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Biomedical subjects

Adrianus J van Vught

Publications and source records attributed to Adrianus J van Vught.

16 recordsLinked to original sources
PubMed2006

Transcranial Doppler ultrasonography to confirm brain death: a meta-analysis.

OBJECTIVE: Barbiturate therapy or hypothermia precludes proper diagnosis of brain death either clinically or by EEG. Specific intracranial flow patterns indicating cerebral circulatory arrest (CCA) can be visualized by transcranial Doppler ultrasonography (TCD). The aim of this study was to assess the validity of TCD in confirming brain death. DESIGN: Meta-analysis of studies assessing the validity of TCD in confirming brain death. METHODS: A systematic review of articles in English on the diagnosis brain death by TCD, published between 1980 and 2004, was performed. An oscillating or reverberating flow and systolic spikes were considered to be compatible with CCA. The quality of each study was assessed using standardized methodological criteria. The literature was searched for any article reporting a false-positive result. RESULTS: Two high-quality and eight low-quality studies were included. Meta-analysis of the two high-quality studies showed a sensitivity of 95% (95% CI 92-97%) and a specificity of 99% (95% CI 97-100%) to detect brain death. Meta-analysis of all ten studies showed a sensitivity of 89% and a specificity of 99%. In the literature we found two false-positive results; however, in both patients brain-stem function did show brain death shortly thereafter. CONCLUSIONS: CCA by TCD in the anterior and posterior circulation predicted fatal brain damage in all patients; therefore, TCD can be used to determine the appropriate moment for angiography. Further research is needed to demonstrate that CCA by TCD on repeated examination can also predict brain death in all patients.

Brain Death↗
PubMed2006

Sequential meta-analysis of past clinical trials to determine the use of a new trial.

BACKGROUND: Clinical trials can be stopped early based on interim analyses or sequential analyses. In principle, sequential analyses can also be used to decide whether enough evidence has been gathered in completed trials to make further trials unnecessary. We demonstrate such an application through a retrospective analysis of clinical trials comparing ventilation methods for the treatment of preterm newborns. METHODS: We identified 5 recent trials that compared high-frequency ventilation with conventional mechanical ventilation in the treatment of preterm newborns. Death or chronic lung disease and chronic lung disease in survivors were the primary clinical outcomes of interest. We applied sequential meta-analyses to these 5 studies. RESULTS: After including the first study of the last 5 trials in a sequential meta-analysis, the boundary of "no clinically relevant effect" was crossed for both outcomes (death or chronic lung disease). A sensitivity analysis using a reduction in the size of assumed clinically relevant effect showed the same findings after 2 trials. CONCLUSIONS: Sequential meta-analyses showed that a lack of clinically relevant effect had been established after the first of the 5 trials. If such an analysis had been conducted after the first or second of these clinical trials, it might have led to changes in the study design of subsequent trials or even to a reassessment of the need for further trials.

High-Frequency Ventilation↗
PubMed2006

Systematic review of determinants of mortality in high frequency oscillatory ventilation in acute respiratory distress syndrome.

INTRODUCTION: Mechanical ventilation has been shown to cause lung injury and to have a significant impact on mortality in acute respiratory distress syndrome. Theoretically, high frequency oscillatory ventilation seems an ideal lung protective ventilation mode. This review evaluates determinants of mortality during use of high frequency oscillatory ventilation. METHODS: PubMed was searched for literature reporting randomized trials and cohort studies of high frequency ventilation in adult patients with acute respiratory distress syndrome. Data on mortality and determinants were extracted for patients treated with high frequency oscillatory ventilation. Linear regression analyses were conducted to produce graphical representations of adjusted effects of determinants of mortality. RESULTS: Cohorts of patients treated with high frequency oscillatory ventilation from two randomized trials and seven observational studies were included. Data from cohorts comparing survivors with non-survivors showed differences in age (42.3 versus 51.2 years), prior time on conventional mechanical ventilation (4.0 versus 6.2 days), APACHE II score (22.4 versus 26.1), pH (7.33 versus 7.26) and oxygenation index (26 versus 34). Each extra day on conventional ventilation was associated with a 20% higher mortality adjusted for age and APACHE II score (relative risk (RR) 1.20, 95% confidence interval (CI) 1.15-1.25). However, this association was confounded by differences in pH (pH adjusted RR 1.03, 95% CI 0.73-1.46). Oxygenation index seemed to have an independent effect on mortality (RR 1.10, 95% CI 0.95-1.28). CONCLUSION: Prolonged ventilation on conventional mechanical ventilation prior to high frequency oscillatory ventilation was not related to mortality. Oxygenation index was a determinant of mortality independent of other disease severity markers.

