Reversal of rocuronium-induced (1.2 mg kg-1) profound neuromuscular block by accidental high dose of sugammadex (40 mg kg-1)

Sugammadex is the first selective relaxant binding agent andreverses rocuronium-induced neuromuscular block. A case is reportedin which a patient accidentally received a high dose of sugammadex(40 mg kg^–1) to reverse a rocuronium-induced (1.2 mg kg^–1)profound neuromuscular block. A fast and efficient recoveryfrom profound neuromuscular block was achieved and no adverseevents or other safety concerns were reported.     

Reversal of rocuronium-induced neuromuscular blockade by pyridostigmine in patients with Duchenne muscular dystrophy

BACKGROUND: The aim of this study was to investigate the effect and safety of pyridostigmine for the reversal of a neuromuscular block (NMB) in patients with Duchenne muscular dystrophy (DMD). In patients with DMD recovery from a rocuronium-induced NMB is markedly delayed. METHODS: Fourteen DMD patients (aged between 11 and 19 years) scheduled for elective scoliosis repair were studied. Following tracheal intubation without muscle relaxant, all patients received a single dose of rocuronium 0.6 mg.kg(-1). NMB was monitored by acceleromyography at the adductor pollicis muscle. When the first twitch height (T1) of the train-of-four (TOF) had recovered to 25% seven patients received either pyridostigmine 0.1 mg.kg(-1) (the anticholinergic drug with a long duration of action) or saline in a blinded manner. The times to attain TOF ratio of 0.9 were recorded. For comparison the Mann-Whitney U-test was used. RESULTS: Recovery to TOF ratio of 0.9 was significantly (P < 0.05) accelerated by pyridostigmine [84 (median), 57-141(range)] compared with controls (148, 84-243 min). The recovery time (time between T1 of 25% and TOF of 90%) was also significantly (P < 0.01) shortened by pyridostigmine (15, 8-49 vs 76, 43-144 min, respectively). Time to recovery of T(1) to 90% was not different between the groups (108, 63-134 vs 169. 61-208 min, respectively). CONCLUSIONS: Pyridostigmine 0.1 mg.kg(-1) effectively reversed a rocuronium-induced NMB in DMD patients.     

Mivacurium in children with Duchenne muscular dystrophy

The authors retrospectively reviewed their experience with mivacurium for neuromuscular blockade in seven children with Duchenne muscular dystrophy. Mivacurium was administered to seven children ranging in age from 8.3 to 14.4 years and in weight from 29 kg to 68 kg during either posterior spinal fusion or lower extremity release. An initial bolus dose of 0.2 mg·kg^?1 was followed by a continuous infusion. Neuromuscular blockade was monitored with a standard twitch monitor and the TOF (2 Hz for 2 s). Complete suppression of all four twitches occurred in 1.5 to 2.6 min. The continuous infusion was started with the return of the first twitch and adjusted to maintain one twitch. Time to recovery of the first twitch varied from 12 to 18 min. Continuous infusion requirements varied from 3 to 20 μg·kg^?1 with an average for the case of less than 10 μg·kg^?1 min^?1 in five of the seven patients. A moderate increase in sensitivity to mivacurium in this patient population is suggested by a decrease in infusion requirements and a prolonged effect following the initial dose.     

Recovery characteristics of patients receiving either sugammadex or neostigmine and glycopyrrolate for reversal of neuromuscular block: a randomised controlled trial

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.     

Onset and duration of mivacurium-induced neuromuscular block in patients with Duchenne muscular dystrophy

