Gilberto Friedman

Combined measurements of blood lactate concentrations and gastric intramucosal pH in patients with severe sepsis

OBJECTIVE To compare the prognostic value of blood lactate concentrations, gastric intramucosal pH, and their combination in patients with severe sepsis. DESIGN Prospective, noninterventional study. SETTING Medical/surgical intensive care unit of a university hospital. PATIENTS The study included 35 consecutive patients (44 to 82 yrs) with severe sepsis as defined by fever or hypothermia (rectal temperature > 38.3 degrees or < 35.5 degrees C), tachycardia (heart rate > 100 beats/min), tachypnea (respiratory rate > 20 breaths/min) or mechanical ventilation, abnormal white blood cell count (> 10 or < 6 x 10(3) cells/mm3), hypotension (systolic arterial pressure < 90 mm Hg), and evidence of organ dysfunction (oliguria or deterioration of mental status). INTERVENTIONS Arterial lactate concentration and intramucosal pH were measured at the time of study entry, and at 4 and 24 hrs later. Hemodynamic data and oxygen-derived variables were determined at the time of study entry and 24 hrs later. Arterial blood and balloon saline gases were also determined to obtain the pH gap (arterial pH-intramucosal pH) and the PCO2 gap (intramural PCO2-PaCO2). MEASUREMENTS AND MAIN RESULTS Of the 35 patients, 19 survived the intensive care unit stay. At the time of study admission, 23 (66%) patients had an increased lactate concentration (> 2 mEq/L) and 26 (74%) had a low intramucosal pH (< 7.32). Initially, there were no significant differences in blood lactate concentrations between nonsurvivors and survivors (3.2 +/- 1.5 vs. 2.8 +/- 2.3 mEq/L). Lactate concentrations remained high in nonsurvivors and progressively decreased in survivors (4 hrs: 3.3 +/- 1.1 mEq/L in nonsurvivors vs. 2.2 +/- 0.9 mEq/L in survivors [p < .01]; 24 hrs: 3.5 +/- 2.0 mEq/L in nonsurvivors vs. 1.9 +/- 1.1 mEq/L in survivors [p < .05]). Intramucosal pH was lower in the nonsurvivors than in the survivors initially (7.19 +/- 0.15 in nonsurvivors vs. 7.30 +/- 0.14 in survivors [p < .05]), at 4 hrs (7.18 +/- 0.17 in nonsurvivors vs. 7.29 +/- 0.13 in survivors [p = .06]), and at 24 hrs (7.19 +/- 0.31 in nonsurvivors vs. 7.30 +/- 0.17 in survivors [p < .05]). Of the 23 patients with initially high lactate concentrations, 12 (60%) of the 20 patients with low intramucosal pH died, as compared with one (33%) of the three patients with normal intramucosal pH (p = .052). Of the 14 patients with persistently high lactate concentrations at 24 hrs, all nine (100%) patients with low intramucosal pH, but only two (40%) of five patients with normal intramucosal pH died (p < .001). No significant relationship was found between lactate or intramucosal pH and oxygen-derived variables. Intramucosal pH correlated better with gastric intramural PCO2 (r2 = .58) than with arterial bicarbonate or base deficit/excess. Intramural PCO2 was a more specific predictor of mortality than intramucosal pH. When compared with patients with normal lactate concentrations, those patients with high lactate concentrations had a higher pH gap (0.22 +/- 0.22 vs. 0.07 +/- 0.13 [p < .01]) and PCO2 gap [21.0 +/- 33.9 vs. 1.8 +/- 9.8 torr [2.79 +/- 4.5 vs. 0.24 +/- 1.34 kPa]; p < .01). CONCLUSIONS Both lactate concentrations and intramucosal pH represent reliable prognostic indicators in severe sepsis, and their combination improves the prognostic assessment in these patients. Both variables are better prognostic indicators than oxygen-derived variables. Intramural PCO2 appears to be a more specific variable than intramucosal pH, which partially reflects systemic metabolic acidosis. Combined determinations of blood lactate concentrations and intramucosal pH or intramural PCO2 may help to predict outcome from severe sepsis.

