Blood transfusion in pediatric patients and strategies to decrease it: a reevaluation

Abstracts

JUSTIFICATIVA E OBJETIVOS: Muitas medidas e técnicas são utilizadas, nos pacientes adultos, na tentativa de reduzir, ou evitar, tanto a perda sangüínea como a administração de sangue homólogo durante atos cirúrgicos para os quais se esperam grandes perdas na volemia. Enquanto as estratégias para evitar a utilização de sangue homólogo em pacientes adultos são largamente empregadas, nos pacientes pediátricos são negligenciadas. Talvez isso se deva ao fato de que em crianças essas técnicas podem não ser tão úteis quanto nos adultos, além dos problemas técnicos próprios do tamanho dos pacientes. O objetivo dessa revisão foi reavaliar as técnicas para reduzir a necessidade de transfusão de sangue homólogo em adultos e discutir sua utilização em pacientes pediátricos. CONTEÚDO: Através da pesquisa bibliográfica apresentam-se às estratégias mais freqüentes para diminuir, ou mesmo evitar, transfusão de sangue homólogo durante atos cirúrgicos nos quais esperam-se grandes perdas volêmicas. Como todos os métodos conhecidos foram desenvolvidos para pacientes adultos, projeta-se, a partir daí, reavaliando-se esses métodos, técnicas e fármacos, uma linha de ação visando a sua aplicabilidade nos pacientes pediátricos. CONCLUSÕES: Mais uma vez fica patente que as soluções obtidas para adultos não são aplicáveis inteiramente aos pacientes pediátricos. As medidas para reduzir o sangramento intra-operatório e a conseqüente redução na necessidade do emprego de sangue homólogo são eficientes em pacientes adultos, porém são de longe mais invasivas, complicadas e muitas delas ineficientes nos pacientes pediátricos, notadamente naqueles abaixo de dois anos de idade.

ANESTESIA; DROGAS; SANGUE; SANGUE

REVIEW ARTICLE

Blood transfusion in pediatric patients and strategies to decrease it: a reevaluation^*

Transfusión sanguínea en niños y los métodos para evitarla: una reevaluación

Mário José da Conceição, TSA, M.D.

Professor de Anestesiologia, Curso de Medicina, Fundação Universidade Regional de Blumenau, SC

^{Correspondence}

SUMMARY

BACKGROUND AND OBJECTIVES: Several approaches and techniques are used in adult patients to decrease or prevent both blood loss and homologous blood transfusion during surgical procedures where massive blood losses are expected. While these blood-sparing strategies are widely used in adults, they are mostly neglected in children. Perhaps in pediatric patients, these blood-sparing techniques may not be as effective as in adults and technical limitations, as the small size of patients could limit its advantages. In the following review, blood-sparing techniques established for adults are described and their applicability in pediatric patients discussed.

CONTENTS: Blood-sparing strategies developed for adult patients aiming at decreasing or even preventing homologous blood transfusion when massive blood losses are expected, are presented through a bibliographic review. Since all known methods were developed for adult patients, an action line was drawn for the reevaluation of these methods, techniques and drugs to be used in pediatric patients.

CONCLUSIONS: It has become once more clear that solutions for adult patients may not be as effective for pediatric patients. Intraoperative blood-sparing techniques and consequent decrease in the need for homologous blood are effective for adult patients but are by far more invasive, complicated, and some of them ineffective in pediatric patients, especially those under two years of age.

Key Words: ANESTHESIA: Pediatric; BLOOD: hemodilution, transfusion; DRUGS: antifibrinolytics

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: Muchas medidas y técnicas son utilizadas, en pacientes adultos, en la tentativa de reducir, o evitar, tanto la pérdida sanguínea como la administración de sangre homólogo durante actos quirúrgicos para los cuales se esperan grandes perdidas en la volemia. Entretanto, las estrategias para evitar la utilización de sangre homólogo en pacientes adultos son largamente utilizadas, en los pacientes pediátricos son negligenciadas. Quizás eso se deba al hecho de que en niños esas técnicas pueden no ser tan útiles cuanto en los adultos, además de los problemas técnicos propios del tamaño de los pacientes. El objetivo de esa revisión fue reevaluar las técnicas para reducir la necesidad de transfusión de sangre homólogo en adultos y discutir su utilización en pacientes pediátricos.

