Luciano Cesar Pontes Azevedo

Positive fluid balance as a prognostic factor for mortality and acute kidney injury in severe sepsis and septic shock

PURPOSE The purpose of this study is to assess whether late positive fluid balances are associated with acute kidney injury and mortality in severe sepsis and septic shock. METHODS In this retrospective study, fluid balances were calculated at 3 different time points: the onset of organ dysfunction attributed to sepsis, sepsis diagnosis, and vasopressors initiation. Data were analyzed in logistic regression models for mortality and acute kidney injury as outcomes. RESULTS We included 116 patients. A RIFLE score F, diuresis less than 0.9 L from the second day after the first organ dysfunction, and fluid balance more than 3 L between the 24th and the 48th hour after diagnosis were independently associated with higher mortality, whereas in the subgroup with shock, only the latter parameter and diuresis less than 0.85 L on the first day of shock were independent risk factors. After adjusting for age, creatinine more than 1.2 mg/dL, a nonrenal Sequential Organ Failure Assessment greater than or equal to 7.5 on the first day and urine output less than 1.3 L on the first day after organ dysfunction were independent risk factors for RIFLE F. No relationship was found between fluid balance and acute kidney injury. CONCLUSION Late positive fluid balance is an independent risk factor for mortality in severe sepsis. Positive fluid balances are not associated with either protection against or risk for acute kidney injury.

Predictive value of pulse pressure variation for fluid responsiveness in septic patients using lung-protective ventilation strategies

BACKGROUND The applicability of pulse pressure variation (ΔPP) to predict fluid responsiveness using lung-protective ventilation strategies is uncertain in clinical practice. We designed this study to evaluate the accuracy of this parameter in predicting the fluid responsiveness of septic patients ventilated with low tidal volumes (TV) (6 ml kg(-1)). METHODS Forty patients after the resuscitation phase of severe sepsis and septic shock who were mechanically ventilated with 6 ml kg(-1) were included. The ΔPP was obtained automatically at baseline and after a standardized fluid challenge (7 ml kg(-1)). Patients whose cardiac output increased by more than 15% were considered fluid responders. The predictive values of ΔPP and static variables [right atrial pressure (RAP) and pulmonary artery occlusion pressure (PAOP)] were evaluated through a receiver operating characteristic (ROC) curve analysis. RESULTS Thirty-four patients had characteristics consistent with acute lung injury or acute respiratory distress syndrome and were ventilated with high levels of PEEP [median (inter-quartile range) 10.0 (10.0-13.5)]. Nineteen patients were considered fluid responders. The RAP and PAOP significantly increased, and ΔPP significantly decreased after volume expansion. The ΔPP performance [ROC curve area: 0.91 (0.82-1.0)] was better than that of the RAP [ROC curve area: 0.73 (0.59-0.90)] and pulmonary artery occlusion pressure [ROC curve area: 0.58 (0.40-0.76)]. The ROC curve analysis revealed that the best cut-off for ΔPP was 6.5%, with a sensitivity of 0.89, specificity of 0.90, positive predictive value of 0.89, and negative predictive value of 0.90. CONCLUSIONS Automatized ΔPP accurately predicted fluid responsiveness in septic patients ventilated with low TV.

Differences in Sepsis Treatment and Outcomes between Public and Private Hospitals in Brazil: A Multicenter Observational Study

Background Previous studies showed higher sepsis mortality rates in Brazil compared to other developed or developing countries. Moreover, another trial demonstrated an increased mortality rate in public hospitals compared to private hospitals in Brazil. The reasons for these findings may include delayed recognition and inadequate treatment of sepsis in public facilities. We designed this study to evaluate the factors associated with mortality in septic patients admitted to intensive care units in a network of public and private institutions. Materials and Methods This study is a retrospective analysis of a prospective cohort of sepsis patients in 19 private and public institutions in Brazil. We analyzed data from the original database and collected additional data to assess compliance to the treatment guidelines and to determine the time from the onset of organ dysfunction and the sepsis diagnosis by the healthcare team. Results A total of 396 patients were analyzed. Patients in public hospitals were younger, had a greater number of dysfunctional organs at baseline and a lower chance to have sepsis diagnosed within two hours of the onset of organ dysfunction. Private hospitals had a better compliance to lactate and blood culture sampling and maintenance of glycemic control. The multivariate analysis showed that age, disease severity at baseline and being treated at a public hospital were independent risk factors for mortality. A delay in the sepsis diagnosis of longer than two hours was associated with mortality only in the public setting. Conclusions We confirmed a lower sepsis mortality rate in the private hospitals of this network. Being treated in a public hospital was an independent factor for mortality. Delayed recognition of sepsis was more frequent in public institutions and this might have been associated with a higher mortality. Improving sepsis recognition and early diagnosis may be important targets in public institutions.

