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Purpose: Oral chlorhexidine is used widely for mechanically ventilated patients to prevent pneumonia, but recent studies show an association with excess mortality. We examined whether de-adoption of chlorhexidine and parallel implementation of a standardized oral care bundle reduces intensive care unit (ICU) mortality in mechanically ventilated patients. Methods: A stepped wedge cluster-randomized controlled trial with concurrent process evaluation in 6 ICUs in Toronto, Canada. Clusters were randomized to de-adopt chlorhexidine and implement a standardized oral care bundle at 2-month intervals. The primary outcome was ICU mortality. Secondary outcomes were time to infection-related ventilator-associated complications (IVACs), oral procedural pain and oral health dysfunction. An exploratory post hoc analysis examined time to extubation in survivors. Results: A total of 3260 patients were enrolled; 1560 control, 1700 intervention. ICU mortality for the intervention and control periods were 399 (23.5%) and 330 (21.2%), respectively (adjusted odds ratio [aOR], 1.13; 95% confidence interval [CI] 0.82 to 1.54; P = 0.46). Time to IVACs (adjusted hazard ratio [aHR], 1.06; 95% CI 0.44 to 2.57; P = 0.90), time to extubation (aHR 1.03; 95% CI 0.85 to 1.23; P = 0.79) (survivors) and oral procedural pain (aOR, 0.62; 95% CI 0.34 to 1.10; P = 0.10) were similar between control and intervention periods. However, oral health dysfunction scores (− 0.96; 95% CI − 1.75 to − 0.17; P = 0.02) improved in the intervention period. Conclusion: Among mechanically ventilated ICU patients, no benefit was observed for de-adoption of chlorhexidine and implementation of an oral care bundle on ICU mortality, IVACs, oral procedural pain, or time to extubation. The intervention may improve oral health. [ABSTRACT FROM AUTHOR]

Purpose: Some patients presenting with acute respiratory failure and meeting the Berlin criteria for acute respiratory distress syndrome (ARDS) lack exposure to common risk factors (CRF). These so-called ARDS mimickers often lack histological diffuse alveolar damage. We aimed to describe such ARDS mimickers lacking CRF (ARDS CRF-) in comparison with others (ARDS CRF+).Methods: Retrospective study including all patients receiving invasive mechanical ventilation for ARDS admitted to the intensive care units (ICUs) of two tertiary care centers from January 2003 to December 2012.Results: The prevalence of ARDS CRF- was 7.5 % (95 % CI [5.5-9.5]; n = 50/665). On the basis of medical history, bronchoalveolar lavage fluid cytology, and chest CT scan patterns, four etiological categories were identified: immune (n = 18; 36 %), drug-induced (n = 13; 26 %), malignant (n = 7; 14 %), and idiopathic (n = 12; 24 %). Although the ARDS CRF- patients had a lower logistic organ dysfunction score (4 [3-8] vs. 10 [6-13]; p < 0.0001) and less often shock upon ICU admission (44 vs. 80 %; p < 0.0001) than their counterparts, their overall ICU mortality rate was very high (66 % [46-74]), and the absence of CRF remained associated with ICU mortality by multivariable logistic regression analysis (adjusted OR = 2.06; 95 % CI [1.02-4.18]; p = 0.044). Among ARDS CRF- patients, the presence of potentially reversible lung lesions with corticosteroids (aOR = 0.14; 95 % CI [0.03-0.62]) was associated with ICU survival.Conclusions: The absence of CRF among patients with ARDS is common and associated with a higher risk of mortality. For such atypical ARDS, a complete diagnostic workup, including bronchoalveolar lavage fluid cytology and chest CT scan patterns, should be performed to identify those patients who might benefit from specific therapies, including corticosteroids. [ABSTRACT FROM AUTHOR]

