Preoperative Evaluation of Patients With Interstitial Lung Disease

      Key Words

      Abbreviations:

      AE (acute exacerbation), AHRF (acute hypoxic respiratory failure), ALI (acute lung injury), ARISCAT (Assess Respiratory Risk in Surgical Patients in Catalonia), ASA (American Society of Anesthesiologists), BiPAP (bilevel positive airway pressure), CCI (Charlson Comorbidity Index), CRP (C-reactive protein), Dlco (diffusing capacity of the lungs for carbon monoxide), GA (general anesthesia), HFNC (high-flow nasal cannula), ILD (interstitial lung disease), IPF (idiopathic pulmonary fibrosis), PEEP (positive end-expiratory pressure), PPC (postoperative pulmonary complication), SLB (surgical lung biopsy), UIP (usual interstitial pneumonia)
      Patients with interstitial lung disease (ILD) experience an increased risk of postoperative pulmonary complications (PPCs), including acute exacerbations/acute lung injury (AEs/ALI), respiratory failure, pneumonia, atelectasis, prolonged air leak, pneumothorax or hemothorax, pulmonary embolism, and mortality when undergoing both pulmonary and nonpulmonary surgery.
      • Choi S.M.
      • Lee J.
      • Park Y.S.
      • et al.
      Postoperative pulmonary complications after surgery in patients with interstitial lung disease.
      • Sato T.
      • Watanabe A.
      • Kondo H.
      • et al.
      Japanese Association for Chest Surgery. Long-term results and predictors of survival after surgical resection of patients with lung cancer and interstitial lung diseases.
      • Hutchinson J.P.
      • Fogarty A.W.
      • McKeever T.M.
      • Hubbard R.B.
      In-hospital mortality after surgical lung biopsy for interstitial lung disease in the United States: 2000 to 2011.
      Mortality rates can be exceedingly high, particularly in patients who experience AEs or undergo emergency surgery.
      • Choi S.M.
      • Lee J.
      • Park Y.S.
      • et al.
      Postoperative pulmonary complications after surgery in patients with interstitial lung disease.
      • Sato T.
      • Watanabe A.
      • Kondo H.
      • et al.
      Japanese Association for Chest Surgery. Long-term results and predictors of survival after surgical resection of patients with lung cancer and interstitial lung diseases.
      • Hutchinson J.P.
      • Fogarty A.W.
      • McKeever T.M.
      • Hubbard R.B.
      In-hospital mortality after surgical lung biopsy for interstitial lung disease in the United States: 2000 to 2011.
      • Park J.S.
      • Kim H.K.
      • Kim K.
      • Kim J.
      • Shim Y.M.
      • Choi Y.S.
      Prediction of acute pulmonary complications after resection of lung cancer in patients with preexisting interstitial lung disease.
      The etiology of this increased risk is not clear, although reduced lung compliance in patients with ILD likely amplifies the duress of positive-pressure ventilation. Ventilator-induced lung injury may accelerate the fibroproliferative process via multiple pathways including regional lung overdistension, atelectrauma, biotrauma, and/or hyperoxia.
      • Faverio P.
      • De Giacomi F.
      • Sardella L.
      • et al.
      Management of acute respiratory failure in interstitial lung diseases: overview and clinical insights.
      • Slutsky A.S.
      • Ranieri V.M.
      Ventilator-induced lung injury.
      Other plausible mechanisms include microaspiration, increased closing volume of the lung, right-sided heart dysfunction, increased circulating fibrocytes, and/or negative-pressure pulmonary edema.
      • Faverio P.
      • De Giacomi F.
      • Sardella L.
      • et al.
      Management of acute respiratory failure in interstitial lung diseases: overview and clinical insights.
      • Ghatol A.
      • Ruhl A.P.
      • Danoff S.K.
      Exacerbations in idiopathic pulmonary fibrosis triggered by pulmonary and nonpulmonary surgery: a case series and comprehensive review of the literature.
      We are not aware that published recommendations exist to guide practicing pulmonologists through risk stratification of patients with ILD for operative intervention. Using a combination of existing published data and expert opinion, we describe which operative parameters, functional assessments, and physiologic variables should be examined when determining whether a patient with ILD can safely undergo surgery, and propose suggestions for perioperative treatment.

