Infusion pumps and red blood cell damage in transfusion therapy: an integrative revision of the academic literature 1

ABSTRACT Objectives: to obtain information from scientific literature concerning infusion pumps used in administering erythrocyte (red blood cells) and to evaluate the implications in the practical use of this equipment by nurses when conducting transfusions. Method: an integrative revision of the following scientific databases: Pubmed/Medline, Scopus, the Virtual Library for Health, SciELO, Web of Science and Cochrane. The following descriptors were used: "infusion pumps", "blood transfusion", "transfused erythrocyte" and "hemolyis". There were no restrictions on the scope of the initial data and it was finalized in December 2014. 17 articles were identified in accordance with the inclusion and exclusion criteria. Results: all of the publications included in the studies were experimental in vitro and covered the use of infusion pumps in transfusion therapy. A summary of the data was presented in a synoptic chart and an analysis of it generated the following categories: cellular damage and the infusion mechanism. Conclusion: infusion pumps can be harmful to erythrocytes based on the infusion mechanism that is used, as the linear peristaltic pump is more likely to cause hemolysis. Cellular damage is related to the plasmatic liberation of markers that largely dominate free hemoglobin and potassium. We reiterate the need for further research and technological investments to guide the development of protocols that promote safe practices and that can contribute to future clinical studies.


Introduction
Blood transfusion is a therapeutic technology that is commonly used in clinical practices in many different health establishments. Approximately 85 million blood transfusions are done annually in the world, with 15 million of them being carried just in the United States (1) .
In Brazil in 2014 3,127,957 transfusions were carried out, in which concentrated erythrocytes (CH) were the blood components most used, covering 57.98% of all transfusions conducted in outpatient units and hospitals in the country (2) .

An indication for a CH transfusion is both clinical
and laboratorial which is based on hemoglobin and hematocrit levels as well as any signs and symptoms presented by the patient (1,3) .
The implementation of transfusion therapy requires the use of an integrated multidisciplinary team where the following occurs: obtaining blood donors, collection, processing, quality control, distribution, the therapy is prescribed for someone, the transfusion takes place and monitoring the clinical responses (3)(4) . The role of nurses is fundamental in this process according to the Nursing Federal Council Resolution (COFEN) nº 306/2006 which provides directives on the procedures to be used by nurses in hemotherapy. Nurses are professionally qualified to plan, execute, coordinate, supervise and watch patients during their transfusion therapy (5) .
In relation to the administration of blood components, nurses are required to use infusion devices that are on the market that present differences concerning: control methods for quality, price, presentation and recommendation of use. The national practice for transfusions involves the use of blood transfusion products that work through the use of gravity with a manual flux control system (4,6) .
The infusion pumps (BI) are devices that regulate the flux of liquid administered under positive pressure to the patient. They are used in intravenous therapy in different areas of health care (7)(8) . Currently BIs are gradually being introduced into the market to be used in blood transfusions. the other devices essentially work through the use of peristaltic mechanisms and cassettes (7)(8) .
The peristaltic mechanism permits the infusion of liquid through forcefully pushing a part of it from the equipment through which the liquid passes. This can be done through two methods: the peristaltic linear method or the rotatory method. The two methods are different in that one works through the use of wave movement and the other works based on compression on the linear plaques or gyrating rollers respectively. This results in pushing the liquid from the bottle that has the solution to be infused in the circulatory vein network in the patient (7)(8) .
The cassette mechanism involves infusion through to be filled or to release the liquid. When the pistons go into the cylinders, the liquid is pushed in the direction of the patient and when the pistons move out, the liquid is sucked up from the container that has it, allowing the cassettes bottles to be refilled (7)(8) .
Although there are innumerable advantages in relation to the safety of the patient through the use of BI in intravenous therapy such as the alarms that it has, the control of the infused volume and providing the adequate time for the liquid to be administered, there is still some uncertainty on their use in transfusion therapy due to the effects of the infusion mechanism on the erythrocytes which may result in hemolysis (9)(10) .
Patients that are transfused with erythrocyte hemolysate, aside from receiving low levels of functional hemoglobin, can be subject to deleterious effects to the organisms through the presence of freed biomarkers when hemolysis occurs (9)(10) . With consideration for the above, the guiding question for this study was: If one transfuses erythrocytes using BI, will this result in cellular damage and hemolysis?

Objectives
To obtain information from scientific literature concerning the effects of infusion pumps used in administering erythrocyte (red blood cells) and to evaluate the implications in the practical use of this equipment by nurses when conducting transfusions.

