Original Article

Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock

Emanuel Rivers, M.D., M.P.H., Bryant Nguyen, M.D., Suzanne Havstad, M.A., Julie Ressler, B.S., Alexandria Muzzin, B.S., Bernhard Knoblich, M.D., Edward Peterson, Ph.D., and Michael Tomlanovich, M.D. for the Early Goal-Directed Therapy Collaborative Group

N Engl J Med 2001; 345:1368-1377November 8, 2001DOI: 10.1056/NEJMoa010307

Abstract

Background

Goal-directed therapy has been used for severe sepsis and septic shock in the intensive care unit. This approach involves adjustments of cardiac preload, afterload, and contractility to balance oxygen delivery with oxygen demand. The purpose of this study was to evaluate the efficacy of early goal-directed therapy before admission to the intensive care unit.

Methods

We randomly assigned patients who arrived at an urban emergency department with severe sepsis or septic shock to receive either six hours of early goal-directed therapy or standard therapy (as a control) before admission to the intensive care unit. Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment. In-hospital mortality (the primary efficacy outcome), end points with respect to resuscitation, and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were obtained serially for 72 hours and compared between the study groups.

Results

Of the 263 enrolled patients, 130 were randomly assigned to early goal-directed therapy and 133 to standard therapy; there were no significant differences between the groups with respect to base-line characteristics. In-hospital mortality was 30.5 percent in the group assigned to early goal-directed therapy, as compared with 46.5 percent in the group assigned to standard therapy (P=0.009). During the interval from 7 to 72 hours, the patients assigned to early goal-directed therapy had a significantly higher mean (±SD) central venous oxygen saturation (70.4±10.7 percent vs. 65.3±11.4 percent), a lower lactate concentration (3.0±4.4 vs. 3.9±4.4 mmol per liter), a lower base deficit (2.0±6.6 vs. 5.1±6.7 mmol per liter), and a higher pH (7.40±0.12 vs. 7.36±0.12) than the patients assigned to standard therapy (P≤0.02 for all comparisons). During the same period, mean APACHE II scores were significantly lower, indicating less severe organ dysfunction, in the patients assigned to early goal-directed therapy than in those assigned to standard therapy (13.0±6.3 vs. 15.9±6.4, P<0.001).

Conclusions

Early goal-directed therapy provides significant benefits with respect to outcome in patients with severe sepsis and septic shock.

Media in This Article

Figure 2Protocol for Early Goal-Directed Therapy.
Figure 1Overview of Patient Enrollment and Hemodynamic Support.
Article

The systemic inflammatory response syndrome can be self-limited or can progress to severe sepsis and septic shock.1 Along this continuum, circulatory abnormalities (intravascular volume depletion, peripheral vasodilatation, myocardial depression, and increased metabolism) lead to an imbalance between systemic oxygen delivery and oxygen demand, resulting in global tissue hypoxia or shock.2 An indicator of serious illness, global tissue hypoxia is a key development preceding multiorgan failure and death.2 The transition to serious illness occurs during the critical “golden hours,” when definitive recognition and treatment provide maximal benefit in terms of outcome. These golden hours may elapse in the emergency department,3 hospital ward,4 or the intensive care unit.5

Early hemodynamic assessment on the basis of physical findings, vital signs, central venous pressure,6 and urinary output7 fails to detect persistent global tissue hypoxia. A more definitive resuscitation strategy involves goal-oriented manipulation of cardiac preload, afterload, and contractility to achieve a balance between systemic oxygen delivery and oxygen demand.2 End points used to confirm the achievement of such a balance (hereafter called resuscitation end points) include normalized values for mixed venous oxygen saturation, arterial lactate concentration, base deficit, and pH.8 Mixed venous oxygen saturation has been shown to be a surrogate for the cardiac index as a target for hemodynamic therapy.9 In cases in which the insertion of a pulmonary-artery catheter is impractical, venous oxygen saturation can be measured in the central circulation.10

Whereas the incidence of septic shock has steadily increased during the past several decades, the associated mortality rates have remained constant or have decreased only slightly.11 Studies of interventions such as immunotherapy,12 hemodynamic optimization,9,13 or pulmonary-artery catheterization14 enrolled patients up to 72 hours after admission to the intensive care unit. The negative results of studies of the use of hemodynamic variables as end points (“hemodynamic optimization”), in particular, prompted suggestions that future studies involve patients with similar causes of disease13 or with global tissue hypoxia (as reflected by elevated lactate concentrations)15 and that they examine interventions begun at an earlier stage of disease.16,17

We examined whether early goal-directed therapy before admission to the intensive care unit effectively reduces the incidence of multiorgan dysfunction, mortality, and the use of health care resources among patients with severe sepsis or septic shock.

Methods

Approval of Study Design

This prospective, randomized study was approved by the institutional review board for human research and was conducted under the auspices of an independent safety, efficacy, and data monitoring committee.

Eligibility

Eligible adult patients who presented to the emergency department of an 850-bed academic tertiary care hospital with severe sepsis, septic shock, or the sepsis syndrome from March 1997 through March 2000 were assessed for possible enrollment according to the inclusion18,19 and exclusion criteria (Figure 1Figure 1Overview of Patient Enrollment and Hemodynamic Support.). The criteria for inclusion were fulfillment of two of four criteria for the systemic inflammatory response syndrome and a systolic blood pressure no higher than 90 mm Hg (after a crystalloid-fluid challenge of 20 to 30 ml per kilogram of body weight over a 30-minute period) or a blood lactate concentration of 4 mmol per liter or more. The criteria for exclusion from the study were an age of less than 18 years, pregnancy, or the presence of an acute cerebral vascular event, acute coronary syndrome, acute pulmonary edema, status asthmaticus, cardiac dysrhythmias (as a primary diagnosis), contraindication to central venous catheterization, active gastrointestinal hemorrhage, seizure, drug overdose, burn injury, trauma, a requirement for immediate surgery, uncured cancer (during chemotherapy), immunosuppression (because of organ transplantation or systemic disease), do-not-resuscitate status, or advanced directives restricting implementation of the protocol.

The clinicians who assessed the patients at this stage were unaware of the patients' treatment assignments. After written informed consent was obtained (in compliance with the Helsinki Declaration20), the patients were randomly assigned either to early goal-directed therapy or to standard (control) therapy in computer-generated blocks of two to eight. The study-group assignments were placed in sealed, opaque, randomly assorted envelopes, which were opened by a hospital staff member who was not one of the study investigators.

Treatment

The patients were treated in a nine-bed unit in the emergency department by an emergency physician, two residents, and three nurses.3 The study was conducted during the routine treatment of other patients in the emergency department. After arterial and central venous catheterization, patients in the standard-therapy group were treated at the clinicians' discretion according to a protocol for hemodynamic support21 (Figure 1), with critical-care consultation, and were admitted for inpatient care as soon as possible. Blood, urine, and other relevant specimens for culture were obtained in the emergency department before the administration of antibiotics. Antibiotics were given at the discretion of the treating clinicians. Antimicrobial therapy was deemed adequate if the in vitro sensitivities of the identified microorganisms matched the particular antibiotic ordered in the emergency department.22

The patients assigned to early goal-directed therapy received a central venous catheter capable of measuring central venous oxygen saturation (Edwards Lifesciences, Irvine, Calif.); it was connected to a computerized spectrophotometer for continuous monitoring. Patients were treated in the emergency department according to a protocol for early goal-directed therapy (Figure 2Figure 2Protocol for Early Goal-Directed Therapy.) for at least six hours and were transferred to the first available inpatient beds. Monitoring of central venous oxygen saturation was then discontinued. Critical-care clinicians (intensivists, fellows, and residents providing 24-hour in-house coverage) assumed the care of all the patients; these physicians were unaware of the patients' study-group assignments. The study investigators did not influence patient care in the intensive care unit.