Comparison between respiratory changes in the inferior vena cava diameter and pulse pressure variation to predict fluid responsiveness in postoperative patients

PURPOSE The objective of our study was to assess the reliability of the distensibility index of the inferior vena cava (dIVC) as a predictor of fluid responsiveness in postoperative, mechanically ventilated patients and compare its accuracy with that of the pulse pressure variation (PPV) measurement. MATERIALS AND METHODS We included postoperative mechanically ventilated and sedated patients who underwent volume expansion with 500mL of crystalloids over 15minutes. A response to fluid infusion was defined as a 15% increase in the left ventricular outflow tract velocity time integral according to transthoracic echocardiography. The inferior vena cava diameters were recorded by a subcostal view using the M-mode and the PPV by automatic calculation. The receiver operating characteristic (ROC) curves were generated for the baseline dIVC and PPV. RESULTS Twenty patients were included. The area under the ROC curve for dIVC was 0.84 (95% confidence interval, 0.63-1.0), and the best cutoff value was 16% (sensitivity, 67%; specificity, 100%). The area under the ROC curve for PPV was 0.92 (95% confidence interval, 0.76-1.0), and the best cutoff was 12.4% (sensitivity, 89%; specificity, 100%). A noninferiority test showed that dIVC cannot replace PPV to predict fluid responsiveness (P=.28). CONCLUSION The individual PPV discriminative properties for predicting fluid responsiveness in postoperative patients seemed superior to those of dIVC.

Daily laxative therapy reduces organ dysfunction in mechanically ventilated patients: a phase II randomized controlled trial

IntroductionConstipation is a common problem in intensive care units. We assessed the efficacy and safety of laxative therapy aiming to promote daily defecation in reducing organ dysfunction in mechanically ventilated patients.MethodsWe conducted a prospective, randomized, controlled, nonblinded phase II clinical trial at two general intensive care units. Patients expected to remain ventilated for over 3 days were randomly assigned to daily defecation or control groups. The intervention group received lactulose and enemas to produce 1–2 defecations per day. In the control group, absence of defecation was tolerated up to 5 days. Primary outcome was the change in Sequential Organ Failure Assessment (SOFA) score between the date of enrollment and intensive care unit discharge, death or day 14.ResultsWe included 88 patients. Patients in the treatment group had a higher number of defecations per day (1.3 ± 0.42 versus 0.7 ± 0.56, p < 0.0001) and lower percentage of days without defecation (33.1 ± 15.7 % versus 62.3 ±24.5 %, p < 0.0001). Patients in the intervention group had a greater reduction in SOFA score (–4.0 (–6.0 to 0) versus –1.0 (–4.0 to 1.0), p = 0.036) with no difference in mortality rates or in survival time. Adverse events were more frequent in the treatment group (4.5 (3.0–8.0) versus 3.0 (1.0–5.7), p = 0.016), including more days with diarrhea (2.0 (1.0–4.0) versus 1.0 (0–2.0) days, p < 0.0001). Serious adverse events were rare and did not significantly differ between groups.ConclusionsLaxative therapy improved daily defecation in ventilated patients and was associated with a greater reduction in SOFA score.Trial registrationClinical Trials.gov NCT01607060, registered 24 May 2012.

Nurse to Bed Ratio and Nutrition Support in Critically Ill Patients

BACKGROUND Inadequate nutrition support is common among critically ill patients, and identification of risk factors for such inadequacy might help in improving nutrition support. OBJECTIVE To determine how often daily calorie goals are met and the factors responsible for inadequate nutrition support. Methods A single-center prospective cohort study. Each patients demographic and clinical characteristics, the need for ventilatory support, the use and dosage of medications, the number of nursing staff per bed, the time elapsed from admission to the intensive care unit until the effective start of enteral feeding, and the causes for nonadministration were recorded. Achievement of daily calorie goals was determined and correlated with risk factors. RESULTS A total of 262 daily evaluations were done in 40 patients. Daily calorie goal was achieved in only 46.2% of the evaluations (n = 121), with a mean of 74.8% of the prescribed volume of enteral nutrition infused daily. Risk factors for inadequate nutrition support were the use of midazolam (odds ratio, 1.58; 95% CI, 1.18-2.11) and fewer nursing professionals per bed (odds ratio, 2.56; 95% CI, 1.43-4.57). Conclusion Achievement of daily calorie goals was inadequate, and the main factors associated with this failure were the use and dosage of midazolam and the number of nurses available.

