Contemporary use of fibrinolytics in the management of pediatric empyema

doi:10.21203/rs.3.rs-4909369/v1

Background: This study seeks to investigate the contemporary use and effectiveness of fibrinolysis as a first-line option in pediatric empyema.

Methods: The Pediatric Health Information System (PHIS) was queried to identify patients with empyema without fistula (2018-2023). First-line treatments were chest drainage (CD), chest drainage with fibrinolysis (CDF), and video-assisted thoracoscopic surgery/open decortication (VATS/OD). Outcomes between groups were compared using Kruskal-Wallis and Chi-Square tests. Multivariate generalized linear model was used to account for covariates.

Results: 581 individuals/cases met inclusion criteria. CD accounted for 11.9% of cases, CDF for 67.6%, and VATS/OD for 20.7%. After adjusting for covariates differences in LOS were not significant (p=0.393). Subsequent VATS/ODs were required in 6.9% of CDF cases, 8.9% of CD, and 3.3% of primary VATS/OD. Additionally, 32.5% of primary VATS/OD received adjuvant fibrinolysis. Complications were more often observed in the VATS/OD group compared to CD and CDF (11.7% vs 5.8% and 4.1% respectively; p= .008). There were no differences in 30-day readmission rate (VATS/OD:1.2%, CTD:1.5%, and CTDF:1%; p=0.83).

Conclusion: Fibrinolysis is now utilized as first-line treatment for most patients and as adjunct in other approaches. The findings justify further implementation as it is the less invasive first-line primary therapy in patients with empyema.

Empyema

VATS

Fibrinolysis

Children

Pediatrics

PHIS

Community acquired pneumonia is the leading cause of hospitalization worldwide with about 8.4% becoming complicated[1]. Approximately 1 out 1,000 (0.6%) of childhood pneumonia progress to empyema, characterized by accumulation of purulent effusion into the pleural space and formation of fibrous septations and thickening of the pleura preventing lung expansion as the disease progresses [2]. Early clearance of the pleural space by chemical or mechanical debridement is recommended, with the American Pediatric Surgical Association (APSA) systematic review [3] published over 10 years ago recommended fibrinolysis as first-line therapy based on the results of two randomized studies showing similar outcomes between fibrinolytics and video assisted thoracoscopic surgery (VATS) [3, 4]. However, the current state of national adoption of this recommendation is unknown. In absence of strong predictors of treatment failure and with results of several observational studies questioning the generalizability of RCTs, there is still ongoing debate about effectiveness of fibrinolysis [5-7]. A recent survey in which half of the responders were surgeons, highlighted the lack of consensus on the first-line treatments for empyema with 42% preferring chest tube with or without fibrinolysis and 41.6% preferring VATS[8].

The aim of the present study was to evaluate current trend in the adoption of fibrinolysis as first-line management of empyema and compare clinical outcomes after treatment.

2.1 Data source and study period.

This study is a retrospective cohort analysis including children ≤ 18 years old treated at freestanding children’s hospital for empyema between January 1^sts2018 and September 30^rd2023. Data were extracted from the Pediatric Health information System (PHIS) database administered and maintained by the Children’s Hospital Association (Lenexa, KS). The PHIS database includes inpatient, ambulatory and emergency department clinical data and resource utilization from 49 children’s hospitals in the United States. Data are deidentified and subject to reliability and validity checks before being incorporated into the database. This study was exempt from Institutional Review Board review and approval as data were obtained from a de-identified database.

2.2 Cohort Construction.

International Classification of Disease, 10h Revision, Clinical Modification and Procedure Coding System (ICD-10-CM; ICD-10-PCS) were used to identify discharge diagnosis of pneumonia associated with empyema and empyema related-procedures (Supplemental Table 1). Patients included in the analysis were those with a principal or secondary discharged diagnosis of empyema without fistula (ICD-10 CM code: J86.9). A stringent inclusion criterion was adopted to capture only patients with a confirmed diagnosis of empyema, with an assumption that the discharged code was used when a fibrinopurulent pleural exudate was documented by ultrasound (US) or computed tomography (CT) and/or by laboratory analysis of the pleural fluid.

