Double-heater-wire circuits and heat-and-moisture exchangers and the risk of ventilator-associated pneumonia

Objective: To compare the incidence of ventilator-associated pneumonia (VAP) in patients ventilated in intensive care by means of circuits humidified with a hygroscopic heat-and-moisture exchanger with a bacterial viral filter (HME) or hot-water humidification with a heater wire in both inspiratory and expiratory circuit limbs (DHW) or the inspiratory limb only (SHW). Design: A prospective, randomized trial. Setting: A metropolitan teaching hospital's general intensive care unit. Patients: Three hundred eighty-one patients requiring a minimum period of mechanical ventilation of 48 hrs. Interventions: Patients were randomized to humidification with use of an HME (n = 190), SHW (n = 94), or DHW (n = 97). Measurements and Main Results. Study end points were VAP diagnosed on the basis of Clinical Pulmonary Infection Score (CPIS) (1), HME resistance after 24 hrs of use, endotracheal tube resistance, and HME use per patient. VAP occurred with similar frequency in all groups (13%, HME; 14%, DHW; 10%, SHW; p = 0.61) and was predicted only by current smoking (adjusted odds ratio [AOR], 2.1; 95% confidence interval [CI], 1.1-3.9; p =.03) and ventilation days (AOR, 1.05; 95% Cl, 1.0-1.2; p =.001); VAP was less likely for patients with an admission diagnosis of pneumonia (AOR, 0.40; 95% Cl, 0.4-0.2; p =.04). HME resistance after 24 hrs of use measured at a gas flow of 50 L/min was 0.9 cm H2O (0.4-2.9). Endotracheal tube resistance was similar for all three groups (16-19 cm H2O min/L; p =.2), as were suction frequency, secretion thickness, and blood on suctioning (p =.32, p =.06, and p =.34, respectively). The HME use per patient per day was 1.13. Conclusions: Humidification technique does not influence either VAP incidence or secretion characteristics, but HMEs may have air-flow resistance higher than manufacturer specifications after 24 hrs of use.

Disease risk and mortality prediction in intensive care patients with pneumonia. Australian and New Zealand practice in intensive care (ANZPIC II)

This study of ventilated patients investigated pneumonia risk factors and outcome predictors in 476 episodes of pneumonia (48% community-acquired pneumonia, 24% hospital-acquired pneumonia, 28% ventilator-associated pneumonia) using a prospective survey in 14 intensive care units within Australia and New Zealand. For community acquired pneumonia, mortality increased with immunosuppression (OR 5.32, CI 95% 1.58-17.99, P < 0. 01), clinical signs of consolidation (OR 2.43, CI 95% 1.09-5.44, P = 0. 03) and Sepsis-Related Organ Failure Assessment (SOFA) scores (OR 1.19, CI 95% 1.08-1.30, P < 0. 001) but improved if appropriate antibiotic changes were made within three days of intensive care unit admission (OR 0.42, CI 95% 0.20-0.86, P = 0.02). For hospital-acquired pneumonia, immunosuppression (OR 6.98, CI 95% 1.16-42.2, P = 0.03) and non-metastatic cancer (OR 3.78, CI 95% 1.20-11.93, P = 0.02) were the principal mortality predictors. Alcoholism (OR 7.80, CI 95% 1.20-1750, P < 0.001), high SOFA scores (OR 1.44, CI 95% 1.20-1.75, P = 0.001) and the isolation of high risk organisms including Pseudomonas aeruginosa, Acinetobacter spp, Stenotrophomonas spp and methicillin resistant Staphylococcus aureus (OR 4.79, CI 95% 1.43-16.03, P = 0.01), were associated with increased mortality in ventilator-associated pneumonia. The use of non-invasive ventilation was independently protective against mortality for patients with community-acquired and hospital-acquired pneumonia (OR 0.35, CI 95% 0.18-0.68, P = 0.002). Mortality was similar for patients requiting both invasive and non-invasive ventilation and non-invasive ventilation alone (21% compared with 20% respectively, P = 0.56). Pneumonia risks and mortality predictors in Australian and New Zealand ICUs vary with pneumonia type. A history of alcoholism is a major risk factor for mortality in ventilator-associated pneumonia, greater in magnitude than the mortality effect of immunosuppression in hospital-acquired pneumonia or community-acquired pneumonia. Non-invasive ventilation is associated with reduced ICU mortality. Clinical signs of consolidation worsen, while rationalising antibiotic therapy within three days of ICU admission improves mortality for community-acquired pneumonia patients.