The protocol was as follows. A 500-ml bolus of crystalloid was given every 30 minutes to achieve a central venous pressure of 8 to 12 mm Hg. If the mean arterial pressure was less than 65 mm Hg, vasopressors were given to maintain a mean arterial pressure of at least 65 mm Hg. If the mean arterial pressure was greater than 90 mm Hg, vasodilators were given until it was 90 mm Hg or below. If the central venous oxygen saturation was less than 70 percent, red cells were transfused to achieve a hematocrit of at least 30 percent. After the central venous pressure, mean arterial pressure, and hematocrit were thus optimized, if the central venous oxygen saturation was less than 70 percent, dobutamine administration was started at a dose of 2.5 μg per kilogram of body weight per minute, a dose that was increased by 2.5 μg per kilogram per minute every 30 minutes until the central venous oxygen saturation was 70 percent or higher or until a maximal dose of 20 μg per kilogram per minute was given. Dobutamine was decreased in dose or discontinued if the mean arterial pressure was less than 65 mm Hg or if the heart rate was above 120 beats per minute. To decrease oxygen consumption, patients in whom hemodynamic optimization could not be achieved received mechanical ventilation and sedatives.

Outcome Measures

The patients' temperature, heart rate, urine output, blood pressure, and central venous pressure were measured continuously for the first 6 hours of treatment and assessed every 12 hours for 72 hours. Arterial and venous blood gas values (including central venous oxygen saturation measured by in vitro co-oximetry; Nova Biomedical, Waltham, Mass.), lactate concentrations, and coagulation-related variables and clinical variables required for determination of the Acute Physiology and Chronic Health Evaluation (APACHE II) score (on a scale from 0 to 71, with higher scores indicating more severe organ dysfunction),23 the Simplified Acute Physiology Score II (SAPS II, on a scale from 0 to 174, with higher scores indicating more severe organ dysfunction),24 and the Multiple Organ Dysfunction Score (MODS, on a scale from 0 to 24, with higher scores indicating more severe organ dysfunction)25 were obtained at base line (0 hours) and at 3, 6, 12, 24, 36, 48, 60, and 72 hours.2,26 The results of laboratory tests required only for purposes of the study were made known only to the study investigators. Patients were followed for 60 days or until death. The consumption of health care resources (indicated by the duration of vasopressor therapy and mechanical ventilation and the length of the hospital stay) was also examined.

Statistical Analysis

In-hospital mortality was the primary efficacy end point. Secondary end points were the resuscitation end points, organ-dysfunction scores, coagulation-related variables, administered treatments, and the consumption of health care resources. Assuming a rate of refusal or exclusion of 10 percent, a two-sided type I error rate of 5 percent, and a power of 80 percent, we calculated that a sample size of 260 patients was required to permit the detection of a 15 percent reduction in in-hospital mortality. Kaplan–Meier estimates of mortality, along with risk ratios and 95 percent confidence intervals, were used to describe the relative risk of death. Differences between the two groups at base line were tested with the use of Student's t-test, the chi-square test, or Wilcoxon's rank-sum test. Incremental analyses of the area under the curve were performed to quantify differences during the interval from base line to six hours after the start of treatment. For the data at six hours, analysis of covariance was used with the base-line values as the covariates. Mixed models were used to assess the effect of treatment on prespecified secondary variables during the interval from 7 to 72 hours after the start of treatment.27 An independent, 12-member external safety, efficacy, and data monitoring committee reviewed interim analyses of the data after one third and two thirds of the patients had been enrolled and at both times recommended that the trial be continued. To adjust for the two interim analyses, the alpha spending function of DeMets and Lan28 was used to determine that a P value of 0.04 or less would be considered to indicate statistical significance.

Results

Base-Line Characteristics

We evaluated 288 patients; 8.7 percent were excluded or did not consent to participate. The 263 patients enrolled were randomly assigned to undergo either standard therapy or early goal-directed therapy; 236 patients completed the initial six-hour study period. All 263 were included in the intention-to-treat analyses. The patients assigned to standard therapy stayed a significantly shorter time in the emergency department than those assigned to early goal-directed therapy (mean [±SD], 6.3±3.2 vs. 8.0±2.1 hours; P<0.001). There was no significant difference between the groups in any of the base-line characteristics, including the adequacy and duration of antibiotic therapy (Table 1Table 1Base-Line Characteristics of the Patients.). Vital signs, resuscitation end points, organ-dysfunction scores, and coagulation-related variables were also similar in the two study groups at base line (Table 2Table 2Vital Signs, Resuscitation End Points, Organ-Dysfunction Scores, and Coagulation Variables.).

Twenty-seven patients did not complete the initial six-hour study period (14 assigned to standard therapy and 13 assigned to early goal-directed therapy), for the following reasons: discontinuation of aggressive medical treatment (in 5 patients in each group), discontinuation of aggressive surgical treatment (in 2 patients in each group), a need for immediate surgery (in 4 patients assigned to standard therapy and in 3 assigned to early goal-directed therapy), a need for interventional urologic, cardiologic, or angiographic procedures (in 2 patients in each group), and refusal to continue participation (in 1 patient in each group) (P=0.99 for all comparisons). There were no significant differences between the patients who completed the initial six-hour study period and those who did not in any of the base-line characteristics or base-line vital signs, resuscitation end points, organ-dysfunction scores, or coagulation-related variables (data not shown).

Vital Signs and Resuscitation End Points

During the initial six hours after the start of therapy, there was no significant difference between the two study groups in the mean heart rate (P=0.25) or central venous pressure (P=0.22) (Table 2). During this period, the mean arterial pressure was significantly lower in the group assigned to standard therapy than in the group assigned to early goal-directed therapy (P<0.001), but in both groups the goal of 65 mm Hg or higher was met by all the patients. The goal of 70 percent or higher for central venous oxygen saturation was met by 60.2 percent of the patients in the standard-therapy group, as compared with 94.9 percent of those in the early-therapy group (P<0.001). The combined hemodynamic goals for central venous pressure, mean arterial pressure, and urine output (with adjustment for patients with end-stage renal failure) were achieved in 86.1 percent of the standard-therapy group, as compared with 99.2 percent of the early-therapy group (P<0.001). During this period, the patients assigned to standard therapy had a significantly lower central venous oxygen saturation (P<0.001) and a greater base deficit (P=0.006) than those assigned to early goal-directed therapy; the two groups had similar lactate concentrations (P=0.62) and similar pH values (P=0.26).

During the period from 7 to 72 hours after the start of treatment, the patients assigned to standard therapy had a significantly higher heart rate (P=0.04) and a significantly lower mean arterial pressure (P<0.001) than the patients assigned to early goal-directed therapy; the two groups had a similar central venous pressure (P=0.68). During this period, those assigned to standard therapy also had a significantly lower central venous oxygen saturation than those assigned to early goal-directed therapy (P<0.001), as well as a higher lactate concentration (P=0.02), a greater base deficit (P<0.001), and a lower pH (P<0.001).

Organ Dysfunction and Coagulation Variables

During the period from 7 to 72 hours, the APACHE II score, SAPS II, and MODS were significantly higher in the patients assigned to standard therapy than in the patients assigned to early goal-directed therapy (P<0.001 for all comparisons) (Table 2). During this period, the prothrombin time was significantly greater in the patients assigned to standard therapy than in those assigned to early goal-directed therapy (P=0.001), as was the concentration of fibrin-split products (P<0.001) and the concentration of D-dimer (P=0.006). The two groups had a similar partial-thromboplastin time (P=0.06), fibrinogen concentration (P=0.21), and platelet count (P=0.51) (Table 2).

Mortality

In-hospital mortality rates were significantly higher in the standard-therapy group than in the early-therapy group (P=0.009), as was the mortality at 28 days (P=0.01) and 60 days (P=0.03) (Table 3Table 3Kaplan–Meier Estimates of Mortality and Causes of In-Hospital Death.). The difference between the groups in mortality at 60 days primarily reflected the difference in in-hospital mortality. Similar results were obtained after data from the 27 patients who did not complete the initial six-hour study period were excluded from the analysis (data not shown). The rate of in-hospital death due to sudden cardiovascular collapse was significantly higher in the standard-therapy group than in the early-therapy group (P=0.02); the rate of death due to multiorgan failure was similar in the two groups (P=0.27).

