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Graham Ramsay

Publications and source records attributed to Graham Ramsay.

At least 19 recordsLinked to original sources
PubMed2006

Oral decontamination with chlorhexidine reduces the incidence of ventilator-associated pneumonia.

RATIONALE: Ventilator-associated pneumonia (VAP) is the most frequently occurring nosocomial infection associated with increased morbidity and mortality. Although oral decontamination with antibiotics reduces incidences of VAP, it is not recommended because of potential selection of antibiotic-resistant pathogens. We hypothesized that oral decontamination with either chlorhexidine (CHX, 2%) or CHX/colistin (CHX/COL, 2%/2%) would reduce and postpone development of VAP, and oral and endotracheal colonization. OBJECTIVES: To determine the effect of oral decontamination with CHX or CHX/COL on VAP incidence and time to development of VAP. METHODS: Consecutive patients needing mechanical ventilation for 48 h or more were enrolled in a randomized, double-blind, placebo-controlled trial with three arms: CHX, CHX/COL, and placebo (PLAC). Trial medication was applied every 6 h into the buccal cavity. Oropharyngeal swabs were obtained daily and quantitatively analyzed for gram-positive and gram-negative microorganisms. Endotracheal colonization was monitored twice weekly. RESULTS: Of 385 patients included, 130 received PLAC, 127 CHX and 128 CHX/COL. Baseline characteristics were comparable. The daily risk of VAP was reduced in both treatment groups compared with PLAC: 65% (hazard ratio [HR]=0.352; 95% confidence interval [CI], 0.160, 0. 791; p=0.012) for CHX and 55% (HR=0.454; 95% CI, 0.224, 0. 925; p=0.030) for CHX/COL. CHX/COL provided significant reduction in oropharyngeal colonization with both gram-negative and gram-positive microorganisms, whereas CHX mostly affected gram-positive microorganisms. Endotracheal colonization was reduced for CHX/COL patients and to a lesser extent for CHX patients. No differences in duration of mechanical ventilation, intensive care unit stay, or intensive care unit survival could be demonstrated. CONCLUSIONS: Topical oral decontamination with CHX or CHX/COL reduces the incidence of VAP.

Administration, Topical↗
PubMed2006

International integrated database for the evaluation of severe sepsis and drotrecogin alfa (activated) therapy: analysis of efficacy and safety data in a large surgical cohort.

BACKGROUND: The International Integrated Database for the Evaluation of Severe Sepsis and Drotrecogin alfa (activated) Therapy includes an extensive cohort of surgical patients (1659/4459; 37%). This database broadens the experience reported on a comparatively small set of surgical patients from the pivotal Protein C Worldwide Evaluation in Severe Sepsis trial to examine issues of safety and efficacy in a much larger cohort. METHODS: We conducted a retrospective analysis of prospectively defined outcomes from 5 integrated clinical studies of severe sepsis. Multivariable analyses incorporated propensity scores, treatment, and significant baseline risk factors as independent variables in logistic regression models for 2 outcomes: serious adverse events that were observed during infusion and 28-day, all-cause mortality rates. Adjusted odds ratios were calculated for clinically important strata. Multiple subcategories of serious bleeding-event rates are presented. RESULTS: Although surgical patients who were treated with drotrecogin alfa [activated] (DrotAA) experienced a greater proportion of serious bleeding events during the infusion period, most of the patients were treated without fatal consequence. A 10.7% absolute all cause mortality risk reduction (adjusted odds ratio, 0.66; 95% CI, 0.45-0.97) was observed for DrotAA-treated, high-risk (Acute Physiology and Chronic Health Evaluation II, >or=25) surgical patients. We could not demonstrate a survival benefit in DrotAA-treated, low-risk (Acute Physiology and Chronic Health Evaluation II, <25) surgical patients. When surgical patients were stratified by number of organ dysfunctions, absolute risk reductions were observed in both categories: multiorgan (4.3%) and single (4.5%). CONCLUSION: International Integrated Database for the Evaluation of Severe Sepsis and Drotrecogin alfa (activated) Therapy analyses affirmed the favorable benefit/risk profile of DrotAA for surgical patients. The serious adverse event rate that was experienced by surgical patients during the study drug infusion period was 7.5% in the DrotAA-treated group versus 6.3% in the placebo-treated group (odds ratio, 1.41; 95% CI, 0.89-2.25). The clinical benefit of DrotAA therapy paralleled baseline risk of death and substantiated findings from the Protein C Worldwide Evaluation in Severe Sepsis study. Future analyses are needed to evaluate the special relationships among sepsis severity, bleeding management, and the postoperative timing of DrotAA administration.

