Original Article
The Effects of Ibuprofen on the Physiology and Survival of Patients with Sepsis
N Engl J Med 1997; 336:912-918March 27, 1997
- Abstract
Background
In patients with sepsis the production of arachidonic acid metabolites by cyclooxygenase increases, but the pathophysiologic role of these prostaglandins is unclear. In animal models, inhibition of cyclooxygenase by treatment with ibuprofen before the onset of sepsis reduces physiologic abnormalities and improves survival. In pilot studies of patients with sepsis, treatment with ibuprofen led to improvements in gas exchange and airway mechanics.
Methods
From October 1989 to March 1995, we conducted a randomized, double-blind, placebo-controlled trial of intravenous ibuprofen (10 mg per kilogram of body weight [maximal dose, 800 mg], given every six hours for eight doses) in 455 patients who had sepsis, defined as fever, tachycardia, tachypnea, and acute failure of at least one organ system.
Results
In the ibuprofen group, but not the placebo group, there were significant declines in urinary levels of prostacyclin and thromboxane, temperature, heart rate, oxygen consumption, and lactic acidosis. With ibuprofen therapy there was no increased incidence of renal dysfunction, gastrointestinal bleeding, or other adverse events. However, treatment with ibuprofen did not reduce the incidence or duration of shock or the acute respiratory distress syndrome and did not significantly improve the rate of survival at 30 days (mortality, 37 percent with ibuprofen vs. 40 percent with placebo).
Conclusions
In patients with sepsis, treatment with ibuprofen reduces levels of prostacyclin and thromboxane and decreases fever, tachycardia, oxygen consumption, and lactic acidosis, but it does not prevent the development of shock or the acute respiratory distress syndrome and does not improve survival.
Media in This Article
Figure 2
Median Time without Organ Failure during the Study.Figure 3
Mean (±SE) Percent Changes from Base Line to 20 Hours after Base Line in Oxygen Delivery, Oxygen Consumption, and Blood Lactate Levels among Patients with Pulmonary-Artery Catheters for Whom Data Were Available.Article Activity
- Article
Sepsis is associated with a mortality rate of 30 to 50 percent and with substantial morbidity.1 The relative contributions of the inflammatory response and infection to these adverse outcomes are unknown.2,3 In animal models of sepsis, treatment with nonsteroidal antiinflammatory drugs improves survival and reduces physiologic abnormalities.4-8 The synthesis of prostaglandin and thromboxane has been linked with abnormalities of airway mechanics, pulmonary hypertension, hypoxemia, cardiovascular collapse, and multiple organ failure in animals and in humans with the sepsis syndrome.9-25
Ibuprofen has been shown to have effects on sepsis in humans, but because of their small samples (fewer than 30 patients), previous studies have been inadequate to assess effects on mortality.26-28 We sought to determine whether ibuprofen can alter rates of organ failure and mortality in patients with the sepsis syndrome, how the drug affects the increased metabolic demand in sepsis (e.g., fever, tachypnea, tachycardia, hypoxemia, and lactic acidosis), and what potential adverse effects the drug has in the sepsis syndrome.
Methods
Study Patients
Seven medical centers in the United States and Canada participated in this trial, which was approved by the institutional review board at each center. Consent was obtained from all the patients or their next of kin before enrollment. Patients were recruited from intensive care units if they had a known or suspected site of serious infection, as determined on the basis of clinical data available at the time of screening, and if they met certain criteria that represented a modification of the criteria for sepsis described by Bone et al.29 and that were similar to those defined at a consensus conference.2 There were two groups of criteria, one (group 1) involving conditions present when the patient was at rest, and the second (group 2) involving dynamic variables unrelated to coexisting disease. To be eligible for the study, a patient had to meet all the group 1 criteria, as follows: a core temperature of at least 38.3°C or less than 35.5°C, a heart rate of at least 90 beats per minute (in the absence of treatment with beta-blockers), and a respiratory rate of 20 breaths per minute or more or, if the patient was receiving mechanical ventilation, a ventilatory rate greater than 10 liters per minute. In addition, the patient had to meet at least one criterion in group 2, as follows: cardiovascular dysfunction, defined as a systolic blood pressure less than 90 mm Hg or a decrease in systolic pressure by at least 40 mm Hg for more than one hour while pulmonary-artery wedge pressures remained adequate (>12 mm Hg) or at least 500 ml of saline was infused; renal-system dysfunction, defined as a urinary output of less than 30 ml per hour or less than 0.5 ml per kilogram of body weight, for at least one hour; dysfunction related to the acute respiratory distress syndrome (ARDS), as defined by a ratio of the partial pressure of arterial oxygen (in millimeters of mercury) to the fraction of inspired oxygen (PaO2/FiO2) of less than 200 in the presence of acute, diffuse bilateral infiltrates; pulmonary-system dysfunction, defined as a PaO2 of less than 70 mm Hg while the patient was breathing room air or a PaO2/FiO2 of less than 333 if the patient was receiving supplemental oxygen (if the patient had pneumonia or chronic lung disease as the solitary cause of sepsis, he or she was also required to meet the definition of ARDS); or central nervous system dysfunction, defined as a decrease in the Glasgow coma score by at least two points.
A maximum of 24 hours was allowed for the patient to meet the entry criteria and for the study drug to be administered. Patients were excluded if they were pregnant, were less than 18 years old, had suspected hypersensitivity to cyclooxygenase inhibitors, had received a cyclooxygenase inhibitor within the preceding 12 hours (or aspirin within the preceding 24 hours), or were enrolled in another experimental study or if consent could not be obtained. We also excluded patients who had suspected brain death, advanced renal failure (serum creatinine, >4 mg per deciliter [354 μmol per liter] unless the patient's condition was stable and the patient was receiving long-term dialysis) or hepatic failure (serum bilirubin, >4 mg per deciliter [68 μmol per liter]), a core temperature of less than 32.2°C, a platelet count of less than 20,000 per cubic millimeter, a granulocyte count of less than 1000 per cubic millimeter due to causes other than sepsis, human immunodeficiency virus infection, gastrointestinal bleeding, or a life expectancy of less than six hours; those who were treated with major immunosuppressive drugs; and those whose physicians were not committed to providing aggressive life support.
Treatment Assignments
Patients were assigned to the study groups in a blinded fashion in each treatment center with the use of a permuted-block randomization algorithm. They received either ibuprofen (Motrin, Upjohn), given intravenously in a dose of 10 mg per kilogram (maximal dose, 800 mg) over a period of 30 to 60 minutes every 6 hours for eight doses or placebo (glycine-buffer vehicle) administered in the same volume and at the same times. Both the patient and the care givers were unaware of the patient's treatment assignment.
Laboratory Data
Before the first dose of the study drug, a base-line medical history was taken and a physical examination was performed to document the presumed cause, site, and time of onset of the sepsis syndrome. Blood was obtained for culture from at least two sites. Infection was classified as occurring in the lungs, peritoneum, or urinary tract or at another site or an unknown site. Chest radiographs were obtained at entry and scored by the chest radiologist to indicate the presence and severity of pulmonary edema.26
The method of calculating the Acute Physiology and Chronic Health Evaluation (APACHE II) score was modified so that the score represented a point in time — that is, it was calculated from the base-line data rather than from the worst values obtained during the first 24 hours of care in the intensive care unit. Data obtained at entry and every 4 hours thereafter for the first 44 hours and then at 72, 96, and 120 hours included the patient's temperature, mean systemic blood pressure, respiratory rate, heart rate, urinary output (as an hourly average), arterial-blood gas measurements, and requirement for antipyretic agents. Values for mean blood pressure were calculated with the following formula: (0.33 × systolic pressure) + (0.67 × diastolic pressure). When a pulmonary-artery catheter was present, the cardiac output, pulmonary-artery pressure, pulmonary-wedge pressure, and central venous pressure were measured at base line and 20 hours later. Blood lactate was measured, and the delivery and consumption of oxygen calculated, at base line and 20 hours.30
Blood samples were obtained at base line and 20, 44, 72, and 120 hours after study entry for the measurement of hemoglobin, the total leukocyte count, the platelet count, bilirubin, serum aspartate aminotransferase, lactate dehydrogenase, creatinine, blood urea nitrogen, and electrolytes. Data were recorded on the patient's requirements for blood transfusion, intensive care, and mechanical ventilation.
Measurements of Ibuprofen and Eicosanoids
Samples of urine and blood were obtained at base line and 20, 44, 72, 96, and 120 hours after study entry and were maintained at -70°C. Batch assays using stable isotope-dilution methods in conjunction with gas chromatography–mass spectrometry to detect urinary 11-dehydro-thromboxane B2 and 2,3-dinor 6-keto-prostaglandin-F1α were performed by the Vanderbilt Prostaglandin Core Laboratory.31,32 Ibuprofen levels were measured in plasma samples obtained at base line and 20 hours after study entry.33
Definitions
We used the entry criteria listed in group 2 above to define shock, ARDS, pulmonary-system dysfunction, and renal dysfunction. Shock was considered to have been reversed when the systolic blood pressure was stable and greater than 90 mm Hg for 12 hours without vasopressor support. Reversal of ARDS was considered to have occurred when the patient no longer met the criteria for ARDS on the basis of either arterial-blood gas measurement or chest radiography, and when the reversal lasted at least 24 hours.
We calculated the number of failure-free days (days without organ-system dysfunction) for the clinically important organ systems, as described above, during the 30 days immediately after study entry. For example, a patient who survived 30 days and had no renal failure (as determined on the basis of urinary output) was assigned a score of 30. If there was renal failure for 10 days and the patient died on day 15, a score of 5 was assigned. To summarize these data, we calculated the total number of failure-free days for all organs as the mean number of days the patients were free of all organ failure.
Statistical Analysis
In this study, we sought to enroll a total of 525 patients who could be evaluated. This figure was based on an expected treatment-related relative reduction in mortality of 35 percent (from 30 percent to 19.5 percent) and a power of 0.80. An independent Data and Safety Monitoring Committee examined the data on each group of 105 patients. Mortality by day 30 was the variable used in considering early termination of the trial (with the O'Brien–Fleming method used to determine sequentially adjusted P values34). After the fourth interim analysis (of 415 patients), the Data and Safety Monitoring Committee was provided with conditional estimates of the power of the study to determine potential differences in mortality between the study groups. A futility index35,36 was derived in which mortality by day 30 was treated as a dichotomous outcome variable. Using this information, we stopped the trial after the enrollment of 455 patients.
