Key messages
We did not find enough evidence to say if sympathetic nerve blocks provide more pain relief than 'usual care'. The risk of harm with sympathetic nerve blocks is unclear.
We did not find enough evidence to say if sympathetic nerve blocks improve or reduce quality of life.
Future research should focus on the different types of sympathetic nerve blocks not well represented in the current studies.
What is persistent pain due to inoperable abdominopelvic cancer?
'Abdominopelvic cancer' is a name given to any type of cancer that affects the belly or pelvis, in people with a wide range of different cancers. The cancer may have started there or spread to that area from somewhere else. Sometimes cancer can cause pain that is felt in the belly area or lower down in the pelvis. This pain can be hard to treat at times, particularly if the cancer cannot be removed or cured (inoperable).
How is pain treated?
Treatments for the cancer pain in the belly and/or pelvis include:
- ‘usual care’, which includes strong painkillers, commonly morphine and/or other pain-relieving medications and treatments;
- anti-cancer treatments (e.g. chemotherapy or radiotherapy);
- treatments to stop pain signals from reaching the brain, where you ‘feel’ the pain. This includes sympathetic nerve blocks and other types of nerve-blocking treatments.
What is a sympathetic nerve block?
This is a name given to a number of different types of treatments that all aim to permanently stop nerves carrying pain signals to the brain. This is to reduce pain being felt by the person having the treatment.
What did we want to find out?
We wanted to find out if having the sympathetic nerve block in addition to ‘usual care’ or placebo would:
- help more people achieve no worse than mild pain;
- improve quality of life;
- be as safe as usual care, or if there is a difference in risk of serious harm;
- reduce the intensity of pain felt and by how much for most people;
- reduce the amount of strong painkiller needed to control pain;
- lead to increased satisfaction in those having the treatment;
- provide lasting pain relief and for how long.
We also wanted to see if two different sympathetic nerve blocks compared to one would affect the above findings.
What did we do?
We searched for studies comparing sympathetic nerve blocks to placebo or ‘usual care’ in people with incurable cancer who have cancer-related pain in the belly and/or pelvis. We also searched for studies comparing two sympathetic nerve blocks to single sympathetic nerve blocks.
We compared and summarised the results of studies and assessed them in a stepwise manner. We rated the quality of the evidence based on the methods used.
What did we find?
We found 17 studies involving 1025 adults with pain in the belly and/or pelvis due to cancer that could not be removed. The biggest study had 139 people and the smallest had 21 people. The studies were conducted in many countries around the world, including the USA, Canada, UK, Italy, China, Japan, Brazil and China. Most studies lasted three months, though the longest was one year and the shortest one month. None were funded by commercial companies or included placebo as a comparison.
When sympathetic nerve blocks are given with usual care:
- it is unclear if more or fewer people have 'no worse than mild pain';
- they may make little to no difference to quality of life;
- it is unclear if the treatment causes more or less serious harm;
- they may make little to no difference to the intensity of pain for most people;
- they may or may not reduce the amount of strong painkillers (like morphine) needed to control pain;
- we do not know the effect on satisfaction or how long any pain-relieving effects last.
When two different sympathetic nerve blocks are given instead of one:
- we do not know if more or fewer people have 'no worse than mild pain';
- we do not know the effect on quality of life;
- it is unclear if the treatment causes more or less serious harm;
- they may make little to no difference to the intensity of pain for most people;
- they may make little to no difference to the amount of strong painkillers needed to control pain;
- we do not know the effect on satisfaction or how long any pain-relieving effects last.
We are very uncertain about these results.
What are the limitations of the evidence?
Most studies were very small and covered only one type of cancer and treatment. Our question was broader than this. There were problems with studies providing all the data we needed, and it is possible many people were aware of which treatment they were getting. We cannot be confident in the evidence we found.
How up-to-date is this evidence?
The evidence is up-to-date to October 2023.
There is limited evidence to support or refute the use of sympathetic nerve blocks for persistent abdominopelvic pain due to inoperable malignancy. We are very uncertain about the effect of combination sympathetic nerve blocks compared with single sympathetic nerve blocks. The certainty of the evidence is very low and these findings should be interpreted with caution.
Persistent visceral pain is an unpleasant sensation coming from one or more organs within the body. Visceral pain is a common symptom in those with advanced cancer. Interventional procedures, such as neurolytic sympathetic nerve blocks, have been suggested as additional treatments that may play a part in optimising pain management for individuals with this condition.
To evaluate the benefits and harms of neurolytic sympathetic nerve blocks for persistent visceral pain in adults with inoperable abdominopelvic cancer compared to standard care or placebo and comparing single blocks to combination blocks.