Adult↗
PubMed2006

Point-of-care blood analyzer during the interhospital transport of critically ill children.

OBJECTIVES: To investigate the influence of point-of-care laboratory results (arterial blood gases, ionized calcium, potassium, sodium, glucose, hematocrit and hemoglobin) on therapeutic interventions during interhospital pediatric intensive care transport. DESIGN: Prospective observational study. SETTINGS: Specialist pediatric intensive care retrieval team of a university hospital. PARTICIPANTS: Critically ill pediatric patients who were referred from a community hospital to a pediatric intensive care of a tertiary center. The retrieval team sampled arterial blood during the time of stabilization in the referring hospital and during transport. All results were recorded and for each result the physician of the specialist retrieval team wrote down the influence on the treatment (none, partly, only). The physician specified the kind of intervention. RESULTS: Point-of-care blood analyses influenced the therapeutic management in 76.5% of all blood samples and in 86.2% of the referred patients. Of all interventions, 42.9% were based only on the laboratory results. The majority of interventions were adjustments of the mechanical ventilation. Point-of-care blood analyses reduced the delay in treatment of potentially life-threatening abnormalities of laboratory results (severe hypokalemia and low hematocrit). CONCLUSIONS: During interhospital pediatric intensive care transport, point-of-care blood analyses frequently led to therapeutic interventions. Some abnormal blood results were potentially life threatening and could not have been discovered without point-of-care measurement. We therefore recommend the use of a point-of-care blood analyzer during interhospital intensive care transports, not only for blood gases but also for electrolytes, glucose and hematocrit.

Autoanalysis↗
PubMed2006

Feasibility and effects of the semirecumbent position to prevent ventilator-associated pneumonia: a randomized study.

CONTEXT: Reducing aspiration of gastric contents by placing mechanically ventilated patients in a semirecumbent position has been associated with lower incidences of ventilator-associated pneumonia (VAP). The feasibility and efficacy of this intervention in a larger patient population, however, are unknown. OBJECTIVE: Assessment of the feasibility of the semirecumbent position for intensive care unit patients and its influence on development of VAP. DESIGN: In a prospective multicentered trial, critically ill patients undergoing mechanical ventilation were randomly assigned to the semirecumbent position, with a target backrest elevation of 45 degrees , or standard care (i.e., supine position) with a backrest elevation of 10 degrees . MAIN OUTCOME MEASURES: Backrest elevation was measured continuously during the first week of ventilation with a monitor-linked device. A deviation of position was defined as a change of the randomized position >5 degrees . Diagnosis of VAP was made by quantitative cultures of samples obtained by bronchoscopic techniques. RESULTS: One hundred nine patients were assigned to the supine group and 112 to the semirecumbent group. Baseline characteristics were comparable for both groups. Average elevations were 9.8 degrees and 16.1 degrees at day 1 and day 7, respectively, for the supine group and 28.1 degrees and 22.6 degrees at day 1 and day 7, respectively, for the semirecumbent group (p < .001). The target semirecumbent position of 45 degrees was not achieved for 85% of the study time, and these patients more frequently changed position than supine-positioned patients. VAP was diagnosed in eight patients (6.5%) in the supine group and in 13 (10.7%) in the semirecumbent group (NS), after a mean of 6 (range, 3-9) and 7 (range, 3-12) days, respectively. There were no differences in numbers of patients undergoing enteral feeding, receiving stress ulcer prophylaxis, or developing pressure sores or in mortality rates or duration of ventilation and intensive care unit stay between the groups. CONCLUSIONS: The targeted backrest elevation of 45 degrees for semirecumbent positioning was not reached in the conditions of the present randomized study. The achieved difference in treatment position (28 degrees vs. 10 degrees ) did not prevent the development of VAP.

APACHE↗
PubMed2005

Meta-analysis of hemodynamic optimization: relationship to methodological quality.

