Comparison of lactated Ringer's, gelatine and blood resuscitation on intestinal oxygen supply and mucosal tissue oxygen tension in haemorrhagic shock.

OBJECTIVES: To evaluate the effects on intestinal oxygen supply, and mucosal tissue oxygen tension during haemorrhage and after fluid resuscitation with either blood (B; n=7), gelatine (G; n=8), or lactated Ringer's solution (R; n=8) in an autoperfused, innervated jejunal segment in anaesthetized pigs. METHODS: To induce haemorrhagic shock, 50% of calculated blood volume was withdrawn. Systemic haemodynamics, mesenteric venous and systemic acid-base and blood gas variables, and lactate measurements were recorded. A flowmeter was used for measuring mesenteric arterial blood flow. Mucosal tissue oxygen tension (PO(2)muc), jejunal microvascular haemoglobin oxygen saturation (HbO(2)) and microvascular blood flow were measured. Measurements were performed at baseline, after haemorrhage and at four 20 min intervals after fluid resuscitation. After haemorrhage, animals were retransfused with blood, gelatine or lactated Ringer's solution until baseline pulmonary capillary wedge pressure was reached. RESULTS: After resuscitation, no significant differences in macrohaemodynamic parameters were observed between groups. Systemic and intestinal lactate concentration was significantly increased in animals receiving lactated Ringer's solution [5.6 (1.1) vs 3.3 (1.1) mmol litre(-1); 5.6 (1.1) vs 3.3 (1.2) mmol litre(-1)]. Oxygen supply to the intestine was impaired in animals receiving lactated Ringer's solution when compared with animals receiving blood. Blood and gelatine resuscitation resulted in higher HbO(2) than with lactated Ringer's resuscitation after haemorrhagic shock [B, 43.8 (10.4)%; G, 34.6 (9.4)%; R, 28.0 (9.3)%]. PO(2)muc was better preserved with gelatine resuscitation when compared with lactated Ringer's or blood resuscitation [20.0 (8.8) vs 13.8 (7.1) mm Hg, 15.2 (7.2) mm Hg, respectively]. CONCLUSION: Blood or gelatine infusion improves mucosal tissue oxygenation of the porcine jejunum after severe haemorrhage when compared with lactated Ringer's solution.

Effects of norepinephrine and phenylephrine on intestinal oxygen supply and mucosal tissue oxygen tension.

OBJECTIVES: To investigate effects of intravenous norepinephrine (NE) and phenylephrine (PE) on intestinal oxygen supply in an autoperfused, innervated jejunal segment. DESIGN AND SETTING: Prospective, randomized animal study in an animal research laboratory. MATERIALS AND METHODS: In 24 anesthetized and normoventilated pigs a segment of the jejunal mucosa was exposed by midline laparotomy and antimesenteric incision. Mucosal oxygen tension (PO2muc; Clark-type surface oxygen electrodes), microvascular hemoglobin oxygen saturation (HbO2, tissue reflectance spectrophotometry), and microvascular blood flow (perfusion units, PU; laser Doppler velocimetry), systemic hemodynamics, mesenteric-venous acid base and blood gas variables, and systemic acid base and blood gas variables were recorded after a resting period and at 20-min intervals during infusion of NE (0.01, 0.05, 0.1, 0.5, 1, 2 micrograms x kg-1 x min-1; n = 8) or PE (0.1, 0.5, 1, 2, 5, 10 micrograms x kg-1 x min-1; n = 8) and in controls (n = 8) without treatment. RESULTS: NE infusion led to significant tachycardia, an increase in cardiac output, and systemic oxygen delivery and consumption while PE progressively increased mean arterial pressure with only small effects on systemic blood flow. NE or PE infusion did not affect mesenteric venous oxygen tension (baseline: PE 53 +/- 5, NE, 52 +/- 4.2 mmHg), mesenteric oxygen extraction ratio (baseline: PE 0.29 +/- 0.08, NE 0.3 +/- 0.06), jejunal microvascular blood flow (baseline: PE 254 +/- 127, NE 282 +/- 72 PU), PO2muc (baseline: PE 31 +/- 9.1, NE 33 +/- 11 mmHg), and HbO2 (baseline: PE 52 +/- 9.6%, NE 58 +/- 11.6%). CONCLUSION: Despite major differences in systemic hemodynamics jejunal tissue oxygen supply is not affected by progressively increasing intravenous infusion of norepinephrine and phenylephrine.

Effects of epinephrine on intestinal oxygen supply and mucosal tissue oxygen tension in pigs.