Australian and New Zealand practice in intensive care (ANZPIC II: The spectrum of practice in the diagnosis and management of pneumonia in patients requiring mechanical ventilation

This study of ventilated patients investigated current clinical practice in 476 episodes of pneumonia (48% community-acquired pneumonia, 24% hospital-acquired pneumonia, 28% ventilator-associated pneumonia) using a prospective survey in 14 intensive care units (ICUs) within Australia and New Zealand. Diagnostic methods and confidence, disease severity, microbiology and antibiotic use were assessed. All pneumonia types had similar mortality (community-acquired pneumonia 33%, hospital-acquired pneumonia 37% and ventilator-associated pneumonia 24%, P = 0.15) with no inter-hospital differences (P = 0.08-0.91). Bronchoscopy was performed in 26%, its use predicted by admission hospital (one tertiary: OR 9.98, CI 95% 5.11-19.49, P < 0.001; one regional: OR 629, CI 95% 3.24-12.20, P < 0.001), clinical signs of consolidation (OR 3.72, CI 95% 2.09-662, P < 0.001) and diagnostic confidence (OR 2.19, CI 95% 1.29-3.72, P = 0.004). Bronchoscopy did not predict outcome (P = 0.11) or appropriate antibiotic selection (P = 0.69). Inappropriate antibiotic prescription was similar for all pneumonia types (11-13%, P = 0.12) and hospitals (0-16%, P = 0.25). Blood cultures were taken in 51% of cases. For community-acquired pneumonia, 70% received a third generation cephalosporin and 65% a macrolide. Third generation cephalosporins were less frequently used for mild infections (OR 0.38, CI 95% 0.16-0.90, P = 0.03), hospital-acquired pneumonia (OR 0.40, CI 95% 0.23-0.72, P < 0.01), ventilator-associated pneumonia (OR 0.04, CI 95% 0.02-0.13, P < 0.001), suspected aspiration (OR 0.20, CI 95% 0.04-0.92, P = 0.04), in one regional (OR 0.26, CI 95% 0.07-0.97, P = 0.05) and one tertiary hospital (OR 0.14, CI 95% 0.03-0.73, P = 0.02) but were more commonly used in older patients (OR 1.02, CI 95% 1.01-1.03, P = 0.01). There is practice variability in bronchoscopy and antibiotic use for pneumonia in Australian and New Zealand ICUs without significant impact on patient outcome, as the prevalence of inappropriate antibiotic prescription is low. There are opportunities for improving microbiological diagnostic work-up for isolation of aetiological pathogens.

Antibiotic resistance in the intensive care unit: A primer in bacteriology

The clinical use of potent, well-tolerated, broad-spectrum antibiotics has been paralleled by the development of resistance in bacteria, and the prevalence of highly resistant bacteria in some intensive care units is despairingly commonplace. The intensive care community faces the realistic prospect of untreatable nosocomial infections and should be searching for new approaches to diagnose and manage resistant bacteria. In this review, we discuss some of the relevant underlying biology, with a particular focus on genetic transfer vehicles and the relationship of selection pressure to their movements. It is an attempt to demystify the relevant language and concepts for the anaesthetist and intensivist, to explain some of the reasons for the emergence of resistance in bacteria, and to provide a contextual basis for discussion of management approaches such as selective decontamination and antibiotic cycling.

Antibacterial dosing in intensive care: Pharmacokinetics, degree of disease and pharmacodynamics of sepsis

Treatment of sepsis remains a significant challenge with persisting high mortality and morbidity. Early and appropriate antibacterial therapy remains an important intervention for such patients. To optimise antibacterial therapy, the clinician must possess knowledge of the pharmacokinetic and pharmacodynamic properties of commonly used antibacterials and how these parameters may be affected by the constellation of pathophysiological changes occurring during sepsis. Sepsis, and the treatment thereof, increases renal preload and, via capillary permeability, leads to 'third-spacing', both resulting in higher antibacterial clearances. Alternatively, sepsis can induce multiple organ dysfunction, including renal and/or hepatic dysfunction, causing a decrease in antibacterial clearance. Aminoglycosides are concentration-dependent antibacterials and they display an increased volume of distribution (V-d) in sepsis, resulting in decreased peak serum concentrations. Reduced clearance from renal dysfunction would increase the likelihood of toxicity. Individualised dosing using extended interval dosing, which maximises the peak serum drug concentration (C-max)/minimum inhibitory concentration ratio is recommended. beta-Lactams and carbapenems are time-dependent antibacterials. An increase in Vd and renal clearance will require increased dosing or administration by continuous infusion. If renal impairment occurs a corresponding dose reduction may be required. Vancomycin displays predominantly time-dependent pharmacodynamic properties and probably requires higher than conventionally recommended doses because of an increased V-d and clearance during sepsis without organ dysfunction. However, optimal dosing regimens remain unresolved. The poor penetration of vancomycin into solid organs may require alternative therapies when sepsis involves solid organs (e.g. lung). Ciprofloxacin displays largely concentration-dependent kill characteristics, but also exerts some time-dependent effects. The V-d of ciprofloxacin is not altered with fluid shifts or over time, and thus no alterations of standard doses are required unless renal dysfunction occurs. In order to optimise antibacterial regimens in patients with sepsis, the pathophysiological effects of systemic inflammatory response syndrome need consideration, in conjunction with knowledge of the different kill characteristics of the various antibacterial classes. In conclusion, certain antibacterials can have a very high V-d, therefore leading to a low C-max and if a high peak is needed, then this would lead to underdosing. The Vd of certain antibacterials, namely aminoglycosides and vancomycin, changes over time, which means dosing may need to be altered over time. Some patients with serum creatinine values within the normal range can have very high drug clearances, thereby producing low serum drug levels and again leading to underdosing. Copyright © 2010 Elsevier Inc. All rights reserved.

