- Email: [email protected]
Exhaled Nitric Oxide Measurements From Different Analyzers
Affiliations: Department of Anesthesiology, Critical Care Medicine, Harborview Medical Center. Financial/nonfinancial disclosures: The author has reported to CHEST that no potential conflicts of interest exist with any companiesⲐorganizations whose products or services may be discussed in this article. Correspondence to: Steven Deem, MD, Anesthesiology, Harborview Medical Center, Box 359724, 325 Ninth Ave, Seattle WA 98104-2499; e-mail: [email protected] © 2010 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/ site/misc/reprints.xhtml). DOI: 10.1378/chest.10-1153
References 1. Afessa B, Shorr AF, Anzueto AR, Craven DE, Schinner R, Kollef MH. Association between a silver-coated endotracheal tube and reduced mortality in patients with ventilator-associated pneumonia. Chest. 2010;137(5):1015-1021. 2. Kollef MH, Afessa B, Anzueto A, et al; NASCENT Investigation Group. Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: the NASCENT randomized trial. JAMA. 2008;300(7):805-813.
Response To the Editor: We thank Dr Deem for the opportunity to elaborate on the mortality imbalance in our retrospective cohort analysis1 of the North American Silver-Coated Endotracheal Tube (NASCENT) study.2 The increased mortality among patients without ventilator-associated pneumonia who received the silver-coated endotracheal tube was unexpected in view of the lack of toxicity in NASCENT2 and previous studies3,4 comparing silver-coated with uncoated tubes. In a randomized, double-blind study of 11 healthy adult dogs,3 no evidence of toxicity was found on histologic examination after 96 h of mechanical ventilation. In a randomized phase 2 study of adults on mechanical ventilation,4 adverse events, including those unrelated to device or procedure, occurred in 47 (63%) of 75 patients in the silver group and in 46 (62%) of 74 patients in the control group. In the NASCENT study,2 adverse events possibly related to the device occurred in 122 (12.6%) of 968 patients in the silver group and in 111 (11.5%) of 964 in the control group (P 5 .46); corresponding numbers for adverse events definitely related to the device were 18 (1.9%) and 27 (2.8%) (P 5 .17). To further evaluate the mortality imbalance in the NASCENT study,2 we examined all patients and found no between-group differences in hepatic failure, multiorgan failure, or other causes of death suggestive of silver toxicity. The only between-group difference in leading causes of death was respiratory failure, which occurred in 45 (19%) of 233 patients in the silver group and in 22 (11%) of 198 patients in the control group (P 5 .02). Collectively, these findings suggest that the mortality imbalance in the NASCENT study2 was more likely to be attributable to risk factors not captured in the case report form than to the silvercoated endotracheal tube. Bekele Afessa, MD, FCCP Rochester, MN Antonio R. Anzueto, MD, FCCP San Antonio, TX Donald E. Craven, MD Boston, MA Marin H. Kollef, MD, FCCP St Louis, MO www.chestpubs.org
Affiliations: From the Mayo Clinic College of Medicine (Dr Afessa); Audie L. Murphy Division (Dr Anzueto), South Texas Veterans Health Care System; University Hospital (Dr Anzueto), University of Texas Health Science Center at San Antonio; Lahey Clinic Medical Center (Dr Craven); Tufts University School of Medicine (Dr Craven); and Washington University School of Medicine (Dr Kollef). Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companiesⲐorganizations whose products or services may be discussed in this article. Correspondence to: Bekele Afessa, MD, FCCP, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 1st St SW, Rochester, MN 55905-0001; e-mail: [email protected] © 2010 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/ site/misc/reprints.xhtml). DOI: 10.1378/chest.10-1724
References 1. Afessa B, Shorr AF, Anzueto AR, Craven DE, Schinner R, Kollef MH. Association between a silver-coated endotracheal tube and reduced mortality in patients with ventilator-associated pneumonia. Chest. 2010;137(5):1015-1021. 2. Kollef MH, Afessa B, Anzueto A, et al; NASCENT Investigation Group. Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: the NASCENT randomized trial. JAMA. 2008;300(7):805-813. 3. Olson ME, Harmon BG, Kollef MH. Silver-coated endotracheal tubes associated with reduced bacterial burden in the lungs of mechanically ventilated dogs. Chest. 2002;121(3): 863-870. 4. Rello J, Kollef M, Diaz E, et al. Reduced burden of bacterial airway colonization with a novel silver-coated endotracheal tube in a randomized multiple-center feasibility study. Crit Care Med. 2006;34(11):2766-2772.
