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Integrated strategies for allogeneic blood saving in major elective surgery
Transfusion and Apheresis Science 45 (2011) 281–285
Contents lists available at SciVerse ScienceDirect
Transfusion and Apheresis Science journal homepage: www.elsevier.com/locate/transci
Integrated strategies for allogeneic blood saving in major elective surgery Maria Beatrice Rondinelli a,⇑, Francesco Pallotta b, Sandro Rossetti b, Francesco Musumeci c, Antonio Menichetti c, Franco Bianco d, Marco Gaffi b, Luca Pierelli a,e a
Department of Transfusion Medicine, San Camillo Forlanini Hospital, Rome, Italy Department of General Surgery, San Camillo Forlanini Hospital, Rome, Italy c Department of Cardiovascular Surgery, San Camillo Forlanini Hospital, Rome, Italy d Department of Anaesthesiology Surgery, San Camillo Forlanini Hospital, Rome, Italy e Department of Experimental Medicine, La Sapienza University, Rome, Italy b
a r t i c l e
i n f o
Keywords: Autologous blood Red blood cell storage Peri-surgical blood transfusions Blood-saving
a b s t r a c t Background: Large use of allogeneic red blood cell concentrates (RBCc), albeit necessary in major surgery, may influence patients’ outcome. Design and methods: We introduced an integrated strategy including patients’ evaluation and supplementation associated with autologous blood collection and saving to support major elective surgery at our hospital since 2008. After 2 years of stabilization of this approach, we analyzed the results obtained in 2010 in terms of allogeneic blood usage and reduction of transfusion of stored RBCc. Results: Analyzing 2010 results we found that usage of total autologous RBCc units was increased by 2.2 folds, of ‘‘not stored’’ autologous RBCc units by 2.4 folds and of allogeneic RBCc unit transfusion reduced by 65%. The significant reduction in the number of transfused allogeneic RBCc units associated with the use of ‘‘fresher’’ blood could prevent patients’ complications due to immunomodulation and biologic/metabolic disregulation. Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction The current use of red blood cell concentrates (RBCc) in transfusion support of patients undergoing major surgery is a standard and effective practice to counteract blood loss and consequent hemodynamic effects related to acute anemia and hemodilution. Tissue oxygenation requires an adequate hemoglobin concentration in circulating blood and a sufficient tissue perfusion is function of heart activity which is sustained by a proper myocardium oxygenation by coronary flow and oxygen transportation. Beyond certain limits acute blood loss reduced oxygen transportation but not tissue perfusion which increases until a ⇑ Corresponding author. Address: Department of Transfusion Medicine, San Camillo Forlanini Hospital, Circonvallazione Gianicolense n. 87, 00152 Rome, Italy. Tel.: +39 0658703546; fax: +39 0658704258. E-mail address: [email protected] (M.B. Rondinelli). 1473-0502/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.transci.2011.10.009
hemoglobin (Hb) concentration is maintained around the value of 10 g/dL; when acute blood loss determines an Hb decrease below 10 to 9 g/dL, tissue oxygenation decreases without increase in tissue perfusion and in the absence of potentiating mechanisms for oxygen tissue delivery due to the lack of so prompt metabolic changes translating into Hb affinity reduction at tissue levels [1–3]. Hence, the reaching of Hb values below 7 to 6 g/dL in an acute fashion determines a progressive failure in aerobic metabolism which results in significant reduction of energetic compounds and acidosis. At this stage, RBCc transfusion is the only chance to recover tissue oxygenation and generalized energy failure. Generally, these circumstances occur when more than 50% of blood volume is lost in a short time in a subject who has a pre-bleeding normal Hb values or after 30–40% of blood loss in subjects who experience hemorrhage with a starting suboptimal Hb. In these conditions, transfusion of a variable amount
No No No
RBCc, red blood cell concentrate; EPO, erythropoietin; PABD, pre-surgical autologous blood donation; PBC, peri-surgical blood collection; ANH, acute normovolemic hemodilution; IBS, intra-surgical blood salvage. a Median no. of RBCc units. b Median no. of units. c % Of patients transfused with allogeneic RBCc.