Short-time-series data were analyzed by deriving the area under the curve of the response variable for each patient, dividing this area by the time the patient spent in the study, and then using a Wilcoxon rank-sum test to compare these univariate statistics.37,38 A variety of other approaches were examined, and they yielded similar results.39,40 Two-by-two contingency tables were analyzed with a chi-square statistic with Yates' correction for continuity.38 Kaplan–Meier survival curves were compared by the log-rank test.38 Ninety-five percent confidence intervals for proportions were calculated by the method of Fleiss.41 P values of less than 0.05 were considered to indicate statistical significance.
Results
Comparison of Study Groups
The seven centers participating in the trial recruited 455 patients from a total of 3311 patients who fulfilled the study criteria between October 1989 and March 1995. Among the 2862 patients excluded from the study for whom data on 30-day outcomes were available, the mortality rate was 41 percent. The major reasons for exclusion were the need for more than 24 hours to meet the entry criteria and receive the study drug (24 percent of patients), gastrointestinal bleeding (16 percent), inability to obtain consent (12 percent), use of a cyclooxygenase-blocking drug (9 percent), and thrombocytopenia or neutropenia (9 percent). All 455 recruited patients were included in the analyses presented here.
Two hundred twenty-four patients were assigned to the ibuprofen group, and 231 patients were assigned to the placebo group. Table 1Table 1
Base-Line Characteristics of the Study Patients According to Treatment Group. compares the base-line characteristics of the two groups and shows that the groups were balanced with respect to a variety of measures that correlate with mortality and morbidity. The mean (±SD) interval that elapsed from the time the patient met the entry criteria to the administration of the study drug was 10.7±0.6 hours in the ibuprofen group and 11.3±0.6 hours in the placebo group (P not significant). The predominant site of infection was the lung. In each group, infections associated with positive blood cultures were considered to have been treated with appropriate antibiotics in 96 percent of cases (Table 1). Rates of organ dysfunction (organ failure) were similar in the two groups at the time of randomization, except that renal dysfunction was significantly more common in the placebo group.Ibuprofen, Prostacyclin, and Thromboxane
At enrollment, the patients in both groups excreted substantial amounts of prostacyclin and thromboxane metabolites — approximately 40 and 15 times the normal amounts, respectively. After 44 hours of ibuprofen therapy, the rate of excretion of the prostacyclin metabolite was 11 percent of that in the placebo group and 4 percent of the base-line value; similar reductions were observed in the ibuprofen group with regard to excretion of the thromboxane metabolite (P<0.05). At 20 hours (2 hours after the fourth dose), ibuprofen levels were 24.4±15.0 mg per deciliter.
Physiologic Responses
The use of acetaminophen to reduce temperature was not dealt with in the study protocol. At the time of randomization, 33 percent of the ibuprofen group and 29 percent of the placebo group were receiving acetaminophen for this purpose. As temperatures decreased in the ibuprofen-treated patients, their use of acetaminophen began to diminish within eight hours. This did not occur in the placebo group. Within the first 24 hours after study-drug administration, the rate of use of acetaminophen decreased to 22 percent in the ibuprofen group, but it increased to 44 percent in the placebo group (P<0.001). The decline in the heart rate during the first eight hours of treatment was significantly greater in the ibuprofen group than in the placebo group (P<0.001). In patients receiving mechanical ventilation, ibuprofen tended to decrease minute ventilation by approximately 2 liters per minute, whereas placebo did not (P = 0.16) (Figure 1Figure 1
Mean (±SE) Temperature, Heart Rate, and Minute Ventilation in the Study Patients.). At base line, the mean blood pressure was 80±1 mm Hg in the ibuprofen group and 79±1 mm Hg in the placebo group; at 2 hours, it was 75±1 and 79±1 mm Hg, respectively; and at 24 hours, it was 80±1 and 82±1 mm Hg (P not significant for any of these comparisons).Mortality and Organ-System Dysfunction
Shock was present at base line in 65 percent of the ibuprofen group and 63 percent of the placebo group. There were no treatment-related differences in the duration of shock. ARDS was present at base line in 29 percent of the ibuprofen group and 28 percent of the placebo group. There was a trend in the ibuprofen group toward more days free of pulmonary dysfunction and ARDS, as well as toward more days free of organ-system failure overall (P not significant) (Figure 2Figure 2
Median Time without Organ Failure during the Study.).With regard to clinical indications, 59 ibuprofen-treated patients and 51 placebo-treated patients had indwelling pulmonary-artery catheters and measurements of oxygen consumption and delivery at base line and 20 hours after study entry. Among these patients, 56 of those treated with ibuprofen and 46 of those receiving placebo had blood lactate levels available for study. Within 20 hours of study entry, oxygen consumption decreased by 8 percent in the ibuprofen group and increased by 6 percent in the placebo group (P = 0.046), and lactate levels decreased by 17 percent and increased by 15 percent, respectively (P = 0.005), but oxygen delivery did not change significantly (a decrease of 5 percent as compared with an increase of 2 percent). The lactate levels available in the study population as a whole showed similar reductions with ibuprofen (P = 0.023) (Figure 3Figure 3
Mean (±SE) Percent Changes from Base Line to 20 Hours after Base Line in Oxygen Delivery, Oxygen Consumption, and Blood Lactate Levels among Patients with Pulmonary-Artery Catheters for Whom Data Were Available.).Mortality by day 30 did not differ significantly in the ibuprofen and placebo groups (37 percent vs. 40 percent) (Table 2Table 2
Mortality in Prospectively Defined Subgroups of Patients 30 Days after Entry into the Study.). Outcomes in the two groups were also similar when the patients with shock and those with positive blood cultures were studied separately. However, there was a trend toward lower mortality in the ibuprofen group among black patients (42 percent vs. 57 percent, P = 0.06) and a significant difference in mortality among patients with hypothermia at entry (54 percent vs. 90 percent, P = 0.02).Complications
Serum creatinine and urinary output were measured serially over a five-day period to evaluate the effects of the study treatment on renal function, and no significant differences were detected between the groups. Hemodialysis was required for the first time in 6 of 224 ibuprofen-treated patients (3 percent) and 13 of 231 placebo-treated patients (6 percent, P = 0.11). Serial hemoglobin levels did not differ significantly between the two groups, nor were there any marked differences in requirements for transfusion. Gastrointestinal bleeding was reported in 9 patients in the ibuprofen group and 16 patients in the placebo group. During the 30 days of follow-up, distinct second episodes of sepsis occurred in 8.2 percent of the ibuprofen group and 11.1 percent of the placebo group.
Discussion
Ibuprofen was chosen for this trial because studies in both animals and humans in which aspirin,4-6 indomethacin, and ibuprofen were used as inhibitors of cyclooxygenase showed improvement in either the morbidity or the mortality associated with sepsis and because clinical experience with ibuprofen suggested that the drug was safe.7-19,22,26-28,42,43 In this study, we demonstrated that ibuprofen reduces fever, tachycardia, and lactic acid levels in patients with sepsis. However, we found no significant effect on mortality or organ failure. Evaluation of renal function and hemorrhagic events failed to demonstrate adverse effects when ibuprofen was administered over a 48-hour period early in the course of sepsis.
In animals in which systemic vasodilatation is prominent, such as primates and dogs with sepsis, ibuprofen increases blood pressure and survival.17-21 In a previous clinical study, we found that ibuprofen was associated with a trend toward increased systemic blood pressure, reversal of shock, and normalization of pH.26 In the current trial, we found reductions in lactic acid and oxygen consumption but no changes in oxygen delivery or blood pressure. These changes may be a result of decreased metabolic demand, as evidenced by the lower temperatures and heart rates in the ibuprofen-treated patients, or by improved matching of the delivery of oxygen to its consumption at the tissue level.
The practice of fever control in critically ill patients is controversial. In this study, 44 percent of patients with sepsis received acetaminophen for this purpose, suggesting that many attending physicians desired to limit fever. Even so, temperatures remained significantly elevated in the placebo group, but they returned to normal in the ibuprofen group. These data suggest that acetaminophen was less effective than ibuprofen in reducing temperature in this population of patients.
The analysis of days free of organ failure was performed to obtain a more sensitive measure of effects than that provided by the analysis of mortality.44 This analysis was especially important because of the confounding effect of early mortality on measures such as the duration of organ failure. No consistent effects of ibuprofen treatment were noted with regard to the number of days free of organ failure, the efficiency of oxygenation, findings on chest radiography, or the requirement for mechanical ventilation. This suggests that the effects of ibuprofen on these measures, if any, are fairly small.44
High circulating levels of the eicosanoid metabolites of prostacyclin and thromboxane have been associated with increased mortality in patients with sepsis.23,24 We found urinary concentrations of prostacyclin metabolites to be approximately 40 times higher than normal, and those of thromboxane metabolites to be approximately 15 times higher than normal. Levels of these metabolites were markedly elevated for at least 48 hours in the placebo group. These findings confirm our earlier work showing marked elevations of eicosanoids in patients with sepsis, with prompt reductions after ibuprofen treatment.
The absence of improved mortality with ibuprofen could have explanations other than the simple lack of efficacy. Perhaps racial differences or physiologic conditions such as hypothermia portend a different response to the drug, as the data in Table 2 show. Selecting the proper dose and duration of ibuprofen treatment is always a concern. Our findings show evidence of marked inhibition of cyclooxygenase, which suggests that the dose of ibuprofen was adequate. However, it is possible that there are effects other than the effects on cyclooxygenase that were not manifested at the dose selected. The treatment period of 48 hours used in this study was based on the information on safety available at the start of the trial regarding the intravenous formulation of ibuprofen. The data on cyclooxygenase metabolites presented here and in our pilot study indicate that the activity of arachidonic acid metabolites persists for at least several days after the onset of sepsis, as do the corresponding changes in vital signs associated with these mediators. It is thus possible that longer-lasting therapy would have produced different results. Finally, although the patients received the study drug quite early in this study, it is possible that treatment given even earlier, or as prophylaxis, may be necessary to produce effects on mortality and organ failure.27,45
Ibuprofen can have adverse effects, especially on the renal21,46 and gastrointestinal47 systems. Measuring renal function in terms of days of renal failure, serial creatinine levels, serial determinations of urinary output, or the need for dialysis did not reveal adverse effects, nor did the serial measurement of transfusion requirements, hemoglobin levels, or the incidence of episodes of serious gastrointestinal bleeding show differences between the study groups. The slight decrease in blood pressure (by approximately 4 mm Hg) in the first hours after the administration of ibuprofen was not statistically significant, but it was intriguing nonetheless. Further analysis indicated that this change could be attributed to the influence of patients who entered the trial with hypertension. We speculate that such patients were experiencing pain or other distress, and that ibuprofen, in relieving these underlying causes of hypertension, may have allowed the blood pressure to return toward normal. It did not lower the blood pressure of normotensive or hypotensive patients.
In summary, from this double-blind, randomized, placebo-controlled study of intravenous ibuprofen in patients with sepsis we conclude that treatment with ibuprofen is safe in such patients and markedly reduces the synthesis of prostacyclin and thromboxane, but that it has no effect on survival or the development of shock or ARDS. Treatment with ibuprofen does have clear physiologic effects on fever, tachycardia, oxygen consumption, and lactic acidosis in patients with sepsis.
Supported in part by grants (HL 43167, HL 19153, HL 07123) from the National Heart, Lung, and Blood Institute and by the Bernard Werthan, Sr., Fund for Pulmonary Research.
We are indebted to the Upjohn Company for providing intravenous ibuprofen, to the attending physicians for referring patients, to the bedside critical care nurses for their help and support, and to the patients and their families for participating in this scientific investigation.
Source Information
From the Divisions of Pulmonary and Critical Care Medicine (G.R.B., A.P.W., B.W.C., B.B.S.), Biostatistics (W.D.D.), and Biomedical Engineering and Computing (S.B.H.), Vanderbilt University Medical Center, Nashville; the Program of Critical Care Medicine, Department of Medicine, St. Paul's Hospital and University of British Columbia, Vancouver, B.C., Canada (J.A.R.); the University of Miami School of Medicine and Department of Veterans Affairs Medical Center, Miami (R.S.); the Department of Pulmonary and Critical Care Medicine, Louisiana State University Medical Center, New Orleans (W.R.S.); the Division of Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, Seattle (K.P.S.); the Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, N.C. (W.J.F.); and the Division of Pulmonary Medicine, Methodist Hospital, Indianapolis (P.E.W.).
Address reprint requests to Dr. Bernard at Rm. T-1217, Medical Center North, Vanderbilt University School of Medicine, Nashville, TN 37232.
Additional institutions and investigators participating in the Ibuprofen in Sepsis Study Group are listed in the Appendix.
Appendix
The following additional institutions and investigators participated in the Ibuprofen in Sepsis Study Group: St. Paul's Hospital, Vancouver, B.C., Canada — A. Drummond; the University of Miami School of Medicine and the Department of Veterans Affairs Medical Center, Miami — M. Pena; Louisiana State University Medical Center, New Orleans — B. deBoisblanc, B. Everett, C. Glenn, and D. Tebbe; Vanderbilt University Medical Center, Nashville — L.C. Carmichael, M.J. Stroud, K. Jiang, W.D. Plummer, Jr., and F.E. Carroll; Harborview Medical Center and the University of Washington, Seattle — L.D. Hudson and D. Anardi; Duke University Medical Center, Durham, N.C. — M.J. Abernathy, L. Mallatratt, and P. Weston; Methodist Hospital, Indianapolis — K. Colvin.
Project Officers and Data and Safety Monitoring Committee: University of California, San Diego — R. Spragg; Harvard University School of Medicine, Boston — R. Demling; Cleveland Clinic Foundation, Cleveland — G. Beck; University of Minnesota, Minneapolis — F. Cerra; Division of Lung Diseases, National Heart, Lung, and Blood Institute, Bethesda, Md. — L. Jensen and C. Bosken.
Study Coordinating Center: the Center for Lung Research, Departments of Medicine, Preventive Medicine, and Biomedical Engineering, Vanderbilt University School of Medicine, Nashville.
- References
References
1
Rangel-Frausto MS ,Pittet D ,Costigan M ,Hwang T ,Davis CS ,Wenzel RP . The natural history of the systemic inflammatory response syndrome (SIRS): a prospective study. JAMA 1995;273:117-123
CrossRef | Web of Science | Medline2
Bone RC ,Balk RA ,Cerra FB , et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 1992;101:1644-1655
CrossRef | Web of Science | Medline3
Parrillo JE , moderator. Septic shock in humans: advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy. Ann Intern Med 1990;113:227-242
Web of Science | Medline4
Northover BJ ,Subramanian G . Analgesic-antipyretic drugs as antagonists of endotoxin shock in dogs. J Pathol Bacteriol 1962;83:463-468
CrossRef | Web of Science | Medline5
Hinshaw LB ,Solomon LA ,Erdos EG ,Reins DA ,Gunter BJ . Effects of acetylsalicylic acid on the canine response to endotoxin. J Pharmacol Exp Ther 1967;157:665-671
Web of Science | Medline6
Fletcher JR ,Ramwell PW . Modification, by aspirin and indomethacin, of the haemodynamic and prostaglandin releasing effects of E. coli endotoxin in the dog. Br J Pharmacol 1977;61:175-181
Web of Science | Medline7
Parratt JR ,Sturgess RM . E. coli endotoxin shock in the cat: treatment with indomethacin. Br J Pharmacol 1975;53:485-488
Web of Science | Medline8
Parratt JR ,Sturgess RM . Evidence that prostaglandin release mediates pulmonary vasoconstriction induced by E. coli endotoxin. J Physiol 1975;246:79P-80P
Web of Science | Medline9
Fletcher JR ,Ramwell PW . Indomethacin improves survival after endotoxin in baboons. Adv Prostaglandin Thromboxane Leukot Res 1980;7:821-82810
Harris RH ,Zmudka M ,Maddox Y ,Ramwell PW ,Fletcher JR . Relationships of TxB2 and 6-keto-PGF1α to the hemodynamic changes during baboon endotoxic shock. Adv Prostaglandin Thromboxane Leukot Res 1980;7:843-84911
Kopolovic R ,Thraikill KM ,Martin DT ,Carey LC ,Cloutier CT . A critical comparison of the hematologic, cardiovascular, and pulmonary response to steroids and nonsteroidal anti-inflammatory drugs in a modelof sepsis and adult respiratory distress syndrome. Surgery 1986;100:679-690
Web of Science | Medline12
Mizus I ,Michael J ,Summer W ,Gurtner G . Acid aspiration induced pulmonary artery pressure rise is attenuated by hypoxia or ibuprofen. Crit Care Med 1983;11:241-241 abstract.
Web of Science13
Perkowski SZ ,Havill AM ,Flynn JT ,Gee MH . Role of intrapulmonary release of eicosanoids and superoxide anion as mediators of pulmonary dysfunction and endothelial injury in sheep with intermittent complement activation. Circ Res 1983;53:574-583
Web of Science | Medline14
Snapper JR ,Hutchison AA ,Ogletree ML ,Brigham KL . Effects of cyclooxygenase inhibitors on the alterations in lung mechanics caused by endotoxemia in the unanesthetized sheep. J Clin Invest 1983;72:63-76
CrossRef | Web of Science | Medline15
Sielaff TD ,Sugerman HJ ,Tatum JL ,Blocher CR . Successful treatment of adult respiratory distress syndrome by histamine and prostaglandin blockade in a porcine Pseudomonas model. Surgery 1987;102:350-357
Web of Science | Medline16
Wright PE ,Bernard GR . Mechanisms of late hemodynamic and airway dynamic responses to endotoxin in awake sheep. Am Rev Respir Dis 1989;140:672-678
CrossRef | Web of Science | Medline17
Almqvist PM ,Ekstrom B ,Kuenzig M ,Haglund U ,Schwartz SI . Increased survival of endotoxin-injected dogs treated with methylprednisolone, naloxone, and ibuprofen. Circ Shock 1984;14:129-136
Medline18
Fink MP ,MacVittie TJ ,Casey LC . Inhibition of prostaglandin synthesis restores normal hemodynamics in canine hyperdynamic sepsis. Ann Surg 1984;200:619-626
CrossRef | Web of Science | Medline19
Jacobs ER ,Soulsby ME ,Bone RC ,Wilson FJ Jr ,Hiller FC . Ibuprofen in canine endotoxin shock. J Clin Invest 1982;70:536-541
CrossRef | Web of Science | Medline20
Soulsby ME ,Jacobs ER ,Perlmutter BH ,Bone RC . Protection of myocardial function during endotoxin shock by ibuprofen. Prostaglandins Leukot Med 1984;13:295-305
CrossRef | Medline21
Fink MP ,MacVittie TJ ,Casey LC . Effects of nonsteroidal anti-inflammatory drugs on renal function in septic dogs. J Surg Res 1984;36:516-525
CrossRef | Web of Science | Medline22
Hanly PJ ,Roberts D ,Dobson K ,Light RB . Effect of indomethacin on arterial oxygenation in critically ill patients with severe bacterial pneumonia. Lancet 1987;1:351-354
CrossRef | Web of Science | Medline23
Halushka PV ,Reines HD ,Barrow SE , et al. Elevated plasma 6-keto-prostaglandin F1α in patients in septic shock. Crit Care Med 1985;13:451-453
CrossRef | Web of Science | Medline24
Reines HD ,Halushka PV ,Cook JA ,Wise WC ,Rambo W . Plasma thromboxane concentrations are raised in patients dying with septic shock. Lancet 1982;2:174-175
CrossRef | Web of Science | Medline25
Michie HR ,Manogue KR ,Spriggs DR , et al. Detection of circulating tumor necrosis factor after endotoxin administration. N Engl J Med 1988;318:1481-1486
Full Text | Web of Science | Medline26
Bernard GR ,Reines HD ,Halushka PV , et al. Prostacyclin and thromboxane A2 formation is increased in human sepsis syndrome: effects of cyclooxygenase inhibition. Am Rev Respir Dis 1991;144:1095-1101
CrossRef | Web of Science | Medline27
Galt SW ,Bech FR ,McDaniel MD , et al. The effect of ibuprofen on cardiac performance during abdominal aortic cross-clamping. J Vasc Surg 1991;13:879-883
CrossRef28
Haupt MT ,Jastremski MS ,Clemmer TP ,Metz CA ,Goris GB . Effect of ibuprofen in patients with severe sepsis: a randomized, double-blind, multicenter study. Crit Care Med 1991;19:1339-1347
CrossRef | Web of Science | Medline29
Bone RC ,Fisher CJ Jr ,Clemmer TP , et al. A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 1987;317:653-658
Full Text | Web of Science | Medline30
Phang PT ,Cunningham KF ,Ronco JJ ,Wiggs BR ,Russell JA . Mathematical coupling explains dependence of oxygen consumption on oxygen delivery in ARDS. Am J Respir Crit Care Med 1994;150:318-323
Web of Science | Medline31
Hubbard HL ,Eller TD ,Mais DE , et al. Extraction of thromboxane B2 from urine using an immobilized antibody column for subsequent analysis by gas chromatography-mass spectrometry. Prostaglandins 1987;33:149-160
CrossRef | Web of Science | Medline32
Christman BW ,Christman JW ,Dworski R ,Blair IA ,Prakash C . Prostaglandin E2 limits arachidonic acid availability and inhibits leukotriene B4 synthesis in rat alveolar macrophages by a nonphospholipase A2 mechanism. J Immunol 1993;151:2096-2104
Web of Science | Medline33
Lockwood GF ,Wagner JG . High-performance liquid chromatographic determination of ibuprofen and its major metabolites in biological fluids. J Chromatogr 1982;232:335-343
CrossRef | Web of Science | Medline34
O'Brien PC ,Fleming TR . A multiple testing procedure for clinical trials. Biometrics 1979;35:549-556
CrossRef | Web of Science | Medline35
Ware JH ,Muller JE ,Braunwald E . The futility index: an approach to the cost-effective termination of randomized clinical trials. Am J Med 1985;78:635-643
CrossRef | Web of Science | Medline36
Halperin M ,Lan KKG ,Ware JH ,Johnson NJ ,DeMets DL . An aid to data monitoring in long-term clinical trials. Control Clin Trials 1982;3:311-323
CrossRef | Medline37
Matthews JNS ,Altman DG ,Campbell MJ ,Royston P . Analysis of serial measurements in medical research. BMJ 1990;300:230-235
CrossRef | Web of Science | Medline38
Armitage P, Berry G. Statistical methods in medical research. 3rd ed. Oxford, England: Blackwell Scientific, 1994.
