Sequential physiologic interactions in pediatric cardiogenic and septic shock

We report that the pediatric cardiogenic shock and septic shock populations show similar hemodynamic and oxygen utilization physiologic relationships during aggressive intensive care therapy. We examined the mathematical relationships between vascular tone and flow, and oxygen utilization and oxygen delivery (DO2) in the early and middle stages of cardiogenic and septic shock. The fitted curves between cardiac index and systemic vascular resistance, and oxygen consumption (VO2) and DO2 were clinically and statistically similar in both shock populations. We found no evidence for decreased oxygen extraction in sepsis as compared to the cardiogenic shock population. In addition, it appears that the major determinant of VO2 in these populations is DO2, not oxygen extraction. We suggest that patients with cardiogenic or septic shock can be treated according to similar physiologic principles.     

Sequential cardiopulmonary variables of infants and children in septic shock

Sequential cardiopulmonary variables were analyzed in 32 infants and children with septic shock. Variables were staged by a system based on therapeutic efforts to control blood pressure. There were 14 survivors and 18 nonsurvivors. Systemic circulation variables (MAP, cardiac index [CI], systemic vascular resistance index [SVRI], wedge pressure [WP], left cardiac work index [LCWI]) and pulmonary circulation variables (mean pulmonary artery pressure [MPAP], pulmonary vascular resistance index [PVRI], CVP, right cardiac work index [RCWI]) were similar in survivors and nonsurvivors. Pulmonary variables (intrapulmonary shunt [Qsp/Qt], fraction of inspired oxygen [FIO2], Pao2, PaCO2) revealed significantly more dysfunction in nonsurvivors than survivors during the postresuscitation (PR) and middle (M) shock stages. Even though oxygen delivery was equivalent in survivors and nonsurvivors, nonsurvivors demonstrated decreased oxygen utilization variables (oxygen consumption [Vo2], arteriovenous oxygen content difference [C(a-v)O2], O2 extraction index, core temperature) during the resuscitation (RS) and PR stages.     

Naloxone in septic shock

Treatment of septic shock is a persistent dilemma. The clinical use of agents such as naloxone has resulted in variable success. Because the dosage and timing of these agents are considered critical factors in their efficacy, we investigated both dosage and timing of naloxone. Thirteen consecutive patients with documented septic shock and resistance to a one-liter fluid challenge underwent invasive hemodynamic monitoring and the administration of naloxone by initial bolus of 0.03 mg/kg followed by infusion at a rate of 0.2 mg/kg.h over one hour. During the one-hour observation period, iv fluid administration, concomitant pressor agents, and respirator values were constant. After infusion, adjustments in fluid administration, respirator status, and pressor agents were made as required by the clinical situation. A significant increase in mean arterial pressure (MAP) over baseline (60 +/- 3 mm Hg) was noted at 5 min (77 +/- 6 mm Hg, p less than .005) and at 30 min (73 +/- 6 mm Hg, p less than .025). Similarly, a significant increase in systolic arterial pressure was noted over prenaloxone levels (89 +/- 3 mm Hg) at 5 min (114 +/- 6 mm Hg, p less than .001), 30 min (107 +/- 8 mm Hg, p less than .05), and at one hour (106 +/- 8 mm Hg, p less than .05). There was a moderate nonsignificant increase in cardiac index, pulmonary capillary wedge pressure, and systemic vascular resistance. No side-effects to naloxone were noted in our group. No effect on survival could be demonstrated. We found no overall effect on mortality. However, by its increase of MAP, naloxone may serve as a temporizing agent during the treatment of critically ill patients with septic shock.     

