Augmentation of the Rocuronium-induced Neuromuscular Block by the Acutely Administered Phenytoin

Background: The effects of an acute administration of phenytoin on the magnitude of the rocuronium-induced neuromuscular block were evaluated.

Methods: Twenty patients (classified as American Society of Anesthesiologists physical status I or II) scheduled for craniotomy were studied:

15 received phenytoin during operation (10 mg/kg), and the others served as controls.Anesthesia was induced with thiopental and fentanyl and maintained with nitrous oxide (65%) in oxygen and end-tidal isoflurane (1%). The ulnar nerve was stimulated supramaximally and the evoked electromyography was recorded using a neuromuscular transmission monitor. Continuous infusion of rocuronium maintained the neuromuscular block with first twitch (T1) between 10 and 15% for 45 min before the start of an infusion of either phenytoin or NaCl, 0.9%. Twitch recordings continued for 60 min thereafter. Arterial blood samples were collected at the predefined time points (four measurements before and four after the start of the infusion) to determine the concentrations of phenytoin and rocuronium and the percentage of rocuronium bound to plasma proteins.

Results: The first twitch produced by an infusion of rocuronium remained constant during the 15 min before and the 60 min after the start of the saline infusion. After the phenytoin infusion, the twitch decreased progressively, but the plasma concentrations and the protein-bound fraction of rocuronium did not change.     

Reversal of Rocuronium-induced Neuromuscular Block by the Selective Relaxant Binding Agent Sugammadex: A Dose-finding and Safety Study

Background: Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block.

Methods: Twenty-seven male surgical patients aged 18-64 yr were randomly assigned to receive placebo or sugammadex (0.5, 1.0, 2.0, 3.0, or 4.0 mg/kg) for reversal of 0.6 mg/kg rocuronium-induced neuromuscular block. Anesthesia was induced and maintained using intravenous fentanyl and propofol. Neuromuscular function was assessed using acceleromyography. Sugammadex or placebo was administered at reappearance of T2 of the train-of-four. The primary efficacy variable was the time required for recovery to a train-of-four ratio of 0.9.

Results: Sugammadex decreased median recovery time in a dose-dependent manner from 21.0 min in the placebo group to 1.1 min in the group receiving 4.0 mg/kg sugammadex. Doses of sugammadex of 2.0 mg/kg or greater reversed rocuronium-induced neuromuscular block within 3 min. A median of 59-77% of sugammadex was excreted unchanged in the urine within 16 h, mostly in the first 8 h. Sugammadex increased the proportion of the rocuronium dose excreted unchanged in the urine (from a median of 19% in the placebo group to 53% in the 4.0-mg/kg group within 16 h). Sugammadex was safe and well tolerated. No evidence of recurarization was observed in any patient.     

Reversal of Rocuronium-induced (1.2 mg/kg) Profound Neuromuscular Block by Sugammadex: A Multicenter, Dose-finding and Safety Study

Background: Reversal of rocuronium-induced neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a modified [gamma]-cyclodextrin derivative. This study investigated the efficacy and safety of sugammadex in reversing rocuronium-induced profound neuromuscular blockade at 5 min in American Society of Anesthesiologists physical status I and II patients.

Methods: Forty-five American Society of Anesthesiologists physical status I and II patients (aged 18-64 yr) scheduled to undergo surgical procedures (anticipated anesthesia duration >= 90 min) were randomly assigned to a phase II, multicenter, assessor-blinded, placebo-controlled, parallel, dose-finding study. Anesthesia was induced and maintained with propofol and an opioid. Profound neuromuscular blockade was induced with 1.2 mg/kg rocuronium bromide. Sugammadex (2.0, 4.0, 8.0, 12.0, or 16.0 mg/kg) or placebo (0.9% saline) was then administered 5 min after the administration of rocuronium. Neuromuscular function was monitored by acceleromyography, using train-of-four nerve stimulation. Recovery time was the time from the start of administration of sugammadex or placebo, to recovery of the train-of-four ratio to 0.9. Safety assessments were performed on the day of the operation and during the postoperative and follow-up period.

Results: A total of 43 patients received either sugammadex or placebo. Increasing doses of sugammadex reduced the mean recovery time from 122 min (spontaneous recovery) to less than 2 min in a dose-dependent manner. Signs of recurrence of blockade were not observed. No serious adverse events related to sugammadex were reported. Two adverse events possibly related to sugammadex were reported in two patients (diarrhea and light anesthesia); however, both patients recovered without sequelae.     