39
SAS/STAT software: changes and enhancements, release 6.07. Technical report P-229. Cary, N.C.: SAS Institute, 1992.
40
Latour D, Latour K, Wolfinger RD. Getting started with PROC MIXED. Cary, N.C.: SAS Institute, 1994.
41
Fleiss JL. Statistical methods for rates and proportions. 2nd ed. New York: John Wiley, 1981:13-4.
42
Rinaldo JE ,Dauber JH . Effect of methylprednisolone and of ibuprofen, a nonsteroidal antiinflammatory agent, on bronchoalveolar inflammation following endotoxemia. Circ Shock 1985;16:195-203
Medline43
Rinaldo JE ,Pennock B . Effects of ibuprofen on endotoxin-induced alveolitis: biphasic dose response and dissociation between inflammation and hypoxemia. Am J Med Sci 1986;291:29-38
CrossRef | Web of Science | Medline44
Bernard GR ,Doig G ,Hudson LD , et al. Quantification of organ failure for clinical trials and clinical practice. Am J Respir Crit Care Med 1995;151:Suppl:A323-A323 abstract.45
Huval WV ,Lelcuk S ,Allen PD ,Mannick JA ,Shepro D ,Hechtman HB . Determinants of cardiovascular stability during abdominal aortic aneurysmectomy (AAA). Ann Surg 1984;199:216-222
CrossRef | Web of Science | Medline46
Delmas PD . Non-steroidal anti-inflammatory drugs and renal function. Br J Rheumatol 1995;34:Suppl 1:25-28
CrossRef | Medline47
Cook DJ ,Fuller HD ,Guyatt GH , et al. Risk factors for gastrointestinal bleeding in critically ill patients. N Engl J Med 1994;330:377-381
Full Text | Web of Science | Medline
- Citing Articles (200)
Citing Articles
1
Howard S. Smith, Bryan Voss. (2012) Pharmacokinetics of Intravenous Ibuprofen. Drugs 72:3, 327-337
CrossRef2
Paul Jeffrey Young, Manoj Saxena, Richard Beasley, Rinaldo Bellomo, Michael Bailey, David Pilcher, Simon Finfer, David Harrison, John Myburgh, Kathryn Rowan. (2012) Early peak temperature and mortality in critically ill patients with or without infection. Intensive Care Medicine
CrossRef3
Peter B Kroll. (2012) Intravenous ibuprofen for postoperative pain. Pain Management 2:1, 47-54
CrossRef4
Byungse Suh, Rafik Samuel. 2011. Drotrecogin Alfa Activated (Recombinant Human Activated Protein C, Xigris). .
CrossRef5
Joseph G. Cannon. (2011) Perspective on fever: The basic science and conventional medicine. Complementary Therapies in Medicine
CrossRef6
Chad A. Baumwart, Tom J. Doherty, James Schumacher, Rebekah S. Willis, Henry S. Adair, Barton W. Rohrbach. (2011) Effects of hyperbaric oxygen treatment on horses with experimentally induced endotoxemia. American Journal of Veterinary Research 72:9, 1266-1275
CrossRef7
Gamze Demirel, Istemi Han Celik, Fuat Emre Canpolat, Omer Erdeve, Serife Suna Oguz, Ugur Dilmen. (2011) The effects of ibuprofen on sepsis parameters in preterm neonates. Early Human Development
CrossRef8
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CrossRef9
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CrossRef10
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CrossRef11
Hollis R. OʼNeal, Tatsuki Koyama, Elizabeth A. S. Koehler, Edward Siew, Blake R. Curtis, Richard D. Fremont, Addison K. May, Gordon R. Bernard, Lorraine B. Ware. (2011) Prehospital statin and aspirin use and the prevalence of severe sepsis and acute lung injury/acute respiratory distress syndrome*. Critical Care Medicine 39:6, 1343-1350
CrossRef12
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CrossRef13
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CrossRef14
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CrossRef15
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CrossRef16
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CrossRef17
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CrossRef18
G. Wright, A. Chattree, R. Jalan. (2011) Management of Hepatic Encephalopathy. International Journal of Hepatology 2011, 1-10
CrossRef19
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CrossRef20
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CrossRef21
Errol R. Norwitz, Hee Joong Lee. 2010. Septic Shock. , 571-595.
CrossRef22
Jane V Carey. (2010) Literature review: should antipyretic therapies routinely be administered to patient fever?. Journal of Clinical Nursing 19:17-18, 2377-2393
CrossRef23
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CrossRef24
Rachel S. Greenberg, Hegang Chen, Jeffrey D. Hasday. (2010) Acetaminophen has limited antipyretic activity in critically ill patients. Journal of Critical Care 25:2, 363.e1-363.e7
CrossRef25
K. Reinhart, F.M. Brunkhorst, H.-G. Bone, J. Bardutzky, C.-E. Dempfle, H. Forst, P. Gastmeier, H. Gerlach, M. Gründling, S. John, W. Kern, G. Kreymann, W. Krüger, P. Kujath, G. Marggraf, J. Martin, K. Mayer, A. Meier-Hellmann, M. Oppert, C. Putensen, M. Quintel, M. Ragaller, R. Rossaint, H. Seifert, C. Spies, F. Stüber, N. Weiler, A. Weimann, K. Werdan, T. Welte. (2010) Prävention, Diagnose, Therapie und Nachsorge der Sepsis. Intensivmedizin und Notfallmedizin 47:3, 185-207
CrossRef26
Lee-Wei Chen, Hsiu-Ting Tseng, Pei-Hsuan Chen, Ching-Mei Hsu. (2010) Peritonitis-induced peroxynitrite and lung damage depends on c-Jun NH2-terminal kinase signaling of hematopoietic cells. Critical Care Medicine 38:4, 1168-1178
CrossRef27
K. Reinhart, F.M. Brunkhorst, H.-G. Bone, J. Bardutzky, C.-E. Dempfle, H. Forst, P. Gastmeier, H. Gerlach, M. Gründling, S. John, W. Kern, G. Kreymann, W. Krüger, P. Kujath, G. Marggraf, J. Martin, K. Mayer, A. Meier-Hellmann, M. Oppert, C. Putensen, M. Quintel, M. Ragaller, R. Rossaint, H. Seifert, C. Spies, F. Stüber, N. Weiler, A. Weimann, K. Werdan, T. Welte. (2010) Prävention, Diagnose, Therapie und Nachsorge der Sepsis. Der Anaesthesist 59:4, 347-370
CrossRef28
Peter C. Minneci, Katherine J. Deans, Michael Haley, Xizhong Cui, Charles Natanson, Peter Q. Eichacker. 2010. Factors Influencing the Efficacy of Mediator-Specific Anti-Inflammatory, Glucocorticoid, and Anticoagulant Therapies for Sepsis. .
CrossRef29
Yasufumi NAKAJIMA. (2010) Investigation for Drawing up the Guidelines in Temperature Management in the Field of Anesthesia and Intensive Care. THE JOURNAL OF JAPAN SOCIETY FOR CLINICAL ANESTHESIA 30:3, 393-397
CrossRef30
Amy E. DeClue, Kurt J. Williams, Claire Sharp, Carol Haak, Elizabeth Lechner, Carol R. Reinero. (2009) Systemic response to low-dose endotoxin infusion in cats
. Veterinary Immunology and Immunopathology 132:2-4, 167-174
CrossRef31
H.-P. Hartung, L. Mouthon, R. Ahmed, S. Jordan, K. B. Laupland, S. Jolles. (2009) Clinical applications of intravenous immunoglobulins (IVIg) - beyond immunodeficiencies and neurology. Clinical & Experimental Immunology 158, 23-33
CrossRef32
Suzanne Heemskerk, Rosalinde Masereeuw, Frans G. M. Russel, Peter Pickkers. (2009) Selective iNOS inhibition for the treatment of sepsis-induced acute kidney injury. Nature Reviews Nephrology 5:11, 629-640
CrossRef33
Philip S. Barie, Lynn J. Hydo, Fredric M. Pieracci, Jian Shou, Soumitra R. Eachempati. (2009) Multiple Organ Dysfunction Syndrome in Critical Surgical Illness. Surgical Infections 10:5, 369-377
CrossRef34
Oddeke van Ruler, Marcus J. Schultz, Johannes B. Reitsma, Dirk J. Gouma, Marja A. Boermeester. (2009) Has Mortality from Sepsis Improved and What to Expect from New Treatment Modalities: Review of Current Insights. Surgical Infections 10:4, 339-348
CrossRef35
Neeraj Badjatia. (2009) Hyperthermia and fever control in brain injury. Critical Care Medicine 37:Supplement, S250-S257
CrossRef36
Kevin B. Laupland. (2009) Fever in the critically ill medical patient. Critical Care Medicine 37:Supplement, S273-S278
CrossRef37
Óscar Martínez, Nicolás Nin, Andrés Esteban. (2009) Evidencias de la posición en decúbito prono para el tratamiento del síndrome de distrés respiratorio agudo: una puesta al día. Archivos de Bronconeumología 45:6, 291-296
CrossRef38
Jason B. Martin, Arthur P. Wheeler. (2009) Approach to the Patient with Sepsis. Clinics in Chest Medicine 30:1, 1-16
CrossRef39
Virginie Maxime, Olivier Lesur, Djillali Annane. (2009) Adrenal Insufficiency in Septic Shock. Clinics in Chest Medicine 30:1, 17-27
CrossRef40
Craig R. Weinert, Shravan Kethireddy, Sabita Roy. (2008) Opioids and Infections in the Intensive Care Unit Should Clinicians and Patients be Concerned?. Journal of Neuroimmune Pharmacology 3:4, 218-229
CrossRef41
Jason Phua, Thomas E. Stewart, Niall D. Ferguson. (2008) Acute respiratory distress syndrome 40 years later: Time to revisit its definition*. Critical Care Medicine 36:10, 2912-2921
CrossRef42
Christoph Schmidt, Klaus Höcherl, Birgül Kurt, Michael Bucher. (2008) Role of nuclear factor-κB-dependent induction of cytokines in the regulation of vasopressin V1A-receptors during cecal ligation and puncture-induced circulatory failure*. Critical Care Medicine 36:8, 2363-2372
CrossRef43
Gustavo A. Ospina-Tascón, Gustavo Luiz Büchele, Jean-Louis Vincent. (2008) Multicenter, randomized, controlled trials evaluating mortality in intensive care: Doomed to fail?. Critical Care Medicine 36:4, 1311-1322
CrossRef44
David A. Talan, Gregory J. Moran, Fredrick M. Abrahamian. (2008) Severe Sepsis and Septic Shock in the Emergency Department. Infectious Disease Clinics of North America 22:1, 1-31
CrossRef45
Marcus J. Schultz, Nicole P. Juffermans. (2008) Maldistribution of interalveolar perfusion—one early step in the pathogenesis of lung injury?*. Critical Care Medicine 36:2, 639-640
CrossRef46
Nicole Gallo-Payet, Jean-Francois Roussy, Frederic Chagnon, Claude Roberge, Olivier Lesur. (2008) Hypothalamic–pituitary–adrenal axis multiple and organ dysfunction syndrome in critical illness: A special focus on arginine-vasopressin and apelin. Journal of Organ Dysfunction 4:4, 216-229
CrossRef47
Cynthia M. Otto. (2007) Clinical trials in spontaneous disease in dogs: a new paradigm for investigations of sepsis. Journal of Veterinary Emergency and Critical Care 17:4, 359-367
CrossRef48
Deborah C. Silverstein, Lori S. Waddell, Kenneth J. Drobatz, Lesley G. King. (2007) Vasopressin therapy in dogs with dopamine-resistant hypotension and vasodilatory shock. Journal of Veterinary Emergency and Critical Care 17:4, 399-408
CrossRef49
Anna Sinistro, Chiara Ciaprini, Silvia Natoli, Emanuele Sussarello, Francesca Calò Carducci, Cristiana Almerighi, Marcella Capozzi, Francesca Bolacchi, Giovanni Rocchi, Alberto Bergamini. (2007) Lipopolysaccharide desensitizes monocytes–macrophages to CD40 ligand stimulation. Immunology 122:3, 362-370
CrossRef50
Venkatesh Aiyagari, Michael N. Diringer. (2007) Fever control and its impact on outcomes: What is the evidence?. Journal of the Neurological Sciences 261:1-2, 39-46
CrossRef51
Z. Xiang, R. M. Minter, X. Bi, P. J. Woolf, Y. He. (2007) miniTUBA: medical inference by network integration of temporal data using Bayesian analysis. Bioinformatics 23:18, 2423-2432
CrossRef52
H. Theilen, M. Ragaller. (2007) Therapie der Hyperthermie bei Sepsis und septischem Schock. Der Anaesthesist 56:9, 949-956
CrossRef53
Karen J Bosma, James F Lewis. (2007) Emerging therapies for treatment of acute lung injury and acute respiratory distress syndrome. Expert Opinion on Emerging Drugs 12:3, 461-477
CrossRef54
Gavin Wright, Rajiv Jalan. (2007) Ammonia and inflammation in the pathogenesis of hepatic encephalopathy: Pandora's box?. Hepatology 46:2, 291-294
CrossRef55
Navid Madershahian, Thorsten Wittwer, Justus Strauch, Ulrich F.W. Franke, Jens Wippermann, Mirko Kaluza, Thorsten Wahlers. (2007) Application of ECMO in Multitrauma Patients With ARDS as Rescue Therapy. Journal of Cardiac Surgery 22:3, 180-184
CrossRef56
Sheng-Wei Jin, Li Zhang, Qin-Quan Lian, Dong Liu, Ping Wu, Shang-Long Yao, Du-Yun Ye. (2007) Posttreatment with Aspirin-Triggered Lipoxin A4 Analog Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice: The Role of Heme Oxygenase-1. Anesthesia & Analgesia 104:2, 369-377
CrossRef57
Tohru Sakuragi, Xinchun Lin, Christine N. Metz, Kaie Ojamaa, Nina Kohn, Yousef Al-Abed, Edmund J. Miller. (2007) Lung-Derived Macrophage Migration Inhibitory Factor in Sepsis Induces Cardio-Circulatory Depression. Surgical Infections 8:1, 29-40
CrossRef58
Keith R. Walley, James A. Russell. (2007) Protein C ???1641 AA is associated with decreased survival and more organ dysfunction in severe sepsis*. Critical Care Medicine 35:1, 12-17
CrossRef59
Richard Henker, Karen K. Carlson. (2007) Fever. AACN Advanced Critical Care 18:1, 76-87
CrossRef60
Edward R. Sherwood, Daniel L. Traber. 2007. The systemic inflammatory response syndrome. , 292-309.
CrossRef61
Russell, James A., . (2006) Management of Sepsis. New England Journal of Medicine 355:16, 1699-1713
Full Text62
Anne-Corn??lie J. M. de Pont. (2006) Does cold-bloodedness protect against sepsis?*. Critical Care Medicine 34:10, 2692-2693
CrossRef63
Germaine Escames, Darío Acuña-Castroviejo, Luis Carlos López, Dun-xian Tan, Maria Dolores Maldonado, Marina Sánchez-Hidalgo, Josefa León, Russel J. Reiter. (2006) Pharmacological utility of melatonin in the treatment of septic shock: experimental and clinical evidence. Journal of Pharmacy and Pharmacology 58:9, 1153-1165
CrossRef64
K. Reinhart, F. M. Brunkhorst, H.-G. Bone, H. Gerlach, M. Gründling, G. Kreymann, P. Kujath, G. Marggraf, K. Mayer, A. Meier-Hellmann, C. Peckelsen, C. Putensen, F. Stüber, M. Quintel, M. Ragaller, R. Rossaint, N. Weiler, T. Welte, K. Werdan. (2006) Diagnose und Therapie der Sepsis. Clinical Research in Cardiology 95:8, 429-454
CrossRef65
R ISTURIZ. (2006) Global Distribution of Infectious Diseases Requiring Intensive Care. Critical Care Clinics 22:3, 469-488
CrossRef66
K. Reinhart, F. M. Brunkhorst, H.-G. Bone, H. Gerlach, M. Gründling, G. Kreymann, P. Kujath, G. Marggraf, K. Mayer, A. Meier-Hellmann, C. Peckelsen, C. Putensen, F. Stüber, M. Quintel, M. Ragaller, R. Rossaint, N. Weiler, T. Welte, K. Werdan. (2006) Diagnose und Therapie der Sepsis. Intensivmedizin und Notfallmedizin 43:5, 369-384
CrossRef67
K. Reinhart, F. M. Brunkhorst, H. G. Bone, H. Gerlach, M. Gründling, G. Kreymann, P. Kujath, G. Marggraf, K. Mayer, A. Meier-Hellmann, C. Peckelsen, C. Putensen, M. Quintel, M. Ragaller, R. Rossaint, F. Stüber, N. Weiler, T. Welte, K. Werdan. (2006) Diagnose und Therapie der Sepsis. Der Internist 47:4, 356-373
CrossRef68
Johanna Osterberg, Mikael Ljungdahl, Ulf Haglund. (2006) INFLUENCE OF CYCLOOXYGENASE INHIBITORS ON GUT IMMUNE CELL DISTRIBUTION AND APOPTOSIS RATE IN EXPERIMENTAL SEPSIS. Shock 25:2, 147-154
CrossRef69
Abed Azab, Sergio Kobal, Mazal Rubin, Jacob Kaplanski. (2006) Inhibition of prostaglandins does not reduce the cardiovascular changes during endotoxemia in rats. Prostaglandins, Leukotrienes and Essential Fatty Acids 74:2, 135-142
CrossRef70
Ulrich Bolder, Marc Gerhard Jeschke, Lukas Landmann, Francine Wolf, Corina de Sousa, Hans-Jürgen Schlitt, René Przkora. (2006) Heat stress enhances recovery of hepatocyte bile acid and organic anion transporters in endotoxemic rats by multiple mechanisms. Cell Stress & Chaperones 11:1, 89