Surface triggering receptor expressed on myeloid cells 1 expression patterns in septic shock

Objective To analyze the pattern of cell-surface expression of the triggering receptor expressed on myeloid cells (TREM) 1 during septic shock.Design and setting Prospective clinical study in an adult 16-bed medical ICU.Patients and methods 25 septic shock patients, 15 patients with shock of noninfectious origin and 7 healthy volunteers. Arterial blood was drawn within 12 h of admission and subjected to flow cytometry analysis after staining with anti-TREM-1 and anti-CD14 antibodies. Repeated sampling was performed on days 2, 3, 5, 7, and 14 in septic shock patients.Results Monocytic TREM-1 expression was significantly higher in septic shock patients (mean fluorescence intensity 2.3±0.2) than in nonseptic patients (1.0±0.1), and healthy volunteers (1.0±0.1). There was no difference in monocytic TREM-1 expression between nonseptic patients and healthy volunteers or between any of the three groups with respect to TREM-1 expression on neutrophils. The time course of TREM-1 expression on monocytes diverged significantly by day 3 between survivors and ns.Conclusions The specificity of TREM-1 regulation by infection is highlighted. Moreover, surface TREM-1 expression on monocytes may prove useful in allowing the follow-up of septic patients during the course of the diseaseElectronic Supplementary Material Electronic supplementary material to this paper can be obtained by using the Springer Link server located at .     

Angiotensin II in septic shock

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2015 and co-published as a series in Critical Care. Other articles in the series can be found online at http://ccforum.com/series/annualupdate2015. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.     

Angiotensin II in septic shock

Septic shock is a life threatening condition and a medical emergency. It is associated with organ dysfunction and hypotension despite optimal volume resuscitation. Refractory septic shock carries a very high rate of mortality and is associated with ischemic and arrhythmogenic complications from high dose vasopressors. Angiotensin II (AT-II) is a product of the renin-angiotensin-aldosterone system. It is a vasopressor agent that has been recently approved by FDA to be used in conjunction with other vasopressors (catecholamines) in refractory shock and to reduce catecholamine requirements. We have reviewed the physiology and current literature on AT-II in refractory septic/vasodilatory shock. Larger trials with longer duration of follow-up are warranted to address the questions which are unanswered by the ATHOS-3 trial, especially pertaining to its effects on lungs, brain, microcirculation, inflammation, and venous thromboembolism risk.     

Myocardial dysfunction in septic shock

Over the last decade, it has become clear that myocardial depression, like vascular dysfunction, is typical of human septic shock. Human septic myocardial depression is characterized by reversible biventricular dilatation, decreased ejection fraction, and decreased response to fluid resuscitation and catecholamine stimulation (in the presence of overall hyperdynamic circulation). A circulating myocardial depressant substance, not myocardial hypoperfusion, is responsible for this phenomenon. This substance has been shown to represent low concentrations of TNF-alpha and IL-1 beta acting in synergy on the myocardium through mechanisms that include NO and cGMP generation. Despite major advances in our understanding of the hemodynamics and pathogenesis of cardiac dysfunction in sepsis, successful attempts to modulate these mechanisms to improve clinical outcomes in human trials have not been demonstrated to date. For the moment, the therapeutic approach to the patient with cardiac dysfunction in distributive or septic shock must be primarily aimed at reestablishing adequate organ perfusion and oxygen delivery by vigorous fluid resuscitation and vasopressor or inotropic support. In the long term, however, only continued research regarding the cellular mechanisms of organ dysfunction, including septic myocardial depression, will lead to successful therapeutic strategies. These strategies will likely involve direct manipulation of intracellular signaling processes that lead to organ dysfunction as manifested by septic myocardial dysfunction and septic shock.     

Coagulation disorders in septic shock

Abnormalities in coagulation and fibrinolysis are frequently observed in septic shock. The most pronounced clinical manifestation is disseminated intravascular coagulation. Recent studies in human volunteers and animal models have clarified the early dynamics and route of activation of both coagulation and fibrinolytic pathways. In healthy subjects subjected to a low dose of either endotoxin or TNF an imbalance in the procoagulant and the fibrinolytic mechanisms is apparent, resulting in a procoagulant state. Also in patients with septic shock a dynamic process of coagulation and fibrinolysis is ongoing with evidence of impaired fibrinolysis. These abnormalities have prognostic significance; the extent of disturbances of coagulation and fibrinolysis is related to the development of multiple organ failure and death.