What is the safety and efficacy data for doxycycline (injectable formulation) vs sterile talc for pleurodesis procedures, to prevent recurrent pleural effusions?

Comment by InpharmD Researcher

The limited evidence suggests talc is consistently more effective than injectable doxycycline at preventing recurrent pleural effusions after pleurodesis. This superior efficacy in achieving long-term pleurodesis is supported by a Cochrane meta-analysis and multiple individual studies. However, talc is associated with a higher incidence of procedure-related fever, though the difference in overall mortality or severe pain appears minimal. Therefore, while talc is the more effective agent, the choice may depend on weighing its higher efficacy against its specific side effect profile.

Background

Based on a 2020 Cochrane meta-analysis of 80 randomized trials, talc (administered as either a slurry or poudrage) is an effective agent for achieving pleurodesis in malignant pleural effusion, with moderate-certainty evidence indicating it is superior to several alternatives. Specifically, talc slurry results in fewer pleurodesis failures than doxycycline (odds ratio [OR[ 2.51; 95% credible interval [CrI] 0.81 to 8.40), though the certainty of this evidence is low. The analysis found little evidence of a difference in effectiveness or the risk of procedure-related fever and pain between talc poudrage and talc slurry. The findings also suggest there may be little difference in overall mortality between the interventions compared to talc slurry. Therefore, the authors conclude that talc is an effective pleurodesis method, but the choice of intervention should also consider patient preference, local availability, and adverse event profiles. [1]

References:

[1] Dipper A, Jones HE, Bhatnagar R, Preston NJ, Maskell N, Clive AO. Interventions for the management of malignant pleural effusions: a network meta-analysis. Cochrane Database Syst Rev. 2020;4(4):CD010529. Published 2020 Apr 21. doi:10.1002/14651858.CD010529.pub3
Literature Review

A search of the published medical literature revealed 3 studies investigating the researchable question:

What is the safety and efficacy data for doxycycline (injectable formulation) vs sterile talc for pleurodesis procedures, to prevent recurrent pleural effusions?

Level of evidence

B - One high-quality study or multiple studies with limitations  Read more→


Please see Tables 1-3 for your response.

Comparisons of doxycycline solution with talc slurry for chemical pleurodesis and risk factors for recurrence in South Korean patients with spontaneous pneumothorax
Design

Retrospective study

N= 83
Objective To compare the effectiveness and safety between talc and doxycycline as a sclerosing agent and to investigate risk factors for recurrence in patients with spontaneous pneumothorax
Study Groups

Talc slurry (n= 16)

Doxycycline solution (n= 67)
Inclusion Criteria Patients with a first episode or recurrence of spontaneous pneumothorax confirmed by chest radiography, who underwent pleurodesis with either talc slurry or doxycycline solution between January 2011 and December 2014
Exclusion Criteria Patients who discontinued treatment, had incomplete data, received both agents, or died during admission
Methods Pleurodesis was performed by instillation of a sclerosing agent through a chest tube. Talc slurry was prepared by adding 100 mL of sterile normal saline to 5 g of talc powder. Doxycycline solution was prepared by dissolving 500 mg of oral doxycycline tablets in 100 mL of sterile normal saline. Patients received premedication with oral oxycodone, intravenous pethidine, and lidocaine. The chest tube was clamped for 2 hours, and patients were rotated to ensure contact of sclerosing agents with pleural surfaces
Duration January 2011 to December 2014
Outcome Measures

Primary: Recurrence of spontaneous pneumothorax

Secondary: Post-procedural complications such as fever, chill, thoracic pain, dyspnea, and nausea/vomiting
Baseline Characteristics  

Talc slurry (n= 16)

Doxycycline solution (n= 67)

 p-Values
Sex - Male 14 (87.5) 56 (83.6) 1.000
Sex - Female 2 (12.5) 11 (16.4) 1.000
Age, yr. 67.3±14.0 48.6±21.5 <0.001
Height, cm 168.2±4.4 168.6±7.8 0.858
Weight, kg 59.3±12.5 57.2±11.2 0.524
Height/weight, cm/kg 2.9±0.6 3.0±0.5 0.595
Body mass index, kg/m2 20.9±4.2 20.1±3.3 0.388
Smoking - Yes 3 (18.8) 18 (26.9) 0.750
Smoking - No 13 (81.2) 49 (73.1) 0.750
Type of SP - PSP 3 (18.8) 27 (40.3) 0.107
Type of SP - SSP 13 (81.3) 40 (59.7) 0.107
Results  

Talc slurry (n= 16)

Doxycycline solution (n= 67)

 p-Values
Recurrence - Yes 0 (0) 16 (23.9) 0.033
Recurrence - No 16 (100.0) 51 (76.1) 0.033
Complication - Fever 5 (31.3) 3 (4.5) 0.001
Complication - Chill 1 (6.3) 1 (1.5) 0.265
Complication - Pain 9 (56.3) 39 (58.2) 0.887
Complication - Dyspnea 2 (12.5) 2 (3.0) 0.110
Complication - Nausea/vomiting 2 (12.5) 3 (4.5) 0.226
Adverse Events Fever was significantly higher in the talc group (31.3% vs. 4.5%; P=0.001). Other complications such as chill, pain, dyspnea, and nausea/vomiting were similar between groups
Study Author Conclusions Talc was more effective without recurrence compared with doxycycline. Clinically insignificant fever associated with pleurodesis was more common with talc. Low weight, high height to weight ratio, and recurrent diagnosis of SP were associated with higher recurrence after doxycycline treatment.
Critique The study provided valuable insights into the effectiveness and safety of talc and doxycycline for chemical pleurodesis. However, the retrospective design and small sample size may limit the generalizability of the findings. Additionally, the lack of standardized dosing or application technique for the agents could impact the results. Further research with a higher dose of doxycycline is recommended to better understand its potential as a sclerosing agent.