Administered Treatments

During the initial six hours, the patients assigned to early goal-directed therapy received significantly more fluid than those assigned to standard therapy (P<0.001) and more frequently received red-cell transfusion (P<0.001) and inotropic support (P<0.001), whereas similar proportions of patients in the two groups required vasopressors (P=0.62) and mechanical ventilation (P=0.90) (Table 4Table 4Treatments Administered.). During the period from 7 to 72 hours, however, the patients assigned to standard therapy received significantly more fluid than those assigned to early goal-directed therapy (P=0.01) and more often received red-cell transfusion (P<0.001) and vasopressors (P=0.03) and underwent mechanical ventilation (P<0.001) and pulmonary-artery catheterization (P=0.04); the rate of use of inotropic agents was similar in the two groups (P=0.14) (Table 4). During the overall period from base line to 72 hours after the start of treatment, there was no significant difference between the two groups in the total volume of fluid administered (P=0.73) or the rate of use of inotropic agents (P=0.15), although a greater proportion of the patients assigned to standard therapy than of those assigned to early goal-directed therapy received vasopressors (P=0.02) and mechanical ventilation (P=0.02) and underwent pulmonary-artery catheterization (P=0.01), and a smaller proportion required red-cell transfusion (P<0.001). Though similar between the groups at base line (P=0.91), the mean hematocrit during this 72-hour period was significantly lower in the standard-therapy group than in the early-therapy group (P<0.001). Despite the transfusion of red cells, it was significantly lower than the value obtained at base line in each group (P<0.001 for both comparisons) (Table 2).

Consumption of Health Care Resources

There were no significant differences between the two groups in the mean duration of vasopressor therapy (2.4±4.2 vs. 1.9±3.1 days, P=0.49), the mean duration of mechanical ventilation (9.0±13.1 vs. 9.0±11.4 days, P=0.38), or the mean length of stay in the hospital (13.0±13.7 vs. 13.2±13.8 days, P=0.54). However, of the patients who survived to hospital discharge, those assigned to standard therapy had stayed a significantly longer time in the hospital than those assigned to early goal-directed therapy (18.4±15.0 vs. 14.6±14.5 days, P=0.04).

Discussion

Severe sepsis and septic shock are common and are associated with substantial mortality and substantial consumption of health care resources. There are an estimated 751,000 cases (3.0 cases per 1000 population) of sepsis or septic shock in the United States each year, and they are responsible for as many deaths each year as acute myocardial infarction (215,000, or 9.3 percent of all deaths).29 In elderly persons, the incidence of sepsis or septic shock and the related mortality rates are substantially higher than those in younger persons. The projected growth of the elderly population in the United States will contribute to an increase in incidence of 1.5 percent per year, yielding an estimated 934,000 and 1,110,000 cases by the years 2010 and 2020, respectively.29 The present annual cost of this disease is estimated to be $16.7 billion.29

The transition from the systemic inflammatory response syndrome to severe sepsis and septic shock involves a myriad of pathogenic changes, including circulatory abnormalities that result in global tissue hypoxia.1,2 These pathogenic changes have been the therapeutic target of previous outcome studies.12 Although this transition occurs over time, both out of the hospital and in the hospital, in outcome studies interventions have usually been initiated after admission to the intensive care unit.12 In studies of goal-directed hemodynamic optimization, in particular, there was no benefit in terms of outcome with respect to normal and supranormal hemodynamic end points, as well as those guided by mixed venous oxygen saturation.9,13 In contrast, even though we enrolled patients with lower central venous oxygen saturation and lower central venous pressure than those studied by Gattinoni et al.9 and with a higher lactate concentration than those studied by Hayes et al.,13 we found significant benefits with respect to outcome when goal-directed therapy was applied at an earlier stage of disease. In patients with septic shock, for example, Hayes et al. observed a higher in-hospital mortality rate with aggressive hemodynamic optimization in the intensive care unit (71 percent) than with control therapy (52 percent), whereas we observed a lower mortality rate in patients with septic shock assigned to early goal-directed therapy (42.3 percent) than in those assigned to standard therapy (56.8 percent).

The benefits of early goal-directed therapy in terms of outcome are multifactorial. The incidence of death due to sudden cardiovascular collapse in the standard-therapy group was approximately double that in the group assigned to early goal-directed therapy, suggesting that an abrupt transition to severe disease is an important cause of early death. The early identification of patients with insidious illness (global tissue hypoxia accompanied by stable vital signs) makes possible the early implementation of goal-directed therapy. If sudden cardiovascular collapse can be prevented, the subsequent need for vasopressors, mechanical ventilation, and pulmonary-artery catheterization (and their associated risks) diminishes. In addition to being a stimulus of the systemic inflammatory response syndrome, global tissue hypoxia independently contributes to endothelial activation and disruption of the homeostatic balance among coagulation, vascular permeability, and vascular tone.30 These are key mechanisms leading to microcirculatory failure, refractory tissue hypoxia, and organ dysfunction.2,30 When early therapy is not comprehensive, the progression to severe disease may be well under way at the time of admission to the intensive care unit.16 Aggressive hemodynamic optimization and other therapy12 undertaken thereafter may be incompletely effective or even deleterious.13

The value of measurements of venous oxygen saturation at the right atrium or superior vena cava (central venous oxygen saturation) instead of at the pulmonary artery (mixed venous oxygen saturation) has been debated,31 in particular, when saturation values are above 65 percent. In patients in the intensive care unit who have hyperdynamic septic shock, the mixed venous oxygen saturation is rarely below 65 percent.32 In contrast, our patients were examined during the phase of resuscitation in which the delivery of supplemental oxygen is required (characterized by a decreased mixed venous oxygen saturation and an increased lactate concentration), when the central venous oxygen saturation generally exceeds the mixed venous oxygen saturation.33,34 The initial central venous oxygen saturation was less than 50 percent in both study groups. The mixed venous oxygen saturation is estimated to be 5 to 13 percent lower in the pulmonary artery33 and 15 percent lower in the splanchnic bed.35 Though not numerically equivalent, these ranges of values are pathologically equivalent and are associated with high mortality.32,36 Among all the patients in the current study in whom the goals with respect to central venous pressure, mean arterial pressure, and urine output during the first six hours were met, 39.8 percent of those assigned to standard therapy were still in this oxygen-dependent phase of resuscitation at six hours, as compared with 5.1 percent of those assigned to early goal-directed therapy. The combined 56.5 percent in-hospital mortality of this 39.8 percent of patients, who were at high risk for hemodynamic compromise, is consistent with the results of previous studies in the intensive care unit.32,36

In an open, randomized, partially blinded trial, there are unavoidable interactions during the initial period of the study. As the study progressed, the patients in the standard-therapy group may have received some form of goal-directed therapy, reducing the treatment effect. This reduction may have been offset by the slight but inherent bias resulting from the direct influence of the investigators on the care of the patients in the treatment group. The potential period of bias was 9.9±19.5 percent of the overall hospital stay in the standard-therapy group and 7.2±12.0 percent of that in the group assigned to early goal-directed therapy (P=0.20). This interval was minimal in comparison with those in previous studies9,13 because the clinicians who assumed responsibility for the remainder of hospitalization were completely blinded to the randomization order.

We conclude that goal-directed therapy provided at the earliest stages of severe sepsis and septic shock, though accounting for only a brief period in comparison with the overall hospital stay, has significant short-term and long-term benefits. These benefits arise from the early identification of patients at high risk for cardiovascular collapse and from early therapeutic intervention to restore a balance between oxygen delivery and oxygen demand. In the future, investigators conducting outcome trials in patients with sepsis should consider the quality and timing of the resuscitation before enrollment as an important outcome variable.

Supported by the Henry Ford Health Systems Fund for Research, a Weatherby Healthcare Resuscitation Fellowship, Edwards Lifesciences (which provided oximetry equipment and catheters), and Nova Biomedical (which provided equipment for laboratory assays).

