An American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference was held in Northbrook in August 1991 with the goal of agreeing on a set of definitions that could be applied to patients with sepsis and its sequelae. New definitions were offered for some terms, while others were discarded. Broad definitions of sepsis and the systemic inflammatory response syndrome were proposed, along with detailed physiologic parameters by which a patient may be categorized. Definitions for severe sepsis, septic shock, hypotension, and multiple organ dysfunction syndrome were also offered. The use of severity scoring methods when dealing with septic patients was recommended as an adjunctive tool to assess mortality. Appropriate methods and applications for the use and testing of new therapies were recommended. The use of these terms and techniques should assist clinicians and researchers who deal with sepsis and its sequelae.

OBJECTIVE

In 1991, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) convened a "Consensus Conference," the goals of which were "to provide a conceptual and a practical framework to define the systemic inflammatory response to infection, which is a progressive injurious process that falls under the generalized term 'sepsis' and includes sepsis-associated organ dysfunction as well." The general definitions introduced as a result of that conference have been widely used in practice and have served as the foundation for inclusion criteria for numerous clinical trials of therapeutic interventions. Nevertheless, there has been an impetus from experts in the field to modify these definitions to reflect our current understanding of the pathophysiology of these syndromes.

METHODS

Several North American and European intensive care societies agreed to revisit the definitions for sepsis and related conditions. This conference was sponsored by the SCCM, The European Society of Intensive Care Medicine (ESICM), The American College of Chest Physicians (ACCP), the American Thoracic Society (ATS), and the Surgical Infection Society (SIS).

METHODS

The conference was attended by 29 participants from Europe and North America. In advance of the conference, five subgroups were formed to evaluate the following areas: signs and symptoms of sepsis, cell markers, cytokines, microbiologic data, and coagulation parameters. The subgroups corresponded electronically before the conference and met in person during the conference. A spokesperson for each group presented the deliberation of each group to all conference participants during a plenary session. A writing committee was formed at the conference and developed the current article based on executive summary documents generated by each group and the plenary group presentations. The present article serves as the final report of the 2001 International Sepsis Definitions Conference.

CONCLUSIONS

This document reflects a process whereby a group of experts and opinion leaders revisited the 1992 sepsis guidelines and found that apart from expanding the list of signs and symptoms of sepsis to reflect clinical bedside experience, no evidence exists to support a change to the definitions. This lack of evidence serves to underscore the challenge still present in diagnosing sepsis in 2003 for clinicians and researchers and also provides the basis for introducing PIRO as a hypothesis-generating model for future research.

The acute respiratory distress syndrome (ARDS), a process of nonhydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies, carries a high morbidity, mortality (10 to 90%), and financial cost. The reported annual incidence in the United States is 150,000 cases, but this figure has been challenged, and it may be different in Europe. Part of the reason for these uncertainties are the heterogeneity of diseases underlying ARDS and the lack of uniform definitions for ARDS. Thus, those who wish to know the true incidence and outcome of this clinical syndrome are stymied. The American-European Consensus Committee on ARDS was formed to focus on these issues and on the pathophysiologic mechanisms of the process. It was felt that international coordination between North America and Europe in clinical studies of ARDS was becoming increasingly important in order to address the recent plethora of potential therapeutic agents for the prevention and treatment of ARDS.

