Transfusion and blood


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  • Blood Conservation Strategies in Pediatric AnesthesiaAnesthesiology Clin 27 (2009) 337–351Recombinant erythropoietinErythropoietin (EPO) is an endogenous hormone produced in the kidney. It has a high affinity for the erythropoietin receptor expressed on the surface of erythroid cells. It is necessary for the survival of developing erythroid progenitor cells and controls the proliferation and differentiation of these cells. The recombinant alfa form of EPO has been available in the United States since 1997. EPO’s role to increase red blood cell mass in pediatric patients has precedence through its use to treat anemia associated with end-stage renal disease, malignancies, and also anemia of prematurity. As a result, its safety profile has been well evaluated. There are several case reports and reviews exploring the use of EPO preoperatively to avoid, or at least minimize, allogeneic blood transfusions in children. Jadhav and colleagues13 administered EPO with iron supplementation 3 times a week for 6 weeksto 3 children scheduled for major elective surgery who were Jehovah’s Witnesses. There was a rise in hemoglobin by a mean of 4.1 g/dL and hematocrit by a mean of 14%, and none required allogeneic blood products intraoperatively or postoperatively, demonstrating that red blood cell mass can increase considerably just weeks before scheduled surgery. There are also studies demonstrating EPO’s role as an adjunct with other blood conservation techniques. In a retrospective review14 of 19 patients, 10 patients, with a mean age between 11 and 13 months, received EPO and iron for several weeks before craniosynostosis repair and oral vitamin K the previous night. Coupled to that strategy was intraoperativeaprotinin, acute normovolemichemodilution (ANH), and controlled hypotension. Patients receiving EPO increased their red cell mass within 4 weeks by an average of 28% (hematocrit 34.9%–44.5%). Compared with those not receiving EPO, the incidence of transfusion and total volume of blood products were lower. Although many blood conservation strategies were used in conjunction with EPO, clouding the individual contribution of EPO, the investigators did find an increase in allowable blood loss measurements having used EPO preoperatively. To them, this represented an advantage to preoperative EPO administration by allowing more patients to qualify for ANH. With EPO administration, the rate of hematocrit increase varies in patients and may be dose dependent;15 therefore consultation with a hematologist to guide candidacy of intervention, response to dosage, and potential side effects is advisable. The first sign that EPO has taken effect is an increase in reticulocyte count within 10 days, whereas a clinically significant increase in hematocrit should be visible by 2 weeks. Iron supplementation is necessary to provide for increased requirements during expansion of red cell mass secondary to marrow stimulation by EPO.PediatrClin N Am 54 (2007) 691–699Erythropoietin and Other Blood-Boosting Methods:Thomas L. PommeringPhysiology of erythropoietinStructure and functionErythropoietin (EPO) is a naturally occurring glycoprotein hormone that regulates red blood cell (RBC) production. The peritubular fibroblast cells of the renal cortex produce 90% of the body’s EPO, whereas mainly the liver, but also the brain, uterus, and lung account for the remaining 10% [9,14,15]. Within the bone marrow, EPO binds various receptor sites, of which colony-forming unit erythroid cells seem to be most sensitive [16,17]. Subsequently, progenitor cells proliferate into normoblasts and eventually, reticulocytes. Regulation of EPO is controlled by a gene on chromosome 7 (band7q21). The transcription of this gene is controlled by hypoxic inducible factor, which responds to tissue hypoxia [15,18]. Strenuous exercise alone does not seem to affect EPO levels significantly [16]. New circulating erythrocytes are seen within 1 to 2 days after plasma EPO levels increase [14].Clinical applications In June 1989, the first rHuEPO product was marketed in the United States. It was isolated and purified from Chinese hamster ovaries and reproduced using DNA recombinant techniques [18]. Until recently, there were two forms of rHuEPO commercially available in the United States: epoetinalfa and epoetin beta. Now, there are at least four erythropoieticisoforms available worldwide that are synthesized by modifying the rHuEPO molecule. rHuEPO is used to treat anemias related to renal failure, chemotherapy, HIV infection, prematurity, hemoglobinopathies, autoimmune disease, and malignancies, and it is used in patients who undergo surgery who are not candidates for blood transfusion (eg, Jehovah’sWitness). It can be administered intravenously (IV) or subcutaneously (SQ). IV dosing results in a shorter half-life and shorter duration of peak plasma levels, which makes SQ administration easier, more effective, and less expensive. The therapeutic range for epoetinalfa is 50 to 300 units/kg given two to three times weekly. Therapeutic increases in hematocrit occur after 2 to 6 weeks, depending on baseline levels and existing iron stores [15,18].Adverse effectsThe most common side effects are headache, fever, nausea, anxiety, and lethargy. Hypertension and hyperkalemia are seen in up to half of patients who are on dialysis [18]. More concerning side effects are associated with hyperviscosity syndromes related to high hematocrits and include myocardial infarction, seizure, stroke and other thromboembolic events, and sudden death [18–21]. When combined with dehydration, athletes are especially at risk for this potentially lethal scenario (see later discussion). Finally, another rare, but serious, side effect is an autoimmune form of pure red cell aplasia that has been linked with SQ administration of rHuEPO [18,22].Recombinant human erythropoietinTainted historyThe popularity and effectiveness of rHuEPO in elite endurance athletes is demonstrated by a long list of anecdotes associated with its misuse during international competition. When the average speed of the cyclists racing in the Tour de France began to increase suddenly during the 1990s, rumors of rHuEPO use began to circulate. The gene that produces EPO was cloned in 1985, and rHuEPO was available in Europe by 1987 [23]. Between 1987 and 1991, more than 20 Dutch and Belgian cyclists died at rest (some of them while sleeping) as a result of unexplainable cardiac arrest [13,14,24]. Between 1997 and 2000, 18 more cyclists died from pulmonary embolisms, stroke, and myocardial infraction [5]. Finally, suspicions of rHuEPO use in professional cyclists competing in Europe were confirmed during the 1998 Tour de France; boxes of ampules containing rHuEPO were found in team vehicles and the personal rooms of riders from many of the biggest and most successful teams [14]. It became embarrassingly clear that rHuEPO use in elite professional cyclists was organized, widespread, and sophisticated.Ergogenic effectiveness of recombinant human erythropoietinThe ability of rHuEPO to enhance endurance is impressive. Athletes can improve their overall performance by as much as 10% to 15% [25]. Although there is a paucity of literature documenting the ergogenic potential of rHuEPO in elite athletes, what has been published using moderately trained subjects shows similarly effective results when comparing rHuEPO with RBC infusion [5]. Specifically, Ekblom and Berglund [26] showed similar increases in VO2max and time to exhaustion on a treadmill run after several weeks of rHuEPO administration compared with an acute infusion of RBCs. In addition, Audran and colleagues [27] demonstrated a significant increase in VO2max, ventilatory threshold, and a decrease in maximal heart rate after only 25 days of rHuEPO administration.
