Scandinavian Journal of Clinical & Laboratory Investigation, 2014; 74: 37–43
ORIGINAL ARTICLE
Cardiopulmonary bypass decreases pulmonary vascular resistance index after coronary artery bypass surgery
VESA TOIKKANEN1, TIMO RINNE2, HEINI HUHTALA3, JARI LAURIKKA1, HELENA PORKKALA2, MATTI TARKKA1 & ARI MENNANDER1 1Heart
Center, Tampere University Hospital and University of Tampere, 2Division of Cardiac Anesthesia, Heart Center, Tampere University Hospital, Tampere, and 3School of Health Sciences, University of Tampere, Tampere, Finland
Abstract Background. Decreased pulmonary vascular resistance index (PVRI) reflects favorable postoperative pulmonary circulation after coronary artery bypass grafting. This randomized study investigated whether cardiopulmonary bypass (CPB) impacts PVRI after coronary artery bypass grafting. Material and methods. A total of 47 patients undergoing coronary artery bypass grafting were randomized into four groups according to the ventilation and surgical technique: (1) No ventilation group, with intubation tube detached from the ventilator, (2) low tidal volume group, with continuous low tidal volume ventilation, (3) continuous 10 cm H2O positive airway pressure (CPAP) group, and (4) randomly selected patients undergoing surgery without CPB. Oxygenation index, pulmonary shunt, alveolar-arterial oxygen gradient and PVRI were determined. PVRI was calculated as the transpulmonary pressure gradient divided by cardiac index multiplied by 80. Results. During the first postoperative morning there were no statistical differences in oxygenation index, pulmonary shunt or alveolar-arterial oxygen gradient between the groups, while PVRI remained elevated in patients without CPB as compared with patients with CPB (263 ⫾ 98 vs. 122 ⫾ 84, dyne-s-cm⫺5, respectively, p ⬍ 0.001). PVRI decreased in all patients with CPB regardless of ventilation technique. In contrast, elevated postoperative PVRI values were predictive for patients without CPB (AUC 0.786; SE 0.043; p ⬍ 0.001; 95% CI. 0.701–0.870). Conclusions. Modified ventilation does not affect PVRI in elective patients with healthy lungs during CPB. Instead, CPB per se may have an important role on diminished PVRI. We suggest that CPB preserves pulmonary arterial endothelial integrity. Key Words: Coronary artery bypass grafting, cardiopulmonary bypass, pulmonary function, ventilation
Introduction Postoperative pulmonary dysfunction remains of major concern while cardiopulmonary bypass (CPB) is used during coronary artery bypass surgery [1]. Mechanical lung ventilation is halted during CPB, and pulmonary blood flow is maintained only to a relatively small extent via the bronchial arteries [2]. Bronchial lung circulation is maintained by direct arterial circulation from the aorta to the lungs in addition to the circulation via the pulmonary artery and veins to the lung. The circulation via the pulmonary arteries and veins is arrested during CPB, though the lungs are constantly flushed from the aorta; the lungs do not suffer from ischemia during CPB, but are devoid of excessive volume load. This
is clearly a distinctive difference compared with patients without CPB, for whom both heart and lungs are under constant pressure and volume flow during surgery. Diminished pulmonary arterial flow is thought to protect the lungs from excessive pulmonary circulation after CABG. Prompt reestablishment of normal pulmonary arterial blood flow after weaning from CPB may cause pulmonary arterial endothelial dysfunction mirroring possible detrimental pulmonary outcome [3,4]. Pulmonary vascular resistance reflects postoperative pulmonary dysfunction after coronary artery bypass grafting [4]. It is not clear whether constant ventilation would impact pulmonary circulation and pulmonary vascular resistance.
Correspondence: Ari Mennander, Department of Cardiothoracic Surgery, Heart Center, Tampere University Hospital, Teiskontie 35, Box 2000, 33521 Tampere, Finland. Tel: ⫹ 358331164945. Fax: ⫹ 358331165756. E-mail: [email protected] (Received 6 April 2013 ; accepted 13 October 2013) ISSN 0036-5513 print/ISSN 1502-7686 online © 2014 Informa Healthcare DOI: 10.3109/00365513.2013.856032
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The available data remain controversial as to whether postoperative pulmonary circulation may be affected during surgery without CPB [5]. Decreasing both lung perfusion and ventilation may diminish pulmonary circulation by preserving pulmonary artery endothelial integrity [6]. In this prospective randomized study, we investigated whether CPB without lung ventilation during coronary artery bypass grafting impacts pulmonary vascular resistance index (PVRI). In addition, we studied whether modified ventilation during CPB affects PVRI as compared with patients without CPB.
Methods Patient selection The study was approved by the Tampere University Hospital Ethics Committee (R04100, 5/25/2004) complying with the principles laid down in the Declaration of Helsinki (Recommendations guiding physicians in biomedical research involving human subjects, adopted by the 18th World Medical Assembly, Helsinki, Finland, June 1964), and all patients gave written consent. Forty-seven consecutive and elective primary CABG patients were enrolled in the study. Careful attention was paid on patient selection and factors which could have an effect on inflammatory status or pulmonary function. The exclusion criteria were as follows: Previous malignancy, pre-existent pulmonary disease, pulmonary hypertension with systolic pulmonary arterial pressure (PAP) ⬎ 40 mmHg, depressed left ventricular ejection function (LVEF) ⬍ 50%, smoking or myocardial infarction during the previous 3 months, cardiac decompensation period, acute coronary syndrome, infection, use of corticosteroids or cyclooxygenase-2 (COX-2) inhibitors within 1 month. Randomization was made using sealed blinded envelopes.
oxygen concentration (FiO2) was initially adjusted to 0.50, with a tidal volume of 7–8 mL/kg, and frequency adjusted for normocapnia. Three groups were randomized according to ventilation management during CPB, and a fourth group was randomly selected to undergo surgery with normal ventilation without CPB. In the no ventilation (NV) group, the intubation tube was detached from the ventilator after achieving full flow CPB. In the low tidal ventilation (LTV) group, continuous mechanical ventilation (3–4 mL/kg) was employed. In the continuous positive airway pressure (CPAP) group, a CPAP level of 10 cmH2O was applied, using an adjustable flow generator WisperFlow (Respironics, Inc. Youngwood, PA, USA). In all patients with CPB, a manual recruitment maneuver was carried out at the end of CPB, keeping airway pressure up to 40 cmH2O for 15 s. At the rest of the time, a positive end-expiratory pressure (PEEP) level of 5 cmH2O was applied. CPB was established with cannulation, including aortic and right atrial two-stage lines. Non-pulsatile perfusion flow (2.4 L/m2) with mild hypothermia (34°C) was provided using a roller pump system Stöckert S3 (Sorin Group Deutchland GmbH, Germany). Alpha-stat blood gas management was applied during CPB. A tubing set with biopassive coating and hollow fiber oxygenator D 903 Avant Phisio (Dideco S.p.A, Mirandola, Italy) was primed with 1500 mL of Ringer’s acetate. Tranexamic acid was used as an antifibrinolytic therapy. Cardioprotection was provided with standard cold blood cardioplegia. Both antegrade and retrograde cardioplegia cannulas were inserted. The first antegrade cardioplegic infusion was given for two minutes, followed by retrograde cardioplegia for another 2 min. Subsequent retrograde cardioplegia infusions were delivered after the completion of each distal coronary artery bypass graft anastomosis for 1 min, and final warm retrograde cardioplegia (37°C) was given during 3 min before aortic declamping.
