Comparative cost analysis of using Pedi-Packs and adult red cell packs in Newborn Intensive Care Units in Southern Iran

Background and objective : In most developing countries, blood transfusions are routinely administered by adult red blood cells (RBCs) packs in infants leading to wastage of a large amount of blood supplies as well as having high donor exposure risk. We aimed to compare the cost-effectiveness of hypothetical pediatric pack compared to adult RBCs pack in neonates. Methods : In this cross-sectional study, all transfused neonates (n=70) who were admitted to the newborn intensive care unit (NICU) of Nemazee Hospital, a tertiary referral hospital in Shiraz, Southern Iran, were evaluated between March and June, 2019. Based on the blood bank information during the study period and transfusion indices, a specific pediatric pack was suggested and cost-effectiveness of new and traditional transfusion methods was compared. Results : Considering the mean number of transfusions per neonate: 3.57 and mean volume of transfused packed red cells: 20 ml per transfusion during the study period; a quadruple pediatric pack (240 ml divided in 4 sub-packs) was purposed and cost-analysis of pediatric and adult pack was performed. Mathematically, we proved higher cost-effectiveness in using pediatric versus adult pack. Additionally, using pediatric packs leads to 13.74% reduction in RBCs wastage per transfusion and 68.13% reduction in donor exposure rate. Conclusions : Assignment of dedicated pediatric pack for infants will be able to substantially reduce donor exposure risk as well as wasted resources leading to higher cost effectiveness. This finding should be taken into consideration especially in developing countries in order to promote both economic situation and child health status.


Introduction
Despite using micro methods blood sampling for premature neonates admitted in the newborn intensive care unit (NICU), newborn babies are highly exposed to blood loss and anemia due to repeated diagnostic phlebotomies. Therefore, multiple small-volume transfusions are often required to replace blood loss and prevent severe anemia in this high-risk group. Several methods of blood transfusions have been suggested and utilized for this purpose worldwide (1)(2)(3)(4)(5)(6).
Unfortunately, in developing countries such as Iran, small frequent blood transfusions are routinely administered by adult blood packs in infants (7)(8)(9). In this practice, a single adult red blood cells (RBCs) pack of 250-450 ml fresh red cells is utilized for infants. Consequently, it leads to not only wastage of a large amount of blood supplies, but also multiple donor exposure risk for infants.
A proportion of 38.3% blood product wastage has been reported in developing countries such as Iran due to this type of transfusion in NICU and surgery units (7).
Specified donor transfusion programs have been suggested in order to reduce the risk of multiple donor exposure and the wasted resources. In this context, some effective strategies have been applied such as using pediatric transfusion guidelines, splitting a single blood donation into limited satellite packs with three or four attached transfer bags or unlimited satellite packs with unlimited connected smaller bags and dedicated for a single infant with RBCs stored for up to 14 to 42 days (5,(10)(11)(12)(13)(14)(15)(16)(17). The cost effectiveness of using such an unlimited donor program which relies on newer technology known as sterile docking has been shown to be equivalent to saving $0.5 and $5.54 per transfusion, respectively (12,15). In another study, assigning single donor pediatric frozen red cell packs (Pedi-Packs) was reported as a safe, convenient, and effective method for transfusion in infants (14). Moreover, cost-effectiveness of various methods of allocation using 4,6 or 8 satellite packs for up to 21-42 days, stored in the Pedi-Packs, for multiple transfused neonates were investigated in other studies (5,10,11,13,17).
Up to our knowledge, at the present time, in Iran, we do not have any specific transfusion method for infants and newborns.
This study was designed to compare the cost-effectiveness via total cost of the hypothetically usage of Pedi-Packs compared to the adult RBCs packs which are routinely administered to neonates in NICU.

