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Pulmonary hemodynamics and gas exchange in off pump coronary artery bypass grafting
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     Department of Cardiothoracic Surgery and Anesthesia, Karolinska University Hospital, 171 76 Stockholm, Sweden

    Abstract

    Objective: To investigate the influence of cardiopulmonary bypass on pulmonary hemodynamics and gas exchange. Methods: Low risk patients admitted for elective coronary artery bypass grafting were randomized to either on (n=25) or off pump (n=25) surgery. Central hemodynamics, gas exchange, and venous admixture were studied during and up to 20 h after surgery. Results: There was no difference in pulmonary vascular resistance index (P=0.16), right ventricular stroke work index (P>0.2), mean pulmonary artery pressure (P>0.2) or pulmonary capillary wedge pressure (P>0.2) between groups. Soon after surgery there was a tendency towards higher cardiac index (P=0.07) in the off pump group. Arterial oxygen tension (P>0.2), hematocrit (P>0.2), venous admixture (P>0.2), and arterial–venous oxygen content difference (P=0.12) did not differ between groups. Conclusions: This prospective, randomized study showed no difference in pulmonary hemodynamics, pulmonary gas exchange, and venous admixture, in low risk patients undergoing off pump compared to on pump coronary artery bypass surgery.

    Key Words: Coronary artery bypass; Off pump; Hemodynamics; Blood gas

    1. Introduction

    Coronary artery bypass surgery with cardiopulmonary bypass (ONCAB) induces a systemic inflammatory response which leads to increased lung capillary permeability and interstitial fluid accumulation [1]. This may result in pulmonary dysfunction and morbidity such as atelectases, pneumonia, interstitial edema and airway obstructivity and ultimately respiratory insufficiency, all known complications after surgery with cardiopulmonary bypass (CPB) [2]. Atelectases caused by CPB have been found to be a major cause of venous admixture and hypoxemia in pigs [3].

    The development of off pump coronary artery bypass grafting (OFFCAB) may consequently be a way of reducing lung complications. Previous randomized studies comparing ONCAB and OFFCAB have suggested better preserved myocardial function, reduced blood loss, earlier mobilization, and lower healthcare costs [4,5].

    However, randomized studies comparing lung parameters have not shown any differences in gas exchange or lung complications [6], but a reduction in venous admixture after OFFCAB [7,8], when following patients for up to 6 h after extubation. In non-randomized studies there have been no differences when comparing lung function variables (as forced expiratory volume, maximal voluntary ventilation or tidal volume), arterial blood gases, pulmonary vascular resistance or right ventricular stroke work index [9,10].

    In this prospective, randomized study we combined studies of central hemodynamics, gas exchange and venous admixture. Measurements were performed during the first 24 h after surgery in a population of elective, low risk patients undergoing elective ONCAB and OFFCAB.

    2. Material and methods

    This study was approved by the local Ethics Committee and informed consent was obtained from the patients. Fifty-six patients scheduled for elective coronary surgery were randomized to ONCAB or OFFCAB. Inclusion criteria were: patients 50–80 years old and first time operation. Exclusion criteria were: unstable angina, tight left main stem stenosis (>70%), small or very diffusely diseased coronary vessels, markedly reduced cardiac function (ejection fraction <30%), serum creatinine >150 μmol/l, history of pulmonary (chronic obstructive pulmonary disease, restrictive lung disease) or cerebrovascular disease. Neither the number of anastomoses nor the location of the stenoses were reasons for exclusion. Six patients had to be excluded due to problems with the Swan-Ganz catheters resulting in missing data. Thus each group consisted of 25 patients completing the study protocol. These patients were also included in a previous study on cardiovascular function and markers of myocardial damage [11].

    2.1. Anesthesia and postoperative care

    All patients received standard anesthesia according to the clinical routine at our department including premedication with i.v. morphine, induction with fentanyl, midazolam and propofol. Pancuronium or atracurium was used for muscular relaxation and isoflurane and intermittent fentanyl to maintain anesthesia. Norepinehrine was administered to keep mean arterial pressure above 50 mmHg. Volume controlled ventilation (900D Servoventilator, Siemens, Germany) with 40–50% oxygen in air was performed. The patients were fully ventilated (minute ventilation 70–90 ml/kg body weight) until full bypass was achieved in the on-pump group and during bypass oxygenated via CPB. The patients were then ventilated with 50% of the original minute ventilation during completion of the proximal anastomoses and again fully ventilated after recruitment of the lungs before weaning off CPB. In the off-pump group the patients were fully ventilated during the operation.

    Patients were sedated with propofol and ventilated mechanically until 4 h after admission to the intensive care unit (ICU) in order to complete the measurements under standardized conditions. The patients were extubated 4–6 h after arrival in the ICU (after the measurements at 4 h). Pain control was obtained with i.v. ketobemidon infusion. After extubation the patients received oxygen via a nasal catheter. Postoperative bleeding was measured from when the drains were activated in the operating room until they were removed on the first postoperative day. When the radial artery was used as a graft, the patients received nitroglycerin infusion (0.5 μg/kgxmin) for 18–24 h post-operatively.

