Further Consideration for Noninvasive Positive Pressure Ventilation in Cardiogenic Pulmonary Edema

Correspondence magnitude. Therefore, one emergency physician declaring that an individual patient has a 10% pretest probability of pulmonary embolism is unlikely to be accurate. Second, pulmonary embolism testing in the ED for low-risk patients does not directly benefit and may actually harm the vast number of patients across the United States who experience adverse effects of chest computed tomography (CT) through ionizing radiation and intravenous contrast. For this reason, we think that the application of the PERC will have a net positive public health benefit, even given an occasional miss. And third, despite their name, clinical decision rules should be used as tools and not as “rules.” In the ED, we treat individual patients, not average ones. So, although the PERC is valid and, we think, can be used broadly, clinical decision rules should complement, not replace, clinical judgment. Dr. Madsen’s letter comments that our assumption of the bleeding risk from anticoagulation may be overestimated in low-risk patients. In the absence of evidence in a truly analogous population, we cited a study that found a 0% prevalence of bleeding in low-risk patients.3 However, we used a bleeding risk of 1.7% in the model to match the original PERC derivation article, which also cited the same study.4 We chose 1.7% because it seemed unlikely that anticoagulation, which is known to have many adverse effects, would have none in people with low risk. However, in retrospect, we concede that it certainly may have been an overestimate. Because of this uncertainty, we used 2-sensitivity analysis to assess how much the testing threshold changed when varying the bleeding risk and found that it was indeed a major driver (ie, changed it by more than 2.0%). According to Figure 3 in our article, if the bleeding risk is much lower than 1.7%, it reduces the testing threshold below the miss rate of 1% reported in the PERC validation,5 suggesting that the actual testing threshold for the PERC should be lower and that a 1% miss rate is too high. On the other hand, recent data also showed that our estimate of the probability of contrast-induced renal failure might have been too low.6 Using this new information, we reran our model with a bleeding risk of 0% and probabilities of death from and dialysisdependent contrast-induced renal failure of 0.6% and 0.3%, respectively. These parameters resulted in a test threshold of 19.6% for the base case 25-year-old woman. This suggests that using intravenous contrast-enhanced CT to test low pretest probability patients may make not make clinical sense altogether. However, according to these results, we would certainly not suggest the cessation of low-risk pulmonary embolism testing but rather illustrate how modifying assumptions in decision models can produce dramatic changes. The greater point of our article is that the variables that are major drivers of the true testing threshold for pulmonary embolism, including the risk of major bleeding from anticoagulation, mortality from contrastinduced renal failure, risk of cancer from CT scan, and mortality from both treated and untreated pulmonary embolism, which are to date unknown in patients assessed as having low pretest probability for pulmonary embolism. So before truly evidence-based recommendations can be made Volume , .  : November 

about patients at low risk for pulmonary embolism, what we really need is a better understanding of these risks. Adam L. Lessler, MD, MBA Department of Emergency Medicine University of Pennsylvania School of Medicine Philadelphia, PA Jesse M. Pines, MD, MBA, MSCE Department of Emergency Medicine George Washington University School of Medicine Department of Health Policy George Washington University School of Public Health and Health Services Washington, DC doi:10.1016/j.annemergmed.2010.05.017

Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article that might create any potential conflict of interest. The authors have stated that no such relationships exist. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. 1. Lessler AL, Isserman JA, Agarwal R, et al. Testing low-risk patients for suspected pulmonary embolism: a decision analysis. Ann Emerg Med. 2010;55:316-326. 2. Runyon MS, Webb WB, Jones AE, et al. Comparison of the unstructured clinician estimate of pretest probability for pulmonary embolism to the Canadian Score and the Charlotte Rule: a prospective observational study. Acad Emerg Med. 2005;12:587-593. 3. Wells PS, Forgie MA, Simms M, et al. The outpatient bleeding risk index: validation of a tool for predicting bleeding rates in patients treated for deep venous thrombosis and pulmonary embolism. Arch Intern Med. 2003;163:917-920. 4. Kline JA, Mitchell AM, Kabrhel C, et al. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. J Thromb Haemost. 2004;2: 1247-1255. 5. Kline JA, Courtney DM, Kabrhel C, et al. Prospective multicenter evaluation of the pulmonary embolism rule-out criteria. J Thromb Haemost. 2008;6:772-780. 6. Mitchell AM, Jones AE, Tumlin JA, et al. Incidence of contrastinduced nephropathy after contrast-enhanced computed tomography in the outpatient setting. Clin J Am Soc Nephrol. 2010;5:4-9.

