Is crystalloid cardioplegia a strong predictor of intra-operative hemodilution?

The effect of hemodilution during cardiopulmonary bypass is extensively studied and lower hematocrit levels (< 22%) caused postoperative organ failure [1]. Renal failure, stroke, perioperative myocardial infarction, prolonged mechanical ventilation and multiorgan failure are much more common in hemodilution conditions [2]. There are several predictors of hemodilution. Prebypass hematocrit values (such as anemia), female gender, Cardiopulmonary bypass (CPB) time, age, renal failure, and small body surface area (BSA) are the strong predictor of hemodilution and consequently blood transfusion [3–5]. We know that allogenic blood transfusion increases the risk of mortality [6] and morbidity such as pulmonary edema [7], renal failure [8], transfusion complications [9]. There are lots of surgeons still using Crystalloid Cardioplegia for its simplicity, economy and fairly good efficacy in the vast majority of patients. Nevertheless, Crystalloid Cardioplegia presents major disadvantages compared with the same volume of blood cardioplegia [10]. It poorly supplies oxygen; it increases the degree of hemodilution which is already high after circulation of the priming volume and it decreases the oncotic pressure [11]. As we mentioned negative effects of hemodilution and blood transfusion are clarified. We have prospectively investigated the effects of Crystalloid Cardioplegia on hemodilution and necessity of blood transfusion by comparing with blood cardioplegia.

Cardioplegia protects the heart from ischemic injury and postoperative heart failure during cardiopulmonary arrest period. Initially crystalloid cardioplegia was introduced as an agent to allow for hypothermic hyperkalemic arrest. Various additives were explored to optimize the myocardium during the time of ischemia [15]. Although cardioplegia is generally accepted to be a mandatory tool for myocardial protection during on-pump cardiac surgery, there is still controversy regarding various aspects including its composition, temperature, and mode of delivery. Blood was then found to be the most logical vehicle for delivery of potassium cardioplegia [16, 17] The optimal cardioplegic temperature, timing, and routes of delivery were further explored [18]. There are still controversies between crystalloid and blood cardioplegia for better myocardial protection. Øvrum E. and colleagues [19] did not found statistically significant differences between crystalloid and blood cardioplegia. Rinne T [20] demonstrated a higher incidence of spontaneous resumption of sinus rhythm after blood cardioplegia compared with that after crystalloid cardioplegia. But Øvrum E and colleagues [19] found no statistical differences concerning conduction disturbances. Blood as opposed to crystalloid cardioplegia could potentially improve postoperative cardiac outcomes, because it more closely approximates normal physiology caused in part by its oxygen carrying capacity and less associated hemodilution [15].

Intraoperative hemodilution and transfusion requirement becomes most critical subjects in the last decade [1–9]. Habib RH [1] specifically showed that major complications, including stroke, myocardial infarction, low cardiac output syndrome, renal failure, pulmonary edema, reoperation due to bleeding, sepsis, and multiorgan failure, were increased as the nadir hematocrit during CPB decreased. Moreover, this hematocrit–complications association inevitably resulted in significantly and systematically greater intensive care requirements, hospital stays, operative costs, and death with increasing levels of hemodilution, particularly for the lowest value less than 22%. Defoe and colleagues [2] found that patients with a lower hematocrit during cardiopulmonary bypass were associated with a higher risk of in-hospital mortality. However they did not provide data on transfusion or try to separate the effect of transfusion versus anemia on in-hospital mortality. In addition, somewhat unexpectedly, Habib RH [1] also found that hemodilutional anemia on bypass was associated with long-term adverse effects as well. Ongoren MC [6] found that blood transfusion during or after cardiac operation is associated with an increased risk of death over the subsequent five years. He showed that transfused patients also had twice the 5-year mortality (15% vs 7%) of nontransfused patients. After correction for comorbidities and other factors, transfusion was still associated with a 70% increase in mortality. We did not find statistically significant difference for mortality between two groups. All these statistical studies emphasized the importance of blood saving both intra-operative and postoperative period. Many blood precaution techniques has been developed for reducing the risk of intra-operative hemodilution and blood transfusion [8, 9]. Predisposing factor for intra-operative hemodilution and transfusion requirement has been described. Multivariate analyses has proved that previous anemia, female gender [13], low BSA, advanced age, CPB time, and renal failure as predictor of intra-operative hemodilution [2–9]. Hemodilution during CPB results from the mixing of pump crystalloid and colloid prime solution with the patient’s blood, and these two relative volumes, along with pre-CPB, will largely determine the nadir value. In addition to above mentioned variables, the type of cardioplegia also effects intra-operative hemodilution. There weren’t any prospective randomized study, identified crystalloid cardioplegia as predictor of hemodilution and transfusion requirement. Eucher PM noticed the hemodilutive effect of crystalloid cardioplegia and described a technique to remove crystalloid cardioplegia by retrograde cardioplegia cannula [14]. We performed this prospective randomized study to identify cristalloid cardioplegia as the predictor of hemodilution. Our multivariate study proved that above mentioned variables (previous anemia, female gender, low BSA, advanced age, CPB time, and renal failure) as predictor of intra-operative hemodilution. But our multivariate analyses also proved that crystalloid cardioplegia is also predictor of intraoperative hemodilution (p < 0.001, OR = 0.19). Transfusion requirement predictors were also well proved. Our study proved that crystalloid cardioplegia is also strong predictor of transfusion requirement (p < 0.001, OR = 0.78). The positive effects of blood cardioplegia are well known. We won’t discuss this preventive ways of blood cardioplegia because of avoiding confounding information.

Another alternative method for applying cardioplegia is minicardioplegia. Its difference from blood cardioplegia consists in the fact that it is applied without diluting the blood in a ratio of 1/4 or 1/8. In the related literature it is possible to find various publications on this topic. In their study, Rıza Türköz et al. found that this method did not necessitate too much volume during pumping and prevented hemodilution from occurring at a high level, while it ensured safe protection of the myocardium [21]. It has been argued in another study that minicardioplegia is more advantageous as regards myocardial edema after ischemic damage [22]. In contrast to these findings, however, there also studies arguing that this method does not provide any advantages over standard blood cardioplegia [23].

Crystalloid cardioplegia, compared to blood cardioplegia not only causes much more intra-operative hemodilution but also increases the blood transfusion requirement. Hemodilution and increased transfusion increases the ICU and hospital stay, in the early postoperative period.