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Geube, Mariya A. MD; Duncan, Andra E. MD, MS; Yang, Dongsheng MS; Sessler, Daniel I. MD; Perez-Protto, Silvia E. MD

doi: 10.1213/ANE.0000000000001374
Letters to the Editor: Letter to the Editor

Department of Cardiothoracic Anesthesia, Cleveland Clinic, Cleveland, Ohio

Departments of Cardiothoracic Anesthesia and Outcomes Research, Cleveland Clinic, Cleveland, Ohio

Departments of Quantitative Health Sciences and Outcomes Research, Cleveland Clinic, Cleveland, Ohio

Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio

Department of Anesthesiology and Critical Care, Cleveland Clinic, Cleveland, Ohio,

Colombo et al1 note that more inotropic and vasopressor support was required in patients who developed grade-3 primary graft dysfunction (PGD) and ask whether our analysis was adjusted for the imbalance in these variables. Using standard statistical techniques, all baseline and perioperative characteristics listed in Table 2 were considered as potential confounders and evaluated for inclusion in the multivariable logistic regression model. Although inotropic agents and vasopressor use were univariably associated with grade-3 PGD (P < 0.05), these variables were removed from the model during backward selection procedures when their effect was not significant. Thus, the effect of inotropic and vasopressor use with grade-3 PGD was considered in our analysis but was not found to be significant.

With regard to the preoperative cardiac function, there are data that pulmonary arterial hypertension is indeed associated with PGD.2,3 Although echocardiographic measures of right and left ventricular function were not included in our model, we captured hemodynamic variables after lung reperfusion including cardiac index, pulmonary arterial pressures, and central venous pressure. None differed significantly in our groups.

We agree that more detail on the overall perioperative fluid balance of patients would be helpful. But inherent limitations of our retrospective study design included the fact that accurate recording of postoperative fluid balance was unavailable. Regarding our hemodynamic management protocol, intraoperative management for lung transplantation at the Cleveland Clinic is standardized and the algorithm for hemodynamic management and mechanical ventilation was described in the Methods section of our article.

Inadequate intravascular volume can harm the heart and kidneys, and we certainly do not recommend fluid restriction to the point of organ malperfusion and dysfunction. However, our results are consistent with 2 other reports, that fluid administration and blood transfusion are associated with development of PGD after lung transplantation.4,5 And finally, minimizing fluid administration improves outcomes in conditions with similar pathophysiology, including severe acute respiratory distress syndrome, lung trauma, and thoracic surgery.6

Retrospective analyses cannot establish causality with certainty. Thus, although the association between fluid and graft failure is clear, it remains unknown whether restricting fluid will actually improve graft survival. The value of our analysis is in identifying a potentially valuable therapeutic intervention that is easy to implement and costs nothing. We agree that a randomized trial is needed to prove whether fluid restriction reduces risk of PGD, and our results provide an excellent basis for estimating treatment effect (and thus sample size) for such trial. However, in light of our results and others5–7 and the general consensus that increased fluid administration is detrimental, patient enrollment, and clinician participation for a randomized study examining liberal versus restrictive fluid strategies may be challenging.

Mariya A. Geube, MD
Department of Cardiothoracic Anesthesia
Cleveland Clinic
Cleveland, Ohio

Andra E. Duncan, MD, MS
Departments of Cardiothoracic
Anesthesia and Outcomes Research
Cleveland Clinic
Cleveland, Ohio

Dongsheng Yang, MS
Departments of Quantitative Health
Sciences and Outcomes Research
Cleveland Clinic
Cleveland, Ohio

Daniel I. Sessler, MD
Department of Outcomes Research
Cleveland Clinic
Cleveland, Ohio

Silvia E. Perez-Protto, MD
Department of Anesthesiology and Critical Care
Cleveland Clinic
Cleveland, Ohio

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1. Colombo J, Arena A, Codazzi D. Lung transplantation is much more than lungs and fluids. Anesth Analg 2016;123:794795.
2. Liu Y, Liu Y, Su L, Jiang SJ. Recipient-related clinical risk factors for primary graft dysfunction after lung transplantation: a systematic review and meta-analysis. PLoS One 2014;9:e92773.
3. Barr M,, Kawut S,, Whelan T,, et al. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction Part IV: recipient-related risk factors and markers. J Heart Lung Transplant 2005;24:146882.
4. McIlroy D, Pilcher D, Snell G. Does anesthetic management affect early outcomes after lung transplant? An exploratory analysis. Br J Anesth 2009;102:50614.
5. Diamond J, Lee J, Kawut S, Shah R, Localio A, Bellamy S, Lederer D, Cantu E, Kohl B, Lama V, Bhorade S, Crespo M, Demissie E, Sonett J, Wille K, Orens J, Shah A, Weinacher A, Arcasoy S, Shah P, Wilkes D, Ware L, Palmer S, Christie J, Lung Transplant Outcomes Group. Clinical risk factors for primary graft dysfunction after lung transplantation. Am J Respir Crit Care Med 2013;187:52734.
6. Chau E, Slinger P. Perioperative fluid management for pulmonary resection and esophagectomy. SAGE 2014;18:3644.
7. Pilcher D, Scheinkestel C, Snell G, Davey-Quinn A, Bailey M, Williams T. High central venous pressure is associated with prolonged mechanical ventilation and increased mortality after lung transplantation. J Thorac Cardiovasc Surg 2005;129:9128.
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