Details of the cohort construction with inclusion and exclusion criteria are depicted in Figure 1.

Since the PHIS database does not contain radiographic, physiologic or laboratory data, we used the following surrogate markers to describe severity of illness: 1) ICD-10 diagnostic codes indicating severity of the underlying pneumonia (J850: gangrene and necrosis of lung; J851:abscess of lung); 2) multiorgan dysfunction ( R7881: bacteriemia; N179: acute kidney failure); 3) resources utilization captured by clinical transaction category (CTC) codes for pharmacy, supply, or other clinical charges, and extractable “Flag”, for clinically important metrics (admission to Intensive Care Unit, need for oxygen supplementation, mechanical ventilation, and total parenteral nutrition). Children who were treated with antibiotics alone were excluded from the analysis.

Primary treatment was defined as the first empyema-related procedure recorded in PHIS procedure file upon hospital admission. Empyema-related procedures were defined by a procedural code indicating percutaneous chest tube placement, VATS (endoscopic chest tube placement with mechanical debridement and/or pleural decortication) and pleural decortication by open thoracotomy (OD). VATS and decortication via open thoracotomy were collapsed into one procedure type as both require general anesthesia and operating room utilization. A separate code for drainage placement was disregarded if the procedure occurred on the same day of VATS or thoracotomy, with the assumption that it was part of the procedure itself.

Pleural instillation of fibrinolytic agent (CDF group) was defined by the procedural code 3E0L3GC (i.e., introduction of therapeutic substance into pleural cavity) and/or pharmacy charges for tissue plasminogen activator (tPA). Patients who were initially treated with chest drainage and intrapleural fibrinolytic injection were assigned to the CDF group, while those who didn’t received any dose of tPA were assigned to the CD group.

Unique medical record number allows for patient data tracking across multiple encounters to determine 30-day emergency department (ED) visits and hospital readmission.

2.3 Outcomes

The primary outcome of interest was total length of hospital stay (LOS) as a proxy for disease resolution.

Secondary outcomes were:

1) duration of intravenous (IV) antibiotic therapy;

2) need for additional procedures/interventions;

3) complications/adverse events related to the treatment, such as acute posthemorrhagic anemia, pneumothorax, and air leak;

4) 30-day ED visit or readmission for the same index condition.

The need for additional salvage procedures/interventions was defined by receiving surgery after CD placement alone, or CDF as primary treatment and any dose of tPA following surgery, and/or by receiving any additional surgery after the initial VATS/OD.

2.4 Statistical analysis

Descriptive statistics were used for demographics (age, gender, insurance payer and census region) and clinical characteristics (associated comorbidities and markers of severity of illness).

Outcomes of interest were compared among the three first-line treatment groups as described above. Continuous variables were reported as mean and standard deviation (SD) for normally distributed data and as median with interquartile range (IQR) for skewed data.

For our primary outcome of interest, we observed that data distribution was skewed, therefore the Kruskal-Wallis test was used to compare differences in total hospital length of stay (LOS) between treatment groups. Chi-Square and Fisher’s exact test as appropriate were used to compare need for additional treatment/procedures, complications and 30-day readmissions.

Bivariate and multivariate generalized linear models were used to estimate the effect of first-line treatment approaches and other patient factors on LOS and duration of intravenous (IV) antibiotic treatment. The multivariate model was built using the procedure types with demographics and clinical characteristics as covariates. Covariates considered for inclusion in the final model were chosen based on findings from the bivariate analysis (p≤0.05).

IBM SPSS Statistics version 28 (International Business Machines Corp, Armonk, New York) was utilized for statistical analysis. Two-tailed testing was completed and a P-value <0.05 were considered statistically significant.

3.1 Cohort characteristics and primary treatment approaches.

During the study period, we captured 3,616 patients who were hospitalized for CP. After applying inclusion and exclusion criteria 581 unique identifiers with a discharge diagnosis of pleural empyema requiring impatient treatment were identified and included in the final cohort.

Source of admission was transfer from another hospital in 259 (44.6%) cases, 3.4% were elective admission. Admission during weekend accounted for 25.1% (n=146) of cases.

Descriptive statistics are summarized in Table 1.

