7.2.2 Priming fluid and haemodilution

Volume and composition

 Before being connected to the patient, the system must be filled with a physiological solution. The priming volume varies from model to model, but ranges from 800 to 1,700 mL, or one quarter to one third of the patient's circulating volume (circulating volume = 7% of body weight). Priming is very depending on institution protocol. It is basically a hydro-electrolyte solution, often mixed with a colloid and possibly matching blood in relation with patient's hematocrit [2,18,25].

• Crystalloids: diffuse throughout the extracellular compartment only 20% of the volume remains in the intravascular space.
• 1st and 2nd generation hydroxyethyl starch (HES) (glucose polymer derived from amylopectin, high molecular weight with high degree of substitution): slow excretion, impaired platelet function and coagulation; maximum dose limited to 1.5 g/kg/d. Risk of renal dysfunction if limit is exceeded.
• 3rd generation hydroxyethyl starch (HES) (low molecular weight and low degree of substitution): no plasma accumulation or renal dysfunction, less effect on coagulation during ECC; maximum dose 3 g/kg/day.
• Albumin: good oncotic effect, no allergic reactions, very expensive; half-life 20 days. No effect on morbidity and mortality compared to other solutions, except in cases of brain injury, where albumin worsens the prognosis.
• Gelatins (derived from bovine collagen): no effect on coagulation, but rapid renal excretion and very limited volume maintenance (< 2 hours); allergic reactions are common.
• Dextrans: increase the risk of bleeding, anaphylactic reaction, and renal failure.

Even if the circulating volume is better preserved with colloids than with crystalloids, pulmonary functions do not seem to be impaired by this choice as long as overload is avoided. Coagulation is certainly less affected by crystalloids than by colloids. The use of colloid is not recommended in cases of hemostasis disorders (hemophilia, Wildebrand's disease), in cirrhotic and in dialysis patients. Albumin is then a better choice, as it does not affect coagulation [25]. Unfortunately, recent literature, particularly in intensive care [10,22], tends to show that HES significantly increases the rate of renal failure (20-35%), the risk of bleeding (40-50%) and, in case of sepsis, mortality (17%). As a result, the Pharmacovigilance Committee of the European Medicines Agency (EMA) ruled in 2013 that the risks associated with HES outweigh the benefits and recommended that these substances be withdrawn from the European market. This abrupt decision extends a probably justified precaution in intensive care, on the contrary to ECC, where lack of data do not confirm concerns in the operating room [20]. As a result, European recommendations for ECC prohibit the use of HES in the priming fluid [17]. The FDA (Federal Drug Agency, USA) has recommended the withdrawal of HES in intensive care, but not in surgery. As a result, HES can no longer be recommended in the composition of priming solutions, which tend to contain only crystalloids with or without added gelatin (Physiogel^®) or albumin. The condemnation of 6% HES is all the more questionable as they are not incriminated in an increased rate of renal failure or mortality in the context of cardiac surgery when renal function is normal [7,32]. A review of 17,742 patients shows that HES has no effect on the incidence of mortality, renal dialysis and myocardial ischemia, whereas albumin increases the risk of hemodialysis [26]. Currently in Europe, a narrow majority of centres use only crystalloids, about a quarter add gelatin and a quarter add HES or albumin [19,23].

 In addition to 5,000-10,000 units of heparin (see Anticoagulation), several substances may be added to the priming fluid depending on the protocols.

• Antifibrinolytic: decreases the risk of bleeding, especially in patients treated with antiplatelets. Since its withdrawal in 2007, most centres have chosen to switch aprotinin to tranexamic acid (Anvitoff^®, Cyclokapron^®). Although slightly less effective, it does not trigger allergic reactions or renal dysfunction. The ECC dose (10-30 mg/kg) is a repeat of the first dose injected at the opening of the pericardium [30].
• Mannitol: the benefit of its oncotic, diuretic and nephroprotective effects has never been demonstrated; it may even impair renal function [3,19].
• Steroids: reduce the intensity of the systemic inflammatory syndrome triggered by ECC and surgery [1], but full effect is reached after 45 minutes, so they are better injected at induction rather than during ECC. Overall, they do not affect morbidity and mortality [5,33].
• Glucose in the priming fluid is avoided because hyperglycemia increases neurological risk.