      Risk Stratification

       General Population-Based Factors

      In the general population, PPCs have been defined heterogeneously to include pneumonia, respiratory failure, atelectasis, pneumothorax, pleural effusion, pulmonary embolism, and bronchospasm. They occur in 2% to 19% of patients undergoing surgery, and have been associated with increased morbidity, mortality, and length of stay.
      • Canet J.
      • Gallart L.
      • Gomar C.
      • et al.
      Prediction of postoperative pulmonary complications in a population-based surgical cohort.
      • Smetana G.W.
      • Lawrence V.A.
      • Cornell J.E.
      American College of Physicians
      Preoperative pulmonary risk stratification for noncardiothoracic surgery: systematic review for the American College of Physicians.
      In a seminal review by Smetana et al,
      • Smetana G.W.
      • Lawrence V.A.
      • Cornell J.E.
      American College of Physicians
      Preoperative pulmonary risk stratification for noncardiothoracic surgery: systematic review for the American College of Physicians.
      145 studies were analyzed to identify risk factors for PPCs. In this large study, patient-related factors predictive of increased PPC risk included older age (≥ 60 years), American Society of Anesthesiologists (ASA) class ≥ 2, the presence of COPD or congestive heart failure, functional dependence, and active smoking. Procedural risk factors for PPCs included thoracic or upper abdominal surgery, emergency surgery, and the need for general anesthesia.
      • Smetana G.W.
      • Lawrence V.A.
      • Cornell J.E.
      American College of Physicians
      Preoperative pulmonary risk stratification for noncardiothoracic surgery: systematic review for the American College of Physicians.
      Canet et al
      • Canet J.
      • Gallart L.
      • Gomar C.
      • et al.
      Prediction of postoperative pulmonary complications in a population-based surgical cohort.
      explored these concepts further in a prospective multicenter study of > 2,000 patients undergoing scheduled or emergency surgery, in which potential risk factors for PPCs were identified a priori. The most predictive patient-related factors for PPCs included age > 80 years, lower preoperative arterial oxygen saturation (percent predicted arterial oxygen saturation [Sao2 % predicted] ≤ 90%), upper or lower respiratory tract infection within 1 month of surgery, and preoperative anemia (hemoglobin ≤ 10 g/dL). Akin to the findings of Smetana et al,
      • Smetana G.W.
      • Lawrence V.A.
      • Cornell J.E.
      American College of Physicians
      Preoperative pulmonary risk stratification for noncardiothoracic surgery: systematic review for the American College of Physicians.
      upper abdominal or intrathoracic surgery and emergency surgery were associated with increased PPC risk, as were longer surgical procedures (> 2 hours). The findings of this article led to the development of the ARISCAT (Assess Respiratory Risk in Surgical Patients in Catalonia) score to predict PPCs, which was subsequently externally validated in a large, multinational European trial of over 5,000 patients.
      • Canet J.
      • Gallart L.
      • Gomar C.
      • et al.
      Prediction of postoperative pulmonary complications in a population-based surgical cohort.
      • Mazo V.
      • Sabate S.
      • Canet J.
      • et al.
      Prospective external validation of a predictive score for postoperative pulmonary complications.
      In addition to ARISCAT, other risk calculators exist but are limited by incomplete inclusion of all PPCs.
      • Arozullah A.M.
      • Daley J.
      • Henderson W.G.
      • Khuri S.F.
      National Veterans Administration Surgical Quality Improvement Program
      Multifactorial risk index for predicting postoperative respiratory failure in men after major noncardiac surgery.
      Gupta et al
      • Gupta H.
      • Gupta P.K.
      • Fang X.
      • et al.
      Development and validation of a risk calculator predicting postoperative respiratory failure.
      established a five-factor risk model (dependent functional status, ASA class, preoperative sepsis, type of surgery, and emergency surgery) to predict postoperative respiratory failure, which performed well. The respiratory failure risk index developed by Arozullah et al
      • Arozullah A.M.
      • Daley J.
      • Henderson W.G.
      • Khuri S.F.
      National Veterans Administration Surgical Quality Improvement Program
      Multifactorial risk index for predicting postoperative respiratory failure in men after major noncardiac surgery.
      also established risk factors for postoperative respiratory failure, although women were excluded from that study, hindering generalizability. Unfortunately, none of the aforementioned studies stipulated how many patients had ILD.