There were no differences in the distribution of demographic characteristics and the types of markers of severity of illness among treatment groups. Among the associated comorbidities a relatively higher proportion of metabolic disorders was found in the CDF group (p=0.037) and chronic respiratory diseases in the CD group (p=0.009). Hospitals with a relatively higher proportion of VATS/OD as first-line approach were geographically located in the South census region (p=0.001).

Two hundred and sixteen patients (37.2%) were admitted to ICU and 90 (15.5%) required mechanical ventilation for a median of 3 days [IQR: 2-5.8 days]. The duration of mechanical ventilation was greater than 14 days in 7 cases. In addition, 232 (39.9%) patients required oxygen supplementation for a median duration of 3 days [IQR: 1-5 days].

Causative microorganisms of underlying pneumonia were isolated in 48.4% of cases. Streptococcus pneumoniae was the most common pathogen, accounting for 17.7% of pneumonia complicated by empyema (Supplemental Table 2); 2.6% of CP were secondary to inhalation of food and vomit.

Most patients (n=392; 67.6%) were treated with CDF as first-line treatment, and tPA was used in all cases. Sixty-nine (11.9%) patients were treated with CD alone and 120 patients (20.7%) with VATS/OD. Only 5 VATS/OD were primary open thoracotomy. Conversion to open thoracotomy was 2.6% (n=3 cases) for primary VATS, and 5.7% (n=2 cases) for secondary VATS. Primary drainage procedure was performed within 48 h upon hospital admission in 90.7% of cases (N=527) ; with patients treated with CD alone having a slightly longer course of preoperative antibiotic treatment before the chest drainage placement, compared with those underwent CDF and VATS/OD: median 1[IQR: 0-2] versus 1 days [IQR: 0-1 days], respectively; p=0.017).

Chest drains were placed by interventional radiologist in 42.3% (n=246) of cases and critical care physicians in 10% (n= 60) of cases, other specialties accounted for 9.3% (n=54). Surgeons performing both VATS/OD and/or chest drainage placement were involved in patient treatment in 38% (n=221) of empyema cases.

There was a trend toward increased used of fibrinolysis in the last two calendar years of the study period, while a relatively greater proportion of VATS were performed between 2019 and 2021 (Fig. 2).

Overall, 74.2% of patients regardless of the primary treatment approach received at list one dose of tPA (Table 2), administered in 54.7% (n=318) within 48 hours from the procedure.

Data for duration of chest tube use were available in 49 cases, and these drains were removed at a median of 6 days [IQR: 3-5 days] following primary placement.

3.2 Outcomes

Unadjusted median total LOS was longer for CDF group compared to VATS/OD: 9 days [IQR:7-11 days] versus 7 days [IQR 5-10 days] (p<0.001).

Using bivariate analysis CD was the treatment approach who remained associated with prolonged LOS (p=0.040). Other significant factors associated with prolonged LOS where admission during weekend (p=0.043), and markers of severity of illness as described before: ICU admission (p<0.001), mechanical ventilation (p< 0.001), TPN (p=0.027), need for oxygen supplementation (p=0.006) and associate diagnosis of gangrene and necrosis of the lung (p=0.024). In addition, the presence of several associated chronic comorbid conditions was also associated with prolonged LOS. Details of the bivariate analysis are reported in Supplemental table 3.

In multivariate analysis when other factors were taken into accounts; the treatment approach was not an independent predictor of the duration of hospital stay (Table 3).

Seventy-two patients (12.4%) required additional procedures following the primary treatment (Table 4). Subsequent VATS/OD was performed in 8.9% of those previously treated with CD alone, 6.9% of those treated with CDF, and 3.3 % of primary VATS. In addition, 39 patients (32.5%) managed with primary VATS/OD also received tPA pleural injection. Median days between primary treatments and additional interventions was shorter for patients initially managed with VATS/OD compared to those treated with less invasive approaches (VAT/OD: 3 days [IQR: 2-5], CD: 3 days [IQR: 3-6.5 days], and CDF: 6 days [IQR: 4-8 days]) (p<0.001). Drain repositioning was performed in 57 cases (9.8%) at median of 6 days[IQR:4,8.5 days] from the initial drainage placement. Post-procedural complications were reported in 34 patients (5.9%), with five patients suffering more than one complication. Major complications occurred in two cases (0.3%); one accidental laceration of lung parenchyma requiring surgical repair occurred following a primary VATS and one during a secondary VATS converted to thoracotomy.

