1 Department of Anaesthesia and Intensive Care, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark. 2 Department of Anaesthesia and Intensive Care, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark
Accepted for publication: July 21, 2002
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Abstract |
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Methods. Nine patients with abdominal septic shock treated with norepinephrine, and ten healthy subjects, were subjected to equilibrium dialysis with a rectal balloon. pH, PCO2 and concentrations of L-lactate were measured by auto-analyser.
Results. In rectal dialysis fluid from patients with septic shock, acidosis was present (pH 7.23, 95% CI 7.117.36) and concentrations of L-lactate were approximately five times greater than controls (2.55.8 vs 0.51.2 mmol litre1). The lactate concentration was related to the dose of norepinephrine (P<0.001). In contrast, values of dialysate PCO2 did not differ significantly between patients and controls (6.411.0 vs 8.913.8 kPa).
Conclusions. The results suggest that, either lactic acidosis in rectal mucosa is related to shock severity, or that norepinephrine causes mucosal ischaemia. In any case, metabolic dysfunction is present in the rectal mucosa in patients with abdominal septic shock treated with norepinephrine.
Br J Anaesth 2002; 89: 91922
Keywords: acidbase equilibrium, acidosis; gastrointestinal tract, intestinal mucosa; infection, sepsis
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Introduction |
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We set out to measure pH, PCO2 and concentrations of L-lactate in the gut of patients with septic shock and healthy subjects. Luminal equilibrium dialysis is a valid, non-invasive method for the estimation of extracellular concentrations of small molecules (<12 kDa) in rectal mucosa.2 Animal studies show that measurement of mucosal lactate by luminal microdialysis is a valid method by which to assess intestinal ischaemia.3
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Methods and results |
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Septic shock was defined as the presence of a positive bacterial culture from the blood or the peritoneal cavity and the need for infusion of norepinephrine (>0.04 µg kg1 min1) to maintain a mean arterial pressure (MAP) >70 mm Hg. We did not include patients with any of the following conditions: (i) any changes in cardiovascular treatment in the preceding 2 h, (ii) systemic hypoxia (PaO2<8 kPa), (iii) abnormal rectum or left colon, (iv) active gastrointestinal bleeding, or (v) an intra-abdominal pressure >20 mm Hg. All patients had been resuscitated with i.v. fluids before the study using Dextran 60 (Macrodex®; Pharmacia-Upjohn, Uppsala, Sweden) and isotonic saline until the arterial pressure was stable, after which another 10002000 ml of fluid were given. Blood was given if the haemoglobin concentration was <5 g dl1. If oliguria was present, dopamine was infused at 4 µg kg1 min1 (four patients). All patients received systemic antibiotics, selective digestive decontamination (except three patients) and enteral nutrition (except one). Three patients had a pulmonary artery catheter in place during the study. All of these patients had a cardiac index >3 litre min1 m2, a pulmonary capillary wedge pressure >16 mm Hg and a systemic vascular resistance index <1000 dyn s cm5 m2.
Luminal equilibrium dialysis
pH, PCO2 and concentrations of L-lactate in rectal mucosa were measured by luminal equilibrium dialysis as previously described.2 Bags of dialysis tubing (semipermeable cellulose, cut-off 12 kDa; Sigma, St Louis, MO, USA) were closed over 5 cm of Tygon® tube (Cole-Parmer Instruments Company, Vernon Hills, IL, USA) with a three-way stopcock at the distal end for airtight sampling. Bags were filled with 4 ml of Dextran 40 10% in isotonic saline (Rheomacrodex®; Pharmacia-Upjohn) and placed in the rectal lumen for 4 h, which was the time required for 100% equilibrium of eicosanoids in vivo.2 Incubation of dialysis bags for 2 h in a saline bath containing 1 mmol litre1 L-lactate (Sigma) at 37°C was sufficient for 100% equilibrium of L-lactate. pH, PCO2 and L-lactate were measured by auto-analyser (ABL 625, Radiometer, Copenhagen, Denmark). As D-lactate may be produced by luminal bacteria, saline solutions containing 1, 10 and 100 mmol litre1 D-lactate (Sigma) were analysed in the ABL 625, but D-lactate was undetectable (n=3).
Statistics
Normal distribution of the variables was tested with the KolmogorowSmirnov statistics and the Levine test was used to test for equal variance. Data were analysed by Students t-test for unpaired or paired variables, or linear regression analysis where appropriate.4 P-values <0.05 (2-tailed) were considered significant.
Results
In dialysis fluid from the patients with septic shock, acidosis and increased concentrations of L-lactate were observed compared with values in fluid from healthy subjects (Table 1). In septic patients, the mean concentration of L-lactate in dialysis fluid was 70% greater than in arterial blood (P=0.03, Table 1), and there was no correlation between the two values (P=0.27). In contrast, dialysate concentrations of L-lactate correlated with the dose of nor epinephrine (Fig. 1, r2=0.89; P=0.0001). The dose of norepinephrine was not related to systemic values of L-lactate (P=0.48).
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Comment |
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Rectal equilibrium dialysis may be a simple, non-invasive method to measure markers of metabolism in gut mucosa in critically ill patients. The 4 h of equilibration used in the present study may hamper its clinical use. However, it is possible that equilibrium can be obtained earlier or that non-equilibrium dialysis with a shorter time of exposure can detect clinically relevant differences. Future studies should address these questions as well as the effects of age, dopamine, antibiotics, enteral nutrition and fluid management.
The high values of PCO2 observed in the rectal lumen of both patients and healthy subjects suggest that carbon dioxide may come from bacterial metabolism. Alternatively, weak acids in faeces may be buffered by HCO3, which is secreted into the lumen by rectal epithelial cells. Consequently, any change in bacterial number or metabolism or epithelial secretion of HCO3 could affect PCO2, pH, or both and complicate the interpretation of these values. In the gastric mucosa, an increased luminalarterial PCO2 gap may indicate regional hypoperfusion. We did not determine arterial PCO2 in the healthy subjects, so comparison between the groups is not possible. Bacterial metabolism may also generate D-lactate, but this was not detectable by the auto-analyser used in the present study. This suggests that bacterial metabolism did not contribute to the high dialysate lactate observed in septic patients.
The observed relationship between dialysate L-lactate and norepinephrine dose suggests that mucosal L-lactate is related to shock severity, which may be indicated by the dose of norepinephrine. Alternatively, norepinephrine treatment may itself cause mucosal ischaemia. In any case, metabolic dysfunction is present at the rectalmucosal barrier in patients with abdominal septic shock treated with norepinephrine.
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References |
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