ICU Admission of the Lung Transplant Recipient Following Hospital Discharge

some of the strengths of the current study and improve its drawbacks by selecting patients with a lower FEV1, stratified by comparators and the severity of the baseline lung function. Clearly, no more equivalence studies are required, and please forget about chronic bronchitis—COPD is the real disease. Who can rely on a diagnosis based on the symptoms a patient had (or said he had) 2 years ago? Marc Miravitlles, MD Antoni Torres, MD, FCCP Barcelona, Spain Dr. Miravitlles is Senior Researcher and Dr. Torres is Director, Institut Clı´nic de Pneumologia i Cirurgia Tora`cica. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: [email protected]). Correspondence to: Antoni Torres, MD, FCCP, Servei de Pneumologia, Institut Clı´nic de Pneumologia i Cirurgia Tora`cica (IDIBAPS), Hospital Clı´nic (escalera 12, planta 0), Villarroel 170, 08036 Barcelona, Spain; e-mail: [email protected]

References 1 Monso´ E, Ruiz J, Rosell A, et al. Bacterial infection in chronic obstructive pulmonary disease: a study of stable and exacerbated outpatients using the protected specimen brush. Am J Respir Crit Care Med 1995; 152:1316 –1320 2 Soler N, Torres A, Ewig S, et al. Bronchial microbial patterns in severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation. Am J Respir Crit Care Med 1998; 157:1498 –1505 3 Sethi S, Evans N, Grant BJ, et al. New strains of bacteria and exacerbations of chronic obstructive pulmonary disease. N Engl J Med 2002; 347:465– 471 4 Crooks SW, Bayley DL, Hill SL, et al. Bronchial inflammation in acute bacterial exacerbations of chronic bronchitis: the role of leukotriene B4. Eur Respir J 2000; 15:274 –280 5 Patel IS, Seemungal TAR, Wilks M, et al. Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations. Thorax 2002; 57:759 –764 6 Wilson R, Schentag JJ, Ball P, et al. A comparison of gemifloxacin and clarithromycin in acute exacerbations of chronic bronchitis and long-term clinical outcomes. Clin Ther 2002; 24:639 – 652 7 Chodosh S, DeAbate CA, Haverstock D, et al. Short-course moxifloxacin therapy for treatment of acute bacterial exacerbations of chronic bronchitis. Respir Med 2000; 94:18 –27 8 Evans AT, Husain S, Durairaj L, et al. Azithromycin for acute bronchitis: a randomised, double-blind, controlled trial. Lancet 2002; 359:1648 –1654 9 Allegra L, Blasi F, de Bernardi B, et al. Antibiotic treatment and baseline severity of disease in acute exacerbations of chronic bronchitis: a re-evaluation of previously published data of a placebo-controlled randomized study. Pulm Pharmacol Ther 2001; 14:149 –155 10 Nouira S, Marghli S, Belghith M, et al. Once daily oral ofloxacin in chronic obstructive pulmonary disease exacerbation requiring mechanical ventilation: a randomised placebocontrolled trial. Lancet 2001; 358:2020 –2025 11 Anthonisen NR, Manfreda J, Warren CPW, et al. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 1987; 106:196 –204 12 British Thoracic Society. BTS guidelines for the management of chronic obstructive pulmonary disease. Thorax 1997; 52(Suppl 5):S16 –S21 www.chestjournal.org

13 Balter MS, La Forge J, Low DE, et al. Canadian guidelines for the management of acute exacerbations of chronic bronchitis. Can Respir J 2003; 10(Suppl B):3B–32B 14 Grupo de Trabajo de la Asociacio´ n Latinoamericana del To´ rax (ALAT). Latin American Thoracic Association (ALAT) guidelines for the management of infectious exacerbations of COPD. Arch Bronconeumol 2001; 37:349 –357 15 Miravitlles M, Murio C, Guerrero T. Factors associated with relapse after ambulatory treatment of acute exacerbations of chronic bronchitis: a prospective multicenter study in the community. Eur Respir J 2001; 17:928 –933 16 Miravitlles M, Espinosa C, Ferna´ ndez-Laso E, et al. Relationship between bacterial flora in sputum and functional impairment in patients with acute exacerbations of COPD. Chest 1999; 116:40 – 46 17 Stockley RA, O’Brien C, Pye A, et al. Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD. Chest 2000; 117:1638 –1645 18 Anzueto A, Rizzo JA, Grossman RF. The infection-free interval: its use in evaluating antimicrobial treatment of acute exacerbation of chronic bronchitis. Clin Infect Dis 1999; 28:1344–1345 19 Spencer S, Jones PW, for the GLOBE Study Group. Time course of recovery of health status following an infective exacerbation of chronic bronchitis. Thorax 2003; 58:589 –593 20 Miravitlles M, Murio C, Guerrero T, et al. Pharmacoeconomic evaluation of acute exacerbations of chronic bronchitis and COPD. Chest 2002; 121:1449 –1455 21 Donaldson GC, Seemungal TAR, Bhomik A, et al. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 2002; 57:847– 852 22 Miravitlles M, Murio C, Guerrero T, et al. Costs of chronic bronchitis and COPD: a 1-year follow-up study. Chest 2003; 123:784 –791 23 Seemungal TAR, Donaldson GC, Paul EA, et al. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998; 157:1418 –1422 24 Alvarez F, Bouza E, Garcı´a-Rodrı´guez JA, et al. Uso de antimicrobianos en la exacerbacio´ n de la enfermedad pulmonar obstructiva cro´ nica. Arch Bronconeumol 2002; 38:81– 89 25 Felmingham D, Reinert RR, Hirakata Y, et al. Increasing prevalence of antimicrobial resistance among isolates of Streptococcus pneumoniae from the PROTEKT surveillance study, and comparative in vitro activity of the ketolide, telithromycin. J Antimicrob Chemother 2002; 50(Suppl S1):25–37 26 Adams SG, Melo J, Luther M, et al. Antibiotics are associated with lower relapse rates in outpatients with acute exacerbations of COPD. Chest 2000; 117:1345–1352

ICU Admission of the Lung Transplant Recipient Following Hospital Discharge issue of CHEST (see page 1040), Hadjiliadis I nandthisassociates report on the outcome of lung

transplant recipients who required admission to medical ICUs (MICUs) after their initial discharge following transplantation. Fifty-one patients who underwent lung transplantation at Duke University after 1999 required admission to the MICU after CHEST / 125 / 3 / MARCH, 2004

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they were discharged. Of those 51 patients, 27 required intubation and mechanical ventilation, and 16 of those 27 patients (59%) died during that admission. The study emphasizes the important observation that admission to the MICU after initial discharge of a lung transplant recipient is associated with a high hospital mortality (37%) and, more importantly, that the need of these patients for mechanical ventilation carries more than a one in two chance of death prior to discharge from the hospital. A careful look at the Kaplan-Meier survival statistics for all lung transplant patients requiring readmission to a MICU reveals that the actuarial 1-year survival rate falls from an expected 77% to 43.1%.1 Hadjiliadis and colleagues have made an important contribution in defining at-risk characteristics for survival of lung transplant patients admitted to the MICU after their initial discharge. While prior studies have evaluated such risks retrospectively,2 theirs is the first prospective analysis of the outcome of these patients. MICU admission after lung transplant is not rare. In their cohort, 23.8% of the recipients were admitted over the surveillance time period; of that subgroup, 27.5% were admitted more than once. The most frequent causes for MICU admission were respiratory failure (69.9%) and sepsis (6.8%). The overall discharge from the hospital following the MICU admission was 62.7%. Lung transplant recipients at higher risk of death after MICU admission were those requiring mechanical ventilation. Of the patients who required mechanical ventilation and died (16 patients), 11 died in the MICU and 5 died after discharge from the MICU during the same hospitalization. Logistic regression analysis suggested that both lower last FEV1/best posttransplant FEV1 ratio and mechanical ventilation were independently associated with higher risk of death. APACHE (acute physiology and chronic health evaluation) III scores did not independently predict a poorer outcome. The presence of bronchiolitis obliterans syndrome was, likewise, not independently associated with death, but the small numbers of such defined recipients may have rendered the subpopulation inadequate to reach statistical significance. Unavailable for evaluation in the patient cohort reported by Hadjiliadis and colleagues was the potentially independently associated factor of bloodstream infection (BSI). Palmer et al,3 reporting from the same institution, in a cohort evaluated few years earlier, showed that BSI after transplant was a significant predictor of posttransplant death independent of other pretransplant and posttransplant factors. In that cohort, BSI occurred in 25% of 176 lung transplant recipients over a 6-year period. Importantly, BSI was associated with significantly worse survival with 3-year survival of only 44% vs 71% in 814

