Andreas Nygren

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.

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.

Low-dose vasopressin increases glomerular filtration rate, but impairs renal oxygenation in post-cardiac surgery patients.

Background: The beneficial effects of vasopressin on diuresis and creatinine clearance have been demonstrated when used as an additional/alternative therapy in catecholamine‐dependent vasodilatory shock. A detailed analysis of the effects of vasopressin on renal perfusion, glomerular filtration, excretory function and oxygenation in man is, however, lacking. The objective of this pharmacodynamic study was to evaluate the effects of low to moderate doses of vasopressin on renal blood flow (RBF), glomerular filtration rate (GFR), renal oxygen consumption (RVO2) and renal oxygen extraction (RO2Ex) in post‐cardiac surgery 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.

Cardiopulmonary bypass in humans – jejunal mucosal perfusion increases in parallel with well-maintained microvascular hematocrit

Background:  An imbalance between splanchnic oxygen supply and demand occurs during cardiopulmonary bypass (CPB) in man, which might disrupt the intestinal mucosal barrier function. The aim of the present study was to evaluate the effects of mild hypothermic CPB on intestinal mucosal perfusion in man undergoing cardiac surgery. Additionally we aimed to identify variables, which independently could predict changes of intestinal mucosal microcirculatory variables during CPB.

Reply to “Haematocrit and plasma volume during induction of anaesthesia”

To the Editor We thank Dr Saito for the interest in our recent article “Pressure‐ dependent changes in haematocrit and plasma volume during anaesthesia, a randomised clinical trial” and for valuable confirmation of our findings of calculated changes in plasma volume during anaesthesia induction. We agree and have also stated in the limitations that indirect calculation of plasma volume by changes in measured haematocrit may underestimate contribution from red blood cell reservoirs such as spleen or liver depots. However, haematocrit did not increase in any patient by the infusion of norepinephrine, which supports a low, if any, alpha‐mediated impact on splenic volume, for the intravenous doses needed to maintain the pre‐anaesthesia blood pressure. In the referred study of O′Brian et al on dogs, anaesthesia with barbiturate or acepromazine was followed by a change the spleen size though propofol, which was used in our study, did not cause measurable splenic enlargement. Any increase in red blood cell count as in the work of Ojiri et al on dogs, was not seen in our study on patients. Differences in splenic response to alpha‐adrenergic stimulation between species as well as differences in experimental and clinical doses add uncertainty which we believe do not change our conclusion.