Hypoxemia after myocardial revascularization: analysis of risk factors

Abstracts

JUSTIFICATIVA E OBJETIVOS: Hipoxemia grave é uma complicação freqüente no pós-operatório imediato de revascularização do miocárdio (RM), promovendo aumento da duração da ventilação mecânica, da incidência de infecções pulmonares, dos custos e da mortalidade. O objetivo desse estudo foi identificar fatores preditivos de hipoxemia grave em pacientes submetidos à RM. MÉTODO: Foram estudados 481 pacientes adultos submetidos à RM eletiva entre outubro de 2003 e março de 2004. Considerou-se hipoxemia grave uma relação PaO2/FiO2 < 150 na admissão à UTI. A análise estatística foi realizada por meio de teste de Qui-quadrado, t de Student ou Wilcoxon, seguida de análise multivariada por meio de regressão logística (RL) para variáveis com valor p < 0,25 na análise univariada. Considerou-se valor de p > 0,2 para exclusão da variável do modelo de RL e p < 0,1 como sendo significativo. RESULTADOS: O tempo para extubação dos pacientes com hipoxemia grave foi maior que nos outros pacientes (p < 0,001). Na análise multivariada, as variáveis idade (p = 0,081), peso (p = 0,001), necessidade de CEC prolongada (p = 0,033) e disfunção ventricular esquerda (p = 0,082) foram identificadas como preditores independentes para hipoxemia grave. CONCLUSÕES: Pacientes com idade e peso elevados, disfunção ventricular esquerda e necessidade de CEC apresentaram risco aumentado para hipoxemia grave após RM. Nesses pacientes, o uso de estratégias ventilatórias perioperatória com pressões positivas expiratórias mais elevadas e manobra de recrutamento alveolar devem ser consideradas tendo como objetivo a prevenção da disfunção pulmonar pós-operatória.

CIRURGIA, Cardíaca; COMPLICAÇÕES: hipoxemia; RISCO

SCIENTIFIC ARTICLE

Hypoxemia after myocardial revascularization: analysis of risk factors

Hipoxemia después de la revascularización miocárdica: análisis de los factores de riesgo

Tais Felix Szeles^I; Eduardo Muracca Yoshinaga^II; Wellington Alencar^II; Marcio Brudniewski^II; Flávio Silva Ferreira^III; José Otavio Costa Auler Jr, TSA^IV; Maria José Carvalho Carmona, TSA^V; Luiz Marcelo Sá Malbouisson, TSA^VI

^IM₃ (2006) do CET/SBA do HC-FMUSP

^IIGraduando em Medicina pela FMUSP (Bolsista do Programa de Iniciação Científica – FAPESP)

^IIIMédico Assistente da Disciplina de Anestesiologia do HC-FMUSP

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

^VProfessora Associada da Disciplina de Anestesiologia da FMUSP; Diretora da Divisão de Anestesiologia do Instituto Central do HC-FMUSP

^VIDoutor em Ciências pela USP; Especialista em Terapia Intensiva – AMIB; Coordenador Médico da Unidade de Terapia Intensiva Cirúrgica e Recuperação Pós-Anestésica da Disciplina de Anestesiologia – HC-FMUSP

^{Correspondence to}

SUMMARY

BACKGROUND AND OBJECTIVES: Severe hypoxemia is complication frequently seen in the immediate postoperative period of myocardial revascularization (MR), increasing the duration of mechanical ventilation, the incidence of pulmonary infections, hospital costs, and mortality. The objective of this study was to identify predictive factors of severe hypoxemia in patients undergoing MR.

METHODS: Four-hundred and eighty-one adult patients undergoing elective MR between October 2003 and March 2004 were enrolled in this study. Severe hypoxemia was defined as PaO₂/FiO₂ < 150 upon admission to the ICU. The Chi-square test, Student's t or Wilcoxon test, followed by multivariate analysis and logistic regression (LR) for parameters with p < 0.25 in the univariate analysis, were used for the statistical analysis. A p > 0.2 was required to exclude the parameter from the LR model, and a p < 0.1 was considered significant.

