Marie-Denise Schaller

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

Early predictors of outcome in comatose survivors of ventricular fibrillation and non-ventricular fibrillation cardiac arrest treated with hypothermia: a prospective study.

Objectives:Current indications for therapeutic hypothermia (TH) are restricted to comatose patients with cardiac arrest (CA) due to ventricular fibrillation (VF) and without circulatory shock. Additional studies are needed to evaluate the benefit of this treatment in more heterogeneous groups of patients, including those with non-VF rhythms and/or shock and to identify early predictors of outcome in this setting. Design:Prospective study, from December 2004 to October 2006. Setting:32-bed medico-surgical intensive care unit, university hospital. Patients:Comatose patients with out-of-hospital CA. Interventions:TH to 33 ± 1°C (external cooling, 24 hrs) was administered to patients resuscitated from CA due to VF and non-VF (including asystole or pulseless electrical activity), independently from the presence of shock. Measurements and Main Results:We hypothesized that simple clinical criteria available on hospital admission (initial arrest rhythm, duration of CA, and presence of shock) might help to identify patients who eventually survive and might most benefit from TH. For this purpose, outcome was related to these predefined variables. Seventy-four patients (VF 38, non-VF 36) were included; 46% had circulatory shock. Median duration of CA (time from collapse to return of spontaneous circulation [ROSC]) was 25 mins. Overall survival was 39.2%. However, only 3.1% of patients with time to ROSC >25 mins survived, as compared to 65.7% with time to ROSC ≤25 mins. Using a logistic regression analysis, time from collapse to ROSC, but not initial arrest rhythm or presence of shock, independently predicted survival at hospital discharge. Conclusions:Time from collapse to ROSC is strongly associated with outcome following VF and non-VF cardiac arrest treated with therapeutic hypothermia and could therefore be helpful to identify patients who benefit most from active induced cooling.

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.

Energy deficit and length of hospital stay can be reduced by a two-step quality improvement of nutrition therapy: the intensive care unit dietitian can make the difference.

Objective: Critically ill patients are at high risk of malnutrition. Insufficient nutritional support still remains a widespread problem despite guidelines. The aim of this study was to measure the clinical impact of a two-step interdisciplinary quality nutrition program. Design: Prospective interventional study over three periods (A, baseline; B and C, intervention periods). Setting: Mixed intensive care unit within a university hospital. Patients: Five hundred seventy-two patients (age 59 ± 17 yrs) requiring >72 hrs of intensive care unit treatment. Intervention: Two-step quality program: 1) bottom-up implementation of feeding guideline; and 2) additional presence of an intensive care unit dietitian. The nutrition protocol was based on the European guidelines. Measurements and Main Results: Anthropometric data, intensive care unit severity scores, energy delivery, and cumulated energy balance (daily, day 7, and discharge), feeding route (enteral, parenteral, combined, none–oral), length of intensive care unit and hospital stay, and mortality were collected. Altogether 5800 intensive care unit days were analyzed. Patients in period A were healthier with lower Simplified Acute Physiologic Scale and proportion of “rapidly fatal” McCabe scores. Energy delivery and balance increased gradually: impact was particularly marked on cumulated energy deficit on day 7 which improved from −5870 kcal to −3950 kcal (p < .001). Feeding technique changed significantly with progressive increase of days with nutrition therapy (A: 59% days, B: 69%, C: 71%, p < .001), use of enteral nutrition increased from A to B (stable in C), and days on combined and parenteral nutrition increased progressively. Oral energy intakes were low (mean: 385 kcal*day−1, 6 kcal*kg−1*day −1). Hospital mortality increased with severity of condition in periods B and C. Conclusion: A bottom-up protocol improved nutritional support. The presence of the intensive care unit dietitian provided significant additional progression, which were related to early introduction and route of feeding, and which achieved overall better early energy balance.

