Effects of thoracic epidural anaesthesia on microvascular gastric mucosal oxygenation in physiological and compromised circulatory conditions in dogs{dagger}

L. A. Schwarte1,*, O. Picker1, C. Höhne2, A. Fournell1 and T. W. L. Scheeren1

1 Department of Anaesthesiology, University Hospital of Düsseldorf, Germany. 2 Department of Experimental Anaesthesia, Campus Virchow-Klinikum, Charité, Berlin, Germany

* Corresponding author. E-mail: schwartelothar{at}aol.com

Accepted for publication May 4, 2004.


    Abstract
 Top
 Footnotes
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Background. The effects of thoracic epidural anaesthesia (TEA) on gastric mucosal microvascular haemoglobin oxygenation (µHbO2) are unclear. At the splanchnic level, reduction of sympathetic tone may promote vasodilation and increase µHbO2. However, these splanchnic effects are counteracted by systemic effects of TEA (e.g., decreased cardiac output (CO) and mean arterial pressure (MAP)), thus making the net effect on µHbO2 difficult to predict. In this respect, effects of TEA on µHbO2 may differ between physiological and compromised circulatory conditions, and additionally may depend on adequate fluid resuscitation. Furthermore, TEA may alter the relationship between regional µHbO2 and systemic oxygen-transport (DO2).

Methods. Chronically instrumented dogs (flow probes for CO measurement) were anaesthetized, their lungs ventilated and randomly received TEA with lidocaine (n=6) or epidural saline (controls, n=6). Animals were studied under physiological and compromised circulatory conditions (PEEP 10 cm H2O), both with and without fluid resuscitation. We measured gastric mucosal µHbO2 by reflectance spectrophotometry, systemic DO2, and systemic haemodynamics (CO, MAP).

Results. Under physiological conditions, TEA preserved µHbO2 (47 (3)% and 49 (5)%, mean (SEM)) despite significantly decreasing DO2 (11.3 (0.8) to 10.0 (0.7) ml kg–1 min–1) and MAP (66 (2) to 59 (3) mm Hg). However, during compromised circulatory conditions, TEA aggravated the reduction in µHbO2 (to 32 (1)%), DO2 (to 6.7 (0.8) ml kg–1 min–1) and MAP (to 52 (4) mm Hg), compared with controls. During TEA, fluid resuscitation completely restored these variables. TEA preserved the correlation between µHbO2 and DO2, compared with controls.

Conclusions. TEA maintains µHbO2 under physiological conditions, but aggravates the reduction of µHbO2 induced by cardiocirculatory depression, thereby preserving the relationship between gastric mucosal and systemic oxygenation.

Keywords: anaesthetic techniques, epidural ; gastrointestinal tract, mucosal perfusion ; model, dog


    Introduction
 Top
 Footnotes
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Adequate splanchnic oxygenation, particularly of the gastrointestinal mucosa, is regarded crucial for the prevention and therapy of critical illness.1 However, perfusion and oxygenation of the gastrointestinal tract is impaired by perioperative stressors, for example surgical trauma or hypovolaemia.2 This impairment is primarily induced by activation of the sympathetic nervous system,3 redistributing perfusion particularly from the splanchnic region to more vital organs. As splanchnic vessels present a dense sympathetic innervation, an extended sympathetic block by thoracic epidural anaesthesia (TEA) should promote splanchnic vasodilation,4 perfusion, and thus tissue oxygenation. However, in contrast to these beneficial regional effects of TEA, undesired systemic effects5 (e.g. reduction of perfusion pressure, cardiac output (CO) and systemic oxygen transport (DO2)) may counteract the intended increase in splanchnic perfusion and thus compromise gastrointestinal mucosal oxygenation.

Furthermore, epidural anaesthesia is increasingly applied during high-risk surgery6 7 as well as in critically ill patients,8 that is in situations in which gastrointestinal oxygenation is at risk as a result of compromised cardiocirculatory conditions (e.g. by hypovolaemia or cardiac depression). To date, the effects of TEA on direct measures of gastrointestinal mucosal oxygenation in compromised cardiocirculatory conditions are unknown. Moreover, during physiological conditions only one study has directly measured mucosal oxygenation.9 This study, however, was performed during laparotomy, where TEA could have modified, by analgesia and blunted stress response, tissue oxygenation.10 11

Thus, several questions arise: (i) under physiological conditions does TEA affect microvascular mucosal oxygenation (µHbO2) in intact animals? (ii) Does TEA modify the response of µHbO2 in compromised circulatory conditions and subsequent fluid resuscitation? (iii) Are the effects of TEA selective for the splanchnic region or do they primarily mirror changes of systemic oxygen transport?

