Yasser Sakr

Sepsis in European intensive care units: Results of the SOAP study

Objective:To better define the incidence of sepsis and the characteristics of critically ill patients in European intensive care units. Design:Cohort, multiple-center, observational study. Setting:One hundred and ninety-eight intensive care units in 24 European countries. Patients:All new adult admissions to a participating intensive care unit between May 1 and 15, 2002. Interventions:None. Measurements and Main Results:Demographic data, comorbid diseases, and clinical and laboratory data were collected prospectively. Patients were followed up until death, until hospital discharge, or for 60 days. Of 3,147 adult patients, with a median age of 64 yrs, 1,177 (37.4%) had sepsis; 777 (24.7%) of these patients had sepsis on admission. In patients with sepsis, the lung was the most common site of infection (68%), followed by the abdomen (22%). Cultures were positive in 60% of the patients with sepsis. The most common organisms were Staphylococcus aureus (30%, including 14% methicillin-resistant), Pseudomonas species (14%), and Escherichia coli (13%). Pseudomonas species was the only microorganism independently associated with increased mortality rates. Patients with sepsis had more severe organ dysfunction, longer intensive care unit and hospital lengths of stay, and higher mortality rate than patients without sepsis. In patients with sepsis, age, positive fluid balance, septic shock, cancer, and medical admission were the important prognostic variables for intensive care unit mortality. There was considerable variation between countries, with a strong correlation between the frequency of sepsis and the intensive care unit mortality rates in each of these countries. Conclusions:This large pan-European study documents the high frequency of sepsis in critically ill patients and shows a close relationship between the proportion of patients with sepsis and the intensive care unit mortality in the various countries. In addition to age, a positive fluid balance was among the strongest prognostic factors for death. Patients with intensive care unit acquired sepsis have a worse outcome despite similar severity scores on intensive care unit admission.

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.

Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock

Objective:To characterize the time course of microcirculatory alterations and their relation to outcome in patients with septic shock. Design:Prospective, observational study. Setting:Thirty-one-bed, medico-surgical intensive care unit in a university hospital. Patients:Forty-nine patients with septic shock. Interventions:The sublingual microcirculation was investigated with an orthogonal polarization spectral imaging device on the day of onset of septic shock (baseline) and each day until resolution of shock. Measurements and Main Results:Five sequences of 20 secs each were recorded and analyzed off-line by a semiquantitative method. Data were analyzed with nonparametric tests and presented as median (25th–75th percentiles). Three patients died after the resolution of shock from unrelated causes and were excluded. Of the other 46 patients, 26 survived and 20 died: 13 due to unresolving shock and seven due to persistent multiple organ failure after resolution of shock. At the onset of shock, survivors and nonsurvivors had similar vascular density (5.6 [4.7–7.0] vs. 6.2 [5.4–7.0]/mL; p = nonsignificant) and percentage of perfused small vessels (65.0 [53.1–68.9] vs. 58.4 [47.5–69.1]%; p = nonsignificant). Small vessel perfusion improved over time in survivors (analysis of variance, p < .05 between survivors and nonsurvivors) but not in nonsurvivors. Despite similar hemodynamic and oxygenation profiles and use of vasopressors at the end of shock, patients dying after the resolution of shock in multiple organ failure had a lower percentage of perfused small vessels than survivors (57.4 [46.6–64.9] vs. 79.3 [67.2–83.2]%; p = .02). Conclusions:Microcirculatory alterations improve rapidly in septic shock survivors but not in patients dying with multiple organ failure, regardless of whether shock has resolved.