OBJECTIVE: To study the effects of increasing dosages of epinephrine given intravenously on intestinal oxygen supply and, in particular, mucosal tissue oxygen tension in an autoperfused, innervated jejunal segment. DESIGN: Prospective, randomized experimental study. SETTING: Animal research laboratory. SUBJECTS: Domestic pigs. INTERVENTIONS: Sixteen pigs were anesthetized, paralyzed, and normoventilated. A small segment of the jejunal mucosa was exposed by midline laparotomy and antimesenteric incision. Mucosal oxygen tension was measured by using Clark-type surface oxygen electrodes. Microvascular hemoglobin oxygen saturation and microvascular blood flow (perfusion units) were determined by tissue reflectance spectrophotometry and laser-Doppler velocimetry. Systemic hemodynamics, mesenteric-venous acid-base and blood gas variables, and systemic acid-base and blood gas variables were recorded. Measurements were performed after a resting period and at 20-min intervals during infusion of increasing dosages of epinephrine (n = 8; 0.01, 0.05, 0.1, 0.5, 1, and 2 microg x kg(-1) x min(-1)) or without treatment (n = 8). In addition, arterial and mesenteric-venous lactate concentrations were measured at baseline and at 60 and 120 mins. MEASUREMENTS AND MAIN RESULTS: Epinephrine infusion led to significant tachycardia; an increase in cardiac output, systemic oxygen delivery, and oxygen consumption; and development of lactic acidosis. Epinephrine significantly increased jejunal microvascular blood flow (baseline, 267 +/- 39 perfusion units; maximum value, 443 +/- 35 perfusion units) and mucosal oxygen tension (baseline, 36 +/- 2.0 torr [4.79 +/- 0.27 kPa]; maximum value, 48 +/- 2.8 torr [6.39 +/- 0.37 kPa]) and increased hemoglobin oxygen saturation above baseline. Epinephrine increased mesenteric venous lactate concentration (baseline, 2.9 +/- 0.6 mmol x L(-1); maximum value, 5.5 +/- 0.2 mmol x L(-1)) without development of an arterial-mesenteric venous lactate concentration gradient. CONCLUSIONS: Epinephrine increased jejunal microvascular blood flow and mucosal tissue oxygen supply at moderate to high dosages. Lactic acidosis that develops during infusion of increasing dosages of epinephrine is not related to development of gastrointestinal hypoxia.

Mucosal tissue oxygenation of the porcine jejunum during normothermic cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) has been associated with intestinal tissue hypoxia, but direct measurements of mucosal oxygenation have not been performed. In anaesthetized pigs, jejunal mucosal oxygen tension and microvascular haemoglobin oxygen saturation were measured by a Clark-type electrode and tissue reflectance spectrophotometry. In pigs, normothermic CPB with systemic oxygen transport equivalent to baseline values was performed. In control animals, mucosal oxygen tension and mucosal haemoglobin oxygen saturation were mean 5.01 (SD 1.08) kPa and 38.0 (2.3)%, respectively. CPB was associated with a decrease in mucosal oxygen tension to 2.26 (1.21) kPa, decrease in mucosal microvascular haemoglobin oxygen saturation to 26.0 (3.9)% and appearance of oscillations in mucosal microvascular haemoglobin oxygen saturation. With CPB, arterial lactate concentrations increased from 1.77 (1.37) to 3.52 (1.58) mmol litre-1, but transvisceral lactate and splanchnic venous-arterial carbon dioxide tension gradients remained unchanged. Our results support the concept that CPB is associated with diminished oxygenation of intestinal mucosa that is probably caused by regional redistribution.

[Intestinal ischemic reperfusion syndrome: pathophysiology, clinical significance, therapy]. / Das Ischämie-Reperfusionssyndrom des Darmes: Pathophysiologie--klinische Relevanz--Therapie.

Gut ischemia-reperfusion injury is a serious condition in intensive care patients. Activation of immune cells within the huge endothelial surface area of gut microcirculation may initiate a systemic inflammatory response with secondary injury to distant organs. Translocation of bacteria and toxins through a leaky gut mucosa may amplify or perpetuate systemic inflammation, leading to multiple organ dysfunction syndrome and death in critically ill patients. Gut ischemia promotes regional production of inflammatory mediators, expression of cell adhesion molecules on endothelial and immune cell surfaces and increases the procoagulatory properties of vascular endothelial cells. During reperfusion, gut injury may be amplified by increased production of oxygen radicals and exhaustion of endogenous antioxidant defence mechanisms. Although several therapeutic strategies to interrupt the pathophysiology of ischemia-reperfusion have been shown to be beneficial in animal experiments, none of these interventions has gained clinical relevance. After initial hemodynamic and respiratory stabilisation of critically ill patients, strategies to prevent secondary gut injury by increasing splanchnic oxygen delivery or augment mucosal cell regeneration may be the only therapeutic options for intensive medical specialists at the present time. Early enteral nutrition and treatment with specific vasoactive drugs may reduce morbidity and costs of treatment in certain critically ill patients. However definitive evidence of a reduction in mortality with these therapies has still not be provided.

Dopamine and intestinal mucosal tissue oxygenation in a porcine model of haemorrhage.