  • to treat anemias related to renal failure, chemotherapy, HIV infection, prematurity, hemoglobinopathies, autoimmune disease, and malignancies, and it is used in patients who undergo surgery who are not candidates for blood transfusion (eg, Jehovah’sWitness
  • Blood Conservation Strategies in Pediatric AnesthesiaAnesthesiology Clin 27 (2009) 337–351Acute normovolemichemodilutionANH involves the removal of whole blood from the patient shortly before the anticipated surgical blood loss and the restoration of the circulating blood volume with a crystalloid or colloid solution to maintain normovolemia. The premise is that the blood lost during the surgery will consist of blood with a lower hematocrit and, hence, proportionately less of the patient’s red blood cell mass is lost. The oxygen carrying capacity can then be restored by administering the previously withdrawn blood, once the major blood loss has abated.There are a few potential concerns when instituting ANH in pediatric patients. Infants younger than 4 months have a higher Hg F concentration. Hg F has a decreased ability to unload oxygen to the tissues, which would be undesirable in a situation where there is already a reduced oxygen supply (dilutional anemia). Children younger than 4 years may not tolerate hypovolemia well because of their limited ability to increase stroke volume and a predominant reliance on increases in heart rate to maintain cardiac output. Although there are very few studies addressing ANH in infants less than 6 months, Friesen and colleagues20 showed benefits in limiting blood losswhen ANH was used before cardiac surgery, where the replacement fluids included the banked blood already used to prime the cardiopulmonary bypass (CPB) pump. In general though, caution is advised in using this technique in the younger infant. There are many alternate algorithms that calculate the amount of blood that is drawnfrom the donating patient and also how one cares for the drawn blood. The option of keeping the donated blood warm allows for the preservation of the maximum level of platelet function; however, if there is significant delay before readministration, then the blood should be refrigerated.ANH in spinal fusion surgeries have shown to be beneficial especially if combined with other blood conserving strategies. Pouliquen-Evrard and colleagues21 retrospectively examined four groups of children who underwent orthopedic surgery, for allogeneic blood use. The groups included (1) patients solely using allogeneic bloodtransfusions, (2) patients using ANH only, (3) patients using PAD and ANH, and (4) patients using PAD, ANH, and controlled hypotension. The hemoglobin target for hemodilution was 8 g/dL, and transfusion was dependent on both clinical indications and hemoglobin with lower limit of 7 g/dL. Overall, 98%, 46%, 19%, and 5% bloodloss was replaced by allogeneic blood transfusion in the first, second, third, and fourth groups, respectively. This study demonstrated that ANH can significantly reduce allogeneic blood transfusion, especially when used in conjunction with additional blood conservation techniques. In craniosynostosis surgeries, ANH has been less successful. Reasons suggested for this include a smaller pediatric population and a smaller volume of red cells, which in turn limit the volumes of whole blood being harvested before a postdilutionalhematocritlevel is reached.6 In a study22 in which infants undergoing craniosynostosis surgery were randomly assigned to receive ANH or standard fluid management, the combined intraoperative blood loss and postoperative blood loss was large enough in the ANH group that the volume of reinfused blood was inadequate to avoid allogeneictransfusion in the majority of patients. If preoperative hematocrit level had been higher, more blood could have been obtained and used for reinfusion. Therefore, the use of preoperative EPO and iron combined with ANH can potentially prove beneficial.21. Pouliquen-Evrard M, Mangin F, Pouliquen JC, et al. Autotransfusion and hemodilutionin orthopaedic surgery in children. Rev ChirOrthopReparatriceAppar Mot1981;67:609–15.22. Hans P, Collin V, Bonhomme V, et al. Evaluation of acute normovolemichemodilutionfor surgical repair of craniosynostosis. J NeurosurgAnesthesiol 2000;12(1):33–6.
  • Hans P, Collin V, Bonhomme V, et al. Evaluation of acute normovolemichemodilution for surgical repair of craniosynostosis. J NeurosurgAnesthesiol 2000;12(1):33–6Evaluation of Acute NormovolemicHemodilution for Surgical Repair of CraniosynostosisHans, Pol; Collin, Vincent; Bonhomme, Vincent; Damas, François; Born, Jacques Daniel; Lamy, MauriceAuthor InformationUniversity Department of Anesthesia and Intensive Care Medicine, Department of Neurosurgery, Liege, BelgiumAddress correspondence and reprint requests to Prof. Pol Hans, University Department of Anesthesia and Intensive Care Medicine, CHR de la Citadelle, boulevard du 12ème de Ligne 1, 4000 Liege, Belgium.Back to Top   Summary:  This clinical report investigated the potential benefit of acute normovolemichemodilution (ANH) as a blood-saving technique in the surgical repair of craniosynostosis. Over a 4-year period, 34 healthy children undergoing surgical repair of scaphocephaly or pachycephaly were randomly assigned to two groups of 17 patients each. Patients of the first group (ANH group) were submitted to ANH (target Ht: 25%) immediately before surgery and patients of the second group (Control group) were not. During surgery, estimated blood loss was compensated with a 5% albumin solution and no autologous or homologous blood was transfused. At the end of surgery, intraoperative blood loss (mean ± SD) calculated on the basis of the Ht value and the children weight was 21.3 ± 8% of the estimated blood volume (EBV) in the ANH group and 24 ± 6.6% in the Control group. Children of the ANH group received their autologous blood (18.9 ± 3.3% of EBV) systematically at the end of surgery. In the postoperative period, homologous blood was transfused when the Ht value was equal or less than 21%. Both groups were comparable regarding age, weight, type of craniosynostosis, duration of surgery, EBV, and preoperative Ht value. No difference was observed between ANH and Control groups in the number of patients who received homologous blood (15/17 and 14/17, respectively), in the amount of homologous blood transfused (17 ± 4.7% and 19.6 ± 6.3% of the EBV, respectively), and in the Ht value before hospital discharge (29.4 ± 5.0% and 30.7 ± 4.9%, respectively). In conclusion, this report suggests that ANH reduces neither the incidence of homologous transfusion nor the amount of homologous blood transfused in this series of children undergoing surgical repair of craniosynostosis.     The surgical correction of craniosynostosis and craniofacial malformations carries a high risk of unavoidable and extensive blood loss during and after the operation (1–3). Intraoperative blood loss is affected by several factors including the patients' weight and age, the type of skull malformation, and the surgical procedure (2–4). It has been reported that 25 to 500% of the patient's blood volume could be lost during these kinds of procedures (5). Homologous blood transfusions are therefore required both during the surgical procedure and in the postoperative period in the majority of cases (2,4). The risks of infective and immunologic complications associated with homologous blood transfusions are well-known. Avoiding homologous blood transfusion is, therefore, an important challenge in the perioperative care of surgical patients and especially of young children.  The main techniques proposed to reduce or avoid homologous blood transfusions include preoperative autologous blood donation, the use of erythropoietin, acute normovolemichemodilution (ANH), intraoperative cell saving and retransfusion, a meticulous surgical technique, the use of antifibrinolytic drugs, and, finally, the acceptance of minimal perioperativehematocrit levels (6). Acute normovolemichemodilution may be active when performed by the anesthetist preoperatively, or passive when a surgical blood loss is replaced by asanguineous fluid intraoperatively to maintain normovolemia(6). According to recent reviews and prospective randomized clinical trials, ANH can be considered as an effective technique to save homologous transfusion in adult surgery (6–9). Hemodilution and autotransfusion procedures are also known to limit the risks of homologous transfusion in patients undergoing craniosynostosis surgery (2). This report investigates the potential benefit of ANH performed immediately before surgery as a blood-saving technique during surgical repair of craniosynostosis.  