To answer these questions, we studied the effects of TEA on gastric mucosal oxygenation and on systemic oxygen-transport, in both physiological and compromised circulatory conditions, without and with subsequent fluid resuscitation in intact dogs.


    Methods
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 Footnotes
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Animals
The data derive from repetitive experiments on healthy dogs (Foxhounds of both sexes, n=6, body weight 29–35 kg) treated in accordance with the national guidelines for animal care and with approval of the local District Governmental Animal Investigation Committee.

For the continuous measurement of CO ultrasonic flow transducers (20 mm S-series, Transonic, Ithaca, NY) were implanted around the pulmonary artery at least 2 weeks before the experiments and calibrated as described previously.12

Before experimentation, food was withheld for 12 h with water provided ad libitum to ensure gastric depletion and to exclude gastric mucosal perfusion/oxygenation changes as a consequence of digestive activity. All experiments were performed under general anaesthesia (sevoflurane, end-tidal concentration 3.0 vol% in air) with mechanical ventilation (tidal volume 12.5 ml kg–1, ventilatory frequency 20 (5) min–1) maintaining normocapnia as verified by continuous capnography (end-tidal CO2 35 mm Hg, Capnomac Ultima, Datex, Helsinki, Finland) and intermittent blood gas analysis (ABL-700, Radiometer, Copenhagen, Denmark). During experiments, the dogs were lying on their right side, covered with warming blankets to maintain body temperature within the physiological range for dogs (37.0–38.5°C, rectal thermoprobe).

Epidural anaesthesia
TEA was performed as detailed previously for the application in dogs of the same breed, size, and weight.13 Briefly, under general anaesthesia, the epidural space was accessed under fluoroscopy at the L5/L6 inter-vertebral segment (loss-of-resistance technique, 16G Tuohy-needle, Perican, B.Braun, Melsungen, Germany) and a radiopaque epidural catheter (Perifix, B.Braun) was advanced cranially to the Th10-level. The final position of the catheter tip was confirmed by typical epidural spread of injected radiopaque dye (2 ml). The epidural drugs (lidocaine or saline) were infused as follows via a pressure-limited infusion pump (M770, IVAC, San Diego, CA, USA).

  1. Lidocaine (n=6). Following a test dose of lidocaine (lidocaine 1%, B.Braun; 3.0 ml infused within 2.5 min, to exclude catheter dislocation), a further 10 ml was infused over 7.5 min to achieve sufficient local anaesthetic spread (loading dose). Thereafter, a continuous infusion of 6.0 ml h–1 was initiated and maintained until the end of the experiment. This dosing regimen achieves sufficient epidural anaesthesia spread in dogs of the same breed, size, and weight.13 Spread of epidural anaesthesia was confirmed at the end of each experiment (awake animals) by paresis of the ocular nictitating membrane, sensory block up to the neck region, and motor block of the limbs.13
  2. Saline (n=6), control group. To unmask possible effects of epidural catheterization and epidural fluid administration, saline was infused epidurally in the same manner as detailed above, so that both groups received equal epidural fluid volumes over time.

Within the experiment, we observed the typical haemodynamic effect of TEA with lidocaine (e.g. a decrease in mean arterial pressure (MAP) and CO), which was absent in the controls. Following experimentation, the animals recovered from general anaesthesia within minutes, and subsequently the spread of epidural anaesthesia was verified (nictitating membrane paresis and paraplegia), as detailed previously.13

Compromised circulatory conditions
Compromised cardiocirculatory conditions were induced by application of positive end-expiratory pressure (PEEP, 10 cm H2O), as detailed previously for this canine model.12 This intervention reproducibly decreases primarily systemic DO2 and regional oxygenation (µHbO2), and is further characterized by relative hypovolaemia and thus fluid responsiveness, that is volume resuscitation increases cardiac output, DO2, and µHbO2.12

