human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objective : The delivery of bronchodilator drugs with metered-dose inhaler ( MDI ) and a spacer in mechanically ventilated patients has become a widespread practice . However , the various ventilator setting s that influence the efficacy of MDI are not well established . The tidal volume ( VT ) during drug delivery has been suggested as one of the factors that might increase the effectiveness of this therapy . To test this , the effect of two different VT on the bronchodilation induced by β2-agonists administered with MDI and a spacer in a group of mechanically ventilated patients with chronic obstructive pulmonary disease ( COPD ) was examined.¶ Methods : Nine patients with COPD , mechanically ventilated on volume-controlled mode , were prospect ively r and omised to receive six puffs of salbutamol ( S , 100 μg/puff ) either with a VT of 8 ml/kg ( normal VT , 582 ± 85 ) or with a VT of 12 ml/kg ( high VT , 912 ± 137 ) . With both modes inspiratory flow was identical . S was administered with an MDI adapted to the inspiratory limb of the ventilator circuit using an aerosol cloud enhancer spacer . After a ¶6-h washout , patients were crossed-over to receive S by the alternative mode of administration . Static and dynamic airway pressures , minimum ( Rint ) and maximum ( Rrs ) inspiratory resistance , the difference between Rrs and Rint ( ΔR ) , static end-inspiratory respiratory system compliance ( Cst , rs ) , intrinsic positive end-expiratory pressure ( PEEPi ) and heart rate ( HR ) were measured before and at 15 , 30 and 60 min after S.¶ Results : S caused a significant decrease in dynamic and static airway pressures , PEEPi , Rint and Rrs . These changes were not influenced by VT and were evident at 15 , 30 and 60 min after S. With normal and high VT , Cst , rs , ΔR and HR did not change after S.¶ Conclusions : We conclude that S delivered with an MDI and a spacer device induces significant bronchodilation in mechanically ventilated patients with COPD , the magnitude of which is not affected by at least a 50 % increase in VT . These results do not support the VT manipulations when bronchodilators are administered in adequate doses during controlled mechanical ventilation Abstract Background Volume-controlled ventilation has been suggested to optimize lung deposition during nebulization although promoting spontaneous ventilation is targeted to avoid ventilator-induced diaphragmatic dysfunction . Comparing topographic aerosol lung deposition during volume-controlled ventilation and spontaneous ventilation in pressure support has never been performed . The aim of this study was to compare lung deposition of a radiolabeled aerosol generated with a vibrating-mesh nebulizer during invasive mechanical ventilation , with two modes : pressure support ventilation and volume-controlled ventilation . Methods Seventeen postoperative neurosurgery patients without pulmonary disease were r and omly ventilated in pressure support or volume-controlled ventilation . Diethylenetriaminepentaacetic acid labeled with technetium-99 m ( 2 mCi/3 mL ) was administrated using a vibrating-mesh nebulizer ( Aerogen Solo ® , provided by Aerogen Ltd , Galway , Irel and ) connected to the endotracheal tube . Pulmonary and extrapulmonary particles deposition was analyzed using planar scintigraphy . Results Lung deposition was 10.5 ± 3.0 and 15.1 ± 5.0 % of the nominal dose during pressure support and volume-controlled ventilation , respectively ( p < 0.05 ) . Higher endotracheal tube and tracheal deposition was observed during pressure support ventilation ( 27.4 ± 6.6 vs. 20.7 ± 6.0 % , p < 0.05 ) . A similar penetration index was observed for the right ( p = 0.210 ) and the left lung ( p = 0.211 ) with both ventilation modes . A high intersubject variability of lung deposition was observed with both modes regarding lung doses , aerosol penetration and distribution between the right and the left lung . Conclusions In the specific conditions of the study , volume-controlled ventilation was associated with higher lung deposition of nebulized particles as compared to pressure support ventilation . The clinical benefit of this effect