Anesthesia Radial and pulmonary arterial lines were inserted for hemodynamic monitoring before commencing anesthesia. Propofol (0.5–1.0 mg/kg), sufentanil (0.8–1.0 μg/kg) and rocuronium were used for the induction of anesthesia. Propofol infusion was continued with a rate of 50–80 mg/kg/min and sufentanil with 0.03–0.05 μg/kg/min for maintenance, supplemented with midazolam boluses as necessary. Halogenated anesthetic gases were avoided due to possible influence on pulmonary hemodynamics. Occasional hypertensive episodes were controlled with nitroglycerine or labetalol. Ventilation of the lungs was provided with a volume-controlled ventilator Dräger Julian Plus (Dräger Medizintechnik GmbH, Germany). Inspired
Surgical approach The surgical technique included coronary artery bypass surgery either with or without CPB [5]. Briefly, a median sternotomy was performed in all patients. The left internal mammary artery was harvested in all cases, and pleurostomy was caseselective. In patients with CPB, all anastomoses were completed during a single period of aortic crossclamping. In patients without CPB, stabilization and exposure of the target vessel was achieved using a combination of pericardial stay sutures, deep pericardial stitch and mechanical stabilator Octopus (Medtronic, Minneapolis, MN, USA). A surgical blower-humidifier device (Axius™, Maquet, NJ, USA) was routinely employed. Target vessel shunting
Pulmonary vascular resistance index
significant and results are presented as means ⫾ SD. Power calculation was set to display the 95% confidence interval and performed with statistical software (PowerAndPrecision 4.0, Biostat, Englewood, NJ, USA).
was selective, depending on the amount of bleeding during completion of anastomoses [5]. Postoperative management Postoperatively, all patients were observed by protocol. Weaning from the ventilator was undertaken when the patient was mentally cooperative, rewarmed and hemodynamically stable, chest tube drainage was ⬍ 100 mL/h and pulmonary function was adequate (PaO2 ⬎ 9 kPa with FiO2 ⱕ 0.45).
Results Demographics and perioperative data There were no major differences between groups with respect to preoperative variables (Table I). A decreased number of distal coronary bypass anastomoses were performed in patients without CPB as compared to patients with CPB (3.6 ⫾ 0.7 vs. 2.4 ⫾ 1.1, p ⫽ 0.012) – though other perioperative parameters including the duration of the operations – were comparable.
Sample collection Blood gas analysis and measurement of hemodynamic parameters to define oxygenation index, pulmonary shunt, alveolar-arterial oxygen gradient and PVRI were calculated at the following time points: 10 min after induction of anesthesia (T1), 1 h after restarting normal ventilation/return of flow in all grafts (T2), 6 h after restarting ventilation/reflow (T3), 1 h after extubation (T4) and during the first postoperative morning (T5). Alveolar-arterial oxygen gradients were measured after induction of anesthesia at FiO2 of 0.45 (T1) and after extubation at FiO2 of 0.35 (T2).
Oxygenation index Oxygenation index was defined as mean arterial oxygen tension (PaO2) divided by FiO2 (PaO2/FiO2, kPa) and shown at various time points in Table II. A decrease of PaO2/FiO2 occurred already at T2, but in the NV group this was not statistically significant. PaO2/FiO2 gradually tended to decrease in all groups, without statistical differences between them.
Statistical analysis Statistical analysis was performed with SPSS software (SPSS Inc, Chicago, IL, USA). A nonprametric Kruskall-Wallis test was employed to account for comparison of changes in pulmonary measurements between all groups. The changes in pulmonary function in patients with CPB were compared with patients without CPB and within all groups by the nonparametric Mann-Whitney U test. The predictive value of PVRI to indicate patients who underwent CABG without CPB was assessed by receiver operating characteristic (ROC) curve. P-values less than 0.05 were considered statistically
Alveolar-arterial oxygen gradient Alveolar-arterial oxygen gradient (mmHg) increased in all groups between at T2 (Table III). The gradient returned towards the base line values 6 h after restoration of ventilation/reflow at T3, and in the first postoperative morning there was no impairment compared to the base line T1. In the LTV group, the gradient was lower at T4 and T5 compared to T1. There were no statistical differences between the groups observed at each time point.
Table I. Patient demographics and perioperative data. With CPB (n ⫽ 37) CPAP (n ⫽ 10) LTV (n ⫽ 13) NV (n ⫽ 14) Age (years) Sex (M/F) Height (cm) Weight (kg) LVEF (%) Number of bypasses (n) Perfusion (min) Aortic clamping (min) Mechanical ventilation (min)
66.7 ⫾ 7.3 8/2 170.7 ⫾ 8.0 81.6 ⫾ 8.8 65 ⫾ 8 3.4 ⫾ 1.1 92 ⫾ 23 74 ⫾ 21 612 ⫾ 322
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72.0 ⫾ 7.6 9/4 168 ⫾ 6.9 83.6 ⫾ 18.9 61 ⫾ 5 3.5 ⫾ 0.7 93 ⫾ 17 76 ⫾ 12 615 ⫾ 168
67.6 ⫾ 9.2 11/3 168.7 ⫾ 7.7 77.7 ⫾ 15.3 62 ⫾ 7 3.6 ⫾ 0.7 99 ⫾ 18 76 ⫾ 17 564 ⫾ 236
Without CPB (n ⫽ 10)
p-value
70.8 ⫾ 7.8 7/3 168.1 ⫾ 8.7 73.9 ⫾ 12.1 58 ⫾ 7 2.4 ⫾ 1.1 – – 575 ⫾ 211
0.342 0.911 0.882 0.427 0.246 0.012 0.606 0.951 0.930
CPAP, continuous positive airway pressure; LTV, low tidal volume; NV, no ventilation; LVEF, left ventricular ejection fraction.
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V. Toikkanen et al. Table II. Oxygenation index (PaO2/FiO2, kPa). With CPB (n ⫽ 37)
After induction of anesthesia 1 h after reventilation/reflow 6 h after reventilation/reflow 1 h after extubation 1st postoperative morning
CPAP (n ⫽ 10)
LTV (n ⫽ 13)
NV (n ⫽ 14)
Without CPB (n ⫽ 10)
p-value
46.0 ⫾ 15.9 33.7 ⫾ 14.8 42.0 ⫾ 10.4 45.3 ⫾ 15.5 34.9 ⫾ 6.4
43.0 ⫾ 11.3 30.7 ⫾ 9.2 37.3 ⫾ 6.8 37.5 ⫾ 9.1 36.0 ⫾ 7.6
46.9 ⫾ 14.7 37.8 ⫾ 11.8 35.6 ⫾ 9.9 41.3 ⫾ 14.6 36.5 ⫾ 8.7
46.6 ⫾ 14.7 37.8 ⫾ 11.8 35.6 ⫾ 9.9 41.3 ⫾ 14.6 40.3 ⫾ 9.8
0.887 0.789 0.427 0.705 0.343
CPAP, continuous positive airway pressure; LTV, low tidal volume; NV, no ventilation.
