Eliezer Silva

International Study of the Prevalence and Outcomes of Infection in Intensive Care Units

CONTEXT Infection is a major cause of morbidity and mortality in intensive care units (ICUs) worldwide. However, relatively little information is available about the global epidemiology of such infections. OBJECTIVE To provide an up-to-date, international picture of the extent and patterns of infection in ICUs. DESIGN, SETTING, AND PATIENTS The Extended Prevalence of Infection in Intensive Care (EPIC II) study, a 1-day, prospective, point prevalence study with follow-up conducted on May 8, 2007. Demographic, physiological, bacteriological, therapeutic, and outcome data were collected for 14,414 patients in 1265 participating ICUs from 75 countries on the study day. Analyses focused on the data from the 13,796 adult (>18 years) patients. RESULTS On the day of the study, 7087 of 13,796 patients (51%) were considered infected; 9084 (71%) were receiving antibiotics. The infection was of respiratory origin in 4503 (64%), and microbiological culture results were positive in 4947 (70%) of the infected patients; 62% of the positive isolates were gram-negative organisms, 47% were gram-positive, and 19% were fungi. Patients who had longer ICU stays prior to the study day had higher rates of infection, especially infections due to resistant staphylococci, Acinetobacter, Pseudomonas species, and Candida species. The ICU mortality rate of infected patients was more than twice that of noninfected patients (25% [1688/6659] vs 11% [ 682/6352], respectively; P < .001), as was the hospital mortality rate (33% [2201/6659] vs 15% [ 942/6352], respectively; P < .001) (adjusted odds ratio for risk of hospital mortality, 1.51; 95% confidence interval, 1.36-1.68; P < .001). CONCLUSIONS Infections are common in patients in contemporary ICUs, and risk of infection increases with duration of ICU stay. In this large cohort, infection was independently associated with an increased risk of hospital death.

The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis.

Objective: The Surviving Sepsis Campaign (SSC or “the Campaign”) developed guidelines for management of severe sepsis and septic shock. A performance improvement initiative targeted changing clinical behavior (process improvement) via bundles based on key SSC guideline recommendations. Design and Setting: A multifaceted intervention to facilitate compliance with selected guideline recommendations in the intensive care unit, emergency department, and wards of individual hospitals and regional hospital networks was implemented voluntarily in the United States, Europe, and South America. Elements of the guidelines were “bundled” into two sets of targets to be completed within 6 hrs and within 24 hrs. An analysis was conducted on data submitted from January 2005 through March 2008. Subjects: A total of 15,022 subjects. Measurements and Main Results: Data from 15,022 subjects at 165 sites were analyzed to determine the compliance with bundle targets and association with hospital mortality. Compliance with the entire resuscitation bundle increased linearly from 10.9% in the first site quarter to 31.3% by the end of 2 yrs (p < .0001). Compliance with the entire management bundle started at 18.4% in the first quarter and increased to 36.1% by the end of 2 yrs (p = .008). Compliance with all bundle elements increased significantly, except for inspiratory plateau pressure, which was high at baseline. Unadjusted hospital mortality decreased from 37% to 30.8% over 2 yrs (p = .001). The adjusted odds ratio for mortality improved the longer a site was in the Campaign, resulting in an adjusted absolute drop of 0.8% per quarter and 5.4% over 2 yrs (95% confidence interval, 2.5–8.4). Conclusions: The Campaign was associated with sustained, continuous quality improvement in sepsis care. Although not necessarily cause and effect, a reduction in reported hospital mortality rates was associated with participation. The implications of this study may serve as an impetus for similar improvement efforts.

