- Email: [email protected]
Sepsis, Lactate, and Oxygen Supply Dependence: Response
© 2012 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.12-0355
References 1. Jones AE. Point: should lactate clearance be substituted for central venous oxygen saturation as goals of early severe sepsis and septic shock therapy? Yes. Chest. 2011;140(6):1406-1408. 2. Rivers EP, Elkin R, Cannon CM. Counterpoint: should lactate clearance be substituted for central venous oxygen saturation as goals of early severe sepsis and septic shock therapy? No. Chest. 2011;140(6):1408-1413. 3. Rivers E, Nguyen B, Havstad S, et al; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368-1377.
Response To the Editor: We appreciate the interest of Dr Manthous in our Counterpoint Editorial 1 in CHEST that lactate clearance is an insufficient replacement for central venous oxygen saturation (Scvo2) as a goal in the treatment of severe sepsis and septic shock. Mathematic coupling results from using cardiac output to calculate both oxygen delivery (Do2) and oxygen consumption ( o2). This “artifact” can be overcome by directly measuring o2 by expired gas analysis.2 In both animal3 and human4 models of early septic shock, decreased Scvo2, intracardiac filling pressures, and cardiac output (hypodynamic state) give way to a hyperdynamic state after adequate resuscitation.4 Thus, a biphasic response in o2 (independent of measurement method) is part of the pathogenesis of this disease and is not an artifact.5 The critical Do2 and o2 (where anaerobic metabolism occurs) can vary because of comorbidities, such as chronic cardiopulmonary disorders.6 Normally, an acute hemodynamic deterioration leads to an increase in systemic oxygen extraction (decreased Scvo2). When this compensatory mechanism ceases to meet o2, lactate production occurs. However, the aforementioned comorbidities give rise to “alactemic” patients who can tolerate a pathologically low o2 before lactate production and are known as “metabolic hibernators.” Thus, lactate production is subject to significant individual variability. We agree with Dr Manthous that factors other than global Do2 dependency likely contribute to lactic acidosis (Table 1), making it an insensitive real-time indicator of tissue perfusion. It is important to note, however, that global estimates, such as Scvo2 or mixed venous oxygen saturation, may be insensitive to regional
Table 1—Causes of Persistent Lactate Elevation With Normalization of DO2 and ScvO2 Washout of accumulated lactate as perfusion increases Reduced clearance as a delayed manifestation of acute or chronic organ failure Sustained production due to inadequate source control Slowly resolving metabolic influences, such as circulating catecholamines Reduced oxygen uptake due to mitochondrial dysfunction or nonviable tissue beds Shunting of blood flow around still viable tissue Thiamine deficiency Do2 5 oxygen delivery; Scvo2 5 central venous oxygen saturation. www.chestpubs.org
imbalances at the microcirculatory level. Nonetheless, the macrocirculation and microcirculation are connected. Early reversible and correctable causes of global tissue hypoxia, such as arterial hypoxia, anemia, myocardial dysfunction, and increased oxygen demands, should be eliminated as early as possible. This physiologic and rational approach has been described for decades. Perhaps the dramatic outcome benefit in the Rivers et al7 trial, acknowledged by Dr Manthous, was at least partially due to this approach leading to recruitment of compromised microcirculatory beds by macrocirculatory resuscitation. In the United States, patients with sepsis wait an average of 5 h in the ED, which is similar to the Early Goal-Directed Therapy study.8 The origin of these patients is the ED for 52.4% (mortality of 27.6%), ICU for 12.8% (mortality of 41.3%), and hospital wards for 34.8% (mortality of 46.8%).9 These data indicate that sepsis is a hospitalwide disease. The mortality rates for acute myocardial infarction, stroke, and trauma were significantly reduced when the “golden hours” were applied. After 1 decade, a similar approach to sepsis, called early-goal directed therapy, has been robustly replicated in . 