1 Department of Anaesthesia and Intensive Care, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark. 2 Department of Cardiothoracic Anaesthesia and 3 Department of Cardiothoracic Surgery, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark
* Corresponding author. E-mail: ap{at}dadlnet.dk
Accepted for publication June 28, 2005.
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Abstract |
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Methods. Patients undergoing coronary artery bypass grafting (CABG) (n=12) or off-pump CABG (n=10) were subjected to equilibrium dialysis of the rectal lumen during the procedure and in the first 4 h afterwards. Dialysate concentrations of L-lactate and were measured using an auto-analyser and compared with values obtained in healthy subjects (n=10).
Results. During CPB, a 2- to 3-fold increase in luminal concentrations of L-lactate was observed (CABG vs off-pump CABG, P=0.05; CABG vs healthy subjects, P<0.01). The dialysate concentrations of L-lactate were higher than the mean systemic values (luminalarterial gradient mean (SD) 0.9 (1.0) mmol litre1, P<0.05), and the two values were positively correlated (P<0.05). Luminal L-lactate concentrations remained elevated 4 h after the operation. In contrast, dialysate was equally high in patient and control groups and substantially higher than values observed in arterial blood.
Conclusions. Uncomplicated CPB is associated with moderate but sustained increases in luminal concentrations of L-lactate in the rectum, indicating metabolic dysfunction of the mucosa in the large bowel.
Keywords: gastrointestinal tract, mucosal perfusion ; heart, cardiopulmonary bypass ; metabolism, lactate ; monitoring, carbon dioxide
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Introduction |
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Luminal equilibrium dialysis is a valid non-invasive method for the estimation of extracellular concentrations of small molecules in rectal mucosa.4 Moreover, previous studies in animals with occlusive gut ischaemia and in patients with septic shock have shown that measurements of lactate by luminal dialysis may be a method of assessing metabolic dysfunction in intestinal mucosa.5 8 The aim of the present study was to measure concentrations of L-lactate and in the rectal lumen in patients undergoing cardiac surgery with or without the use of CPB.
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Methods and results |
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Anaesthesia
Patients received diazepam 1015 mg orally 1 h prior to induction. Anaesthesia was induced with fentanyl 10 µg kg1 and midazolam 25 mg. Tracheal intubation was facilitated by pancuronium 0.1 mg kg1, and anaesthesia was maintained with isoflurane (0.51.0%) and fentanyl 2.55 µg kg1 h1. The patients in the CPB group received 500 ml isotonic saline. The off-pump CABG group received isotonic saline and 6% dextran 70 in saline (Macrodex®, Pharmacia-Upjohn, Uppsala, Sweden). In the intensive care unit (ICU), all patients were sedated with an infusion of propofol (100250 mg h1) during the study.
Treatment with vasoactive drugs
Hypotension prior to CPB (mean arterial pressure [MAP] <60 mm Hg) was treated with i.v. ephedrine 5 mg or i.v. phenylephrine 0.1 mg depending on the heart rate. Hypotension during CPB (MAP <50 mm Hg) was treated with increased flow; if this was ineffective, phenylephrine was administered in i.v. boluses of 0.1 mg. Post-CPB hypotension (MAP <60 mm Hg) was treated with infusion of 500 ml dextran 70 and dopamine 210 µg kg1 min1.
In the off-pump CAGB group, hypotension (MAP <60 mm Hg) was treated with 500 ml dextran 70; if this was ineffective, phenylephrine was administered in i.v. boluses of 0.1 mg. The latter was supplemented by dopamine 210 µg kg1 min1 if several doses had to be given.
Perioperative hypertension (MAP >90 mm Hg) was treated by either increasing the depth of anaesthesia or infusion of nitroglycerin.
Cardiopulmonary bypass
Normothermic non-pulsatile CPB, using a membrane oxygenator and flow of 2.4 litre min1 m2, was provided by a heartlung machine primed with Ringer's lactate, which contains L-lactate 28 mmol litre1. Cardiac arrest was induced by antegrade blood cardioplegia and distal grafting was performed during complete aortic clamping.
Study protocol
L-Lactate concentrations and in the rectal lumen were measured by equilibrium dialysis as previously described.5 After the induction of anaesthesia, a 12 cm long bag of dialysis tubing (semipermeable cellulose, cut-off 12 kDa) (Sigma, St Louis, MO, USA) was placed in the rectal lumen. The bag was filled with 4 ml of 10% dextran 40 in isotonic saline (Rheomacrodex®, MEDA, Solna, Sweden) and closed over 5 cm of Tygon® tube (Cole-Parmer Instruments Company, Vernon Hills, IL, USA) with a three-way stopcock at the distal end to allow airtight sampling. At the end of the procedure the dialysate was sampled and the bag was removed. Dialysis for 4 h is required to ensure full equilibrium in the rectal lumen.4 In two CABG and three off-pump CABG patients, the procedure lasted <4 h, and so 1020 min of the postoperative period was included in the time of equilibration in these patients. Upon arrival in the ICU, a new bag was placed and another full equilibrium dialysis was performed during the first 4 h after the operation. Arterial blood samples were taken before anaesthesia and every hour during the study. L-Lactate concentrations and
in dialysates and arterial blood were measured by auto-analyser (ABL 725, Radiometer, Copenhagen, Denmark). The healthy subjects were subjected to a single rectal equilibrium dialysis of 4 h.