Back to Top   PATIENTS AND METHODS  After obtaining parents' consent and institutional board approval, 34 healthy children scheduled for surgical repair of scaphocephaly or pachycephaly, from January 1992 to January 1996, were randomly assigned to two groups of 17 patients each. Patients of the first group (ANH group) were submitted to ANH after induction of anesthesia and immediately before surgery, to achieve a hematocrit value (Ht) of 25%. Patients of the second group (Control group) were taken as control.  In all patients, premedication consisted of midazolam 0.4 mg/kg and atropine 0.125 mg administered intrarectally before transfer to the operating room. Anesthesia was induced intravenously with thiopental 5 mg/kg and sufentanil 0.3 mcg/kg. Muscle relaxation was obtained with atracurium 0.5 mg/kg. Anesthesia was maintained using additional doses of sufentanil, if required, and controlled ventilation with isoflurane (1–2% end-tidal) and 50% nitrous oxide in oxygen. All patients were equipped with two peripheral venous catheters and an arterial catheter for invasive measurement of blood pressure. Additional monitoring included continuous electrocardiogram (ECG), pulse oximetry, noninvasive automated hemodynamic device, urine output, and core temperature. The end-tidal isoflurane concentration was monitored continuously with a Datex AS3 (Datex, Helsinki, Finland) anesthetic agent monitor.  All patients were operated by the same surgeon and managed by the same anesthetist. The estimated blood volume (EBV) was calculated using a reference volume of 80 mL/kg. The ANH consisted of blood removal via the arterial line to achieve a target Ht of 25% and simultaneous replacement with a 5% albumin solution, such as to maintain the circulating volume. The amount of blood to be removed was calculated using the following formula: EBV × (Hti - 25%)/Hti, where Hti was the preoperative hematocrit value. During surgery, baseline fluid requirement was ensured in both groups by continuous administration of 4 of isotonic cristalloid solution, and blood loss was estimated by the anesthetist referring to sponges, suction volume, and the aspect of surgical drapes. Blood loss was replaced by a 5% albumin solution to maintain isovolemia and stable hemodynamic variables. According to the protocol, perioperative blood transfusion was scheduled if the Ht value, measured at the discretion of the anesthetist, was 21% or less. At the end of surgery, the Ht value (Hte) was measured in each patient and the estimated blood loss (EBL) was calculated according to the following formula: EBL = EBV × (Hts - Hte)/Hts, where Hts represents the Ht value measured after ANH and immediately before surgery. The patients of the ANH group were then given their autologous blood.  All patients were extubated at the end of surgery and were transferred to the intensive care unit (ICU) for a 24-hour observation period. In the ICU, serial blood samples were regularly obtained and homologous blood was tranfused when the Ht value was 21% or less. The amount of homologous blood scheduled for transfusion ranged between 15 and 20% of the EBV. A blood cell count and Ht were obtained before hospital discharge.  Data were expressed as means ±SD. Age, weight, and height were compared between groups using an unpaired Student's t test. The distribution by sex, the distribution of the two types of craniosynostosis, and the proportions of patients who required homologous blood transfusion were analyzed with the Fischer exact test. The Ht value at the end of surgery, the intraoperative blood loss, the amount of homologous blood transfused, and the Ht value before hospital discharge were compared between groups with an unpaired Student's t test. A P value less than .05 was considered significant.  Back to Top   RESULTS  Demographic data, nature of skull deformations, duration of surgery, and preoperative Ht values are shown in Table 1. No significant difference was observed for any of these parameters between the two groups. Isolated occipital synostosis resulting in pachycephaly was the most frequent malformation.Table 1 The ANH procedure allowed us to collect a mean autologous blood volume of 122 ± 30 mL (18.9 ± 3.3% of EBV) to achieve a target Ht of 25% (range 24–26%). During surgery, no Ht value was measured and no patient was transfused. The main results of the study are shown in Table 2. The Ht value at the end of surgery was significantly lower in the ANH group (19.2 ± 2.1%) than in the Control group (24.1 ± 2.4%). Intraoperative blood loss expressed as a percentage of EBV was 21.35 ± 8% (range 7.1–33.7%) in the ANH group and 24 ± 6.6% (range 12.1–37%) in the Contol group (not significant). Likewise, no difference was observed between the ANH and the Control group in the number of patients who required homologous blood transfusion (15/17 versus 14/17), in the amount of homologous blood transfused (106 ± 26 mL versus 121 ± 26 mL, corresponding to 17 ± 4.7% and 19.6 ± 6.3% of the EBV, respectively), and the Ht value obtained at hospital discharge (29.4 ± 5 versus 30.7 ± 4.9%). All patients who required homologous blood transfusion received blood from one single donor.Table 2 Back to Top   DISCUSSION  This study was conducted in 34 patients presenting with scaphocephaly or pachycephaly and admitted in the neurosurgical department over a 4-year period. These types of malformation are the most frequently treated in our pediatric patient population and allowed us to design a prospective study comparing two homogenous groups. All patients underwent primary complete surgical correction of their malformation and no strip craniectomy was performed. The Ht value of 25%, which was targeted in the ANH group, may be considered as an acceptable Ht in healthy children aged 3 months to 1 year. However, this value is arbitrary and must be supported by clinical judgement. Extreme hemodilution with target hematocrit of 20% or less is likely to be more efficient in reducing homologous blood transfusion requirements, but the risks are correspondingly greater (10). In conscious healthy adults, it has been reported that acute isovolemic reduction of blood Hb concentration to 50 g/l does not produce evidence of inadequate systemic oxygen delivery, as assessed by lack of change of oxygen consumption and plasma lactate concentration (11). All the ANH procedures were uneventful in our patients.  The EBL during surgery, expressed as a percentage of the EBV, was 21.35 ± 8% and 24.0 ± 6.6% in the ANH and in the Control group, respectively. These data warrant two comments. First, intraoperative blood loss was probably not always appropriately estimated by the anesthetist. The evaluation of blood loss by referring to weighted sponges, measured suction volume, and aspect of surgical drapes is not reliable. The fact that Ht was not actually measured during surgery introduces a potential bias. A more precise technique would have been to systematically measure Ht during surgery in all patients. Second, intraoperative blood loss in our series is substantially less than what is commonly reported in the literature and the amount of homologous blood transfused was also very small. Indeed, Kearney et al. reported mean blood losses of 64.7% of the EBV for scaphocephaly(4). Meyer et al. reported an estimated red cell volume loss during surgery of 92.1% of the estimated red cell volume for the same malformation (2). According to Eaton et al., the surgical correction of pachycephaly may require transfusion of more than 50% of the estimated red cell mass (3). These data clearly indicate that a meticulous surgical technique is a determinant factor in the amount of blood loss and transfusion requirements for craniosynostosis surgery (6).  The results of the present study show that ANH reduces neither the incidence of homologous blood transfusion, nor the amount of homologous blood transfused. The difference in blood requirement between the two groups amounted to 2.6% of the EBV in favor of the ANH group, but was not significant at the 0.05 level. On the other hand, there was approximately an 80% chance of erroneously reporting such a difference as not significant. Considering the sample size of 17 and the estimated population variance of 6.3% (SD of our control group), this type II error may look quite high. However, 2.6% of the EBV represents about 20 mL of blood for a child of 10 kg body weight and is even lower than the SD of blood requirement of our patient population. Considering now a 10% difference of the EBV in blood requirement between the same groups of patients (same sample size, same variance) as clinically meaningful, there would be less than a 2% chance of erroneously reporting it as not significant. Therefore, although the risk of type II error is high when considering that the observed difference of 2.6% between the two groups is not significant, the small size of this difference, which is much smaller than what could be considered as clinically meaningful (10%), allows us to conclude that, even if the difference was significant, it would not be clinically relevant. The small difference in blood requirement between the two groups can probably be explained by the following. The theoretical amount of blood that could be saved by ANH depends on the patient's initial Ht, the Ht at the end of ANH, the patient's EBV, and the surgical blood loss during the procedure. Because of the small circulating blood volume of our patients (mean 640.1 ± 17.5 mL) and their relatively low preoperative Ht value (mean 33.4 ± 4.6%), the amount of autologous blood that could be removed during ANH to achieve a minimal safe Ht of 25% was also small (mean 122.1 ± 30.2 mL). On the other hand, the amount of blood lost in our patients during surgery was minimal (133.6 ± 46.01 mL in the ANH group, that is 21.4 ± 8% of the EBV). In adults, guidelines for autologous transfusion recommend ANH only when the potential blood loss is likely to be greater than 20% of blood volume (10).  