Background. To determine the response to mivacurium, we prospectivelystudied onset time and complete spontaneous recovery from mivacurium-inducedneuromuscular block in patients with Duchenne muscular dystrophy(DMD). Methods. Twelve boys with DMD, age 5–14 yr, seven of themwheelchair-bound, ASA II–III, and 12 age- and sex-matchedcontrols (ASA I) were enrolled in the study. Anaesthesia wasinduced with fentanyl 2–3 µg kg^–1 and propofol3–4 mg kg^–1 titrated to effect, and maintained bycontinuous i.v. infusion of propofol 8–12 mg kg^–1and remifentanil as required. The lungs were ventilated withoxygen in air. Neuromuscular transmission was assessed by acceleromyographyusing train-of-four (TOF) stimulation every 15 s. After baselinereadings, a single dose of mivacurium 0.2 mg kg^–1 wasgiven. The following variables were recorded: (i) lag time;(ii) onset time; (iii) peak effect; (iv) recovery of first twitchfrom the TOF response to 10, 25 and 90% (T₁₀, T₂₅, T₉₀) relativeto baseline; (v) recovery index (time between 25 and 75% recoveryof first twitch); and (vi) recovery time (time between 25% recoveryof first twitch and recovery of TOF ratio to 90%). For comparisonbetween the groups the Mann–Whitney U-test was applied. Results. There were no differences between the groups in lagtime, onset time and peak effect. However, all recorded recoveryindices were significantly (P<0.05) prolonged in the DMDgroup. The median (range) for time points T₁₀, T₂₅ and T₉₀ inthe DMD and control group was 12.0 (8–16) vs 8.4 (5–15)min, 14.1 (9–20) vs 10.5 (7–17) min and 26.9 (15–40)vs 15.9 (12–23) min, respectively. The recovery indexand recovery time were similarly prolonged in the DMD group. Conclusions. These results support the assumption that mivacurium-inducedneuromuscular block is prolonged in patients with DMD. This study was presented at the Annual Meeting of the AmericanSociety of Anaesthesiologists, Las Vegas, October 2004. These authors contributed equally to this work.     

Lung function in Duchenne muscular dystrophy

Summary Over 90% of patients with Duchenne muscular dystrophy develop a scoliosis when they become wheelchair bound. The scoliosis is progressive and is associated with deteriorating lung function. The purpose of this study was firstly to assess whether a standing regimen, in patients who had gone off their feet, protected against the development of scoliosis and affected their lung function, and secondly to evaluate the effect of spinal stabilisation in patients who had developed a progressive scoliosis. The results of the first part of this study showed that a standing regimen significantly delayed the progression of scoliosis and that patients who complied with the standing regimen had a significantly better lung function, as measured by vital capacity and peak expiratory flow rate, than those patients who did not stand. Spinal stabilisation prevented deterioration in the scoliosis, whereas the deformity continued to progress relentlessly in patients who did not undergo surgery. The patients who underwent spinal stabilisation maintained a significantly better lung function and had an improved survival compared with the patients who refused surgery.Paper read at the ESDS meeting, Birmingham 1994, and selected for full publication.     

Duchenne muscular dystrophy: an old anesthesia problem revisited

Patients with Duchenne and Becker muscular dystrophy suffer from a progressive deterioration in muscle secondary to a defect in the dystrophin gene. As such, they are susceptible to perioperative respiratory, cardiac and other complications, such as rhabdomyolysis. Inhalational anesthetic agents have been implicated as a cause of acute rhabdomyolysis that can resemble malignant hyperthermia (MH). This article reviews perioperative 'MH-like' reactions reported in muscular dystrophy patients and groups them into three categories according to clinical presentation. The etiology and underlying pathophysiological process responsible for these reactions is discussed and recommendations are proposed for the safe anesthetic management of these patients.     

Org 25969 (sugammadex), a selective relaxant binding agent for antagonism of prolonged rocuronium-induced neuromuscular block