A positive fluid balance is associated with a worse outcome in patients with acute renal failure

IntroductionDespite significant improvements in intensive care medicine, the prognosis of acute renal failure (ARF) remains poor, with mortality ranging from 40% to 65%. The aim of the present observational study was to analyze the influence of patient characteristics and fluid balance on the outcome of ARF in intensive care unit (ICU) patients.MethodsThe data were extracted from the Sepsis Occurrence in Acutely Ill Patients (SOAP) study, a multicenter observational cohort study to which 198 ICUs from 24 European countries contributed. All adult patients admitted to a participating ICU between 1 and 15 May 2002, except those admitted for uncomplicated postoperative surveillance, were eligible for the study. For the purposes of this substudy, patients were divided into two groups according to whether they had ARF. The groups were compared with respect to patient characteristics, fluid balance, and outcome.ResultsOf the 3,147 patients included in the SOAP study, 1,120 (36%) had ARF at some point during their ICU stay. Sixty-day mortality rates were 36% in patients with ARF and 16% in patients without ARF (P < 0.01). Oliguric patients and patients treated with renal replacement therapy (RRT) had higher 60-day mortality rates than patients without oliguria or the need for RRT (41% versus 33% and 52% versus 32%, respectively; P < 0.01). Independent risk factors for 60-day mortality in the patients with ARF were age, Simplified Acute Physiology Score II (SAPS II), heart failure, liver cirrhosis, medical admission, mean fluid balance, and need for mechanical ventilation. Among patients treated with RRT, length of stay and mortality were lower when RRT was started early in the course of the ICU stay.ConclusionIn this large European multicenter study, a positive fluid balance was an important factor associated with increased 60-day mortality. Outcome among patients treated with RRT was better when RRT was started early in the course of the ICU stay.

The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects.

Objective:To evaluate the effects of dobutamine on microcirculatory blood flow alterations in patients with septic shock. Design:Prospective, open-label study. Setting:A 31-bed, medico-surgical intensive care unit of a university hospital. Patients:Twenty-two patients with septic shock. Interventions:Intravenous administration of dobutamine (5 &mgr;g/kg·min) for 2 hrs (n = 22) followed by the addition of 10−2 M acetylcholine (topically applied, n = 10). Measurements and Main Results:Complete hemodynamic measurements were obtained before and after dobutamine administration. In addition, the sublingual microcirculation was investigated with an orthogonal polarization spectral imaging technique before and after dobutamine administration and after topical application of acetylcholine. Dobutamine significantly improved capillary perfusion (from 48 ± 15 to 67 ± 11%, p = .001), but with large individual variation, whereas capillary density remained stable. The addition of topical acetylcholine completely restored capillary perfusion (98 ± 1%, p = .001) and capillary density. The changes in capillary perfusion during dobutamine administration were not related to changes in cardiac index (p = .45) or arterial pressure (p = .29). Interestingly, the decrease in lactate levels was proportional to the improvement in capillary perfusion (y = 0.07 − 0.02x, r2 = .46, p = .005) but not to changes in cardiac index (p = .55). Conclusions:The administration of 5 &mgr;g/kg·min dobutamine can improve but not restore capillary perfusion in patients with septic shock. These changes are independent of changes in systemic hemodynamic variables.

Does dopamine administration in shock influence outcome? Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study*

Objective:The optimal adrenergic support in shock is controversial. We investigated whether dopamine administration influences the outcome from shock. Design:Cohort, multiple-center, observational study. Setting:One hundred and ninety-eight European intensive care units. Patients:All adult patients admitted to a participating intensive care unit between May 1 and May 15, 2002. Interventions:None. Measurements and Main Results:Patients were followed up until death, until hospital discharge, or for 60 days. Shock was defined as hemodynamic compromise necessitating the administration of vasopressor catecholamines. Of 3,147 patients, 1,058 (33.6%) had shock at any time; 462 (14.7%) had septic shock. The intensive care unit mortality rate for shock was 38.3% and 47.4% for septic shock. Of patients in shock, 375 (35.4%) received dopamine (dopamine group) and 683 (64.6%) never received dopamine. Age, gender, Simplified Acute Physiology Score II, and Sequential Organ Failure Assessment score were comparable between the two groups. The dopamine group had higher intensive care unit (42.9% vs. 35.7%, p = .02) and hospital (49.9% vs. 41.7%, p = .01) mortality rates. A Kaplan-Meier survival curve showed diminished 30 day-survival in the dopamine group (log rank = 4.6, p = .032). In a multivariate analysis with intensive care unit outcome as the dependent factor, age, cancer, medical admissions, higher mean Sequential Organ Failure Assessment score, higher mean fluid balance, and dopamine administration were independent risk factors for intensive care unit mortality in patients with shock. Conclusions:This observational study suggests that dopamine administration may be associated with increased mortality rates in shock. There is a need for a prospective study comparing dopamine with other catecholamines in the management of circulatory shock.