Purpose: Our objective was to revise the definition of acute respiratory distress syndrome (ARDS) using a conceptual model incorporating reliability and validity, and a novel iterative approach with formal evaluation of the definition. Methods: The European Society of Intensive Care Medicine identified three chairs with broad expertise in ARDS who selected the participants and created the agenda. After 2 days of consensus discussions a draft definition was developed, which then underwent empiric evaluation followed by consensus revision. Results: The Berlin Definition of ARDS maintains a link to prior definitions with diagnostic criteria of timing, chest imaging, origin of edema, and hypoxemia. Patients may have ARDS if the onset is within 1 week of a known clinical insult or new/worsening respiratory symptoms. For the bilateral opacities on chest radiograph criterion, a reference set of chest radiographs has been developed to enhance inter-observer reliability. The pulmonary artery wedge pressure criterion for hydrostatic edema was removed, and illustrative vignettes were created to guide judgments about the primary cause of respiratory failure. If no risk factor for ARDS is apparent, however, objective evaluation (e.g., echocardiography) is required to help rule out hydrostatic edema. A minimum level of positive end-expiratory pressure and mutually exclusive PaO/FiO thresholds were chosen for the different levels of ARDS severity (mild, moderate, severe) to better categorize patients with different outcomes and potential responses to therapy. Conclusions: This panel addressed some of the limitations of the prior ARDS definition by incorporating current data, physiologic concepts, and clinical trials results to develop the Berlin definition, which should facilitate case recognition and better match treatment options to severity in both research trials and clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficiency, safety and outcome of high flow nasal cannula oxygen (HFNC) in ICU patients with acute respiratory failure. Methods: Pilot prospective monocentric study. Thirty-eight patients were included. Baseline demographic and clinical data, as well as respiratory variables at baseline and various times after HFNC initiation during 48 h, were recorded. Arterial blood gases were measured before and after the use of HFNC. Noise and discomfort were monitored along with outcome and need for invasive mechanical ventilation. Results: HFNC significantly reduced the respiratory rate, heart rate, dyspnea score, supraclavicular retraction and thoracoabdominal asynchrony, and increased pulse oxymetry. These improvements were observed as early as 15 min after the beginning of HFNC for respiratory rate and pulse oxymetry. PaO and PaO/FiO increased significantly after 1 h HFNC in comparison with baseline (141 ± 106 vs. 95 ± 40 mmHg, p = 0.009 and 169 ± 108 vs. 102 ± 23, p = 0.036; respectively). These improvements lasted throughout the study period. HFNC was used for a mean duration of 2.8 days and a maximum of 7 days. It was never interrupted for intolerance. No nosocomial pneumonia occurred during HFNC. Nine patients required secondary invasive mechanical ventilation. Absence of a significant decrease in the respiratory rate, lower oxygenation and persistence of thoracoabdominal asynchrony after HFNC initiation were early indicators of HFNC failure. Conclusions: HFNC has a beneficial effect on clinical signs and oxygenation in ICU patients with acute respiratory failure. These favorable results constitute a prerequisite to launching a randomized controlled study to investigate whether HFNC reduces intubation in these patients. [ABSTRACT FROM AUTHOR]

Traditionally, specific ventilators have been manufactured to only provide neonatal mechanical ventilation. However, many of the current generation of ICU ventilators also include a neonatal mode. Using the IngMar ASL5000 lung simulator the Puritan Bennett 840, the Maquet Servo i, the Viasys AVEA, the GE Engström, the Drager Evita XL and Babylog 8000 Plus were evaluated during assisted ventilation in the pressure assist/control mode. Three lung mechanics were set: resistance 50 cmH2O/L/s, compliance 2 mL/cmH2O; resistance 100 cmH2O/L/s, compliance 1 mL/cmH2O; and resistance 150 cmH2O/L/s, compliance 0.5 mL/cmH2O. A maximum negative pressure drop of 4 and 7 cmH2O was achieved during simulated inspirations. Each ventilator was evaluated with PEEP 5 cmH2O, peak pressure 20 cmH2O and inspiratory time 0.3 s and with PEEP 10 cmH2O, peak pressure 30 cmH2O and inspiratory time 0.4 s. Each ventilator setting was then repeated with a leak of 0.3 L/min at a constant pressure of 5 cmH2O. Overall each of the 5 ICU ventilators responded faster or greater than the Babylog with respect to: pressure to trigger (except the Servo i), time to trigger (except the Evita XL), time between trigger and return of pressure to baseline, time from start of breath to 90% of peak pressure (except the Avea) and pressure time product of breath activation. Expiratory tidal volume was also greater with all ICU ventilators except the Avea. Variation in mechanics, leak, PEEP and muscular effort had little effect on these differences. All ICU ventilators tested were able to at least equal the performance of the Babylog 8000 Plus on all variables evaluated. [ABSTRACT FROM AUTHOR]