 

References:

Park EH, Kim JH, Yee J, et al. Comparisons of doxycycline solution with talc slurry for chemical pleurodesis and risk factors for recurrence in South Korean patients with spontaneous pneumothorax. Eur J Hosp Pharm. 2019;26(5):275-279. doi:10.1136/ejhpharm-2017-001465

Talc powder vs doxycycline in the control of malignant pleural effusion: a prospective, randomized trial
Design

Prospective, randomized trial

N= 33
Objective To assess the efficiency of talc powder and doxycycline in pleurodesis in patients with malignant pleural effusion in comparable conditions
Study Groups

Talc group (n=18)

Doxycycline group (n=15)
Inclusion Criteria Patients with malignant pleural effusion, comparable in age, sex, primary malignancy, and stage of metastatic involvement of the pleura
Exclusion Criteria Not specified
Methods

Patients were randomized into two groups: talc powder 10 g insufflated on the whole surface of the pleura with a hand insufflator, or doxycycline 500 mg in 25 mL solution instilled in the pleural cavity. Efficiency of pleurodesis was prospectively assessed.
Duration Not specified
Outcome Measures

Short-term effectiveness of pleurodesis (effectiveness after a single dose of talc or 1-3 doses of doxycycline)

Long-term effectiveness of pleurodesis (no fluid reaccumulation until death or up to 12 month post-procedure)
Baseline Characteristics   Talc group (n=18) Doxycycline group (n=15)
Age, years Comparable Comparable
Sex Comparable Comparable
Primary malignancy Comparable Comparable
Stage of metastatic involvement Comparable Comparable
Results   Talc group (n=18) Doxycycline group (n=15) p-value
Short-term effectiveness Superior Inferior 0.009
Long-term effectiveness Superior Inferior 0.00003
Adverse Events Not specified
Study Author Conclusions Talc powder is superior to doxycycline in achieving pleurodesis in patients with malignant pleural effusion, in both short- and long-term observations.
Critique

Data was primarily presented as a graph and measured as 'superior' or 'inferior' which is a very limited measure of analysis. The quality of this study should be classified as low or very low as a result.

 

References:

Kuzdzał J, Sładek K, Wasowski D, et al. Talc powder vs doxycycline in the control of malignant pleural effusion: a prospective, randomized trial. Med Sci Monit. 2003;9(6):PI54-PI59.

Comparison between thoracoscopic pleurodesis results by talc, doxycycline poudrage, and silver nitrate slurry in patients with malignant pleural effusion
Design

Randomized control double-blind study

N= 45
Objective To compare the effectiveness and safety of thoracoscopic pleurodesis by talc, doxycycline poudrage, and silver nitrate (SN) slurry in patients with malignant pleural effusion
Study Groups

Group I: Doxycycline poudrage (n= 15)

Group II: Talc powder (n= 15)

Group III: Silver nitrate slurry (n= 15)
Inclusion Criteria Improved respiratory symptoms especially dyspnea after pleurocentesis Highly recurrent undiagnosed exudative effusion Cytologically or histologically confirmed malignant effusion
Exclusion Criteria Patient refusal or contraindication to thoracoscopy Trapped lung Patients with a history of previous pleurodesis or radiotherapy to the affected site
Methods

Participants were randomly assigned to receive 1-g doxycycline poudrage, 4–5 g of sterilized medical talc powder, or 50 ml SN 1% through thoracoscopy using a spraying catheter. The procedure involved thoracoscopy with mechanical adhesiolysis and pleurodesis using the assigned agent. Post-procedure monitoring included clinical and radiological assessments at one week, one month, and three months.
Duration Follow-up from 13 September 2018 to 7 February 2019
Outcome Measures

Primary: Improvement of dyspnea, postthoracoscopic hospital stay
Baseline Characteristics Characteristic Group I (n= 15) Group II (n= 15) Group III (n= 15)
Mean age, years 51.80 ±10.93 48.60±9.96 54.47±13.28
Male 66.7% 66.7% 33.3%
Female 33.3% 33.3% 66.7%
Karnofsky scoring >60 100% 100% 100%
Right-sided effusion 66.7% 40% 53.3%
Left-sided effusion 33.3% 60% 46.7%
Results Outcome Group I (n= 15) Group II (n= 15) Group III (n= 15) p-Value
Complete lung expansion 73.3% 93.3% 73.3% >0.05
Partial lung expansion 6.7% 6.7% 13.3% >0.05
Failed pleurodesis 33.3% 0% 33.3% >0.05
Immediate recurrence 20% 0% 13.3% >0.05
Late recurrence 13.3% 6.7% 26.7% >0.05
Adverse Events Minor adverse effects included chest pain and fever, with a statistically significant difference in pain VAS between groups I and II (P1=0.014). Fever was more common in group I compared to group II (P1=0.034)
Study Author Conclusions

Talc, doxycycline poudrage, and SN slurry are approximately equal regarding the improvement of dyspnea and postthoracoscopic hospital stay. However, talc showed a higher success rate in pleurodesis without significant adverse effects.
Critique

The study's strengths include its randomized control design and focus on comparing three different pleurodesing agents. Limitations include a small sample size and the lack of availability of talc in Egypt, which may affect the generalizability of the findings. Additionally, the study did not explore long-term outcomes beyond three months.

 

References:

Yo SA, Mo EB, El AA, Ah EH, Hassan MS. Comparison between thoracoscopic pleurodesis results by talc, doxycycline poudrage, and silver nitrate slurry in patients with malignant pleural effusion. The Egyptian Journal of Chest Diseases and Tuberculosis. 2020;69(1):105. doi:10.4103/ejcdt.ejcdt_63_19