Exhaled Nitric Oxide Measurements From Different Analyzers To the Editor: Adult studies report differences in the fraction of exhaled nitric oxide (FeNO) measured from different analyzers,1,2 but pediatric data are lacking. FeNO in children and adults measured by a singlebreath online technique using NIOX (Aerocrine; Solna, Sweden) and EcoMedics CLD88 (EcoMedics; Duernten, Switzerland) analyzers is reported. Institutional review board approval, patient consent, and parental consent, when appropriate, were obtained. The analyzers were in adjacent rooms with similar ambience (nitric oxide [NO] , 5 ppb) and calibrated according to manufacturers’ instructions. FeNO was measured in subjects who had the ability to maintain an expiratory flow of ⵑ 50 mLⲐs, using the two analyzers within 30 min of each other, in random order. Subjects inhaled NO-free air from a built-in NO filter in the NIOX analyzer and an NO-free air supply (DENOX-88) connected to the EcoMedics analyzer. Pressing a button on the DENOX-88 when inhalation began delivered continuous zero-NO air, which stopped on release of the button when exhalation began. Subjects did not wear nose clips and exhaled within 10% of 50 mLⲐs for 6 s. Mean FeNO from three measurements within 10% of each other and with valid plateaus was recorded from both analyzers.3 Primary analysis included FeNO from 60 subjects: 30 children, median age (range) 6.6 (4.3-13.6) years, and 30 adults, mean age 34.7 (22.7-51) years. Subanalysis included FeNO from 11 adults while exhaling at ⵑ 50 mLⲐs for 10 s from both analyzers and for 6 s with and without pressing the DENOX-88 button. CHEST / 138 / 5 / NOVEMBER, 2010
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on November 8, 2010 © 2010 American College of Chest Physicians
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Figure 1. Bland-Altman plots showing LA between NIOX and EcoMedics analyzers with different settings. A, 6-s exhalation in children with DENOX-88 button pressed. B, 6-s exhalation in adults with DENOX-88 button pressed. C, 10-s exhalation in adults with DENOX-88 button pressed. D, 6-s exhalation in adults without pressing DENOX-88 button. FeNO 5 fraction of exhaled nitric oxide; LA 5 limits of agreement. FeNO values were log-transformed and Bland-Altman plots used to determine limits of agreement (LA) between analyzers.4 All FeNO measurements were higher with NIOX than EcoMedics after 6-s exhalation. With the DENOX-88 button pressed, FeNO in children and adults demonstrated poor agreement between the two analyzers after 6 s (Figs 1A, 1B), but not after 10-s exhalation (Fig 1C). However, when the DENOX-88 button was not pressed, there was good agreement after 6-s exhalation (Fig 1D). Furthermore, the EcoMedics showed lower FeNO values at the preset 2- to 4-s plateau than adjusted 4- to 6-s plateau (mean difference, 16%; 95% LA, 23%, 55%). FeNO from EcoMedics after 6-s exhalation was significantly lower than FeNO from NIOX. It is likely that residual zero-NO air in the tubing dilutes the FeNO on releasing the DENOX-88 button when exhalation begins, increasing time to stable plateau. Moreover, EcoMedics analyzer is preset to read FeNO at 2- to 4-s plateau for 6-s exhalation, whereas NIOX analyzer is preset to choose the best plateau, which further increases differences. EcoMedics and NIOX analyzers have built-in NO filters, and if ambient NO is , 5 ppb, inhaling continuous zero-NO air is not
