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Ann Thorac Surg 1996;62:1164-1171
© 1996 The Society of Thoracic Surgeons
Departments of Cardiothoracic Surgery and Anesthesiology, St. Vincent Medical Center, Toledo, Ohio
Accepted for publication May 19, 1996.
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Abstract |
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 TopFootnotes Abstract IntroductionMaterial and MethodsResultsCommentAppendix 1.Appendix 2.AcknowledgmentsReferences |
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Methods. We retrospectively examined the role of 48 variables in determining the period of ventilatory support in 507 patients having coronary artery bypass grafting.
Results. Fifteen (<3%) of 507 patients required ventilatory support in excess of 24 hours. Among the remaining patients, extubation was achieved early (
8 hours) (mean time, 5.65 ± 1.31 hours) in 53% and late (>8 hours) (mean time, 13.7 ± 3.4 hours) in 47%. Logistic and linear multivariate regression analyses implicated increased age, New York Heart Association functional class IV, intraoperative fluid retention, postoperative intraaortic balloon pump requirement, and bank blood transfusions as predictors of late extubation. Also, the linear regression linked lower body weight and number of anastomoses (or grafts) to increased mechanical ventilatory support.
Conclusions. Analysis of the fluid balance and cardiopulmonary bypass data suggests that earlier extubation may be achieved by actively reducing fluid retention (eg, by hemoconcentration) and time on bypass (eg, normothermia). Finally, intensive care unit stay and postoperative length of stay were significantly lower in the early versus late extubation groups without an increase in pulmonary complications.
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Introduction |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAppendix 1.Appendix 2.AcknowledgmentsReferences |
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Methods of weaning cardiac surgical patients from mechanical ventilation continue to evolve and can vary greatly among institutions. Advances in techniques of anesthesia and cardiopulmonary bypass as well as analgesic medications have been instrumental in reducing postoperative ventilatory dependency without increasing the incidence of pulmonary complications in patients who have undergone an open heart procedure [4]. These advances, in turn, have led to appreciable declines in duration of intensive care and hospitalization. However, duration of ventilatory support remains highly variable among patients, and studies that systematically explore the causes of this variability are needed.
The primary goal of this study was to elucidate the patient characteristics and operative variables responsible for prolonged postoperative respiratory insufficiency in patients undergoing coronary artery bypass grafting (CABG). We also sought to establish a model capable of predicting the need of increased postoperative ventilatory support in CABG patients. Arguably, such a model would help identify areas of current practice where modifications might facilitate improved postoperative pulmonary function.
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Material and Methods |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAppendix 1.Appendix 2.AcknowledgmentsReferences |
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Perfusion
Cardiopulmonary bypass was conducted with an extracorporeal circuit consisting of a membrane oxygenator (Baxter Healthcare Corp, Irvine, CA), a centrifugal pump (Medtronic, Inc, Anaheim, CA), and the capacity for ultrafiltration. Typically, the pump was primed with 1,800 mL of Plasmalyte, 50 g of mannitol (250 mL), and 50 g of albumin (200 mL). One surgeon (surgeon A) did not use albumin (n = 106 patients). Normothermic (lowest core temperature >35°C) perfusion was used in the majority of patients (89%) with the circuit's heater/cooler temperature set at 38°C. Mild (lowest core temperature = 32° to 35°C) hypothermia and moderate (27°C < lowest core temperature < 32°C) hypothermia were used less frequently (2% and 9%, respectively). Ultrafiltration was used in a few patients diagnosed with anasarca (5/507, 1%). Cardioplegia was mostly antegrade and consisted of Plegisol with 1 g of lidocaine hydrochloride, 50 mEq of KCl, and 15 g of NaHCO3 (8.4%) in either cold oxygenated crystalloid solution or cold blood. Arterial blood flows were determined on the basis of a cardiac index of 2.5 to 3.0 (L•min-1•m-2), and mean arterial pressures were maintained between 50 and 60 mm Hg.