warrants further studies . Clinical trial registration BACKGROUND Patients with cystic fibrosis spend as much 30 min a day inhaling tobramycin . Could a new rapid system deposit the equivalent amount of tobramycin faster ? METHODS Six healthy adult males inhaled 5 ml ( 300 mg ) of tobramycin from a breath enhanced nebulizer and either 125 mg ( n = 3 ) or 150 mg ( n = 3 ) from a vibrating membrane system with a large or small aerosol mixing chamber respectively . A radiolabel was added to the solution and shown to " track " with the tobramycin . Imaging was done with a dual headed gamma camera . Because the radiolabel will be cleared by mucociliary action during administration , algorithms were developed to allow the comparison of a slower system to a faster one . RESULTS Both formulations were well tolerated . The lung deposition was 16.6 + /- 3.2 % ( mean + /- SD ) of the charge dose delivered in 10.9 + /- 1.0 min for the breath enhanced nebulizer versus 32.0 + /- 5.1 % delivered in 2.5 + /- 0.4 min from the vibrating membrane system . The absolute pulmonary delivery of tobramycin was 49.9 + /- 9.6 versus 43.9 + /- 4.8 mg for the two systems respectively , differences that were statistically significant ( pair t-test ) but unlikely to be clinical ly significant . There was a similar deposition of tobramycin for the 125 and 150 mg dose . CONCLUSIONS It is possible to deliver an equivalent amount of tobramycin in a shorter period of time with the new vibrating membrane system and a more concentrated formulation . These data will allow the design of a comparison in patients with CF BACKGROUND BAY41 - 6551 , a drug-device combination in development for adjunctive treatment of Gram-negative pneumonia in intubated and mechanically ventilated patients , consists of amikacin formulated for inhalation coupled with the Pulmonary Drug Delivery System ( PDDS ) Clinical aerosol delivery platform . Given the predominantly renal clearance of aminoglycosides , underst and ing systemic amikacin exposure and safety during administration of BAY41 - 6551 to patients with acute renal failure ( ARF ) is clinical ly important . METHODS Seven mechanically ventilated patients with Gram-negative pneumonia and ARF receiving continuous veno-venous hemodiafiltration ( CVVHDF ) were treated with multiple administrations of BAY41 - 6551 400 mg amikacin twice daily using the PDDS Clinical on-ventilator device [ in addition to st and ard intravenous ( i.v . ) antimicrobial therapy ] . CVVHDF parameters were recorded and a PK analysis was performed using serum , urine , and bronchoalveolar lavage fluid sample s. RESULTS Maximum serum amikacin concentration [ median 1.93 ( range : 0.63 - 3.99 ) mg/L ] and area under the concentration-time curve from zero to 12 h on day 3 [ median 19.32 ( range 6.32 - 36.87 ) mg · h/L ] were elevated compared with mechanically ventilated patients with normal renal function ; however , serum amikacin trough concentrations were within accepted safety limits . The median amikacin concentration in epithelial lining fluid [ 887 ( range : 406 - 12,819 ) mg/L ] was similar to that reported previously in mechanically ventilated patients with normal renal function . BAY41 - 6551 demonstrated acceptable safety and tolerability with most adverse events ( AEs ) as expected for the patient population . One serious AE of bronchospasm was attributed to the study medication ; no reported AEs were related to the PDDS Clinical device . CONCLUSIONS CVVHDF appears to provide adequate clearance of systemically absorbed amikacin in mechanically ventilated patients with ARF , suggesting that dose adjustments for BAY41 - 6551 are probably not necessary for this patient population . Nonetheless , the st and ard pre caution ary measures for critically ill patients receiving i.v . amikacin should be followed for patients with ARF who are treated with BAY41 - 6551 BACKGROUND The optimal method of delivering bronchodilators in mechanically ventilated patients is unclear . The purpose of this study was to compare the pulmonary bioavailability of albuterol delivered by the nebulizer , the metered-dose inhaler ( MDI ) and spacer , and the right-angle MDI adaptor in ventilated patients using urinary