recommended, particularly in young children in whom the duration of exhalation is shorter. These findings highlight the importance of determining equipment-specific reference ranges and reporting true stable FeNO plateaus. Samatha Sonnappa, MD, PhD Cristina M. Bastardo, MD Andrew Bush, MD Paul Aurora, PhD London, England Affiliations: From the Portex Unit: Respiratory Medicine and Physiology (Drs Sonnappa, Bastardo, and Aurora), UCL Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust; and the Department of Paediatric Respiratory Medicine (Dr Bush), Royal Brompton Hospital and Imperial College. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
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Correspondence
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on November 8, 2010 © 2010 American College of Chest Physicians
Correspondence to: Samatha Sonnappa, MD, PhD, Portex Unit: Respiratory Medicine and Physiology, UCL Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust, 30, Guilford St, London, WC1N 1EH, England; e-mail: [email protected] © 2010 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/ site/misc/reprints.xhtml). DOI: 10.1378/chest.10-1061
companiesⲐorganizations whose products or services may be discussed in this article. Correspondence to: Seza Apiliogullari, MD, Selcuklu Medical Faculty, Department of Anesthesia and Intensive Care, Selcuk University, 42075, Konya, Turkey; e-mail: [email protected] © 2010 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.orgⲐ siteⲐmiscⲐreprints.xhtml). DOI: 10.1378/chest.10-1237
References References 1. Müller KC, Jörres RA, Magnussen H, Holz O. Comparison of exhaled nitric oxide analysers. Respir Med. 2005;99(5): 631-637. 2. Borrill Z, Clough D, Truman N, Morris J, Langley S, Singh D. A comparison of exhaled nitric oxide measurements performed using three different analysers. Respir Med. 2006;100(8): 1392-1396. 3. American Thoracic Society; European Respiratory Society. ATSⲐERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med. 2005;171(8):912-930. 4. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;1(8476):307-310.
1. Cowl CT. Use of antisialogogues in bronchoscopy. Chest. 2010;137(3):738. 2. Malik JA, Gupta D, Agarwal AN, Jindal SK. Anticholinergic premedication for flexible bronchoscopy: a randomized, double-blind, placebo-controlled study of atropine and glycopyrrolate. Chest. 2009;136(2):347-354. 3. Cowl CT, Prakash UBS, Kruger BR. The role of anticholinergics in bronchoscopy: a randomized clinical trial. Chest. 2000;118(1):188-192. 4. Apiliogullari S, Sener Y, Can S, Yegin Y, Tosun G, Celik JB. Effect of midazolam on salivary flow rate in children. J Selcuk U Dent Fac. 2010;19(2):3-7.
