What is the aim of this review?
The aim of this review was to find out whether NSAID pain medication reduces pain around the time of any breast surgery compared to no medication (placebo) or other pain medication (e.g. opioids). Possible side effects from NSAIDS were reviewed and compared to side effects for patients either having no medication or other types of pain relief. NSAID pain medications include ketorolac, flurbiprofen, ibuprofen, and celecoxib.
Why does it matter?
NSAIDs have been shown to decrease inflammation, pain, and fever, while potentially increasing the risks of bleeding complications. There are concerns about the safety of NSAID pain medication during breast surgery, but they still may be better than other drugs (opioids) which have different side effects of concern.
What was studied in the review?
Studies included women who received either a NSAID pain medication or placebo, other pain medication, or no medication. We wanted to assess breast bleeding, pain following surgery, postoperative nausea and vomiting, bleeding from any location, need for blood transfusion, any other side effects reported from NSAID use, opioid use within 24 hours of surgery, length of hospital stay, breast cancer recurrence, and non-prescribed NSAID use.
What did we find?
We found 12 studies with a total of 1596 participants. The evidence is current to September 2020. Seven studies compared NSAIDs (ketorolac, diclofenac, flurbiprofen, parecoxib and celecoxib) to placebo. Four studies compared NSAIDs (ketorolac, flurbiprofen, ibuprofen, and celecoxib) to other pain medications. One study compared NSAIDs (diclofenac) to no medication.
NSAIDs compared to placebo : the use of NSAIDs seems to make little difference to the incidence of breast hematoma (a collection of blood inside the armpit or breast surgical site) and bleeding from any location or increase in blood transfusions within 90 days of breast surgery. There was no increase in postoperative nausea and vomiting. NSAIDs may reduce pain within 24 hours after surgery and reduce the use of opioids within 24 hours after surgery.
NSAIDs compared to other pain medications : the use of NSAIDs may make little difference to the incidence of breast hematoma or bleeding from any location or need for blood transfusion within 90 days of breast surgery. NSAIDs may reduce pain within 24 hours and reduce the chance of nausea and vomiting after surgery. There is little to no difference in the incidence of other side effects. NSAIDS may reduce opioid use within 24 hours of surgery compared to other pain medications.
NSAIDs compared to no medication : the use of NSAIDs appears to make little to no difference in pain within 24 hours after surgery compared to no medication.
Many studies did not collect or report data on the need for blood transfusions, length of hospital stay, breast cancer recurrence, and non-prescribed NSAID pain medication use.
What do the findings mean?
In summary, the studies were small, different to each other and did not report all the possible side effects well. Therefore we could not make firm conclusions about the benefits or harms of NSAIDs. This review provides preliminary evidence, but more studies are needed to make sure there is no harm from the use of NSAIDS after breast surgery. Good-quality large-scale studies are required before any definitive conclusions can be made.
How up-to-date is this review?
The review authors searched for studies that had been published up to 21 September 2020.
Low-certainty evidence suggests that NSAIDs may reduce postoperative pain, nausea and vomiting, and postoperative opioid use. However, there was very little evidence to indicate whether NSAIDs affect the rate of breast hematoma or bleeding from any location within 90 days of breast surgery, the need for blood transfusion and incidence of other side effects compared to placebo or other analgesics. High-quality large-scale RCTs are required before definitive conclusions can be made.
Breast surgery encompasses oncologic, reconstructive, and cosmetic procedures. With the recent focus on the over-prescribing of opioids in the literature, it is important to assess the effectiveness and safety of non-opioid pain medication regimens including nonsteroidal anti-inflammatory drugs (NSAIDs) or NSAID pain medications. Clinicians have differing opinions on the safety of perioperative (relating to, occurring in, or being the period around the time of a surgical operation) NSAIDs for breast surgery given the unclear risk/benefit ratio. NSAIDs have been shown to decrease inflammation, pain, and fever, while potentially increasing the risks of bleeding complications.
To assess the effects of perioperative NSAID use versus non-NSAID analgesics (other pain medications) in women undergoing any form of breast surgery.
The Cochrane Breast Information Specialist searched the Cochrane Breast Cancer Group (CBCG) Specialized Register, CENTRAL (the Cochrane Library), MEDLINE, Embase, The WHO International Clinical Trials Registry Platform (ICTRP) and Clinicaltrials.gov registries to 21 September 2020. Full articles were retrieved for potentially eligible trials.
We considered all randomized controlled trials (RCTs) looking at perioperative NSAID use in women undergoing breast surgery.
Two review authors independently screened studies, extracted data and assessed risk of bias, and certainty of the evidence using the GRADE approach. The main outcomes were incidence of breast hematoma within 90 days (requiring reoperation, interventional drainage, or no treatment) of breast surgery and pain intensity 24 hours following surgery, incidence rate or severity of postoperative nausea, vomiting or both, bleeding from any location within 90 days, need for blood transfusion, other side effects of NSAID use, opioid use within 24 hours of surgery, length of hospital stay, breast cancer recurrence, and non-prescribed NSAID use. Data were presented as risk ratios (RRs) for dichotomous outcomes and standardized mean differences (SMDs) for continuous outcomes.
We included 12 RCTs with a total of 1596 participants. Seven studies compared NSAIDs (ketorolac, diclofenac, flurbiprofen, parecoxib and celecoxib) to placebo. Four studies compared NSAIDs (ketorolac, flurbiprofen, ibuprofen, and celecoxib) to other analgesics (morphine, hydrocodone, hydromorphone, fentanyl). One study compared NSAIDs (diclofenac) to no intervention.
NSAIDs compared to placebo
Most outcomes are judged to have low-certainty evidence unless stated otherwise. There may be little to no difference in the incidence of breast hematomas within 90 days of breast surgery (RR 0.33, 95% confidence interval (CI) 0.05 to 2.02; 2 studies, 230 participants; I2 = 0%). NSAIDs may reduce pain intensity 24 (± 12) hours following surgery compared to placebo (SMD -0.26, 95% CI -0.49 to -0.03; 3 studies, 310 participants; I2 = 73%). There may be little to no difference in the incidence rates or severities of postoperative nausea, vomiting, or both (RR 1.15, 95% CI 0.58 to 2.27; 4 studies, 939 participants; I2 = 81%), bleeding from any location within 90 days (RR 1.05, 95% CI 0.89 to 1.24; 2 studies, 251 participants; I2 = 8%), or need for blood transfusion compared to placebo groups, but we are very uncertain (RR 4.62, 95% CI 0.23 to 91.34; 1 study, 48 participants; very low-certainty evidence). There may be no difference in other side effects (RR 1.12, 95% CI 0.44 to 2.86; 2 studies, 251 participants; I2 = 0%). NSAIDs may reduce opioid use within 24 hours of surgery compared to placebo (SMD -0.45, 95% CI -0.85 to -0.05; 4 studies, 304 participants; I2 = 63%).
NSAIDs compared to other analgesics
There is little to no difference in the incidence of breast hematomas within 90 days of breast surgery, but we are very uncertain (RR 0.33, 95% CI 0.01 to 7.99; 1 study, 100 participants; very low-certainty evidence). NSAIDs may reduce pain intensity 24 (± 12) hours following surgery (SMD -0.68, 95% CI -0.97 to -0.39; 3 studies, 200 participants; I2 = 89%; low-certainty evidence) and probably reduce the incidence rates or severities of postoperative nausea, vomiting, or both compared to other analgesics (RR 0.18, 95% CI 0.06 to 0.57; 3 studies, 128 participants; I2 = 0%; moderate-certainty evidence). There is little to no difference in the development of bleeding from any location within 90 days of breast surgery or in other side effects, but we are very uncertain (bleeding: RR 0.33, 95% CI 0.01 to 7.99; 1 study, 100 participants; other side effects: RR 0.11, 95% CI 0.01 to 1.80; 1 study, 48 participants; very low-certainty evidence). NSAIDs may reduce opioid use within 24 hours of surgery compared to other analgesics (SMD -6.87, 95% CI -10.93 to -2.81; 3 studies, 178 participants; I2 = 96%; low-certainty evidence).
NSAIDs compared to no intervention
There is little to no difference in pain intensity 24 (± 12) hours following surgery compared to no intervention, but we are very uncertain (SMD -0.54, 95% CI -1.09 to 0.00; 1 study, 60 participants; very low-certainty evidence).