Adriano José Pereira

Impact of Plasma-Lyte pH 7.4 on acid-base status and hemodynamics in a model of controlled hemorrhagic shock

OBJECTIVE: Intravenous infusion of crystalloid solutions is a cornerstone of the treatment of hemorrhagic shock. However, crystalloid solutions can have variable metabolic acid-base effects, perpetuating or even aggravating shock-induced metabolic acidosis. The aim of this study was to compare, in a controlled volume–driven porcine model of hemorrhagic shock, the effects of three different crystalloid solutions on the hemodynamics and acid-base balance. METHODS: Controlled hemorrhagic shock (40% of the total blood volume was removed) was induced in 18 animals, which were then treated with normal saline (0.9% NaCl), Lactated Ringers Solution or Plasma-Lyte pH 7.4, in a blinded fashion (n = 6 for each group). Using a predefined protocol, the animals received three times the volume of blood removed. RESULTS: The three different crystalloid infusions were equally capable of reversing the hemorrhage-induced low cardiac output and anuria. The Lactated Ringers Solution and Plasma-Lyte pH 7.4 infusions resulted in an increased standard base excess and a decreased serum chloride level, whereas treatment with normal saline resulted in a decreased standard base excess and an increased serum chloride level. The Plasma-Lyte pH 7.4 infusions did not change the level of the unmeasured anions. CONCLUSION: Although the three tested crystalloid solutions were equally able to attenuate the hemodynamic and tissue perfusion disturbances, only the normal saline induced hyperchloremia and metabolic acidosis.

Angiotensin Ii in Septic Shock: Effects on Tissue Perfusion, Organ Function, and Mitochondrial Respiration in a Porcine Model of Fecal Peritonitis*

Objectives:To compare effects of norepinephrine and angiotensin II in experimental sepsis on hemodynamics, organ function, and mitochondrial respiration. Design:Randomized, controlled, study. Setting:University experimental laboratory. Subjects:Twenty-eight anesthetized, mechanically ventilated pigs. Interventions:Sixteen pigs were randomized to receive after 12 hours of fecal peritonitis fluid resuscitation and either norepinephrine (group NE; n = 8) or angiotensin II (group AT-II; n = 8) for 48 hours. A separate group (n = 8), treated with enalapril for 1 week before peritonitis and until study end, received fluids and norepinephrine (group E). The blood pressure dose-response to angiotensin II was evaluated in additional four nonseptic pigs. Measurements and Main Results:Blood pressure target (75–85 mm Hg) was reached in both NE and AT-II, and cardiac output increased similarly (NE: from 64 mL/kg/min [60–79 mL/kg/min] to 139 mL/kg/min [126–157 mL/kg/min]; AT-II from 79 mL/kg/min [65–86 mL/kg/min] to 145 mL/kg/min [126–147 mL/kg/min]; median, interquartile range). Renal plasma flow, prevalence of acute kidney injury, inflammation and coagulation patterns, and mitochondrial respiration did not differ between NE and AT-II. In group E, blood pressure targets were not achieved (mean arterial pressure at study end: NE: 81 mm Hg [76–85 mm Hg]; AT-II: 80 mm Hg [77–84 mm Hg]; E: 53 mm Hg [49–66 mm Hg], p = 0.002, compared to NE), whereas skeletal muscle adenosine triphosphate concentrations were increased. During resuscitation one animal died in groups AT-II and E. Conclusions:Angiotensin II reversed sepsis-induced hypotension with systemic and regional hemodynamic effects similar to those of norepinephrine. Inhibition of angiotensin-converting enzyme before sepsis worsened the hypotension but enhanced skeletal muscle adenosine triphosphate. Modifying the renin-angiotensin system in sepsis should be further evaluated.