We are indebted to the nurses, residents, senior staff attending physicians, pharmacists, patient advocates, technicians, and billing and administrative personnel of the Department of Emergency Medicine; to the nurses and technicians of the medical and surgical intensive care units; and to the staff members of the Department of Respiratory Therapy, Department of Pathology, Department of Medical Records, and Department of Admitting and Discharge for their patience and their cooperation in making this study possible.

Source Information

From the Departments of Emergency Medicine (E.R., B.N., J.R., A.M., B.K., M.T.), Surgery (E.R.), Internal Medicine (B.N.), and Biostatistics and Epidemiology (S.H., E.P.), Henry Ford Health Systems, Case Western Reserve University, Detroit.

Address reprint requests to Dr. Rivers at the Department of Emergency Medicine, Henry Ford Hospital, 2799 West Grand Blvd., Detroit, MI 48202, or at .

The members of the Early Goal-Directed Therapy Collaborative Group are listed in the Appendix.

Appendix

The following persons participated in the study: External Safety, Efficacy, and Data Monitoring Committee: A. Connors (Charlottesville, Va.), S. Conrad (Shreveport, La.), L. Dunbar (New Orleans), S. Fagan (Atlanta), M. Haupt (Portland, Oreg.), R. Ivatury (Richmond, Va.), G. Martin (Detroit), D. Milzman (Washington, D.C.), E. Panacek (Palo Alto, Calif.), M. Rady (Scottsdale, Ariz.), M. Rudis (Los Angeles), and S. Stern (Ann Arbor, Mich.); the Early-Goal-Directed-Therapy Collaborative Group: B. Derechyk, W. Rittinger, G. Hayes, K. Ward, M. Mullen, V. Karriem, J. Urrunaga, M. Gryzbowski, A. Tuttle, W. Chung, P. Uppal, R. Nowak, D. Powell, T. Tyson, T. Wadley, G. Galletta, K. Rader, A. Goldberg, D. Amponsah, D. Morris, K. Kumasi-Rivers, B. Thompson, D. Ander, C. Lewandowski, J. Kahler, K. Kralovich, H. Horst, S. Harpatoolian, A. Latimer, M. Schubert, M. Fallone, B. Fasbinder, L. Defoe, J. Hanlon, A. Okunsanya, B. Sheridan, Q. Rivers, H. Johnson, B. Sessa-Boji, K. Gunnerson, D. Fritz, K. Rivers, S. Moore, D. Huang, and J. Farrerer (Henry Ford Hospital, Detroit).

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    Christoph K. Hofer, Annette Kaoru Mizuguchi, Wanda M. Popescu. (2013) Monitoring the Patient at Risk of Hemodynamic Instability in Remote Locations. International Anesthesiology Clinics 50:2, 141-172

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    A. A. SCHRAMKO. (2013) Removal of colloids: evidence- or emotional-based medicine?. Acta Anaesthesiologica Scandinavica 57:6, 809-809

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    Cláudio F. Oliveira, Flávio R. Nogueira de Sá, Débora S.F. Oliveira, Adriana F.C. Gottschald, Juliana D.G. Moura, Audrey R.O. Shibata, Eduardo J. Troster, Flávio A.C. Vaz, Joseph A. Carcillo. (2008) Time- and Fluid-Sensitive Resuscitation for Hemodynamic Support of Children in Septic Shock. Pediatric Emergency Care 24:12, 810-815

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    Fabrice Vallée, Benoit Vallet, Olivier Mathe, Jacqueline Parraguette, Arnaud Mari, Stein Silva, Kamran Samii, Olivier Fourcade, Michèle Genestal. (2008) Central venous-to-arterial carbon dioxide difference: an additional target for goal-directed therapy in septic shock?. Intensive Care Medicine 34:12, 2218-2225

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    Ali Al-Khafaji, Emanuel Rivers, William Shoemaker. (2008) The prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients article of shoemaker et al with expert commentary by Dr. Emanuel Rivers. Journal of Critical Care 23:4, 603-606

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    Rhonda S Rea, Blair Capitano, Robert Bies, Kristin L Bigos, Randall Smith, Howard Lee. (2008) Suboptimal Aminoglycoside Dosing in Critically Ill Patients. Therapeutic Drug Monitoring 30:6, 674-681

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    Maryn McKenna. (2008) Controversy Swirls Around Early Goal-Directed Therapy in Sepsis: Pioneer Defends Ground-Breaking Approach to Deadly Disease. Annals of Emergency Medicine 52:6, 651-654

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    Philip S. Barie, Lynn J. Hydo, Jian Shou, Soumitra R. Eachempati. (2008) Decreasing Magnitude of Multiple Organ Dysfunction Syndrome Despite Increasingly Severe Critical Surgical Illness: A 17-Year Longitudinal Study. The Journal of Trauma: Injury, Infection, and Critical Care 65:6, 1227-1235

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    Seth R. Bauer, Simon W. Lam, Stephen S. Cha, Lance J. Oyen. (2008) Effect of corticosteroids on arginine vasopressin–containing vasopressor therapy for septic shock: a case control study. Journal of Critical Care 23:4, 500-506

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    Paolo Calzavacca, Elisa Licari, Augustine Tee, Moritoki Egi, Michael Haase, Anja Haase-Fielitz, Rinaldo Bellomo. (2008) A prospective study of factors influencing the outcome of patients after a Medical Emergency Team review. Intensive Care Medicine 34:11, 2112-2116

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    Christian Ertmer, Andrea Morelli, Martin Westphal. (2008) Vasopressin and the kidney: Two false friends?*. Critical Care Medicine 36:11, 3111-3112

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    Jean-Louis Vincent. (2008) Clinical sepsis and septic shock—definition, diagnosis and management principles. Langenbeck's Archives of Surgery 393:6, 817-824

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    Richard Sinert, Leah Bright. (2008) Empiric Antibiotic Therapy for Sepsis Patients: Monotherapy With β-Lactam or β-Lactam Plus an Aminoglycoside?. Annals of Emergency Medicine 52:5, 557-560

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    X. Wittebole, C. Collienne, D. Castanares-Zapatero, P.F. Laterre. (2008) Adjunctive therapies for severe sepsis. International Journal of Antimicrobial Agents 32, S34-S38

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    Peter M. Suter, Jukka Takala. (2008) Science, medicine and industry: are we getting out of the black hole in sepsis research?. Intensive Care Medicine 34:11, 1950-1954

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    Kristina Sullivan, Michael A. Gropper. (2008) Laboratory testing guidelines in the intensive care unit: Less red and more green*. Critical Care Medicine 36:11, 3102-3103

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    Gilberto Friedman, Stanislaw Jankowski, Mohammad Shahla, Jussara Gomez, Jean-Louis Vincent. (2008) Hemodynamic effects of 6% and 10% hydroxyethyl starch solutions versus 4% albumin solution in septic patients. Journal of Clinical Anesthesia 20:7, 528-533

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    Jean-Louis Vincent, Michael R. Pinsky, Charles L. Sprung, Mitchell Levy, John J. Marini, Didier Payen, Andrew Rhodes, Jukka Takala. (2008) The pulmonary artery catheter: In medio virtus. Critical Care Medicine 36:11, 3093-3096

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    Julien Amour, Olivier Langeron, Pierre Hausfater. (2008) The authors reply:. Critical Care Medicine 36:11, 3121-3122

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    Inneke E. laet, Mariska Ravyts, Wesley Vidts, Jody Valk, Jan J. Waele, Manu L. N. G. Malbrain. (2008) Current insights in intra-abdominal hypertension and abdominal compartment syndrome: open the abdomen and keep it open!. Langenbeck's Archives of Surgery 393:6, 833-847

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    Diogo Diniz Gomes Bugano, Luis Fernando Aranha Camargo, Jaime Freitas Bastos, Eliezer Silva. (2008) Antibiotic management of sepsis: current concepts. Expert Opinion on Pharmacotherapy 9:16, 2817-2828

