Therapeutic Advantages of an Inotropic Vasodilator in Endotoxin Shock

Siegel, John H.

doi:10.1001/jama.1967.03120210082015

Cited by 17 publications

(3 citation statements)

References 21 publications

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“…Total peripheral resistance was increased in both groups 15 min postendotoxin, but the differences Heart work/min was considerably reduced immediately after endotoxin and the values were still below the base line at 60 min, being 43% in group I and 41 % in group II. Heart work in group I remained essentially unchanged during 10 hr of infusion, but at 13 hr it was 38% of the control value, which was a significant difference (P < 0.02).…”

Section: Hemodynamic Alterations After Endotoxinmentioning

confidence: 80%

Hemodynamic effects of isoproterenol in canine endotoxin shock

Starzecki¹,

Spink²

1968

J. Clin. Invest.

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A B S T R A C T Myocardial function and peripheral hemodynamic alterations were measured through the late stages of canine endotoxin shock. 60 min postendotoxin paired animals were given infusions of either 5 ml/kg per hr of 5%o dextrose or dextrose plus isoproterenol (0.25 pg/kg per min). Comparable blood lactic and pyruvic acid levels were determined, the excess lactic acid calculated, and pH values were obtained. During the initial stages the classic pattern of hemodynamic alterations was observed; an excess of lactic acid appeared and the pH decreased. Outstanding was evidence of markedly reduced myocardial function in the late stages of shock with progressive rise in left ventricular end diastolic pressure (LVEDP), low cardiac index, rise of central venous pressure, increased central blood 'volume, tachycardia, and declining arterial pressure. Analyses of left ventricular function curves also indicated myocardial failure.Infusion of dextrose alone failed to decrease mortality rate (10 of 18 dying), whereas the rate was significantly decreased with isoproterenol (2 of 18). Dextrose infusion did not benefit myocardial function. Isoproterenol resulted in a marked improvement in myocardial action with a significant increase in heart work associated with, yet very minor, increments of LVEDP. In addition, tachycardia subsided, peripheral resistance decreased, and the blood pressure stabilized. The Address requests for reprints to Dr.

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Section: Hemodynamic Alterations After Endotoxinmentioning

confidence: 80%

Hemodynamic effects of isoproterenol in canine endotoxin shock

Starzecki¹,

Spink²

1968

J. Clin. Invest.

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“…The findings may be taken as supportive of Levy and coworker's (22) original "sepsis change bundle" focused on avoiding refractory hypotension (here, reflected by glucocorticoids), hypoperfusion (inotropes and red cell transfusions), and organ dysfunction (lung-protective ventilation). Inotropes and red cell transfusions for septic shock date back more than 40 years (23) and are part of early goal-directed therapy (6). Although improving oxygen delivery in the first 6 hours seemed to improve mortality in early goal-directed therapy with a special catheter in the ED environment (6), optimizing oxygen delivery during the first 24 hours of established septic shock has not held up in randomized clinical trials (24,25).…”

Section: Discussionmentioning

confidence: 99%

Multicenter Implementation of a Severe Sepsis and Septic Shock Treatment Bundle

Miller

Dong

Nelson

et al. 2013

Am J Respir Crit Care Med

223

116

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“…However, one problem with using indomethacin in this experimental model is that it can cause substantial myocardial depression (Parratt & Sturgess, 1974). Although it is not known whether the pulmonary changes that occur in septic shock are modified by drugs like indomethacin it seemed worthwhile exploring the effect of other antipyretic-analgesic drugs on the pulmonary effects of endotoxin in the cat; such drugs might be more effective than indomethacin and cause less myocardial depression, an important consideration since myocardial function is often depressed in septic shock (Siegel & Fabian, 1967). This paper describes the effects, in experimental endotoxin shock, of flurbiprofen (2-(2-fluoro-4-biphenylyl)-propionic acid) a potent, orally active non-steroidal anti-inflammatory drug (Glenn, Rohloff, Bowman & Lyster, 1973;Adams, McCullough & Nicholson, 1975) which recently has been shown to be extremely active in inhibiting human platelet aggregation (Nishizawa, Wynalda, Suydam & Molony, 1973;Davies, Lederer, Spencer & McNicol, 1974;Sim, McCraw & Sim, 1975).…”

Section: Introductionmentioning

confidence: 99%

THE EFFECT OF A NEW ANTI‐INFLAMMATORY DRUG, FLURBIPROFEN, ON THE RESPIRATORY, HAEMODYNAMIC AND METABOLIC RESPONSES TO E. coli ENDOTOXIN SHOCK IN THE CAT

Parratt

Sturgess

1976

British J Pharmacology

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I The intravenous administration of E. coli endotoxin (2.0 mg/kg) in cats anaesthetized with sodium pentobarbitone resulted in immediate pulmonary hypertension and reductions in lung compliance and systemic arterial Po2. These effects were abolished, or greatly reduced, by the prior intravenous administration of flurbiprofen in doses (100 and 250 ,ug/kg and 1.0 mg/kg) which were devoid of cardiovascular or metabolic effects. Flurbiprofen is thus the most active antipyretic-analgesic drug so far examined in this experimental model. 2 Production of lactate, characteristic of the severe, secondary endotoxin shock phase, was delayed only by the highest dose of flurbiprofen; hypotension, hypoglycaemia and the reduction in cardiac output which occurs during this phase, were unaffected. 3 These findings are discussed with reference to the treatment of the 'shocked lung' syndrome of human septicaemia.

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Therapeutic Advantages of an Inotropic Vasodilator in Endotoxin Shock

Cited by 17 publications

References 21 publications

Hemodynamic effects of isoproterenol in canine endotoxin shock

Hemodynamic effects of isoproterenol in canine endotoxin shock

Multicenter Implementation of a Severe Sepsis and Septic Shock Treatment Bundle

THE EFFECT OF A NEW ANTI‐INFLAMMATORY DRUG, FLURBIPROFEN, ON THE RESPIRATORY, HAEMODYNAMIC AND METABOLIC RESPONSES TO E. coli ENDOTOXIN SHOCK IN THE CAT

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