Search

BACKGROUND: Perioperative resuscitation with large amounts of fluid may cause tissue edema, especially in the gut, and thereby impair its functions. This is especially relevant in sepsis where capillaries become leaky and fluid rapidly escapes to the pericapillary tissue. We assessed the effects of endotoxemia and peritonitis, and the use of high and moderate volume fluid resuscitation on jejunal contractility. We hypothesized that both endotoxemia and peritonitis impair jejunum contractility and relaxation, and that this effect is aggravated in peritonitis and with high fluid administration. METHODS: Pigs were randomized to endotoxin (n = 16), peritonitis (n = 16), or sham operation (n = 16), and either high (20 mL/kg/h) or moderate volume (10 mL/kg/h) fluid resuscitation for 24 hours or until death. At the end of the experiment, jejunal contractility and relaxation were measured in vitro using acetylcholine and sodium nitroprusside reactivity, and the effect of nitric oxide synthase inhibition (NOS-I) was assessed. RESULTS: Mortality in the respective groups was 88% (peritonitis high), 75% (endotoxemia high), 50% (peritonitis moderate), 13% (endotoxemia moderate and sham operation high) and 0% (sham operation moderate volume resuscitation). While gut perfusion was preserved in all groups, jejunal contractility was impaired in the two peritonitis and in the two endotoxemia groups, and similarly also in the sham operation group treated with high but not with moderate volume fluid resuscitation [model-fluid-contraction-interaction, p = 0.036; maximal contractility 136 ± 28% (average of both peritonitis, both endotoxemia and sham operation high volume groups) vs. 170 ± 74% of baseline (sham operation moderate volume group)]. NOS-I reduced contractility (contraction-inhibition-interaction, p = 0.011) without significant differences between groups and relaxation was affected neither by peritonitis and endotoxemia nor by the fluid regimen. CONCLUSIONS: Intestinal contractility is similarly impaired during peritonitis and during endotoxemia. Moreover, perioperative high volume fluid resuscitation in sham operated animals also decreases intestinal contractility. This may have consequences for post-operative recovery.

Low cardiac output impairs the hepatic arterial buffer response (HABR). Whether this is due to low abdominal blood flow per se is not known. Dobutamine is commonly used to increase cardiac output, and it may further modify hepatosplanchnic and renal vasoregulation. We assessed the effects of isolated abdominal aortic blood flow changes and dobutamine on hepatosplanchnic and renal blood flow. Twenty-five anesthetized pigs with an abdominal aorto-aortic shunt were randomized to 2 control groups [zero (n = 6) and minimal (n = 6) shunt flow], and 2 groups with 50% reduction of abdominal blood flow and either subsequent increased abdominal blood flow by shunt reduction (n = 6) or dobutamine infusion at 5 and 10 microg kg(-1) min(-1) with constant shunt flow (n = 7). Regional (ultrasound) and local (laser Doppler) intra-abdominal blood flows were measured. The HABR was assessed during acute portal vein occlusion. Sustained low abdominal blood flow, by means of shunt activation, decreased liver, gut, and kidney blood flow similarly and reduced local microcirculatory blood flow in the jejunum. Shunt flow reduction partially restored regional blood flows but not jejunal microcirculatory blood flow. Low-but not high-dose dobutamine increased gut and celiac trunk flow whereas hepatic artery and renal blood flows remained unchanged. Neither intervention altered local blood flows. The HABR was not abolished during sustained low abdominal blood flow despite substantially reduced hepatic arterial blood flow and was not modified by dobutamine. Low-but not high-dose dobutamine redistributes blood flow toward the gut and celiac trunk. The jejunal microcirculatory flow, once impaired, is difficult to restore.

We evaluated the hepatic arterial buffer response (HABR) to portal vein (PV) occlusion during 2 h of reduced superior mesenteric arterial blood flow (median 2 mL min(-1) kg(-1), range of 1-3 mL min(-1) kg(-1)) and 1 h of reperfusion in seven pigs and in seven controls. In animals with reduced mesenteric blood flow, celiac trunk blood flow (Qtr) increased during mesenteric hypoperfusion from 4 +/- 1 mL min(-1) kg(-1) (mean +/- SD) to 16 +/- 3 mL min(-1) kg(-1) (P = 0.028), and hepatic arterial blood flow (Qha) increased from 2 +/- 1 to 10 +/- 4 mL min(-1) kg(-1) (P= 0.018). The extra-hepatic fraction of Qtr (Qtr-Qha) also increased (P = 0.028). In controls, Qtr and Qha also increased, but to lower levels. At baseline, acute PV occlusion increased Qha by 5.0 +/- 2.8 mL min(-1) kg(-1) (P < 0.001), whereas Qtr-Qha decreased by 1.6 +/- 1.6 mL min(-1) kg(-1) (P = 0.007). After 120 min of reduced mesenteric blood flow, the HABR was exhausted (change in Qha to PV occlusion of 0.7 +/- 1.6 mL min(-1) kg(-1) [P= 0.27]). The efficacy of the HABR was also reduced in controls animals. Despite increased cardiac output, all flows from the celiac trunk decreased during reperfusion (P = 0.028) and the HABR partially recovered. We conclude that reduced mesenteric perfusion impairs the HABR, which recovers only partially after reperfusion. The distribution of the increased celiac trunk flow secondary to PV occlusion ranges from increased HABR and decreased non-hepatic blood flow (a steal) to decreased hepatic arterial blood flow and increased non-hepatic blood flow (an inverse steal).