Material and method
We undertook an integrative revision of the relevant literature. We collected data from secondary sources based on a list that we had sourced out. We then analyzed the data obtained in a systemized manner.
The study had six steps: 1) An identification of the theme and a selection of the theory or questions for the research, 2) establishing inclusion and exclusion criteria for the study, as well as conducting searches in the literature, 3) defining the information to be extracted from the research that was selected, 4) categorization and evaluation of the included studies, 5) interpreting the results and 6) summarizing the knowledge obtained (11)(12)(13) . This research method brings scientific rigor to clinical practices. This permits the inclusion of different types of studies which allows for the following: the maximization of research, critical evaluation and the summarization of evidence that is obtained based on the theme (11)(12)(13) .
In order to select the articles, we used the following portals and databases: U.S. National Library of Medicine (PUBMED), Virtual Library for Health (BVS), SciELO, The Cochrane Library (Cochrane), SCOPUS and ISI Web of Science. When using the SciELO database, the descriptors were researched using the basic (not advanced) research field.
In the Science of Health (DECS) and Medical Subject Headings Section (MESH) we used the following descriptors in response to the research question: "infusion pumps", "blood transfusion", "erythrocyte transfusion" and "hemolysis" . In our searches we used the words AND and OR.
Our research covered all of the articles published up until the 31 December 2014. The inclusion criteria for the publications were the following: 1) articles published in Portuguese, English and Spanish; 2) complete articles that covered the use of BIs in transfusion therapy; 3) any of relevant study. The exclusion criteria was: 1) Opinions from specialists, chapters from books, summaries of journals, patents and editorials, 2) articles that described cellular damage that occurs when using extracorporeal circulation devices and those which provide circulatory assistance with oxygen for extracorporeal membranes (ECMO).
The strategy used to find the articles was modified based on each the database due to the different ways to access each of them. As a guide, we used the research question and the inclusion criteria that had been previously defined. Figure 1 shows the strategy used for the searches done in the Pubmed database.
This strategy was used in analyzing the other databases.  The Procedures for collecting the data Initially we looked at the title and the summary of the studies to check that they met the inclusion criteria.
The next step was to analyze the complete article that was selected. We needed to see whether the study was pertinent to our study. The publications that did

Procedures for analyzing the data
From the six databases included in the study, we managed to obtain a total of 566 articles. Of these, 511 All of the studies that were included were experimental designs in vitro. No classification of the levels of the evidence was carried out as they were considered to be pre-clinical studies.
Further on in the research, the studies were analyzed and grouped based on their similar content with two categories to be analyzed: the mechanism of the BI and the cellular damage.
The presentation of the results from the data that was obtained, was presented in a summary chart which had the following information: information on the authors, the objective of the study, type of study, results, conclusion and the implications in the practices of transfusions done by nurses. This last element had relevant points that were summarized from each article that we analyzed that covered the use of infusion pumps in transfusions done by nurses. It was noted that in some places the aforementioned devices were used in blood transfusions.

Results
Out of the 17 articles that we found, the majority were in English being: 15 (82%), 5.9% were in Spanish  Haemolytic results found however below the recommendation for the last day (35°) of the collection. The conclusion was the hemolysis presented was insignificant.
BI cassette mechanism considered safe by the authors, with small variations in the standards of control of quality. Thompson    There was no significant increase in Hb free in the two blood components groups. The cassette BI did not affect the integrity of the erythrocytes.
BI considered safe for transfusion for both blood components with flux that simulates the scenario of fast transfusion.
Burch KJ, Fhelps SJ, Constance TD, Tennessee, EUA, 1991 (23) To evaluate the effect of Linear peristaltic pump on the integrity of the erythrocytes.

Infusion pump mechanisms
Amongst the 17 studies that were selected, we identified 40 types of infusion systems used in transfusion therapy with 39 (97.5%) being BI and 01 (2.5%) being a pressure system. Some work opted for analyzing just the infusion mechanism in isolation or the different manufacturers while others evaluated the differences between the mechanisms.
The studies covered volumetric infusion pumps, Flow meters and syringe pumps that, in one study, the type of devices were not described. Of the 39 that were described, volumetric infusion pumps were described the most (32 or 82.0%). The next were 5 syringe pumps (12.8%) and lastly 2 flow meters (5.2%).
Amongst the total number of pumps described, the following infusion mechanism were found: five In relation to infusion pressure, two of the studies (11.8%) covered an inflatable pressurized device with a pressure gauge. The other was able to obtain the maximum pressure for linear peristaltic pumps (20,25) .

