Over the 3-year study period, 170 patients had an ICU LOS of 30 days or longer, representing 5.4% of the total 3172 ICU admissions. Five patients who had ICU LOS longer than 21 days in other hospitals before transfer to the study hospital and 10 patients for whom phlebotomy and transfusion data were unavailable were excluded. Baseline characteristics at ICU admission and clinical outcomes for the remaining 155 patients are summarized in Tables and . The patients included in the cohort had an average age of 62 ± 16 years, moderate severity of illness, multiple pre-existing comorbidities, and relatively stable mean daily SOFA scores, which on average declined by approximately 1 point between day 21 and ICU discharge. ICU admission hemoglobin was 11.1 ± 2.5 g/dl, which is well below the lower limit of normal for our laboratory (13.0 g/dl). Table describes weekly hemoglobin values up to day 21. Figure shows daily hemoglobin values for all patients over time after day 21 separated by transfusion status. It appears that the hemoglobin values reach a 'steady state' of around 9.0 g/dl by days 7–14 (Table and Figure ).
Baseline demographic information
ICU course and outcome parameters after day 21
Hemoglobin trend over time by transfusion status. ICU, intensive care unit.
Ninety-six of the 155 (62%) patients were transfused with 1 or more units of PRBC after day 21. A total of 542 units of PRBC (median [interquartile range] = 1 [0–4] unit/patient) were transfused on 354 separate occasions. The majority (81%) of the transfusions was administered between ICU days 22 and 57, with the remainder occurring after day 57. These transfusions were given at a mean hemoglobin trigger of 7.7 ± 0.9 g/dl (range 5.1–10.7 g/dl), and 73% of the transfusions were given at a trigger above 70 g/l. Reasons for transfusion after day 21 were as follows: active bleeding (17%), low hemoglobin concentration (40%), postoperative resuscitation (7%), to improve oxygenation or hemodynamic status (10%), and no identifiable reason (26%; Figure ). Although the total number of units of PRBC transfused decreased over time, the number per patient (mean = 0.075 ± 0.056 units/patient per day, which is equivalent to 0.051 ± 0.034 transfusion events/patient per day or 5.1 ± 3.4% of patients transfused daily) remained fairly constant, especially by around days 50–60 (Figure ).
Transfusion over time. ICU, intensive care unit; PRBC, packed red blood cells.
A significant number of phlebotomy procedures were conducted in this cohort of ICU patients after day 21. A total of 129 l blood was phlebotomized over 9,191 patient-days. An average of 13.3 ± 7.3 ml/day was phlebotomized after day 21, and 3.8 ± 1.5 vials of blood/patient per day were obtained. The amount of blood phlebotomized each day in the entire cohort decreased as the LOS increased (Figure ). The largest group of tests was arterial blood gas, followed by chemistry profile, complete blood count, and coagulation profile (Figure ). Although the proportion of chemistry profiles, complete blood count, and coagulation profiles remained fairly constant over time, the amount of arterial blood gas tests decreased.
Phlebotomy volume over time. ICU, intensive care unit.
Types of phlebotomy over time. Figures in parenthesis on the x-axis denote the number of patients. ABG, arterial blood gas; CBC, complete blood count; CHEM, chemistry; COAG, coagulation; Other, blood cultures and others.
When 25 patients with active bleeding (and thus a definitive therapeutic reason for PRBC transfusions) were excluded, the remaining 71 patients who received a blood transfusion after day 21 had greater acuity of illness than did nonbleeding patients who never received a blood transfusion after day 21, as reflected by higher admission APACHE II scores, mean daily SOFA scores, requirements for life support therapies, ICU LOS, and mortality (Tables and ). In addition, nonbleeding patients who received transfusions had lower hemoglobin levels, were more likely to receive iron or erythropoietin, and were more likely to lose more blood to phlebotomy during their ICU stay than were non-bleeding patients who never required a blood transfusion (Tables and ). Overall, 24 patients (15%) received one or more doses of erythropoietin. Of those, all but one patient received the drug because of anemia associated with acute or chronic kidney disease requiring dialysis, frequently after having required a blood transfusion.
Based on these results, the following variables were entered into the multivariate logistic regression model as dependent variables: the continuous variables of admission APACHE II score, mean daily SOFA score and phlebotomy volumes (both after day 21), and ICU LOS; and the binary variables of sex, surgical admission, coronary artery disease, erythropoietin therapy, iron therapy, day 21 hemoglobin, inotrope/vasopressor therapy, and acute renal failure requiring dialysis. (This was based on the predefined analysis plan to include only variables with P < 0.20 on univariate analysis. However, the multivariate results are unchanged when all possible explanatory variables found in Tables and are entered into the regression analyses regardless of the P value on univariate analysis.) After day 21, the characteristics independently associated with PRBC transfusion in the nonbleeding patients were as follows: average daily phlebotomy volume while in the ICU (OR 1.22 per incremental ml/day phlebotomized, 95% CI 1.11–1.34; P < 0.0001), ICU LOS (OR 1.025 per additional day in ICU, 95% CI 1.006–1.045; P = 0.008), baseline (day 21) hemoglobin level (OR 2.1 per 1 g/dl lower hemoglobin, 95% CI 1.4–3.4; P = 0.001), and treatment with erythropoietin (OR 6.4, 95% CI 1.2–34.3; P = 0.03). Stated in other terms, the odds of being transfused after day 21 in these patients doubled with any of the following: an average 3.5 (95% CI 2.4–6.8) ml/day blood loss to phlebotomy, an additional 28 (95% CI 16–116) days in ICU, or a day 21 hemoglobin level that was 0.9 (95% CI 0.6–2.3) g/dl lower than the average. The area under the receiver operating characteristic curve for this model was 0.86. There were no significant second order interactions among these variables.
Sensitivity analysis using a discard volume of 0–7 ml (base case of 2 ml) resulted in no change to the regression model with respect to the statistically significant predictive risk factors. The ORs for average daily phlebotomy were 1.27 (95% CI 1.13–1.42; P < 0.0001) and 1.15 (95% CI 1.08–1.23; P < 0.0001) per incremental ml/day phlebotomized, assuming a 0 and 7 ml discard volume, respectively. This corresponds to an extra 2.9 (95% CI 2.0–5.7) and 4.9 (95% CI 3.3–9.6) ml/day of additional phlebotomy to double the odds of being transfused after day 21 in these patients, assuming a 0 and 7 mL discard volume, respectively.
Results from the secondary analysis using multivariate linear regression demonstrated that the number of PRBC transfused was significantly and independently associated with daily phlebotomy volume, ICU LOS, and acute renal failure requiring dialysis. After day 21, 1 unit of PRBC was transfused for every additional 2.2 (95% CI 1.7–3.4; P = 0.0002) ml blood drawn/day in patients with acute renal failure and 5.4 (95% CI 4.5–8.8; P < 0.0001) ml blood drawn/day in patients without acute renal failure. Similarly, 1 unit of PRBC was transfused for every 12 (95% CI 8–24; P = 0.004) additional days in ICU in patients with acute renal failure and 45 (95% CI 29–103; P = 0.0007) additional days in ICU in patients without acute renal failure.