The production of monoethylglycine xylidide (MEGX) from lidocaine is thought to be dependent on hepatic blood flow. We assessed the relationship between hepatosplanchnic blood flow, lidocaine uptake, and the production of MEGX from lidocaine in seven patients after cardiac surgery and in nine septic patients. Systemic (pulmonary artery catheter) and splanchnic (hepatic vein catheter and dye dilution) hemodynamics and arterial and hepatic venous lidocaine and MEGX concentrations were measured after a lidocaine bolus injection (1 mg/kg) before and 90 min after increasing cardiac output by at least 25% with dopamine. Dopamine infusion [in cardiac surgery patients 4.2 (1.4-8.5) microg x kg(-1) x min(-1) (median, range) and in septic patients 4.0 (2.1-9.0) microg x kg(-1) x min(-1)] increased splanchnic blood flow in cardiac surgery patients from 0.65 (0.12) L x min(-1) x m(-2) to 0.84 (0.14) L x min(-1) x m(-2) mean (standard deviation) P = 0.018) and in septic patients from 0.91 (0.32) L x min(-1) x m(-2) to 1.12 (0.40) L x min(-1) x m(-2) (P = 0.038). Splanchnic MEGX production for the 30 min after lidocaine injection was higher in cardiac surgery patients than in septic patients both at baseline [4130 (1100) microg x m(-2) vs. 930 (420) microg x m(-2) (P < 0.005)] and afterdopamine infusion [4480 (1000) microg x m(-2) vs. 1090 (620) microg x m(-2) (P = 0.005)]. We found no correlation between changes in MEGX production and changes in splanchnic blood flow. Patients with sepsis have severe impairment of cytochrome P450-dependent liver function, which is not influenced by acute changes in hepatosplanchnic blood flow. MEGX production cannot be used as an estimate of changes in splanchnic blood flow.

Dopamine is used in the clinical setting to support cardiac output and blood pressure and to improve diuresis. Experimental studies suggest that dopamine may reduce splanchnic perfusion and redistribute blood flow locally. To assess the effects of dopamine on splanchnic perfusion, we used dopamine to increase cardiac output by 25% in nine septic patients and 11 patients after cardiac surgery. Systemic (pulmonary artery catheter) and splanchnic (hepatic vein catheter and dye dilution) hemodynamics and oxygen transport were measured at baseline and 90 min after increasing the cardiac output. Dopamine infusion [in cardiac surgery patients 4.2 (1.4-8.5) microg x kg(-1) x min(-1) (median, range) and in septic patients 4.0 (2.1-9.0) microg x kg(-1) x min(-1)] increased splanchnic blood flow in cardiac surgery patients from 0.61 (0.13) L x min(-1) x m(-2) to 0.82 (0.13) L x min(-1) x m(-2) [mean (standard deviation; SD); P = 0.018] and in septic patients from 0.91 (0.32) L x min(-1) x m(-2) to 1.12 (0.40) L x min(-1) x m(-2) (P = 0.038). Splanchnic oxygen consumption increased in cardiac surgery patients from 39 (5) mL x min(-1) x m(-2) to 46 (6) mL x min(-1) x m(-2) (P = 0.003) but decreased in septic patients from 61 (19) mL x min(-1) x m(-2) to 51 (17) L x min(-1) x m(-2) (p = 0.021). Because of the unexpected results, we compared these data post hoc with data obtained from another group of 15 septic patients with acute lung injury, where dobutamine was used to increase cardiac output in a similar design. Dobutamine in these patients [6.4 (4.2-9.5) microg x kg(-1) x min(-1)] increased splanchnic blood flow from 1.20 (0.44) L x min(-1) x m(-2) to 1.43 (0.57) L x min(-1) x m(-2) (P = 0.008), while splanchnic oxygen consumption did not change 72 (25) mL x min(-1) x m(-2) vs. 76 (22) mL x min(-1) x m(-2) (not significant)]. The reduction of splanchnic oxygen consumption by dopamine in sepsis suggests an impairment of hepatosplanchnic metabolism despite an increase in regional perfusion. The safety and indications of dopamine use in sepsis should be re-evaluated.