Procalcitonin used as a marker of infection in the intensive care unit

OBJECTIVE To determine the value of procalcitonin (ProCT) as a marker of infection in critically ill patients. DESIGN Prospective, observational study. SETTING Medicosurgical department of intensive care (31 beds). PATIENTS One hundred eleven infected and 79 noninfected patients. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS ProCT and C-reactive protein (CRP) concentrations were monitored daily. The best cutoff values for ProCT and CRP were 0.6 ng/mL and 7.9 mg/dL, respectively. Compared with CRP, ProCT had a lower sensitivity (67.6 vs. 71.8), specificity (61.3 vs. 66.6), and area under the receiver operating characteristic curve (0.66 vs. 0.78, p < .05). The combination of ProCT and CRP increased the specificity for infection to 82.3%. In the infected patients, plasma ProCT, but not CRP, values were higher in nonsurvivors than in survivors. Infected patients with bacteremia had higher ProCT concentrations than those without bacteremia, but similar CRP concentrations. ProCT levels were particularly high in septic shock patients. CONCLUSIONS ProCT is not a better marker of infection than CRP in critically ill patients, but it can represent a useful adjunctive parameter to identify infection and is a useful marker of the severity of infection.

Early changes in organ function predict eventual survival in severe sepsis

Objective:Early identification and treatment of severe sepsis can significantly reduce mortality rate. We hypothesized that a risk prediction model based on early (baseline to day 1 of study) response to standard care should be significantly related to 28-day survival. Design:Analysis of organ dysfunction data from two placebo-controlled severe sepsis trials (PROWESS and secretory phospholipase A2 inhibitor trials). Setting:Research laboratory. Patients:The placebo arms of two randomized, double-blind sepsis trials were combined (n = 1036). These patients met criteria for severe sepsis and received supportive standard intensive care and fluid resuscitation. Interventions:None. Measurements and Main Results:Sequential Organ Failure Assessment (SOFA) scores were calculated daily using the most aberrant physiologic or laboratory variables. Baseline and postbaseline SOFA scores categorized as improved, unchanged, or worsened were used in regression analyses correlating organ dysfunction changes with 28-day mortality. Improvement in cardiovascular (p = .0010), renal (p < .0001), or respiratory (p = .0469) function from baseline to day 1 was significantly related to survival. Odds ratios (95% confidence intervals) associated with improved vs. worsened respiratory, cardiovascular, or renal function before start of day 1 were 0.56 (0.35–0.91), 0.33 (0.18–0.59), and 0.30 (0.17–0.52), respectively. Continued improvement in cardiovascular function before start of day 2 and start of day 3 was associated with further improvement in survival (p <. 0001), with odds ratios of 0.15 (0.06–0.39) and 0.11 (0.04–0.31) for patients who improved compared with those who worsened. No other organ system was retained in the model, and improvement beyond day 1 in any other organ function did not add to the models predictive power. Conclusions:These analyses suggest that outcomes for patients with severe sepsis are closely related to early (baseline to day 1 here) improvement, or lack thereof, in organ function. Also, clinical improvement on subsequent days may have little additional impact on the likelihood of survival. LEARNING OBJECTIVESOn completion of this article, the reader should be able to: Explain organ function abnormalities associated with poor patient outcomes from sepsis. Describe the significant time periods to predict outcome. Use this information in a clinical setting. Dr. Levy has disclosed that he is/was the recipient of direct grant/research funds from Eli Lilly & Co., Chiron, Moguel, Phillips, and Edwards; is a consultant for Chiron and Phillips; and is/was on the speakers bureau of Eli Lilly & Co., Edwards, Phillips, and Ortho. Dr. Macias has disclosed that he is/was an employee and a current stock shareholder of Eli Lilly & Co. Dr. Vincent has disclosed that he is/was the recipient of direct grant/research funds from, a consultant for, and on the speakers bureau of Eli Lilly & Co. Mr. Trzaskoma and Dr. Williams have disclosed that they were/are employees and stock shareholders of Eli Lilly & Co. Dr. Silva has disclosed that he is/was a consultant for and was on the speakers bureau of Eli Lilly & Co. Dr. Russell has disclosed that he has no financial relationships with or interests in any commercial companies pertaining to this educational activity. Wolters Kluwer Health has identified and resolved all faculty conflicts of interests regarding this educational activity. Visit the Critical Care Medicine Web site (www.ccmjournal.org) for information on obtaining continuing medical education credit.