Measurements
Gastric mucosal oxygenation. Gastric mucosal oxygenation was assessed continuously by measuring microvascular haemoglobin oxygen saturation (µHbO2) using reflectance spectrophotometry (EMPHO II, BGT, Friedrichshafen, Germany), as detailed previously.12 Briefly, light (502–628 nm) is transmitted to the tissue of interest via a microlightguide and the reflected light is analysed for the percentage of oxygenated microvascular haemoglobin. This method has been validated in vitro and in vivo,14 and previously applied both in experimental12 and clinical studies.15 The flexible lightguide probe (outer diameter 2.0 mm) was introduced into the stomach via an orogastric silicone tube (14 Charriere). During experimentation the correct position of the tip was confirmed continuously by online-evaluation of the signal quality (EMPHO II software v2.0) to detect pressure- and dislocation-artifacts, as detailed previously.12 15 The µHbO2 values reported are the means of the last 4 min (150 spectra, 1.6 s each) of each intervention under steady state conditions.

Systemic haemodynamics and oxygenation
We continuously measured heart rate (HR, Digitalscope, Vuko, Kelkheim, Germany), MAP, and central venous pressures (CVP (right atrium), respectively, Gould–Statham pressure transducers P23ID, Elk Grove, USA), and CO (ultrasonic transit-time flowmeter, T101, Transonic Systems, Ithaca, USA). All variables were recorded on computer systems following analogue to digital conversion (Chart-software v4.1.2, AD-Instruments, Castle Hill, Australia).

Arterial and central venous (i.e. right atrial) blood gas tensions (, ), acid/base related variables (pH, HCO3) and lactate concentrations (ABL-700, Radiometer, Copenhagen, Denmark) were measured intermittently.

According to standard formulae, we calculated arterial and central venous oxygen content (, ), systemic oxygen-transport (DO2=COx), systemic oxygen-consumption (=COx()), oxygen extraction ratio (ERO2=VO2/DO2) and systemic vascular resistance (SVR=[MAP–CVP]/CO).

Experimental protocol
Following induction of general anaesthesia and instrumentation, 30 min were allowed to establish steady state conditions of all measured variables. Blood (arterial and central venous) was sampled for baseline analysis, and the dogs were randomly allocated either to the study (TEA with lidocaine) or control group (epidural saline). The experimental protocol is presented in Figure 1, and detailed below.



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Fig 1 Experimental protocol. BL=baseline; PEEP=positive end-expiratory pressure; EPI=epidural drug infusion; FL=fluid resuscitation; POST=post-PEEP period.

 
After baseline measurements (BL-1), PEEP (10 cm H2O) was applied for 15 min to record the individual effects of PEEP with respect to circulation and oxygenation. Thereafter, PEEP was discontinued and a second baseline period (BL-2) was allowed to ensure reversibility of any PEEP-induced changes.

Epidural drug infusion was then initiated (lidocaine or saline), and establishment of steady state values was allowed (30 min). Thereafter, PEEP was applied again as described, followed by a third baseline (BL-3), ensuring reversibility of PEEP effects also under study drug infusion.

PEEP was initiated again, and the PEEP-induced decrease in CO was subsequently restored by colloid infusion (HES 6%, 200/0.5, Fresenius-Kabi, Bad Homburg, Germany). Subsequently, two CO target values were achieved: first (FL-1), HES was infused to restore CO to the level associated with epidural drug infusion alone (i.e. BL-3), and secondly (FL-2) to the level before administration of the study drug (i.e. BL-2).

PEEP was finally terminated and measurements were taken with epidural drugs still infused (POST). After these final measurements, general anaesthesia was terminated and the animals recovered within minutes, allowing evaluation of the spread of epidural anaesthesia, as detailed above (AWAKE).

In summary, this protocol allowed assessment of the following conditions: compromised circulation without TEA, TEA under physiological conditions, TEA under compromised circulatory conditions, and TEA under compromised circulatory conditions with subsequent fluid resuscitation, with each intervention followed by recovery periods, sufficiently long to establish new steady state baseline conditions.