In conclusion, acute normovolemichemodilution reduces neither the incidence of homologous blood transfusion, nor the amount of blood transfused in our series of patients undergoing complete surgical correction of craniosynostosis. However, the possibility that ANH may be efficacious in another setting or another institution cannot be ruled out. Our conclusion may be explained by the low estimated blood volume and the low preoperative Ht value of our patients, as well as by a minimal amount of blood lost during surgery. A meticulous surgical technique allowed us to limit the risks of homologous blood transfusion by transfusing our patients with less than one packed red blood cell unit coming from one single donor. Besides considerations on the surgical technique, improvements to avoid homologous blood transfusion in the surgical correction of craniosynostoses will result from a multifactorial strategy including stimulation of the hematopoietic system with erythropoietin, preoperative autologous blood donation, and intraoperative blood salvage (12). Control ANH# of patients 17 17Age 8.1 6.3Weight 8.05 8.0Surgery duration 140 151PreOpHct 32.9 33.4
  • Blood Conservation Strategies in Pediatric AnesthesiaAnesthesiology Clin 27 (2009) 337–351ε-aminocaproic acid and tranexamic acid3-Aminocaproic acid and tranexamic acid are synthetic lysine analogs that competitively inhibit activation of plasminogen to plasmin, thus serving as alternatives to aprotinin. Tranexamic acid has a longer half-life, is 7 to 10 times more potent, and is more active in tissue than aminocaproic acid, with no greater toxicity.15 Studies on aminocaproic acid and tranexamic acid in children have been promising. Chauhan and colleagues33 compared the efficacy of aminocaproic acid and tranexamic acid in reducing postoperative blood loss and blood and blood product requirements in children with cyanotic congenital heart disease. Children from age 2 months to 14.5 years (150 total) underwent corrective surgery on CPB. Patients were randomized into 3 groups based on receiving aminocaproic acid, tranexamic acid, or no antifibrinolytic (control). The control group had the maximum blood loss at 24 hours and maximum requirements of blood products. There was no significant difference in postoperative blood loss or blood product requirement in the two groups given antifibrinolytics; however, both agents were equally effective compared with controls. Similar beneficial effects have been shown in noncardiac surgery. Studies in scoliosis surgery,34,35 despite different dosing between studies, demonstrated a reduction in blood loss and allogeneic blood transfusion requirements in pediatric patients. A Cochrane systematic review of antifibrinolytic agents36 concluded similarly.31. Fergusson DA, Hebert PC, Mazer CD, et al. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med 2008;358(22):2319–31.32. Available at: Accessed May, 2008.33. Chauhan S, Das SN, Bisoi A, et al. Comparison of epsilon aminocaproic acid and tranexamic acid in pediatric cardiac surgery. J CardiothoracVascAnesth 2004; 18(2):141–3.34. Senthna NF, Zurakowski D, Brustowicz RM, et al. Tranexamic acid reduces intraoperative blood loss in pediatric patients undergoing scoliosis surgery. Anesthesiology 2005;102:727–32.35. Neilipovitz DT, Murto K, Hall L, et al. A randomized trial of tranexamic acid to reduce blood transfusion for scoliosis surgery. AnesthAnalg 2001;93:82–7.36. Tzortzopoulou A, Cepeda MS, Schumann R, et al. Antifibrinolytic agents for reducing blood loss in scoliosis surgery in children. Cochrane Database Syst Rev 2008;3:CD006883.
  • Blood Conservation Strategies in Pediatric AnesthesiaAnesthesiology Clin 27 (2009) 337–351Deliberate hypotensionDeliberate hypotension (DH) is the technique of purposely lowering the blood pressure through the use of intravenous agents or inhaled anesthetic agents leading to less blood loss. Concerns regarding impaired oxygen delivery to tissues during hypotension are not as significant in children compared with adults with preexisting atherosclerotic disease of the heart, brain, or kidney. However, caution still must be taken in the pediatric population. According to Gibson,27 DH can obscure the findings of spinal cord monitoring during surgical correction of scoliosis secondary to spinal cord hypoperfusion. To avoid spinal cord hypoperfusion, there is now less reliance on DH and an emphasis on proper patient positioning and the use of antifibrinolytics in patients undergoing scoliosis repair. However, as with other blood conservation techniques, DH has its application in a chosen population undergoing specific surgeries. It has been found to significantly reduce blood loss and surgery time and to improvesurgical operative conditions by enhancing visualization and allowing better delineation and dissection of lesions and structures.28,29 Dolman and colleagues30 compared DH to normotension in a randomized, double-blind, controlled study in patients scheduled to have Le Fort I osteotomies. They found that the quality of the surgical field was improved, and there was a significant reduction in blood loss.Contraindications to DH in children are similar to those in adults: any pathology involving significant reduction in the availability of oxygen to the tissues, including decreased oxygen saturation, cardiac output, or anemia; cardiac, cerebral, or renal disease; and increased intracranial pressure. Factors enhancing the safety of the techniqueinclude the proper selection of cases, maintenance of near-normal acid-base balance, accurate monitoring of pressure, maintenance of high arterial oxygen tension, and avoidance of hyperventilation, as this may significantly reduce cerebral blood flow.28 Of all the hemodynamic variables, mean arterial pressure correlates best to the degree of blood-loss reduction.1428. Salem MR, Wong AY, Bennett EJ, et al. Deliberate hypotension in infants and children.AnesthAnalg 1974;53:975.29. Diaz JH, Lockhart CH, et al. Deliberate hypotension for craniectomies in infancy.Br J Anaesth 1979;51:233.30. Dolman RM, Bentley KC, Head TW, et al. The effect of hypotensive anesthesia on blood loss and operative time during Le Fort I osteotomies. J Oral MaxillofacSurg 2000;58(8):834–9.Patient may have significant blood loss but not have enough to process.Dolman R.M.,  Bentley K.C.,  Head T.W.,  The effect of hypotensiveanesthesia on blood loss and operative time during Le Fort I osteotomies. J Oral MaxillofacSurg(2000) 58 : pp 834-839. PURPOSE: The purpose of this prospective study was to compare the quality of the surgical field, blood loss, and operative time with either hypotensive or normotensiveanesthesia during Le Fort I osteotomies. PATIENTS AND METHODS: Twenty-three patients were randomized into normotensiveor hypotensiveanesthesia (mABP between 50 and 60 mm Hg, with a systolic blood pressure < 80 mm Hg) treatment groups. The quality of the surgical field was assessed intraoperatively by direct observation and again postoperatively using video imaging. A standardized rating scale was applied at specific intervals by surgeons blinded to the anesthetic technique. The surgical time was measured on the videotape, and blood loss was measured by volumetric and gravimetric techniques. RESULTS: There was a statistically significant correlation (P < .0001) between the surgeon's perception of the quality of the surgical field and the blood pressure. There was also a statistically significant reduction (P < .01) in blood loss when using hypotensiveanesthesia. However, there was no statistically significant reduction (P = .44) in operative time when using hypotensiveanesthesia. CONCLUSIONS: It was concluded that hypotensiveanesthesia is valuable in reducing blood loss and improving the quality of the surgical field during Le Fort I osteotomies, allowing for easier, more deliberate, and careful dissection. However, it does not reduce operative time.
