Deep NMB ameliorates surgical conditions for laparoscopic cholecystectomy by improved visibility and reduction of involuntary movements.

Botulinum toxin causes dose-dependent long-term neuromuscular changes. The loss of tension generating capacity is almost exclusively related to muscle atrophy, because the specific tension did not change. The decreased ED10, unaltered ED50, and increased ED90 to atracurium suggest its interactions with different isoforms of receptors having varying sensitivity to atracurium. The absence of fade, despite the persistent botulinum toxin-induced denervation (increased nAChRs), suggests that the up-regulated nAChRs may have compensated for the prejunctional effects of botulinum toxin.

Continuous pyridostigmine infusion improves muscle weakness after 7 days and 14 days of immobilization. The up-regulation of acetylcholine receptors and the concomitant resistance to atracurium is attenuated in animals treated with pyridostigmine after 7 days of immobilization.

The trial is registered at ClinicalTrials.gov (NCT01101139).

Central venous injection of E. coli bacteria induces systemic inflammation evidenced as loss of body weight, muscle mass and increased alpha1-acid glycoprotein levels. The inflammation-induced muscle weakness is due to muscle atrophy and not to upregulated AChRs. This model may prove useful for studying maneuvers to prevent muscle wasting with inflammation.

Background We tested the hypothesis that a single injection of botulinum toxin not only has local, but also distant effects on muscle function, biochemistry, and pharmacodynamics of atracurium. Methods Botulinum toxin (2.5U) was injected into the tibialis muscle of anesthetized rats (n=26). The contralateral side with no injection served to study distant effects. Control animals (n=25) received a saline injection. Neuromuscular function, pharmacology and expression of acetylcholine receptors (nAChRs) were evaluated in the tibialis at 0, 4 and 16 days after injection and compared to saline injected controls. Results On day 4, botulinum toxin caused complete paralysis of the tibialis, while its contralateral side showed a decrease in absolute twitch tension (1.8N [1.6; 1.9] vs. 3.0N [2.8; 3.1], Newton, p<0.05). On day 16, muscle weakness was only present on the toxin-injected side where absolute twitch tension was decreased (0.6N [0.6; 0.7] vs. 3.4N [3.1; 3.7], p<0.05). Tibialis mass was decreased on the toxin-injected side at day 4 (1.46mg/g [1.43; 1.48] vs. 1.74mg/g [1.72; 1.75], P<0.05) and on day 16 (0.78mg/g [0.76; 0.79] vs. 1.73 mg/g [1.69; 1.77], P<0.05). Effects distant from the site of injection were seen on day 16, when muscle atrophy was also present in the adjacent gastrocnemius and soleus muscles. Normalized to tibialis mass, specific twitch tension (tension/ g muscle) was reduced on the contralateral side at day 4 and on the toxin-injected side at day 16 relative to saline controls. At day 16, an increased sensitivity to atracurium was seen on the toxin-injected side, evidenced as a decreased ED50 (0.23mg/kg [0.13; 0.33] vs. 0.72 mg/kg [0.63; 0.82], p<0.05), and a lower infusion rate (38 μl/kg/min [32; 43] vs.135μl/kg/min [126; 144], p<0.05) together with a reduced plasma concentration requirement of atracurium (0.5μg/ml [0.4; 0.7] vs. 4.5μg/ml [3.8; 5.2], P<0.05) to achieve a steady–state 50% reduction in baseline (absolute) twitch tension. ED50 of atracurium was also decreased on the contralateral side at day 16 relative to saline controls. The nAChRs in the tibialis were increased on the toxin-injected side to 123fmol/mg [115; 131] vs. 28fmol/mg [25; 29], (p<0.05) in time-matched saline-injected controls at day 4 and to 378 [341; 413] vs. 27 fmol/mg [25; 29], (p<0.05) at day 16. Conclusions Botulinum toxin has local and distant effects on muscle. The decrease in specific twitch tension indicates that the muscle atrophy alone cannot explain the functional changes; neuromuscular transmission is also impaired. An increased sensitivity to atracurium on the toxin-injected side, despite up-regulation of nAChRs, seems unique to botulinum toxin.

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