Anders Thorén

Vasopressors and intestinal mucosal perfusion after cardiac surgery: Norepinephrine vs. phenylephrine.

Objectives:To evaluate the potential differential effects of norepinephrine, an &agr;1-, &bgr;1-, and &bgr;2-receptor agonist, to the &agr;1-agonist phenylephrine on jejunal mucosal perfusion, gastric-arterial Pco2 gradient, and the global splanchnic oxygen demand-supply relationship after cardiac surgery. Design:A randomized, prospective, interventional crossover study. Setting:A university cardiothoracic intensive care unit. Patients:Ten patients were studied during propofol sedation and mechanical ventilation after uncomplicated coronary artery bypass surgery. Interventions:Each patient received randomly and sequentially norepinephrine (0.052 ± 0.009 &mgr;g/kg/min) and phenylephrine (0.50 ± 0.22 &mgr;g/kg/min) to increase mean arterial blood pressure by 30%. Measurements and Main Results:Data on jejunal mucosal perfusion, jejunal mucosal hematocrit, and red blood cell velocity (laser Doppler flowmetry) as well as gastric-arterial Pco2 gradient (tonometry) and splanchnic oxygen extraction were obtained before (control) and during a 30-min drug infusion period after the target mean arterial blood pressure was reached. The procedure was sequentially repeated for the second vasopressor. Both drugs induced a 40–46% increase in systemic vascular resistance with no change in cardiac index. Neither jejunal mucosal perfusion, jejunal mucosal hematocrit, red blood cell velocity, nor gastric-arterial Pco2 gradient was affected by any of the vasopressors. Splanchnic oxygen extraction increased from 38.2% to 43.1% (p < .001) with norepinephrine and from 39.3% to 47.5% (p < .001) with phenylephrine. This increase was significantly more pronounced with phenylephrine compared with norepinephrine (p < .05). Mixed venous-hepatic vein oxygen saturation gradient increased with both drugs (p < .01), and the increase was more pronounced with phenylephrine (p < .05). Splanchnic lactate extraction was not significantly affected by any of the vasopressors. Conclusions:Phenylephrine induced a more pronounced global &agr;1-mediated splanchnic vasoconstriction compared with norepinephrine. Neither of the vasoconstrictors impaired perfusion of the gastrointestinal mucosa in postcardiac surgery patients. The lack of norepinephrine-induced, &agr;1-mediated impairment of gastrointestinal perfusion is not explained by a &bgr;2-mediated counteractive vasodilation but instead by possible mucosal autoregulatory escape.

Differential effects of dopamine, dopexamine, and dobutamine on jejunal mucosal perfusion early after cardiac surgery

Objective To evaluate the potential differential effects of dopamine, dopexamine, and dobutamine on jejunal mucosal perfusion, assessed by endoluminal laser Doppler flowmetry in uncomplicated postcardiac surgical patients. Design A prospective, blinded, randomized, crossover study. Setting A cardiothoracic intensive care unit in a tertiary care center. Patients A total of ten postoperative cardiac surgical patients were studied. Interventions Each patient received sequentially, randomly, and in a blinded fashion 2.7 ± 0.2 &mgr;g·kg−1·min−1 dopamine, 0.7 ± 0.1 &mgr;g·kg−1·min−1 dopexamine, and 2.7 ± 0.1 &mgr;g·kg−1·min−1 dobutamine. Each inotropic agent was titrated to increase cardiac output by 25% from baseline. Data on jejunal mucosal perfusion, splanchnic lactate, and oxygen extraction were obtained during a 5-min control period and a 5-min drug infusion period after the target cardiac output was reached. The procedure was sequentially repeated for each agent, and there was a 20- to 30-min washout period between each agent. Measurements and Main Results Dopamine, dopexamine, and dobutamine increased jejunal mucosal perfusion by 27% (p < .01), 20% (p < .001), and 7% (p < .001), respectively. The increase in jejunal mucosal perfusion by dopamine and dopexamine were significantly more pronounced compared with dobutamine (p < .05 and p < .01, respectively), whereas there was no difference between dopamine and dopexamine. Splanchnic oxygen extraction decreased to the same extent with all three drugs. Splanchnic lactate extraction did not change for any of the drugs. The effects on central hemodynamics were similar for the three inotropic agents. Conclusions Endoluminal laser Doppler flowmetry is a new tool for the detection of perfusion changes at the local intestinal mucosal level. Dopamine, dopexamine, and dobutamine have differential effects on jejunal mucosal perfusion probably because of their different receptor stimulating properties. These findings may be of clinical importance when the therapeutic goal is to improve gut mucosal perfusion.