3 (1–4) 100% 4.5 (2–6) 4.5 (2–6)
2 (0–4) 70% 2.5 (1–3.5) 2.5 (1–3.5)
Yes IBS (2.5) range 1–3, 5 Yes IBS (4.5) range 2–6 No No
No
3 (0–4) 90% 0 0 No No
Laparotomic nefrectomy (77 patients) Thoracic aortic surgery (61 patients) Aortic dissection (44 patients)
No
3 (0–3) 80% 0 1 (0–2) No No Knee replacement (110 patients)
No
2 (0–3) 90% 0 2 (0–2) No
Yes (2; 0–2) Yes (1; 0–2) No No
No
Total ‘‘non stored’’ autologous RBCcb Total autologous RBCcb PBCa ANHa PABDa
Hip replacement (98 patients)
Since January 2008 at San Camillo Forlanini Hospital (a tertiary care hospital which includes full programs of hemato-oncology with stem cell transplantation, heart, kidney and liver transplantation and a large trauma center, major abdominal, cardio-vascular and orthopedic surgery) we have introduced a multi-phase integrated approach for patient’s evaluation prior to major elective surgery which includes CE with specific care to hematologic status, in case, ST, PABD with or without EPO administration, perisurgical EPO and a program of PBC, whenever possible and appropriate. Only patients for whom a request of a minimum of 2 RBCc units had been made, according to
EPO administration
2. Materials and methods
Surgical setting
of RBCc provides a Hb rise through which tissue oxygenation is gradually recovered. On the other hand, transfusion of allogeneic blood components influences patient outcome in a dose-related fashion so that, in several settings of major surgery, the greater is the number of allogeneic blood component transfused, the higher is the rate of intervention-related complications such as infections, respiratory distress or other organ dysfunction [4–6]. The reasons of this negative relation between patient transfusion load and outcome is only speculative and likely due to recipient immunomodulation, inflammatory cytokine release and clotting/fibrinolysis activation. An attempt to reduce these detrimental effects may be that of transfusing pre-storage leukoreduced RBCc with a storage length no longer than 2 weeks to minimize the negative contribution of the so called ‘‘ storage lesion’’ on patients’ outcome following transfusion. However, allogeneic blood shortage occurring for various reasons at certain geographical site, including seasonal outbreak of new emerging pathogens, may vanish strategies to reduce the usage of ‘‘older’’ allogeneic RBCc [7–9]. In the setting of major surgery, where the intervention is programmed since several days or weeks before, an alternative option is that of planning a program of patient’s preparation to increase his own tolerance to blood loss. The key point of this possible option is that of preliminary patient’s clinical examination (CE) to plan supplementation treatment (ST), erythropoietin (EPO) administration, whenever appropriate, followed by patient’s enrollment in a specific program of autologous blood collection (i.e., pre-surgical autologous blood donation, PABD, peri-surgical blood collection, PBC) [10,11]. Hence, integration of patient’s CE, ST (with or without EPO) with PABD/PBC strategies may contribute to reduce patient’s exposure to stored allogeneic RBCc, providing a contribution for donated blood saving and, likely, for improvement of post-surgical patient’s outcome. Last but not least, the rate of transfusion transmitted infection for hepatitis B virus (HBV) is still 1:282,000 in developed countries of Mediterranean areas and emerging pathogens due to donor’s travelling or migration is increasing the risk of transfusion transmitted infections [12–14]. Here we report a single-institution experience in the application of an integrated strategy of CE/TS/PABD/PBC to support major elective surgery in a large tertiary care hospital of the city of Rome.
Allogeneic RBCc -median no. of unitsc
M.B. Rondinelli et al. / Transfusion and Apheresis Science 45 (2011) 281–285 Table 1 Characteristics of RBCc support for elective major surgery prior to the systematic introduction of the integrated approach for allogeneic blood alternatives (started from January 2008): results observed in the year 2007.
282
M.B. Rondinelli et al. / Transfusion and Apheresis Science 45 (2011) 281–285
local maximum surgery blood order schedule (MSBOS), were enrolled in the present project. 2.1. CE and ST All patients underwent a CE and subjected to blood counts, blood chemistry, clotting parameters and iron status and, on the basis of mean corpuscular volume (MCV) of RBC, folate and vitamin B12 serum levels. In the case of a serum ferritin lower than 15 ng/mL all patients were treated by daily oral therapy with ferrous sulfate (200 mg/day), which had been continued until 4 weeks after surgery. In the case of folic acid deficiency, patients were treated with oral therapy at the daily dose of 5 mg for 30 days; in patients with suspected or diagnosed gastrointestinal malabsorption, folic acid was given through the intramuscular route at proper schedule and dosage [15]. Similarly, cyanocobalamin was given to patients showing vitamin B12 deficiency through the proper route and at schedule and dosage depending on the case. All patients treated by ST were reevaluated after 1 month from treatment start to define the need for further treatments or additional clinical and laboratory investigations [16]. 2.2. EPO and PABD All patients not suffering from metastatic cancer, without an active ischemic disease of myocardium or a serious dysfunction of aortic valve, with a left ventricular ejection fraction higher than 50%, without cerebral hemorrhage or thrombosis in the previous 2 years, without history of seizures refractory to pharmacological prophylaxis, without a HIV infection and with a Hb level higher than 10 g/dL were evaluated for PABD, with or without EPO administration. PABD were carried out by collecting 1 unit of 350 mL of whole blood by a sterile dedicated two-bag collection system every 4 days until the 7th day before surgery for a maximum of 3 units. EPO were administered when patients had a Hb value comprised between 10 and 13 g/dL and associated in all cases with daily intake of ferrous sulfate at the dose of 200 mg per day. EPO (Epoetin alfa) was administered subcutaneously at the dose of 80,000 IU per week until the day of surgery [17,18]. 2.3. Peri-surgical use of EPO without PABD Patients who waited for major elective surgery and showed suboptimal Hb value (<13 and >10 g/dL) and were not eligible for PABD and who had not a recent history of thromboembolic disease, received EPO subcutaneously at the dose 40,000 IU every 3 days since the week prior to surgery and continued until the first week after surgery, for a maximum of 4 injections, associated with daily oral intake of ferrous sulfate (200 mg/day) [18]. 2.4. PBC All patients showing a Hb concentration higher than 13.5 g/dL and prepared for aortic surgery underwent PBC by acute normovolemic hemodilution (ANH) with collection of 2 units of at least 350 mL of whole blood each by
283
a dedicated two-bag collection system which were briefly stored at room temperature in the surgical area and reinfused as soon as possible. Volemic balance was acutely provided by injection of a volume of crystalloid solution equal to three times the total blood volume collected. Patients with documented alteration of clotting factors other than that related to heparin administration and with unstable angina or active myocardial ischemia were excluded from this procedure. Patients not suffering from neoplastic disease involving the surgical field, without infections in the surgical area or subjected to surgical manoeuvres on gastrointestinal, biliary or urinary tracts, in the absence of irrigating procedures of surgical areas, underwent PBC by intra-surgical and/or post-surgical blood salvage (IBS/PBS) by Cardiopath (PBS), Ortopath (IBS/PBS) Cell Saver (IBS) technologies (Haemonetics, Braintree, MA,USA technologies) and C.A.T.S. (IBS) (Fresenius, Bad Hamburg, Germany).