Prospective monitoring of cefepime in intensive care unit adult patients

IntroductionCefepime has been associated with a greater risk of mortality than other beta-lactams in patients treated for severe sepsis. Hypotheses for this failure include possible hidden side-effects (for example, neurological) or inappropriate pharmacokinetic/pharmacodynamic (PK/PD) parameters for bacteria with cefepime minimal inhibitory concentrations (MIC) at the highest limits of susceptibility (8 mg/l) or intermediate-resistance (16 mg/l) for pathogens such as Enterobacteriaceae, Pseudomonas aeruginosa and Staphylococcus aureus. We examined these issues in a prospective non-interventional study of 21 consecutive intensive care unit (ICU) adult patients treated with cefepime for nosocomial pneumonia.MethodsPatients (median age 55.1 years, range 21.8 to 81.2) received intravenous cefepime at 2 g every 12 hours for creatinine clearance (CLCr) ≥ 50 ml/min, and 2 g every 24 hours or 36 hours for CLCr < 50 ml/minute. Cefepime plasma concentrations were determined at several time-points before and after drug administration by high-pressure liquid chromatography. PK/PD parameters were computed by standard non-compartmental analysis.ResultsSeventeen first-doses and 11 steady states (that is, four to six days after the first dose) were measured. Plasma levels varied greatly between individuals, from two- to three-fold at peak-concentrations to up to 40-fold at trough-concentrations. Nineteen out of 21 (90%) patients had PK/PD parameters comparable to literature values. Twenty-one of 21 (100%) patients had appropriate duration of cefepime concentrations above the MIC (T>MIC ≥ 50%) for the pathogens recovered in this study (MIC ≤ 4 mg/l), but only 45 to 65% of them had appropriate coverage for potential pathogens with cefepime MIC ≥ 8 mg/l. Moreover, 2/21 (10%) patients with renal impairment (CLCr < 30 ml/minute) demonstrated accumulation of cefepime in the plasma (trough concentrations of 20 to 30 mg/l) in spite of dosage adjustment. Both had symptoms compatible with non-convulsive epilepsy (confusion and muscle jerks) that were not attributed to cefepime-toxicity until plasma levels were disclosed to the caretakers and symptoms resolved promptly after drug arrest.ConclusionsThese empirical results confirm the suspected risks of hidden side-effects and inappropriate PK/PD parameters (for pathogens with upper-limit MICs) in a population of ICU adult patients. Moreover, it identifies a safety and efficacy window for cefepime doses of 2 g every 12 hours in patients with a CLCr ≥ 50 ml/minute infected by pathogens with cefepime MICs ≤ 4 mg/l. On the other hand, prompt monitoring of cefepime plasma levels should be considered in case of lower CLCr or greater MICs.

Negative Pressure Post-Tracheal Extubation Alveolar Hemorrhage

egative pressure pulmonary edema is an un-common complication of extubation of the tra-chea (>0.1%) mostly caused by laryngospasm(1). Upper airway obstruction from glottis closureleads to marked inspiratory efforts, which generatevery negative intrathoracic pressure. This may causepulmonary edema (1,2) and, rarely, hemoptysis (3,4).This report is the first to document both broncho-scopic and computed tomography (CT) findings con-sistent with alveolar hemorrhage and capillary failurein this setting.

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

Ventricular arrhythmia in coronary artery disease: limits of a risk stratification strategy based on the ejection fraction alone and impact of infarct localization

AIMS Estimates of the left ventricular ejection fraction (LVEF) in patients with life-threatening ventricular arrhythmias related to coronary artery disease (CAD) have rarely been reported despite it has become the basis for determining patients eligibility for prophylactic defibrillator. We aimed to determine the extent and distribution of reduced LVEF in patients with sustained ventricular tachycardia or ventricular fibrillation. METHODS AND RESULTS 252 patients admitted for ventricular arrhythmia related to CAD were included: 149 had acute myocardial infarction (MI) (Group I, 59%), 54 had significant chronic obstructive CAD suggestive of an ischaemic arrhythmic trigger (Group II, 21%) and 49 patients had an old MI without residual ischaemia (Group III, 19%). 34% of the patients with scar-related arrhythmias had an LVEF > or =40%. Based on pre-event LVEF evaluation, it can be estimated that less than one quarter of the whole study population had a known chronic MI with severely reduced LVEF. In Group III, the proportion of inferior MI was significantly higher than anterior MI (81 vs. 19%; absolute difference, -62; 95% confidence interval, -45 to -79; P < or = 0.0001), though median LVEF was higher in inferior MI (0.37 +/- 10 vs. 0.29 +/- 10; P = 0.0499). CONCLUSION Patients included in defibrillator trials represent only a minority of the patients at risk of sudden cardiac death. By applying the current risk stratification strategy based on LVEF, more than one third of the patients with old MI would not have qualified for a prophylactic defibrillator. Our study also suggests that inferior scars may be more prone to ventricular arrhythmia compared to anterior scars.

Fatal cardiac arrhythmias and shock following yew leaves ingestion

A 40-year-old woman presented with vomiting and abdominal pain following voluntary ingestion of 150 yew leaves. She developed ventricular conduction defects and arrhythmias unresponsive to medical treatment after admission. She expired five hours after yew ingestion from irreversible cardiogenic shock. More attention should be given to this rare but severe intoxication for which no effective therapy is known.