Background. Org 25969 is a cyclodextrin compound designed toreverse a rocuronium-induced neuromuscular block. The aim ofthis study was to explore the efficacy, dose–responserelation and safety of Org 25969 for reversal of a prolongedrocuronium-induced neuromuscular block. Methods. Thirty anaesthetized adult patients received rocuronium0.6 mg kg^–1 as an initial dose followed by incrementsto maintain a deep block at a level of <10 PTCs (post-tetaniccounts) recorded every 6 min. Neuromuscular monitoring was carriedout using accelerometry, in a train-of-four (TOF) mode usingTOF-Watch®SX. At recovery of T₂, following at least 2 hof neuromuscular block, patients received their randomly assigneddose of 0.5, 1.0, 2.0, 4.0 or 6.0 mg kg^–1 of Org 25969.Anaesthesia and neuromuscular monitoring were continued fora minimum period of 30 min after Org 25969 administration. Themain end-point of the study was the time to achieve a sustainedrecovery of TOF ratio to 0.9. Patients were followed up for7 days after anaesthesia. Results. The results showed a dose-related decrease in the averagetime taken to attain a TOF ratio of 0.9 from 6:49 (min:s) withthe 0.5 mg kg^–1 dose to 1:22 with the 4.0 mg kg^–1dose. Weighted non-linear regression analysis showed the fastestachievable time to TOF ratio of 0.9 to be 1:35. Org 25969 producedno major adverse effects. Conclusion. Org 25969 effectively reversed a deep and prolongedneuromuscular block induced by rocuronium. The effective reversaldose appears to be 2–4 mg kg^–1.     

Scoliosis correction with pedicle screws in Duchenne muscular dystrophy

This report describes the spinal fixation with pedicle-screw-alone constructs for the posterior correction of scoliosis in patients suffering from Duchene muscular dystrophy (DMD). Twenty consecutive patients were prospectively followed up for an average of 5.2 years (min 2 years). All patients were instrumented from T3/T4 to the pelvis. Pelvic fixation was done with iliac screws similar to Galveston technique. The combination of L5 pedicle screws and iliac screws provided a stable caudal foundation. An average of 16 pedicle screws was used per patient. The mean total blood loss was 3.7 l, stay at the intensive care unit was 77 h and hospital stay was 19 days. Rigid stabilisation allowed immediate mobilisation of the patient in the wheel chair. Cobb angle improved 77% from 44° to 10°, pelvic tilt improved 65% from 14° to 3°. Lumbar lordosis improved significantly from 20° to 49°, thoracic kyphosis remained unchanged. No problems related to iliac fixation, no pseudarthrosis or implant failures were observed. The average percentage of predicted forced vital capacity (%FVC) of the patients was 55% (22–94%) preoperatively and decreased to 44% at the last follow-up. There were no pulmonary complications. One patient with a known cardiomyopathy died intraoperatively due to a sudden cardiac arrest. The rigid primary stability with pedicle screws allowed early mobilisation of the patients, which helped to avoid pulmonary complications.     

Magnesium‐induced recurarisation after reversal of rocuronium‐induced neuromuscular block with sugammadex

A 61‐year‐old woman (57 kg, 171 cm) underwent surgery under general anaesthesia with desflurane 5.8–6.1 vol. % end‐tidal, remifentanil 0.2–0.4 μg/kg/min and rocuronium 35 mg (0.61 mg/kg). On return of the second twitch in the train‐of‐four (TOF) stimulation measured by acceleromyography, sugammadex 120 mg (2.1 mg/kg) was given. After complete neuromuscular recovery, magnesium sulphate 3600 mg (60 mg/kg) was injected intravenously over 5 min to treat atrial fibrillation. This was associated with recurarisation with a nadir [first twitch = 25%, TOF ratio (TOFR) = 67%] 7 min after the start of the magnesium sulphate infusion (magnesium plasma level: 2.67 mM). A spontaneous twitch value and a TOFR of > 90% were observed 45 min after the beginning of the magnesium sulphate infusion under general anaesthesia. Rapid infusion of magnesium sulphate may re‐establish a sugammadex‐reversed, rocuronium‐induced neuromuscular block during general anaesthesia, probably because of the high plasma level of magnesium (2.67 mM). Desflurane and a small fraction of unbound rocuronium may amplify the known muscle relaxing effects of magnesium. Intravenous injection of magnesium sulphate is not recommended in patients after general anaesthesia with neuromuscular relaxants, particularly after sugammadex reversal. Quantitative neuromuscular monitoring should be used for reversing aminosteroid muscle relaxants with sugammadex ? particularly in combination with magnesium injection ? to prevent post‐operative residual curarisation.     

