Moderate-dose vasopressin therapy may impair gastric mucosal perfusion in severe sepsis: a pilot study.

BACKGROUND: The effects of moderate-dose vasopressin on gastric mucosal perfusion and its relation to global and hepatosplanchnic hemodynamic and oxygen transport variables were investigated in patients with severe sepsis. METHODS: Vasopressin was administered at a dose of 0.04 IU · kg⁻¹ · h⁻¹ over 4 h in 12 patients with severe sepsis who were receiving norepinephrine. During the study period, the norepinephrine infusion rate was reduced to keep mean arterial blood pressure constant. Hepatosplanchnic blood flow, oxygen delivery, and oxygen consumption (via hepatic venous catheterization using the Fick principle and continuous indocyanine green infusion technique), global hemodynamics (transpulmonary thermodilution method), and the difference between the gastric mucosal and arterial carbon dioxide tension (Pco2-gap) were measured at baseline and 4 h after the start of the vasopressin infusion. RESULTS: The administration of 0.04 IU · kg⁻¹ · h⁻¹ vasopressin over 4 h was associated with minimal changes in global hemodynamics. Heart rate decreased slightly from 99 [81-115] (median [interquartile range]) to 96 [74-109] beats/min (P = 0.016) and cardiac index from 3.7 [2.8-4.7] to 3.5 [2.7-3.6] L · min⁻¹ · m⁻² (P = 0.003). Global oxygen delivery index decreased significantly from 461 [375-637] to 419 [352-551] ml · min⁻¹ · m⁻² (P = 0.002), whereas hepatosplanchnic blood flow and oxygen uptake remained unchanged. Gastric mucosal Pco2-gap increased significantly from 13.3 [8.0-16.7] to 17.1 [10.3-28.7] mmHg (P = 0.002), suggesting that blood flow may have been redistributed away from the gut mucosa. CONCLUSIONS: Vasopressin at a dosage of 0.04 IU · kg⁻¹ · h⁻¹ may impair gastric mucosal perfusion with minimal global hemodynamic effects.

Characterization of buccal microvascular response in patients with septic shock.

BACKGROUND AND OBJECTIVE: Microcirculatory alterations are thought to be responsible for much of the morbidity and mortality from sepsis. The aim of the present study was to characterize the buccal microvascular response in patients with septic shock using combined laser Doppler flowmetry/visual light spectroscopy measurements. METHODS: Microvascular measurements were performed daily on the buccal mucosa in 21 consecutive ICU patients within 24 h of the onset of septic shock, in 20 healthy volunteers, and in eight ICU patients after uncomplicated elective surgery (ICU controls). RESULTS: In ICU controls, buccal mucosal flow was higher in the superficial (231.7+/-69.5 vs. 134+/-105.3 arbitrary unit, P=0.03) and lower in the deep (235.3+/-30.8 vs. 376.2+/-107.3 arbitrary unit, P=0.001) channel compared with healthy volunteers; microvascular oxygen haemoglobin saturations (microHbO2) were similar in the two groups. Microvascular flow within 24 h of onset of shock was similar in patients with septic shock and healthy individuals; however, microHbO2 was lower in the deep channel (78.3+/-10.3 vs. 91.1+/-4.5%, P<0.001). Superficial buccal mucosal microHbO2 within 24 h of onset of septic shock was lower in nonsurvivors than in survivors. Superficial buccal mucosal flow increased during the 2nd day of septic shock in survivors and decreased thereafter; microHbO2 decreased steadily. CONCLUSION: Buccal laser Doppler flowmetry/visual light spectroscopy may be useful for tracing microvascular alterations in critically ill patients. The surgical stress response was associated with alterations in local flow with preserved microHbO2. However, in patients with septic shock, microHbO2 was reduced in the deep channel, probably muscular tissue, with no changes in microvascular flow.

Hydrocortisone does not affect major platelet receptors in inflammation in vitro.

HYPOTHESIS: Platelet function is an important factor for the fate of intensive care patients. Several factors may influence this function. Recently, it was demonstrated that hydrocortisone has immunologic effects in septic shock and therefore may affect cell adhesion molecules. The aim of the present study was to examine effects of hydrocortisone on platelet receptor expression in healthy individuals and septic patients in vitro. METHODS: Citrated blood samples were drawn from 10 healthy volunteers and 10 septic patients. Samples were adjusted with hydrocortisone to final concentrations of 4.5 microg mL(-1), 9.0 microg mL(-1) (sepsis-equivalent bolus) and 90 microg mL(-1), respectively. A control group received no additional hydrocortisone. Expression of CD62P, CD41, PAC-1 and CD42b on the surface of resting or agonist-stimulated platelets was determined by whole blood flow cytometry using fluorescence-labeled monoclonal antibodies. RESULTS: Hydrocortisone had no significant influence on the expression of CD62P, CD41 and PAC-1. After administration of 90 microg mL(-1) hydrocortisone the expression of CD42b was decreased compared to controls after activation. Differences between volunteers and sepsis patients were found for all receptors after activation. CONCLUSIONS: Hydrocortisone mediates immunmodulating effects in therapy of patients suffering of septic shock without involvement of specific platelet receptors in vitro.

High-dose vasopressin is not superior to norepinephrine in septic shock.

OBJECTIVE: We examined the effects of arginine vasopressin, when substituted for norepinephrine as a vasopressor in septic shock, on global and hepatosplanchnic hemodynamic and oxygen transport variables. DESIGN: Experimental study. SETTING: Intensive care unit. SUBJECTS: Twelve septic shock patients. INTERVENTIONS: Norepinephrine was replaced by vasopressin in a dose sufficient to keep mean arterial blood pressure constant. Blood flow, oxygen delivery, and oxygen consumption of the hepatosplanchnic region (calculated by a hepatic venous catheter technique using the Fick principle during continuous infusion of indocyanine green), global hemodynamics (by thermodilution), and gastric regional PCO2 gap (by air tonometry) were calculated during infusion of norepinephrine (mean, 0.56 microg.kg-1.min-1; range, 0.18-1.1 microg.kg-1.min-1) and again 2 hrs after replacement by vasopressin (mean, 0.47 IU/min; range, 0.06-1.8 IU/min). MEASUREMENTS AND MAIN RESULTS: Cardiac index decreased significantly from 3.8 +/- 1.3 to 3.0 +/- 1.1 L.min-1.m-2, heart rate decreased from 96 +/- 14 to 80 +/- 16 min-1 (p <.01), and global oxygen uptake decreased from 248 +/- 67 to 218 +/- 75 mL/min (p <.05). Absolute splanchnic blood flow tended to increase, although not significantly, whereas fractional splanchnic blood flow increased from 10.8 +/- 7.6 to 25.9 +/- 16.6% of cardiac output (p <.05). Gastric regional PCO2 gap increased from 17.5 +/- 26.6 to 36.5 +/- 26.6 mm Hg (p <.01). CONCLUSION: Vasopressin, in doses sufficient to replace the vasopressor norepinephrine, had mixed effects in septic shock patients. Hepatosplanchnic blood flow was preserved during substantial reduction in cardiac output. An increased gastric PCO2 gap suggests that the gut blood flow could have been redistributed to the disadvantage of the mucosa. Based on these limited data, it does not appear beneficial to directly replace norepinephrine with vasopressin in septic shock.