Postoperative pulmonary complications contribute importantly

Transcription

1 Aals of Iteral Medicie Cliical Guidelies Preoperative Pulmoary Risk Stratificatio for Nocardiothoracic Surgery: Systematic Review for the America College of Physicias Gerald W. Smetaa, MD; Valerie A. Lawrece, MD; ad Joh E. Corell, PhD Backgroud: The importace of cliical risk factors for postoperative pulmoary complicatios ad the value of preoperative testig to stratify risk are the subject of debate. Purpose: To systematically review the literature o preoperative pulmoary risk stratificatio before ocardiothoracic surgery. Data Sources: MEDLINE search from 1 Jauary 1980 through 30 Jue 2005 ad had search of the bibliographies of retrieved articles. Study Selectio: Eglish-laguage studies that reported the effect of patiet- ad procedure-related risk factors ad laboratory predictors o postoperative pulmoary complicatio rates after ocardiothoracic surgery ad that met predefied iclusio criteria. Data Extractio: The authors used stadardized abstractio istrumets to extract data o study characteristics, hierarchy of research desig, study quality, risk factors, ad laboratory predictors. Data Sythesis: The authors determied radom-effects pooled estimate odds ratios ad, whe appropriate, trim-ad-fill estimates for patiet- ad procedure-related risk factors from studies that used multivariable aalyses. They assiged summary stregth of evidece scores for each factor. Good evidece supports patietrelated risk factors for postoperative pulmoary complicatios, icludig advaced age, America Society of Aesthesiologists class 2 or higher, fuctioal depedece, chroic obstructive pulmoary disease, ad cogestive heart failure. Good evidece supports procedure-related risk factors for postoperative pulmoary complicatios, icludig aortic aeurysm repair, oresective thoracic surgery, abdomial surgery, eurosurgery, emergecy surgery, geeral aesthesia, head ad eck surgery, vascular surgery, ad prologed surgery. Amog laboratory predictors, good evidece exists oly for serum albumi level less tha 30 g/l. Isufficiet evidece supports preoperative spirometry as a tool to stratify risk. Limitatios: For certai risk factors ad laboratory predictors, the literature provides oly uadjusted estimates of risk. Prescreeig, variable selectio algorithms, ad publicatio bias limited reportig of risk factors amog studies usig multivariable aalysis. Coclusios: Selected cliical ad laboratory factors allow risk stratificatio for postoperative pulmoary complicatios after ocardiothoracic surgery. A Iter Med. 2006;144: For author affiliatios, see ed of text. Postoperative pulmoary complicatios cotribute importatly to the risk for surgery ad aesthesia. The most importat ad morbid postoperative pulmoary complicatios are atelectasis, peumoia, respiratory failure, ad exacerbatio of uderlyig chroic lug disease. Sice the publicatio of the first cardiac risk idex i 1977 (1), cliicias have bee aware of the importace of, ad the risk factors for, cardiac complicatios. Cliicias who care for patiets i the perioperative period may be surprised to lear that postoperative pulmoary complicatios are equally prevalet ad cotribute similarly to morbidity, mortality, ad legth of stay. For example, i a large retrospective cohort study of 8930 patiets udergoig hip fracture repair, 1737 (19%) patiets had postoperative medical complicatios (2). Serious pulmoary complicatios occurred i 229 (2.6%) patiets ad serious cardiac complicatios occurred i 178 (2.0%) patiets. Similarly, i a study of 2964 patiets udergoig elective ocardiac surgery, postoperative pulmoary ad cardiac complicatios occurred i 53 patiets ad 64 patiets, respectively (3). Rates of postoperative cardiac ad pulmoary complicatios are similar i other large cohort studies of patiets udergoig ocardiac surgery (4 6). Pulmoary complicatios may also be more likely tha cardiac complicatios to predict log-term mortality after surgery. For example, amog postoperative complicatios i a recet study of patiets older tha 70 years of age who were udergoig ocardiac surgery, oly pulmoary ad real complicatios predicted log-term mortality (7). I aother report of patiets udergoig esophagectomy for cacer, postoperative peumoia was secod oly to tumor stage i predictig log-term survival after surgery ad predicted log-term mortality to a greater degree tha postoperative cardiac, real, or hepatic complicatios (8). Office ad hospital cosultatio for patiets preparig for surgery is a importat activity for iterists. While guidelies ad cosesus statemets for perioperative cardiac evaluatio have bee published (9, 10), o similar guidelie is available to assist i perioperative pulmoary evaluatio. The quality ad umber of studies that estimate perioperative pulmoary risk have icreased i the past 2 decades, ad this is o loger a eglected area of iquiry. We prepared this 2-part systematic review 1) to See also: Prit Related articles , 596 Summary for Patiets....I-40 Web-Oly Appedix Appedix Tables CME quiz Coversio of figure ad tables ito slides 2006 America College of Physicias 581 Dowloaded From: o 05/16/2016

2 Cliical Guidelies Preoperative Pulmoary Risk Stratificatio for Nocardiothoracic Surgery guide cliicias o cliical ad laboratory predictors of perioperative pulmoary risk before ocardiothoracic surgery ad 2) to evaluate the efficacy of strategies to reduce the risk for postoperative pulmoary complicatios (11). Risk factors for postoperative veous thromboembolism differ substatially from those for postoperative pulmoary complicatios, ad they are ot the subject of our review. METHODS Literature Search ad Selectio Criteria The Appedix (available at cotais a detailed descriptio of our methodology. We performed a MEDLINE search to idetify relevat publicatios from 1 Jauary 1980 through 30 Jue We used the followig Medical Subject Headig (MeSH) terms ad specified that they be the article s primary focus: itraoperative complicatios, postoperative complicatios, preoperative care, itraoperative care, ad postoperative care, plus the text term perioperative complicatios i the title or abstract. We idetified