Anesthesia and Analgesia
Anesthesia and analgesia were standardized for all patients to minimize respiratory drive and thus facilitate earlier extubation. Briefly, patients were premedicated mostly with lorazepam. After the establishment of an arterial line and a peripheral venous line, anesthesia was induced with fentanyl and diazepam. Sodium thiopental (0 to 250 mg) was given to achieve a mean arterial pressure of 70 mm Hg. Pancuronium bromide was used for muscle relaxation. After direct laryngoscopy, 4 mL of lidocaine solution (4%) was applied to the trachea and larynx, and the patient was intubated. Anesthesia and muscle relaxation were maintained with isoflurane and small additional doses of fentanyl, diazepam, and pancuronium. The total amounts of diazepam and fentanyl were controlled fairly rigidly so as not to exceed 10 mg/kg and 30 µg/kg, respectively.
Postoperative analgesia was achieved with ketorolac unless contraindicated (Appendix 1). Contraindications were age greater than 70 years, a serum creatinine level higher than 1.3 mg/dL, and a history of sensitivity to nonsteroid, antiinflammatory drugs. Morphine was used in patients when ketorolac was not sufficient. Diazepam and haloperidol were used for anxiolysis and agitation, respectively. Small doses (12.5 to 25 mg) of meperidine hydrochloride were administered to reverse shivering, and doses of pancuronium or vecuronium bromide (0.5 to 1 mg) were used when meperidine was inadequate.
Criteria for Extubation
Once patients were hemodynamically stable and responsive to commands, ventilator weaning was started as described in Appendix 2 [5]. Briefly, patients were extubated when they met standard mechanical function criteria and were able to maintain normal blood gases on continuous positive-airway pressure or an intermittent mandatory ventilation rate of 4 breaths/min with an inspired oxygen fraction of less than or equal to 40%. Standard criteria included an appropriate respiratory rate, tidal volume greater than 5 mL/kg, vital capacity greater than 10 mL/kg, and negative inspiratory force greater than 20 mm Hg. Time to extubation (Text) or hours on mechanical ventilation were calculated from time out of the operating room, rounded to the closest half hour, and recorded.
Statistical Methods
Patients were divided into early (Text 8 hours) and late (8 < Text < 24 hours) extubation groups. Twenty-eight preoperative (Table 1
), 13 intraoperative, and 7 postoperative variables (Table 2) were compared. Univariate analysis (SigmaStat; Jandel Scientific, San Raphael, CA) was done with 
2 or Fisher's exact test for categoric variables and either the unpaired t test or the nonparametric Mann-Whitney rank sum test for continuous variables, depending on applicability.
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Results |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAppendix 1.Appendix 2.AcknowledgmentsReferences |
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illustrates the frequency distribution of Text in 507 CABG patients. Briefly, 51% of patients were extubated within 8 hours (median Text = 8 hours), and less than 3% of patients (15/507) required ventilatory support for more than 24 hours. In general, the patients were divided into two groups on the basis of the nearly bimodal frequency distribution of Text: (1) an early extubation group (Text 8 hours, median = 5.5 hours, n = 259) and (2) a late extubation group (8 < Text 24, median = 13.5 hours, n = 233).
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. Here, the retrospective univariate analysis revealed that patients in the late extubation group were an average of 4.5 years older, included more female patients (33% versus 21%), and were an average of 6.4 kg smaller. Also, patients in this group were generally sicker than those in the early extubation group, as they had twice the incidence of congestive heart failure (8.8% versus 4.0%), a higher percentage of them were in New York Heart Association class IV, and the preoperative blood urea nitrogen and creatinine levels were higher. The decreased preoperative hemoglobin level, the increased creatinine level, and the more frequent use of preoperative diuretics in the late extubation group all approached significance.
