G R Bernard

Publications (74)764.4 Total impact

• Article: Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU).

  E W Ely, S K Inouye, G R Bernard, S Gordon, J Francis, L May, B Truman, T Speroff, S Gautam, R Margolin, R P Hart, R Dittus
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  ABSTRACT: Delirium is a common problem in the intensive care unit (ICU). Accurate diagnosis is limited by the difficulty of communicating with mechanically ventilated patients and by lack of a validated delirium instrument for use in the ICU. To validate a delirium assessment instrument that uses standardized nonverbal assessments for mechanically ventilated patients and to determine the occurrence rate of delirium in such patients. Prospective cohort study testing the Confusion Assessment Method for ICU Patients (CAM-ICU) in the adult medical and coronary ICUs of a US university-based medical center. A total of 111 consecutive patients who were mechanically ventilated were enrolled from February 1, 2000, to July 15, 2000, of whom 96 (86.5%) were evaluable for the development of delirium and 15 (13.5%) were excluded because they remained comatose throughout the investigation. Occurrence rate of delirium and sensitivity, specificity, and interrater reliability of delirium assessments using the CAM-ICU, made daily by 2 critical care study nurses, compared with assessments by delirium experts using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. A total of 471 daily paired evaluations were completed. Compared with the reference standard for diagnosing delirium, 2 study nurses using the CAM-ICU had sensitivities of 100% and 93%, specificities of 98% and 100%, and high interrater reliability (kappa = 0.96; 95% confidence interval, 0.92-0.99). Interrater reliability measures across subgroup comparisons showed kappa values of 0.92 for those aged 65 years or older, 0.99 for those with suspected dementia, or 0.94 for those with Acute Physiology and Chronic Health Evaluation II scores at or above the median value of 23 (all P<.001). Comparing sensitivity and specificity between patient subgroups according to age, suspected dementia, or severity of illness showed no significant differences. The mean (SD) CAM-ICU administration time was 2 (1) minutes. Reference standard diagnoses of delirium, stupor, and coma occurred in 25.2%, 21.3%, and 28.5% of all observations, respectively. Delirium occurred in 80 (83.3%) patients during their ICU stay for a mean (SD) of 2.4 (1.6) days. Delirium was even present in 39.5% of alert or easily aroused patient observations by the reference standard and persisted in 10.4% of patients at hospital discharge. Delirium, a complication not currently monitored in the ICU setting, is extremely common in mechanically ventilated patients. The CAM-ICU appears to be rapid, valid, and reliable for diagnosing delirium in the ICU setting and may be a useful instrument for both clinical and research purposes.
  JAMA The Journal of the American Medical Association 12/2001; 286(21):2703-10. · 30.03 Impact Factor
• Article: Safety and dose relationship of recombinant human activated protein C for coagulopathy in severe sepsis.

  G R Bernard, E W Ely, T J Wright, J Fraiz, J E Stasek, J A Russell, I Mayers, B A Rosenfeld, P E Morris, S B Yan, J D Helterbrand
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  ABSTRACT: To assess the safety and effect on coagulopathy of a range of doses of recombinant human activated protein C (rhAPC). To determine an effective dose and duration of rhAPC for use in future clinical trials. Double-blind, randomized, placebo-controlled, multicenter, dose-ranging (sequential), phase II clinical trial. Forty community or academic medical institutions in United States and Canada. One hundred thirty-one adult patients with severe sepsis. Intravenous infusion of rhAPC (12, 18, 24, or 30 microg/kg/hr) or placebo for 48 or 96 hrs. No significant differences in incidence of serious bleeding events (4% rhAPC, 5% placebo, p >.999) or incidence of serious adverse events (39% rhAPC, 46% placebo, p = 0.422) between rhAPC- and placebo-treated patients were observed. One of 53 rhAPC-treated patients with suitable immunogenicity samples had a low level, transient, non-neutralizing anti-APC antibody response not associated with any clinical adverse event. Significant dose-dependent decreases in both D-dimer (p <0.001) and end of infusion interleukin 6 levels (p =.021) were demonstrated. No statistically significant effects on fibrinogen or platelet counts were observed. A nonstatistically significant 15% relative risk reduction in 28-day all-cause mortality was observed between rhAPC- and placebo-treated patients. rhAPC was safe and well-tolerated and demonstrated a dose-dependent reduction in D-dimer and interleukin 6 levels relative to placebo. The dose of 24 microg/kg/hr for 96 hrs was selected for use in future clinical studies.
  Critical Care Medicine 11/2001; 29(11):2051-9. · 6.33 Impact Factor
• Article: Low levels of protein C are associated with poor outcome in severe sepsis.

