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Intramucosal–arterial PCO2 gap fails to reflect intestinal dysoxia in hypoxic hypoxia

  • 1Email author,
  • 2,
  • 3,
  • 4,
  • 5,
  • 2,
  • 4,
  • 6,
  • 7 and
  • 8
Critical Care20026:514

https://doi.org/10.1186/cc1813

  • Received: 1 May 2002
  • Accepted: 6 August 2002
  • Published:

Abstract

Introduction

An elevation in intramucosal–arterial PCO2 gradient (ΔPCO2) could be determined either by tissue hypoxia or by reduced blood flow. Our hypothesis was that in hypoxic hypoxia with preserved blood flow, ΔPCO2 should not be altered.

Methods

In 17 anesthetized and mechanically ventilated sheep, oxygen delivery was reduced by decreasing flow (ischemic hypoxia, IH) or arterial oxygen saturation (hypoxic hypoxia, HH), or no intervention was made (sham). In the IH group (n = 6), blood flow was lowered by stepwise hemorrhage; in the HH group (n = 6), hydrochloric acid was instilled intratracheally. We measured cardiac output, superior mesenteric blood flow, gases, hemoglobin, and oxygen saturations in arterial blood, mixed venous blood, and mesenteric venous blood, and ileal intramucosal PCO2 by tonometry. Systemic and intestinal oxygen transport and consumption were calculated, as was ΔPCO2. After basal measurements, measurements were repeated at 30, 60, and 90 minutes.

Results

Both progressive bleeding and hydrochloric acid aspiration provoked critical reductions in systemic and intestinal oxygen delivery and consumption. No changes occurred in the sham group. ΔPCO2 increased in the IH group (12 ± 10 [mean ± SD] versus 40 ± 13 mmHg; P < 0.001), but remained unchanged in HH and in the sham group (13 ± 6 versus 10 ± 13 mmHg and 8 ± 5 versus 9 ± 6 mmHg; not significant).

Discussion

In this experimental model of hypoxic hypoxia with preserved blood flow, ΔPCO2 was not modified during dependence of oxygen uptake on oxygen transport. These results suggest that ΔPCO2 might be determined primarily by blood flow.

Keywords

  • blood flow
  • carbon dioxide
  • hypoxia
  • oxygen consumption
  • tonometry

Introduction

Tonometry is one of the few clinical tools available for the monitoring of tissue oxygenation [1]. Decreases in gastrointestinal intramucosal pH (pHi) have usually been considered as indicators of dysoxia [2,3,4,5]; that is, as heralds of insufficient O2 to meet tissue demands. Recently, the intramucosal–arterial PCO2 gradient (ΔPCO2) has been claimed to be a better marker of gastrointestinal mucosal state of oxygenation [6]. PCO2 can increase in intestinal lumen by two mechanisms [7]. One is by bicarbonate buffering of protons from the breakdown of high-energy phosphates and metabolic acids generated anaerobically, such as lactate, in which case increased PCO2 would represent tissue dysoxia. Alternatively, in an aerobic state, it might be the result of hypoperfusion and decreased washout. In this latter case, oxygen metabolism could be preserved if the flow were adequate.

Grum et al. [2] found that pHi and intestinal oxygen uptake (VO2) were correlated in ischemia, in hypoxemia, and in a combination of both. However, in hypoxemic experiments, neither VO2 nor pHi fell. Hence, the value of tonometry in hypoxemia remains uncertain. If a rise in ΔPCO2 reflected only a decrease in blood flow, this gradient might not be altered in hypoxemia, in which cardiac output (CO) is usually maintained and even increased. Our hypothesis was that ΔPCO2 would not be modified in hypoxic hypoxia (HH) with preserved blood flow.

Methods

Surgical preparation

This study was approved by the local Animal Care Committee. Care of studied animals was in accordance with National Institutes of Health guidelines. Seventeen adult sheep (26.0 ± 9.1 kg [mean ± SD]) were anesthetized with 30 mg/kg sodium pentobarbital, tracheostomized and then ventilated (Harvard Pump Ventilator; Harvard Apparatus, South Natick, Massachusetts, USA) with a tidal volume of 15 ml/kg, a respiratory rate of 12 per minute, and a positive end-expiratory pressure of 5 cm H2O throughout the experiment. The starting fraction of inspired oxygen (FiO2) was 0.21. Additional pentobarbital was administered if necessary. Neuromuscular blockade was provided with a single dose of pancuronium (0.06 mg/kg). Catheters were placed into the femoral artery and vein and into the pulmonary artery (flow-directed thermod-ilution fiberoptic pulmonary artery catheter; Abbott Critical Care Systems, Mountain View, California, USA).

