Blocking central leukotrienes synthesis affects vasopressin release during sepsis

Abstract

Background The morbidity and mortality from severe sepsis depends largely on how quickly and comprehensively evidencebased therapies are administered. As such, a huge opportunity exists. However, optimal care requires not only factual knowledge, but also numerous practical strategies including the ability to recognize a disease, to identify impending crises, to communicate effectively, to run a team, to work under stress and to simultaneously coordinate multiple tasks. Medical simulation offers a way to practice these essential crisis management skills, and without any risk to patients. Methods Following a didactic lecture on the key components of the Surviving Sepsis Campaign Guidelines, we trained 20 emergency medicine residents on a portable Laerdal Patient Simulator. Pre-programmed sepsis scenarios were developed following a needs assessment and modified Delphi technique. To maximize realism, this was performed in the acute care area of the Emergency Department and included a pre-briefed respiratory therapist and nurse. We videotaped resident performance and provided nonpunitive feedback, focusing on the comprehensiveness of therapy (for example, whether broad-spectrum antibiotics were given) and crisis resource management strategies (for example, whether help was asked for and tasks were appropriately allocated). Results Evaluation using a five-point Likert scale demonstrated that participants found this very useful (4.5/5), that lessons were complementary and supplementary to those learned from lectures (4.5/5) and that medical simulation was realistic (4/5). In addition, despite prior sepsis lectures, comparison of pre-tests and posttests showed that more emergency medicine residents would: administer broad-spectrum antibiotics as soon as possible following hypotension (14/20 pre-test, compared with 16/20 posttest), administer low-dose corticosteroids for those with refractory shock (10/20 pre-test, compared with 13/20 post-test), and would favour norepinephrine as a vasopressor (8/20 pre-test, compared with 12/20 post-test). Participants specifically valued the chance to observe and practice crisis resource management skills, which they felt had not been previously addressed (19/20). Conclusion Medical simulation appears to be an effective way to change both knowledge and behaviours in the treatment of severe sepsis. Many education and licensing boards also expect trainees to become not only content experts, but also effective communicators, collaborators, resource managers and advocates. These laudable goals are difficult to capture with traditional lectures but are comparably easy using medical simulation. We hope others will consider medical simulation as a complementary teaching and quality-assurance strategy in the fight against sepsis. P2 Protective potential of 2-chloroadenosine in Klebsiella pneumoniae B5055 induced sepsis in BALB/c mice

Interleukin-1 Receptor Antagonist Decreases Hypothalamic Oxidative Stress During Experimental Sepsis

“…AVP secretion during sepsis can be separated into two distinct phases [1][2][3]. In the initial phase, AVP secretion is increased in response to the drop in blood pressure, representing a normal endocrine response pattern, but in the late phase, its secretion is inappropriately low regardless of progressive, life-threatening hypotension [1][2][3][4][5][6][7].…”

Vasopressin Synthesis by the Magnocellular Neurons is Different in the Supraoptic Nucleus and in the Paraventricular Nucleus in Human and Experimental Septic Shock

“…Endotoxin injection, and cecal ligation and puncture have been shown to rapidly increase plasma AVP levels by activating magnocellular neurons of paraventricular (18,31) and supraoptic nuclei (13,18). Conversely, it has been experimentally evidenced that relative AVP deficiency is present at 24 h (4,11). It would be of interest to determine whether this phenomenon persists beyond the 24 h of experimental sepsis, as it is during the post-acute phase that relative AVP deficiency occurs in septic patients.…”

Leukotriene synthesis inhibitor decreases vasopressin release in the early phase of sepsis

“…Additionally we asked whether this modulation could be through NO production because the LTs seem to affect the production of this mediator (Wilson et al, 2001;Knigge et al, 2003;Won et al, 2005). During the initial phase of sepsis, CLP produced a significant increase in plasma AVP levels at 4 h, which returned to basal ones at 24 h, as shown in previous studies (Pancoto et al, 2008;Athayde et al, 2009). Intraperitoneal injection of MK-886, a LTs synthesis inhibitor, attenuated or prevented this increase in a dose-dependent manner.…”

“…The central administration of an inhibitor of leukotriene synthesis in rat abolished the secretion of AVP in the initial phase of the sepsis. Furthermore, its injection improved survival and attenuated the increase of LTC 4 enzyme in the hypothalamus and of serum nitrate levels seen during sepsis (Athayde et al, 2009). As already shown, NOS inhibitor may also affect vasopressin secretion during sepsis, though the results depend on the route of inhibitor administration (Carnio et al, 2006;Corrêa et al, 2007).…”

“…Severe sepsis was induced by CLP, as previously described (Corrêa et al, 2007;Pancoto et al, 2008;Athayde et al, 2009;Oliveira-Pelegrin et al, 2009). Briefly, rats were anesthetized with 2, 2, 2-tribromoethanol (Acros Organics, Geel, Belgium, 250 mg/kg i.p.).…”