Brazilian Sepsis Epidemiological Study (BASES study).

IntroductionConsistent data about the incidence and outcome of sepsis in Latin American intensive care units (ICUs), including Brazil, are lacking. This study was designed to verify the actual incidence density and outcome of sepsis in Brazilian ICUs. We also assessed the association between the Consensus Conference criteria and outcomeMethodsThis is a multicenter observational cohort study performed in five private and public, mixed ICUs from two different regions of Brazil. We prospectively followed 1383 adult patients consecutively admitted to those ICUs from May 2001 to January 2002, until their discharge, 28th day of stay, or death. For all patients we collected the following data at ICU admission: age, gender, hospital and ICU admission diagnosis, APACHE II score, and associated underlying diseases. During the following days, we looked for systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock criteria, as well as recording the sequential organ failure assessment score. Infection was diagnosed according to CDC criteria for nosocomial infection, and for community-acquired infection, clinical, radiological and microbiological parameters were used.ResultsFor the whole cohort, median age was 65.2 years (49–76), median length of stay was 2 days (1–6), and the overall 28-day mortality rate was 21.8%. Considering 1383 patients, the incidence density rates for sepsis, severe sepsis and septic shock were 61.4, 35.6 and 30.0 per 1000 patient-days, respectively. The mortality rate of patients with SIRS, sepsis, severe sepsis and septic shock increased progressively from 24.3% to 34.7%, 47.3% and 52.2%, respectively. For patients with SIRS without infection the mortality rate was 11.3%. The main source of infection was lung/respiratory tract.ConclusionOur preliminary data suggest that sepsis is a major public health problem in Brazilian ICUs, with an incidence density about 57 per 1000 patient-days. Moreover, there was a close association between ACCP/SCCM categories and mortality rate.

Effects of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in septic shock: which is best?

OBJECTIVE To assess the effects of different doses of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in patients with septic shock. DESIGN Prospective, randomized, open-label study. SETTING A 31-bed, medicosurgical intensive care unit of a university hospital. PATIENTS Convenience sample of 20 patients with septic shock, separated into two groups according to whether (moderate shock group, n = 10) or not (severe shock, n = 10) dopamine alone was able maintain mean arterial pressure >65 mm Hg. INTERVENTIONS Dopamine was progressively withdrawn and replaced successively by norepinephrine and then epinephrine (the order of the two agents was randomly determined) to maintain mean arterial pressure constant (moderate shock) or to increase mean arterial pressure above 65 mm Hg (severe shock). MEASUREMENTS AND MAIN RESULTS Systemic circulation (pulmonary artery catheter) and splanchnic circulation (indocyanine green dilution and hepatic vein catheter) and gastric mucosal Pco(2) (gas tonometry) were measured during dopamine (moderate shock only), norepinephrine, and epinephrine administration (both groups). Data were analyzed with nonparametric tests and are presented as median [percentiles 25-75]. In moderate shock, cardiac index was similar to dopamine and norepinephrine (3.1 [2.7-3.8] vs. 2.9 [2.7-4.1] L/min.m2, p = nonsignificant) but greater with epinephrine (4.1 [3.5-4.4] p <.01 vs. dopamine and norepinephrine). Splanchnic blood flow was similar with the three agents (732 [413-1483] vs. 746 [470-1401] vs. 653 [476-1832] mL/min.m, p = nonsignificant). The gradient between mixed-venous and hepatic venous oxygen saturations was lower with dopamine than with norepinephrine and epinephrine, but the Pco(2) gap was similar with the three agents. In severe shock, cardiac index was higher, but splanchnic blood flow was lower, with epinephrine than with norepinephrine (4.6 [3.7-5.3] vs. 3.4 [3.0-4.1] L/min.m2, p <.01 and 860 [684-1334] vs. 977 [806-1802] mL/min.m2, p <.05, respectively). Epinephrine increased the mixed-venous and hepatic venous oxygen saturation gradient but did not alter Pco(2) gap. CONCLUSIONS Dopamine and norepinephrine have similar hemodynamic effects, but epinephrine can impair splanchnic circulation in severe septic shock.