Vasopressin decreases intestinal mucosal perfusion: a clinical study on cardiac surgery patients in vasodilatory shock

Background: Low to moderate doses of vasopressin have been used in the treatment of cathecholamine‐dependent vasodilatory shock in sepsis or after cardiac surgery. We evaluated the effects of vasopressin on jejunal mucosal perfusion, gastric‐arterial pCO2 gradient and the global splanchnic oxygen demand/supply relationship in patients with vasodilatory shock after cardiac surgery.

Jejunal mucosal perfusion is well maintained during mild hypothermic cardiopulmonary bypass in humans

In the present study, the effects of mild hypothermic (34°C) cardiopulmonary bypass (CPB) on jejunal mucosal perfusion (JMP), gastric tonometry, splanchnic lactate, and oxygen extraction were studied in low-risk cardiac surgical patients (n = 10), anesthetized and managed according to clinical routine. JMP was assessed by endoluminal laser Doppler flowmetry. Patients were studied during seven 10-min measurement periods before, during, and 1 h after the end of CPB. Splanchnic oxygen extraction increased during hypothermia and particularly during rewarming and warm CPB. JMP increased during hypothermia (26%), rewarming (31%), and warm CPB (38%) and was higher 1 h after CPB (42%), compared with pre-CPB control. The gastric-arterial Pco2 difference was slightly increased (range 0.04–2.26 kPa) during rewarming and warm CPB as well as 1 h after CPB, indicating a mismatch between gastric mucosal oxygen delivery and demand. None of the patients produced lactate during CPB. We conclude that jejunal mucosal perfusion appears well preserved during CPB and moderate (34°C) hypothermia; this finding is in contrast to previous studies showing gastric mucosal hypoperfusion during CPB. IMPLICATIONS Jejunal mucosal perfusion increases during mild hypothermic cardiopulmonary bypass (CPB). Intestinal laser Doppler flowmetry, gastric tonometry, and measurements of splanchnic lactate extraction could not reveal a local or global splanchnic ischemia during or after CPB. A mismatch between splanchnic oxygen delivery and demand was seen, particularly during rewarming and warm CPB.

Jejunal and gastric mucosal perfusion versus splanchnic blood flow and metabolism: an observational study on postcardiac surgical patients.

ObjectivesTo evaluate the association between changes in total splanchnic and mucosal perfusion, assessed either by gastric tonometry or jejunal laser Doppler flowmetry in postcardiac surgical patients. DesignA prospective, observational study. SettingsA general intensive care unit in a tertiary care center. PatientsTwelve, postoperative cardiac surgery patients were studied. InterventionsPatients were treated according to clinical routine. Total splanchnic blood flow (indocyanine green extraction), jejunal mucosal perfusion (laser Doppler flowmetry), gastric mucosal-arterial Pco2 gradients, and splanchnic lactate uptake were studied during four 30-min measurements periods, each separated by a period of 1 hr. Measurements and Main ResultsThere was no consistent association between either total splanchnic and local mucosal perfusion or between gastric and jejunal perfusion as assessed by two different techniques. The Pco2 gradient increased from 0.73 ± 0.21 kPa to 1.15 ± 0.30 kPa (p < .05), and splanchnic oxygen extraction increased from 40% ± 9% to 49% ± 14% (p < .01). ConclusionsIn this observational study on postcardiac surgical patients, local mucosal perfusion did not reflect total splanchnic blood flow and vice versa. Either changes in gastric and jejunal mucosal perfusion were different or increasing tissue metabolism was responsible for the observed lack of association between tonometry, laser Doppler flowmetry, and total splanchnic blood flow. Increasing mucosal arterial Pco2 gradient and splanchnic oxygen extraction may reflect a mismatch between splanchnic perfusion and metabolic demands.

