Measuring the impact of ambulatory red blood cell transfusion on home functional status: study protocol for a pilot randomized controlled trial

Dennis H Murphree, Theresa N Kinard, Nandita Khera, Curtis B Storlie, Che Ngufor, Sudhindra Upadhyaya, Jyotishman Pathak, Emma Fortune, Eapen K Jacob, Rickey E Carter, Karl A Poterack, Daryl J Kor, Dennis H Murphree, Theresa N Kinard, Nandita Khera, Curtis B Storlie, Che Ngufor, Sudhindra Upadhyaya, Jyotishman Pathak, Emma Fortune, Eapen K Jacob, Rickey E Carter, Karl A Poterack, Daryl J Kor

Abstract

Background: Red blood cell (RBC) transfusion is frequently employed in both ambulatory and hospital environments with the aim of improving patient functional status. In the ambulatory setting, this practice is particularly common in patients with malignancy due to anemia associated with their cancer therapy. Increasingly, the efficacy of this US$10.5 billion per year practice has been called into question. While it is often standard of care for patients with chemotherapy-induced anemia to receive ambulatory RBC transfusions, it is unclear to what extent such transfusions affect home functional status. It is also unclear whether or not changes in functional status in this population can be objectively quantified using wearable activity monitors. We propose to directly measure the impact of outpatient RBC transfusions on at-home functional status by recording several physiological parameters and quantifiable physical activity metrics, e.g., daily energy expenditure and daily total step count, using the ActiGraph wGT3X-BT. This device is an accelerometer-based wearable activity monitor similar in size to a small watch and is worn at the waist. Study participants will wear the device during the course of their daily activities giving us quantifiable insight into activity levels in the home environment.

Methods/design: This will be a randomized crossover pilot clinical trial with a participant study duration of 28 days. The crossover nature allows each patient to serve as their own control. Briefly, patients presenting at a tertiary medical center's Ambulatory Infusion Center (AIC) will be randomized to either: (1) receive an RBC transfusion as scheduled (transfusion) or (2) abstain from the scheduled transfusion (no transfusion). After an appropriate washout period, participants will crossover from the transfusion arm to the no-transfusion arm or vice versa. Activity levels will be recorded continuously throughout the study using an accelerometry monitor. In addition to device data, functional status and health outcomes will be collected via a weekly telephone interview. The primary outcome measure will be daily energy expenditure. Performance metrics, such as step count changes, will also be evaluated. Additional secondary outcome measures will include daily sedentary time and Patient-reported Outcomes Measurement Information System (PROMIS) Global 10 Survey scores.

Discussion: This trial will provide important information on the feasibility and utility of using accelerometry monitors to directly assess the impact of RBC transfusion on patients' functional status. The results of the study will inform the merit and methods of a more definitive future trial evaluating the impact of ambulatory RBC transfusions in the target population.

Trial registration: ClinicalTrials.gov, identifier: NCT02835937 . Registered on 15 July 2016.

Keywords: Clinical trial; Functional status; Outpatient; Transfusion.