Haemorrhage is associated with intestinal mucosal hypoxia and impaired gut barrier function. Dopamine increases oxygen delivery to the intestinal mucosa and may thus counteract haemorrhage-induced mucosal hypoxia. Jejunal mucosal tissue oxygen tension (mucosal PO2) and jejunal oxygen saturation of mucosal microvascular haemoglobin (mucosal HbO2) were measured in 14 anaesthetized pigs. Seven animals served as controls (group C) and seven received continuous infusion of dopamine 16 micrograms kg-1 min-1 (group D) while 45% of blood volume was removed in three equal increments. Resuscitation was performed using shed blood and fluid. Mean arterial pressure and systemic oxygen delivery decreasing significantly during haemorrhage and returned to baseline after resuscitation in both groups. Mucosal PO2 decreased from 4.4 to 1.7 kPa after haemorrhage (P < 0.01) and further to 1.5 kPa after resuscitation (P < 0.01) in group C whereas group D showed an increase from 3.9 to 5.9 kPa after the start of the dopamine infusion (P < 0.05), but no significant difference from baseline after haemorrhage (2.3 kPa) (ns) or resuscitation (3.1 kPa) (ns). Mucosal HbO2 decreased from 52 to 32% after haemorrhage (P < 0.05) and increased to near baseline (37%) (ns) after resuscitation in group C whereas group D showed no significant changes from baseline (54%) throughout the experiment. Comparison between groups showed higher mucosal PO2 and HbO2 values for group D animals after the start of the dopamine infusion (P < 0.05 each), after the first two steps of haemorrhage (P < 0.01 each) and after resuscitation (P < 0.05 each). We conclude that i.v. dopamine 16 micrograms kg-1 min-1 improved tissue oxygenation of the small intestinal mucosa during moderate haemorrhage and subsequent resuscitation.

The effects of progressive anemia on jejunal mucosal and serosal tissue oxygenation in pigs.

Anemia may promote intestinal hypoxia. We studied the effects of progressive isovolemic hemodilution on jejunal mucosal (Po2muc), and serosal tissue oxygen tension (Po2ser, Clark-type surface electrodes), mucosal microvascular hemoglobin oxygen saturation (Hbo2muc), and hematocrit (Hctmuc; tissue reflectance spectophotometry) in a jejunal segment. Twelve domestic pigs were anesthetized, paralyzed, and mechanically ventilated. Laparatomy was performed, arterial supply of a jejunal segment isolated, and constant pressure pump perfused. Seven animals were progressively hemodiluted to systemic hematocrits (Hctsys) of 20%, 15%, 10%, and 6%. Baseline for Po2muc, Po2ser and Hbo2muc was 23.5 +/- 2.1 mm Hg, 57.5 +/- 4 mm Hg, and 47.0% +/- 6.4% which were not different from the five controls. Despite a significant increase in jejunal blood flow, jejunal oxygen delivery decreased and oxygen extraction ratio increased significantly at Hctsys 10% and 6%. Po2ser decreased significantly below or at Hctsys of 15%, whereas Po2muc and Hbo2muc were maintained to Hctsys of 10%, but less than 10% Hbo2muc and mesenteric venous pH decreased significantly, implying that physiological limits of jejunal microvascular adaptation to severe anemia were reached. Decrease of Hctmuc was less pronounced than Hctsys. In conclusion, redistribution of jejunal blood flow and an increase in the ratio of mucosal to systemic hematocrit are the main mechanisms maintaining mucosal oxygen supply during progressive anemia.

Factors influencing transcutaneous oxygen and carbon dioxide measurements in adult intensive care patients.

Transcutaneous PO2 (PtcO2) is suggested to reflect tissue oxygenation in intensive care patients, whereas transcutaneous PCO2 (PtcCO2) is advocated as a noninvasive method for assessing PaCO2. In 24 critically ill adult patients (mean Apache II score 14.2, SD 4.7) we investigated the impact of variables that are commonly thought to determine PtcO2 and PtcCO2 measurements. A linear correlation was found between PtcO2 and PaO2 (r = 0.6; p less than or equal to 0.0001) and between PtcO2 and mean arterial blood pressure (MAP; r = 0.42; p less than or equal to 0.003). Cardiac index (CI) correlated with tc-index (PtcO2/PaO2; r = 0.31; p less than or equal to 0.03). There was no relationship between PtcO2 and hemoglobin concentration (Hb) and the position of the oxygen dissociation curve (ODC). Stepwise multiple regression analysis demonstrated a significant influence of PaO2 and MAP on PtcO2. The contribution of CI, Hb and the ODC was not significant. Only 40% of the variability of a single PtcO2 measurement could be explained by PaO2 and MAP. A significant linear correlation was demonstrated between PtcCO2 and PaCO2 (r = 0.76; p less than or equal to 0.0001) but not between PtcCO2 and CI, MAP and arterial base excess (BEa). Stepwise multiple regression analysis revealed an influence of PaCO2 and of CI on PtcCO2; 66% of the variability of a single PtcCO2-value could be explained by PaCO2 and CI. Our data demonstrate that transcutaneous derived gas tensions result from complex interaction between hemodynamic, respiratory and local factors, which can hardly be defined in ICU-patients.