    2.2. Monitoring and sampling

    A Swan-Ganz catheter (Thermodilution Paceport Catheter, Edwards Lifescience, Irvine, CA, USA) was introduced through the right internal jugular vein after induction of anesthesia. Arterial pressure was monitored through a radial artery line. Arterial and mixed venous blood were sampled from the radial arterial line and from the Swan-Ganz catheter, respectively, for blood gas measurements. For standardization all patients were ventilated with 50% oxygen for 15 min before sampling.

    Mean pulmonary artery pressure (MPAP), central venous pressure (CVP), pulmonary artery wedge pressure (PCWP), pulmonary vascular resistance index (PVRI), right ventricular stroke work index (RVSWI) and cardiac index (CI), were measured after induction, but before surgery, and at 1, 4 and 20 h after admission to the ICU. Arterial and mixed venous blood gases were measured concomitantly. (ABL 505, Radiometer, Copenhagen, Denmark).

    Arterial–venous (a–v) oxygen content difference was calculated as CaO2–CvO2 where CaO2 is arterial blood oxygen content and CvO2 is mixed venous blood oxygen content. Venous admixture was calculated as (Cc'O2– CaO2)/(Cc'O2–CvO2) where Cc'O2 is the oxygen content in pulmonary end-capillary blood [12]. The respiratory quote was set to 0.8.

    2.3. Surgical technique

    The patients were operated through a median sternotomy by six different surgeons. The left pleura was usually opened in the patients where the left internal mammary artery (LIMA) was taken down. All proximal anastomoses were performed by the use of a side-biting clamp. Protamine was administered at the end of the operation to fully reverse the heparin effect.

    2.4. ONCAB

    Heparin 300 IU/kg was given to obtain activated clotting time (ACT) over 480 s before start of CPB. The aorta and right atrium was cannulated with a standard technique. The CPB system used was a standard tube kit (Medtronics, Minneapolis, MN, USA), a centrifugal pump (Biomedicus 550, Medtronics, Minneapolis, MN, USA) and membrane oxygenator (Affinity NT, Medtronics, Minneapolis, MN, USA). CPB was conducted with a flow rate of 2.4 l/m2 min, alpha stat acid-base management and a nasopharyngeal temperature of 34–35 °C. The heart was arrested after aortic cross-clamping with 600–1000 ml of antegrade cold blood cardioplegia (20 mM potassium) and thereafter intermittent cardioplegia (300–400 ml, 10 mM potassium) either between each anastomosis or every 15 min antegradely or retrogradely according to the surgeon.

    2.5. OFFCAB

    Heparin, 150 IU/kg was administered to maintain ACT over 300 s. Positioning of the heart was achieved by a deep retrocardial pericardial sling-suture or a suction device (Xpose CTS, Guidant, Indianapolis, IN, USA). We used three different kinds of stabilizers according to the surgeon's choice: Octopus II/III stabilizer (Medtronics, Minneapolis, MN, USA), OPCAB multi use stabilizer (Guidant, Indianapolis, IN, USA) or CTS stabilizer Axius or Ultima (Guidant, Indianapolis, IN, USA). Ischemic preconditioning was not used and intracoronary shunts were only used in cases when an anastomosis was performed on the main stem of the right coronary artery. In some cases, the right pleura was opened to expose the circumflex area better (Table 2).

    2.6. Statistics

    For between group analysis of operative and postoperative data, t test and Fisher's exact P test were used. For interaction data measured during 24 h, repeat measures analysis of variance was used [ANOVA, STATISTICA 6 (StatSoft Inc., Tulsa, USA)]. In the graphs, data are presented as mean with 95% confidence intervals. The exact P value is given except when P<0.001 and P>0.2.

    3. Results

    3.1. Patient characteristics and clinical outcome data

    There were no major inter-group differences in baseline characteristics including history of pulmonary disease (Table 1). No patient had major pneumothorax (>3 cm apical), lobular atelectasis or respiratory insufficiency. One patient in the OFFCAB group initially had a normal post-operative course. This patient died of sepsis and multiorgan failure after 60 days in the ICU due to intestinal perforation by placement of the mediastinal drainage. Since this complication was unrelated to ONCAB or OFFCAB, this patient was excluded from ‘Length of stay’ and ‘Hemoglobin value at discharge’ in Table 2.

    3.2. Central and systemic hemodynamics

    CI tended to be higher (P=0.07) in the OFFCAB group early after surgery (Fig. 1). Since this difference did not reach statistical significance, calculations for each time point were not made. There was no difference in MPAP (P>0.2), PVRI (P>0.2) or RVSWI (P>0.2) between groups; PVRI (P<0.001) decreased and RVSWI increased (P<0.001) over time for all patients. Other parameters for central and systemic hemodynamics are presented in Table 3. No intergroup difference was seen. Heart rate (P<0.001) and MAP (P=0.003) increased, CVP (P<0.001) and PCWP (P<0.001) decreased over time.

