TIME1 Challenges NSAID, Chest Tube Size Guidelines For Malignant Pleural Effusion Pleurodesis

Researchers argue against the avoidance of nonsteroidal anti-inflammatory drugs in malignant pleural effusion patients undergoing pleurodesis and for the use of large-bore over small-bore chest tubes

  • Date: 24 Dec 2015
  • Author: By Shreeya Nanda, Senior medwireNews Reporter
  • Topic: Palliative Care

medwireNews: Randomised trial findings show similar pleurodesis efficacy with nonsteroidal anti-inflammatory (NSAID) drugs and opiates in patients with malignant pleural effusions undergoing talc pleurodesis, but differences between small- and large-bore chest tubes.

The TIME1 investigators suggest that NSAIDs could be considered for pain relief in this patient population, but that the use of small-bore chest tubes during pleurodesis should be avoided – recommendations that contradict current guidelines.

In the trial, patients with symptomatic malignant pleural effusion who clinically required thoracoscopy, in which large-bore tubes are used, were randomly allocated to receive an NSAID (ibuprofen) or an opiate (oral morphine; control) for pain control. Additionally, patients not undergoing thoracoscopy were randomly assigned to either NSAID or opiate analgesic treatment and to either a 12F or 24F chest tube, where the latter served as the control.

Pain control with NSAIDs was not superior to opioid treatment, with comparable mean pain scores while the chest tube was in situ, as assessed by the visual analogue scale, of 22.1 and 23.8 mm, respectively. Moreover, significantly more NSAID- than opioid-treated patients needed rescue analgesia, at 38.1% of 160 patients versus 26.3% of 160.

But pleurodesis failure at 3 months, defined as the requirement for additional pleural intervention, occurred in 22.9% of 144 analysed participants in the NSAID group and in a comparable 20.0% of 150 in the opioid group, thereby meeting the criteria for noninferiority with regard to pleurodesis efficacy.

The team, therefore, observes that although there appears to be no advantage to NSAID-based analgesia, there is also no reason to avoid it and NSAIDs could be a reasonable treatment alternative for patients at risk of opiate toxicity.

By contrast, although use of a 12F compared with a 24F chest tube led to a significant reduction in mean pain scores (22.0 vs 26.8 mm), the smaller tubes were associated with higher pleurodesis failure (30 vs 24% of 50 patients each) and did not meet the 15% margin of noninferiority for pleurodesis efficacy.

Additionally, the study authors note that the absolute difference in pain scores on average was small between smaller and larger tubes and below the minimum clinically significant threshold for the visual analogue scale.

“It appears that there are no clinically significant advantages of use of smaller tubes for malignant pleural effusion pleurodesis and the potential to reduce pleurodesis success, despite their current widespread use and the recommendations in national guidelines”, they write in JAMA.

However, Najib Rahman, from the University of Oxford in the UK, and co-workers, caution that “the number of patients in the primary comparison of chest tube size for pleurodesis efficacy was limited” and the analysis may be underpowered for this outcome.

Nonetheless, the TIME1 trial “remains the largest study to directly address this question”, they conclude.


Rahman NM, Pepperell J, Rehal S, et al.Effect of Opioids vs NSAIDs and Larger vs Smaller Chest Tube Size on Pain Control and Pleurodesis Efficacy Among Patients With Malignant Pleural Effusion. The TIME1 Randomized Clinical Trial.JAMA 2015; 314: 2641–2653. doi:10.1001/jama.2015.16840

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