Characteristics and outcomes of patients with cancer requiring admission to intensive care units: A prospective multicenter study*

Objective:To evaluate the characteristics and outcomes of patients with cancer admitted to several intensive care units. Knowledge on patients with cancer requiring intensive care is mostly restricted to single-center studies. Design:Prospective, multicenter, cohort study. Setting:Intensive care units from 28 hospitals in Brazil. Patients:A total of 717 consecutive patients included over a 2-mo period. Interventions:None. Measurements and Main Results:There were 667 (93%) patients with solid tumors and 50 (7%) patients had hematologic malignancies. The main reasons for intensive care unit admission were postoperative care (57%), sepsis (15%), and respiratory failure (10%). Overall hospital mortality rate was 30% and was higher in patients admitted because of medical complications (58%) than in emergency (37%) and scheduled (11%) surgical patients (p < .001). Adjusting for covariates other than the type of admission, the number of hospital days before intensive care unit admission (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.01–1.37), higher Sequential Organ Failure Assessment scores (OR, 1.25; 95% CI, 1.17–1.34), poor performance status (OR, 3.40; 95% CI, 2.19 –5.26), the need for mechanical ventilation (OR, 2.42; 95% CI, 1.51–3.87), and active underlying malignancy in recurrence or progression (OR, 2.42; 95% CI, 1.51–3.87) were associated with increased hospital mortality in multivariate analysis. Conclusions:This large multicenter study reports encouraging survival rates for patients with cancer requiring intensive care. In these patients, mortality was mostly dependent on the severity of organ failures, performance status, and need for mechanical ventilation rather than cancer-related characteristics, such as the type of malignancy or the presence of neutropenia.

Sepse Brasil: estudo epidemiológico da sepse em Unidades de Terapia Intensiva brasileiras

BACKGROUND AND OBJECTIVES: Sepsis represents the major cause of death in the ICUs all over the world. Many studies have shown an increasing incidence over time and only a slight reduce in mortality. Many new treatment strategies are arising and we should define the incidence and features of sepsis in Brazil. METHODS: Prospective cohort study in sixty-five hospitals all over Brazil. The patients who were admitted or who developed sepsis during the month of September, 2003 were enrolled. They were followed until the 28th day and/or until their discharge. The diagnoses were made in accordance to the criteria proposed by ACCP/SCCM. It were evaluated demographic features, APACHE II score, SOFA (Sepsis-related Organ Failure Assessment) score, mortality, sources of infections, microbiology, morbidities and length of stay (LOS). RESULTS: Seventy-five ICUs from all regions of Brazil took part in the study.3128 patients were identified and 521 (16.7%) filled the criteria of sepsis, severe sepsis or septic shock. Mean age was 61.7 (IQR 39-79), 293 (55.7%) were males, and the overall 28-day mortality rate was 46.6%. Average APACHE II score was 20 and SOFA score on the first day was 7 (IQR 4-10). SOFA score in the mortality group was higher on day 1 (8, IQR 5-11), and had increased on day 3 (9, IQR 6-12). The mortality rate for sepsis, severe sepsis and septic shock was 16.7%, 34.4% and 65.3%, respectively. The average LOS was 15 days (IQR 5-22). The two main sources of infection were the respiratory tract (69%) and the abdomen one (23.1%). Gram-negative bacilli were more prevalent (40.1%). Gram-positive cocci were identified in 32.8% and fungi infections in 5%. Mechanical ventilation was observed in 82.1% of the patients, Swan-Ganz catheter in 18.8%, vasopressors in 66.2% and hemotransfusion in 44.7%. CONCLUSIONS: It was observed a high mortality of sepsis in the ICUs in Brazil. The high frequency of septic shock demonstrated a group at high risk of death. In order to have a better use of the resources and reduce in mortality during the next 5 years, it is very important to identify our specific features related to this syndrome.

