Werner Pajk

Effects of phenylephrine on the sublingual microcirculation during cardiopulmonary bypass

BACKGROUNDnThe objective of the present study was to investigate sublingual microvascular blood flow and microcirculatory haemoglobin oxygen saturation (Smc(O(2))) during cardiopulmonary bypass (CPB) using constant systemic blood flow but different perfusion pressures achieved by phenylephrine administration.nnnMETHODSnFifteen patients undergoing coronary artery bypass grafting were enrolled in this pilot study. Systemic haemodynamics, oxygen transport variables, arterial and mixed venous blood gas analysis, and microcirculatory variables were determined after initiation of general anaesthesia, during CPB (systemic blood flow=2.4 litre m(-2)), after increasing perfusion pressure by 20 mm Hg with a continuous infusion of phenylephrine, and after termination of phenylephrine infusion.nnnRESULTSnCPB immediately resulted in a significant (P<0.05) decrease in systemic oxygen transport without alterations in sublingual microcirculatory blood flow and Smc(O(2)). Increasing perfusion pressure from 47 (SD 9) to 68 (7) mm Hg using phenylephrine=1.4 (1.0) microg kg(-1) min(-1) resulted in a significant decrease in sublingual small vessel blood flow (from median 2.5 to 1.8 arbitrary units) representing mostly capillary blood flow, but not in medium-sized vessels (median 3 to 2.8 arbitrary units). Concurrently, global tissue blood flow from 110 (54) to 197 (100) perfusion units and Smc(O(2)) increased from 72 (11)% to 84 (7)%, suggesting significant microcirculatory blood flow shunting in vessels with diameters >25 microm.nnnCONCLUSIONSnOur data demonstrate that an increased perfusion pressure produced by phenylephrine at constant CPB flow may decrease microcirculatory blood flow in the sublingual mucosal microcirculation due to microvascular blood flow shunting.

Arginine vasopressin does not alter mucosal tissue oxygen tension and oxygen supply in an acute endotoxemic pig model

ObjectiveTo determine the effects of increasing dosages of continuously infused arginine-vasopressin (AVP) on mucosal tissue oxygen tension and oxygen supply in an auto-perfused, innervated jejunal segment in an acute endotoxic porcine model.DesignProspective, randomized, experimental study.SettingUniversity hospital animal research laboratory.InterventionsJejunal mucosal tissue PO2 was measured employing two Clark-type surface oxygen electrodes. Oxygen saturation of jejunal microvascular hemoglobin was determined by tissue reflectance spectrophotometry. Systemic hemodynamic variables, mesenteric-venous and systemic acid base and blood gas variables and lactate measurements were recorded. Measurements were performed at baseline, after E. coli lipopolysaccharide (LPS) administration and at 20xa0min intervals during incremental AVP infusion ( n =8; 0.014, 0.029, 0.057, 0.114 and 0.229xa0IUxa0kg-1xa0h-1, respectively) or infusion of saline ( n =8).Measurements and resultsLPS infusion leads to a significant ( P <0.05) decrease of mucosal tissue oxygen tension (PO2muc, 24±3 to 12±2xa0mmHg) and microvascular hemoglobin oxygen saturation (HbO2, 38±4 to 21±4%). Mesenteric venous lactate level increased (2.4±0.3 to 4.7±1.7xa0mmolxa0l-1), while mesenteric venous pH decreased (7.38±0.02 to 7.26±0.12), indicating tissue hypoxia. AVP significantly increased mean arterial pressure (MAP, 81±15 to 97±17 at 0.057xa0IUxa0kg-1xa0h-1). No differences in jejunal mucosal oxygenation occurred between study groups at any dosage during the experimental protocol.ConclusionAVP administration did not further compromise mucosal tissue oxygen tension and oxygen supply in the acute phase of endotoxic pigs.

Cutaneous vascular reactivity and flow motion response to vasopressin in advanced vasodilatory shock and severe postoperative multiple organ dysfunction syndrome