Response To the Editor:
Midazolam Can Decrease Salivation During Bronchoscopy To the Editor: We read with interest the response letter by Cowl1 (March 2010) to the study by Malik et al2 (August 2009) concerning the use of antisialogogues in broncoscopy. Based on the results of two previous studies, Cowl points out that antisecretory drugs do not result in clinically significant differences in cough or secretion control and can even be considered harmful. We have a major concern about the designs of the studies by Malik et al2 and Cowl et al.3 In a recent randomized, double-blind, placebo-controlled, prospective, quantitative study,4 we demonstrated that midazolam decreases both unstimulated and stimulated saliva flow rates (from 0.31 g/min to 0.18 g/min and from 0.78 g/min to 0.31 g/min, respectively, P 5 .00). The study included 40 children aged 9 to 12. Unstimulated and paraffin-stimulated saliva was collected from each child at baseline and 10 min after midazolam injection. This antisialogogue effect of midazolam can be responsible for the barely statistically significant difference in visual analog scale scores between placebo and the anticholinergic drugs observed in the studies by Malik et al2 and Cowl et al.3 We are of the opinion that future studies should exclude midazolam from the design when the antisialogue effects of anticholinergic drugs are assessed. Seza Apiliogullari, MD Jale Bengi Celik, MD Ates Duman, MD Konya, Turkey Affiliations: From the Selcuklu Medical Faculty, Department of Anesthesia and Intensive Care, Selcuk University. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any www.chestpubs.org
Dr Apiliogullari and colleagues express concerns about the design of two studies in CHEST (July 2000 and August 2009) that compared the use of antisialogogic agents as pretreatment strategies for adult bronchoscopy,1,2 citing that midazolam used concurrently for sedation can confound results because midazolam itself can also result in a reduction in secretions (as shown in their own recent study of a small cohort of pediatric patients [N 5 40] who underwent measured simulated salivary flow rates).3 Unfortunately, they seem to have missed the entire point of the prior discussion.4 The clinical question hinges on whether the use of antisialogogic agents such as atropine or glycopyrrolate is necessary prior to adult bronchoscopy to increase patient tolerance of the procedure or improve visualization of the airway anatomy. The use of these drugs adds cost to each procedure and, in some cases, can actually result in unnecessary, untoward side effects. It has been known for years that midazolam can, by itself or in combination with other sedative-analgesic agents, have some minor antisialogogic properties.5,6 The study by Apiliogullari et al3 further bolsters the argument that if there is indeed an antisialogogic effect from the use of midazolam, then the use of other secretion-reducing agents is clearly not needed. A clinically significant result in the initial randomized trials would have meant that the use of antisialogogic drugs provides a clear benefit to the bronchoscopist and patient in terms of the ability to inspect the airway and improves the overall comfort of the procedure above and beyond that provided without their use. That was not determined in those studies, even after randomization of . 1,000 patients between the two trials. Although Apiliogullari and colleagues3 should be congratulated for their efforts in quantitating salivary flow rates, that result does not alter the fact that the use of antisialogogues is unnecessary prior to routine adult bronchoscopy and does not ultimately affect the measured clinical endpoints, as outlined in the original randomized trials. Clayton T. Cowl, MD, FCCP Rochester, MN CHEST / 138 / 5 / NOVEMBER, 2010
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on November 8, 2010 © 2010 American College of Chest Physicians
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References 1. Afessa B, Shorr AF, Anzueto AR, Craven DE, Schinner R, Kollef MH. Association between a silver-coated endotracheal tube and reduced mortality in patients with ventilator-associated pneumonia. Chest. 2010;137(5):1015-1021. 2. Kollef MH, Afessa B, Anzueto A, et al; NASCENT Investigation Group. Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: the NASCENT randomized trial. JAMA. 2008;300(7):805-813.