50 publications and thousands of patients. We agree that although pathogenic questions remain, they should not stand in the way of providing today’s best evidence-based care. Emanuel P. Rivers, MD, MPH, FCCP Detroit, MI Ronald Elkin, MD San Francisco, CA Chad Cannon, MD Kansas City, KA Affiliations: From the Department of Emergency Medicine and Surgery (Dr Rivers), Henry Ford Hospital, Wayne State University; the Department of Medicine (Dr Elkin), Pulmonary and Critical Care Medicine, California Pacific Medical Center; and the Department of Emergency Medicine (Dr Cannon), University of Kansas Hospital. Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: In the past 3 years, Dr Rivers has received funding from the National Institutes of Health, Aggennix AG, and Alere Corporation. He has been a one-time consultant for Aggennix AG; Eisai Co, Ltd; Idaho Technologies Inc; AstraZeneca; Massimo; and Sangard. He is a consultant to the Institute of Medicine, National Academies. The Early Goal-Directed Therapy (EGDT) study was performed without external industry support or funding of any kind. Any intellectual properties associated with Dr Rivers’ research are exclusively owned by Henry Ford Hospital. Dr Rivers holds no past or present intellectual properties and has never received royalties or stock interest related to technologies in EGDT research and practice. Dr Elkin has received funding from the Gordon and Betty Moore Foundation, has been a one-time consultant for Eisai Co, Ltd, and participated on the speaker’s bureau for Edwards Lifesciences LLC on three occasions. Dr Cannon has been a one-time consultant for Aggennix AG and Eisai Co, Ltd. Correspondence to: Emanuel P. Rivers, MD, MPH, FCCP, Department of Emergency Medicine, Wayne State University, 270-Clara Ford Pavilion, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI 48202; e-mail: [email protected] © 2012 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.12-0740
References 1. Rivers EP, Elkin R, Cannon CM. Counterpoint: should lactate clearance be substituted for central venous oxygen saturation as goals of early severe sepsis and septic shock therapy? No. Chest. 2011;140(6):1408-1413. 2. Hanique G, Dugernier T, Laterre PF, Dougnac A, Roeseler J, Reynaert MS. Significance of pathologic oxygen supply dependency in critically ill patients: comparison between CHEST / 141 / 5 / MAY, 2012
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on May 3, 2012 © 2012 American College of Chest Physicians
1363
3.
4. 5. 6. 7. 8. 9.
measured and calculated methods. Intensive Care Med. 1994; 20(1):12-18. Rosário AL, Park M, Brunialti MK, et al. SvO(2)-guided resuscitation for experimental septic shock: effects of fluid infusion and dobutamine on hemodynamics, inflammatory response, and cardiovascular oxidative stress. Shock. 2011;36(6):604-612. Friedman G, De Backer D, Shahla M, Vincent JL. Oxygen supply dependency can characterize septic shock. Intensive Care Med. 1998;24(2):118-123. Kasnitz P, Druger GL, Yorra F, Simmons DH. Mixed venous oxygen tension and hyperlactatemia. Survival in severe cardiopulmonary disease. JAMA. 1976;236(6):570-574. Rady M, Jafry S, Rivers E, Alexander M. Characterization of systemic oxygen transport in end-stage chronic congestive heart failure. Am Heart J. 1994;128(4):774-781. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368-1377. Wang HE, Shapiro NI, Angus DC, Yealy DM. National estimates of severe sepsis in United States emergency departments. Crit Care Med. 2007;35(8):1928-1936. Levy MM, Dellinger RP, Townsend SR, et al; Surviving Sepsis Campaign. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med. 2010;38(2):367-374.