analysis of drug levels . METHODS Mechanically ventilated patients who had not received a bronchodilator in the previous 48 h and who had normal renal function were r and omized to receive the following : ( 1 ) five puffs ( 450 microg ) of albuterol delivered by the MDI with a small volume spacer ; ( 2 ) five puffs of albuterol delivered by the MDI port on a right-angle adaptor ; or ( 3 ) 2.5 mg albuterol delivered by a nebulizer . Urine was collected 6 h after the administration of the drug , and the amounts of albuterol and its sulfate conjugate were determined in the urine by a chromatographic assay . RESULTS Thirty patients were studied , 10 in each group : their mean age and serum creatinine level were 62 years and 1.3 mg/dL , respectively . With the MDI and spacer , ( mean + /- SD ) 169+/-129 microg albuterol ( 38 % ) was recovered in the urine ; with the nebulizer , 409+/-515 microg albuterol ( 16 % ) was recovered in the urine ; and with the MDI port on the right-angle adaptor , 41+/-61 microg albuterol ( 9 % ) was recovered in the urine ( p = 0.02 between groups ) . The level of albuterol in the urine was below the level of detection in four patients in whom the drug was delivered using the right-angle MDI adaptor . CONCLUSION The three delivery systems varied markedly in their efficiency of drug delivery to the lung . As previous studies have confirmed , this study has demonstrated that using an MDI and spacer is an efficient method for delivering inhaled bronchodilators to the lung . The pulmonary bioavailability was poor with the right-angle MDI port . This port should not be used to deliver bronchodilators in mechanically ventilated patients STUDY OBJECTIVE To compare aerosol delivery to the lungs in ventilated patients from two devices with holding chamber and two devices without holding chamber . DESIGN A controlled clinical trial with r and omization to one of four delivery devices . SETTING An academic university-affiliated Canadian ICU . PATIENTS Forty-eight patients undergoing mechanically assisted ventilation for a variety of clinical reasons and each judged to require inhaled bronchodilator therapy by the attending physician . INTERVENTIONS Patients received 4 puffs of fenoterol labeled with technetium 99 m pertechnetate delivered by metered-dose inhaler via 1 of the following : A , a 167-ml chamber device ; B , a 700-ml chamber device ; C , a nonchamber device ( A , B , and C , all in the ventilator inspiratory line ) ; and D , a nonchamber device on the end of the endotracheal tube . MEASUREMENTS AND RESULTS One-minute images of the thorax were made by a portable gamma camera at the bedside . Deposition of radioactivity in the lungs ( uncorrected for tissue absorption and calculated as a percentage of the radioactivity delivered from 4 puffs ) was 5.53 + /- 0.72 ( mean + /- 1 SEM ) , 6.33 + /- 1.16 , 1.67 + /- 0.43 , and 3.89 + /- 0.52 percent for devices A , B , C , and D , respectively ( p = 0.004 ) . Subgroup analysis showed a statistically significant difference in delivery between devices A and C and between devices B and C only . CONCLUSION There were statistically significant differences between delivery from both chamber devices and the inline nonchamber device , but not between delivery from other devices . Further work will be necessary to determine the effect of device position in the ventilator circuit on aerosol delivery BACKGROUND Therapeutic aerosols are commonly used in mechanically ventilated patients . The position of the nebulizer in the ventilator circuit and the humidification of inhaled gases can influence the efficiency of aerosol delivery . We evaluated the effect of nebulizer position on the pulmonary bioavailability of nebulized ipratropium  in ventilated patients without known preexisting respiratory disease . METHODS The study included 38 mechanically ventilated and se date d patients after open heart surgery .  