CrossRef71
James A. Cook. (2005) Eicosanoids. Critical Care Medicine 33:Suppl, S488-S491
CrossRef72
Xinchun Lin, Tohru Sakuragi, Christine N Metz, Kaie Ojamaa, Hal A Skopicki, Ping Wang, Yousef Al-Abed, Edmund J Miller. (2005) MACROPHAGE MIGRATION INHIBITORY FACTOR WITHIN THE ALVEOLAR SPACES INDUCES CHANGES IN THE HEART DURING LATE EXPERIMENTAL SEPSIS. Shock 24:6, 556-563
CrossRef73
Michael Oppert, Ralf Schindler, Claudia Husung, Katrin Offermann, Klaus-J??rgen Gr??f, Olaf Boenisch, Detlef Barckow, Ulrich Frei, Kai-Uwe Eckardt. (2005) Low-dose hydrocortisone improves shock reversal and reduces cytokine levels in early hyperdynamic septic shock*. Critical Care Medicine 33:11, 2457-2464
CrossRef74
Rubenfeld, Gordon D., Caldwell, Ellen, Peabody, Eve, Weaver, Jim, Martin, Diane P., Neff, Margaret, Stern, Eric J., Hudson, Leonard D., . (2005) Incidence and Outcomes of Acute Lung Injury. New England Journal of Medicine 353:16, 1685-1693
Full Text75
Pajman Danai, Greg S. Martin. (2005) Epidemiology of sepsis: Recent advances. Current Infectious Disease Reports 7:5, 329-334
CrossRef76
John C. Marshall, Jean-Louis Vincent, Gordon Guyatt, Derek C. Angus, Edward Abraham, Gordon Bernard, Claire Bombardier, Thierry Calandra, Henrik Stig J??rgensen, Richard Sylvester, Maarten Boers. (2005) Outcome measures for clinical research in sepsis: A report of the 2nd Cambridge Colloquium of the International Sepsis Forum. Critical Care Medicine 33:8, 1708-1716
CrossRef77
Scott D. Imahara, Sandra Jelacic, Christopher E. Junker, Grant E. O'Keefe. (2005) The influence of gender on human innate immunity. Surgery 138:2, 275-282
CrossRef78
Koji Takayama, Koh-ichi Yuhki, Kyoichi Ono, Takayuki Fujino, Akiyoshi Hara, Takehiro Yamada, Shuhko Kuriyama, Hideji Karibe, Yuji Okada, Osamu Takahata, Takanobu Taniguchi, Toshihiko Iijima, Hiroshi Iwasaki, Shuh Narumiya, Fumitaka Ushikubi. (2005) Thromboxane A2 and prostaglandin F2α mediate inflammatory tachycardia. Nature Medicine 11:5, 562-566
CrossRef79
Annette M Esper, Greg S Martin. (2005) Evolution of treatments for patients with acute lung injury. Expert Opinion on Investigational Drugs 14:5, 633-645
CrossRef80
David J. van Westerloo, Sebastiaan Weijer, Marco J. Bruno, Alex F. de Vos, Cornelis van???t Veer, Tom van der Poll. (2005) Toll-like receptor 4 deficiency and acute pancreatitis act similarly in reducing host defense during murine Escherichia coli peritonitis. Critical Care Medicine 33:5, 1036-1043
CrossRef81
Karen Bosma, Vito Fanelli, V Marco Ranieri. (2005) Acute respiratory distress syndrome: update on the latest developments in basic and clinical research. Current Opinion in Anaesthesiology 18:2, 137-145
CrossRef82
Alastair J O'Brien, Gita Thakur, James F Buckley, Mervyn Singer, Lucie H Clapp. (2005) The pore-forming subunit of the K ATP channel is an important molecular target for LPS-induced vascular hyporeactivity in vitro. British Journal of Pharmacology 144:3, 367-375
CrossRef83
Jay Steinberg, Jeffrey Halter, Henry Schiller, Louis Gatto, Gary Nieman. (2005) THE DEVELOPMENT OF ACUTE RESPIRATORY DISTRESS SYNDROME AFTER GUT ISCHEMIA/REPERFUSION INJURY FOLLOWED BY FECAL PERITONITIS IN PIGS: A CLINICALLY RELEVANT MODEL. Shock 23:2, 129-137
CrossRef84
Todd W. Rice, Gordon R. Bernard. (2005) Therapeutic Intervention and Targets for Sepsis*. Annual Review of Medicine 56:1, 225-248
CrossRef85
BW SYKES, MO FURR. (2005) Equine endotoxaemia - A state-of-the-art review of therapy. Australian Veterinary Journal 83:1-2, 45-50
CrossRef86
Jean-Louis Vincent. (2005) Organ dysfunction scores in critical illness. Journal of Organ Dysfunction 1:1, 18-23
CrossRef87
Djillali Annane, Eric Bellissant, Jean-Marc Cavaillon. (2005) Septic shock. The Lancet 365:9453, 63-78
CrossRef88
Sharma S. Prabhakar. (2004) Regulatory and functional interaction of vasoactive factors in the kidney and extracellular pH. Kidney International 66:5, 1742-1754
CrossRef89
Neill KJ Adhikari, Karen EA Burns, Maureen O Meade, Mohana Ratnapalan, Neill KJ Adhikari. 2004. Pharmacologic therapies for adults with acute lung injury and acute respiratory distress syndrome. .
CrossRef90
Scott D Imahara, Grant E O’Keefe. (2004) Genetic determinants of the inflammatory response. Current Opinion in Critical Care 10:5, 318-324
CrossRef91
Tonya Jagneaux, David E. Taylor, Stephen P. Kantrow. (2004) Coagulation in Sepsis. The American Journal of the Medical Sciences 328:4, 196-204
CrossRef92
Todd W. Rice, Gordon R. Bernard. (2004) Drotrecogin Alfa (Activated) for the Treatment of Severe Sepsis and Septic Shock. The American Journal of the Medical Sciences 328:4, 205-214
CrossRef93
Yoram Klein, Lorne Blackbourne, Erik S. Barquist. (2004) Non-Ventilatory–Based Strategies in the Management of Acute Respiratory Distress Syndrome. The Journal of Trauma: Injury, Infection, and Critical Care 57:4, 915-924
CrossRef94
V BANDI, U MUNNUR, M MATTHAY. (2004) Acute lung injury and acute respiratory distress syndrome in pregnancy. Critical Care Clinics 20:4, 577-607
CrossRef95
Joseph John, Steven Idell. (2004) Strategies for Optimizing Oxygenation in Acute Respiratory Distress Syndrome. Clinical Pulmonary Medicine 11:5, 318-327
CrossRef96
John C Marshall. (2004) Sepsis: current status, future prospects. Current Opinion in Critical Care 10:4, 250-264
CrossRef97
Todd C. Duffy, Rebecca Kirby, Elke Rudloff. (2004) Critical role of the vascular endothelial cell in health and disease: a review article. Journal of Veterinary Emergency and Critical Care 14:2, 84-99
CrossRef98
Jean-Louis Vincent. (2004) Endpoints in sepsis trials: More than just 28-day mortality?. Critical Care Medicine 32:Supplement, S209-S213
CrossRef99
A. G. Tsiotou, G. H. Sakorafas. (2004) Management of septic shock: current concepts, with a particular emphasis on the role of source control, and future perspectives. European Journal of Anaesthesiology 21:5, 337-360
CrossRef100
Henry J. Silverman, Franklin G. Miller. (2004) Control group selection in critical care randomized controlled trials evaluating interventional strategies: An ethical assessment*. Critical Care Medicine 32:3, 852-857
CrossRef101
Peter C. Minneci, Katherine J. Deans, Steven M. Banks, Peter Q. Eichacker, Charles Natanson. (2004) Should we continue to target the platelet-activating factor pathway in septic patients? *. Critical Care Medicine 32:2, 585-588
CrossRef102
Christopher James Doig, David A Zygun, Anthony Delaney, Braden J Manns. (2004) Drotrecogin alfa (activated; Xigris®): an effective and cost-efficient treatment for severe sepsis. Expert Review of Pharmacoeconomics & Outcomes Research 4:1, 15-26
CrossRef103
Abed N. Azab, Jacob Kaplanski. (2004) Involvement of eicosanoids in the hypothermic response to lipopolysaccharide during endotoxemia in rats. Prostaglandins, Leukotrienes and Essential Fatty Acids 70:1, 67-75
CrossRef104
Hilmar Burchardi, Heinz Schneider. (2004) Economic Aspects of Severe Sepsis. PharmacoEconomics 22:12, 793-813
CrossRef105
R. Phillip Dellinger, Joseph E. Parrillo. (2004) Mediator modulation therapy of severe sepsis and septic shock: Does it work? *. Critical Care Medicine 32:1, 282-286
CrossRef106
Neill Adhikari, Karen E A Burns, Maureen O Meade. (2004) Pharmacologic Treatments for Acute Respiratory Distress Syndrome and Acute Lung Injury. Treatments in Respiratory Medicine 3:5, 307-328
CrossRef107
James M. O'Brien, Edward Abraham. (2003) New approaches to the treatment of sepsis. Clinics in Chest Medicine 24:4, 521-548
CrossRef108
Yasuyuki Kuwagata, Jun Oda, Taro Irisawa, Shigenari Matsuyama, Yasushi Nakamori, Masayuki Takahashi, Hisashi Sugimoto. (2003) Effect of Ibuprofen on Interleukin-1??-Induced Abnormalities in Hemodynamics and Oxygen Metabolism in Rabbits. Shock 20:6, 558-564
CrossRef109
Michael A. Gropper. (2003) Sepsis and Hypothermia. Anesthesiology 99:5, 1041-1043
CrossRef110
Christopher James Doig, Kevin B Laupland, David A Zygun, Braden J Manns. (2003) The epidemiology of severe sepsis syndrome and its treatment with recombinant human activated protein C. Expert Opinion on Pharmacotherapy 4:10, 1789-1799
CrossRef111
I CHENG, M MATTHAY. (2003) Acute lung injury and the acute respiratory distress syndrome. Critical Care Clinics 19:4, 693-712
CrossRef112
Fernando A. Rivera-Chavez, Dixie L. Peters-Hybki, Robert C. Barber, Grant E. O'Keefe. (2003) Interleukin-6 Promoter Haplotypes and Interleukin-6 Cytokine Responses. Shock 20:3, 218-223
CrossRef113
Kazuyuki Ono, Toshio Takahashi, Masanori Kamei, Takashi Mato, Shuichi Hashizume, Shigeru Kamiya, Haruhiko Tsutsumi. (2003) Effects of an aqueous extract of cocoa on nitric oxide production of macrophages activated by lipopolysaccharide and interferon-γ. Nutrition 19:7-8, 681-685
CrossRef114
