Supplementary Online Content

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1 Supplementary Online Content Fernandez-Bustamante A, Frendl G, Sprung J, et al. Multicenter assessment of postoperative pulmonary complications, early mortality, and hospital stay following noncardiothoracic surgery: a study by the Perioperative Research Network Investigators. JAMA Surg. Published online November 9, 206. doi:0.00/jamasurg eappendix. Definitions of Comorbidities, Outcomes, and Other Relevant Variables. ereferences etable. All variables. This supplementary material has been provided by the authors to give readers additional information about their work. 206 American Medical Association. All rights reserved. Downloaded From: on 2/5/208

2 2 eappendix. Definitions of Comorbidities, Outcomes, and Other Relevant Variables.. Definitions of comorbidities, as determined by the presence in the preoperative interview or medical record of the following diagnoses: a. Cerebrovascular disease: cerebrovascular accident, stroke, transient ischemic accident, mini-stroke; b. Neurological disease: diagnoses affecting motor, sensory, or cognitive dysfunction; c. Hypertension: hypertension, high blood pressure; d. Coronary artery disease: myocardial infarct; heart attack; angina; history of interventional angioplasty or Coronary Artery Bypass Graft surgery; e. Heart Failure: systolic or diastolic heart failure, CHF, cardiomyopathy; f. Cardiac valvular disease: Ao/M/P/T valvular disease; g. Chronic Obstructive Pulmonary Disease: COPD, chronic bronchitis, emphysema; h. Asthma: asthma, reactive airway disease; i. Interstitial lung disease: interstitial lung disease, pulmonary fibrosis, sarcoidosis, asbestosis, silicosis, siderosis, Farmer s lung; j. Sleep Apnea: sleep apnea, OSA, Apnea Hypopnea Index (AHI 5 or AHI 5 with OSA symptoms, presence of >3 STOP BANG criteria (Snoring, Tiredness, Observed nocturnal apnea; hypertension, BMI>35, Age>50yo, thick Neck or circumference >40cm/6in, Gender male; k. Smoking history: smoking l. Renal Failure: acute or chronic renal failure m. Liver Disease: cirrhosis, hepatomegaly, liver failure, liver disease related ascites; n. Diabetes: diabetes type or 2; o. Thyroid Disease: hypo/hyperthyroidism, thyroiditis, or prescribed thyroid medications; p. Ethanol abuse: average >2 drinks/day (>4/week in males, average > drink/day (>7/week in females, drink being 4.0 grams (0.6 ounces of pure alcohol (2oz of beer, 8oz of malt liquor, 5oz of wine,.5oz or a shot of 80-proof distilled spirits or liquor ( 2. Other relevant definitions: a. Body Mass Index (BMI was calculated as height(m x weight(kg -2. b. Predicted Body Weight (PBW was calculated as: PBW (Men = x ((height (cm 52.4 and PBW (Women = (0.9 x height (cm c. Medications were collected as current if they had been used during the 30 days prior to surgery. d. Length of surgery: start (incision time to end surgery end time e. Length of ventilation: intubation to extubation time (Extubation time to be replaced as out of room if patients extubated in post-anesthesia care unit, PACU, and no precise time can be obtained f. Morphine equivalents. Morphine equivalents were calculated with the following conversion factors 2 : morphine dose *, hydromorphone dose *5, oxymorphone dose *0, fentanyl dose *00, sufentanil dose *,000. Remifentanil was excluded from this calculation because of its ultra-short residual effect for analgesia and respiratory depression. 3. Postoperative Outcomes (within 7 days from surgery end: a. Respiratory Failure, defined as in 3 : When postoperative PaO 2 <60mmHg on room air, a ratio of PaO 2 to inspired oxygen fraction <300 or arterial oxyhemoglobin saturation measured with pulse oxymetry <90% and requiring oxygen therapy. b. Unplanned intubation with postoperative mechanical ventilation (POMV, defined as placement of a breathing tube that was not intended or planned, excluding instances of intubation during an unplanned return to the operating room. Also excluded those patients that were transferred intubated and ventilated to the intensive care unit (ICU from the operating room. c. ARDS, based on the Berlin definition American Medical Association. All rights reserved. Downloaded From: on 2/5/208

3 3 d. Pneumonia or Respiratory infection as defined per NSQIP criteria 5 : having at least definitive chest radiologic examination and at least sign of pneumonia (fever, leukocytosis, or altered mental status with no other cause, as well as at least microbiologic laboratory finding (positive cultures from blood, bronchoalveolar lavage, or pleural fluid specimens or at least 2 symptoms (purulent sputum, worsening cough, dyspnea or tachypnea, rales or rhonchi, or worsening gas exchange. e. Pneumothorax defined as in 3 : Air in the pleural space with no vascular bed surrounding the visceral pleura. f. Atelectasis, defined as in 3 : Lung opacification with a shift of the mediastinum, hilum, or hemidiaphragm toward the affected area, and compensatory overinflation in the adjacent nonatelectatic lung (based on radiology reports/medical chart. g. Pleural effusion, defined as in 3 : Chest x-ray demonstrating blunting of the costophrenic angle, loss of the sharp silhouette of the ipsilateral hemipiaphragm in upright position, evidence of displacement of the adjacent anatomical structures, or (in the supine position a hazy opacity in one hemithorax with preserved vascular shadows (based on radiology reports/medical chart. h. Bronchospasm, defined as presence in medical chart of bronchospasm and/or wheezing + bronchodilators (not bronchodilators alone. ereferences. ARDSNet. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342(8: Barash PGea. Clinical anesthesia 7th ed., chapter 56. 7th ed. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins; Canet J, Gallart L, Gomar C, et al. Prediction of postoperative pulmonary complications in a population-based surgical cohort. Anesthesiology. 200;3(6: ARDS Definition Task Force T. Acute Respiratory Distress Syndrome: The Berlin definition. JAMA: The Journal of the American Medical Association. 202;307(23: Cassidy MR, Rosenkranz P, McCabe K, Rosen JE, McAneny D. I COUGH: reducing postoperative pulmonary complications with a multidisciplinary patient care program. JAMA surgery. 203;48(8: American Medical Association. All rights reserved. Downloaded From: on 2/5/208

4 4 etable. All variables. Study group characteristics and bivariable analysis results for PPC composite. Data represent Mean (SD or n (% of column of selected variables as appropriate unless otherwise stated. Variables Demographics Total Patients (n=,202 PPC (n=40 No PPC (n=80 Relativ e Risk P value Age 62.( ( (4.2 <0.000 Siteadjuste d P value <0.000 a Gender Male 636( ( ( Body Mass Index 30.0( ( ( Comorbidities Cerebrovascular Disease 03 (8.6 33(8.2 70( Neurological Disease 265(22. 90( ( Hypertension 790( ( ( a Coronary Artery Disease Cardiac Valvular Disease 246( ( ( (6.0 27(6.7 45( Heart Failure 68(5.7 3(7.7 37( a Anemia (Hemoglobin <0g/dL Chronic Obstructive Pulmonary Disease 24(0.3 50(2.4 74( a 03(8.6 52(3.0 5( a Asthma 72(4.3 52(3.0 20( Obstructive Sleep Apnea 234(9.5 88(2.9 46( Smoking, Current 6(3.4 59(4.7 02( Smoking, Former 478( ( ( a Cancer 499(4.5 87( ( a Gastro-Esophageal Reflux Disease 43( ( ( a Renal Disease 245(20.4 9( ( Chronic Renal failure 38(.5 54(3.5 84( Liver Disease 46(2.2 58(4.5 88( Diabetes 30(25.0 0(27.4 9( Thyroid Disease 99(6.6 74(8.5 25( American Medical Association. All rights reserved. Downloaded From: on 2/5/208

5 5 Alcohol Abuse 92(7.7 35(8.7 57( Current Medications Beta Agonists 43(.9 52(3.0 9( Ipratropium 48(4.0 6(4.0 32( Inhaled Steroids 50(2.5 44(.0 06( Oral Steroids 4(9.5 36(9.0 78( Leukotriene Inhibitor 33(2.7 7(.7 26( Beta Blockers 463( (4. 298( Aspirin 493(4.0 72( ( Statin 502(4.8 74( ( Calcium Channel Blocker Angiotensin Converting Enzyme Inhibitor Angiotensin Receptor Blocker 246(20.5 9( ( ( ( ( (.5 50(2.5 88( Nitrate 35(2.9 5( ( Diuretic 293( (25.4 9( Insulin 08(9.0 45(.2 63( a Other Diabetes Medication 78(4.8 68(7.0 0( Proton Pump Inhibitor 423( ( ( Histamine-2 (H 2 Receptor Inhibitor Surgical procedure Surgery category 78(6.5 37(9.2 4( b Abdominal/pelvic 545( ( ( <0.000 Nonabdominal/pelvic 657(54.7 6( (6.9 Emergency 6(5. 34(8.5 27( < a a Any regional block 266(22. 2( ( b Surgery Duration (h 3.6( ( (.7 <0.000 Anesthesia Duration (h 4.7( ( (.9 <0.000 <0.000 b <0.000 a Preoperative SpO 2 (% 97.2( ( ( a Preoperative 2.4(2. 2.(2. 2.5( b 206 American Medical Association. All rights reserved. Downloaded From: on 2/5/208

6 6 Hemoglobin (g/dl Intraoperative Mechanical Ventilation Ventilatory Modes Volume Control (VCV Pressure Control (PCV, PCV-VG Assisted/Supporte d (PSV, SIMV 824( ( ( d 78(4.8 80( ( (4.0 (2.8 37( Unspecified 5(2.6 49(2.3 02( Median Exhaled V T (ml/kgpbw 8.0(.6 8.0(.6 8.0( a,c Median FiO 2 (% 54.4( ( ( a,c Median PEEP (cmh 2 O 5.(.7 5.2(.7 5.0( a,c Respiratory Rate (breaths/minute Peak Inspiratory Pressure (cmh 2 O Plateau Airway Pressure (cmh 2 O 2.0(2.2.9(2.3 2.( ( ( ( ( ( ( SpO 2 (% 98.8( ( ( SpO 2 <90% (minutes 0.8( (3. 0.5( E T CO 2 (mmhg 35.( ( ( Intraoperative Hemodynamic Data Systolic Blood Pressure (mmhg Systolic Blood Pressure <90mmHg (minutes Diastolic Blood Pressure (mmhg Mean Blood Pressure (mmhg Mean Blood Pressure <60mmHg (minutes Heart Rate (beats/minute Median Temperature ( C 6.8( ( ( ( (.6 4.6( ( ( ( b 82.6( ( ( ( ( ( b 69.8( ( (2.0 < b 36.( (. 36.7( b 206 American Medical Association. All rights reserved. Downloaded From: on 2/5/208

7 7 Perioperative Fluid Management Crystalloids (ml/kg/h 6.3( (3.8 6.( a Colloids (ml/kg/h 0.3( (. 0.2(0.6 <0.000 Any Blood Product 32(.0 70(7.5 62(7.7 <0.000 Packed Red Blood Cells Fresh Frozen Plasma <0.000 a a 8(9.8 62(5.5 56(7.0 < (3.5 29(7.2 3(.6 < Platelets 9(.6 (2.7 8( Estimated blood loss (ml 343( ( (493 <0.000 <0.000 a Urine Output (ml/kg/h.2(.5.2(.3.3( b Intraoperative Medications Anesthesia Desflurane 340( ( (22.8 < b Sevoflurane 670( ( ( Isoflurane 248(20.6 8( ( Nitrous Oxide 20(7.5 72(8.0 38( Propofol 5( ( ( Analgesia Patients, n(% Dose Fentanyl,4( ( ( Sufentanil 59(4.9 2(5.2 38( Hydromorphone 635( ( ( Morphine 69(5.7 7(4.2 52( Remifentanil 20(7.5 56(4.0 54( Ketamine 59(3.2 72(8.0 87( b Fentanyl Sufentanil Hydromorphone.0(0.8.0(0.8.0( ( (2. 2.2( ( ( ( American Medical Association. All rights reserved. Downloaded From: on 2/5/208

8 8 Morphine Morphine Equivalents Remifentanil (mcg/kg/min.7(8.7.0(5. 2.0( b 2.2(8.6.4( ( a 0.03( ( ( Ketamine (mg 2(84 4(272 2( a Neuro-Muscular Blockade Depolarizing NMBA Non-depolarizing NMBA 440( ( ( ,038( ( ( a NMBA Monitoring 749( ( ( NMBA Reversal 883( ( ( Neostigmine (mcg/kg Vasoactive Drugs 3.5( ( ( a Phenylephrine 859( ( ( b Ephedrine 527( ( ( b Vasopressin 27(2.2 6(4.0 ( (E T CO 2 =End-tidal partial pressure of carbon dioxide; FiO 2 =Inspired oxygen fraction; NMBA=Neuromuscular blocking agent; PBW=Predicted Body Weight; PEEP=Positive End-Expiratory Pressure; SpO 2 =peripheral saturation of oxygen ( a Variables included in the logistic regression analysis; b Variables that were statistically significant in the univariable analysis but were excluded from the logistic regression analysis because of their clinical and/or statistical correlation with other included covariates; c Variables that were included in the logistic model as focus of this study, independently of the p value; d compared to VCV as reference mode 206 American Medical Association. All rights reserved. Downloaded From: on 2/5/208