Department of Anaesthesiology and Intensive Care Medicine, Friedrich-Schiller-University of Jena, Bachstrasse 18, D-07740 Jena, Germany*Corresponding author
Accepted for publication: November 20, 2000
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Abstract |
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Br J Anaesth 2001; 86: 65762
Keywords: complications, septic shock; heart, cardiac output; sympathetic nervous system, norepinephrine; heart, splanchnic blood flow; monitoring, indicator dilution technique; carbon dioxide, partial pressure
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Introduction |
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Partitioning of blood flow to various regional vascular beds is still an important issue in sepsis.24 It is now well known that global parameters do not necessarily reflect regional oxygenation and perfusion. Consequently, guidance of fluid resuscitation by indicators of regional blood flow, especially to those areas that are involved in the outcome from sepsis, has been proposed.1 Thus, we designed the present study to investigate whether an increase in cardiac output via fluid loading during a decrease in norepinephrine infusion (maintaining mean arterial pressure constant) could improve splanchnic blood flow and oxygenation in patients with septic shock.
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Patients and methods |
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Arterial and hepatic venous blood gas samples were analysed immediately for measurement of oxygen and carbon dioxide tensions, pH, haematocrit, haemoglobin concentration, haemoglobin oxygen saturation, glucose and lactate concentrations (Radiometer System 625®, Copenhagen, Denmark).
A hepatic venous catheter (7.5 French gauge five-lumen pulmonary artery catheter, Edwards Swan Ganz®, CCO/SvO2, Model 744H 7.5 F, Baxter Healthcare Corporation, Irvine, CA, USA) was inserted from the right internal jugular vein under fluoroscopic control for continuous measurement of oxygen saturation (SvO2) and assessment of splanchnic blood flow. The correct hepatic venous position of the catheter was verified before and after each study by x-ray.
Pressures were measured with patients in the horizontal position and connected to the ventilator. Besides continuous monitoring of arterial and liver venous arterial pressures, haemodynamic monitoring included measurement of central venous pressure, ITBV index (ITBVI), TBV index (TBVI), and transpulmonary thermodilution cardiac index (CI).
Splanchnic blood flow was evaluated by the steady state ICG (Pulsion Medical Systems, Germany) dye technique. Plasma ICG concentrations were measured spectrophotometrically at a wavelength of 805 nm. Hepatic ICG extraction (E) was calculated as described by Uusaro and colleagues.7 Gastric mucosal PRCO2 was measured with a 16-French guage tonometric probe (Trip® NGS catheter, Tonometrics Division, Helsinki, Finland). No patient received enteral nutrition or antacids during the study period. Furthermore, neither H2-inhibitors nor proton pump inhibitors were given during the study. Because of a Boerhaave syndrome in patient 5, PRCO2 was not obtained in this patient. After conversion of arterial oxygen-partial pressure from [kPa] to [mm Hg], systemic oxygen delivery (DO2I) was calculated as DO2I=(haemoglobin concentration xoxygen saturationx1.36+oxygen partial pressurex 0.0031)xCI. Systemic oxygen consumption (VO2I was measured using a metabolic cart (Deltatrac II®, Datex-Engstroem, Helsinki, Finland). In patient 1, no calorimetric data could be obtained because of technical problems.
After an initial ICG bolus of 30 mg, a continuous ICG infusion was started (37.5 mg h1). After 20, 25, and 30 min of infusion, arterial and hepatic venous blood samples were taken to confirm steady-state ICG concentrations. After 30 min of ICG infusion, baseline haemodynamic measurements were made. Then, fluid resuscitation was started by the infusion of 200 kD hydroxyethylstarch 10% (HAES 10 steril®, Fresenius AG, Bad Homburg, Germany) at a rate of 10 ml kg1 over 90 min. To maintain haemoglobin concentration above 10 g dl1, each patient received 1 unit (300 (30) ml) of packed red blood cells during the study period. The norepinephrine dosage was reduced in each patient and was adjusted individually to keep mean arterial pressure constant. The study period was 2 h.