Cohort Studies↗
PubMed2005

High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial [ISRCTN24242669].

INTRODUCTION: To compare the safety and efficacy of high frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CV) for early intervention in adult respiratory distress syndrome (ARDS), a multi-centre randomized trial in four intensive care units was conducted. METHODS: Patients with ARDS were randomized to receive either HFOV or CV. In both treatment arms a priority was given to maintain lung volume while minimizing peak pressures. CV ventilation strategy was aimed at reducing tidal volumes. In the HFOV group, an open lung strategy was used. Respiratory and circulatory parameters were recorded and clinical outcome was determined at 30 days of follow up. RESULTS: The study was prematurely stopped. Thirty-seven patients received HFOV and 24 patients CV (average APACHE II score 21 and 20, oxygenation index 25 and 18 and duration of mechanical ventilation prior to randomization 2.1 and 1.5 days, respectively). There were no statistically significant differences in survival without supplemental oxygen or on ventilator, mortality, therapy failure, or crossover. Adjustment by a priori defined baseline characteristics showed an odds ratio of 0.80 (95% CI 0.22-2.97) for survival without oxygen or on ventilator, and an odds ratio for mortality of 1.15 (95% CI 0.43-3.10) for HFOV compared with CV. The response of the oxygenation index (OI) to treatment did not differentiate between survival and death. In the HFOV group the OI response was significantly higher than in the CV group between the first and the second day. A post hoc analysis suggested that there was a relatively better treatment effect of HFOV compared with CV in patients with a higher baseline OI. CONCLUSION: No significant differences were observed, but this trial only had power to detect major differences in survival without oxygen or on ventilator. In patients with ARDS and higher baseline OI, however, there might be a treatment benefit of HFOV over CV. More research is needed to establish the efficacy of HFOV in the treatment of ARDS. We suggest that future studies are designed to allow for informative analysis in patients with higher OI.

APACHE↗
PubMed2005

Concurrent bacterial infection and prolonged mechanical ventilation in infants with respiratory syncytial virus lower respiratory tract disease.

OBJECTIVE: To identify demographic, clinical, and laboratory variables predictive for a concurrent bacterial pulmonary infection in ventilated infants with respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) and investigate antimicrobial drug use. DESIGN AND SETTING: Retrospective, observational study in a 14-bed pediatric intensive care unit. PATIENTS: 82 infants younger than 1 year of age with a virologically confirmed RSV LRTD during 1996-2001, of whom 65 were mechanically ventilated. RESULTS: Microbiological data were available from 38 ventilated infants, 10 of whom had a positive blood culture (n=1) or endotracheal aspirate (n=9) obtained upon admission to the pediatric intensive care unit (PICU). Infants with a positive culture had a lower mean gestational age but were otherwise demographically comparable to those with negative culture results. Infants with a positive culture were ventilated 4 days longer. Indicators for a concurrent bacterial infection were comparable between ventilated and nonventilated infants. Antimicrobial drugs were used in 95.1% of infants (100% of ventilated infants) with a mean duration of 7.8+/-0.3 days. The moment of initiation and duration of antimicrobial drug treatment varied considerably. CONCLUSIONS: We observed in ventilated infants a low occurrence of concurrent bacterial pulmonary infection, but infants with positive cultures needed prolonged ventilatory support. Improvement in the diagnosis of a pulmonary bacterial infection is warranted to reduce the overuse of antimicrobial drugs among ventilated infants with RSV LRTD and to restrict these drugs to the proper patients.