Ipratropium ( 500 microg ) was delivered by an ultrasonic nebulizer . Patients were r and omized into 2 groups : the nebulizer positioned before the heat humidification system ( group 1 , n = 19 ) or at the end of the inspiratory limb before the Y-piece ( group 2 , n = 19 ) . The amount of i 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objective : The delivery of bronchodilator drugs with metered-dose inhaler ( MDI ) and a spacer in mechanically ventilated patients has become a widespread practice . However , the various ventilator setting s that influence the efficacy of MDI are not well established . The tidal volume ( VT ) during drug delivery has been suggested as one of the factors that might increase the effectiveness of this therapy . To test this , the effect of two different VT on the bronchodilation induced by β2-agonists administered with MDI and a spacer in a group of mechanically ventilated patients with chronic obstructive pulmonary disease ( COPD ) was examined.¶ Methods : Nine patients with COPD , mechanically ventilated on volume-controlled mode , were prospect ively r and omised to receive six puffs of salbutamol ( S , 100 μg/puff ) either with a VT of 8 ml/kg ( normal VT , 582 ± 85 ) or with a VT of 12 ml/kg ( high VT , 912 ± 137 ) . With both modes inspiratory flow was identical . S was administered with an MDI adapted to the inspiratory limb of the ventilator circuit using an aerosol cloud enhancer spacer . After a ¶6-h washout , patients were crossed-over to receive S by the alternative mode of administration . Static and dynamic airway pressures , minimum ( Rint ) and maximum ( Rrs ) inspiratory resistance , the difference between Rrs and Rint ( ΔR ) , static end-inspiratory respiratory system compliance ( Cst , rs ) , intrinsic positive end-expiratory pressure ( PEEPi ) and heart rate ( HR ) were measured before and at 15 , 30 and 60 min after S.¶ Results : S caused a significant decrease in dynamic and static airway pressures , PEEPi , Rint and Rrs . These changes were not influenced by VT and were evident at 15 , 30 and 60 min after S. With normal and high VT , Cst , rs , ΔR and HR did not change after S.¶ Conclusions : We conclude that S delivered with an MDI and a spacer device induces significant bronchodilation in mechanically ventilated patients with COPD , the magnitude of which is not affected by at least a 50 % increase in VT . These results do not support the VT manipulations when bronchodilators are administered in adequate doses during controlled mechanical ventilation Abstract Background Volume-controlled ventilation has been suggested to optimize lung deposition during nebulization although promoting spontaneous ventilation is targeted to avoid ventilator-induced diaphragmatic dysfunction . Comparing topographic aerosol lung deposition during volume-controlled ventilation and spontaneous ventilation in pressure support has never been performed . The aim of this study was to compare lung deposition of a radiolabeled aerosol generated with a vibrating-mesh nebulizer during invasive mechanical ventilation , with two modes : pressure support ventilation and volume-controlled ventilation . Methods Seventeen postoperative neurosurgery patients without pulmonary disease were r and omly ventilated in pressure support or volume-controlled ventilation . Diethylenetriaminepentaacetic acid labeled with technetium-99 m ( 2 mCi/3 mL ) was administrated using a vibrating-mesh nebulizer ( Aerogen Solo ® , provided by Aerogen Ltd , Galway , Irel and ) connected to the endotracheal tube . Pulmonary and extrapulmonary particles deposition was analyzed using planar scintigraphy . Results Lung deposition was 10.5 ± 3.0 and 15.1 ± 5.0 % of the nominal dose during pressure support and volume-controlled ventilation , respectively ( p < 0.05 ) . Higher endotracheal tube and tracheal deposition was observed during pressure support ventilation ( 27.4 ± 6.6 vs. 20.7 ± 6.0 % , p < 0.05 ) . A similar penetration index was observed for the right ( p = 0.210 ) and the left lung ( p = 0.211 ) with both ventilation modes . A high intersubject variability of lung deposition was observed with both modes regarding lung doses , aerosol penetration and distribution between the right and the left lung . Conclusions In the specific conditions of the study , volume-controlled ventilation was associated with higher lung deposition of nebulized particles as compared to pressure support ventilation . The clinical benefit of this effect warrants further