3. Results The surgical areas where we were able to consistently introduce the integrated approach for allogeneic blood alternatives in our Hospital were 4 and included the orthopedic surgery, cardio-vascular surgery, urologic surgery. In cardiovascular surgery we performed the entire process for allogeneic blood saving including CE/ST/PABD/PBC even though the use of PBS was limited to those cases who needed surgical reintervention. In urologic and orthopedic surgery we consistently omitted ANH due to the scarce applicability of this method in this specific setting which was mainly related to patients’ advanced age and scarce compliance of the anesthesiology staff with respect to this technique. In orthopedic surgery interventions for knee replacement were subjected to a modified PBC approach which includes sterile blood aspiration during surgery with a stand-by application of IBS followed by a second-step aspiration from drainage line for further six hours postsurgery (PBS) and by blood processing and washing by Orthopat device, whenever a proper blood volume had been collected. During hip replacement PBC consisted mainly of IBS in a stand-by approach followed by blood processing and washing by Orthopat in the case of a minimum of 300 mL of blood has been aspirated. At the starting of the present project the average use of allogeneic RBCc in the distinct surgery settings was that shown in Table 1. In detail, surgical interventions for thoracic aortic surgery were supported with a median of 2 RBCc units, aortic dissection with 3 units, hip replacement with 3 units, knee replacement with median of 3 and urologic surgery for laparotomic nefrectomy with 3 units. The use of allogeneic RBCc units was necessary in a proportion of patients ranging from 70% to 100%, with the minimum for thoracic aortic surgery and the maximum for aortic dissection. Following 2 years in which we gradually introduced the integrated strategies for allogeneic blood saving including CE/TS/PABD/PBC techniques, we observed, in the course of 2010, a substantial change in the use of allogeneic RBCc units as shown in Table 2. The number of allogeneic RBCc units had been reduced by 1 per patient in thoracic aortic surgery, aortic
RBCc, red blood cell concentrate; EPO, erythropoietin; PABD, pre-surgical autologous blood donation; PBC, peri-surgical blood collection; ANH, acute normovolemic hemodilution; IBS, intra-surgical blood salvage; PBS, post-surgical blood salvage. a Median no. of RBCc units. b Median no. of units. c % Of patients transfused with allogeneic RBCc.
2 (1–4) 100% 6 (2–7) No
No
No
Yes (2) range (0–2) Yes (2) range (0–2)
Yes IBS (4.5) range (2–6)
6 (2–7)
1 (0–2) 70% 4 (1–5) 4 (1–5) Yes IBS (2.5) range (1–3, 5)
0.5 (0–1) 40% 2 (1–3) 4 (1–5) Yes (120,000 IU)
Laparotomic nefrectomy (80 patients) Thoracic aortic surgery (60 patients) Aortic dissection (45 patients)
No
Yes IBS (2) range (1–3)
0 (0–1) 25% 3 (1–3) Yes (80,000 IU) Knee replacement (130 patients)
No
Yes PBS (3) range (1–3)
4 (1–5)
1 (0–1) 55% 1 (0–3) 3 (0–4)
Yes (2; 0–2) Yes (1; 0–2) Yes (2; 0–2) No Yes (120,000 IU) Hip replacement (100 patients)
No
Yes IBS (1) range (0–3)
Total ‘‘non stored’’ autologous RBCcb PABDa EPO administration Surgical setting
ANHa
PBCa
Total autologous RBCcb
Allogeneic RBCc -median no. of unitsc
M.B. Rondinelli et al. / Transfusion and Apheresis Science 45 (2011) 281–285
Table 2 Characteristics of RBCc support for elective major surgery after 2 years of the systematic introduction of the integrated approach for allogeneic blood alternatives: results observed in the year 2010.
284
dissection and hip replacement; moreover, we were able to reduce RBCc units by 2.5 and 3 per patient in laparotomic nefrectomy and knee replacement, respectively. Apart from thoracic aortic surgery and aortic dissection where allogeneic blood was still required in 70% and 100% of cases, we needed allogeneic RBCc transfusions only in 25% of knee replacements, 55% of hip replacements and 40% of laparotomic nefrectomy. Collectively, in the entire patients’ cohort total autologous RBCc units were increased by 2.2 folds, ‘‘not stored’’ autologous RBCc units by 2.4 folds and allogeneic RBCc unit transfusion was reduced by 65%. An additional considerable result of our integrated approach is represented by the fact that we transfused in all cases, except the setting of hip replacement, a proportion of autologous ‘‘not stored’’ RBCc units ranging from 50% to 80% (50% in laparotomic nefrectomy, 75% in both knee replacement and aortic dissection and 80% in thoracic aortic surgery). In hip replacement we were unable to transfuse more than 25% of autologous ‘‘not stored’’ RBCc units due to the prevalent contribution of PABD strategy as an alternative to allogeneic transfusion in this specific setting.