Anti-Bacterial Agents↗
PubMed2005

Breath-to-breath analysis of abdominal and rib cage motion in surfactant-depleted piglets during high-frequency oscillatory ventilation.

OBJECTIVE: To assess the value of monitoring abdominal and rib cage tidal displacement as an indicator of optimal mean airway pressure (Paw) during high-frequency oscillatory ventilation (HFOV). DESIGN AND SETTING: Prospective observational study in a university research laboratory. ANIMALS: Eight piglets weighing 12.0+/-0.5 kg, surfactant depleted by lung lavage. INTERVENTIONS: Compliance of the respiratory system (C(rs)) was calculated from a quasistatic pressure volume loop. After initiation of HFOV lung volume was recruited by increasing Paw to 40 cmH(2)O. Then mean Paw was decreased in steps until PaO(2)/FIO(2) was below 100 mmHg. Proximal pressure amplitude remained constant. MEASUREMENTS AND RESULTS: Abdominal and rib cage tidal displacement was determined using respiratory inductive plethysmography. During HFOV there was maximum in tidal volume (Vt) in seven of eight piglets. At maximal mean Paw abdominal and rib cage displacement were in phase. Phase difference between abdominal and rib cage displacement increased to a maximum of 178+/-28 degrees at minimum mean Paw. A minimum in abdominal displacement and a maximum of Vt was found near the optimal mean Paw, defined as the lowest mean Paw where shunt fraction is below 0.1. CONCLUSIONS: During HFOV abdominal and rib cage displacement displayed mean Paw dependent asynchrony. Maximal Vt and minimal abdominal displacement coincided with optimal C(rs), oxygenation, and ventilation, suggesting potential clinical relevance of monitoring Vt and abdominal displacement during HFOV.

Abdomen↗
PubMed2004

Static pressure-volume curve characteristics are moderate estimators of optimal airway pressures in a mathematical model of (primary/pulmonary) acute respiratory distress syndrome.

OBJECTIVE: To study the value of objective pressure-volume characteristics for predicting optimal airway pressures and the development of atelectasis and overstretching during a structured lung volume recruitment procedure with subsequent reduction in airway pressures. METHODS: We used a mathematical model of a lung with adjustable characteristics of acute respiratory distress syndrome (ARDS) characteristics. Simulations were performed in five grades of ARDS in the presence of pure alveolar or combined alveolar-small airway closure as well complete or incomplete lung volume recruitability. For each simulation optimal end-expiratory pressure was determined. A static pressure-volume curve was constructed and objective characteristics of this curve calculated. The predictive value of these characteristics for end-expiratory atelectasis, overstretching, and optimal end-expiratory pressure was assessed. RESULTS: Simultaneous alveolar recruitment and overstretching during inflation were more pronounced than alveolar derecruitment and overstretching during deflation. End-expiratory pressure needed to prevent significant alveolar collapse in severe ARDS resulted in maximal safe tidal volumes that may be insufficient for adequate ventilation using conventional mechanical ventilatory modes. Plateau pressures well below the "upper corner point" (airway pressure where compliance decreases) resulted in significant alveolar overstretching. CONCLUSIONS: A recruitment maneuver followed by subsequent reduction in airway pressure limits end-expiratory atelectasis, overstretching, and pressure. None of the objective characteristics of the pressure-volume curve was predictive for end-expiratory atelectasis, overstretching, or optimal airway pressure.

Humans↗
PubMed2004

Ventilator-induced lung injury and multiple system organ failure: a critical review of facts and hypotheses.

