Frederique Paulus

Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized controlled trial

IntroductionRecent cohort studies have identified the use of large tidal volumes as a major risk factor for development of lung injury in mechanically ventilated patients without acute lung injury (ALI). We compared the effect of conventional with lower tidal volumes on pulmonary inflammation and development of lung injury in critically ill patients without ALI at the onset of mechanical ventilation.MethodsWe performed a randomized controlled nonblinded preventive trial comparing mechanical ventilation with tidal volumes of 10 ml versus 6 ml per kilogram of predicted body weight in critically ill patients without ALI at the onset of mechanical ventilation. The primary end point was cytokine levels in bronchoalveolar lavage fluid and plasma during mechanical ventilation. The secondary end point was the development of lung injury, as determined by consensus criteria for ALI, duration of mechanical ventilation, and mortality.ResultsOne hundred fifty patients (74 conventional versus 76 lower tidal volume) were enrolled and analyzed. No differences were observed in lavage fluid cytokine levels at baseline between the randomization groups. Plasma interleukin-6 (IL-6) levels decreased significantly more strongly in the lower-tidal-volume group ((from 51 (20 to 182) ng/ml to 11 (5 to 20) ng/ml versus 50 (21 to 122) ng/ml to 21 (20 to 77) ng/ml; P = 0.01)). The trial was stopped prematurely for safety reasons because the development of lung injury was higher in the conventional tidal-volume group as compared with the lower tidal-volume group (13.5% versus 2.6%; P = 0.01). Univariate analysis showed statistical relations between baseline lung-injury score, randomization group, level of positive end-expiratory pressure (PEEP), the number of transfused blood products, the presence of a risk factor for ALI, and baseline IL-6 lavage fluid levels and the development of lung injury. Multivariate analysis revealed the randomization group and the level of PEEP as independent predictors of the development of lung injury.ConclusionsMechanical ventilation with conventional tidal volumes is associated with sustained cytokine production, as measured in plasma. Our data suggest that mechanical ventilation with conventional tidal volumes contributes to the development of lung injury in patients without ALI at the onset of mechanical ventilation.Trial registrationISRCTN82533884

The incidence, risk factors and outcome of transfusion-related acute lung injury in a cohort of cardiac surgery patients: a prospective nested case control study

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality. Both antibodies and bioactive lipids that have accumulated during storage of blood have been implicated in TRALI pathogenesis. In a single-center, nested, case-control study, patients were prospectively observed for onset of TRALI according to the consensus definition. Of 668 patients, 16 patients (2.4%) developed TRALI. Patient-related risk factors for onset of TRALI were age and time on the cardiopulmonary bypass. Transfusion-related risk factors were total amount of blood products (odds ratio [OR] = 1.2; 95% confidence interval [CI], 1.03-1.44), number of red blood cells stored more than 14 days (OR = 1.6; 95% CI, 1.04-2.37), total amount of plasma (OR = 1.2; 95% CI, 1.03-1.44), presence of antibodies in donor plasma (OR = 8.8; 95% CI, 1.8-44), and total amount of transfused bioactive lipids (OR = 1.0; 95% CI, 1.00-1.07). When adjusted for patient risk factors, only the presence of antibodies in the associated blood products remained a risk factor for TRALI (OR = 14.2; 95% CI, 1.5-132). In-hospital mortality of TRALI was 13% compared with 0% and 3% in transfused and nontransfused patients, respectively (P < .05). In conclusion, the incidence of TRALI is high in cardiac surgery patients and associated with adverse outcome. Our results suggest that cardiac surgery patients may benefit from exclusion of blood products containing HLA/HNA antibodies.

Medical-Grade Honey Kills Antibiotic-Resistant Bacteria In Vitro and Eradicates Skin Colonization

BACKGROUND Antibiotic resistance among microbes urgently necessitates the development of novel antimicrobial agents. Since ancient times, honey has been used successfully for treatment of infected wounds, because of its antibacterial activity. However, large variations in the in vitro antibacterial activity of various honeys have been reported and hamper its acceptance in modern medicine. METHODS We assessed the in vitro bactericidal activity of Revamil (Bfactory), a medical-grade honey produced under controlled conditions, and assessed its efficacy for reduction of forearm skin colonization in healthy volunteers in a within-subject-controlled trial. RESULTS With Bacillus subtilis as a test strain, we demonstrated that the variation in bactericidal activity of 11 batches of medical-grade honey was <2-fold. Antibiotic-susceptible and -resistant isolates of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecium, Escherichia coli, Pseudomonas aeruginosa, Enterobacter cloacae, and Klebsiella oxytoca were killed within 24 h by 10%-40% (vol/vol) honey. After 2 days of application of honey, the extent of forearm skin colonization in healthy volunteers was reduced 100-fold (P < .001), and the numbers of positive skin cultures were reduced by 76% (P < .001). CONCLUSIONS Revamil is a promising topical antimicrobial agent for prevention or treatment of infections, including those caused by multidrug-resistant bacteria.