Transfusões de sangue no choque séptico: 7,0g/dL é mesmo o limite adequado?

Objective To evaluate the immediate effects of red blood cell transfusion on central venous oxygen saturation and lactate levels in septic shock patients with different transfusion triggers. Methods We included patients with a diagnosis of septic shock within the last 48 hours and hemoglobin levels below 9.0g/dL Patients were randomized for immediate transfusion with hemoglobin concentrations maintained above 9.0g/dL (Group Hb9) or to withhold transfusion unless hemoglobin felt bellow 7.0g/dL (Group Hb7). Hemoglobin, lactate, central venous oxygen saturation levels were determined before and one hour after each transfusion. Results We included 46 patients and 74 transfusions. Patients in Group Hb7 had a significant reduction in median lactate from 2.44 (2.00 - 3.22) mMol/L to 2.21 (1.80 - 2.79) mMol/L, p = 0.005, which was not observed in Group Hb9 [1.90 (1.80 - 2.65) mMol/L to 2.00 (1.70 - 2.41) mMol/L, p = 0.23]. Central venous oxygen saturation levels increased in Group Hb7 [68.0 (64.0 - 72.0)% to 72.0 (69.0 - 75.0)%, p < 0.0001] but not in Group Hb9 [72.0 (69.0 - 74.0)% to 72.0 (71.0 - 73.0)%, p = 0.98]. Patients with elevated lactate or central venous oxygen saturation < 70% at baseline had a significant increase in these variables, regardless of baseline hemoglobin levels. Patients with normal values did not show a decrease in either group. Conclusion Red blood cell transfusion increased central venous oxygen saturation and decreased lactate levels in patients with hypoperfusion regardless of their baseline hemoglobin levels. Transfusion did not appear to impair these variables in patients without hypoperfusion. ClinicalTrials.gov NCT01611753Objective: To evaluate the immediate effects of red blood cell transfusion on central venous oxygen saturation and lactate levels in septic shock patients with different transfusion triggers. Methods: We included patients with a diagnosis of septic shock within the last 48 hours and hemoglobin levels below 9.0g/dL Patients were randomized for immediate transfusion with hemoglobin concentrations maintained above 9.0g/dL (Group Hb9) or to withhold transfusion unless hemoglobin felt bellow 7.0g/dL (Group Hb7). Hemoglobin, lactate, central venous oxygen saturation levels were determined before and one hour after each transfusion. Results: We included 46 patients and 74 transfusions. Patients in Group Hb7 had a significant reduction in median lactate from 2.44 (2.00 - 3.22) mMol/L to 2.21 (1.80 - 2.79) mMol/L, p = 0.005, which was not observed in Group Hb9 [1.90 (1.80 - 2.65) mMol/L to 2.00 (1.70 - 2.41) mMol/L, p = 0.23]. Central venous oxygen saturation levels increased in Group Hb7 [68.0 (64.0 - 72.0)% to 72.0 (69.0 - 75.0)%, p < 0.0001] but not in Group Hb9 [72.0 (69.0 - 74.0)% to 72.0 (71.0 - 73.0)%, p = 0.98]. Patients with elevated lactate or central venous oxygen saturation < 70% at baseline had a significant increase in these variables, regardless of baseline hemoglobin levels. Patients with normal values did not show a decrease in either group. Conclusion: Red blood cell transfusion increased central venous oxygen saturation and decreased lactate levels in patients with hypoperfusion regardless of their baseline hemoglobin levels. Transfusion did not appear to impair these variables in patients without hypoperfusion. ClinicalTrials.gov NCT01611753

Serum concentrations of vitamin D and organ dysfunction in patients with severe sepsis and septic shock.

Objectives To evaluate the serum concentrations of vitamin D and their variations in patients with severe sepsis or septic shock and in control subjects upon admission and after 7 days of hospitalization in the intensive care unit and to correlate these concentrations with the severity of organ dysfunction. Methods This case-control, prospective, observational study involved patients aged > 18 years with severe sepsis or septic shock paired with a control group. Serum vitamin D concentrations were measured at inclusion (D0) and on the seventh day after inclusion (D7). Severe deficiency was defined as vitamin D levels < 10ng/ml, deficiency as levels between 10 and 20ng/ml, insufficiency as levels between 20 and 30ng/ml, and sufficiency as levels ≥ 30ng/mL. We considered a change to a higher ranking, together with a 50% increase in the absolute concentration, to represent an improvement. Results We included 51 patients (26 with septic shock and 25 controls). The prevalence of vitamin D concentration ≤ 30ng/ml was 98%. There was no correlation between the serum concentration of vitamin D at D0 and the SOFA score at D0 or D7 either in the general population or in the group with septic shock. Patients with improvement in vitamin D deficiency had an improved SOFA score at D7 (p = 0.013). Conclusion In the population studied, patients with septic shock showed improvement in the serum concentrations of vitamin D on the seventh day compared with the controls. We also found a correlation between higher vitamin D concentrations and a greater decrease in the severity of organ dysfunction.

