Acute normovolaemic haemodilution: a forgotten friend Yves OZIER Division of Anaesthesia, Critical Care and Emergency Medicine Brest University Hospital, France

Acute normovolaemic haemodilution is NOT forgotten Is Acute normovolaemic haemodilution REALLY A GOOD FRIEND or should we forget it ?

There are 2 types of acute isovolaemic haemodilution Preop Intraop Postop This is the one we talk about

Acute normovolaemic haemodilution Theoretical benefits Reduced total red cell loss Supply of fresh autologous blood providing red cells, platelets and clotting factors near the end of surgery

Acute normovolaemic haemodilution A cost-effective alternative to autologous predonation ? Less costly More convenient for patients Units collected / kept at the patient’s bedside Less chance of a wrong unit error Fresher blood

Acute isovolaemic haemodilution Which efficacy ? Mathematical models Simple exponential haemodilution equation Brecher. Transfusion 1994;34:176-9 Feldman. Anesth Analg 1995;80:108-13 Weiskopf. Transfusion 1995;35:37-41

Acute isovolaemic haemodilution Theoretical efficacy Weiskopf et al. Transfusion 1995;35:37-41 1 2 3 4 5 Initial Hct = 45% Initial Hct = 40% PRBCs saved (units) Initial Hct = 35% 30 25 20 15 Final haematocrit (%)

Acute isovolaemic haemodilution Theoretical efficacy PRBCs saved (units) 2 ∆Hct = 45-25% Male ∆Hct = 40-25% Female 1 9 8 7 6 5 4 3 Weight (kg)

Acute isovolaemic haemodilution Theoretical conditions for efficacy High preoperative haematocrit (40-45%) Low target haematocrit (<30%) High estimated total blood volume Substantial amount of surgical blood loss L’hémodilution isovolémique préopératoire est une technique d’intérêt très controversé Déjà, on peut modéliser l’économie théorique que l’on peut en attendre et il est facile de se rendre compte que pour espérer en obtenir quelque chose, le malade et l’opérations doivent satisfaire a certaines conditions Hématocrite initial élevé (≥ 45%) Hématocrite cible bas (< 30%) Volume sanguin total estimé élevé Saignement prévisible abondant Feldman et al. Anesth Analg 1995;80:108-13 Weiskopf et al. Transfusion 1995;35:37-41

Nb allogeneic PRBCs units Nb whole-blood autologous units to collect Acute isovolaemic haemodilution How many whole blood units to collect ? Change in Hct Nb allogeneic PRBCs units Potentially saved Nb whole-blood autologous units to collect 40-25 % 1.1 5 45-25 % 1.7 6-7 45-20 % 2.9 9 Calculations for a 70 kg man Feldman et al. Anesth Analg 1995;80:108-13

Acute isovolaemic haemodilution Which efficacy ? Mathematical models Clinical trials

ANH Meta-analysis 2004 JB Segal, et al. Transfusion 2004;44:632-44 RR of allogeneic transfusion Haemodilution vs usual care

ANH Meta-analysis 2004 JB Segal, et al. Transfusion 2004;44:632-44 RR of allogeneic transfusion Haemodilution vs another blood conservation method

Transfusion 2004;44:632-44

ANH Meta-analysis 2015 X. Zhou, et al Anesth Analg 2015;121:1443–55 Haemodilution vs usual care RR of allogeneic transfusion 0.74 95%CI = 0.63 - 0.88

ANH Meta-analysis 2015 X. Zhou, et al Anesth Analg 2015;121:1443–55 Haemodilution vs usual care Allogeneic RBC units WMD −0.94 units 95%CI, −1.27 to −0.61 units

Diverse surgical procedures and settings Anesth Analg 2015;121:1443–55 Diverse surgical procedures and settings Small sample size of most studies Magnitude of haemodilution & transfusion triggers unknown in most studies Considerable heterogeneity Obvious publication biases, overestimation of benefit Low rates of reported adverse events

Anesth Analg 2015;121:1443–55 Conclusion Although these results suggest that preoperative ANH is effective in reducing allogeneic blood transfusion, we identified significant heterogeneity and publication bias, which raises concerns about the true efficacy of preoperative ANH

Cardiac surgery Haemodilution vs usual care Allogeneic RBC units L. Barile, et al. Anesth Analg 2017;124:743–52 Haemodilution vs usual care Allogeneic RBC units MD −0.79 units 95%CI, −1.25 to −0.34 units

Cardiac surgery Haemodilution vs usual care Allogeneic RBC units L. Barile, et al. Anesth Analg 2017;124:743–52 Haemodilution vs usual care Allogeneic RBC units MD −0.79 units 95%CI, −1.25 to −0.34 units

Acute isovolaemic haemodilution Are there any drawbacks ? Labor-intensive and time-consuming Potential for added OR time Invasive intravascular access required, potential for added cardiovascular monitoring Reinfusion of anaesthetic agents with collected blood Postoperative edema Management of unecessary units ? Profound haemodilution and oxygen supply ??

JP Mathew, et al. Anesthesiology 2007;107:577– 84

with increasing change in hematocrit from baseline JP Mathew, et al. Anesthesiology 2007;107:577– 84 Decline in cognition with increasing change in hematocrit from baseline

In summary : Safety and efficacy of ANH still in question after 50 yrs of experience Technique not standardized Inconsistent data on efficacy Lack of high level evidence of safety Subpopulation likely to benefit uncertain Surgical techniques and patient blood management methods have evolved - Is ANH useful to-day ?