4. Discussion The pursuit of allogeneic blood self-sufficiency, of reducing the risk of blood transfusion and of emergent blood-transmittable pathogens is a major goal in modern transfusion medicine. Reported adverse reactions to allogeneic blood, reduction of patients’ survival and with increase in infectious complications in the outcome of those patients receiving a larger number of allogeneic RBCc justify the hypothesis of a transfusion dose-related modulation of patients’ defense with disruption of immune, biologic and metabolic equilibrium which is required for prompt recovery from major surgery and general narcosis [16]. A realistic and alternative approach to allogeneic blood transfusion is that of autologous blood collection preceded by correction of anemic conditions and, whenever possible, by expansion of patient’s circulating RBC volume. In our experience, the introduction of an integrated approach which includes CE/ST/PABD/PBC produced an evident change in allogeneic RBCc usage in patients subjected to elective major surgery in the course of 2 years. Allogeneic blood saving was greater in the setting of knee replacement where we were able to consistently perform PBS which produced a considerable autologous blood saving due to the specific nature of bleeding that, in this kind of surgery, is higher within 6–8 h from the intervention. On the contrary, in hip replacement the introduction of IBS failed to collect more than a median of 1 RBCc unit and this result could be related to the different timing of bleeding in this setting which mostly occur after 24 h from intervention. In the setting of thoracic aortic surgery or aortic dissection the additional use (in these cases IBS was active also in 2008) of ANH did not change the proportion of patients who received allogeneic RBCc units while reduced the median number of allogeneic units transfused per patient by 1. In this context, we believe that a further improvement in allogeneic RBCc saving is unfeasible due
M.B. Rondinelli et al. / Transfusion and Apheresis Science 45 (2011) 281–285
to the specific characteristics of the surgery which requires a high amount of RBCc to counteract a naturally high intraoperative blood loss. Another surgical setting which showed a major result is that of laparotomic nefrectomy where the use of both PABD and IBS allowed us to reduce the need of RBCc transfusion of 67%, with the production and transfusion of 4 autologous RBCc units in 2010, as compared to none in 2008. Collectively, our approach permitted us to reduce by 65% patients exposure to allogeneic blood and by 40% to stored RBCc units (autologous + allogeneic). As outlined in the introduction of this report, the increased use of allogeneic RBCc in patients subjected to surgery relates to a higher number of clinical complications due to immunomodulation, erythrocyte lesions occurring during conservation or transfusion-transmitted infections [17,18]. All of these unfavorable circumstances may be overcome by a significant reduction in the number of transfused allogeneic RBCc units. Here, the observed decrease in the allogeneic blood and stored RBCc unit usage in patients with major surgery demonstrated that this result may be obtained by an integrated approach which includes CE/ST/PABD/PBC; a further analysis should be carried out in the near future to investigate whether this modification in blood usage translates into a better patients’ outcome in a larger cohort of patients [19,20]. Finally, an additional challenge in this setting should be that of reducing even more the residual transfusional load of stored RBCc units (autologous + allogeneic) in those patients who show an Hb level which allows a greater toleration of blood loss during and after surgery.
Funding source No funding was necessary to complete this article.
Acknowledgements The authors thank Salvatore Scali, Fabrizio Schirripa, Stefano Villani, Angela Accarino for performing IBS/PBS during surgical interventions.
