an ANA test “positive” for lupus or a rheumatoid factor as “positive for rheumatoid arthritis,” nor should heparin antibodies be denoted as “positive” or “negative.” Rather, the numerical titer should be reported and interpreted by the physician in the clinical context of his patient. So then, how do you diagnose HIT in 2015? • Consider HIT whenever a patient exposed to heparin has an unexpected fall in platelet count, new thrombotic events, or both. • Timing is critical. HIT occurs 5 to 12 days after beginning heparin exposure (but delayed onset with recent exposure or rapid onset with reexposure should also be considered). • The test is your friend, but only when ordered appropriately with reasonable suspicion for HIT (it is not for “screening”), and it must be interpreted appropriately. Low titer (less than OD 1.0) almost always rules out HIT; moderate titer must be interpreted in the clinical context. In 2015, there is much to celebrate about the occurrence of HIT. Even as awareness and concern peak, the incidence of true HIT is declining, owing largely to the decreasing use of unfractionated heparin (more low-molecularweight heparin and nonheparin anticoagulants are being used) and the downturn in cardiovascular surgeries. Safer and more refined anticoagulant strategies for HIT are coming to the fore, and even nonanticoagulant interventions are under study.12 Diagnostic assays are emerging with higher sensitivity/specificity profiles and real-time availability,13,14 but it remains difficult to conceive of a test that would not require careful consideration of when to order it and how to interpret it. If we can address the overdiagnosis problem, some of we HIT-ophiles may begin to contemplate retirement.
References 1. Rice L. Heparin-induced thrombocytopenia in the cardiac patient: 10 points to help the physician. Methodist Debakey Cardiovasc J. 2011;7(4):6-9. 2. Nader ND, Khadra WZ, Reich NT, Bacon DR, Salerno TA, Panos AL. Blood product use in cardiac revascularization: comparison of on- and off-pump techniques. Ann Thorac Surg. 1999;68(5): 1640-1643. 3. Rice L, Huffman DM, Waddell CC, Luper WE, Udden MM, Levine ML. Therapy of thromboembolic disease: the heparin thrombocytopenia/ thrombosis syndrome. In: Thrombosis, Anticoagulants and Antiplatelet Agents in Clinical Practice. New York, NY: Park Row Publishers; 1988:31-36. 4. Rice L. Cases of heparin-induced thrombocytopenia elucidate the syndrome. Chest. 2005;127(2_suppl):21S-26S. 5. Warkentin TE, Sheppard JI, Moore JC, Sigouin CS, Kelton JG. Quantitative interpretation of optical density measurements using PF4-dependent enzyme-immunoassays. J Thromb Haemost. 2008;6(8):1304-1312.
journal.publications.chestnet.org
6. Rice L. Heparin-induced thrombocytopenia: myths and misconceptions (that will cause trouble for you and your patient). Arch Intern Med. 2004;164(18):1961-1964. 7. Cuker A, Gimotty PA, Crowther MA, Warkentin TE. Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood. 2012;120(20):4160-4167. 8. Cuker A, Cines DB. How I treat heparin-induced thrombocytopenia. Blood. 2012;119(10):2209-2218. 9. Smythe MA, Koerber JM, Fitzgerald M, Mattson JC. The financial impact of heparin-induced thrombocytopenia. Chest. 2008;134(3): 568-573. 10. Chan CM, Woods CJ, Warkentin TE, Sheppard J-AI, Shorr AF. The role for optical density in heparin-induced thrombocytopenia: a cohort study. Chest. 2015;148(1):55-61. 11. Wanat M, Fitousis K, Hall J, Rice L. PF4/heparin antibody testing and treatment of heparin-induced thrombocytopenia in the intensive care unit. Clin Appl Thromb Hemost. 2013;19(3):297-302. 12. Joglekar MV, Quintana Diez PM, Marcus S, et al. Disruption of PF4/H multimolecular complex formation with a minimally anticoagulant heparin (ODSH). Thromb Haemost. 2012;107(4):717-725. 13. Cuker A, Rux AH, Hinds JL, et al. Novel diagnostic assays for heparin-induced thrombocytopenia. Blood. 2013;121(18):3727-3732. 14. Padmanabhan A, Jones CG, Bougie DW, et al. Heparin-independent, PF4-dependent binding of HIT antibodies to platelets: implications for HIT pathogenesis. Blood. 2015;125(1):155-161.