CONTENIDO: Por medio de la pesquisa bibliográfica se presentan las estrategias más frecuentes para disminuir, o mismo evitar, transfusión de sangre homólogo durante actos quirúrgicos en los cuales se esperan grandes perdidas volémicas. Como todos los métodos conocidos fueron desarrollados para pacientes adultos, se proyecta, a partir de aquí, reevaluandose esos métodos, técnicas y fármacos, una línea de acción mirando su aplicabilidad a los pacientes pediátricos.

CONCLUSIONES: Mas una vez queda patente que las soluciones obtenidas para adultos no son aplicables enteramente a los pacientes pediátricos. Las medidas para reducir el sangramiento intra-operatorio y la consecuente reducción en la necesidad del uso de sangre homólogo son eficientes en pacientes adultos, no obstante son de lejos más invasivas, complicadas y muchas de ellas ineficientes en los pacientes pediátricos, notadamente en aquellos menores de dos años de edad.

INTRODUCTION

Several approaches and techniques are used in adult patients to decrease or prevent both blood loss and homologous blood transfusion during surgical procedures where massive blood losses are expected ^1-3. Most patients are informed about blood transfusion adverse effects, especially after the advent of the risk of contamination by human immunodeficiency virus (HIV). There is also a religious faith-related problem, such as the Witnesses of Jehovah. While these blood-sparing strategies are widely used in adults, they are mostly neglected in children, as it can be seen by the few studies in the literature about the subject. Perhaps in pediatric patients, these blood-sparing techniques may not be as effective as in adults and technical limitations, as the small size of patients could limit its advantages. However, some strategies based on adult patients experiences may be used to decrease or even prevent homologous blood transfusion in some pediatric surgeries where patients have been previously selected and indications were adequately defined. In the following review, blood-sparing techniques established for adults are described and their applicability for pediatric patients is discussed.

PREOPERATIVE AUTO-DONATION

To date, the most widely accepted technique to decrease or prevent the risks of homologous transfusion is preoperative autologous blood donation, followed or not by hemodilution ⁴. If there are sound scientific basis and practical usefulness for adults, this practice has several complicating factors which increase the risk for pediatric patients and may be described as follows:

1. Children may need sedation or anesthesia for donation and for such, inhaled anesthetics might be preferred. Propofol, thiopental and opioids should be avoided because they may trigger adverse events at re-transfusion;

2. Collection bags have to be special and smaller because traditional bags have anticoagulant solutions calculated for large adult volumes, which would be excessive for small pediatric volumes;

3. Problems with venous access may prevent auto-donation in several pediatric patients where there will be problems with adequate needle size for blood collection

   ⁵.

Regardless of these complicating factors, many authors advocate auto-transfusion in children for believing that benefits overcome risks and already mentioned problems. However, due to the complexity of pediatric auto-donation, this should only be indicated for patients above 20 kg and in whom large intraoperative blood volume losses are expected ⁵.

HEMODILUTION

Theoretically, hemodilution in pediatric patients is much easier to be performed than preoperative auto-donation. However, Bryson et al. ⁶ have shown in a recent meta analysis that intraoperative hemodilution has not decreased the need for homologous blood. Still according to the authors, several studies included in the meta analysis have not taken into consideration basic hemodilution principles, such as: initial hematocrit above 35% and minimum tolerated hematocrit below 25%. If these criteria were not considered, removed blood volume would be insufficient to establish a difference as to the need for homologous blood. Most times, these criteria cannot be adopted for children. First, in infants up to 6 month of age, hemodilution is counterindicated due to high fetal hemoglobin concentration. As it is well known, fetal hemoglobin shifts oxyhemglobin curve to the left, limiting tissue oxygen availability. Low hematocrit in this situation may lead to hypoxia and/or tissue ischemia. From 6 months to 1 year of age, there will be the so-called "physiological anemia" again counterindicating very low hematocrit for the same reasons. This way, hemodilution should only be used in children above 1 year of age. However there are few studies in this area to prove the efficacy and discuss potential problems like in adults ⁶.

INTRAOPERATIVE AUTO-TRANSFUSION

Although good results obtained in adult patients with intraoperative auto-transfusions, decreasing losses and the need for homologous blood, such techniques cannot be directly applied to pediatric patients ⁸.

The volume of "lost" blood is almost always too low to be collected although being high for patients' volume. Very often the blood is not even aspired because it has already been absorbed by compresses, surgical drapes of surgeons gloves themselves. Even if compresses are washed with saline, at least 50% of blood volume is lost. For the auto-transfusion machine to adequately operate, a minimum blood volume has to be washed and re-transfused. This volume is approximately 300 mL, which may mean much more than half the volume of a 20-kg patient. Children below this weight certainly will not tolerate 300 ml volume loss without receiving homologous blood ⁹. However, children above 20 kg may tolerate such losses. In these patients, auto-transfusion techniques may be useful. But a different problem should be raised: which is the minimum hematocrit considered "safe" for pediatric patients? Most specialized pediatric anesthesiologists do not allow hematocrit below 30%, especially in patients below 1 year of age and due to the above mentioned reasons, as opposed to adults or children above 30 kg, when values well below this may be used. However, other authors suggest using hematocrit as low as 17% in patients weighing 11 to 23 kg without tissue oxygenation problems ¹⁰. For those authors, higher losses may be tolerated without the need for homologous blood, even by patients below 20 kg ^10,11. There are already auto-transfusion machines for pediatric patients, however with disadvantages still not solved by technology ¹². One of these machines tried to solve the problem with lower capacity of the container for drained blood from the surgical field, allowing equipment operation with 100 mL blood. The problem is that very often the container is not totally filled and one unit of autologous blood with unpredictable quality and hematocrit is administered. Another machine is the continuous auto-transfusion equipment which has eliminated drained blood container. Drained blood is pumped to a separation chamber with capacity of up to 30 mL, while 0.9% saline solution is added for washing. This equipment allows the processing of blood volumes below 100 ml and auto-transfusion in patients below 10 kg.

In cardiac surgeries with cardiopulmonary bypass (CPB), part of the blood remaining in the CPB machine circuit may be re-transfused after filtration, thus decreasing the need for homologous blood ¹³.

A simple solution would be direct re-transfusion of drained blood from the surgical field without washing it. However, the re-transfusion of non washed blood activates the fibrinolytic system with consequent fibrinolysis and increased blood loss ¹⁴.

DESMOPRESSIN

Von Willebrand's factor is critical in the beginning of clot formation, favoring adhesiveness of platelets to injured regions of the vascular endothelium. Desmopressin favors von Willebrand's factor release from endothelial reserves and increases glycoprotein receptors expression on platelets surface. This way, platelets adhesiveness to injured endothelial regions is increased. Normal dose is in general 0.3 µg.kg^-1. Initially, it was used after cardiopulmonary bypass aiming at decreasing bleeding and improving blood coagulation. It has also been used preventively with the same purpose in major surgeries where massive losses are expected ¹⁵. Its use in adults, however, is surrounded by controversies. For pediatric patients, desmopressin also does not add any advantage ¹⁶. Not only it does not interfere with blood loss, but von Willebrand's factor dosage, in controlled studies, was the same in patients receiving or not desmopressin ¹⁷. Pediatric patients do not increase the amount of von Willebrand's factor released from reserves after receiving desmopressin ¹⁷.

it seems that this fact is related to the surgical procedure itself, the stimulation of which releases maximum von Willebrand's factor in a way that there are no extra releases with desmopressin.

ANTIFIBRINOLYTIC AGENTS

Currently, antifibrinolytic agents are used preventively to decrease intraoperative bleeding in patients submitted to surgeries with CPB ^18,19. Some studies have shown significant blood loss decrease when aprotinin or lysin analogs (transexamic and epsilon-amino-caproic acids) are used ²⁰. These studies, however, were performed with adult patients submitted to cardiac surgery with CPB. During CPB, there is in fact an abnormal activation of coagulation and fibrinolysis systems. Coagulation is prevented with heparin however fibrinolysis is neglected. Since during CPB there is plasminogen activator factor stimulation, fibrinolysis is started with increased bleeding. In pediatric patients this seems to work in the opposite direction ²¹. The balance between coagulation and fibrinolysis is more unstable and subject to exogenous stimulation. Hemostasis in pediatric patients is not as efficient as in adults and coagulation and fibrinolysis stimulation is poorer. Before one year of age, plasma concentrations of vitamin K (II, VI and X) dependent coagulation factors, of S and C proteins and of other components (prekallikrein, kininogen, factor XI and Hageman's factor) are lower due to liver immaturity ²². In heart diseases with cyanosis there is an extra problem, typical of these patients as consequence of polycythemia, decreased number of platelets, decreased concentration of coagulation factors V, VII and VIII, and increased fibrinolysis ²¹. When these children are submitted to CPB they also face the disproportion between the size of the CPB machine and their weight, forcing major hemodilution and consequent coagulation factors dilution.

Aprotinin has been used in adults submitted to major surgeries and major blood losses, however with inconclusive results ^23,24. In children, aprotinin and other antifibrinolytic agents which could be useful at the first sight, are controversial. Some studies have shown the inefficacy of aprotinin in pediatric patients submitted to CPB ²⁵, while others, studying patients above 1 year of age with complex heart malformations, have used high aprotinin doses and have observed decreased intraoperative bleeding ²⁶.

Definitely in children below 1 year of age, or in patients operated on just one time, aprotinin, even in high doses, has no benefits justifying its use ²⁵. It has to be mentioned that all these studies have used very different doses. For pediatric cardiac surgery aprotinin dose should be calculated by body surface and not by mg/weight. In addition, aprotinin has to be added to pre-filling (prime) volume of the CPB machine to compensate hemodilution. If plasma dose is below 200 Ul.mL^-1 (0.03 mg.mL^-1) there will be no prevention of coagulation system contact activation. The same reasoning could be applied to other antifibrinolytic agents ^27,28.

MINIMUM TRANSFUSION EXPOSURE

Minimum transfusion exposure (MTE) is an expression created to define homologous blood or its blood products coming from a minimum number of donors. This strategy would be aimed at decreasing immune problems and potentially higher infection risks when patients receive blood from a high number of donors. This technique has been widely implemented in pediatric patients with an adequate transfusion planning due to the low volumes to be transfused. Although the loss is considerable for the patient, transfused volume will be low as compared to 400 ml collection bags. Hence, it will be easy to give blood and blood products from a single donor.

CONTROLLED ARTERIAL HYPOTENSION

Intentional blood pressure decrease has been used for a long time to decrease intraoperative blood losses ^29-31. Several techniques are preconized to decrease blood pressure, such as: continuous infusion of vasodilators (sodium nitroprusside, nitroglycerin) ²⁹, beta-blockers ³⁰, deep inhalational anesthesia levels ^30,31, calcium channel blockers ³² and adenosine. None of them have support for routine use in pediatric patients, unless in older children and adolescents. Deep anesthesia may be dangerous due to myocardial depression which takes time to be reverted in case of poor results. Children below 2 years of age have cardiac output dependent on heart rate. Beta-blockers are counterindicated in this group of patients.

Induced hypotension risks are major ³¹, so risk/benefit ratio should be evaluated in a case-by-case basis. Ages below 2 years are a counterindication, as well as systemic diseases with vital functions involvement. As in the past, experience with techniques and familiarity with drugs to be used are critical success factors ³³.

CONCLUSION

Once more it has been shown that adult solutions are not totally applicable to pediatric patients. Methods to decrease intraoperative bleeding and the need for homologous blood are effective for adults, but are by far more invasive, complicated and several of them are ineffective for pediatric patients, especially those below 2 years of age.

REFERENCES

Apresentado (Submitted) em 14 de abril de 2003

Aceito (Accepted) para publicação em 01 de julho de 2003

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*

Recebido do (

Received from) Serviço de Anestesiologia do Hospital Infantil Joana de Gusmão - CET integrado da SES-SC - Florianópolis

Publication Dates

• Publication in this collection
  29 June 2004
• Date of issue
  Apr 2004

History

• Received
  14 Apr 2003
• Accepted
  01 July 2003