The findings of our study suggest that the total volume of DLT-associated blood loss contributes to both the incidence and magnitude of anemia and was associated with more frequent RBC transfusions in critically ill patients. Likewise, the severity of anemia correlated with the volume of blood drawn (figure 1). Furthermore, CVC access was predictive of increased total blood loss, transfusion, and anemia. The observations of our investigation correspond with those reported in previous studies.1,4−9
CVC placement associated with an increase in blood draws for laboratory testing and a resultant increase in iatrogenic blood loss, both for DLT as well as line clearance blood discards. While the critically ill require extensive DLT to guide therapy, the number of accesses as well as the utilization of blood conserving devices (BCD) to reduce discards represent modifiable factors. BCD use may be especially impactful as there was a significant amount of cumulative blood loss associated with line clearance, 204 mL/admission, which nears the red cell volume of 1 unit of RBCs. A recent meta-analysis by Whitehead et al., demonstrated that utilization of BCDs were associated with a reduction in iatrogenic blood loss as well as the use of pediatric tubes.5
While the overall rate of transfusion was 32% (95/299), CVC access was predictive of a higher rate compared to those without CVC access. Transfusion increases morbidity and mortality amongst ICU patients and thus, DLT blood loss represents an area which could be impacted with implementation of common-sense blood saving interventions, such as BCD. We found that CVC line placement >7-days was predictive of a higher rate of RBC transfusions. ICU services often have goals to remove CVCs as quickly as possible, to reduce the risk of central line associated bloodstream infection (CLABSI), which are associated with high mortality, and our findings suggest reduction in DLT blood loss represents a further motive for early CVC removal.33
One critique of BCDs is an increased cost. A charge analysis performed demonstrated bedside CVC placement was roughly equivalent to the charge for a single RBC transfusion ($1,340 vs. $1,450). Though many services place lines at bedside there has been a shift in some centers with the majority being placed by interventional radiology, which we show to be significantly more expensive. Although determining clear pricing information is challenging, utilization of BCDs would prevent doubling the cost of having a bedside CVC if an RBC transfusion is not required.
CVC placement led to lower Hb nadirs and discharge Hb levels. This is impactful, as the body increases cardiac output and shunts blood away from visceral organs through compensatory mechanisms in response to anemia, which may lead to further end organ stress or failure. Also, severe discharge anemia has been shown to be predictive of anemia on long term follow-up for ICU patients, further contributing to readmission, need for transfusion, and poor general health as an outpatient.13,16
Under physiologic conditions the body can readily produce sufficient red cell mass for maintenance of Hb levels, ~10-20 mL per day, and though this number may increase exponentially in states of anemia with adequate iron stores, the critically ill patient has been shown to have reduced red cell production, making any blood loss likely more impactful.18,34−37 Many ICU patients are anemic on presentation with nutritional deficiency being a contributing factor in 13% of ICU patients as follows: 2% B12 deficient, 2% folate deficient, and 9% iron deficient.17 To that end, each ml of blood contains 1 mg of iron, and while patients generally have iron stores of 300-1000 mg, this iron may be rendered inaccessible due to an ongoing inflammatory response.34,38,39 Moreover, though healthy blood donors have been shown to have a maximum absorption between 3-5 mg/day iron it is likely that critically ill patients have suboptimal absorption of nutrients.40 Erythropoietin is produced predominantly in the kidney with a small percentage produced in the liver, and work shows ICU patients have both reduced production of EPO as well as a blunted response.41,42 Ongoing blood draws represent an identifiable loss of red cell mass and iron which the critically ill patient cannot effectively replace, further contributing to iatrogenic anemia.
While we observed a total mean daily loss of blood of 20.0 mL, a volume below that observed ~50-100 mL in other studies, this volume is actually equivalent to steady state RBC production in healthy individuals.4–7, 36,43 A mathematical model by Lyon et al. suggested that loss of 53 mL per day in healthy patients with adequate iron stores would lead to anemia in approximately 40 to 70 days.44 Conversely, critically ill patients with compromised RBC production would demonstrate anemia in approximately 9 to 14 days.44 The observed SICU LOS in our study 15 days, and though 20 mL was significantly less than 53 ml, 95.3% of patients were anemic at time of unit discharge.
One limitation of the study that many patients had both CVC and PICC placement. As such those with only CVC were compared with PICC and those with both PICC and CVC to compare discard volumes. As a single predictor both DLT-associated and total blood loss was significantly lower in those without CVC, and CVC placement alone was predictive of increased blood draws.
As this is a retrospective analysis, we could not actively monitor these patients or obtain additional studies that may have been informative, such as nutritional or inflammatory markers. Moreover, these are complex, critically ill patients and numerous factors, as discussed above, contribute to the incidence of anemia, though we attempt to characterize this with CCI values and by comparing surgical and non-surgical patients. Our group does show a contemporary ‘baseline’ of iatrogenic blood loss in an SICU setting, which may be generalizable to other SICU services. Likewise, we also showed lower rates of transfusion compared to prior work, showing some movement toward more conservative transfusion practice. The goal of a “bloodless” ICU admission without transfusion should still be pursued as RBC transfusion in this population is associated with higher rates of mortality, increased LOS, and ongoing anemia as an outpatient.13,28Several limitations including the accuracy of data recorded within the electronic medical records and selection bias. Moreover, the decision to transfuse RBCs was left to the discretion of the treating physician and therefore the rationale for RBC transfusions was not always clear. Finally, chargemaster values were used as opposed to direct costs to the hospital or patient. Chargemaster rates have been shown to have high variability and are likely not predictive of cost to patient, but may provide some insight into billing for these procedures.45