In vitro equilibration
Dialysis bags were incubated for 0.54 h in saline baths containing 1 mmol litre1 L-lactate (Sigma) or 5% carbon dioxide (AGA, Copenhagen, Denmark) at 37°C (n=5). Dialysates were analysed as described above. The median (range) dialysate values of L-lactate reached 50 (3356)%, 78 (5478)%, 89 (75100)% and 100 (88100)% equilibrium at 0.5 h, 1 h, 2 h and 4 h, respectively. The equivalent values for were 91 (8993)%, 98 (93101)%, 101 (99104)% and 105 (103108)%.
Statistics
Data are presented as median (range) and analysed using the MannWhitney or Wilcoxon tests or Spearman's rank correlation test where appropriate (GraphPad Prism v. 4.00, GraphPad Software, San Diego, CA, USA). P-values <0.05 (two-tailed) were considered significant. The sample size was not calculated prior to the study, but we have previously detected clinically relevant differences in sepsis using similar numbers of patients and controls.5
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Results |
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Luminal was the same in all groups of patients and controls and substantially higher than the mean values observed in arterial blood (Fig. 3). There was no difference in the luminalarterial
gradient between the groups of patients (Fig. 3).
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Discussion |
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The correlation between the luminal and systemic values in the present study suggests that the production of L-lactate in gut mucosa contributes to the hyperlactataemia observed in these patients. Alternatively, a common cause exists for the increased concentrations of L-lactate. This could be generalized vascular dysfunction, but it is currently not known whether increased luminal concentration of L-lactate indicates bowel ischaemia. Epinephrine may cause systemic lactic acidosis through aerobic glycolysis,10 but to our knowledge this has not been shown for phenylephrine or dopamine, which were the sympathomimetics used in the present study.
From a theoretical point of view, metabolic dysfunction of the gut in patients undergoing CPB is better assessed in the large bowel, which contains most of the bacteria and endotoxins. As previous studies of this matter have measured gastric pH or , future studies should include luminal measurements of gastric
and L-lactate.
The increased concentration of L-lactate in the rectal lumen during and after the off-pump CABG procedure indicates metabolic dysfunction in the mucosa in these patients, albeit to a lesser degree than in patients subjected to CPB. This is not surprising as the patients were old and had undergone major surgery. It is unlikely that this difference in luminal L-lactate was clinically relevant because all patients had an uneventful perioperative course. However, we can speculate that this might make a difference to patients with lower cardiovascular reserves.
The high values of in the rectal lumen of patients are within the range previously observed in patients with septic shock.5 As the values were equally raised in healthy subjects, luminal carbon dioxide in the rectum may originate from bacterial metabolism. Alternatively, acids in faeces may be buffered by bicarbonate ions, which are secreted into the lumen by epithelial cells. Consequently, any change in bacterial metabolism or epithelial secretion of bicarbonate ions could affect
and complicate the interpretation of these values. On the other hand, changes in luminalarterial carbon dioxide difference, as detected by gas tonometry in the sigmoid colon during surgery, may predict complications in patients undergoing repair of abdominal aortic aneurysm.11 It is currently not known whether
in the rectum is higher than in the sigmoid colon, but the
values observed in the rectum in our healthy subjects were within the range of those observed in the sigmoid colon during aortic repair.11 12 Taken together, it is unlikely that the measurement of luminal
in the rectum is a useful marker of regional flow or metabolism. Luminal bacteria may also generate lactate, but these produce the D-isoform, which is not detected by the auto-analyser used in the present study.5 However, systemic concentrations of D-lactate have been suggested to be a marker of metabolic dysfunction of the large bowel in critically ill patients.13 The elimination kinetics of this isoform in humans,14 including the influence of critical illness, need to be established before this simple measure can be used to assess the metabolic state of the colonic mucosa.
Luminal dialysis in the rectum has the potential to be used clinically to estimate mucosal concentrations of L-lactate. This is substantiated by observations in patients with septic shock, where luminal values of L-lactate correlated with mucosal permeability in the large bowel.15 Future studies of patients on CPB should address these matters, as well as the effects of fluid management and different vasoactive drugs.
In summary, uncomplicated normothermic CPB is associated with a moderate but sustained increase in luminal concentrations of L-lactate in the rectum, indicating metabolic dysfunction of the mucosa. In contrast, luminal in the rectum was equally raised in patients and healthy subjects, questioning its use as a marker of metabolism. It can be speculated that mucosal ischaemia of the large bowel contributes to the endotoxaemia observed with the use of CPB.
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Acknowledgments |
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Footnotes |
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References |
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