Aerosols and Details To the Editor: Although I hate to “rain on the parade” of Khorfan and colleagues,1 it is possible, if not likely, that methodologic nuances of aerosol delivery undermine the validity of their conclusions in their article in CHEST (December 2011), which states that “nebulized albuterol does not cause significant tachycardia or tachyarrhythmias.”1 In delivery of therapeutic aerosols, the devil is in the details, and the “Materials and Methods” section in the article does not provide any information regarding the aerosol delivery techniques used for study patients.1 This is especially true in patients who are mechanically ventilated, who composed . 50% of the sample, in which we proved that veritably none of 100 puffs of albuterol was delivered to patients’ airways.2 Multiple variables, including circuit design, humidification, flow rates, and tidal volumes, impact aerosol delivery to critically ill patients.3 Poor techniques can lead to the illusion of treatment (ie, doses administered but not delivered to the airways because they rain out in the circuit). Accordingly, this study should be interpreted cautiously, because no evidence (eg, of reduced airway resistance) is provided to support that any of the administered doses were delivered. Constantine A. Manthous, MD, FCCP Bridgeport, CT Affiliations: From the Bridgeport Hospital and Yale University School of Medicine. Financial/nonfinancial disclosures: The author has reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: Constantine A. Manthous, MD, FCCP, Bridgeport Hospital and Yale University School of Medicine, 267 Grant St, Bridgeport, CT 06610; e-mail: [email protected] © 2012 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.11-3118
References 1. Khorfan FM, Smith P, Watt S, Barber KR. Effects of nebulized bronchodilator therapy on heart rate and arrhythmias in critically ill adult patients. Chest. 2011;140(6):1466-1472. 2. Manthous CA, Hall JB, Schmidt GA, Wood LD. Metereddose inhaler versus nebulized albuterol in mechanically ventilated patients. Am Rev Respir Dis. 1993;148(6 pt 1):1567-1570. 3. Manthous CA, Hall JB. Administration of therapeutic aerosols to mechanically ventilated patients. Chest. 1994;106(2): 560-571.
Response To the Editor: We thank Dr Manthous for his interest in our recent article in CHEST1 and appreciate his comments. Our article concluded that the use of short-acting b-agonist albuterol and a short-acting anticholinergic ipratropium bromide in the recommended commonly used doses and frequency appear not to have a clinically significant detrimental effect on heart rate and rhythm.1 The study was a real-life bedside clinical study in the ICU. Our work was not to investigate the most effective dose or delivery method of aerosolized bronchodilator in this population. Most patients had airflow obstruction, but some had ARDS and other respiratory failures requiring mechanical ventilation. Metereddose inhalers (MDIs) were not used in this study. All treatments were previously written by attending physicians to be given by jet nebulizers. The dose of albuterol sulfate was 2.5 mg in a total volume 3 mL (in addition to ipratropium bromide 500 mg), alternating with two different doses of levalbuterol, 0.63 mg and 1.25 mg. These treatments were delivered every 4 to 6 h. The jet nebulizer used was the Micro Mist Nebulizer (Hudson RCI). For patients receiving mechanical ventilation, the Valved Tee Adapter (Thayer Medical Corporation) was used with the Hudson nebulizer. We used the modified protocol of Hess et al as described by Dhand and Tobin2 to deliver the nebulized bronchodilator treatment. We do not routinely measure airway resistance by the rapid airway occlusion method. We observed peek airway pressure, resistive airway pressure, and changes in auto-positive endexpiratory pressure. All patients were given the same dose and intervals. This is the most common clinically relevant method used in ICUs currently. Dhand and Tobin2 noted that both nebulizers and MDIs are effective at delivering aerosols to the lower respiratory tract of patients receiving mechanical ventilation when careful attention is given to technique. Jantz and Collop3 concluded that in patients receiving mechanical ventilation, four to 10 puffs from an MDI and 2.5 to 5.0 mg of albuterol through a small volume nebulizer every 4 h is the most recommended dose. Sims4 noted that clinical trial evidence suggests that when used with the proper technique, various devices are equally effective. Our conclusion agrees with that of Dhand and Tobin2 that adverse cardiac effects are unlikely to occur with doses recommended in clinical practice. Much higher doses (7.5-15.0 mg albuterol delivered through a small volume nebulizer), as Dr Manthous has demonstrated, could cause sinus tachycardia and premature beats.5 However, we consider these doses to be experimental rather than clinically recommended. Fahim M. Khorfan, MD, FCCP Kimberly R. Barber, PhD Grand Blanc, MI
1364
Correspondence
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on May 3, 2012 © 2012 American College of Chest Physicians
References 1. Jones AE. Point: should lactate clearance be substituted for central venous oxygen saturation as goals of early severe sepsis and septic shock therapy? Yes. Chest. 2011;140(6):1406-1408. 2. Rivers EP, Elkin R, Cannon CM. Counterpoint: should lactate clearance be substituted for central venous oxygen saturation as goals of early severe sepsis and septic shock therapy? No. Chest. 2011;140(6):1408-1413. 3. Rivers E, Nguyen B, Havstad S, et al; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368-1377.