  • Blood Conservation Strategies in Pediatric AnesthesiaAnesthesiology Clin 27 (2009) 337–351Fibrin sealant is prepared from two plasma-derived protein fractions: a fibrinogen-rich concentrateand a thrombin concentrate.37 Mixing fibrinogen and thrombin mimics the last step of the blood coagulation cascade, resulting in formation of a fibrin clot that adheres to the application site and acts as a fluid-tight sealing agent able to stop bleeding. Resorption of the clot is achieved within days to weeks following application. It hasbeen used to successfully reduce the amount of clotting factor replacement in children with hemophilia A undergoing circumcision.38 As this product is derived from donor plasma, one must keep in mind the potential for transmission of infection. The fibrinogen and thrombin fractions are exposed to several robust viral inactivation steps, such as solvent-detergent, pasteurization, vapor-heat treatment, and nanofiltration. However, there have been case reports of possible transmission of parvovirus B19 (B19V) by 1 commercial product identified in Japan. Implementation of nucleic acid tests to screen for B19V may reduce this risk.37
  • Blood Conservation Strategies in Pediatric AnesthesiaAnesthesiology Clin 27 (2009) 337–351Temperature controlInfants, particularly the neonate, are highly susceptible to hypothermia in the operating room environment. There is a fairly high rate of heat loss in proportion to heat production in the infant; this is caused by an immature thermoregulatory mechanism, a relatively thin layer of subcutaneous brown fat for insulation,39 and extensive superficial circulation that facilitates rapid dissipation of heat from the body. Studies dating back to the 1970s have demonstrated the effect of hypothermia on coagulation in the newborn. Chadd and Gray40 found that infants whose temperature was allowed to drift to 34C and below had a reduced platelet count and prolonged thrombin times. Hypothermia-related coagulation disorders are caused by anomalies in clotting factor enzyme function, platelet function, and fibrinolytic activity.41
  • Transfusion and blood

    1. 1. 05/05/2010<br />Pediatric Transfusion PracticesDr Gary Simon<br /><ul><li>Physiology
    2. 2. Differences between adult and neonate
    3. 3. Implications
    4. 4. Transfusion reactions
    5. 5. Acute transfusion reactions
    6. 6. Delayed transfusion reaction
    7. 7. Coagulopathy
    8. 8. Transmission of infectious diseases
    9. 9. Sepsis
    10. 10. Metabolic changes
    11. 11. Physicial </li></ul>Dept of Anesthesiology and Perioperative Care<br />
    12. 12. Pediatric Transfusion Practices<br />Blood Conservation<br /><ul><li>Preoperative Autologous Donation
    13. 13. Preoperative Erythropoetin
    14. 14. Acute NormovolemicHemodilution
    15. 15. Antifibrinolytics
    16. 16. Intraoperative Blood Salvage
    17. 17. Controlled hypotension
    18. 18. Topical agents
    19. 19. Temperature control</li></ul>05/05/2010<br />
    20. 20. Pediatric transfusions - Physiology<br />Physiology differences neonate vs child/adult<br />Children have higher oxygen consumption and a higher cardiac output to blood volume ratio than adults <br />The neonatal myocardium operates at near maximum level of performance as a baseline.<br />The newborn’s heart may be unable to compensate for a decreased oxygen carrying capacity by increasing cardiac output. <br />The neonatal myocardium will also suffer a greater degree of decompensation when exposed to decreased oxygen delivery.<br />05/05/2010<br />
    21. 21. Pediatric transfusions - Physiology<br />Fetal hemoglobin (HbF) comprises 70% of full term and 97% of premature infants’ total hemoglobin at birth. Red blood cells (RBCs) containing HbF have a shorter life span (90 days) than those containing primarily adult hemoglobin (HbA) (120 days)<br />HbF interacts poorly with 2,3,DPG. Therefore the P50 decreases from 26 mmHg with HbA to 19 mmHg with HbF<br />The optimal hemoglobin values in the newborn are higher than those of older patients (14-20 g/dl).<br />Physiologic nadir for hemoglobin occurs at approximately 2–3 months of age (term -11, prem – 9.5)<br />05/05/2010<br />
    22. 22. Pediatric transfusions - Physiology<br />05/05/2010<br />
    23. 23. Pediatric transfusions - Physiology<br />The P50 decreases from 26 mmHg with HbA to 19 mmHg with HbF. This leftward displacement of the oxygen–hemoglobin dissociation curve means decreased oxygen delivery to tissue because of the high affinity of HbF for oxygen.<br />HbF production diminishes until only a trace is present at 6 months of age.The younger the infant, the higher the fraction of HbF and thus the lower the oxygen delivering capacity.<br />Hemoglobin levels that are adequate for the older patient may be suboptimal in the younger infant or neonate.<br />05/05/2010<br />
    24. 24. Pediatric transfusions - Physiology<br />05/05/2010<br />
    25. 25. Pediatric transfusions -Physiology<br />Immature coagulation system in neonate and is not comparable with adult level until six months of age.<br />Main differences:<br />vitamin K dependent factors (II, VII, IX, X) that are less than 70% of adult levels<br />inhibitors of coagulation (including antithrombin III and proteins C and S) are 50% of adult levels<br />Platelets numbers are at a similar level to that of adults but take 2 weeks to develop adult levels of reactivity<br />05/05/2010<br />
    26. 26. Blood volume (neonate to adult)<br />05/05/2010<br />
    27. 27. Transfusion reactions<br />Acute transfusion reactions<br />Acute hemolytic reaction<br />Febrile nonhemolytic reaction<br />Urticarial/allergic reaction<br />clerical error<br />Delayed transfusion reaction<br />Coagulopathy<br />Thrombocytopenia<br />Decreased clotting factors<br />Immune<br />TRALI<br />Immunomodulation<br />05/05/2010<br />
    28. 28. Transfusion reactions<br />Transmission of infectious diseases<br />Sepsis<br />Metabolic changes<br />Electrolyte - ↑K+; ↓Ca++; ↓Mg++<br />Acid Base<br />shifts in the oxygen–hemoglobin dissociation curve<br />Physicial<br />Volume overload<br />Temperature<br />05/05/2010<br />
    29. 29. Transfusion reactions - acute<br />Acute hemolytic reaction<br />preformed IgM antibodies to ABO antigens<br />result of blood group incompatibility<br />fever, chills, tachycardia, hypotension, shock, coagulopathy<br />hemolytic reactions due to ABO incompatibility rarely occur in young infant (<4 mo) due to immature immune systems<br />non-ABO antigens involve IgG-mediated reactions<br />often are delayed (ie, 2 to 10 days)<br />not detected by pretransfusion testing, because they represent an anamnestic response<br />Rh disease most likely involving the immigrant population<br />05/05/2010<br />
    30. 30. Transfusion reactions - acute<br />Transfusion-related graft vs host disease <br />foreign lymphocytes in immunocompromised patients proliferate causing host tissue destruction. Pancytopenia that develop 1–6 wks after a transfusion<br />At risk patient includes - premature infants, children suffering from cancer or severe systemic illness, children experiencing rapid acute blood loss, and cardiopulmonary bypass <br />immunocompetent children who receive directed donor transfusion from a biological relative<br />Gamma-irradiation of blood renders donor lymphocytes incapable of proliferating<br />High mortality rate (90%)<br />05/05/2010<br />