Figures

Fig. 1
Fig. 1
Study design

References

    1. The 2011 National Blood Collection and Utilization Survey Report. . Accessed 7 June 2016.
    1. Shander A, Hofmann A, Ozawa S, Theusinger OM, Gombotz H, Spahn DR, SABM, MSBM. Activity-based costs of blood transfusions in surgical patients at four hospitals. Transfusion. 2010;50:753–65.
    1. Nielsen K, Johansson PI, Dahl B, Wagner M, Frausing B, Borglum J, Jensen K, Sturup J, Hvolris J, Rasmussen LS. Perioperative transfusion threshold and ambulation after hip revision surgery—a randomized trial. BMC Anesthesiol. 2014;14. DOI: 10.1186/1471-2253-14-89.
    1. Carson JL, Guyatt G, Heddle NM, Grossman BJ, Cohn CS, Fung MK, Gernsheimer T, Holcomb JB, Kaplan LJ, Katz LM, et al. Clinical practice guidelines from the AABB: red blood cell transfusion thresholds and storage. JAMA. 2016;316:2025–35. doi: 10.1001/jama.2016.9185.
    1. Whitman CB, Shreay S, Gitlin M, van Oijen MG, Spiegel BM. Clinical factors and the decision to transfuse chronic dialysis patients. Clin J Am Soc Nephrol. 2013;8:1942–51. doi: 10.2215/CJN.00160113.
    1. Carson JL, Terrin ML, Noveck H, Sanders DW, Chaitman BR, Rhoads GG, Nemo G, Dragert K, Beaupre L, Hildebrand K, et al. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med. 2011;365:2453–62. doi: 10.1056/NEJMoa1012452.
    1. So-Osman C, Nelissen R, Brand R, Brand A, Stiggelbout AM. Postoperative anemia after joint replacement surgery is not related to quality of life during the first two weeks postoperatively. Transfusion. 2011;51:71–81. doi: 10.1111/j.1537-2995.2010.02784.x.
    1. Conlon NP, Bale EP, Herbison GP, McCarroll M. Postoperative anemia and quality of life after primary hip arthroplasty in patients over 65 years old. Anesth Analg. 2008;106:1056–61. doi: 10.1213/ane.0b013e318164f114.
    1. Wallis JP, Wells AW, Whitehead S, Brewster N. Recovery from post-operative anaemia. Transfus Med. 2005;15:413–8. doi: 10.1111/j.1365-3148.2005.00607.x.
    1. Fatalities Reported to FDA Following Blood Collection and Transfusion: Annual Summary for Fiscal Year 2014. . Accessed 1 June 2016.
    1. Murphree D, Ngufor C, Upadhyaya S, Madde N, Clifford L, Kor DJ, Pathak J. Ensemble learning approaches to predicting complications of blood transfusion. Conf Proc IEEE Eng Med Biol Soc. 2015;2015:7222–5.
    1. Murphree DH, Clifford L, Lin Y, Madde N, Ngufor C, Upadhyaya S, Pathak J, Kor DJ. Predicting adverse reactions to blood transfusion. In: Healthcare Informatics (ICHI), 2015 International Conference: 21–23 Oct 2015. 2015: 82–89.
    1. Murphree DH, Clifford L, Lin Y, Madde N, Ngufor C, Upadhyaya S, Pathak J, Kor DJ. A clinical decision support system for preventing adverse reactions to blood transfusion. In: Healthcare Informatics (ICHI), 2015 International Conference: 21–3 Oct 2015. 2015: 100–104.
    1. Clifford L, Singh A, Wilson GA, Toy P, Gajic O, Malinchoc M, Herasevich V, Pathak J, Kor DJ. Electronic health record surveillance algorithms facilitate the detection of transfusion-related pulmonary complications. Transfusion. 2013;53:1205–16. doi: 10.1111/j.1537-2995.2012.03886.x.
    1. Kopko PM, Marshall CS, MacKenzie MR, Holland PV, Popovsky MA. Transfusion-related acute lung injury: report of a clinical look-back investigation. JAMA. 2002;287:1968–71. doi: 10.1001/jama.287.15.1968.
    1. Narick C, Triulzi DJ, Yazer MH. Transfusion-associated circulatory overload after plasma transfusion. Transfusion. 2012;52:160–5. doi: 10.1111/j.1537-2995.2011.03247.x.
    1. McMinn D, Acharya R, Rowe DA, Gray SR, Allan JL. Measuring activity energy expenditure: accuracy of the GT3X+ and actiheart monitors. Int J Exerc Sci. 2013;6:217–29.
    1. Fortune E, Lugade VA, Amin S, Kaufman KR. Step detection using multi-versus single tri-axial accelerometer-based systems. Physiol Meas. 2015;36:2519–35. doi: 10.1088/0967-3334/36/12/2519.