Risk factors for agitation in critically ill patients

Objective: To evaluate the incidence of agitation in the first 7 days after intensive care unit admission, its risk factors and its associations with clinical outcomes. Methods: This single-center prospective cohort study included all patients older than 18 years with a predicted stay > 48 hours within the first 24 hours of intensive care unit admission. Agitation was defined as a Richmond Agitation Sedation Scale score ≥ +2, an episode of agitation or the use of a specific medication recorded in patient charts. Results: Agitation occurred in 31.8% of the 113 patients. Multivariate analysis showed that delirium [OR = 24.14; CI95% 5.15 - 113.14; p < 0.001], moderate or severe pain [OR = 5.74; CI95% 1.73 - 19.10; p = 0.004], mechanical ventilation [OR = 10.14; CI95% 2.93 - 35.10; p < 0.001], and smoking habits [OR = 4.49; CI95% 1.33 - 15.17; p = 0.015] were independent factors for agitation, while hyperlactatemia was associated with a lower risk [OR = 0.169; CI95% 0.04 - 0.77; p = 0.021]. Agitated patients had fewer mechanical ventilation-free days at day 7 (p = 0.003). Conclusion: The incidence of agitation in the first 7 days after admission to the intensive care unit was high. Delirium, moderate/severe pain, mechanical ventilation, and smoking habits were independent risk factors. Agitated patients had fewer ventilator-free days in the first 7 days.Objective To evaluate the incidence of agitation in the first 7 days after intensive care unit admission, its risk factors and its associations with clinical outcomes. Methods This single-center prospective cohort study included all patients older than 18 years with a predicted stay > 48 hours within the first 24 hours of intensive care unit admission. Agitation was defined as a Richmond Agitation Sedation Scale score ≥ +2, an episode of agitation or the use of a specific medication recorded in patient charts. Results Agitation occurred in 31.8% of the 113 patients. Multivariate analysis showed that delirium [OR = 24.14; CI95% 5.15 - 113.14; p < 0.001], moderate or severe pain [OR = 5.74; CI95% 1.73 - 19.10; p = 0.004], mechanical ventilation [OR = 10.14; CI95% 2.93 - 35.10; p < 0.001], and smoking habits [OR = 4.49; CI95% 1.33 - 15.17; p = 0.015] were independent factors for agitation, while hyperlactatemia was associated with a lower risk [OR = 0.169; CI95% 0.04 - 0.77; p = 0.021]. Agitated patients had fewer mechanical ventilation-free days at day 7 (p = 0.003). Conclusion The incidence of agitation in the first 7 days after admission to the intensive care unit was high. Delirium, moderate/severe pain, mechanical ventilation, and smoking habits were independent risk factors. Agitated patients had fewer ventilator-free days in the first 7 days.

Association between early glycemic control and improvements in markers of coagulation and fibrinolysis in patients with septic shock-induced stress hyperglycemia.

PURPOSE The purpose of this study is to evaluate the coagulation and inflammatory profiles in septic shock patients with baseline hyperglycemia under glycemic control. METHODS Prospective, observational study conducted in an intensive care unit of a university hospital, including 41 septic shock nondiabetic patients with hyperglycemia (n = 21) or normoglycemia (n = 20) profiles at baseline. Hyperglycemic patients received a glucose control protocol (target glycemia, <150 mg/dL). Metabolic, inflammatory, and coagulation markers were measured at baseline and after 24 hours. RESULTS Median glycemic values between groups were different at baseline but not after 24 hours. Baseline coagulation profile was similar in both groups with elevated levels of coagulation markers, reduced factor VII, protein C, and antithrombin activities and fibrinolysis impairment. Normoglycemic patients had unchanged coagulation markers after 24 hours. After treatment, previously hyperglycemic patients exhibited increased plasminogen concentrations (P = .03) and reduced levels of plasminogen activator inhibitor 1 (P = .01) and tissue plasminogen activator (P = .03) as compared with baseline. They also had higher factor VII (P = .03), protein C (P = .04), and antithrombin (P = .04) activities than normoglycemic patients. Inflammatory markers were elevated in both groups and improved after 24 hours, independently of the glycemic profile. CONCLUSIONS Glycemic control during septic shock is associated with improvements in coagulation and fibrinolysis parameters compared with baseline and normoglycemic patients.