Table III. Alveolar-arterial oxygen gradient (mmHg). With CPB (n ⫽ 37) CPAP (n ⫽ 10) LTV (n ⫽ 13) NV (n ⫽ 14) After induction of anesthesia 1 h after reventilation/reflow 6 h after reventilation/reflow 1 h after extubation 1st postoperative morning
14.4 ⫾ 6.9 22.4 ⫾ 7.5 16.7 ⫾ 5.3 10.4 ⫾ 6.6 12.9 ⫾ 6.1
17.6 ⫾ 4.2 23.9 ⫾ 4.9 18.5 ⫾ 6.0 14.1 ⫾ 4.2 13.7 ⫾ 5.2
16.4 ⫾ 6.1 24.1 ⫾ 8.1 17.6 ⫾ 5.6 13.7 ⫾ 3.2 17.0 ⫾ 7.5
Without CPB (n ⫽ 10)
p-value
14.8 ⫾ 7.1 20.2 ⫾ 5.0 18.2 ⫾ 5.0 12.7 ⫾ 5.4 14.3 ⫾ 5.0
0.967 0.852 0.672 0.495 0.383
CPAP, continuous positive airway pressure; LTV, low tidal volume; NV, no ventilation.
Pulmonary shunt Pulmonary shunt (Qs/Qt, %) increased in all study groups between at T2 (Table IV).The shunt decreased thereby in every group, and in patients without CPB, the shunt was observed to decrease further till the first postoperative morning at T5 as compared with the base line T1. However, the findings between the study groups were not different at any time point.
Pulmonary vascular resistance index PVRI was calculated as the transpulmonary pressure gradient divided by cardiac index multiplied by 80. Regardless of ventilation, the pulmonary vascular resistance index PVRI (dynes-s-cm⫺5) decreased during CPB postoperatively, but remained elevated in patients without CPB (Figure 1). The cardiac index was comparable between the groups (data not shown), and the observation was related to differences in the transpulmonary pressure gradient.
At base line T1, PVRI remained similar among the CPAP, LTV, NV groups and patients without CPB (318 ⫾ 76, 291 ⫾ 111, 269 ⫾ 109 and 197 ⫾ 108, dynes-s-cm⫺5, respectively). PVRI decreased in patients with CPB at T3 as compared with patients without CPB (167 ⫾ 90, 322 ⫾ 157, dynes-s-cm⫺5, respectively, p ⬍ 0.002). The decrease endured till the last measured time point T5 in CPAP, LTV, NV groups, regardless of modified ventilation during CPB (100 ⫾ 30, 119 ⫾ 59, 140 ⫾ 122, dynes-s-cm⫺5, respectively). In contrast, PVRI remained unchanged in patients without CPB till time point T5 (263 ⫾ 99 dynes-s-cm⫺5). At time points T1–T5, for the effect size (group means of 194.7 vs. 264.3), SD (115.8 and 115.9), patient number (181 vs. 44), alpha (0.050, 2-tailed), the power was 94.3%. At time point T3, for the effect size of PVRI in patients with CPB vs. without CPB (group means of 167.2 vs. 322.4), SD (90.6 and 157.9), patient number (36 vs. 9), alpha (0.050, 2-tailed), the power was 81.2%. At time point T4 for
Table IV. Pulmonary shunt Qs/Qt (%). With CPB (n ⫽ 37)
After induction of anesthesia 1 h after reventilation/reflow 6 h after reventilation/reflow 1 h after extubation 1st postoperative morning
CPAP (n ⫽ 10)
LTV (n ⫽ 13)
NV (n ⫽ 14)
11.0 ⫾ 5.5 17.8 ⫾ 9.1 11.9 ⫾ 6.1 10.1 ⫾ 7.3 11.9 ⫾ 5.9
11.0 ⫾ 4.9 16.4 ⫾ 5.9 12.2 ⫾ 3.7 14.2 ⫾ 5.1 13.6 ⫾ 6.1
10.2 ⫾ 4.8 17.1 ⫾ 6.2 13.4 ⫾ 5.6 13.8 ⫾ 6.2 12.9 ⫾ 4.3
Without CPB (n ⫽ 10)
p-value
11.3 ⫾ 7.9 15.3 ⫾ 6.0 12.5 ⫾ 4.9 12.6 ⫾ 8.1 9.6 ⫾ 5.7
0.561 0.484 0.865 0.308 0.395
CPAP, continuous positive airway pressure; LTV, low tidal volume; NV, no ventilation.
Pulmonary vascular resistance index
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with patients without CPB (AUC 0.786; SE 0.043; p ⬍ 0.001; 95% CI. 0.701–0.870). Outcome There were three resternotomy operations due to postoperative bleeding; one patient with CPAP, NV, and without CPB. No patients were excluded from the study because of reintervention or complication. The duration of mechanical ventilation and the length of stay were similar among all groups. One patient in the LTV group experienced a stroke and one patient without CPB developed multiorgan failure after uneventful immediate postoperative course and died. Figure 1. Pulmonary vascular resistance index (PVRI) in patients with CPB and without CPB. Horizontal lines of the box show the median. Lines above and below the box indicate the 75th and 25th percentiles, respectively. Whiskers above and below show the maximum and minimum values, respectively. T1 ⫽ 10 min after induction of anesthesia,T2 ⫽ 1 h after restarting normal ventilation/ reflow, T3 ⫽ 6 h after restarting ventilation/reflow, T4 ⫽ 1 h after extubation, T5 ⫽ first postoperative morning.
the effect size of PVRI in patients with CPB vs. without CPB (group means of 118.8 vs. 274.8), SD (63.4 and 108.4), patient number (35 vs. 9), alpha (0.050, 2-tailed), the power was 98.4%. At time point T5, for the effect size of PVRI in patients with CPB vs. without CPB (group means of 121.9 vs. 262.8), SD (83.8 and 98.4), patient number (37 vs. 8), alpha (0.050, 2-tailed), the power was 96.3%. ROC curve analysis The diagnostic performance of PVRI associated with patients who underwent coronary artery bypass grafting without CPB was assessed by ROC analysis (Figure 2). Increased PVRI values were associated
Figure 2. Receiver operating characteristic curve (ROC) analysis showing that increased PVRI was associated with patients without CPB (AUC 0.786; SE 0.043; p ⬍ 0.001; 95% CI. 0.701–0.870).