recipients without BSI. BSI in that group remained a significant predictor of death in all bivariant analyses, including analysis in conjunction with mechanical ventilation, and was the strongest of all predictors in a multivariant analysis.3 Analyses of the International Society for Heart and Lung Transplantation regarding the cause of death among lung transplant recipients indicate that between 2% and 5% of the deaths after transplant are directly related to rejection, whereas between 20% and 40% of the deaths are caused by infections.4 These statistics are alarming and imply that in the most critical of outcome analyses, ie, death and cause of death, lung transplant recipients may be overimmunosuppressed. In this context, it is rational to suggest that gentler, kinder, and less immunosuppressive drug protocols should be considered. In addition, other variables such as use of marginal donors, recipient weight, ethnicity, gender, nutritional status, perioperative blood albumin levels, cytomegalovirus status, and the presence or absence of diabetes among other recipient risks factors for transplant also need to be addressed in similar prospective studies to help determine if these variables may impact MICU readmission rates and survival after transplant. In the study of Hadjiliadis et al, and as noted above, the overall 1-year actuarial survival after MICU admission dropped from 73% (United Network for Organ Sharing expected 1-year survival) to 43.1%. Hadjiliadis and colleagues note that admission to the MICU is associated with significant short-term morbidity and mortality. They have shown prospectively that along with the previously studied BSI, respiratory failure and the need for mechanical ventilation harbor a significantly greater risk of death after lung transplant. These data will help in assessing the risks and benefits of both MICU admission and support with mechanical ventilation. Also, these data are helpful for providing patients and their families with realistic expectations regarding the prognosis. The authors have made an important contribution in moving the basis of patient and family counseling in the setting of critical illness from experience- to evidence-based practice. Further prospective analyses of this type are needed. Malek G. Massad, MD, FCCP Jacques Kpodonu, MD H. Ari Jaffe, MD Chicago, IL Dr. Massad is Associate Professor of Surgery and Surgical Director of Thoracic Organ Transplantation, Dr. Kpodonu is a cardiothoracic surgery fellow in training, and Dr. Jaffe is Associate Professor of Medicine and Medical Director of the Lung Transplantation Program, The University of Illinois at Chicago. Reproduction of this article is prohibited without written permisEditorials

sion from the American College of Chest Physicians (e-mail: [email protected]). Correspondence to: Malek G. Massad, MD, FCCP, The University of Illinois at Chicago, Division of Cardiothoracic Surgery, 840 S. Wood St, CSB Suite 417 (MC 958), Chicago, IL 60612; e-mail: [email protected]

References 1 United Network for Organ Sharing. Lung transplant national survival statistics, 1996 –2001. Available at: http://www.optn. org/latestData/rptStrat.asp. Accessed October 1, 2003 2 Pietrantoni C, Minai OA, Yu NC, et al. Respiratory failure and sepsis are the major causes of ICU admissions and mortality in survivors of lung transplants. Chest 2003; 123: 504 –509 3 Palmer SM, Alexander BD, Sanders LL, et al. Significance of blood stream infection after lung transplantation: analysis in 176 consecutive patients. Transplantation 2000; 69:2360 – 2366 4 Trulock EP, Edwards LB, Taylor DO, et al. The Registry of the International Society for Heart and Lung Transplantation: twentieth official adult lung and heart-lung transplant report. J Heart Lung Transplant 2003; 22:625– 635