Response To the Editor: We thank Dr Deem for the opportunity to elaborate on the mortality imbalance in our retrospective cohort analysis1 of the North American Silver-Coated Endotracheal Tube (NASCENT) study.2 The increased mortality among patients without ventilator-associated pneumonia who received the silver-coated endotracheal tube was unexpected in view of the lack of toxicity in NASCENT2 and previous studies3,4 comparing silver-coated with uncoated tubes. In a randomized, double-blind study of 11 healthy adult dogs,3 no evidence of toxicity was found on histologic examination after 96 h of mechanical ventilation. In a randomized phase 2 study of adults on mechanical ventilation,4 adverse events, including those unrelated to device or procedure, occurred in 47 (63%) of 75 patients in the silver group and in 46 (62%) of 74 patients in the control group. In the NASCENT study,2 adverse events possibly related to the device occurred in 122 (12.6%) of 968 patients in the silver group and in 111 (11.5%) of 964 in the control group (P 5 .46); corresponding numbers for adverse events definitely related to the device were 18 (1.9%) and 27 (2.8%) (P 5 .17). To further evaluate the mortality imbalance in the NASCENT study,2 we examined all patients and found no between-group differences in hepatic failure, multiorgan failure, or other causes of death suggestive of silver toxicity. The only between-group difference in leading causes of death was respiratory failure, which occurred in 45 (19%) of 233 patients in the silver group and in 22 (11%) of 198 patients in the control group (P 5 .02). Collectively, these findings suggest that the mortality imbalance in the NASCENT study2 was more likely to be attributable to risk factors not captured in the case report form than to the silvercoated endotracheal tube. Bekele Afessa, MD, FCCP Rochester, MN Antonio R. Anzueto, MD, FCCP San Antonio, TX Donald E. Craven, MD Boston, MA Marin H. Kollef, MD, FCCP St Louis, MO www.chestpubs.org
Affiliations: From the Mayo Clinic College of Medicine (Dr Afessa); Audie L. Murphy Division (Dr Anzueto), South Texas Veterans Health Care System; University Hospital (Dr Anzueto), University of Texas Health Science Center at San Antonio; Lahey Clinic Medical Center (Dr Craven); Tufts University School of Medicine (Dr Craven); and Washington University School of Medicine (Dr Kollef). Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companiesⲐorganizations whose products or services may be discussed in this article. Correspondence to: Bekele Afessa, MD, FCCP, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 1st St SW, Rochester, MN 55905-0001; e-mail: [email protected] © 2010 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/ site/misc/reprints.xhtml). DOI: 10.1378/chest.10-1724
References 1. Afessa B, Shorr AF, Anzueto AR, Craven DE, Schinner R, Kollef MH. Association between a silver-coated endotracheal tube and reduced mortality in patients with ventilator-associated pneumonia. Chest. 2010;137(5):1015-1021. 2. Kollef MH, Afessa B, Anzueto A, et al; NASCENT Investigation Group. Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: the NASCENT randomized trial. JAMA. 2008;300(7):805-813. 3. Olson ME, Harmon BG, Kollef MH. Silver-coated endotracheal tubes associated with reduced bacterial burden in the lungs of mechanically ventilated dogs. Chest. 2002;121(3): 863-870. 4. Rello J, Kollef M, Diaz E, et al. Reduced burden of bacterial airway colonization with a novel silver-coated endotracheal tube in a randomized multiple-center feasibility study. Crit Care Med. 2006;34(11):2766-2772.
Exhaled Nitric Oxide Measurements From Different Analyzers To the Editor: Adult studies report differences in the fraction of exhaled nitric oxide (FeNO) measured from different analyzers,1,2 but pediatric data are lacking. FeNO in children and adults measured by a singlebreath online technique using NIOX (Aerocrine; Solna, Sweden) and EcoMedics CLD88 (EcoMedics; Duernten, Switzerland) analyzers is reported. Institutional review board approval, patient consent, and parental consent, when appropriate, were obtained. The analyzers were in adjacent rooms with similar ambience (nitric oxide [NO] , 5 ppb) and calibrated according to manufacturers’ instructions. FeNO was measured in subjects who had the ability to maintain an expiratory flow of ⵑ 50 mLⲐs, using the two analyzers within 30 min of each other, in random order. Subjects inhaled NO-free air from a built-in NO filter in the NIOX analyzer and an NO-free air supply (DENOX-88) connected to the EcoMedics analyzer. Pressing a button on the DENOX-88 when inhalation began delivered continuous zero-NO air, which stopped on release of the button when exhalation began. Subjects did not wear nose clips and exhaled within 10% of 50 mLⲐs for 6 s. Mean FeNO from three measurements within 10% of each other and with valid plateaus was recorded from both analyzers.3 Primary analysis included FeNO from 60 subjects: 30 children, median age (range) 6.6 (4.3-13.6) years, and 30 adults, mean age 34.7 (22.7-51) years. Subanalysis included FeNO from 11 adults while exhaling at ⵑ 50 mLⲐs for 10 s from both analyzers and for 6 s with and without pressing the DENOX-88 button. CHEST / 138 / 5 / NOVEMBER, 2010