Discussion We show in this study that CPB during coronary artery bypass grafting decreases PVRI compared to patients without CPB. The decrease in PVRI is unrelated to additional ventilation or major pulmonary dysfunction during CPB. Early ventilation parameters such as oxygenation index, pulmonary shunt and alveolar-arterial oxygen gradient were comparable to patients without CPB. CPB afforded a resting state of pulmonary arterial circulation owing to decreased pulmonary artery flow leading to decreased PVRI. Due to the arrested circulation in patients with CPB, the heart and the lungs have minimal oxygen consumption and circulatory resistance in contrast to the patients without CPB who must maintain constant cardiac and pulmonary circulatory flow during surgery. Decreased PVRI indicates the preservation of endothelial vasorelaxation after CABG and reperfusion [4]. Strategies aiming at preserving pulmonary endothelial integrity may enhance recovery after CPB. Preservation of the vasorelaxation of the pulmonary arterial endothelium to acetylcholine and the associated decrease of PVRI may predict reduced postoperative lung dysfunction after CPB [7,8]. An effect of CPB on pulmonary dysfunction following cardiac surgery has been speculated [1,9,10]. Lamarche et al. demonstrated in an experimental setting that CPB with reperfusion altered pulmonary endothelial relaxation to acetylcholine, in contrast to CPB without reperfusion [4], suggesting that pulmonary arterial endothelial dysfunction is dependent on pulmonary arterial flow. However, as pointed by the authors, the selective impairment of relaxation to acetylcholine is not associated with increased irreversible endothelial damage since histological outcome of endothelium remained intact after CPB and reperfusion [4]. Though impairment of relaxation to acetylcholine is suggestive for temporal reperfusion injury after CPB [11], pulmonary ischemia reperfusion injury does not seem to be detrimental, while
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at least some bronchial arterial flow is preserved during CPB [2,7]. According to a few previous studies, CPB improves pulmonary gas exchange postoperatively in some cardiac surgery patients [12–15]. Nevertheless, the plausible protective role of continuous ventilation during CPB remains controversial with regard to pulmonary dysfunction [16–18]. In our study, controlling ventilation during CPB did not influence the decrease in PVRI. This is in accordance with a study by Gagnon et al. [7], in which PVRI changes were not observed in patients during CPB despite additional ventilation as compared with non-ventilated patients [7]. Additional ventilation does not increase protection from plausible pulmonary dysfunction due to CPB. Instead, decreased pulmonary arterial flow may be secured during relaxation of lungs with CPB. Strategies aiming to preserve pulmonary arterial endothelial integrity – such as antithrombotic treatment – may enhance the protection after CPB. For example, heparin-coated circuits utilized during CPB may impact PVRI; heparin-coated circuits enhance hemodynamic outcome after CPB, again suggesting that vascular endothelial protection may be beneficial to pulmonary function [19]. Supporting the above, unchanged PVRI was observed in patients undergoing CABG without CPB with constant normal ventilation and pulmonary arterial flow [5]. We compared the PVRI values of patients without CPB to those patients with CPB. As shown in Figure 1, PVRI values remained relatively constant in patients without CPB in contrast to significant decreased PVRI values observed in patients with CPB. Avoiding CPB did not add to pulmonary protection as compared with CABG surgery with CPB [5]. In addition to constant ventilation, CABG without CPB requires manipulation of the working heart during surgery, affecting both preload and afterload thus maintaining elevated PVRI [20]. Pulmonary blood flow and right ventricle output remain stable during surgery without CPB, explaining in part the unchanged PVRI in these patients. Comparable lung volume and cardiac output in patients with CPB and decreased PVRI hint that strategies for limiting postoperative pulmonary dysfunction associated with arterial endothelial protection after surgery may be beneficial [5]. Our study may be important during the planning of elective coronary artery bypass grafting; the preference to use CPB in these patients may prevail in order to obtain decreased pulmonary vascular resistance. PVRI was chosen as the endpoint describing circulatory resistance. There is a vast interest in the surgical community to identify a clinically feasible and quantifiable parameter describing vascular relaxation during surgery. PVRI is measured and followed during cardiac surgery, as it reveals the end-systolic capacity of the right side of the heart
on-time. PVRI is one of the most reliable parameter in predicting a beneficial outcome after cardiac surgery [21]. In this study, we showed that an impact on PVRI can be exerted by the choice of surgical technique. It is however, beyond the scope of this study to show that decreased PVRI is associated with long-term beneficial outcome. The limitations of our study should be mentioned. The small sample size of our study precludes assessing any differences in the clinical outcome. Only stable patients with preoperatively impeccable lung function were included. We could not perform histological analysis of the pulmonary arterial tree. Our strict inclusion criteria provided comparable patients, since smoking, anti-inflammatory medication and recent acute events were among the exclusion criteria. The role of inflammation associated with CPB and PVRI also remains to be established [22]. The purpose of the study was to compare PVRI in patients with CPB vs. without CPB. According to power calculation in comparing PVRI in patients with CPB vs. without CPB, from 81–98% of studies would be expected to yield a significant effect, rejecting the null hypothesis that the two group means are equal. Differences of ventilation strategies did not interfere with the finding that PVRI decreased in patients with CPB, in contrast to patients without CPB. The ventilatory parameters remained comparable within all patients with CPB, regardless of ventilation adjustment. Increasing the number of patients with varied ventilation strategies is safe in patients with CPB, and may be regarded as fortifying the results of this study. In conclusion, our findings suggest that modified ventilation techniques during CPB do not affect pulmonary circulation during the first 24 h after elective CABG in patients with normal lung function. Rather, CPB per se may have an important role on diminished PVRI. We find that the investigation of pulmonary endothelial integrity after CPB on PVRI is warranted. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. The trial was supported by grants from the Competitive Research Funding of the Pirkanmaa Hospital District, Tampere University Hospital and Tampere Tuberculosis Foundation, Tampere, Finland.
