Using non-steroidal anti-inflammatory drugs (NSAIDs) following pleurodesis
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《血管的通路杂志》
a Department of Thoracic Surgery, Guy's Hospital, St Thomas Street, London, UK
b Department of Cardiothoracic Surgery, Brompton, Sydney Street, London, UK
c Library Services Manager, Royal Surrey County Hospital, Guildford, Surrey, UK
Abstract
A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was whether non-steroidal anti-inflammatory drugs (NSAIDs) decrease the effect of pleurodesis. Only 17 papers were identified using the search below. Three papers presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of the papers are tabulated. We conclude that despite a limited number and type of study, there is some histopathological evidence to support the concern that NSAIDs may reduce effectiveness of pleurodesis. Until further clinical studies with appropriate outcome measures are available, NSAIDs following pleurodesis should be used with caution and probably avoided routinely.
Key Words: Evidence-based medicine; Thoracic surgery; Pleural disease; Pleurodesis; NSAIDs
1. Introduction
A best evidence topic was constructed according to a structured protocol. This protocol is fully described in the ICVTS [1].
2. Clinical scenario
A 25-year-old man with his second spontaneous right-sided pneumothorax has undergone VATS bullectomy and talc pleurodesis this morning. Patient controlled analgesia (PCA) was set up at completion of surgery and oral paracetamol prescribed. You are asked to see him on the ward later that evening because he is in a lot of pain, and his morphine PCA is making him feel very sick. You think the pain is likely to be muscular and aggravated by his chest drain, and you think he would benefit from a NSAID such as diclofenac, but the thoracic surgical nurse looking after him is unhappy to give it. She was told that it may reduce the chances of a successful pleurodesis.
3. Three part question
In [patients undergoing pleurodesis] is the use of [NSAIDs] detrimental in terms of [successful pleurodesis].
4. Search strategy
Medline 1950–Apr 2006 and Embase 1974–Apr 2006 using the Dialog Datastar interface.
[Pleurodesis.W.DE.OR Pleurodesis] AND [Voltarol OR Diclofenac OR Diclofenac.W.DE. OR Anti-Inflammatory-Agents-Non-Steroidal.DE. OR NSAIDs or non-steroids$ ADJ antinflammatory OR nonsteroid$ ADJ antiinflammtory OR Nonsteroid-Antinflammatory-Agent.DE. OR Ibuprofen.W.DE. OR Ibuprofen-Arginine.DE. OR Ibuprofen-Lysine.DE. OR Ibuprofen-Plus-Oxycodone.DE. OR ibuprofen]. Limit to English. This search was repeated in Cochrane Central Register of Controlled Trials.
5. Search outcome
A total of 17 papers were identified. No human studies were found and all the animal studies were small prospective histopathological assessments of pleurodesis using different agents or mechanical abrasion. Three were deemed to be relevant.
6. Comments
The use of non-steroidal anti-inflammatory agents (NSAIDs) such as diclofenac following interventional procedures, is widespread as they provide effective analgesia with few central nervous system effects. It works by blocking cyclo-oxygenase and the production of prostaglandins, which are produced in response to injury or certain diseases and would otherwise go on to cause pain, swelling and inflammation. Lardinosis et al. [2] note that in animal models the breaking strength and collegen concentration at wound sites was less after the use of NSAIDs. Whether mechanical abrasion or a chemical sclerosing agents such as talc is used, pleurodesis relies on the generation of inflammation and consequent adhesion between the two layers of pleura to prevent the build of fluid in the pleural cavity. The studies reviewed address whether the use of NSAIDs inhibits pleurodesis. All studies were in animals. In two studies rabbits were used and in one study pigs. Kaya et al. [3] used intrapleural tetracycline and compared macroscopic and microscopic evidence of pleurodesis after 3 weeks in animals on diclofenac or acetaminophen (paracematol). Following IM adminstration of diclofenac for 10 days tetracycline pleurodesis was reduced both macroscopically and microscopically, though not significantly. Teixeira et al. [4], using the same animal model, albeit a larger number of animals, concluded that systemic administration of both steroidal and non-steroidal anti-inflammatory agents reduces the degree of pleurodesis with talc but not silver nitrate.
