We thank Zealley et al. for their comments regarding our clinical trial comparing postoperative patient-focused symptoms after reversal with either neostigmine or sugammadex 1. Ours was a pragmatic trial designed in 2011, which used equipment available at the time, namely either the Datex NMT (GE Healthcare, Little Chalfont, UK) or the Stimpod (Xavant Technology, Pretoria, South Africa). A survey published in 2013 noted that quantitative neuromuscular function monitors were not available in 42% of the Australian and New Zealand hospitals in which the respondents practiced 2. Details of the efficacy of recovery from neuromuscular block, such as the time to recovery of a train-of-four (TOF) ratio of 0.9, were not consistently available and data were not recorded. The study protocol asked that blinded study reversal drugs were not administered until the TOF count was at least 2. However, there were 17 protocol violations in which they were given at deeper levels of block (8 in the neostigmine group and 9 in the sugammadex group, 6 at a count of 0 and 11 at a count of 1); these 17 data sets were included in the intention-to-treat analysis. Of 300 complete data sets, 45% were reversed at a TOF count of 4% and 38% at a count of 2 or 3. As TOF ratios at the time of extubation were unknown, we agree that a possible explanation for a higher incidence of symptoms of blurred vision in the recovery room after neostigmine reversal was residual neuromuscular block. This phenomenon is acknowledged to occur frequently (40–60%) after reversal with neostigmine 3. To suggest that this higher incidence of an adverse effect “is only of clinical significance if the patient groups had comparable TOF ratios at extubation” may be scientifically sound, but fails to acknowledge the reality that many anaesthetists do not routinely use pharmacological reversal, or reverse with neostigmine without any monitoring of neuromuscular function 4. Whether this survey finding still holds true in 2018 is uncertain, but we suspect the aforementioned remains common practice. Naguib et al. in their recent consensus statement of peri-operative monitoring of neuromuscular monitoring, appear to concur. They state “despite an editorial consensus that monitoring of neuromuscular function should be mandatory…., this standard is far from being implemented universally” 3. Zealley et al. ask whether the decision to terminate the study due to the protocol using single drug antiemetic prophylaxis and volatile anaesthetic for maintenance might have occurred earlier. We accept this criticism and certainly agree that current standards 5 are such that the study protocol would be considered unacceptable by many anaesthetists in well-resourced countries. At the time of the study design almost 7 years ago, we indeed reflected on the topic of acceptable prophylaxis against postoperative nausea and vomiting. We audited the practice of our department members within a busy gynaecological hospital and determined that dual antiemetic prophylaxis was not widely used; and that total intravenous anaesthesia was rarely used. Once the study started, we did not perform an interim analysis and were thus unaware of the overall or within-group incidence of postoperative nausea and vomiting. Ultimately, we opted to terminate the study, in part due to our concern that it no longer reflected current standards. Zealley et al. support the continued use of neostigmine as a means of “effective neuromuscular block reversal, with minimal postoperative sequelae.” Our study showed no reduction in postoperative nausea and vomiting with sugammadex reversal, but the findings with respect to other patient symptoms and outcomes were secondary outcomes and should be considered explorative. The authors advocate adequate dosing of neostigmine, ideally after recovery of the TOF count to 4, adequate time allowed before awakening and quantitative neuromuscular block measurement throughout. They make no mention of the fact that these caveats they apply are not easily applicable and rarely pertain in real-world clinical practice 2-4. In addition, reversal from moderate or profound block from rocuronium or vecuronium is both much more rapid and reliable after sugammadex. Furthermore, they have not acknowledged that residual neuromuscular block is much more common than after reversal with sugammadex; or that this problem can lead to adverse airway or pulmonary complications 3. The potential superiority of sugammadex reversal with respect to a reduction in clinically important respiratory complications and improved respiratory outcomes has not been demonstrated convincingly to date, but research is continuing. Neostigmine still has a place as a reversal drug, but as the price of sugammadex falls and new reversal drugs are in the development pipeline 6, in our opinion this may well prove short-lived.
This is a summary document that provides an Australian perspective on the Fourth Consensus Guidelines for the management of postoperative nausea and vomiting. The Australian Society of Anaesthetists has endorsed the Fourth Consensus Guidelines for the management of postoperative nausea and vomiting and has written this document with permission from the authors and the American Society for Enhanced Recovery to provide an Australia-specific summary.
Sugammadex more rapidly and reliably reverses rocuronium-induced neuromuscular block compared with neostigmine, but it is not known if subsequent patient outcomes, including nausea, vomiting and other aspects of recovery are modified. In this study, we compared the recovery characteristics of sugammadex and neostigmine/glycopyrrolate following reversal of neuromuscular block. This was a single-centre, randomised, blinded, parallel-group clinical trial in women undergoing elective day-surgical laparoscopic gynaecological surgery, with a standardised general anaesthesia regimen that included rocuronium. Neuromuscular block was reversed with either sugammadex 2 mg.kg-1 or neostigmine 40 μg.kg-1 and glycopyrrolate 400 μg. The primary outcome was the incidence of nausea and vomiting during the first six postoperative hours. Secondary outcomes included other measures of postoperative recovery such as patient symptoms and recovery scores. Three-hundred and four women were analysed by intention-to-treat (sugammadex n = 151, neostigmine n = 153), which included four major protocol violations. There was no significant difference between sugammadex and neostigmine groups in the incidence of early nausea and vomiting (49.0% vs. 51.0%, respectively; OR 0.92, 95%CI 0.59-1.45; p = 0.731). Double vision (11.5% vs. 20.0%; p = 0.044) and dry mouth (71.6% vs. 85.5%; p = 0.003) were less common after sugammadex. Sedation scores at 2 h were also lower after sugammadex (median (IQR [range]) 0 (0-3 [0-10]) vs. 2 (0-4.[0-10]); p = 0.021). Twenty-four-hour recovery scores were not significantly different between groups. Reversal with sugammadex in this patient population did not reduce postoperative nausea or vomiting compared with neostigmine/glycopyrrolate.
The benefit of combining non-opioid analgesics with neuraxial opioids for analgesia after caesarean delivery has not been clearly established. Larger doses of paracetamol or cyclooxygenase-2 inhibitors have not been evaluated. A randomised, double blind, double-dummy, parallel group placebo-controlled clinical trial was conducted among women having elective caesarean delivery under spinal anaesthesia, followed by pethidine patient-controlled epidural analgesia. Patients received placebos (group C); intravenous parecoxib 40 mg then oral celecoxib 400 mg at 12 hours (group PC); intravenous paracetamol 2 g then oral 1 g six-hourly (group PA); or these regimens combined (group PCPA). The primary outcome was 24-hour postoperative patient-controlled epidural pethidine use and the main secondary outcome was postoperative pain. One hundred and thirty-eight women were recruited but 27 subsequently met exclusion criteria, leaving 111 who were randomised, allocated and analysed by intention-to-treat (n=23, 30, 32 and 26 in groups C, PC, PA and PCPA respectively). There were no differences between groups for pethidine consumption, based on either intention-to-treat (median 365, 365, 405 and 360 mg in groups C, PC, PA and PCPA respectively, P=0.84) or per protocol analysis (17 major violations). Dynamic pain scores did not differ between groups but requirement for, and dose of, supplementary oral tramadol was least in group PCPA (incidence 23% versus 48%, 70% and 58% in groups C, PC and PA respectively, P=0.004). The addition of regular paracetamol, cyclooxygenase-2 inhibitors or both to pethidine patient-controlled epidural post-caesarean analgesia did not provide a pethidine dose-sparing effect during the first 24 hours.
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