  S B Yan, J D Helterbrand, D L Hartman, T J Wright, G R Bernard
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  ABSTRACT: To investigate whether protein C levels predict 30-day mortality rate, shock status, duration of ICU stay, and ventilator dependence in patients with sepsis. Retrospective analysis of a subset of a previously published, prospective, randomized, double-blind, placebo-controlled trial ("Effects of Ibuprofen on the Physiology and Survival of Patients With Sepsis" [ISS]). A multicenter study performed in the United States and Canada (seven sites). Seventy hospitalized patients with acute severe sepsis and failure in one or more organs at entry into the ISS trial. Blood samples were obtained from all patients at baseline and at 20, 44, 72, and 120 h after the initiation of study drug (ibuprofen or placebo) infusion. Data obtained at these times included platelet count, prothrombin time, and partial thromboplastin time. The results described in this article are based on a subset of the total ISS population for whom additional coagulation assays were performed on the blood samples obtained at baseline and 44 h. These assays included protein C antigen, D-dimer, and fibrinogen levels. A total of 63 of the 70 patients (90%) studied in this report had acquired protein C deficiency at entry to the ISS trial (baseline). The presence and severity of acquired protein C deficiency were associated with poor clinical outcome, including lower survival rate, higher incidence of shock, and fewer ICU-free and ventilator-free days. Acquired protein C deficiency may be useful in predicting clinical outcome in patients with sepsis. Clinical studies are warranted to determine whether the replacement of protein C in sepsis patients may improve outcome.
  Chest 10/2001; 120(3):915-22. · 5.25 Impact Factor
• Source

  Available from: ottawa-anesthesia.org

  Article: Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).

  E W Ely, R Margolin, J Francis, L May, B Truman, R Dittus, T Speroff, S Gautam, G R Bernard, S K Inouye
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  ABSTRACT: To develop and validate an instrument for use in the intensive care unit to accurately diagnose delirium in critically ill patients who are often nonverbal because of mechanical ventilation. Prospective cohort study. The adult medical and coronary intensive care units of a tertiary care, university-based medical center. Thirty-eight patients admitted to the intensive care units. We designed and tested a modified version of the Confusion Assessment Method for use in intensive care unit patients and called it the CAM-ICU. Daily ratings from intensive care unit admission to hospital discharge by two study nurses and an intensivist who used the CAM-ICU were compared against the reference standard, a delirium expert who used delirium criteria from the Diagnostic and Statistical Manual of Mental Disorders (fourth edition). A total of 293 daily, paired evaluations were completed, with reference standard diagnoses of delirium in 42% and coma in 27% of all observations. To include only interactive patient evaluations and avoid repeat-observer bias for patients studied on multiple days, we used only the first-alert or lethargic comparison evaluation in each patient. Thirty-three of 38 patients (87%) developed delirium during their intensive care unit stay, mean duration of 4.2 +/- 1.7 days. Excluding evaluations of comatose patients because of lack of characteristic delirium features, the two critical care study nurses and intensivist demonstrated high interrater reliability for their CAM-ICU ratings with kappa statistics of 0.84, 0.79, and 0.95, respectively (p <.001). The two nurses' and intensivist's sensitivities when using the CAM-ICU compared with the reference standard were 95%, 96%, and 100%, respectively, whereas their specificities were 93%, 93%, and 89%, respectively. The CAM-ICU demonstrated excellent reliability and validity when used by nurses and physicians to identify delirium in intensive care unit patients. The CAM-ICU may be a useful instrument for both clinical and research purposes to monitor delirium in this challenging patient population.
  Critical Care Medicine 08/2001; 29(7):1370-9. · 6.33 Impact Factor
• Article: Acute respiratory distress syndrome: innovative therapies.

