Severe sepsis and septic shock are among the most important causes of morbidity and mortality in patients admitted to the intensive care unit. The purpose of this review is to review current ...understanding of sepsis-induced cardiac dysfunction and discuss pertinent findings regarding its clinical presentation, underlying mechanisms of disease, and therapy.
Cardiac dysfunction in sepsis is characterized by decreased contractility, impaired ventricular response to fluid therapy, and in some patients ventricular dilatation. Current data support a complex underlying physiopathology with a host of potential pathways leading to myocardial depression. Circulating factors such as cytokines (TNF-alpha, IL-1beta), lysozyme c, endothelin-1 have direct inhibitory actions on myocyte contractility. Nitric oxide has a complex role in sepsis-induced cardiac dysfunction. Current data suggest a combination of deleterious and positive effects on the myocardium determined by the specific type of nitric oxide expressed. Recent studies have shown that mitochondrial dysfunction and apoptosis also play a role in the development of sepsis-induced cardiac dysfunction. Current treatment for sepsis-induced cardiac dysfunction is based on appropriate treatment for the infectious focus (antibiotics and source control) and hemodynamic support (fluids, vasopressors, and inotropes).
Cardiac dysfunction is common in patients with severe sepsis and septic shock. Current understanding of the underlying mechanisms responsible is rapidly evolving and future novel therapeutic targets may be soon available. Present therapy for sepsis-induced cardiac dysfunction is based on treatment of underlying sepsis with antibiotics and hemodynamic support.
Myocardial dysfunction in sepsis may be associated with changes in left ventricular (LV) size. The goal of this study was to evaluate the impact of myocardial dysfunction and changes in LV diameter ...on hemodynamics and survival in a murine model of sepsis.
C57Bl/6 mice (N = 30) were used. Septic mice (n = 24) had cecal ligation and puncture (CLP) followed by fluid and antibiotic resuscitation and control mice (n = 6) received sham ligation. Echocardiography with a 30-mHz probe was performed at baseline and at frequent predefined time points after CLP. Stroke volume (SV), cardiac output (CO), LV internal diameter in diastole (LVIDd), and fractional shortening (FS) were measured. LV dilation was prospectively defined as an increase in LVIDd ≥ 5% from baseline values. Septic animals were classified as dilators or nondilators.
Among septic animals, 37% were dilators and 63% were nondilators. After CLP, SV and CO decreased early in both groups. With resuscitation, SV and CO improved to a greater extent in dilators than nondilators (for SV, 46.0 ± 8.2 vs 36.1 ± 12.7 μL at 24 h, P = .05; for CO, 20.4 ± 4.8 vs 14.8 ± 6.7 mL/min, P = .04). Survival at 72 h was significantly improved in dilators compared with nondilators (88% vs 40%, P = .01).
In a clinically relevant murine model of sepsis, animals with LV dilation had better cardiovascular performance and increased survival. Our results suggest that LV dilation is associated with improved SV and CO, a pattern resulting in greatly improved survival. These studies highlight the importance of diastolic function in septic shock.
Animal models of sepsis Zanotti-Cavazzoni, Sergio L; Goldfarb, Roy D
Critical care clinics,
10/2009, Letnik:
25, Številka:
4
Journal Article
Recenzirano
In this review, we start with a general discussion of relevant factors that can determine the validity of a sepsis animal model. We briefly review some of the currently used animal models of sepsis ...(small animal models and large animal models). We discuss the clinical relevance of animal models in sepsis research today and address potential reasons for the apparent underperformance of animal models in predicting therapeutic success of novel drugs in clinical trials.