The objective of this study was to refine the APACHE (Acute Physiology, Age, Chronic Health Evaluation) methodology in order to more accurately predict hospital mortality risk for critically ill hospitalized adults. We prospectively collected data on 17,440 unselected adult medical/surgical intensive care unit (ICU) admissions at 40 US hospitals (14 volunteer tertiary-care institutions and 26 hospitals randomly chosen to represent intensive care services nationwide). We analyzed the relationship between the patient's likelihood of surviving to hospital discharge and the following predictive variables: major medical and surgical disease categories, acute physiologic abnormalities, age, preexisting functional limitations, major comorbidities, and treatment location immediately prior to ICU admission. The APACHE III prognostic system consists of two options: (1) an APACHE III score, which can provide initial risk stratification for severely ill hospitalized patients within independently defined patient groups; and (2) an APACHE III predictive equation, which uses APACHE III score and reference data on major disease categories and treatment location immediately prior to ICU admission to provide risk estimates for hospital mortality for individual ICU patients. A five-point increase in APACHE III score (range, 0 to 299) is independently associated with a statistically significant increase in the relative risk of hospital death (odds ratio, 1.10 to 1.78) within each of 78 major medical and surgical disease categories. The overall predictive accuracy of the first-day APACHE III equation was such that, within 24 h of ICU admission, 95 percent of ICU admissions could be given a risk estimate for hospital death that was within 3 percent of that actually observed (r2 = 0.41; receiver operating characteristic = 0.90). Recording changes in the APACHE III score on each subsequent day of ICU therapy provided daily updates in these risk estimates. When applied across the individual ICUs, the first-day APACHE III equation accounted for the majority of variation in observed death rates (r2 = 0.90, p less than 0.0001).

OBJECTIVE

To construct a scoring system for the prediction of early mortality in cardiac surgical patients in Europe on the basis of objective risk factors.

METHODS

The EuroSCORE database was divided into developmental and validation subsets. In the former, risk factors deemed to be objective, credible, obtainable and difficult to falsify were weighted on the basis of regression analysis. An additive score of predicted mortality was constructed. Its calibration and discrimination characteristics were assessed in the validation dataset. Thresholds were defined to distinguish low, moderate and high risk groups.

RESULTS

The developmental dataset had 13,302 patients, calibration by Hosmer Lemeshow Chi square was (8) = 8.26 (P < 0.40) and discrimination by area under ROC curve was 0.79. The validation dataset had 1479 patients, calibration Chi square (10) = 7.5, P < 0.68 and the area under the ROC curve was 0.76. The scoring system identified three groups of risk factors with their weights (additive % predicted mortality) in brackets. Patient-related factors were age over 60 (one per 5 years or part thereof), female (1), chronic pulmonary disease (1), extracardiac arteriopathy (2), neurological dysfunction (2), previous cardiac surgery (3), serum creatinine >200 micromol/l (2), active endocarditis (3) and critical preoperative state (3). Cardiac factors were unstable angina on intravenous nitrates (2), reduced left ventricular ejection fraction (30-50%: 1, <30%: 3), recent (<90 days) myocardial infarction (2) and pulmonary systolic pressure >60 mmHg (2). Operation-related factors were emergency (2), other than isolated coronary surgery (2), thoracic aorta surgery (3) and surgery for postinfarct septal rupture (4). The scoring system was then applied to three risk groups. The low risk group (EuroSCORE 1-2) had 4529 patients with 36 deaths (0.8%), 95% confidence limits for observed mortality (0.56-1.10) and for expected mortality (1.27-1.29). The medium risk group (EuroSCORE 3-5) had 5977 patients with 182 deaths (3%), observed mortality (2.62-3.51), predicted (2.90-2.94). The high risk group (EuroSCORE 6 plus) had 4293 patients with 480 deaths (11.2%) observed mortality (10.25-12.16), predicted (10.93-11.54). Overall, there were 698 deaths in 14,799 patients (4.7%), observed mortality (4.37-5.06), predicted (4.72-4.95).

CONCLUSIONS

EuroSCORE is a simple, objective and up-to-date system for assessing heart surgery, soundly based on one of the largest, most complete and accurate databases in European cardiac surgical history. We recommend its widespread use.

OBJECTIVE

To relate morbidity and mortality risk to preoperative severity of illness in patients undergoing coronary artery bypass grafting.

METHODS

Retrospective analysis of 5051 patients using univariate and logistic regression to identify risk factors associated with perioperative morbidity and mortality. Prospective application of models to a subsequent 2-year validation cohort (n = 4069).

METHODS

Cleveland Clinic Foundation.