  G S Martin, G R Bernard
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  ABSTRACT: Since its description in 1967, the acute respiratory distress syndrome (ARDS) has become one of the most studied pathophysiological processes in intensive care units worldwide. The current state of knowledge about this severe illness and its associated mediators has come from the study of relevant animal models. In the mid-1970s, the development of the sheep model of ARDS and later, the porcine model, led to the discovery of a wide variety of inflammatory lipid mediators, cytokines, and proteases, to name but a few. Recognition of the presence of such highly toxic mediators associated with the development of ARDS has led to numerous potential targets for drug development toward therapeutic intervention. Through implementation of a standardized definition for ARDS and its less severe sibling acute lung injury (ALI), growth in patient-oriented research has been possible. Substantial numbers of new therapies have been brought forth and examined in recent years, many of which remain controversial. This article is a critical appraisal of the potential therapeutic options investigated in recent years for the management of ALI/ARDS.
  Seminars in Respiratory and Critical Care Medicine 07/2001; 22(3):293-306. · 2.43 Impact Factor
• Source

  Available from: Gary E Garber

  Article: Efficacy and safety of recombinant human activated protein C for severe sepsis.

  G R Bernard, J L Vincent, P F Laterre, S P LaRosa, J F Dhainaut, A Lopez-Rodriguez, J S Steingrub, G E Garber, J D Helterbrand, E W Ely, C J Fisher
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  ABSTRACT: Drotrecogin alfa (activated), or recombinant human activated protein C, has antithrombotic, antiinflammatory, and profibrinolytic properties. In a previous study, drotrecogin alfa activated produced dose-dependent reductions in the levels of markers of coagulation and inflammation in patients with severe sepsis. In this phase 3 trial, we assessed whether treatment with drotrecogin alfa activated reduced the rate of death from any cause among patients with severe sepsis. We conducted a randomized, double-blind, placebo-controlled, multicenter trial. Patients with systemic inflammation and organ failure due to acute infection were enrolled and assigned to receive an intravenous infusion of either placebo or drotrecogin alfa activated (24 microg per kilogram of body weight per hour) for a total duration of 96 hours. The prospectively defined primary end point was death from any cause and was assessed 28 days after the start of the infusion. Patients were monitored for adverse events; changes in vital signs, laboratory variables, and the results of microbiologic cultures; and the development of neutralizing antibodies against activated protein C. A total of 1690 randomized patients were treated (840 in the placebo group and 850 in the drotrecogin alfa activated group). The mortality rate was 30.8 percent in the placebo group and 24.7 percent in the drotrecogin alfa activated group. On the basis of the prospectively defined primary analysis, treatment with drotrecogin alfa activated was associated with a reduction in the relative risk of death of 19.4 percent (95 percent confidence interval, 6.6 to 30.5) and an absolute reduction in the risk of death of 6.1 percent (P=0.005). The incidence of serious bleeding was higher in the drotrecogin alfa activated group than in the placebo group (3.5 percent vs. 2.0 percent, P=0.06). Treatment with drotrecogin alfa activated significantly reduces mortality in patients with severe sepsis and may be associated with an increased risk of bleeding.
  New England Journal of Medicine 04/2001; 344(10):699-709. · 53.30 Impact Factor
• Article: Airway and lung in sepsis.

  G S Martin, G R Bernard
  Intensive Care Medicine 02/2001; 27 Suppl 1:S63-79. · 5.40 Impact Factor
• Article: Changing pattern of organ dysfunction in early human sepsis is related to mortality.

  J A Russell, J Singer, G R Bernard, A Wheeler, W Fulkerson, L Hudson, R Schein, W Summer, P Wright, K R Walley
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  ABSTRACT: We examined the pattern of organ system dysfunction, the evolution of this pattern over time, and the relationship of these features to mortality in patients who had sepsis syndrome. Prospective, multicenter, observational study. Intensive care units in tertiary referral teaching hospitals. A total of 287 patients who had sepsis syndrome were prospectively identified in intensive care units. MATERIALS AND MEASUREMENTS: Cardiovascular, pulmonary, neurologic, coagulation, renal, and hepatic dysfunction were assessed at onset and on day 3 of sepsis syndrome. Organ dysfunction was classified as normal, mild, moderate, severe, and extreme dysfunction. We calculated the occurrence rate and associated 30-day mortality rate of organ dysfunction at the onset of sepsis syndrome. We then measured the change in organ dysfunction from onset to day 3 of sepsis syndrome and determined, for individual organ systems, the associated 30-day mortality rate. At the onset of sepsis syndrome, clinically significant pulmonary dysfunction was the most common organ failure, but was not related to 30-day mortality. Clinically significant cardiovascular, neurologic, coagulation, renal, and hepatic dysfunction were less common at the onset of sepsis syndrome but were significantly associated with the 30-day mortality rate. Worsening neurologic, coagulation, and renal dysfunction from onset to day 3 of sepsis syndrome were associated with significantly higher 30-day mortality than with improvement or no change in organ dysfunction. Increased mortality rate in sepsis syndrome is associated with a pattern characterized by failure of nonpulmonary organ systems and, in particular, worsening neurologic, coagulation, and renal dysfunction over the first 3 days. Although initial pulmonary dysfunction is common in patients with sepsis syndrome, it is not associated with an increased mortality rate.
  Critical Care Medicine 11/2000; 28(10):3405-11. · 6.33 Impact Factor
• Article: Acute respiratory distress syndrome. Potential pharmacologic interventions.