Methods
In this cross-sectional study, medical charts of all neonates who were admitted to NICU of Nemazee Hospital, a tertiary referral hospital in Shiraz, Southern Iran were evaluated between March and June, 2019. All newborn babies who received blood transfusion in this period were considered as our study population (n=70). Based on the values of above-mentioned indices, we suggested a specific type of Pedi-Pack dedicating to a single infant over his/her admission period. In this model, the total red cells capacity, and the number of sub-packs were determined with the assumption that each sub-pack is used only once. The expiration date or maximum duration of usage was estimated based on the average time interval of the first and last transfusion in the evaluated neonates during the study period (5,17).
Finally, total costs of the suggested Pedi-Pack and routine adult RBCs pack were compared mathematically. For this purpose, we specified the total cost (TC) per transfusion for each of the two methods ( Table 1) which consists of two components: acquisitioned RBCs costs and wasted resources cost per transfusion. The first component includes two subgroups: first subgroup contained handling hospital blood bank's cost (HC) that is administrative activities associated with handling blood products as well as laboratory tests (LC) that both of them are performed by the hospital blood bank and are considered the same for both Pedi-Pack and adult pack; the second subgroup is defined as RBCs preparation cost (PC) which is different between the two methods as much as "x" and is related to the preparation process by the Blood Transfusion Organization (BTO). Moreover the second component of the TC is the wasted resources cost consisting of the wasted RBCs cost (WC) that is difference between the two methods as much as" f" and calculated by the wasted volume of packed RBCs multiplying in the final acquisitioned RBCs cost (HC + LC + PC) of one ml packed RBCs in each method. Another subgroup of the wasted resources is the transfusion risk cost (WRC) which is different between Pedi-Pack and adult pack as much as "m" (Table 1) (12,18).

Statistical analysis
Data analysis was performed using Statistical Package for the Social Sciences (SPSS) software version 18 (SPSS Inc., Chicago, Illinois, USA). Descriptive information was presented as mean, standard deviation, median, frequency, and percentage. Cost-effectiveness comparison between the two methods was done mathematically.
The details of packed RBCs consumption and wastage using adult packs in NICU in the study period are described in Table 3. The total number of adult packs which were used in this duration was 221, while the total number of transfusions were 250, indicating that 29 units were shared amongst the neonates in this period. Moreover, the mean volume transfused packed red cells was 20 ml per transfusion and 71.42 ml per neonate during admission.
In our estimated Pedi-Pack model, we suggest a total capacity of 240 ml packed red cells divided into four 60-ml sub-packs based on the mean number of transfusions per neonate: 3.57 or nearly 4 that totally gives a 240-ml capacity that is approximately close to 250 ml in adult pack. Since the mean volume of transfused RBCs per transfusion was calculated as 20 ml, each sub-pack with 60ml packed red cells can definitely supply the neonatal requirement in each time of transfusion.
In addition, the expiration date can be considered as 20 days based on the average time interval between the first and the last transfusion in the evaluated neonates.
Then, blood wastage based on using this model was calculated and compared with the volume of blood wastage using current transfusion practice in NICU ( Table 4). The volume of wasted red cells per transfusion was determined 201 ml using adult pack compared to 40 ml using Pedi-Pack owning to mean volume of transfused RBCs per transfusion: 20 ml and considering that each subpack pack is used only once.
In the next step, we compared total cost per transfusion between the two methods ( Table 1).
As mentioned above, components of HC and LC are equal in both methods, so the differences between the total costs of Pedi-Pack and adult pack arise from variations in PC, WC, and WRC.
It seems that PC in Pedi-Pack is more than adult pack that we considered this difference as much whereas the "f" value was specified as the differential cost in the wasted RBCs. Afterwards using equation [1], [ [1], [2], [3] , [ On the other hand, the mean number of donor exposure rate in the adult pack system was 3.16 compared to 1 in Pedi-Pack that is equivalent to 68.13% reduction in donor exposure rate using Pedi-Pack.