285
References [1] Vamvakas EC. Meta-analysis of clinical studies of the purported deleterious effect of ‘‘old’’ (versus ‘‘fresh’’) red blood cells: are we at equipoise. Transfusion 2010;50:600–10. [2] Koch GC, Li L, Sessler DI, Figueroa P, Hoeltge GA, Mihaljevic T, et al. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med 2008;358:1229–39. [3] Liumbruno GM, AuBuchon JP. Old blood, new blood or better stored blood. Blood Transfus 2010;8(4):217–9. [4] Dzik W. Fresh blood for everyone? Balancing availability and quality of stored RBCs. Transfus Med 2008;18(4):260–5. [5] Ranucci M, Carlucci C, Isgrò G, Boncilli A, De Benedetti D, Della Torre T, et al. Duration of red blood cell storage and outcomes in pediatric cardiac surgery: an association found for pump prime blood. Crit Care 2009;13(6):R207. [6] Vandromme MJ, McGwin G J, Weinberg JA. Blood transfusion in the critically ill: does storage age matter. Trauma Resusc Emerg Med. 2009;17:35. [7] Yoshida T, Shevkoplyas SS. Anaerobic storage of red blood cells. Blood Transfusion 2010;8(4):220–36. [8] D’Alessandro A, Liumbruno G, Grazzini G, Zolla L. Red blood cell storage: the story so far. Blood Transfus 2010;8(2):82–8. [9] Hod EA, Zhang N, Sokol SA, Wojczyk BS, Francis RO, Ansaldi D, et al. Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation. Blood 2010;115:4284–92. [10] Kor DJ, Van Buskirk CM, Gajic O. Red blood cell storage lesion. Bosn J Basic Med Sci 2009;9(Suppl. 1):S21–7. [11] Zimrin AB, Hess JR. Current issues relating to the transfusion of stored red blood cells. Vox Sang 2009;96(2):93–103. [12] Dwyre DM, Fernando LP, Holland PV. Hepatitis B, hepatitis C and HIV transfusion-transmitted infections in the 21 st century. Vox Sang 2011;100:92–8. [13] Offner MD, Moore EE, Biffl WL, Johnson JL, Silliman CC. Increased rate of infection associated with transfusion of old blood after severe injury. Arch Surg 2002;137:711–7. [14] Sparrow RL. Red blood cell storage and transfusion-related immunomodulation. Blood Transfus 2010;8(Suppl. 3):s26–30. [15] Levy JH. Pharmacological methods to reduce perioperative bleeding. Transfusion 2008;48:31S–8S. [16] Mannucci PM, Levi M. Prevention and treatment of major blood loss. N.England J Med 2007:3562301–11. [17] Stoneham M, Iqbal R. Clinical strategies to avoid blood transfusion. Anaesth Intensive Care Med 2007;8:52–5. [18] Auerbach M, Goodnough LT, Picard D, Maniatis A. The role of intravenous iron in anemia management and transfusion avoidance. Transfusion 2007;47:1905–18. [19] Pape A, Habler O. Alternatives to allogeneic blood transfusions. Best Pract Res Clin Anaesthesiol 2007;21:221–39. [20] Wells PS. Safety and efficacy of methods for reducing perioperative allogeneic transfusion: a critical review of the literature. Am J Ther 2002;9:377–88.
Contents lists available at SciVerse ScienceDirect
Transfusion and Apheresis Science journal homepage: www.elsevier.com/locate/transci
Integrated strategies for allogeneic blood saving in major elective surgery Maria Beatrice Rondinelli a,⇑, Francesco Pallotta b, Sandro Rossetti b, Francesco Musumeci c, Antonio Menichetti c, Franco Bianco d, Marco Gaffi b, Luca Pierelli a,e a
Department of Transfusion Medicine, San Camillo Forlanini Hospital, Rome, Italy Department of General Surgery, San Camillo Forlanini Hospital, Rome, Italy c Department of Cardiovascular Surgery, San Camillo Forlanini Hospital, Rome, Italy d Department of Anaesthesiology Surgery, San Camillo Forlanini Hospital, Rome, Italy e Department of Experimental Medicine, La Sapienza University, Rome, Italy b
a r t i c l e
i n f o
Keywords: Autologous blood Red blood cell storage Peri-surgical blood transfusions Blood-saving
a b s t r a c t Background: Large use of allogeneic red blood cell concentrates (RBCc), albeit necessary in major surgery, may influence patients’ outcome. Design and methods: We introduced an integrated strategy including patients’ evaluation and supplementation associated with autologous blood collection and saving to support major elective surgery at our hospital since 2008. After 2 years of stabilization of this approach, we analyzed the results obtained in 2010 in terms of allogeneic blood usage and reduction of transfusion of stored RBCc. Results: Analyzing 2010 results we found that usage of total autologous RBCc units was increased by 2.2 folds, of ‘‘not stored’’ autologous RBCc units by 2.4 folds and of allogeneic RBCc unit transfusion reduced by 65%. The significant reduction in the number of transfused allogeneic RBCc units associated with the use of ‘‘fresher’’ blood could prevent patients’ complications due to immunomodulation and biologic/metabolic disregulation. Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction The current use of red blood cell concentrates (RBCc) in transfusion support of patients undergoing major surgery is a standard and effective practice to counteract blood loss and consequent hemodynamic effects related to acute anemia and hemodilution. Tissue oxygenation requires an adequate hemoglobin concentration in circulating blood and a sufficient tissue perfusion is function of heart activity which is sustained by a proper myocardium oxygenation by coronary flow and oxygen transportation. Beyond certain limits acute blood loss reduced oxygen transportation but not tissue perfusion which increases until a ⇑ Corresponding author. Address: Department of Transfusion Medicine, San Camillo Forlanini Hospital, Circonvallazione Gianicolense n. 87, 00152 Rome, Italy. Tel.: +39 0658703546; fax: +39 0658704258. E-mail address: [email protected] (M.B. Rondinelli). 1473-0502/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.transci.2011.10.009
hemoglobin (Hb) concentration is maintained around the value of 10 g/dL; when acute blood loss determines an Hb decrease below 10 to 9 g/dL, tissue oxygenation decreases without increase in tissue perfusion and in the absence of potentiating mechanisms for oxygen tissue delivery due to the lack of so prompt metabolic changes translating into Hb affinity reduction at tissue levels [1–3]. Hence, the reaching of Hb values below 7 to 6 g/dL in an acute fashion determines a progressive failure in aerobic metabolism which results in significant reduction of energetic compounds and acidosis. At this stage, RBCc transfusion is the only chance to recover tissue oxygenation and generalized energy failure. Generally, these circumstances occur when more than 50% of blood volume is lost in a short time in a subject who has a pre-bleeding normal Hb values or after 30–40% of blood loss in subjects who experience hemorrhage with a starting suboptimal Hb. In these conditions, transfusion of a variable amount
No No No
RBCc, red blood cell concentrate; EPO, erythropoietin; PABD, pre-surgical autologous blood donation; PBC, peri-surgical blood collection; ANH, acute normovolemic hemodilution; IBS, intra-surgical blood salvage. a Median no. of RBCc units. b Median no. of units. c % Of patients transfused with allogeneic RBCc.