additioal MeSH ad text terms by a review of the MEDLINE idexig for the retrieved articles. These icluded terms for pulmoary, respiratory, or cardiopulmoary diseases, coditios, or complicatios ad terms for oxygeatio ad chest roetgeography. We performed additioal searches specific to preoperative chest radiography ad preoperative spirometry. We idetified additioal refereces by reviewig bibliographies of retrieved studies. We icluded oly Eglish-laguage publicatios ad excluded publicatio types without primary data (that is, letters, editorials, case reports, coferece proceedigs, ad arrative reviews). We excluded 1) studies with fewer tha 25 participats per study group; 2) studies that used oly admiistrative data (for example, Iteratioal Classificatio of Diseases, Nith Revisio, Cliical Modificatio [ICD-9-CM] codes) or lacked explicit criteria or defiitios for pulmoary complicatios; 3) studies from developig coutries (because of potetial differeces i respiratory ad itesive care techology); 4) studies of ambulatory surgery; 5) studies of physiologic (for example, lug volumes ad flow, oximetry) rather tha cliical outcomes; 6) studies of gastric ph maipulatio; 7) studies of complicatios uique to a particular type of surgery (for example, upper airway obstructio after uvulectomy); 8) studies of cardiopulmoary or pediatric surgery; ad 9) studies of orga trasplatatio surgery (because of profoudly immuosuppressive drugs). Of citatios idetified by the search, 1223 citatios were duplicates ad citatios were ot relevat by title ad abstract review (Figure). Of the remaiig 943 potetially relevat citatios, we excluded 626 citatios after review of the full publicatio ad abstracted 145 citatios i detail. Assessig Study Quality We used the U.S. Prevetive Services Task Force (USPSTF) criteria for assigig hierarchy of research desig, gradig a study s iteral validity as our basis for assessig study quality, ad assigig summary stregth of recommedatios for each risk factor ad laboratory test (12). Statistical Aalysis Our literature search yielded primarily uadjusted estimates for most laboratory factors of iterest. Limited multivariable, adjusted studies were available for serum albumi level less tha 30 g/l ad elevated blood urea itroge level. However, rather tha attempt to compute potetially biased summary estimates, we provided arrative descriptios of the patter of results for these potetial risk factors. The eligible multivariable risk factor studies varied cosiderably i the umber ad type of competig risks ad cofouders icluded i the aalyses. Extesive use of prescreeig methods ad variable selectio algorithms ofte limited reportig to the subset of risk factors that were determied to be statistically sigificat i a give sample. The result is a subtle form of publicatio bias, which we verified by examiatio of the fuel plots ad trim-adfill estimates for each risk factor. We extracted odds ratios from each study, alog with their respective SEs, 95% cofidece limits, or both. We used the I 2 statistic (13) ad the Cochra Q statistic (14) to assess study heterogeeity. We also recomputed pooled estimates with ad without studies that produced extreme results. A I 2 statistic of 50% or more idicates substatial heterogeeity amog study estimates. We used the DerSimoia Laird method to compute radom-effects estimates whe the set of studies was heterogeeous (15). I cases where 3 or more studies cotributed estimates for a risk factor, we used the trim-ad-fill method to adjust pooled estimates of a risk factor s effect o postoperative pulmoary complicatios for publicatio bias (16). Trimad-fill estimates check the sesitivity of pooled estimates to potetial publicatio bias (17). We used meta-aalysis procedures available i Stata software, versio 8 (Stata Corp., College Statio, Texas), to coduct these aalyses (18). Role of the Fudig Source The Veteras Evidece-based Research, Dissemiatio, ad Implemetatio Ceter (VERDICT) (Veteras Affairs Health Services Research ad Developmet, HFP ) provided the research libraria ad admiistrative support for the study. The fudig source had o role i the desig, coduct, or reportig of the study or i the decisio to submit the mauscript for publicatio. RESULTS Eighty-three publicatios provided uivariate data o cliical predictors of postoperative pulmoary complicatios. Appedix Table 1 (available at summarizes the characteristics of these studies (2, 3, April 2006 Aals of Iteral Medicie Volume 144 Number 8 Dowloaded From: o 05/16/2016

3 Preoperative Pulmoary Risk Stratificatio for Nocardiothoracic Surgery Cliical Guidelies Figure 1. Flow chart for article selectio process. PPC postoperative pulmoary complicatio. 99). Sevety-three (88.0%) publicatios were cohort studies; 3 (3.6%) were radomized, cotrolled trials; 2 (2.4%) were case cotrol studies; ad the remaiig 5 (6.0%) were case-series studies. Slightly less tha half (45.8%) of the cohort studies used a prospective desig. Te studies were of good quality, 18 studies were of fair quality, ad 55 studies were of poor quality. Eligible studies icluded postoperative pulmoary complicatio evets amog patiets. Twety-seve studies reportig multivariable aalyses ( postoperative pulmoary complicatio evets amog patiets) met our iclusio criteria (Appedix Table 2, available at ( ). These studies form the pricipal basis of our review. Most studies (96%) were prospective cohort studies, ad oly 1 report was a case cotrol study. The 3 largest studies (118, 120, 123) used subsets of patiets from the Veteras Affairs Natioal Surgical Quality Improvemet Project (NSQIP) (127). These 3 studies accouted for 89.8% of all patiets icluded i the multivariable studies ad 82.3% of the observed postoperative pulmoary complicatios. The crude postoperative pulmoary complicatio rate amog the cohort studies was 3.4%. The studies were heterogeeous with respect to study objectives, study samples, ad criteria for defiig a postoperative pulmoary complicatio. Sevetee of the 27 (63.0%) studies aimed to idetify potetial risk factors for postoperative pulmoary complicatios. The objective i 3 studies was to develop a risk idex for postoperative pulmoary complicatios (113, 118, 120). The remaiig studies focused o high-risk subgroups, such as patiets udergoig aortic surgery (104, 125), patiets with smokig histories (114), elderly patiets (102, 117, 121), or patiets with chroic obstructive pulmoary disease who required prologed stays i the itesive care uit (108). Postoperative pulmoary complicatio defiitios varied cosiderably across studies. While 16 (59.3%) of the studies icluded some combiatio of peumoia or respiratory ifectio alog with respiratory isufficiecy or failure, the studies varied i the iclusio of other complica April 2006 Aals of Iteral Medicie Volume 144 Number Dowloaded From: o 05/16/2016