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[13] Reis MD, Struijs A, Koetsier P, van Thiel R, Schepp R, Hop W, Klein J, Lachmann B, Bogers AJ, Gommers D. Open lung ventilation improves functional residual capacity after extubation in cardiac surgery. Crit Care Med 2005; 33:2253–8. [14] Celebi S, Köner Ö, Menda F, Korkut K, Suzer K, Cakar N. The pulmonary and hemodynamic effects of two different recruitment maneuvers after cardiac surgery. Anesth Analg 2007;104:384–90. [15] Chaney MA, Nikolov MP, Blakeman BP, Bakhos M. Protective ventilation attenuates postoperative pulmonary dysfunction in patients undergoing cardiopulmonary bypass. J Cardiothoracic Vasc Anest 2000;14:514–8. [16] Loeckinger A, Kleinsasser A, Lindner K, Margreiter J, Keller C, Hoermann C. Continuous positive airway pressure at 10 cm H2O during cardiopulmonary bypass improves postoperative gas exchange. Anesth Analg 2000; 91:522–7. [17] Altmay E, Karaca P, Yurtseven N, Ozkul V, Aksoy T, Ozler A, Canik S. Continuous positive airway pressure does not improve lung function after cardiac surgery. Can J Anesth 2006;53:919–25. [18] Schreiber J-U, Lance MD, de Korte M, Artmann T, Aleksic I, Kranke P. The effect of different lung-protective strategies in patients during cardiopulmonary bypass: a meta-analysis and semi-quantitative review of randomized trials. J Cardiothoracic Vasc Anest 2012;26:448–54. [19] de Vroege R, Huybregts R, van Oeveren W, van Klarenbosch J, Linley G, Mutlu J, Jansen E, Hack E, Eijsman L, Wildevuur C. The impact of heparin-coated circuits on hemodynamics during and after cardiopulmonary bypass. Artif Org 2005;29:490–7. [20] Staton GW, Williams WH, Mahoney EM, Hu J, Chu H, Duke PG, Puskas JD. Pulmonary outcomes of off-pump vs. on- pump coronary artery bypass surgery in a randomized trial. Chest 2005;127:892–901. [21] Schulze-Neick I, Li J, Penny DJ, Redington AN. Pulmonary vascular resistance after cardiopulmonary bypass in infants: effect on postoperative recovery. J Thorac Cardiovasc Surg 2001;121:1033–9. [22] Wan S, DeSmet JM, Barvais L, Goldstein M, Vincent JL, LeClerc JL. Myocardium is a major source of proinflammatory cytokines in patients undergoing cardiopulmonary bypass, J Thorac Cardiovasc Surg 1996;112:806–11.
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ORIGINAL ARTICLE
Cardiopulmonary bypass decreases pulmonary vascular resistance index after coronary artery bypass surgery
VESA TOIKKANEN1, TIMO RINNE2, HEINI HUHTALA3, JARI LAURIKKA1, HELENA PORKKALA2, MATTI TARKKA1 & ARI MENNANDER1 1Heart
Center, Tampere University Hospital and University of Tampere, 2Division of Cardiac Anesthesia, Heart Center, Tampere University Hospital, Tampere, and 3School of Health Sciences, University of Tampere, Tampere, Finland
Abstract Background. Decreased pulmonary vascular resistance index (PVRI) reflects favorable postoperative pulmonary circulation after coronary artery bypass grafting. This randomized study investigated whether cardiopulmonary bypass (CPB) impacts PVRI after coronary artery bypass grafting. Material and methods. A total of 47 patients undergoing coronary artery bypass grafting were randomized into four groups according to the ventilation and surgical technique: (1) No ventilation group, with intubation tube detached from the ventilator, (2) low tidal volume group, with continuous low tidal volume ventilation, (3) continuous 10 cm H2O positive airway pressure (CPAP) group, and (4) randomly selected patients undergoing surgery without CPB. Oxygenation index, pulmonary shunt, alveolar-arterial oxygen gradient and PVRI were determined. PVRI was calculated as the transpulmonary pressure gradient divided by cardiac index multiplied by 80. Results. During the first postoperative morning there were no statistical differences in oxygenation index, pulmonary shunt or alveolar-arterial oxygen gradient between the groups, while PVRI remained elevated in patients without CPB as compared with patients with CPB (263 ⫾ 98 vs. 122 ⫾ 84, dyne-s-cm⫺5, respectively, p ⬍ 0.001). PVRI decreased in all patients with CPB regardless of ventilation technique. In contrast, elevated postoperative PVRI values were predictive for patients without CPB (AUC 0.786; SE 0.043; p ⬍ 0.001; 95% CI. 0.701–0.870). Conclusions. Modified ventilation does not affect PVRI in elective patients with healthy lungs during CPB. Instead, CPB per se may have an important role on diminished PVRI. We suggest that CPB preserves pulmonary arterial endothelial integrity. Key Words: Coronary artery bypass grafting, cardiopulmonary bypass, pulmonary function, ventilation
Introduction Postoperative pulmonary dysfunction remains of major concern while cardiopulmonary bypass (CPB) is used during coronary artery bypass surgery [1]. Mechanical lung ventilation is halted during CPB, and pulmonary blood flow is maintained only to a relatively small extent via the bronchial arteries [2]. Bronchial lung circulation is maintained by direct arterial circulation from the aorta to the lungs in addition to the circulation via the pulmonary artery and veins to the lung. The circulation via the pulmonary arteries and veins is arrested during CPB, though the lungs are constantly flushed from the aorta; the lungs do not suffer from ischemia during CPB, but are devoid of excessive volume load. This
is clearly a distinctive difference compared with patients without CPB, for whom both heart and lungs are under constant pressure and volume flow during surgery. Diminished pulmonary arterial flow is thought to protect the lungs from excessive pulmonary circulation after CABG. Prompt reestablishment of normal pulmonary arterial blood flow after weaning from CPB may cause pulmonary arterial endothelial dysfunction mirroring possible detrimental pulmonary outcome [3,4]. Pulmonary vascular resistance reflects postoperative pulmonary dysfunction after coronary artery bypass grafting [4]. It is not clear whether constant ventilation would impact pulmonary circulation and pulmonary vascular resistance.
Correspondence: Ari Mennander, Department of Cardiothoracic Surgery, Heart Center, Tampere University Hospital, Teiskontie 35, Box 2000, 33521 Tampere, Finland. Tel: ⫹ 358331164945. Fax: ⫹ 358331165756. E-mail: [email protected] (Received 6 April 2013 ; accepted 13 October 2013) ISSN 0036-5513 print/ISSN 1502-7686 online © 2014 Informa Healthcare DOI: 10.3109/00365513.2013.856032
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The available data remain controversial as to whether postoperative pulmonary circulation may be affected during surgery without CPB [5]. Decreasing both lung perfusion and ventilation may diminish pulmonary circulation by preserving pulmonary artery endothelial integrity [6]. In this prospective randomized study, we investigated whether CPB without lung ventilation during coronary artery bypass grafting impacts pulmonary vascular resistance index (PVRI). In addition, we studied whether modified ventilation during CPB affects PVRI as compared with patients without CPB.
Methods Patient selection The study was approved by the Tampere University Hospital Ethics Committee (R04100, 5/25/2004) complying with the principles laid down in the Declaration of Helsinki (Recommendations guiding physicians in biomedical research involving human subjects, adopted by the 18th World Medical Assembly, Helsinki, Finland, June 1964), and all patients gave written consent. Forty-seven consecutive and elective primary CABG patients were enrolled in the study. Careful attention was paid on patient selection and factors which could have an effect on inflammatory status or pulmonary function. The exclusion criteria were as follows: Previous malignancy, pre-existent pulmonary disease, pulmonary hypertension with systolic pulmonary arterial pressure (PAP) ⬎ 40 mmHg, depressed left ventricular ejection function (LVEF) ⬍ 50%, smoking or myocardial infarction during the previous 3 months, cardiac decompensation period, acute coronary syndrome, infection, use of corticosteroids or cyclooxygenase-2 (COX-2) inhibitors within 1 month. Randomization was made using sealed blinded envelopes.