Systemic inflammation triggered by insults like sepsis and acute pancreatitis may play a role in development of indirect acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Because little is known about the course of systemic inflammation on the days preceding diagnosis of ARDS, we prospectively monitored immune inflammatory status in 52 patients at risk and we assessed the presence of ALI and ARDS on day 7 after admission to the intensive care unit. On admission, serum interleukin (IL) 8, IL-6, and soluble IL-2 receptor concentrations were significantly higher in patients with subsequent ALI (n = 18) than in patients without ALI (n = 30). During a 4-day follow-up, IL-8 and IL-6 levels of ALI patients remained high and those of non-ALI patients decreased. None of the markers discriminated ARDS patients (n = 9) from non-ARDS ALI patients (n = 9). Among 11 patients with acute pancreatitis, ALI patients had significantly higher IL-8, IL-6, and phagocyte CD11b expression levels than did non-ALI patients, whereas among 14 patients with massive transfusion, respective findings in ALI and non-ALI patients were comparable. Results give credence to the view that systemic inflammation plays a role in development of ALI triggered by pancreatitis, but not in that by massive transfusion. This finding, if confirmed in studies with sufficient statistical power, suggests that the patients with massive transfusion do not necessarily benefit from novel biotherapies aimed at altering the course of systemic inflammation.

Increased hepatosplanchnic inflammation precedes the development of organ dysfunction after elective high-risk surgery.Poeze M, Ramsay G, Buurman WA, Greve JW, Dentener M, Takala J.Department of Surgery, University Hospital Maastricht, The Netherlands.This study investigated the relationship of the hepatosplanchnic production and uptake of inflammatory mediators, hepatosplanchnic perfusion, and outcome during major abdominal surgery to evaluate the hypothesis that regional production of inflammatory mediators precedes the development of hepatic dysfunction. This retrospective analysis of data and blood samples collected during a randomized controlled clinical trial included high-risk surgical patients undergoing major abdominal surgery in a 24-bed university-afilliated intensive care unit. Patients were divided into a subgroup that developed hepatic dysfunction (HD+) postoperatively and a subgroup without hepatic dysfunction (HD-). Hepatic vein and arterial plasma levels of IL-6, IL-8, s-E-selectin, s-ICAM-1, and the TNF-receptors 55 and 75 were measured, and the flux was calculated by multiplying the difference in hepatic vein minus arterial levels of the mediators by the hepatosplanchnic flow. Systemic (thermodilution) and total hepatosplanchnic blood flow (using indocyanine green [ICG]-dilution method) and gastric intramucosal pH (pHi) were assessed preoperatively, 4, 24, and 36 h postoperatively. Of a total of 26 patients, 6 patients developed hepatic dysfunction after their abdominal surgery (mean 6 days postoperatively). The number of sepsis-related deaths and postoperative days on the ventilator were significantly higher in this group. A higher production of IL-8, TNF-receptor-75 and 55 in the hepatosplanchnic area in the HD+ subgroups was found, which preceded the development of organ dysfunction (P = 0.04, P = 0.02, and P = 0.02, respectively). Moreover, the uptake of s-ICAM-1 was significantly increased in this subgroup. Furthermore, total hepatosplanchnic blood flow was significantly higher and pHi was significantly lower in the HD+ group, whereas global hemodynamic data were similar in the two subgroups. In conclusion, the development of postoperative organ dysfunction is preceded by an increased regional inflammatory response, indicated by an increased soluble TNF-receptor shedding and IL-8 production from the hepatosplanchnic area together with an increased uptake of s-ICAM-1. Moreover, an increased total hepatosplanchnic blood flow with intramucosal acidosis was associated with this regional inflammatory response.