       ILD-Specific Factors

      Postoperative pulmonary complications occur at higher rates in patients with ILD undergoing pulmonary and nonpulmonary surgery, although data regarding the latter are more scarce. Described rates of PPCs in patients with ILD include a large number of studies focusing on patients undergoing surgical lung biopsy (SLB) and lung cancer resection, and range broadly from 0 to 65.6%.
      • Choi S.M.
      • Lee J.
      • Park Y.S.
      • et al.
      Postoperative pulmonary complications after surgery in patients with interstitial lung disease.
      • Sato T.
      • Watanabe A.
      • Kondo H.
      • et al.
      Japanese Association for Chest Surgery. Long-term results and predictors of survival after surgical resection of patients with lung cancer and interstitial lung diseases.
      • Hutchinson J.P.
      • Fogarty A.W.
      • McKeever T.M.
      • Hubbard R.B.
      In-hospital mortality after surgical lung biopsy for interstitial lung disease in the United States: 2000 to 2011.
      • Park J.S.
      • Kim H.K.
      • Kim K.
      • Kim J.
      • Shim Y.M.
      • Choi Y.S.
      Prediction of acute pulmonary complications after resection of lung cancer in patients with preexisting interstitial lung disease.
      • Raj R.
      • Raparia K.
      • Lynch D.A.
      • Brown K.K.
      Surgical Lung Biopsy for Interstitial Lung Diseases.
      Acute lung injury/AEs comprise a significant portion of observed PPCs, from which attributable mortality rates are exceedingly high.
      Data describing PPC rates in patients with ILD undergoing nonthoracic surgery are limited. Choi et al
      • Choi S.M.
      • Lee J.
      • Park Y.S.
      • et al.
      Postoperative pulmonary complications after surgery in patients with interstitial lung disease.
      reported that 11% of patients with ILD developed PPCs in a single-center series of 336 patients undergoing both thoracic and nonthoracic surgeries. Lower BMI (< 23 kg/m2), pulmonary surgery, emergency surgery, and longer anesthesia time predicted an increased PPC risk in multivariate analysis. Furuya et al
      • Furuya K.
      • Sakamoto S.
      • Takai Y.
      • Sato N.
      • Matsumoto K.
      • Homma S.
      Acute exacerbation of idiopathic interstitial pneumonia after nonpulmonary surgery under general anesthesia: a retrospective study.
      found that 7.8% of 103 patients with ILD developed AEs after undergoing nonthoracic surgery. Emergency surgery, preoperative corticosteroid use, and elevated C-reactive protein (CRP) were predictors of AE in univariate analysis, although only the use of propofol anesthesia remained a predictor in multivariate analysis. A more recent single-center study showed a 6.3% AE rate in 80 patients with ILD undergoing nonthoracic surgery.
      • Takao S.
      • Masuda T.
      • Yamaguchi K.
      • et al.
      High preoperative C-reactive protein level is a risk factor for acute exacerbation of interstitial lung disease after non-pulmonary surgery.
      Elevated CRP level, longer operative time, usual interstitial pneumonia (UIP) pattern on chest high-resolution CT imaging, and the need for transfusion were AE risk factors in univariate analysis, although only an elevated CRP remained predictive in multivariate analysis. Notably, lung function parameters (FVC and diffusing capacity of the lungs for carbon monoxide [Dlco]) were not predictive of increased PPC risk in any of these small studies.
      Increased PPC rates have been consistently seen in patients with ILD undergoing lung cancer resection. Kumar et al
      • Kumar P.
      • Goldstraw P.
      • Yamada K.
      • et al.
      Pulmonary fibrosis and lung cancer: risk and benefit analysis of pulmonary resection.
      demonstrated higher rates of ALI (21% vs 3.7%; P < .01) and mortality (17% vs 3.1%; P < .01) in patients with ILD undergoing lobectomy (12% vs 2.6%; P < .01) or pneumonectomy (33% vs 5.1%; P < .01) as compared with less extensive surgery. A lower median preoperative Dlco (58% predicted vs 70% predicted; P = .03) was also associated with an increased risk of ALI. Sato et al
      • Sato T.
      • Teramukai S.
      • Kondo H.
      • et al.
      Impact and predictors of acute exacerbation of interstitial lung diseases after pulmonary resection for lung cancer.