RESULTS: Time for extubation was greater in patients with severe hypoxemia (p < 0.001). Multivariate analysis identified age (p = 0.081), weight (p = 0.001), need of prolonged CBP (p = 0.033), and left ventricular dysfunction (p = 0.082) as independent predictors of severe hypoxemia.

CONCLUSIONS: Older and overweighted patients, those with left ventricular dysfunction, and those who needed CPB presented an increased risk of severe hypoxemia after MR. In those patients, the use of perioperative ventilatory strategies, with elevated positive expiratory pressures and alveolar recruitment maneuver should be considered to prevent postoperative pulmonary dysfunction.

Key Words: COMPLICATIONS: hypoxemia; RISK, factors; SURGERY, Cardiac: myocardial revascularization.

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: La hipoxemia grave es una complicación frecuente en el postoperatorio inmediato de revascularización del miocardio (RM), promoviendo un aumento de la duración de la ventilación mecánica, de la incidencia de infecciones pulmonares, de los costos y de la mortalidad. El objetivo de este estudio fue identificar factores de predicción de hipoxemia grave en pacientes sometidos a la RM.

MÉTODO: Se estudiaron 481 pacientes adultos sometidos a la RM electiva entre octubre de 2003 y marzo de 2004. Se tomó en consideración hipoxemia grave en una relación PaO₂/FiO₂ < 150 en la admisión a la UCI. El análisis estadístico fue realizada a través de test de cui cuadrado, t de Student o Wilcoxon, seguido de análisis multivariado a través de regresión logística (RL) para variables con valor p < 0,25 en el análisis univariado. Se tuvo en cuenta el valor de p > 0,2 para la exclusión de la variable del modelo de RL y p < 0,1 como siendo significativo.

RESULTADOS: El tiempo para la extubación de los pacientes con hipoxemia grave fue mayor que en los otros pacientes (p < 0,001). En el análisis multivariado, las variables edad (p = 0,081), peso (p = 0,001), necesidad de CEC prolongada (p = 0,033) y disfunción ventricular izquierda (p = 0,082) fueron identificadas como de predicción independientes para hipoxemia grave.

CONCLUSIONES: Pacientes con edad y peso elevados, disfunción ventricular izquierda y necesidad de CEC presentaron un riesgo aumentado para hipoxemia grave después de la RM. NE estos pacientes, el uso de estrategias ventilatorias perioperatoria con presiones positivas de expiración más elevadas y la maniobra de reclutamiento alveolar deben ser consideradas teniendo en cuenta la prevención de la disfunción pulmonar postoperatoria.

INTRODUCTION

Recent advances in anesthetic and surgical techniques have allowed for increased perioperative agility (fast-track), with early extubation and discharge from the hospital ^1,2. Among the postoperative complications observed, hypoxemia is one of the most frequent ³, increasing the duration of mechanical ventilatory support ⁴, the incidence of pulmonary infections ⁵, duration of hospitalization and hospital costs. Different mechanisms, such as reduction of functional residual capacity (FRC) due to intraoperative atelectasis, pulmonary edema, and changes in ventilation/perfusion ratio have been deemed responsible for this complication ^6-12. Some factors have been suggested as probable pre and intraoperative predictors for the development of postoperative hypoxemia, with emphasis on cardiopulmonary bypass (CPB). Due to the high incidence of this complication, determination of predictive factors could identify high-risk patients for postoperative hypoxemia and the need to implement differentiated intra and postoperative ventilatory strategies to reduce this complication.

The objective of this study was to determine which pre and intraoperative factors are related with the development of severe hypoxemia in the immediate postoperative period of myocardial revascularization (MR).

METHODS

After approval by the Ethics Committee of the institution, 481 patients admitted to the intensive care unit of the Instituto do Coração do Hospital das Clínicas da FMUSP in the immediate postoperative period of myocardial revascularization (MR), between October 2003 and March 2004, were enrolled in the study. This was an observational, transversal study without signed consents, following the orientation of the Ethics Committee.

Inclusion criteria were as follows: 1) patients older than 30 years undergoing myocardial revascularization, with or without circulatory assistance, and 2) absence of chronic obstructive pulmonary disease with hypoxemia, which was defined as PaO2 < 60 mmHg before the surgery. Exclusion criteria were: 1) preoperative respiratory failure requiring supplemental oxygen; 2) need of mechanical ventilation due to postoperative bleeding; 3) non-corrected intracardiac communication; 4) high output broncho-pleural fistulas; 5) neurological changes or circulatory shock; and 6) patients admitted to the ICU with abnormalities of respiratory function and electrocardiographic and enzymatic changes compatible with perioperative myocardial infarction.

The form used to collect the data on the morning of the first postoperative day was composed of two parts: 1) preoperative evaluation, and 2) intraoperative evaluation. In the preoperative evaluation, parameters evaluated included: gender, age, weight, height, and left ventricular dysfunction (left ventricular ejection fraction below 55%) demonstrated by echocardiogram or ventriculography. Other parameters also included in the preoperative evaluation were: chronic obstructive pulmonary disease, smoking, preexisting renal failure (serum creatinine greater than 1.5 mg.dL^-1) and diabetes mellitus. The intraoperative evaluation included: duration of the surgery, need and duration of the CPB, minimal temperature during MR, need of inotropic and vasopressor drugs, clamping of the aorta or cardioplegia, fluid and blood balance, use of internal thoracic arteries for myocardial revascularization, and need of mechanical circulatory support after the cardiopulmonary bypass.

According to the protocol of the Anesthesiology Department, patients were monitored with cardioscope, pulse oximetry, and invasive blood pressure before anesthetic induction. After induction, a central venous catheter or pulmonary artery catheter, depending on the complexity of the case, was introduced. Esophageal temperature and urine output were also monitored after anesthetic induction. Mechanical ventilation was adjusted by the anesthesiologist responsible for the patient, usually with a tidal volume between 8 and 10 mLkg^-1 and respiratory rate between 10 and 14 bpm to maintain PaCO₂ between 30 and 40 mmHg. Positive end-expiratory pressure was used whenever the anesthesiologist considered necessary, usually between 3 and 5 cmH₂O.

The need for CPB was defined by the surgical team before the surgery; however, eventually the care had to be changed intraoperatively. Membrane oxygenator was used in patients undergoing CPB. Temperature and type of myocardial protection (cardioplegia or intermittent clamping) were determined by the surgeon. In patients undergoing dissection of the internal thoracic arteries, manual pulmonary insufflation, with airways pressures between 20 and 30 cmH₂O was performed to reverse atelectasis related to the dissection.

During the surgery, vasoactive drugs were administered to maintain the patient hemodynamically stable. Circulatory support with intra-aortic balloon counterpulsation was instituted if the patient was not hemodynamically stable after volume and pharmacologic adjustments. Red blood cells and blood products were transfused when needed, at the discretion of the anesthesiologist. After the surgery, patients were transferred to the intensive care unit.

The SPSS 10 (SPSS Inc., Chicago, Illinois, USA) was used for the statistical analysis. In the first phase of the study, pre and intraoperative risk factors for postoperative hypoxemia were evaluated, regarding their distribution, by using the Kolmogorov-Smirnov test if the parameter was continuous or discrete. Non-paired Student's t test was used to evaluate the relationship between quantitative parameters with normal distribution and severe hypoxemia. The Wilcoxon test was used to analyze quantitative parameters without normal distribution. The Chi-square test was used to analyze the association between categorical parameters and hypoxemia. Parameters with p < 0.25 on univariate statistical tests were selected for the model of multivariate analysis and logistic regression. Backward LLR was the logistic regression technique used. Once in the model, a p > 0.2 was used to exclude the parameter on the different steps of the regression and a p < 0.1 in the multivariate analysis was considered significant.

RESULTS

Among the patients admitted to the intensive care unit during the study, 481 fulfilled the inclusion criteria. Three of those were excluded for lack of data on PaO₂/FiO₂ at the time of admission and 17 were excluded due to increased postoperative bleeding. Table I presents the anthropometric data of the patients. The mean age of the patients was 64 years (34-86 years). Left ventricular function was normal in 71.8% of the patients. A smoking history was present in 19.7% of the patients and mild chronic pulmonary obstructive disease was prevalent in 8.2% of the patients but none dependent on oxygen. Serum creatinine greater than 1.4 mg.dL-1 was present in 20.4% of the patients. No patients in this study were in a dialysis program. The prevalence of diabetes mellitus in the study population was 34.3%.