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    L. E. M. van Lelyveld-Haas, A. R. H. van Zanten, G. F. Borm, D. H. T. Tjan. (2008) Clinical validation of the non-invasive cardiac output monitor USCOM-1A in critically ill patients. European Journal of Anaesthesiology 25:11, 917-924

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    Michael D. Seear, Jennifer C. Scarfe, Jacques G. LeBlanc. (2008) Predicting major adverse events after cardiac surgery in children. Pediatric Critical Care Medicine 9:6, 606-611

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    Dominique M. Vandijck, Stijn I. Blot, Johan M. Decruyenaere. (2008) Update on the Management of Infection in Patients With Severe Sepsis. Dimensions of Critical Care Nursing 27:6, 244-248

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    Thomas E. Stewart. (2008) Implementing the best evidence; do not forget to be a good clinician*. Critical Care Medicine 36:11, 3106-3107

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    Alain Eid, Christian J. Wiedermann, Gary T. Kinasewitz. (2008) Early Administration of High-Dose Antithrombin in Severe Sepsis: Single Center Results from the KyberSept-Trial. Anesthesia & Analgesia 107:5, 1633-1638

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    Jose Otavio C. Auler, Filomena R.B.G. Galas, Marcia R. Sundin, Ludhmila A. Hajjar. (2008) ARTERIAL PULSE PRESSURE VARIATION PREDICTING FLUID RESPONSIVENESS IN CRITICALLY ILL PATIENTS. Shock 30:Suppl 1, 18-22

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    Alan E. Jones, Michael D. Brown, Stephen Trzeciak, Nathan I. Shapiro, John S. Garrett, Alan C. Heffner, Jeffrey A. Kline. (2008) The effect of a quantitative resuscitation strategy on mortality in patients with sepsis: A meta-analysis*. Critical Care Medicine 36:10, 2734-2739

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    Kati Järvelä, Pasi Maaranen, Tero Sisto, Esko Ruokonen. (2008) Levosimendan in Aortic Valve Surgery: Cardiac Performance and Recovery. Journal of Cardiothoracic and Vascular Anesthesia 22:5, 693-698

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    K. J. VAN DOORN, H. SPAPEN, C. GEERS, M. DILTOER, W. SHABANA. (2008) Sepsis-related acute kidney injury: a protective effect of drotrecogin alfa (activated) treatment?. Acta Anaesthesiologica Scandinavica 52:9, 1259-1264

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    Eirini Christaki, Steven M Opal. (2008) Is the mortality rate for septic shock really decreasing?. Current Opinion in Critical Care 14:5, 580-586

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    Marin H. Kollef, Lena M. Napolitano, Joseph S. Solomkin, Richard G. Wunderink, In‐Gyu Bae, Vance G. Fowler, Robert A. Balk, Dennis L. Stevens, James J. Rahal, Andrew F. Shorr, Peter K. Linden, Scott T. Micek. (2008) Health Care–Associated Infection (HAI): A Critical Appraisal of the Emerging Threat—Proceedings of the HAI Summit. Clinical Infectious Diseases 47:s2, S55-S99

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    MARCO RANUCCI, GIUSEPPE ISGRÒ, TERESA DE LA TORRE, FEDERICA ROMITTI, DANIELA CONTI, CONCETTA CARLUCCI. (2008) Near-infrared spectroscopy correlates with continuous superior vena cava oxygen saturation in pediatric cardiac surgery patients. Pediatric Anesthesia

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    Dawn Tucker. (2008) Role of Noninvasive Venous Oximetry in Critically Ill Pediatric Patients. AACN Advanced Critical Care 19:4, 358-363

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    Gernot Keyßer, Carola Schwerdt, Christiane Taege. (2008) Right-heart failure after right heart catheterization in a patient with scleroderma and suspected pulmonary hypertension. Rheumatology International 28:12, 1269-1271

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    Indumathy Santhanam, Shanthi Sangareddi, Shekhar Venkataraman, Niranjan Kissoon, Vaidehi Thiruvengadamudayan, R. Kulandhai Kasthuri. (2008) A Prospective Randomized Controlled Study of Two Fluid Regimens in the Initial Management of Septic Shock in the Emergency Department. Pediatric Emergency Care 24:10, 647-655

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    Frank M. Brunkhorst, Christoph Engel, Max Ragaller, Tobias Welte, Rolf Rossaint, Herwig Gerlach, Konstantin Mayer, Stefan John, Frank Stuber, Norbert Weiler, Michael Oppert, Onnen Moerer, Holger Bogatsch, Konrad Reinhart, Markus Loeffler, Christiane Hartog. (2008) Practice and perception—A nationwide survey of therapy habits in sepsis*. Critical Care Medicine 36:10, 2719-2725

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    Flavia R. Machado, Flávio G.R. Freitas. (2008) CONTROVERSIES OF SURVIVING SEPSIS CAMPAIGN BUNDLES. Shock 30:Suppl 1, 34-40

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    Reda Salem, Fabrice Vallee, Marco Rusca, Alexandre Mebazaa. (2008) Hemodynamic monitoring by echocardiography in the ICU: the role of the new echo techniques. Current Opinion in Critical Care 14:5, 561-568

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    Mark D. Siegel. (2008) Sepsis (mis) management: The hazards of a faith-based approach*. Critical Care Medicine 36:10, 2929-2930

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    Dominique M. Vandijck, Dominique D. Benoit. (2008) Impact of recent intravenous chemotherapy on outcome in severe sepsis and septic shock patients with haematological malignancies: reply to letter by Meyer et al.. Intensive Care Medicine 34:10, 1930-1931

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    David J. Kramer, Juan M. Canabal, Lisa C. Arasi. (2008) Application of intensive care medicine principles in the management of the acute liver failure patient. Liver Transplantation 14:S2, S85-S89

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    Sean A. Josephs. (2008) The Use of Current Hemodynamic Monitors and Echocardiography in Resuscitation of the Critically Ill or Injured Patient. International Anesthesiology Clinics 45:3, 31-59

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    Fathima Paruk. (2008) Infection in obstetric critical care. Best Practice & Research Clinical Obstetrics & Gynaecology 22:5, 865-883

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    Luciano Cesar Pontes Azevedo, Marcelo Park, Guilherme Paula Pinto Schettino. (2008) NOVEL POTENTIAL THERAPIES FOR SEPTIC SHOCK. Shock 30:Suppl 1, 60-66

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    Sean K. Kane, Matthew J. MacCallum, Andrew D. Friedrich. (2008) Resuscitation of the Trauma Patient. International Anesthesiology Clinics 45:3, 61-81

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    N SHAPIRO, R WOLFE, S WRIGHT, R MOORE, D BATES. (2008) Who Needs a Blood Culture? A Prospectively Derived and Validated Prediction Rule. Journal of Emergency Medicine 35:3, 255-264

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    Edward G. Seferian, Bekele Afessa, Ognjen Gajic, Mark T. Keegan, Rolf D. Hubmayr. (2008) Comparison of community and referral intensive care unit patients in a tertiary medical center: Evidence for referral bias in the critically ill*. Critical Care Medicine 36:10, 2779-2786

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    Kristine E. Mulier, David E. Skarda, Jodie H. Taylor, Dean E. Myers, Michelle K. McGraw, Barbara L. Gallea, Greg J. Beilman. (2008) Near-Infrared Spectroscopy in Patients with Severe Sepsis: Correlation with Invasive Hemodynamic Measurements. Surgical Infections 9:5, 515-519

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    F. M. E. Wagenlehner, A. Pilatz, K. G. Naber, W. Weidner. (2008) Therapeutic challenges of urosepsis. European Journal of Clinical Investigation 38, 45-49

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    Jonathan Sevransky. (2008) More evidence that timing matters in the treatment of patients with sepsis*. Critical Care Medicine 36:10, 2932-2933

