Claude Perret

Nosocomial Pneumonia in Mechanically Ventilated Patients Receiving Antacid, Ranitidine, or Sucralfate as Prophylaxis for Stress Ulcer A Randomized Controlled Trial

Intensive care patients are at risk for bleeding from stress ulcers of the upper gastrointestinal tract [1]. Despite the decline of this complication over the last two decades [2], certain patients, such as those requiring prolonged mechanical ventilation, remain at high risk and may benefit from stress ulcer prophylaxis [1, 3-5]. Over the last few years, studies have shown that agents that raise the gastric pH may promote proliferation of bacteria in the stomach, particularly gram-negative bacilli that may originate in the duodenum [6-10]. Passive esophageal reflux and microaspiration of the gastric content along the endotracheal tube may lead to the colonization of the trachea and then to pneumonia [6, 7, 10-18]. Thus, concerns have arisen that the risk for nosocomial pneumonia may outweigh the benefit of stress ulcer prophylaxis when agents raising the gastric pH are used. Sucralfate is a complex salt of sucrose sulfate and aluminum hydroxide that appears to be as effective as antacids or histamine-2 (H2) antagonists for stress ulcer prophylaxis [2, 19, 20] but by mechanisms of action that do not result in clinically relevant gastric pH modification. Several studies have documented that gastric colonization is less frequent and of a lesser magnitude in ventilated patients treated with this agent compared with antacids or H2-antagonists [8, 21-23]. However, whether this would result in a decreased risk for nosocomial pneumonia is controversial [18, 24] because a reduction was found in some [21-23, 25] but not all [17, 21-23, 25-29] comparative studies. Methodologic differences among these studies might explain these conflicting findings [18]. For example, small numbers of patients for analysis [17, 26], low risk for pneumonia in the study patients [27, 28], periods of observation that were too brief [28], insufficient dosages of the agents that raise pH [27, 29], and wide use of enteral feeding [17] might account for the absence of reduction in the incidence of pneumonia noted in some studies. On the other hand, differences in the distribution of the base-line characteristics among the patients [22, 23], the grouping of patients receiving antacids and H2-antagonists, and analysis of subgroups of patients not randomly assigned to a treatment group [21, 25] may have biased the studies in which sucralfate was associated with lower rates of pneumonia. In addition, in two of these latter studies, the reduction of pneumonia developing in patients treated with sucralfate compared with other treatment did not reach the usual 0.05 level of significance [21, 23]. Furthermore, previous studies did not distinguish between pneumonia occurring early or late after intubation. This may be important because it is likely that early-onset pneumonia may be related to the introduction of bacteria in the trachea at the time of intubation [30-32], a process that is not expected to be influenced by the type of anti-stress ulcer prophylaxis. Therefore, we compared three anti-stress ulcer prophylaxis regimens (antacid, ranitidine, and sucralfate) in a large group of ventilated patients for the occurrence of bacterial colonization, early and late-onset nosocomial pneumonia, and overt gastrointestinal bleeding. Methods Patients The Centre Hospitalier Universitaire Vaudois is a 1100-bed hospital serving both as a municipal facility and a tertiary referral center. During a 2-year period (January 1989 to January 1991), all patients admitted to the adult medical and surgical intensive care units who were receiving mechanical ventilation and had a nasogastric tube in place were eligible for the study. Exclusion criteria were as follows: active upper gastrointestinal bleeding; treatment with antacids, H2-blockers, or sucralfate during the preceding 48 hours; creatinine levels greater than 200 mol/L; esogastric surgery; cardiac surgery; or organ transplantations. Patients likely to be extubated within 24 hours were also excluded. At intubation, patients were stratified into five categories according to the following underlying conditions: trauma (surgical intensive care unit), intervention after surgery (surgical intensive care unit), cardiac disease (medical intensive care unit), pulmonary disease (medical intensive care unit), and other medical conditions [medical intensive care unit]. Randomization was done using a random permutable table to generate a random treatment list. Treatment regimens were included in opaque, sealed envelopes. The patients were assigned to one of the following anti-stress ulcer prophylactic regimens: 1) antacid, a hospital-made suspension containing 5.4% aluminum hydroxide and 1.5% magnesium hydroxide with a buffer capacity of 1.2 mEq/mL, administered every 2 hoursthe standard dose of 20 mL was doubled if the gastric pH (tested with pH-indicator strips [Merck and Co., Darmstadt, Germany] before each administration) was less than 4.0; 2) ranitidine (Zantac, Glaxo, Bern, Switzerland) administered