Mechanically ventilated patients with status asthmaticus who undergo prolonged paralysis are at risk for severe weakness due to myopathy. In the mid-1990s, we changed our usual method of achieving tolerance of ventilatory support in asthmatic patients from continuous paralysis to deep sedation. This study examines the impact of this change in practice on the development of clinically significant weakness in status asthmaticus. Retrospective cohort study in university-affiliated county hospital. Mechanically ventilated asthmatic patients seen before ( n = 96) and after ( n = 74) a clinical practice change in 1995 that markedly restricted use of paralytics. The duration of neuromuscular paralysis declined sharply after 1995 (23.7 ± 42.2 vs. 1.8 ± 4.0 h, P < 0.001), but this was not associated with a significant difference in the incidence of weakness (21 vs. 14%, P = 0.23). Within the post-1995 cohort, there was no significant difference in the duration of paralysis for weak and non-weak patients (3.5 ± 6.2 vs. 1.5 ± 3.5 h, P = 0.10). However, weak patients had a much longer duration of mechanical ventilation than did patients without weakness (11.9 ± 3.6 vs. 1.9 ± 1.8 days, P < 0.001). Mechanically ventilated patients with status asthmaticus who are immobilized for prolonged periods of time by deep sedation remain at risk for clinically significant weakness. [ABSTRACT FROM AUTHOR]

Nebulized amikacin may be an attractive option for the treatment of lung infections. Low systemic absorption may permit the use of high doses, leading to high lung concentrations without systemic toxicity. We evaluated the pharmacokinetics and safety of an optimized high-dose amikacin nebulization technique. in vitro and in vivo pharmacokinetic study. Six healthy volunteers (age 21–30 years, weight 49–68 kg). The Aeroneb Pro nebulizer with an Idehaler vertical spacer was evaluated in a bench study. Amikacin was administered intravenously (15 mg/kg) and nebulized (40, 50, and 60 mg/kg) during noninvasive pressure-support ventilation through a mouthpiece. Median (interquartile range) in vitro inhaled fraction was 31% (30–32) and inhalable output was 681 mg/h (630–743). Serum concentrations after nebulization were less than or equal to those after infusion. The area under the serum concentration curve was significantly higher after infusion (138 mg h–1l–1, 122–143) than after nebulization (49 mg h–1l–1, 39–55, at 40 mg/kg; 63, 53–67 at 50; 66, 50–71, at 60). Peak serum concentration was also higher after infusion: 48 mg/l (45–49) after infusion compared to 8.2 (5.6–8.7), 9.2 (7.6–10.2), and 9.2 (5.2–10.3), respectively. Mean absorption times after nebulization were 2 h 24 min (2,07–2,45), 2 h 21 min (2,07–2,35), and 2 h 5 min (2,00–2,25), respectively. No side effect was observed. Nebulization of up to 60 mg/kg amikacin appears to be safe in healthy subjects and associated with lower serum concentrations than a 15 mg/kg infusion. [ABSTRACT FROM AUTHOR]

To avoid ventilator induced lung injury, tidal volume should be low in acute lung injury (ALI). Reducing dead space may be useful, for example by using a pattern of inspiration that prolongs the time available for gas distribution and diffusion within the respiratory zone, the mean distribution time (MDT). A study was conducted to investigate how MDT affects CO2 elimination in pigs at health and after ALI. Randomised crossover study in the animal laboratory of Lund University Biomedical Center. Healthy pigs and pigs with ALI, caused by surfactant perturbation and lung-damaging ventilation were ventilated with a computer-controlled ventilator. With this device each breath could be tailored with respect to insufflation time and pause time ( T I and T P) as well as flow shape (square, increasing or decreasing flow). The single-breath test for CO2 allowed analysis of the volume of expired CO2 and the volume of CO2 re-inspired from Y-piece and tubes. With a long MDT caused by long T I or T P, the expired volume of CO2 increased markedly in accordance with the MDT concept in both healthy and ALI pigs. High initial inspiratory flow caused by a short T I or decreasing flow increased the re-inspired volume of CO2. Arterial CO2 increased during a longer period of short MDT and decreased again when MDT was prolonged. CO2 elimination can be enhanced by a pattern of ventilation that prolongs MDT. Positive effects of prolonged MDT caused by short T I and decreasing flow were attenuated by high initial inspiratory flow. [ABSTRACT FROM AUTHOR]

