Stimulated by Zhang et al 2023.[1] TEAS – transcutaneous electrical acupoint stimulation (ie a form of TENS)TENS – transcutaneous electrical nerve stimulationPONV – post-operative nausea and vomitingCI – confidence intervalIV – intravenous key to acronyms This paper came out...
Stimulated by Zhang et al 2023.[1]
Diagram by MC illustrating TEAS applied to PC6 in a patient following breast surgery.
TEAS – transcutaneous electrical acupoint stimulation (ie a form of TENS)
TENS – transcutaneous electrical nerve stimulation
PONV – post-operative nausea and vomiting
CI – confidence interval
IV – intravenous
This paper came out in June 2023, but I did not pay attention to it, or missed it completely, until I spotted a letter to the editor concerning the methods.[2] I am often interested to read the comments of others concerning trials, either from peer review or publication, because an individual reviewer cannot possibly spot all the issues with a paper, particularly if they are not an expert in the field.
I very often act as an expert in terms of the intervention (in acupuncture trials), but I am rarely an expert in the condition being studied or the circumstances. In this case we have 280 women undergoing breast surgery for cancer. This group tends to be at high risk of PONV, so it is a good choice for this sort of comparative (non-inferiority) trial. But surgery, anaesthesia, and breast cancer are all outside of my scope of expertise!
Perhaps the most critical thing to determine in a non-inferiority trial is the maximum difference that would still be considered non-inferior to the comparator. In this case they calculated the figure to be a 15% reduction in PONV in the first 24 hours after surgery. This was derived from the percentage risk reduction associated with dexamethasone over placebo in other research on breast surgery. Dexamethasone was associated with a mean 40% risk reduction (95% CI -50% to -30%). It seems as though they have simply halved the figure for the lower CI. I’m not sure if this is a valid approach. A 15% difference in the incidence of PONV seems on the high side to consider non-inferiority.
Dexamethasone was given pre-operatively in a dose of 8mg IV. TEAS was applied with a pad on each wrist at the PC6 point for periods of 20 minutes and at a frequency of 2/10Hz. Stimulation was set at an intensity considered tolerable to the patient. It was applied from 30 minutes prior to surgery, as soon as the patient arrived in the recovery room, and every 3 hours afterwards.
The incidence of PONV in this trial was 30%, with the mean in the dexamethasone group being a few percentage points lower than the TEAS group. Importantly, the 95% CI did not cross 15% line set for non-inferiority in the primary outcome, so the trial confirmed the hypothesis that TEAS at PC6 was non-inferior to IV dexamethasone.
There was no significant difference in the use of rescue medication for PONV (ondansetron) although the time to extubating was 3 minutes less (mean) in the TEAS group, and that was a high significant difference statistically. There were no other differences of note.
The “Methodology is critical” letter from Wang et al, raises several points that I would not have considered. First, they want to know how many patients had chemotherapy in the lead up to surgery, since this can influence PONV rates. This is not reported, but with 140 in each arm of the trial, we might expect this sort of thing to be balanced by randomisation.
Next, they ask about preoperative fasting and intraoperative haemodynamic variables (hypotension specifically). That is a bit fastidious, since a standardised anaesthetic procedure, which is comprehensively described in the paper, would aim to maintain blood pressure in a certain range. Preoperative fasting is likely to be either standardised or balanced through randomisation.
Finally, they ask about cumulative opioid consumption, which is clearly relevant, but also reported in Table 2 of the paper. It was balanced, but if anything, the means were marginally higher in the TEAS group, hence increasing the risk of PONV in that group.
Wang et al make one further comment on the generalisability of the data (or lack thereof) based on the fact that the majority of patients were high risk of PONV and therefore should have received two interventions for PONV rather than one. For me, this does not detract from the generalisability of the data since there are very few interventions for PONV that have been subjected to the required 2×2 factorial design trials, let alone the 3×3 trials that might be required from an ethical perspective.
I thought I better just check PubMed after making such a statement. I found just 3 trials using PONV as a mesh term (spelt out, not the acronym) and ‘factorial’ at a title word.[3–5] One of them tested 6 different interventions in a trial with 5199 patients and concluded:[4]
Because antiemetic interventions are similarly effective and act independently, the safest or least expensive should be used first. Prophylaxis is rarely warranted in low-risk patients, moderate-risk patients may benefit from a single intervention, and multiple interventions should be reserved for high-risk patients.
Apfel et al N Engl J Med 2004References
1 Zhang Y, Li Y, Ji F, et al. Transcutaneous electrical acupoint stimulation versus dexamethasone for prophylaxis of postoperative nausea and vomiting in breast surgery: A non-inferiority randomized controlled trial. Surgery. 2023;174:787–93.
2 Wang X-D, Meng Q-W, Xue F-S. Comparing prophylactic efficacy of different interventions on postoperative nausea and vomiting: Methodology is critical-Re: Zhang Y, et al. Transcutaneous electrical acupoint stimulation versus dexamethasone for prophylaxis of postoperative nausea and vomiting in breast surgery: A non-inferiority randomized controlled trial. Surgery. 2023;S0039-6060(23)00840-1.
3 Apfel CC, Kranke P, Katz MH, et al. Volatile anaesthetics may be the main cause of early but not delayed postoperative vomiting: a randomized controlled trial of factorial design. Br J Anaesth. 2002;88:659–68.
4 Apfel CC, Korttila K, Abdalla M, et al. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med. 2004;350:2441–51.
5 Gunter JB, McAuliffe JJ, Beckman EC, et al. A factorial study of ondansetron, metoclopramide, and dexamethasone for emesis prophylaxis after adenotonsillectomy in children. Paediatr Anaesth. 2006;16:1153–65.