oxygen concentration (FiO2) was initially adjusted to 0.50, with a tidal volume of 7–8 mL/kg, and frequency adjusted for normocapnia. Three groups were randomized according to ventilation management during CPB, and a fourth group was randomly selected to undergo surgery with normal ventilation without CPB. In the no ventilation (NV) group, the intubation tube was detached from the ventilator after achieving full flow CPB. In the low tidal ventilation (LTV) group, continuous mechanical ventilation (3–4 mL/kg) was employed. In the continuous positive airway pressure (CPAP) group, a CPAP level of 10 cmH2O was applied, using an adjustable flow generator WisperFlow (Respironics, Inc. Youngwood, PA, USA). In all patients with CPB, a manual recruitment maneuver was carried out at the end of CPB, keeping airway pressure up to 40 cmH2O for 15 s. At the rest of the time, a positive end-expiratory pressure (PEEP) level of 5 cmH2O was applied. CPB was established with cannulation, including aortic and right atrial two-stage lines. Non-pulsatile perfusion flow (2.4 L/m2) with mild hypothermia (34°C) was provided using a roller pump system Stöckert S3 (Sorin Group Deutchland GmbH, Germany). Alpha-stat blood gas management was applied during CPB. A tubing set with biopassive coating and hollow fiber oxygenator D 903 Avant Phisio (Dideco S.p.A, Mirandola, Italy) was primed with 1500 mL of Ringer’s acetate. Tranexamic acid was used as an antifibrinolytic therapy. Cardioprotection was provided with standard cold blood cardioplegia. Both antegrade and retrograde cardioplegia cannulas were inserted. The first antegrade cardioplegic infusion was given for two minutes, followed by retrograde cardioplegia for another 2 min. Subsequent retrograde cardioplegia infusions were delivered after the completion of each distal coronary artery bypass graft anastomosis for 1 min, and final warm retrograde cardioplegia (37°C) was given during 3 min before aortic declamping.
Anesthesia Radial and pulmonary arterial lines were inserted for hemodynamic monitoring before commencing anesthesia. Propofol (0.5–1.0 mg/kg), sufentanil (0.8–1.0 μg/kg) and rocuronium were used for the induction of anesthesia. Propofol infusion was continued with a rate of 50–80 mg/kg/min and sufentanil with 0.03–0.05 μg/kg/min for maintenance, supplemented with midazolam boluses as necessary. Halogenated anesthetic gases were avoided due to possible influence on pulmonary hemodynamics. Occasional hypertensive episodes were controlled with nitroglycerine or labetalol. Ventilation of the lungs was provided with a volume-controlled ventilator Dräger Julian Plus (Dräger Medizintechnik GmbH, Germany). Inspired
Surgical approach The surgical technique included coronary artery bypass surgery either with or without CPB [5]. Briefly, a median sternotomy was performed in all patients. The left internal mammary artery was harvested in all cases, and pleurostomy was caseselective. In patients with CPB, all anastomoses were completed during a single period of aortic crossclamping. In patients without CPB, stabilization and exposure of the target vessel was achieved using a combination of pericardial stay sutures, deep pericardial stitch and mechanical stabilator Octopus (Medtronic, Minneapolis, MN, USA). A surgical blower-humidifier device (Axius™, Maquet, NJ, USA) was routinely employed. Target vessel shunting
Pulmonary vascular resistance index
significant and results are presented as means ⫾ SD. Power calculation was set to display the 95% confidence interval and performed with statistical software (PowerAndPrecision 4.0, Biostat, Englewood, NJ, USA).
was selective, depending on the amount of bleeding during completion of anastomoses [5]. Postoperative management Postoperatively, all patients were observed by protocol. Weaning from the ventilator was undertaken when the patient was mentally cooperative, rewarmed and hemodynamically stable, chest tube drainage was ⬍ 100 mL/h and pulmonary function was adequate (PaO2 ⬎ 9 kPa with FiO2 ⱕ 0.45).
Results Demographics and perioperative data There were no major differences between groups with respect to preoperative variables (Table I). A decreased number of distal coronary bypass anastomoses were performed in patients without CPB as compared to patients with CPB (3.6 ⫾ 0.7 vs. 2.4 ⫾ 1.1, p ⫽ 0.012) – though other perioperative parameters including the duration of the operations – were comparable.
Sample collection Blood gas analysis and measurement of hemodynamic parameters to define oxygenation index, pulmonary shunt, alveolar-arterial oxygen gradient and PVRI were calculated at the following time points: 10 min after induction of anesthesia (T1), 1 h after restarting normal ventilation/return of flow in all grafts (T2), 6 h after restarting ventilation/reflow (T3), 1 h after extubation (T4) and during the first postoperative morning (T5). Alveolar-arterial oxygen gradients were measured after induction of anesthesia at FiO2 of 0.45 (T1) and after extubation at FiO2 of 0.35 (T2).
Oxygenation index Oxygenation index was defined as mean arterial oxygen tension (PaO2) divided by FiO2 (PaO2/FiO2, kPa) and shown at various time points in Table II. A decrease of PaO2/FiO2 occurred already at T2, but in the NV group this was not statistically significant. PaO2/FiO2 gradually tended to decrease in all groups, without statistical differences between them.
Statistical analysis Statistical analysis was performed with SPSS software (SPSS Inc, Chicago, IL, USA). A nonprametric Kruskall-Wallis test was employed to account for comparison of changes in pulmonary measurements between all groups. The changes in pulmonary function in patients with CPB were compared with patients without CPB and within all groups by the nonparametric Mann-Whitney U test. The predictive value of PVRI to indicate patients who underwent CABG without CPB was assessed by receiver operating characteristic (ROC) curve. P-values less than 0.05 were considered statistically
Alveolar-arterial oxygen gradient Alveolar-arterial oxygen gradient (mmHg) increased in all groups between at T2 (Table III). The gradient returned towards the base line values 6 h after restoration of ventilation/reflow at T3, and in the first postoperative morning there was no impairment compared to the base line T1. In the LTV group, the gradient was lower at T4 and T5 compared to T1. There were no statistical differences between the groups observed at each time point.
Table I. Patient demographics and perioperative data. With CPB (n ⫽ 37) CPAP (n ⫽ 10) LTV (n ⫽ 13) NV (n ⫽ 14) Age (years) Sex (M/F) Height (cm) Weight (kg) LVEF (%) Number of bypasses (n) Perfusion (min) Aortic clamping (min) Mechanical ventilation (min)
66.7 ⫾ 7.3 8/2 170.7 ⫾ 8.0 81.6 ⫾ 8.8 65 ⫾ 8 3.4 ⫾ 1.1 92 ⫾ 23 74 ⫾ 21 612 ⫾ 322
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72.0 ⫾ 7.6 9/4 168 ⫾ 6.9 83.6 ⫾ 18.9 61 ⫾ 5 3.5 ⫾ 0.7 93 ⫾ 17 76 ⫾ 12 615 ⫾ 168
67.6 ⫾ 9.2 11/3 168.7 ⫾ 7.7 77.7 ⫾ 15.3 62 ⫾ 7 3.6 ⫾ 0.7 99 ⫾ 18 76 ⫾ 17 564 ⫾ 236
Without CPB (n ⫽ 10)
p-value
70.8 ⫾ 7.8 7/3 168.1 ⫾ 8.7 73.9 ⫾ 12.1 58 ⫾ 7 2.4 ⫾ 1.1 – – 575 ⫾ 211
0.342 0.911 0.882 0.427 0.246 0.012 0.606 0.951 0.930
CPAP, continuous positive airway pressure; LTV, low tidal volume; NV, no ventilation; LVEF, left ventricular ejection fraction.
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V. Toikkanen et al. Table II. Oxygenation index (PaO2/FiO2, kPa). With CPB (n ⫽ 37)
After induction of anesthesia 1 h after reventilation/reflow 6 h after reventilation/reflow 1 h after extubation 1st postoperative morning
CPAP (n ⫽ 10)
LTV (n ⫽ 13)
NV (n ⫽ 14)
Without CPB (n ⫽ 10)
p-value
46.0 ⫾ 15.9 33.7 ⫾ 14.8 42.0 ⫾ 10.4 45.3 ⫾ 15.5 34.9 ⫾ 6.4
43.0 ⫾ 11.3 30.7 ⫾ 9.2 37.3 ⫾ 6.8 37.5 ⫾ 9.1 36.0 ⫾ 7.6
46.9 ⫾ 14.7 37.8 ⫾ 11.8 35.6 ⫾ 9.9 41.3 ⫾ 14.6 36.5 ⫾ 8.7
46.6 ⫾ 14.7 37.8 ⫾ 11.8 35.6 ⫾ 9.9 41.3 ⫾ 14.6 40.3 ⫾ 9.8
0.887 0.789 0.427 0.705 0.343
CPAP, continuous positive airway pressure; LTV, low tidal volume; NV, no ventilation.
Table III. Alveolar-arterial oxygen gradient (mmHg). With CPB (n ⫽ 37) CPAP (n ⫽ 10) LTV (n ⫽ 13) NV (n ⫽ 14) After induction of anesthesia 1 h after reventilation/reflow 6 h after reventilation/reflow 1 h after extubation 1st postoperative morning
14.4 ⫾ 6.9 22.4 ⫾ 7.5 16.7 ⫾ 5.3 10.4 ⫾ 6.6 12.9 ⫾ 6.1
17.6 ⫾ 4.2 23.9 ⫾ 4.9 18.5 ⫾ 6.0 14.1 ⫾ 4.2 13.7 ⫾ 5.2
16.4 ⫾ 6.1 24.1 ⫾ 8.1 17.6 ⫾ 5.6 13.7 ⫾ 3.2 17.0 ⫾ 7.5
Without CPB (n ⫽ 10)
p-value
14.8 ⫾ 7.1 20.2 ⫾ 5.0 18.2 ⫾ 5.0 12.7 ⫾ 5.4 14.3 ⫾ 5.0
0.967 0.852 0.672 0.495 0.383
CPAP, continuous positive airway pressure; LTV, low tidal volume; NV, no ventilation.
Pulmonary shunt Pulmonary shunt (Qs/Qt, %) increased in all study groups between at T2 (Table IV).The shunt decreased thereby in every group, and in patients without CPB, the shunt was observed to decrease further till the first postoperative morning at T5 as compared with the base line T1. However, the findings between the study groups were not different at any time point.
Pulmonary vascular resistance index PVRI was calculated as the transpulmonary pressure gradient divided by cardiac index multiplied by 80. Regardless of ventilation, the pulmonary vascular resistance index PVRI (dynes-s-cm⫺5) decreased during CPB postoperatively, but remained elevated in patients without CPB (Figure 1). The cardiac index was comparable between the groups (data not shown), and the observation was related to differences in the transpulmonary pressure gradient.
At base line T1, PVRI remained similar among the CPAP, LTV, NV groups and patients without CPB (318 ⫾ 76, 291 ⫾ 111, 269 ⫾ 109 and 197 ⫾ 108, dynes-s-cm⫺5, respectively). PVRI decreased in patients with CPB at T3 as compared with patients without CPB (167 ⫾ 90, 322 ⫾ 157, dynes-s-cm⫺5, respectively, p ⬍ 0.002). The decrease endured till the last measured time point T5 in CPAP, LTV, NV groups, regardless of modified ventilation during CPB (100 ⫾ 30, 119 ⫾ 59, 140 ⫾ 122, dynes-s-cm⫺5, respectively). In contrast, PVRI remained unchanged in patients without CPB till time point T5 (263 ⫾ 99 dynes-s-cm⫺5). At time points T1–T5, for the effect size (group means of 194.7 vs. 264.3), SD (115.8 and 115.9), patient number (181 vs. 44), alpha (0.050, 2-tailed), the power was 94.3%. At time point T3, for the effect size of PVRI in patients with CPB vs. without CPB (group means of 167.2 vs. 322.4), SD (90.6 and 157.9), patient number (36 vs. 9), alpha (0.050, 2-tailed), the power was 81.2%. At time point T4 for
Table IV. Pulmonary shunt Qs/Qt (%). With CPB (n ⫽ 37)
After induction of anesthesia 1 h after reventilation/reflow 6 h after reventilation/reflow 1 h after extubation 1st postoperative morning
CPAP (n ⫽ 10)
LTV (n ⫽ 13)
NV (n ⫽ 14)
11.0 ⫾ 5.5 17.8 ⫾ 9.1 11.9 ⫾ 6.1 10.1 ⫾ 7.3 11.9 ⫾ 5.9
11.0 ⫾ 4.9 16.4 ⫾ 5.9 12.2 ⫾ 3.7 14.2 ⫾ 5.1 13.6 ⫾ 6.1
10.2 ⫾ 4.8 17.1 ⫾ 6.2 13.4 ⫾ 5.6 13.8 ⫾ 6.2 12.9 ⫾ 4.3
Without CPB (n ⫽ 10)
p-value
11.3 ⫾ 7.9 15.3 ⫾ 6.0 12.5 ⫾ 4.9 12.6 ⫾ 8.1 9.6 ⫾ 5.7
0.561 0.484 0.865 0.308 0.395
CPAP, continuous positive airway pressure; LTV, low tidal volume; NV, no ventilation.
Pulmonary vascular resistance index
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with patients without CPB (AUC 0.786; SE 0.043; p ⬍ 0.001; 95% CI. 0.701–0.870). Outcome There were three resternotomy operations due to postoperative bleeding; one patient with CPAP, NV, and without CPB. No patients were excluded from the study because of reintervention or complication. The duration of mechanical ventilation and the length of stay were similar among all groups. One patient in the LTV group experienced a stroke and one patient without CPB developed multiorgan failure after uneventful immediate postoperative course and died. Figure 1. Pulmonary vascular resistance index (PVRI) in patients with CPB and without CPB. Horizontal lines of the box show the median. Lines above and below the box indicate the 75th and 25th percentiles, respectively. Whiskers above and below show the maximum and minimum values, respectively. T1 ⫽ 10 min after induction of anesthesia,T2 ⫽ 1 h after restarting normal ventilation/ reflow, T3 ⫽ 6 h after restarting ventilation/reflow, T4 ⫽ 1 h after extubation, T5 ⫽ first postoperative morning.
the effect size of PVRI in patients with CPB vs. without CPB (group means of 118.8 vs. 274.8), SD (63.4 and 108.4), patient number (35 vs. 9), alpha (0.050, 2-tailed), the power was 98.4%. At time point T5, for the effect size of PVRI in patients with CPB vs. without CPB (group means of 121.9 vs. 262.8), SD (83.8 and 98.4), patient number (37 vs. 8), alpha (0.050, 2-tailed), the power was 96.3%. ROC curve analysis The diagnostic performance of PVRI associated with patients who underwent coronary artery bypass grafting without CPB was assessed by ROC analysis (Figure 2). Increased PVRI values were associated
Figure 2. Receiver operating characteristic curve (ROC) analysis showing that increased PVRI was associated with patients without CPB (AUC 0.786; SE 0.043; p ⬍ 0.001; 95% CI. 0.701–0.870).
Discussion We show in this study that CPB during coronary artery bypass grafting decreases PVRI compared to patients without CPB. The decrease in PVRI is unrelated to additional ventilation or major pulmonary dysfunction during CPB. Early ventilation parameters such as oxygenation index, pulmonary shunt and alveolar-arterial oxygen gradient were comparable to patients without CPB. CPB afforded a resting state of pulmonary arterial circulation owing to decreased pulmonary artery flow leading to decreased PVRI. Due to the arrested circulation in patients with CPB, the heart and the lungs have minimal oxygen consumption and circulatory resistance in contrast to the patients without CPB who must maintain constant cardiac and pulmonary circulatory flow during surgery. Decreased PVRI indicates the preservation of endothelial vasorelaxation after CABG and reperfusion [4]. Strategies aiming at preserving pulmonary endothelial integrity may enhance recovery after CPB. Preservation of the vasorelaxation of the pulmonary arterial endothelium to acetylcholine and the associated decrease of PVRI may predict reduced postoperative lung dysfunction after CPB [7,8]. An effect of CPB on pulmonary dysfunction following cardiac surgery has been speculated [1,9,10]. Lamarche et al. demonstrated in an experimental setting that CPB with reperfusion altered pulmonary endothelial relaxation to acetylcholine, in contrast to CPB without reperfusion [4], suggesting that pulmonary arterial endothelial dysfunction is dependent on pulmonary arterial flow. However, as pointed by the authors, the selective impairment of relaxation to acetylcholine is not associated with increased irreversible endothelial damage since histological outcome of endothelium remained intact after CPB and reperfusion [4]. Though impairment of relaxation to acetylcholine is suggestive for temporal reperfusion injury after CPB [11], pulmonary ischemia reperfusion injury does not seem to be detrimental, while
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at least some bronchial arterial flow is preserved during CPB [2,7]. According to a few previous studies, CPB improves pulmonary gas exchange postoperatively in some cardiac surgery patients [12–15]. Nevertheless, the plausible protective role of continuous ventilation during CPB remains controversial with regard to pulmonary dysfunction [16–18]. In our study, controlling ventilation during CPB did not influence the decrease in PVRI. This is in accordance with a study by Gagnon et al. [7], in which PVRI changes were not observed in patients during CPB despite additional ventilation as compared with non-ventilated patients [7]. Additional ventilation does not increase protection from plausible pulmonary dysfunction due to CPB. Instead, decreased pulmonary arterial flow may be secured during relaxation of lungs with CPB. Strategies aiming to preserve pulmonary arterial endothelial integrity – such as antithrombotic treatment – may enhance the protection after CPB. For example, heparin-coated circuits utilized during CPB may impact PVRI; heparin-coated circuits enhance hemodynamic outcome after CPB, again suggesting that vascular endothelial protection may be beneficial to pulmonary function [19]. Supporting the above, unchanged PVRI was observed in patients undergoing CABG without CPB with constant normal ventilation and pulmonary arterial flow [5]. We compared the PVRI values of patients without CPB to those patients with CPB. As shown in Figure 1, PVRI values remained relatively constant in patients without CPB in contrast to significant decreased PVRI values observed in patients with CPB. Avoiding CPB did not add to pulmonary protection as compared with CABG surgery with CPB [5]. In addition to constant ventilation, CABG without CPB requires manipulation of the working heart during surgery, affecting both preload and afterload thus maintaining elevated PVRI [20]. Pulmonary blood flow and right ventricle output remain stable during surgery without CPB, explaining in part the unchanged PVRI in these patients. Comparable lung volume and cardiac output in patients with CPB and decreased PVRI hint that strategies for limiting postoperative pulmonary dysfunction associated with arterial endothelial protection after surgery may be beneficial [5]. Our study may be important during the planning of elective coronary artery bypass grafting; the preference to use CPB in these patients may prevail in order to obtain decreased pulmonary vascular resistance. PVRI was chosen as the endpoint describing circulatory resistance. There is a vast interest in the surgical community to identify a clinically feasible and quantifiable parameter describing vascular relaxation during surgery. PVRI is measured and followed during cardiac surgery, as it reveals the end-systolic capacity of the right side of the heart
on-time. PVRI is one of the most reliable parameter in predicting a beneficial outcome after cardiac surgery [21]. In this study, we showed that an impact on PVRI can be exerted by the choice of surgical technique. It is however, beyond the scope of this study to show that decreased PVRI is associated with long-term beneficial outcome. The limitations of our study should be mentioned. The small sample size of our study precludes assessing any differences in the clinical outcome. Only stable patients with preoperatively impeccable lung function were included. We could not perform histological analysis of the pulmonary arterial tree. Our strict inclusion criteria provided comparable patients, since smoking, anti-inflammatory medication and recent acute events were among the exclusion criteria. The role of inflammation associated with CPB and PVRI also remains to be established [22]. The purpose of the study was to compare PVRI in patients with CPB vs. without CPB. According to power calculation in comparing PVRI in patients with CPB vs. without CPB, from 81–98% of studies would be expected to yield a significant effect, rejecting the null hypothesis that the two group means are equal. Differences of ventilation strategies did not interfere with the finding that PVRI decreased in patients with CPB, in contrast to patients without CPB. The ventilatory parameters remained comparable within all patients with CPB, regardless of ventilation adjustment. Increasing the number of patients with varied ventilation strategies is safe in patients with CPB, and may be regarded as fortifying the results of this study. In conclusion, our findings suggest that modified ventilation techniques during CPB do not affect pulmonary circulation during the first 24 h after elective CABG in patients with normal lung function. Rather, CPB per se may have an important role on diminished PVRI. We find that the investigation of pulmonary endothelial integrity after CPB on PVRI is warranted. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. The trial was supported by grants from the Competitive Research Funding of the Pirkanmaa Hospital District, Tampere University Hospital and Tampere Tuberculosis Foundation, Tampere, Finland.
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