Transfusion-related acute lung injury in cardiac surgery patients is characterized by pulmonary inflammation and coagulopathy: a prospective nested case-control study.

Objective: Transfusion-related acute lung injury is the leading cause of transfusion-related morbidity and mortality. Clinical data on the pathogenesis of transfusion-related acute lung injury are sparse. The objective of the present study was to determine inflammation and coagulation pathways involved in the onset of transfusion-related acute lung injury. Design: Nested case-control study. Setting: Operating theatre and intensive care department of a tertiary referral hospital. Patients: Elective cardiac surgery patients requiring postsurgery intensive care admission. Interventions: None. Measurements: Cardiac surgery patients (n = 668) were prospectively screened for the onset of transfusion-related acute lung injury. Transfusion-related acute lung injury cases (n = 16) were randomly assigned to transfused and nontransfused cardiac surgery controls in a 1:2 ratio. Blood samples were taken pre- and postoperatively and at onset of transfusion-related acute lung injury. In addition, at onset of transfusion-related acute lung injury, bronchoalveolar lavage fluid was obtained. In plasma and bronchoalveolar lavage fluid, levels of interleukin-6, interleukin-8, elastase-&agr;(1)-antitrypsin complexes, thrombin–antithrombin complexes, plasminogen activator activity, and plasminogen activator inhibitor-1 were determined by means of enzyme-linked immunosorbent assay. Main Results: In all patients, cardiac surgery was associated with systemic inflammation, evidenced by an increase in plasma levels of interleukin-6, interleukin-8, and elastase-&agr;(1)-antitrypsin complexes compared with presurgery levels (p < .001). Prior to onset of transfusion-related acute lung injury, systemic interleukin-8 and interleukin-6 levels were higher compared with nontransfused controls (p < .01). In transfusion-related acute lung injury cases, bronchoalveolar lavage fluid levels of interleukin-8, interleukin-6, and elastase-&agr;(1)-antitrypsin complexes were elevated compared with control groups (p < .05). Both plasma and bronchoalveolar lavage fluid levels of thrombin–antithrombin complexes were enhanced in transfusion-related acute lung injury cases compared with control groups (p < .01). Bronchoalveolar lavage fluid levels of plasminogen activator activity were decreased due to an increase in plasminogen activator inhibitor-1 levels in transfusion-related acute lung injury cases compared with control groups (p < .01), indicating suppressed fibrinolysis. Conclusions: Prior to onset of transfusion-related acute lung injury, there is systemic inflammation and neutrophil sequestration. Transfusion-related acute lung injury is characterized by both systemic and pulmonary inflammation and activation of neutrophils, as well as enhanced coagulation and suppressed fibrinolysis.

Benefits and risks of manual hyperinflation in intubated and mechanically ventilated intensive care unit patients: a systematic review

IntroductionManual hyperinflation (MH), a frequently applied maneuver in critically ill intubated and mechanically ventilated patients, is suggested to mimic a cough so that airway secretions are mobilized toward the larger airways, where they can easily be removed. As such, MH could prevent plugging of the airways.MethodsWe performed a search in the databases of Medline, Embase, and the Cochrane Library from January 1990 to April 2012. We systematically reviewed the literature on evidence for postulated benefits and risks of MH in critically ill intubated and mechanically ventilated patients.ResultsThe search identified 50 articles, of which 19 were considered relevant. We included 13 interventional studies and six observational studies. The number of studies evaluating physiological effects of MH is limited. Trials differed too much to permit meta-analysis. It is uncertain whether MH was applied similarly in the retrieved studies. Finally, most studies are underpowered to show clinical benefit of MH. Use of MH is associated with short-term improvements in lung compliance, oxygenation, and secretion clearance, without changes in outcomes. MH has been reported to be associated with short-term and probably clinically insignificant side effects, including decreases in cardiac output, alterations of heart rates, and increased central venous pressures.ConclusionsStudies have failed to show that MH benefits critically ill intubated and mechanically ventilated patients. MH is infrequently associated with short-term side effects.