METHODS

All adult patients undergoing coronary artery bypass graft surgery between July 1, 1986, and June 30, 1988 (reference group), and July 1, 1988, and June 30, 1990 (validation group).

METHODS

Mortality and morbidity (myocardial infarction and use of intra-aortic balloon pump, mechanical ventilation for 3 or more days, neurological deficit, oliguric or anuric renal failure, or serious infection).

RESULTS

Emergency procedure, preoperative serum creatinine levels of greater than 168 mumol/L, severe left ventricular dysfunction, preoperative hematocrit of 0.34, increasing age, chronic pulmonary disease, prior vascular surgery, reoperation, and mitral valve insufficiency were found to be predictive of mortality. In addition to these factors, diabetes mellitus, body weight of 65 kg or less [corrected], aortic stenosis, and cerebrovascular disease were predictive of morbidity. Logistic regression equations were developed, and a simple additive score for clinical use was designed by allocating each of these risk-factor values of 1 to 6 points. Both methods predict mortality. Increased morbidity was demonstrated with increases in score.

CONCLUSIONS

The logistic or clinical models developed are superior to the currently available methods for comparing mortality outcome and provide previously unavailable information on morbidity based on preoperative status. The clinical scoring system is useful for preoperative estimates of morbidity and mortality risks.

Until recently, more than 30 different definitions of acute renal failure (ARF) had been used in the literature. This lack of a common reference point created confusion and made comparisons difficult. It also led to strong advocacy of a consensus definition. In response to the need for a common definition and classification of ARF, the Acute Dialysis Quality Initiative (ADQI) group of experts developed and published a consensus definition of ARF. This definition goes under the acronym of RIFLE to indicate that it classifies patients with renal dysfunction according to the degree of impairment into patients at risk (R), with injury (I), with failure (F), with sustained loss (L) and with end-stage (E) status in relation to their renal function. This editorial aims to summarize and interpret recent findings concerning the application of the RIFLE criteria to the assessment of the epidemiology and the prediction of the outcome of ARF.

BACKGROUND

The inflammatory response triggered by cardiac surgery with cardiopulmonary bypass (CPB) is a primary mechanism in the pathogenesis of postoperative myocardial infarction (PMI), a multifactorial disorder with significant inter-patient variability poorly predicted by clinical and procedural factors. We tested the hypothesis that candidate gene polymorphisms in inflammatory pathways contribute to risk of PMI after cardiac surgery.

RESULTS

We genotyped 48 polymorphisms from 23 candidate genes in a prospective cohort of 434 patients undergoing elective cardiac surgery with CPB. PMI was defined as creatine kinase-MB isoenzyme level>> or = 10x upper limit of normal at 24 hours postoperatively. A 2-step analysis strategy was used: marker selection, followed by model building. To minimize false-positive associations, we adjusted for multiple testing by permutation analysis, Bonferroni correction, and controlling the false discovery rate; 52 patients (12%) experienced PMI. After adjusting for multiple comparisons and clinical risk factors, 3 polymorphisms were found to be independent predictors of PMI (adjusted P<0.05; false discovery rate <10%). These gene variants encode the proinflammatory cytokine interleukin 6 (IL6 -572G>C; odds ratio [OR], 2.47), and 2 adhesion molecules: intercellular adhesion molecule-1 (ICAM1 Lys469Glu; OR, 1.88), and E-selectin (SELE 98G>T; OR, 0.16). The inclusion of genotypic information from these polymorphisms improved prediction models for PMI based on traditional risk factors alone (C-statistic 0.764 versus 0.703).

CONCLUSIONS

Functional genetic variants in cytokine and leukocyte-endothelial interaction pathways are independently associated with severity of myonecrosis after cardiac surgery. This may aid in preoperative identification of high-risk cardiac surgical patients and development of novel cardioprotective strategies.