Microcirculatory alterations in patients with severe sepsis: Impact of time of assessment and relationship with outcome

Objectives:Sepsis induces microvascular alterations that may play an important role in the development of organ dysfunction. However, the relationship of these alterations to systemic variables and outcome is still not well defined. We investigated which factors may influence microcirculatory alterations in patients with severe sepsis and whether these are independently associated with mortality. Design:Analysis of prospectively collected data from previously published studies by our group. Setting:A 36-bed, medicosurgical university hospital Department of Intensive Care. Patients:A total of 252 patients with severe sepsis in whom the sublingual microcirculation was visualized using orthogonal polarization spectral or sidestream darkfield imaging techniques. Measurements and Main Results:Microcirculatory measurements were obtained either early, within 24h of the onset of severe sepsis (n = 204), or later, after 48h (n = 48). When multiple measurements were obtained, only the first was considered. Although global hemodynamic variables were relatively preserved (mean arterial pressure 70 [65–77] mm Hg, cardiac index 3.3 [2.7–4.0] L/min.m2, and SvO2 68.3 [62.8–74.7]%), microvascular variables were markedly altered (proportion of perfused small vessels 65 [50–74]%, microvascular flow index 2.15 [1.80–2.60], and heterogeneity of proportion of perfused small vessels 35 [20–50]%). Among microcirculatory variables, proportion of perfused small vessels was the strongest predictor of outcome (receiver operating characteristic curve area 0.818 [0.766–0.871], p < 0.001). Survival rates decreased markedly with severity of alterations in the proportion of perfused small vessels (70% and 75% in the two upper proportion of perfused small vessel quartiles compared with 3% and 44% in the two lower quartiles, p < 0.0001). Multivariable analysis identified proportion of perfused small vessels and sequential organ failure assessment score as independent predictors of outcome. Microcirculatory alterations were less severe in the later than in the earlier (proportion of perfused small vessels, 74 [57–82]% vs. 63 [48–71]%, p = 0.004) phase of sepsis. In multivariable analysis focused on the early period of sepsis, proportion of perfused small vessels and lactate were independent predictors of outcome. Conclusions:Microcirculatory alterations are stronger predictors of outcome than global hemodynamic variables.

Assessment of the worldwide burden of critical illness: the Intensive Care Over Nations (ICON) audit

BACKGROUND Global epidemiological data regarding outcomes for patients in intensive care units (ICUs) are scarce, but are important in understanding the worldwide burden of critical illness. We, therefore, did an international audit of ICU patients worldwide and assessed variations between hospitals and countries in terms of ICU mortality. METHODS 730 participating centres in 84 countries prospectively collected data on all adult (>16 years) patients admitted to their ICU between May 8 and May 18, 2012, except those admitted for fewer than 24 h for routine postoperative monitoring. Participation was voluntary. Data were collected daily for a maximum of 28 days in the ICU and patients were followed up for outcome data until death or hospital discharge. In-hospital death was analysed using multilevel logistic regression with three levels: patient, hospital, and country. FINDINGS 10,069 patients were included from ICUs in Europe (5445 patients; 54·1%), Asia (1928; 19·2%), the Americas (1723; 17·1%), Oceania (439; 4·4%), the Middle East (393; 3·9%), and Africa (141; 1·4%). Overall, 2973 patients (29·5%) had sepsis on admission or during the ICU stay. ICU mortality rates were 16·2% (95% CI 15·5-16·9) across the whole population and 25·8% (24·2-27·4) in patients with sepsis. Hospital mortality rates were 22·4% (21·6-23·2) in the whole population and 35·3% (33·5-37·1) in patients with sepsis. Using a multilevel analysis, the unconditional model suggested significant between-country variations (var=0·19, p=0·002) and between-hospital variations (var=0·43, p<0·0001) in the individual risk of in-hospital death. There was a stepwise increase in the adjusted risk of in-hospital death according to decrease in global national income. INTERPRETATION This large database highlights that sepsis remains a major health problem worldwide, associated with high mortality rates in all countries. Our findings also show a significant association between the risk of death and the global national income and suggest that ICU organisation has an important effect on risk of death. FUNDING None.

