Download NUCLEATED RED BLOOD CELLS AS AN INDEPENDENT

NUCLEATED RED BLOOD CELLS AS AN INDEPENDENT PREDICTOR OF ICU
MORTALITY AND ICU RECIDIVISM
Mooney, Owen1; Zarychanski, Ryan2; Bell, Dean3; Rimmer, Emily3; Kumar, Anand4; Houston,
Don5; Turgeon, Alexis6; Doucette, Steve7
1
University of Manitoba, Department of Internal Medicine/Critical Care, Winnipeg, Canada;
2
University of Manitoba, Department of Hematology and Critical Care, Winnipeg, Canada;
3
University of Manitoba, Department of Anesthesia and Critical Care, Winnipeg, Canada;
3
University of Manitoba, Hematology, Winnipeg, Canada; 4University of Manitoba, Critical
Care, Winnipeg, Canada; 5University of Manitoa, Hematology, Winnipeg, Canada; 6Laval
University, Anesthesiology and Critical Care, Quebec City, Canada; 7Dalhousie University,
Epidemiology, Halifax, Canada
Introduction: Since the late 1940’s it has been recognized that the presence of nucleated red
blood cells (nRBC’s) in a peripheral blood sample of patients portends a poor outcome. In the
absence of certain hematologic conditions, such as sickle-cell disease or thalassemia major, these
types of cells a generally absent from peripheral blood. It has been reported that the presence of
these cells suggests a severe physiologic stress has been endured. To date, the precise nature of
this stress is unclear. Although previously published in observational reports, recent
prospectively collected studies confirms that a significant percentage (17-35%) of critically ill
patients will have detectable nRBC’s in their peripheral blood at sometime during their illness.
The identification of nRBC’s in peripheral blood has not been limited to a single diagnosis or
physiologic derangement and has been described in a diverse number of disease states, from
congestive heart failure to septicemia. What links these conditions mechanistically with the
presence of nRBC’s and why their presence predicts poor outcomes is not understood.
Objectives: The objectives of our study were to examine the independent association of nRBCs
on ICU mortality. Secondly, we aimed to examine readmission rates of patients who remained
nRBC-positive within 24 hours of ICU transfer compared to those patients who where nRBCnegative.
Methods: We conducted a retrospective cohort study of patients admitted to tertiary care
hospitals in Winnipeg, Canada from January 1st, 2006 to December 31st, 2011. A patient was
determined to be ‘nRBC-positive’ if they had detectable levels of nRBCs (>19/ul) at any point
during their ICU admission. A ‘nRBC-negative’ patient was defined as any patient who never
demonstrated detectable nRBC’s during their ICU admission. Our primary outcome of interest
was mortality. The independent prognostic significance of nRBCs was assessed using Cox
proportional hazards regression modeling.
Results: Of the 9809 admitted patients, 1391 (14%) had circulating nRBCs during their ICU
admission. The mean age of the nRBC-positive and negative patients was 60.1 years. Males
made up 54.9% of the nRBC-positive group and 64.5% of the nRBC-negative group. The most
common diagnosis in the nRBC-positive group was septic shock (39.1%). Patients with nRBCs
detected had a higher acuity of illness on admission as defined by APACHE II score (23.8 vs.
16.3). The baseline use of vasopressors (83% vs. 48.9%), and mechanical ventilation (91% vs.
65.3%) were higher in the nRBC-positive group. Baseline acidosis, defined by a blood pH <7.20,
occurred more frequently in patients who were nRBC-positive (61.8% vs. 50.7%). In a Cox
proportional-hazards model, adjusted for age, sex, APACHE II score, use of vasopressors,
mechanical ventilation, acidosis, admission diagnosis, and the use of acute dialysis, the hazard
ratio for ICU mortality associated with nRBC positivity was 1.3 (95% CI 1.15-1.48).
Readmission rates between patients who remained nRBC positive within 24 hours of ICU
transfer was significantly higher, 10% (18/189) vs. 4% (368 /8570) p=0.002. Mortality at 30
days did not differ significantly between those patients who remained positive prior to transfer.
References: 1. Groen, J, Godfried G. The occurrence of normoblasts in the peripheral blood in
congestive heart failure: an indication of unfavorable prognosis. Blood. 1948; 3: 1445-1452. 2.
Swartz, S, Stansbury, F. Significance of Nucleated Red Blood Cells in Peripheral Blood:
Analysis of 1496 cases. JAMA. 1954; 154(16): 1339-40. 3.. Stachon A, Bo¨ning A, Krismann M,
et al. Prognostic significance of erythroblasts in blood after cardiothoracic surgery. Clin Chem
Lab Med. 2001; 39:239 –243. 4.. Stachon A, Bolulu O, Holland-Letz T, Krieg M: Association
between nucleated red blood cells in blood and the levels of erythropoietin, interleukin-3,
interleukin-6, and interleukin-12p70. Shock 2005; 24:34-39. 5. Stachon, A, Becker A, et al. Reevaluation of Established Risk Scores by Measurement of Nucleated Red Blood Cells in Blood
of Surgical Intensive Care Patients. J of Trauma, Injury, Infection, and Critical Care. 2008;
65:666–673. 6. Stachon, A, et al. Nucleated red blood cells in the blood of medical intensive care
patients indicate increased mortality risk: a prospective cohort study. Critical Care. 2007; 11:R62
(doi:10.1186/cc5932).