Further Consideration for Noninvasive Positive Pressure Ventilation in Cardiogenic Pulmonary Edema To the Editor: The article by Seupaul et al1 about use of noninvasive positive pressure ventilation was superb but could lead to the misuse of the technique if evidence from a trial published after the Cochrane Review2 is not emphasized. The more recent and larger 3 Cardiogenic Pulmonary Oedema (3CPO) Trial Annals of Emergency Medicine 587

Correspondence (prospective, randomized, controlled trial with 1,069 total patients) by Gray et al3 also investigated noninvasive positive pressure ventilation in cardiogenic edema. The investigators confirmed the Cochrane Review data that there was no mortality benefit to noninvasive positive pressure ventilation, even when separating continuous positive airway pressure (CPAP) and bilevel noninvasive positive pressure ventilation (BiPAP). It is our opinion that the most important finding in this trial was that, according to the 2 modes of noninvasive positive pressure ventilation (CPAP and BiPAP), BiPAP resulted in significant intolerance compared with CPAP or conventional medical therapy. The trial by Nava et al4 (included in the Cochrane Review), which used bilevel noninvasive positive pressure ventilation, failed to show a decrease in tracheal intubation or hospital mortality in the noninvasive positive pressure ventilation group compared with the medical therapy group. However, in subset analysis (by Nava et al4), the percentage of patients needing tracheal intubation was significantly lower for patients with a PaCO2 greater than 45 mm Hg and using BiPAP. The data of Gray et al3 confirm and expand the finding by Nava et al4 of more rapid resolution of symptoms and oxygenation indices with use of not only BiPAP but also CPAP. Keeping in mind the lack of strong evidence for mortality benefit but clear evidence for more rapid symptomatic improvement, these trials showed that the emergency physician should strongly consider noninvasive positive pressure ventilation for cardiogenic pulmonary edema. We are unaware of any literature showing a benefit of BiPAP over CPAP either for mortality benefits or as a mode that appears to be tolerated better than CPAP. However, the data of Gray et al3 provide evidence that BiPAP is less tolerated in cardiogenic edema than CPAP alone, and patients are less likely to continue receiving BiPAP than CPAP for cardiogenic pulmonary edema. We thus suggest that these data should be considered for patients who

present to the emergency department with cardiogenic pulmonary edema when noninvasive positive pressure ventilation is being considered as a mode of treatment. Please be advised that the data by Nava et al4 were included to show that the trial by Gray et al3 was not the first one to show that there is no mortality benefit to noninvasive positive pressure ventilation in cardiogenic pulmonary edema. However, the trial by Nava et al4 also reflects the need to consider BiPAP in the presence of hypercapnia. Brandon Allen, MD George A. Mitchell, DO Florida State University College of Medicine Regional Campus Fort Pierce, FL doi:10.1016/j.annemergmed.2010.05.019

Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article that might create any potential conflict of interest. The authors have stated that no such relationships exist. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. 1. Seupaul RA. Should I consider treating patients with acute cardiogenic pulmonary edema with noninvasive positive pressure ventilation? Ann Emerg Med. 2010;55:299-300. 2. Vital FMR, Saconato H, Ladeira MT, et al. Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary edema. Cochrane Database Syst Rev. 2008;(3):CD005351. 3. Gray A, Goodacre S, Newby DE, et al, and the 3CPO Trialists. Noninvasive ventilation in acute cardiogenic pulmonary edema. N Engl J Med. 2008;359:142-151. 4. Nava S, Carbone G, DiBattista N, et al. Noninvasive ventilation in cardiogenic pulmonary edema: a multicenter randomized trial. Am J Respir Crit Care Med. 2003;168:1432-1437.

CORRECTION NOTICE In the September issue of Annals, the Journal Club questions referenced the incorrect article. The Journal Club questions refer to Schmitz GR, Bruner D, Pitotti R, et al. Randomized controlled trial of trimethoprim-sulfamethoxazole for uncomplicated skin abscesses in patients at risk for community-associated methicillin-resistant Staphylococcus aureus infection. Ann Emerg Med. 2010;56:283-287. We apologize for this inconvenience.

588 Annals of Emergency Medicine

Volume , .  : November 