OBJECTIVE: To review how biotrauma leads to the development of multiple system organ failure (MSOF). DESIGN AND SETTING: Published articles on experimental and clinical studies and review articles in the English language were collected and analyzed. RESULTS: The concept that ventilation strategies using "large" tidal volumes and zero PEEP of injured lungs can enhance injury by the release of inflammatory mediators into the lungs and circulation, a mechanism that has been called biotrauma, is supported by evidence from experimental models ranging from mechanically stressed cell systems, to isolated lungs, intact animals, and humans. Biotrauma may lead to MSOF via spillover of lung-borne inflammatory mediators into the systemic circulation. However, spillover of other agents such as bacteria and soluble proapoptotic factors may also contribute to the onset of MSOF. Other less well studied mechanisms such as peripheral immunosuppression and translocation of bacteria and/or products from the gut may play an important role. Finally, genetic variability is a crucial factor. CONCLUSIONS: The development of MSOF is a multifactorial process. Our proposed mechanisms linking mechanical ventilation and MSOF suggest several novel therapeutic approaches. However, it will first be necessary to study the mechanisms described above to delineate more precisely the contribution of each proposed factor, their interrelationships, and their time course. We suggest that scientific advances in immunology may offer novel approaches for prevention of MSOF secondary to ventilator-induced lung injury.

Animals↗
PubMed2004

Regional lung volume during high-frequency oscillatory ventilation by electrical impedance tomography.

OBJECTIVE: To investigate the value of electrical impedance tomography for the assessment of regional lung mechanics during high-frequency oscillatory ventilation (HFOV). DESIGN: Prospective, interventional animal study. SETTING: University research laboratory. SUBJECTS: Eight pigs with lavage-induced lung injury. INTERVENTIONS: Electrical impedance tomography measurements were performed during a pressure-volume maneuver and during a recruitment-derecruitment maneuver on HFOV by stepwise variation of continuous distending pressure (CDP). MEASUREMENTS AND MAIN RESULTS: Lung volume was estimated by calibrated strain-gauge plethysmography; regional lung volume changes were assessed by electrical impedance tomography in various regions of interest. We found that inflation during the pressure-volume maneuver was distributed nonhomogeneously, whereas deflation was homogeneous. During HFOV, no major regional differences were found during either inflation or deflation. The upper inflection point on the deflation limb was at a slightly higher continuous distending pressure (26+/-3 cm H2O) than the minimal physiologic shunt fraction (at continuous distending pressure of 23+/-7), where there were hemodynamic signs of overdistension. Maximal compliance on the deflation limb (at continuous distending pressure of 13+/-3 cm H2O) agreed well with the minimal continuous distending pressure, where shunt fraction was just below 0.1 (14+/-2 cm H2O). CONCLUSIONS: HFOV has a homogenizing effect on lung volume distribution. Regional lung volume distribution can be assessed using electrical impedance tomography. However, thoracic fluid accumulation may complicate its interpretation.

Animals↗
PubMed2003

Invasive group A streptococcal infection after tonsillectomy.

Tonsillectomy is a very common procedure in childhood. Infectious complications after tonsillectomy are infrequently reported. We describe two children with severe group A beta-hemolytic streptococcal infection after tonsillectomy, and we review the literature about bacteremia and infectious complications after tonsillectomy.

Anti-Bacterial Agents↗
PubMed2002

Estimation of regional lung volume changes by electrical impedance pressures tomography during a pressure-volume maneuver.

OBJECTIVE: To assess the degree of linearity between lung volume and impedance change by electrical impedance tomography (EIT) in pigs with acute lung injury and to investigate regional impedance changes during a pressure-volume maneuver. DESIGN AND SETTING: Experimental animal study in a university research laboratory. PATIENTS AND PARTICIPANTS: Nine pigs with lung injury induced by lung lavage. INTERVENTIONS: The lungs were insufflated to four different lung volumes. Next the lungs were inflated in steps up to 40 cm H(2)O and then in steps deflated. MEASUREMENTS AND RESULTS: EIT measurements were performed. Impedance was highly linear with lung volume ( r(2)=0.97). From the pressure-volume maneuver regional pressure-impedance (P-I) curves were obtained in the upper half (ventral) and lower half (dorsal) of the thoracic cross-section. Excellent fit was found of the regional P-I curves with a predefined sigmoid equation ( r(2)=0.998). The P-I curves after lavage were markedly different than before lavage. The P-I curves recorded after lavage displayed a strong heterogeneity on the inflation limb: Lower corner pressure (traditionally lower inflection point) was significantly higher in the dorsal (28.3+/-4.1 cm H(2)O) than in the ventral region (17.5+/-4.3 cm H(2)O). The deflation limb displayed a more homogeneous pattern. Upper corner pressure and true inflection point, where the curve slope is maximal, in the dorsal region were only slightly higher than in the ventral region (1-2 cm H(2)O). CONCLUSIONS: EIT and automated curve fitting provide information on regional lung inflation and deflation which may be of clinical use for optimizing ventilator settings.

