Microcirculatory dysfunction plays a pivotal role in the pathogenesis of severe sepsis and septic shock; hence, microcirculation blood flow monitoring has gained increasing attention. However, microcirculatory imaging is still investigational in human sepsis and has not yet been incorporated into routine clinical practice for several reasons, including the difficult interpretation of microcirculation imaging data, difficulty to draw a parallel between sublingual microcirculation imaging and organ microcirculation dysfunction, as well as the absence of microvessel dysfunction parameters defining sequential microcirculatory changes from the early to late stages of the disease, which could aid in the context of therapeutic approaches and of prognostic parameters. The purpose of this review was to bridge the experimental abdominal organ microvascular derangement kinetics and clinical aspects of microcirculatory findings in the early phase of severe sepsis/septic shock.
BackgroundThe 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.
Sepsis causes long-term disability, such as immune dysfunction, neuropsychological disorders, persistent inflammation, catabolism, and immunosuppression, leading to a high risk of death in survivors, although the contributing factors of mortality are unknown. The purpose of this experimental study in rats was to examine renal (rSNA) and splanchnic (sSNA) sympathetic nerve activity, as well as baroreflex sensitivity, in acute and chronic post-sepsis periods. The rats were divided into two groups: control group with naïve Wistar rats and sepsis group with 2-mL intravenous inoculation of Escherichia coli at 108 CFU/mL. Basal mean arterial pressure, heart rate, rSNA, sSNA, and baroreflex sensitivity were evaluated in all groups at the acute (6 h) and chronic periods (1 and 3 months). Basal rSNA and sSNA were significantly reduced in the surviving rats, as was their baroreflex sensitivity, for both pressor and hypotensive responses, and this effect lasted for up to 3 months. A single episode of sepsis in rats was enough to induce long-term alterations in renal and splanchnic sympathetic vasomotor nerve activity, representing a possible systemic event that needs to be elucidated. These findings showed that post-sepsis impairment of sympathetic vasomotor response may be one of the critical components in the inability of sepsis survivors to respond effectively to new etiological illness factors, thereby increasing their risk of post-sepsis morbidity.
Atypical enteropathogenic Escherichia coli (aEPEC) inject various effectors into intestinal cells through a type three secretion system (T3SS), causing attaching and effacing (A/E) lesions. We investigated the role of T3SS in the ability of the aEPEC 1711-4 strain to interact with enterocytes in vitro (Caco-2 cells) and in vivo (rabbit ileal loops) and to translocate the rat intestinal mucosa in vivo . A T3SS isogenic mutant strain was constructed, which showed marked reduction in the ability to associate and invade but not to persist inside Caco-2 cells. After rabbit infection, only aEPEC 1711-4 was detected inside enterocytes at 8 and 24 hours pointing to a T3SS-dependent invasive potential in vivo . In contrast to aEPEC 1711-4, the T3SS-deficient strain no longer produced A/E lesions or induced macrophage infiltration. We also demonstrated that the ability of aEPEC 1711-4 to translocate through mesenteric lymph nodes to spleen and liver in a rat model depends on a functional T3SS, since a decreased number of T3SS mutant bacteria were recovered from extraintestinal sites. These findings indicate that the full virulence potential of aEPEC 1711-4 depends on a functional T3SS, which contributes to efficient adhesion/invasion in vitro and in vivo and to bacterial translocation to extraintestinal sites.
Although enteropathogenic Escherichia coli (EPEC) are well-recognized diarrheal agents, their ability to translocate and cause extraintestinal alterations is not known. We investigated whether a typical EPEC (tEPEC) and an atypical EPEC (aEPEC) strain translocate and cause microcirculation injury under conditions of intestinal bacterial overgrowth. Bacterial translocation (BT) was induced in female Wistar-EPM rats (200-250 g) by oroduodenal catheterization and inoculation of 10 mL 10(10) colony forming unit (CFU)/mL, with the bacteria being confined between the duodenum and ileum with ligatures. After 2 h, mesenteric lymph nodes (MLN), liver and spleen were cultured for translocated bacteria and BT-related microcirculation changes were monitored in mesenteric and abdominal organs by intravital microscopy and laser Doppler flow, respectively. tEPEC (N = 11) and aEPEC (N = 11) were recovered from MLN (100%), spleen (36.4 and 45.5%), and liver (45.5 and 72.7%) of the animals, respectively. Recovery of the positive control E. coli R-6 (N = 6) was 100% for all compartments. Bacteria were not recovered from extraintestinal sites of controls inoculated with non-pathogenic E. coli strains HB101 (N = 6) and HS (N = 10), or saline. Mesenteric microcirculation injuries were detected with both EPEC strains, but only aEPEC was similar to E. coli R-6 with regard to systemic tissue hypoperfusion. In conclusion, overgrowth of certain aEPEC strains may lead to BT and impairment of the microcirculation in systemic organs.
Sepsis is the result from a complex bacterial-host interaction, which is an often-fatal response when host protective molecular mechanisms designed to fight invading bacteria surpass the beneficial intensity to the point of causing injury to the host. Increasing evidences have implicated the bacterial translocation (BT) as the main source for the induction of sepsis, although the beneficial effect of BT process has been related to the development of the intestinal immune response by physiological interaction between bacteria and host. In this article, we examined evolving concepts concerning to BT and discussed about its potential role in the promotion of microcirculation injury, moreover, its possible participation in the sepsis induction. According to our data obtained from in-vivo BT animal-model, both bacterial overgrowth and bacterial pathogenic determinants seem to be major predisposing factors for the induction of BT. Besides, translocation of luminal bacteria through the lymphatic via elicits the activation of the GALT inflammatory response contributing to microcirculation injuries, and the haematological via of BT was responsible to the systemic bacterial spread. On other hand, the combination of BT process to the pre-existing host systemic infection played a crucial role in the worsening of the clinical outcome. In our understanding, studies concerning to intestinal immune response and the pathophysiology of bacterial-host interaction, under normal and disease conditions, seems to be the key elements to the development of therapeutic approaches towards sepsis.
BackgroundThe 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.