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on November 8, 2010 © 2010 American College of Chest Physicians
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Figure 1. Bland-Altman plots showing LA between NIOX and EcoMedics analyzers with different settings. A, 6-s exhalation in children with DENOX-88 button pressed. B, 6-s exhalation in adults with DENOX-88 button pressed. C, 10-s exhalation in adults with DENOX-88 button pressed. D, 6-s exhalation in adults without pressing DENOX-88 button. FeNO 5 fraction of exhaled nitric oxide; LA 5 limits of agreement. FeNO values were log-transformed and Bland-Altman plots used to determine limits of agreement (LA) between analyzers.4 All FeNO measurements were higher with NIOX than EcoMedics after 6-s exhalation. With the DENOX-88 button pressed, FeNO in children and adults demonstrated poor agreement between the two analyzers after 6 s (Figs 1A, 1B), but not after 10-s exhalation (Fig 1C). However, when the DENOX-88 button was not pressed, there was good agreement after 6-s exhalation (Fig 1D). Furthermore, the EcoMedics showed lower FeNO values at the preset 2- to 4-s plateau than adjusted 4- to 6-s plateau (mean difference, 16%; 95% LA, 23%, 55%). FeNO from EcoMedics after 6-s exhalation was significantly lower than FeNO from NIOX. It is likely that residual zero-NO air in the tubing dilutes the FeNO on releasing the DENOX-88 button when exhalation begins, increasing time to stable plateau. Moreover, EcoMedics analyzer is preset to read FeNO at 2- to 4-s plateau for 6-s exhalation, whereas NIOX analyzer is preset to choose the best plateau, which further increases differences. EcoMedics and NIOX analyzers have built-in NO filters, and if ambient NO is , 5 ppb, inhaling continuous zero-NO air is not
recommended, particularly in young children in whom the duration of exhalation is shorter. These findings highlight the importance of determining equipment-specific reference ranges and reporting true stable FeNO plateaus. Samatha Sonnappa, MD, PhD Cristina M. Bastardo, MD Andrew Bush, MD Paul Aurora, PhD London, England Affiliations: From the Portex Unit: Respiratory Medicine and Physiology (Drs Sonnappa, Bastardo, and Aurora), UCL Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust; and the Department of Paediatric Respiratory Medicine (Dr Bush), Royal Brompton Hospital and Imperial College. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
1276
Correspondence
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on November 8, 2010 © 2010 American College of Chest Physicians
Correspondence to: Samatha Sonnappa, MD, PhD, Portex Unit: Respiratory Medicine and Physiology, UCL Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust, 30, Guilford St, London, WC1N 1EH, England; e-mail: [email protected] © 2010 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/ site/misc/reprints.xhtml). DOI: 10.1378/chest.10-1061
companiesⲐorganizations whose products or services may be discussed in this article. Correspondence to: Seza Apiliogullari, MD, Selcuklu Medical Faculty, Department of Anesthesia and Intensive Care, Selcuk University, 42075, Konya, Turkey; e-mail: [email protected] © 2010 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.orgⲐ siteⲐmiscⲐreprints.xhtml). DOI: 10.1378/chest.10-1237
References References 1. Müller KC, Jörres RA, Magnussen H, Holz O. Comparison of exhaled nitric oxide analysers. Respir Med. 2005;99(5): 631-637. 2. Borrill Z, Clough D, Truman N, Morris J, Langley S, Singh D. A comparison of exhaled nitric oxide measurements performed using three different analysers. Respir Med. 2006;100(8): 1392-1396. 3. American Thoracic Society; European Respiratory Society. ATSⲐERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med. 2005;171(8):912-930. 4. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;1(8476):307-310.