We searched the following databases without language restrictions on 19 October 2022 and ran a top-up search on 31 October 2023: CENTRAL; MEDLINE via Ovid; Embase via Ovid; LILACS. We searched trial registers without language restrictions on 2 November 2022: ClinicalTrials.gov; WHO International Clinical Trials Registry Platform (ICTRP). We searched grey literature, checked reference lists of reviews and retrieved articles for additional studies, and performed citation searches on key articles. We also contacted experts in the field for unpublished and ongoing trials. Our trial protocol was preregistered in the Cochrane Database of Systematic Reviews on 21 October 2022.
We searched for randomised controlled trials (RCTs) comparing any sympathetic nerve block targeting sites commonly used to treat abdominal pelvic pain from inoperable malignancies in adults to standard care or placebo.
We independently selected trials based on predefined inclusion criteria, resolving any differences via adjudication with a third review author. We used a random-effects model as some heterogeneity was expected between the studies due to differences in the interventions being assessed and malignancy types included in the study population. We chose three primary outcomes and four secondary outcomes of interest. We sought consumer input to refine our review outcomes and assessed extracted data using Cochrane's risk of bias 2 tool (RoB 2). We assessed the certainty of evidence using the GRADE system.
We included 17 studies with 1025 participants in this review. Fifteen studies with a total of 951 participants contributed to the quantitative analysis.
Single block versus standard care
Primary outcomes
No included studies reported our primary outcome, 'Proportion of participants reporting no worse than mild pain after treatment at 14 days'. The evidence is very uncertain about the effect of sympathetic nerve blocks on reducing pain to no worse than mild pain at 14 days when compared to standard care due to insufficient data (very low-certainty evidence). Sympathetic nerve blocks may provide small to 'little to no' improvement in quality of life (QOL) scores at 14 days after treatment when compared to standard care, but the evidence is very uncertain (standardised mean difference (SMD) -0.73, 95% confidence interval (CI) -1.70 to 0.25; I² = 87%; 4 studies, 150 participants; very low-certainty evidence). The evidence is very uncertain about the risk of serious adverse events as defined in our review as only one study contributed data to this outcome. Sympathetic nerve blocks may have an 'increased risk' to 'no additional risk' of harm compared with standard care (very low-certainty evidence).
Secondary outcomes
Sympathetic nerve blocks showed a small to 'little to no' effect on participant-reported pain scores at 14 days using a 0 to 10 visual analogue scale (VAS) for pain compared with standard care, but the evidence is very uncertain (mean difference (MD) -0.44, 95% CI -0.98 to 0.11; I² = 56%; 5 studies, 214 participants; very low-certainty evidence). There may be a 'moderate to large' to 'little to no' reduction in daily consumption of opioids postprocedure at 14 days with sympathetic nerve blocks compared with standard care, but the evidence is very uncertain (change in daily consumption of opioids at 14 days as oral milligrams morphine equivalent (MME): MD -41.63 mg, 95% CI -78.54 mg to -4.72 mg; I² = 90%; 4 studies, 130 participants; very low-certainty evidence).
The evidence is very uncertain about the effect of sympathetic nerve blocks on participant satisfaction with procedure at 0 to 7 days and time to need for retreatment or treatment effect failure (or both) due to insufficient data.
Combination block versus single block
Primary outcomes
There is no evidence about the effect of combination sympathetic nerve blocks compared with single sympathetic nerve blocks on the proportion of participants reporting no worse than mild pain after treatment at 14 days because no studies reported this outcome. There may be a small to 'little to no' effect on QOL score at 14 days after treatment, but the evidence is very uncertain (very low-certainty evidence). The evidence is very uncertain about the risk of serious adverse events with combination sympathetic nerve blocks compared with single sympathetic nerve blocks due to limited reporting in the included studies (very low-certainty evidence).
Secondary outcomes
The evidence is very uncertain about the effect of combination sympathetic nerve blocks compared with single sympathetic nerve blocks on participant-reported pain score and change in daily consumption of opioids postprocedure, at 14 days. There may be a small to 'little to no' effect, but the evidence is very uncertain (very low-certainty evidence). There is no evidence about the effect on participant satisfaction with procedure at 0 to 7 days and time to need for retreatment or treatment effect failure (or both) due to these outcomes not being measured by the studies.
Risk of bias
The risk of bias was predominately high for most outcomes in most studies due to significant concerns regarding adequate blinding. Very few studies were deemed as low risk across all domains for any outcome.