4 Cliical Guidelies Preoperative Pulmoary Risk Stratificatio for Nocardiothoracic Surgery Table 1. Patiet-Related Risk Factors for Postoperative Pulmoary Complicatios* Risk Factor Studies, Pooled Estimate Odds Ratio (95% CI) I 2, % Trim-ad-Fill Estimate Odds Ratio (95% CI) Age y ( ) y ( ) ( ) y ( ) ( ) 80 y ( ) ASA class II ( ) ( ) III ( ) ( ) Abormal chest radiograph ( ) 0.0 CHF ( ) ( ) Arrhythmia ( ) Fuctioal depedece Partial ( ) 82.6 Total ( ) 67.9 COPD ( ) ( ) Weight loss ( ) 91.7 Medical comorbid coditio ( ) Cigarette use ( ) ( ) Impaired sesorium ( ) 63.0 Corticosteroid use ( ) Alcohol use ( ) 0.0 * ASA America Society of Aesthesiologists; CHF cogestive heart failure; COPD chroic obstructive pulmoary disease. For I 2 defiitio ad values, see the Appedix, available at Estimates derived from meta-aalysis of adjusted odds ratios from multivariable studies. Whe compared with patiets with lower ASA class values. tios. Two studies icluded pulmoary edema (102, 121) ad 2 studies icluded pulmoary embolus i additio to traditioal postoperative pulmoary complicatio defiitios (102, 125). Three studies used atelectasis as a exclusio criterio (110, 118, 120). Oe study explicitly excluded patiets who required postoperative mechaical vetilatio (128). The 2 largest studies derived from the NSQIP limited their aalyses to either postoperative respiratory failure (118) or peumoia (120). Appedix Table 3 (available at details the pricipal results of the studies that reported multivariable aalyses. Patiet-Related Risk Factors We cosidered patiet- ad procedure-related risk factors separately ad divided the patiet-related risk factors ito the followig geeral categories: age, chroic lug disease, cigarette use, cogestive heart failure, comorbid coditio measures, fuctioal depedece, obesity, obstructive sleep apea, impaired sesorium, ad other factors. Table 1 displays the DerSimoia Laird pooled ad trimad-fill estimate odds ratios for the patiet-related risk factors. Age The ifluece of age o postoperative pulmoary complicatio rates is ot well established. Most previous reviews have cosidered age to be a mior risk factor for the developmet of postoperative pulmoary complicatios. Studies that reported postoperative pulmoary complicatios by age categories varied with respect to the cutoff ages used to defie age strata (Appedix Table 4, available at Te studies reported uadjusted postoperative pulmoary complicatio rates by age strata for patiets older tha 65 years of age (5 studies) ad for patiets older tha 70 years of age (5 studies). Uadjusted postoperative pulmoary complicatio estimates for patiets older tha 65 years of age raged from 1% to 34%, with a media postoperative pulmoary complicatio rate of 14%. For patiets 70 years of age ad older, the uadjusted postoperative pulmoary complicatio estimates raged from 4% to 45%, with a media postoperative pulmoary complicatio rate of 15%. Eleve multivariable risk factor studies reported statistically sigificat effects for age. This was the secod most commoly idetified risk factor i our review. Seve of these studies 4 good-quality studies, 2 fair-quality studies, ad 1 poor-quality study provided odds ratios alog with SEs or CIs. The remaiig studies did ot report values, used age as a cotiuous or ordered categorical variable, or reported results from a multivariate discrimiat fuctio aalysis. Three studies reported age-related odds ratios i several strata. We orgaized study estimates ito 4 age strata based o deciles (50 to 59 years, 60 to 69 years, 70 to 79 years, ad 80 years). While several studies used this stratificatio scheme for age, some studies used 1 age category stratificatio, such as 65 years ad older or 60 years ad older. We grouped these study values withi the 60 to 69 years of age stratificatio i our aalyses. Two studies reported age strata as 50 to 69 years ad 70 years ad older. We assiged the 50 to 69 years of age category to the 60 to 69 years of age group ad the 70 years ad April 2006 Aals of Iteral Medicie Volume 144 Number 8 Dowloaded From: o 05/16/2016

5 Preoperative Pulmoary Risk Stratificatio for Nocardiothoracic Surgery Cliical Guidelies older age category to the 70 to 79 years of age group. Sesitivity aalyses showed that reassigig the 50 to 69 years of age category to the 50 to 59 years of age group or reassigig the 70 years ad older age category to the 80 years ad older age group had little effect o the results. The odds that patiets experieced a postoperative pulmoary complicatio icrease systematically with age (Table 1), with older age categories coferrig higher postoperative pulmoary complicatio risk, eve after trim-ad-fill correctio for publicatio bias. Odds ratios for the 60 to 69 years of age group ad 70 to 79 years of age group are 2.09 (95% CI, 1.66 to 2.64) ad 3.04 (CI, 2.11 to 4.39), respectively. While uadjusted risk due to icreasig age was previously believed to be due to accumulatig comorbid coditios, our review idicates that advaced age is a importat idepedet predictor of postoperative pulmoary complicatios eve after adjustmet for comorbid coditios. Chroic Lug Disease Amog studies reportig multivariable aalyses, chroic obstructive pulmoary disease was the most frequetly idetified risk factor for postoperative pulmoary complicatios. Thirtee of 15 studies that etered this factor ito a multivariate model reported it to be a statistically sigificat predictor of postoperative pulmoary complicatios. Eight