The mean length of surgery was 370 ± 86 minutes. Two-hundred and eighty-eight patients (62.5%) underwent MR with CPB, and the mean duration of the CPB was 101 ± 37 minutes. In 222 of those patients CPB lasted less than 2 hours. In 173 patients (37.5%) surgery was done without CPB. Of the patients undergoing CPB, intermittent clamping of the aorta was the technique of myocardial protection used more often (60.6%) while cardioplegia was used in 39.4% of the patients. Internal thoracic arteries (ITA) were used in 390 patients (84.6%) and the remainder received venous or radial artery grafts. Inotropic support was used in 82.9% of the patients and intra-aortic balloon counterpulsation was used in 10.2% of the patients.

Mean PaO₂/FiO₂ determined immediately after admission to the ICU was 210 ± 81, with a minimum of 82 and maximum of 595. Figure 1 shows the distribution histogram for mean PaO₂/FiO₂. When evaluated regarding the severity of the hypoxemia, 45.8% out of the 461 patients included in the study had a PaO₂/FiO₂ greater than 200 upon admission to the surgical ICU, between 150 and 200 in 26.9% of the patients, and 27.3% of the patients had severe hypoxemia, defined as a PaO₂/FiO₂ below 150.

The mean length of time to wean patients from ventilatory support in 388 patients was 446 ± 332 minutes. Thirty-two patients (8.25%) were extubated up to 4 hours after admission to the ICU, 106 (27.31%) between 4 and 6 hours, and 250 (64.43%) in more than 6 hours. To determine the impact of the severity of hypoxemia in the immediate postoperative period on the mean duration of mechanical ventilatory support, three groups of patients, divided according to the PaO₂/FiO, were evaluated: G1 – greater than 200; G2 – between 150 and 200; and G3 – less than 150. As can be seen in Figure 2, the mean duration of mechanical ventilatory support was significantly greater in patients with severe hypoxemia (G3), when compared with the other two groups, being 68.3% greater than G1 and 48.9% greater than G2.

As can be seen in Table II, the mean weight of the patients in the group with severe hypoxemia was 9.7% greater than in patients with PaO₂/FiO₂ > 150 after admission to the ICU; however, no significant differences in height and age were observed. The incidence of severe hypoxemia was greater in male (53%) than in females (23.6%) patients. The presence of left ventricular dysfunction was related with the development of hypoxemia, which affected 30% of the patients with left ventricular ejection fraction (LV) below 55% and only 20% of patients with normal LV. The presence of preoperative renal failure was also associated statistically with the development of severe postoperative hypoxemia, affecting 37.5% in comparison to 26.5% of the patients without renal failure. Severe hypoxemia was also more frequent in patients who were re-operated. Other preoperative parameters, such as history of mild COPD or smoking were not statistically related with the development of severe postoperative hypoxemia.

Considerin the intraoperative period, duration of the surgery was greater in patients who developed severe hypoxemia. The use of CPB was another factor associated with severe hypoxemia in the univariate analysis, with an incidence of 37.9% in patients who underwent more than 120 minutes of CPB, 29.3% in those in CPB for up to 120 minutes, and 20% of patients undergoing myocardial revascularization without CPB. Among patients undergoing surgery with CPB, the incidence of hypoxemia was greater among patients submitted to cardioplegia for myocardial protection. The use of inotropic drugs and need of mechanical circulatory assistance were also associated with the development of severe hypoxemia. Other factors, including intraoperative hypothermia, need of vasopressors, use of ITA and fluid balance were not statistically associated with severe postoperative hypothermia, as shown in Table III.

Among all parameters in the univariate analysis, age, weight, gender, presence of left ventricular dysfunction, duration of the procedure, need and duration of cardiopulmonary bypass, renal failure, need of inotropic support, mechanical circulatory support with intra-aortic balloon counterpulsation and re-operation had a p < 0.25, and were selected for the logistic regression model. After adjusting confounding factors in the logistic regression model, it was observed that the following parameters were independent predictive factors for the development of severe hypoxemia: CPB, ejection fraction below 55%, age and weight. Table IV shows that there was a 0.3% increase in the risk of severe postoperative hypoxemia for every year above the age of 34. The same result was observed regarding weight, with a 0.4% increase in risk for every kilogram above 43kg. The use of CPB doubled the risk of severe hypoxemia in the immediate postoperative period, and prolonged CPB (> 120 minutes) tripled the risk. Left ventricular dysfunction increased by almost twice the risk of severe hypoxemia.

DISCUSSION

Hypoxemia is a common postoperative complication in cardiac surgeries, being responsible for an increase in the duration of mechanical ventilation, length of stay in the intensive care unit and hospital costs ¹³. In the present study, 54.2% of the patients without a relevant respiratory history developed hypoxemia, defined as a PaO₂/FiO₂ below 200, in the immediate postoperative period of MR and 27.3% of the patients developed severe hypoxemia, defined as a PaO₂/FiO₂ below 150, and the duration of mechanical ventilation was significantly greater than in other patients.

The risk (odds ratio) of hypoxemia was 2.3 for up to 120 minutes of CPB and 3.1 for CPB greater than 120 minutes. Despite technological advances, CPB is still mentioned as an important cause of postoperative hypoxemia in MR ¹³. Using CT scan of the chest, Magnusson et al. demonstrated, in an experimental model in pigs, that CPB promoted more widespread pulmonary collapse than what was seen in animals that were only anesthetized or underwent thoracotomy without CPB ⁹. Similar results regarding the role of CPB in the genesis of atelectasis and hypoxemia have been reported by several authors ^7,14-16. Activation of the inflammatory response induced by the surgical trauma and CPB, with activation and trapping of neutrophils in the pulmonary circulation, leading to endothelial lesion ¹⁷ and disruption of the air-blood barrier ¹⁸ has been proposed to explain the development of hypoxemia in this group of patients. Changes in the surfactant system as a consequence of the inflammatory response post-CPB also seem to contribute for the development of atelectasis. Although CPB is a risk factor for the development of hypoxemia, there is a controversy on whether the duration of CPB is related with the degree of hypoxemia. In the present study, we observed that the group undergoing CPB for more than 120 minutes had a significantly greater risk of severe hypoxemia than the group undergoing CPB for less than 120 minutes. It is possible that more prolonged inflammatory aggression to the pulmonary circulation caused by CPB is responsible for greater interstitial-alveoli lesion and edema ¹⁹. It should be noticed that patients scheduled for surgery without CPB are in better clinical conditions than patients who ordinarily undergo surgery with CPB and that could be characterized as a selection bias.

Age is frequently mentioned as a risk factor for hypoxemia after myocardial revascularization ^13,15,20-23. In the present study, age was an independent risk factor for hypoxemia, and each year above the age of 34 was related with a 0.32% increase in risk when analysis biases were controlled by multivariate analysis. Physiologically, a decrease in arterial oxygenation associated with aging has been reported, which corroborates the result that age isolatedly can be considered a risk factor for hypoxemia. However, the association of other co-morbidities such as ventricular dysfunction is also more frequent in the elderly and should be considered in the evaluation of risk factors of hypoxemia in this group of patients.

The presence of left ventricular dysfunction was another risk factor for postoperative hypoxemia identified in this study. Multivariate analysis demonstrated a risk of 1.8 with a left ventricular ejection fraction (EF) below 55%. In patients with ventricular dysfunction, the presence of cardiomegaly, change in the spatial position of the heart due to the relaxation of the diaphragm, increasing the area of the heart resting on the inferior lobes, and myocardial edema, contribute to increase the pressure on the inferior lobes, increasing the formation of atelectasis ^24,25. It was observed, in a previous study, that the presence of left ventricular dysfunction was related with the difficulty to wean patients off ventilatory support and the need for prolonged mechanical ventilation after cardiac surgery ¹⁹. Similar results have been reported in several studies evaluating the role of ventricular function in the genesis of postoperative hypoxemia ^{4,13,22,23, 26,27}.

