Influence of human albumin on pulmonary function of patients submitted to heart surgery with cardiopulmonary bypass

Abstracts

JUSTIFICATIVA E OBJETIVOS: O emprego de albumina humana em cirurgias cardíacas com circulação extracorpórea (CEC) é controverso, embora seja procedimento utilizado com freqüência. O objetivo deste estudo foi analisar os efeitos do uso da albumina humana sobre a função de troca gasosa pulmonar em pacientes submetidos à cirurgia de revascularização do miocárdio com CEC. MÉTODO: Vinte pacientes foram divididos aleatoriamente em dois grupos, em relação à solução utilizada no perfusato da CEC: no grupo controle (n = 10) utilizou-se diluição total com solução de Ringer com lactato, também utilizada na hidratação intra-operatória. No grupo albumina (n = 10) foram adicionados 20 g de albumina humana ao perfusato da CEC ou como parte da hidratação no período pós-CEC. A relação entre a pressão arterial de oxigênio e sua fração inspirada (PaO2/FiO2), o gradiente alvéolo-arterial de oxigênio (GA-aO2) e o shunt pulmonar foram avaliados após a indução anestésica, ao final da cirurgia e no primeiro e segundo dias de pós-operatório e comparados nos dois grupos através de Análise de Variância para medidas repetidas (p < 0,05). RESULTADOS: Os dois grupos estudados foram comparáveis em relação às características pré-operatórias, tempo de CEC e de cirurgia. Os valores de PaO2/FiO2, GA-aO2 e shunt pulmonar não mostraram diferença estatisticamente significativas entre os grupos. CONCLUSÕES: Este estudo demonstrou que a adição de albumina humana no perfusato da CEC ou como parte da hidratação intra-operatória em cirurgia revascularização do miocárdio com circulação extracorpórea não resultou em benefícios para a função pulmonar. Como a albumina apresenta custo elevado, o seu uso rotineiro não está justificado.

CIRURGIA; CIRURGIA; SISTEMA RESPIRATÓRIO; VOLEMIA

SCIENTIFIC ARTICLE

Influence of human albumin on pulmonary function of patients submitted to heart surgery with cardiopulmonary bypass^*

Influencia del empleo de albúmina humana sobre la función pulmonar de pacientes sometidos a la cirugía cardíaca con circulación extracorpórea

Hugo Leonardo de Moura Luz, M.D.^I; Mara Regina Guerreiro Moreira, M.D.^II; José Otávio Costa Auler Júnior, TSA, M.D.^III; Maria José Carvalho Carmona, TSA, M.D.^IV

^IGraduando em Medicina na FMUSP, Bolsista do Programa Institucional de Bolsas de Iniciação Científica do CNPq, Bolsa PIBIC/CNPq, 2001/2002

^IIAssistente do Serviço de Anestesiologia do Incor HCFMUSP. Mestre em Anestesiologia pela FMUSP

^IIIProfessor Titular da Disciplina de Anestesiologia da FMUSP; Diretor do Serviço de Anestesiologia e Terapia Intensiva Cirúrgica do Instituto do Coração do HC da FMUSP

^IVProfessora Doutora da Disciplina de Anestesiologia da FMUSP; Supervisora do Serviço de Anestesiologia e Terapia Intensiva Cirúrgica do Instituto do Coração do HC da FMUSP

^{Correspondence}

SUMMARY

BACKGROUND AND OBJECTIVES: Human albumin in heart surgeries with cardiopulmonary bypass (CPB) is controversial although being a frequent procedure. This study aimed at evaluating the effects of human albumin on pulmonary gaseous exchange function in patients submitted to myocardial revascularization with CPB.

METHODS: Participated in this study 20 patients randomly distributed in two groups according to CPB perfusate solution: control group (n = 10) - total dilution with lactated Ringer's solution, also used for intraoperative hydration; albumin group (n = 10) - 20 g human albumin were added to CPB perfusate or as part of post-CPB hydration. Oxygen arterial tension and inspired fraction ratio (PaO₂/FiO₂), oxygen alveolar-arterial gradient (GA-aO₂) and pulmonary shunt were evaluated after anesthetic induction, at surgery completion and in the first and second postoperative day and were compared in both groups by Analysis of Variance for repeated measures (p < 0.05).

RESULTS: Both groups were comparable in preoperative characteristics, CPB and surgery duration. PaO₂/FiO₂, GA-aO₂ and pulmonary shunt values were not statistically different between groups.

CONCLUSIONS: Our study has shown that the addition of human albumin to CPB perfusate or as part of intraoperative hydration during myocardial revascularization with cardiopulmonary bypass has not improved pulmonary function. Since albumin is expensive, its routine use is not justified.

Key Words: RESPIRATORY SYSTEM: pulmonary function; SURGERY, Cardiac: cardiopulmonary bypass; VOLEMIA: human albumin

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: La utilización de albúmina humana en cirugías cardíacas con circulación extracorpórea (CEC) es controvertida, aun cuando sea procedimiento utilizado con frecuencia. El objetivo de este estudio fue analizar los efectos del uso de la albúmina humana sobre la función del cambio gaseoso pulmonar en pacientes sometidos a la cirugía de revascularización del miocardio con CEC.

MÉTODO: Veinte pacientes fueron divididos aleatoriamente en dos grupos, en relación a la solución utilizada en el perfusato de la CEC: en el grupo control (n = 10) se utilizó dilución total con solución de Ringer con lactato también utilizada en la hidratación intra-operatória. En el grupo albúmina (n = 10) fueron adicionados 20 g de albúmina humana al perfusato da CEC o como parte de la hidratación en el período pós-CEC. La relación entre la presión arterial de oxígeno y su fracción inspirada (PaO₂/FiO₂), o gradiente alvéolo-arterial de oxígeno (GA-aO₂) y el shunt pulmonar fueron evaluados después de la inducción anestésica, al final de la cirugía y en el primer y segundo día de pós-operatorio y comparados en los dos grupos a través de Análisis de Variancia para medidas repetidas (p < 0,05).

RESULTADOS: Los dos grupos estudiados fueron comparables en relación a las características pré-operatorias, tiempo de CEC y de cirugía. Los valores de PaO₂/FiO₂, GA-aO₂ y shunt pulmonar no mostraron diferencia estadísticamente significativa entre los grupos.

CONCLUSIONES: Este estudio demostró que la adición de albúmina humana en el perfusato de la CEC o como parte de la hidratación intra-operatoria en cirugía revascularización del miocardio con circulación extracorpórea no resultó en beneficios para la función pulmonar. Como la albúmina presenta costo elevado, su uso rutinario no está justificado.

INTRODUCTION

Depending on the oxygenator, cardiopulmonary bypass circuits during heart surgery are filled with approximately 30 mL.kg^-1 or 40% of blood volume (approximately 2000 mL in 70 kg adult), which is called "perfusate". Several solutions have been used for this aim. The addition of colloids to cardiopulmonary bypass perfusate is controversial. Human albumin is the colloid solution most commonly added to CPB circuit perfusate¹ or as part of intraoperative hydration.

It is known that pulmonary function changes in patients submitted to heart surgery with CPB are major causes for morbidity and mortality^2,3 and depend on several factors such as preoperative pulmonary function, surgery type and duration, cardiopulmonary bypass duration, surgical manipulation, number of chest drains and type and volume of intraoperative fluids^4,5.

CPB with crystalloids as perfusate changes pulmonary intra and extravascular fluid volumes, as well as pulmonary exchanges and several mechanisms may be involved^6,7. Several studies have also shown that colloids in general determine increased plasma colloidosmotic pressure^5,8-10. Albumin as perfusate component could attenuate pulmonary function changes observed during heart surgeries with CPB. Some studies^11-13 point to most adequate colloidosmotic pressure maintenance with colloids, in addition to decreased fluid loss to the extravascular space during cardiopulmonary bypass.

This study aimed at comparing parameters indicating pulmonary gaseous exchanges in patients submitted to myocardial revascularization with albumin in CPB perfusate or as part of post-CPB hydration, to patients in whom total dilution with lactated Ringer's alone has been used.

METHODS

The study was approved by the Scientific Committee, Instituto do Coração and by the Medical Ethics Committee, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo and has evaluated 20 patients submitted to heart surgery with cardiopulmonary bypass in the period October 2001 - July 2002.

Participated in this study adult patients of both genders, aged 20 to 60 years, indicated to elective myocardial revascularization. Exclusion criteria were renal failure, liver and lung diseases, and left ventricle ejection fraction below 40%.

Patients were premedicated with oral 0.1 to 0.2 mg.kg^-1 midazolam 30 minutes before surgery, until the maximum dose of 15 mg. Patients were monitored in the operating room with continuous ECG with 5 electrodes to evaluate D_II and V5 leads, and pulse oximetry, in addition to peripheral venoclysis with 16G catheter. Invasive blood pressure monitoring consisted of radial artery puncture with 20G catheter. After pre-oxygenation, general anesthesia was induced with fentanyl (20 to 30 µg.kg^-1) and midazolam (0.1 to 0.3 mg.kg^-1) followed by muscle relaxation with pancuronium (0.1 to 0.2 mg.kg^-1). Manual ventilation under mask was applied followed by tracheal intubation with adequate tube and mechanically controlled ventilation was then started (KT-676 ventilator, São Paulo, Brazil) with tidal volume of 8 mL.kg^-1, respiratory rate of 12 inspirations per minute, I:E ratio = 1:2 and FiO₂ = 0.6 (oxygen and compressed air). P_ETCO₂ started to be monitored after tracheal intubation by side stream method (Dixtal - São Paulo, Brazil), in addition to nasopharyngeal temperature and diuresis. Anesthesia was maintained with fentanyl, midazolam and pancuronium boli doses associated to variable concentrations of inhalational isoflurane.

Hemodynamic monitoring was complemented by 7F Swan-Ganz catheter insertion (Pulmonary Artery Catheter, Baxter Clinical Care, California, USA) through right internal jugular vein puncture to measure pulmonary artery pressure (PAP), systolic, diastolic and mean blood pressure, right atrium pressure (RAP), pulmonary wedge pressure (PWP), cardiac output (CO) measured by thermodilution. Three subsequent measurements were taken and their mean value was used.

Arterial and mixed venous blood samples were collected to evaluate hemoglobin concentration (Hb), blood gases and acid-base balance; with oxygen tension in arterial (PaO₂) and venous (PvO₂) blood, from arterial (SaO₂) and mixed venous (SvO₂) oxygen saturation, arterial (PaCO₂) and venous (PvCO₂) CO₂ tensions; arterial (pHa) and venous (pHv) pH, arterial (Bic art) and venous (Bicven) bicarbonate, and base excess arterial (BEa) and venous (BEv).

Tissue oxygenation parameters, ratio between oxygen arterial tension and oxygen inspired fraction, oxygen alveolar-arterial gradient and pulmonary shunt were calculated for the studied periods as from previously obtained data and with adequate formulas.

Oxygen arterial tension/oxygen inspired fraction (PaO₂/FiO₂, Normal Value (NV) above 200), being:

PaO₂: Oxygen arterial tension;

FiO₂: Oxygen inspired fraction.

Oxygen alveolar-arterial gradient (GA-aO₂), calculated by the following formula:

GA-aO₂= PAO₂ - PaO₂

Being:

PAO₂ =oxygen alveolar tension;

PaO₂ = oxygen arterial tension.

Oxygen alveolar pressure (PAO₂) is calculated by the formula:

PAO₂ = {(PB - PH₂O) x FiO₂} - PaCO₂

Being:

PB = barometric tension;

PH₂O = water vapor pressure;

FiO₂ = oxygen inspired fraction;

PaCO₂ = arterial blood CO₂ tension.

Normal 21% FiO₂ values: 10 to 15 mmHg.

Normal 100% FiO₂ values: 10 to 65 mmHg.

Pulmonary shunt (normal values 3% to 5%), calculated by the following formular:

Shunt = (CcO₂ - CaO₂)/(CcO₂ - CvO₂)

Being:

CcO₂ = capillary oxygen content;

CaO₂ = arterial oxygen content;

CvO₂ = venous oxygen content.

Capillary oxygen content is calculated by the following formula:

CcO₂ = (Hb x 1.34) + (PAO₂ x 0.0031)

Being:

Hb = hemoglobin;

PAO₂ = alveolar oxygen tension.

Alveolar oxygen tension (PAO₂) is calculated by the formula:

PAO₂ = {(PB - PH₂O) x FiO₂} - PaCO₂

Being:

PB = barometric pressure;

PH₂O = water vapor pressure;

FiO₂ = oxygen inspired fraction;

PaCO₂ = arterial blood CO₂ tension.

Arterial oxygen content (CaO₂, NV = 17 to 20 mL/dL) was calculated by the following formula:

CaO₂ = (1.34 x Hb x SaO₂/100) + (PaO₂ x 0.0031)

Being:

Hb = hemoglobin;

SaO₂ = arterial oxygen saturation;

PaO₂ = arterial blood oxygen tension.

Venous oxygen content (CvO₂, NV = 12 to 15 mL/dL), was calculated by the following formula:

CvO₂ = (1.34 xHb x SvO₂/100) + (PvO₂ x 0.0031)

Being:

Hb = hemoglobin;

SvO₂ = venous oxygen saturation;

PvO₂ = venous oxygen pressure.

Oxygen arterial-venous difference (DavO₂, NV = 4 to 5 mL/dL), DavO₂=CaO₂-CvO₂.

All patients were submitted to cardiopulmonary bypass with membrane oxygenator (Braile, Brasil) with non-pulsatile flow and under moderate hypothermia (minimum nasopharyngeal temperature of 32 ºC). At cardiopulmonary bypass completion, vasodilators and/or inotropics were introduced in variable doses according to clinical indication.

Patients were divided in two groups according to intraoperative hydration: lactated Ringer's group (LR) using lactated Ringer's as perfusate and for intraoperative hydration, and Albumin group (A), with albumin in CPB perfusate or as part of intraoperative hydration. Study involved pre and postoperative periods with evaluations in the following moments:

M₁ - After anesthetic induction;

M₂ - At surgery completion;

M₃ - Immediate postoperative period (IPO);

M₄ - 1^st postoperative day (1^st PO);

M₅ - 2^nd postoperative day (2^nd PO).

Analysis of Variance of double factor was used for statistical analysis considering significant level of 5%.

RESULTS

From 20 patients, 4 were females being 1 from group A and 3 from group LR. Age has varied 41 to 78 years (mean 60.2 ± 11.2 years). Data on age, weight, height and body surface for lactated Ringer's (LR) and Albumin (A) groups are shown in table I. There were no statistical differences between groups.

Brazilian Journal of Anesthesiology, 2004; 54: 4: 532 - 541

Influence of human albumin on pulmonary function of patients submitted to

heart surgery with cardiopulmonary bypass

Hugo Leonardo de Moura Luz; Mara Regina Guerreiro Moreira;

José Otávio Costa Auler Júnior; Maria José Carvalho Carmona

Mean surgery and cardiopulmonary bypass duration, diuresis volume during CPB, mean flow and minimum temperature during cardiopulmonary bypass are shown in table II. Lactated Ringer's solution volume used as prime for group LR was 1915 ± 445 and for group A was 1730 ± 411, without statistical difference. Each group A patient has received 20 g human albumin (100 mL at 20%).

Brazilian Journal of Anesthesiology, 2004; 54: 4: 532 - 541

Influence of human albumin on pulmonary function of patients submitted to

heart surgery with cardiopulmonary bypass

Hugo Leonardo de Moura Luz; Mara Regina Guerreiro Moreira;

José Otávio Costa Auler Júnior; Maria José Carvalho Carmona

Hemoglobin and blood oxygenation values are shown in table III.

Brazilian Journal of Anesthesiology, 2004; 54: 4: 532 - 541

Influence of human albumin on pulmonary function of patients submitted to

heart surgery with cardiopulmonary bypass

Hugo Leonardo de Moura Luz; Mara Regina Guerreiro Moreira;

José Otávio Costa Auler Júnior; Maria José Carvalho Carmona

Hydric balance during surgery, in the immediate postoperative period and during 1^st postoperative day is shown in figure 1.

Brazilian Journal of Anesthesiology, 2004; 54: 4: 532 - 541

Influence of human albumin on pulmonary function of patients submitted to

heart surgery with cardiopulmonary bypass

Hugo Leonardo de Moura Luz; Mara Regina Guerreiro Moreira;

José Otávio Costa Auler Júnior; Maria José Carvalho Carmona

Pulmonary function parameters were evaluated in proposed moments and their results are summarized in figure 2, 3 and 4 and table IV. There has been significant variation in PaO₂/FiO₂ ratio along time (p < 0.0001), but there have been no differences between groups (p = 0.2483). The same behavior was observed for GA-aO₂ and pulmonary shunt with time effect for those variables (p < 0.0001 for GA-aO₂ and p = 0.0007 for pulmonary shunt), without differences between groups (p = 0.675 for GA-aO₂ and p = 0.1798 for pulmonary shunt).

Brazilian Journal of Anesthesiology, 2004; 54: 4: 532 - 541

Influence of human albumin on pulmonary function of patients submitted to

heart surgery with cardiopulmonary bypass

Hugo Leonardo de Moura Luz; Mara Regina Guerreiro Moreira;

José Otávio Costa Auler Júnior; Maria José Carvalho Carmona

Brazilian Journal of Anesthesiology, 2004; 54: 4: 532 - 541

Influence of human albumin on pulmonary function of patients submitted to

heart surgery with cardiopulmonary bypass

Hugo Leonardo de Moura Luz; Mara Regina Guerreiro Moreira;

José Otávio Costa Auler Júnior; Maria José Carvalho Carmona

Brazilian Journal of Anesthesiology, 2004; 54: 4: 532 - 541

Influence of human albumin on pulmonary function of patients submitted to

heart surgery with cardiopulmonary bypass

Hugo Leonardo de Moura Luz; Mara Regina Guerreiro Moreira;

José Otávio Costa Auler Júnior; Maria José Carvalho Carmona

Brazilian Journal of Anesthesiology, 2004; 54: 4: 532 - 541

Influence of human albumin on pulmonary function of patients submitted to

heart surgery with cardiopulmonary bypass

Hugo Leonardo de Moura Luz; Mara Regina Guerreiro Moreira;

José Otávio Costa Auler Júnior; Maria José Carvalho Carmona

DISCUSSION

Data on the literature about pulmonary function changes with colloids are controversial. Significantly higher PaO₂/FiO₂ ratio values have been shown in patients submitted to hypovolemic shock resuscitation with the addition of albumin as compared to cases in which lactated Ringer's solution has been used¹⁴. In a different study¹⁰ with patients submitted to heart surgery with CPB, a lower increase in postoperative pulmonary extravascular water has been observed with albumin as compared to cases with lactated Ringer's. Sade et al.¹⁵ have observed significantly higher pulmonary shunt and pulmonary fluid build-up when only crystalloids were used as perfusate, as compared to a group with the additional use of colloids.

Our study has not shown statistically significant changes between groups in pulmonary gaseous exchange parameters. There has been variation along time for such variables, however similar for both groups. In addition to surgery-related factors, inflammatory response determined by CPB in circulation and pulmonary parenchyma itself^6,17 would be involved in the pathogenesis of postoperative pulmonary dysfunction, which could explain variation along time of observed pulmonary function parameters. The addition of albumin to perfusate could also be theoretically justified for promoting delay in circulating fibrinogen adsorption and decreasing platelet activation during CPB. However, this fact has been randomly studied by Boks et al. and no oxygenators resistance to CPB flow decrease or decreased platelet activation has been observed with the addition of albumin to perfusate, as compared to crystalloid solution alone¹⁸. This shows that the addition of albumin for normal individuals is still questionable, although decreasing blood viscosity and helping maintaining better colloidosmotic pressure during CPB¹⁹. On the other hand, the existence of a significant preoperative hypoalbuminemia on postoperative heart surgery morbidity and mortality²⁰ would justify its use in selected cases.

This study has shown that human albumin added to CPB perfusate or as part of intraoperative hydration in elective myocardial revascularization surgeries with CPB has not resulted in significant changes in pulmonary gaseous exchanges. This fact suggests that there are no benefits in the additional use of this colloid in normal patients submitted to heart surgery, in terms of pulmonary function. Since albumin is expensive and may place patients at risk of adverse reactions²¹ its routine use is not justified. Albumine in CPB perfusate for elderly, children or patients with preoperative cachexia is still to be investigated.

REFERENCES

Submitted for publication July 21, 2003

Accepted for publication December 15, 2003

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*

Received from Serviço de Anestesiologia e Divisão de Cirurgia do Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC - FMUSP), SP

Publication Dates

• Publication in this collection
  22 Sept 2004
• Date of issue
  Aug 2004

History

• Accepted
  15 Dec 2003
• Received
  21 July 2003