 As an example, the routine in our institution (CHUV, Lausanne) consists of 800-1500 mL Plasmalyte^® + 10'000 IU heparin. Plasmalyte^® is an isotonic solution with a neutral pH, containing no Ca²⁺ (in mEq/L: Na⁺ 140, K⁺ 5.0, Mg²⁺ 3.0, Cl- 98, acetate 27, gluconate 23, 295 mosm/L, pH 7.4).

 Haemodilution

 The desired hematocrit (Ht) for ECC is 24-28%, depending on the expected lowest temperature. The decrease in Ht is necessary to reduce blood viscosity and improve microcirculation in hypothermia. Indeed, viscosity increases by 30% at 27°C, but drops by 30% when Ht decreases from 40% to 25% [11]. Thus, in hypothermia, viscosity remains more or less stable when the Ht value in percent is the same as the temperature in degrees C [12]. The hematocrit sought during ECC (Ht_CEC) is calculated as follows:

 Ht_CEC =         Ht - CV / (CV + ECC volume)

 where:          CV = circulating volume (7% of patient's body weight)

        ECC volume = priming volume

        Ht = patient's current hematocrit

Normovolemic hemodilution is well tolerated and compensates for the effects of hypothermia, but simultaneously decreases O₂ transport and affects organs differently. At Hb < 70 g/L, coronary reserve decreases by 50% and splanchnic perfusion is at the limit of clinical ischemia, but cerebral blood flow increases by 45% and renal plasma flow increases in the cortical area [21,28].

 Hemodilution in ECC has limitations. Ht less than 23%, for example, has been proved to be an independent predictor of postoperative morbidity and mortality [8,27]. Ht has no influence on postoperative neurological status as long as it remains above 30% in normal adults [31], but cognitive impairment becomes more important when the minimum Ht is 15-17% [4] and the risk for stroke increases by 10% for each percent of Ht below 25% [16]. Neurological sequelae clearly increase when Ht falls below 26% [4]. In children, a comparison between low (21%) and high (28%) Ht shows that the neurological score and psychomotor development are better in the latter case [15].

 On the other hand, renal function worsens linearly with the decrease in haemoglobin when the hematocrit is below 30% [29]. Correction of anaemia by transfusion is not curative because, for similar Ht values, transfused patients systematically show a worsening of their renal function compared with those who are not transfused; their mortality is higher (3.8% versus 1.4%) and their incidence of renal failure higher (12% versus 3.4%) (see Figure 7.27) [9]. Anemia thus worsens the situation, but transfusion, instead of correcting it, adds an additional deleterious factor.

 When Ht falls by >14%, hemodilution tends to increase bleeding, dilute fibrinogen and determine a hypocoagulable state on the thromboelastogram; in addition, HES decreases the firmness of the blood clot. As the transfusion of blood, platelets and coagulation factors increases in this situation, the risk of thromboembolic complications also increases [24].

 A value of 25-28% is therefore the safe lower limit for Ht during ECC. There are several ways to avoid falling below this level [14].

• Causal treatment of preoperative anaemia (Hb < 120 g/L) and preparation of patients with iron and/or erythropoietin;
• Limitation of crystalloid infusions before ECC, preferential use of vasopressor in case of hypotension;
• Rigorous haemostasis of the sternotomy and mammary artery space prior to pump start.
• Limitation of priming volume, restriction of tubing length and volume (mini-ECC);
• Autologous retrograde priming;
• Blood cardioplegia instead of crystalloid, microcardioplegia;
• Hemofiltration during and at the end of ECC.

Autologous priming involves replacing the priming volume with the patient's own blood at the start of ECC.

• Retro-priming: storage of approximately 500 mL stored into a bag or venous reservoir from the arterial filter purge line;
• Anterograde priming: siphoning of about 500 mL per gravity from the venous cannula (normal direction of the circuit);
• In both cases, the patient's blood replaces part of the priming solution, which is drained outside. The storage bag must never be below the level of the oxygenator, which would then be in depression (risk of air aspiration and gas embolism).

Both techniques reduce the total amount of crystalloid  in the machine and infused into the patient to a few hundred milliliters. This reduces the drop in oncotic pressure and drug hemodilution at the start of ECC (20-25% instead of 40%) and therefore improves cerebral oxygenation during ECC [6,13]. They may decrease the transfusion rate and interstitial oedema in the lungs and heart [6]. The momentary loss of circulating volume for the patient is compensated by vasopressors and elevation of the lower limbs. Although not always possible, retrograde priming should be attempted in all patients.

© CHASSOT PG, GRONCHI F, last update December 2019

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