Pneumothorax Following Thoracentesis a Systematic Review and Meta-Analysis

REVIEW ARTICLE Pneumothorax Following Thoracentesis A Systematic Review and Meta-analysis

Craig E. Gordon, MD, MS; David Feller-Kopman, MD; Ethan M. Balk, MD, MPH; Gerald W. Smetana, MD

Background: Little is known about the factors related to but this was nonsignificant within studies directly com- the development of pneumothorax following thoracente- paring this factor (OR, 0.7; 95% CI, 0.2-2.3). Pneumotho- sis. We aimed to determine the mean pneumothorax rate rax was more likely following therapeutic thoracentesis (OR, following thoracentesis and to identify risk factors for pneu- 2.6; 95% CI, 1.8-3.8), in conjunction with periprocedural mothorax through a systematic review and meta-analysis. symptoms (OR, 26.6; 95% CI, 2.7-262.5), and in association with, although nonsignificantly, mechanical ventila- Methods: We reviewed MEDLINE-indexed studies from tion (OR, 4.0; 95% CI, 0.95-16.8). Two or more needle January 1, 1966, through April 1, 2009, and included stud- passes conferred a nonsignificant increased risk of pneu- ies of any design with at least 10 patients that reported mothorax (OR, 2.5; 95% CI, 0.3-20.1). the pneumothorax rate following thoracentesis. Two investigators independently extracted data on the pneu- Conclusions: Iatrogenic pneumothorax is a common mothorax rate, risk factors for pneumothorax, and study complication of thoracentesis and frequently requires methodological quality. chest tube insertion. Real-time ultrasonography use is a modifiable factor that reduces the pneumothorax rate. Results: Twenty-four studies reported pneumothorax rates Performance of thoracentesis for therapeutic purposes and following 6605 thoracenteses. The overall pneumothorax in patients undergoing mechanical ventilation confers a rate was 6.0% (95% confidence interval [CI], 4.6%-7.8%), higher likelihood of pneumothorax. Experienced opera- and 34.1% of pneumothoraces required chest tube tors may have lower pneumothorax rates. Patient safety insertion. Ultrasonography use was associated with sig- may be improved by changes in clinical practice in ac- nificantly lower risk of pneumothorax (odds ratio [OR], cord with these findings. 0.3; 95% CI, 0.2-0.7). Lower pneumothorax rates were observed with experienced operators (3.9% vs 8.5%, P=.04), Arch Intern Med. 2010;170(4):332-339

EDICAL ERRORS HAVE talization. Chest tube insertion may be re- received increasing at- quired in up to 50% of cases, with a mean tention since the pub- duration of placement of approximately lication of the 1999 4 days.4,5 InstituteofMedicinere- According to a 1998 National Center for port ToErrIsHuman:BuildingaSaferHealth Health Statistics study,6 physicians per- M1 System. Among medical errors, procedural form an estimated 173 000 thoracenteses complications are an important source of annually in the United States. Although tho- morbidity. Procedural complications were racentesis generally is considered techni- second in frequency only to medication er- cally straightforward, safe, and well toler- rors among nonoperative adverse events in ated,7 there is wide variation in published the Harvard Medical Practice Study.2 More- pneumothorax rates, ranging from 0%8 to Author Affiliations: Renal over,proceduralcomplicationsconfera17% 19%.9 Researchers have variably investi- Section, Department of Medicine, Boston University gated the role of real-time ultrasonogra- Medical Center (Dr Gordon), CME available online at phy guidance and operator experience as Center for Clinical Evidence www.jamaarchivescme.com modifiable factors that may reduce pneu- Synthesis, Tufts Medical Center and questions on page 315 mothorax rates following thoracentesis. (Dr Balk), and Division of Some uncertainty exists about the magni- General Medicine and Primary excess mortality rate compared with con- tude of the benefit of ultrasonography guid- Care, Beth Israel Deaconess trol subjects matched by the Acute Physi- ance in lowering pneumothorax rates fol- Medical Center, Harvard ology and Chronic Health Evaluation lowing thoracentesis. Investigators have Medical School (Dr Smetana), score.3 Patients who develop procedural attempted to identify patient and proce- Boston, Massachusetts; and Interventional Pulmonology, complications have a 7-day increase in the dural risk factors for the development of Department of Medicine, length of inpatient stay and incur $12 913 pneumothorax following thoracentesis, but 3 The Johns Hopkins Hospital, in excess costs. Iatrogenic pneumothora- results have been inconsistent. Baltimore, Maryland ces resulting from thoracentesis increase To our knowledge, no systematic re- (Dr Feller-Kopman). morbidity, mortality, and length of hospi- view of the pneumothorax rate of thora-