Blood interleukin 10 levels parallel the severity of septic shock

PURPOSE The aim of this study was to investigate the relation between interleukin (IL) 10, tumor necrosis factor alpha (TNF alpha), IL-1, and IL-6 levels in patients with septic shock and relate these cytokine levels to the development of organ failure. PATIENTS AND METHODS In 11 patients with septic shock of recent onset, blood was sampled for determinations of TNF, IL-1, IL-6, and IL-10. The degree of organ failure was scored for four organ systems (respiratory, hepatic, renal, hematologic) in the first 48 hours of the study. RESULTS The APACHE II score was 21 +/- 4. Three patients died. IL-10 levels were directly correlated with TNF levels (r = 0.73, P < .05) and IL-6 levels (r = 0.67, P < .05); and inversely correlated with total C3 (r = -0.73, P < .05) and CH50 (r = -0.68, P < .05). Both IL-10 and TNF levels were correlated to the organ failure score (r = 0.75 and r = 0.68, both P < .01). Six patients with high IL-10 levels (> 60 pg/mL) had lower C3 (37 +/- 11 v 62 +/- 10 mg/dL) and CH50 (32 +/- 7 v 68 +/- 19%), and higher organ failure scores (5.7 +/- 0.8 v 3.8 +/- 1.3) than those with low IL-10 levels (all P < .05). CONCLUSION Although IL-10 has an inhibitory effect on the production of cytokines, it is released together with TNF and IL-6 in patients with septic shock. IL-10 blood levels are directly related to the severity of inflammation and the development of organ failure in septic shock.

Outcomes for Patients With Cancer Admitted to the ICU Requiring Ventilatory Support: Results From a Prospective Multicenter Study

BACKGROUND This study was undertaken to evaluate the clinical characteristics and outcomes of patients with cancer requiring nonpalliative ventilatory support. METHODS This was a secondary analysis of a prospective cohort study conducted in 28 Brazilian ICUs evaluating adult patients with cancer requiring invasive mechanical ventilation (MV) or noninvasive ventilation (NIV) during the first 48 h of their ICU stay. We used logistic regression to identify the variables associated with hospital mortality. RESULTS Of 717 patients, 263 (37%) (solid tumors = 227; hematologic malignancies = 36) received ventilatory support. NIV was initially used in 85 patients (32%), and 178 (68%) received MV. Additionally, NIV followed by MV occurred in 45 patients (53%). Hospital mortality rates were 67% in all patients, 40% in patients receiving NIV only, 69% when NIV was followed by MV, and 73% in patients receiving MV only (P < .001). Adjusting for the type of admission, newly diagnosed malignancy (OR, 3.59; 95% CI, 1.28-10.10), recurrent or progressive malignancy (OR, 3.67; 95% CI, 1.25-10.81), tumoral airway involvement (OR, 4.04; 95% CI, 1.30-12.56), performance status (PS) 2 to 4 (OR, 2.39; 95% CI, 1.24-4.59), NIV followed by MV (OR, 3.00; 95% CI, 1.09-8.18), MV as initial ventilatory strategy (OR, 3.53; 95% CI, 1.45-8.60), and Sequential Organ Failure Assessment score (each point except the respiratory domain) (OR, 1.15; 95% CI, 1.03-1.29) were associated with hospital mortality. Hospital survival in patients with good PS and nonprogressive malignancy and without tumoral airway involvement was 53%. Conversely, patients with poor functional capacity and cancer progression had unfavorable outcomes. CONCLUSIONS Patients with cancer with good PS and nonprogressive disease requiring ventilatory support should receive full intensive care, because one-half of these patients survive. On the other hand, provision of palliative care should be considered the main goal for patients with poor PS and progressive underlying malignancy.

Mechanical ventilation with high tidal volume induces inflammation in patients without lung disease.

IntroductionMechanical ventilation (MV) with high tidal volumes may induce or aggravate lung injury in critical ill patients. We compared the effects of a protective versus a conventional ventilatory strategy, on systemic and lung production of tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) in patients without lung disease.MethodsPatients without lung disease and submitted to mechanical ventilation admitted to one trauma and one general adult intensive care unit of two different university hospitals were enrolled in a prospective randomized-control study. Patients were randomized to receive MV either with tidal volume (VT) of 10 to 12 ml/kg predicted body weight (high VT group) (n = 10) or with VT of 5 to 7 ml/kg predicted body weight (low VT group) (n = 10) with an oxygen inspiratory fraction (FIO2) enough to keep arterial oxygen saturation >90% with positive end-expiratory pressure (PEEP) of 5 cmH2O during 12 hours after admission to the study. TNF-α and IL-8 concentrations were measured in the serum and in the bronchoalveolar lavage fluid (BALF) at admission and after 12 hours of study observation time.ResultsTwenty patients were enrolled and analyzed. At admission or after 12 hours there were no differences in serum TNF-α and IL-8 between the two groups. While initial analysis did not reveal significant differences, standardization against urea of logarithmic transformed data revealed that TNF-α and IL-8 levels in bronchoalveolar lavage (BAL) fluid were stable in the low VT group but increased in the high VT group (P = 0.04 and P = 0.03). After 12 hours, BALF TNF-α (P = 0.03) and BALF IL-8 concentrations (P = 0.03) were higher in the high VT group than in the low VT group.ConclusionsThe use of lower tidal volumes may limit pulmonary inflammation in mechanically ventilated patients even without lung injury.Trial RegistrationClinical Trial registration: NCT00935896