Statistical analysis
After confirming normal data distribution (Kolmogorov–Smirnov test, StatView V4.1, SAS-Institute Inc., Cary, USA), we tested for differences within and between the TEA (epidural lidocaine) and control (epidural saline) groups using analysis of variance for repeated measurements (ANOVA), and applied Fisher's PLSD (protected least square difference) test, where appropriate. Data presented were adjusted for multiple testing using the Bonferroni correction. Significance was assumed at P<0.05. The results are given as mean (SEM). Linear regression analysis was applied to describe the correlation between µHbO2/DO2 and the resulting regression lines were compared with respect to slope and position between the study groups (StatView V4.1).


    Results
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 Footnotes
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Physiological conditions
Under physiological conditions (Fig. 2), TEA maintained µHbO2 (47 (3) and 49 (5)%), despite significantly reducing systemic oxygen-transport (DO2, from 11.3 (0.8) to 10.0 (0.7) ml kg–1 min–1) and haemodynamics; that is MAP (from 66 (20) to 59 (3) mm Hg) and CO (76 (5) to 69 (5) ml kg–1 min–1) (Table 1). TEA maintained HR and SVR (Table 1) and preserved systemic oxygen consumption () (3.3 (0.4) vs 3.1 (0.5) ml kg–1 min–1) and ERO2 (0.29 (0.04) vs 0.32 (0.06)) (Table 2). In the control group, no significant changes were seen in regional (µHbO2) or systemic variables (DO2 11.1 (1.0) vs 11.2 (1.2) ml kg–1 min–1, MAP 64 (1) vs 65 (2) mm Hg, and CO 74 (7) vs 74 (7) ml kg–1 min–1).



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Fig 2 Effects of TEA and epidural saline infusion (controls) on gastric mucosal microvascular haemoglobin oxygenation (µHbO2), systemic oxygen-transport (DO2), and MAP under physiological conditions. Data presented as absolute values, n=6 dogs per group, mean (SEM), *P<0.05. TEA maintained µHbO2, despite significantly decreasing DO2 and MAP.

 

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Table 1 Systemic haemodynamics. Effects of TEA and epidural saline (control) on systemic haemodynamics under the following conditions: BL=baseline; PEEP=positive end-expiratory pressure; EPI=epidural drug infusion; FL=fluid resuscitation; POST=post-PEEP period. Data are mean (SEM) from n=6 dogs per group.

 

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Table 2 Ventilation and oxygenation related variables. Effects of TEA and epidural saline (control) under the following conditions: BL=baseline; PEEP=positive end-expiratory pressure; EPI=epidural drug infusion; FL=fluid resuscitation; POST=post-PEEP period. Variables: =arterial CO2 tension; pHa=arterial pH; HCO3a=arterial bicarbonate concentration, Hb=arterial haemoglobin concentration, =arterial oxygen saturation, Vo2=systemic oxygen consumption, Lactate=arterial lactate concentration. Data are means (SEM) from n=6 dogs per group.

 
Compromised circulatory conditions
Under compromised circulatory conditions (Fig. 3), TEA aggravated the reduction of µHbO2 (47 (1) to 33 (1)%) and DO2 (9.9 (0.6) to 6.5 (0.7) ml kg–1 min–1), compared with controls. Control animals responded to the application of PEEP with a reduction in CO (74 (7) to 57 (6) ml kg–1 min–1), but were still capable of maintaining MAP (65 (2) vs 65 (3) mm Hg) (Table 1). TEA aggravated this PEEP-induced depression in CO (69 (5) to 46 (5) ml kg–1 min–1), and TEA-treated animals were no longer capable of maintaining MAP during PEEP, which decreased from 59 (3) to 52 (4) mm Hg. During application of PEEP, SVR increased similarly during TEA (from 29 (1) to 39 (3) mm Hg litre–1 min–1) and in control (from 28 (2) to 37 (4) mm Hg litre–1 min–1). Under these compromised circulatory conditions, decreased during TEA, whereas it remained stable in control (Table 2).



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Fig 3 Effect of TEA and epidural saline infusion (controls) on gastric mucosal microvascular haemoglobin oxygenation (µHbO2), systemic oxygen-transport (DO2), and MAP under compromised cardiocirculatory conditions, before and after fluid resuscitation. Data presented as absolute values, n=6 dogs per group, mean (SEM), *P<0.05. TEA aggravated the PEEP-induced decrease of µHbO2 and DO2, compared with controls, whereas fluid resuscitation restored µHbO2 and DO2.

