Acute Normovolemic Haemodilution in Urological malignancies: A randomized control study at a tertiary cancer center in Northern India

Background

Acute Normovolemic Hemodilution (ANH) is one of the blood conservation strategies wherein the patient’s whole blood is removed in a controlled manner immediately prior to surgery simultaneously maintaining the intravascular volume by administration of intravenous fluids. This reduces the patient’s intraoperative hematocrit thereby reducing the surgical red cell loss. The autologous blood collected is transfused to the patient at the end of the surgery or after the step of maximal blood loss [1]. Utility of ANH in oncology patients is not widely reported in India and hence, this study has been proposed anticipating the reduction in need for allogeneic blood and the expenditures incurred.

Aims and Objectives

The Aim of the study is to evaluate Acute Normovolemic Hemodilution (ANH) in the setting of Urological malignancies.

The Objectives of the study are to

a. To determine if Acute Normovolemic Hemodilution (ANH) would decrease the allogeneic blood

requirement in Urological malignancies. (The null hypothesis is that ANH does not lead to reduction in allogeneic blood requirement)

b. To estimate the differences in expenses by avoiding allogeneic transfusions

c. To determine if ANH leads to reduction in morbid events and length of hospital stay. (The null hypothesis is that there is no reduction in morbid events and length of hospital stay with ANH)

Subjects and Methods

The participants will be selected from the Elective surgical OT list published on the previous day of the surgery. They will be screened for inclusion and exclusion criteria based on the clinical and laboratory reports available on EMR. These patients will be explained the study in detail. They will be given a period of 10 to 12 hours for giving consent. The consenting participants will be randomized into either test or control arms by Simple randomization.

The participants in the standard arm will receive allogeneic blood transfusions when indicated intra and post operatively which is the usual institutional practice.

The participants randomized into the test arm will receive autologous blood when indicated intra operatively**. If blood requirement arises post operatively, or if the intraoperative blood demand surpasses the autologous units, they will be transfused allogeneic blood**. The autologous blood units will be collected after the induction of anesthesia under controlled conditions. The amount of whole blood to be removed will be calculated as per the formula:

V= EBV (H – Hf)/Hav

where V is the volume of blood collected preoperatively, H is the patient’s initial Hb, Hf is the patient’s final Hb after ANH. Hf will be fixed as 10g/dL for all the patients

Hav is the average of H and Hf

EBV-Estimated Blood Volume of the patient

EBV of the patient= Ideal body weight of patient x Blood volume (ml/Kg body weight) {Gilcher’s rule} [2]

Ideal body weight is computed in men as 50 + (0.91 × [height in centimeters - 152.4]) and in women as 45.5 + (0.91 × [height in centimeters - 152.4]). Blood volume (ml/kg) will be decided based on Gilcher’s rule.

Blood collection will be performed by a Co-investigator after induction of anesthesia, immediately before the commencement of the surgery. The target Hb of the patient will be fixed as 10g/dL. Blood will be collected into 350 ml standard blood collection bags  sterile connected with a three way cannula. The bag will be gently mixed to aid in anticoagulation. The bag’s weight will be constantly monitored to collect the optimum volume of blood into each bag. The patient will be simultaneously infused with crystalloids in the ratio 1:1 ie; for every 1 ml of whole blood collected, 1ml of crystalloid solution will be infused. As soon as the bag has the desired volume, it will be disconnected and labeled with the following information:

a. Name of the patient

b. Case number

c. Volume of blood

d. Sequential number of collection

e. Time of the collection.

f. Advice to transfuse within 6 hours

g. Signature of the blood collector

Heart rate, blood pressure, electrocardiogram, Central Venous Pressure, End tidal CO2 and oxygen saturation will be constantly monitored throughout the hemodilution procedure. The bags will be stored at room temperature for a maximum of 6 hours. They will be transfused when indicated intraoperatively. At the end of 6 hours, if there was no point of maximum blood loss, the blood units will be transfused within the Operating Room. The blood units will never be taken out of the Operation Room.

 The following variables will be documented for participants of both arms:

Patient name, Age, Gender, Diagnosis, Surgery planned, Number of allogeneic blood units transfused intra and post operatively, Indications for transfusions, Complications in the post operative phase- Will be documented in descriptive manner, Length of hospital stay, Costs incurred throughout the hospital stay

The following variables will be additionally documented for test arm participants: Body weight, Height, Ideal body weight, Initial Hemoglobin H, Final Hemoglobin Hf, Hemoglobin average (Hav), Hematocrit, Estimated blood volume, Volume to be collected intraoperatively (V), Volume actually collected intraoperatively, Total hemodilution time, Volume of crystalloids infused during hemodilution, Descriptions of complications during hemodilution

The number of allogeneic blood units transfused intraoperatively will be the Primary end point of the study. For the secondary endpoints, the patients will be followed up for 30 days post surgery for morbid events as per Clavien Dindo classification [3], length of hospital stay and the expenses incurred during hospital stay.

Statistical analysis

For preliminary analysis, descriptive statistics will be calculated for both continuous and categorical variables. The continuous variables will be presented as the mean±standard deviation (SD) or Median (IQR) based on the normality of the data. The categorical variables will be presented as numbers (percentages). Normality of the data will be assessed using Shapiro Wilk Test. A level of significance of 0.05 (= α) and 80% power of the study will be used for analysis. For the primary objective, to determine if Acute Normovolemic Hemodilution (ANH) would decrease the allogeneic blood requirement a two-sample t-test will be performed between the two arms. For comparing between categorical variables, chi-square test or fisher’s exact test will be performed. Any factors responsible for ANH will be determined using regression analysis. A p-value < 0.05 will be considered. All analysis will be performed using R Software (version 4.2.2).

 The information in the study records will be kept confidential and the data will be housed in the Department of Transfusion Medicine. Principal Investigator and Co-Principal Investigator will have the rights to ’View’ and ’Edit’ the master chart. The Co-Investigators will have ’View’ rights. Data will be stored securely for a period of five years and will be made available only to persons conducting the study and to the regulatory authorities. The data will not be made available to another individual unless you specifically give permission in writing. No reference will be made in oral or written reports which could link you to the study. Result of the study will not be communicated to the participant unless deemed necessary

 References

1. Murray D. Acute normovolemic hemodilution. Eur Spine J. 2004 Oct;13 Suppl 1(Suppl 1):S72-5

2. Neyrinck MM, Vrielink H; Joint Task Force for Education and Certification. Calculations in apheresis. J Clin Apher. 2015 Feb;30(1):38-42.

3. Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibañes E, Pekolj J, Slankamenac K, Bassi C, Graf R, Vonlanthen R, Padbury R, Cameron JL, Makuuchi M. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009 Aug;250(2):187-96