INTRODUCTION: To review systematically the effect of interventions aimed at hemodynamic optimization and to relate this to the quality of individual published trials. METHODS: A systematic, computerized bibliographic search of published studies and citation reviews of relevant studies was performed. All randomized clinical trials in which adult patients were included in a trial deliberately aiming at an optimized or maximized hemodynamic condition of the patients (with oxygen delivery, cardiac index, oxygen consumption, mixed venous oxygen saturation and/or stroke volume as end-points) were selected. A total of 30 studies were selected for independent review. Two reviewers extracted data on population, intervention, outcome and methodological quality. Agreement between reviewers was high: differences were eventually resolved by third-party decision. The methodological quality of the studies was moderate (mean 9.0, SD 1.7), and the outcomes of the randomized clinical trials were not related to their quality. RESULTS: Efforts to achieve an optimized hemodynamic condition resulted in a decreased mortality rate (relative risk ratio (RR) 0.75 (95% confidence interval (CI) 0.62 to 0.90) in all studies combined. This was due to a significantly decreased mortality in peri-operative intervention studies (RR 0.66 (95% CI 0.54 to 0.81). Overall, patients with sepsis and overt organ failure do not benefit from this method (RR 0.92 (95% CI 0.75 to 1.11)). CONCLUSION: This systematic review showed that interventions aimed at hemodynamic optimization reduced mortality. In particular, trials including peri-operative interventions aimed at the hemodynamic optimization of high-risk surgical patients reduce mortality. Overall, this effect was not related to the trial quality.

Critical Care↗
PubMed2005

Monitoring global volume-related hemodynamic or regional variables after initial resuscitation: What is a better predictor of outcome in critically ill septic patients?

OBJECTIVE: Regional variables of organ dysfunction are thought to be better monitoring variables than global pressure-related hemodynamic variables. Whether a difference exists between regional and global volume-related variables in critically ill patients after resuscitation is unknown. DESIGN: Prospective diagnostic test evaluation. SETTING: University-affiliated mixed intensive care unit. PATIENTS: Twenty-eight critically ill patients. INTERVENTIONS: Using standardized resuscitation, hemodynamic optimization was targeted at mean arterial pressure, heart rate, occlusion pressure, cardiac output, systemic vascular resistance, and urine output. Primary outcome variable was in-hospital mortality. MEASUREMENTS AND MAIN RESULTS: During resuscitation, global volume-related hemodynamic variables were measured simultaneously and compared with regional variables. At admission no variable was superior as a predictor of outcome. During resuscitation, significant changes were seen in mean arterial pressure, central venous pressure, oxygen delivery, systemic vascular resistance, total blood volume, right heart and ventricle end-diastolic volume, right ventricle ejection fraction, right and left stroke work index, intramucosal carbon dioxide pressure, gastric mucosal pH, mucosal-end tidal Pco2 gap, indocyanine green blood clearance, indocyanine green plasma clearance, and plasma disappearance rate. Multivariate analysis identified lactate, gastric mucosal pH, mucosal-end tidal Pco2 gap, mucosal-arterial Pco2 gap, indocyanine green plasma clearance, and plasma disappearance rate of dye as nondependent predictors of outcome. Patients who subsequently died had a significantly lower gastric mucosal pH, higher intramucosal carbon dioxide pressure and mucosal-end tidal Pco2 gap, and lower indocyanine green blood clearance, indocyanine green plasma clearance, plasma disappearance rate, and right ventricular end-diastolic volume index, of which gastric mucosal pH, mucosal-end tidal Pco2 gap, and indocyanine green blood clearance were the most important predictors of outcome. CONCLUSIONS: Initial resuscitation of critically ill patients with shock does not require monitoring of regional variables. After stabilization, however, regional variables are the best predictors of outcome.

Aged↗
PubMed2004

An international sepsis survey: a study of doctors' knowledge and perception about sepsis.