Response To the Editor: We appreciate the interest of Dr Manthous in our Counterpoint Editorial 1 in CHEST that lactate clearance is an insufficient replacement for central venous oxygen saturation (Scvo2) as a goal in the treatment of severe sepsis and septic shock. Mathematic coupling results from using cardiac output to calculate both oxygen delivery (Do2) and oxygen consumption ( o2). This “artifact” can be overcome by directly measuring o2 by expired gas analysis.2 In both animal3 and human4 models of early septic shock, decreased Scvo2, intracardiac filling pressures, and cardiac output (hypodynamic state) give way to a hyperdynamic state after adequate resuscitation.4 Thus, a biphasic response in o2 (independent of measurement method) is part of the pathogenesis of this disease and is not an artifact.5 The critical Do2 and o2 (where anaerobic metabolism occurs) can vary because of comorbidities, such as chronic cardiopulmonary disorders.6 Normally, an acute hemodynamic deterioration leads to an increase in systemic oxygen extraction (decreased Scvo2). When this compensatory mechanism ceases to meet o2, lactate production occurs. However, the aforementioned comorbidities give rise to “alactemic” patients who can tolerate a pathologically low o2 before lactate production and are known as “metabolic hibernators.” Thus, lactate production is subject to significant individual variability. We agree with Dr Manthous that factors other than global Do2 dependency likely contribute to lactic acidosis (Table 1), making it an insensitive real-time indicator of tissue perfusion. It is important to note, however, that global estimates, such as Scvo2 or mixed venous oxygen saturation, may be insensitive to regional
Table 1—Causes of Persistent Lactate Elevation With Normalization of DO2 and ScvO2 Washout of accumulated lactate as perfusion increases Reduced clearance as a delayed manifestation of acute or chronic organ failure Sustained production due to inadequate source control Slowly resolving metabolic influences, such as circulating catecholamines Reduced oxygen uptake due to mitochondrial dysfunction or nonviable tissue beds Shunting of blood flow around still viable tissue Thiamine deficiency Do2 5 oxygen delivery; Scvo2 5 central venous oxygen saturation. www.chestpubs.org
imbalances at the microcirculatory level. Nonetheless, the macrocirculation and microcirculation are connected. Early reversible and correctable causes of global tissue hypoxia, such as arterial hypoxia, anemia, myocardial dysfunction, and increased oxygen demands, should be eliminated as early as possible. This physiologic and rational approach has been described for decades. Perhaps the dramatic outcome benefit in the Rivers et al7 trial, acknowledged by Dr Manthous, was at least partially due to this approach leading to recruitment of compromised microcirculatory beds by macrocirculatory resuscitation. In the United States, patients with sepsis wait an average of 5 h in the ED, which is similar to the Early Goal-Directed Therapy study.8 The origin of these patients is the ED for 52.4% (mortality of 27.6%), ICU for 12.8% (mortality of 41.3%), and hospital wards for 34.8% (mortality of 46.8%).9 These data indicate that sepsis is a hospitalwide disease. The mortality rates for acute myocardial infarction, stroke, and trauma were significantly reduced when the “golden hours” were applied. After 1 decade, a similar approach to sepsis, called early-goal directed therapy, has been robustly replicated in . 