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Acute Pain | Chronic Pain | General

Intracerebroventricular opioid therapy compared with epidural and subarachnoid opioids for intractable cancer pain

Clinical bottom line:

Intracerebroventricular (ICV) opioid therapy appears to be at least as effective as epidural or subarachnoid opioid therapy in patients with intractable cancer pain. Adverse effects and catheter/system related problems do not clearly favour one route. These should be carefully weighed when making a decision about method of delivery, but more rigorous data are needed in order to assess whether ICV is an appropriate first-line neuraxial treatment. Central or neuraxial opioid treatments have been used for the small number of cancer patients who do not respond to systemic treatment. Epidural, subarachnoid and ICV catheters can all be used for chronic treatment, although the additional devices such as pumps and reservoirs which have been designed to prolong catheter life also increase cost and require a surgical procedure.

Systematic review

Ballantyne JC, Carr DB, Berkey CS, Chalmers TC, Mosteller, F. Comparative efficacy of epidural, subarachnoid, and intracerebroventricular opioids in patients with pain due to cancer. Regional Anesthesia. 1996; 21: 542-556.

Inclusion criteria were trials of intracerebroventricular (ICV), epidural or subarachnoid administration of opioids for cancer pain; extractable data. Reviewers did not find any controlled trials, and therefore carried out a meta-analysis to analyse the accumulated incidence data on efficacy and side effects/complications for uncontrolled trials. Reviewers note the limitations of this approach, namely that patient groups may not be comparable (e.g. patients receiving ICV treatment may be those who have failed spinal opioid treatment), and that the data will be more biased than that of properly randomised controlled trials. Pain data were extracted and categorised as either excellent, good or unsatisfactory. Adverse effects were categorised as either transient or protracted. When this was unclear, adverse effects were regarded as protracted. Catheter/system complications were categorised as major infection, minor infection, other (pump failure, reservoir malfunction, leakage, blockage and misplacement). Adverse effects and complications data were compared using the difference in the percent rates with standard error of the difference. These were used to indicate likely statistical differences - that is, a difference more than two standard errors was regarded as a probable significant difference between two groups. Findings Thirteen trials of ICV (268 patients), 29 of epidural (909 patients) and 21 of subarachnoid therapy (410 patients) were found. ICV trials were of ICV plus implanted reservoir. Epidural and subarachnoid trials were of catheter alone, catheter with reservoir or catheter with pump. Included trials did not measure pain relief using standardised measures.

Analgesic efficacy

Reviewers compared numbers of patients receiving excellent pain relief across routes, in seven ICV, thirteen epidural and nine subarachnoid trials. There were no differences between numbers of patients reporting excellent pain relief for ICV versus epidural (75% versus 72% and ICV versus subarachnoid (75% versus 58%). Reviewers compared numbers of patients receiving unsatisfactory pain relief across routes, in seven ICV, 23 epidural and 14 subarachnoid trials. There was a significant difference between numbers of patients reporting unsatisfactory pain relief for the ICV versus epidural comparison (4% versus 10% p=0.045), but not the ICV versus subarachnoid comparison (4% versus 6%).

Adverse effects

ICV versus subarachnoid delivery: ICV was associated with less persistent nausea, persistent and transient urinary retention, persistent and transient pruritus compared with subarachnoid delivery. These were regarded as probable statistical differences. There were no differences for transient nausea or respiratory depression. ICV versus epidural delivery: ICV was associated with less persistent nausea, persistent urinary retention, persistent and transient pruritus compared with epidural delivery. Epidural was associated with less transient nausea and less respiratory depression than ICV. These were regarded as probable statistical differences. There were no differences for transient urinary retention. Most commonly reported other effects for ICV were sedation (4% and 9% of patients reporting protracted and transient sedation) and confusion (5% and 16%). These symptoms were rare for other routes. Constipation was reported less frequently with ICV (3%) compared with a statement that it occurred in the majority of patients using other routes. Catheter/system complications: ICV is probably associated with more major infections compared with other pump routes, but probably less complications involving removal compared with epidural with or without reservoir.

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