    3.3. Blood gas analyses

    There were no differences between groups in arterial oxygen tension, a–v oxygen content difference, hematocrit or venous admixture (P>0.2 for all) (Fig. 2). Arterial oxygen content and hematocrit decreased (P<0.001) and venous admixture increased over time in both groups (P<0.001).

    4. Discussion

    Pulmonary complications are common and well documented after CPB [2]. During the last decade, OFFCAB has become an alternative to ONCAB [4], and it has been suggested that OFFCAB may reduce lung complications after coronary artery bypass surgery.

    4.1. Central hemodynamics

    This prospective, randomized study showed no difference in central hemodynamics during the first 20 h after OFFCAB compared to ONCAB. In a previous study, we found higher CI and lower SVRI at the measurement at 4 h postoperatively, but not later, in OFFCAB patients [11]. In the present study there was a tendency towards a difference in CI between these groups (P=0.07). This may be a statistical type II error and if more patients were included, this study would have verified the difference found previously. However, this borderline significance suggests that the difference in postoperative cardiovascular performance between ONCAB and OFFCAB may be rather minimal.

    Two other investigators report no difference in central hemodynamics comparing ONCAB and OFFCAB [8,10]. Nor did Cox et al. [6] when measuring hemodynamics (MAP, CPV) in a randomized study. In two of these studies either the number of peripheral anastomoses differed significantly between groups [10] or the circumflex area was graftedto a very small extent [6]. In our study, the number of distal anastomoses and grafting of the circumflex were equal.

    In the present study, very few patients required inotropic or vasopressor drugs and it was not possible to draw any conclusions from this. Cox et al. [6] and Louagie et al. [10] both had a trend towards less use of inotropic support in OFFCAB groups.

    4.2. Gas exchange and venous admixture

    We found no difference in gas exchange between groups. In consistency with our study, Cox et al. [6] measured the alveolar–arterial oxygen gradient up to 6 h postoperatively in a randomized ONCAB vs. OFFCAB study with no differences between groups. Cimen et al. [9] performed blood gas analyses (partial arterial oxygen and carbon dioxide pressure, arterial pH and hematocrit) and spirometry in ONCAB and OFFCAB patients without randomization. They found a decline in all parameters most prominent on the first postoperative day. Parameters then increased, but did not reach preoperative values during the hospital stay.

    In a randomized study, Kochamba et al. [7] measured gas exchange (arterial partial oxygen pressure), alveolar–arterial oxygen gradient and venous admixture and found increased venous admixture in both groups immediately postoperatively, but a larger increase in the ONCAB group. In this study patients who required grafting to the circumflex area were excluded due to problems with the stabilization technique. This might have influenced the results since grafting the circumflex area most likely has the greatest effect on hemodynamics.

    Tschernko et al. [8] randomized patients to three groups: ONCAB with total vital capacity maneuver (lung inflation to 40 cm H2O three times before termination of CPB), ONCAB with no total vital capacity maneuver, and OFFCAB. Venous admixture increased in all groups during and up to 4 h after surgery but increased significantly less in the OFFCAB group. The total vital capacity maneuver resulted in decreased shunting after termination of CPB and at the end of surgery but not at extubation. In our study, we made the last measurement on the morning after surgery, approximately 16 h after extubation not seeing any differences between groups. In the Tschernko study, the last measurement was made 4 h after extubation possibly explaining the difference with our study.

    One limitation with our study is that we did not register atelectases, for example with CT. Neither did we measure lung function with spirometry or pulmonary mechanics with compliance or airway pressure.

    There were no patients with severe pulmonary disease included in the study. Guler and colleagues [13] show that patients with severe chronic obstructive pulmonary disease (COPD) have higher forced expiratory volumes two months after surgery if operated OFFCAB. Possibly patients with preoperatively reduced lung function, such as COPD, might be more sensitive to the damaging effects of surgery, anesthesia or CPB, and might benefit from OFFCAB.

    In a recently published meta-analysis with 3369 patients, Cheng and co-workers [14] show less use of inotropic drugs and less respiratory infections in OFFCAB patients (Cheng DC. Anesthesiology 2005;102:188–203). It is possible that the decrease in respiratory infections might be linked to a difference in pulmonary mechanics. This will have to be investigated in a further study.

    In conclusion, this study could not show a difference in pulmonary gas exchange or central hemodynamics between ONCAB and OFFCAB patients. Our results suggest that itis the single effect of, or the combination of anesthesia, mechanical ventilation and surgical trauma that it responsible for increased venous admixture postoperatively and not cardiopulmonary bypass per se.

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