Effects of norepinephrine alone and norepinephrine plus dopamine on human intestinal mucosal perfusion

ObjectivesTo evaluate the effect of norepinephrine alone and norepinephrine combined with dopamine on jejunal mucosal perfusion, gastric-arterial pCO2 gradient, and global splanchnic oxygen demand-supply relationship after cardiac surgery.DesignA prospective interventional study.SettingA university cardiothoracic intensive care unit.PatientsEighteen patients were studied during propofol sedation and mechanical ventilation after uncomplicated coronary artery bypass surgery.InterventionsAfter control measurements, each patient received norepinephrine (50±26xa0ng·kg·min) to increase mean arterial blood pressure by 30% followed by addition of low-dose dopamine (2.6±0.3xa0µg·kg·min). Postdrug control measurements were performed 120xa0min after discontinuation of the catecholamines.Measurements and resultsNorepinephrine induced a 32% increase in systemic vascular resistance with no change in cardiac index. Neither jejunal mucosal perfusion, assessed by laser Doppler flowmetry, nor gastric-arterial pCO2 gradient (tonometry) was affected by norepinephrine. Splanchnic O2-extraction increased (P<0.05) and this increase was positively correlated to the individual dose of norepinephrine (r = 0.78, P<0.0001). Splanchnic lactate extraction was increased by norepinephrine (P<0.05). None of the patients had splanchnic lactate production during norepinephrine infusion. The addition of dopamine increased cardiac index by 27% (P<0.001) and decreased splanchnic O2 extraction. Dopamine increased jejunal mucosal perfusion by 32% (P<0.001) while the gastric-arterial pCO2 gradient remained unchanged.ConclusionsVasopressor therapy with norepinephrine after cardiac surgery did not jeopardize intestinal mucosal perfusion in spite of a dose-dependent increase of the global splanchnic oxygen demand-supply relationship. The addition of dopamine increased intestinal mucosal perfusion.

Baroreceptor-mediated reduction of jejunal mucosal perfusion, evaluated with endoluminal laser Doppler flowmetry in conscious humans

Reduction of central blood volume elicits a peripheral vasoconstrictor reflex in various tissues including skin, skeletal muscle and the hepatomesenteric region. The aim of the present study was to investigate whether this reaction includes a decreased perfusion of the jejunal mucosa in man. Laser Doppler flowmetry (LDF) was used to monitor jejunal mucosal and skin perfusion simultaneously in eleven healthy volunteers. LDF recordings were performed during quiescent (phase 1) periods of the migrating motor complex. Seven subjects demonstrated cycling changes of jejunal mucosal perfusion (vasomotion). The average minimum jejunal flux value was 72 +/- 6 perfusion units. The average intraindividual coefficient of variation was 18 +/- 2%. Lower body negative pressure (LBNP) was used to elicit controlled reductions of central blood volume. LBNP of 10 mm Hg induced a 12 +/- 4% (P < 0.05) decrease in jejunal perfusion and a 43 +/- 11 (P < 0.001) decrease in cutaneous perfusion. Corresponding responses to LBNP of 20 mm Hg were 17 +/- 5% (P < 0.01) and 37 +/- 10% (P < 0.01) reductions in jejunal mucosal and skin perfusion, respectively. Cardiac index was significantly reduced by the LBNP procedure, whereas heart rate remained unchanged and blood pressure changes were minor and inconsistent. These findings indicate that the reflex vasoconstriction induced by mild central hypovolemia includes a significant reduction of jejunal mucosal perfusion in supine resting humans. This reflex may provide one mechanism for the intestinal ischemia often occurring in critically ill patients.

Norepinephrine and intestinal mucosal perfusion in vasodilatory shock after cardiac surgery.