Airway Resistance↗
PubMed2002

Attenuation of pressure swings along the endotracheal tube is indicative of optimal distending pressure during high-frequency oscillatory ventilation in a model of acute lung injury.

We tested the hypothesis that during high-frequency oscillatory ventilation, the oscillatory pressure ratio (OPR) is minimal at the optimal mean airway pressure (Paw). OPR is defined as the ratio of pressure swings at the distal end and the proximal opening of the endotracheal tube. Optimal Paw was assumed to be the lowest Paw at which the physiological shunt fraction was below 0.1. Acute lung injury was produced by saline lung lavage of pigs who were then subjected to a stepwise increase of Paw to impose underinflation, optimal inflation, and overdistention (inflation phase), followed by a stepwise decrease of Paw (deflation phase). OPR reached a minimum of 0.10 +/- 0.01 at Paw = 31 +/- 4 cm H(2)O during the inflation phase and a minimum of 0.04 +/- 0.01 at Paw = 18 +/- 1 cm H(2)O during the deflation phase. Optimal Paw was 31 +/- 4 cm H(2)O on the inflation limb and 14 +/- 2 cm H(2)O on the deflation limb. Paw at the minimal OPR was not significantly different from the optimal Paw during the inflation phase, and slightly but significantly higher (4.1 +/- 1.6 cm H(2)O) during the deflation phase. In conclusion, a consistent relationship was found between OPR and Paw, with a minimum in all animals. The minimal OPR coincides fairly well with the Paw where oxygenation is optimal.

Animals↗
PubMedDate not supplied

Exogenous surfactant restores lung function but not peripheral immunosuppression in ventilated surfactant-deficient rats.

The authors have previously shown that mechanical ventilation can result in increased pulmonary inflammation and suppressed peripheral leukocyte function. In the present study the effect of surfactant therapy on pulmonary inflammation and peripheral immune function in ventilated surfactant-deficient rats was assessed. Surfactant deficiency was induced by repeated lung lavage, treated rats with surfactant or left them untreated, and ventilated the rats during 2 hours. Nonventilated rats served as healthy control group. Expression of macrophage inflammatory protein (MIP)-2 was measured in bronchoalveolar lavage (BAL), interleukin (IL)-1beta, and heat shock protein 70 (HSP70) were measured in total lung homogenates. Outside the lung phytohemagglutinin (PHA)-induced lymphocyte proliferation, interferon (IFN)-gamma and IL-10 production, and natural killer activity were measured in splenocytes. After 2 hours of mechanical ventilation, expression of MIP-2, IL-1beta, and HSP70 increased significantly in the lungs of surfactant-deficient rats. Outside the lung, mitogen-induced proliferation and production of IFN-gamma and IL-10 reduced significantly. Only natural killer cell activity remained unaffected. Surfactant treatment significantly improved lung function, but could not prevent increased pulmonary expression of MIP-2, IL-1beta, and HSP70 and decreased peripheral mitogen-induced lymphocyte proliferation and IFN-gamma and IL-10 production in vitro. In conclusion, 2 hours of mechanical ventilation resulted in increased lung inflammation and partial peripheral leukocyte suppression in surfactant-deficient rats. Surfactant therapy ameliorated lung function but could not prevent or restore peripheral immunosuppression. The authors postulate that peripheral immunosuppression may occur in ventilated surfactant deficient patients, which may enhance susceptibility for infections.

Animals↗