University of Mississippi Medical Center University of Mississippi Health Care. Pharmacy and Therapeutics Committee Medication Use Evaluation

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1 University of Mississippi Medical Center University of Mississippi Health Care Pharmacy and Therapeutics Committee Medication Use Evaluation Cisatracurium (Nimbex ) and Vecuronium (Norcuron ) PURPOSE The purpose of this activity is to evaluate the utilization of cisatracurium (Nimbex ) and vecuronium (Norcuron ) in the ICU setting. Parameters used to monitor these neuromuscular blockers will be evaluated as assessment of the depth of blockade in ICU patients is recommended to avoid excessive paralysis. BACKGROUND Cisatracurium and vecuronium are both intermediate acting intravenous non depolarizing neuromuscular blocking agents (NMBAs). Both agents competitively bind to and antagonize acetylcholine receptors, preventing neuromuscular transmission. Cisatracurium and vecuronium are indicated as adjuncts to general anesthesia, to facilitate tracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation in the ICU. The clearance of these agents differs significantly with vecuronium being 50% renally excreted and 50% excreted by the biliary system versus cisatracurium that is metabolized by Hoffman elimination. Due to the higher cost of cisatracurium, its use should be reserved for patients with renal or hepatic impairment. METHODOLOGY Data was collected retrospectively on all patients who received either a continuous infusion of cisatracurium or vecuronium between January 1, 2011 and June 30, Patients were also excluded if they were in a pediatric hospital area or if they were participants of the Mississippi Organ Recovery Agency (MORA). Twenty three patients that received cisatracurium and twenty six patients that received vecuronium were evaluated. Data collected for analysis included indication, dosing, duration of treatment, monitoring, patient outcome, and current medication profile. RESULTS The results of the cisatracurium and vecuronium usage are summarized in the tables and graphs below. The total number of orders written for either neuromuscular blocking agent during the 6 month period was 79. A random sample of 49 medical records was used for this retrospective evaluation. The average patient age in the cisatracurium group was 53 years and the average age in the vecuronium group was 44. The majority of patients (95%) received either NMBA for an FDA approved indication. Skeletal muscle relaxation for mechanical ventilation was identified as the most common indication for neuromuscular blockade use.

2 Page 2 of 9 Figure 1. Ordering location for cisatracurium Figure 2. Ordering location for vecuronium

3 Page 3 of 9 Table 1: Results Hospital Stay 0 2 weeks >2 weeks Cisatracurium 9 (39%) 14 (61%) Vecuronium 8 (31%) 18 (69%) Maintenance infusion initiated at mcg/kg Yes No 1 Cisatracurium 21 (91%) 2 (9%) Maintenance infusion initiated at mcg/kg Vecuronium 21 (81%) 5 (19%) Drug Titrated? Yes No Cisatracurium 9 (39%) 14 (61%) Vecuronium 19 (73%) 7 (27%) Duration of infusion <24 hours >24 hours Cisatracurium 11 (48%) 12 (52%) Vecuronium 11 (42%) 15 (58%) Outcome Discharge Death Cisatracurium 14 (61%) 9 (39%) Vecuronium 20 (77%) 6 (23%) Ocular Lubricants Ordered? Yes No Cisatracurium 16 (70%) 7 (30%) Vecuronium 16 (62%) 10 (38%) Price Cost per vial (UMC) Charge per vial (patient) Cisatracurium $246 (200mg) $1008 (200mg) Vecuronium $89 (100mg) $382 (100mg) 1 Initial infusion rate not stated/documented

4 Page 4 of 9 Figure 3. Cisatracurium: Renal function at baseline Number of Patients SCr <1.3 SCr SCr 3 5 Figure 4. Cisatracurium: Hepatic function at baseline Number of Patients WNL LFT 1 2X UNL LFT > 2X UNL Note: Seven patients in the cisatracurium group had neither renal nor hepatic dysfunction at baseline

5 Page 5 of 9 Figure 5. Vecuronium: Renal function at baseline Number of Patients SCr <1.3 SCr SCr 3 5 Figure 6. Vecuronium: Hepatic function at baseline Number of Patients WNL LFT 1 2 X UNL LFT > 2X UNL Note: Eleven patients in the vecuronium group had some form of renal or hepatic dysfunction at baseline

