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On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.58 no.5 Campinas Sept./Oct. 2008
Complications and prognosis of intraoperative blood transfusion*
Transfusión sanguínea en el intraoperatorio, complicaciones y pronóstico
João Manoel Silva JuniorI; Thiago Abreu CezarioII; Diogo O. ToledoIII; Danielle Dourado MagalhãesIV; Marco Aurélio Cícero PintoIV; Luiz Gustavo F. Victoria, TSAV
Coordenador da Unidade Pós-Operatória do HSPE
IIResidente do HSPE
IIIMédico Assistente do Serviço de Terapia Intensiva do HSPE
IVME3 do CET/SBA HSPE
VAnestesiologista; Supervisor da Residência do Serviço de Anestesia do HSPE
OBJECTIVES: Intraoperative blood transfusions are associated with an increase
in postoperative complications and hospital costs. Thus, this study evaluated
the characteristics, complications, and probable risk factors for death in surgical
patients who needed intraoperative blood transfusions.
METHODS: This is a prospective study that spanned a one-year period, undertaken at the surgical suite of a tertiary hospital. Patients older than 18 years who needed intraoperative blood transfusions were included in this study. Jehovah witnesses, patients with a history of prior blood transfusions, coronary failure, and acute brain lesions were excluded.
RESULTS: Eighty patients with mean age of 68.4 ± 14.1 years participated in the study. Most patients were ASA II, representing 69.6% of the study group; APACHE and POSSUM scores were 13.6 ± 4.4 and 37.5 ± 11.4, respectively. Mean hemoglobin at the time of transfusion was 8.2 ±1.8 g.dL-1 and 19% of the patients had hemoglobin levels higher than 10 g.dL-1. Patients received an average of 2.2 ± 0.9 IU of packed red blood cells. Hospital mortality was 26.3%. Post-transfusion complications totaled 57.5% of the cases in the postoperative period, and most of them were due to infections. In the logistic regression, independent factors for death included APACHE II (OR = 1.34; 95% CI 1.102-1.622), POSSUM (OR = 1.08; 95% CI 1.008-1.150) and the number of packed red blood cells received (OR = 2.22; 95% CI 1.100-4.463). Thus, the higher the number of transfusions, the greater the incidence of complications and mortality.
CONCLUSIONS: Hemoglobin level, and the number of packed red blood cells used were elevated when compared with studies that suggest restrictive strategies. This sample presented a high incidence of complications, especially infections, and complications. APACHE II and POSSUM scores and the number of transfusions were independent risk factors for a worse postoperative prognosis.
Key Words: BLOOD: intraoperative, transfusion; COMPLICATIONS: blood transfusion.
Y OBJETIVOS: Transfusiones sanguíneas en el intraoperatorio están
asociadas al aumento de complicaciones en el postoperatorio y costes hospitalarios.
Por tanto, este estudio evaluó las características, complicaciones
y los posibles factores de riesgos para muerte en pacientes quirúrgicos
que necesitaron transfusiones sanguíneas en el intraoperatorio.
MÉTODO: Categoría prospectiva, durante el período de un año, en el centro quirúrgico de hospital terciario. Se incluyeron pacientes con edad por encima de los 18 años que necesitaron transfusiones sanguíneas en el intraoperatorio. Testigos de Jeová, pacientes que recibieron transfusiones previas, fracaso coronario y lesión encefálica aguda quedaron excluidos del estudio.
RESULTADOS: El estudio involucró a 80 pacientes, con una edad promedio entre los 68,4 ± 14,1 años. Los pacientes ASA II eran prevalecientes con 69,6% de los casos, las puntuaciones APACHE II y POSSUM fueron, como promedio respectivamente de 13,6 ± 4,4 y 37,5 ± 11,4. La hemoglobina promedio al momento de la transfusión era de 8,2 ± 1,8 g.dL-1 y un 19% de los pacientes tuvieron hemoglobina por encima de 10 g.dL-1. Los pacientes recibieron como promedio 2,2 ± 0,9 UI de concentrados de hematíes. La mortalidad hospitalaria fue de un 26,3%. Las complicaciones postransfusiones totalizaron un 57,5% de los casos en el postoperatorio y la más frecuente fue la infección. Fueron factores independientes de muerte en la regresión logística las puntuaciones APACHE II (OR = 1,34; IC 95% 1,102-1,622), POSSUM (OR = 1,08; IC 95% 1,008 - 1,150) y número de unidades de concentrados de hematíes recibidos (OR = 2,22; IC 95% 1,100 - 4,463). Mientras mayor es el número de transfusiones sanguíneas, mayores son las incidencias de las complicaciones y de la mortalidad.
CONCLUSIONES: El valor de la hemoglobina y el número de unidades de concentrados de hematíes utilizados fueron elevados comparados con los estudios que preconizan estrategias restrictivas. Fue encontrada en esa muestra una alta incidencia de complicaciones, principalmente infecciones, y una elevada mortalidad. Los puntajes APACHE II, POSSUM y mayor número de transfusiones fueron factores de riesgos independientes de un peor pronóstico en el postoperatorio.
In the United States, in 1986, almost 12.2 million units of red blood packed cells were transfused, and currently more than 14 million units of blood are administered each year, two thirds of which are administered in the perioperative period1,2. Thus, considerable evidence suggests that blood transfusions increase the risk of complications and death3,4, especially in surgical patients5,6.
Blood transfusion has a fundamental role in the treatment of severe anemia in surgical patients. Anemia can lead to an increase in morbidity and mortality associated with generalized tissue hypoxia. On the other hand, the treatment with blood transfusion is not devoid of adverse effects.
Patients who received blood transfusions have the higher mortality rate in the intensive care unit (ICU) and during hospitalization, greater incidence of multiple organ failure, and increased length of stay in the ICU7,8. Besides, blood transfusions are associated with nosocomial infections and this association is directly related to the number of units transfused (the higher the number of units transfused, the higher the incidence of nosocomial infections) 9.
Herbert et al. undertook a large, randomized, multi-center study in an attempt to define the best treatment strategy of anemia in patients with severe disorders that would bring about more benefits and less risks. The authors demonstrated that a restrictive transfusion strategy (transfusion with hemoglobin levels below 7.0 g.dL-1) is probably more effective than a liberal strategy (transfusions with hemoglobin levels below 10.0 g.dL-1). Based on those results, currently blood transfusions are recommended to treat anemia when serum hemoglobin concentrations are below 7.0 g.dL-1 to maintain hemoglobin levels between 7.0 and 9.0 g.dL-1 10.
Recent data have demonstrated that the changes in the policy of blood transfusion are subtle. Some studies demonstrated that mean hemoglobin levels of 8.4 g.dL-1 were a trigger for blood transfusions, and 30% of them were done with hemoglobin levels above 9.0 g.dL-1.
However, there are very few prospective clinical studies with surgical patients that evaluate the real need of intraoperative blood transfusions. In this context, the practical evaluation of blood transfusions in surgical patients is relevant, besides considering possible complications associated with this procedure, which is so common in modern medical practice.
Thus, the objective of this study was to evaluate the current practice of blood transfusions, verifying its characteristics, associated complications, and risk factors of death in surgical patients who need intraoperative blood transfusions.
After approval by the Ethics Commission of the hospital, this study was conducted in the operating room of a tertiary hospital.
Consecutive patients undergoing surgeries who needed intraoperative blood transfusions from November 1st, 2006 to November 1st, 2007 participated in this study.
All patients were 18 years or older. Jehovah witnesses, patients with acute cerebral ischemia or intracranial hypertension, undergoing cardiac surgeries or with acute coronary insufficiency, with a history of recent blood transfusion (less than 2 weeks), and those who refused to participate were not included in this study.
To standardize the data, the worst physiological and laboratorial levels 24 hours before the surgery were used to determine APACHE II12, SOFA13, MODS14, and POSSUM15 scores. Those indexes were used to determine the severity of the patients' conditions, as well as the ASA (American Society of Anesthesiologists) classification16.
APACHE II (Acute Physiology and Chronic Health Evaluation) is a two-part score: the physiological score with 12 parameters, which represents the current compromise of the disease and assessment of the patient's health condition before admission to the hospital that indicates pre-morbid conditions. SOFA (Sequential Organ Failure Assessment) and MODS (Multiple Organ Dysfunction Score) scores added information related to organ dysfunction, such as cerebral, respiratory, cardiac, hepatic, renal, and coagulation. The POSSUM (Physiological and Operative Severity Score in the enUmeration of Mortality and morbidity) score, developed to evaluate the severity of the conditions of surgical patients, which uses physiological parameters prior to the surgery, intraoperative parameters, and of the immediate postoperative period.
Besides, hemoglobin levels 24 hours before the surgery, immediately before the transfusion, and after the procedure were considered. The researchers did not have any influence in the treatment of the patients.
Patients were followed-up until the end of hospitalization, determining whether they developed organ failure, such as shock (need of vasoactive drugs for more than one hour), acute renal failure (ARF), acute respiratory distress syndrome (ARDS), changes in cognition and behavior, infections, tissue hypoperfusion, the presence of fistulae in the gastrointestinal tract, and whether the patient was discharged from the hospital or evolved to death.
The markers of tissue hypoperfusion used included arterial levels of lactate, base excess, central venous saturation, urine output, and the difference between the partial venous and arterial pressure of CO2. Whenever two of those markers showed changes, the diagnosis of tissue hypoperfusion was made. The levels of change of the different parameters were: arterial lactate greater than 2 mmol.L-1 17, base excess below -4 mEq/L-1 18, venous oxygen saturation below 70% 19, urine output below 0.5 mL.kg-1.h-1 20, and a difference between arterial and venous pCO2 greater than 7 mmHg21.
The data were inserted in an electronic data bank (Excell - Microsoft) for posterior analysis by a statistical software (SPSS 13.0).
Initially, the demographic, clinical, and physiological characteristics of the patients were described. For the description of the categorical variables, frequencies and percentages were calculated. Quantitative variables were described as a function of the central tendency and dispersion.
Patients who received blood transfusions were divided in survivors (Group 1) and non-survivors (Group 2). The Chi-square test was used for the categorical variables and the Student t test was used for the continuous variables. Bicaudal statistical tests were used and the level of significance used was 0.05.
The logistic regression used through a stepwise analysis was aimed at identifying independent risk factors and to control the effects of the different confounding variables (mutually adjusted variables). Variables that showed a probability of significance (p) less than 0.2 in the univariate analysis among survivors and non-survivors were considered candidates for the multiple regression analysis. Odds ratio (OR) and their respective 95% confidence intervals were estimated by logistic regression.
From November 1st, 2006 to November 1st, 2007, 80 patients, 37 males and 43 females, mean age of 68.4 years, were included in this study. Twenty-one patients were excluded according to the criteria established. Elective surgeries were more frequent (81.3%), abdominal surgeries were prevalent with an incidence of 43.8%, and general anesthesia with neuroaxis blockade were used more often (48.1%) followed by general combined anesthesia (46.8%) (Table I).
At the time of the blood transfusion, mean hemoglobin and hematocrit levels were 8.2 ± 1.8 g.dL-1 and 24.3 ± 5.3%, respectively. The incidence of blood transfusion was higher in patients with pre-transfusion hemoglobin levels between 8 and 9 g.dL-1 (Table II) (Figure 1).
Postoperative serum hemoglobin levels decreased when compared to preoperative levels (Figure 2).
Postoperative complications affected 57.5% of the patients, the most frequent occurred up to 28 days after the blood transfusion, and included infections (36.3%), changes in the markers of tissue hypoperfusion (30.0%), shock (22.5%), ARF (12.5%), cognitive changes (11.33%), fistulas of the digestive tract (6.3%), and ARDS (5.0%) (Figure 3).
In the univariate analysis of the different parameters there were statistically significant differences between non-survivors and survivors, as follows: age (77.3 ± 9.9 years in non-survivors versus 65.3 ± 14.2 in the survivors, p = 0.001), APACHE II scores (16.7 ± 5.5 in non-survivors versus 12.5 ± 3.2 in survivors, p < 0.001), POSSUM scores (46.1 ± 11.1 in non-survivors versus 34.4 ± 9.9 in survivors, p < 0.001), ASA III and IV (42.9 in non-survivors versus 15.5% in survivors, p = 0.01), emergency surgeries (47.6% in non-survivors versus 8.5% in survivors, p < 0.001), basal hemoglobin levels (11.6 ± 1.6 g.dL-1 in non-survivors versus 12.4 ± 1.5 g.dL-1 in survivors, p = 0.05), and heart rate at the time of transfusion (85.8 ±17.3 bpm in non-survivors versus 77.8 ± 14.5 bpm in survivors, p = 0.04) (Table III).
However, all variables that showed p < 0.2 in the univariate analysis underwent logistic regression in an attempt to control the confounding effects (mutually adjusted variables). APACHE II scores (OR = 1.34 95% CI 1.102-1.622), POSSUM scores (OR = 1.08, 95% CI 1.008-1.150), and the number of units of packed red blood cells transfused (OR = 2.22 95% CI 1.100-4.463) were considered independent risk factors for death in the regression analysis (Table IV).
Therefore, the number of units of blood transfused was directly proportional to the incidence of complications and mortality, i.e., the greater the number of units transfused intraoperatively, the higher the chances of complications and death in the postoperative period (Figures 4 and 5).
Several studies have demonstrated that the restrictive strategy of blood transfusion is safe and effective; however, similar to other studies11, this study demonstrated that the level of hemoglobin that triggered blood transfusion was elevated, and most patients received transfusions when their hemoglobin levels were between 8 and 9 g.dL-1, and a considerable number of patients who received blood transfusions with a hemoglobin level greater than 10 g.dL-1. Besides, a mean of 2.2 units of blood were transfused.
Thus, the high mortality (26%) observed, despite the number of patients with a low risk of death, in which most were classified as ASA II and with an APACHE II score around 13, could be related to the decision to transfuse large quantities of blood in the presence of elevated hemoglobin levels. Besides, it was observed a high incidence of postoperative complications (57.5%), with a significant incidence of infections.
Currently, blood transfusions are considered safe. However, patients continue to develop complications associated with blood transfusions. The immediate improvement of oxygen delivery is the expected benefit of this procedure and, therefore, prevents cellular lesions, but it is difficult to demonstrate those benefits on clinical grounds.
Complications secondary to blood transfusions can be divided in infectious and non-infectious. Non-infectious complications include those related with immune modulation that can increase the inherent risk of infections, as well as acute pulmonary lesions, and other types of human errors, such as the mistaken identification of the blood type, which can cause severe hemolytic reactions22.
The pulmonary lesion related with blood transfusions is one of the most severe complications among the non-infectious complications. Its incidence is estimated to be approximately 1 to 5,000 transfusions22. The incidence of ARDS in this study was small, but considerable for the size of the study population, which could be related to the elevated number of blood transfusions.
Additionally, in the present study, both pre- and postoperative hemoglobin levels were not capable of affecting the prognosis of the patients. Therefore, just the hemoglobin level seems to be insufficient to make a decision to transfuse blood.
Serum hemoglobin levels are easily obtainable and, in fact, it was used for several years as a guide to initiate blood transfusions; however, optimal hemoglobin levels vary considerable among patients, and include several factors, such as age, preexisting chronic diseases (coronary heart disease), the current diagnosis, and the underline cause of anemia.
The simple use of a minimal level of hemoglobin below which every patient should be transfused and specific levels for specific groups of patients are also inflexible.
Current recommendations support hemoglobin levels around 7 g.dL-1 as indicative of blood transfusions23. Besides, studies in human volunteers with isovolumetric hemodilution demonstrated that hemoglobin levels < 5.0 g.dL-1 did not lead to anaerobic metabolism. Studies in patients who were Jehovah witnesses demonstrated that survival is possible with even lower levels of hemoglobin. The case of a patient whose hemoglobin level dropped to 1.8 g.dL-1 and did not demonstrate significant complications, with a good evolution at the hospital, was reported25; however, extrapolating this result is very risky to daily medical practice.
The continuous debate between the risks and benefits of blood transfusions rise doubts regarding the profile of the patient who really should received packed red blood cells, and the individual evaluation of each patient and the degree of anemia that he/she can tolerate are more important.
However, it should be known how such patients should be evaluated in order to decide whether to administer packed red blood cells. Thus, clinical exams, along with the data regarding the diagnosis and comorbidities, can help determine the need of blood transfusions.
In the population of the present study, two scores showed a higher degree of importance in the evaluation of patients, namely APACHE II12 and POSSUM15, and several studies have demonstrated that they are important prognostic evaluators, being better than the ASA classification, SOFA or MODS score according to the logistic regression of the present study, increasing the risk of death with higher scores. However, those scores involve several clinical and physiological parameters, decreasing the routine use in the evaluation of surgical patients. APACHE II scores have been widely used on the admission of patients to the intensive care unit, and POSSUM scores have been recently validated for use in surgical patients; thus, it was demonstrated that those scores were important in the evaluation of the present cohort.
On the other hand, determining the number of blood units that should be administered seems to be important in the evolution of surgical patients. A important study4 with intensive care patients demonstrated that the number of transfusions had a direct correlation with the incidence of infections, which is similar to the results of the present study, since the higher number of units of blood transfused increased the incidence of postoperative complications and, consequently, the mortality, and in this study the risk of death of an additional unit of blood was 2.2.
The decision to transfuse and the number of units transfused should be economical and precise. Patients who need intraoperative blood transfusions, regardless of the type of surgery, should be carefully evaluated and are patients with increased postoperative risks. Strategies to prevent the loss of blood26,27 and to increase the production of red blood cells could also be important in the management of surgical patients.
Although this study demonstrated some issues regarding the practice of intraoperative blood transfusions, one should consider that this was not a multicenter study and the size of the study population was small, indicating the need of further studies to confirm our results.
Under the conditions of the present study, it was possible to conclude that anemia was common in surgical patients and resulted in several instances of blood transfusions; however, there is not enough evidence that blood transfusions are beneficial in surgical patients, according to the observed in this prospective cohort.
Despite the large number of publications regarding the restrictive strategy of blood transfusions, higher hemoglobin levels and number of units of blood transfused were observed in the present study. Elevated APACHE II and POSSUM scores and the higher number of units of blood transfused were independent risk factors that determined a worse postoperative prognosis in this population.
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Correspondence to: Submitted em 27
de maio de 2008 *
Received from CET/SBA Hospital Servidor Publico Estadual (HSPE), São
Dr. João Manoel Silva Jr.
CET Hospital Servidor Publico Estadual de São Paulo
Rua Pedro de Toledo, 1.800/6º andar - Vila Clementino
04039-901 São Paulo, SP
Accepted para publicação em 9 de junho de 2008
Submitted em 27
de maio de 2008
* Received from CET/SBA Hospital Servidor Publico Estadual (HSPE), São Paulo, SP