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Targeting the affective component of pain with ketamine

A tool to improve the postoperative experience?

Robu, Bianca; Lavand’homme, Patricia

European Journal of Anaesthesiology (EJA): January 2019 - Volume 36 - Issue 1 - p 4–5
doi: 10.1097/EJA.0000000000000915
Invited commentary

From the Department of Anesthesiology and Postoperative Pain Service, Cliniques Universitaires St Luc, University Catholic of Louvain, Brussels, Belgium (BR, PL)

Correspondence to Patricia Lavand’homme, MD, PhD, Department of Anesthesiology, Cliniques Universitaires St Luc, University Catholic of Louvain, Av Hippocrate 10-1821, 1200 Brussels, Belgium Tel: +32 2 764 18 21; fax: +32 2 764 36 99; e-mail:

This Invited Commentary accompanies the following original article:

Wang J, Echevarria GC, Doan L, et al. Effects of a single, subanaesthetic dose of ketamine on pain and mood after laparoscopic bariatric surgery. A randomised, double-blind, placebo controlled study. Eur J Anaesthesiol 2019; 36: 16–24.

The body's system for processing the sensation of pain is very complex and many intercurrent factors are involved in the modulation of the pain message and its individual expression. The complexity of the pain experience may explain why postoperative pain still remains poorly controlled in 15 to 30% of our patients. 1

The study from Wang et al. 2 possesses some limitations but deserves comment for several reasons that the authors have considered. First, the study involves obese patients scheduled for bariatric surgery. Today there is a clear lack of recommendations concerning peri-operative pain management in these patients who carry a high risk for mood disorders like major anxiety and depression. The prevalence of depression has increased more than 18% between 2005 and 2015. 3 Today it seems that 20 to 38% of patients scheduled for surgery present with a degree of depression a condition associated with increased postoperative pain and worse surgical outcome. 1,4

Second, the study 2 is exemplative of peri-operative medicine. Measuring the effect of our therapeutic intervention on the patient's global experience after anaesthesia and surgery is really important if we are to make progress in peri-operative management. It is time to move beyond pain ratings and to consider the global postoperative experience which includes not only pain but also physical function, comfort and emotional well being. 5 Here things become difficult: how do we identify the best, the more suitable tools with which to assess the different facets of peri-operative experience? We currently dispose of many questionnaires that measure the physical, sensory and emotional aspects of life, comfort and satisfaction. However, there are no clear guidelines to help clinicians chose the best questionnaire to evaluate a specific aspect of postoperative recovery. For example, how do we assess the affective component of pain, which is of major importance in anxious and depressed patients? Tools like QoR (quality of recovery) scores provide a quantitative measure of overall postoperative health status including mental well being (emotional state). 5 The SF-MPQ (short form-McGill Pain Questionnaire) is better known in the chronic pain field and provides a comprehensive evaluation of pain, distinguishing between its affective and sensory components. Although the SF-MPQ has not been validated in the postoperative pain setting, its use in the current study allowed the mood enhancing effect of ketamine to be highlighted while the results from QoR-15 did not. 2 Looking to Wang et al. 2 such tools deserve to be used more frequently because they narrow the gap between the clinician's and the patient's view of postoperative reality and they might help to tailor treatments to better meet the patient's needs.

Finally, the study questions the benefits of a single postoperative dose of ketamine on different patient-centred outcome measures. Postoperative use of subanaesthetic doses of ketamine (<1 mg kg−1) has been a long debate in the last decade. Recent US consensus guidelines have reviewed the benefits of intravenous ketamine for acute pain management; that is how effective it is when added to a multimodal analgesic regimen. 6 Evidence supports the use of ketamine for acute pain in a variety of contexts 6 and particularly for the relief of postoperative pain. 7 Ketamine is a use-dependent drug: the worst the pain, the more efficient ketamine administration. 8 In the current study, 2 a single dose of 0.4 mg kg−1 of ketamine did not reduce postoperative pain scores although initial pain reported by patients was around 5 to 6 on a scale from 0 to 10. Either the dose of ketamine was not adequate or visceral pain after laparoscopic surgery was not the best indication for ketamine treatment. Does it mean that patients will not get any benefit of ketamine administration? The question is of interest because ketamine has unwanted dysphoric effects. 8 As aforementioned, pain is a highly complex experience. Recently, the fact that ketamine may link pain modulation and mood to facilitate recovery has got attention. 3,9 With its dissociative effects, ketamine may have the power to selectively improve the affective component of pain. Indeed, the drug possess rapid antidepressant effects, that contrasts with the slow onset of classical antidepressant drugs. The antidepressant response, which seems to be dose-related (between 0.1 and 0.75 mg kg−1) occurs within the first hours after administration and may last up to 1 week. 3,9 Significantly, other N-methyl-D-aspartate (NMDA) receptor antagonists (e.g. MK801, memantine) do not produce the same antidepressant effect as ketamine and the use of racemic ketamine is required because (R)-ketamine is mediating the effect. This has caused us to question the mechanisms underlying such a rapid-onset antidepressant effect. 9 Different hypothesis include the role of a metabolite of (R)-ketamine, the modulation of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the increase of brain-derived neurotrophic factor levels in some brain areas. 4,9 Some studies already have reported that intra-operative ketamine (doses >0.4 mg kg−1) improved depressed mood and relieved postoperative pain in depressed patients after orthopaedic surgery. 4,10 In the current study 2 the patients did not suffer severe depression symptoms which might explain the low impact of ketamine observed on both pain and mood. Nevertheless, ketamine effect on the affective component of pain was present and that certainly deserves further studies, specifically targeting other outcome measures (e.g. functional recovery, chronic postsurgical pain).

In conclusion, although for a long time we have considered only the effect of ketamine on recovery, Wang et al.'s 2 article nicely highlights that, the drug may offer unsuspected benefits for some of our patients and thereby perhaps might affect their postoperative recovery. It is now time to target those patients and to move to more patient's centred outcome measures of peri-operative experience and recovery.

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Acknowledgements relating to this article

Assistance with the commentary: none.

Financial support and sponsorship: none.

Conflicts of interest: none.

Comment from the Editor: this Invited Commentary was checked by the editors but was not sent for external peer review. PldH is an Associate Editor of the European Journal of Anaesthesiology.

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