6 Page 6 of 9 Figure7: Train of Four (TOF) Monitoring 90% 80% 85% 70% Percentage of Patients 60% 50% 40% 30% 57% Cisatracurium (13/23) Vecuronium (22/26) 20% 10% 0% Cisatracurium (13/23) Vecuronium (22/26) Table 2: Frequency of TOF Monitoring Frequency Q 2 H Q 4 H Daily Not documented/ Variable written Cisatracurium 0% 23% (3/13) 31% (4/13) 8% (1/13) 38% (5/13) Vecuronium 9% (2/22) 14% (3/22) 5% (1/22) 45% (10/22) 27% (6/22) Clinical practice guidelines recommend that patients receiving NMBAs be assessed both clinically and by TOF monitoring to achieve one or two twitches with peripheral nerve stimulation (Grade B recommendation). The number of twitches necessary for optimal blockade is influenced by the patient s level of sedation and overall condition. Dr. Baumann of UMMC performed a study comparing TOF monitoring to clinical assessment during continuous ICU cisatracurium infusion (CHEST 2004). Thirty patients in the medical ICU were randomized to TOF monitoring (at least every 4 hours) or clinical assessment during continuous cisatracurium administration. The study showed that TOF monitoring did not lead to improved recovery time or lower cisatracurium dosing compared to clinical assessment. Studies with vecuronium have showed a decrease in vecuronium use and recovery times with TOF monitoring compared to clinical assessment. This discrepancy is thought to be due to the dependence of vecuronium on adequate liver and renal function for clearance.

7 Page 7 of 9 Figure 8: MAR Documentation 70% 60% Percentage of Patients 50% 40% 30% 20% 64% 10% 20% 0% Cisatracurium (14/22) Vecuronium (5/25) Note: This accounts for correct documentation on MAR in addition to the number of doses the patient was charged for and the number of doses sent from pharmacy; MAR could not be accessed for one patient in each treatment group Figure 9. Cisatracurium: Sedation/Analgesia Note: Twenty patients received both sedation and analgesia; two patients received only sedation (lorazepam); one patient received only analgesia (morphine)

8 Page 8 of 9 Figure 10. Vecuronium: Sedation/Analgesia Note: Twenty four patients received both sedation and analgesia; two patients received only sedation (one midazolam and one propofol) Discussion: The primary ordering location for cisatracurium was the MICU and the primary ordering location for vecuronium was the SICU. The results of this medication utilization review demonstrate that cisatracurium and vecuronium are being utilized for FDA approved indications. Seven out of twenty three patients in the cisatracurium group had neither hepatic nor renal impairment at baseline. In contrast, eleven out of twenty six patients had some form of renal or hepatic impairment in the vecuronium group. No reversal agents were used during therapy with either group. No patients receiving concomitant corticosteroid therapy or interacting antibiotics experienced acute quadriplegic myopathy syndrome (AQMS). There are discrepancies in MAR documentation of bags administered and charges to the patient. There is also a lack of consistency in TOF documentation such that it is difficult to determine if a patient is appropriately paralyzed. Recommendations: The Department of Pharmacy Services recommends implementing a standard ordering process that includes dosing, monitoring (including frequency), and criteria to guide cisatracurium and vecuronium use. The use of ocular and sedative agents will also be encouraged in this process. The Department of Pharmacy Services recommends educating all services about the importance of documentation, including doses administered and doses credited when not administered to the patient.

9 Page 9 of 9 References: Society of Critical Care Medicine and American Society of Health System Pharmacists. Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient. Am J Health Syst Pharm. 2002;59: Baumann MH, McAlpin BW, Brown K, et al. A prospective randomized comparison of train of four monitoring and clinical assessment during continuous ICU cisatracurium paralysis. Chest. 2004;126: Rudis MI, Sikora CA, Angus E, et al. Retrospective pharmacoeconomic evaluation of dosing vecuronium by peripheral nerve stimulation versus standard clinical assessment in critically ill patients. Pharmacotherapy. 1997;17: