Luciano Cesar Pontes Azevedo

C-Reactive Protein/Albumin Ratio Predicts 90-Day Mortality of Septic Patients

Introduction Residual inflammation at ICU discharge may have impact upon long-term mortality. However, the significance of ongoing inflammation on mortality after ICU discharge is poorly described. C-reactive protein (CRP) and albumin are measured frequently in the ICU and exhibit opposing patterns during inflammation. Since infection is a potent trigger of inflammation, we hypothesized that CRP levels at discharge would correlate with long-term mortality in septic patients and that the CRP/albumin ratio would be a better marker of prognosis than CRP alone. Methods We evaluated 334 patients admitted to the ICU as a result of severe sepsis or septic shock who were discharged alive after a minimum of 72 hours in the ICU. We evaluated the performance of both CRP and CRP/albumin to predict mortality at 90 days after ICU discharge. Two multivariate logistic models were generated based on measurements at discharge: one model included CRP (Model-CRP), and the other included the CRP/albumin ratio (Model-CRP/albumin). Results There were 229 (67%) and 111 (33%) patients with severe sepsis and septic shock, respectively. During the 90 days of follow-up, 73 (22%) patients died. CRP/albumin ratios at admission and at discharge were associated with a poor outcome and showed greater accuracy than CRP alone at these time points (p = 0.0455 and p = 0.0438, respectively). CRP levels and the CRP/albumin ratio were independent predictors of mortality at 90 days (Model-CRP: adjusted OR 2.34, 95% CI 1.14–4.83, p = 0.021; Model-CRP/albumin: adjusted OR 2.18, 95% CI 1.10–4.67, p = 0.035). Both models showed similar accuracy (p = 0.2483). However, Model-CRP was not calibrated. Conclusions Residual inflammation at ICU discharge assessed using the CRP/albumin ratio is an independent risk factor for mortality at 90 days in septic patients. The use of the CRP/albumin ratio as a long-term marker of prognosis provides more consistent results than standard CRP values alone.

Sepsis-associated encephalopathy: not just delirium

Sepsis is a major cause of mortality and morbidity in intensive care units. Organ dysfunction is triggered by inflammatory insults and tissue hypoperfusion. The brain plays a pivotal role in sepsis, acting as both a mediator of the immune response and a target for the pathologic process. The measurement of brain dysfunction is difficult because there are no specific biomarkers of neuronal injury, and bedside evaluation of cognitive performance is difficult in an intensive care unit. Although sepsis-associated encephalopathy was described decades ago, it has only recently been subjected to scientific scrutiny and is not yet completely understood. The pathophysiology of sepsis-associated encephalopathy involves direct cellular damage to the brain, mitochondrial and endothelial dysfunction and disturbances in neurotransmission. This review describes the most recent findings in the pathophysiology, diagnosis, and management of sepsis-associated encephalopathy and focuses on its many presentations.

Evolutive standard base excess and serum lactate level in severe sepsis and septic shock patients resuscitated with early goal-directed therapy: still outcome markers?

PURPOSE To compare the evolution of standard base excess and serum lactate level between surviving and non surviving patients with severe sepsis and septic shock resuscitated with early goal-directed therapy. METHODS This is a retrospective study in an intensive care unit of a university tertiary hospital where 65 consecutive severe sepsis and septic shock patients were observed without any intervention in the treatment by the authors of this report. RESULTS In our study, the mortality of severe sepsis and septic shock patients was 38%. The central venous oxygen saturation of both groups was above 70% after the resuscitative period, excluding the second day of the non survivors group (69.8%). After the second day, the central venous oxygen saturation was significantly higher in the survivors group (P < .001). Standard base excess was initially low in both groups, but from the second day on, the correction of standard base excess was significantly more successful and linear in the survivor group (P < .001). Lactate levels were similar during the evolution of both groups. CONCLUSIONS Although evolutive standard base excess and serum lactate level are still outcome markers in severe sepsis and septic shock patients resuscitated with early goal-directed therapy, other studies must be performed to clarify if hemodynamic interventions based on standard base excess and serum lactate level could be reliable to improve clinical outcomes in severe sepsis and septic shock patients.