Christopher H. Goss, Roy G. Brower, Leonard D. Hudson, Gordon D. Rubenfeld. (2003) Incidence of acute lung injury in the United States*. Critical Care Medicine 31:6, 1607-1611
CrossRef115
Jay Steinberg, Jeffrey Halter, Henry J Schiller, Monica Dasilva, Steve Landas, Louis A Gatto, Paivi Maisi, Timo Sorsa, Minna Rajamaki, Hsi-Ming Lee, Gary F Nieman. (2003) Metalloproteinase inhibition reduces lung injury and improves survival after cecal ligation and puncture in rats. Journal of Surgical Research 111:2, 185-195
CrossRef116
Robert Goldman, Monica Zilkoski, Richard Mullins, John Mayberry, Clifford Deveney, Donald Trunkey. (2003) Delayed celiotomy for the treatment of bile leak, compartment syndrome, and other hazards of nonoperative management of blunt liver injury. The American Journal of Surgery 185:5, 492-497
CrossRef117
JEFFREY P. BURNS. (2003) Septic shock in the pediatric patient: Pathogenesis and novel treatments. Pediatric Emergency Care 19:2, 112-115
CrossRef118
Kelly A. Wood, David Huang, Derek C. Angus. (2003) Improving clinical trial design in acute lung injury. Critical Care Medicine 31:Supplement, S305-S311
CrossRef119
Niels C Riedemann, Peter A Ward. (2003) Anti-inflammatory strategies for the treatment of sepsis. Expert Opinion on Biological Therapy 3:2, 339-350
CrossRef120
Gordon D. Rubenfeld. (2003) Epidemiology of acute lung injury. Critical Care Medicine 31:Supplement, S276-S284
CrossRef121
David R. Williamson, Marc Lapointe. (2003) The Hypothalamic-Pituitary-Adrenal Axis and Low-Dose Glucocorticoids in the Treatment of Septic Shock. Pharmacotherapy 23:4, 514-525
CrossRef122
John M. Luce. (2003) Is the concept of informed consent applicable to clinical research involving critically ill patients?. Critical Care Medicine 31:Supplement, S153-S160
CrossRef123
Eric R. Pacht, Stephen J. DeMichele, Jeffrey L. Nelson, Judy Hart, Ann K. Wennberg, James E. Gadek. (2003) Enteral nutrition with eicosapentaenoic acid, γ-linolenic acid, and antioxidants reduces alveolar inflammatory mediators and protein influx in patients with acute respiratory distress syndrome. Critical Care Medicine 31:2, 491-500
CrossRef124
Hotchkiss, Richard S., Karl, Irene E., . (2003) The Pathophysiology and Treatment of Sepsis. New England Journal of Medicine 348:2, 138-150
Full Text125
B. Lambermont, A. Ghuysen, J.-M. Dogné, P. Kolh, V. Tchana-Sato, P. Morimont, P. Benoit, P. Gérard, B. Masereel, V. D’Orio. (2003) Effects of BM-573, a Novel Thromboxane A2 Inhibitor, on Pulmonary Hemodynamics in Endotoxic Shock. Archives Of Physiology And Biochemistry 111:3, 224-231
CrossRef126
Gordon R. Bernard. (2003) Drotrecogin alfa (activated) (recombinant human activated protein C) for the treatment of severe sepsis. Critical Care Medicine 31:Supplement, S85-S93
CrossRef127
Christine Smith Schulman, Kathy Hare. (2003) New Thoughts on Sepsis. Dimensions of Critical Care Nursing 22:1, 20-30
CrossRef128
Vladimir Bumbasirevic, Miroslav Milicevic, V. Bukumirovic, Vitomir Rankovic, A. Pavlovic, Vladimir Djukic, Dejan Radenkovic, Z. Lausevic, Ana Sijacki. (2003) Prevention and treatment of progressive multiple organ disfunction in acute pancreatitis. Acta chirurgica iugoslavica 50:2, 115-125
CrossRef129
Jean-Pierre Sollet, Gary E Garber. (2002) Selecting patients with severe sepsis for drotrecogin alfa (activated) therapy. The American Journal of Surgery 184:6, S11-S18
CrossRef130
Daniela Salvemini, Salvatore Cuzzocrea. (2002) Oxidative stress in septic shock and disseminated intravascular coagulation. Free Radical Biology and Medicine 33:9, 1173-1185
CrossRef131
Greg S. Martin, Robert J. Mangialardi, Arthur P. Wheeler, William D. Dupont, John A. Morris, Gordon R. Bernard. (2002) Albumin and furosemide therapy in hypoproteinemic patients with acute lung injury*. Critical Care Medicine 30:10, 2175-2182
CrossRef132
Lisa A. Greisman, Philip A. Mackowiak. (2002) Fever: beneficial and detrimental effects of antipyretics. Current Opinion in Infectious Diseases 15:3, 241-245
CrossRef133
Jean‐Louis Vincent, Qinghua Sun, Marc‐Jacques Dubois. (2002) Clinical Trials of Immunomodulatory Therapies in Severe Sepsis and Septic Shock. Clinical Infectious Diseases 34:8, 1084-1093
CrossRef134
Ulrich Bolder, Andrea Schmidt, Lukas Landmann, Verena Kidder, Stefan Tange, Karl-Walter Jauch. (2002) Heat stress prevents impairment of bile acid transport in endotoxemic rats by a posttranscriptional mechanism. Gastroenterology 122:4, 963-973
CrossRef135
Jürgen Graf, Gordon S. Doig, Deborah J. Cook, Jean-Louis Vincent, William J. Sibbald. (2002) Randomized, controlled clinical trials in sepsis: Has methodological quality improved over time?. Critical Care Medicine 30:2, 461-472
CrossRef136
Greg Martin, Stephanie Eaton. (2002) Clinical developments for treating ARDS. Expert Opinion on Investigational Drugs 11:1, 37-48
CrossRef137
J VINCENT. (2002) New management strategies in ARDS: Immunomodulation. Critical Care Clinics 18:1, 69-78
CrossRef138
Salmaan Kanji, John W. Devlin, Krista A. Piekos, Eric Racine. (2001) Recombinant Human Activated Protein C, Drotrecogin Alfa (activated): A Novel Therapy for Severe Sepsis. Pharmacotherapy 21:11, 1389-1402
CrossRef139
Paul E Marik, Joseph Varon. (2001) Sepsis: State of the art. Disease-a-Month 47:10, 462-532
CrossRef140
Epstein, Franklin H., , Landry, Donald W., Oliver, Juan A., . (2001) The Pathogenesis of Vasodilatory Shock. New England Journal of Medicine 345:8, 588-595
Full Text141
Hoang S. Tran, James V. Quinn, Matthew M. Puc, Daniel S. Woolley, Roberto N. Puglisi, Gus J. Slotman. (2001) Prostacyclin is neither sufficient alone nor necessary to cause pulmonary dysfunction: Results from infusions of prostacyclin and antiprostacyclin antibody in porcine septic shock. Critical Care Medicine 29:7, 1445-1451
CrossRef142
John C. Marshall. (2001) Inflammation, coagulopathy, and the pathogenesis of multiple organ dysfunction syndrome. Critical Care Medicine 29, S99-S106
CrossRef143
Derek C. Angus, Walter T. Linde-Zwirble, Jeffrey Lidicker, Gilles Clermont, Joseph Carcillo, Michael R. Pinsky. (2001) Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Critical Care Medicine 29:7, 1303-1310
CrossRef144
A J O'Brien, A J Wilson, R Sibbald, M Singer, L H Clapp. (2001) Temporal variation in endotoxin-induced vascular hyporeactivity in a rat mesenteric artery organ culture model. British Journal of Pharmacology 133:3, 351-360
CrossRef145
David Johnson, Irvin Mayers. (2001) Multiple organ dysfunction syndrome: a narrative review. Canadian Journal of Anesthesia/Journal canadien d'anesthésie 48:5, 502-509
CrossRef146
Kohei Uriu, Akihiko Osajima, Masayuki Kamochi, Hiroyuki Watanabe, Keiji Aibara, Kazo Kaizu. (2001) The Severity of Hyperdynamic Circulation May Predict the Effects of Direct Hemoperfusion with the Adsorbent Column Using Polymyxin B-Immobilized Fiber in Patients with Gram-Negative Septic Shock. Therapeutic Apheresis and Dialysis 5:1, 25-30
CrossRef147
Sreenandh Krishnagopalan, R. Phillip Dellinger. (2001) Innovative Therapies for Sepsis. BioDrugs 15:10, 645-654
CrossRef148
Elisabeth L. Hahn, Li-Ke He, and Richard L. Gamelli. (2000) Prostaglandin E2 Synthesis and Metabolism in Burn Injury and Trauma. The Journal of Trauma: Injury, Infection, and Critical Care 49:6, 1147-1154
CrossRef149
Jeffrey D Hasday, Karen D Fairchild, Carl Shanholtz. (2000) The role of fever in the infected host. Microbes and Infection 2:15, 1891-1904
CrossRef150
Karen D. Fairchild, Rose M. Viscardi, Lisa Hester, Ishwar S. Singh, Jeffrey D. Hasday. (2000) Effects of Hypothermia and Hyperthermia on Cytokine Production by Cultured Human Mononuclear Phagocytes from Adults and Newborns. Journal of Interferon & Cytokine Research 20:12, 1049-1055
CrossRef151
James A. Russell, Joel Singer, Gordon R. Bernard, Arthur Wheeler, William Fulkerson, Leonard Hudson, Roland Schein, Warren Summer, Patrick Wright, Keith R. Walley. (2000) Changing pattern of organ dysfunction in early human sepsis is related to mortality. Critical Care Medicine 28:10, 3405-3411
CrossRef152
J. D. Hasday, A. Garrison. (2000) Antipyretic Therapy in Patients with Sepsis. Clinical Infectious Diseases 31:Supplement 5, S234-S241
CrossRef153
P. A. Mackowiak. (2000) Antipyretic Therapy's Future. Clinical Infectious Diseases 31:Supplement 5, S242-S243
CrossRef154
P. A. Mackowiak. (2000) Diagnostic Implications and Clinical Consequences of Antipyretic Therapy. Clinical Infectious Diseases 31:Supplement 5, S230-S233
CrossRef155
Robert J. Mangialardi, Greg S. Martin, Gordon R. Bernard, Arthur P. Wheeler, Brian W. Christman, William D. Dupont, Stanley B. Higgins, Bridget B. Swindell. (2000) Hypoproteinemia predicts acute respiratory distress syndrome development, weight gain, and death in patients with sepsis. Critical Care Medicine 28:9, 3137-3145
CrossRef156