as a continuous intravenous infusion of 150 mg/d [100 mg/d if the blood creatinine level was between 150 and 200 mol/L]; or 3) sucralfate (Ulcogant, Merck and Co., Zurich, Switzerland) administered every 4 hours as 1 gram of suspension diluted in 20 mL of sterile water. After antacid or sucralfate was administered, the nasogastric tube was flushed with 10 mL of sterile water and clamped for 30 minutes. Each prophylactic regimen was continued until extubation unless interrupted earlier for any of the following predetermined reasons: an increase of the blood creatinine level to more than 200 mol/L, removal of the nasogastric tube, moribund state, discharge from the intensive care units, or side effects likely to be related to the stress ulcer regimen. Data Collection and Definitions For all eligible patients, demographic characteristics, diagnosis, underlying diseases, physical signs, laboratory tests, and medications were recorded prospectively by one of the investigators. However, only patients eventually intubated for more than 24 hours were followed and included in the final analysis. Glasgow coma and Acute Physiology and Chronic Health Evaluation (APACHE II) scoring systems were used to assess the severity of the acute illness [33]. The adult respiratory distress syndrome was defined by the following criteria: acute bilateral diffuse pulmonary infiltrates and severe hypoxemia without evidence of cardiogenic edema [34]. Gastric aspirates were examined for the macroscopic presence of blood (coffee ground material or fresh blood). The severity of gastric hemorrhage was assessed by clinical criteria (physical signs, blood transfusion requirements, and outcome). Chest radiographs were obtained on a daily basis or more often if clinically indicated. They were interpreted by a pneumologist who had knowledge of all relevant data except for the patients stress ulcer prophylactic regimen, gastric pH, or colonization data. Criteria for the diagnosis of ventilator-associated pneumonia were predetermined and derived from those of Salata and colleagues [35]: presence of a new or progressive infiltrate on the chest radiograph consistent with pneumonia, without other obvious cause, and associated with conditions A or B or both, defined as follows. Condition A refers to any of the following findings: pleural fluid or blood culture positive for an organism also isolated in the tracheal aspirate, radiographic cavitation, or histopathologic evidence of pneumonia. Condition B includes at least two of the following: tracheal aspirates with more than 25 leukocytes per low-power field (x 100) on a Gram stain, new leukocytosis defined as a leukocyte count greater than 10 109/L with an increase of at least 25% over baseline, or body temperature greater than 38.5 C with an increase of at least 1 C above baseline. The latter two criteria were considered only when other causes for these findings were excluded. Pneumonia was considered to be caused by a pathogen when it was cultured in high counts as the sole or predominant microorganism in the tracheal aspirate culture. Using the criteria of Langer and colleagues [30], early-onset and late-onset pneumonia were diagnosed if they occurred during the first 4 days of or 4 days after the initiation of mechanical ventilation, respectively. Consequently, only patients observed for more than 4 days could be evaluated for the development of late-onset pneumonia. A second episode of pneumonia was diagnosed when it was clearly temporally distinct from the first episode and when it involved other areas of the lungs. Pneumonia was attributed to a given anti-stress ulcer prophylactic regimen if it developed during treatment or within 2 days after extubation or treatment interruption. Death was considered to be directly related to nosocomial pneumonia when it occurred during the episode and when no other major contributing cause was present. Bacteriologic Investigations and pH Measurements Gastric and tracheal aspirates and oropharyngeal swabs were obtained twice daily and cultured quantitatively (gastric juice) or semi-quantitatively in aerobic conditions. Aerobic bacteria were identified by standard microbiologic methods. Cultures for Chlamydia species, Legionella pneumophila, or Mycoplasma pneumoniae were not done. Blood or pleural fluid cultures were ordered by the primary care physician according to the clinical situation. Gastric pH was measured twice a day using a pH meter (except in 11 patients for whom values were derived only from pH-indicator strips [Merck and Co.]). A cut-off value of 4.0 for median pH was chosen for further analysis within the three treatment groups because it has been shown to be a critical value for the growth of gram-negative bacilli in the stomach [6, 7, 25]. Colonization was defined by the presence of one microorganism at a given site on at least two occasions. A patient was considered to have gastric colonization with high counts when quantitative culture of at least one speci

Treatment with N-acetylcysteine during acute respiratory distress syndrome: A randomized, double-blind, placebo-controlled clinical study