All results are expressed as mean and standard deviation (SD). For inter-individual comparison, values were normalized by body surface area according to DuBois. Changes between time points were compared using the non-parametric Wilcoxon signed rank test. Statistical significance was considered at P<0.05. Associations between measurements are demonstrated using scattergrams and Pearson correlation coefficients (r). For the statistical analysis, we used SigmaStat® for Windows (version 1.0) which was installed on a Compaq® Armada 1590DT computer with a Pentium processor and Microsoft Windows® 95 system.
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Results |
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Discussion |
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Another reason for the heterogeneous effects of fluid loading in our study might also have been that fluid loading did not really increase cardiac preload and consequently cardiac output in all patients. As clearly demonstrated in Figure 1, an increase in cardiac output was observed in every patient. Furthermore, the ratio between ITBV and TBV remained unchanged (35 (4) and 34 (5) %), indicating that fluid loading increased ITBV proportionally. The techniques that we used in this study for the measurement of cardiac preload and cardiac output are well validated. For the measurement of cardiac output we used transpulmonary thermodilution, which has been extensively validated against reference techniques; for example, pulmonary artery thermodilution and Fick principle derived values.1016 Furthermore, the transpulmonary double-indicator dilution technique allows the measurement of the ITBV, which has been found to be an appropriate or even better indicator of cardiac preload in critically ill patients when compared with cardiac filling pressures.1719
As PEEP itself may affect splanchnic blood flow and hepatic function2022 we maintained airway pressures constant. Droperidol may have influenced splanchnic blood flow, but in our study, droperidol doses remained stable.
Of course, in our study we cannot separate the effects of the two different therapeutic interventions, i.e. fluid loading and reduction in norepinephrine, on splanchnic blood flow. On the other hand, the aim of our study was to mimic clinical practice. In the clinical setting, when perfusion pressure increases after fluid loading, norepinephrine support is normally reduced.
The effects on norepinephrine on splanchnic blood flow cannot be assessed in our study. However, the combination of fluid loading with a reduction in vasopressor support did not always increase splanchnic blood flow. Norepinephrine has been shown to increase splanchnic vascular resistance and, thus, decrease splanchnic blood flow in animal and human studies during non-septic conditions.23 24 Thus, one could speculate that decreasing vasopressor support should be associated with an increase in splanchnic blood flow. On the other hand, Bersten and colleagues24 demonstrated that a redistribution of blood flow with norepinephrine infusion, away from the kidneys, liver and pancreas, was not observable in septic animals. Moreover, a beneficial effect of norepinephrine on splanchnic oxygenation, by increasing mean arterial pressure in septic patients, was shown by Marik and colleagues25 who compared norepinephrine and high-dose dopamine as vasopressors. In their study, dopamine increased mean arterial pressure largely by increasing CI whereas norepinephrine increased mean arterial pressure by increasing systemic vascular resistance while maintaining CI. Although oxygen delivery and oxygen consumption increased in both groups of patients, gastric mucosal pH (pHi)an indicator of microcirculatory perfusionincreased significantly in those patients treated with norepinephrine whereas pHi decreased significantly in those patients receiving dopamine.
Thus, norepinephrine seems to have potential beneficial effects on splanchnic blood flow in patients with sepsis. By maintaining mean arterial pressure constant while reducing norepinephrine in the present study, we controlled for perfusion pressure alone as the cause of these effects. However, some patients showed a decrease in splanchnic blood flow after optimization of CI.
Variation in responses of septic patients to vasoactive substances has been reported previously.26 27 In these studies, the effects of norepinephrine and low-dose dopamine on splanchnic blood flow were found to be unpredictable.
In conclusion, we have shown that an increase in cardiac output as a result of fluid loading while keeping mean arterial pressure constant is not necessarily associated with an increase in regional blood flow. Further studies are necessary to better understand this varying response of splanchnic perfusion.
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References |
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