      similarly demonstrated an increased risk of ALI (9.3%) and associated mortality (43.9%) in over 1,000 patients with ILD undergoing lung cancer resection. Risk factors for ALI again included more extensive surgery, but also lower FVC (< 80% predicted), preoperative steroid use, chest CT imaging with UIP pattern, and male sex. Finally, multiple studies have shown an increased risk of PPCs in patients with ILD undergoing lung cancer resection with reduced postoperative predicted Dlco (OR, 0.728 for each 10% increase; CI, 0.565-0.939).
      • Ferguson M.K.
      • Vigneswaran W.T.
      Diffusing capacity predicts morbidity after lung resection in patients without obstructive lung disease.
      • Alam N.
      • Park B.J.
      • Wilton A.
      • et al.
      Incidence and risk factors for lung injury after lung cancer resection.
      Mortality and morbidity associated with SLB in patients with ILD have been extensively examined. Hutchinson et al
      • Hutchinson J.P.
      • Fogarty A.W.
      • McKeever T.M.
      • Hubbard R.B.
      In-hospital mortality after surgical lung biopsy for interstitial lung disease in the United States: 2000 to 2011.
      evaluated risk factors for mortality in over 32,000 patients with ILD who underwent SLB. Higher mortality was associated with male sex, older age, a greater Charlson Comorbidity Index score (CCI ≥ 2), open rather than thoracoscopic surgery, idiopathic pulmonary fibrosis (IPF) and connective tissue disease-ILD diagnosis, and most notably, the need for nonelective biopsy. Older age (> 55 years in men, > 74 years in women), male sex, and a higher CCI score remained significant predictors of mortality in patients who underwent elective rather than emergency SLB.
      • Hutchinson J.P.
      • Fogarty A.W.
      • McKeever T.M.
      • Hubbard R.B.
      In-hospital mortality after surgical lung biopsy for interstitial lung disease in the United States: 2000 to 2011.
      In studies published since 2000, mortality rates for patients with ILD undergoing outpatient SLB have ranged from 0 to 16.7%.
      • Raj R.
      • Raparia K.
      • Lynch D.A.
      • Brown K.K.
      Surgical Lung Biopsy for Interstitial Lung Diseases.
      • Kreider M.E.
      • Hansen-Flaschen J.
      • Ahmad N.N.
      • et al.
      Complications of video-assisted thoracoscopic lung biopsy in patients with interstitial lung disease.
      • Rotolo N.
      • Imperatori A.
      • Dominioni L.
      • et al.
      Efficacy and safety of surgical lung biopsy for interstitial disease: experience of 161 consecutive patients from a single institution in Italy.
      • Park J.H.
      • Kim D.K.
      • Kim D.S.
      • et al.
      Mortality and risk factors for surgical lung biopsy in patients with idiopathic interstitial pneumonia.
      The need for preoperative long-term oxygen therapy, reduced Dlco, pulmonary hypertension on echocardiogram (right ventricular systolic pressure ≥ 40 mm Hg) or right-sided heart catheterization, presence of an AE and/or preoperative respiratory failure, UIP histology or high-resolution CT scan findings, and immunosuppressed status have also demonstrated an increased risk of PPCs.
      • Raj R.
      • Raparia K.
      • Lynch D.A.
      • Brown K.K.
      Surgical Lung Biopsy for Interstitial Lung Diseases.
      • Kreider M.E.
      • Hansen-Flaschen J.
      • Ahmad N.N.
      • et al.
      Complications of video-assisted thoracoscopic lung biopsy in patients with interstitial lung disease.
      • Rotolo N.
      • Imperatori A.
      • Dominioni L.
      • et al.
      Efficacy and safety of surgical lung biopsy for interstitial disease: experience of 161 consecutive patients from a single institution in Italy.
      • Park J.H.
      • Kim D.K.
      • Kim D.S.
      • et al.
      Mortality and risk factors for surgical lung biopsy in patients with idiopathic interstitial pneumonia.
      Last, an increased risk of spontaneous AEs in patients with IPF has been reported in association with lower 6-minute walk test distance, lower Pao2, greater dyspnea (UCSD Shortness of Breath Questionnaire), and recent 10% decline in FVC.
      • Collard H.R.
      • Ryerson C.J.
      • Corte T.J.
      • et al.
      Acute exacerbation of idiopathic pulmonary fibrosis: an international working group report.
      These factors may confer an increased AE risk in the surgical setting as well.