After performing a midline laparotomy, we performed splenectomy and a gastrostomy with drainage of gastric contents. We placed an electromagnetic blood flow transducer around the superior mesenteric artery. A catheter was advanced into the superior mesenteric vein, and a tonometer was inserted into the ileum.

Measurements and derived calculations

CO was measured in triplicate by the thermodilution technique, with 5 ml of iced saline (HP OmniCare Model 24 A 10; Hewlett Packard, Andover, Massachusetts, USA), and was referred to body weight. Superior mesenteric artery blood flow (intestinal blood flow) was measured by the electromagnetic method (Spectramed Blood Flowmeter model SP 2202 B; Spectramed Inc., Oxnard, California, USA) and indexed to intestinal weight.

Arterial mixed venous and mesenteric venous PO2, PCO2, and pH, and haemoglobin concentrations and saturations were measured with a blood gas analyzer and a co-oximeter, respectively (ABL 30 and OSM 3; Radiometer, Copenhagen, Denmark). Systemic and intestinal oxygen transport and uptake (DO2, VO2, intestinal DO2, and intestinal VO2 respectively) were calculated with standard formulae.

Intramucosal PCO2 was measured by saline tonometry (TRIP Sigmoid Catheter; Tonometrics, Inc., Worcester, Massachu-setts, USA) [8]. After an equilibration period of 30 minutes, 1.0 ml was discarded. PCO2 was measured in the remnant (ABL 30; Radiometer). pHi and ΔPCO2 were calculated with a correction factor for the equilibration time. Kolkman et al. [9] showed that the variability of intramucosal PCO2 measurements is independent of dwell time. Assessments at short dwell times should therefore be reliable.

We calculated venoarterial and intramucosal–arterial CO2 content differences to evaluate the changes in the CO2 dissociation curve [10]. To compute intramucosal CO2 content, intramucosal PCO2, pH, and mesenteric venous oxygen saturation were considered as representative of mucosal blood.

Experimental procedure

After a stabilization period of at least 30 minutes, we performed basal measurements (0 minutes). Sheep were then assigned to ischemic hypoxia (IH [n = 6]), HH (n = 6), or sham (n = 5) groups. In the IH group, bleeding was performed in three steps of 10 ml/kg at intervals of 30 minutes. In the HH group, 2 ml/kg 0.1 M hydrochloric acid was instilled into the trachea, and FiO2 was raised to 0.50. Saline solution was infused to keep intestinal blood flow constant. Measurements were repeated at 30, 60, and 90 minutes. Body temperature was maintained stable with a heating lamp.

Finally, animals were killed with supplemental pentobarbital and a KCl bolus. Indian ink was infused through the superior mesenteric artery, and dyed intestinal segments were dissected and weighed.

Statistical analysis

Data are expressed as means ± SD except where noted otherwise. Analysis within groups was performed with a repeated-measures analysis of variance (ANOVA) and a paired t-test with Bonferroni correction. One-way ANOVA and unpaired t-test with Bonferroni correction were used for one-time comparisons. In both cases, t-tests were used when ANOVA results were significant; P < 0.05 was considered significant.

Results

Hemoglobin concentration, and arterial, mixed venous, and mesenteric venous blood gases and oxygen saturations in basal conditions, and during IH and HH and in the sham group are shown in Table 1.
Table 1

Hemoglobin concentration and arterial, mixed venous, and mesenteric venous blood gases and oxygen saturations in basal conditions and during ischemic hypoxia (HI) and hypoxic hypoxia (HH), and in the sham group

Parameter

Group

Basal

30 minutes

60 minutes

90 minutes

Hemoglobin (g%)

IH

9.1 ± 0.6

8.6 ± 0.6

7.9 ± 1.1*

7.4 ± 1.3*

 

HH

10.2 ± 1.2

10.7 ± 1.0‡‡

11.2 ± 1.1‡‡

11.4 ± 1.2*‡‡

 

SHAM

10.7 ± 1.6

11.0 ± 1.4‡‡

11.4 ± 1.3‡‡

11.2 ± 1.1‡‡

Arterial pH

IH

7.36 ± 0.10

7.35 ± 0.07

7.31 ± 0.10

7.25 ± 0.11*

 

HH

7.41 ± 0.07

7.26 ± 0.10**

7.21 ± 0.12**

7.15 ± 0.13**

 

SHAM

7.37 ± 0.09

7.39 ± 0.10

7.38 ± 0.10

7.36 ± 0.13

Arterial PCO2 (mmHg)

IH

33 ± 3

31 ± 4

28 ± 3**

24 ± 4**††

 

HH

29 ± 3

40 ± 8*

45 ± 11*

49 ± 13**

 

SHAM

30 ± 4

28 ± 3†

28 ± 3†

28 ± 6†

Arterial PO2 (mmHg)

IH

79 ± 10

81 ± 12

82 ± 12†

91 ± 7††

 

