To our knowledge, this is the first study to evaluate the course of postoperative hemoglobin drift after CS. We undertook this study to better understand the natural history of hemoglobin levels in postoperative CS patients, anticipating that a better understanding of these trends would better guide transfusion related therapy. In order to assess the normal pattern, or drift, of hemoglobin levels, we analyzed all postoperative hemoglobin levels in a cohort of CS patients, none of whom received any postoperative blood transfusions. We included patients who received intraoperative transfusions, though, as our study was meant to guide postoperative transfusions.
These data show that in CS patients who are not transfused postoperatively, hemoglobin gradually drifts downward over the first 4 postoperative days, with a maximal drift of slightly less than 2 g/dL, followed by a gradual upward drift, with a recovery of close to 50% of the maximal drift by postoperative day 10. There was a trend in patients who received intraoperative blood transfusions not to recover from their nadir as much as those who were not transfused, but the difference in recovery between these two groups did not reach statistical significance. Although this recovery from maximal drift may differ slightly between patients who did or did not receive intraoperative transfusions, it is notable that 80% of all patients recovered from their nadir to some degree. Analysis of multiple variables showed that the maximal drift appeared to be increased by the duration of CPB, and, to a lesser degree, increasing body weight.
The purpose of this study was to help guide transfusion therapy by describing the natural course of hemoglobin levels postoperatively. It is becoming increasingly evident that a more restrictive approach to red blood cell transfusion is associated with equivalent and in some cases improved outcomes compared to a liberal strategy.[1
] Blood product transfusions can be associated with the transmission of viral and bacterial disease, acute hemolytic and non-hemolytic reactions, transfusionrelated acute lung injury, and immunosuppression.[1
] In CS, red blood cell transfusions have been associated with increased short and long-term mortality,[4
] an increased length of stay,[4
] and neurologic,[8
] and infectious complications.[4
] Furthermore, several studies have suggested that the negative impact of red blood cell transfusions may be additive, with each transfused unit causing an incremental increase in risk.[4
] Given the risk associated with each transfusion, it is crucial that every unnecessary transfusion be avoided.
In clinical practice, it is not uncommon to transfuse hemodynamically stable patients with declining hemoglobin levels either before they leave the ICU or the hospital, with the presumption that their hemoglobin levels will continue to decline. In our study, although we found that all patients experience a decline in their hemoglobin levels, the vast majority of patients’ hemoglobin levels recover significantly prior to discharge. Moreover, since most CS patients do not remain in the hospital for 10 days, the data suggests final hemoglobin levels will continue to drift upward after discharge. Physicians should therefore be cautious about prophylactic postoperative transfusions in anticipation of increasing anemia, as the majority of the time, the exact opposite occurs: Hemoglobin rises between the 4th and 10th postoperative day, and may continue to do so.
However, if patients transfused intraoperatively do recover less hemoglobin, it suggests that CPB may affect transfused red cell survival. Although data suggests that transfused red blood cells have a mean survival of approximately 90 days,[15
] it is possible that interaction with the CPB circuit decreases the survival of transfused red blood cells. Thus, while intraoperatively transfused blood keeps hemoglobin levels high in the early postoperative period, these cells have poor survival, are removed from circulation over the first postoperative week, and account for the lack of rebound in the hemoglobin level.
Alternatively, intraoperative transfusions may result in an increased inflammatory response, delaying the upward drift beyond the 10 postoperative days of our study, and therefore the upward drift still occurs but is not evident in this study. Regardless, although patients who receive intraoperative transfusions may not experience the same degree of upward drift as those who were not transfused, their hemoglobin levels did rise and were stable prior to discharge.
