Effectiveness of Modified Steroid-Antibiotic Therapies for Lethal Sepsis in the Dog

Beller, B. K.

doi:10.1001/archsurg.1983.01390110045011

Cited by 23 publications

(6 citation statements)

References 22 publications

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“…These studies clearly documented the outstanding effectiveness of the combined treatment regimen of ste-25 roid and antibiotics in several species of animals subjected to lethal septic shock. 24,[28][29][30][31][32][33][34][35][36][37][38][39][40][41] These findings add support to the results of the human clinical study reported by Schumer ( Table 5).…”

Section: Animal Studiessupporting

confidence: 79%

“…9 Of great importance is the observation that neither steroid nor antibiotic administered alone is effective in preventing pathophysiologic changes and promoting survival in dogs or baboons infused with LD 100 E. coli. 24,38,42 Furthermore, in canine experiments, 41 the probability of recovery from shock is significantly increased when animals are treated with a constant infusion of steroid and intermittent infusions of antibiotic, but is only moderately increased when treated with intermittent bolus infusions of steroid and intermittent infusions of antibiotic. This research strongly suggests that combination therapy is effective because the antibiotic aids the host's defense system in eliminating the bacteria and the steroid, by its many vascular actions, concomitantly prevents or reverses the maldistribution of blood flow and volume that occurs in shock.…”

Section: Animal Studiesmentioning

confidence: 99%

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Corticosteroids in Shock

Hinshaw¹

1985

Semin Respir Crit Care Med

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Section: Animal Studiessupporting

confidence: 79%

Section: Animal Studiesmentioning

confidence: 99%

Corticosteroids in Shock

Hinshaw¹

1985

Semin Respir Crit Care Med

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“…Glucocorticoid therapy improved the outcome in experimental models of lethal sepsis [52–54], however early clinical trials reported that glucocorticoids cause deleterious immunosuppression [55–57]. These trials used short treatment courses with high doses of steroids (up to 600 mg/kg of steroid over the course of 24 hours), which upon meta-analysis were found to be detrimental to the patients receiving treatment [57, 58].…”

Section: Glucocorticoids: Endocrine-mediated Systemic Immune Suppressionmentioning

confidence: 99%

Scientific and Clinical Challenges in Sepsis

Ulloa

Brunner

Ramos

et al. 2009

CPD

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Advances in intensive care and antibiotics have prevented the spread of some infections, though sepsis mortality rates remain high. With failure of over thirty clinical trials, sepsis remains a scientific and clinical challenge in modern medicine. Sepsis is defined by the clinical signs of a systemic inflammatory response to infection. “Severe sepsis” is when these symptoms are associated with multiple organ dysfunction. These definitions of sepsis may be too broad and common to heterogeneous groups of patients who do not necessarily have the same disorder. This consideration has become especially evident in the clinical trials that have failed to obtain consistent results in similar studies of patients diagnosed with severe sepsis. In these trials, patients with infections caused by different microorganisms, and affecting different organs, have been combined under the general diagnosis of severe sepsis. The situation is analogous to attempting a clinical trial based on the general definition of cancer, combining all patients with tumor independent of the type of malignancy. In this consideration, it would not be very surprising that activated protein C, the only treatment in sepsis approved by the Food and Drug Administration, is projected for use in only a small subset of patients with severe sepsis. This article reviews novel inflammatory molecular aspects and the experimental anti-inflammatory strategies for sepsis, as they may represent particular pathological processes in specific subsets of patients.

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“…11,[13][14][15] Glucocorticoids were among the earliest agents tested in the treatment of sepsis. 11,13,16,17 Glucocorticoid therapy improves the outcome in experimental models of lethal sepsis; [18][19][20] however, early clinical trials reported that ad-ministration of glucocorticoids contributes to hyperglycemia and causes deleterious immunosuppression. [21][22][23] Meta-analyses of these trials, which involved short treatment courses with high doses of corticosteroids (up to 600 mg/kg of steroid over the course of 24 h), revealed detrimental effects to the patients.…”

Section: Glucocorticoidsmentioning

confidence: 99%

Experimental Therapeutic Strategies for Severe Sepsis

Parrish

Gallowitsch-Puerta

Czura

et al. 2008

Annals of the New York Academy of Sciences

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Severe sepsis is the leading cause of mortality in intensive care units. The limited ability of current therapies to reduce sepsis mortality rates has fueled research efforts for the development of novel treatment strategies. Through the close collaboration between clinicians and scientists, progress can be seen in the struggle to develop effective therapeutic approaches for the treatment of sepsis and other immune and inflammatory disorders. Indeed, significant advances in intensive care, such as lung protective mechanical ventilation, improved antibiotics, and superior monitoring of systemic perfusion, are improving patient survival. Nonetheless, specific strategies that target the pathophysiological disorders in sepsis patients are essential to further improve clinical outcomes. This article reviews current clinical management approaches and experimental interventions that target pleiotropic or late-acting inflammatory mediators like caspases, C5a, MIF, and HMGB1, or the body's endogenous inflammatory control mechanisms such as the cholinergic anti-inflammatory pathway. These inflammatory mediators and anti-inflammatory mechanisms, respectively, show significant potential for the development of new experimental therapies for the treatment of severe sepsis and other infectious and inflammatory disorders.

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Effectiveness of Modified Steroid-Antibiotic Therapies for Lethal Sepsis in the Dog

Cited by 23 publications

References 22 publications

Corticosteroids in Shock

Corticosteroids in Shock

Scientific and Clinical Challenges in Sepsis

Experimental Therapeutic Strategies for Severe Sepsis

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