Size and How You Measure It Matters Arthur P. Wheeler, MD, FCCP Nashville, TN
For many years, a practice known as vanity sizing has been increasing the physical dimensions of women’s clothing relative to its nominal size, resulting from the lack of an industry standard that is adhered to.1 Vanity sizing impedes the reliable selection of properly fitting garments without donning them since similarly labeled clothing may be proportioned using different scales and vary significantly in size. An analogous predicament faces clinicians and researchers when they attempt to properly tailor tidal volume for a patient with ARDS who is mechanically ventilated. Unlike fashion where actual weight determines fit, tidal volumes are best indexed to AFFILIATIONS: From the Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center. FINANCIAL/NONFINANCIAL DISCLOSURES: The author has reported to CHEST the following conflicts of interest: Dr Wheeler was an investigator in the National Institutes of Health, National Heart, Lung, and Blood Institute ARDS Network. CORRESPONDENCE TO: Arthur P. Wheeler, MD, FCCP, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, T-1210 Medical Center North, Nashville, TN 37232-2650; e-mail: [email protected] © 2015 AMERICAN COLLEGE OF CHEST PHYSICIANS. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.15-0395
3
predicted, not actual, body weight; being overweight does not grow lung and being underweight does not shrink lung. Yet, even knowing the major determinants of predicted body weight (height, age, and sex), there is no accepted standard for predicted body weight calculation and, in the past, researchers have used several different equations.2-5 In this issue of CHEST (see page 73), Linares-Perdomo and colleagues6 concisely illustrate how poorly correlated and widely discrepant tidal volumes can be when calculated using several different published prediction equations despite identical input variables. The authors compare recommended tidal volumes across a broad range of clinically relevant heights and ages for both sexes using three equations used in clinical trials.2-5 They found that the equation used by the National Institutes of Health/National Heart, Lung, and Blood Institute’s ARDS Network overall yielded the lowest predicted tidal volumes.3 Furthermore, at the edges of the age and height envelope, differences among methods ranged from 15% to 30% and were greatest for older, shorter subjects, especially women. It is to be expected that predicted body weights and the corresponding tidal volumes would differ when using different equations, but the magnitude of the variance is impressive, especially considering that the variance is not uniformly distributed but is rather disproportionately biased toward certain phenotypes such as the diminutive older patient. Two questions are likely to be asked about this report. First, are these calculated differences really relevant? And second, might the authors’ findings serve to explain why one clinical trial of lower tidal volume in ARDS might be successful and another not? The latter question cannot be answered with certainty, but use of an overall lower tidal volume is one plausible explanation for the lower mortality and shorter time on ventilation seen in the ARDS Network trial but not in all studies of lung protective ventilation. One skeptical of this possibility could argue that if the tidal volume derived from a given equation were too large it would be reduced when the resulting plateau pressure exceeded the recommended target. Unfortunately, in practice, plateau pressures are not always measured or acted upon, and lower tidal volumes might offer benefits even if the plateau pressure did not exceed a recommended threshold. The answer to the first question, however, is almost certainly yes; tidal volume differences of 30% could amount to . 100 mL of inflation for some patients and almost certainly could contribute to volutrauma in vulnerable individuals. Fortunately, lower, or perhaps more accurately described
4 Editorials
as normal, tidal volumes determined using predicted body weight have now become widely accepted for care of many patients who are ventilated with and without ARDS.7,8 But the question remains: Which equation should be used? Undoubtedly, the authors’ recommendation that the predicted body weight equations used by the ARDS Network become the “industry standard” will generate controversy among some readers who will claim that we do not know those equations are the “best.” While it is clear that we do not know if the equations used by the ARDS Network will be the best choice forever, it is clear that for now, they are the best we know.
References 1. Clifford S. One size fits nobody: seeking a steady 4 or a 10. New York Times. April 24, 2011. http://www.nytimes.com/2011/04/25/ business/25sizing.html?_r50. Accessed February 17, 2015. 2. Stewart TE, Meade MO, Cook DJ, et al; Pressure- and VolumeLimited Ventilation Strategy Group. Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. N Engl J Med. 1998;338(6):355-361. 3. Brower RG, Shanholtz CB, Fessler HE, et al. Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients. Crit Care Med. 1999;27(8):1492-1498. 4. Morris AH, Wallace CJ, Menlove RL, et al. Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome. Am J Respir Crit Care Med. 1994;149(2 pt 1):295-305. 5. East TD, Heermann LK, Bradshaw RL, et al. Efficacy of computerized decision support for mechanical ventilation: results of a prospective multi-center randomized trial. Proc AMIA Symp. 1999;251-255. 6. Linares-Perdomo O, East TD, Brower R, Morris AH. Standardizing predicted body weight equations for mechanical ventilation tidal volume settings. Chest. 2015;148(1):73-78. 7. Serpa Neto A, Cardoso SO, Manetta JA, et al. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA. 2012;308(16):1651-1659. 8. Esteban A, Frutos-Vivar F, Muriel A, et al. Evolution of mortality over time in patients receiving mechanical ventilation. Am J Respir Crit Care Med. 2013;188(2):220-230.