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Downloaded From: https://jamanetwork.com/ on 10/03/2021 [https://research.tufts-nemc.org/ Table 1. Quality Score metaanalyst]). We tested for heteroge- 448 Total records of Included Studiesa neity using the Cochran ␹2 statistic. 41 Duplicate To explore relationships between Quality Factor pneumothorax rates and a priori se- 407 Records screened by title Prospective study design lected procedural and patient charac- and abstract Sequential selection of patients teristics known to be associated with in- Inclusion and exclusion criteria stated creased complication rates following 342 Not relevant or met exclusion explicitly other procedures,11-13 we performed sub- criteria Postprocedural chest radiography group meta-analyses. Patient factors in- performed in 100.0% of subjects 65 Potentially relevant full cluded sex, pleural effusion size, locu- article reviewed Chest radiograph reviewed by independent lation of effusion, and site of procedure clinician (inpatient, outpatient, or intensive care 41 Excluded unit [ICU]). Procedural factors in- a Methodological reasons Each factor receives 1 of 5 potential points. cluded the use of real-time ultrasonog- 11 Pneumothorax not defined 3 Postprocedural chest raphy guidance, level of operator expe- radiography in <95% of patients STUDY SELECTION rience, number of needle passes, and 2 n <10 3 Not specific to thoracentesis whether the procedure was performed for Type of publication Two of us (C.E.G. and D.F.-K.) inde- diagnostic or therapeutic purposes. When 18 Letter to the editor pendently reviewed the 65 retrieved studies reported pneumothorax rates for 2 Summary or review article 1 Position statement studies to determine their eligibility for thoracenteses with and without puta- 1 Abstract our review. Because our focus was on the tive risk factors, we determined the odds development of pneumothorax follow- ratio (OR) of pneumothorax for those risk 24 Reviewed in detail ing thoracentesis, we included only those factors. However, when the study de- studies in which routine chest radiog- sign precluded comparative analysis, we raphy was performed in more than 95% instead calculated summary pneumotho- Figure 1. Results of the literature search. of subjects. We included only articles rax rates across all studies reporting data that (1) provided explicit criteria for the on specific risk factors using random- centesis exists. Our objectives were diagnosis of postprocedural pneumo- effects model meta-analysis (ie, we com- to conduct a systematic review and thorax, (2) clearly stated patient selec- bined all studies that reported pneumo- meta-analysis of the mean pneumo- tion criteria, (3) defined the primary op- thorax rates with ultrasonography thorax rate following thoracentesis erator of the procedure, and (4) enrolled guidance and separately combined all and the procedure- and patient- at least 10 patients. We included pro- studies that reported on unguided tho- related factors associated with the spective and retrospective studies but ex- racentesis). We used a z score to calcu- cluded letters to the editor, editorials, re- late the statistical significance of differ- development of pneumothorax, and view articles, position statements, ences in summary pneumothorax rates to identify modifiable risk factors abstracts, and studies that did not re- between studies with and without spe- that could lead to improved patient port complication rates. Using these cri- cific risk factors (indirect comparisons). safety. teria, we excluded an additional 41 stud- We selected cutoffs to categorize sub- ies (Figure 1). The remaining 24 studies groups after considering the distribution METHODS formed the basis of our review. of our data and after reviewing relevant previous literature. For operator experi- DATA EXTRACTION AND ence, we defined less experienced opera- DATA SOURCES QUALITY ASSESSMENT tors as physicians in residency training AND SEARCHES compared with pulmonary medicine or radiology faculty. We considered thoracen- The same 2 of us independently ex- We performed a MEDLINE search of En- tesis to be therapeutic when source stud- tracted available data about complica- glish-language articles from January 1, ies reported that the primary purpose of tion rates and patient and procedural risk 1966, through April 1, 2009. Search the procedure was therapeutic. Typi- factors for pneumothorax. We resolved terms included the Medical Subject cally, this involved drainage of greater vol- any discrepancies by consensus among all Headings terms pneumothorax, ultra- umes of fluid and larger pleural effusions authors. We established an a priori 5-point sound, ultrasonography, complications, than diagnostic thoracentesis, but this was scale for study quality (Table 1). We fo- medical errors, risk, and injuries and the not universal. Conversely, we defined di- cused our analysis on the rate of pneu- free-text terms thoracentesis, thoraco- agnostic thoracenteses as those per- mothorax following thoracentesis and did centesis, and error. The full search strat- formed primarily for diagnostic pur- not systematically review other reported egy is available on request from the au- poses. We defined small needles as those complications, as these were not re- thors. We identified additional references smaller than 20 gauge and included larger ported consistently in the source studies. through a manual search of the bibliog- needles and needle catheter sets in our raphies of retrieved articles. Figure 1 definition of large needles. We defined fol- shows the flow of articles. We identi- DATA SYNTHESIS low-up procedures as a second or greater fied 448 potentially eligible studies. Of AND ANALYSIS procedure in the same patient, without re- these, we excluded 41 duplicate refer- gard to whether the first procedure was ences. After screening titles and ab- We performed meta-analysis of the pneu- described in the study. Reporting of ef- stracts, we deemed 342 publications in- mothorax event rates using the random- fusion size was heterogeneous, so we de- eligible as not reporting complications effects model by DerSimonian and Laird10 fined a large effusion as involving greater of thoracentesis. We retrieved and re- and a software program (Metaanalyst, than one-third of a hemithorax. This viewed the remaining 65 studies for pos- beta 3.0; Schmid CH, Wallace B, Lau J, threshold was based on the distribution sible data extraction. Trikalinos TA, Tufts Medical Center of effusion size across source studies.