50 publications and thousands of patients. We agree that although pathogenic questions remain, they should not stand in the way of providing today’s best evidence-based care. Emanuel P. Rivers, MD, MPH, FCCP Detroit, MI Ronald Elkin, MD San Francisco, CA Chad Cannon, MD Kansas City, KA Affiliations: From the Department of Emergency Medicine and Surgery (Dr Rivers), Henry Ford Hospital, Wayne State University; the Department of Medicine (Dr Elkin), Pulmonary and Critical Care Medicine, California Pacific Medical Center; and the Department of Emergency Medicine (Dr Cannon), University of Kansas Hospital. Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: In the past 3 years, Dr Rivers has received funding from the National Institutes of Health, Aggennix AG, and Alere Corporation. He has been a one-time consultant for Aggennix AG; Eisai Co, Ltd; Idaho Technologies Inc; AstraZeneca; Massimo; and Sangard. He is a consultant to the Institute of Medicine, National Academies. The Early Goal-Directed Therapy (EGDT) study was performed without external industry support or funding of any kind. Any intellectual properties associated with Dr Rivers’ research are exclusively owned by Henry Ford Hospital. Dr Rivers holds no past or present intellectual properties and has never received royalties or stock interest related to technologies in EGDT research and practice. Dr Elkin has received funding from the Gordon and Betty Moore Foundation, has been a one-time consultant for Eisai Co, Ltd, and participated on the speaker’s bureau for Edwards Lifesciences LLC on three occasions. Dr Cannon has been a one-time consultant for Aggennix AG and Eisai Co, Ltd. Correspondence to: Emanuel P. Rivers, MD, MPH, FCCP, Department of Emergency Medicine, Wayne State University, 270-Clara Ford Pavilion, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI 48202; e-mail: [email protected] © 2012 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.12-0740
References 1. Rivers EP, Elkin R, Cannon CM. Counterpoint: should lactate clearance be substituted for central venous oxygen saturation as goals of early severe sepsis and septic shock therapy? No. Chest. 2011;140(6):1408-1413. 2. Hanique G, Dugernier T, Laterre PF, Dougnac A, Roeseler J, Reynaert MS. Significance of pathologic oxygen supply dependency in critically ill patients: comparison between CHEST / 141 / 5 / MAY, 2012
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on May 3, 2012 © 2012 American College of Chest Physicians
1363
3.
4. 5. 6. 7. 8. 9.
measured and calculated methods. Intensive Care Med. 1994; 20(1):12-18. Rosário AL, Park M, Brunialti MK, et al. SvO(2)-guided resuscitation for experimental septic shock: effects of fluid infusion and dobutamine on hemodynamics, inflammatory response, and cardiovascular oxidative stress. Shock. 2011;36(6):604-612. Friedman G, De Backer D, Shahla M, Vincent JL. Oxygen supply dependency can characterize septic shock. Intensive Care Med. 1998;24(2):118-123. Kasnitz P, Druger GL, Yorra F, Simmons DH. Mixed venous oxygen tension and hyperlactatemia. Survival in severe cardiopulmonary disease. JAMA. 1976;236(6):570-574. Rady M, Jafry S, Rivers E, Alexander M. Characterization of systemic oxygen transport in end-stage chronic congestive heart failure. Am Heart J. 1994;128(4):774-781. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368-1377. Wang HE, Shapiro NI, Angus DC, Yealy DM. National estimates of severe sepsis in United States emergency departments. Crit Care Med. 2007;35(8):1928-1936. Levy MM, Dellinger RP, Townsend SR, et al; Surviving Sepsis Campaign. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med. 2010;38(2):367-374.
Aerosols and Details To the Editor: Although I hate to “rain on the parade” of Khorfan and colleagues,1 it is possible, if not likely, that methodologic nuances of aerosol delivery undermine the validity of their conclusions in their article in CHEST (December 2011), which states that “nebulized albuterol does not cause significant tachycardia or tachyarrhythmias.”1 In delivery of therapeutic aerosols, the devil is in the details, and the “Materials and Methods” section in the article does not provide any information regarding the aerosol delivery techniques used for study patients.1 This is especially true in patients who are mechanically ventilated, who composed . 50% of the sample, in which we proved that veritably none of 100 puffs of albuterol was delivered to patients’ airways.2 Multiple variables, including circuit design, humidification, flow rates, and tidal volumes, impact aerosol delivery to critically ill patients.3 Poor techniques can lead to the illusion of treatment (ie, doses administered but not delivered to the airways because they rain out in the circuit). Accordingly, this study should be interpreted cautiously, because no evidence (eg, of reduced airway resistance) is provided to support that any of the administered doses were delivered. Constantine A. Manthous, MD, FCCP Bridgeport, CT Affiliations: From the Bridgeport Hospital and Yale University School of Medicine. Financial/nonfinancial disclosures: The author has reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: Constantine A. Manthous, MD, FCCP, Bridgeport Hospital and Yale University School of Medicine, 267 Grant St, Bridgeport, CT 06610; e-mail: [email protected] © 2012 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.11-3118
References 1. Khorfan FM, Smith P, Watt S, Barber KR. Effects of nebulized bronchodilator therapy on heart rate and arrhythmias in critically ill adult patients. Chest. 2011;140(6):1466-1472. 2. Manthous CA, Hall JB, Schmidt GA, Wood LD. Metereddose inhaler versus nebulized albuterol in mechanically ventilated patients. Am Rev Respir Dis. 1993;148(6 pt 1):1567-1570. 3. Manthous CA, Hall JB. Administration of therapeutic aerosols to mechanically ventilated patients. Chest. 1994;106(2): 560-571.
Response To the Editor: We thank Dr Manthous for his interest in our recent article in CHEST1 and appreciate his comments. Our article concluded that the use of short-acting b-agonist albuterol and a short-acting anticholinergic ipratropium bromide in the recommended commonly used doses and frequency appear not to have a clinically significant detrimental effect on heart rate and rhythm.1 The study was a real-life bedside clinical study in the ICU. Our work was not to investigate the most effective dose or delivery method of aerosolized bronchodilator in this population. Most patients had airflow obstruction, but some had ARDS and other respiratory failures requiring mechanical ventilation. Metereddose inhalers (MDIs) were not used in this study. All treatments were previously written by attending physicians to be given by jet nebulizers. The dose of albuterol sulfate was 2.5 mg in a total volume 3 mL (in addition to ipratropium bromide 500 mg), alternating with two different doses of levalbuterol, 0.63 mg and 1.25 mg. These treatments were delivered every 4 to 6 h. The jet nebulizer used was the Micro Mist Nebulizer (Hudson RCI). For patients receiving mechanical ventilation, the Valved Tee Adapter (Thayer Medical Corporation) was used with the Hudson nebulizer. We used the modified protocol of Hess et al as described by Dhand and Tobin2 to deliver the nebulized bronchodilator treatment. We do not routinely measure airway resistance by the rapid airway occlusion method. We observed peek airway pressure, resistive airway pressure, and changes in auto-positive endexpiratory pressure. All patients were given the same dose and intervals. This is the most common clinically relevant method used in ICUs currently. Dhand and Tobin2 noted that both nebulizers and MDIs are effective at delivering aerosols to the lower respiratory tract of patients receiving mechanical ventilation when careful attention is given to technique. Jantz and Collop3 concluded that in patients receiving mechanical ventilation, four to 10 puffs from an MDI and 2.5 to 5.0 mg of albuterol through a small volume nebulizer every 4 h is the most recommended dose. Sims4 noted that clinical trial evidence suggests that when used with the proper technique, various devices are equally effective. Our conclusion agrees with that of Dhand and Tobin2 that adverse cardiac effects are unlikely to occur with doses recommended in clinical practice. Much higher doses (7.5-15.0 mg albuterol delivered through a small volume nebulizer), as Dr Manthous has demonstrated, could cause sinus tachycardia and premature beats.5 However, we consider these doses to be experimental rather than clinically recommended. Fahim M. Khorfan, MD, FCCP Kimberly R. Barber, PhD Grand Blanc, MI
1364
Correspondence
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on May 3, 2012 © 2012 American College of Chest Physicians