 
Fluid resuscitation (HES) under compromised circulatory conditions during TEA subsequently restored CO to target levels both before application of PEEP (FL-1; 69 (4) vs 69 (5) ml kg–1 min–1) and of TEA (FL-2; 76 (5) vs 76 (5) ml kg–1 min–1). Fluid resuscitation also increased µHbO2 to levels seen before application of PEEP (45 (2) vs 48 (2)%) and of TEA (51 (2) vs 53 (4)%). Thereby, the volume load returned SVR from 39 (4) to 30 (1) and 28 (1) mm Hg litre–1 min–1, respectively. Fluid resuscitation also restored (Table 2). The total required volume of HES used was 13 (3) ml kg–1 in the TEA group, and 6 (1) ml kg–1 in controls, respectively.

Ventilation- and oxygen-derived variables
Mechanical ventilation, targeted to maintain E'CO2 at 35 mm Hg, resulted in stable ventilation derived variables throughout the study (, ) (Table 2). Lactate concentration remained stable at around 2 mmol litre–1 (i.e. normal values for this breed of dogs) under all interventions, except for fluid resuscitation, when infusion of HES slightly decreased (diluted) lactate concentrations.

Correlation between µHbO2 and systemic haemodynamics
TEA preserved the relationship between regional (µHbO2) and systemic oxygenation (DO2), compared with controls, as indicated by the virtually identical slope and position of both graphs (Fig. 4). Additionally, Figure 4 illustrates that TEA proportionally worsened the impact of compromised cardiocirculatory conditions on µHbO2 and DO2, thereby also maintaining their correlation, as indicated by the linear extension of the TEA graph to the lower data points.



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Fig 4 Effects of TEA (solid line, r2=0.77) and epidural saline infusion (controls, dashed line, r2=0.90) on the relationship between systemic oxygen-transport (DO2) and regional mucosal oxygenation (µHbO2). Data are absolute values (mean (SEM)) from n=6 dogs per group.

 

    Discussion
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 Footnotes
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
The main findings of the present study are that (i) under physiological conditions, TEA did not impair regional µHbO2, whereas (ii) it worsened the impact of impaired circulatory conditions on both µHbO2 and DO2, thereby preserving the correlation between both variables.

Critique of methods
Repetitive experiments (randomized, placebo-controlled) were performed on healthy, chronically instrumented dogs with intervals of at least 2 weeks to exclude carry-over effects, and to minimize inter-individual differences.

In previous studies on splanchnic effects of TEA, splanchnic organs were acutely accessed for instrumentation via a laparotomy,9 16 where surgery or splanchnic organ handling might have induced a stress response, which can be blunted by epidural anaesthesia. This recently discussed methodological problem of confounding analgesia and a blunted stress-response by epidural anaesthesia in studies on tissue oxygenation10 11 was circumvented in the present study by using intact animals. This different experimental approach may explain, why in the present study TEA alone did not change SVR, whereas in other studies TEA significantly decreased SVR,9 probably reflecting a higher baseline sympathetic tone before TEA in those studies, for example caused by the preceding surgical instrumentation. Thus, although we intentionally selected a non-traumatic model to study the effects of TEA in the absence of analgesic effects, we are aware that our results may not apply directly to the clinical setting, where epidural anaesthesia is usually explicitly performed because of its analgesic potency. Beneficial splanchnic effects of TEA could even be pronounced under conditions of intense pain/trauma, where epidural anaesthesia may exert its positive effects also by blunting pain-mediated input to the nervous system.

Compromised circulatory conditions were induced by application of PEEP, an intervention that reproducibly decreased both systemic (DO2) and regional (µHbO2) oxygenation, as detailed previously.12 This intervention comprises both, backward (i.e. venous congestion, as suggested by the doubled central venous pressures) and forward circulatory impairment (i.e. reduced CO). Additionally, this model is characterized by a marked fluid responsiveness; that is volume resuscitation with HES increases both systemic and regional oxygenation. We are aware that the (patho-)physiologic consequences within this model of circulatory impairment may differ from other forms of circulatory impairment (e.g. haemorrhage) so that the conclusions derived from this model may not be directly transferred to other experimental or clinical forms of circulatory compromise.