To improve our understanding of the factors responsible for the course of hemoglobin levels postoperatively, we conducted a multivariable analysis of predictors of drift. Increased CPB time and, to a lesser degree, an increase in patient weight proved to be important factors in magnifying the drift a patient experienced during his or her hospitalization. CPB is associated with a significant systemic inflammatory response which leads to a capillary leak syndrome and a decrease in circulating blood volume.[12
] Studies have shown that this third-spacing of fluid begins within minutes of the initiation of CPB and can result in an increase in the extravascular fluid volume of several liters over the first 24 hours.[16
] The decreased circulating blood volume necessitates fluid resuscitation leading to hemodilution. We speculate that an increased duration of CPB leads to greater inflammation resulting in more third-spacing necessitating more fluid resuscitation. The resultant hemodilution causes greater total hemoglobin drift.
The inflammation caused by CPB may explain the entire pattern of hemoglobin drift observed in our study. Tschaikowksy et al.[17
] have shown that post-CPB inflammatory third-spacing peaks at 4 hours postoperatively. Subsequent fluid mobilization occurs and circulating blood volume normalizes and may actually exceed normal levels by 48–72 hours. Thus, the combined effects of initial postoperative bleeding, inflammatory third-spacing, and fluid resuscitation result in an initial hemodilution causing downward hemoglobin drift. As the inflammatory process dissipates over the first 24–48 hours, fluid mobilization begins, increasing circulating blood volume and causing further hemodilution. By postoperative day 4, the circulating blood volume has reached its maximum and thus hemoglobin levels reach their nadir. As the patient diureses over the next several days without being offset by fluid mobilization because it is complete, circulating blood volume decreases, resulting in hemoconcentration and upward hemoglobin drift.
Furthermore, previous research suggests that capillary leakage and thus thirdspacing is proportional to body weight which may explain why patient weight was also a significant driver of maximal drift.[13
] Although reoperative sternotomy did not prove to be a significant factor driving drift, our numbers were too small to evaluate this. It is highly likely that there were insufficient reoperative sternotomy patients in this analysis to truly understand the behavior of postoperative hemoglobin concentration in the reoperative population. Further investigation of the drivers of hemoglobin drift is warranted.
Our study has several limitations. First, a subset of our patients received their own blood, recovered with a cell saver device, upon arrival in our ICU. We elected to include these patients in our study because cell recovery is a common and recommended technique of blood conservation.[18,19] However, it is possible that these transfusions affected hemoglobin drift. Thus, these results are best generalized to patients who undergo similar cardiotomy blood recovery. Furthermore, although it is rare for patients to receive preoperative blood transfusion, they occasionally do. There is no evidence that preoperative transfusion affects postoperative drift and thus we included these patients in this study. However, this is a possible confounder.
Second, our study is retrospective in nature. Although we attempted to control for relevant confounders, it is possible that important variables were not included and that residual confounding remains. In this retrospective study, it was hard to quantify postoperative bleeding and thus this variable was excluded. While chest tube output is a surrogate for bleeding, retrospectively it is impossible to evaluate its sanguinity. We would argue that although initial postoperative blood loss may have affected the maximal drift, it should not have affected the subsequent recovery that occurred after postoperative day 4. However, blood loss may be an important consideration and our study should be considered in light of this deficiency.
Third, in an effort to understand the natural history of postoperative hemoglobin drift, we limited our study to patients who were not transfused postoperatively. While this allows us to examine the natural drift of hemoglobin values, it represents a significant selection bias. It is thus possible that our findings can only be applied to patients who do not receive postoperative transfusions. Hemoglobin drift following a postoperative transfusion may follow a different pattern.
Fourth, our study only captures hemoglobin values during the initial hospitalization. During the 10 day follow-up period, patients are gradually discharged and subsequent hemoglobin data represents an increasingly smaller number of patients. This attrition may introduce a sample size bias and may limit the widespread applicability of our findings.
Finally, the sample size is relatively modest and thus the study is susceptible to type II errors. The sample size may be inadequate to fully identify all the predictors of hemoglobin drift and to identify practitioner-specific differences in blood transfusion practices. Further investigation with larger sample sizes is warranted to further understand hemoglobin drift.