IntroductionDisturbances in microcirculatory homeostasis have been hypothesized to play a key role in the pathophysiology of multiple organ dysfunction syndrome and vasopressor-associated ischemic skin lesions. The effects of a supplementary arginine vasopressin (AVP) infusion on microcirculation in vasodilatory shock and postoperative multiple organ dysfunction syndrome are unknown.MethodIncluded in the study were 18 patients who had undergone cardiac or major surgery and had a mean arterial blood pressure below 65 mmHg, despite infusion of more than 0.5 μg/kg per min norepinephrine. Patients were randomly assigned to receive a combined infusion of AVP/norepinephrine or norepinephrine alone. Demographic and clinical data were recorded at study entry and after 1 hour. A laser Doppler flowmeter was used to measure the cutaneous microcirculatory response at randomization and after 1 hour. Reactive hyperaemia and oscillatory changes in the Doppler signal were measured during the 3 minutes before and after a 5-minute period of forearm ischaemia.ResultsPatients receiving AVP/norepinephrine had a significantly higher mean arterial pressure (P = 0.047) and higher milrinone requirements (P = 0.025) than did the patients who received norepinephrine only at baseline. Mean arterial blood pressure significantly increased (P < 0.001) and norepinephrine requirements significantly decreased (P < 0.001) in the AVP/norepinephrine group. Patients in the AVP/norepinephrine group exhibited a significantly higher oscillation frequency of the Doppler signal before ischaemia and during reperfusion at randomization. During the study period, there were no differences in either cutaneous reactive hyperaemia or the oscillatory pattern of vascular tone between groups.ConclusionSupplementary AVP infusion in patients with advanced vasodilatory shock and severe postoperative multiple organ dysfunction syndrome did not compromise cutaneous reactive hyperaemia and flowmotion when compared with norepinephrine infusion alone.

Intravenous tezosentan improves gas exchange and hemodynamics in acute lung injury secondary to meconium aspiration

ObjectiveMeconium aspiration induces acute lung injury (ALI) and subsequent pulmonary arterial hypertension (PAH) which may lead to right ventricular failure. Increase of endothelin-1, thromboxane-A, and phosphodiesterases are discussed molecular mechanisms.We investigated the intrapulmonary and hemodynamic effects of the intravenous dual endothelin Axa0and B receptor blocker tezosentan and inhalational iloprost in axa0model of ALI due to meconium aspiration.DesignAnimal study.SettingUniversity-affiliated research laboratory.SubjectsWhite farm pigs.InterventionsAcute lung injury was induced in 24 pigs by instillation of meconium. Animals were randomly assigned to four groups to receive either intravenous tezosentan, inhalational iloprost, or combined tezosentan and iloprost, or to serve as controls.Measurements and resultsAfter meconium aspiration-induced lung injury each treatment increased oxyhemoglobin saturations (TEZO: 88u202f±u202f6% (pu202f=u202f0.02), ILO: 85u202f±u202f13% (pu202f=u202f0.05), TEZO-ILO: 89u202f±u202f6% (pu202f=u202f0.02), control: 70u202f±u202f18%). TEZO but not ILO significantly decreased pulmonary arterial pressure and pulmonary vascular resistance (both pu202f<u202f0.01). ILO alone decreased intrapulmonary shunt blood flow (pu202f<u202f0.01). Compared with control, TEZO-ILO yielded the highest arterial partial pressure of oxygen (70u202f±u202f6 torr vs.49u202f±u202f9 torr, pu202f=u202f0.04), although it decreased arterial blood pressure (change from 71u202f±u202f13u202fmmHg to 62u202f±u202f12u202fmmHg vs.85u202f±u202f14u202fmmHg to 80 u202f±u202f11u202fmmHg (pu202f=u202f0.01).ConclusionsIntravenous TEZO improves pulmonary gas exchange and hemodynamics in experimental acute lung injury secondary to meconium aspiration. Inhaled ILO improves gas exchange only, thereby reducing intrapulmonary shunt blood flow. Combination of TEZO and ILO marginally improves pulmonary gas exchange at the disadvantage of pulmonary selectivity.

Tezosentan Decreases Pulmonary Artery Pressure and Improves Survival Rate in an Animal Model of Meconium Aspiration

Acute pulmonary arterial hypertension in acute lung injury aggravates the clinical course and complicates treatment. Increased release and turnover of endogenous endothelin-1 is known to be a major determinant in the pathophysiology of pulmonary arterial hypertension of various etiologies. We tested whether intravenous tezosentan, a dual endothelin receptor antagonist, reduced pulmonary artery pressure in a pig model of acute lung injury induced by meconium aspiration. Acute pulmonary arterial hypertension was induced in 12 anesthetized and instrumented pigs by instillation of human pooled meconium in a 20% solution. Hemodynamic and gas exchange parameters were recorded every 30 min. Six animals received tezosentan 5 mg/kg after 0 and 90 min; six animals served as controls. Tezosentan led to a decrease of mean pulmonary artery pressure (PAP) from 33.4 ± 4.0 mm Hg to 24.7 ± 2.1 mm Hg and pulmonary vascular resistance (PVR) from 7.8 ± 1.4 mm Hg · L–1 · min · m2 to 5.2 ± 0.7 mm Hg · L–1 · min · m2. All animals treated with tezosentan survived, whereas in the control group four out of six animals died. Tezosentan improved survival and decreased pulmonary artery pressure in a porcine model of acute pulmonary arterial hypertension after meconium aspiration. Tezosentan has the potential for effective pharmacological treatment of pulmonary arterial hypertension following acute lung injury.