3 (1–4) 100% 4.5 (2–6) 4.5 (2–6)
2 (0–4) 70% 2.5 (1–3.5) 2.5 (1–3.5)
Yes IBS (2.5) range 1–3, 5 Yes IBS (4.5) range 2–6 No No
No
3 (0–4) 90% 0 0 No No
Laparotomic nefrectomy (77 patients) Thoracic aortic surgery (61 patients) Aortic dissection (44 patients)
No
3 (0–3) 80% 0 1 (0–2) No No Knee replacement (110 patients)
No
2 (0–3) 90% 0 2 (0–2) No
Yes (2; 0–2) Yes (1; 0–2) No No
No
Total ‘‘non stored’’ autologous RBCcb Total autologous RBCcb PBCa ANHa PABDa
Hip replacement (98 patients)
Since January 2008 at San Camillo Forlanini Hospital (a tertiary care hospital which includes full programs of hemato-oncology with stem cell transplantation, heart, kidney and liver transplantation and a large trauma center, major abdominal, cardio-vascular and orthopedic surgery) we have introduced a multi-phase integrated approach for patient’s evaluation prior to major elective surgery which includes CE with specific care to hematologic status, in case, ST, PABD with or without EPO administration, perisurgical EPO and a program of PBC, whenever possible and appropriate. Only patients for whom a request of a minimum of 2 RBCc units had been made, according to
EPO administration
2. Materials and methods
Surgical setting
of RBCc provides a Hb rise through which tissue oxygenation is gradually recovered. On the other hand, transfusion of allogeneic blood components influences patient outcome in a dose-related fashion so that, in several settings of major surgery, the greater is the number of allogeneic blood component transfused, the higher is the rate of intervention-related complications such as infections, respiratory distress or other organ dysfunction [4–6]. The reasons of this negative relation between patient transfusion load and outcome is only speculative and likely due to recipient immunomodulation, inflammatory cytokine release and clotting/fibrinolysis activation. An attempt to reduce these detrimental effects may be that of transfusing pre-storage leukoreduced RBCc with a storage length no longer than 2 weeks to minimize the negative contribution of the so called ‘‘ storage lesion’’ on patients’ outcome following transfusion. However, allogeneic blood shortage occurring for various reasons at certain geographical site, including seasonal outbreak of new emerging pathogens, may vanish strategies to reduce the usage of ‘‘older’’ allogeneic RBCc [7–9]. In the setting of major surgery, where the intervention is programmed since several days or weeks before, an alternative option is that of planning a program of patient’s preparation to increase his own tolerance to blood loss. The key point of this possible option is that of preliminary patient’s clinical examination (CE) to plan supplementation treatment (ST), erythropoietin (EPO) administration, whenever appropriate, followed by patient’s enrollment in a specific program of autologous blood collection (i.e., pre-surgical autologous blood donation, PABD, peri-surgical blood collection, PBC) [10,11]. Hence, integration of patient’s CE, ST (with or without EPO) with PABD/PBC strategies may contribute to reduce patient’s exposure to stored allogeneic RBCc, providing a contribution for donated blood saving and, likely, for improvement of post-surgical patient’s outcome. Last but not least, the rate of transfusion transmitted infection for hepatitis B virus (HBV) is still 1:282,000 in developed countries of Mediterranean areas and emerging pathogens due to donor’s travelling or migration is increasing the risk of transfusion transmitted infections [12–14]. Here we report a single-institution experience in the application of an integrated strategy of CE/TS/PABD/PBC to support major elective surgery in a large tertiary care hospital of the city of Rome.
Allogeneic RBCc -median no. of unitsc
M.B. Rondinelli et al. / Transfusion and Apheresis Science 45 (2011) 281–285 Table 1 Characteristics of RBCc support for elective major surgery prior to the systematic introduction of the integrated approach for allogeneic blood alternatives (started from January 2008): results observed in the year 2007.