BACKGROUND: To be able to diagnose and treat sepsis better it is important not only to improve the knowledge about definitions and pathophysiology, but also to gain more insight into specialists' perception of, and attitude towards, the current diagnosis and treatment of sepsis. METHODS: The study was conducted as a prospective, international survey by structured telephone interview. The subjects were intensive care physicians and other specialist physicians caring for intensive care unit (ICU) patients. RESULTS: The 1058 physicians who were interviewed (including 529 intensivists) agreed that sepsis is a leading cause of death on the ICU and that the incidence of sepsis is increasing, but that the symptoms of sepsis can easily be misattributed to other conditions. Physicians were concerned that this could lead to under-reporting of sepsis. Two-thirds (67%) were concerned that a common definition is lacking and 83% said it is likely that sepsis is frequently missed. Not more than 17% agreed on any one definition. CONCLUSION: There is a general awareness about the inadequacy of the current definitions of sepsis. Physicians caring for patients with sepsis recognise the difficulty of defining and diagnosing sepsis and are aware that they miss the diagnosis frequently.

Adult↗
PubMed2004

Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock.

OBJECTIVE: To develop management guidelines for severe sepsis and septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. The modified Delphi methodology used for grading recommendations built upon a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along 5 levels to create recommendation grades from A-E, with A being the highest grade. Pediatric considerations were provided to contrast adult and pediatric management. PARTICIPANTS: Participants included 44 critical care and infectious disease experts representing 11 international organizations. RESULTS: A total of 46 recommendations plus pediatric management considerations. CONCLUSIONS: Evidence-based recommendations can be made regarding many aspects of the acute management of sepsis and septic shock that will hopefully translate into improved outcomes for the critically ill patient. The impact of these guidelines will be formally tested and guidelines updated annually, and even more rapidly when some important new knowledge becomes available.

Adult↗
PubMed2004

Oral decontamination is cost-saving in the prevention of ventilator-associated pneumonia in intensive care units.

OBJECTIVE: Although the development of ventilator-associated pneumonia (VAP) is assumed to increase costs of intensive care unit stay, it is unknown whether prevention of VAP by means of oropharyngeal decontamination is cost-effective. Because of wide ranges of individual patient costs, crude cost comparisons did not show significant cost reductions. DESIGN: Based on actual cost data of 181 individual patients included in a former randomized clinical trial, cost-effectiveness of prevention of VAP was determined using a decision model and univariate sensitivity analyses, and bootstrapping was used to assess the impact of variability in the various outcomes. DATA SOURCE: Published data on prevention of VAP by oropharyngeal decontamination, which resulted in a relative risk for VAP of 0.45, with a baseline rate of VAP of 29% among control patients. The mean costs of the intervention were 351 dollars per patient (32 dollars per patient per day). All other costs were derived from the hospital administrative database for all individual patients. RESULTS OF BASE-CASE ANALYSIS: Prevention of VAP led to mean total costs of 16,119 dollars and 18,268 dollars for patients without preventive measures administered. Thus, costs were saved and instances of VAP were prevented. Similar results were observed in terms of overall survival. RESULTS OF SENSITIVITY ANALYSIS: Prevention of VAP remains cost-saving if the relative risk for VAP because of intervention is <0.923, the costs of the intervention are less than 2,500 dollars, and the prevalence of VAP without intervention is >4%. Bootstrapping confirmed that, with about 80% certainty, oropharyngeal decontamination results in prevention of VAP and simultaneously saves costs. In terms of a survival benefit, the results are less evident; the results indicate that with only about 60% certainty can we confirm that oropharyngeal decontamination would result in a survival benefit and simultaneously save costs. CONCLUSIONS: This study provides strong evidence that prevention of VAP by means of oropharyngeal decontamination is cost-effective.

Antibiotic Prophylaxis↗
PubMed2004

Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock.

OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for severe sepsis and septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. METHODS: We used a modified Delphi methodology for grading recommendations, built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations were provided to contrast adult and pediatric management. RESULTS: Key recommendations, listed by category and not by hierarchy, include early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition; appropriate diagnostic studies to ascertain causative organisms before starting antibiotics; early administration of broad-spectrum antibiotic therapy; reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate; a usual 7-10 days of antibiotic therapy guided by clinical response; source control with attention to the method that balances risks and benefits; equivalence of crystalloid and colloid resuscitation; aggressive fluid challenge to restore mean circulating filling pressure; vasopressor preference for norepinephrine and dopamine; cautious use of vasopressin pending further studies; avoiding low-dose dopamine administration for renal protection; consideration of dobutamine inotropic therapy in some clinical situations; avoidance of supranormal oxygen delivery as a goal of therapy; stress-dose steroid therapy for septic shock; use of recombinant activated protein C in patients with severe sepsis and high risk for death; with resolution of tissue hypoperfusion and in the absence of coronary artery disease or acute hemorrhage, targeting a hemoglobin of 7-9 g/dL; appropriate use of fresh frozen plasma and platelets; a low tidal volume and limitation of inspiratory plateau pressure strategy for acute lung injury and acute respiratory distress syndrome; application of a minimal amount of positive end-expiratory pressure in acute lung injury/acute respiratory distress syndrome; a semirecumbent bed position unless contraindicated; protocols for weaning and sedation/analgesia, using either intermittent bolus sedation or continuous infusion sedation with daily interruptions/lightening; avoidance of neuromuscular blockers, if at all possible; maintenance of blood glucose <150 mg/dL after initial stabilization; equivalence of continuous veno-veno hemofiltration and intermittent hemodialysis; lack of utility of bicarbonate use for pH > or =7.15; use of deep vein thrombosis/stress ulcer prophylaxis; and consideration of limitation of support where appropriate. Pediatric considerations included a more likely need for intubation due to low functional residual capacity; more difficult intravenous access; fluid resuscitation based on weight with 40-60 mL/kg or higher needed; decreased cardiac output and increased systemic vascular resistance as the most common hemodynamic profile; greater use of physical examination therapeutic end points; unsettled issue of high-dose steroids for therapy of septic shock; and greater risk of hypoglycemia with aggressive glucose control. CONCLUSION: Evidence-based recommendations can be made regarding many aspects of the acute management of sepsis and septic shock that are hoped to translate into improved outcomes for the critically ill patient. The impact of these guidelines will be formally tested and guidelines updated annually and even more rapidly as some important new knowledge becomes as available.

Adult↗
PubMed2004

Sepsis: an arginine deficiency state?

OBJECTIVE: Sepsis is a major health problem considering its significant morbidity and mortality rate. The amino acid L-arginine has recently received substantial attention in relation to human sepsis. However, knowledge of arginine metabolism during sepsis is limited. Therefore, we reviewed the current knowledge about arginine metabolism in sepsis. DATA SOURCE: This review summarizes the literature on arginine metabolism both in general and in relation to sepsis. Moreover, arginine-related therapies are reviewed and discussed, which includes therapies of both nitric oxide (NO) and arginine administration and therapies directed toward inhibition of NO. DATA: In sepsis, protein breakdown is increased, which is a key process to maintain arginine delivery, because both endogenous de novo production from citrulline and food intake are reduced. Arginine catabolism, on the other hand, is markedly increased by enhanced use of arginine in the arginase and NO pathways. As a result, lowered plasma arginine levels are usually found. Clinical symptoms of sepsis that are related to changes in arginine metabolism are mainly related to hemodynamic alterations and diminished microcirculation. NO administration and arginine supplementation as a monotherapy demonstrated beneficial effects, whereas nonselective NO synthase inhibition seemed not to be beneficial, and selective NO synthase 2 inhibition was not beneficial overall. CONCLUSIONS: Because sepsis has all the characteristics of an arginine-deficiency state, we hypothesise that arginine supplementation is a logical option in the treatment of sepsis. This is supported by substantial experimental and clinical data on NO donors and NO inhibitors. However, further evidence is required to prove our hypothesis.

Arginine↗
PubMed2003

Comparison of interhospital pediatric intensive care transport accompanied by a referring specialist or a specialist retrieval team.