As expected, a positive correlation between weight and the development of postoperative hypoxemia was observed, increasing the risk by 0.4% for each kilogram of body weight above 43 kg. Cephalad shifting of the relaxed diaphragm induced by the pressure from abdominal viscera is frequently seen in anesthetized patients and has been described as one of the factors related with collapse in the bases of the lungs ²⁸. In overweight patients, the abdominal wall is usually thicker and contributes to increase the abdominal pressure exerted on the diaphragm, therefore increasing the volume of collapsed parenchyma in caudal and dependent areas of the lungs. This result has been corroborated by other authors, who described overweight as a risk factor for hypoxemia.

The results of the multivariate analysis contrast with those of the univariate analysis in which male gender, use of inotropic drugs, mechanical support, re-operation surgery and length of the surgery were related with the presence of postoperative hypoxemia. The use of inotropic drugs and the need for mechanical circulatory support were controlled in the analysis, since their use is associated with ventricular dysfunction. Duration of the surgery may be related to the duration of the CPB and that might be the reason it does not appear as an isolated risk factor.

The use of uni or bilateral ITA as grafts for MR was not related with the severity of postoperative hypoxemia in the present study. Since alveolar recruitment maneuver at the end of the dissection of the internal thoracic arteries to expand collapsed pulmonary areas induced by placing dressing on the lungs to improve exposition of the area is routine in our service the impact of internal thoracic arteries dissection on oxygenation might have been decreased. Daganou et al., comparing uni and bilateral dissection of mammary arteries, showed an increase in the incidence of atelectasis in the upper right lobe in the group of bilateral dissection. However, there were no changes in gas exchange, pleural effusion, duration of mechanical ventilation, pneumonia and other complications between both groups ²⁹. Although alveolar recruitment maneuver is routinely done after the dissection of internal thoracic arteries, the use of this maneuver, as well as elevated positive pressure at the end of expiration to prevent intraoperative pulmonary collapse, can have a negative effect on exposure of the surgical field and therefore is not routine in every cardiac surgery services.

This observational, transversal study was designed to evaluate the incidence of hypoxemia in a specific patient population undergoing MR, the correlation between the severity of hypoxemia and duration of postoperative mechanical ventilation due to hypoxemia and pre- and intraoperative risk factors for the development of hypoxemia in the immediate postoperative period. Since it was an observational study, parameters were gathered from the records of the patients. In some patients included in the study, lifestyle and smoking history, pre-existing diseases and left ventricular function were only qualitatively qualified in the charts of the patients. Despite the inevitable loss of information, parameters were categorized in order to obtain the best use of the information available.

The knowledge of the outcome by the examiner responsible for gathering the data was a source of error during the study. To minimize selection bias, it was stipulated that every patient undergoing MR during the study would be included, except in the presence of exclusion criteria defined previously. The cutting level selected for PaO₂/FiO₂ to define severe hypoxemia is another methodological aspect that should be discussed. In the present study, a large portion of patients developed transient hypoxemia in the first hours after admission to the ICU, with a PaO₂/FiO₂ between 150 and 200, which did not translate longer mechanical ventilation. However, patients with PaO₂/FiO₂ below 150 needed mechanical ventilation for a significantly longer period; therefore, this level was chosen as the limit to define severe hypoxemia.

To conclude, the identification of risk factors for hypoxemia in MR allows specific preoperative preparation of high-risk patients, adjustment of the intraoperative treatment and postoperative care. In those patients at high risk for the development of severe hypoxemia, implementation of intraoperative mechanical ventilation strategies to prevent and treat intraoperative pulmonary collapse could minimize the impact of hypoxemia on postoperative mechanical ventilation, reduce morbidity and mortality of the cardiac surgery, decrease length of stay in the intensive care unit and reduce hospital costs.

REFERENCES

Submitted em 10 de abril de 2007

Accepted para publicação em 31 de dezembro de 2007

* Received from Serviço de Anestesiologia e Terapia Intensiva Cirúrgica do Instituto do Coração (InCor) – Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), São Paulo, SP

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Publication Dates

• Publication in this collection
  11 Mar 2008
• Date of issue
  Apr 2008

History

• Accepted
  31 Dec 2007
• Received
  10 Apr 2007