Gastric mucosal oxygenation was continuously assessed by measuring microvascular µHbO2 by tissue reflectance spectrophotometry, a method validated in vitro and in vivo using -electrodes.14 This detects splanchnic ischaemia with similar precision as laser flowmetry17 or intravital microscopy.18 As detailed previously, the lightguide was non-traumatically introduced via an orogastric tube into the stomach,12 a site demonstrated to represent the microvascular oxygenation of other gastric and upper intestinal mucosal regions.19 Reflectance spectrophotometry allows direct determination of intracapillary haemoglobin oxygen-saturation, and gastric endoluminal reflectance spectroscopy has been reported recently to measure predominantly capillary haemoglobin oxygen-saturation of the mucosa,20 rather than of outer wall layers. Spectrophotometry reliably detects even clinically asymptomatic reductions in gastric mucosal oxygenation,15 and correlates highly with the morphologic severity and extent of gastric mucosal tissue injury.21

The values for microvascular mucosal oxygenation (µHbO2) at baseline observed in our study are in close agreement with values obtained from previous studies on gastrointestinal mucosal oxygenation in dogs12 and pigs.22 Furthermore, a decrease in gastrointestinal mucosal µHbO2 from about 50 to 30% has also been observed in pigs, haemorrhaged to half their initial blood volume,22 indicating the extent of our intervention.

Accordingly, from a methodological point of view, our experimental design was appropriate to study the effects of TEA on gastric mucosal oxygenation and systemic oxygen-transport, both under physiological and compromised circulatory conditions.

Interpretation of results
Effects of TEA under physiological conditions. Few studies have addressed the effects of TEA on the splanchnic region, mainly focusing on splanchnic blood flow. Most studies report reduced splanchnic perfusion combined with reduced CO,5 23 which, at first glance, contrasts with our finding of a preserved gastric mucosal oxygenation during TEA. However, the splanchnic mucosa particularly possesses powerful autoregulation, preserving microcirculatory oxygenation even during decreased systemic and splanchnic oxygen-delivery.24

Those studies reporting the effects of epidural anaesthesia on the gastrointestinal mucosa mainly studied surrogate markers (e.g., tonometrically assessed -gap or pHi), and report divergent results,25 for example improved,8 unchanged,6 7 or even decreased26 mucosal perfusion. These conflicting results may be a result of differences in study design, including type (e.g. spread) of epidural anaesthesia,25 but may also depend on the measurement site. For example, high epidural anaesthesia improved pHi of the native stomach and colon, but decreased pHi of a surgically manipulated colon segment within the same patients.26 Moreover, even direct, intravital microscopic measurements of mucosal perfusion remain contradictory. In a study on rats, TEA increased perfusion of the intestinal mucosa by 37%,16 whereas a recent study on a similar model failed to demonstrate an improvement in intestinal mucosal perfusion by TEA.27

However, measurements of tissue perfusion do not always predict microvascular tissue oxygenation, which has also been demonstrated for the gastric mucosa.28 Furthermore, TEA particularly may increase pre-capillary arteriovenous shunting,5 23 which may, even at stable total organ blood flow, decrease gastrointestinal capillary nutrient perfusion and thus microcirculatory oxygenation. Collectively, this underlines the importance of studying the effects of epidural anaesthesia on direct measures of gastrointestinal tissue oxygenation, which has only been performed in two studies so far; that is by -electrodes.9 29 The first study29 reports that epidural anaesthesia during abdominal surgery increased intestinal at the serosa (from 34 to 41 mm Hg), but this effect may be explained partly by a parallel, significant increase in (from 132 to 141 mm Hg). In the second study,9 TEA had no effect on gastrointestinal tissue in pigs, neither at the serosa ( ~30 mm Hg), nor at the mucosa ( ~15 mm Hg). The latter finding further supports our observation of preserved mucosal oxygenation during TEA. However, in contrast to our results, this latter study failed to demonstrate an increase in mucosal oxygenation to fluid (HES) administration, which may be a result of a more liberal fluid load before induction of TEA in that study.

