Pain tablets taken by mouth for post-caesarean pain

Tablets are convenient and easy to take to ease the pain after caesarean section, which involves cutting through the abdomen and uterus to deliver the baby. We aimed to assess the effectiveness, safety and cost-effectiveness of different types of tablets for the pain. Different types of pain tablets relieve the pain in different ways. Opioids decrease the feeling of pain, decrease reaction to pain as well as increase pain tolerance by their action on the nervous system. Some non-opioid pain tablets act on the tissues to reduce the response to the inflammatory substances released at the site of tissue damage. Combination drugs (such as paracetamol and codeine) may have more pronounced effects because of the different mechanism of action of their components. We do not know how some other tablets, such as alpha-2 agonists (clonidine) and gabapentin (usually used for nerve pain that follows shingles and long-term pain) relieve pain. Good pain control may shorten the time spent in hospital after caesarean section, improve satisfaction and reduce healthcare costs.

Searching the literature we found 63 articles assessing post-caesarean pain but only 13 studies met our inclusion criteria, of which only eight studies (involving 962 women) reported on outcomes that we assessed in this review. Of the eight trials contributing data to our review, only four trials had low risk of bias. All of the included studies involved small numbers of women (40 to 136 women).

We compared non-opioid, opioid and combination oral tablets with placebo or no treatment. There was insufficient evidence to determine the effect of additional pain killers (tablets or injections) among women who took opioid or non-opioid or combination pain killers in comparison to placebo. There was also insufficient evidence to establish the effect of opioid versus non-opioid drugs and opioid versus combination drugs on requirement for additional pain relief. When assessing different non-opioid drugs individually, we found some evidence that gabapentin resulted in less need for additional pain relief in comparison to placebo, but the analysis of data for other tablets (celexocib, ibuprofen, ketoprofen, naproxen, paracetamol) gave more uncertain results. The use of paracetamol plus codeine resulted in less need for additional pain relief in comparison to placebo. We found that high and low dose of gabapentin, and high dose of ketoprofen were more effective than placebo in relation to the need for additional pain relief. On the other hand, low dose of ketoprofen as well as high and low dose of tramadol did not differ with placebo with in effect on the need for additional pain relief. However, it is important to note that these additional analyses (i.e. different drugs and different doses) are based on relatively few studies (one to two trials) and numbers of women (40 to 136).

Women developed more side effects including nausea, vomiting and drowsiness with the use of opioid, non-opioid or combination painkillers in comparison to placebo or no treatment. All trials used additional pain relief as a standard and for breakthrough pain and they all used different drugs.

No studies reported on the following outcomes: adequate pain relief, number of days in hospital post operatively, re-hospitalisation due to incisional pain, fully breast feeding on discharge, mixed feeding at discharge, maternal postpartum depression and cost-effectiveness of the studied interventions.

Due to limited data available no conclusions can be made regarding the safest and the most effective form of oral analgesia for post-caesarean pain. Further studies are necessary. More research is needed to compare different types of pain killers and in relation to different outcomes such as safety, efficacy and cost.

Authors' conclusions: 

Eight trials with 962 women were included in the analysis, but only four trials were of high quality. All the trials were small. We carried out subgroup analysis for different drugs within the same group and for high versus low doses of the same drug. However, the relatively few studies (one to two trials) and numbers of women (40 to 136) limits the reliability of these subgroup analyses.

Due to limited data available no conclusions can be made regarding the safest and the most effective form of oral analgesia for post-caesarean pain. Further studies are necessary.

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Background: 

Oral analgesia is a convenient and widely used form of pain relief following caesarean section. It includes various medications used at different doses alone or in adjunction to other form of analgesia.

Objectives: 

To determine the effectiveness, safety and cost-effectiveness of oral analgesia for post-caesarean pain relief.

Search strategy: 

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2014) and reference lists of retrieved studies.

Selection criteria: 

Randomised controlled trials (RCTs). Cluster-randomised trials were eligible for inclusion but none were identified. Quasi-randomised and cross-over trials were not eligible for inclusion.

Interventions included oral medication given to women for post-caesarean pain relief compared with oral medication, or placebo/no treatment.

Data collection and analysis: 

Two review authors independently assessed for inclusion all the potential studies and independently assessed trial quality, extracted the data using the agreed data extraction form, and checked them for accuracy.

Main results: 

Eight small trials involving 962 women (out of 13 included trials) contributed data to the analysis, of which only four trials had low risk of bias.

None of the included studies reported on 'adequate pain relief', which is one of this review's primary outcomes.

1. Opiod analgesics versus placebo

Based on one trial involving 120 women, the effect of opioids versus placebo was not significant in relation to the need for additional pain relief (primary outcome) (risk ratio (RR) 0.33, 95% confidence interval (CI) 0.06 to 1.92), and the effect in terms of adverse drug effects outcomes was also uncertain (RR 6.58, 95% CI 0.38 to 113.96).

Low (75 mg) and high (150 mg) doses of tramadol had a similar effect on the need for additional pain relief (RR 0.67, 95% CI 0.12 to 3.78 and RR 0.14, 95% CI 0.01 to 2.68, respectively, one study, 80 women).

2. Non-opioid analgesia versus placebo

The confidence interval for the lower requirement for additional analgesia (primary outcome) with the non-opioid analgesia group was wide and includes little or no effect (average RR 0.70, 95% CI 0.48 to 1.01, six studies, 584 women). However, we observed substantial heterogeneity due to the variety of non-opioid drugs used (I2 = 85%). In a subgroup analysis of different drugs, only gabapentin use resulted in less need for additional pain relief (RR 0.34, 95% CI 0.23 to 0.51, one trial, 126 women). There was no difference in need for additional pain relief with the use of celexocib, ibuprofen, ketoprofen, naproxen, paracetamol. Maternal drug effects were more common with the use of non-opioid analgesics (RR 11.12, 95% CI 2.13 to 58.22, two trials, 267 women).

Gabapentin 300 mg (RR 0.25, 95% CI 0.13 to 0.49, one study, 63 women) and 600 mg (RR 0.44, 95% CI 0.27 to 0.71, one study, 63 women) as well as ketoprofen 100 mg (RR 0.55, 95% CI 0.39 to 0.79, one study 72 women) were both more effective than placebo with respect to the need for additional pain relief. However, the 50 mg ketoprofen group and the placebo group did not differ in terms of the number of women requiring additional pain relief (RR 0.82, 95% CI 0.64 to 1.07, one study, 72 women).

3. Combination analgesics versus placebo

Our pooled analysis for the effect of combination analgesics on the need for additional pain relief was RR 0.70 (95% CI 0.35 to 1.40, three trials, 242 women, I2 = 69%). When comparing different drugs within the combination oral analgesics versus placebo comparison we observed subgroup differences (P = 0.05; I² = 65.8%). One trial comparing paracetamol plus codeine versus placebo resulted in fewer women requiring additional pain relief (RR 0.44, 95% CI 0.23 to 0.82, one trial, 65 women). However, there were no differences in the the number of women requiring additional pain relief when comparing paracetamol plus oxycodone versus placebo, or paracetamol plus propoxyphene (RR 1.00, 95% CI 0.78 to 1.28, one trial, 96 women and RR 0.65, 95% CI 0.11 to 3.69, one trial, 81 women, respectively).

Maternal drug effects were more common in combination analgesics group versus placebo (RR 13.18, 95% CI 2.86 to 60.68, three trials, 252 women).

4. Opioid analgesics versus non-opioid analgesics

The confidence interval for the effect on additional pain relief between opioid and non-opioid drugs was very wide (RR 0.51, 95% CI 0.07 to 3.51, one trial, 121 women). Side effects were more common with the use opioids versus non-opioids analgesics (RR 2.32, 95% CI 1.15 to 4.69, two trials 241 women).

5. Opioid analgesics versus combination analgesics

There was no difference in need for additional pain relief in opioid analgesics versus combination analgesics based on one study involving 121 women comparing tramadol and paracetamol plus propoxyphene (RR 0.51, 95% CI 0.07 to 3.51). Maternal adverse effects also did not differ between the two groups (RR 6.74, 95% CI 0.39 to 116.79).

6. Non-opioid versus combination analgesics

The need for additional pain relief was greater in the group of women who received non-opoid analgesics (RR 0.87, 95% CI 0.81 to 0.93, one trial, 192 women) compared with the group of women who received combination analgesics.

Secondary outcomes not reported in the included studies

No data were found on the following secondary outcomes: number of days in hospital post-operatively, re-hospitalisation due to incisional pain, fully breastfeeding on discharge, mixed feeding at discharge, incisional pain at six weeks after caesarean section, maternal post partum depression, effect (negative) on mother and baby interaction and cost of treatment.

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