Arginine-vasopressin attenuates beneficial norepinephrine effect on jejunal mucosal tissue oxygenation during endotoxinaemia

BACKGROUNDnThe objective of the present study was to investigate the effects of increasing doses of norepinephrine (NE) with or without arginine-vasopressin (AVP) on intestinal oxygen supply and jejunal mucosal tissue oxygen tension in an acute endotoxic pig model.nnnMETHODSnIn this prospective, randomized, experimental study on 24 domestic pigs, jejunal mucosal tissue PO2 (PO2muc) was measured using two Clark-type surface oxygen electrodes. Oxygen saturation of jejunal microvascular haemoglobin (HbO2j) was determined by tissue reflectance spectrophotometry. Systemic haemodynamic variables, mesenteric-venous and systemic acid-base and blood gas variables, and lactate measurements were recorded. Measurements were performed at baseline, after Escherichia coli lipopolysaccharide (LPS) administration, and at 20 min intervals during incremental NE infusion (0.05, 0.1, 0.5, 1.0, and 2 microg kg(-1) min(-1), respectively) with 57 mU kg(-1) h(-1) AVP (n=8; NE+AVP group) or without (n=8; NE group); or infusion of an equal amount of normal saline (n=8; CON group).nnnRESULTSnLPS infusion led to a significant (P<0.05) decrease of PO2muc and HbO2j. Both NE and NE+AVP increased arterial pressure, cardiac output, and mesenteric artery blood flow. Concomitant to an increase in systemic oxygen delivery, NE improved PO2muc and HbO2j. NE alone was superior in restoration of PO2muc when compared with NE+AVP.nnnCONCLUSIONSnBoth NE and NE+AVP improved global haemodynamics and systemic oxygen transport variables when compared with control animals in an acute endotoxic pig model. NE improved jejunal PO2muc at all dosages. NE effects were significantly blunted by simultaneous administration of AVP.

Oscillation frequency of skin microvascular blood flow is associated with mortality in critically ill patients

Background:u2002 Microcirculatory dysfunction has been hypothesized to play a key role in the pathophysiology of multiple organ failure and, consequently, patient outcome. The objective of this study was to investigate the differences in reactive hyperemia response and oscillation frequency in surviving and non‐surviving patients with multiple organ dysfunction syndrome.

Vasopressin as adjunct vasopressor for vasodilatory shock due to non-occlusive mesenteric ischemia.

We present the case of an 83-year-old patient who underwent cardiac surgery and developed postoperative non-occlusive mesenteric ischemia (NOMI), which was treated with a local intra-arterial papaverine and prostaglandin E1 infusion. After successful mesenteric reperfusion, a multiple organ dysfunction syndrome with severe cardiovascular failure developed. High norepinephrine dosages (1.09xa0µg/kg body weight/min) and catecholamine-related complications (tachycardiac atrial fibrillation) required initiation of supplementary argininevasopressin (AVP) infusion (4xa0U/h). AVP stabilized vasodilatory shock, ensured adequate gut perfusion pressure and had no adverse clinical or angiographic effects on restitution of gut integrity. In conclusion, after reperfusion of NOMI in this patient, adjunct AVP therapy combined with local vasodilator infusion was beneficial as a potentially life-saving vasopressor.ZusammenfassungWir berichten über einen 83-jährigen Mann, der nach einem kardiochirurgischen Eingriff eine nichtokklusive mesenteriale Ischämie (NOMI) entwickelte, die mit einer lokalen intraarteriellen Infusion mit Papaverin und Prostaglandinxa0E1 behandelt wurde. Nach erfolgreicher mesenterialer Reperfusion entwickelte sich ein Multiorgandysfunktionssyndrom mit schwerem Herzkreislaufversagen. Hohe Noradrenalindosen (1,09xa0µg/kgKG/min) und katecholamininduzierte Komplikationen (tachykardes Vorhofflimmern) erforderten eine zusätzliche Arginin-Vasopressin- (AVP-)Infusion. Arginin-Vasopressin stabilisierte den vasodilatorischen Schock, sicherte einen adäquaten Perfusionsdruck des Darms und hatte keine negativen klinischen oder angiographischen Auswirkungen auf die Erholung der Darmintegrität. Zusammenfassend erwies sich bei diesem Patienten nach Reperfusion einer NOMI AVP in Kombination mit Noradrenalin und lokaler Vasodilatatorinfusion als potenziell lebensrettender Vasopressor.

The impact of endotoxin on jejunal tissue oxygenation

We examined the effects of systemic ETX on jejunal mucoal microcirculatory parameters in anesthetized pigs.