      Approach to Risk Stratifying the Patient With ILD and Recommended Baseline Testing

      In summary, patients with ILD are at higher risk for PPCs than those without. Observational studies suggest that patients with ILD undergoing lung cancer resection or emergency surgery have a higher risk for PPCs than patients undergoing nonthoracic surgery or elective SLB for ILD diagnosis, and cite specific risk factors linked to poorer outcomes. Unfortunately, however, evidence-based models to approach risk stratification in this group do not currently exist. As recognition rates of ILD rise, the pressing need for prospective studies to define a standardized method to evaluate patients with ILD, and address outstanding questions in reference to perioperative risk, is clear
      • Raghu G.
      • Chen S.Y.
      • Hou Q.
      • Yeh W.S.
      • Collard H.R.
      Incidence and prevalence of idiopathic pulmonary fibrosis in US adults 18-64 years old.
      (Table 1).
      Table 1Treatment Dilemmas in Patients With ILD Undergoing Surgery
      • Do patients with ILD have the same risk of PPCs when undergoing nonthoracic surgery as compared with thoracic surgery?
      • Does the radiographic and/or histologic pattern (ie, subtype of ILD) impact PPC risk in ILD?
      • Should lung function thresholds be utilized to define which patients can safely undergo surgery?
      • Is there a Pao2 threshold or supplemental oxygen requirement that should define which patients can safely undergo surgery?
      • Should immunosuppressive therapy be routinely withheld in the perioperative setting in patients with ILD undergoing elective surgery?
      • Should antifibrotic therapy be routinely withheld in the perioperative setting in patients with IPF undergoing elective surgery?
      • Does lung-protective ventilation minimize the risk of PPCs in patients with ILD?
      • Does extubation to high-flow nasal cannula reduce the rate of PPCs in patients with ILD undergoing surgery?
      ILD = interstitial lung disease; IPF = idiopathic pulmonary fibrosis; PPC = postoperative pulmonary complication.
      We advocate utilizing an established index for predicting PPCs as a starting point for risk determination in patients with ILD. As the ARISCAT index (Table 2) predicts a broader range of PPCs than other calculators, we suggest using this scoring system to stratify patients into low-, intermediate-, and high-risk categories. In addition, smoking cessation, not a specific component of the ARISCAT index, is essential in all patients with ILD undergoing surgery. Based on the ILD literature, we additionally advise factoring in the patient’s comorbidities (CCI score), the need for long-term oxygen therapy, Dlco < 60%, preoperative FVC < 80% predicted in patients undergoing lung cancer resection, immunosuppressed status, and the presence of pulmonary hypertension.
      • Hutchinson J.P.
      • Fogarty A.W.
      • McKeever T.M.
      • Hubbard R.B.
      In-hospital mortality after surgical lung biopsy for interstitial lung disease in the United States: 2000 to 2011.
      • Kumar P.
      • Goldstraw P.
      • Yamada K.
      • et al.
      Pulmonary fibrosis and lung cancer: risk and benefit analysis of pulmonary resection.
      Some studies have shown an increased PPC risk in patients with UIP or an IPF diagnosis, although others have shown increased risk associated with a connective tissue disease-ILD diagnosis or no effect associated with the presence of UIP.
      • Choi S.M.
      • Lee J.
      • Park Y.S.
      • et al.
      Postoperative pulmonary complications after surgery in patients with interstitial lung disease.
      • Hutchinson J.P.
      • Fogarty A.W.
      • McKeever T.M.
      • Hubbard R.B.
      In-hospital mortality after surgical lung biopsy for interstitial lung disease in the United States: 2000 to 2011.
      • Kreider M.E.
      • Hansen-Flaschen J.
      • Ahmad N.N.
      • et al.
      Complications of video-assisted thoracoscopic lung biopsy in patients with interstitial lung disease.
      • Rotolo N.
      • Imperatori A.
      • Dominioni L.
      • et al.
      Efficacy and safety of surgical lung biopsy for interstitial disease: experience of 161 consecutive patients from a single institution in Italy.
      • Park J.H.
      • Kim D.K.
      • Kim D.S.
      • et al.
      Mortality and risk factors for surgical lung biopsy in patients with idiopathic interstitial pneumonia.
      As such, the role ILD morphology and subtype play in modulating perioperative risk is uncertain and should be examined prospectively. Procedural risk factors requiring deliberation include the need for emergency surgery or general anesthesia and open rather than thoracoscopic surgery. Lastly, patients with ILD have higher rates of OSA than the general population. Given that there is a well-documented increased PPC risk associated with OSA and a higher rate of OSA in IPF, it is vital to assess patients with ILD for OSA prior to surgery.
      • Lancaster L.H.
      • Mason W.R.
      • Parnell J.A.
      • et al.
      Obstructive sleep apnea is common in idiopathic pulmonary fibrosis.
      • Opperer M.
      • Cozowicz C.
      • Bugada D.
      • et al.
      Does obstructive sleep apnea influence perioperative outcome? A qualitative systematic review for the Society of Anesthesia and Sleep Medicine Task Force on Preoperative Preparation of Patients with Sleep-Disordered Breathing.
      Table 2ARISCAT Index
      Independent Predictor of PPC RiskRisk Score
      Age, y
       ≤ 500
       51-803
       > 8016
      Preoperative Spo2 %
       ≥ 960
       91-958
       ≤ 9024
      Respiratory infection in the last month17
      Preoperative anemia (< 10 g/dL)11
      Surgical incision site
       Peripheral0
       Upper abdominal15
       Intrathoracic24
      Duration of surgery, h
       ≤ 20
       > 2 to 316
       > 323
      Emergency procedure8
      PPC Risk (Based on Cumulative Score)ARISCAT Score
      Low risk: 1.6% PPC risk0-25
      Intermediate risk: 13.3% PPC risk26-44
      High risk: 42.1% PPC risk45-123
      Adapted with permission from Canet et al.
      • Canet J.
      • Gallart L.
      • Gomar C.
      • et al.
      Prediction of postoperative pulmonary complications in a population-based surgical cohort.
      ARISCAT = Assess Respiratory Risk in Surgical Patients in Catalonia; Spo2 % predicted = percent predicted peripheral arterial oxygen saturation. See Table 1 legend for expansion of other abbreviation.
      Clearly, the contribution of each individual risk factor cannot be directly quantified without prospectively validated models. Inherently, however, the greater the number of risk factors a patient has, the higher the cumulative risk of any planned surgical procedure (Table 3, Fig 1). Bearing in mind the indices and risk factors noted above, we advise that patients with ILD undergo the following tests prior to potential surgery: spirometry, Dlco, 6-minute walk test, assessment of ASA class and CCI, transthoracic echocardiogram, and screening for OSA. Most importantly, for elective surgery, patients should be advised of potential risks to enable informed decisions concerning these procedures.