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M.B. Rondinelli et al. / Transfusion and Apheresis Science 45 (2011) 281–285
local maximum surgery blood order schedule (MSBOS), were enrolled in the present project. 2.1. CE and ST All patients underwent a CE and subjected to blood counts, blood chemistry, clotting parameters and iron status and, on the basis of mean corpuscular volume (MCV) of RBC, folate and vitamin B12 serum levels. In the case of a serum ferritin lower than 15 ng/mL all patients were treated by daily oral therapy with ferrous sulfate (200 mg/day), which had been continued until 4 weeks after surgery. In the case of folic acid deficiency, patients were treated with oral therapy at the daily dose of 5 mg for 30 days; in patients with suspected or diagnosed gastrointestinal malabsorption, folic acid was given through the intramuscular route at proper schedule and dosage [15]. Similarly, cyanocobalamin was given to patients showing vitamin B12 deficiency through the proper route and at schedule and dosage depending on the case. All patients treated by ST were reevaluated after 1 month from treatment start to define the need for further treatments or additional clinical and laboratory investigations [16]. 2.2. EPO and PABD All patients not suffering from metastatic cancer, without an active ischemic disease of myocardium or a serious dysfunction of aortic valve, with a left ventricular ejection fraction higher than 50%, without cerebral hemorrhage or thrombosis in the previous 2 years, without history of seizures refractory to pharmacological prophylaxis, without a HIV infection and with a Hb level higher than 10 g/dL were evaluated for PABD, with or without EPO administration. PABD were carried out by collecting 1 unit of 350 mL of whole blood by a sterile dedicated two-bag collection system every 4 days until the 7th day before surgery for a maximum of 3 units. EPO were administered when patients had a Hb value comprised between 10 and 13 g/dL and associated in all cases with daily intake of ferrous sulfate at the dose of 200 mg per day. EPO (Epoetin alfa) was administered subcutaneously at the dose of 80,000 IU per week until the day of surgery [17,18]. 2.3. Peri-surgical use of EPO without PABD Patients who waited for major elective surgery and showed suboptimal Hb value (<13 and >10 g/dL) and were not eligible for PABD and who had not a recent history of thromboembolic disease, received EPO subcutaneously at the dose 40,000 IU every 3 days since the week prior to surgery and continued until the first week after surgery, for a maximum of 4 injections, associated with daily oral intake of ferrous sulfate (200 mg/day) [18]. 2.4. PBC All patients showing a Hb concentration higher than 13.5 g/dL and prepared for aortic surgery underwent PBC by acute normovolemic hemodilution (ANH) with collection of 2 units of at least 350 mL of whole blood each by
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a dedicated two-bag collection system which were briefly stored at room temperature in the surgical area and reinfused as soon as possible. Volemic balance was acutely provided by injection of a volume of crystalloid solution equal to three times the total blood volume collected. Patients with documented alteration of clotting factors other than that related to heparin administration and with unstable angina or active myocardial ischemia were excluded from this procedure. Patients not suffering from neoplastic disease involving the surgical field, without infections in the surgical area or subjected to surgical manoeuvres on gastrointestinal, biliary or urinary tracts, in the absence of irrigating procedures of surgical areas, underwent PBC by intra-surgical and/or post-surgical blood salvage (IBS/PBS) by Cardiopath (PBS), Ortopath (IBS/PBS) Cell Saver (IBS) technologies (Haemonetics, Braintree, MA,USA technologies) and C.A.T.S. (IBS) (Fresenius, Bad Hamburg, Germany).
3. Results The surgical areas where we were able to consistently introduce the integrated approach for allogeneic blood alternatives in our Hospital were 4 and included the orthopedic surgery, cardio-vascular surgery, urologic surgery. In cardiovascular surgery we performed the entire process for allogeneic blood saving including CE/ST/PABD/PBC even though the use of PBS was limited to those cases who needed surgical reintervention. In urologic and orthopedic surgery we consistently omitted ANH due to the scarce applicability of this method in this specific setting which was mainly related to patients’ advanced age and scarce compliance of the anesthesiology staff with respect to this technique. In orthopedic surgery interventions for knee replacement were subjected to a modified PBC approach which includes sterile blood aspiration during surgery with a stand-by application of IBS followed by a second-step aspiration from drainage line for further six hours postsurgery (PBS) and by blood processing and washing by Orthopat device, whenever a proper blood volume had been collected. During hip replacement PBC consisted mainly of IBS in a stand-by approach followed by blood processing and washing by Orthopat in the case of a minimum of 300 mL of blood has been aspirated. At the starting of the present project the average use of allogeneic RBCc in the distinct surgery settings was that shown in Table 1. In detail, surgical interventions for thoracic aortic surgery were supported with a median of 2 RBCc units, aortic dissection with 3 units, hip replacement with 3 units, knee replacement with median of 3 and urologic surgery for laparotomic nefrectomy with 3 units. The use of allogeneic RBCc units was necessary in a proportion of patients ranging from 70% to 100%, with the minimum for thoracic aortic surgery and the maximum for aortic dissection. Following 2 years in which we gradually introduced the integrated strategies for allogeneic blood saving including CE/TS/PABD/PBC techniques, we observed, in the course of 2010, a substantial change in the use of allogeneic RBCc units as shown in Table 2. The number of allogeneic RBCc units had been reduced by 1 per patient in thoracic aortic surgery, aortic
RBCc, red blood cell concentrate; EPO, erythropoietin; PABD, pre-surgical autologous blood donation; PBC, peri-surgical blood collection; ANH, acute normovolemic hemodilution; IBS, intra-surgical blood salvage; PBS, post-surgical blood salvage. a Median no. of RBCc units. b Median no. of units. c % Of patients transfused with allogeneic RBCc.