OPCAB vs CABG Who, What, When, Where? surgeon’s decision to perform myocardial revasA cularization using conventional techniques (ie,

coronary artery bypass grafting [CABG]) on cardiopulmonary bypass (CPB) or to use newer techniques without the aid of CPB (ie, off-pump coronary artery bypass [OPCAB]) has been influenced by many factors. CPB is known to cause a complex of systemic inflammatory responses and has been associated with several adverse postoperative outcomes, including renal, pulmonary, neurologic, and coagulopathic complications and even end organ dysfunction.1 Surgeons driven to reduce both the short-term and long-term morbidity associated with CPB find OPCAB to be an attractive alternative. First performed in the early 1960s simply because the CPB technology did not yet exist, OPCAB has experienced a resurgence of interest as a potential solution to the vexing problems associated with the use of CPB.2 The excellent outcomes obtained with CABG mandate that studies be done to confirm that OPCAB provides a statistically significant improvement. The subtle effects of CPB such as mild memory loss or confusion are hard to quantify, making it difficult to demonstrate a clear advantage of one technique over the other.3 Conversely, gross effects such as blood loss or transfusion requirements can be assessed accurately but may be of less importance when compared to the completeness of revascularization or graft patency.4 Nevertheless, www.chestjournal.org

studies have compared CABG to OPCAB focusing on important parameters of outcome (ie, mortality, stroke, graft patency, completeness of revascularization, and renal dysfunction) and total cost (ie, length of stay, cost of materials, time to extubation, and time in the ICU). Important questions need to be asked by surgeons when choosing which operation to perform. Should the experience of the operative surgeon determine whether to use OPCAB or CABG? When should surgeons potentially sacrifice graft patency or safety to justify learning a new, but potentially better, technique? When and how often should graft patency be intraoperatively assessed in patients undergoing myocardial revascularization? Should the experience of the operative surgeon be considered when deciding to confirm graft patency? In teaching institutions, should CABG techniques be taught before or simultaneously with OPCAB techniques? There are several prospectively randomized trials and a recently published meta-analysis, either in progress or recently completed, that attempt to definitively answer some of these questions. Parolari et al5 performed a meta-analysis of all randomized trials of OPCAB vs CABG from 1990 to 2002. They found nine comparable trials (peer reviewed, prospective, and randomized) with a total of 1,090 patients (CABG, 558 patients; OPCAB, 532 patients). Using a composite end point of death, stroke, or myocardial infarction, there was a trend toward reduction in risk (odds ratio, 0.48; p ⫽ 0.08) in patients in the OPCAB groups but no clear benefit. Most of the studies were from Europe, and four of the studies had the same author. Another carefully performed and statistically robust study6 comparing OPCAB with CABG also suggested improved clinical outcomes with OPCAB. In particular, this conclusion may apply to important subgroups of patients (eg, octogenarians).7 Other studies3,8,9 have found no difference in outcomes referable to the technique chosen, and one article10 simply concluded by saying that patients undergoing OPCAB are not exposed to a greater risk of short-term adverse outcomes. A well-done but only partially published manuscript (the graft patency data were not included and will not be published until the 1-year angiograms are completed) by Puskas et al4 has demonstrated that a single experienced surgeon who is well-versed in OPCAB and CABG techniques can have improved results without CPB. With similar patient characteristics, unselected prospectively randomized patients receiving OPCAB had the same following results: number of grafts; number of grafts to the lateral wall; number of arterial grafts; rates of death, atrial fibrillation, and stroke; and rate of hospital readmission when compared to CABG patients. OPCAB patients CHEST / 125 / 3 / MARCH, 2004

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