Intraoperative and postoperative data are summarized in Table 2. Eleven variables (nine intraoperative and two postoperative) differed significantly between the early and late extubation groups. Patients in the late group generally received more grafts (3.22 versus 3.02), and total cardiopulmonary bypass time was longer by an average of 7.1 minutes. Although employed in only a small number of patients, use of moderate hypothermia was nearly twice as frequent for the late group (12.8% versus 6.7%). Also, absolute fluid retention (liters) calculated from the total fluid input versus output was 22% higher after bypass in the late extubation group compared with the early extubation group. This difference was increased to 30% when fluid balance was normalized to the patient's body surface area. On the other hand, hemoglobin concentrations were generally lower for the late extubation group than the early extubation group. Postoperative bank blood transfusions (32.6% versus 14.7%) and use of intraaortic balloon pumps (9.3% versus 4.0%) were more frequent in the late group.
Several of the 18 variables linked to late extubation by univariate analysis are correlated (eg, numbers of grafts and perfusion time) and hence may not all be independent predictors of prolonged mechanical ventilation. Accounting for codependence of variables, the multivariate logistic model included a total of five independent predictors of late extubation (Table 3). These were older age, New York Heart Association class IV, increased positive fluid balance normalized to body surface area, use of postoperative intraaortic balloon pump, and bank blood transfusions. In addition to these five variables, the stepwise multivariate linear regression analysis also implicated smaller patient weight and increased number of anastomoses or grafts as predictors of increased Text (Table 4).
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Comment |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAppendix 1.Appendix 2.AcknowledgmentsReferences |
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The main goals of this study were to identify the patient characteristics and operative variables that distinguish early extubation and late extubation patient groups, to build a model capable of predicting delayed extubation in CABG patients, and to identify and explore possible areas of surgical and medical practice where modifications may allow earlier extubation.
Four of the seven factors implicated by the retrospective multivariate analysis have a direct impact on postoperative recovery. Of these, increased age, New York Heart Association class IV, and more frequent blood transfusions indicate a weaker or sicker patient, and increased postoperative use of the intraaortic balloon pump indicates persistent hemodynamic instability and left ventricular dysfunction.
Intraoperative fluid retention associated with cardiopulmonary bypass can lead to substantial lung dysfunction [6–8]. A major component of the positive fluid balance retained by the patient at the end of operation is in the form of increased extravascular lung water. Obviously, such pulmonary edema can impair pulmonary function by its deleterious effects on lung mechanics and gas exchange. Extravascular lung water can be further increased in the early postoperative hours after pulmonary reperfusion commences [6]. Movement of fluid between the intravascular and extravascular spaces of the lung can depend on both the degree of hemodilution, through its effects on oncotic pressures, and the endothelial integrity of the pulmonary vasculature [6].
The linear regression analysis provided evidence in support of this notion (see Table 4). Here, analysis of the time on mechanical ventilation as a continuous variable implicated two additional factors: number of anastomoses and patient weight. Time on cardiopulmonary bypass increases with the number of grafts (or anastomoses) and has been shown to cause endothelial injury, which increases permeability of the pulmonary vasculature [6–8]. This phenomenon has been linked to complement activation and release of inflammatory mediators subsequent to the exposure of blood (leukocytes) to the surface of the extracorporeal circuit during bypass [6–8].
We speculate that decreased patient body weight has an indirect impact on postoperative lung function through its role in fluid retention. To explain this contention, we suggest the following scenario: The oncotic pressures retarding fluid flow from the intravascular bed to the extravascular space may be lower in the reperfused lungs of patients in whom hemodilution is greater. Other things being equal, a smaller patient blood volume (or smaller body weight) combined with the constant prime volume of the extracorporeal circuit will necessarily result in a greater degree of hemodilution. This, in turn, alters the balance of the relevant oncotic pressures and favors fluid flow from the intravascular to the extravascular space. As indirect evidence, we found that postoperative hemoglobin levels were generally higher as patient weight increased (Fig 2). Note, however, that other factors such as preoperative hemoglobin level, blood removal, diuresis, urine output, fluids added to the circuit during bypass, perfusion time, and intraoperative transfusions undoubtedly affect the relationship between postoperative hemoglobin level and body weight. Indeed, the interpatient variability of all these factors is probably responsible for the observed variability in postoperative hemoglobin level at any given body weight (see Fig 2). Also consistent with this contention, Magovern and co-workers [9] found that low body surface area and body mass index in CABG patients were predictors of increased postoperative blood transfusions because of decreased blood volume in general and red cells mass in particular.
