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Could opioid sparing, rather than a direct non-steroidal anti-inflammatory drug effect, be responsible for improved survival after conservative breast surgery?

Declaration of interest None declared. N. S. Bailard* R. A. Flores Houston, TX, USA * E-mail: [email protected] 1 Forget P, Bentin C, Machiels JP, Berliere M, Coulie PG, De Kock M. Intraoperative use of ketorolac or diclofenac is associated with improved disease-free survival and overall survival in conservative breast cancer surgery. Br J Anaesth 2014; 113(Suppl): i82 –7 2 De Oliveira GS Jr, Agarwal D, Benzon HT. Perioperative single dose ketorolac to prevent postoperative pain: a meta-analysis of randomized trials. Anesth Analg 2012; 114: 424– 33 3 Beilin B, Shavit Y, Hart J, et al. Effects of anesthesia based on large versus small doses of fentanyl on natural killer cell cytotoxicity in the perioperative period. Anesth Analg 1996; 82: 492–7 4 Afsharimani B, Cabot P, Parat MO. Morphine and tumor growth and metastasis. Cancer Metastasis Rev 2011; 30: 225–38 5 Forget P, Vandenhende J, Berliere M, et al. Do intraoperative analgesics influence breast cancer recurrence after mastectomy? A retrospective analysis. Anesth Analg 2010; 110: 1630–5

doi:10.1093/bja/aev014

Direct non-steroidal anti-inflammatory drug effect, rather than an opioid-sparing effect, is the most important factor for possibly improved survival after conservative breast surgery Editor—We thank Drs Bailard and Flores for their interesting letter. As they stated, we did not describe intraoperative and postoperative opioid consumption in the study groups, nor did we address the possibility that the apparent survival benefits of receiving non-steroidal anti-inflammatory drugs (NSAIDs) may have resulted in part from their opioid-sparing effect. There are reasons for that. Concerning intraoperative opioids, when we addressed the influence of opioids previously, we did not detect any effect.1 This absence of effect remains after adjustment for the use of ketorolac. Conversely, the ketorolac effect was still present after adjustment for sufentanil use. This may be a consequence of the relatively low doses used during mastectomy in our hospital (median, 15 mg of sufentanil; interquartile range, 0– 18 mg). In conservative surgery, opioid doses are typically even lower, because the surgery is of shorter duration. Thus, we chose to not plan for likely inconclusive analyses on intraoperative opioid use. Nevertheless, we agree that, with these data, we cannot exclude an effect of opioids on outcome, if used at higher doses, as we found during prostatectomy [mean, 23 (SD 14) mg of sufentanil].2 Concerning postoperative opioid consumption, in our experience, 5% of the patients receive it on the wards after breast cancer surgery. In this context, therefore, it seems very improbable that the ketorolac effect, the diclofenac effect, or both would have been a consequence of an opioid-sparing effect. Inevitably, such a low incidence would render any statistical analysis challenging. Additionally, and in contrast with intraoperative opioid administration, postoperative opioid consumption is probably more dependent on the patient’s characteristics than on the anaesthetist’s preferences, complicating the interpretation. We can reassure our colleagues that pain and opioid consumption data are being collected in our ongoing confirmatory randomized controlled trial (http://clinicaltrials.gov/show/ NCT01806259).3

Declaration of interest None declared. P. Forget* M. De Kock Brussels, Belgium * E-mail: [email protected] 1 Forget P, Bentin C, Machiels JP, Berliere M, Coulie PG, De Kock M. Intraoperative use of ketorolac or diclofenac is associated with improved disease-free survival and overall survival in conservative breast cancer surgery. Br J Anaesth 2014; 113(Suppl): i82–7

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Editor—We read with great interest the recent retrospective report by Forget and colleagues1 describing improved disease-free survival in patients who received non-steroidal anti-inflammatory drugs (NSAIDs; ketorolac or diclofenac) during conservative breast-cancer surgery compared with those who did not. Unfortunately, the authors did not describe intraoperative and postoperative opioid consumption in the study groups, nor did they address the possibility that the apparent survival benefits of receiving NSAIDs may have resulted in part from their opioid-sparing effect. Non-steroidal anti-inflammatory drugs, even in a single dose, have been shown to reduce perioperative opioid consumption.2 Furthermore, opioids may be immunosuppressive,3 4 angiogenic,4 and pro-inflammatory.4 All of these effects may encourage locoregional recurrence or distant metastasis. Forget and colleagues5 have addressed the influence of opioids previously, which makes this present omission all the more surprising. The data from this and other retrospective studies are exciting and highlight the contributions we can make in the perioperative period that affect long-term outcomes. We are hopeful that data on opioid consumption will be provided in the confirmatory randomized controlled trials, such as the one currently being conducted by Forget’s group (http://clinicaltrials.gov/show/ NCT01806259).