    31. 31. Transfusion reactions - acute<br />Febrile nonhemolytic reaction<br />0.5% to 1.5% of red cell transfusions<br />host antibody response to donor leukocyte antigens<br />common in previously transfused patients<br />Use leukocyte-poor PRBCs<br />antipyretics, antihistamines, and corticosteroids<br />Nonimmune hemolytic transfusion reactions<br />temperature (eg, overwarming with blood warmers, microwave ovens) , hypotonic solutions<br />mechanical damage during administration (ie, pressure infusion pumps, pressure cuffs, and small-bore needles)<br />05/05/2010<br />
    32. 32. Transfusion reactions - urticarial/allergic<br />Severe anaphylactic reactions occur infrequently<br />Reaction to donor plasma proteins<br />Manifestations include IgE-mediated symptoms involving the skin, respiratory, GI or circulatory systems.<br />Anaphylactoid reactions with bronchospasm, laryngeal edema and urticaria typically occur in IgA-deficient individuals.<br />Rx includes antihistamines, steroids and sympathomimetics<br />Use washed or filtered RBCs with the next transfusion<br />05/05/2010<br />
    33. 33. Transfusion reactions - delayed<br /> Delayed transfusion reaction:<br />due to minor blood group antigen incompatibility<br />fatigue, jaundice, and dark urine<br />3 to 10 days after transfusion<br />Laboratory findings include anemia, a positive Coombs test, new RBC antibodies, and hemoglobinuria.<br />05/05/2010<br />
    34. 34. Transfusion reactions – dilutional coagulopathy<br />dilutional thrombocytopenia<br />normal patients: a platelet count greater than 50 000 mm3 is required in order to maintain hemostasis<br />chronically thrombocytopenic may not have bleeding tendencies even when the platelet count is in the 10 000–20 000 mm3 range<br />– platelet counts which begin as normal (>150 000 mm3) are unlikely to be the cause of clinically significant coagulopathy until three blood volumes have been transfused (ie platelet count down by 70% from baseline). <br />05/05/2010<br />
    35. 35. Transfusion reactions – dilutional coagulopathy<br />dilution of clotting factors depends upon the type and volume of transfused blood<br />whole blood contains all clotting factors including fibrinogen at normal values except for the labile factors (FV and FVIII); even these factors are present in 20–50% of their normal values. Pathological coagulation generally does not occur until 3+ blood volumes have been lost if whole blood being infused.<br />PRBCs - approximately 80% of the coagulation factors have been separated into the plasma fraction. Clotting factor deficiency likely once blood loss exceeds one blood volume.  <br />05/05/2010<br />
    36. 36. Transfusion reactions<br />Immune<br />Transfusion Related Acute Lung Injury<br />1 in 5000 transfusions. In most cases the reaction occurs within 30 minutes to 2 hours (may occur up to 6 hours after).<br />pathophysiology is still unclear<br />platelet concentrates derived from whole blood are most commonly implicated, followed by fresh-frozen plasma, packed red blood cells, whole blood, granulocytes, cryoprecipitate and intravenous immunoglobulin <br />acute onset of severe hypoxemia, bilateral noncardiogenic pulmonary edema, tachycardia/hypotension, and fever.<br />most common cause of major organ dysfunction secondary to blood product administration<br />In 2006, TRALI was the leading cause of transfusion-related death reported to the FDA (35 deaths, 50.7% of transfusion-related fatalities). Differential diagnosis - TACO<br />05/05/2010<br />
    37. 37. Transfusion reactions - Immune<br />Immunomodulation<br />Alloimmunization to HLA antigens, which occurs commonly (ie, 20% to 70% of the time) in transfused and multiparous patients. Three manifestations:<br />immune-mediated platelet refractoriness (insignificant rise in platelet count)<br />febrile non hemolytic transfusion reaction<br />autoimmune hemolytic anemia<br />post-transfusion purpura (platelet antibodies) 5 to 10 days post transfusion <br />beneficial effects: improved renal allograft survival, reduced risk of recurrent spontaneous abortion, and reduced severity of autoimmune diseases such as rheumatoid arthritis.<br />detrimental effects: increased cancer recurrence, perioperative infections, multiorgan system failure, and +/- overall mortality<br />05/05/2010<br />
    38. 38. Transfusion - infectious diseases<br />Units tested for:<br />Hepatitis B Surface Antigen ; Syphilis <br />Antibodies to Hepatitis B core antigen, Hepatitis C Virus, Human T-cell Lymphotropic Virus (1 and 2), Human Immune Deficiency Virus (1 & 2) <br />Nucleic Acid Testing for presence of HCV RNA, HIV-1 RNA and West Nile Virus RNA<br />05/05/2010<br />
    39. 39. Transfusion - infectious diseases<br />Transmission risk of infectious diseases<br />HIV 1/725,000–835,000; HTLV 1/641,000; parvovirus, 1 in 10,000 hepatitis B 1/63,000–500,000; hepatitis C 1/250,000–500,000 <br />CMV, hepatitis A, parasitic diseases (eg, malaria, babesiosis, toxoplasmosis, and Chagas’ disease), and variant Creutzfeldt–Jakob disease (vCJD) <br />syphilis, Epstein-Barr virus, leishmaniasis, Lyme disease, brucellosis, B-19 parvovirus (increased prevalence in hemophiliacs), tick-borne encephalitis virus, Colorado tick fever virus, severe acute respiratory syndrome (SARS), West Nile virus, human herpes viruses<br />05/05/2010<br />
    40. 40. Transfusion - infectious diseases<br />Sepsis<br />bacteria contamination (particularly platelets as they are stored at room temperature)<br />20 deaths per million units of transfused platelets<br />Occult donor bacteremia and contamination of the product during collection have been the main avenues for entry of bacteria<br />70% of contaminates isolated were gram-positive bacteria; while 80% of fatalities were caused by gram-negative organisms. Better disinfection of skin at the phlebotomy site and diversion of the skin plug have helped.<br />Asymptomatic donor bacteremia (eg a case of transfusion associated Staphylococcus aureus platelet contamination has been reported in a blood donor who had undergone a tooth extraction 3 hours prior to donation)<br />05/05/2010<br />
    41. 41. Pediatric transfusions - Metabolic changes<br />Hypocalcemia<br />Citrate is a chelating agent for calcium.<br />Degree of ionized hypocalcemia depends upon the blood product transfused, the rate of transfusion, and hepatic blood flow/function<br />Highest risk with fresh frozen plasma (FFP) and whole blood<br />Neonates have decreased ability to metabolize citrate<br />Management:<br />Slow the rate of blood product infusion<br />Calcium chloride 5-10 mg/kg : gluconate 15-30 mg/kg<br />05/05/2010<br />
    42. 42. Pediatric transfusions - Metabolic changes<br />Hypomagnesemia<br />Usually associated with massive transfusion<br />result of citrate toxicity and is seen with its greatest severity during the anhepatic phase of liver transplantation<br />magnesium sulfate (25–50 mg/kg) followed by an infusion of 30–60 mg/kg)/24 h.<br />05/05/2010<br />
    43. 43. Pediatric transfusions - Metabolic changes<br />Hyperkalemia<br />Blood components with the highest levels of potassium include whole blood, irradiated units and units approaching their expiration date<br />Rate of rise of serum potassium values occurs quickly in pediatric patients with small blood volumes during large volume or exchange transfusions <br />Interventions include using more recently donated blood and washing it before infusion<br />Calcium chloride 5-10 mg/kg : calcium gluconate 15-30 mg/kg<br />Therapy includes - glucose and insulin, bicarbonate, hyperventilation, β agonists, dialysis and Kayexalate<br />05/05/2010<br />
    44. 44. 05/05/2010<br />