Discharge disposition was home self-care in 556 cases (95.7%), 3 patients (0.5%) were transfer to a skilled nursing facility/rehabilitation, 3 (0.5%) were transferred to another hospital and 19 (3.3%) were discharged home under the care of home health care organizations.

The rate of 30-days readmission/ED visit was 1.4%(n=8); the median time to readmission was 11 days [IQR: 2-28 days]. Diagnosis at readmission were empyema without fistula in 6 cases, pneumothorax in 1 case and empyema with fistula in another. Four patients (0.7%) required additional interventions. Treatments at readmission were chest drain placement in three cases previously treated with CDF (n=2) and VATS (n=1). A repeat VATS procedure was performed in a patient previously treated with VATS.

This database study suggests that the treatment paradigm for empyema in children continues to shift toward the use of fibrinolytics, both as first-line and adjuvant or rescue treatment at pediatric centers in the United States.

During the study period, the utilization of fibrinolysis as first-line treatment increased from 66.7% in 2018 to 74.8% in 2023, with a fluctuation toward a relative higher utilization of VATS during the COVID-19 pandemic. VATS utilization has slowed over the past decade as it was used in half of cases in 2008 [9]. After a literature review was published by the APSA Evidence Based Practice and Outcomes Committee [10], VATS utilization as primary treatment dropped from 36% in 2014 [9, 11] to 5.3% in 2017 [7]. Surprisingly, in this PHIS analysis, we observed a relatively increased utilization of VATS as primary treatment in more recent years, which overall accounted for 20.7% of empyema-related procedures . The reason is unknown, posing the question if this emerging trend is the result of physician preferences over guideline recommendation in absence of strong predictors of treatment failure.

Due to the high morbidity and financial burden on the health care system associated with the management of empyema, LOS is one of the main outcomes used across studies to compare effectiveness of treatment approaches [3-7, 12-16]. The RCTs conducted to date have found no differences in LOS between surgical and non-surgical approaches [3, 4, 13]. The data in the present study also saw no difference in LOS after adjusting for comorbidities.

In contrast with this data several observational studies have reported shorter LOS in empyema cases treated with VATS, leading proponent of early VATS to question the generalizability of RCTs [5, 7, 15-18].

Proponents of VATS therefore suggest to performed thoracoscopy early in the disease process over the concern that the presence of thick pleural peels may increase the risks of conversion rate to thoracotomy and parenchymal injuries [15, 19, 20]. It has also been argued that a rescue VATS following an unsuccessful fibrinolytic treatment may pose surgical challenges [13, 21, 22]. In contrast with this observation, in our experience rescue VATS performed for incomplete resolution of empyema following fibrinolysis was associated with shorter operating room times and LOS compared with de novo VATS [4, 23]. Others argue that because most children may require general anesthesia for chest tube placement, it is reasonable to propose VATS as first-line approach [19, 24, 25]. In a RCTs comparing placebo vs. intrapleural urokinase for the treatment of pediatric empyema, it was found that a larger chest tube did not improve drainage[26]. Success rate of fibrinolysis reported in the literature range from 62.8% to 98 % [13, 17, 28, 29]

The success rate of fibrinolysis in the present study was 93.1% which compares favorably with the previously reported rates by studies based on data from large administrative databases, in which progression to VATS/OD ranged from 12% to 40% [6, 9, 16]. The utilization of a second cycle of fibrinolysis with unresolved empyema after the first round may have contributed to the decreased progression to VATS. In the present study 15.5% of patients received a second cycle of fibrinolysis treatment. As previously published, the adoption of a protocol including a second cycle of tPA intrapleural injection at our institution was effective in reducing the need for surgery, progression to VATS initially dropped from 16.6% in 2009 to 4% by 2016 [29]. Of note, has been reported that pediatric centers in which the surgical team is rarely involved in the initial treatment of children with empyema have the tendency to use less rescue VATS[28]. In our institution, after removing automatic triggers for surgery, no cases of rescue VATS have been performed in past 8 years [29].