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2 Forget P, Tombal B, Scholte`s JL, et al. Do intraoperative analgesics influence oncological outcome after radical prostatectomy for prostate cancer? Eur J Anaesthesiol 2011; 28: 830– 5 3 Forget P, Berlie`re M, van Maanen A, et al. Ketorolac in Breast Cancer trial (KBCtrial) group. Perioperative ketorolac in high risk breast cancer patients. Rationale, feasibility and methodology of a prospective randomized placebo-controlled trial. Med Hypotheses 2013; 81: 707–12

doi:10.1093/bja/aev022

An additional mechanism of visual loss

Declaration of interest None declared. C. Chamos Papworth, UK E-mail: [email protected] 1 Mongardon N, Zraier S, Haouache H, et al. Postoperative visual loss due to complicated mediastinal dissection and haemorrhagic shock treatment during cardiac surgery. Br J Anaesth 2014; 112: 832–4

doi:10.1093/bja/aev015

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Another hypothesis for postoperative visual loss after cardiac surgery Editor—We thank Dr Chamos for his valuable comment on our article.1 The hypothesis of an extremely high concentration of

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Declaration of interest None declared. N. Mongardon G. Dhonneur Cre´teil, France E-mail: [email protected] 1 Mongardon N, Zraier S, Haouache H, et al. Postoperative visual loss due to complicated mediastinal dissection and haemorrhagic shock treatment during cardiac surgery. Br J Anaesth 2014; 112: 832–4

doi:10.1093/bja/aev023

Simulation-based training in anaesthesia: have we been training non-technical skills? Editor—We read with interest the recent article by Lorello and colleagues,1 in which they performed a meta-analysis regarding the evidence for the effectiveness of simulation-based anaesthesia training. They concluded that simulation training is at least as good as non-simulator training, and is certainly better than no intervention. They identified 17 studies comparing alternative simulation-based training interventions. They divided these studies into three categories to facilitate the analysis: simulation modality (e.g. box-trainer, mannikin, virtual reality); information sources during debriefing (e.g. video, instructor); and addition of non-technical skills (NTS) training. Specifically, in the third group, they compared ‘routine’ simulation-based training (defined as training in medical management) against interventions with non-technical skills training (e.g. incorporating live interactive actors or including broad ‘human factors’ training). Surprisingly, their search strategy found only four studies; three of them showed a negligible effect for skill outcomes, one study showed a negligible effect for knowledge, and one study showed a large and statistically significant effect for satisfaction. Among these three studies assessing skills, the interventions described were a psychological intensive briefing, a crew resource management (CRM) training, which contains psychological teaching, and an extensive debriefing of NTS. The three studies compared these interventions against a simpler debriefing that focused solely on medical management.

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Editor—I would like to thank Mongardon and colleagues1 for submitting a very interesting case report on a devastating (and, fortunately, rather uncommon) complication after cardiac surgery. In addition to the two mechanisms of visual loss proposed by the authors (hypotension coupled with increased pressure in the venous drainage system of the eye), I think that the administration of norepinephrine through the central venous catheter in the right internal jugular could have led to extremely high concentrations of the vasoconstrictor in the upper body venous system, particularly after the clamping of the superior vena cava in order to facilitate the surgical repair. It is not unreasonable to assume that a venoconstrictive effect could have further aggravated the impaired venous drainage from the orbital cavities and, thus, could have contributed to the reduced perfusion and the visual loss. Regarding the authors’ proposal of securing additional venous access through the inferior vena cava territories, although it should be assessed on an individual basis, it could reduce the possibility of deleterious concentrations of vasoactive drugs in the upper body compartment, apart from providing an additional route of fluid and drug administration in an urgent situation.

norepinephrine in the superior vena cava territory, and thus, the accumulation of this vasoconstrictor agent in the venous drainage from the orbital cavities, is very likely to be a supplementary explanation for the clinical feature of the patient. Conversely, it explains plausible low concentrations of norepinephrine in the rest of the vascular system, and thus, systemic hypoperfusion contributing to the postcardiotomy shock we observed in the intensive care unit. This possibility calls for discussion of a second central venous access in inferior vena cava territory in potentially complex cardiac surgery.

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