Patients with norepinephrine-dependent vasodilatory shock after cardiac surgery (n = 10) were compared with uncomplicated postcardiac surgery patients (n = 10) with respect to jejunal mucosal perfusion, gastric-arterial PCO2 gradient, and splanchnic oxygen demand/supply relationship. Furthermore, the effects of norepinephrine-induced variations in MAP on these variables were evaluated in vasodilatory shock. Norepinephrine infusion rate was randomly and sequentially titrated to target MAPs of 60, 75, and 90 mmHg (0.25 ± 0.24, 0.37 ± 0.21, and 0.55 ± 0.39 μg/kg per minute, respectively). Data on jejunal mucosal perfusion, jejunal mucosal hematocrit, and red blood cell (RBC) velocity (laser Doppler flowmetry) as well as gastric-arterial PCO2 gradient (gastric tonometry) and splanchnic oxygen and lactate extraction (hepatic vein catheter) were obtained. Splanchnic oxygen extraction was 71 ± 16% in the vasodilatory shock group and 41 ± 9% in the control group (P < 0.001), whereas splanchnic lactate extraction did not differ between the two groups. Jejunal mucosal perfusion (61%; P < 0.001), RBC velocity (35%; P < 0.01), and gastric-arterial mucosal PCO2 gradient (150%; P < 0.001) were higher in the vasodilatory shock group compared with those of the control group. Jejunal mucosal perfusion, jejunal mucosal hematocrit, RBC velocity, gastric-arterial mucosal PCO2 gradient, splanchnic oxygen extraction, and splanchnic lactate extraction were not affected by increasing infusion rates of norepinephrine. In patients with norepinephrine-dependent vasodilatory shock after cardiac surgery, intestinal mucosal perfusion was higher, whereas splanchnic and gastric oxygen demand/supply relationships were impaired compared with postoperative controls, suggesting that intestinal mucosal perfusion is prioritized in vasodilatory shock. Increasing MAP from 60 to 90 mmHg with norepinephrine in clinical vasodilatory shock does not affect intestinal mucosal perfusion and gastric or global splanchnic oxygen demand/supply relationships.

Autoregulation of human jejunal mucosal perfusion during cardiopulmonary bypass.

Animal studies have suggested that autoregulation of intestinal blood flow is severely impaired during cardiopulmonary bypass (CPB). We investigated the jejunal mucosal capacity to autoregulate perfusion during nonpulsatile CPB (34°C) in 10 patients undergoing elective cardiac surgery. Changes in mean arterial blood pressure (MAP) were induced by altering the CPB flow rate randomly for periods of 3 min from 2.4 L/min/m2 to either 1.8 or 3.0 L/min/m2. Jejunal mucosal perfusion (JMP) was continuously recorded by laser Doppler flowmetry. A typical pattern of flow motion (vasomotion) was recorded in all patients during CPB. Variations in CPB flow rates caused no significant changes in mean JMP, jejunal mucosal hematocrit, or red blood cell velocity within a range of MAP from 50 ± 15 to 74 ± 16 mm Hg. The vasomotion frequency and amplitude was positively correlated with CPB flow rate. IV injections of prostacyclin (10 &mgr;g, Flolan®) blunted vasomotion and increased JMP from 192 ± 53 to 277 ± 70 (P < 0.05) perfusion units despite a reduction in MAP from 59 ± 12 to 45 ± 10 mm Hg (P < 0.05). Prostacyclin-induced vasodilation resulted in loss of mucosal autoregulation (pressure-dependent perfusion). We conclude that autoregulation of intestinal mucosal perfusion is maintained during CPB in humans.

Norepinephrine causes a pressure‐dependent plasma volume decrease in clinical vasodilatory shock

Background: Recent experimental studies have shown that a norepinephrine‐induced increase in blood pressure induces a loss of plasma volume, particularly under increased microvascular permeability. We studied the effects of norepinephrine‐induced variations in the mean arterial pressure (MAP) on plasma volume changes and systemic haemodynamics in patients with vasodilatory shock.