studies 2 good-quality studies, 4 fair-quality studies, ad 2 poor-quality studies provided odds ratios with SEs, 95% CIs, or both. The trim-ad-fill bias-corrected odds ratio for chroic obstructive pulmoary disease is 1.79 (CI, 1.44 to 2.22). Two small, poor-quality studies reported uadjusted postoperative pulmoary complicatio rates for patiets with ad without abormal fidigs o chest examiatio (40, 73). Postoperative pulmoary complicatios occurred i 35 of 57 patiets with abormal fidigs. Oly 1 of these 2 studies reported postoperative pulmoary complicatio rates for patiets with chroic obstructive pulmoary disease (40). Oe multivariable study reported that abormal fidigs o chest examiatio (defied as decreased breath souds, prologed expiratio, rales, wheezes, or rhochi) were the strogest predictor of postoperative pulmoary complicatio rates (odds ratio, 5.8 [CI, 1.04 to 32.1]) (110). While the data idicate a higher postoperative pulmoary complicatio risk for patiets with abormal fidigs, the magitude of this effect is ucertai because of the small umber of studies. Oe study evaluated the cough test as a potetial tool to stratify risk (126). To perform a cough test, the patiet takes a deep breath ad coughs oce. A positive test result is recurret coughig. The adjusted odds ratio for postoperative pulmoary complicatio was 3.8 (P 0.01). No eligible study determied the icremetal postoperative pulmoary complicatio risk for patiets with chroic restrictive lug disease or restrictive physiology due to euromuscular disease or chest wall deformity, such as kyphoscoliosis. Cigarette Use Five multivariable studies (3 good-quality ad 2 fairquality studies) provided odds ratios, with SEs, 95% CIs, or both, of the effect of cigarette use o postoperative pulmoary complicatio rates. The trim-ad-fill bias-adjusted odds ratio for cigarette use is 1.26 (CI, 1.01 to 1.56), suggestig a modest icrease i postoperative pulmoary complicatio risk amog patiets with a smokig history. Studies evaluatig the effect of smokig cessatio o postoperative pulmoary complicatio rates have geerally evaluated patiets udergoig pulmoary or cardiac surgery, which we excluded from our review. Oe multivariable study of 410 patiets udergoig elective geeral, orthopedic, urologic, or cardiovascular surgery reported a adjusted odds ratio of 5.5 (CI, 1.9 to 16.2) for the risk for postoperative pulmoary complicatios i curret smokers versus osmokers (114). Of iterest, curret smokers who attempted to reduce cigarette use shortly before surgery were more likely to develop a postoperative pulmoary complicatio tha those who cotiued usual smokig habits. The adjusted odds ratio was 6.7 (CI, 2.6 to 17.1). Possible explaatios iclude selectio bias (patiets who correctly perceived themselves as beig at high risk for complicatios may have bee more likely to attempt to reduce cigarette use before surgery) or a trasiet icrease i cough ad sputum productio i the first 1 to 2 moths after cigarette cessatio. I a study of self-reported duratio of smokig cessatio before mior surgeries, 2 moths of preoperative smokig cessatio was ecessary for itraoperative sputum volume to decrease to the baselie levels of osmokers (129). Cogestive Heart Failure Three good-quality multivariable risk factor studies idetified cogestive heart failure as a statistically sigificat risk factor for postoperative pulmoary complicatios. While the estimates are variable (I 2 91%), the DerSimoia Laird radom-effects estimate for the risk associated with cogestive heart failure is 2.93 (CI, 1.02 to 8.43). Both the stadard ad trim-ad-fill bias-adjusted methods produce similar estimates (Table 1). Comorbid Coditio Measures Ivestigators have evaluated several itegrated measures of comorbid coditios as potetial predictors of postoperative pulmoary complicatios. The America Society of Aesthesiologists (ASA) classificatio aims to predict perioperative mortality but has sice bee prove to predict both postoperative pulmoary ad cardiac complicatios (102). The 5 ASA classes are 1) a ormally healthy patiet (class I), 2) a patiet with mild systemic disease 18 April 2006 Aals of Iteral Medicie Volume 144 Number Dowloaded From: o 05/16/2016

6 Cliical Guidelies Preoperative Pulmoary Risk Stratificatio for Nocardiothoracic Surgery (class II), 3) a patiet with systemic disease that is ot icapacitatig (class III), 4) a patiet with a icapacitatig systemic disease that is a costat threat to life (class IV), ad 5) a moribud patiet who is ot expected to survive for 24 hours with or without operatio (class V) (130). I our review, 12 studies (1 good-quality study, 2 fair-quality studies, ad 9 poor-quality studies) stratified postoperative pulmoary complicatio rates by ASA class. Sice ASA class is a subjective composite cliical judgmet based o several risk factors, we orgaized the data accordig to 2 criteria, ASA class II or higher versus ASA class lower tha II ad ASA class III or higher versus ASA class lower tha III, ad we geerated pooled odds ratios for each criterio (Table 1 ad Appedix Table 5, available at Usig either approach, higher ASA class is associated with a substatial icrease i postoperative pulmoary complicatio risk (odds ratios, 4.87 [CI, 3.34 to 7.10] ad 2.55 [CI, 1.73 to 3.76], respectively). I 1 eligible ested case cotrol study of patiets udergoig elective abdomial surgery, the authors studied the predictive value of the Charlso comorbidity idex for postoperative pulmoary complicatios (110). This is a multidisease-specific (icorporatig 19 medical coditios), weighted summary measure that cosiders both umber ad severity of diseases. Possible summary scores rage from 0 to 37 (131). Amog 82 patiets with postoperative pulmoary complicatios ad cotrols without postoperative pulmoary complicatios matched by operatio type ad age, the Charlso comorbidity idex score was 1 of 4 idepedet, statistically sigificat risk factors i a multivariable aalysis (odds ratio, 1.6 [CI, 1.0 to 2.6] per poit). Fuctioal Depedece The 2 largest eligible trials from the NSQIP evaluated fuctioal depedece as a potetial risk factor for postoperative pulmoary complicatios (118, 120). Total depedece was the iability to perform ay activities of daily livig (for example, a depedet patiet i a ursig home). Partial depedece was the eed for equipmet or devices ad assistace from aother perso for some activities of daily livig. Our pooled estimates of odds ratios for total ad partial depedece are 2.51 (CI, 1.99 to 3.15) ad 1.65 (CI, 1.36 to 2.01), respectively. Obesity Decreased lug volumes after surgery is a pricipal cause of postoperative pulmoary complicatios. Obesity may lead to restrictive pulmoary physiology ad may further reduce lug volumes ad the ability to take a deep breath after surgery. However, studies evaluatig cliically meaigful pulmoary complicatios after surgery have geerally foud o icreased risk, eve for patiets with morbid obesity (132, 133). I our review, 9 studies (4 fair-quality ad 5 poor-quality studies) reported oly uadjusted data (7134 total patiets [rage, 114 patiets to 2964 patiets]) ad 2 of 8 multivariable studies (1 goodquality study ad 1 fair-quality study) determied postoperative pulmoary complicatio rates for obese patiets (Appedix Table 6, available at Defiitios of obesity varied from a body mass idex (BMI) of 25 kg/m 2 or greater to morbid obesity. Of the 8 studies that reported multivariable models, obesity was a idepedet risk factor i oly 1 study. I studies that reported oly uivariate results, postoperative pulmoary complicatio rates are similar i obese ad oobese patiets (6.3% ad 7.0%, respectively). Eve amog obese patiets, those with greater obesity did ot seem to have a icreased postoperative pulmoary complicatio risk. I a study of 197 morbidly obese patiets udergoig gastric bypass surgery, authors stratified patiets by BMI (99). Postoperative pulmoary complicatio rates were 10% for patiets with a BMI of 43 kg/m 2 or less ad 12% for those with a BMI greater tha 43 kg/m 2. This differece was ot statistically sigificat. Obstructive Sleep Apea Obstructive sleep apea icreases the risk for airway maagemet difficulties i the immediate postoperative period, but its ifluece o postoperative pulmoary complicatio rates has ot bee well studied. We idetified 1 uivariate study that evaluated the risk due to obstructive sleep apea amog patiets udergoig hip or kee replacemet (92). The case cotrol study (101 patiets with obstructive sleep apea ad 101 matched cotrols) foud o statistically sigificat treds toward higher rates of reitubatio, hypercapia, ad hypoxemia for patiets with obstructive sleep apea. The authors did ot measure rates of postoperative peumoia or respiratory failure. However, differeces for uplaed itesive care uit trasfers (20% vs. 6%), all serious complicatios (24% vs. 9%), ad legth of stay (6.8 days vs. 5.1 days) were statistically sigificat. While we await further research, these fidigs suggest that postoperative pulmoary complicatio rates may be higher amog patiets with obstructive sleep apea. Impaired Sesorium Two large trials from the NSQIP evaluated the ifluece of impaired sesorium o respiratory failure (118) ad peumoia (120) after major ocardiac surgery. The authors defied impaired sesorium as 1) a acutely cofused or delirious patiet who ca respod to verbal or mild tactile stimulatio or both or 2) a patiet with metal status chages, delirium, or both i the cotext of curret illess. This defiitio excluded patiets with stable chroic metal illess or demetia. Our pooled odds ratio estimate for impaired sesorium is 1.39 (CI, 1.08 to 1.79) April 2006 Aals of Iteral Medicie Volume 144 Number 8 Dowloaded From: o 05/16/2016

7 Preoperative Pulmoary Risk Stratificatio for Nocardiothoracic Surgery Cliical Guidelies Table 2. Procedure-Related Risk Factors for Postoperative Pulmoary Complicatios Risk Factor Studies, Pooled Estimate Odds Ratio (95% CI)* I 2, % Trim-ad-Fill Estimate Odds Ratio (95% CI)* Surgical site Aortic ( ) Thoracic ( ) ( ) Ay abdomial ( ) ( ) Upper abdomial ( ) ( ) Neurosurgery ( ) Head ad eck ( ) 0.00 Vascular ( ) Emergecy surgery ( ) ( ) Prologed surgery ( ) ( ) Geeral aesthesia ( ) ( ) Trasfusio ( 4 uits) ( ) 0.00 * Estimates derived from meta-aalysis of adjusted odds ratios from multivariable studies. For I 2 defiitio ad values, see the Appedix, available at Other Patiet-Related Factors Amog eligible studies i our review, diabetes ad asthma did ot ifluece postoperative pulmoary complicatio rates (see Appedix, available at for details). Five studies (2 fair-quality ad 3 poor-quality studies) provided uadjusted estimates for postoperative pulmoary complicatio rates amog patiets with diabetes. Postoperative pulmoary complicatio rates for diabetes varied from 6% to 40% amog these studies, with a media rate of 21%. Amog 4 studies that provided uadjusted data o postoperative pulmoary complicatio rates for patiets with asthma ( 895), the uadjusted postoperative pulmoary complicatio rate was 3.0%, which is similar to the crude adjusted postoperative pulmoary complicatio rate for all studies i our review (3.4%). For 2 additioal patiet-related factors, exercise capacity ad HIV ifectio, the evidece (o the basis of 1 study each) was isufficiet to determie the ifluece o postoperative pulmoary complicatio rates (see Appedix, available at Procedure-Related Risk Factors Table 2 displays the uadjusted ad adjusted summary estimates for procedure-related risk factors, icludig surgical site, duratio of surgery, aesthetic techique, ad emergecy surgery. Surgical Site We obtaied uadjusted postoperative pulmoary complicatio rates for upper abdomial, lower abdomial, ad ay abdomial surgery from 43 studies. These were 19.7%, 7.7% ad 14.2%, respectively (Appedix Table 7, available at The uadjusted postoperative pulmoary complicatio rate for 11 studies of patiets udergoig esophagectomy was 18.9%. Amog 16 studies of patiets udergoig abdomial aortic aeurysm repair, the uadjusted postoperative pulmoary complicatio rate was 25.5%. Head ad eck surgery (6 studies) carried a itermediate risk (uadjusted postoperative pulmoary complicatio rate, 10.3%). Low-risk procedures were hip surgery (5 studies) ad gyecologic or urologic procedures (2 studies), ad the uadjusted postoperative pulmoary complicatio rates were 5.1% ad 1.8%, respectively. The multivariable risk factor studies were heterogeeous i how each hadled type of surgery, surgical site, or both. The I 2 idex for surgical sites raged from 66.4% to 98.7% for all surgical sites except head ad eck surgeries. Seve studies icluded all ocardiac surgeries but provided oly crude postoperative pulmoary complicatio rates for each type of surgery. Amog the 14 studies providig iformatio o abdomial surgeries, 5 studies restricted their sample to patiets udergoig upper or lower abdomial surgery, 2 studies compared major abdomial surgery with mior abdomial surgery, 3 studies compared geeral abdomial surgery with other ocardiac surgeries, ad 4 studies compared upper abdomial surgery with lower abdomial or other ocardiac surgeries. Two studies focused o specific high-risk surgical procedures, such as esophagectomy (124) ad thoracoabdomial aortic (104) surgeries. Oly the 2 largest good-quality NSQIP studies provided a comprehesive assessmet of the effect of type of surgery o postoperative pulmoary complicatio rates (118, 120). These 2 studies are the oly source of adjusted estimates for aortic, head ad eck, eurologic, ad peripheral vascular surgeries (Appedix Table 3, available at Patiets udergoig ope aortic surgeries are at the highest risk for postoperative pulmoary complicatios (odds ratio, 6.90 [CI, 2.74 to 17.36]). Oe cohort study compared postoperative pulmoary complicatio rates for ope surgical repair of abdomial aortic aeurysms ad edovascular repair (125). After multivariable adjustmet for patiet-related cofouders, the hazard ratio for edovascular repair was 0.14 (CI, 0.04 to 0.47) compared with ope surgery. Other high-risk surgeries iclude thoracic (odds ratio, 4.24 [CI, 2.89 to 6.23]) ad upper abdomial operatio (odds ratio, 2.91 [CI, 2.35 to 3.60]). Three 18 April 2006 Aals of Iteral Medicie Volume 144 Number Dowloaded From: o 05/16/2016

8 Cliical Guidelies Preoperative Pulmoary Risk Stratificatio for Nocardiothoracic Surgery good-quality ad 3 fair-quality multivariable risk factor studies provided estimates of the effect of ay abdomial surgery o postoperative pulmoary complicatio rates. The trim-ad-fill bias-corrected odds ratio for ay abdomial surgery is 3.01 (CI, 2.43 to 3.72). For surgical procedures with 3 or more studies, trim-ad-fill estimates for the surgical procedures differ little from the origial radomeffects estimates. Much of the observed heterogeeity (I %) is attributable to differeces i compositio of the referece group or criteria for defiig a postoperative pulmoary complicatio. Duratio of Surgery Five fair-quality multivariable risk factor studies provided odds ratios, with SEs, CIs, or both, for prologed surgery. The defiitio of prologed surgery raged from 2.5 hours to 4 hours. Publicatio bias for estimates of the effect of prologed surgery o postoperative pulmoary complicatio rates was ot very evidet. The pooled odds ratio for prologed surgery is 2.26 (CI, 1.47 to 3.47). This fidig cotrasts with data o postoperative cardiac complicatios, where duratio of surgery is ot a idepedet predictor ad does ot appear i ay commoly used cardiac risk idex (1, 134). Aesthetic Techique Two good-quality ad 4 fair-quality studies provided estimates for postoperative pulmoary complicatio risk attributable to the use of geeral aesthesia. The studies were heterogeeous (I %). The trim-ad-fill biascorrected odds ratio is 1.83 (CI, 1.35 to 2.46). Emergecy Surgery Six multivariable risk factor studies 2 good-quality, 2 fair-quality, ad 2 poor-quality studies provided odds ratios, with SEs ad CIs, for emergecy versus elective surgery. The trim-ad-fill bias-corrected odds ratio for emergecy surgery is 2.21 (CI, 1.57 to 3.11). Patiets udergoig emergecy surgery icur a modest risk for the developmet of postoperative pulmoary complicatios. Laboratory Testig To Estimate Risk Spirometry The first systematic review of the predictive value of preoperative spirometry, published i 1989, cocluded that its value was uprove (135). A subsequet ecoomic evaluatio foud that estimated aual real costs for preoperative spirometry are $25 millio to $45 millio i 1991 U.S. dollars (136). If use of spirometry were reduced to meet curret guidelies, potetial savigs to third-party payers would rage from $29 millio to $111 millio. We idetified 14 additioal eligible studies for our review that evaluated the ability of preoperative spirometry to stratify postoperative pulmoary complicatio risk (Appedix Table 8, available at (28, 50, 52, 57, 60, 73, 102, 108, 112, 115, ). Te studies provided uadjusted uivariate data for postoperative pulmoary complicatios o the basis of particular laboratory fidigs. I 1 study, 6 of 22 (27%) patiets with abormal results o spirometry had a postoperative pulmoary complicatio, while fewer patiets with ormal spirometry results (16 of 100 [16%] patiets) had a postoperative pulmoary complicatio (28). I 3 of 4 studies that determied mea FEV 1 values ad 3 studies that determied mea FVC values, the value was lower for patiets who developed a postoperative pulmoary complicatio tha for those who did ot. These differeces were, however, small ad were ulikely to help cliicias udertake risk stratificatio. Three studies ( 505) provided categorical groupigs of FEV 1 values. The postoperative pulmoary complicatio rates for patiets i the highest ad lowest FEV 1 categories were 14.6% ad 31.4%, respectively. Oe study each ( 324 total) performed a similar aalysis by usig either FVC or FEV 1 FVC ratio ad reported similar results (52, 102). Noe of these studies compared the predictive value of abormal spirometry results with that of abormal fidigs o history or physical examiatio. Oly 4 eligible studies used multivariable aalysis to adjust for potetially relevat cliical variables to determie the idepedet predictive value of spirometry. Wog ad colleagues (108) studied 105 patiets udergoig ocardiothoracic surgery who had severe chroic obstructive pulmoary disease (as defied by a FEV L ad FEV 1 FVC ratio 75%). I their small, select cohort, FEV 1 :FVC less tha 50% was 1 of 5 idepedet risk factors. Three other factors (abdomial surgery, ASA class IV or V, ad geeral aesthesia) coferred higher odds ratios i the multivariable model. I a study of 460 patiets udergoig abdomial surgery, FEV 1 less tha 61% predicted, PaO 2 less tha 9.33 kpa (70 mm Hg), FEV 1 of 61% to 79% predicted, ischemic heart disease, cacer operatio, ad age were each idepedet predictors (140). The sigle strogest factor was FEV 1 less tha 61% predicted. I a third study of 361 patiets udergoig upper abdomial surgery, residual volume, diffusig capacity of carbo mooxide (% predicted), ad FEV 1 (% predicted) were statistically sigificat idepedet predictors of postoperative pulmoary complicatios (112). Chroic mucus hypersecretio (sputum productio for at least 3 moths of each year) was the strogest factor ad predicted risk to a greater degree tha ay spirometric value. Fially, the fourth study used a case cotrol desig to study 116 patiets udergoig elective abdomial surgery ad matched cotrols (110). I this report, FEV 1 results were similar betwee case-patiets ad cotrols (2.4 L vs. 2.6 L, respectively) ad FVC results were idetical (3.6 L). Abormal fidigs o chest examiatio, abormal results o chest radiography, Goldma cardiac risk idex, ad Charlso comorbidity idex were idepedet predictors of postop April 2006 Aals of Iteral Medicie Volume 144 Number 8 Dowloaded From: o 05/16/2016

9 Preoperative Pulmoary Risk Stratificatio for Nocardiothoracic Surgery Cliical Guidelies erative pulmoary complicatio. I cotrast, spirometry results were ot statistically sigificat i the fial model. No eligible studies provided data o the use of spirometry to stratify risk for patiets with restrictive pulmoary disease or restrictive physiology due to chest wall or euromuscular disease. The available literature suggests that spirometry may idetify patiets at higher risk for developmet of postoperative pulmoary complicatios; however, the data are mixed. A additioal problem is that while spirometry diagoses obstructive lug disease, this diagostic clarity does ot traslate ito effective risk predictio for idividual patiets. Furthermore, the few studies that have compared spirometric data with cliical data have ot cosistetly show spirometry to be superior to history ad physical examiatio. While cosesus exists o the value of spirometry before lug resectio ad i determiig cadidacy for coroary artery bypass, its value before extrathoracic surgery remais uprove. Fially, the data do ot suggest a prohibitive spirometric threshold below which the risk for surgery is uacceptable. For example, i a study of 107 operatios i patiets with severe chroic obstructive pulmoary disease (FEV 1 50% predicted ad FEV 1 FVC ratio 70%), 6 deaths ad 7 severe postoperative pulmoary complicatios occurred (50). While this risk is substatial, it may be acceptable whe cotemplatig life-savig surgery. Chest Radiography Cliicias frequetly order chest radiography as part of a routie preoperative evaluatio. This practice is ofte due to local istitutioal guidelies requirig chest radiography for all patiets older tha a particular age. Oly 2 uivariate studies that met our iclusio criteria stratified postoperative pulmoary complicatio rates o the basis of the fidig of a ormal or abormal preoperative chest radiograph (28, 139). I their small, pooled patiet sample ( 150), 46% of patiets with a abormal preoperative chest radiograph had a postoperative pulmoary complicatio, ad the rate for patiets with a ormal preoperative study was 25%. Two eligible studies used multivariable aalysis to determie the effect of a abormal chest radiograph, ad both reported that it was a statistically sigificat predictor of postoperative pulmoary complicatio rates (110, 114). Most studies of the value of preoperative chest radiography, however, have ot studied postoperative pulmoary complicatio as the primary outcome measure but have evaluated the frequecy with which a abormal study chages perioperative maagemet. While these studies do ot meet the iclusio criteria for our review, we discuss them i our report to provide additioal isight ito the value of this commoly ordered test. I a recet review of the value of routie preoperative testig, the authors idetified 8 studies ( ) published from 1980 to 2000 of the frequecy with which preoperative chest radiography results iflueced perioperative maagemet (141). While 23.1% of preoperative chest radiographs i the sample were abormal, oly 3.0% of studies iflueced maagemet. Oly 4.9% of chest radiographs amog patiets youger tha 50 years of age were abormal. I a earlier review of 21 studies ( ) published betwee 1966 ad 1993 (2 of the studies were icluded i both reviews), 10% of all routie preoperative chest radiographs were abormal (142). However, oly 1.3% of all studies showed uexpected abormalities ad oly 0.1% of all studies iflueced maagemet. From these observatios, we coclude that cliicias may predict most abormal preoperative chest radiographs o the basis of the history ad physical examiatio ad that chest radiography oly rarely provides uexpected iformatio that iflueces preoperative maagemet. While existig data o cliical outcomes do ot allow firm coclusios, the icremetal value of the test i estimatig postoperative pulmoary complicatio risk is small. Limited evidece from multivariable risk factor studies supports the use of preoperative chest radiography for patiets with kow cardiopulmoary disease ad those older tha 50 years of age who are udergoig upper abdomial, thoracic, or abdomial aortic aeurysm surgery. Serum Measures of Real Fuctio Two studies usig NSQIP data idetified a serum blood urea itroge level of 7.5 mmol/l or greater ( 21 mg/dl) as a statistically sigificat predictor after multivariable adjustmet (118, 120). The risk icreased with icreasig blood urea itroge levels. Oe study idetified serum creatiie level greater tha 133 mol/l ( 1.5 mg/ dl) as a risk factor after multivariable aalysis (123). Serum Albumi Measuremet Four studies that reported uivariate aalyses ( ) stratified postoperative pulmoary complicatio rates by serum albumi level ad used a threshold of 