Adaptive support ventilation with protocolized de-escalation and escalation does not accelerate tracheal extubation of patients after nonfast-track cardiothoracic surgery.

BACKGROUND:It is uncertain whether adaptive support ventilation (ASV) accelerates weaning of nonfast-track cardiothoracic surgery patients. A lower operator set %-minute ventilation with ASV may allow for an earlier definite switch from controlled to assisted ventilation, potentially hastening tracheal extubation. We hypothesized that ASV using protocolized de-escalation and escalation of operator set %-minute ventilation (ASV-DE) reduces time until tracheal extubation compared with ASV using a fixed operator set %-minute ventilation (standard ASV) in uncomplicated patients after nonfast-track coronary artery bypass graft. METHODS:We performed a randomized controlled trial comparing ASV-DE with standard ASV. With ASV-DE, as soon as body temperature was >35.0°C with pH >7.25, operator set %-minute ventilation was decreased stepwise to a minimum of 70%. RESULTS:Sixty-three patients were randomized to ASV-DE, and 63 patients to standard ASV. The duration of mechanical ventilation was not different between groups (10.8 [6.5–16.1] vs 10.7 [6.6–13.9] hours, ASV-DE versus standard ASV; P = 0.32). Time until the first assisted breathing period was shorter (3.1 [2.0–6.7] vs 3.9 [2.1–7.5] hours) and the number of assisted ventilation episodes was higher (78 [34–176] vs 57 [32–116] episodes), but differences did not reach statistical significance. The duration of assisted ventilation episodes that ended with tracheal extubation was different between groups (2.5 [0.9–4.6] vs 1.4 [0.3–3.5] hours, ASV-DE versus standard ASV; P < 0.05). CONCLUSION:Compared with standard ASV, weaning of patients after nonfast-track coronary artery bypass graft using ASV with protocolized de-escalation and escalation does not shorten time to tracheal extubation.

Manual hyperinflation of intubated and mechanically ventilated patients in Dutch intensive care units—A survey into current practice and knowledge

BACKGROUND In the daily bedside routine of the intensive care, potentially hazardous interventions that lack evidence need critical consideration. Therefore we examined current practice and knowledge of basic principles of manual hyperinflation (MH) in intubated and mechanically ventilated patients among intensive care unit nurses in the Netherlands. METHODS A written survey method was used, questionnaires were sent to ICU nurses specialised in mechanical ventilation in 115 Dutch hospitals. The questions related to following domains: (1) demographics; (2) use of MH; (3) presumed benefits; (4) essential elements of the MH procedure; (5) equipment and safety. RESULTS The response rate was 77%. From responding ICUs the majority (96%) stated they performed MH; 27% as a daily routine procedure, 69% performed MH on indication only. MH was mainly performed by ICU nurses. Half of ICUs reported to have a MH guideline available. Improved oxygenation and better removal of sputum were presumed benefits of MH. While slow inspiration and rapid expiration are considered to be essential elements of MH procedures, the majority of respondents stated to use rapid inspiration and slow expiration. CONCLUSIONS This survey indicates that MH is widely used as an important item of airway management. Importantly, there is no uniformity in the performance of the procedure. Before definitive research can be developed, standards for the MH procedure should be established.

Adaptive Support Ventilation May Deliver Unwanted Respiratory Rate–Tidal Volume Combinations in Patients with Acute Lung Injury Ventilated According to an Open Lung Concept

BACKGROUND With adaptive support ventilation, respiratory rate and tidal volume (V(T)) are a function of the Otis least work of breathing formula. We hypothesized that adaptive support ventilation in an open lung ventilator strategy would deliver higher V(T)s to patients with acute lung injury. METHODS Patients with acute lung injury were ventilated according to a local guideline advising the use of lower V(T) (6-8 ml/kg predicted body weight), high concentrations of positive end-expiratory pressure, and recruitment maneuvers. Ventilation parameters were recorded when the ventilator was switched to adaptive support ventilation, and after recruitment maneuvers. If V(T) increased more than 8 ml/kg predicted body weight, airway pressure was limited to correct for the rise of V(T). RESULTS Ten patients with a mean (±SD) Pao(2)/Fio(2) of 171 ± 86 mmHg were included. After a switch from pressure-controlled ventilation to adaptive support ventilation, respiratory rate declined (from 31 ± 5 to 21 ± 6 breaths/min; difference = 10 breaths/min, 95% CI 3-17 breaths/min, P = 0.008) and V(T) increased (from 6.5 ± 0.8 to 9.0 ± 1.6 ml/kg predicted body weight; difference = 2.5 ml, 95% CI 0.4-4.6 ml/kg predicted body weight, P = 0.02). Pressure limitation corrected for the rise of V(T), but minute ventilation declined, forcing the user to switch back to pressure-controlled ventilation. CONCLUSIONS Adaptive support ventilation, compared with pressure-controlled ventilation in an open lung strategy setting, delivers a lower respiratory rate-higher V(T) combination. Pressure limitation does correct for the rise of V(T), but leads to a decline in minute ventilation.