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    Avi A. Weinbroum, Philippe Biderman, Dror Soffer, Joseph M. Klausner, Oded Szold. (2008) Reliability of Cardiac Output Calculation by the Fick Principle and Central Venous Oxygen Saturation in Emergency Conditions. Journal of Clinical Monitoring and Computing 22:5, 361-366

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    José Mário Meira Teles, Eliezer Silva, Glauco Westphal, Rubens Costa Filho, Flavia Ribeiro Machado. (2008) SURVIVING SEPSIS CAMPAIGN IN BRAZIL. Shock 30:Suppl 1, 47-52

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    Heiko Lier, Henning Krep, Stefan Schroeder, Frank Stuber. (2008) Preconditions of Hemostasis in Trauma: A Review. The Influence of Acidosis, Hypocalcemia, Anemia, and Hypothermia on Functional Hemostasis in Trauma. The Journal of Trauma: Injury, Infection, and Critical Care 65:4, 951-960

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    Laura Claire Price, Andrew Slack, Catherine Nelson-Piercy. (2008) Aims of obstetric critical care management. Best Practice & Research Clinical Obstetrics & Gynaecology 22:5, 775-799

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    A. YAZIGI, H. ABOU-ZEID, S. MADI-JEBARA, F. HADDAD, G. HAYEK, K. JABBOUR. (2008) Correlation between central venous oxygen saturation and oxygen delivery changes following fluid therapy. Acta Anaesthesiologica Scandinavica 52:9, 1213-1217

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    Mark Hamilton, Monty Mythen. Transesophageal Doppler. In: Practical Ultrasound in Anesthesia for Critical Care and Pain Management. CRC Press, 2008:167-177.

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    N. Lameire, W. Van Biesen, E. Hoste, R. Vanholder. (2008) The prevention of acute kidney injury: an in-depth narrative review Part 1: volume resuscitation and avoidance of drug- and nephrotoxin-induced AKI. NDT Plus 1:6, 392-402

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    Corstian A. den Uil, E. Klijn, W.K. Lagrand, J.J. Brugts, C. Ince, P.E. Spronk, M.L. Simoons. (2008) The Microcirculation in Health and Critical Disease. Progress in Cardiovascular Diseases 51:2, 161-170

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    (2008) 21st ESICM Annual Congress. Intensive Care Medicine 34:S1, 181-268

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    James D. Fortenberry. (2008) Pediatric Critical Care Management of Septic Shock Prior to Acute Kidney Injury and Renal Replacement Therapy. Seminars in Nephrology 28:5, 447-456

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    Manu L. N. G. Malbrain, Inneke laet. (2008) AIDS is coming to your ICU: be prepared for acute bowel injury and acute intestinal distress syndrome…. Intensive Care Medicine 34:9, 1565-1569

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    Constantine A. Manthous. (2008) Starling's equation and bedside critical care. Journal of Critical Care 23:3, 354-356

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    Wolfgang Huber, Felix Rockmann. (2008) Invasive und nichtinvasive Möglichkeiten des haemodynamischen Monitorings. Intensivmedizin und Notfallmedizin 45:6, 337-359

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    Jeffrey F. Barletta. (2008) Conducting a Successful Residency Research Project. American Journal of Pharmaceutical Education 72:4, 92

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    (2008) 21st ESICM Annual Congress. Intensive Care Medicine 34:S1, 5-92

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    A ANDERSSON, J FENHAMMAR, R FRITHIOF, E WEITZBERG, A SOLLEVI, H HJELMQVIST. (2008) Mixed Endothelin Receptor Antagonism With Tezosentan Improves Intestinal Microcirculation in Endotoxemic Shock. Journal of Surgical Research 149:1, 138-147

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    Paul E. Marik, Howard L. Corwin. (2008) Efficacy of red blood cell transfusion in the critically ill: A systematic review of the literature*. Critical Care Medicine 36:9, 2667-2674

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    Miguel Carrera, Alexandre Palou, Ernest Sala, Catalina Balaguer, Mónica de la Peña, Àlvar Agustí. (2008) Impacto de la presencia de un neumólogo de guardia sobre la actividad de un servicio de neumología. Archivos de Bronconeumología 44:9, 484-488

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    (2008) EXTENDING DAMAGE CONTROL PHILOSOPHY TO NON-HAEMORRHAGIC SITUATIONS: IMPLICATIONS FOR A RECLASSIFICATION OF SHOCK STATES. ANZ Journal of Surgery 78:8, 634-637

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    Martin W. Dünser, Walter R. Dünser. (2008) Surviving Sepsis Campaign Guidelines 2008: Revisiting vasopressor recommendations. Critical Care Medicine 36:8, 2488

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    Henry Boret, Ambroise Montcriol, Eric Meaudre. (2008) Letters to the Editor. The Journal of Trauma: Injury, Infection, and Critical Care 65:2, 499

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    Praveen Khilnani, Satish Deopujari, Joe Carcillo. (2008) Recent advances in sepsis and septic shock. The Indian Journal of Pediatrics 75:8, 821-830

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    Hidehiko Kushi, Takahiro Miki, Yuichiro Sakagami, Jun Sato, Takeshi Saito, Katsuhisa Tanjoh. (2008) Early Hemoperfusion With a Polymyxin B Column Improves Gastric Intramucosal pH in Sepsis. Therapeutic Apheresis and Dialysis 12:4, 278-284

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    Jukka Takala, R. Philip Dellinger, Kati Koskinen, Arthur St. Andre, Martyn Read, Mitchell Levy, Stephan M. Jakob, Patricia Veiga C. Mello, Raymond Friolet, Esko Ruokonen. (2008) Development and simultaneous application of multiple care protocols in critical care: a multicenter feasibility study. Intensive Care Medicine 34:8, 1401-1410

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    Armand R.J. Girbes, Albert Beishuizen, Rob J.M. Strack van Schijndel. (2008) Pharmacological treatment of sepsis. Fundamental & Clinical Pharmacology 22:4, 355-361

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    Michael H. Catenacci, Kaira King. (2008) Severe Sepsis and Septic Shock: Improving Outcomes in the Emergency Department. Emergency Medicine Clinics of North America 26:3, 603-623

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    Peter E. Morris, Amanda Goad, Clifton Thompson, Karen Taylor, Bethany Harry, Leah Passmore, Amelia Ross, Laura Anderson, Shirley Baker, Mary Sanchez, Lauretta Penley, April Howard, Luz Dixon, Susan Leach, Ronald Small, R Duncan Hite, Edward Haponik. (2008) Early intensive care unit mobility therapy in the treatment of acute respiratory failure*. Critical Care Medicine 36:8, 2238-2243

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    Wolfgang Huber, Andreas Umgelter, Wolfgang Reindl, Michael Franzen, Christian Schmidt, Stefan von Delius, Fabian Geisler, Florian Eckel, Ralph Fritsch, Jens Siveke, Benedikt Henschel, Roland M. Schmid. (2008) Volume assessment in patients with necrotizing pancreatitis: A comparison of intrathoracic blood volume index, central venous pressure, and hematocrit, and their correlation to cardiac index and extravascular lung water index*. Critical Care Medicine 36:8, 2348-2354

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    Laurent Muller, Guillaume Louart, Christian Bengler, Pascale Fabbro-Peray, Julie Carr, Jacques Ripart, Jean-Emmanuel de La Coussaye, Jean-Yves Lefrant. (2008) The Intrathoracic Blood Volume Index as an Indicator of Fluid Responsiveness in Critically Ill Patients with Acute Circulatory Failure: A Comparison with Central Venous Pressure. Anesthesia & Analgesia 107:2, 607-613

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    Ednan K. Bajwa, James L. Januzzi, Michelle N. Gong, B Taylor Thompson, David C. Christiani. (2008) Prognostic value of plasma N-terminal probrain natriuretic peptide levels in the acute respiratory distress syndrome*. Critical Care Medicine 36:8, 2322-2327

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    Karel Tyml, Fuyan Li, John X. Wilson. (2008) Septic impairment of capillary blood flow requires nicotinamide adenine dinucleotide phosphate oxidase but not nitric oxide synthase and is rapidly reversed by ascorbate through an endothelial nitric oxide synthase-dependent mechanism*. Critical Care Medicine 36:8, 2355-2362

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    Tommaso Mauri, Andrea Coppadoro, Giacomo Bellani, Michela Bombino, Nicolo’ Patroniti, Giuseppe Peri, Alberto Mantovani, Antonio Pesenti. (2008) Pentraxin 3 in acute respiratory distress syndrome: An early marker of severity*. Critical Care Medicine 36:8, 2302-2308

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    Joseph Varon, Pilar Acosta. (2008) Is the Mortality in the Emergency Department Sepsis score a reliable predictive tool for the ED physician?. The American Journal of Emergency Medicine 26:6, 693-694

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    K. Reinhart, F.M. Brunkhorst, C. Engel, F. Bloos, A. Meier-Hellmann, M. Ragaller, N. Weiler, O. Moerer, M. Gruendling, M. Oppert, S. Grond, D. Olthoff, U. Jaschinski, S. John, R. Rossaint, T. Welte, M. Schaefer, P. Kern, E. Kuhnt, M. Kiehntopf, T. Deufel, C. Hartog, H. Gerlach, F. Stüber, H.-D. Volk, M. Quintel, M. Loeffler, . (2008) Studienprotokoll der VISEP-Studie. Der Anaesthesist 57:7, 723-728

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    W.R. Hasibeder, M.W. Dünser. (2008) Intensive Insulintherapie und Volumentherapie mit 10%iger Hemohes® zur Behandlung von Patienten mit schwerer Sepsis. Der Anaesthesist 57:7, 720-722

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    Emanuel P. Rivers, Tom Ahrens. (2008) Improving Outcomes for Severe Sepsis and Septic Shock: Tools for Early Identification of At-Risk Patients and Treatment Protocol Implementation. Critical Care Clinics 24:3, 1-47

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    H. Bryant Nguyen, Jim E. Banta, Thomas W. Cho, Chad Van Ginkel, Kristy Burroughs, William A. Wittlake, Stephen W. Corbett. (2008) MORTALITY PREDICTIONS USING CURRENT PHYSIOLOGIC SCORING SYSTEMS IN PATIENTS MEETING CRITERIA FOR EARLY GOAL-DIRECTED THERAPY AND THE SEVERE SEPSIS RESUSCITATION BUNDLE. Shock 30:1, 23-28

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    Fredrick M. Abrahamian, Peter M. DeBlieux, Charles L. Emerman, Marin H. Kollef, Eric Kupersmith, Kenneth V. Leeper, David L. Paterson, Andrew F. Shorr. (2008) Health care–associated pneumonia: identification and initial management in the ED. The American Journal of Emergency Medicine 26:6, 1-11

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    Manu L. N. G. Malbrain, Inneke De Laet. (2008) Epidemiology on intra-abdominal hypertension: An urgent call for multicenter trials*. Critical Care Medicine 36:6, 1972-1974

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    A. Tuttolomondo, A. Pinto, D. Raimondo, P. Fernandez, G. Licata. (2008) Plasma derived protein C in severe sepsis: report of two cases. Internal and Emergency Medicine 3:2, 179-182

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    Werner Baulig, Alexander Dullenkopf, Andreas Kobler, Barbara Baulig, Hans Rudolf Roth, Edith R. Schmid. (2008) Accuracy of Continuous Central Venous Oxygen Saturation Monitoring in Patients Undergoing Cardiac Surgery. Journal of Clinical Monitoring and Computing 22:3, 183-188

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    Lothar Engelmann. (2008) Die VISEP-Studie: ein Schritt vorwärts, zwei Schritte zurück. Intensivmedizin und Notfallmedizin 45:5, 255-262

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    Maria Gabriela Vidal, Javier Ruiz Weisser, Francisco Gonzalez, Maria America Toro, Cecilia Loudet, Carina Balasini, Hector Canales, Rosa Reina, Elisa Estenssoro. (2008) Incidence and clinical effects of intra-abdominal hypertension in critically ill patients. Critical Care Medicine 36:6, 1823-1831

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    Antoine Vieillard-Baron, Vincent Caille, Cyril Charron, Guillaume Belliard, Bernard Page, François Jardin. (2008) Actual incidence of global left ventricular hypokinesia in adult septic shock. Critical Care Medicine 36:6, 1701-1706

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    Joana da Costa P. d’Avila, Ana Paula S. A. Santiago, Rodrigo T. Amâncio, Antonio Galina, Marcus F. Oliveira, Fernando A. Bozza. (2008) Sepsis induces brain mitochondrial dysfunction. Critical Care Medicine 36:6, 1925-1932

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    Cláudio F. Oliveira, Débora S. F. Oliveira, Adriana F. C. Gottschald, Juliana D. G. Moura, Graziela A. Costa, Andréa C. Ventura, José Carlos Fernandes, Flávio A. C. Vaz, Joseph A. Carcillo, Emanuel P. Rivers, Eduardo J. Troster. (2008) ACCM/PALS haemodynamic support guidelines for paediatric septic shock: an outcomes comparison with and without monitoring central venous oxygen saturation. Intensive Care Medicine 34:6, 1065-1075

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    Herbert Spapen. (2008) Liver Perfusion in Sepsis, Septic Shock, and Multiorgan Failure. The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology 291:6, 714-720

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    Christian Ertmer, Martin Westphal, Andrea Morelli. (2008) Levo is in the air: Take a deep breath!*. Critical Care Medicine 36:6, 1979-1981

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    Danny M. Takanishi, Mihae Yu, Fedor Lurie, Elisabeth Biuk-Aghai, Hideko Yamauchi, Hao Chih Ho, Alyssa D. Chapital. (2008) Peripheral Blood Hematocrit in Critically Ill Surgical Patients: An Imprecise Surrogate of True Red Blood Cell Volume. Anesthesia & Analgesia 106:6, 1808-1812

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    S FUJISHIMA, H MORISAKI, A ISHIZAKA, Y KOTAKE, M MIYAKI, K YOH, K SEKINE, J SASAKI, S TASAKA, N HASEGAWA. (2008) Neutrophil elastase and systemic inflammatory response syndrome in the initiation and development of acute lung injury among critically ill patients. Biomedicine & Pharmacotherapy 62:5, 333-338

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    T. Lisboa, J. Rello. (2008) Prevención de infecciones nosocomiales: estrategias para mejorar la seguridad de los pacientes en la Unidad de Cuidados Intensivos. Medicina Intensiva 32:5, 248-252

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    Andreas Valentin. (2008) Das Konzept des Medical Emergency Team – Intensivmedizin außerhalb der Intensivstation. Intensivmedizin und Notfallmedizin 45:4, 217-221

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    Jesse M. Pines. (2008) Timing of Antibiotics for Acute, Severe Infections. Emergency Medicine Clinics of North America 26:2, 245-257

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    Samir Benchekroune, Peter C. J. Karpati, Christine Berton, Cédric Nathan, Joaquim Mateo, Mansour Chaara, Florence Riché, Marie-Josèphe Laisné, Didier Payen, Alexandre Mebazaa. (2008) Diastolic Arterial Blood Pressure: A Reliable Early Predictor of Survival in Human Septic Shock. The Journal of Trauma: Injury, Infection, and Critical Care 64:5, 1188-1195

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    Ahmed N. Zakariah, Simona M. Cozzi, Marc Van Nuffelen, Carla Maria Clausi, Olivier Pradier, Jean-Louis Vincent. (2008) Combination of biphasic transmittance waveform with blood procalcitonin levels for diagnosis of sepsis in acutely ill patients. Critical Care Medicine 36:5, 1507-1512

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    Peter Spiegler, Heather Kessler-Reyes. (2008) Hydrocortisone Therapy for Patients With Septic Shock. Clinical Pulmonary Medicine 15:3, 183-184

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    Naeem A. Ali. (2008) Moving toward preventive therapy in acute lung injury*. Critical Care Medicine 36:5, 1666-1667

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    Chiaki Inadomi, Yoshiaki Terao, Kazunori Yamashita, Makoto Fukusaki, Masafumi Takada, Koji Sumikawa. (2008) Comparison of oxygen consumption calculated by Fick’s principle (using a central venous catheter) and measured by indirect calorimetry. Journal of Anesthesia 22:2, 163-166

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    Matthias Lange, Christian Ertmer, Martin Westphal. (2008) Vasopressin vs. terlipressinin the treatmentof cardiovascular failure in sepsis. Intensive Care Medicine 34:5, 821-832

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    Shyoko Honiden, Atara Schultz, Shelly A. Im, David M. Nierman, Michelle N. Gong. (2008) Early versus late intravenous insulin administration in critically ill patients. Intensive Care Medicine 34:5, 881-887

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    Alain Cariou, Michael R. Pinsky, Mehran Monchi, Ivan Laurent, Christophe Vinsonneau, Jean-Daniel Chiche, Julien Charpentier, Jean-François Dhainaut. (2008) Is myocardial adrenergic responsiveness depressed in human septic shock?. Intensive Care Medicine 34:5, 917-922

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    Stijn I. Blot, Alejandro Rodriguez, Jordi Rello. (2008) Delayed oxygenation assessment in patients with severe community-acquired pneumonia. Critical Care Medicine 36:5, 1694-1695

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    Gustavo A. Ospina-Tascón, Ricardo L. Cordioli, Jean-Louis Vincent. (2008) What type of monitoring has been shownto improve outcomes in acutely ill patients?. Intensive Care Medicine 34:5, 800-820

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    Remzi Iscimen, Rodrigo Cartin-Ceba, Murat Yilmaz, Hasrat Khan, Rolf D. Hubmayr, Bekele Afessa, Ognjen Gajic. (2008) Risk factors for the development of acute lung injury in patients with septic shock: An observational cohort study*. Critical Care Medicine 36:5, 1518-1522

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    Simon W Lam, Seth R Bauer, Stephen S Cha, Lance J Oyen. (2008) Lack of an Effect of Body Mass on the Hemodynamic Response to Arginine Vasopressin During Septic Shock. Pharmacotherapy 28:5, 591-599

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    Jeffrey M. Caterino. (2008) Evaluation and Management of Geriatric Infections in the Emergency Department. Emergency Medicine Clinics of North America 26:2, 319-343

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    Wei-Lung Chen, Jiann-Hwa Chen, Chien-Cheng Huang, Cheng-Deng Kuo, Chun-I Huang, Liang-Shong Lee. (2008) Heart rate variability measures as predictors of in-hospital mortality in ED patients with sepsis. The American Journal of Emergency Medicine 26:4, 395-401

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    K. Kofoed, J. Eugen-Olsen, J. Petersen, K. Larsen, O. Andersen. (2008) Predicting mortality in patients with systemic inflammatory response syndrome: an evaluation of two prognostic models, two soluble receptors, and a macrophage migration inhibitory factor. European Journal of Clinical Microbiology & Infectious Diseases 27:5, 375-383

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    Stephen Trzeciak, Ismail Cinel, R. Phillip Dellinger, Nathan I. Shapiro, Ryan C. Arnold, Joseph E. Parrillo, Steven M. Hollenberg, . (2008) Resuscitating the Microcirculation in Sepsis: The Central Role of Nitric Oxide, Emerging Concepts for Novel Therapies, and Challenges for Clinical Trials. Academic Emergency Medicine 15:5, 399-413

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    Uma B. Samant, Christopher D. Mack, Thomas Koepsell, Frederick P. Rivara, Monica S. Vavilala. (2008) Time of Hypotension and Discharge Outcome in Children with Severe Traumatic Brain Injury. Journal of Neurotrauma 25:5, 495-502

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    Ricardo L. Levin, Marcela A. Degrange, Rafael Porcile, Flavio Salvagio, Norberto Blanco, Alejandro L. Botbol, Eduardo Tanus, Carlos D. del Mazo. (2008) Superioridad del sensibilizante al calcio levosimendán comparado con dobutamina en el síndrome de bajo gasto cardiaco postoperatorio. Revista Española de Cardiología 61:5, 471-479

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    Makoto Kobayashi, Masayoshi Ko, Toshimoto Kimura, Eiji Meguro, Yoshiro Hayakawa, Takashi Irinoda, Akinori Takagane. (2008) Perioperative monitoring of fluid responsiveness after esophageal surgery using stroke volume variation. Expert Review of Medical Devices 5:3, 311-316

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    Sheik Humarr Khan, Augustine Goba, May Chu, Cathy Roth, Tim Healing, Arthur Marx, Joseph Fair, Mary C. Guttieri, Philip Ferro, Tiffany Imes, Corina Monagin, Robert F. Garry, Daniel G. Bausch. (2008) New opportunities for field research on the pathogenesis and treatment of Lassa fever. Antiviral Research 78:1, 103-115

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    Daniel Talmor, Dan Greenberg, Michael D. Howell, Alan Lisbon, Victor Novack, Nathan Shapiro. (2008) The costs and cost-effectiveness of an integrated sepsis treatment protocol. Critical Care Medicine 36:4, 1168-1174

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    Alan E. Jones, Nathan I. Shapiro, J. Hope Kilgannon, Stephen Trzeciak. (2008) Goal-directed hemodynamic optimization in the post-cardiac arrest syndrome: A systematic review. Resuscitation 77:1, 26-29

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    Daniel G. Bausch, A.G. Sprecher, Benjamin Jeffs, Paul Boumandouki. (2008) Treatment of Marburg and Ebola hemorrhagic fevers: A strategy for testing new drugs and vaccines under outbreak conditions. Antiviral Research 78:1, 150-161

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    Paolo Malacarne, Martin Langer, Ennio Nascimben, Maria Luisa Moro, Daniela Giudici, Laura Lampati, Guido Bertolini. (2008) Building a continuous multicenter infection surveillance system in the intensive care unit: Findings from the initial data set of 9,493 patients from 71 Italian intensive care units. Critical Care Medicine 36:4, 1105-1113

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    Matthias Lange, Atsumori Hamahata, Perenlei Enkhbaatar, Aimalohi Esechie, Rhykka Connelly, Yoshimitsu Nakano, Collette Jonkam, Robert A. Cox, Lillian D. Traber, David N. Herndon, Daniel L. Traber. (2008) Assessment of vascular permeability in an ovine model of acute lung injury and pneumonia-induced Pseudomonas aeruginosa sepsis. Critical Care Medicine 36:4, 1284-1289

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    Mark D. Piehl, James E. Manning, Shane L. McCurdy, Tim S. Rhue, Keith C. Kocis, Charles B. Cairns, Bruce A. Cairns. (2008) Pulse contour cardiac output analysis in a piglet model of severe hemorrhagic shock*. Critical Care Medicine 36:4, 1189-1195

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    Nathan I. Shapiro, Kiichiro Yano, Hitomi Okada, Christopher Fischer, Michael Howell, Katherine C. Spokes, Long Ngo, Derek C. Angus, William C. Aird. (2008) A PROSPECTIVE, OBSERVATIONAL STUDY OF SOLUBLE FLT-1 AND VASCULAR ENDOTHELIAL GROWTH FACTOR IN SEPSIS. Shock 29:4, 452-457

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    Kirsty Buising. (2008) Severity scores for community-acquired pneumonia. Expert Review of Respiratory Medicine 2:2, 261-271

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    Margaret M. Parker. (2008) Measuring preload—One size doesn’t necessarily fit all*. Critical Care Medicine 36:3, 1024-1025

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    Frédéric Pène, Stéphanie Percheron, Virginie Lemiale, Vivian Viallon, Yann-Erick Claessens, Sophie Marqué, Julien Charpentier, Derek C. Angus, Alain Cariou, Jean-Daniel Chiche, Jean-Paul Mira. (2008) Temporal changes in management and outcome of septic shock in patients with malignancies in the intensive care unit*. Critical Care Medicine 36:3, 690-696

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