Hand Grip Function Assessed by the Box and Block Test Is Affected by Object Surfaces

Study DesignN/A.BackgroundOne of the hand function assessment tools is the Box and Block Test (BBT).PurposeTo examine if the BBT score is affected by grip surfaces.MethodsThirteen adults performed the BBT with wooden, rubber-covered, and paper-covered blocks. The BBT scores and time for seven movements (finger closing, contact to lift-off, transport before barrier, transport after barrier, release, return, and reach) were compared across the three block types.ResultsThe mean BBT score was 8% higher for the rubber blocks than the paper and wooden blocks (p < 0.01) due to the reduced time for contact to lift-off (when the finger touches a block until the block is lifted).ConclusionsHand function assessments should be controlled for object surfaces. Therapists may vary grip difficulties by changing object surfaces. Redesigning daily objects with high-friction surfaces may increase grip function.Level of EvidenceN/A.     

Onset and Duration of Rocuronium-induced Neuromuscular Blockade in Patients with Duchenne Muscular Dystrophy

Background: In patients with Duchenne muscular dystrophy (DMD) the response to nondepolarizing muscle relaxants is scarcely documented and conflicting. The current study was conducted to determine the time to peak effect and the time for complete spontaneous recovery after a single dose of 0.6 mg/kg of rocuronium in patients with DMD.

Methods: Twenty-four patients (12 with DMD, 12 controls, aged 10-16 yr) were studied. All patients were anesthetized with propofol and fentanyl/remifentanil. Neuromuscular transmission was monitored by acceleromyography. After induction all patients received a single dose of 0.6 mg/kg of rocuronium. The complete time course of onset and spontaneous recovery were recorded

Results: Significant (P < 0.01) increase in the onset times to 95% neuromuscular block was observed in DMD patients (median, 203 s; range, 90-420 s) compared with controls (median, 90 s; range, 60-195 s). The time between rocuronium administration and recovery of first twitch of the train-of-four to 90% was significantly (P < 0.01) prolonged in DMD compared with controls (median, 132 min; range, 61-209 min versus 39 min; 22-55 min). The recovery index was also significantly prolonged in the DMD group compared with controls (median, 28 min, range, 15-70 min versus 8 min; 3-14 min).     

乌司他丁对阿曲库铵神经肌肉阻滞效应的影响

目的观察乌司他丁对阿曲库铵神经肌肉阻滞效应的影响。方法选择择期胆道探查手术病人30例,随机分成两组乌司他丁组,麻醉诱导按顺序静脉注射咪唑安定1mg/kg、丙泊酚1mg/kg、芬太尼5μg/kg,然后给予乌司他丁5000U/kg,2min后给予阿曲库铵0.6mg/kg;对照组,麻醉诱导后,给予同等剂量生理盐水,2min后给予阿曲库铵0.6mg/kg。观测两组患者拇内收肌群TOF,记录T1消失所需时间及第1次TOF恢复时T1出现的时间。结果乌司他丁组阿曲库铵起效时间为(289.0±19.7)s,比对照组(226.4±11.2)s明显延长,恢复时间为(14.4±0.8)min,比对照组(19.8±1.7)min明显缩短(P<0.05)。结论乌司他丁可影响阿曲库胺对胆道探查手术全麻病人的神经肌肉阻滞效应。     

Early Reversal of Profound Rocuronium-induced Neuromuscular Blockade by Sugammadex in a Randomized Multicenter Study: Efficacy, Safety, and Pharmacokinetics

Background: Sugammadex reverses the neuromuscular blocking effects of rocuronium by chemical encapsulation. The efficacy, safety, and pharmacokinetics of sugammadex for reversal of profound rocuronium-induced neuromuscular blockade were evaluated.

Methods: Ninety-eight male adult patients were randomly assigned to receive sugammadex (1, 2, 4, 6, or 8 mg/kg) or placebo at 3, 5, or 15 min after 0.6 mg/kg rocuronium. Patients were anesthetized with propofol and fentanyl. The primary endpoint of the study was the time to achieve a recovery of train-of-four ratio to 0.9. Neuromuscular blockade was measured using acceleromyography. Concentrations of rocuronium and sugammadex were determined in venous blood and urine samples. A population pharmacokinetic model using NONMEM (GloboMax LLC, Hanover, MD) was applied.

Results: The mean time to recovery of the train-of-four ratio to 0.9 after dosing at 3, 5, and 15 min decreased from 52.1, 51.7, and 35.6 min, respectively, after administration of placebo to 1.8, 1.5, and 1.4 min, respectively, after 8 mg/kg sugammadex. Sugammadex was safe and well tolerated. However, 20.4% of patients showed signs of inadequate anesthesia after its administration. The median cumulative excretion of rocuronium in the urine over 24 h was 26% in the placebo group and increased to 58-74% after 4-8 mg/kg sugammadex. The mean plasma clearances of sugammadex and rocuronium were 0.084 and 0.26 l/min, respectively.     

Efficacy of Tactile-guided Reversal from Cisatracurium-induced Neuromuscular Block

Background: Because tactile evaluation is the most common form of clinical neuromuscular monitoring, this study examines the relative efficacy of antagonizing residual block at different levels of recovery of the tactile train-of-four (TOF) response.