Discussion
Total cost of the routine adult pack and the suggested Pedi-Pack was compared based on the situation analysis of packed RBCs consumption and wastage as well as donor exposure rate in a three-month period in NICU. Based on these values, we proved that using Pedi-Pack instead of the routine adult pack in NICU can decrease the total cost of transfusion and donor exposure rate in neonates.  (1,2,5,13,19). Accordingly, several studies succeeded to prove reduction in donor exposure rate by replacement of the alternative blood transfusion methods in NICU using diverse donor programs such as the "sterile docking device" (12,15), or pack-sets with 4-8 satellite packs, by dedicating single donor units for just single neonate with increasing the expiration date of RBCs pack (5,13,16,17).
Based on our results, using Pedi-Pack sets can also be associated with 13.74% less RBCs wastage compared to adult pack. It is consistent with some other studies that show using the limited donor program followed by the specific pack sets such as Pedi-Packs may contain an additional cost, but global costs decrease due to reduction in the wasted resources associated costs of multiple donor exposure risk and the RBCs wastage which consequently increases the cost-effectiveness (12,15 (14).They concluded that despite higher cost, the Pedi-Pack can be more economical because it uses for more than one transfusion. Moreover, it has less donor exposure risk for infants.
Our study was limited due to the fact that our cost analysis was based on the hypothetically model rather than actually usage due to unavailability of pediatric pack and low financial support for intentionally production of this specific type of blood bag. For instance, in calculation of the total wasted resources which consisted of wasted RBCs cost and wasted costs related to clinical complications or WRC, we were able to compare only the first one, but due to the lack of Pedi-Packs set, we were not able to compare clinical complications΄ cost between the two methods in reality. However, this issue was shown previously that reducing the number of donor exposure leads to a significant impact on reducing the clinical complications (12). So as you noticed in mathematical terms we were not able to calculate the exact specified differential cost of RBCs preparation (x) in the Pedi-Pack set and the summation of burden costs related to donor exposure risk (m) and wasted RBCs (f), and thus, it was not possible to calculate the exact total costs. However, according to the reduction in wasted RBCs with Pedi-Pack (13.74 % per transfusion) compared to adult pack as well as the higher rate of clinical complications due to higher number of donor exposures in adult pack compared to Pedi-Pack (3.16 times) the value of "x" is not expected to exceed "f +m", because the related costs of donor-exposure complications are generally higher than the RBCs preparation cost, so the application of new method would seem to be more cost effective with very high possibility.
Taken together, our hypothetical model made us be able to show increased cost-effectiveness using Pedi-Packs compared to the routine adult pack for new borne babies admitted in NICU. Our results is in line with the implementation of alternative programs in practice leading to impressive outcomes in previous studies (11,12,15,16). The results of this study can be very helpful for policy makers especially in developing countries where faces with shortage in financial resources.
The next step recommended based on the result of this study, is providing the suggested Pedi-Pack by collaboration of BTO and medical equipment companies in order to investigating this method in practice and establishing it as a cost-efficient method of pediatric transfusion.

Conclusion
Assignment of dedicated standardized pediatric pack with reserving RBCs from one donor for each neonate will be able to substantially reduce donor exposure risk as well as wasted resources leading to higher cost effectiveness. This finding should be taken into consideration especially in developing countries in order to promote both economic situation and child health status.

Consent for publication
Not applicable.

Competing interests
The authors declare that they have no competing interests.

Funding
Shiraz University of Medical Sciences supported this work financially. The funding body had no role in study design, data gathering, data analysis, data interpretation, or manuscript writing.

Availability of data and materials
The methodology is listed in detail in the methods section of the manuscript. All data are available upon request.

Authors' contributions
SH and Maryam Gholami developed the concept for the manuscript, drafted and revised the manuscript. SM conducted data analysis and drafted the manuscript. AZ, AMK and Marjan Gholami cooperated in data gathering and drafted the manuscript. All authors read and approved the final manuscript.