PURPOSE Intravenous N-acetylcysteine (NAC) has been reported to improve systemic oxygenation and reduce the need for ventilatory support in patients with an acute lung injury. In the more serious form, namely established adult respiratory distress syndrome (ARDS) (PaO2/FIO2 < or = 200 mm Hg), we tested the hypothesis that treatment with intravenous NAC may be beneficial. MATERIALS AND METHODS Respiratory dysfunction was graded daily according to the need for mechanical ventilation and FIO2 and to the evolution of the lung injury score (LIS) and the PaO2/FIO2 ratio in 42 patients with established ARDS receiving either NAC 190 mg/kg/day or placebo as a continuous intravenous infusion over the first 3 days of their clinical course. RESULTS NAC and placebo groups (22 and 20 patients, respectively) were comparable for demographic characteristics, ARDS categories, severity of illness (simplified acute physiology score [SAPS II]) LIS and PaO2/FIO2 ratio. Mortality rate was 32% for the NAC and 25% for the placebo group (difference not significant). At admission (day 1), 91% of patients in the NAC and 95% in the placebo group required ventilatory support; at days 2, 3, 5, and 7 after admission, the percentage of patients receiving ventilatory support was not significantly reduced for both groups in comparison with day 1. Moreover, there were no differences between the two groups at the same observation days. In both groups, the FIO2 was significantly lower and the PaO2/FIO2 ratio was significantly higher than the initial values during the evolution (FiO2 at day 3, P < .01 for NAC and P < .05 for placebo; PaO2/FIO2 at day 3: P < .01 for NAC and P < .02 for placebo), but this improvement was similar for both groups and, moreover, the between-group comparison was never significantly different at the various collection days. The LIS decreased significantly in NAC group between days 1 and 3 (2.23 +/- 0.62 v 1.76 +/- 0.17; P < .05), whereas no changes were observed in the placebo group; at day 5, there was a significant difference between the two groups (1.53 +/- 0.21 for the NAC v 2.15 +/- 0.19 for the placebo group; P < .05). In the prevalent sepsis category (10 patients in the NAC and 9 in the placebo group), the mortality rate, the need of ventilatory support, the intensive care unit stay, and the PaO2/FIO2 evolution did not differ significantly in both subgroups. CONCLUSIONS In this relatively small group of patients presenting with an established ARDS subsequent to a variety of underlying diseases, intravenous NAC treatment during 72 hours neither improved systemic oxygenation nor reduced the need for ventilatory support.

Nonselective versus Selective Inhibition of Inducible Nitric Oxide Synthase in Experimental Endotoxic Shock

The effects of two nitric oxide synthase (NOS) inhibitors with different isoform selectivity were compared in a murine model of endotoxemia. Mice challenged with 70 mg/kg intraperitoneal (ip) lipopolysaccharide (LPS) were treated 6 h after LPS with either NG-gamma-L-arginine methyl ester (L-NAME, nonselective NOS inhibitor, 10-60 mg/kg), L-canavanine (selective inhibitor of inducible NOS, 50-300 mg/kg), or saline (0.2 mL) given ip. In a subset of mice, plasma concentrations of nitrate (NO breakdown product), lipase (pancreas injury), lactate dehydrogenase, and transaminases (liver injury) were measured 16 h after LPS. Although both inhibitors reduced plasma nitrate, they produced contrasting effects on survival and organ injury. L-NAME enhanced liver damage and tended to accelerate the time of death, while L-canavanine significantly reduced mortality and had no deleterious effects in terms of organ damage. These results indicate that nonselective NOS inhibitors are detrimental in endotoxic shock and support the potential usefulness of selective inducible NOS inhibitors in this setting.

Cardiac arrest: prognostic factors and outcome at one year.

This study was designed to determine by multivariate statistical methods the influence of 38 variables on outcome after cardiopulmonary resuscitation (CPR) and to assess neuropsychological status in long-term survivors. The charts of 181 consecutive patients resuscitated in a 1,100-bed University Hospital over a 2-year period were analyzed retrospectively. Of the 181 resuscitated patients, 23 (13%) could be discharged. Outcome was significantly affected by the following variables: presence of shock or renal failure before cardiac arrest (CA) (odds ratio = 10.6; 95% confidence interval = 1.3-85.8 and odds ratio = 13.8; 95% confidence interval = 1.7-109.2, respectively), administration of epinephrine (odds ratio = 11.2; 95% confidence interval = 3.2-39.2) or prolonged CPR (> 15 min) (odds ratio = 4.9; 95% confidence interval = 1.7-13.7). By contrast, when CA occurred in uncomplicated acute myocardial infarction a significantly better prognosis could be demonstrated (odds ratio = 0.2; 95% confidence interval = 0.0-0.6). The 10 long-term survivors investigated lead an independent life and all returned to former occupation. The most common complaint was moderate memory disturbance (five patients). The conclusion is that this study confirms the critical influence of cellular anoxia on prognosis and allows the improved delineation of the situations in which cardiopulmonary resuscitation appears to be hopeless or likely to be successful. The follow up in a small number of survivors has shown a good quality of life and minor neuropsychological sequellae.