Lung-Protective Ventilation With Low Tidal Volumes and the Occurrence of Pulmonary Complications in Patients Without Acute Respiratory Distress Syndrome: A Systematic Review and Individual Patient Data Analysis.

Objective:Protective mechanical ventilation with low tidal volumes is standard of care for patients with acute respiratory distress syndrome. The aim of this individual patient data analysis was to determine the association between tidal volume and the occurrence of pulmonary complications in ICU patients without acute respiratory distress syndrome and the association between occurrence of pulmonary complications and outcome in these patients. Design:Individual patient data analysis. Patients:ICU patients not fulfilling the consensus criteria for acute respiratory distress syndrome at the onset of ventilation. Interventions:Mechanical ventilation with low tidal volume. Measurements and Main Results:The primary endpoint was development of a composite of acute respiratory distress syndrome and pneumonia during hospital stay. Based on the tertiles of tidal volume size in the first 2 days of ventilation, patients were assigned to a “low tidal volume group” (tidal volumes⩽ 7 mL/kg predicted body weight), an “intermediate tidal volume group” (> 7 and < 10 mL/kg predicted body weight), and a “high tidal volume group” (≥ 10 mL/kg predicted body weight). Seven investigations (2,184 patients) were included. Acute respiratory distress syndrome or pneumonia occurred in 23% of patients in the low tidal volume group, in 28% of patients in the intermediate tidal volume group, and in 31% of the patients in the high tidal volume group (adjusted odds ratio [low vs high tidal volume group], 0.72; 95% CI, 0.52–0.98; p = 0.042). Occurrence of pulmonary complications was associated with a lower number of ICU-free and hospital-free days and alive at day 28 (10.0 ± 10.9 vs 13.8 ± 11.6 d; p < 0.01 and 6.1 ± 8.1 vs 8.9 ± 9.4 d; p < 0.01) and an increased hospital mortality (49.5% vs 35.6%; p < 0.01). Conclusions:Ventilation with low tidal volumes is associated with a lower risk of development of pulmonary complications in patients without acute respiratory distress syndrome.

Oxygen supply dependency can characterize septic shock

Objective: To demonstrate that oxygen consumption (VO2) can be dependent on oxygen delivery (DO2) during hemodynamic instability and independent of DO2 following stabilization.Design: We retrospectively reviewed hemodynamic and blood gas data collected from ten patients in whom DO2 was acutely altered during an episode of septic shock (phase A) and after recovery from this episode (phase B).Setting: General intensive care unit of a university hospital.Patients: 10 critically ill adult patients (aged 55 ± 19 years).Interventions: DO2 was altered by fluid challenge, administration of vasoactive agents, or application of positive end-expiratory pressure.Results: In phase A, changes in VO2 (121 ± 32 vs 165 ± 36 ml/min · m2; p<0.001) paralleled changes in DO2 (415 ± 153 vs 607 ± 217 ml/min · m2; p<0.001), but oxygen extraction (O2ER) remained stable (31.9 ± 11.2 vs. 30.2 ± 8.9 %; NS). In phase B, changes in DO2 (412 ± 118 vs 526 ± 152 ml/min · m2; p<0.001) were associated with opposite changes in O2ER (36.1 ± 4.2 vs 28.9 ± 4.9t%; p<0.001), and VO2 was unchanged (147 ± 35 vs 149 ± 33 ml/min · m2; NS). The mean VO2/DO2 slope was greater in phase A than in phase B (0.26 ± 0.09 vs. 0.08 ± 0.08; p<0.004). Blood lactate levels were higher in phase A than in phase B (3.3 ± 1.8 vs 1.6 ±0.6 mEq/l; p<0.05).Conclusions: Oxygen supply independency and dependency can be found at different times in the same critically ill patient. Our findings are consistent with the concept that VO2/DO2 dependency is a marker of septic shock. Interventions to increase DO2 are probably justified when this phenomenon is present.