    1. Jarrett H, Fitzgerald L, Routen AC. Interinstrument reliability of the ActiGraph GT3X+ ambulatory activity monitor during free-living conditions in adults. J Phys Act Health. 2015;12:382–7. doi: 10.1123/jpah.2013-0070.
    1. Johnson MJ, Turek J, Dornfeld C, Drews J, Hansen N. Energy expenditure and step count accuracy of the Actigraph wGT3X-BT during walking and running: 1265 Board #4 June 2, 8:00 AM–10:00 AM. Med Sci Sports Exerc. 2016;48:328. doi: 10.1249/01.mss.0000485990.79517.0e.
    1. Santos-Lozano A, Santin-Medeiros F, Cardon G, Torres-Luque G, Bailon R, Bergmeir C, Ruiz JR, Lucia A, Garatachea N. Actigraph GT3X: validation and determination of physical activity intensity cut points. Int J Sports Med. 2013;34:975–82. doi: 10.1055/s-0033-1337945.
    1. Westerterp KR. Reliable assessment of physical activity in disease: an update on activity monitors. Curr Opin Clin Nutr Metab Care. 2014;17:401–6. doi: 10.1097/MCO.0000000000000080.
    1. Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, Lancaster GA, PAFS Consensus Group CONSORT 2010 Statement: extension to randomised pilot and feasibility trials. BMJ. 2016;355:i5239. doi: 10.1136/bmj.i5239.
    1. Fortune E, Tierney M, Scanaill CN, Bourke A, Kennedy N, Nelson J. Activity level classification algorithm using SHIMMER wearable sensors for individuals with rheumatoid arthritis. Conference proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society IEEE Engineering in Medicine and Biology Society Annual Conference 2011, 2011:3059–3062.
    1. Troiano RP, Berrigan D, Dodd KW, Masse LC, Tilert T, McDowell M. Physical activity in the United States measured by accelerometer. Med Sci Sports Exerc. 2008;40:181–8. doi: 10.1249/mss.0b013e31815a51b3.
    1. ActiGraph: ActiLife. vol. . Accessed 7 June 2016.
    1. Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharm Stat. 2005;4:287–91. doi: 10.1002/pst.185.
    1. Sharma S, Sharma P, Tyler LN. Transfusion of blood and blood products: indications and complications. Am Fam Physician. 2011;83:719–24.
    1. Carson JL. Effect of anaemia and cardiovascular disease on surgical mortality and morbidity. Lancet. 1996;348:1055–60. doi: 10.1016/S0140-6736(96)04330-9.
    1. Carson JL, Noveck H, Berlin JA, Gould SA. Mortality and morbidity in patients with very low postoperative Hb levels who decline blood transfusion. Transfusion. 2002;42:812–8. doi: 10.1046/j.1537-2995.2002.00123.x.
    1. Carson JL, Sieber F, Cook DR, Hoover DR, Noveck H, Chaitman BR, Fleisher L, Beaupre L, Macaulay W, Rhoads GG, et al. Liberal versus restrictive blood transfusion strategy: 3-year survival and cause of death results from the FOCUS randomised controlled trial. Lancet. 2015;385:1183–9. doi: 10.1016/S0140-6736(14)62286-8.
    1. Shander A, Javidroozi M, Naqvi S, Aregbeyen O, Caylan M, Demir S, Juhl A. An update on mortality and morbidity in patients with very low postoperative hemoglobin levels who decline blood transfusion. Transfusion. 2014;54:2688–95. doi: 10.1111/trf.12565.
    1. Wu WC, Schifftner TL, Henderson WG, Eaton CB, Poses RM, Uttley G, Sharma SC, Vezeridis M, Khuri SF, Friedmann PD. Preoperative hematocrit levels and postoperative outcomes in older patients undergoing noncardiac surgery. JAMA. 2007;297:2481–8. doi: 10.1001/jama.297.22.2481.
    1. Shander A, Javidroozi M, Ozawa S, Hare GMT. What is really dangerous: anaemia or transfusion? Br J Anaesth. 2011;107:41–59. doi: 10.1093/bja/aer350.
    1. Hare GMT, Freedman J, David MC. Review article: risks of anemia and related management strategies: can perioperative blood management improve patient safety? Can J Anesth. 2013;60:168–75. doi: 10.1007/s12630-012-9861-y.
    1. Goodnough LT, Maggio P, Hadhazy E, Shieh L, Hernandez-Boussard T, Khari P, Shah N. Restrictive blood transfusion practices are associated with improved patient outcomes. Transfusion. 2014;54:2753–9. doi: 10.1111/trf.12723.