  B D Conner, G R Bernard
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  ABSTRACT: Remarkable progress has been made in the past 10 years with regard to understanding the interplay of potent physiologic mediators in patients with acute lung injury. Because there are so many mediators and the interaction of these agents is complex, true insight into the process has been slow in coming. Clinical studies in ARDS, as well as sepsis, the leading cause of ARDS, have increased in number, size, and quality over this same period. Although none of these studies has produced an accepted new therapy for ARDS, each has laid the groundwork for more efficient and more elegant studies of the problem. The stage is now set for the real advances to be brought forward and put to rigorous, efficient clinical testing.
  Clinics in Chest Medicine 10/2000; 21(3):563-87. · 3.28 Impact Factor
• Article: Hypoproteinemia predicts acute respiratory distress syndrome development, weight gain, and death in patients with sepsis. Ibuprofen in Sepsis Study Group.

  R J Mangialardi, G S Martin, G R Bernard, A P Wheeler, B W Christman, W D Dupont, S B Higgins, B B Swindell
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  ABSTRACT: Starling's equation indicates that reduced oncotic pressure gradients will favor edema formation, and the current consensus definition of acute respiratory distress syndrome (ARDS) excludes only the hydrostatic pressure contribution. We hypothesized that low serum total protein levels might correlate with the likelihood of ARDS in at-risk patients because serum total protein is the chief determinant of oncotic pressure in humans. Regression analysis to compare outcomes in patients with low serum total protein levels with outcomes in patients with normal serum total protein levels with respect to weight change, development of ARDS, and mortality. Intensive care units (ICUs) of seven clinical centers in North America. A total of 455 ICU patients who met consensus criteria for severe sepsis (178 of whom developed ARDS) from a recently completed prospective clinical trial. None. We found that 92% of the patients developing ARDS had low or borderline serum total protein levels (<6 g/dL). Logistic and multiple regression analyses confirmed that of 18 clinical variables, initial serum total protein level and protein change over time were the most statistically significant predictors of weight gain, prolonged mechanical ventilation, ARDS development, and mortality in the study population. This correlation remained significant after adjustment for the other major predictors of outcome present at baseline (ie, Acute Physiology and Chronic Health Evaluation II score). Hypoproteinemia is significantly correlated with fluid retention and weight gain, development of ARDS and poor respiratory outcome, and mortality in patients with sepsis. Prospective, randomized trials of serum protein manipulation are needed to establish whether there is a cause-effect relationship to this association.
  Critical Care Medicine 09/2000; 28(9):3137-45. · 6.33 Impact Factor
• Article: Pulmonary artery catheterization and clinical outcomes: National Heart, Lung, and Blood Institute and Food and Drug Administration Workshop Report. Consensus Statement.

  G R Bernard, G Sopko, F Cerra, R Demling, H Edmunds, S Kaplan, L Kessler, H Masur, P Parsons, D Shure, C Webb, H Weidemann, G Weinmann, D Williams
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  ABSTRACT: The efficacy and safety of the pulmonary artery catheter are under scrutiny because of its association with increased morbidity and mortality in observational studies. In response, the National Heart, Lung, and Blood Institute (NHLBI) and the US Food and Drug Administration (FDA) conducted the Pulmonary Artery Catheterization and Clinical Outcomes workshop in Alexandria, Va, on August 25 and 26, 1997, to develop recommendations regarding actions to improve pulmonary artery catheter utility and safety. The NHLBI and FDA planning task force selected a workshop chairperson, subcommittee chairs, and participants. Approximately 85 participants were selected for their collective expertise in critical care, pulmonary medicine, cardiovascular medicine and surgery, pediatrics, nursing, biostatistics, and medical economics. The meeting was open to industry representatives and other government and lay observers. This workshop was funded by the NHLBI and the FDA's Division of Devices. Published reports relating to the efficacy and safety of the pulmonary artery catheter, especially consensus documents developed by professional societies. The planning task force disseminated materials, held teleconferences, and developed draft position papers prior to the workshop. These were modified during the workshop and thereafter in the course of several teleconferences, and presented to the entire group for final modifications and approval. A need exists for collaborative education of physicians and nurses in performing, obtaining, and interpreting information from the use of pulmonary artery catheters. This effort should be led by professional societies, in collaboration with federal agencies, with the purpose of developing and disseminating standardized educational programs. Areas given high priority for clinical trials were pulmonary artery catheter use in persistent/refractory congestive heart failure, acute respiratory distress syndrome, severe sepsis and septic shock, and low-risk coronary artery bypass graft surgery. JAMA. 2000;283:2568-2572
  JAMA The Journal of the American Medical Association 06/2000; 283(19):2568-72. · 30.03 Impact Factor
• Article: Effects of ibuprofen on the physiology and survival of hypothermic sepsis. Ibuprofen in Sepsis Study Group.