36 g/l to defie low serum albumi level (62, 88, 143, 144). Uadjusted postoperative pulmoary complicatio rates for patiets with low ad ormal serum albumi levels were 27.6% ad 7.0%, respectively. Our review of studies reportig multivariable aalyses cofirms the value of a low serum albumi level as a importat predictor of postoperative pulmoary complicatios. I 4 of 5 eligible studies that cosidered albumi level, it was a idepedet risk factor for postoperative pulmoary complicatios (low level values defied variably from 30 g/l to 39 g/l) (100, 101, 109, 118, 145). I the 1 study that provided a adjusted estimate of risk, the odds ratio was 2.53 (CI, 2.04 to 2.56) (118). This is cosistet with the NSQIP report that a low serum albumi level was also the most importat predictor of 30-day perioperative morbidity ad mortality (88). I the report, the relatioship betwee serum albumi levels 18 April 2006 Aals of Iteral Medicie Volume 144 Number Dowloaded From: o 05/16/2016

10 Cliical Guidelies Preoperative Pulmoary Risk Stratificatio for Nocardiothoracic Surgery Table 3. Summary Stregth of the Evidece for the Associatio of Patiet, Procedure, ad Laboratory Factors with Postoperative Pulmoary Complicatios* Factor Stregth of Recommedatio Odds Ratio Potetial patiet-related risk factor Advaced age A ASA class II A CHF A 2.93 Fuctioally depedet A COPD A 1.79 Weight loss B 1.62 Impaired sesorium B 1.39 Cigarette use B 1.26 Alcohol use B 1.21 Abormal fidigs o chest examiatio B NA Diabetes C Obesity D Asthma D Obstructive sleep apea I Corticosteroid use I HIV ifectio I Arrhythmia I Poor exercise capacity I Potetial procedure-related risk factor Aortic aeurysm repair A 6.90 Thoracic surgery A 4.24 Abdomial surgery A 3.01 Upper abdomial surgery A 2.91 Neurosurgery A 2.53 Prologed surgery A 2.26 Head ad eck surgery A 2.21 Emergecy surgery A 2.21 Vascular surgery A 2.10 Geeral aesthesia A 1.83 Perioperative trasfusio B 1.47 Hip surgery D Gyecologic or urologic surgery D Esophageal surgery I Laboratory tests Albumi level 35 g/l A 2.53 Chest radiography B 4.81 BUN level 7.5 mmol/l B NA ( 21 mg/dl) Spirometry I * ASA America Society of Aesthesiologists; BUN blood urea itroge; CHF cogestive heart failure; COPD chroic obstructive pulmoary disease; NA ot available. Recommedatios: A good evidece to support the particular risk factor or laboratory predictor; B at least fair evidece to support the particular risk factor or laboratory predictor; C at least fair evidece to suggest that the particular factor is ot a risk factor or that the laboratory test does ot predict risk; D good evidece to suggest that the particular factor is ot a risk factor or that the laboratory test does ot predict risk; I isufficiet evidece to determie whether the factor icreases risk or whether the laboratory test predicts risk, ad evidece is lackig, is of poor quality, or is coflictig. From referece 12. For factors with A or B ratigs. Odds ratios are trim-ad-fill estimates. Whe these estimates were ot possible, we provide the pooled estimate. ad mortality was cotiuous for values less tha approximately 35 g/l without a clear threshold value. Oropharygeal Culture Oe eligible uivariate study evaluated the value of preoperative oropharygeal culture to predict postoperative pulmoary complicatio risk before upper abdomial surgery (51). The evidece is isufficiet to determie the ifluece of this test o postoperative pulmoary complicatio rates (see Appedix, available at for details). Pulmoary Risk Idices While cliicias have used preoperative cardiac idices for more tha 3 decades (1), early efforts to develop perioperative pulmoary risk idices for pulmoary ad opulmoary surgery were limited by coflictig results i validatio cohorts (113, ). More recetly, Arozullah ad colleagues (118, 120) developed 2 idices o the basis of NSQIP data. I the multifactorial postoperative respiratory failure idex, Arozullah ad colleagues (118) idetified statistically sigificat risk factors i a multivariable aalysis of male veteras udergoig major ocardiac surgery ad validated the idex i a additioal cohort. The defiitio of respiratory failure was mechaical vetilatio for more tha 48 hours or uplaed itubatio. The fial weighted idex icluded 7 factors. Procedure-related factors domiated the idex, which icluded type of surgery (abdomial aortic aeurysm [27 poits]; thoracic [21 poits]; eurosurgery, upper abdomial, or peripheral vascular [14 poits]; eck [11 poits]), emergecy surgery (11 poits), albumi level less tha 30 g/l (9 poits), blood urea itroge level greater tha mmol/l ( 30 mg/dl) (8 poits), partially or fully depedet fuctioal status (7 poits), chroic obstructive pulmoary disease (6 poits), ad age ( 70 years [6 poits] or 60 to 69 years [4 poits]). A similarly derived postoperative peumoia idex differed by greater relative weight to age ad the iclusio of weight loss, geeral aesthesia, impaired sesorium, history of cerebrovascular accidet, trasfusio of more tha 4 uits, emergecy surgery, steroid use for chroic coditio, curret smoker withi 1 year, ad alcohol itake of more tha 2 driks per day i the past 2 weeks (120). These rigorously derived idices from a large cohort advace the field of pulmoary risk stratificatio. The promiece of umodifiable risk factors was otable i both idices. These idices, however, allow cliicias to recosider the idicatios for surgery i a high-risk patiet ad suggest patiets who will most beefit from strategies to reduce the risk for postoperative pulmoary complicatios. DISCUSSION Postoperative pulmoary complicatios are commo ad are a importat cause of perioperative morbidity. We preset data from a systematic review of the literature o preoperative risk stratificatio for postoperative pulmoary complicatios after ocardiothoracic surgery. Table 3 provides the summary stregth of the evidece ad odds ratios for the associatio of patiet, procedure, ad laboratory factors with postoperative pulmoary complicatios. Amog patiet-related risk factors, good evidece supports advaced age, ASA class II or greater, fuctioal depe April 2006 Aals of Iteral Medicie Volume 144 Number 8 Dowloaded From: o 05/16/2016