    1. Acheson AG, Brookes MJ, Spahn DR. Effects of allogeneic red blood cell transfusions on clinical outcomes in patients undergoing colorectal cancer surgery. A systematic review and meta-analysis. Ann Surg. 2012;256:235–44. doi: 10.1097/SLA.0b013e31825b35d5.
    1. Carson JL, Carless PA, Hebert PC. Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion. The Cochrane database of systematic reviews. 2012;4:CD002042. doi: 10.1002/14651858.CD002042.pub3.
    1. Glance LG, Dick AW, Mukamel DB, Fleming FJ, Zollo RA, Wissler R, Salloum R, Meredith UW, Osler TM. Association between intraoperative blood transfusion and mortality and morbidity in patients undergoing noncardiac surgery. Anesthesiology. 2011;114:283–92. doi: 10.1097/ALN.0b013e3182054d06.
    1. Hopewell S, Omar O, Hyde C, Yu LM, Doree C, Murphy MF. A systematic review of the effect of red blood cell transfusion on mortality: evidence from large-scale observational studies published between 2006 and 2010. BMJ Open. 2013;3. PMID: 23645909, PMCID: PMC3646177. DOI: 10.1136/bmjopen-2012-002154.
    1. Koch CG, Li L, Sessler DI, Figueroa P, Hoeltge GA, Mihaljevic T, Blackstone EH. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med. 2008;358:1229–39. doi: 10.1056/NEJMoa070403.
    1. Liu L, Wang ZW, Jiang SQ, Shao BF, Liu JB, Zhang SQ, Zhou YL, Zhou Y, Zhang YX: Perioperative allogenenic blood transfusion is associated with worse clinical outcomes for hepatocellular carcinoma: a meta-analysis. PLoS One. 2013;8. doi: 10.1371/journal.pone.0064261.
    1. Perkins HA, Busch MP. Transfusion-associated infections: 50 years of relentless challenges and remarkable progress. Transfusion. 2010;50:2080–99. doi: 10.1111/j.1537-2995.2010.02851.x.
    1. Schiergens TS, Rentsch M, Kasparek MS, Frenes K, Jauch KW, Thasler WE. Impact of perioperative allogeneic red blood cell transfusion on recurrence and overall survival after resection of colorectal liver metastases. Dis Colon Rectum. 2015;58:74–82. doi: 10.1097/DCR.0000000000000233.
    1. Villanueva C, Colomo A, Bosch A, Concepcion M, Hernandez-Gea V, Aracil C, Graupera I, Poca M, Alvarez-Urturi C, Gordillo J, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013;368:11–21. doi: 10.1056/NEJMoa1211801.
    1. Koutsavlis I. Transfusion thresholds, quality of life, and current approaches in myelodysplastic syndromes. Anemia. 2016;2016:8494738. doi: 10.1155/2016/8494738.
    1. Nilsson-Ehle H, Birgegard G, Samuelsson J, Antunovic P, Astermark J, Garelius H, Engstrom LM, Kjeldsen L, Nilsson L, Olsson A, et al. Quality of life, physical function and MRI T2* in elderly low-risk MDS patients treated to a haemoglobin level of ≥120 g/L with darbepoetin alfa ± filgrastim or erythrocyte transfusions. Eur J Haematol. 2011;87:244–52. doi: 10.1111/j.1600-0609.2011.01654.x.
    1. Gu Y, Estcourt LJ, Doree C, Trivella M, Hopewell S, Vyas P. Comparison of a restrictive versus liberal red cell transfusion policy for patients with myelodysplasia, aplastic anaemia, and other congenital bone marrow failure disorders. The Cochrane database of systematic reviews. 2015;3:CD011577. doi: 10.1002/14651858.CD011577.
    1. Sciortino AD, Carlton DC, Axelrod A, Eng M, Zhukovsky DS, Vinciguerra V. The efficacy of administering blood transfusions at home to terminally ill cancer patients. J Palliat Care. 1993;9:14–7.
    1. Gleeson C, Spencer D. Blood-transfusion and its benefits in palliative care. Palliat Med. 1995;9:307–13. doi: 10.1177/026921639500900405.
    1. Preston NJ, Hurlow A, Brine J, Bennett MI. Blood transfusions for anaemia in patients with advanced cancer. Cochrane Database Syst Rev. 2012 Feb 15;(2):CD009007. doi: 10.1002/14651858.CD009007.pub2.
    1. Shander A, Hofmann A, Gombotz H, Theusinger OM, Spahn DR. Estimating the cost of blood: past, present, and future directions. Best Pract Res Clin Anaesthesiol. 2007;21:271–89. doi: 10.1016/j.bpa.2007.01.002.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir