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Eur J Cardiothorac Surg 2003;23:917-924
© 2003 Elsevier Science NL
a Department of Cardiac Surgery, Wessex Cardiothoracic Centre, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
b Department of Anaesthesia, Wessex Cardiothoracic Centre, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
Received 27 August 2002; received in revised form 17 January 2003; accepted 3 February 2003.
* Corresponding author. Tel.: +44-23-8077-7222; fax: +44-23-8079-8508
e-mail: theo{at}velissaris.com
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Abstract |
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 Top Abstract 1. Introduction2. Materials and methods3. Results4. DiscussionAppendix A. Conference...References |
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Key Words: Cardiopulmonary bypass • Off-pump surgery • Gut • Gastric mucosal oxygenation • Tonometry
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1. Introduction |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionAppendix A. Conference...References |
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Off-pump coronary artery bypass grafting (OPCAB) is currently an accepted modality of surgical coronary revascularization. The continuous improvements in myocardial stabilizers and coronary exposure techniques have made OPCAB accessible to many surgeons worldwide for the treatment of multi-vessel coronary artery disease. Benefits of OPCAB over conventional coronary artery bypass grafting (CABG) with CPB have been demonstrated, such as reduced perioperative blood loss [6] and attenuation of the inflammatory response [7]. However, OPCAB does not eliminate the potential of significant perioperative organ injury, the magnitude of which may be comparable to surgery with CPB [8,9]. The development of significant perioperative gastric mucosal hypoxia during CPB has been well documented [10,11]. To date a similar evaluation of patients undergoing OPCAB surgery has not been reported. It is therefore important to specifically evaluate the role of OPCAB in gut protection before defining those who may benefit from this strategy. The aim of this study was to evaluate in a prospective randomized fashion global oxygen flux and gastric mucosal oxygenation during CABG with and without CPB.
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2. Materials and methods |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionAppendix A. Conference...References |
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2.3. CPB management
A standardized CPB protocol was used for the ONCAB patients. CPB was established using bicaval cannulation and an arterial cannula (Medtronic DLP®; Medtronic Ltd., Watford, UK) placed in the ascending aorta. Pulsatile CPB was conducted under mild core hypothermia (35°C), using a hollow-fibre membrane oxygenator (D903 Avant, Sorin Biomedica, Mirandola, Italy) and arterial line filtration (D734 Micro 40, Sorin Biomedica, Mirandola, Italy). The circuit was primed with 1 l of Hartman's solution, 500 ml of gelofusine and 5000 IU of sodium heparin. Intermittent antegrade cold blood cardioplegia (4°C) delivered through a 12G aortic root cannula was used for myocardial protection. The cardioplegic mixture consisted of 20% St Thomas’ Hospital No. 2 solution (Martindale Pharmaceuticals, Essex, UK) and 80% autologous blood. A dose of 12 ml/kg was delivered to induce diastolic cardiac arrest and a maintenance dose of 3 ml/kg was administered after completion of each distal anastomosis. The left ventricle was vented through the aortic root during aortic cross-clamping. Flow was maintained at 2.5 l/min per m2 during CPB with judicious use of phenylephrine and phentolamine to maintain the mean perfusion pressure between 50 and 80 mmHg. Alpha-stat management of acid-base status was used. Proximal graft anastomoses on the ascending aorta were performed following aortic cross-clamp removal using a partially occlusive clamp.
2.4. OPCAB technique
A median sternotomy was used for surgical access in all cases. Partial systemic heparinization was employed with a target activated clotting time of 300–400 s prior to cardiac manipulation. Trendelenburg posture was employed throughout the period of distal anastomoses and a single suture technique [12] was used to facilitate exposure of the target coronary arteries. A mechanical suction-based myocardial tissue stabilizer (Octopus®3; Medtronic Ltd., Watford, UK) was used to immobilize the operative field during coronary anastomosis. Following arteriotomy, an intraluminal coronary shunt (Flo-Thru; Biovascular Inc., MN, USA) was inserted to maintain distal myocardial perfusion and was removed prior to completion of the anastomosis. Core temperature was maintained at or above 35°C throughout the procedure by minimizing heat loss and active warming techniques. Haemodynamic stability was achieved primarily with preload management (intravenous fluid administration and Trendelenburg posture) and vasoactive agents as required. Construction of the proximal anastomoses to the ascending aorta was performed within a single aortic side-biting clamp period, with the systolic arterial pressure maintained around 100 mmHg to minimize aortic trauma.
2.5. Assessment of gastric mucosal oxygenation
An automated air tonometry technique was used to measure the partial pressure of carbon dioxide in the gastric lumen (PgCO2), using a 14F nasogastric catheter connected to a Tonocap monitor (Datex-Ohmeda Ltd., Hatfield, Herts, UK). The catheter was inserted during anaesthetic induction. Correct placement was confirmed by auscultating the epigastrium while 20 ml of air was insufflated through the nasogastric tube. Measurements were obtained at the start and end of operation and 2, 4 and 6 h postoperatively. Two additional intraoperative measurements were made; in the ONCAB group at the onset of CPB and 10 min after discontinuation of CPB. The corresponding measurements in the OPCAB group were made immediately prior to the onset of the distal anastomotic phase and 10 min after completion of the proximal anastomoses. The following formulae were used:
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2.6. Whole body oxygen utilization
The cardiac index (CI) was measured using a continuous cardiac output Swan-Ganz catheter (Edwards Lifesciences, Newbury, UK) inserted through the right internal jugular vein shortly after anaesthetic induction. Whole-body oxygen utilization was measured at the same time-points as gastric mucosal oxygenation. Blood was simultaneously drawn from the arterial line and the pulmonary artery port of the Swan-Ganz catheter (mixed venous blood). The following formulae were used:
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2.7. Statistical analysis
Patient characteristics and perioperative clinical data in the two groups were compared using a two-sample Student's t-test or a Mann–Whitney U-test if normal distribution could not be assumed. Categorical variables were compared using the Pearson's chi-square or Fisher's exact test as appropriate. Repeated measures analysis of variance was used to assess the effect of time, group and group-time interaction on pHi, CO2 gap, DO2, VO2 and Oxygen extraction fraction. Because the data contained subgroups (ONCAB versus OPCAB), the association between different variables was investigated using Spearman's rank correlation analysis. The Statistical Package for Social Sciences version 10.1 software was used for all descriptive statistics and inferential testing. A P value of less than 0.05 was considered statistically significant.
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3. Results |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionAppendix A. Conference...References |
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The demographic variables for the two groups are presented in Table 2. As outlined in the methods, these were low-risk cases and there were no significant differences between the groups. Table 3 summarizes the intraoperative data and clinical outcome. The groups received similar extent of revascularization using comparable mixture of conduits. There were no differences in operation duration and mechanical ventilation time. Rewarming to a core (nasopharyngeal) temperature of 37°C required a similar period of time in both groups. There was a significant difference between the groups in the use of vasoconstrictors, this was mainly due to the use of phenylephrine during CPB in all but one patients in the ONCAB group. No mortality or major complications, such as myocardial infarction, major neurological deficit or end-organ failure were observed. No patient required the use of an intraaortic balloon pump.
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3.3. Whole body oxygen utilization
Perioperative DO2, VO2 and whole-body oxygen extraction fraction are displayed in Fig. 2
. There were no preoperative differences between the groups. DO2 was higher in the OPCAB group throughout the study period, this was largely due to the effect of haemodilution during CPB in the ONCAB group (Table 4). There was a significant effect of time (P=0.01) and group (P=0.004) on outcome, however the effect of group-time interaction was not significant (P=0.30), i.e. the difference between the groups did not depend on the sampling time.
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There was also a significant trend towards increasing levels of oxygen extraction fraction with time (P<0.001), however there were no differences between the groups (P=0.11 for the effect of group and P=0.59 for group-time interaction).
Spearman's rank correlation revealed a highly significant association (P<0.001) between pHi and VO2 (r=-0.22) and pHi and global oxygen extraction fraction (P=-0.20).
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4. Discussion |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionAppendix A. Conference...References |
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Our study confirms previous findings of significant perioperative gastric intramucosal acidosis after CPB [10,11]. More interestingly, we observed a similar degree of intraoperative injury to the gastric mucosa during OPCAB, with a worsening trend for OPCAB patients in the early postoperative period. Given the single-surgeon and randomized nature of the study design, the standardized anaesthetic protocol and the absence of any significant differences in the preoperative characteristics of the two groups, these results may at first appear surprising. One would intuitively expect some benefit conferred by the avoidance of CPB. There are certainly factors associated with the use of CPB per se that would partly explain the development of gastric mucosal hypoxia. These factors include the use of subphysiological flow levels during CPB and the release of various endogenous vasoconstrictors, including angiotensin II, with a concomitant rise in systemic vascular resistance [14]. Indeed CPB duration has been shown to be a predictor of gastrointestinal complications [4,5].
However, considering that perioperative gastric mucosal hypoxia has been well described in the context of major abdominal and vascular surgery [15,16], it becomes plainly obvious that factors other than the use of CPB play an important role in its development. The paramount factor that determines gut mucosal oxygenation status is global haemodynamic stability, since the gut is perhaps the first tissue in the body to become compromised at times of haemodynamic stress [3]. The GI tract is known to receive a disproportionately small portion of the cardiac output at times of haemodynamic deterioration [17], and the gut mucosa is especially susceptible to hypoperfusion due to the counter-current flow of its microcirculation [18]. Therefore, it is not surprising that the main predictors of GI complications after cardiac surgery are factors such as older age, perioperative hypoperfusion episodes, peripheral vascular disease and congestive cardiac failure, which indicate the importance of haemodynamic performance and implicate an ischaemic nature of injury [4,5]. This also explains why the use of acid-neutralizing or acid-reducing therapy does not affect the incidence of GI haemorrhage after CPB [19].
Several studies have documented the presence of significant transient haemodynamic impairment during distal anastomoses in OPCAB [20]. Significant drops in cardiac output may occur despite relatively well-preserved systemic arterial pressures. Haemodynamic deterioration is worse during grafting of the less accessible coronary targets that require extensive cardiac manipulation for adequate exposure. Cardiac verticalization results in compression of the right heart chambers against the surrounding fibrous pericardium and pleura and mechanical dysfunction of the right ventricle [21]. Moreover, despite a preserved mean arterial pressure, elevation of the central venous pressure due to a combination of Trendelenburg posture and cardiac elevation results in significant drops in perfusion pressure. It is conceivable that the cumulative effect of these transient episodes of reduced cardiac output and reduced perfusion pressure in the course of distal anastomoses during OPCAB resulted in a degree of ischaemic injury to the gastric mucosa at least comparable to CPB. It is important to note that these transient haemodynamic alterations are not reflected in our global oxygen utilization measurements. These measurements were made at time-points of relative haemodynamic stability, as one of the limitations of continuous cardiac output thermodilution catheters is that they have a long response time when there is an acute change in cardiac output [22]. The acute and often dramatic haemodynamic changes that occur during cardiac manipulation and distal anastomoses in OPCAB would require a continuous real-time cardiac output monitoring technique.
Our results confirm previous findings of a progressive rise in DO2, VO2 and oxygen extraction fraction after cardiac surgery [11,23]. We observed superior DO2 in the OPCAB group, which was largely related to lower haemoglobin levels in the ONCAB patients from CPB-related haemodilution. Despite the disparity in DO2, there was a progressive and similar rise in global oxygen extraction fraction in the two groups, resulting in higher VO2 in the OPCAB group. There were no differences in mechanical ventilation time or speed of systemic rewarming postoperatively that would easily account for this difference in VO2. We are currently investigating the stress hormonal response after OPCAB to obtain more insight into these findings.
A significant inverse relationship between VO2 and pHi has been previously reported [23] and was confirmed in this study. This may partly explain the difference in gut mucosal oxygenation between the groups postoperatively. However, the latter observation may primarily reflect a difference in the accumulated intraoperative ischaemic injury, as there were no clinical differences in the early postoperative period that would provide an alternative explanation. We also found a significant association between pHi and global oxygen extraction fraction, with worsening gastric mucosal oxygenation during increased global oxygen extraction. This finding is similar to the previously reported association between pHi and SvO2 [23] and indicates that the gut becomes particularly susceptible to injury at times of increased global oxygen demand.
The use of pulsatile flow during CPB reflects our current practice but more importantly has been associated with superior perioperative pHi and enhanced gastric mucosal perfusion compared to non-pulsatile CPB [10,24]. Pulsatile flow maintains capillary patency by delivering more energy into the vasculature and ameliorates the increase in systemic vascular resistance by reducing the release of vasoconstrictors, such as angiotensin II [14]. Although core temperature during CPB has not been shown to influence gastric pHi [25], a systemic temperature of 35°C during CPB was used in this study to avoid the confounding effect of different intraoperative core temperatures in the two groups. It is likely that the choice of CPB protocol, particularly the use of pulsatile flow, had a significant effect on the study findings, and this must be taken into account in future studies.
One limitation of this study is that only low-risk patients with normal cardiac function were studied. This strategy was adopted to ensure homogeneity of the groups, which is essential in prospective randomized studies with small numbers of patients. However, patients with poor left ventricular function or other co-morbidities, such as diabetes mellitus or extracardiac arteriopathy may behave in a rather different manner and the results of this study cannot be extrapolated to such populations. With hindsight, we would also recommend that future studies document postoperative gut mucosal oxygenation beyond 6 h, possibly up to 24 h, to reveal potential differences between ONCAB and OPCAB in the pattern of recovery of pHi or CO2 gap towards baseline values.
In conclusion this study has demonstrated the presence of significant perioperative gastric mucosal hypoxia during CABG either with or without CPB. How these findings may relate to the incidence of GI complications after OPCAB versus surgery with CPB remains to be seen. Whether these findings may be applicable to a high-risk patient population also requires further investigation. However, our results suggest that haemodynamic impairment during OPCAB, though transient, causes significant subclinical end-organ injury.
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Acknowledgments |
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Footnotes |
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Appendix A. Conference discussion |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionAppendix A. Conference...References |
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Now, one of the problems is, as you have rightly pointed out, in patients with poor LV function, that they remain with a nasogastric tube for more than 48 h; some of them, quite a large proportion of them. And when – it is now getting rare – when they go on pump because of persistent hypertension or unacceptable arrhythmias, postoperative period, they do better.
And I think we like to think that it has probably a lot to do with the rewarming. Because in the on-pump, we can rewarm the patients to an acceptable temperature. And often patients, particularly during a long operation, when they come out of operating room, the core temperature is high, or reasonable, but the peripheral temperature is pretty low. And they rewarm over a period of 5–6 h. I think this experience universal.
So that is a comment. I think we have to just accept this unacceptable scenario in gut oxygenation, but with the benefit of off-pump surgery.
Dr Velissaris: I can't give a direct answer to your comments, because actually this study was done on low-risk patients. In fact, we have a study ongoing now in high-risk patients.
With regards to the temperature difference that you mentioned, I have to say that we didn't actually have this problem in the patients we studied. In fact, there was no difference between the groups in terms of temperature pattern postoperatively. They took a similar time to rewarm.
Dr S. Hagl (Heidelberg, Germany): In the pump group, did you use hypothermia, and if yes, to what degree?
Dr Velissaris: We used a core temperature of 35 degrees. The reason why we did that was to avoid the confounding factor of different intraoperative temperatures between the groups. We had noticed that our off-pump patients usually dropped their core temperature to about these levels.
Dr Hagl: But even with that, let's say, high temperatures, you may expect changes in the vasomotor activity in the splanchnic area. So I'm not very sure that what you showed us, is really a failure of the system. It is possible that it is more or less some sort of autoregulation we are looking at?
Dr Velissaris: You mean in terms of intramucosal pH?
Dr Hagl: Yes.
Dr Velissaris: Well, the intramucosal pH, by definition, examines the adequacy of perfusion. So regardless what the levels of perfusion are, when you assess intramucosal pH, you assess essentially adequacy of oxygenation.
Dr Hagl: But oxygen consumption was not different in both groups; is that right?
Dr Velissaris: No. In fact it was higher in the off-pump group.
Dr Hagl: And the next question is, you are looking at, let's say, a normal patient population, with high ejection fraction, normal cardiac function. May we suggest that these are patients with normal vessels?
Dr Velissaris: Correct.
Dr Hagl: So I think if you really want to say something, you have to select a certain group of patients who are at high risk of, let's say, decreased flow in the splanchnic area during extracorporeal circulation.
Dr Velissaris: I fully agree that this would be a valid study, and we're currently doing that. But I think it's important in a randomized study with small number of patients to keep the study groups as homogenous as possible. And we preferred, naturally, to start from a low-risk patient population and now we're continuing with a high-risk study.
Dr J. Habicht (Aarau, Switzerland): Both groups were low-risk patients, but you didn't mention if you used any adrenaline or noradrenaline or any other catecholamines, or if there was any difference between the two groups in this concern.
Dr Velissaris: In terms of vasoconstrictors, all but one patient in the cardiopulmonary bypass group received phenylephrine as a vasoconstrictor during bypass. In the off-pump group, 14, so that's just over 50% of the patients, received either boluses of phenylephrine or noradrenaline infusion intraoperatively. Postoperatively, seven patients in the off-pump group and four in the on-pump group received vasoconstrictors. And three patients in the on-pump group and two in the off-pump group received inotropes for a low cardiac output.
I think what is important is that this is obviously a clinical study, it's not an experimental protocol, so you have to treat the patients optimally. And the only thing you can do is to standardize the inotropic agents you give. So we used dopamine as a first-line inotrope for patients who had a low cardiac output, and either boluses of phenylephrine or a noradrenaline infusion for vasoconstriction.
Dr Habicht: Did you investigate if there was a significant difference?
Dr Velissaris: The on-pump patients, as I said, essentially all of them received phenylephrine during bypass, so it's an inherent part of the protocol. Postoperatively there was no difference in the pHi between the patients who received vasoconstrictors and those who didn't in either group.
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References |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionAppendix A. Conference...References |
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