The utilization of rescue or adjuvant fibrinolysis appears to be underestimated in the literature [7, 9, 30]. One study found that none of the patients underwent primary VATS or open surgery required a rescue fibrinolysis [16], while a few other studies reported the utilization of fibrinolysis following VATS as adjuvant therapy [13, 31]. These data are in contrast with the results of the present study in which 32.5 % of primary VATS/OD required fibrinolytics to obtain process resolution, and 64.1 % of them received intrapleural instillation of tPA within 48 hours from the primary thoracoscopy. Whether the combination of these two approaches was planned as part of an emerging protocol or if the decision to proceed to fibrinolysis following VATS was based on radiologic signs of incomplete debridement, cannot be established in this analysis. This emerging trend indicates the central role of fibrinolysis both as primary and adjuvant/rescue procedure for the management of pediatric empyema.

In this study, complications were more often observed in patients treated with VATS/OD, with the most common complications being air leak and post-procedural pneumothorax. This finding is consistent with a recent large cohort of pediatric empyema captured in National Readmission Database [30]. Persistent air leak and bronchopleural fistula have been previously associated with removal of the pleural peel from the lung [13, 32]. With this latest complication more often observed in patients with associated necrotizing pneumonia [13, 32].

This study has several limitations inherent to the retrospective administrative dataset. First, clinical and laboratory data and imaging finding are not captured in the PHIS database limiting our ability to classified disease stages. Although we used a stringent selective criterion to build the cohort there is still some degree of selection bias as misclassification of data can occur secondary to error coding or data entry. Second, improvement or deterioration of clinical condition cannot be assessed in this dataset therefore it is not possible to establish if the decision to proceed to VATS or thoracotomy in patient initially treated with chest tube alone was based on contraindications to fibrinolytic agents, treatment failure or if the chest drain was intendent to be temporary. In addition, for those who didn’t complete a 3-dose cycle of fibrinolytic injections and progressed to VATS/OD, we were not able to capture if the decision was based on lack of response to the primary treatments or other clinical considerations, as coding for allergic reaction or adverse events may have been not reported in all cases as secondary associated discharge diagnosis.

Finally, although LOS if often used as a proxy of disease resolution factors inherent interhospital differences in practice patterns and patient characteristics not captured in the multivariate analysis may have played a role in determine the duration of hospitalization.

Fibrinolytic agents have a central role for the current management of empyema and pleural decortication is rarely necessary. The low rate of reoperation and readmission in patients treated with fibrinolytics indicates that a full resolution can be achieved in the majority of cases with this less invasive approach.

AKF: Acute Kidney Failure

APSA: American Pediatric Surgical Association

CCC: Complex Chronic Condition

CD: Chest drainage

CDF: Chest drainage with fibrinolysis

CP: Complicated pneumonia

CTC: clinical transaction category

CT: Computed tomography

ED: Emergency department

IQR: Interquartile range

IV: Intravenous

OD: Open decortication

PHIS: Pediatric Health Information System

RCT: Randomized control trial

SD: Standard Deviation

tPA: Tissue Plasminogen Activator

Us: Ultrasound

VATS: Video assisted thoracoscopic surgery

Compliance with ethical standard

Authors contribution: All authors contributed to the study design, data analysis and manuscript writing.

Funding: No funding was received for conducting this study and assist with the preparation of this manuscript.

Study approval: This study was exempted from our Institutional Review Board review and approval as data were obtained from a de-identified database.

Declaration of conflicting interest: None

Data availability: Anonymous data not included in this article can be made available upon request to qualified investigators after institutional review board approval in accordance with PHIS data accessibility requirements.