studies . Clinical trial registration BACKGROUND Patients with cystic fibrosis spend as much 30 min a day inhaling tobramycin . Could a new rapid system deposit the equivalent amount of tobramycin faster ? METHODS Six healthy adult males inhaled 5 ml ( 300 mg ) of tobramycin from a breath enhanced nebulizer and either 125 mg ( n = 3 ) or 150 mg ( n = 3 ) from a vibrating membrane system with a large or small aerosol mixing chamber respectively . A radiolabel was added to the solution and shown to " track " with the tobramycin . Imaging was done with a dual headed gamma camera . Because the radiolabel will be cleared by mucociliary action during administration , algorithms were developed to allow the comparison of a slower system to a faster one . RESULTS Both formulations were well tolerated . The lung deposition was 16.6 + /- 3.2 % ( mean + /- SD ) of the charge dose delivered in 10.9 + /- 1.0 min for the breath enhanced nebulizer versus 32.0 + /- 5.1 % delivered in 2.5 + /- 0.4 min from the vibrating membrane system . The absolute pulmonary delivery of tobramycin was 49.9 + /- 9.6 versus 43.9 + /- 4.8 mg for the two systems respectively , differences that were statistically significant ( pair t-test ) but unlikely to be clinical ly significant . There was a similar deposition of tobramycin for the 125 and 150 mg dose . CONCLUSIONS It is possible to deliver an equivalent amount of tobramycin in a shorter period of time with the new vibrating membrane system and a more concentrated formulation . These data will allow the design of a comparison in patients with CF BACKGROUND BAY41 - 6551 , a drug-device combination in development for adjunctive treatment of Gram-negative pneumonia in intubated and mechanically ventilated patients , consists of amikacin formulated for inhalation coupled with the Pulmonary Drug Delivery System ( PDDS ) Clinical aerosol delivery platform . Given the predominantly renal clearance of aminoglycosides , underst and ing systemic amikacin exposure and safety during administration of BAY41 - 6551 to patients with acute renal failure ( ARF ) is clinical ly important . METHODS Seven mechanically ventilated patients with Gram-negative pneumonia and ARF receiving continuous veno-venous hemodiafiltration ( CVVHDF ) were treated with multiple administrations of BAY41 - 6551 400 mg amikacin twice daily using the PDDS Clinical on-ventilator device [ in addition to st and ard intravenous ( i.v . ) antimicrobial therapy ] . CVVHDF parameters were recorded and a PK analysis was performed using serum , urine , and bronchoalveolar lavage fluid sample s. RESULTS Maximum serum amikacin concentration [ median 1.93 ( range : 0.63 - 3.99 ) mg/L ] and area under the concentration-time curve from zero to 12 h on day 3 [ median 19.32 ( range 6.32 - 36.87 ) mg · h/L ] were elevated compared with mechanically ventilated patients with normal renal function ; however , serum amikacin trough concentrations were within accepted safety limits . The median amikacin concentration in epithelial lining fluid [ 887 ( range : 406 - 12,819 ) mg/L ] was similar to that reported previously in mechanically ventilated patients with normal renal function . BAY41 - 6551 demonstrated acceptable safety and tolerability with most adverse events ( AEs ) as expected for the patient population . One serious AE of bronchospasm was attributed to the study medication ; no reported AEs were related to the PDDS Clinical device . CONCLUSIONS CVVHDF appears to provide adequate clearance of systemically absorbed amikacin in mechanically ventilated patients with ARF , suggesting that dose adjustments for BAY41 - 6551 are probably not necessary for this patient population . Nonetheless , the st and ard pre caution ary measures for critically ill patients receiving i.v . amikacin should be followed for patients with ARF who are treated with BAY41 - 6551 BACKGROUND The optimal method of delivering bronchodilators in mechanically ventilated patients is unclear . The purpose of this study was to compare the pulmonary bioavailability of albuterol delivered by the nebulizer , the metered-dose inhaler ( MDI ) and spacer , and the right-angle MDI adaptor in ventilated patients using urinary analysis