State of the art in Acute Pain Medicine - “CLINICAL CHALLENGES”
“Acute Pain Management: Second Edition” provides easy access to the current best evidence, and is aimed to assist clinical decision-making. Guidelines do not provide a universal “recipe book”, and each clinician must evaluate the importance and relevance of current evidence in the context of individual patients within a specific clinical practice setting. Recent meta-analyses are used to highlight ongoing issues that require interpretation of the available evidence.
1. Differentiation of clinically versus statistically significant change
The importance of appropriate outcome measures has recently been emphasised in pain management trials1. Whereas in adult trials, 30% pain reduction is considered to be a clinically significant degree of change by the majority of patients, the same information is not available for paediatric trials. Pain scales do not have equal interval properties in young children as they often choose the extremes of the scale, and there is little information on the minimum degree of change in physiological or behavioural measures to produce clinically significant alterations in pain level.
The degree of change in pain score is also context-dependent. Lignocaine and mexiletine have recently been reported to be statistically superior to placebo for relief of neuropathic pain and reduce pain scores by 10.6 (95% CI: 6.68-14.52) on a scale of 0-1002. This degree of change is relatively small, and while not acceptable for acute postoperative pain, it may reflect the difficulty in managing neuropathic pain. However, the clinical significance of this result also depends on the relative efficacy and side-effect profile when compared with other agents used for neuropathic pain, and this information may not be obtained from a single meta-analysis.
Many studies report a reduction in opioid consumption as a significant outcome. However, this may be of limited clinical significance if there is no associated reduction in opioid-related side-effects. Ketamine has been reported to reduce opioid consumption in recent meta-analyses, but effects on side-effects have been conflicting, with two reporting no additional advantage4,5 and one reporting a decrease in postoperative nausea and vomiting (PONV)6. Again, this evidence must be interpreted with the individual patient in mind, as ketamine may offer additional advantages for preventive analgesia or for the opioid tolerant patient.
Side-effects are often inadequately reported, or the sample size of individual randomised controlled trials may be insufficient to detect significant differences in this secondary outcome measure. PONV is an important outcome for individual patients, but the likelihood of seeing significant changes in a meta-analysis will depend on the incidence of this side-effect in different patient populations. Addition of a non-steroidal anti-inflammatory drug (NSAID) was reported to reduce the incidence of nausea and vomiting by 30% when added to PCA morphine7. However, the likelihood of a significant change will be influenced by the baseline rate of PONV. If many of the studies relate to procedures with a high rate of PONV, a reduction of 30% is clinically significant. If the rate of PONV is low, the degree of change will be less, and the number needed to treat (NNT) to achieve a statistically significant effect is higher8. Similar alterations in statistical versus clinically significant change can be seen when high risk groups are added to a meta-analysis
2. Evaluating the balance between risk and benefit
The incidence of complications can rarely be determined from individual studies, and valuable information may only be gained from audit and case reports. Meta-analyses can also come to conflicting results depending on the trials included and the method of analysis. This is clearly evident in the multiple meta-analyses investigating the likelihood of post-tonsillectomy bleeding with the use of NSAIDs. At this stage, the literature is insufficient to definitively evaluate the risk of this complication with different doses of different NSAIDs (eg. ketorolac vs diclofenac) in different populations (eg. paediatric vs adult patients).
It may be difficult to assign causality versus association in clinical trials. Six of seven cases of postoperative renal failure in patients who received COX-2 inhibitors were in patients having coronary artery bypass grafts and therefore other factors may have contributed to the renal impairment.
The severity and clinical impact of any potential complication will also have an impact on individual practice. Major neurological complications may be rare following regional anaesthesia/analgesia, but the potential for permanent debilitating sequelae may have a greater impact on the individual’s evaluation of risk and benefit, and therefore significantly alter clinical practice.
3. Changes in clinical practice
There is an inevitable delay between current clinical practice and the publication of meta-analyses and clinical practice guidelines. Comparisons of outcomes of spinal versus general anaesthesia for hip surgery are influenced by changes in rehabilitation, thromboprophylaxis, and surgical technique since the initial studies were published9. Early paediatric trials of ketorolac used 0.5mg/kg, which is now considered to an excessively high dose. Changes in medical practice such as the use of long acting antiplatelet drugs (eg. clopidogrel), or activated protein C for sepsis, can have an impact on the risk of epidural haematoma and the use of regional analgesia. Therefore, not only the availability of further evidence from controlled clinical trials but also more general changes in knowledge and clinical practice, contribute to the need for individual interpretation and implementation of current best evidence, and for ongoing updates of clinical practice guidelines.
Time of Presentation
Saturday 13 May 2006 - 1030-1200
References
1. McQuay HJ, Barden J, Moore RA: Clinically important changes-what's important and whose change is it anyway? J Pain Symptom Manage 2003; 25: 395-6
2. Tremont-Lukats IW, Challapalli V, McNicol ED, Lau J, Carr DB: Systemic administration of local anesthetics to relieve neuropathic pain: a systematic review and meta-analysis. Anesth Analg 2005; 101: 1738-49
3. Rathmell JP, Ballantyne JC: Local anesthetics for the treatment of neuropathic pain: on the limits of meta-analysis. Anesth Analg 2005; 101: 1736-7
4. Subramaniam K, Subramaniam B, Steinbrook RA: Ketamine as adjuvant analgesic to opioids: a quantitative and qualitative systematic review. Anesth Analg 2004; 99: 482-95, table of contents
5. Elia N, Tramer MR: Ketamine and postoperative pain--a quantitative systematic review of randomised trials. Pain 2005; 113: 61-70
6. Bell RF, Dahl JB, Moore RA, Kalso E: Peri-operative ketamine for acute post-operative pain: a quantitative and qualitative systematic review (Cochrane review). Acta Anaesthesiol Scand 2005; 49: 1405-28
7. Marret E, Kurdi O, Zufferey P, Bonnet F: Effects of nonsteroidal antiinflammatory drugs on patient-controlled analgesia morphine side effects: meta-analysis of randomized controlled trials. Anesthesiology 2005; 102: 1249-60
8. Elia N, Lysakowski C, Tramer MR: Does multimodal analgesia with acetaminophen, nonsteroidal antiinflammatory drugs, or selective cyclooxygenase-2 inhibitors and patient-controlled analgesia morphine offer advantages over morphine alone? Meta-analyses of randomized trials. Anesthesiology 2005; 103: 1296-304
9. Ballantyne JC, Kupelnick B, McPeek B, Lau J: Does the evidence support the use of spinal and epidural anesthesia for surgery? J Clin Anesth 2005; 17: 382-91