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). Also, we found that fluid retention was significantly higher for patients in whom albumin was not used in the pump prime solution.
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). In the univariate analysis, hypothermia was associated with delayed extubation possibly because patient rewarming at the end of bypass increases time on cardiopulmonary bypass, which, in turn, can increase fluid retention in the lungs. Normothermia may also reduce the period of mechanical ventilatory support in the cardiac surgical patient by avoiding or minimizing the need of active rewarming in the intensive care unit (ICU). Pathi and colleagues [10] recently reported shorter Text in patients who are rewarmed faster in the ICU after hypothermic bypass. This coupled with the relatively short ventilatory support period in our CABG patients (89% had normothermic cardiopulmonary bypass) indicates that normothermia may facilitate earlier extubation. This contention is supported by Tonz and associates [11], who prospectively found that patients undergoing normothermic bypass were extubated earlier than those having hypothermic bypass (13.3 versus 16.4 hours). However, although compelling, it is unclear whether the decrease in time on cardiopulmonary bypass expected with normothermia will cause a systematic reduction in the net positive fluid balance at the end of operation. Studies designed specifically to address this question are necessary.
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In a study similar to ours, Arom and associates [3] reported that log of age, female sex, congestive heart failure with preoperative diuretics, and unstable angina were predictors of late extubation by multivariate analysis. Their results are consistent with those of our univariate analysis, but of these factors, only older age predicted late extubation in our multivariate models. Comparing statistical models from different studies can lead to tenuous conclusions unless the same variables are considered. We believe that the differing results between our study and that of Arom and associates [3] are mostly a consequence of the analyses used. First, Arom and co-workers divided patients into early and late groups on the basis of an a priori chosen ventilatory support period of 12 hours as opposed to the statistical approach used by us (see Fig 1). Second, and more importantly, we analyzed a larger number of variables (48 versus 25). To illustrate, both studies found that extubation is more likely to be delayed in female patients, but, unlike Arom and associates, we did not find sex to be an independent predictor of late extubation. We contend that in our multivariate model, the effect of female sex was replaced by that of two other variables, incidence of postoperative bank blood transfusions (44.1% versus 15.6%) and smaller patient weight. Both variables were independent predictors of late extubation, were more prevalent in female patients, and were not included in the analysis by Arom and colleagues.
Clinical benefits of early extubation, especially on respiratory and cardiovascular function, have been described elsewhere [14–22]. The economic benefits of early hospital discharge can also be substantial and have become increasingly important in the current health care environment. Early extubation has recently been presented as one of the central components of critical paths designed to expedite discharge from the ICU and the hospital. Our results are consistent with this contention, as both ICU and postoperative hospital stays were significantly decreased with early extubation in this series (Table 7). These reductions in ICU and postoperative length of stay are similar to those reported by Arom and associates [3], who also reported an average decrease in hospital charges of $6,000 per patient as a result of early extubation.
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Appendix 1. |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAppendix 1.Appendix 2.AcknowledgmentsReferences |
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Appendix 2. |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAppendix 1.Appendix 2.AcknowledgmentsReferences |
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Acknowledgments |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAppendix 1.Appendix 2.AcknowledgmentsReferences |
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Dr Habib's current address is Department of Pediatrics, Robert Wood Johnson Medical School, 401 Haddon Ave, Camden, NJ 08103.
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Footnotes |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAppendix 1.Appendix 2.AcknowledgmentsReferences |
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References |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAppendix 1.Appendix 2.AcknowledgmentsReferences |
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