BACKGROUND

Postoperative atrial fibrillation (AF) occurs in as many as 50% of cardiac surgery patients and represents the most common postoperative rhythm complication. The cause of AF after cardiac surgery is incompletely understood, and its prevention remains suboptimal. Currently the role of inflammation and oxidative stress on electrical remodeling is under investigation, and recent studies have demonstrated that C-reactive protein levels are elevated in AF. The purpose of the present study was to investigate the correlation between the postoperative white blood cell (WBC) count as a marker of inflammation and the development of postoperative AF after cardiac surgery.

RESULTS

Patients undergoing elective cardiac surgery in the absence of significant left ventricular dysfunction (n = 253; average age, 65 +/- 11 years) were recruited to the present prospective study. Atrial fibrillation developed during the postoperative period in 99 patients (39.1%) of the total study population. The WBC count was prospectively assessed in all patients to determine the predictive value of baseline and postoperative WBC count on development of postoperative AF. Baseline WBC count was 6.8 +/- 1.9 x 10(9)/L and 6.8 +/- 2.2 x 10(9)/L (p = 0.95), respectively, in patients with and without postoperative AF; and postoperative peak WBC count was 16.3 +/- 6.5 x 10(9)/L and 15 +/- 4.2 x 10(9)/L (p = 0.048), respectively, in patients without postoperative AF. However, neither baseline nor peak monocyte count differed significantly among patients with and without postoperative AF: 0.43 +/- 0.15 x 10(9)/L and 0.46 +/- 0.46 x 10(9)/L (p = 0.5), and 0.91 +/- 0.3 x 10(9)/L and 0.93 +/- 0.4 x 10(9)/L (p = 0.8), respectively. In addition to a more pronounced increase in peak WBC count (above v below median; odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-2.7; p < 0.05), increasing age (above v below median; OR, 2.6; CI, 1.2-3.9; p < 0.01), surgery for valvular heart disease versus coronary artery bypass grafting (OR, 2.8; CI, 1.1-3.5; p < 0.01), development of postoperative complications, such as stroke, infections, or unstable hemodynamics (OR, 1.9; CI, 1.0-7.5; p < 0.05), and perioperative nonuse of beta-adrenergic blockers (OR, 1.7; CI, 1.1-4.9; p < 0.05) were identified as independent predictors of postoperative AF by multivariate logistic regression analysis.

CONCLUSIONS

Cardiac surgery is associated with an elevated postoperative WBC count that represents a common marker of inflammation. A more pronounced increase in postoperative WBC count independently predicts development of postoperative AF. These data provide additional evidence to support the association between the inflammatory response and postoperative AF.

BACKGROUND

Delirium is a frequent form of psychopathology in elderly hospitalized patients; it is a symptom of acute somatic illness. The consequences of delirium include high morbidity and mortality, lengthened hospital stay, and nursing home placement. Early recognition of delirium symptoms enables the underlying cause to be diagnosed and treated and can prevent negative outcomes. The aim of this study was to determine which of the two delirium observation screening scales, the NEECHAM Confusion Scale or the Delirium Observation Screening (DOS) scale, has the best discriminative capacity for diagnosing delirium and which is more practical for daily use by nurses.

METHODS

The project was conducted on four wards of a university hospital; 87 patients were included. During 3 shifts, these patients were observed for symptoms of delirium, which were rated on both scales. A DSM-IV diagnosis of delirium was made or rejected by a geriatrician. Nurses were asked to rate the practical value of both scales using a structured questionnaire.

RESULTS

The sensitivity (0.89-1.00) and specificity (0.86-0.88) of the DOS and the NEECHAM were high for both scales. Nurses rated the practical use of the DOS scale as significantly easier than the NEECHAM.

CONCLUSIONS

Successful implementation of standardized observation depends largely on the consent of professionals and their acceptance of a scale. In our hospital, we therefore chose to involve nurses in the choice between two instruments. During the study they were able to experience both scales and give their opinion on ease of use. In the final decision on the instrument we found that both scales were very acceptable in terms of sensitivity and specificity, so the opinion of the nurses was decisive. They were positive about both instruments; however, they rated the DOS scale as significantly easier to use and relevant to their practice. Our findings were obtained from a single site study with a small sample, so a large comparative trial to study the value of both scales further is recommended. On the basis of our experience during this study and findings from the literature with regard to the implementation of delirium guidelines, we will monitor the further implementation of the DOS Scale in our hospital with intensive consultation.

