Our results suggest a lack of agreement among anesthesia providers about the best way to monitor neuromuscular function. Efforts to improve awareness by developing formal training programs and/or publishing official guidelines on best practices to reduce the incidence of postoperative neuromuscular weakness and patient morbidity are warranted.
A panel of clinician scientists with expertise in neuromuscular blockade (NMB) monitoring was convened with a charge to prepare a consensus statement on indications for and proper use of such monitors. The aims of this article are to: (a) provide the rationale and scientific basis for the use of quantitative NMB monitoring; (b) offer a set of recommendations for quantitative NMB monitoring standards; (c) specify educational goals; and (d) propose training recommendations to ensure proper neuromuscular monitoring and management. The panel believes that whenever a neuromuscular blocker is administered, neuromuscular function must be monitored by observing the evoked muscular response to peripheral nerve stimulation. Ideally, this should be done at the hand muscles (not the facial muscles) with a quantitative (objective) monitor. Objective monitoring (documentation of train-of-four ratio ≥0.90) is the only method of assuring that satisfactory recovery of neuromuscular function has taken place. The panel also recommends that subjective evaluation of the responses to train-of-four stimulation (when using a peripheral nerve stimulator) or clinical tests of recovery from NMB (such as the 5-second head lift) should be abandoned in favor of objective monitoring. During an interim period for establishing these recommendations, if only a peripheral nerve stimulator is available, its use should be mandatory in any patient receiving a neuromuscular blocking drug. The panel acknowledges that publishing this statement per se will not result in its spontaneous acceptance, adherence to its recommendations, or change in routine practice. Implementation of objective monitoring will likely require professional societies and anesthesia department leadership to champion its use to change anesthesia practitioner behavior.
Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder with distinct facies, growth failure, intellectual disability, distal limb anomalies, gastrointestinal and neurological disease. Mutations in NIPBL, encoding a cohesin regulatory protein, account for >80% of cases with typical facies. Mutations in the core cohesin complex proteins, encoded by the SMC1A, SMC3 and RAD21 genes, together account for ∼5% of subjects, often with atypical CdLS features. Recently, we identified mutations in the X-linked gene HDAC8 as the cause of a small number of CdLS cases. Here, we report a cohort of 38 individuals with an emerging spectrum of features caused by HDAC8 mutations. For several individuals, the diagnosis of CdLS was not considered prior to genomic testing. Most mutations identified are missense and de novo. Many cases are heterozygous females, each with marked skewing of X-inactivation in peripheral blood DNA. We also identified eight hemizygous males who are more severely affected. The craniofacial appearance caused by HDAC8 mutations overlaps that of typical CdLS but often displays delayed anterior fontanelle closure, ocular hypertelorism, hooding of the eyelids, a broader nose and dental anomalies, which may be useful discriminating features. HDAC8 encodes the lysine deacetylase for the cohesin subunit SMC3 and analysis of the functional consequences of the missense mutations indicates that all cause a loss of enzymatic function. These data demonstrate that loss-of-function mutations in HDAC8 cause a range of overlapping human developmental phenotypes, including a phenotypically distinct subgroup of CdLS.
The use of anticholinesterases to reverse residual neuromuscular block is efficacious only if recovery is already established. It was originally advised that at least the second twitch (T2) of the train-of-four response should be detectable before neostigmine is administered. Even in these circumstances, the full effect of anticholinesterases takes up to 10 min to achieve. Anticholinesterases also have muscarinic side-effects that require an antimuscarinic to be administered concomitantly. An ideal reversal agent could be given at any time after the administration of a neuromuscular blocking agent (NMBA), and should have no muscarinic side-effects. The gamma cyclodextrin, sugammadex, has been demonstrated to effectively antagonize even profound block produced by the aminosteroid NMBAs, rocuronium and vecuronium, by chelating them. The complex is then excreted in the urine. Sugammadex is ineffective in antagonizing the benzylisoquinolinium NMBAs. The dose should be adjusted according to the degree of residual block: sugammadex 16 mg kg(-1) for immediate reversal; 4-8 mg kg(-1) for antagonizing profound block (post-tetanic count 1-2); and 2 mg kg(-1) to antagonize moderate block (when T2 is detectable). As yet, the extent of any side-effects that may occur with this new antagonist is not fully known, although rarely adverse cardiovascular effects (hypotension, hypertension, prolonged QT interval) have already been reported.
Large differences in the PKs of sugammadex and rocuronium between patients with renal failure and healthy controls were observed. The effect of renal impairment on the PK variables of rocuronium was less than with sugammadex. Urinary excretion of both drugs was reduced in renal patients.
Key points † An innovative economic approach to evaluating the use of a new drug. † There are potential time savings using sugammadex for reversal. † The clinical value of any time saved is less clear. † Further studies are needed to allow development of the model.
Summary.The cost-effectiveness of sugammadex for the routine reversal of muscle relaxation produced by rocuronium or vecuronium in UK practice is uncertain. We performed a systematic review of randomized controlled trials of sugammadex compared with neostigmine/glycopyrrolate and an economic assessment of sugammadex for the reversal of moderate or profound neuromuscular block (NMB) produced by rocuronium or vecuronium. The economic assessment aimed to establish the reduction in recovery time and the 'value of time saved' which would be necessary for sugammadex to be potentially cost-effective compared with existing practice. Three trials indicated that sugammadex 2 mg kg 21 (4 mg kg 21 ) produces more rapid recovery from moderate (profound) NMB than neostigmine/glycopyrrolate. The economic assessment indicated that if the reductions in recovery time associated with sugammadex in the trials are replicated in routine practice, sugammadex would be cost-effective if those reductions are achieved in the operating theatre (assumed value of staff time, £4.44 per minute), but not if they are achieved in the recovery room (assumed value of staff time, £0.33 per minute). However, there is considerable uncertainty in these results. Sugammadex has the potential to be cost-effective compared with neostigmine/glycopyrrolate for the reversal of rocuronium-induced moderate or profound NMB, provided that the time savings observed in trials can be achieved and put to productive use in clinical practice. Further research is required to evaluate the effects of sugammadex on patient safety, predictability of recovery from NMB, patient outcomes, and efficient use of resources.
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