  M M Arons, A P Wheeler, G R Bernard, B W Christman, J A Russell, R Schein, W R Summer, K P Steinberg, W Fulkerson, P Wright, W D Dupont, B B Swindell
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  ABSTRACT: The objective was to compare the clinical and physiologic characteristics of febrile septic patients with hypothermic septic patients; and to examine plasma levels of cytokines tumor necrosis factor alpha (TNF-alpha and interleukin 6 (IL-6) and the lipid mediators thromboxane B2 (TxB2) and prostacyclin in hypothermic septic patients in comparison with febrile patients. Most importantly, we wanted to report the effect of ibuprofen treatment on vital signs, organ failure, and mortality in hypothermic sepsis. The study was performed in the intensive care units (ICUs) of seven clinical centers in the United States and Canada. Four hundred fifty-five patients admitted to the ICU who met defined criteria for severe sepsis and were suspected of having a serious infection. Ibuprofen at a dose of 10 mg/kg (maximum 800 mg) was administered intravenously over 30 to 60 mins every 6 hrs for eight doses vs. placebo (glycine buffer vehicle). Forty-four (10%) septic patients met criteria for hypothermia and 409 were febrile. The mortality rate was significantly higher in hypothermic patients, 70% vs. 35% for febrile patients. At study entry, urinary metabolites of TxB2, prostacyclin, and serum levels of TNF-alpha and IL-6 were significantly elevated in hypothermic patients compared with febrile patients. In hypothermic patients treated with ibuprofen, there was a trend toward an increased number of days free of major organ system failures and a significant reduction in the 30-day mortality rate from 90% (18/20 placebo-treated patients) to 54% (13/24 ibuprofen-treated patients). Hypothermic sepsis has an incidence of approximately 10% and an untreated mortality twice that of severe sepsis presenting with fever. When compared with febrile patients, the hypothermic group has an amplified response with respect to cytokines TNF-alpha and IL-6 and lipid mediators TxB2 and prostacyclin. Treatment with ibuprofen may decrease mortality in this select group of septic patients.
  Critical Care Medicine 05/1999; 27(4):699-707. · 6.33 Impact Factor
• Article: Research in sepsis and acute respiratory distress syndrome: are we changing course?

  G R Bernard
  Critical Care Medicine 03/1999; 27(2):434-6. · 6.33 Impact Factor
• Article: Transfusions in critically ill patients.

  E W Ely, G R Bernard
  New England Journal of Medicine 03/1999; 340(6):467-8. · 53.30 Impact Factor
• Article: Treating patients with severe sepsis.

  A P Wheeler, G R Bernard
  New England Journal of Medicine 02/1999; 340(3):207-14. · 53.30 Impact Factor
• Article: The American-European Consensus Conference on ARDS, part 2. Ventilatory, pharmacologic, supportive therapy, study design strategies and issues related to recovery and remodeling.

  A Artigas, G R Bernard, J Carlet, D Dreyfuss, L Gattinoni, L Hudson, M Lamy, J J Marini, M A Matthay, M R Pinsky, R Spragg, P M Suter
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  ABSTRACT: The acute respiratory distress syndrome (ARDS) continues as a contributor to the morbidity and mortality of patients in intensive care units throughout the world, imparting tremendous human and financial costs. During the last ten years there has been a decline in ARDS mortality without a clear explanation. The American-European Consensus Committee on ARDS was formed to re-evaluate the standards for the ICU care of patients with acute lung injury (ALI), with regard to ventilatory strategies, the more promising pharmacologic agents, and the definition and quantification of pathological features of ALI that require resolution. It was felt that the definition of strategies for the clinical design and coordination of studies between centers and continents was becoming increasingly important to facilitate the study of various new therapies for ARDS.
  Intensive Care Medicine 05/1998; 24(4):378-98. · 5.40 Impact Factor
• Article: The American-European Consensus Conference on ARDS, part 2: Ventilatory, pharmacologic, supportive therapy, study design strategies, and issues related to recovery and remodeling. Acute respiratory distress syndrome.