The final animal study involved thorascopic abrasion pleurodesis of pigs and evaluated gross and microscopic evidence of pleurodesis after 21 days in pigs given oral diclofenac or controls (Lardinosis et al. [2]). Macroscopically pleurodesis appeared to be reduced in animals taking NSAIDs but microscopically no statistically significant difference between the two groups was found. However, a trend toward a higher amount of organised collagen fibres suggestive of dense adhesions was observed in the control group. The authors concluded that peri-operative use of NSAIDs affects quality of pleural adhesions obtained after mechanical abrasion in pig models.
In the available animal studies the histopathological influence of NSAIDs on pleurodesis was assessed. The authors suggest that there is a reduction in the quality of pleurodesis achieved at a macroscopic and/or microscopic level. There are no studies which assess clinical outcomes such as recurrence of pneumothorax or pleural effusion. Clinical studies would be very hard to perform because the only realistic means of assessing outcome is to await recurrence; a substantial proportion do not recur in the natural history of the condition and the stapling of the apex may on its own be sufficient to prevent some of the recurrences (Table 1).
7. Clinical bottom line
Best evidence suggests that there is some histopathological evidence derived from animal experiments that the use of NSAIDs may decrease the effect of pleurodesis. Until clinical evidence becomes available, the routine use of NSAIDs following pleurodesis should probably be avoided.
References
Dunning J, Prendergast B, Mackway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: best BETS. Interact J CardioVasc Thorac Surg 2003; 1:405–409.
Lardinois D, Vogt P, Yang L, Hegyi I, Baslam M, Weder W. Non-steroidal anti-inflammatory drugs decrease the quality of pleurodesis after mechanical pleural abrasion. Eur J CardioThorac Surg 2004; 25:865–871.
Ors KS, Bir F, Atalay H, Onem G, Aytekin FO, Sacar M. Effect of diclofenac on experimental pleurodesis induced by tetracycline in rabbits. J Invest Med 2005; 53:267–270.
Teixeira LR, Vargas FS, Acencio MM, Paz PF, Antonangelo L, Vaz MA, Marchi E. Influence of antiinflammatory drugs (methylprednisolone and diclofenac sodium) on experimental pleurodesis induced by silver nitrate or talc. Chest 2005; 128:4041–4045.(Ian Hunta,, Elaine Tehb, Rachel Southonc)
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c Library Services Manager, Royal Surrey County Hospital, Guildford, Surrey, UK
Abstract
A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was whether non-steroidal anti-inflammatory drugs (NSAIDs) decrease the effect of pleurodesis. Only 17 papers were identified using the search below. Three papers presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of the papers are tabulated. We conclude that despite a limited number and type of study, there is some histopathological evidence to support the concern that NSAIDs may reduce effectiveness of pleurodesis. Until further clinical studies with appropriate outcome measures are available, NSAIDs following pleurodesis should be used with caution and probably avoided routinely.
Key Words: Evidence-based medicine; Thoracic surgery; Pleural disease; Pleurodesis; NSAIDs
1. Introduction
A best evidence topic was constructed according to a structured protocol. This protocol is fully described in the ICVTS [1].
2. Clinical scenario
A 25-year-old man with his second spontaneous right-sided pneumothorax has undergone VATS bullectomy and talc pleurodesis this morning. Patient controlled analgesia (PCA) was set up at completion of surgery and oral paracetamol prescribed. You are asked to see him on the ward later that evening because he is in a lot of pain, and his morphine PCA is making him feel very sick. You think the pain is likely to be muscular and aggravated by his chest drain, and you think he would benefit from a NSAID such as diclofenac, but the thoracic surgical nurse looking after him is unhappy to give it. She was told that it may reduce the chances of a successful pleurodesis.
3. Three part question
In [patients undergoing pleurodesis] is the use of [NSAIDs] detrimental in terms of [successful pleurodesis].
4. Search strategy
Medline 1950–Apr 2006 and Embase 1974–Apr 2006 using the Dialog Datastar interface.