Cellular damage
Out of the 17 studies, the blood components which were prevalent were the CH in 10 of them (58.8%). One In relation to storage time, the time period for storing hemolysis varied from 24 to 44 days. In eight studies (47.1%) there was a description of a lot of hemolysis when the erythrocytes were near to expiration (16,18,(26)(27)29) .
In the life span of the hemolysis there is a liberation of hemoglobin in the plasma. There is also an increase for values where the level of hemolysis was above 0.8% (18,20,25,28) .
None of the publications mentioned the clinical consequences of cellular damage and the liberation of biomarkers to patients.

Discussion
The studies selected in the literature show that alterations in the integrity of the erythrocytes can occur when CH and ST are transfused by BI. This is that case for the action with the infusion mechanism and the variables related to the equipment such as flux.
All of the evidence found in the study came from such as LDH, haptoglobin and potassium (9)(10)32) .
Free potassium in the plasma can bring about adverse events for the patient such as arrhythmia and even sudden death. Other correlated studies increased the level of potassium with an increase in storage time and the preservative solution in the collection bag [33][34][35] .
There is evidence of the occurrence of hyperkalemia and even heart attacks when there are transfusions with CH after long storage periods (33)(34)(35) . The concentrations of potassium in the stored blood increase about 1 milliequivalent (mEq) per day (9) . However none of the publications that were selected touched on the clinical consequences of cellular damage to patients because they mainly dealt with in vitro studies. In spite of this, they placed a lot of emphasis on the biomarkers as a consequence of cellular damage and hemolysis.

Nowadays, national agencies, Europeans and North
Americans establish a maximum level of hemolysis at 0.8% until the last storage day. This is obligatory in the control of the quality of blood banks (36)  washed and radiated (19,28) . measuring the drips to be administered (6) ..
The volumetric mechanism with the cassette is efficient and excellent for intravenous therapy. This is because it has little interference with the mechanical force of the BI on the fluid to be administered. In the articles included in the present revision, it was identified as a safe mechanism for blood transfusions (6,17,21-22.26) .
An English studied noted that hemolysis is caused by multi factors associated with the increase in hematocrit, storage time for the blood components and the pressure placed on the red blood cells (9) . The manufacturers ought to pay attention to the international standard in the International Organization for Standardization (ISO) 1135-4 (38) , that determines the maximum pressure level for infusion at 40 kilopascal (kPa) (9,25,38) . No publication stated the value of the infusion pressure as a possible factor for cellular damage. They only stated the pressor variation in the equipment in high infusion fluxes (20) .
Aspects related to accessories to infusion pumps such as catheters, were described and evaluated only in conjunction with the infusion system. This gave us inconclusive and conflicting results.
The linear peristaltic pumps are the most common pumps in the health care system in the country. They have advantages in comparison to the cassette system, such as similar alarms and their accessories are less onerous (6) . More studies in the linear peristaltic pumps should be done to established standards for its use.
The studies should also cover: infusion pressure and occlusion, defining the worst case scenario, fluxes that mimic the practice of transfusions, temperature control during the procedure and a wide analysis of biomarkers for evaluation of hemolysis which has consensus in the literature.
We reiterate the importance of institutional protocols for blood banks and assistant units that ensure safety in the transfusion process to prevent untoward events.
For example there can be double checks of the blood component data and the individual who will receive the blood. Health and safety analysis of the equipment can be conducted for transfusions in institutions. There can also be: more improvements made in the technology used and more visual inspections of the collection bags because this visual check may be useful in detecting hemolysis (note this has not be proven) (39) .
Multi professional teams need to do the following to In the team, the nurse evaluates and implements the intravenous therapy and selects the adequate materials for the patient and the treatment (5) . In the publications that we studied there was a greater likelihood for hemolysis with catheters at low gauges principally where there are high flows. This is due to the force of the blood with few lumes. Nevertheless, all of the researchers evaluated the infusion system as a whole being part of BIs with the catheter and not only the catheter in isolation (8,18,26) .
The technology is a part of everyday nursing.
Progress in the use of BI in intravenous therapy has future studies that aim to promote safe practices for the protection of patients.

Limitations of the Study
We opted for not limiting the scope of the data and our searches, but some of the data was far from being relevant to the study. Although the theme was related to technology and innovation in transfusion therapy, there was a scarcity in publications on this topic covering the use of BIs in blood transfusions.
Additional we could not evaluate the quality of the methods used in the in vitro experimental studies as they did not fit into the system for classifying data from epidemiological studies. They were considered to be pre-clinical. We therefore opted to describe the rigor in the methods used.