Is the pulmonary artery catheter misused? A European view.

OBJECTIVES To review the problems associated with pulmonary artery catheter use in the intensive care unit; to discuss the need for clinical trials to assess its benefits; and to present original data on the use of the pulmonary artery catheter in European countries. DATA SOURCES Selected relevant articles from the literature and data from a recent multicenter European study. DATA EXTRACTION AND SYNTHESIS It has recently been suggested that pulmonary artery catheter use increases mortality. As a result, some have recommended placing a moratorium on pulmonary catheter use or suggested conducting large multicenter trials to assess the positive and negative effects of pulmonary catheter use. Although there is limited evidence showing an improved outcome with pulmonary artery catheter use, many leaders in intensive care medicine feel that the pulmonary catheter is a useful tool, when used correctly. We believe that misuse of the pulmonary artery catheter is common. The incidence of complications is low and, with improved training of insertion techniques, the frequency of complication would decrease further. The pulmonary artery catheter is a monitoring tool and, as such, is only as good as the interpretation of the data it generates. Clinical trials on such an accepted technique are difficult to conduct and their cost/benefit ratio is debatable. CONCLUSIONS A moratorium on pulmonary artery catheter use is not necessary and clinical trials in heterogeneous ICU populations are not warranted. Improved training in the insertion, interpretation, and implementation of the pulmonary artery catheter and the data it generates is required. As an alternative to expensive clinical trials on the pulmonary artery catheter, we propose that our limited financial resources for clinical investigation be invested in the development of innovative techniques that may reduce the need for pulmonary artery catheter in the future.

Mycoplasma pneumonia with fulminant evolution into diffuse interstitial fibrosis.

A fatal case of interstitial pneumonia caused by Mycoplasma pneumoniae with fulminant evolution into diffuse interstitial fibrosis is reported. Treatment with tetracycline and corticosteroids failed to arrest the progress of the disease. Fatal Mycoplasma pneumoniae infections have been reported previously and some degree of pulmonary fibrosis has been described in a few cases but as far as could be ascertained there are no other well-documented cases of diffuse interstitial fibrosis with proved Mycoplasma pneumoniae infection.

A novel score for predicting the mortality of septic shock patients

ObjectiveTo establish a prognostic scoring system for septic shock patients. DesignThe clinical, biological, and hemodynamic data of these patients were retrospectively explored to select variables independently associated with outcome. According to the risk of death, ratings from 0 to 2 points were attributed to each value. SettingMedical intensive care service of a 1,000-bed tertiary care university medical center. PatientsEighty-eight patients in septic shock in whom hemodynamic measurements were performed using pulmonary artery flotation catheters. ResultsFourteen clinical, biological, and hemodynamic variables were selected and rated for each patient. A Simplified Septic Shock Score, available immediately after admission and catheterization, was established by adding the rates of these variables. The mean Simplified Septic Shock Score was 2.5 ± 1.7 (SD) in 43 survivors and 6.5 ± 2.3 in 45 nonsurvivors (p < .0001). Some underlying diseases and characteristics of infections also correlated with the outcome. Further ratings from 0 to 2 points were attributed to these conditions. A Complete Septic Shock Score was calculated by adding these rates to the Simplified Septic Shock Score. The Complete Septic Shock Score had a slightly better prognostic value than the Simplified Septic Shock Score, but it could be determined only after the availability of the microbiological data. The mean Complete Septic Shock Score was 3.1 ± 1.9 in survivors and 8.4 ± 2.6 in nonsurvivors (p < .0001). Both Simplified and Complete Septic Shock Scores showed better association with patient outcome than the Simplified Acute Physiology Score or the Acute Physiology and Chronic Health Evaluation (APACHE II) score. ConclusionsThe Simplified and the Complete Septic Shock Scores are simple scoring systems that appear to predict the outcome of septic shock patients more accurately than general scoring systems, such as the Simplified Acute Physiology Score and APACHE II score. These septic shock scores might be useful in assessing the severity of septic shock patients.