OBJECTIVE: Interhospital transfers of critically ill pediatric patients in The Netherlands are accompanied by referring specialists or by specialist retrieval teams. We compared the interventions before and directly after transports and the complications and the equipment available during transports in the two groups. DESIGN AND SETTING: Prospective observational clinical study in pediatric intensive care units of Dutch university hospitals. PATIENTS: 249 pediatric patients requiring interhospital intensive care transport. METHODS: Data were collected on interhospital pediatric intensive care transports. We compared patient characteristics, interventions before and directly after transport, complications and equipment available during transport (137 accompanied by referring specialists, 112 by specialist retrieval teams). RESULTS: Interhospital transports accompanied by referring specialists had a longer average transport time (74.6 vs. 60.2 min), higher incidence of respiratory insufficiency (56.9% vs. 41.1%), and lower incidence of circulatory insufficiency (27.0% vs. 41.1%) than primary admission diagnoses. These transports had a lower percentage of ventilatory support (47.4% vs. 72.3%), higher need for acute interventions directly upon arrival on the pediatric ICU, and higher incidence of critical and serious complications. In 75% of the transfers accompanied by retrieval teams interventions before the transport were deemed to be necessary. During the transports accompanied by referring specialists the equipment and materials available proved rather limited. CONCLUSIONS: During pediatric intensive care transports accompanied by nontrained referring specialists there appears to be a higher incidence of complications, specialized equipment is more often not available, and more acute interventions are required upon arrival in the pediatric ICU.

Child↗
PubMed2003

Gastric PgCO2 and Pg-aCO2 gap are related to D-lactate and not to L-lactate levels in patients with septic shock.

OBJECTIVE: Intestinal ischemia causes an increase in lactate production and gastric intramucosal carbon dioxide partial pressure (PgCO(2)). However, no linear relationship between systemic l-lactate levels and gastric tonometry during intestinal ischemia has been found, probably since l-lactate is rapidly cleared from the circulation by the liver. In contrast, the rate of d-lactate clearance from the circulation by the liver is considerably lower than that of l-lactate, and d-lactate may therefore be more closely related to measurements of gastric tonometry than l-lactate values. DESIGN AND SETTING: Prospective, observational study in a university-affiliated mixed intensive care unit. SUBJECTS: Twenty critically ill patients with septic shock. MEASUREMENTS AND RESULTS: During the first 24 h of admission to the intensive care unit at least two blood samples were taken for d- and l-lactate measurements and arterial blood gases, Simultaneously, gastric PgCO(2) was measured using capnographic tonometry. The intramucosal-arterial PCO(2) gap was calculated using gastric intramucosal PgCO(2) and arterial PCO(2) from arterial blood. d-Lactate was significantly correlated to PgCO(2) values and to the mucosal-arterial PCO(2) gap. There was no relationship between l-lactate and PgCO(2) or the mucosal-arterial PCO(2) gap. d-lactate and l-lactate values were significantly correlated. CONCLUSIONS: During sepsis intestinal production of d-lactate is related to gastric intramucosal PCO(2). No such relationship was found between l-lactate values and PgCO(2)

Acid-Base Equilibrium↗
PubMed2003

Pulmonary glutamine production: effects of sepsis and pulmonary infiltrates.

OBJECTIVE: To define the role of the lung in the production of glutamine in the critically ill and to determine the effects of the presence of pulmonary infiltrates and the presence and severity of sepsis. DESIGN AND SETTING: Prospective clinical study in a single center; interdisciplinary intensive care unit at a university hospital. PATIENTS: Eleven critically ill patients were compared to ten patients prior to cardiac bypass surgery. MEASUREMENTS AND RESULTS: Fluxes of glutamine and other amino acids were measured. Chest radiography was performed, and APACHE II and multiple-organ failure scores were calculated. Septic patients showed significantly higher glutamine efflux from the lungs than controls. At least one-half of this glutamine is estimated to result from protein breakdown. Severity of illness had no impact on glutamine fluxes. In the presence of pulmonary infiltrates on chest radiographs glutamine efflux did not differ from zero. CONCLUSIONS: The lungs produce significant amounts of glutamine in septic patients. Pulmonary infiltrates decrease the glutamine efflux from the lung in septic patients. We suggest that this is caused by uptake of glutamine by white cells in the lung exerting immunological functions.

Adult↗
PubMed2003

All great truths are iconoclastic: selective decontamination of the digestive tract moves from heresy to level 1 truth.