Arterial blood lactate increases as a result of poor tissue perfusion. In splanchnic hypoperfusion, increased hepatic lactate uptake may delay increases in arterial blood lactate. We hypothesized that during isolated reduction of mesenteric blood flow, maintaining systemic blood volume and flow by fluid resuscitation may prevent systemic hyperlactatemia and therefore mask splanchnic ischemia. In a randomized study, 7 pigs were subjected to 4 h of splanchnic hypoperfusion by reducing the superior mesenteric artery blood flow to 4 +/- 0.8 mL/kg min [mean +/- standard deviation (SD)]. Seven pigs served as controls. Fluid was administered in order to keep the pulmonary artery occlusion pressure at 5 to 8 mm Hg. Cardiac output, portal vein, superior mesenteric, and hepatic arterial blood flow were measured every 30 min. Arterial, mixed venous, hepatic, portal, and mesenteric venous blood lactate, and jejunal mucosal pCO2 were measured at baseline and thereafter at 30-min intervals. The initial decrease in portal venous blood flow in the ischemic animals was subsequently counterbalanced by increasing hepatic arterial blood flow from 2 +/- 1 mL x kg(-1) x min(-1) at baseline to 11 +/- 4 mL x kg(-1) x min(-1) [after 4 h of ischemia; mean +/- standard deviation (SD), P = 0.02]. Jejunal mucosal- and mesenteric vein-arterial pCO2 gradients increased in the ischemic group from 11 +/- 8 mm Hg to 73 +/- 5 mm Hg (P = 0.02), and from 10 +/- 4 mm Hg to 44 +/- 8 mm Hg, respectively (P = 0.02). Mesenteric and portal venous lactate increased in the ischemic animals from 1.1 +/- 0.3 mmol/L to 4.2 +/- 1.0 mmol/L (P = 0.02), and from 1.0 +/- 0.2 mmol/L to 1.6 +/- 0.3 mmol/L, respectively (P = 0,03). While mesenteric lactate production and hepatic lactate uptake increased in parallel in the ischemic animals from 5 +/- 6 micromol x kg(-1) x min(-1) to 14 +/- 5 micromol x kg(-1) x min(-1) (P = 0.04), and from 14 +/- 7 micromol x kg(-1) x min(-1) to 24 +/- 6 micromol x kg(-1) x min(-1), respectively (P = 0.02), hepatic venous and arterial lactate, and apparent splanchnic lactate uptake and extraction did not change. We conclude that the hepatic lactate uptake increases in response to hepatic lactate influx. Systemic hyperlactatemia and increased hepatic venous lactate concentrations are late consequences of mesenteric hypoperfusion if hypovolemia is prevented. The net exchange of lactate across the splanchnic region does not reflect hepato-portal lactate kinetics in this animal model of intestinal hypoperfusion.

Gastric mucosal-arterial PCO 2 gradient (P g-a CO 2 ) is used to assess splanchnic perfusion and oxygenation. We evaluated whether P g-a CO 2 reflects whole body (Q) and splanchnic (Qsp) blood flow, oxygen delivery (DO 2 ) and consumption (VO 2 ) after coronary artery by pass graft (CABG) operation. Thirty patients received dobutamine or dopexamine to increase cardiac index, 15 patients enalapril or sodium nitroprusside to lower blood pressure, and 30 patients were controls. We measured Q, Qsp (hepatic vein catheter and indocyanine green), and gastric mucosal PCO 2 (nasogastric tonometer) before and after interventions. Multiple linear regression model showed that none of the changes in Q, Qsp, and splanchnic or systemic DO 2 and VO 2 significantly explained changes in P g-a CO 2 (ΔP g-a CO 2 ). All independent variables together explained only 7% of ΔP g-a CO 2 . Increased splanchnic blood flow (0.65 ±.19 vs. 0.94 ±.31 L/min/m 2 , P < 0.001) and increased splanchnic DO 2 (101 ± 28 vs. 143 ± 42 mL/min/m 2 , P < 0.001) during catecholamine infusions were associated with increased P g-a CO 2 (8 ± 8 vs. 11 ± 7 mmHg, P = 0.003). P g-a CO 2 does not reflect whole body or splanchnic blood flow, DO 2 or VO 2 after CABG operations. The physiology of P g-a CO 2 is complex and therefore it is difficult for clinicians to interpret changes in gastric mucosal-arterial PCO 2 gradient in individual patients after cardiac surgery.

The difference in CO2 tension between venous and arterial blood (delta PCO2) increases in low-flow states. Therefore, delta PCO2 has been suggested as an additional variable in the monitoring of perfusion. We measured CO2 tensions in arterial, mixed venous, hepatic venous, and femoral venous blood in 42 postoperative cardiac surgery patients. Splanchnic and leg blood flow was measured with dye dilution. Forty-three preoperative abdominal surgery patients served as controls. Systemic and femoral delta PCO2 was increased in cardiac patients, whereas there was no difference in splanchnic delta PCO2 between the groups. In cardiac patients, systemic delta PCO2 correlated well with both splanchnic and femoral delta PCO2 (r2 = .74 and r2 = .56, respectively). Femoral delta PCO2 was higher than splanchnic delta PCO2 (1.27 +/- .44 kPa versus .66 +/- .41; p.001) after cardiac surgery, but not in the control group. The correlation between delta PCO2 and respective blood flow was weak in the whole body, the splanchnic region, and the leg. When splanchnic blood flow was low, systemic and splanchnic delta PCO2 varied widely. In the cardiac patients with an increased systemic delta PCO2 (.93 kPa), systemic and regional blood flow was low, but there were no differences in systemic or regional oxygen consumption or lactate levels. After cardiac surgery, high systemic delta PCO2 is associated with marginal systemic and regional perfusion. The adequacy of regional blood flow cannot be assessed on the basis of the systemic delta PCO2.