2 (1–4) 100% 6 (2–7) No
No
No
Yes (2) range (0–2) Yes (2) range (0–2)
Yes IBS (4.5) range (2–6)
6 (2–7)
1 (0–2) 70% 4 (1–5) 4 (1–5) Yes IBS (2.5) range (1–3, 5)
0.5 (0–1) 40% 2 (1–3) 4 (1–5) Yes (120,000 IU)
Laparotomic nefrectomy (80 patients) Thoracic aortic surgery (60 patients) Aortic dissection (45 patients)
No
Yes IBS (2) range (1–3)
0 (0–1) 25% 3 (1–3) Yes (80,000 IU) Knee replacement (130 patients)
No
Yes PBS (3) range (1–3)
4 (1–5)
1 (0–1) 55% 1 (0–3) 3 (0–4)
Yes (2; 0–2) Yes (1; 0–2) Yes (2; 0–2) No Yes (120,000 IU) Hip replacement (100 patients)
No
Yes IBS (1) range (0–3)
Total ‘‘non stored’’ autologous RBCcb PABDa EPO administration Surgical setting
ANHa
PBCa
Total autologous RBCcb
Allogeneic RBCc -median no. of unitsc
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Table 2 Characteristics of RBCc support for elective major surgery after 2 years of the systematic introduction of the integrated approach for allogeneic blood alternatives: results observed in the year 2010.
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dissection and hip replacement; moreover, we were able to reduce RBCc units by 2.5 and 3 per patient in laparotomic nefrectomy and knee replacement, respectively. Apart from thoracic aortic surgery and aortic dissection where allogeneic blood was still required in 70% and 100% of cases, we needed allogeneic RBCc transfusions only in 25% of knee replacements, 55% of hip replacements and 40% of laparotomic nefrectomy. Collectively, in the entire patients’ cohort total autologous RBCc units were increased by 2.2 folds, ‘‘not stored’’ autologous RBCc units by 2.4 folds and allogeneic RBCc unit transfusion was reduced by 65%. An additional considerable result of our integrated approach is represented by the fact that we transfused in all cases, except the setting of hip replacement, a proportion of autologous ‘‘not stored’’ RBCc units ranging from 50% to 80% (50% in laparotomic nefrectomy, 75% in both knee replacement and aortic dissection and 80% in thoracic aortic surgery). In hip replacement we were unable to transfuse more than 25% of autologous ‘‘not stored’’ RBCc units due to the prevalent contribution of PABD strategy as an alternative to allogeneic transfusion in this specific setting.
4. Discussion The pursuit of allogeneic blood self-sufficiency, of reducing the risk of blood transfusion and of emergent blood-transmittable pathogens is a major goal in modern transfusion medicine. Reported adverse reactions to allogeneic blood, reduction of patients’ survival and with increase in infectious complications in the outcome of those patients receiving a larger number of allogeneic RBCc justify the hypothesis of a transfusion dose-related modulation of patients’ defense with disruption of immune, biologic and metabolic equilibrium which is required for prompt recovery from major surgery and general narcosis [16]. A realistic and alternative approach to allogeneic blood transfusion is that of autologous blood collection preceded by correction of anemic conditions and, whenever possible, by expansion of patient’s circulating RBC volume. In our experience, the introduction of an integrated approach which includes CE/ST/PABD/PBC produced an evident change in allogeneic RBCc usage in patients subjected to elective major surgery in the course of 2 years. Allogeneic blood saving was greater in the setting of knee replacement where we were able to consistently perform PBS which produced a considerable autologous blood saving due to the specific nature of bleeding that, in this kind of surgery, is higher within 6–8 h from the intervention. On the contrary, in hip replacement the introduction of IBS failed to collect more than a median of 1 RBCc unit and this result could be related to the different timing of bleeding in this setting which mostly occur after 24 h from intervention. In the setting of thoracic aortic surgery or aortic dissection the additional use (in these cases IBS was active also in 2008) of ANH did not change the proportion of patients who received allogeneic RBCc units while reduced the median number of allogeneic units transfused per patient by 1. In this context, we believe that a further improvement in allogeneic RBCc saving is unfeasible due
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to the specific characteristics of the surgery which requires a high amount of RBCc to counteract a naturally high intraoperative blood loss. Another surgical setting which showed a major result is that of laparotomic nefrectomy where the use of both PABD and IBS allowed us to reduce the need of RBCc transfusion of 67%, with the production and transfusion of 4 autologous RBCc units in 2010, as compared to none in 2008. Collectively, our approach permitted us to reduce by 65% patients exposure to allogeneic blood and by 40% to stored RBCc units (autologous + allogeneic). As outlined in the introduction of this report, the increased use of allogeneic RBCc in patients subjected to surgery relates to a higher number of clinical complications due to immunomodulation, erythrocyte lesions occurring during conservation or transfusion-transmitted infections [17,18]. All of these unfavorable circumstances may be overcome by a significant reduction in the number of transfused allogeneic RBCc units. Here, the observed decrease in the allogeneic blood and stored RBCc unit usage in patients with major surgery demonstrated that this result may be obtained by an integrated approach which includes CE/ST/PABD/PBC; a further analysis should be carried out in the near future to investigate whether this modification in blood usage translates into a better patients’ outcome in a larger cohort of patients [19,20]. Finally, an additional challenge in this setting should be that of reducing even more the residual transfusional load of stored RBCc units (autologous + allogeneic) in those patients who show an Hb level which allows a greater toleration of blood loss during and after surgery.
Funding source No funding was necessary to complete this article.
Acknowledgements The authors thank Salvatore Scali, Fabrizio Schirripa, Stefano Villani, Angela Accarino for performing IBS/PBS during surgical interventions.
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