regression analysis including multinomial, ordinal (proportional odds), and binary logistic regression for nominal endpoints: brain dysfunction CAM-ICU, logistic regression for dichotomous endpoints: cardiac dysfunction (measured by whether troponin >0.1or not) and mechanical ventilation (Y/N), proportional odds logistic regression for ordinal endpoints: renal dysfunction (renal SOFA 0-4 scale) and respiratory dysfunction (resp SOFA 0-4 scale), Cox proportional hazards regression with time- varying covariates was used to assess the survival analysis was used to study the adjusted relationship association between current day hemoglobin and time to death. We used logistic regression to assess the independent association between the daily hemoglobin level and the following daily dichotomous organ dysfunction outcomes; delirium vs. normal; presence or absence of renal and respiratory dysfunctions (respective organ SOFA scores >2), need for mechanical ventilation, and dead versus alive status; proportional odds logistic regression to assess the relationship between hemoglobin levels and the respiratory SOFA score (on an ordinal 0-4 scale) and Cox regressions for the survival analysis. In each analysis, Wwe adjusted for covariates such including as age, the APACHE II score, Charlson comorbidity index, Framingham stroke risk profile, ICU day, ICU type (medical vs. surgical), current sepsis, current organ dysfunction, and current lowest hemoglobin level. and interactions between baseline organ dysfunction, hemoglobin levels .and ICU day. Statistical significance was indicated for p-values less than 0.05, or for 95% confidence intervals that fail to include the relevant null value.

Results: We enrolled 821 patients with a median (interquartile, IQR) age of 61 (51, 71), APACHE II score of 21 (15, 26) of 25 (19,31) and 30% had septsics on enrollment. Current lowest hemoglobin level was significantly associated with respiratory SOFA score the following day. For each increasing unit of the current lowest hemoglobin measurement, the odds of more severe respiratory SOFA score the following day were decreased by 30.6% (95% CI: 16.0, 62.7). This protective effect was significantly reduced in patients with greater current respiratory SOFA score (p-value: <0.001). There was no evidence of an association between current hemoglobin level and brain dysfunction, renal dysfunction, or the odds of mechanical ventilation the following day, or time to death.Daily Daily hemoglobin level was found marginally statistically significant associated with the following days respiratory function, the odds of having an overall higher (worse) respiratory SOFA score was greater among patients with lower hemoglobin level. (p=0.046). There is lack of evidence to conclude that daily hemoglobin was hemoglobin level was not associated with the development of delirium (p=0.49618), , cardiac dysfunction measured by troponin (p=0.626), renal dysfunction (p=0.87569) and respiratory dysfunction (p=0.49) or requirement of mechanical ventilation death (p=0.244p=0.95) ) during the following day, also lack of evidence to conclude hemoglobin was associated with time to death (p=0.400)though lower levels of hemoglobin were associated with a greater odds of having an overall higher (worse) respiratory SOFA score (p=0.019).

There was a significant three-way interaction between the troponin level, hemoglobin level and ICU day (p=0.014; Figure 1), implying that the relationship between the previous day’s troponin level and cardiac ischemia the next day (troponin >0.1) differed according to baseline troponin level, hemoglobin level and ICU day (once we see figure we can tweak sentence).

Conclusion: In ourthis study population, lower hemoglobin levels were not associated with daily risk of development of brain, or renal or cardiac respiratory organ dysfunctions, or death. ,However, lower hemoglogin levels were associated with more severe respiratory dysfunction, as indicated by the respiratory SOFA criteria (lesser PaO2/FiO2 ratio and mechanical ventilation) though associated with a greater probability of worse PaO2/FiO2 ratios. Anemia early during an ICU course, however, may be associated with an increased risk for cardiac ischemia, depending on the baseline troponin level.