Effectiveness of percutaneous transluminal coronary angioplasty in cardiogenic shock during acute myocardial infarction

Abstract The prognosis of cardiogenic shock during acute myocardial infarction (AMI) is poor; the mortality rate varies from 80 to 100%.1,2 Recently, interventional therapy including intracoronary thrombolysis and mechanical recanalization have been proposed and seem to improve prognosis.3–5

An extreme form of the hyperdynamic syndrome in septic shock

We classified 41 patients in septic shock on the basis of cardiac index (CI) after volume expansion with plasma protein solution, in order to obtain adequate filling pressures. Five had decreased CI (<3.5 l/min per m2), 31 had moderately increased CI (3.5–7.0 l/min per m2) and 5 had extreme hyperdynamic shock with CI superior to 7.0 l/min per m2. Among the patients with increased CI, those with extreme hyperdynamic state (EHS) had lower total systemic and pulmonary arteriolar resistances (370 vs 658 and 52 vs 119 dynes·s·cm-5, respectively) and a higher stroke index (67 vs 46 ml/m2), in spite of similar right atrial pressures. In this latter group, blood lactate was higher (6.5 vs 2.1 mmol/l), acidosis was more severe and coagulation disorders more pronounced; all five patients maintained an extremely high CI until death, which supervened after a brief episode of sinus bradycardia. A similar clinical course was rarely observed in the remaining moderately hyperdynamic group, in which mortality rate was significantly lower (35%). Three of five patients with EHS (compared to 2 of 31 in the moderately hyperdynamic group) had liver cirrhosis, the fourth died of fulminant meningococcemia and the fifth had prolonged polymicrobial bacteremia before adequate treatment was begun. Thus, underlying liver disease or particularly severe and uncontrolled infection seems to predispose to EHS. It is concluded that septic shock with extremely high cardiac output and excessively low peripheral resistances represents a distinct subset with more severe metabolic and coagulation disorders, an unusual hemodynamic evolution and a particularly poor prognosis.

Oxidative metabolism of circulating granulocytes in adult respiratory distress syndrome

Among the different mechanisms involved, polymorphonuclear leukocytes (PMNs) may play a central role in the pathogenesis of adult respiratory distress syndrome (ARDS). PMNs were evaluated in 15 patients with ARDS, in 21 at risk of developing ARDS (AR), and in 36 controls (C). Spontaneous and opsonized zymosan (OZ), phorbol myristate acetate (PMA), and F-Met-Leu-Phe (F-M-L-P)-stimulated oxygen radical production was measured by luminol- and lucigenin-enhanced chemiluminescence (CL). Spontaneous CL activity of PMNs from ARDS patients was significantly greater than that from the PMN control (luminol CL, 2.8 +/- 0.6 vs. 0.8 +/- 0.1 mV, p less than 0.001; lucigenin CL, 2.0 +/- 0.6 vs. 0.30 +/- 0.04 mV, p less than 0.001), and the CL value from AR patients (luminol CL, 1.3 +/- 0.2 mV, p less than 0.001 vs. C; lucigenin CL, 0.8 +/- 0.1 mV, p less than 0.001 vs. C) was found to be between the ARDS and C patients. The peak of PMA-stimulated CL occurred earlier and it was significantly higher in ARDS patients than in AR patients (p less than 0.05) and controls (p less than 0.001). When the CL response was elicited with F-M-L-P, no difference among the three groups was found. When stimulated with OZ, the peak CL generated by PMNs from ARDS patients was significantly depressed compared with controls (luminol CL, 26.7 +/- 1.8 vs. 40.9 +/- 2.3 mV, p less than 0.01; lucigenin CL, 5.0 +/- 0.4 vs. 7.4 +/- 0.5 mV, p less than 0.005) with a similar result being obtained from AR patients (luminol CL, 32.1 +/- 2.5 mV, p less than 0.01 vs. C). Plasma from ARDS and AR patients showed a defective opsonizing capacity, suggesting in vivo complement consumption in both patient groups. No correlation between the severity of hypoxemia, the cause of ARDS, the outcome, and the different PMN functions could be established. Our results are in agreement with a determinant role of PMNs in the development of ARDS. The opposite metabolic responses may explain both the pulmonary injury and the increased susceptibility to infections observed in patients at risk of or with ARDS.