Eikermann M, Zaremba S, Malhotra A, Jordan A S, Rosow C, Chamberlin N L
Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Br J Anaesth. 2008 Sep;101(3):344-9. doi: 10.1093/bja/aen176. Epub 2008 Jun 16.
Cholinesterase inhibitor-based reversal agents, given in the absence of neuromuscular block, evoke a partial upper airway obstruction by decreasing skeletal upper airway muscle function. Sugammadex reverses neuromuscular block by encapsulating rocuronium. However, its effects on upper airway integrity and breathing are unknown.
Fifty-one adult male rats were anaesthetized with isoflurane, tracheostomized, and a femoral artery and vein were cannulated. First, we compared the efficacy of sugammadex 15 mg kg(-1) and neostigmine 0.06 mg kg(-1) to reverse respiratory effects of rocuronium-induced partial paralysis [train-of-four ratio (T4/T1)=0.5]. Subsequently, we compared the safety of sugammadex and neostigmine given after recovery of the T4/T1 to 1, by measuring phasic genioglossus activity and breathing.
During partial paralysis (T4/T1=0.5), time to recovery of minute volume to baseline values was 10.9 (2), 75.8 (18), and 153 (54) s with sugammadex, neostigmine, and placebo, respectively (sugammadex was significantly faster than neostigmine and placebo, P<0.05). Recovery of T4/T1 was also faster for sugammadex than neostigmine and placebo. Neostigmine administration after complete recovery of T4/T1 decreased upper airway dilator muscle activity to 64 (30)% of baseline and decreased tidal volume (P<0.05 for both variables), whereas sugammadex had no effect on either variable.
In contrast to neostigmine, which significantly impairs upper airway dilator muscle activity when given after recovery from neuromuscular block, a reversal dose of sugammadex given under the same conditions does not affect genioglossus muscle activity and normal breathing. Human studies will be required to evaluate the clinical relevance of our findings.
在不存在神经肌肉阻滞的情况下给予基于胆碱酯酶抑制剂的逆转剂，会通过降低上呼吸道骨骼肌功能引起部分上呼吸道梗阻。舒更葡糖钠通过包裹罗库溴铵来逆转神经肌肉阻滞。然而，其对上呼吸道完整性和呼吸的影响尚不清楚。
51只成年雄性大鼠用异氟烷麻醉，行气管切开术，并分别插入股动脉和静脉导管。首先，我们比较了15mg/kg的舒更葡糖钠和0.06mg/kg的新斯的明逆转罗库溴铵诱导的部分麻痹[四个成串刺激比值（T4/T1）=0.5]对呼吸的影响。随后，我们通过测量颏舌肌的阶段性活动和呼吸，比较了在T4/T1恢复到1后给予舒更葡糖钠和新斯的明的安全性。
在部分麻痹期间（T4/T1=0.5），使用舒更葡糖钠、新斯的明和安慰剂时，分钟通气量恢复到基线值的时间分别为10.9（2）秒、75.8（18）秒和153（54）秒（舒更葡糖钠明显快于新斯的明和安慰剂，P<0.05）。舒更葡糖钠使T4/T1恢复的速度也比新斯的明和安慰剂更快。在T4/T1完全恢复后给予新斯的明，会使上呼吸道扩张肌活动降至基线的64（30）%，并降低潮气量（两个变量P均<0.05），而舒更葡糖钠对这两个变量均无影响。
与新斯的明不同，在从神经肌肉阻滞恢复后给予新斯地明会显著损害上呼吸道扩张肌活动，而在相同条件下给予逆转剂量的舒更葡糖钠不会影响颏舌肌活动和正常呼吸。需要进行人体研究以评估我们研究结果的临床相关性。
