Selection of neuromuscular blocking agents in patients undergoing renal transplantation under general anesthesia

OBJECTIVE: To study the pharmacodynamics of vecuronium,atracurium, mivacurium and rocuronium in patients with end-stage renal failure. METHODS: Forty-six patients with end-stage renal failure scheduled for renal transplantation and 53 patients with normal renal function were given either vecuronium, atracurium, mivacurium or rocuronium. The neuromuscular effects were monitored by the evoked response of the adductor pollicis to train-of-four stimulation of the ulnar nerve. RESULTS: Onset of vecuronium, atracurium and mivacurium occurred faster or tended to be faster in patients with end-stage renal failure, but there was no significant difference in onset by rocuronium between the control patients and renal failure patients. Furthermore, the no-response period, duration of action and recovery of atracurium did not differ between the two groups. There was no significant difference in duration of action or recovery of mivacurium between the two groups, whereas its no-response period was significantly prolonged in the patients with end-stage renal failure. There was no difference in no-response period or duration of action after the initial dose of vecuronium or rocuronium between the two groups. However, no-response period and duration of effect by vecuronium and rocuronium were prolonged with increasing incremental doses in patients with end-stage renal failure. CONCLUSIONS: All four muscle relaxants could be safely used in patients with end-stage renal failure. Onset of the relaxants were, in some cases, accelerated and no-response period of mivacurium was prolonged in patients with end-stage renal failure undergoing dialysis therapy. End-stage renal failure prolonged the no-response period and duration of action of vecuronium and rocuronium after repeated incremental doses, but did not alter those attributed to atracurium.

Reversing neuromuscular blocking agent decamethonium by carboxylatopillar[6]arene based on host-guest encapsulation

Neuromuscular blocking agents(NMBAs)are extensively used during anesthesia to improve surgical conditions by relaxing skeletal muscle movements.Rapid neuromuscular recovery after surgery is desirable to facilitate the recovery of muscle function and prevent residual blockade.Decamethonium(C10)is a classic NMBA,which has been restricted over the past decades ascribed to lack of a suitable antidote in clinic.Herein we used carboxylatopillar[6]arene(CP6A)to reverse neuromuscular blocker effect of C10 through direct host-guest encapsulation.NMR and isothermal titration calorimetry served to confirm the complexation between CP6A and C10 with robust affinity[(1.07±0.14)×10^(7)L/mol].The CP6A was further used as a reversal agent of C10,which facilitated to decrease C10 concentration in mice blood and excrete via urinary clearance,resulting in rapid recovery from muscle relaxation.These favorable outcomes might lead us to suggest that this supramolecular strategy could allow patients to regain lucidity much faster than spontaneous recovery from anesthesia.

Donepezil-related inadequate neuromuscular blockade during laparoscopic surgery: A case report

BACKGROUND Donepezil is an acetylcholinesterase inhibitor used to improve cognition and delay disease progression in dementia patients by increasing acetylcholine levels.This drug may potentially interact with neuromuscular blocking agents(NMBAs)that act on muscular acetylcholine receptors during general anesthesia.Herein,we present a case of inadequate neuromuscular blockade with rocuronium,a nondepolarizing NMBA,in a dementia patient who had taken donepezil.CASE SUMMARY A 71-year-old man was scheduled for laparoscopic gastrectomy.He had been taking donepezil 5 mg for dementia.General anesthesia was induced with propofol and remifentanil.The depth of neuromuscular blockade was monitored by train-of-four(TOF)stimulation.After the administration of rocuronium,the TOF ratio decreased at an unusually slow rate,and a TOF count of 0 was detected 7 min later.After intubation,a TOF count of 1 was detected within 1 min,and a TOF ratio of 12%was detected within 2 min.The TOF count remained at 4 even with an additional bolus and continuous infusion of rocuronium,suggesting resistance to this NMBA.Instead of propofol,an inhalation anesthetic was administered alongside another NMBA(cisatracurium).Then,the quality of neuromuscular blockade improved,and the TOF count remained at 0-1 for the next 70 min.No further problems were encountered with respect to surgery or anesthesia.CONCLUSION Donepezil may be responsible for inadequate neuromuscular blockade during anesthesia,especially when total intravenous anesthesia is used.

Suspected Anaphylactic Shock Associated with Rocuronium in an Infant: A Case Report

We report a case of severe anaphylactic shock in a 5-month-old infant who was scheduled to undergo an external inguinal hernia repair under general anesthesia. Rocuronium used for anesthesia induction was the most likely cause of anaphylaxis. High levels of serum tryptase and histamine detected in the blood sample collected during the anaphylactic reaction confirmed the diagnosis of anaphylactic shock. The patient’s clinical status improved within 90 min of intervention by the intravenous injection of vasopressors and a steroid. Surgery was canceled, and the patient stayed in the pediatric intensive care unit (PICU) under artificial ventilation for 5 h before safe extubation. The patient achieved full recovery the next day, without any sequelae. The rescheduled surgery was successfully completed 5 months later under general anesthesia without the use of neuromuscular blocking agents.

Impairment of recovery of muscle function by residual rocuronium after re-transfusion of intraoperative salvaged blood

Background Recurarization has previously been described in the context of acute normovolemic hemodilution.The aim of this study was to investigate the impairment of recovery of neuromuscular function after re-transfusion of intraoperative salvaged blood in patients treated with rocuronium.Methods We enrolled 50 patients undergoing general anesthesia for lumbar surgery.Intraoperative blood salvage （IBS） was used in 30 patients （group Ⅰ）; the remaining 20 comprised a control group （group C）.Anesthesia was induced with fentanyl,midazolam,propofol and rocuronium.Rocuronium was infused to maintain neuromuscular blockade during surgery.Blood was collected from the operative field and re-transfused in the post-anesthesia care unit （PACU）.Neuromuscular function was monitored using the train-of-four ratio （TOFr）.Once the train-of-four ratio exceeded 90 in the PACU,neuromuscular function was evaluated every 5 minutes for 30 minutes.The TOFr and incremental recovery of TOFr from baseline were recorded.Salvaged blood was re-transfused at the beginning of the evaluation for patients in group Ⅰ,and afterwards for patients in group C.Blood gas analysis was assessed before anesthesia and in the PACU.Results Incremental recovery of TOFr from baseline was significantly less in group Ⅰ than controls at 25 minutes （6.1±3.2vs.9.1±3.2,respectively; P=0.001） and 30 minutes （7.1±3.2 vs.10.0±2.2,respectively; P=-0.001）.There were no significant differences in gas exchange between the groups.Conclusions In patients who had received a rocuronium infusion during anesthesia,re-transfusion of salvaged blood significantly impaired recovery of neuromuscular function recovery in the PACU,but without significant impairment of respiratory function.

Asymmetric synthesis of some new tetrahydroisoquinolinium salts

Several new tetrahydroisoquinolinium salts, analogues of atracurium, were designed and synthesized. These compounds were prepared from optically pure tetrahydropapaverine and hexamethylene diglycidate.