2,833 publications from this institution
Nitric oxide (NO), an endothelium-derived relaxing factor (EDRF), is released by different types of cells under the influence of endotoxin and various cytokines: a causative role of endothelium-derived NO in the endotoxin-induced hypotension has thus been suggested. To test the hypothesis that NO may be involved in the acute hypotension following endotoxin challenge, we administered a competitive inhibitor of NO synthase, L-N-monomethylarginine (L-NMMA) to anesthetized dogs in the presence and absence of endotoxin. Dogs were randomly allocated to three groups. Group 1 (n = 3) was given Escherichia coli endotoxin (3 mg/kg, i.v.), group 2 (n = 3) was given L-NMMA (5 mg/kg, i.v. bolus) 15 min after endotoxin and group 3 (n = 3) was given L-NMMA only. One additional dog was given L-arginine (100 mg/kg, i.v. bolus) after L-NMMA and endotoxin to reverse the inhibition of NO synthase. In each animal, saline was infused intravenously throughout the experiment to restore and maintain pulmonary artery occluded pressure at baseline level. After L-NMMA, the increases in mean arterial pressure were similar in group 2 (from 55 +/- 18 to 75 +/- 15 mm Hg, p < 0.01) and in group 3 (from 107 +/- 27 to 128 +/- 24 mm Hg, p < 0.01). Systemic vascular resistance increased from 2,994 +/- 72 to 3,658 +/- 673 dyn.s.cm-5 (p < 0.01) in group 3. Group 1 had lower plasma lactate levels than group 2 (3.5 +/- 2.3 +/- vs. 2.0 +/- 1.6 mEq/l, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
The postoperative period after laparotomy is characterized by a decrease in pulmonary volumes combined with a maldistribution of the ventilation and the perfusion. Together with manual techniques, intermittent pressure breathing and incentive spirometry have been suggested to maintain open alveoli and to prevent atelactasissis. The shortcomings related to the use of pressure-controlled devices include patient's resistance to the technique, overinflation of normal alveoli, excessive total ventilation, decrease in venous return and various gastrointestinal side effects. The incentive spirometry has been designed to promote sustained maximal inspirations and reproduce sighing mechanisms. The decrease in pleural pressure can result in high transpulmonary pressures. For many investigators, incentive spirometry represents a very easy and efficient method to prevent atelectasis.
info:eu-repo/semantics/published
Introduction: The non-selective vasopressin agonist, arginine vasopressin (AVP) is widely used as second line vasopressor in septic shock patients as add-on to norepinephrine (NE). However, animal septic shock studies have shown selective V1a receptor agonists to be superior to AVP in alleviating organ dysfunction. Selepressin (FE 202158) is the first selective V1a agonist to be evaluated in septic shock patients. Hypothesis: Selepressin reduces NE requirements and duration of organ dysfunction in human septic shock. Methods: In a randomized double-blind, placebo controlled trial, septic shock patients in need of vasopressor support (?0.1 µg/kg/min NE for?2h) received selepressin (1.25 ng/kg/min (n=10) or 2.5 ng/kg/min (n=19) or placebo (n=21) until shock resolution or for up to 7 days. If target mean arterial pressure (MAP) of 65 mmHg could not be achieved, open-label NE was added. The co-primary endpoints were ability to maintain target MAP without NE, NE infusion rate and cumulative dose of NE. Secondary endpoints included organ dysfunction and fluid balance. Results: Selepressin dose-dependently reduced the 7-day cumulative dose of open-label NE (placebo: 772 µg/kg, 1.25 ng/kg/min selepressin: 617 µg/kg and 2.5 ng/kg/min selepressin: 249 µg/kg, p=0.007). NE was weaned more rapidly in the selepressin group: 2.5 ng/kg/min selepressin increased the proportion of patients maintaining target MAP without open-label NE compared to placebo (69% vs. 20%, p=0.005) and reduced mean NE infusion rate (0.04 vs. 0.18, p=0.0001) in the first 24h following initiation of study drug. Interestingly, the 2.5 ng/kg/min selepressin group had faster recovery than placebo as shown by a higher proportion of patients out of shock at 48h (57.9 vs. 28.6%, p=0.1) and higher proportion of days alive and free of ventilation within the first 7 days (53.8 vs. 23.1%, p=0.01) in spite of similar baseline NE requirements and SOFA score. Moreover, 7-day cumulative fluid balance was lower in the 2.5 ng/kg/min selepressin group than in placebo (9.0 vs. 6.5 L, p=0.1). Conclusions: Selepressin dose-dependently reduced NE requirements, as well as the need for mechanical ventilation, and appeared to shorten time to shock resolution in septic shock patients.
Editorial