Adaptive support ventilation: A translational study evaluating the size of delivered tidal volumes

Purpose Adaptive support ventilation (ASV) is a microprocessor-controlled, closed-loop mode of mechanical ventilation that adapts respiratory rates and tidal volumes (VTs) based on the Otis least work of breathing formula. We studied calculated VTs in a computer simulation model, and VTs delivered in a test lung setting as well as in clinical practice. Materials and Methods In a computer simulation model using the Otis formula, VTs were calculated for increasing predicted body weights (from 50 to 80 kg) and increasing minute volumes (from 0.7 to 1.5 ml/kg). Different compliance-resistance combinations were chosen to mimic “acute lung injury (ALI)” (compliance 27 ml/cmH2O, resistance 20 cmH20 l/s), “ALI using an open lung approach” (compliance 50 ml/cmH2O, resistance 20 cmH20 l/s), “healthy lungs” (compliance 65 ml/cmH2O, resistance 20 cmH20 l/s) and “chronic obstructive pulmonary disease (COPD)” (compliance 80 ml/cmH2O, resistance 50 cmH2O l/s). In a test setting using a human ventilator connected to a test lung set to mimic similar pulmonary conditions, VTs delivered by the ASV were studied. In a series of stable intensive care unit patients after cardiothoracic surgery, the delivered VTs were collected and analyzed. Results VTs with the Otis formula resembled those in the test setting. With ALI, the ventilator delivered VTs between 6 and 8 ml/kg. With ALI using an open lung approach and with healthy lungs, the ventilator delivered VTs between 8 and 10 ml/kg. With COPD, all VTs were above 10 ml/kg. In patients after coronary artery bypass surgery ASV delivered VTs between 7 and 9 ml/kg and VTs never exceeded 10 ml/kg. Discussion The ASV performed as intended, bearing in mind that the ASV algorithm was originally designed to provide VTs between 8 and 12 ml/kg. However, the VTs that were calculated and delivered were frequently higher than those presently recommended in the guidelines. Considering the size of VT delivered in the setting of ALI using an open lung approach as well as in the setting of COPD, we feel caution should be taken when applying ASV in patients with these conditions.

The influence of body composition on therapeutic hypothermia: a prospective observational study of patients after cardiac arrest

IntroductionPatients after out-of-hospital cardiac arrest (OHCA) benefit from therapeutic hypothermia for 24 hours. The time needed to reach hypothermia (target temperature of 32°C to 34°C) varies widely. In this study, we explore the relation between measures of body composition and the time needed to reach target temperature with hypothermia.MethodWe conducted a prospective observational study in patients treated with hypothermia after OHCA. Data collected included weight and height, body composition by anthropometric measures and by single-frequency body impedance, and waist-to-hip ratio. Analysis of concordance between impedance and anthropometric measures and hazard ratios of achieving target temperature (event) corrected for different body composition measures.ResultsTwenty-seven patients were included. The median (interquartile range) time to reach target temperature after admission to the intensive care unit was 191 (105 to 382) minutes. Intraclass correlation for total body fat (TBF) measures was 0.94 (95% confidence interval [CI] 0.89 to 0.97). Only TBF percentage (anthropometrics by the Durnins table) appeared to be associated with time to reach target temperature: 0.93 (95% CI 0.87 to 0.99; P = 0.03).ConclusionThe body composition measures from single-frequency impedance and anthropometrics appear to be very concordant. Only TBF percentage (anthropometrics) showed a significant but clinically irrelevant influence on time needed to achieve target temperature with hypothermia. We conclude that there are no indications to adjust current cooling practice toward the body composition of patients.