Pharmacodynamic Dose-Response and Safety Study of Cisatracurium (51W89) in Adult Surgical Patients During N2 O-O2-Opioid Anesthesia

Abstract

After administration of doses ranging from 0.025 to 0.25 mg/kg, the neuromuscular blocking effect of cisatracurium was assessed in 119 adult surgical patients receiving N,O-opioid-midazolam-thiopental anesthesia. The calculated 95% effective dose (ED,,) for inhibition of adductor pollicis twitch evoked at 0.1 Hz was 0.053 mg/kg. With 0.10 mg/kg injected over 5-10 and 20-30 s, median onset times (range) were 5.8 (3.0-7.7) and 4.8 (1.2-l 0.2) min, respectively, and median times to 5% and 95% recovery (range) were 27 (19-46) and 48 (25-68) min, respectively. For doses of 0.10,0.20, and 0.25 mg/kg, median 5%-95% and 25%-75% recovery indexes ranged from 48 to 90 min and 8 to 9 min, respectively.After administration of neostigmine (0.06 mg/kg) at lo%-15% or 16%-30% recovery, the median times to 95% recovery (range) were 6 (2-22) and 4 (2-5) min, respectively. There were no changes in heart rate, blood pressure, or plasma histamine concentrations during the first 5 min after administration of cisatracurium at doses up to 5 X ED,, injected over 5-10 s. No cutaneous flushing or bronchospasm was noted. In summary, cisatracurium is a potent neuromuscular blocking drug with an intermediate duration of action, characterized by excellent cardiovascular stability, with no apparent histamine release.

Neuromuscular blocking effects and train‐of‐four fade with cisatracurium: comparison with other nondepolarising relaxants

“…Other reports are, however, conflicting. Whereas Lepage et al [3] observed median clinical duration of action of 0.1 mg.kg ¹1 cisatracurium to be about 9 min shorter than that of 0.5 mg.kg ¹1 of atracurium, Boyd et al found the recovery to be longer with this dose of cisatracurium compared to 0.4 mg.kg ¹1 of atracurium [12]. The differences between cisatracurium and atracurium may have been exaggerated in the study of Boyd et al who used a comparatively lower dose of atracurium [12].…”

Bloqueio neuromuscular residual após o uso de rocurônio ou cisatracúrio

“…Increasing cisatracurium dose prolongs deep neuromuscular block (without response to neurostimulation). However, at the beginning of spontaneous recovery, there is a similar profile, in spite of the difference in dose, thus allowing the calculation of the recovery period 15 . A similar study has concluded that atracurium dose is not associated to RPOC 4 .…”

Dose preparatória versus injeção única: estudo comparativo entre diferentes doses de cisatracúrio

“…O u r s t u d y h a s s h o w n hemodynamic stability after bolus or fractional injections of different cisatracurium doses. Previous studies with healthy or coronary disease patients have also shown that cisatracurium in doses varying from 2 to 8 times DE 95 does not induce histamine release and cardiovascular changes [40][41][42][43] doses have provided acc e p t a b l e t r a c h e a l i n t u b a t i o n c o n d i t i o n s w i t h o u t hemodynamic changes. …”

“…Os resultados deste estudo mostram estabilidade hemodinâmi-ca após a administração em injeção única ou fracionada das diferentes doses de cisatracúrio. Estudos anteriores em pacientes hígidos ou portadores de doença coronariana também demonstraram que o cisatracúrio, em doses que variam de 2 a 8 vezes a DE 95 , não causa liberação de histamina e alterações cardiovasculares [40][41][42][43] . Independente da dose utilizada (2 ou 4 DE 95 ), o cisatracúrio em doses fracionadas não encurtou o tempo para a instalação do bloqueio neuromuscular máximo, em relação ao seu emprego em injeção única.…”