Charles J. Fisher, S. Betty Yan. (2000) Protein C levels as a prognostic indicator of outcome in sepsis and related diseases. Critical Care Medicine 28:Supplement, S49-S56
CrossRef157
Barrett D. Conner, Gordon R. Bernard. (2000) ACUTE RESPIRATORY DISTRESS SYNDROME. Clinics in Chest Medicine 21:3, 563-587
CrossRef158
David H. Ingbar. (2000) MECHANISMS OF REPAIR AND REMODELING FOLLOWING ACUTE LUNG INJURY. Clinics in Chest Medicine 21:3, 589-616
CrossRef159
Robert C. McIntyre, Edward J. Pulido, Denis D. Bensard, Brian D. Shames, Edward Abraham. (2000) Thirty years of clinical trials in acute respiratory distress syndrome. Critical Care Medicine 28:9, 3314-3331
CrossRef160
N. Penel, M. Degardin, F. Frippiat, E. Hachulla. (2000) Existe-t-il des critères diagnostiques en faveur d'une fièvre paranéoplasique ?. La Revue de Médecine Interne 21:8, 684-692
CrossRef161
David M. Forrest, Francisco Baigorri, Dean R. Chittock, John J. Spinelli, James A. Russell. (2000) Volume expansion using pentastarch does not change gastric-arterial CO2 gradient or gastric intramucosal pH in patients who have sepsis syndrome. Critical Care Medicine2254-2258
CrossRef162
Bradley D Freeman, Charles Natanson. (2000) Anti-inflammatory therapies in sepsis and septic shock. Expert Opinion on Investigational Drugs 9:7, 1651-1663
CrossRef163
R. J. MacKAY, C. A. DANIELS, H. F. BLEYAERT, J. E. BAILEY, K. D. GILLIS, A. M. MERRITT, T. L. KATZ, J. C. JOHNSON, K. C. THOMPSON. (2000) Effect of eltenac in horses with induced endotoxaemia. Equine Veterinary Journal 32:S32, 26-31
CrossRef164
B.F. McAdam, I.A. Mardini, A. Habib, A. Burke, J.A. Lawson, S. Kapoor, G.A. FitzGerald. (2000) Effect of regulated expression of human cyclooxygenase isoforms on eicosanoid and isoeicosanoid production in inflammation. Journal of Clinical Investigation 105:10, 1473-1482
CrossRef165
Steve Santangelo, Margo Shoup, Richard L. Gamelli, Ravi Shankar. (2000) Prostaglandin E2 Receptor Antagonist (SC-19220) Treatment Restores the Balance to Bone Marrow Myelopoiesis after Burn Sepsis. The Journal of Trauma: Injury, Infection, and Critical Care 48:5, 826-831
CrossRef166
Oscar Arrieta, Tatiana Sofia Rodriguez-Reyna, Julio Sotelo. (2000) Pharmacological treatment of septic shock. Expert Opinion on Therapeutic Patents 10:5, 601-622
CrossRef167
Ping Wang, Mian Zhou, William G. Cioffi, Kirby I. Bland, Zheng F. &NA;, Irshad H. Chaudry. (2000) Is prostacyclin responsible for producing the hyperdynamic response during early sepsis?. Critical Care Medicine 28:5, 1534-1539
CrossRef168
Mary H. van Soeren, William L. Diehl-Jones, Robert J. Maykut, Wael M.R. Haddara. (2000) Pathophysiology and Implications for Treatment of Acute Respiratory Distress Syndrome. AACN Clinical Issues: Advanced Practice in Acute & Critical Care 11:2, 179-197
CrossRef169
Eileen M. Bulger, Ronald V. Maier. (2000) Lipid mediators in the pathophysiology of critical illness. Critical Care Medicine 28:Supplement, N27-N36
CrossRef170
Jonathan Sevransky, Charles Natanson. (2000) Clinical trials in sepsis: an update. Current Opinion in Anaesthesiology 13:2, 125-129
CrossRef171
Michael R. DePietro, Peter Q. Eichacker. (2000) Lidocaine for acute lung injury: Questions still to answer. Critical Care Medicine 28:2, 589-591
CrossRef172
Edward Abraham, Michael A. Matthay, Charles A. Dinarello, Jean-Louis Vincent, Jonathan Cohen, Steven M. Opal, Michel Glauser, Polly Parsons, Charles J. Fisher, John E. Repine. (2000) Consensus conference definitions for sepsis, septic shock, acute lung injury, and acute respiratory distress syndrome: Time for a reevaluation. Critical Care Medicine 28:1, 232-235
CrossRef173
Lena M. Napolitano, E. Faist, M.W. Wichmann, Raul Coimbra. (1999) IMMUNE DYSFUNCTION IN TRAUMA. Surgical Clinics of North America 79:6, 1385-1416
CrossRef174
Cornelia Blume, Gunhild Heise, Anja Muhlfeld, Dieter Bach, Karsten Schror, Claus Dieter Gerhardz, Bernd Grabensee, Peter Heering. (1999) Effect of flosulide, a selective cyclooxygenase 2 inhibitor, on passive Heymann nephritis in the rat. Kidney International 56:5, 1770-1778
CrossRef175
Grant E. O???Keefe, Ronald V. Maier. (1999) Are we winning the battle in the surgical intensive care unit?. Current Opinion in Critical Care 5:4, 308
CrossRef176
James E. Gadek, Stephen J. DeMichele, Michael D. Karlstad, Eric R. Pacht, Michael Donahoe, Timothy E. Albertson, Chi Van Hoozen, Ann K. Wennberg, Jeffrey L. Nelson, Mojtaba Noursalehi. (1999) Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome. Critical Care Medicine 27:8, 1409-1420
CrossRef177
Steven M. Opal, Alan S. Cross. (1999) CLINICAL TRIALS FOR SEVERE SEPSIS. Infectious Disease Clinics of North America 13:2, 285-297
CrossRef178
J. Raymond Fletcher. (1999) The effects of ibuprofen on eicosanoid synthesis in sepsis. Critical Care Medicine 27:4, 669-670
CrossRef179
Murray M. Arons, Arthur P. Wheeler, Gordon R. Bernard, Brian W. Christman, James A. Russell, Roland Schein, Warren R. Summer, Kenneth P. Steinberg, William Fulkerson, Patrick Wright, William D. Dupont, Bridgett B. Swindell. (1999) Effects of ibuprofen on the physiology and survival of hypothermic sepsis. Critical Care Medicine 27:4, 699-707
CrossRef180
Risuke Karima, Shigeru Matsumoto, Hidemitsu Higashi, Kouji Matsushima. (1999) The molecular pathogenesis of endotoxic shock and organ failure. Molecular Medicine Today 5:3, 123-132
CrossRef181
Gordon R. Bernard. (1999) Research in sepsis and acute respiratory distress syndrome. Critical Care Medicine 27:2, 434-436
CrossRef182
Stanley A. Nasraway. (1999) Sepsis research. Critical Care Medicine 27:2, 427-430
CrossRef183
Wheeler, Arthur P., Bernard, Gordon R., . (1999) Treating Patients with Severe Sepsis. New England Journal of Medicine 340:3, 207-214
Full Text184
Charles Natanson, Claire J. Esposito, Steven M. Banks. (1998) The sirens' songs of confirmatory sepsis trials. Critical Care Medicine 26:12, 1927-1931
CrossRef185
Jean-Francois A. Dhainaut, Alain Tenaillon, Margaret Hemmer, Pierre Damas, Yves Le Tulzo, Peter Radermacher, Marie-Denise Schaller, Jean-Pierre Sollet, Michel Wolff, Laurent Holzapfel, Fabrice Zeni, Jean-Marc Vedrinne, Florent de Vathaire, Marie-Laurence Gourlay, Philippe Guinot, Jean-Paul Mira. (1998) Confirmatory platelet-activating factor receptor antagonist trial in patients with severe Gram-negative bacterial sepsis. Critical Care Medicine 26:12, 1963-1971
CrossRef186
Gordon R. Bernard. (1998) Quantification of organ dysfunction. Critical Care Medicine 26:11, 1767-1768
CrossRef187
T ALBERTSON, G MARELICH. (1998) PHARMACOLOGIC ADJUNCTS TO MECHANICAL VENTILATION IN ACUTE RESPIRATORY DISTRESS SYNDROME. Critical Care Clinics 14:4, 581-610
CrossRef188
PHILIP A. MACKOWIAK, KAREN I. PLAISACNE. (1998) Benefits and Risks of Antipyretic Therapya. Annals of the New York Academy of Sciences 856:1 MOLECULAR MEC, 214-223
CrossRef189
Paul E. Marik, Joseph Varon. (1998) The Management of Sepsis: A Practical Review. Journal of Intensive Care Medicine 13:5, 229-240
CrossRef190
. (1998) Ibuprofen bij mensen met sepsis doet wat, maar helpt niet. Medisch-Farmaceutische Mededelingen 36:8, 186-186
CrossRef191
Margo Shoup, Li-Ke He, Hong Liu, Ravi Shankar, Richard Gamelli. (1998) Cyclooxygenase-2 Inhibitor NS-398 Improves Survival and Restores Leukocyte Counts in Burn Infection. The Journal of Trauma: Injury, Infection, and Critical Care 45:2, 215-221
CrossRef192
DANIEL E. NOYOLA, MARISOL FERNANDEZ, SHELDON L. KAPLAN. (1998) Reevaluation of antipyretics in children with enteric fever. The Pediatric Infectious Disease Journal 17:8, 691-695
CrossRef193
Mary Leach, Lorna C Hamilton, Antje Olbrich, Gillian M Wray, Christoph Thiemermann. (1998) Effects of inhibitors of the activity of cyclo-oxygenase-2 on the hypotension and multiple organ dysfunction caused by endotoxin: A comparison with dexamethasone. British Journal of Pharmacology 124:3, 586-592
CrossRef194
Mark E Astiz, Eric C Rackow. (1998) Septic shock. The Lancet 351:9114, 1501-1505
CrossRef195
Maria Ohara, Teiji Sawa, Kiyoyasu Kurahashi, Jeanine P. Wiener-Kronish, Vatsal Doshi, Ichidai Kudoh, Michael A. Gropper. (1998) Induction of Cyclooxygenase-2 in Alveolar Macrophages after Acid Aspiration. Anesthesiology 88:4, 1014-1022
CrossRef196
R. M. Grocott-Mason, A. M. Shah. (1998) Cardiac dysfunction in sepsis: new theories and clinical implications. Intensive Care Medicine 24:4, 286-295
CrossRef197
(1997) Ibuprofen in Patients with Sepsis. New England Journal of Medicine 337:10, 710-710
Full Text198
James W. Van Hook. (1997) Acute respiratory distress syndrome in pregnancy. Seminars in Perinatology 21:4, 320-327
CrossRef199
Fabrice Zeni, Bradley Freeman, Charles Natanson. (1997) Anti-inflammatory therapies to treat sepsis and septic shock. Critical Care Medicine 25:7, 1095-1100
CrossRef200
Warren, H. Shaw, . (1997) Strategies for the Treatment of Sepsis. New England Journal of Medicine 336:13, 952-953
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