  A Artigas, G R Bernard, J Carlet, D Dreyfuss, L Gattinoni, L Hudson, M Lamy, J J Marini, M A Matthay, M R Pinsky, R Spragg, P M Suter
  [show abstract] [hide abstract]
  ABSTRACT: The acute respiratory distress syndrome (ARDS) continues as a contributor to the morbidity and mortality of patients in intensive care units throughout the world, imparting tremendous human and financial costs. During the last 10 years there has been a decline in ARDS mortality without a clear explanation. The American-European Consensus Committee on ARDS was formed to re-evaluate the standards for the ICU care of patients with acute lung injury (ALI), with regard to ventilatory strategies, the more promising pharmacologic agents, and the definition and quantification of pathologic features of ALI that require resolution. It was felt that the definition of strategies for the clinical design and coordination of studies between centers and continents was becoming increasingly important to facilitate the study of various new therapies for ARDS.
  American Journal of Respiratory and Critical Care Medicine 05/1998; 157(4 Pt 1):1332-47. · 11.08 Impact Factor
• Article: Impact of a critical care pathway for unstable mechanically ventilated patients.

  B J Price, G R Bernard, K Drew, J Foss, A P Wheeler
  Critical Care Nursing Clinics of North America 04/1998; 10(1):75-85.
• Article: Right heart catheterization in acute respiratory failure.

  W J Fulkerson, G R Bernard
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  ABSTRACT: To review the literature addressing the use of the pulmonary artery catheter (PAC) in patients with respiratory failure. All pertinent English language articles dealing with pulmonary artery catheterization in patients with respiratory failure were retrieved from 1983 through 1996. Articles were chosen for review if the use of pulmonary artery catheterization in patients with respiratory failure was studied or reviewed. From the articles selected, information was obtained about changes in therapy and changes in outcome associated with PAC use in patients with respiratory failure. Evidence exists to suggest that use of the PAC in patients with respiratory failure often results in a change in diagnosis and therapy. Inadequate evidence exists to accurately determine benefit or harm from PAC use in patients with respiratory failure. The optimal role of the PAC as a diagnostic and monitoring device in different types of respiratory failure has not been clearly defined. Research is needed to determine the role of the PAC in very carefully defined groups of patients with respiratory failure.
  New horizons (Baltimore, Md.) 09/1997; 5(3):239-43.
• Article: A trial of antioxidants N-acetylcysteine and procysteine in ARDS. The Antioxidant in ARDS Study Group.

  G R Bernard, A P Wheeler, M M Arons, P E Morris, H L Paz, J A Russell, P E Wright
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  ABSTRACT: To determine the levels of glutathione and cysteine in patients with ARDS and examine the effect of treatment with N-acetylcysteine (NAC) and L-2-oxothiazolidine-4-carboxylate (Procysteine; Clintec Technologies Inc; Chicago [OTZ]) on these levels and on common physiologic abnormalities, and organ dysfunction associated with ARDS. Randomized, double-blind, placebo-controlled, prospective clinical trial. ICUs in five clinical centers in the United States and Canada. Patients meeting a predetermined definition of ARDS and requiring mechanical ventilation. Standard care for ARDS and I.V. infusion, every 8 h for 10 days, of one of the following: NAC (70 mg/kg, n=14), OTZ (63 mg/kg, n=17), or placebo (n=15). Both antioxidants effectively repleted RBC glutathione gradually over the 10-day treatment period (47% and 49% increases from baseline values for NAC and OTZ, respectively). There was no difference in mortality among groups (placebo, 40%; NAC, 36%; OTZ, 35%). However, the number of days of acute lung injury was decreased and there was also a significant increase in cardiac index in both treatment groups (NAC/OTZ [+]14%; placebo [-]6%). Our findings suggest that repletion of glutathione may safely be accomplished with NAC or OTZ in patients with acute lung injury/ARDS. Such treatment may shorten the duration of acute lung injury, but larger studies are needed to confirm this.
  Chest 08/1997; 112(1):164-72. · 5.25 Impact Factor