Methods: Anesthesia was induced in 64 adults with 2-5 [mu]g/kg fentanyl and 1-3 mg/kg propofol and maintained with fentanyl, propofol, and nitrous oxide. The tactile response of the adductor pollicis to TOF stimulation was evaluated at one arm, and the mechanomyographic response was recorded at the other. Patients received 0.15 mg/kg cisatracurium and were randomized to receive 0.07 mg/kg neostigmine on reappearance of the first (group I), second (group II), third (group III), or fourth (group IV) tactile TOF response (16 patients per group). Times from administration of neostigmine until the TOF ratio recovered to 0.7 (R0.7), 0.8 (R0.8), and 0.9 (R0.9) were measured.

Results: Data are presented as median with range in parentheses. R0.7 was 10.3 (5.9-23.4), 7.6 (3.2-14.1), 5.0 (2.0-18.4), and 4.1 (2.4-11.0) min in groups I, II, III, and IV, respectively (P < 0.05, group I > II, III, and IV, group II > IV). R0.8 was 16.6 (8.9-30.7), 9.8 (5.3-25.0), 8.3 (3.8-27.1), and 7.5 (3.0-74.5) min in groups I, II, III, and IV, respectively (P < 0.05, group I > II, III, and IV, group II > IV). R0.9 was 22.2 (13.9-44.0), 20.2 (6.5-70.5), 17.1 (8.3-46.2), and 16.5 (6.5-143.3) min in groups I, II, III, and IV, respectively (no intergroup differences). Ten minutes after neostigmine, a TOF ratio of 0.7 or greater was achieved in 50, 75, 88, and 93% of patients in groups I, II, III, and IV, respectively (P < 0.05 group I > II, III, and IV). At 30 min, a TOF ratio of 0.9 or less was observed in 21, 13, 13, and 7% of patients in groups I, II, III, and IV respectively (no intergroup differences).     

Rocuronium-induced neuromuscular blockade is affected by chronic phenytoin therapy

Patients receiving chronic anticonvulsant therapy have been reported to show resistance to certain nondepolarizing neuromuscular blockers. In this study, the effects of chronic phenytoin therapy on the onset, duration, and recovery of rocuronium action was assessed. Thirty-six patients scheduled for various neurosurgical procedures were studied: 18 receiving chronic phenytoin therapy (Group I) and 18 controls (Group II). Rocuronium 0.6 mg/kg (2 x DE95) was administered after induction of general anesthesia with 4-6 mg/kg thiopental sodium and 3-5 microg/kg intravenous (IV) fentanyl. Maintenance anesthesia consisted of N2O in O2, 0.5% end-tidal isoflurane, and a fentanyl infusion. Neuromuscular block was monitored with acceleromyography of the adductor pollicis-brevis muscle by using a TOF-GUARD Biometer monitor (Biometer International A/S, Odense, Denmark). According to the amplitude of the first response of train-of-four, neither the lag time nor the onset time differed between the two groups. However, the recovery index was significantly shorter in patients chronically treated with phenytoin (mean recovery index: control group, 8.3 +/- 1.7 minutes; phenytoin group, 6.7 +/- 2.3 minutes; P < .05). In addition, the times of recovery to 10%, 25%, 75%, and 90% of the baseline response were also significantly shorter in the phenytoin group than in the control group. We conclude that the duration of action of rocuronium and the recovery index were affected by chronic phenytoin therapy.     

Comparison of Physostigmine and Neostigmine for Antagonism of Neuromuscular Block

The ability of physostigmine alone and in combination with neostigmine to reverse d-tubocurarine-induced neuromuscular block was evaluated in surgical patients. The relaxation was maintained at a level of90 % twitch suppression during balanced anaesthesia, and antagonism was attempted with physostigmine 1.5 mgX3; neostigmine 0.5 mgX3; neostigmine 1.0 mgX3; or with a combination of physostigmine 0.75 mg and neostigmine 0.5 mg × 3.
The measured parameters included the twitch force or EMG amplitude of the adductor pollicis brevis muscle after supramaximal 0.1 Hz stimulation and fading of these responses after repetitive 2 and 50 Hz stimuli. Although the restitution rate of twitch height and EMG amplitude were essentially the same with both antagonists, there was a considerable time-lag in regeneration of the fades after repetitive stimuli with physostigmine as compared with the neostigmine group. The addition of physostigmine to a subeffective dose of neostigmine resulted in antagonism comparable to that seen in other groups. The clinical antagonism was satisfactory in all patients receiving physostigmine. The divergence of relaxation-indicating parameters (twitch responses and fades) after physostigmine suggests dissimilar modes of action of the two antagonists at the neuromuscular junction.     

The Maximum Depth of an Atracurium Neuromuscular Block Antagonized by Edrophonium to Effect Adequate Recovery

Background: The inability of edrophonium to rapidly reverse a deep nondepolarizing neuromuscular block may be due to inadequate dosage or a ceiling effect to antagonism of neuromuscular block by edrophonium. A ceiling effect means that only a certain level of neuromuscular block could be antagonized by edrophonium. Neuromuscular block greater than this could not be completely antagonized irrespective of the dose of edrophonium administered. The purpose of this study was to determine whether a ceiling effect occurred for antagonism of an atracurium-induced neuromuscular block by edrophonium and, if so, the maximum level of block that could be antagonized by edrophonium.

Methods: In 30 adult patients, atracurium was administered to maintain a constant neuromuscular block. The level of block varied between patients. Evoked adductor pollicis twitch tension was monitored. Incremental doses of edrophonium were administered while the infusion of atracurium continued. Increments were given until adequate recovery occurred, as defined by a train-of-four (TOF) ratio greater or equal to 70%, or until no further antagonism of the block could be achieved. The probability of being able to effect adequate recovery by antagonism with edrophonium was determined using a logistic regression model. Cumulative dose-response curves were constructed using the logit transformation of the neuromuscular effect versus the logarithm of the cumulative dose of edrophonium.

Results: In 14 patients with a block of 25-77% depression of the first twitch response, antagonism by edrophonium to a TOF ratio greater or equal to 70% was possible, whereas in 16 patients with a 60-92% depression of T1, a TOF ratio > 70% was not achievable, indicating that a ceiling effect for antagonism by edrophonium occurred. A block of 67 plus/minus 3% (mean plus/minus SE) had a 50% probability of adequate antagonism. In patients in whom block was antagonized to a TOF ratio < 70%, 95% of the peak antagonistic effect occurred with an edrophonium dose of 0.8 plus/minus 0.33 mg *symbol* kg sup -1 (mean plus/minus SD).     

七氟醚对心脏病病人维库溴铵肌松效力的影响

目的 :观察吸入七氟醚对维库溴铵肌松效力的影响。方法 :4 0例择期体外循环心内直视术病人随机分成两组 ,分别为静脉麻醉组 (对照组 )和静脉麻醉复合吸入 1 3MAC七氟醚组 (七氟醚组 ) ,采用累积剂量反应的方法测定两组维库溴铵的量效关系曲线。结果 :诱导期吸入七氟醚 15分钟后使维库溴铵的量效关系曲线左移 ,七氟醚组的ED50 和ED95分别为 19 2± 5 6和 3 7 0± 10 3 μg/kg ,与对照组的 3 0 7± 8 6和 5 7 8± 11 6μg/kg相比 ,分别减少3 6 5 %和 3 5 8% (P <0 0 1)。结论 :七氟醚麻醉能明显增强维库溴铵的肌松效力。     

Chronic Biofiltration Therapy

Abstract: Long-term follow-up evaluation of biofiltration treatment in 7 patients is presented. These patients experienced frequent episodes of hypotension during acetate hemodialysis. A 3-year biofiltration treatment reduced by 43% episodes of symptomatic hypotension and produced a significant increase in the pretreatment pH and plasma bicarbonate levels. The β2-microglobulin level was significantly reduced during biofiltration therapy. The mean systolic and diastolic blood pressures slightly increased during biofiltration. Uremic polyneuropathy, as demonstrated by an increase in motor nerve conduction velocity, slightly improved. The patients reported increased comfort during biofiltration therapy.     

Genotyping the Butyrylcholinesterase in Patients with Prolonged Neuromuscular Block after Succinylcholine

Background: Succinylcholine remains the standard neuromuscular blocking drug for tracheal intubation in emergency situations. The short duration of action is due to its rapid hydrolytic degradation by butyrylcholinesterase (plasmacholinesterase). Multiple variants of this enzyme are known (A, F, S, H, J, K variants) with different effects on enzyme activity. This study was undertaken to evaluate the use of molecular genetic methods in patients with clinically prolonged neuromuscular block.

Methods: Nine patients with a neuromuscular block of 14 min to 5 h were selected. All four exons of the butyrylcholinesterase were amplified by polymerase chain reaction and analyzed by automated sequencing. Molecular genetic results were compared with clinical relaxation time and with biochemical test results (total butyrylcholinesterase activity, dibucaine and fluoride inhibition).

Results: Seven of nine patients were mutation carriers. Five of these had more than one mutation. The A and K variants were the most frequent variations. Three of four patients who were homozygous for the A variant were also carriers of the K allele. The authors identified one novel mutation (G1294T) introducing a stop codon at amino acid position 432. The duration of neuromuscular block was substantially different between patients with identical butyrylcholinesterase genotypes.