    45. 45. Pediatric transfusions - Metabolic changes<br />SAGM RBC Leukocyte Reduced <br />Red cell concentrate prepared from approximately 480 ml whole blood collected in 70 ml of CPD anticoagulant.<br />The unit is plasma reduced by centrifugation, platelet reduced by either centrifugation or filtration and leukoreduced by filtration. RBC’s are resuspended in 100 ml of SAGM nutrient. <br />CPD/SAGM<br />Citrate is an anticoagulant, phosphate is a buffer, and dextrose is a red cell energy source.<br /> Adenine allows RBCs to resynthesize adenosine triphosphate (ATP) which extends the storage time. Mannitol helps maintain integrity of RBC cell wall.<br />Stored at 1º-6º which slows the rate of glycolysis by 40 times. Shelf life 42 days. <br />05/05/2010<br />
    46. 46. Pediatric transfusions - transfusion risks<br />Acid–base changes<br />After donation, the RBC’s continue to undergo aerobic metabolism and elevate dissolved carbon dioxide to 180–210 mmHg within several hours<br />After oxygen expended anaerobic metabolism increases the lactic acid content<br />Rapid blood transfusion may initially cause a transient combined respiratory and metabolic acidosis.<br />Carbon dioxide is rapidly removed by the lungs; the small amount of lactic acid is rapidly buffered so that there is no net effect upon acid–base status<br />As long as the patient is volume resuscitated there is no need for exogenous bicarbonate therapy<br />05/05/2010<br />
    47. 47. Pediatric transfusions - transfusion risks<br />Hypothermia results from<br />Unwarmed intravenous fluids – esp RBC’s<br />heat loss because of their large surface area to weight ratio and relatively large head size<br />GA causes a shift in heat distribution from core to periphery<br />Radiation and convexion result in most heat loss<br />cool irrigation solutions, and cold operating rooms<br />Hypothermia causes:<br />apnea, hypoglycemia, ↓drug metabolism<br />leftward displacement of the ODC<br />increases oxygen consumption (due to shivering and nonshivering thermogenesis)<br />coagulopathy <br />+/- increase mortality<br />05/05/2010<br />
    48. 48. Pediatric transfusions - replacement<br />MABL = (starting hct - target hct)/starting hct x EBV<br />Higher target hct for:<br />preterm and term infants, children with cyanotic congenital heart disease, large ventilation/perfusion mismatch, high metabolic demand, and children with respiratory failure<br />Replacement:<br />Hct in packed RBCs is about 70%<br />Loss in excess of MABL x desired hct (30%)/0.7<br />Approximately 0.5 ml packed RBCs for each ml of blood loss beyond the MABL<br />05/05/2010<br />
    49. 49. Pediatric transfusions –guidelines<br />RBC transfusions:<br />Leukocyte reduced<br />CMV neg<br />Less than 2-3 wks old<br />Platelet transfusions<br />platelet count is less than 50 * 109/L<br />5 mL/kg - 10 mL/kg causes a rise of platelets of 50 to 100 * 109/L<br />Fresh frozen plasma<br />Maintain minimum of 30% plasma factor concentration<br />10-15 ml/kg<br />Cryoprecipitate<br />1 unit /10 kg BW raises plasma fibrinogen by 50 mg/dl<br />05/05/2010<br />
    50. 50. Pediatric transfusions - triggers<br />Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. Hébert PC - N Engl J Med - 11-FEB-1999; 340(6): 409-17<br />Restrictive strategy: RBC’s transfused if the Hb < 7 g/dl and Hb concentrations were kept at 7 - 9 g/dl; and a liberal strategy: in which RBC’s given when the Hb concentration < 10 g/dl and Hb concentrations were maintained at 10 - 12 g/dl<br />CONCLUSIONS: A restrictive strategy of red-cell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients, with the possible exception of patients with acute myocardial infarction and unstable angina.<br />05/05/2010<br />
    51. 51. Pediatric transfusions - triggers<br />Pediatric red blood cell transfusions increase resource use, Allyson M. Goodman - Journal of Pediatrics Vol 142 • Num 2 • Feb 2003<br />3 groups: hemoglobin 6.5 to 7.4 g/dL (54 patients), 7.5 to 7.9 g/dL (40 patients), and 8 to 9 g/dL (105 patients); 131 were transfused and 109 were not transfused<br />significant increase in hospital and intensive care resources used for transfused patients. PICU and hospital length of stay significantly increased by more than 4 days and 7 days, respectively, and there was substantial increases in the use of oxygen, mechanical ventilation, and vasoactive agent infusions.<br />retrospective multicenter analysis rather than a randomized clinical trial.<br />05/05/2010<br />
    52. 52. Pediatric transfusions - neonates<br />Neonates have some specific considerations with respect to anesthesia and blood products.<br />Major hemolytic reaction (ABO) occurs less frequently in neonates compared with older children and adults.<br />For the first 3–4 months of life, infants are unable to form alloantibodies to RBC antigens.<br />After 4 months of age, hemolytic reactions become a potential factor<br />05/05/2010<br />
    53. 53. Pediatric transfusions – special considerations<br />Tonsillectomy:<br />majority of early bleeding episodes occur within the first 4–6 h after the procedure. Late bleeding occurs 5–10 days postoperatively<br />Several studies have demonstrated increased perioperative bleeding associated with ketorolac use for analgesia following tonsillectomy.<br />Can J Anaesth - 01-JUN-1996: Preoperative ketorolac increases bleeding after tonsillectomy in children.<br />Study terminated early due to interim analysis revealing ↑ risk.<br />Consclusion: “Preoperative ketorolac increases perioperative bleeding among children undergoing tonsillectomy without beneficial effects.” <br />05/05/2010<br />
    54. 54. Blood Conservation<br />Preoperative Autologous Donation<br />Preoperative Erythropoetin<br />Acute NormovolemicHemodilution<br />Antifibrinolytics<br />Intraoperative Blood Salvage<br />Controlled hypotension<br />Topical agents<br />Temperature control<br />05/05/2010<br />
    55. 55. Blood Conservation - PAD<br />An analysis of a preoperative pediatric autologous blood donation program. Can J Surg (2000) 43 : pp 125-129<br />173 patients (ages 8-19) with mininum Hb 110. 400 ml removed if weight >45 kg; less for those < 45 kg. Scoliosis repair.<br />Preoperative Autologous Donation - Children younger than 10 years or weighing less than 40 kg were included had a compliance rate at or above 70%, with the compliance rate in adolescents equal or superior to that of adults.. Allogeneic transfusion rate was 26.6%<br />Wastage rate (percentage of blood units that were unused and discarded) in these studies varied from 6% to 31% of the total number of donated units <br />When PAD was the sole blood conservation method, 73% to 89% of subjects avoided allogeneic transfusion.<br />The addition of deliberate hypotension to PAD resulted in a 10% allogeneic exposure rate.<br />05/05/2010<br />
    56. 56. Blood Conservation - PAD<br />Unique pediatric PAD problems:<br />Smaller total blood volume – smaller donation volumes<br />Inability of younger children to tolerate repeated vascular access<br />Deep sedation or general anesthesia in infants and toddlers for interval of time to remove blood.<br />must be a candidate for elective surgery where blood transfusion likelihood is high<br />admission and operation days must be guaranteed<br />Sufficient time to enable optimal collection of the blood prior to surgery (limited by five week window for stored blood)<br />Same transfusion triggers - many units wasted<br />Directed donations – risk of Graft Versus Host Disease<br />05/05/2010<br />