HH

91 ± 16

59 ± 23**

50 ± 13**

44 ± 7**

 

SHAM

88 ± 12

86 ± 20

85 ± 20†

80 ± 17††

Arterial O2 saturation

IH

91.2 ± 2.9

90.7 ± 3.4

90.1 ± 3.0†

91.8 ± 2.8††

 

HH

96.3 ± 3.0

69.9 ± 21.9*

60.0 ± 22.0*

52.3 ± 15.8**

 

SHAM

96.1 ± 3.6

95.7 ± 3.2

94.9 ± 4.6†

93.0 ± 7.5††

Mixed venous pH

IH

7.31 ± 0.06

7.28 ± 0.08

7.19 ± 0.11*

7.09 ± 0.11**

 

HH

7.36 ± 0.08

7.23 ± 0.10**

7.17 ± 0.13**

7.10 ± 0.13**

 

SHAM

7.33 ± 0.09

7.33 ± 0.10

7.33 ± 0.10

7.34 ± 0.12§

Mixed venous PCO2 (mmHg)

IH

41 ± 3

43 ± 4

46 ± 4

49 ± 5*

 

HH

36 ± 5

47 ± 9*

52 ± 12*

59 ± 15*

 

SHAM

36 ± 5

35 ± 6

33 ± 4§§

32 ± 6§§

Mixed venous PO2 (mmHg)

IH

34 ± 4

27 ± 6**

20 ± 5**

18 ± 4**

 

HH

38 ± 7

30 ± 11

28 ± 10**

24 ± 8**

 

SHAM

40 ± 6

36 ± 8

42 ± 9§

43 ± 9§§

Mixed venous O2 saturation

IH

44.6 ± 11.0

28.4 ± 14.3*

16.4 ± 10.1**

11.2 ± 3.3**

 

HH

52.9 ± 11.8

33.4 ± 21.5*

26.6 ± 18.6*

19.0 ± 12.0**

 

SHAM

55.2 ± 12.1

53.3 ± 10.9‡

48.5 ± 16.5§§

48.8 ± 18.5§§

Mesenteric venous pH

IH

7.30 ± 0.09

7.28 ± 0.10

7.21 ± 0.12*

7.15 ± 0.14*

 

HH

7.35 ± 0.10

7.21 ± 0.13**

7.16 ± 0.15**

7.10 ± 0.16**

 

SHAM

7.35 ± 0.09

7.35 ± 0.09

7.33 ± 0.10

7.34 ± 0.10§

Mesenteric venous PCO2 (mmHg)

IH

42 ± 4

43 ± 4

44 ± 4

44 ± 5

 

HH

39 ± 9

49 ± 14

54 ± 18

60 ± 21

 

SHAM

36 ± 4

33 ± 4§

33 ± 4§

32 ± 6§

Mesenteric venous PO2 (mmHg)

IH

38 ± 8

32 ± 6*

25 ± 4*

25 ± 4*

 

HH

38 ± 6

33 ± 10

29 ± 10*

26 ± 9*

 

SHAM

43 ± 7

42 ± 10

42 ± 9‡

43 ± 9§

Mesenteric venous O2 saturation

IH

52.3 ± 16.8

41.6 ± 13.3**

30.2 ± 11.5**

20.3 ± 4.9**

 

HH

57.5 ± 15.0

36.2 ± 23.1*

29.1 ± 23.2*

23.9 ± 17.5**

 

SHAM

67.5 ± 10.5

63.3 ± 14.6

63.3 ± 14.6‡‡†

65.1 ± 16.4§§

*P < 0.05 versus basal; **P < 0.01 versus basal; † P < 0.05 versus hypoxic hypoxia; †† P < 0.01 versus hypoxic hypoxia; ‡ P< 0.05 versus ischemic hypoxia; ‡‡ P < 0.01 versus ischemic hypoxia; §P < 0.05 versus ischemic and hypoxic hypoxia; §§ P < 0.01 versus ischemic and hypoxic hypoxia (paired or unpaired t-tests with Bonferroni correction, after analysis of variance < 0.05).

Systemic and intestinal supply dependence was induced in both the IH and HH groups. There were no significant changes in systemic and intestinal DO2 and VO2 in the sham group (Figure 1). In the IH group, supply dependence appeared with critical decreases in CO and superior mesenteric artery blood flow (0.104 ± 0.024 versus 0.048 ± 0.006 l/min per kg, and 0.664 ± 0.227 versus 0.258 ± 0.082 l/min per kg, respectively; P < 0.0001). In the HH group it was due to a progressive decrease in arterial oxygenation. CO and intestinal blood flow were maintained (0.446 ± 0.085 versus 0.431 ± 0.140 ml/min per kg, respectively; not significant), owing to the administration of normal saline (median 630 ml; range 20–1310 ml). Arterial and intra-mucosal pH fell significantly in the IH and HH groups. In the HH group it was primarily related to systemic respiratory and metabolic acidosis (Tables 1 and 2), because ΔPCO2 did not increase. In addition, systemic and intestinal venoarterial PCO2 gradients were not modified. CO2 content differences also did not change (Table 2 and Figure 2). In contrast, in the IH group, ΔPCO2, systemic and intestinal venoarterial PCO2, and CO2 content gradients increased significantly (Table 2 and Figure 2). In the sham group, CO2 gradients and pHi remained unchanged.
Figure 1
Figure 1

Systemic and intestinal oxygen supply dependence. (a) Relationship between systemic oxygen transport and consumption during ischemic and hypoxic hypoxia, and in the sham group. (b) Relationship between intestinal oxygen transport and consumption during ischemic and hypoxic hypoxia, and in the sham group. Data are expressed as means ± SEM. *P < 0.05 versus basal oxygen consumption. §P < 0.05 versus sham group.

Figure 2
Figure 2

Relationship between intestinal oxygen transport and intramucosal–arterial PCO2 difference during ischemic and hypoxic hypoxia, and in the sham group. Data are expressed as means ± SEM. *P < 0.05 versus basal intramucosal–arterial PCO2 difference. § P < 0.05 versus hypoxic hypoxia and sham group.

Table 2

CO2 gradients and intramucosal pH during ischemic hypoxia (IH) and hypoxic hypoxia (HH), and in the sham group

Parameter

Group

Basal

30 minutes

60 minutes

90 minutes

Mixed venous–arterial PCO2 (mmHg)

IH

8 ± 2

12 ± 3*

19 ± 5**††

25 ± 4**††

 

HH

7 ± 2

7 ± 3

8 ± 3

9 ± 3

 

SHAM

5 ± 2

7 ± 3†

6 ± 3‡‡

5 ± 3‡‡

Mixed venous–arterial CO2 content (vol%)

IH

4.3 ± 1.6

7.2 ± 4.8

10.9 ± 2.5*††

14.3 ± 3.6*††

 

HH

4.6 ± 1.7

3.5 ± 1.4

3.4 ± 2.0

3.2 ± 1.0

 

SHAM

4.0 ± 4.8

5.7 ± 3.1

6.9 ± 2.1

2.7 ± 1.8‡‡

Mesenteric venous–arterial PCO2 (mm Hg)

IH

9 ± 4

12 ± 3*††

16 ± 4**

19 ± 5††‡

 

HH

9 ± 5

5 ± 3

20 ± 10

6 ± 2

 

SHAM

6 ± 3

5 ± 2‡‡

6 ± 1‡‡

5 ± 2‡‡

Mesenteric venous–arterial CO2 content (vol%)

IH

4.7 ± 1.2

7.2 ± 3.2

8.2 ± 2.4*††

9.8 ± 2.2*††

 

HH

6.6 ± 5.7

3.8 ± 2.6

3.4 ± 2.4

3.4 ± 2.3

 

SHAM

3.0 ± 1.9

3.3 ± 1.1

5.4 ± 2.4

2.6 ± 1.8‡‡

Intramucosal–arterial PCO2 (mmHg)

IH

12 ± 10

19 ± 12*

32 ± 17**††

40 ± 13**††¶

 

HH

13 ± 6

8 ± 8

13 ± 11

10 ± 13

 

SHAM

8 ± 5

11 ± 3‡

10 ± 4‡‡

9 ± 6‡‡

Intramucosal–arterial CO2 content (vol%)

IH

2.0 ± 0.4

2.4 ± 0.6††

2.8 ± 0.8*††

3.3 ± 0.8**††

 

HH

2.0 ± 0.5

0.7 ± 0.8

0.9 ± 0.9

0.3 ± 1.2

 

SHAM

1.7 ± 0.4

1.9 ± 0.7

2.1 ± 0.9

1.7 ± 0.5‡

Intramucosal Ph

IH

7.24 ± 0.14

7.16 ± 0.16**

7.01 ± 0.22**

6.84 ± 0.21**

 

HH

7.26 ± 0.14

7.19 ± 0.13**

7.10 ± 0.16**

7.07 ± 0.18**

 

SHAM

7.28 ± 0.06

7.26 ± 0.09

7.17 ± 0.08

7.25 ± 0.10§§

*P < 0.05 versus basal; **P < 0.01 versus basal; † P < 0.05 versus hypoxic hypoxia; †† P < 0.01 versus hypoxic hypoxia; ‡ P < 0.05 versus ischemic hypoxia; ‡‡ P < 0.01 versus ischemic hypoxia; §P < 0.05 versus ischemic and hypoxic hypoxia; §§ P < 0.01 versus ischemic and hypoxic hypoxia (paired or unpaired t-tests with Bonferroni correction, after analysis of variance < 0.05).

Discussion

Increased mucosal intestinal PCO2 is used as a tool to detect delivery can no tissue dysoxia, the condition in which O2 longer sustain O2 uptake [11]. A great body of literature supports the role of intestinal PCO2 as an early marker of dysoxia and regional hypoperfusion. Early studies considered pHi as the reference parameter. Recently, some investigators have claimed that intramucosal PCO2, the variable actually measured by the tonometer, and ΔPCO2 could more adequately reflect mucosal oxygenation [6,12]. pHi is a calculated variable, from the Henderson–Hasselbach equation, with the assumption that arterial bicarbonate is representative of intra-mucosal bicarbonate. In a steady state, both values might be similar. However, in rapidly changing physiological situations, differences between arterial and mucosal CO2 might arise owing to slow CO2 equilibrium kinetics [13]. Therefore, pHi values calculated from tonometry might differ from those directly measured with tissue electrodes [14]. Moreover, acid–base states could influence in the absence of pHi altered mucosal oxygenation. As a result, the acid–base status of arterial blood will be reflected in both mucosal pHi and PCO2 [6,14]. In our experiments, pHi fell progressively during hydrochloric acid-induced lung injury and decreased DO2, reflecting ongoing systemic respiratory and metabolic acidosis. However, ΔPCO2 remained unchanged.

Another issue that has been discussed extensively is the relative impact on mucosal PCO2 of anaerobic production of CO2 in comparison with decreased washout of aerobically generated CO2 during low flow states. Many investigators [15,16,17] have ascribed increased PCO2 found in shock states to continuing aerobic CO2 production with decreased elimination; that is, to 'respiratory acidosis'. However, Schlichtig and Bowles [7] showed evidence supporting the role of intramu-cosal PCO2 as a marker of dysoxia in extreme hypoperfusion, when VO2 falls. In a dog model of cardiac tamponade, they demonstrated that mucosal PCO2 could rise because of anaerobic CO2 production below the critical DO2. These conclusions were drawn by using the Dill nomogram, which can theoretically detect anaerobic CO2 production from a comparison of the measured (%HbO2,v) and calculated (%HbO2,vDill) venous oxyhemoglobin, within a given venous PCO2 value. Because venous PCO2 is considered to be representative of tissue PCO2, Schlichtig and Bowles made the calculation with its intestinal equivalent, intramucosal PCO2. If %HbO2,vDill is lower than the measured %HbO2,v, anaerobic production of CO2 might be assumed. Similar values would represent aerobic CO2 generation. Notwithstanding the original contribution of Schlichtig and Bowles [7] to the analysis of these topics, the use of low flow to produce critical oxygen delivery and falling VO2 has been signaled as a potential confounding factor [18].

We studied these issues in a model of HH with preserved flow, because it allows a clear discrimination between hypoxia and hypoperfusion. There have been attempts to analyze pHi behavior in HH, but critical intestinal DO2 was not attained, and intestinal VO2 and pHi remained unchanged [2]. Our model consisted of an acute lung injury produced by endotracheal instillation of hydrochloric acid that rapidly generated severe hypoxemia, shown by the decrease in arterial PO2 and pH. The acid also enhanced microvascular permeability [19,20,21], demonstrated by increased requirements of saline solution to maintain intestinal blood flow and by the increase in hemoglobin levels. However, other mechanisms could be acting to preserve blood flow, such as tachycardia and enhanced left ventricular contractility [22]. Deep arterial hypoxemia caused significant reductions in systemic and intestinal DO2, but systemic and intestinal blood flow were preserved and hemoglobin concentration increased. Despite the increase in systemic and intestinal oxygen extraction, systemic and intestinal VO2 values decreased, and dependence of O2 uptake on transport ensued. Dependence of oxygen consumption on transport during HH has been described by Cain et al. in a classical study [23], and it has been considered an indicator of anaerobic metabolism. Additional evidence of tissue dysoxia was the appearance of metabolic acidosis. Cain [24] also showed that there is a correlation between pH and lactate/pyruvate relationship in HH.

Another potential confounding factor that could affect arterial and intestinal PCO2 and their differences is the shift of the CO2 dissociation curve. As Jakob et al. [25] have shown, there can be a lack of correlation of CO2 contents and PCO2, and, consequently, of their differences. Many determinants of the shifts of the CO2 dissociation curve, such as changes in pH, in hemoglobin concentrations, and especially in oxygen saturations (the Haldane effect), were present. To discard a possible increase in venoarterial and intramucosal–arterial CO2 contents without changes in PCO2 differences in the HH group, we calculated CO2 content differences. There were no increases in venoarterial and intramucosal–arterial CO2 content differences during the period of supply dependence, as there were no changes in both PCO2 differences. Shifts of the CO2 dissociation curve therefore do not seem to influence our results.