[Pleurodesis.W.DE.OR Pleurodesis] AND [Voltarol OR Diclofenac OR Diclofenac.W.DE. OR Anti-Inflammatory-Agents-Non-Steroidal.DE. OR NSAIDs or non-steroids$ ADJ antinflammatory OR nonsteroid$ ADJ antiinflammtory OR Nonsteroid-Antinflammatory-Agent.DE. OR Ibuprofen.W.DE. OR Ibuprofen-Arginine.DE. OR Ibuprofen-Lysine.DE. OR Ibuprofen-Plus-Oxycodone.DE. OR ibuprofen]. Limit to English. This search was repeated in Cochrane Central Register of Controlled Trials.
5. Search outcome
A total of 17 papers were identified. No human studies were found and all the animal studies were small prospective histopathological assessments of pleurodesis using different agents or mechanical abrasion. Three were deemed to be relevant.
6. Comments
The use of non-steroidal anti-inflammatory agents (NSAIDs) such as diclofenac following interventional procedures, is widespread as they provide effective analgesia with few central nervous system effects. It works by blocking cyclo-oxygenase and the production of prostaglandins, which are produced in response to injury or certain diseases and would otherwise go on to cause pain, swelling and inflammation. Lardinosis et al. [2] note that in animal models the breaking strength and collegen concentration at wound sites was less after the use of NSAIDs. Whether mechanical abrasion or a chemical sclerosing agents such as talc is used, pleurodesis relies on the generation of inflammation and consequent adhesion between the two layers of pleura to prevent the build of fluid in the pleural cavity. The studies reviewed address whether the use of NSAIDs inhibits pleurodesis. All studies were in animals. In two studies rabbits were used and in one study pigs. Kaya et al. [3] used intrapleural tetracycline and compared macroscopic and microscopic evidence of pleurodesis after 3 weeks in animals on diclofenac or acetaminophen (paracematol). Following IM adminstration of diclofenac for 10 days tetracycline pleurodesis was reduced both macroscopically and microscopically, though not significantly. Teixeira et al. [4], using the same animal model, albeit a larger number of animals, concluded that systemic administration of both steroidal and non-steroidal anti-inflammatory agents reduces the degree of pleurodesis with talc but not silver nitrate.
The final animal study involved thorascopic abrasion pleurodesis of pigs and evaluated gross and microscopic evidence of pleurodesis after 21 days in pigs given oral diclofenac or controls (Lardinosis et al. [2]). Macroscopically pleurodesis appeared to be reduced in animals taking NSAIDs but microscopically no statistically significant difference between the two groups was found. However, a trend toward a higher amount of organised collagen fibres suggestive of dense adhesions was observed in the control group. The authors concluded that peri-operative use of NSAIDs affects quality of pleural adhesions obtained after mechanical abrasion in pig models.
In the available animal studies the histopathological influence of NSAIDs on pleurodesis was assessed. The authors suggest that there is a reduction in the quality of pleurodesis achieved at a macroscopic and/or microscopic level. There are no studies which assess clinical outcomes such as recurrence of pneumothorax or pleural effusion. Clinical studies would be very hard to perform because the only realistic means of assessing outcome is to await recurrence; a substantial proportion do not recur in the natural history of the condition and the stapling of the apex may on its own be sufficient to prevent some of the recurrences (Table 1).
7. Clinical bottom line
Best evidence suggests that there is some histopathological evidence derived from animal experiments that the use of NSAIDs may decrease the effect of pleurodesis. Until clinical evidence becomes available, the routine use of NSAIDs following pleurodesis should probably be avoided.
References
Dunning J, Prendergast B, Mackway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: best BETS. Interact J CardioVasc Thorac Surg 2003; 1:405–409.
Lardinois D, Vogt P, Yang L, Hegyi I, Baslam M, Weder W. Non-steroidal anti-inflammatory drugs decrease the quality of pleurodesis after mechanical pleural abrasion. Eur J CardioThorac Surg 2004; 25:865–871.
Ors KS, Bir F, Atalay H, Onem G, Aytekin FO, Sacar M. Effect of diclofenac on experimental pleurodesis induced by tetracycline in rabbits. J Invest Med 2005; 53:267–270.
Teixeira LR, Vargas FS, Acencio MM, Paz PF, Antonangelo L, Vaz MA, Marchi E. Influence of antiinflammatory drugs (methylprednisolone and diclofenac sodium) on experimental pleurodesis induced by silver nitrate or talc. Chest 2005; 128:4041–4045.(Ian Hunta,, Elaine Tehb, Rachel Southonc)