NIMBEX recovery in patients with renal or hepatic impairment1,2

chronic-renal
  • Time to 25% recovery after NIMBEX administration was similar in both groups1
  • The half-life of metabolites are longer in patients with renal failure and hepatic disease and concentrations may be higher after long-term administration3
  • It is recommended that a peripheral nerve stimulator be used during the administration of NIMBEX to monitor drug effect, determine the need for additional doses, and confirm recovery from neuromuscular block3
  • NIMBEX had an intermediate duration of action that was not significantly affected by the presence of chronic renal failure.

STUDY DESIGN

  • 17 patients with chronic renal failure undergoing surgery for fashioning of an arteriovenous fistula (n=9), insertion of a CAPD catheter (n=5), renal transplant nephrectomy (n=2) or femoropopliteal graft (n=1); 15 patients with normal renal function; an additional group of 15 healthy patients were given a commensurate dose of atracurium. Healthy/normal renal function patients were undergoing intermediate surgical procedures such as inguinal hernia repair or laparoscopic surgery. 
  • ASA status I or II mean patient age was 42.4-43.8 years
  • Premedication comprised diazepam 5-10 mg orally, 2 h before surgery. Anesthesia was induced with midazolam 0.05 mg/kg, fentanyl 1 µg/kg and thiopentone 2-5 mg/kg. Patients then inhaled 70% nitrous oxide in oxygen and anesthesia was maintained with increments of fentanyl, midazolam or thiopentone as necessary
  • Patients received either cisasatracurium 0.1 mg/kg (2 x ED95) (n=32) or atracurium
    0.4 mg/kg (2 x ED95) (n=15) given over 10-s into a fast flowing peripheral I.V. infusion
  • Endpoints were mean time to depression, mean time to recovery and tracheal intubation time 
liver-transplant

The pharmacodynamic variables of NIMBEX were similar in organ-impaired and healthy patients2

  • The half-life of metabolites are longer in patients with renal failure and hepatic disease and concentrations may be higher after long-term administration3
  • It is recommended that a peripheral nerve stimulator be used during the administration of NIMBEX to monitor drug effect, determine the need for additional doses, and confirm recovery from neuromuscular block3

SUMMARY

  • Organ-independent Hofmann elimination allows for appropriate administration in renally and hepatically compromised patients1-3
    • NIMBEX undergoes Hofmann elimination through the production of laudanosine and monoquaternary acrylate3,4
    • In healthy adults, 80% of NIMBEX is cleared through Hofmann elimination rather than through the renal or hepatic systems3,4 
    • A chemical process dependent on pH and temperature3
  • Laudanosine, a metabolite of cisatracurium, has been noted to cause transient hypertension and, in higher doses cerebral excitatory effects when administered to several animal species. The relationship between CNS excitation and laudanosine concentrations in humans has not been established3

STUDY DESIGN

  • 25 adult surgical patients; 14 with end stage liver disease undergoing liver transplantation (ASA III-IV); 11 patients with no hepatic or renal disease  (ASA I-II). Mean patient age was 37-48 years
  • 17 of 25 patients received preoperative midazolam 0.026 mg/kg; anesthesia was induced with thiopentone 4.6 mg/kg and fentanyl 4.4 µg/kg and maintained with isoflurane (0.5% end-tidal concentration) and 50-70% of nitrous oxide in oxygen with incremental doses of fentanyl PRN. Tracheal intubation was facilitated by administration of suxamethonium 1.3 (0.7) mg/kg
  • Patients received cisasatracurium 0.1 mg/kg (2 x ED95) (n= 25) in a single bolus administered via an I.V. cannula over a 5-10 second period 
  • Endpoints were time to maximum block and pharmacokinetic variables: AUC, Cl, Vss and T½