Our model of HH is useful for discriminating the effects of hypoxia and low blood flow, because this last factor was kept constant throughout the experiment. ΔPCO2 remained stable, although there were signs of anaerobic metabolism. Systemic and venoarterial PCO2 differences also remained unchanged. Conversely, during supply dependence of VO2 induced by hemorrhage, ΔPCO2 and systemic and intestinal venoarterial PCO2 differences widened, as well as the respective ΔPCO2 content differences. Moreover, these parameters increased before any change in VO2, as we have described previously [26]. These results suggest that, at least in our experiments, tissue perfusion is a key determinant of increased ΔPCO2.

Nevière et al. [27] tested a similar hypothesis in pigs. They compared the effects of diminished blood flow with diminished inspired fraction of oxygen. In IH, ΔPCO2 increased to 60 mmHg. In HH, ΔPCO2 increased to 30 mmHg only in the last step of hypoxemia, although mucosal blood flow measured by laser Doppler flowmetry was preserved. The authors concluded that elevated intramucosal PCO2 indicated local CO2 generation. However, in the two previous stages of reduced FiO2 there was supply dependence, and ΔPCO2 remained unchanged. In our HH model, ΔPCO2 was also stable. The differences between our data and those of Nevière et al. [27] could be ascribed to distinct microvascular features of the experimental subjects (pigs and sheep) or to different degrees of hypoxemia. In addition, as Nevière et al. pointed out, some degree of decrease in gut mucosal blood flow and heterogeneity might have been present, because only global microvascular blood flow changes can be assessed by laser Doppler flowmetry. Nevertheless, both studies show that ΔPCO2 could fail to reflect tissue dysoxia at some time during HH. In results similar to ours, Vallet et al. [28] showed that perfusion is a major determinant of venoarterial PCO2 difference during critical IH or HH in isolated hindlimb. This gradient increases in ischemia and is preserved in hypoxia.

Venoarterial and intramucosal–arterial PCO2 gradients are the result of interactions of changes in aerobic and anaerobic CO2 production, the CO2 dissociation curve, and blood flow to tissues. During oxygen supply dependence induced by hemorrhage, opposite changes in aerobic and anaerobic CO2 production are present: aerobic CO2 production decreases as a consequence of depressed aerobic metabolism, but anaerobic CO2 production starts because of bicarbonate buffering of protons from fixed acids. Total CO2 production might not increase, but O2 consumption falls, so there is an increase in respiratory quotient [29,30]. This increase in VCO2 relative to VO2 might generate tissue and venous hypercarbia only in low flow states, in which there is diminished CO2 removal. Other situations in which intramucosal acidosis could arise with preserved tissue perfusion are reperfusion injury [31] and cytopathic hypoxia generated by endotoxemia [32], with cellular damage and metabolic abnormalities as underlying mechanisms. However, impaired villous microcirculation has been advocated as the causal phenomenon in the latter [33].

Conclusions

To our knowledge, this is the first study showing that ΔPCO2 fails to mirror intestinal tissue dysoxia. Our findings also suggest that blood flow might be the main determinant of ΔPCO2. Tonometry seems to be a useful method for monitoring perfusion, with rather limited value in detecting anaerobic metabolism when blood flow is preserved. Additional studies in other models of hypoxic and anemic hypoxia are needed to confirm our findings and to resolve discrepancies between studies.

Key messages

  • The intramucosal–arterial PCO2 gradient fails to reflect intestinal oxygen supply dependence during hypoxic hypoxia

  • Blood flow seems to be the main determinant of venoarterial and intramucosal–arterial PCO2 gradients

  • Tonometry seems to be a useful method for monitoring perfusion, with limited value in detecting anaerobic metabolism when flow is preserved

Abbreviations

ANOVA: 

ANOVA = analysis of variance

CO: 

CO = cardiac output

D: 

DO2 = oxygen transport

ΔP: 

ΔPCO2 = intramucosal–arterial PCO2 gradient

F: 

FiO2 = fraction of inspired oxygen

HH: 

HH = hypoxic hypoxia

IH: 

IH = ischemic hypoxia

pH: 

pHi = intramucosal pH

V: 

VO2 = oxygen uptake.

Declarations

Authors’ Affiliations

(1)
Principal Investigator, Cátedra de Farmacologia Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Argentina
(2)
Research Fellow Cátedra de Farmacología Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Argentina
(3)
Medical Director Servicio de Terapia Intensiva, Hospital San Martín de La Plata, Argentina
(4)
Staff physician Servicio de Terapia Intensiva, Hospital San Martín de La Plata, Argentina
(5)
Research Fellow, Cátedra de Farmacología Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Argentina
(6)
Medical Director, Unidad de Transplante Renal CRAI Sur CUCAIBA, Argentina
(7)
Medical Director Servicio de Terapia Intensiva, Clínica Bazterrica de Buenos Aires, Argentina
(8)
Director, Servicio de Laboratorio, Hospital San Martín de La Plata, Argentina

References

  1. Third European Consensus Conference in Intensive Care Medicine: Tissue hypoxia: how to detect, how to correct, how to prevent? Am JRespir Crit Care Med 1996, 154: 1573-1578.View ArticleGoogle Scholar
  2. Grum CM, Fiddian-Green RG, Pittenger GL, Grant BJ, Rothman ED, Dantzker DR: Adequacy of tissue oxygenation in intact dog intestine. J Appl Physiol 1984, 56: 1065-1069.PubMedGoogle Scholar
  3. Doglio GR, Pusajo JF, Egurrola MA, Bonfigli GC, Parra C, Vetere L, Hernandez MS, Fernandez S, Palizas F, Gutierrez G: Gastric mucosal pH as a prognostic index of mortality in critically ill patients. Crit Care Med 1991, 19: 1037-1040.View ArticlePubMedGoogle Scholar
  4. Marik PE: Gastric intramucosal pH. A better predictor of multi-organ dysfunction and death than oxygen-derived variables in patients with sepsis. Chest 1993, 104: 225-229.View ArticlePubMedGoogle Scholar
  5. Maynard N, Bihari D, Beale R, Smithies M, Baldock G, Mason R, McColl I: Assessment of splanchnic oxygenation by gastric tonometry in patients with acute circulatory failure. JAMA 1993, 270: 1203-1210. 10.1001/jama.270.10.1203View ArticlePubMedGoogle Scholar
  6. Schlichtig R, Metha N, Gayowski TJP: Tissue-arterial PCO 2 difference is a better marker of ischemia than intramural pH (pHi) or arterial pH-pHi difference. J Crit Care 1996, 11: 51-56.View ArticlePubMedGoogle Scholar
  7. Schlichtig R, Bowles SA: Distinguishing between aerobic and in intestine during anaerobic appearance of dissolved CO 2 low flow. J Appl Physiol 1994, 76: 2443-2451.PubMedGoogle Scholar
  8. Taylor DE, Gutierrez G: Tonometry. A review of clinical studies. Crit Care Clin 1996, 12: 1007-1018.View ArticlePubMedGoogle Scholar
  9. Kolkman JJ, Steverink PJGM, Groeneveld ABJ, Meuwissen SGM: Characteristics of time-dependent PCO 2 tonometry in the normal human stomach. Br JAnaesth 1998, 81: 669-675.View ArticleGoogle Scholar
  10. Giovannini I, Chiarla C, Boldrini G, Castagneto M: Calculation of venoarterial CO 2 concentration difference. J Appl Physiol 1993, 74: 959-964.PubMedGoogle Scholar
  11. Connett RJ, Honig CR, Gayeski TE, Brooks GA: Defining hypoxia: a systems view of VO 2 , glycolysis, energetics and intracellular PO 2 . J Appl Physiol 1990, 68: 833-842.PubMedGoogle Scholar
  12. Vincent JL, Creteur J: Gastric mucosal pH is definitely obsolete – please tell us more about gastric mucosal PCO 2 . Crit Care Med 1998, 26: 1479-1481. 10.1097/00003246-199809000-00008View ArticlePubMedGoogle Scholar
  13. Fiddian-Green RG: Gastric intramucosal pH, tissue oxygenation and acid-base status. Br JAnaesth 1995, 74: 591-606.View ArticleGoogle Scholar
  14. Puyana JC, Soller BR, Parikh B, Heard SO: Directly measured tissue pH is an earlier indicator of splanchnic acidosis than tonometric parameters during hemorrhagic shock in swine. Crit Care Med 2000, 28: 2557-2562.View ArticlePubMedGoogle Scholar
  15. Adrogue HJ, Rashad MN, Gorin AB, Yacoub J, Madias NE: Assessing acid-base status in circulatory failure. Differences between arterial and central venous blood. N Engl J Med 1989, 320: 1312-1316.View ArticlePubMedGoogle Scholar
  16. Grundler W, Weil MH, Rackow EC: Arteriovenous carbon dioxide and pH gradients during cardiac arrest. Circulation 1986, 74: 1071-1074.View ArticlePubMedGoogle Scholar
