Review question
The purpose of this review was to determine which, if any, pain relief drug is effective at reducing the discomfort experienced with outpatient hysteroscopy.
Background
Hysteroscopy is a diagnostic test undertaken to identify the cause of abnormal uterine bleeding. Hysteroscopy involves fluid or gas being injected via the cervix into the uterus, enabling the visualisation of the cervical canal and uterine cavity with a hysteroscope, which can be painful. There is disagreement regarding the best form of pain relief during the procedure.
Study characteristics
We included 32 randomised controlled trials (RCTs), with 3304 participants, of which only 19 reported data suitable for analysis.
All studies took place in a clinical setting. The age of the participants ranged from 33 to 61 years. Studies took place in Australia, Belgium, Brazil, Canada, China, France, Greece, India, Italy, Spain, Taiwan, UK, USA. Baseline pain scores in all groups were relatively low. The evidence is current to September 2016.
Key results
There was no consistent good-quality evidence of a clinically meaningful difference in safety or effectiveness between different types of pain relief compared with each other or with placebo or no treatment in women undergoing outpatient hysteroscopy.
Quality of the evidence
Most studies were at unclear or high risk of bias in most of the domains assessed. The evidence was low or very low quality, mainly due to risk of bias and imprecision.
There was no consistent good-quality evidence of a clinically meaningful difference in safety or effectiveness between different types of pain relief compared with each other or with placebo or no treatment in women undergoing outpatient hysteroscopy.
Hysteroscopy is increasingly performed in an outpatient setting. Pain is the primary reason for abandonment of procedure or incomplete assessment. There is no consensus upon routine use of analgesia during hysteroscopy.
To assess the effectiveness and safety of pharmacological interventions for pain relief in women undergoing outpatient hysteroscopy, compared with placebo, no treatment or other pharmacological therapies.
In September 2016 we searched the Cochrane Gynaecology and Fertility (CGF) Trials Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two trials registers (ClinicalTrials.gov and WHO ICTRP), together with reference checking and contact with study authors and experts.
We included randomised controlled trials (RCTs) comparing use of pharmacological interventions with other pharmacological interventions and pharmacological interventions versus placebo or no treatment.
We used standard methodological procedures expected by Cochrane. Our primary outcome was mean pain score.
We included 32 RCTS (3304 participants), of which only 19 reported data suitable for analysis. Most studies were at unclear or high risk of bias in most of the domains assessed. The evidence was low or very low quality, mainly due to risk of bias and imprecision. Baseline pain scores were relatively low in all groups.
Analgesic versus placebo or no treatment
Local anaesthetics
Local anaesthetics reduced mean pain scores during the procedure [(SMD) -0.29, 95% CI -0.39 to -0.19, 10 RCTs, 1496 women, I2 = 80%, low-quality evidence)] and within 30 minutes (SMD 0.50, 95% CI -0.67 to -0.33, 5 RCTs, 545 women, I2 = 43%, low-quality evidence). This translates to a difference of up to 7 mm on a 0-10 cm visual analogue scale (VAS) during the procedure and up to 13 mm within 30 minutes, which is unlikely to be clinically meaningful. There was no clear evidence of a difference between the groups in mean pain scores after > 30 minutes (SMD -0.11, 95% CI -0.30 to 0.07, 4 RCTs, 450 women, I2 = 0%, low-quality evidence), or in rates of vasovagal reactions (OR 0.70, 95% CI 0.43 to 1.13, 8 RCTs, 1309 women, I2 = 66%, very low-quality evidence). There was insufficient evidence to determine whether there was a difference in rates of non-pelvic pain (OR 1.76, 95% CI 0.53 to 5.80, 1 RCT, 99 women, very low-quality evidence).
Nonsteroidal anti-inflammatory drugs (NSAIDs)
There was insufficient evidence to determine whether there was a difference between the groups in mean pain scores during the procedure (SMD -0.18, 95% CI -0.35 to 0.00, 3 RCTs, 521 women, I2 = 81%, low-quality evidence). Pain scores were lower in the NSAIDs group within 30 minutes (SMD -0.25, 95% CI -0.46 to -0.04, 2 RCTs, 340 women, I2=29%, low-quality evidence) and at over 30 minutes (SMD -0.27, 95% CI -0.49 to -0.05, 2 RCTs, 321 women, I2 = 78%, low-quality evidence). This equates to maximum differences of under 7.5 mm on a 0-10 cm scale, which are unlikely to be clinically significant. One RCT (181 women) reported adverse events: there was insufficient evidence to determine whether there was a difference between the groups in vasovagal reactions (OR 0.76, 95% CI 0.20 to 2.94, very low-quality evidence). For other reported adverse events (non pelvic pain and allergic reactions) evidence was lacking.
Opioids
One RCT utilised sublingual buprenorphine and one utilised oral tramadol. Data on pain scores during the procedure were unsuitable for pooling due to inconsistency. Tramadol was associated with a benefit of up to 22 mm on a 0-10 cm scale (SMD -0.76, 95% CI -1.10 to -0.42, 1 RCT, 140 women). However, the effect estimate for this outcome for sublingual opioids did not support a benefit from the intervention (SMD 0.08, 95% CI -0.22 to 0.39, 164 women). Compared with placebo, the pain score within 30 minutes of the procedure was reduced in the tramadol group, with a difference of up to 17mm on a 0-10cm scale (SMD -0.57, 95% CI -0.91 to -0.23 , 1 RCT, 140 women, low-quality evidence. There was no clear evidence of a difference between the tramadol and placebo groups at over 30 minutes (SMD -0.17, 95% CI -0.51 to 0.16, 1 RCT, 140 women, low-quality evidence). Nausea and vomiting occurred in 39% of the buprenorphine group, and in none of the placebo group (OR 107.55, 95% CI 6.44 to 1796.46)
Analgesic versus any other analgesic
Some comparisons did not report pain scores at all time frames of interest, and none reported data on adverse events.
One RCT (84 women) compared local intracervical anaesthesia versus combined intracervical and paracervical anaesthesia. Pain scores were higher in the group with local intracervical anaesthesia during the procedure (SMD 4.27, 95% CI 3.49 to 5.06, very low-quality evidence), within 30 minutes (SMD 1.55, 95% CI 1.06 to 2.05, very low-quality evidence) and at more than 30 minutes (SMD 3.47, 95% CI 2.78 to 4.15, very low-quality evidence). This translates to a possible benefit in the combined group of up to 12 mm on a 0-10 cm scale during the procedure. Benefits at longer follow-up were smaller.
One RCT compared antispasmodic + NSAID versus local paracervical anaesthesia. Pain scores were lower in the NSAID group than in the local anaesthesia group (during procedure: SMD -1.40, 95% CI -1.90 to -0.91; >30 minutes after procedure: SMD -0.87, 95% CI -1.33 to -0.41; 80 women, very low-quality evidence). This suggests a possible benefit of during the procedure of up to 23 mm on a 0-10 VAS scale and up to 11 mm >30 minutes after the procedure.
Other comparisons included local intracervical anaesthesia versus combined intracervical, paracervical and topical anaesthesia, and opioid versus NSAIDs. Findings were inconclusive.