Safety and tolerability of single intravenous doses of sugammadex administered simultaneously with rocuronium or vecuronium in healthy volunteers

BACKGROUND: Sugammadex rapidly reverses rocuronium- and vecuronium-induced neuromuscular block. To investigate the effect of combination of sugammadex and rocuronium or vecuronium on QT interval, it would be preferable to avoid the interference of anaesthesia. Therefore, this pilot study was performed to investigate the safety, tolerability, and plasma pharmacokinetics of single i.v. doses of sugammadex administered simultaneously with rocuronium or vecuronium to anaesthetized and non-anaesthetized healthy volunteers. METHODS: In this phase I study, 12 subjects were anaesthetized with propofol/remifentanil and received sugammadex 16, 20, or 32 mg kg(-1) combined with rocuronium 1.2 mg kg(-1) or vecuronium 0.1 mg kg(-1); four subjects were not anaesthetized and received sugammadex 32 mg kg(-1) with rocuronium 1.2 mg kg(-1) or vecuronium 0.1 mg kg(-1) (n=2 per treatment). Neuromuscular function was assessed by TOF-Watch SX monitoring in anaesthetized subjects and by clinical tests in non-anaesthetized volunteers. Sugammadex, rocuronium, and vecuronium plasma concentrations were measured at several time points. RESULTS: No serious adverse events (AEs) were reported. Fourteen subjects reported 23 AEs after study drug administration. Episodes of mild headache, tiredness, cold feeling (application site), dry mouth, oral discomfort, nausea, increased aspartate aminotransferase and gamma-glutamyltransferase levels, and moderate injection site irritation were considered as possibly related to the study drug. The ECG and vital signs showed no clinically relevant changes. Rocuronium/vecuronium plasma concentrations declined faster than those of sugammadex. CONCLUSIONS: Single-dose administration of sugammadex 16, 20, or 32 mg kg(-1) in combination with rocuronium 1.2 mg kg(-1) or vecuronium 0.1 mg kg(-1) was well tolerated with no clinical evidence of residual neuromuscular block, confirming that these combinations can safely be administered simultaneously to non-anaesthetized subjects. Rocuronium and vecuronium plasma concentrations decreased faster than those of sugammadex, reducing the theoretical risk of neuromuscular block developing over time.     

Surgical treatment of spinal deformities in Duchenne muscular dystrophy: a long term follow-up study

Background Surgical treatment of spinal deformities in Duchenne muscular dystrophy (DMD) is influenced by a number of factors which have proven to be a difficult challenge. Each case should be carefully evaluated, considering not only the natural history of the spinal deformity, but also the patients general condition. These should be thoroughly assessed through clinical and radiographic investigations together with other medical specialists. Life expectancy should be determined according to the cardio-respiratory function, and both preoperative and postoperative quality of life should be taken into consideration, trying to imagine the functional status of each patient after surgery.Methods From February 1985 to February 2000, 58 patients with spinal deformity in DMD were surgically treated. Of 25 patients that were operated on between 1985 and 1995, only 20 were followed-up after 5 years because 5 of them had died during this time. Therefore, the present study focuses on the results obtained in 20 cases. The 20 cases reviewed presented with a mean angular value of scoliosis equal to 48° (range 10–92°). Spinal fusion with our modified Luque technique [6] was performed in 19 cases, whereas CD instrumentation was applied in only one case.Results At the 5 year follow-up (range 5.6–10 years), the age ranged from 18 to 24 years and averaged 20.4 years. The postoperative angular value of scoliosis averaged 22° (58%, range 0–43°), the mean correction at follow-up was 28° (range 0–60°), and the mean loss of correction was equal to 6° (range, 0–11°). Vital capacity showed a slow progression, slightly inferior to its natural evolution in untreated patients. The severest complication was the death that occurred in one of the patients.Conclusions According to the present study, an early surgery (angular value lower than 35–40°) dramatically reduces the rate of risk factors associated with spinal deformities in DMD, and its advantages far exceed the disadvantages, above all in terms of quality of life.     