Effects of TEA in compromised cardiocirculatory conditions
Circulatory impairment evokes splanchnic sympathetic vasoconstriction and thus blood flow redistribution from the splanchnic viscera to more vital organs. PEEP in particular, as applied in our model of circulatory impairment, activates the sympathetic nervous system.23 By inference, extended sympatholysis produced by TEA should prevent splanchnic vasoconstriction, leading to preserved splanchnic tissue perfusion and oxygenation. However, our results suggest the opposite, that TEA worsened the impairment of mucosal oxygenation. Several mechanisms may contribute: TEA did not selectively aggravate the impairment of regional oxygenation (µHbO2) produced by PEEP, but concomitantly also worsened the depression of systemic haemodynamics and DO2, the latter finding also being supported by others.23 Thus, changes in µHbO2 may primarily reflect a depression of systemic oxygen-transport, which in turn may result from decreased cardiac sympathetic drive, and reduced capacitance vessel tone (attenuating cardiac preload via venous blood pooling) and blunted adrenoceptor-mediated renin–angiotensin release.23 This concept of systemic-to-regional dependency during TEA is further supported by our findings that fluid resuscitation alone, directed to restore CO during impaired cardiocirculatory conditions, was sufficient to also completely restore regional µHbO2, and that the correlation between µHbO2 and DO2 was not altered by TEA.

Additionally, during compromised circulatory conditions, TEA-treated animals were not able to maintain arterial pressure, compared with controls. This uncompensated hypotension may have triggered the release of non-adrenergic reserve vasopressors (e.g. endothelin or vasopressin) both acting as potent splanchnic vasoconstrictors, finally preventing an increase or even decreasing splanchnic perfusion and oxygenation.

Finally, diverging effects of TEA on vessels of the mucosa and the outer layers of the gastrointestinal tract (i.e. serosa and muscularis) may contribute to the aggravated depression of gastric mucosal oxygenation during circulatory impairment: during experimental hypovolaemia, TEA is reported to increase capillary perfusion of outer gastrointestinal layers, but fails to improve perfusion of the mucosa.27 This selective increase in vascular conductance of the outer tissue layers by TEA is attributed to different sympathetic innervation patterns (i.e. outer gastrointestinal vessels present dense innervation by sympathetic nerve fibres) whereas mucosal vessels lack sympathetic innervation.27 Thus, the selective increase in vascular conductance and capacitance of the outer gastrointestinal layers during TEA may redistribute the already PEEP-impaired splanchnic perfusion away from the mucosa (intramural steal). At this stage, the autoregulatory capacity of the mucosa may exhaust and mucosal oxygenation may become supply dependent. This is in accordance with our finding of an aggravated reduction in mucosal oxygenation by TEA during compromised circulatory conditions, in proportion to the reduction in systemic oxygen transport.

Clinical implications. There is increasing evidence that splanchnic ischaemia, especially of the gastrointestinal mucosa as the gut barrier, plays a crucial role in the pathogenesis of critical illness and multiple organ failure.1 The major defence mechanism, protecting mucosal integrity, is adequate microcirculatory perfusion and oxygenation.30 Therefore, it appears important that clinical interventions, particularly when applied in patients with an elevated risk for the development of splanchnic hypoperfusion, do not compromise gastrointestinal mucosal oxygenation. An intervention with unclear impact on splanchnic mucosal oxygenation, which is increasingly applied in high-risk patients, is TEA. Although we are aware that experimental results may not be translated directly to the clinical setting, the present study indicates that TEA maintains µHbO2 and thus did not compromise gastric mucosal oxygenation. Furthermore, TEA preserved the correlation between regional and systemic oxygenation, although it worsened the response to cardiocirculatory impairment. Restoring systemic oxygen-transport by volume loading, as a routine measure during TEA, completely restored gastric mucosal oxygenation. According to our data, we conclude that with the prerequisite of maintaining adequate systemic oxygen-transport, TEA preserves gastrointestinal mucosal oxygenation.

In summary, we demonstrate for the first time, that TEA maintained µHbO2 under physiological conditions, and preserved the correlation between regional splanchnic and systemic oxygenation in impaired circulatory conditions. This was despite worsening the impact of compromised circulation on both variables.


    Acknowledgments
 
Supported by a grant from the research commission, Medical Faculty, University of Düsseldorf, and departmental funds.


    Footnotes
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 Footnotes
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
{dagger} Presented in part at the German Anaesthesia Congress 2003 (April 9–12, Munich, Germany) and the European Society of Intensive Care Congress 2003 (October 5–8, Amsterdam, The Netherlands). Back


    References
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 Footnotes
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
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