      Table 3Patient- and Procedure-Related Risk Factors for ILD-Related PPCs
      FactorReference(s)
      Patient-related factors
       Male sex
      • Hutchinson J.P.
      • Fogarty A.W.
      • McKeever T.M.
      • Hubbard R.B.
      In-hospital mortality after surgical lung biopsy for interstitial lung disease in the United States: 2000 to 2011.
      ,
      • Takao S.
      • Masuda T.
      • Yamaguchi K.
      • et al.
      High preoperative C-reactive protein level is a risk factor for acute exacerbation of interstitial lung disease after non-pulmonary surgery.
       Dlco < 60% predicted
      • Furuya K.
      • Sakamoto S.
      • Takai Y.
      • Sato N.
      • Matsumoto K.
      • Homma S.
      Acute exacerbation of idiopathic interstitial pneumonia after nonpulmonary surgery under general anesthesia: a retrospective study.
      ,
      • Kumar P.
      • Goldstraw P.
      • Yamada K.
      • et al.
      Pulmonary fibrosis and lung cancer: risk and benefit analysis of pulmonary resection.
      ,
      • Sato T.
      • Teramukai S.
      • Kondo H.
      • et al.
      Impact and predictors of acute exacerbation of interstitial lung diseases after pulmonary resection for lung cancer.
       Preoperative home oxygen requirement
      • Ferguson M.K.
      • Vigneswaran W.T.
      Diffusing capacity predicts morbidity after lung resection in patients without obstructive lung disease.
      ,
      • Alam N.
      • Park B.J.
      • Wilton A.
      • et al.
      Incidence and risk factors for lung injury after lung cancer resection.
       Presence of acute exacerbation of ILD
      • Raj R.
      • Raparia K.
      • Lynch D.A.
      • Brown K.K.
      Surgical Lung Biopsy for Interstitial Lung Diseases.
      ,
      • Kreider M.E.
      • Hansen-Flaschen J.
      • Ahmad N.N.
      • et al.
      Complications of video-assisted thoracoscopic lung biopsy in patients with interstitial lung disease.
       Pulmonary hypertension
      a Transthoracic echocardiogram (right ventricular systolic pressure ≥ 40 mm Hg) or right-sided heart catheterization with mean pulmonary arterial pressure > 25 mm Hg.
      • Ferguson M.K.
      • Vigneswaran W.T.
      Diffusing capacity predicts morbidity after lung resection in patients without obstructive lung disease.
       Charlson Comorbidity Index score ≥ 2
      • Hutchinson J.P.
      • Fogarty A.W.
      • McKeever T.M.
      • Hubbard R.B.
      In-hospital mortality after surgical lung biopsy for interstitial lung disease in the United States: 2000 to 2011.
       Immunosuppressed status
      • Raj R.
      • Raparia K.
      • Lynch D.A.
      • Brown K.K.
      Surgical Lung Biopsy for Interstitial Lung Diseases.
      ,
      • Takao S.
      • Masuda T.
      • Yamaguchi K.
      • et al.
      High preoperative C-reactive protein level is a risk factor for acute exacerbation of interstitial lung disease after non-pulmonary surgery.
       OSA
      b Not specifically described in patients with ILD, although given increased rates of OSA in the IPF population is inferred to be of significance in the ILD population.
      Procedure-related factors
       General anesthesia
      • Lancaster L.H.
      • Mason W.R.
      • Parnell J.A.
      • et al.
      Obstructive sleep apnea is common in idiopathic pulmonary fibrosis.
      ,
      • Opperer M.
      • Cozowicz C.
      • Bugada D.
      • et al.
      Does obstructive sleep apnea influence perioperative outcome? A qualitative systematic review for the Society of Anesthesia and Sleep Medicine Task Force on Preoperative Preparation of Patients with Sleep-Disordered Breathing.
       Emergency surgery
      • Choi S.M.
      • Lee J.
      • Park Y.S.
      • et al.
      Postoperative pulmonary complications after surgery in patients with interstitial lung disease.
      ,
      • Hutchinson J.P.
      • Fogarty A.W.
      • McKeever T.M.
      • Hubbard R.B.
      In-hospital mortality after surgical lung biopsy for interstitial lung disease in the United States: 2000 to 2011.
       Longer duration of anesthesia/longer operative time (> 2 h)
      • Choi S.M.
      • Lee J.
      • Park Y.S.
      • et al.
      Postoperative pulmonary complications after surgery in patients with interstitial lung disease.
      ,
      • Furuya K.
      • Sakamoto S.
      • Takai Y.
      • Sato N.
      • Matsumoto K.
      • Homma S.
      Acute exacerbation of idiopathic interstitial pneumonia after nonpulmonary surgery under general anesthesia: a retrospective study.
      ,
      • Takao S.
      • Masuda T.
      • Yamaguchi K.
      • et al.
      High preoperative C-reactive protein level is a risk factor for acute exacerbation of interstitial lung disease after non-pulmonary surgery.
       Pulmonary/thoracic surgery
      • Choi S.M.
      • Lee J.
      • Park Y.S.
      • et al.
      Postoperative pulmonary complications after surgery in patients with interstitial lung disease.
       Open rather than thorascopic surgery
      • Hutchinson J.P.
      • Fogarty A.W.
      • McKeever T.M.
      • Hubbard R.B.
      In-hospital mortality after surgical lung biopsy for interstitial lung disease in the United States: 2000 to 2011.
       Pneumonectomy or lobectomy (vs wedge resection)
      c In patients undergoing lung cancer resection.
      • Furuya K.
      • Sakamoto S.
      • Takai Y.
      • Sato N.
      • Matsumoto K.
      • Homma S.
      Acute exacerbation of idiopathic interstitial pneumonia after nonpulmonary surgery under general anesthesia: a retrospective study.
      ,
      • Takao S.
      • Masuda T.
      • Yamaguchi K.
      • et al.
      High preoperative C-reactive protein level is a risk factor for acute exacerbation of interstitial lung disease after non-pulmonary surgery.
      Dlco = diffusing capacity of the lungs for carbon monoxide. See Table 1 legend for expansion of other abbreviations.
      a Transthoracic echocardiogram (right ventricular systolic pressure ≥ 40 mm Hg) or right-sided heart catheterization with mean pulmonary arterial pressure > 25 mm Hg.
      b Not specifically described in patients with ILD, although given increased rates of OSA in the IPF population is inferred to be of significance in the ILD population.
      c In patients undergoing lung cancer resection.
      Figure thumbnail gr1
      Figure 1Approach to preoperative evaluation of ILD patients undergoing surgery. Note: The figure is derived based on a combination of the published ARISCAT index and expert opinion regarding ILD specific factors. *Transthoracic echocardiogram-right ventricular systolic pressure estimated at > 50 mm Hg or right heart catheterization with mean pulmonary artery pressure > 35 mm Hg; **To calculate ARISCAT index, please see ; ***For ILD specific risk factors, please see . ARISCAT = Assess Respiratory Risk in Surgical Patients in Catalonia; ILD = interstitial lung disease; PPC = postoperative pulmonary complication.

      Perioperative Treatment Considerations

      Given the higher incidence of PPCs in patients with ILD, prudent perioperative treatment is crucial in reducing morbidity and mortality (Table 4). As noted in the preoperative risk assessment indices, the type and duration of surgery influences PPC risk. In general, minimally invasive procedures and shorter surgical times are preferred. There is incremental risk of PPCs in patients with high preoperative risk with general anesthesia (GA) when compared with regional anesthesia.
      • Rodgers A.
      • Walker N.
      • Schug S.
      • et al.
      Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview of randomised trials.
      Extrapolating from data obtained in patients with COPD, we recommend avoidance of GA when possible.
      • Hausman Jr., M.S.
      • Jewell E.S.
      • Engoren M.
      Regional versus general anesthesia in surgical patients with chronic obstructive pulmonary disease: does avoiding general anesthesia reduce the risk of postoperative complications?.
      Studies show that SLBs obtained under epidural anesthesia or intercostal blocks are feasible, efficacious, and associated with lower morbidity compared with those obtained under GA.
      • Pompeo E.
      • Rogliani P.
      • Cristino B.
      • Schillaci O.
      • Novelli G.
      • Saltini C.
      Awake thoracoscopic biopsy of interstitial lung disease.
      Neuromuscular blockade used with GA was shown to be associated with an increased risk of PPCs in the general population.
      • Kirmeier E.
      • Eriksson L.I.
      • Lewald H.
      • et al.
      POPULAR Contributors
      Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study.
      In patients with ILD and limited pulmonary reserve, residual postoperative neuromuscular blockade may result in hypoventilation and atelectasis, potentially increasing the risk of PPCs.
      Table 4Perioperative Considerations in Patients With ILD
      Treatment ConsiderationReference(s)
      Avoidance of surgery during active pulmonary infection
      a Based on expert opinion.
      Smoking cessation
      • Smetana G.W.
      • Lawrence V.A.
      • Cornell J.E.
      American College of Physicians
      Preoperative pulmonary risk stratification for noncardiothoracic surgery: systematic review for the American College of Physicians.
      Avoidance of general anesthesia, when possible
      • Lancaster L.H.
      • Mason W.R.
      • Parnell J.A.
      • et al.
      Obstructive sleep apnea is common in idiopathic pulmonary fibrosis.
      ,
      • Opperer M.
      • Cozowicz C.
      • Bugada D.
      • et al.
      Does obstructive sleep apnea influence perioperative outcome? A qualitative systematic review for the Society of Anesthesia and Sleep Medicine Task Force on Preoperative Preparation of Patients with Sleep-Disordered Breathing.
      Avoidance of neuromuscular blockade, when possible
      • Hausman Jr., M.S.
      • Jewell E.S.
      • Engoren M.
      Regional versus general anesthesia in surgical patients with chronic obstructive pulmonary disease: does avoiding general anesthesia reduce the risk of postoperative complications?.
      Lung-protective ventilation
      • Pompeo E.
      • Rogliani P.
      • Cristino B.
      • Schillaci O.
      • Novelli G.
      • Saltini C.
      Awake thoracoscopic biopsy of interstitial lung disease.
      ,
      • Kirmeier E.
      • Eriksson L.I.
      • Lewald H.
      • et al.
      POPULAR Contributors
      Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study.
      ,
      • Brower R.G.
      • Matthay M.A.
      • et al.
      Acute Respiratory Distress Syndrome Network
      Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.
      ,
      • Futier E.
      • Constantin J.M.
      • Paugam-Burtz C.
      • et al.
      A trial of intraoperative low-tidal-volume ventilation in abdominal surgery.
      ,
      • Fernandez-Perez E.R.
      • Yilmaz M.
      • Jenad H.
      • et al.
      Ventilator settings and outcome of respiratory failure in chronic interstitial lung disease.
      ,
      • Hemmes S.N.
      • Gama de Abreu M.
      • Pelosi P.
      • Schultz M.J.
      PROVE Network Investigators for the Clinical Trial Network of the European Society of Anaesthesiology
      High versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial.
      Judicious intraoperative intravenous fluid use
      • Dikmen Y.
      • Onur A.
      Perioperative hyperoxia: perhaps a malady in disguise.
      Extubation to HFNC
      • Koksal G.M.
      • Dikmen Y.
      • Erbabacan E.
      • et al.
      Hyperoxic oxidative stress during abdominal surgery: a randomized trial.
      DVT prophylaxis
      • do Nascimento Junior P.
      • Módolo N.S.
      • Andrade S.
      • Guimarães M.M.
      • Braz L.G.
      • El Dib R.
      Incentive spirometry for prevention of postoperative pulmonary complications in upper abdominal surgery.
      Incentive spirometry and early mobilization postoperatively
      a Based on expert opinion.
      HFNC = high-flow nasal cannula. See Table 1 legend for expansion of other abbreviation.
      a Based on expert opinion.
      Optimizing mechanical ventilation is the cornerstone of perioperative treatment of patients with ILD undergoing GA. Lung-protective ventilation focusing on low tidal volumes and positive end-expiratory pressure (PEEP) reduces mortality in patients with ARDS.
      • Brower R.G.
      • Matthay M.A.
      • et al.
      Acute Respiratory Distress Syndrome Network
      Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.
      This approach has gained broad acceptance in the surgical setting, with increasing evidence of reduced PPCs with application of lung-protective ventilation in the operating room.
      • Futier E.
      • Constantin J.M.
      • Paugam-Burtz C.
      • et al.
      A trial of intraoperative low-tidal-volume ventilation in abdominal surgery.
      • Maslow A.D.
      • Stafford T.S.
      • Davignon K.R.
      • Ng T.
      A randomized comparison of different ventilator strategies during thoracotomy for pulmonary resection.
      However, as a fibrotic lung has a reduced fraction of recruitable lung, an approach of increasing PEEP in response to hypoxemia will often not result in enhanced lung recruitment in ILD
      • Fernandez-Perez E.R.
      • Yilmaz M.
      • Jenad H.
      • et al.
      Ventilator settings and outcome of respiratory failure in chronic interstitial lung disease.
      and may actually increase the incidence of intraoperative hypotension.
      • Hemmes S.N.
      • Gama de Abreu M.
      • Pelosi P.
      • Schultz M.J.
      PROVE Network Investigators for the Clinical Trial Network of the European Society of Anaesthesiology
      High versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial.
      As such, we recommend a lung-protective ventilatory strategy with tidal volumes 6 to 8 mL/kg of ideal body weight, plateau pressures ≤ 30 cm H2O, and the least PEEP necessary to maintain adequate oxygenation in patients with ILD.
      Underappreciated potential perils of supplemental oxygen include the clinical consequences of high perioperative Fio2,
      • Dikmen Y.
      • Onur A.
      Perioperative hyperoxia: perhaps a malady in disguise.
      such as absorptive atelectasis and increased oxidative stress from exposure to high Fio2.
      • Koksal G.M.
      • Dikmen Y.
      • Erbabacan E.
      • et al.
      Hyperoxic oxidative stress during abdominal surgery: a randomized trial.
      These events, observed in the general population, may similarly increase PPC risk in patients with ILD. As such, we recommend use of the lowest possible Fio2 that maintains the Sao2 at ≥ 88% to 92%. In addition to the cellular stress from mechanical ventilation, risk of lung injury in patients with ILD can be exacerbated by perioperative fluid overload.
      • Mizuno Y.
      • Iwata H.
      • Shirahashi K.
      • et al.
      The importance of intraoperative fluid balance for the prevention of postoperative acute exacerbation of idiopathic pulmonary fibrosis after pulmonary resection for primary lung cancer.
      We suggest minimizing intraoperative fluid infusion in patients with ILD while maintaining euvolemia.

      Postoperative Treatment Considerations

      The benefit of extubation to noninvasive ventilation, including high-flow nasal cannula (HFNC) and bilevel positive airway pressure (BiPAP), has not been ascertained in patients with ILD. However, in patients undergoing cardiothoracic surgery, the use of HFNC or BiPAP similarly reduced reintubation rates in those at high risk for acute hypoxic respiratory failure (AHRF) or those who had developed AHRF.
      • Stephan F.
      • Barrucand B.
      • Petit P.
      • et al.
      High-flow nasal oxygen vs noninvasive positive airway pressure in hypoxemic patients after cardiothoracic surgery: a randomized clinical trial.
      These findings suggest that extubation to an HFNC in patients with ILD may plausibly mitigate the risk of postoperative AHRF. The role of postextubation BiPAP in patients with ILD is more difficult to ascertain. While it may abrogate postoperative obstructive events and hypoxia due to undiagnosed OSA, it delivers a greater degree of positive pressure, which in our opinion could also be detrimental in patients with ILD.
      • Faverio P.
      • De Giacomi F.
      • Sardella L.
      • et al.
      Management of acute respiratory failure in interstitial lung diseases: overview and clinical insights.
      Atelectasis develops in a majority of patients undergoing GA, with persistence in the postoperative period. Incentive spirometry is routinely used, despite low-quality evidence supporting its effectiveness in PPC prevention.
      • do Nascimento Junior P.
      • Módolo N.S.
      • Andrade S.
      • Guimarães M.M.
      • Braz L.G.
      • El Dib R.
      Incentive spirometry for prevention of postoperative pulmonary complications in upper abdominal surgery.
      This stated, given its safety and low cost, we recommend using it in patients with ILD. Small observational studies support early mobilization and physical therapy to help with reduction of atelectasis and is advised for patients with ILD.
      • Stephan F.
      • Barrucand B.
      • Petit P.
      • et al.
      High-flow nasal oxygen vs noninvasive positive airway pressure in hypoxemic patients after cardiothoracic surgery: a randomized clinical trial.
      • do Nascimento Junior P.
      • Módolo N.S.
      • Andrade S.
      • Guimarães M.M.
      • Braz L.G.
      • El Dib R.
      Incentive spirometry for prevention of postoperative pulmonary complications in upper abdominal surgery.
      There is a high incidence of VTE in patients with ILD.
      • Balestro E.
      • Solidoro P.
      • Parigi P.
      • Boffini M.
      • Lucianetti A.
      • Rea F.
      Safety of nintedanib before lung transplant: an Italian case series.
      Hence, we recommend use of current guidelines for appropriate prophylactic anticoagulation for these patients when there are no absolute contraindications.
      • Iwata T.
      • Yoshino I.
      • Yoshida S.
      • et al.
      A phase II trial evaluating the efficacy and safety of perioperative pirfenidone for prevention of acute exacerbation of idiopathic pulmonary fibrosis in lung cancer patients undergoing pulmonary resection: West Japan Oncology Group 6711 L (PEOPLE Study).
      There is no evidence that perioperative antibiotics prevent postoperative pneumonia; they should be used only when clinically indicated for increased sputum production and/or fevers with opacities on thoracic imaging. In patients scheduled for elective surgery, we recommend postponing surgery until completion of a treatment course with antibiotics and resolution of symptoms.
      Stress-dose steroids are recommended only for patients considered to have a suppressed hypothalamic-pituitary axis (prednisone at > 20 mg/d, or equivalent, for more than 3 weeks, or Cushing’s syndrome). In all other patients, we recommend continuing the current dose of steroids and/or testing the hypothalamic-pituitary axis.
      • Mortensen A.
      • Cherrier L.
      • Walia R.
      Effect of pirfenidone on wound healing in lung transplant patients.
      Based on their mechanisms of action, theoretically the antifibrotic agents pirfenidone and nintedanib may impair wound healing following surgery. However, small observational studies have thus far failed to show any major postoperative complications with either of these agents.
      • Balestro E.
      • Solidoro P.
      • Parigi P.
      • Boffini M.
      • Lucianetti A.
      • Rea F.
      Safety of nintedanib before lung transplant: an Italian case series.
      • Iwata T.
      • Yoshino I.
      • Yoshida S.
      • et al.
      A phase II trial evaluating the efficacy and safety of perioperative pirfenidone for prevention of acute exacerbation of idiopathic pulmonary fibrosis in lung cancer patients undergoing pulmonary resection: West Japan Oncology Group 6711 L (PEOPLE Study).
      • Mortensen A.
      • Cherrier L.
      • Walia R.
      Effect of pirfenidone on wound healing in lung transplant patients.
      Because of the lack of larger trials evaluating the potential adverse effects of pirfenidone and nintedanib, we cannot make a recommendation regarding perioperative dosing of these medications.

      Conclusions

      The risk of postoperative pulmonary complications in patients undergoing thoracic or nonthoracic surgery in the ILD population is elevated. Retrospective data to guide clinicians on treatment strategies are available, although limited. Clinical recommendations and scoring systems for the general population that stratify patients into low-, intermediate-, and high-risk categories can be helpful. However, prospective studies that specifically evaluate the safest treatment strategies for patients with interstitial lung disease in the operative setting are urgently needed.

      Acknowledgments

      Financial/nonfinancial disclosures: The authors have reported to CHEST the following: N. M. P.: Boehringer Ingelheim (speaker and consultant on advisory boards, investigator in clinical trials), Roche/Genentech (speaker); T. K.: Boehringer Ingelheim (speaker), Biogen (investigator in clinical trial); D. D.: Roche/Genentech (speaker, advisory board, investigator in clinical trials), Boehringer Ingelheim (speaker, advisory board, investigator in clinical trials), Gilead (investigator in clinical trials); M. B. S.: Boehringer Ingelheim (advisory board, investigator in clinical trials), Roche/Genentech (advisory board, investigator in a clinical trial), Fibrogen (investigator in a clinical trial), Global Blood Therapeutics (investigator in a clinical trial).
      *Interstitial and Diffuse Lung Disease Network Steering Committee collaborators: Nishant Gupta, MD; Mary Strek, MD; Joanne Shirine Allam, MD; Joao de Andrade, MD; Lisa Lancaster, MD; Roberto Carbone, MD; Samantha D’Annunzio, MD; Avanthika Thanushi Wickramarathne, MD; Tracy Luckhardt, MD; Corey Kershaw, MD.
      Other contributions: All authors and collaborators contributed to critical revision of the manuscript for important intellectual content.

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