1. Cowl CT. Use of antisialogogues in bronchoscopy. Chest. 2010;137(3):738. 2. Malik JA, Gupta D, Agarwal AN, Jindal SK. Anticholinergic premedication for flexible bronchoscopy: a randomized, double-blind, placebo-controlled study of atropine and glycopyrrolate. Chest. 2009;136(2):347-354. 3. Cowl CT, Prakash UBS, Kruger BR. The role of anticholinergics in bronchoscopy: a randomized clinical trial. Chest. 2000;118(1):188-192. 4. Apiliogullari S, Sener Y, Can S, Yegin Y, Tosun G, Celik JB. Effect of midazolam on salivary flow rate in children. J Selcuk U Dent Fac. 2010;19(2):3-7.
Response To the Editor:
Midazolam Can Decrease Salivation During Bronchoscopy To the Editor: We read with interest the response letter by Cowl1 (March 2010) to the study by Malik et al2 (August 2009) concerning the use of antisialogogues in broncoscopy. Based on the results of two previous studies, Cowl points out that antisecretory drugs do not result in clinically significant differences in cough or secretion control and can even be considered harmful. We have a major concern about the designs of the studies by Malik et al2 and Cowl et al.3 In a recent randomized, double-blind, placebo-controlled, prospective, quantitative study,4 we demonstrated that midazolam decreases both unstimulated and stimulated saliva flow rates (from 0.31 g/min to 0.18 g/min and from 0.78 g/min to 0.31 g/min, respectively, P 5 .00). The study included 40 children aged 9 to 12. Unstimulated and paraffin-stimulated saliva was collected from each child at baseline and 10 min after midazolam injection. This antisialogogue effect of midazolam can be responsible for the barely statistically significant difference in visual analog scale scores between placebo and the anticholinergic drugs observed in the studies by Malik et al2 and Cowl et al.3 We are of the opinion that future studies should exclude midazolam from the design when the antisialogue effects of anticholinergic drugs are assessed. Seza Apiliogullari, MD Jale Bengi Celik, MD Ates Duman, MD Konya, Turkey Affiliations: From the Selcuklu Medical Faculty, Department of Anesthesia and Intensive Care, Selcuk University. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any www.chestpubs.org
Dr Apiliogullari and colleagues express concerns about the design of two studies in CHEST (July 2000 and August 2009) that compared the use of antisialogogic agents as pretreatment strategies for adult bronchoscopy,1,2 citing that midazolam used concurrently for sedation can confound results because midazolam itself can also result in a reduction in secretions (as shown in their own recent study of a small cohort of pediatric patients [N 5 40] who underwent measured simulated salivary flow rates).3 Unfortunately, they seem to have missed the entire point of the prior discussion.4 The clinical question hinges on whether the use of antisialogogic agents such as atropine or glycopyrrolate is necessary prior to adult bronchoscopy to increase patient tolerance of the procedure or improve visualization of the airway anatomy. The use of these drugs adds cost to each procedure and, in some cases, can actually result in unnecessary, untoward side effects. It has been known for years that midazolam can, by itself or in combination with other sedative-analgesic agents, have some minor antisialogogic properties.5,6 The study by Apiliogullari et al3 further bolsters the argument that if there is indeed an antisialogogic effect from the use of midazolam, then the use of other secretion-reducing agents is clearly not needed. A clinically significant result in the initial randomized trials would have meant that the use of antisialogogic drugs provides a clear benefit to the bronchoscopist and patient in terms of the ability to inspect the airway and improves the overall comfort of the procedure above and beyond that provided without their use. That was not determined in those studies, even after randomization of . 1,000 patients between the two trials. Although Apiliogullari and colleagues3 should be congratulated for their efforts in quantitating salivary flow rates, that result does not alter the fact that the use of antisialogogues is unnecessary prior to routine adult bronchoscopy and does not ultimately affect the measured clinical endpoints, as outlined in the original randomized trials. Clayton T. Cowl, MD, FCCP Rochester, MN CHEST / 138 / 5 / NOVEMBER, 2010
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on November 8, 2010 © 2010 American College of Chest Physicians
1277