Quality Improvement Initiatives in Sepsis in an Emerging Country: Does the Institution’s Main Source of Income Influence the Results? An Analysis of 21,103 Patients

Objective: We aimed to assess the results of a quality improvement initiative in sepsis in an emerging setting and to analyze it according to the institutions’ main source of income (public or private). Design: Retrospective analysis of the Latin American Sepsis Institute database from 2005 to 2014. Settings: Brazilian public and private institutions. Patients: Patients with sepsis admitted in the participant institutions. Interventions: The quality improvement initiative was based on a multifaceted intervention. The institutions were instructed to collect data on 6-hour bundle compliance and outcomes in patients with sepsis in all hospital settings. Outcomes and compliance was measured for eight periods of 6 months each, starting at the time of the enrollment in the intervention. The primary outcomes were hospital mortality and compliance with 6-hour bundle. Measurements and Main Results: We included 21,103 patients; 9,032 from public institutions and 12,071 from private institutions. Comparing the first period with the eigth period, compliance with the 6-hour bundle increased from 13.5% to 58.2% in the private institutions (p < 0.0001) and from 7.4% to 15.7% in the public institutions (p < 0.0001). Mortality rates significantly decreased throughout the program in private institutions, from 47.6% to 27.2% in the eighth period (adjusted odds ratio, 0.45; 95% CI, 0.32–0.64). However, in the public hospitals, mortality diminished significantly only in the first two periods. Conclusion: This quality improvement initiative in sepsis in an emerging country was associated with a reduction in mortality and with improved compliance with quality indicators. However, this reduction was sustained only in private institutions.

Interference of angiotensin II and enalapril with hepatic blood flow regulation

Acute reduction of portal vein blood flow (Qpv) increases hepatic arterial perfusion (Qha) [the hepatic arterial buffer response (HABR)]. Angiotensin II (AT-II) reduces Qpv, but its effect on HABR is not known. We explored interactions of AT-II and enalapril with hepatic blood flow regulation. Twenty healthy anesthetized pigs were randomized to receive AT-II (n = 8) from 5 to 61 ng/kg per min, enalapril (n = 8) from 3 to 24 μg/kg per h, or saline (n = 4). HABR was assessed by occluding portal vein and expressed as 1) ratio between changes in Qha and Qpv, 2) hepatic arterial conductance (Cha). AT-II infusion increased mean arterial blood pressure from 74 (66-77) mmHg to 116 (109-130) mmHg (median, IQR; P < 0.0001) and decreased cardiac output, Qpv, and renal artery flow (-24%, -28% and -45%, respectively). The fraction of cardiac output of Qha, carotid, and femoral flows increased. With enalapril, blood pressure decreased, whereas cardiac output was maintained with flow redistribution favoring hepatic and renal arteries. In AT-II group, dQha/dQpv increased from 0.06 (0.03, 0.17) to 0.24 (0.13, 0.31) (P = 0.002), but Cha during acute portal vein occlusion decreased from 4.3 (1.6, 6.6) to 2.9 (1.2, 3.7) ml/mmHg (P = 0.003). Both variables remained unchanged in the enalapril group and in controls. AT-II infusion reduces portal flow in parallel with cardiac output and induces a dose-dependent redistribution of flow, favoring brain, hepatic artery, and peripheral tissues at the expense of renal perfusion. During HABR, AT-II decreases Cha but increases Qha compensation, likely as result of increased hepatic arterial perfusion pressure. Enalapril had no effect on HABR.

Current concepts on hemodynamic support and therapy in septic shock

Severe sepsis and septic shock represent a major healthcare challenge. Much of the improvement in mortality associated with septic shock is related to early recognition combined with timely fluid resuscitation and adequate antibiotics administration. The main goals of septic shock resuscitation include intravascular replenishment, maintenance of adequate perfusion pressure and oxygen delivery to tissues. To achieve those goals, fluid responsiveness evaluation and complementary interventions - i.e. vasopressors, inotropes and blood transfusion - may be necessary. This article is a literature review of the available evidence on the initial hemodynamic support of the septic shock patients presenting to the emergency room or to the intensive care unit and the main interventions available to reach those targets, focusing on fluid and vasopressor therapy, blood transfusion and inotrope administration.

Conceitos atuais sobre suporte hemodinâmico e terapia em choque séptico

Severe sepsis and septic shock represent a major healthcare challenge. Much of the improvement in mortality associated with septic shock is related to early recognition combined with timely fluid resuscitation and adequate antibiotics administration. The main goals of septic shock resuscitation include intravascular replenishment, maintenance of adequate perfusion pressure and oxygen delivery to tissues. To achieve those goals, fluid responsiveness evaluation and complementary interventions - i.e. vasopressors, inotropes and blood transfusion - may be necessary. This article is a literature review of the available evidence on the initial hemodynamic support of the septic shock patients presenting to the emergency room or to the intensive care unit and the main interventions available to reach those targets, focusing on fluid and vasopressor therapy, blood transfusion and inotrope administration.