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Table 1 Cohort Characteristics

Distribution of demographics and clinical characteristics of the study population according to the primary treatment approach

	Primary Treatment group
	CD (n=69)	CDF(n=392)	VATS/OD (n=120)	Total (n=581)
Demographics and Clinical Characteristics	N (%)	N (%)	N (%)	N	*P value*
Age					0.046
≤ 5 years	33 (47.8)	207 (52.8)	66 (55)	306
6-12 years	12 (17.4)	106 (27)	24 (20)	142
13-18 years	24 (34.8)	79 (20.2)	30 (25)	133
Gender (Female)	27(39.1)	181(46.2)	60 (50)	268	0.353
Race					0.228
White	48 (69.6)	271 (69)	79 (66.4)	398
Black	3 (4.3)	42 (10.7)	13 (10.9)	58
Asian	4 (5.8)	20 (5.1)	6 (5)	30
Other	7 (10.1)	40 (10.2)	19 (15.8)	66
Unknown	7 (10.1)	19 (4.8)	3 (5.9)	29
Hispanic or Latino	13 (18.8)	80 (20.4)	38 (31.7)	131	0.116
Relevant Comorbidities
Cardiovascular	6 (8.7)	27 (6.9)	2 (1.7)	35	0.057
Gastrointestinal	9 (13)	27 (6.9)	7 (5.8)	43	0.151
Hematologic/Immunologic	3 (4.3)	11 (2.8)	3 (2.5)	17	0.745
Malignancy	5 (7.2)	8 (2)	3 (2.5)	16	0.050
Metabolic Disorders	10 (14.5)	92 (23.4)	17 (14.2)	119	0.037
Neurologic/Neuromuscular	3 (4.3)	28 (7.1)	5 (4.2)	36	0.394
Congenital/Genetic Defects	2 (2.9)	26 (6.6)	6 (5)	34	0.431
Renal	1 (1.4)	6 (1.5)	2 (1.7)	9	0.992
Chronic Respiratory	7 (10.1)	10 (2.6)	5 (4.2)	22	0.009
Technology Dependent	6 (8.7)	29 (7.4)	10 (8.3)	45	0.900
Complex Chronic Conditions	25 (36.8)	152 (38.8)	35 (29.2)	212	0.160
Markers of Severity of illness
Gangrene and Necrosis of lung	4 (5.8)	34 (8.7)	10 (8.4)	48	0.728
Abscess of lung	2 (2.9)	9 (2.3)	1 (0.8)	12	0.544
ICU Admission	18 (26.1)	153 (39)	45 (37.5)	216	0.122
Mechanical Ventilation	8 (11.6)	66 (16.8)	16 (13.3)	90	0.413
Oxygen Supplementation	25 (36.2)	150 (38.3)	57 (47.5)	232	0.156
TPN	3 (4.3)	13 (3.3)	1 (0.8)	17	0.279
Bacteriemia	NA	10 (2.6)	1 (0.8)	11	0.226
Acute Kidney Failure	3 (4.3)	12 (3.1)	3 (2.5)	18	0.777
Non-chronic	31 (44.9)	188 (47.8)	61 (51.3)	280
Hospital Region					0.001
Midwest	11(15.9)	78 (19.9)	14 (11.6)	103
Northeast	13(18.8)	57 (14.5)	3 (2.5)	73
South	25(36.2)	160 (40.8)	68 (56.6)	253
West	20(28.9)	97 (24.7)	35 (29.2)	152
Primary expected payor					0.748
Government	28 (40.6)	178 (45.4)	60 (50)	266
Private	36 (52.2)	194 (49.4)	51(42.9)	281
Other	4 (5.8)	17 (4.3)	8 (6.7)	29
CD: Chest drainage; CDF: Chest Drainage with fibrinolysis; VATS: Video-assisted thoracoscopic surgery; OD: Open Decortication; TPN: Total Parenteral Nutrition; NA: not available

Table 2 Number of cycles of intrapleural instillation of tissue plasminogen activator.

	Treatment groups
	CDF	VATS/OD	Total
Cycles of tPA	N (%)	N (%)	N (%)
< 3 days of tPA	80(20.4)	15(38.5)	95(22)
One 3-days course of tPA	246(62.8)	21(53.8)	267(61.9)
> one course of tPA	64(16.3)	3(7.7)	67(15.5)
Nonconsecutive days of tPA	2(0.5)		2(0.5)
Total	392	39	431
tPA: Tissue Plasminogen Activator; CDF: chest drainage with fibrinolysis; VATS/OD: Video-assisted Thoracoscopic surgery/Open Decortication