OBJECTIVE: The objective was to compare evidence of the effectiveness, costs and safety of the traditional parenteral antibiotic-only approach against that gathered from 53 randomised trials involving more than 8,500 patients and six meta-analyses on selective decontamination of the digestive tract (SDD) to control infection on the intensive care unit (ICU). PHILOSOPHY: Traditionalists believe that all infections are due to breaches of hygiene except those established in the first 2 days, and that all micro-organisms can cause death. In contrast, newer insights show that transmission via the hands of carers are responsible only for infections occurring after one week, and that only a limited range of 15 potential pathogens contribute to mortality. INTERVENTIONS TO PREVENT ICU INFECTION: The traditional approach is based on hand disinfection aiming at the prevention of transmission of all micro-organisms, to control all infections that occur after 2 days on the ICU. The second feature is the restrictive use of systemic antibiotics, only in cases of microbiologically proven infection. In contrast, SDD aims to control the three types of infection: primary, secondary endogenous and exogenous due to 15 potential pathogens. The classical SDD tetralogy comprises four components: (i) a parenteral antibiotic, cefotaxime, administered for three days to prevent primary endogenous infections typically occurring "early"; (ii) the oropharyngeal and enteral antimicrobials, polymyxin E, tobramycin and amphotericin B administered in throat and gut throughout the treatment on the ICU to prevent secondary endogenous infections tending to develop "late"; (iii) a high standard of hygiene to control transmission of potential pathogens; and (iv) surveillance samples of throat and rectum to monitor the efficacy of the treatment. ENDPOINTS: (i) Infectious morbidity; (ii) mortality; (iii) antimicrobial resistance; and (iv) costs. RESULTS: Properly designed trials on hand disinfection have never demonstrated a reduction in either pneumonia and septicaemia, or mortality. Two randomised trials using restrictive antibiotic policies failed to show a survival benefit at 28 days. In both trials the proportion of resistant isolates obtained from the lower ways was >60% despite significantly less use of antibiotics in the test group. A formal cost effectiveness analysis of the traditional antibiotic policies has not been performed. On the other hand, two meta-analyses have shown that SDD reduces the odds ratio for lower airway infections to 0.35 (0.29-0.41) and mortality to 0.80 (0.69-0.93), with a 6% overall mortality reduction from 30% to 24%. No increase in the rate of super infections due to resistant bacteria could be demonstrated over a period of 20 years of clinical research. Four randomised trials found the cost per survivor to be substantially lower in patients receiving SDD than for those traditionally managed. CONCLUSIONS: The traditionalists still rely on level 5 evidence, i.e. expert opinion, with a grade E recommendation, whilst the proponents of SDD are able to cite level 1 evidence allowing a grade A recommendation in their attempts to control infection on the ICU. The main reason for SDD not being widely used is the primacy of opinion over evidence.

Anti-Bacterial Agents↗
PubMed2003

2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference.

OBJECTIVE: In 1991, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) convened a "Consensus Conference," the goals of which were to "provide a conceptual and a practical framework to define the systemic inflammatory response to infection, which is a progressive injurious process that falls under the generalized term 'sepsis' and includes sepsis-associated organ dysfunction as well. The general definitions introduced as a result of that conference have been widely used in practice, and have served as the foundation for inclusion criteria for numerous clinical trials of therapeutic interventions. Nevertheless, there has been an impetus from experts in the field to modify these definitions to reflect our current understanding of the pathophysiology of these syndromes. DESIGN: Several North American and European intensive care societies agreed to revisit the definitions for sepsis and related conditions. This conference was sponsored by the Society of Critical Care Medicine (SCCM), The European Society of Intensive Care Medicine (ESICM), The American College of Chest Physicians (ACCP), the American Thoracic Society (ATS), and the Surgical Infection Society (SIS). METHODS: 29 participants attended the conference from Europe and North America. In advance of the conference, subgroups were formed to evaluate the following areas: signs and symptoms of sepsis, cell markers, cytokines, microbiologic data, and coagulation parameters. The present manuscript serves as the final report of the 2001 International Sepsis Definitions Conference. CONCLUSION: 1. Current concepts of sepsis, severe sepsis and septic shock remain useful to clinicians and researchers. 2. These definitions do not allow precise staging or prognostication of the host response to infection. 3. While SIRS remains a useful concept, the diagnostic criteria for SIRS published in 1992 are overly sensitive and non-specific. 4. An expanded list of signs and symptoms of sepsis may better reflect the clinical response to infection. 6. PIRO, a hypothetical model for staging sepsis is presented, which, in the future, may better characterize the syndrome on the basis of predisposing factors and premorbid conditions, the nature of the underlying infection, the characteristics of the host response, and the extent of the resultant organ dysfunction.

Humans↗