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Downloaded From: https://jamanetwork.com/ on 10/03/2021 Table 2. Characteristics of Eligible Studies

Primary Sample Complicated Quality Patient Mechanical Operator Ultrasonography Size No. of Pneumothorax Pneumothorax Source Scorea Study Design Population Ventilation of Procedures Guidance, % (n) Procedures Rate, % Rate, %b Mayo et al,29 5 Prospective ICU Yes Residents with 100.0 211 232 1.3 1.3 2004 cohort staff supervision Lichtenstein 5 Prospective ICU Yes Pulmonary 100.0 40 45 0 0 et al,8 1999 cohort medicine Doyle et al,21 5 Prospective Inpatient No Medicine residents 0 110 174 5.2c 2.9 1996 cohort or students Bartter et al,16 5 Prospective Inpatient No Pulmonary 0 33 50 4.0 0 1993 cohort medicine Grogan et al,9 5 Prospective Inpatient No Medicine residents 50.0 52 52 19.2 3.8 1990 randomized or radiology controlled Pihlajamaa 4 Retrospective Inpatient Some Radiology 100.0 212 264 4.2 0.4 et al,32 2004 Jones et al,27 4 Prospective Inpatient No Radiology 100.0 605 941 2.6 0.9 2003 cohort Alema´n et al,14 4 Prospective Inpatient No Medicine interns 4.5 370 506 3.6 1.8 1999 cohort (68%), senior residents or staff (32%) Coltetal,20 1999 4 Prospective Referral to No data Pulmonary 100.0 205 255 5.5 0.8 cohort pulmonary medicine medicine Gervais et al,22 4 Retrospective Inpatient Some Radiology 100.0 425 425 2.4 0.5 1997 Grodzin and 4 Prospective Inpatient with No Pulmonary 02323d 8.7 4.3 Balk,24 1997 cohort malignant medicine effusion Brandstetter 4 Prospective Inpatient No Third-year 0 106 426 6.6 2.1 et al,18 1994 cohort medicine residents or faculty Kohan et al,28 4 Prospective Inpatient No Residents and 50.0 205 205 10.2e 1.5 1986 randomized clinicians controlled Barnes et al,15 3 Retrospective Inpatient and No data No data 67.8 450 450 6.7 1.8 2005 outpatient Godwin and 3 Retrospective ICU Yes Medicine residents 0 29 32 6.2 6.3 Sahn,23 1990 (84%), pulmonary medicine (16%) Collins and 3 Prospective Inpatient No Medicine residents 0 86 129 11.6 5.4 Sahn,19 1987 cohort Seneff et al,34 3 Prospective Inpatient No Medicine residents 11.2 91 125 11.2 2.4 1986 (91%) (90%) Heidecker 2 Retrospective Inpatient and No data Authors 100.0 367 367 2.5 0.3 et al,25 2006 outpatient performed or supervised Bass and 2 Retrospective Patients with No No data 32.0 100 100 7.0e No data White,17 2005 hematologic malignancy Mynarek et al,30 2 Retrospective Inpatient, some No data No data 100.0 298 570 2.8 0 2004 in ICU Boland et al,35 2 Retrospective Patients with No Radiology 100.0 445 512 7.8 5.7 1998 malignant effusion Raptopoulos 2 Retrospective Inpatient Some Medicine residents 54.9 342 342 9.4 4.1 et al,33 1991 (45.0%), radiology (54.9%) O’Moore et al,31 1 Retrospective Inpatient No Radiology 100.0 170 159 10.7f 4.4 1987 Jenkins et al,26 1 Retrospective Inpatient No data Residents and 0 No data 221 6.8 1.8 1983 staff

Abbreviation: ICU, intensive care unit. a Quality score is the aggregate score of the quality factors listed in Table 1. b Complicated pneumothorax is defined as pneumothorax requiring chest tube insertion, whether a clinical decision or by study protocol. c Two additional hemothoraces occurred. d Catheter remained in place, and pleural effusion was drained on a daily basis. Number of procedures refers to initial needle insertion only. e One additional hemothorax occurred. f Pneumothorax was reported only if it was symptomatic or required chest tube insertion. The authors did not report asymptomatic small pneumothoraces.

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Downloaded From: https://jamanetwork.com/ on 10/03/2021 Source No. 95% Confidence Interval Quality Score Ultrasonography used Mayo et al,29 2004 232 0.013 (0.004-0.039) 5 Lichtenstein et al,8 1999 45 0.000 (0.000-0.151) 5 ∗ Grogan et al,9 1990 19 0.000 (0.000-0.298) 5 Pihlajamaa et al,32 2004 264 0.042 (0.023-0.074) 4 Jones et al,27 2003 941 0.026 (0.017-0.038) 4 Alemán et al,14 1999 23 0.043 (0.006-0.252) 4 Colt et al,20 1999 255 0.055 (0.033-0.091) 4 Gervais et al,22 1997 425 0.024 (0.013-0.043) 4 ∗ Kohan et al,28 1986 103 0.087 (0.046-0.159) 4 Barnes et al,15 2005† 305 0.049 (0.030-0.080) 3 Seneff et al,34 1986† 16 0.000 (0.000-0.336) 3 Heidecker et al,25 2006 367 0.025 (0.013-0.046) 2 Mynarek et al,30 2004 570 0.028 (0.017-0.045) 2 Boland et al,35 1998 512 0.078 (0.058-0.105) 2 Raptopoulos et al,33 1991† 188 0.027 (0.011-0.062) 2 O’Moore et al,31 1987 159 0.107 (0.068-0.165) 1 Overall 4424 0.040 (0.029-0.056) …

No ultrasonography used Doyle et al,21 1996 174 0.052 (0.027-0.096) 5 Bartter et al,16 1993 50 0.040 (0.010-0.146) 5 ∗ Grogan et al,9 1990 33 0.303 (0.171-0.477) 5 Alemán et al,14 1999 483 0.035 (0.022-0.056) 4 Grodzin and Balk,24 1997 23 0.087 (0.022-0.289) 4 Brandstetter et al,18 1994 426 0.066 (0.046-0.094) 4 ∗ Kohan et al,28 1986 102 0.127 (0.075-0.207) 4 Barnes et al,15 2005† 145 0.103 (0.063-0.165) 3 Godwin and Sahn,23 1990 32 0.063 (0.016-0.218) 3 Collins and Sahn,19 1987 129 0.116 (0.071-0.184) 3 Seneff et al,34 1986† 109 0.128 (0.078-0.205) 3 Raptopoulos et al,33 1991† 154 0.175 (0.123-0.244) 2 Jenkins et al,26 1983 221 0.068 (0.041-0.110) 1 Overall 2081 0.093 (0.066-0.130) …

Combined data Bass and White,17 2005 100 0.070 (0.034-0.140) 2

Overall 6605 0.060 (0.046-0.078) …

0.01 0.10 1.00 Proportion

Figure 2. Forest plot of pneumothorax rates following thoracentesis. The x-axis is drawn on a log scale. Studies are organized by whether real-time ultrasonography guidance was used during the procedures and then by quality score. Squares indicate the proportion of thoracenteses complicated by pneumothorax in each study; horizontal lines, the 95% confidence interval. Diamonds at the bottom of the each subgroup and the overall total at the bottom of the figure show the pooled estimates (with 95% confidence intervals) from the random-effects models. The study by Bass and White17 did not present data on the pneumothorax rate with or without ultrasonography guidance and is presented separately. All studies were included in the overall total analysis, with the study arms of the randomized controlled trials analyzed separately. *Randomized controlled trial comparing real-time ultrasonography-guided thoracentesis vs unguided thoracentesis. Study arms were analyzed separately in the overall total meta-analysis. †Study presented data on procedures performed with real-time ultrasonography guidance and on procedures performed without ultrasonography guidance, which are presented in the appropriate section. For the overall total meta-analysis, the studies are analyzed as single cohorts.

8,22,23,29,33 RESULTS ies enrolled patients in an ICU yielding a summary pneumothorax undergoing mechanical ventilation, rate (by meta-analysis) of 6.0% and 1 study20 evaluated outpatients (95% CI, 4.6%-7.8%), as shown in DESCRIPTION in a special procedures clinic. The pri- Figure 2. Pneumothorax rates OF INCLUDED STUDIES mary operators of procedures were in- among individual studies varied Twenty-four studies8,9,14-35 provided ternal medicine residents (30.0% of from 0% to 19.2% and were statis- data on the pneumothorax rate fol- studies), pulmonary faculty (20.0%), tically heterogeneous across stud- lowing 6605 unique thoracentesis radiology faculty (30.0%), or a com- ies (PϽ.001). Chest tube insertion procedures. Table 2 summarizes the bination of these groups (20.0%). Ul- was required in 1.7% of all thora- study design, patient population, trasonography guidance was used in centeses to evacuate symptomatic pneumothorax rate, and quality score 16 studies,* including the treatment pneumothoraces (Table 2). There- for eligible studies. The studies in- arm of the 2 randomized trials. fore, 34.1% of pneumothoraces fol- cluded 11 prospective cohort stud- Twelve studies achieved a high qual- lowing thoracenteses required chest ies, 11 retrospective analyses, and 2 ity score of 4 or 5 based on our pre- tube insertion. randomized controlled trials9,28 that defined criteria; 5 of these studies met Pneumothorax rates were simi- compared ultrasonography-guided all criteria. lar in prospective and retrospective thoracentesis by radiologists with un- studies (5.1% and 5.5%, respec- guided bedside thoracentesis by in- PNEUMOTHORAX RATE tively) but were lower in studies with ternists. Sample sizes ranged from 23 a quality score of 4 or 5 (4.8%) than A total of 349 pneumothoraces oc- to 605 patients undergoing 23 to 941 in studies with lower quality scores curred among 6605 thoracenteses, (median, 227) thoracenteses. Eigh- (7.0%); however, this difference was teen studies included patients on a nonsignificant. Studies published af- general medicine service, 5 stud- *References 8, 9, 14, 15, 20, 22, 25, 27-35. ter 2000 had significantly lower

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Downloaded From: https://jamanetwork.com/ on 10/03/2021 Table 3. Unadjusted Odds Ratios for Pneumothorax by Procedural or Patient Factor (Direct Comparisons)

No. of No. of Patients With Odds Ratio (95% Confidence Interval) Variable Studiesa (Without) Variable for Pneumothorax Procedural Factors Ultrasonography vs no ultrasonography 6 654 (1026) 0.3 (0.2-0.7) Experienced operator vs inexperienced 4 308 (622) 0.7 (0.2-2.3) Therapeutic thoracentesis vs diagnostic 12 1048 (1323) 2.6 (1.8-3.8) Larger needle or catheter vs small needle 7 700 (1178) 2.5 (1.1-6.0) Ն2 Needle passes vs 1 pass 3 145 (580) 2.5 (0.3-20.1) Follow-up thoracentesis vs initial 3 377 (993) 1.1 (0.3-3.6) Periprocedural Factors Aspiration of air vs none 2 19 (661) 104.0 (2.0-5355.0) Periprocedural symptoms vs none 3 57 (1504) 26.6 (2.7-262.5) Patient Factors Large effusion size vs small 7 758 (697) 1.3 (0.8-1.9) Male vs female sex 3 272 (220) 0.8 (0.3-1.7) ICU inpatient location vs non-ICU inpatient 3 142 (620) 0.9 (0.4-1.8) Non-ICU inpatient location vs outpatient 2 213 (448) 1.0 (0.5-2.0) Mechanical ventilation vs not 2 100 (589) 4.0 (0.95-16.8) Loculated pleural effusion vs nonloculated 3 106 (377) 0.7 (0.3-1.7)

Abbreviation: ICU, intensive care unit. a Only studies that reported results for both the presence and absence of a variable.

pneumothorax rates (2.9%) than than unguided thoracentesis (OR, CI, 0.5-7.2). The studies reporting earlier studies (6.8%) (P =.003). 0.3; 95% CI, 0.2-0.7). Among these data for different needle sizes did not Pneumothorax rates were also sig- studies, the 2 randomized con- supply information about the indi- nificantly lower in studies of more trolled trials9,28 found a similar effect cation for thoracentesis or effusion than 200 thoracenteses (4.7%) than size, but the difference was not sig- size, so we were unable to further ex- in smaller studies (9.2%) (P=.002). nificant (OR, 0.3; 95% CI, 0.0-2.8). amine these factors. Pneumothorax rates were lower The number of needle passes re- RISK FACTORS FOR for procedures performed by expe- quired to complete thoracentesis was PNEUMOTHORAX rienced operators than for proce- reported in 3 studies.8,14,21 Pneumo- dures performed by less experi- thorax rates were higher for proce- We calculated ORs for procedure- and enced clinicians (3.9% vs 8.5%, dures requiring 2 or more passes than patient-related risk factors for pneu- P =.04). When we restricted our for those completed in 1 pass (6.6% mothorax from studies that re- analysis to 4 studies that provided di- vs 3.5%, P=.42). The risk of pneu- ported pneumothorax rates for rect comparisons, this relationship mothorax was higher with 2 or more procedures with and without the par- was nonsignificant (OR, 0.7; 95% CI, needle passes (OR, 2.5; 95% CI, 0.3- ticular risk factor (Table 3). We de- 0.2-2.3). No differences were noted 20.1), but this relationship was non- termined summary estimates of pneu- in pneumothorax rates between ex- significant. There was no difference mothorax rates and 95% confidence perienced radiologists and experi- in pneumothorax rates for first-time intervals (CIs) for the same risk fac- enced pulmonologists (4.3% vs 4.4%, procedures vs follow-up procedures. tors (Table 4) when the study de- P=.81). Pneumothorax rates were Although only 3 studies14,21,27 re- sign precluded our measuring ORs. higher for therapeutic thoracenteses ported the association between peri- than for diagnostic procedures (8.4% procedural symptoms and pneumo- Procedure-Related Risk Factors vs 5.2%, P=.12); this difference was thorax, the development of any statistically significant among stud- symptom (cough, dyspnea, or chest Among 16 study cohorts, investiga- ies that provided direct compari- pain) conferred a markedly higher tors estimated the effect of ultraso- sons (OR, 2.6; 95% CI, 1.8-3.8). The risk of pneumothorax (OR, 26.6; nography-guided thoracentesis on risk of pneumothorax was increased 95% CI, 2.7-262.5). The risk of pneumothorax rates and reported when larger needles or catheters were pneumothorax also was substan- significantly lower rates than among used compared with smaller needles tially increased when operators wit- 13 cohorts with unguided thoracen- (OR, 2.5; 95% CI, 1.1-6.0). Pneumo- nessed the aspiration of air into the tesis (Table 4 and Figure 2) (4.0% thorax rates were similar for cath- pleural space (Tables 3 and 4). vs 9.3%, P=.001). In 6 comparative eters and for larger needles (8.3% vs studies9,14,15,28,33,34 that reported pneu- 5.9%, P=.19), but the available stud- Patient-Related Risk Factors mothorax rates with and without ul- ies did not allow a direct compari- trasonography guidance (Table 3), son. Catheter use was associated with In contrast to procedure-related fac- ultrasonography-guided thoracen- a nonsignificant increased risk of tors, few patient factors were asso- tesis was associated with a signifi- pneumothorax compared with the ciated with increased likelihood of cantly lower risk of pneumothorax use of smaller needles (OR, 1.9; 95% pneumothorax (Tables 3 and 4). The

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Downloaded From: https://jamanetwork.com/ on 10/03/2021 pneumothorax rate was similar for large and small effusion size and for Table 4. Effect of Patient- and Procedural-Related Factors on Pneumothorax Rates men and women. Pneumothorax (Indirect Comparisons) rates were similar for procedures per- Pneumothorax Rate P Value formed among non-ICU inpatients, No. of No. of (95% Confidence for Difference ICU inpatients, and outpatients. In Variable Studiesa Procedures Interval), % by t Test 2 studies22,32 describing thoracente- Overall 24 6605 6.0 (4.6-7.8) sis in patients with and without mechanical ventilation, the risk of pneu- Procedural Factors mothorax was increased with Ultrasonography Yes 16 4424 4.0 (2.9-5.6) .001 mechanical ventilation (OR, 4.0; 95% No 13 2081 9.3 (6.6-13.0) CI, 0.95-16.8). However, this rela- Operator experience tionship may have been con- Yes 10 1800 3.9 (2.4-6.4) .04 founded because the comparison No 7 958 8.5 (4.8-14.8) groups of nonventilated patients Thoracentesis Therapeutic 13 1474 8.4 (5.7-12.1) were not ICU patients. No study di- .12 Diagnostic 12 1323 5.2 (3.2-8.4) rectly compared pneumothorax rates Needle or catheter size in ICU patients with and without me- Large needle or catheter 7 700 9.8 (4.4-20.2) .20 chanical ventilation. Investigating Small needle 7 1178 5.4 (3.1-9.4) whether other factors may have con- No. of needle passes Ն2 3 145 6.6 (1.5-25.2) founded this relationship, we found .42 that the pneumothorax rate in me- 1 3 580 3.5 (2.3-5.3) Initial vs follow-up thoracentesis chanically ventilated patients with Follow-up 3 377 4.5 (1.2-15.6) .75 and without ultrasonography guid- Initial 3 993 3.6 (2.6-5.0) ance were not significantly differ- Periprocedural Factors ent (2.9% vs 6.3%, P=.20). Aspiration of air Yes 2 19 38.8 (15.9-68.0) .001 Other Reported Complications No 2 661 0.8 (0.1-9.2) of Thoracentesis Periprocedural symptoms Yes 3 57 31.1 (6.6-74.4) .001 The studies variably reported com- No 3 1504 1.7 (1.1-2.4) plications of thoracentesis other than Patient Factors pneumothorax. Hemothoraces were Effusion size Large 8 781 8.1 (5.4-12.2) reported in 6 patients from 4 stud- .71 ies.17,21,26,34 Vasovagal response to tho- Small 7 697 7.1 (4.0-12.3) Sex racentesis was described in 2 stud- Male 3 272 7.8 (4.5-13.2) 19,27 .50 ies. Subcutaneous or subpleural Female 3 220 9.9 (6.3-15.2) hematomas were described in 5 stud- Patient location 9,20,21,27,28 Non-ICU inpatient 14 3412 7.1 (5.2-9.8) ies. Reexpansion pulmo- NS (all ICU inpatient 7 541 4.5 (2.5-8.2) nary edema developed in 2 patients comparisons) from 1 study.27 Splenic34 and he- Outpatient 2 213 6.1 (3.6-10.3) 26 Mechanical ventilation patic lacerations were described in Yes 2 409 3.5 (1.5-8.1) .16 1 study each, and splenic aspiration No 14 3691 6.7 (4.7-9.4) without injury was described in 1 Loculated pleural effusion 26 Yes 3 106 5.4 (2.3-12.0) study. A sheared-off catheter was .30 described in 1 study.34 Reported pa- No 3 377 8.8 (5.7-13.5) tient symptoms included anxiety, lo- Abbreviations: ICU, intensive care unit; NS, nonsignficant. cal pain at the procedural site, dys- a The number of studies contributing to the subgroup analysis exceeds the total number of studies pnea, cough, and pleuritic chest pain. when studies reported data on patients with and without a putative risk factor.

lowing thoracentesis is an impor- of pneumothorax compared with un- COMMENT tant cause of morbidity and likely re- guided thoracentesis and was the sults in increased length of stay for strongest predictor of low pneumo- We present the first systematic re- hospitalized patients. Because sub- thorax rates. The pneumothorax rate view and meta-analysis to date of the stantial heterogeneity existed in the seemed to be lower when more ex- pneumothorax rate following tho- pneumothorax rates across stud- perienced clinicians were the pri- racentesis. Overall, 6.0% of thora- ies, we explored patient and proce- mary operators of the procedure, but centeses were complicated by the de- dural risk factors for the develop- there were no differences between velopment of pneumothorax, and ment of pneumothorax. experienced radiology and pulmo- 34.1% of pneumothoraces (1.7% of Real-time ultrasonography- nary medicine faculty. Important fac- all thoracenteses) required chest guided thoracentesis was associ- tors that increase the risk of pneu- tube insertion. Pneumothorax fol- ated with a significantly lower risk mothorax include therapeutic