OBJECTIVE

The aim of the present study was to evaluate the performance of three different preoperative risk models in the prediction of postoperative morbidity and mortality in coronary artery bypass (CAB) surgery.

METHODS

Data on 1132 consecutive CAB patients were prospectively collected, including preoperative risk factors and postoperative morbidity and in-hospital mortality. The preoperative risk models CABDEAL, EuroSCORE and Cleveland model were used to predict morbidity and mortality. A C statistic (receiver operating characteristic (ROC) curve) was used to test the discrimination of these models.

RESULTS

The area under the ROC curve for morbidity was 0.772 for the CABDEAL, 0.694 for the EuroSCORE and 0.686 for the Cleveland model. Major morbidity due to postoperative complications occurred in 268 patients (23.6%). The mortality rate was 3.4% (n=38 patients). The ROC curve areas for prediction of mortality were 0.711 for the CABDEAL, 0.826 for the EuroSCORE and 0.858 for the Cleveland model.

CONCLUSIONS

The CABDEAL model was initially developed for the prediction of major morbidity. Thus, it is not surprising that this model evinced the highest predictive value for increased morbidity in this database. Both the Cleveland and the EuroSCORE models were better predictive of mortality. These results have implications for the selection of risk indices for different purposes. The simple additive CABDEAL model can be used as a hand-held model for preoperative estimation of patients' risk of postoperative morbidity, while the EuroSCORE and Cleveland models are to be preferred for the prediction of mortality in a large patient sample.

The systemic inflammatory response to cardiopulmonary bypass was assessed in 20 patients who underwent elective coronary artery bypass grafting with flat-sheet membrane oxygenation (group I; n = 10; age, 59 +/- 5 years) or bubble oxygenation (group II; n = 10; age, 62 +/- 8 years). The duration of cardiopulmonary bypass was 46 +/- 12 minutes in group I and 47 +/- 15 minutes in group II. Plasma interleukin-6, plasma interleukin-1 beta, transpulmonary leukocyte counts, pulmonary hemodynamic variables, and respiratory index were determined in all patients perioperatively. The plasma interleukin-6 response (median [range]) was similar in both groups at the end of the operation, peaked 4 hours postoperatively (99 [30 to 320] pg/mL in group I; 123 [21 to 300] pg/mL in group II; p greater than 0.05), and remained elevated 48 hours postoperatively (76 [9 to 140] pg/mL in group I; 65 [25 to 159] pg/mL in group II; p greater than 0.05). No significant interleukin-1 beta response was demonstrated. Pulmonary neutrophil and lymphocyte sequestration was observed on commencement of cardiopulmonary bypass in group II but did not occur in either group on discontinuation of cardiopulmonary bypass. Pulmonary vascular resistance at the end of the operation (82 [48 to 320] dynes.s.cm-5 in group I; 119 [54 to 385] dynes.s.cm-5 in group II; p greater than 0.05) was similar to preoperative values (151 [30 to 327] dynes.s.cm-5 in group I; 185 [62 to 291] dynes.s.cm-5 in group II; p greater than 0.05). The respiratory index at the end of the operation was similarly and significantly increased in both groups (1.26 [0.92 to 4.17] in group I; 1.44 [0.73 to 3.30] in group II).(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND

Although some data suggest that the individual genetic predisposition for developing major or minor degrees of postoperative systemic inflammatory reaction may influence postoperative morbidity, this hypothesis has not been clinically tested to date. Methods and results The -174 G/C polymorphism of the promoter of the interleukin 6 gene was determined preoperatively in 111 consecutive patients submitted to primary isolated coronary artery bypass. The results of the genetic analysis were then correlated with the postoperative interleukin 6 levels and the development of postoperative renal and pulmonary complications. G homozygotes had significantly higher interleukin 6 levels postoperatively (P <.0001 for the difference between areas under the curve). These patients also had worse postoperative pulmonary and renal function. The mean perioperative difference in serum creatinine, potassium, and nitrogen was 0.82 +/- 0.34, 0.99 +/- 0.44, and 10.1 +/- 7.8 mg/dL versus 0.18 +/- 0.14, 0.15 +/- 0.48, and 2.6 +/- 4.1 mg/dL for GG versus non-GG carriers (P <.0001), respectively. The mean respiratory index at 6 and 12 hours was 2.9 +/- 0.8 and 2.8 +/- 0.3 versus 2.1 +/- 0.5 and 1.3 +/- 0.1, respectively (P <.0001). The mean duration of mechanical ventilation was 22.5 +/- 2.1 versus 12.7 +/- 6.7 hours (P <.01). A correlation was found between postoperative interleukin 6 levels and renal and pulmonary complications.

CONCLUSIONS

The interleukin 6 -174 G/C polymorphism modulates postoperative interleukin 6 levels and is associated with the degree of postoperative renal and pulmonary dysfunction and in-hospital stay after coronary surgery.

A relationship between the inflammatory response to cardiopulmonary bypass (CPB) and fever after coronary artery bypass graft surgery (CABG) is assumed, but has not been studied. Therefore, we sought to assess the temporal pattern of cytokines' elevation and its association with post-CABG fever. In 355 primary elective CABG patients, serum cytokines (TNF-alpha, IL-1ra, IL-1beta, IL-6, and IL-8) were measured before surgery, at cessation of CPB and 2.5, 4.5, 24, and 48 h post-CPB. Fever was defined as a temperature >38 degrees C. TNF-alpha, IL-1beta and IL-8 peaked within the first 2.5 h after bypass, returning to near normal levels by 24h and increasing again by 48 h. IL-6 peaked early after bypass and remained elevated at 48 h. IL-1ra was elevated early, before returning to baseline by 24 h. Postoperative fever developed in 27% of patients. Increased IL-6 levels and male gender were significant predictors of fever (C-index=0.68; p=0.0003). No other cytokine showed a significant association with fever development. Of note is the previously undescribed bimodal pattern of cytokines' secretion after CABG. The association of fever with IL-6 levels suggests inflammatory mediation.

The purpose of inflammation is to combat various agents that may injure the tissues. Conditions such as CPB can often cause systemic inflammation and dysfunction of major organs. Pulmonary, renal, myocardial and intestinal function may suffer various degrees of impairment during and after cardiac surgery. Although changes in major organs usually remain clinically insignificant, severe organ failure is not uncommon. The process of systemic inflammation proceeds through activation of serum proteins, activation of leucocytes and endothelial cells, secretion of cytokines, leucocyte-endothelial cell interaction, leucocyte extravasation and tissue damage. Several anti-inflammatory strategies have already been used, some of which have given promising results pertaining to further reduction in the rate of the inflammation-related complications in cardiac surgical patients.

The potential of pentoxifylline (PTX) to modify systemic inflammatory responses and lung injury following cardiopulmonary bypass (CPB) was studied in 20 patients undergoing elective coronary artery surgery. Ten control patients were compared with ten patients who received a PTX infusion of 1 mg kg-1 h-1 during surgery. Intra-vascular pulmonary leukocyte sequestration was observed in neither group following discontinuation of CPB. Plasma elastase-alpha-1-antiprotease complex rose three-fold from baseline in both groups to peak at sternal closure. No significant plasma interleukin-1 (IL-1) response was detected. Plasma interleukin-6 (IL-6) rose in both groups from baseline to peak 4 h postoperatively. There was no correlation between plasma levels of elastase complex, IL-1 or IL-6 and impairment of postoperative oxygenation. CPB was associated with significant postoperative hypoxaemia and systemic release of neutrophil elastase and IL-6 but PTX, at the given dose, did not abrogate these responses.