Objective: To compare the effectiveness of open and closed endotracheal suction in recovering thin and thick secretions in normal and injured lungs during conventional and high frequency ventilation.Design and Setting: Randomised study in a paediatric intensive care model in the animal research laboratory of a tertiary paediatric hospital.Subjects: 16 New Zealand White rabbits.Interventions: Anaesthetised animals were intubated with a 3.5-mm endotracheal tube. Simulated thin and thick secretions (iopamidol 2 ml, a watery radio-opaque fluid, and fluorescent mucin 1 ml) were instilled in turn 1 cm below the tube tip through a catheter placed via a tracheostomy. Open or closed suction, randomly assigned, was applied for 6s at -140 mmHg using a 6-F gauge catheter. Following lung injury with repeated saline lavage the procedure was repeated on conventional and high frequency ventilation.Measurements and Results: Iopamidol recovery was determined by digitally subtracting the post-contrast and post-suction radiographic images. Mucin recovery was determined by fluorescence assay of the aspirate. In the normal lung similar amounts were recovered by both suction methods. In the lavaged lung closed suction recovered less iopamidol during conventional (22 +/- 7.5%) and high frequency ventilation (11 +/- 2.4%) than open suction (36 +/- 2% and 22 +/- 8.1%, respectively). Mucin recovery was less with closed suction during conventional 32 +/- 28 microl) and high frequency ventilation (30 +/- 31 microl) than with open suction (382 +/- 235 microl and 24 +/- 153 microl).Conclusions: In the injured lung closed suction was less effective than open suction at recovering thin and thick simulated secretions, irrespective of ventilation mode. [ABSTRACT FROM AUTHOR]

Objective: Invasive aspergillosis is associated with a poor prognosis, especially in critically ill patients with cerebral involvement. We present two cases of cerebral invasive aspergillosis successfully treated in the intensive care unit with combination antifungal therapies and without surgery.Case Presentation: The first patient was a 49-year-old man with rheumatoid arthritis who received corticosteroid and cyclophosphamide treatment and developed pulmonary and cerebral invasive aspergillosis. After failure of voriconazole the patient had a successful outcome with voriconazole and liposomal amphotericin B therapy. The patient returned home after an 8-month hospital stay. The second patient was a 54-year-old woman with pulmonary neoplasia and corticosteroid treatment who developed pulmonary and cerebral invasive aspergillosis. After failure of voriconazole and liposomal amphotericin B therapy the patient had a favorable outcome with liposomal amphotericin B and caspofungin therapy. The patient died 10 months after initial diagnosis of cardiac tamponade unrelated to fungal infection.Discussions: These cases illustrate the improving prognosis of invasive aspergillosis due to the availability of new treatments, especially in cases of cerebral involvement. It also demonstrates that the outcome of critically ill patients requiring mechanical ventilation for invasive aspergillosis can be favorable. The treatment of patients with invasive cerebral aspergillosis in the intensive care setting should be encouraged. [ABSTRACT FROM AUTHOR]

Objective: Use of lung-protective mechanical ventilation (MV) by applying lower tidal volumes is recommended in patients suffering from acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Recent data suggest that lung-protective MV may benefit non-ALI/ARDS patients as well. This study analyzed tidal volume settings in three ICUs in The Netherlands to determine the effect of feedback and education concerning use of lung-protective MV.Design and Setting: Observational study in one academic and two nonacademic "closed format" ICUs.Patients: Intubated mechanically ventilated subjects.Interventions: Feedback and education concerning lung-protective MV with special attention to the importance of closely adjusting tidal volumes to predicted body weight (PBW).Results: Tidal volumes declined significantly within 6 months after intervention (from 9.8+/-2.0 at baseline to 8.1+/-1.7 ml/kg PBW) as the percentage of undesirable ventilation data points, defined as tidal volumes greater than 8 ml/kg PBW (84% vs. 48%). There were no differences between patients meeting the international definition criteria for ALI/ARDS and those not. Only four patients received tidal volumes less than 6 ml/kg PBW. Lower tidal volumes were still used after 12 months. Tidal volumes in patients on mandatory MV and patients breathing on spontaneous modes were similar.Conclusions: Feedback and education improve physician compliance in use of lung-protective MV. [ABSTRACT FROM AUTHOR]