  17. Dubin A, Silva C, Calvo G, Valli J, Fariña O, Estenssoro E, Mordu-jovich P: End-tidal CO 2 pressure in the monitoring of cardiac output during canine hemorrhagic shock. J Crit Care 1990, 5: 42-46.View ArticleGoogle Scholar
  18. Vallet B, Tavernier V, Lund N: Assessment of tissue oxygenation in the critically ill. In Yearbook of intensive care and emergency medicine (Edited by: Vincent JL). Berlin: Springer-Verlag; 2000, 715-725.Google Scholar
  19. Manny J, Manny N, Lelcuk S, Alexander F, Feingold H, Kobzik L, Valeri CR, Shepro D, Hechtman HB: Pulmonary and systemic consequences of localized acid aspiration. Surg Gynecol Obstet 1986, 162: 259-267.PubMedGoogle Scholar
  20. St John RC, Mizer LA, Kindt GC, Weisbrode SE, Moore SA, Dorinsky PM: Acid aspiration-induced acute lung injury causes leukocyte-dependent systemic organ injury. J Appl Physiol 1993, 74: 1994-2003.PubMedGoogle Scholar
  21. Crouser ED, Julian MW, Weisbrode SE, Dorinsky PM: Acid aspiration results in ileal injury without altering ileal VO 2 /DO 2 relationships. Am JRespir Crit Care Med 1996, 153: 1965-1971.View ArticleGoogle Scholar
  22. Schertel ER, Pratt JW, Schaeffer SL, Valentine AK, McCreary MR, Myerowitz PD: Effects of acid-induced lung injury on left ventricular function. Surgery 1996, 119: 81-88.View ArticlePubMedGoogle Scholar
  23. Cain SM: Oxygen delivery and uptake in dogs during anemic and hypoxic hypoxia. J Appl Physiol 1977, 42: 228-234.PubMedGoogle Scholar
  24. Cain SM: pH effects on lactate and excess lactate in relation to O 2 deficit in hypoxic dogs. J Appl Physiol 1977, 42: 44-49.PubMedGoogle Scholar
  25. Jakob SM, Kosonen P, Ruokonen E, Parviainen I, Takala J: The Haldane effect – an alternative explanation for increasing gastric mucosal PCO 2 gradients? Br J Anaesth 1999, 83: 740-746.View ArticlePubMedGoogle Scholar
  26. Dubin A, Estensoro E, Murias G, Canales H, Sottile P, Badie J, Barán M, Pálizas F, Laporte M, Rivas Díaz M: Effects of hemorrhage on gastrointestinal oxygenation. Intensive Care Med 2001, 27: 1931-1936. 10.1007/s00134-001-1138-9View ArticlePubMedGoogle Scholar
  27. Nevière R, Chagnon J-L, Teboul J-L, Vallet B, Wattel FB: Small and microvascular blood flow intestine intramucosal PCO 2 during hypoxic and ischemic hypoxia. Crit Care Med 2002, 30: 379-384.View ArticlePubMedGoogle Scholar
  28. Vallet B, Teboul JL, Cain S, Curtis S: Venoarterial CO 2 difference during regional ischemic or hypoxic hypoxia. J Appl Physiol 2000, 89: 1317-1321.PubMedGoogle Scholar
  29. Cohen IL, Sheik FM, Perkins RJ, Feustel PJ, Foster ED: Effects of hemorrhagic shock and reperfusion on the respiratory quotient in swine. Crit Care Med 1995, 23: 545-552. 10.1097/00003246-199503000-00021View ArticlePubMedGoogle Scholar
  30. Dubin A, Murias G, Estenssoro E, Canales H, Sottile P, Badie J, Barán M, Rossi S, Laporte M, Pálizas F, Giampieri J, Mediavilla D, Vacca E, Botta D: End-tidal CO 2 pressure determinants during hemorrhagic shock. Intensive Care Med 2000, 26: 1619-1623. 10.1007/s001340000669View ArticlePubMedGoogle Scholar
  31. Nielsen VG, Tan S, Baird MS, McCammon AT, Parks DA: Gastric intramucosal pH and multiple organ failure: impact of ischemia-reperfusion and xanthneoxidase. Crit Care Med 1996, 24: 1339-1344. 10.1097/00003246-199608000-00012View ArticlePubMedGoogle Scholar
  32. VanderMeer TJ, Wang H, Fink MP: Endotoxemia causes ileal mucosal acidosis in the absence of mucosal hypoxia in a nor-modynamic porcine model of septic shock. Crit Care Med 1995, 23: 1217-1226. 10.1097/00003246-199507000-00011View ArticlePubMedGoogle Scholar
  33. Tugtekin IF, Radermacher P, Theisen M, Matejovic M, Stehr A, Ploner F, Matura K, Ince C, Georgieff M, Trager K: Increased ileal–mucosal–arterial PCO 2 gap is associated with impaired villus microcirculation in endotoxic pigs. Intensive Care Med 2001, 27: 757-766. 10.1007/s001340100871View ArticlePubMedGoogle Scholar

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