of drug levels . METHODS Mechanically ventilated patients who had not received a bronchodilator in the previous 48 h and who had normal renal function were r and omized to receive the following : ( 1 ) five puffs ( 450 microg ) of albuterol delivered by the MDI with a small volume spacer ; ( 2 ) five puffs of albuterol delivered by the MDI port on a right-angle adaptor ; or ( 3 ) 2.5 mg albuterol delivered by a nebulizer . Urine was collected 6 h after the administration of the drug , and the amounts of albuterol and its sulfate conjugate were determined in the urine by a chromatographic assay . RESULTS Thirty patients were studied , 10 in each group : their mean age and serum creatinine level were 62 years and 1.3 mg/dL , respectively . With the MDI and spacer , ( mean + /- SD ) 169+/-129 microg albuterol ( 38 % ) was recovered in the urine ; with the nebulizer , 409+/-515 microg albuterol ( 16 % ) was recovered in the urine ; and with the MDI port on the right-angle adaptor , 41+/-61 microg albuterol ( 9 % ) was recovered in the urine ( p = 0.02 between groups ) . The level of albuterol in the urine was below the level of detection in four patients in whom the drug was delivered using the right-angle MDI adaptor . CONCLUSION The three delivery systems varied markedly in their efficiency of drug delivery to the lung . As previous studies have confirmed , this study has demonstrated that using an MDI and spacer is an efficient method for delivering inhaled bronchodilators to the lung . The pulmonary bioavailability was poor with the right-angle MDI port . This port should not be used to deliver bronchodilators in mechanically ventilated patients STUDY OBJECTIVE To compare aerosol delivery to the lungs in ventilated patients from two devices with holding chamber and two devices without holding chamber . DESIGN A controlled clinical trial with r and omization to one of four delivery devices . SETTING An academic university-affiliated Canadian ICU . PATIENTS Forty-eight patients undergoing mechanically assisted ventilation for a variety of clinical reasons and each judged to require inhaled bronchodilator therapy by the attending physician . INTERVENTIONS Patients received 4 puffs of fenoterol labeled with technetium 99 m pertechnetate delivered by metered-dose inhaler via 1 of the following : A , a 167-ml chamber device ; B , a 700-ml chamber device ; C , a nonchamber device ( A , B , and C , all in the ventilator inspiratory line ) ; and D , a nonchamber device on the end of the endotracheal tube . MEASUREMENTS AND RESULTS One-minute images of the thorax were made by a portable gamma camera at the bedside . Deposition of radioactivity in the lungs ( uncorrected for tissue absorption and calculated as a percentage of the radioactivity delivered from 4 puffs ) was 5.53 + /- 0.72 ( mean + /- 1 SEM ) , 6.33 + /- 1.16 , 1.67 + /- 0.43 , and 3.89 + /- 0.52 percent for devices A , B , C , and D , respectively ( p = 0.004 ) . Subgroup analysis showed a statistically significant difference in delivery between devices A and C and between devices B and C only . CONCLUSION There were statistically significant differences between delivery from both chamber devices and the inline nonchamber device , but not between delivery from other devices . Further work will be necessary to determine the effect of device position in the ventilator circuit on aerosol delivery BACKGROUND Therapeutic aerosols are commonly used in mechanically ventilated patients . The position of the nebulizer in the ventilator circuit and the humidification of inhaled gases can influence the efficiency of aerosol delivery . We evaluated the effect of nebulizer position on the pulmonary bioavailability of nebulized ipratropium  in ventilated patients without known preexisting respiratory disease . METHODS The study included 38 mechanically ventilated and se date d patients after open heart surgery .  Ipratropium ( 500 microg ) was delivered by an ultrasonic nebulizer . Patients were r and omized into 2 groups : the nebulizer positioned before the heat humidification system ( group 1 , n = 19 ) or at the end of the inspiratory limb before the Y-piece ( group 2 , n = 19 ) . The amount of i 
    Output:
    