Admitting What We Do Not Know About Pneumonia Readmissions Andrew F. Shorr, MD, MPH, FCCP Washington, DC Marya D. Zilberberg, MD, MPH, FCCP Goshen, MA
Section 3025 of the Affordable Care Act created the Hospital Readmission Reduction Program (HRRP).1 Under the HRRP, the Centers for Medicare & Medicaid Services (CMS) is charged with working to reduce hospital readmissions for select conditions. The initial
[
1 4 8 # 1 C H E S T J U LY 2 0 1 5
]
References 1. Rice L. Heparin-induced thrombocytopenia in the cardiac patient: 10 points to help the physician. Methodist Debakey Cardiovasc J. 2011;7(4):6-9. 2. Nader ND, Khadra WZ, Reich NT, Bacon DR, Salerno TA, Panos AL. Blood product use in cardiac revascularization: comparison of on- and off-pump techniques. Ann Thorac Surg. 1999;68(5): 1640-1643. 3. Rice L, Huffman DM, Waddell CC, Luper WE, Udden MM, Levine ML. Therapy of thromboembolic disease: the heparin thrombocytopenia/ thrombosis syndrome. In: Thrombosis, Anticoagulants and Antiplatelet Agents in Clinical Practice. New York, NY: Park Row Publishers; 1988:31-36. 4. Rice L. Cases of heparin-induced thrombocytopenia elucidate the syndrome. Chest. 2005;127(2_suppl):21S-26S. 5. Warkentin TE, Sheppard JI, Moore JC, Sigouin CS, Kelton JG. Quantitative interpretation of optical density measurements using PF4-dependent enzyme-immunoassays. J Thromb Haemost. 2008;6(8):1304-1312.
journal.publications.chestnet.org
6. Rice L. Heparin-induced thrombocytopenia: myths and misconceptions (that will cause trouble for you and your patient). Arch Intern Med. 2004;164(18):1961-1964. 7. Cuker A, Gimotty PA, Crowther MA, Warkentin TE. Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood. 2012;120(20):4160-4167. 8. Cuker A, Cines DB. How I treat heparin-induced thrombocytopenia. Blood. 2012;119(10):2209-2218. 9. Smythe MA, Koerber JM, Fitzgerald M, Mattson JC. The financial impact of heparin-induced thrombocytopenia. Chest. 2008;134(3): 568-573. 10. Chan CM, Woods CJ, Warkentin TE, Sheppard J-AI, Shorr AF. The role for optical density in heparin-induced thrombocytopenia: a cohort study. Chest. 2015;148(1):55-61. 11. Wanat M, Fitousis K, Hall J, Rice L. PF4/heparin antibody testing and treatment of heparin-induced thrombocytopenia in the intensive care unit. Clin Appl Thromb Hemost. 2013;19(3):297-302. 12. Joglekar MV, Quintana Diez PM, Marcus S, et al. Disruption of PF4/H multimolecular complex formation with a minimally anticoagulant heparin (ODSH). Thromb Haemost. 2012;107(4):717-725. 13. Cuker A, Rux AH, Hinds JL, et al. Novel diagnostic assays for heparin-induced thrombocytopenia. Blood. 2013;121(18):3727-3732. 14. Padmanabhan A, Jones CG, Bougie DW, et al. Heparin-independent, PF4-dependent binding of HIT antibodies to platelets: implications for HIT pathogenesis. Blood. 2015;125(1):155-161.
Size and How You Measure It Matters Arthur P. Wheeler, MD, FCCP Nashville, TN
For many years, a practice known as vanity sizing has been increasing the physical dimensions of women’s clothing relative to its nominal size, resulting from the lack of an industry standard that is adhered to.1 Vanity sizing impedes the reliable selection of properly fitting garments without donning them since similarly labeled clothing may be proportioned using different scales and vary significantly in size. An analogous predicament faces clinicians and researchers when they attempt to properly tailor tidal volume for a patient with ARDS who is mechanically ventilated. Unlike fashion where actual weight determines fit, tidal volumes are best indexed to AFFILIATIONS: From the Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center. FINANCIAL/NONFINANCIAL DISCLOSURES: The author has reported to CHEST the following conflicts of interest: Dr Wheeler was an investigator in the National Institutes of Health, National Heart, Lung, and Blood Institute ARDS Network. CORRESPONDENCE TO: Arthur P. Wheeler, MD, FCCP, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, T-1210 Medical Center North, Nashville, TN 37232-2650; e-mail: [email protected] © 2015 AMERICAN COLLEGE OF CHEST PHYSICIANS. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.15-0395
3
predicted, not actual, body weight; being overweight does not grow lung and being underweight does not shrink lung. Yet, even knowing the major determinants of predicted body weight (height, age, and sex), there is no accepted standard for predicted body weight calculation and, in the past, researchers have used several different equations.2-5 In this issue of CHEST (see page 73), Linares-Perdomo and colleagues6 concisely illustrate how poorly correlated and widely discrepant tidal volumes can be when calculated using several different published prediction equations despite identical input variables. The authors compare recommended tidal volumes across a broad range of clinically relevant heights and ages for both sexes using three equations used in clinical trials.2-5 They found that the equation used by the National Institutes of Health/National Heart, Lung, and Blood Institute’s ARDS Network overall yielded the lowest predicted tidal volumes.3 Furthermore, at the edges of the age and height envelope, differences among methods ranged from 15% to 30% and were greatest for older, shorter subjects, especially women. It is to be expected that predicted body weights and the corresponding tidal volumes would differ when using different equations, but the magnitude of the variance is impressive, especially considering that the variance is not uniformly distributed but is rather disproportionately biased toward certain phenotypes such as the diminutive older patient. Two questions are likely to be asked about this report. First, are these calculated differences really relevant? And second, might the authors’ findings serve to explain why one clinical trial of lower tidal volume in ARDS might be successful and another not? The latter question cannot be answered with certainty, but use of an overall lower tidal volume is one plausible explanation for the lower mortality and shorter time on ventilation seen in the ARDS Network trial but not in all studies of lung protective ventilation. One skeptical of this possibility could argue that if the tidal volume derived from a given equation were too large it would be reduced when the resulting plateau pressure exceeded the recommended target. Unfortunately, in practice, plateau pressures are not always measured or acted upon, and lower tidal volumes might offer benefits even if the plateau pressure did not exceed a recommended threshold. The answer to the first question, however, is almost certainly yes; tidal volume differences of 30% could amount to . 100 mL of inflation for some patients and almost certainly could contribute to volutrauma in vulnerable individuals. Fortunately, lower, or perhaps more accurately described
4 Editorials
as normal, tidal volumes determined using predicted body weight have now become widely accepted for care of many patients who are ventilated with and without ARDS.7,8 But the question remains: Which equation should be used? Undoubtedly, the authors’ recommendation that the predicted body weight equations used by the ARDS Network become the “industry standard” will generate controversy among some readers who will claim that we do not know those equations are the “best.” While it is clear that we do not know if the equations used by the ARDS Network will be the best choice forever, it is clear that for now, they are the best we know.
References 1. Clifford S. One size fits nobody: seeking a steady 4 or a 10. New York Times. April 24, 2011. http://www.nytimes.com/2011/04/25/ business/25sizing.html?_r50. Accessed February 17, 2015. 2. Stewart TE, Meade MO, Cook DJ, et al; Pressure- and VolumeLimited Ventilation Strategy Group. Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. N Engl J Med. 1998;338(6):355-361. 3. Brower RG, Shanholtz CB, Fessler HE, et al. Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients. Crit Care Med. 1999;27(8):1492-1498. 4. Morris AH, Wallace CJ, Menlove RL, et al. Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome. Am J Respir Crit Care Med. 1994;149(2 pt 1):295-305. 5. East TD, Heermann LK, Bradshaw RL, et al. Efficacy of computerized decision support for mechanical ventilation: results of a prospective multi-center randomized trial. Proc AMIA Symp. 1999;251-255. 6. Linares-Perdomo O, East TD, Brower R, Morris AH. Standardizing predicted body weight equations for mechanical ventilation tidal volume settings. Chest. 2015;148(1):73-78. 7. Serpa Neto A, Cardoso SO, Manetta JA, et al. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA. 2012;308(16):1651-1659. 8. Esteban A, Frutos-Vivar F, Muriel A, et al. Evolution of mortality over time in patients receiving mechanical ventilation. Am J Respir Crit Care Med. 2013;188(2):220-230.
Admitting What We Do Not Know About Pneumonia Readmissions Andrew F. Shorr, MD, MPH, FCCP Washington, DC Marya D. Zilberberg, MD, MPH, FCCP Goshen, MA
Section 3025 of the Affordable Care Act created the Hospital Readmission Reduction Program (HRRP).1 Under the HRRP, the Centers for Medicare & Medicaid Services (CMS) is charged with working to reduce hospital readmissions for select conditions. The initial
[
1 4 8 # 1 C H E S T J U LY 2 0 1 5
]