Objective: Measurements from the pulmonary pressure-volume (PV) curve have been proposed to adjust ventilator settings. We investigated the effects of repeated construction of an inflation PV curve implemented in a standard ventilator on recruitment or derecruitment in acutely injured lungs.Design and Setting: Prospective experimental animal study in eight anesthetized and mechanically ventilated pigs.Interventions: Acute lung injury was induced by lung lavage and animals were ventilated in volume controlled mode with PEEP 10 cmH(2)O. The PV curve was constructed five times repeatedly by constant pressure rise, after which ventilation with the preset PEEP was resumed immediately. Studies of hemodynamics, lung mechanics, blood gases and computed tomography were carried out before and after maneuvers.Measurements and Results: Derecruitment was assessed as an increase in nonaerated lung volume (V(NON)), and V(PEEP) was the end-expiratory volume difference between PEEP and ZEEP. There was a significant decrease in PaO(2) from 90.4+/-33.3 to 70.9+/-36.3 mmHg and a rise in venous admixture from 47.8+/-12.7 to 59.1+/-16.6%. V(PEEP) was reduced from 244 to 202 ml. A corresponding decrease in normally aerated lung volume was observed, while regression analysis revealed increase in V(NON) depending on the amount of preexisting atelectasis.Conclusions: Repeated generation of the PV curve with a readily available tool resulted in worsened oxygenation. Derecruitment of the lungs occurred with loss of PEEP at the start of the maneuver, which could not be recovered by a maximum inflation pressure of 40 cmH(2)O. Repeated use of the investigated tool should be cautioned, and users should consider measures to preserve aerated lung volumes. [ABSTRACT FROM AUTHOR]

Objective: Earlier reports suggested that transthoracic (TTE) determination of the ratio of mitral inflow E wave velocity to early diastolic mitral annulus velocity (E/E') measured by tissue Doppler imaging (TDI) closely approximates PAOP in cardiac patients. However, the value of E/E' for PAOP assessment in ICU patients has not been evaluated. This study assessed whether the E/E' ratio provides an accurate estimation of pulmonary artery occlusion pressure (PAOP) in mechanically ventilated ICU patients.Design and Setting: Prospective, open, clinical study in the ICU of a university hospital.Patients: Twenty-three consecutive mechanically ventilated patients.Interventions: Volume expansion in 14 patients.Measurements and Results: Doppler TTE or TEE mitral inflow and TDI mitral annulus velocities were determined and compared with PAOP measured using a Swan-Ganz catheter. Of all the Doppler variables studied the best correlations were observed between PAOP and the lateral (r=0.84) and medial (r=0.76) annulus E/E' ratio and remained highly significant when the analysis was restricted to TEE (r=0.91 and 0.86) or TTE (r=0.73 and 0.61). The sensitivities and specificities of estimating PAOP at 15 mmHg or higher were, respectively, 86% and 81% for lateral E/E' above 7.5 and 76% and 80% for medial E/E' above 9. PAOP changes after volume expansion (700+/-230 ml) were limited and accurately assessed by repeated E/E' determinations.Conclusions: In mechanically ventilated ICU patients TTE or TEE E/E' determinations using TDI closely approximate PAOP. [ABSTRACT FROM AUTHOR]

Objective: Inhalation of perfluorocarbons (PFC) has been suggested as a new and promising technique of PFC delivery in animal models of severe lung injury. However, no in vitro data were available on the efficacy of PFC aerosolization during mechanical ventilation. Therefore, the aim of the in vitro study was to investigate the influence of physical properties of PFC and the ventilatory settings on the amount of PFC delivered into the lung.Design: In vitro lung model study.Setting: University research laboratory.Measurements and Results: Two different PFC (PF 5080 and PFOB) were aerosolized with a PariBoy jet nebulizer. Using a PFC selective adsorber, the effect of endotracheal tube size (2 mm and 3 mm diameter) on delivery of PFC was investigated. PFC delivery was estimated by continuous measurement of weight gain of the adsorber (adsorption rate). Finally, the influence of respiratory rate and tidal volume on adsorption rate (AR) was studied. AR was significantly reduced by a decreasing tube diameter and ranged from 1.45+/-0.03 ml/min (no tube) to 0.93+/-0.03 ml/min (2.0 mm) for PF 5080 (vapor pressure 51 mmHg) and from 0.49+/-0.06 ml/min to 0.32+/-0.04 ml/min for PFOB (11 mmHg). PFC-aerosolization into a ventilatory circuit with simulation of spontaneous tidal breathing (minute volume 600 ml) reduced AR to 0.16+/-0.02 ml/min. During mechanical ventilation, changes in respiratory rate and tidal volume, which reduce minute ventilation, caused a decrease in AR.Conclusion: The amount of PFC that can be delivered into the lung by aerosolization is very small and is influenced by PFC properties, tube size, and ventilatory settings. [ABSTRACT FROM AUTHOR]