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Downloaded From: https://jamanetwork.com/ on 10/03/2021 indication for the thoracentesis, wit- risk of pneumothorax and operator tainty about the true effect of these nessed aspiration of air, and any peri- experience may have been con- variables. It is possible that some of procedural symptoms. Although not founded by the use of ultrasonogra- these factors would be associated with statistically significant, other pos- phy. Bias also may have existed such higher risk of pneumothorax if more sible predictors of pneumothorax in- that more dangerous procedures in studies reported data on these vari- clude the need for 2 or more needle mechanically ventilated ICU pa- ables. For example, a recent study46 insertions and concurrent mechani- tients or in those with small locu- (which did not meet our prespeci- cal ventilation. These findings are lated effusions were performed by fied inclusion criteria because only consistent with those observed for more experienced operators or with 60% of patients underwent posttho- central venous catheter insertion, real-time ultrasonography guid- racentesis chest radiography) dem- in which ultrasonography guidance, resulting in false-negative asso- onstrated increased risk of pneumo- ance,36,37 more experienced opera- ciations between these factors and the thorax for increasing volumes of tors,13 and fewer needle passes12 con- risk of pneumothorax. Pneumotho- drained effusions. Moreover, few fer lower complication rates. rax rates also were lower in more re- studies directly compared pneumo- Our results highlight the impor- cent studies, larger studies, and stud- thorax outcomes in patients with or tance of trainee supervision during ies of higher quality. The secular without putative risk factors. Al- thoracentesis because of lower pneu- trends may represent more careful pa- though the results of our direct and mothorax rates with direct ultraso- tient selection, increased use of real- indirect analyses were largely con- nography guidance and with more time ultrasonography guidance, or cordant, most of the analyses of risk experienced operators. In many aca- greater use of expert faculty as the pri- factors relied heavily on indirect com- demic medical centers, trainees per- mary operator of thoracenteses. parisons across studies. These analy- form thoracenteses without supervi- Because of the potential for con- ses, in particular, can only be con- sion from expert faculty members. founding relationships between the sidered hypothesis-generating. Future Some internal medicine residents re- patient- and procedure-related risk research should report data for all pu- port a lack of comfort in performing factors for pneumothorax, we at- tative risk factors that we identified bedside procedures, despite having tempted to analyze combinations of and preferably should be of random- completed a moderate number by the variables. This analysis was limited be- ized controlled trial study design or end of their residency.38-40 One study39 cause the study design, collection, and should allow multivariable analyses found that residents required comple- presentation of data in the source stud- of patient-level data to more fully ac- tion of a mean of 8.1 (95% CI, 4.0- ies did not allow analysis of most com- count for unmeasured confounders 16.5) thoracenteses before report- binations. To lessen bias, we limited and to measure independent effects ing being comfortable with the analyses to direct comparisons only. of the various risk factors. procedure. Supporting this finding, Ultrasonography guidance reduced Despite these limitations, this is the only 79% of internal medicine pro- the risk of pneumothorax for large and first summary to date of a large num- gram directors surveyed believed that small effusions. In the unadjusted ber of studies that allows an estimate their graduating residents had mas- analysis, the risk of pneumothorax of the pneumothorax rate following tered thoracentesis.41 In another was similar for both effusion sizes; this thoracentesis and an analysis of risk study,42 surveyed internists be- observation persisted after adjusting factors for its development. The sub- lieved that clinicians must perform for ultrasonography guidance. The ab- stantial between-study heteroge- 5 to 10 thoracenteses to attain com- sence of patient-level data limited our neity allowed us to investigate rela- petence and must perform 1 to 5 an- ability to perform direct compari- tionships between procedural and nually to maintain competence. No- sons of therapeutic thoracentesis, op- patient risk factors and the develop- tably, 66% of internists in the study erator experience, needle size, or other ment of pneumothorax. The most still reported performing thoracen- combined analyses of factors associ- important strategy to reduce pneu- tesis in their clinical practice. Al- ated with pneumothorax in univari- mothorax rates is the use of ultraso- though our analysis was not de- ate analysis. A meta-analysis of pa- nography guidance. Uniform use of signed to determine operator comfort tient-level data using the primary data ultrasonography guidance across in- level with thoracentesis, previous re- from these studies or new random- stitutions would reduce the burden search has demonstrated that resi- ized trials would be necessary to de- of pneumothorax and allow a greater dent comfort with thoracentesis is in- termine which factors are con- degree of safety for this commonly creased by faculty supervision.40 founded and which are independent performed procedure. Other risk fac- These results may provide addi- predictors of pneumothorax. tors include mechanical ventilation, tional support of the recent concept This study had several limita- therapeutic procedures, and symp- of medical procedure service staffed tions. Publication bias is a frequent toms during thoracentesis. Pneumo- by expert faculty43 and of the role of concern with meta-analysis, al- thorax rates are also lower for expe- medical simulation for thoracente- though there is no consensus that rienced clinicians, regardless of sis in the education of trainees.44 methods to measure the bias (such as specialty, and may be lower when Some of the relationships we ob- funnel plots) are reliable.45 In addi- only 1 needle pass is required. Fu- served may have been subject to con- tion, few studies reported data on im- ture research should clarify which fac- founding and resultant false-positive portant risk factors such as operator tors are independent predictors or false-negative associations. For ex- experience, number of needle passes, through randomized controlled trials ample, the relationship between the and effusion size, leading to uncer- or analysis of patient-level data in

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Downloaded From: https://jamanetwork.com/ on 10/03/2021 observational studies. Institutional 8. Lichtenstein D, Hulot JS, Rabiller A, Tostivint I, raphy for thoracentesis. Am Rev Respir Dis. 1986; Meziere G. Feasibility and safety of ultrasound-aided 133(6):1124-1126. policies that require supervision or thoracentesis in mechanically ventilated patients. 29. Mayo PH, Goltz HR, Tafreshi M, Doelken P. Safety performance of thoracentesis by Intensive Care Med. 1999;25(9):955-958. of ultrasound-guided thoracentesis in patients re- experienced operators may lower the 9. Grogan DR, Irwin RS, Channick R, et al. Complica- ceiving mechanical ventilation. Chest. 2004; pneumothorax rate. We encourage in- tions associated with thoracentesis: a prospective, 125(3):1059-1062. randomizedstudycomparingthreedifferentmethods. 30. Mynarek G, Brabrand K, Jakobsen JA, Kolben- stitutions to consider a policy of uni- Arch Intern Med. 1990;150(4):873-877. stvedt A. 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N Engl J Med. 1994; and the value of chest radiography after ultrasound- ment of Medicine, Boston Univer- 331(26):1735-1738. guided thoracocentesis. Acta Radiol. 2004;45 sity Medical Center, Boston, MA 13. Sznajder JI, Zveibil FR, Bitterman H, Weiner P, Bursz- (8):828-832. 02118 ([email protected]). tein S. Central vein catheterization: failure and com- 33. Raptopoulos V, Davis LM, Lee G, Umali C, Lew R, Author Contributions: Dr Gordon plication rates by three percutaneous approaches. Irwin RS. Factors affecting the development of pneu- Arch Intern Med. 1986;146(2):259-261. mothorax associated with thoracentesis. AJR Am had full access to all the data in the 14. Alema´n C, Alegre J, Armadans L, et al. The value J Roentgenol. 1991;156(5):917-920. study and takes responsibility for the of chest roentgenography in the diagnosis of pneu- 34. Seneff MG, Corwin RW, Gold LH, Irwin RS. Com- integrity of the data and the accu- mothorax after thoracentesis. Am J Med. 1999; plications associated with thoracocentesis. Chest. racy of the data analysis. Study con- 107(4):340-343. 1986;90(1):97-100. 15. Barnes TW, Morgenthaler TI, Olson EJ, Hesley GK, 35. Boland GW, Gazelle GS, Girard MJ, Mueller PR. cept and design: Gordon, Feller- Decker PA, Ryu JH. Sonographically guided thora- Asymptomatic hydropneumothorax after thera- Kopman, and Smetana. Acquisition of centesis and rate of pneumothorax. J Clin Ultra- peutic thoracentesis for malignant pleural effusions. data: Gordon and Feller-Kopman. sound. 2005;33(9):442-446. AJR Am J Roentgenol. 1998;170(4):943-946. Analysis and interpretation of data: 16. Bartter T, Mayo PD, Pratter MR, Santarelli RJ, Leeds 36. Hind D, Calvert N, McWilliams R, et al. Ultrasonic WM, Akers SM. Lower risk and higher yield for tho- locating devices for central venous cannulation: Gordon, Feller-Kopman, Balk, and racentesis when performed by experienced meta-analysis. BMJ. 2003;327(7411):e361. http:// Smetana. Drafting of the manuscript: operators. Chest. 1993;103(6):1873-1876. www.ncbi.nlm.nih.gov/pmc/articles/PMC175809/ Gordon, Feller-Kopman, and 17. Bass J, White DA. Thoracentesis in patients with ?tool=pubmed. Accessed November 3, 2009. Smetana. Critical revision of the manu- hematologic malignancy: yield and safety. Chest. 37. Randolph AG, Cook DJ, Gonzales CA, Pribble CG. 2005;127(6):2101-2105. Ultrasound guidance for placement of central ve- script for important intellectual con- 18. Brandstetter RD, Karetzky M, Rastogi R, Lolis JD. nous catheters: a meta-analysis of the literature. tent: Gordon, Feller-Kopman, Balk, Pneumothorax after thoracentesis in chronic ob- Crit Care Med. 1996;24(12):2053-2058. and Smetana. Statistical analysis: Gor- structive pulmonary disease. Heart Lung. 1994; 38. Wickstrom GC, Kolar MM, Keyserling TC, et al. 23(1):67-70. Confidence of graduating internal medicine resi- don and Balk. Study supervision: 19. Collins TR, Sahn SA. Thoracocentesis: clinical dents to perform ambulatory procedures. J Gen Feller-Kopman and Smetana. value, complications, technical problems, and pa- Intern Med. 2000;15(6):361-365. Financial Disclosure: Dr Feller- tient experience. Chest. 1987;91(6):817-822. 39. Hicks CM, Gonzalez R, Morton MT, Gibbons RV, Kopman has received lecture fees 20. Colt HG, Brewer N, Barbur E. Evaluation of patient- Wigton RS, Anderson RJ. Procedural experience related and procedure-related factors contribut- and comfort level in internal medicine trainees. from SonoSite, Inc. Dr Smetana serves ing to pneumothorax following thoracentesis. J Gen Intern Med. 2000;15(10):716-722. as a consultant to SafeMed. Chest. 1999;116(1):134-138. 40. Huang GC, Smith CC, Gordon CE, et al. Beyond 21. Doyle JJ, Hnatiuk OW, Torrington KG, Slade AR, the comfort zone: residents assess their comfort Howard RS. Necessity of routine chest roentgen- performing inpatient medical procedures. 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