Characteristics and outcomes of cancer patients in European ICUs

IntroductionIncreasing numbers of cancer patients are being admitted to the intensive care unit (ICU), either for cancer-related complications or treatment-associated side effects, yet there are relatively few data concerning the epidemiology and prognosis of cancer patients admitted to general ICUs. The aim of this study was to assess the characteristics of critically ill cancer patients, and to evaluate their prognosis.MethodsThis was a substudy of the Sepsis Occurrence in Acutely Ill Patients (SOAP) study, a cohort, multicentre, observational study that included data from all adult patients admitted to one of 198 participating ICUs from 24 European countries during the study period. Patients were followed up until death, hospital discharge or for 60 days.ResultsOf the 3147 patients enrolled in the SOAP study, 473 (15%) had a malignancy, 404 (85%) had solid tumours and 69 (15%) had haematological cancer. Patients with solid cancers had the same severity of illness as the non-cancer population, but were older, more likely to be a surgical admission and had a higher frequency of sepsis. Patients with haematological cancer were more severely ill and more commonly had sepsis, acute lung injury/acute respiratory distress syndrome, and renal failure than patients with other malignancies; these patients also had the highest hospital mortality rate (58%). The outcome of all cancer patients was comparable with that in the non-cancer population, with a 27% hospital mortality rate. However, in the subset of patients with more than three failing organs, more than 75% of patients with cancer died compared with about 50% of patients without cancer (p = 0.01).ConclusionsIn this large European study, patients with cancer were more often admitted to the ICU for sepsis and respiratory complications than other ICU patients. Overall, the outcome of patients with solid cancer was similar to that of ICU patients without cancer, whereas patients with haematological cancer had a worse outcome.

Are blood transfusions associated with greater mortality rates? Results of the Sepsis Occurrence in Acutely Ill Patients study.

Background:Studies have suggested worse outcomes in transfused patients and improved outcomes in patients managed with restricted blood transfusion strategies. The authors investigated the relation of blood transfusion to mortality in European intensive care units (ICUs). Methods:The Sepsis Occurrence in Acutely Ill Patients study was a multicenter, observational study that included all adult patients admitted to 198 European ICUs between May 1 and May 15, 2002 and followed them until death, until hospital discharge, or for 60 days. Patients were classified depending on whether they had received a blood transfusion at any time during their ICU stay. Results:Of 3,147 patients, 1,040 (33.0%) received a blood transfusion. These patients were older (mean age, 62 vs. 60 yr; P = 0.035) and were more likely to have liver cirrhosis or hematologic cancer, to be a surgical admission, and to have sepsis. They had a longer duration of ICU stay (5.9 vs. 2.5 days; P < 0.001) and a higher ICU mortality rate (23.0 vs. 16.3%; P < 0.001) but were also more severely ill on admission (Simplified Acute Physiology Score II, 40.2 vs. 34.7; P < 0.001; Sequential Organ Failure Assessment score, 6.5 vs. 4.5; P < 0.001). There was a direct relation between the number of blood transfusions and the mortality rate, but in multivariate analysis, blood transfusion was not significantly associated with a worse mortality rate. Moreover, in 821 pairs matched according to a propensity score, there was a higher 30-day survival rate in the transfusion group than in the other patients (P = 0.004). Conclusion:This observational study does not support the view that blood transfusions are associated with increased mortality rates in acutely ill patients.