Table 3 Generalized bivariate and multivariate linear model results

	Primary outcome : Length of stay
Treatment groups	Length of stay Days*	Unadjusted β Coefficient (95% CI)	P value	Adjusted ^a β Coefficient (95% CI)	P value
CD	5[7-12]	-1.412 (-2.756 to - 0.068)	.040	-1.206 (-2.477 to 0.065)	0.063
VATS/OD	5[7-10]	-1.328 (-2.868 to 2.852)	.091	-0.613 (-2.020 to 0.794)	0.393
CDF	7[9-10]	Ref.		Ref.
	Secondary outcome: Duration of Intravenous antibiotic therapy
	IV antibiotic duration Days *	Unadjusted β Coefficient (95% CI)	P value	Adjusted ^b β Coefficient (95% CI)	P value
CD	6[4-10]	-1.568 (-3.127 to -0.008)	0.049	-1.046 (-2.425 to 0.333)	0.137
VATS/OD	6[5-8]	-1.341 (-2.583 to -0.098)	0.034	-0.912 (-2.019 to 0.195)	0.106
CDF	7[6-10]	Ref.		Ref.
Median [interquartile range]*; CI: Confidence Interval; CD: Chest Drainage; CDF: Chest Drainage with Fibrinolysis; VATS/OD: Video-assisted Thoracoscopic Surgery/Open Decortication; Ref.: Reference Category Variables entered in the final model(p ≤ 0.05): weekend admission ^{(a, b)}; ICU admission^{(a, b)}; mechanical ventilation^{(a, b)}; total parenteral nutrition^{(a, b)}; oxygen supplementation^{(a, b)}; gangrene and necrosis of lung^{(a, b)}; methicillin resistant staphylococcus aureus(MRSA) ^(b);gastrointestinal^(a), hematologic/immunologic^(a), metabolic^{(a, b)} ,congenital/genetic^{(a, b)}, cardiovascular ^{(a, b)},neurologic/neuromuscular^{(a, b),}chronic respiratory disorders^(a), technology dependence^(a), and complex chronic conditions^(a) .

Table 4 Secondary outcomes

	Primary treatment groups
	CD (n=69)	CDF (n=392)	VATS/OD (n=120)	Total (n=581)
Secondary Outcomes	N (%)	N (%)	N (%)	N (%)	P value
Additional Treatments/Procedures ^a	6	27	43	76
VATS/Open Decortication	6(8.9)	27(6.9)	4(3.3)	37(6.4)	<0.001
Fibrinolysis			39(32.5)	39(6.7)
Percutaneous Chest Drainage Replacement	4(5.8)	51(13)	2(1.7)	57(9.8)	<0.001
Complications ^b	4(5.8)	16(4.1)	14(11.6)	34(5.9)	0.008
Air Leak	1(1.4)	3(0.7)	4(3.4)
Post-procedural Pneumothorax		3(0.7)	7(5.9)
Acute Posthemorrhagic Anemia	3(4.4)	4(1)	4(3.4)
Subcutaneous Emphysema		1(0.3)
Accidental laceration of lung		1(0.3)	1(0.8)
Hematoma of respiratory system		1(0.3)
Acute post-procedural respiratory failure	1(1.4)	2(0.5)
Sepsis following a procedure		1(0.3)
Organ and Space SSI		1(0.3)
Adverse reaction to infusion of thrombolytic		1(0.3)
30-days Impatient Readmission	1(1.5)	4(1)	2(1.7)	7(1.2)	0.828
Requiring interventions		2(0.5)	2(1.7)
Length of stay at readmission (days)	6	3[1.5-8.5]*	23 and 28
CD: Chest Drainage; CDF: Chest Drainage with Fibrinolysis^;VATS/OD: Video-assisted thoracoscopic surgery/ Open Decortication;Four patients required more than one additional procedure ^a;Five patients suffered more than one complication^b; SSI: Surgical site Infection; median[interquartile range] *

No competing interests reported.

Contemporary use of fibrinolytics in the management of pediatric empyema

Status:

Journal Publication

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Abstract

Figures

1. Introduction

2. Methods

3. Results

4. Discussion

5. Conclusion

Abbreviations

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Journal Publication

Version 1