Reversal of Rocuronium-Induced Neuromuscular Block with Sugammadex and Resulting Histopathological Effects in Rat Kidneys

Background: This study investigated the effect of injection of rocuronium or sugammadex alone and rocuronium + sugammadex on urea, creatinine, electrolyte levels, and histopathological findings in rats. Methods: Thirty-six Sprague-Dawley male rats were divided to receive intravenously 16 or 96 mg/kg sugammadex, 1 mg/kg rocuronium, 1 mg/kg rocuronium + 16 mg/kg sugammadex, or 1 mg/kg rocuronium + 96 mg/kg sugammadex. The control group received an equal volume of physiological serum. Rats receiving rocuronium were ventilated until resumption of spontaneous ventilation and followed for 72 h. Blood samples were withdrawn from the tail vein to measure urea, creatinine, and electrolyte values; then both kidneys were excised, and the tissues were used for histopathological examination. Results: Rats receiving rocuronium and high doses of sugammadex (96 mg/kg) showed increased glomerular vacuolation, tubular dilatation, vascular vacuolation and hypertrophy, lymphocyte infiltration, and tubular cell sloughing compared to the control group (p = 0.002). Biochemical markers of renal function were not significantly altered after treatment with high doses of sugammadex. Conclusion: The elimination half-life of the rocuronium–sugammadex complex was found to be greater than that of free rocuronium or sugammadex, which led to marginal histopathological changes in the kidney without affecting any renal functions.     

Comparison of reversal with neostigmine of low‐dose rocuronium vs. reversal with sugammadex of high‐dose rocuronium for a short procedure

Some short procedures require deep neuromuscular blockade, which needs to be reversed at the end of the procedure. Forty‐four patients undergoing elective laryngeal micro‐surgery were randomly allocated into two groups: rocuronium 0.45 mg.kg^?1 with neostigmine (50 μg.kg^?1 with glycopyrrolate 10 μg.kg^?1) reversal (moderate block group) vs. rocuronium 0.90 mg.kg^?1 with sugammadex (4 mg.kg^?1) reversal (deep block group). The primary outcome was the intubating conditions during laryngoscopy secondary outcomes included recovery of neuromuscular block; conditions for tracheal intubation; satisfaction score as determined by the surgeon; onset of neuromuscular block; and postoperative sore throat. The onset of neuromuscular block was more rapid, and intubation conditions and ease of intra‐operative laryngoscopy were more favourable, and the satisfaction score was lower in the moderate block group compared with the deep block group. No difference was found in the incidence of postoperative sore throat. In laryngeal micro‐surgery, the use of rocuronium 0.9 mg.kg^?1 with sugammadex for reversal was associated with better surgical conditions and a shorter recovery time than rocuronium 0.45 mg.kg^?1 with neostigmine.     

Serum osteocalcin in patients with immobilization osteoporosis due to Duchenne muscular dystrophy

Serum osteocalcin (OC), serum alkaline phosphatase (ALP) and urine hydroxyproline (Hyp) were measured in normal children and patients with Duchenne muscular dystrophy (DMD). Serum OC, ALP, and urine Hyp values were decreased in DMD patients (p<0.01). A significant correlation was found between serum ALP and OC values (Y=0.44X+2.33; r=0.78; p<0.05), and between urine Hyp and serum OC (Y=0.03X+0.33; r=0.56; p<0.05). Vertebral trabecular mineral density was measured in DMD patients using the quantitative computed tomography (QCT) method. Degree of severity of osteoporosis in DMD patients advanced with aging. No significant correlation was found between urine Hyp and QCT values (Y=0.02X+0.33; r=0.29; p>0.2) and a tendency of correlation was noted between serum ALP and QCT values (Y=0.05X+1.11; r=0.56; 0.05<p<0.1). The most intimate correlation was found between serum OC and QCT values (Y=0.17X−9.52; r=0.82 p<0.05). Serum OC was elevated (p<0.01) on administration of 1α (OH) vitamin D₃ but ALP and Hyp showed no remarkable changes. Our studies indicate that serum OC may serve as a specific and useful indicator for the evaluation of immobilization osteoporosis in DMD.