Extracorporeal membrane oxygenation for severe respiratory failure in adult patients: A systematic review and meta-analysis of current evidence

BACKGROUND Extracorporeal membrane oxygenation (ECMO) for acute respiratory failure is still a matter of debate. METHODS We performed a structured search on Pubmed, EMBASE, Lilacs, and the Cochrane Library for randomized controlled trials and observational case-control studies with severity-paired patients, evaluating the use of ECMO on severe acute respiratory failure in adult patients. A random-effect model using DerSimonian and Laird method for variance estimator was performed to evaluate the effect of ECMO use on hospital mortality. Heterogeneity between studies was assessed with Cochrans Q statistic and Higgins I(2). RESULTS Three studies were included on the metanalysis, comprising 353 patients in the main analysis, in which 179 patients were ECMO supported. One study was a randomized controlled trial and two were observational studies with a propensity score matching. The most common reason for acute respiratory failure was influenza H1N1 pneumonia (45%) and pneumonia (33%). ECMO was not associated with a reduction in hospital mortality (OR = 0.71; CI 95% = 0.34 - 1.47; P = 0.358). If alternative severity-pairing method presented by the two observational studies was included, a total of 478 cases were included, in which 228 received ECMO support. In the former analysis, ECMO had a benefit on hospital mortality (OR = 0.52; CI 95% = 0.35 - 0.76; P < 0.001). CONCLUSION Extracorporeal membrane oxygenation benefit on hospital mortality is unclear. Results were sensitive to statistical analysis, and no definitive conclusion can be drawn from the available data. More studies are needed before the widespread use of ECMO can be recommended.

Hemodynamic And Perfusion End Points For Volemic Resuscitation In Sepsis

Sepsis is the systemic inflammatory response syndrome secondary to a local infection, and severe sepsis and septic shock are the more devastating scenarios of this disease. In the last decade, considerable achievements were obtained in sepsis knowledge, and an international campaign was developed to improve the treatment of this condition. However, sepsis is still one of the most important causes of death in intensive care units. The early stages of sepsis are characterized by a variety of hemodynamic derangements that induce a systemic imbalance between tissue oxygen supply and demand, leading to global tissue hypoxia. This dysfunction, which may occur in patients presenting normal vital signs, can be accompanied by a significant increase in both morbidity and mortality. The early identification of high-risk sepsis patients through tissue perfusion markers such as lactate and venous oxygen saturation is crucial for prompt initiation of therapeutic support, which includes early goal-directed therapy as necessary. The purpose of this article was to review the most commonly used hemodynamic and perfusion parameters for hemodynamic optimization in sepsis, emphasizing the physiological background for their use and the studies that demonstrated their effectiveness as goals of volemic resuscitation.

The use of sodium-chloride difference and chloride-sodium ratio as strong ion difference surrogates in the evaluation of metabolic acidosis in critically ill patients

PURPOSE Inorganic apparent strong ion difference (SIDai) improves chloride-associated acidosis recognition in dysnatremic patients. We investigated whether the difference between sodium and chloride (Na(+)-Cl(-)) or the ratio between chloride and sodium (Cl(-)/Na(+)) could be used as SIDai surrogates in mixed and dysnatremic patients. PATIENTS AND METHODS Two arterial blood samples were collected from 128 patients. Physicochemical analytical approach was used. Correlation, agreement, accuracy, sensitivity, and specificity were measured to examine whether Na(+)-Cl(-) and Cl(-)/Na(+) could be used instead of SIDai in the diagnosis of acidosis. RESULTS Na(+)-Cl(-) and Cl(-)/Na(+) were well correlated with SIDai (R = 0.987, P < 0.001 and R = 0.959, P < 0.001, respectively). Bias between Na(+)-Cl(-) and SIDai was high (6.384 with a limit of agreement of 4.463-8.305 mEq/L). Accuracy values for the identification of SIDai acidosis (<38.9 mEq/L) were 0.989 (95% confidence interval [CI], 0.980-0.998) for Na(+)-Cl(-) and 0.974 (95% CI, 0.959-0.989) for Cl(-)/Na(+). Receiver operator characteristic curve showed that values revealing SIDai acidosis were less than 32.5 mEq/L for Na(+)-Cl(-) and more than 0.764 for Cl(-)/Na(+) with sensitivities of 94.0% and 92.0% and specificities of 97.0% and 90.0%, respectively. Na(+)-Cl(-) was a reliable SIDai surrogate in dysnatremic patients. CONCLUSIONS Na(+)-Cl(-) and Cl(-)/Na(+) are good tools to disclose SIDai acidosis. In patients with dysnatremia, Na(+)-Cl(-) is an accurate tool to diagnose SIDai acidosis.

Characterization of an animal model of severe sepsis associated with respiratory dysfunction

PURPOSE Pathophysiological studies in humans regarding sepsis are difficult to perform due to ethical and methodological concerns. In this context, animal models of sepsis can be useful to better understand this condition and to test therapeutic strategies. The purpose of this study was to characterize a feasible and clinically relevant model of sepsis in pigs that could be useful for testing different therapeutic interventions. METHODS 5 White Large pigs were anesthetized, arterial and pulmonary catheters were introduced, and sepsis was induced by fecal peritonitis. Several biochemical indicators of organ dysfunction and infectious parameters were measured. The pigs were monitored until death, when fragments of organs were removed for pathology. Three animals without peritonitis served as controls and were sacrificed 24 hours after surgery without developing significant changes in organ function. RESULTS Septic pigs survived 17 hours on average (range, 16-18 h), and Escherichia coli was recovered from blood cultures. They developed a significant decrease in left ventricular work and a nonsignificant reduction in mixed venous oxygen saturation. Respiratory dysfunction was characterized by a decrease in the PaO2/FiO2 ratio and respiratory compliance. Pathology of the lungs revealed areas of pulmonary collapse, hemorrhage, pulmonary congestion, and discrete neutrophil infiltrate. CONCLUSIONS Fecal peritonitis in pigs is a clinically relevant model of sepsis associated with acute lung injury without direct pulmonary insult. This model may prove to be useful for studying pathogenic aspects of secondary lung injury as well as for validating ventilatory or pharmacologic interventions.

Bacterial Meningitis in Brazil: Baseline Epidemiologic Assessment of the Decade Prior to the Introduction of Pneumococcal and Meningococcal Vaccines

Background Bacterial meningitis is associated with significant burden in Brazil. In 2010, both 10-valent pneumococcal conjugate vaccine and meningococcal capsular group C conjugate vaccine were introduced into the routine vaccination schedule. Haemophilus influenzae type b vaccine was previously introduced in 1999. This study presents trends in demographics, microbiological characteristics and seasonality patterns of bacterial meningitis cases in Brazil from 2000 to 2010. Methods and Findings All meningitis cases confirmed by clinical and/or laboratory criteria notified to the national information system for notifiable diseases between 2000 and 2010 were analyzed. Proportions of bacterial meningitis cases by demographic characteristics, criteria used for confirmation and etiology were calculated. We estimated disease rates per 100,000 population and trends for the study period, with emphasis on H. influenzae, N. meningitidis and S. pneumoniae cases. In the decade, 341,805 cases of meningitis were notified in Brazil. Of the 251,853 cases with defined etiology, 110,264 (43.8%) were due to bacterial meningitis (excluding tuberculosis). Of these, 34,997 (31.7%) were due to meningococcal disease. The incidence of bacterial meningitis significantly decreased from 3.1/100,000 population in 2000–2002 to 2.14/100,000 in 2009–2010 (p<0.01). Among cases of meningococcal disease, the proportion of those associated with group C increased from 41% in 2007 to 61.7% in 2010, while the proportion of group B disease progressively declined. Throughout the study period, an increased number of cases occurred during winter. Conclusions Despite the reduction in bacterial meningitis incidence during the last decade, it remains a significant healthcare issue in Brazil. Meningococcal disease is responsible for the majority of the cases with group C the most common capsular type. Our study demonstrates the appropriateness of introduction of meningococcal vaccination in Brazil. Furthermore, this study provides a baseline for future evaluation of the impact of the vaccines introduction in Brazil and changes in disease epidemiology.

Novel potential therapies for septic shock.

Sepsis is the systemic inflammatory response syndrome secondary to a local infection. Septic shock, the severe complication of sepsis associated with refractory hypotension, is frequently a near-fatal condition requiring prompt diagnosis and management. Although the recent years have been associated with considerable improvements in the knowledge of the pathophysiology of the disease and remarkable advances have been achieved in sepsis treatment, the morbidity and mortality of this disease are still unacceptably high. In this review, we will briefly discuss the ongoing standard treatment of septic shock and describe novel potential therapies, aiming to improve hemodynamic support and/or control inflammatory response in sepsis. These therapies were associated with benefits in experimental studies and have been tested or are currently under testing in randomized controlled studies with septic patients.

Therapeutic strategies for high-dose vasopressor-dependent shock.

There is no consensual definition of refractory shock. The use of more than 0.5 mcg/kg/min of norepinephrine or epinephrine to maintain target blood pressure is often used in clinical trials as a threshold. Nearly 6% of critically ill patients will develop refractory shock, which accounts for 18% of deaths in intensive care unit. Mortality rates are usually greater than 50%. The assessment of fluid responsiveness and cardiac function can help to guide therapy, and inotropes may be used if hypoperfusion signs persist after initial resuscitation. Arginine vasopressin is frequently used in refractory shock, although definite evidence to support this practice is still missing. Its associations with corticosteroids improved outcome in observational studies and are therefore promising alternatives. Other rescue therapies such as terlipressin, methylene blue, and high-volume isovolemic hemofiltration await more evidence before use in routine practice.