    57. 57. Blood Conservation - PAD<br />Transfusion Medicine, 2007: Guidelines for policies on alternatives to allogeneic blood transfusion. Predeposit autologous blood donation and transfusion.<br />PAD is not recommended unless exceptional circumstances may include: <br />Rare blood groups where allogeneic blood is difficult to obtain<br />Children with scoliosis (Ib, A)<br />Patients at serious psychiatric risk if blood transfusion is thought to be likely to cover their elective surgery <br />Patients who refuse to consent to allogeneic transfusion but who would consent to PAD<br />05/05/2010<br />
    58. 58. Blood Conservation erythropoietin<br />Erythropoietin is produced in the kidney – 90%; liver, brain, uterus, lung – 10% <br />receptor is on the surface of erythroid cells. EPO is necessary for the survival, proliferation & differentiation of these cells.<br />rate of hematocrit increase varies in patients and may be dose dependent<br />an increase in reticulocyte count within 10 days, whereas a clinically significant increase in hematocrit should be present by 2 weeks (depending on existing iron stores)<br />05/05/2010<br />
    59. 59. Blood Conservation erythropoietin<br />Side effects are headache, fever, nausea, anxiety, and lethargy. Hypertension and hyperkalemia are seen in up to half of patients who are on dialysis <br />Hyperviscosity syndromes related to high hematocrits - myocardial infarction, seizure, stroke and other thromboembolic events.<br />Combined with dehydration, athletes are especially at risk for sudden death. <br />Another rare, but serious, side effect is an autoimmune form of pure red cell aplasia that has been linked with SQ administration of rHuEPO<br />05/05/2010<br />
    60. 60. Blood Conservation –Preoperative Erythropoieten<br />Children who received EPO (300 U/kg three times per week for 3 weeks preoperatively) had significantly higher Hct values (43%) on the day of surgery compared with historical controls (Hct 35%) and had a 36% reduction in allogeneic transfusions. J Neurosurg (1998) <br />Children undergoing surgery for idiopathic scoliosis who received EPO required fewer transfusions and had shorter hospitalizations. Pediatr Orthop B (1998)<br />Preoperative erythropoietin significantly raised starting hemoglobin levels and reduced the need for a blood transfusion with craniosynostosis correction (30 of 30 contols vs 19 of 30 treated). Plast Reconstr Surg (2002) <br />05/05/2010<br />
    61. 61. Blood Conservation -ANH<br />removal of whole blood after induction with replacement with crystalloid/colloid to maintain normovolemia.<br />Autologous plasma, platelets and RBC’s are returned after major blood loss <br />Children tolerate Acute NormovolemicHemodilution better than adults (lower comorbid disease)<br />Lowest Hct (9-17) in small studies revealed no lactic acidosis or decreased oxygen consumption. This would suggest that critical oxygen delivery was not reached.<br />Younger than 4 to 6 months of age are not ideal candidates (myocardial performance and fetalhemoglobin issues)<br />05/05/2010<br />
    62. 62. Blood Conservation -ANH<br />Few small studies evaluating ANH in avoidance of allogenic blood in pediatrics. Tend to indicate a reduction in allogenic transfusion<br />ANH in spinal fusion surgeries have shown to be beneficial especially if combined with other blood conserving strategies<br />05/05/2010<br />
    63. 63. Blood Conservation -ANH<br />Evaluation of acute normovolemichemodilution for surgical repair of craniosynostosis. Hans J NeurosurgAnesthesiol 2000<br />Craniosynostosis repair in 34 healthy patients 1992-1996.<br />17 had mean of 122 ml blood removed after induction. Average weight 8 kg (blood vloume ~ 640 ml), preopHct 33.<br />15/17 vs 14/17 had homologous transfusions (~ 110 ml in both groups)<br />“In conclusion, acute normovolemichemodilution reduces neither the incidence of homologous blood transfusion, nor the amount of blood transfused in our series of patients undergoing complete surgical correction of craniosynostosis.” <br />05/05/2010<br />
    64. 64. Antifibrinolytics<br />ε-aminocaproic acid and tranexamic acid<br />synthetic lysine analogs that competitively inhibit activation of plasminogen to plasmin<br />tranexamic acid has a longer half-life, is 7 to 10 times more potent, and is more active in tissue than aminocaproic acid<br />Chauhan S, et al. Comparison of epsilon aminocaproic acid and tranexamic acid in pediatric cardiac surgery. J CardiothoracVascAnesth 2004; 18(2):141–3.<br />Both agents were equally effective in decreasing blood loss and blood product requirement compared to controls for cardiac surgery<br />Similar benefit has been documented for scoliosis surgery<br />05/05/2010<br />
    65. 65. Blood Conservation – Intop Blood Salvage<br />Cell Saver<br />Few pediatric studies with conflicting results<br />Smaller pediatric “bowls” have been developed, but the ability to avoid allogenic blood has not been consistent<br />Best if blood pools in incision – effective for scoliosis surgery<br />Craniosynostosis has very high allogenic transfusion rate<br />9 mo of age, relatively large blood loss, difficult cell salvage<br /><ul><li>Reducing Allogenic Blood Transfusions during Pediatric Cranial Vault Surgical Procedures: A Prospective Analysis of Blood RecyclingFearon,.PlastReconstrSurg 2004;113:1126–30</li></ul>Avg age 4 years. Avg surgery 196 min. 53% 1º, 47% repeat.<br />60 patients (3 mo to 19 yrs). 5-900 mls blood salvaged. 18 of 60 (30%) received allogenic blood. No complications .<br />05/05/2010<br />
    66. 66. Blood Conservation – Controlled ↓BP <br />Controlled hypotension<br />mABP between 50 and 60 mm Hg<br />impaired oxygen delivery to tissues during hypotension are not as significant in children compared with adults with preexisting atherosclerotic disease of the heart, brain, or kidney<br />Contraindications: significant reduction in the availability of oxygen to the tissues (↓ SaO2, ↓ CO, ↓ Hb); or cardiac, cerebral, or renal disease; and increased intracranial pressure<br />The effect of hypotensiveanesthesia on blood loss and operative time during Le Fort I osteotomies. - J Oral MaxillofacSurg 2000<br />Twenty-three patients were randomized into normotensive or hypotensiveanesthesia. It reduced blood loss and improved the quality of the surgical field. It did not reduce operative time.<br />05/05/2010<br />
    67. 67. Topical agents<br />Fibrin sealant is prepared from two plasma-derived protein fractions:<br />a fibrinogen-rich concentrate<br />a thrombin concentrate<br />formation of a fibrin clot that adheres to the application site and acts as a fluid-tight sealing agent able to stop bleeding<br />product is derived from donor plasma<br />exposed to several viral inactivation steps<br />solvent-detergent<br />Pasteurization<br />vapor-heat treatment<br />nanofiltration<br />05/05/2010<br />
    68. 68. Temperature<br />Neonates and infants at risk of hypothermia<br />immature thermoregulatory mechanism<br />relatively thin layer of subcutaneous brown fat for insulation<br />extensive superficial circulation that facilitates rapid dissipation of heat from the body<br />Hypothermia causes<br />platelet dysfunction<br />clotting factor enzyme dysfunction<br />Abnormal fibrinolytic activity<br />05/05/2010<br />
    69. 69. Pediatric Transfusion – Summary<br />Physiology<br />Transfusion reactions<br />Blood Conservation<br />Multimodal approach<br />High initial hemoglobin and low target hemoglobin decreases need or amount of transfusion<br />Study results have varied – patient population, surgical procedure and anesthetic/conservation technique impact on success of a particular approach<br />05/05/2010<br />