Pharmacodynamics of cisatracurium in the intensive care unit: an observational study

Abstract

BackgroundData from previous studies indicate that optimal conditions for intubation are met 120 seconds after administration of 0.15 mg.kg-1 cisatracurium (ED95 × 3) following the induction of anesthesia. The aim of this study was to compare the doses required for complete paralysis after induction of anesthesia in ICU patients with the dose used in patients undergoing elective surgery.MethodsSeventeen ICU patients undergoing percutaneous tracheostomy and 17 patients undergoing an elective surgical procedure under muscle relaxation were included. In both groups, an initial intravenous bolus of cisatracurium besylate was given at a dose of 0.15 mg.kg-1 followed by repeated boluses of 0.03 mg.kg-1 every four minutes. The objective was to obtain no response to the train-of-four (TOF). The contractile response of the corrugator supercilii muscle was monitored every minute by observing the TOF in response to a peripheral nerve stimulator with a constant current set to 60 mA.ResultsAfter the initial dose of cisatracurium, none of ICU patients (0/17) versus 15/17 of the elective surgery patients were completely paralyzed (P < 0.0001). There was a delay in the onset of neuromuscular blockade among the ICU patients. The cumulative doses of cisatracurium were significantly higher in the ICU group with 38 ± 14 mg (that is, 10 ± 4.7 ED95) versus 11 ± 2 mg (that is, 3 ± 0.3 ED95) in the elective surgery group (P < 0.0001).ConclusionThe dosing of cisatracrurium for ICU patients, which is based on the dose recommended for elective anesthesia, is unsuitable because the onset is too slow. This phenomenon is probably caused by changes in the pharmacodynamics and pharmacokinetics. These data suggest that neuromuscular monitoring should be used in the ICU.

Evidence and consensus based guideline for the management of delirium, analgesia, and sedation in intensive care medicine. Revision 2015 (DAS-Guideline 2015) – short version

“…When there is a specific indication for NMBAs, adequate analgesia and sedation should be provided [ 39 ]. Furthermore, the depth of blockade should be monitored [ 40 ], and the duration should be kept as short as possible (Table 17 (Tab. 17) ).…”

Clinical assessment and train-of-four measurements in critically ill patients treated with recommended doses of cisatracurium or atracurium for neuromuscular blockade: a prospective descriptive study

“…The pharmacokinetics of NMBAs in critically ill patients can be affected by many conditions, such as sepsis and/or shock [12]. In addition, it has been shown that ICU patients are less sensitive to neuromuscular blockade than patients in the operating room [14]. …”

“…The benefits and limitations of TOF stimulation were primarily determined from studies performed in operative room patients [10, 11], with results that may not be generalizable to ICU patients. In critically ill patients, the duration of neuromuscular blockade is longer, sepsis and/or shock is often present, and pharmacokinetic is difficult to predict [12–14]. Lastly, agreement between subjective and objective means of assessing the degree of neuromuscular blockade has been little studied in ICU [15–17].…”

Phlebitis as a consequence of peripheral intravenous administration of cisatracurium besylate in critically ill patients

“…In a study of 33 patients requiring neuromuscular blockade for ventilation in the ICU, using atracurium via a peripheral vein, phlebitis was observed in two patients 9. Both atracurium and cisatracurium are non-depolarising muscle relaxants from the benzylisoquinoline family that undergo degradation in plasma at physiological pH and temperature by organ-independent Hofmann elimination 10. Cisatracurium is a stereoisomer of atracurium and as such has the same molecular weight 11.…”