Mitochondrial function of immune cells in septic shock: A prospective observational cohort study

Background Reduced cellular ATP synthesis due to impaired mitochondrial function of immune cells may be a factor influencing the immune response in septic shock. We investigate changes in mitochondrial function and bioenergetics of human monocytes and lymphocyte subsets. Methods Thirty patients with septic shock were studied at ICU admission, after 24 and 48 hours, and after resolution of shock. Enzymatic activities of citrate synthase and mitochondrial complexes I, IV, and ATP synthase and ATP content of monocytes, T-cells and B-cells and pro-inflammatory (IL-1β and IL-6) and anti-inflammatory (IL-10) cytokine plasma concentrations were compared to samples from 20 healthy volunteers. Results Large variations in mitochondrial enzymatic activities of immune cells of septic patients were detected. In monocytes, maximum levels of citrate synthase activity in sepsis were significantly lower when compared to controls (p = 0.021). Maximum relative enzymatic activity (ratio relative to citrate synthase activity) of complex I (p<0.001), complex IV (p = 0.017) and ATP synthase (p<0.001) were significantly higher. In T-cells, maximum levels of citrate synthase (p = 0.583) and relative complex IV (p = 0.602) activity did not differ between patients and controls, whereas levels of relative complex I (p = 0.006) and ATP synthase (p = 0.032) were significantly higher in septic patients. In B-cells of patients, maximum levels of citrate synthase activity (p = 0.004) and relative complex I (p<0.001) were significantly higher, and mean levels of relative complex IV (p = 0.042) lower than the control values, whereas relative ATP synthase activity did not differ (p = 1.0). No significant difference in cellular ATP content was detected in any cell line (p = 0.142–0.519). No significant correlations between specific cytokines and parameters of mitochondrial enzymatic activities or ATP content were observed. Conclusions Significant changes of mitochondrial enzymatic activities occur in human peripheral blood immune cells in septic shock when compared to healthy controls. Assessed sub-types of immune cells showed differing patterns of regulation. Total ATP-content of human immune cells did not differ between patients in septic shock and healthy volunteers.

Central venous catheterization: a randomized comparison between external and internal jugular access

Central venous catheterization is a routine procedure in intensive care, and internal jugular access (IJA) is often used due to its high success rates. However, complications can happen in up to 4.2% of internal jugular punctures and it is contraindicated in the presence of coagulopathy. The external jugular access (EJA) is underused, has low complications rates and is successful in up to 90% of cases. So far, there has been no randomized, controlled trial comparing both accesses. The objective of this study was to determine the success and early complication rates of internal and external jugular vein access [1].

Tissue Response to Different Hypoxic Injuries and Its Clinical Relevance

Classical understanding about tissue hypoxia has evolved over time from a simple lack of oxygen to a complex net of effects involving hemodynamic and metabolic factors, endocrine and neural stimuli, inflammation, and complex molecular pathways. Hypoxia-inducible factor (HIF) discovery opened a new chapter in hypoxia understanding, due to its pleiotropic and ubiquitous interactions, physiologically or during diseases. Global responses to specific hypoxic insults are described in literature, but tissue-specific responses were usually studied on a restricted number of organs, or in mixed models, from which not always the impact of each hypoxic injury can be isolated. Different insults seem to elicit different effects on tissues, and tolerance may be not the same. New concepts are rapidly emerging from this field as permissive hypoxia, VO2 manipulation, obesity paradox, and adipose tissue hypoxia, and such insights should serve as driving forces for advances in mechanistic research and the search for new therapeutic targets in critical illness in the near future.

Value-Based Health Care in a Public Hospital in Brazil

Healthcare associated costs are growing. For instance, in developed countries as in United States, they may reach sums that encompass 17% of the GDP. In Brazil, total healthcare costs comprise 9% of the GDP, with around half of that related to the public system