Australian and New Zealand practice in intensive care (ANZPIC II): Predictors of physician confidence to diagnose pneumonia and determine illness severity in ventilated patients

The manner in which elements of clinical history, physical examination and investigations influence subjectively assessed illness severity and outcome prediction is poorly understood. This study investigates the relationship between clinician and objectively assessed illness severity and the factors influencing clinician's diagnostic confidence and illness severity rating for ventilated patients with suspected pneumonia in the intensive care unit (ICU). A prospective study of fourteen ICUs included all ventilated admissions with a clinical diagnosis of pneumonia. Data collection included pneumonia type - community-acquired (CAP), hospital-acquired (HAP) and ventilator-associated (VAP), clinician determined illness severity (CDIS), diagnostic methods, clinical diagnostic confidence (CDC), microbiological isolates and antibiotic use. For 476 episodes of pneumonia (48% CAP, 24% HAP, 28% VAP), CDC was greatest for CAP (64% CAP, 50% HAP and 49% VAP, P < 0.01) or when pneumonia was considered life-threatening (84% high CDC, 13% medium CDC and 3% low CDC, P < 0.001). Life-threatening pneumonia was predicted by worsening gas exchange (OR 4.8, CI 95% 2.3-10.2, P < 0.001), clinical signs of consolidation (OR 2.0, CI 95% 1.2-3.2, P < 0.01) and the Sepsis-Related Organ Failure Assessment (SOFA) Score (OR 1.1, CI 95% 1.1-1.2, P < 0.001). Diagnostic confidence increased with CDIS (OR 163, CI 95% 8.4-31.4, P < 0.001), definite pathogen isolation (OR 3.3, CI 95% 2.0-5.6) and clinical signs of consolidation (OR 2.1, CI 95% 1.3-3.3, P = 0.001). Although the CDIS, SOFA Score and the Simplified Acute Physiologic Score (SAPS II) were all associated with mortality, the SAPS II Score was the best predictor of mortality (P = 0.02). Diagnostic confidence for pneumonia is moderate but increases with more classical presentations. A small set of clinical parameters influence subjective assessment. Objective assessment using SAPS II Scoring is a better predictor of mortality.

Low mannose-binding lectin function is associated with sepsis in adult patients

Mannose-binding lectin (MBL) is an innate immune system pattern recognition molecule that kills a wide range of pathogens via the lectin complement pathway. MBL deficiency is associated with severe infection but the best measure of this deficiency is undecided. We investigated the influence of MBL functional deficiency on the development of sepsis in 195 adult patients, 166 of whom had bloodstream infection and 35 had pneumonia. Results were compared with 236 blood donor controls. MBL function (C4b deposition) and levels were measured by enzyme-linked immunosorbent assay. Using receiver-operator characteristics of MBL function in healthy controls, we identified a level of < 0.2 U mu L-1 as a highly discriminative marker of low MBL2 genotypes. Median MBL function was lower in sepsis patients (0.18 U mu L-1) than in controls (0.48 U mu L-1, P < 0.001). MBL functional deficiency was more common in sepsis patients than controls (P < 0.001). MBL functional deficient patients had significantly higher sequential organ failure assessment (SOFA) scores and higher MBL function and levels were found in patients with SOFA scores predictive of good outcome. Deficiency of MBL function appears to be associated with bloodstream infection and the development of septic shock. High MBL levels may be protective against severe sepsis. © 2006 Federation of European Microbiological Societies Published by Blackwell Publishing Ltd. All rights reserved.