Original ResearchCritical CareFeaturedOutcomes for Patients With Cancer Admitted to the ICU Requiring Ventilatory Support: Results From a Prospective Multicenter Study

BACKGROUND This study was undertaken to evaluate the clinical characteristics and outcomes of patients with cancer requiring nonpalliative ventilatory support. METHODS This was a secondary analysis of a prospective cohort study conducted in 28 Brazilian ICUs evaluating adult patients with cancer requiring invasive mechanical ventilation (MV) or noninvasive ventilation (NIV) during the first 48 h of their ICU stay. We used logistic regression to identify the variables associated with hospital mortality. RESULTS Of 717 patients, 263 (37%) (solid tumors = 227; hematologic malignancies = 36) received ventilatory support. NIV was initially used in 85 patients (32%), and 178 (68%) received MV. Additionally, NIV followed by MV occurred in 45 patients (53%). Hospital mortality rates were 67% in all patients, 40% in patients receiving NIV only, 69% when NIV was followed by MV, and 73% in patients receiving MV only (P < .001). Adjusting for the type of admission, newly diagnosed malignancy (OR, 3.59; 95% CI, 1.28-10.10), recurrent or progressive malignancy (OR, 3.67; 95% CI, 1.25-10.81), tumoral airway involvement (OR, 4.04; 95% CI, 1.30-12.56), performance status (PS) 2 to 4 (OR, 2.39; 95% CI, 1.24-4.59), NIV followed by MV (OR, 3.00; 95% CI, 1.09-8.18), MV as initial ventilatory strategy (OR, 3.53; 95% CI, 1.45-8.60), and Sequential Organ Failure Assessment score (each point except the respiratory domain) (OR, 1.15; 95% CI, 1.03-1.29) were associated with hospital mortality. Hospital survival in patients with good PS and nonprogressive malignancy and without tumoral airway involvement was 53%. Conversely, patients with poor functional capacity and cancer progression had unfavorable outcomes. CONCLUSIONS Patients with cancer with good PS and nonprogressive disease requiring ventilatory support should receive full intensive care, because one-half of these patients survive. On the other hand, provision of palliative care should be considered the main goal for patients with poor PS and progressive underlying malignancy.

Early hemodynamic course of septic shock

OBJECTIVE To assess the relative contributions of changes in vascular tone and changes in cardiac function to hemodynamic recovery from septic shock. DESIGN Case series, observational study. SETTING Multidisciplinary department of intensive care in an academic hospital. PATIENTS Sixty-seven patients with septic shock (prolonged hypotension, signs of tissue hypoperfusion, signs of sepsis, suspected source of infection, or documented bacteremia). In addition to the antibiotic therapy and the removal of the source of sepsis whenever possible, each patient received intravenous fluids and vasoactive agents (dopamine, norepinephrine, and dobutamine). Each patient was also treated with mechanical ventilation. Twenty-four (36%) patients survived their intensive care unit course. INTERVENTIONS Hemodynamic measurements were obtained at baseline, after initial resuscitation (as soon as apparent hemodynamic stability was achieved), after 12 hrs, and after 24 hrs. MEASUREMENTS AND MAIN RESULTS There were no significant differences in hemodynamic or oxygen-derived variables at baseline between the survivors and the nonsurvivors. During the initial resuscitation period, only the survivors demonstrated a significant increase in mean arterial pressure (from 69 +/- 17 to 82 +/- 18 mm Hg; p < .02) and left ventricular stroke work index (from 25.2 +/- 11.0 to 35.5 +/- 19.4 g.m/m2; p < .05). The increases in cardiac index and systemic vascular resistance were greater in the survivors than in the non-survivors, but the differences did not reach statistical significance. Study of the left ventricular function curves indicated an improvement of left ventricular function in the survivors but not in the nonsurvivors. CONCLUSION An early improvement in left ventricular function is a hallmark of the survivors from septic shock.