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.

Epidemiology of Severe Sepsis Around the World

Severe sepsis is an ongoing challenge for clinicians and health-care administrators mainly because is associated with a high incidence, mortality rate and costs. In recent years, several epidemiological studies about the incidence of sepsis have come out in different and prestigious journals. However, it is not advisable to draw direct conclusions from those studies considering methodological flaws or even different approaches. Hence, we have to be familiar with those obstacles and know how to overcome them. This review paper highlights the methods which have been used in these studies and depicts the results of occurrence rate or incidence of sepsis in countries and in intensive care units.

Promoting Global Research Excellence in Severe Sepsis (PROGRESS): Lessons from an International Sepsis Registry

Background:The PROGRESS Registry (Promoting Global Research Excellence in Severe Sepsis) was designed to provide comparative data reflecting everyday clinical practice, thereby allowing participating institutions to explore and benchmark medical interventions in severe sepsis.Materials and Methods:PROGRESS was an international, noninterventional, prospective, observational registry collecting data that describe the management and outcomes of severe sepsis patients in intensive care units (ICUs). Patients were enrolled who had been diagnosed with severe sepsis (suspected or proven infection and ≥ 1 acute sepsis-induced organ dysfunction) at the participating institutions, where de-identified data were entered directly into a secured website. PROGRESS was governed by an independent international medical advisory board.Results:PROGRESS took place in 276 ICUs in 37 countries, and 12,881 patients were identified as having severe sepsis. There was considerable variation among countries in enrollment levels, provision of standard treatment and supportive therapies, and ICU and hospital outcomes. Eight countries accounted for 65.2% of the enrolled patients. Males (59.3%) and Caucasian (48.6%) patients predominated the patient cohort. Diagnosis of severe sepsis was prior to ICU admission in 45.7% of patients, at ICU admission in 29.1% of patients, and after ICU admission in the remainder. Globally, ICU and hospital mortality rates were 39.2% and 49.6%, respectively. The mean length of ICU and hospital stay was 14.6 days and 28.2 days, respectively.Conclusions:The PROGRESS international sepsis registry demonstrates that a large web-based sepsis registry is feasible. Wide variations in outcomes and use of sepsis therapies were observed between countries. These results also suggest that additional opportunities exist across countries to improve severe sepsis outcomes.

Effects of vasoactive drugs on gastric intramucosal pH

OBJECTIVE To review current knowledge about the effects of vasoactive agents on gastric intramucosal pH (pHi). DATA SOURCES All studies involving pHi and vasoactive agents were retrieved from a computerized MEDLINE search from 1980 to 1997. We also reviewed the reference lists of all available review articles and primary studies to identify references not found in the computerized searches. STUDY SELECTION Clinical and experimental studies using dopamine, dopexamine, dobutamine, norepinephrine, epinephrine, nitric oxide, N-acetylcysteine, prostaglandins, or pentoxifylline were considered if splanchnic perfusion and/or pHi measurements were utilized. DATA EXTRACTION From the selected studies, information was obtained regarding patient population, dosing regimen, duration of study, and effects on splanchnic blood flow (SBF), splanchnic oxygenation, and pHi. DATA SYNTHESIS Although dopaminergic effects increase SBF, dopamine does not generally increase pHi. Data on the effects of dopexamine on pHi are scarce and inconsistent. Dobutamine can significantly increase SBF and usually increases pHi. In septic patients, norepinephrine seems to increase pHi. Epinephrine may have detrimental effects on gastric perfusion. Prostacyclin seems to increase pHi but data are limited. Insufficient evidence exists to support the beneficial effects of nitric oxide donors or blockers, pentoxifylline, or N-acetylcysteine on pHi. CONCLUSIONS Overall, the effects of vasoactive agents on pHi are unpredictable. Among the catecholamines, dopamine is the least likely, and dobutamine the most likely, to increase pHi.