Sepsis is associated with cardiovascular changes that may lead to development of tissue hypoperfusion. Early recognition of sepsis and tissue hypoperfusion is critical to implement appropriate ...hemodynamic support and prevent irreversible organ damage. End points for resuscitation need to be defined and invasive hemodynamic monitoring is usually required. Targets for hemodynamic optimization should include intravascular volume, blood pressure, and cardiac output. Therapeutic interventions aimed at optimizing hemodynamics in patients with sepsis include aggressive fluid resuscitation, the use of vasopressor agents, inotropic agents and in selected cases transfusions of blood products. This review will cover the most important aspects of hemodynamic optimization for treatment of sepsis induced tissue-hypoperfusion.
Rationale
Current murine models of sepsis do not account for the effects of aggressive fluid resuscitation on hemodynamics and mortality.
Objectives
Evaluate the impact of fluid resuscitation ...regimens on cardiovascular performance and survival in a murine model of sepsis.
Methods
Mice (
n
= 90) were made septic by cecal ligation and puncture (CLP), and received antibiotics plus Low, Intermediate
,
or High fluid resuscitation regimens. Stroke volume (SV), cardiac output (CO), and fractional shortening (FS) were measured by echocardiography at predefined time points.
Measurements and main results
Baseline echocardiographic measurements were similar in all groups. After CLP, SV and CO decreased early in all groups; High: 57.2 ± 9.2 to 23.9 ± 7.2 µL, and 26.8 ± 4.9 to 13.1 ± 5.8 ml/min; Intermediate: 52.1 ± 7.0 to 21.5 ± 6.6 µL, and 24.9 ± 4.1 to 11.9 ± 3.9 ml/min; Low: 54.0 ± 7.0 to 20.3 ± 5.6 µL, and 25.8 ± 4.0 to 11.3 ± 3.9 ml/min (
P
< 0.05 for all vs. baseline). With resuscitation there was a dose-dependent improvement in SV and CO (
P
< 0.05). At 24 h SV and CO were 44.0 ± 13.8 µL and 20.7 ± 8.5 ml/min in the High group, 39.8 ± 12.3 µL and 16.7 ± 6.5 ml/min in the Intermediate group, and 30.1 ± 12.4 µL and 14.0 ± 7.2 ml/min in the Low group. Survival was improved in the High fluid group (75%) compared to the Intermediate (58%) and the Low (35%) resuscitation groups (
P
< 0.05).
Conclusions
In this model, as in human sepsis, the intensity of fluid resuscitation modulates hemodynamic response and mortality. Incorporation of early and aggressive fluid resuscitation can significantly enhances the clinical relevance of murine models of sepsis.
Bone cement implantation syndrome (BCIS) is a rare but potentially fatal intraoperative complication that occurs in patients undergoing cemented orthopedic surgeries. Lack of a robust definition of ...the syndrome due to rarity of the condition has probably contributed to under reporting of cases. We report a case of a 72-year-old woman hospitalized for an elective orthopedic procedure with a postoperative course complicated by BCIS requiring supportive care in the intensive care unit setting.
Angioedema is a rare but life-threatening adverse effect of administration of angiotensin-converting enzyme inhibitors (ACEIs) administration. It has been classically associated with ACEIs, although ...angioedema has also been reported with angiotensin receptor blockers (ARBs). Angioedema is a deep swelling of tissues just below the skin and mucous membranes, characterized by non-pitting asymmetric swelling that is usually non-pruritic. ARBs may cause an increase in plasma angiotensin II levels, which may lead to a negative feedback inhibition of ACE activity, predisposing to angioedema development. We report a case of valsartan-induced angioedema that occurred in a patient who was on ACEIs for years, with no incidence of angioedema.
Drug-induced lupus erythematosus differs in its manifestation from drug-induced vasculitis. The former is associated with characteristic symptoms that improve following discontinuation, whereas the ...latter is predominantly an antineutrophil cytoplasmic antibody (ANCA) positive small vessel vasculitis involving the kidneys, skin, and lungs. We present a case of advanced disease in an elderly Caucasian woman requiring corticosteroids, and immunosuppressive therapy, who was on hydralazine for >2 years.
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