Management of Rocuronium Neuromuscular Block using a Protocol for Qualitative Monitoring and Reversal with Neostigmine

Thilen R, Ng IC, Cain KC et al.

British Journal of Anaesthesia 2018: 121 (2): 367-377

Aim of Study

Background: The RECITE Study found an incidence of postoperative residual neuromuscular blockade (PRNB) of 64% at the time of tracheal extubation and 57% at the time of arrival to the post-anaesthesia care unit (PACU).

Hypothesis: Implementation of a protocol for the management of muscle relaxation and reversal with neostigmine would be associated with a lower risk of PRNB (nTOF <0.9) and of severe residual paralysis (nTOF <0.7) at the time of tracheal extubation.

Design and Location

• Prospective cohort study
• January to June 2016 (6 months)
• Harborview Medical Centre
• University of Washington Medical Centre

Methodology

Inclusion criteria: Elective abdominal surgery; Anticipated use of NMBDs; ASA 1-4; Free from underlying neuromuscular disorders

Exclusion criteria: Age <18 years; Pregnant or lactating women; Non-English speaking patients

Control period: Managed at the discretion of the anaesthesia providers.

Protocol period: Neuromuscular block and reversal according to the below protocol. No standardisation of any other aspects of care.

Intubation dose	Rocuronium 0.6mg/kg
Weight adjustment	All doses of NMBD and Neostigmine based on IBW
Gender adjustment	Dose reduction for females (15%)
Age adjustment	Dose reduction (1%) for each year >55 years
Incremental dosing	25% of intubation dose
Intraoperative management	Monitor adductor pollicis if feasible. If surgical need for relaxation re-dose at TOF count of 3; avoid total twitch depression; try to avoid re-dose during the last 30 min of the surgical procedure
Pre-reversal assessment	Always obtained by assessing the adductor pollicis response
Neostigmine timing	TOF count of 4 at the adductor pollicis confirmed by both the primary provider and the attending anaesthesiologist
Neostigmine dosing	TOF count of 4 with fade: 40mcg/kg TOF count of 4 without fade: 15-25mcg/kg
Extubation timing	Minimum of 10 minutes after neostigmine administration

Measurements: Three Train-of-Four (TOF) Ratios; Anaesthetic providers blinded to results

1. Baseline after induction of GA
2. Immediately before extubation
3. On arrival to PACU

Primary Outcome

• Incidence of postoperative residual neuromuscular block at the time of tracheal extubation defined as normalised train-of-four ratio <0.9.

Secondary Outcomes

• Incidence of severe postoperative residual neuromuscular block at the time of tracheal extubation defined as normalised train-of-four ratio <0.7
• Incidence of postoperative residual neuromuscular block at the time of arrival to the PACU
• Incidence of severe postoperative residual neuromuscular block at the time of arrival to the PACU

Statistics

• Students t-test and Fisher’s exact test to compare measures between protocol and control groups
• Sensitivity analyses to explore potential confounders

Results

• Incidence of postoperative residual neuromuscular block at tracheal extubation (TOF <0.9):
  • Protocol group: 14/40 (35%)
  • Control group: 22/38 (58%)
    • P=0.068
  • Controlling for duration of surgery, BMI and gender using exact logistic regression: P=0.020
• Incidence of severe postoperative residual neuromuscular block (TOF <0.7) at tracheal extubation:
  • Protocol group: 1/40 (3%)
  • Control group: 12/38 (32%)
    • P=0.001
• Incidence of postoperative residual neuromuscular block on arrival to PACU
  • Protocol group: 0 (0%)
  • Control group: 13 (38%)
    • P <0.001
• Incidence of severe postoperative residual neuromuscular block on arrival to PACU
  • Protocol group: 0 (0%)
  • Control group: 7 (21%)
    • P <0.001
• Short PACU Length of Stay
  • Protocol group: 42%
  • Control group: 16%
    • P=0.029
• No significant difference in timings of drug doses to extubation or transfer to PACU

Conclusions/Discussions

• The incidence of severe postoperative residual neuromuscular block was significantly reduced after the protocol was introduced.
• Strong evidence that the protocol is associated with a reduction in the incidence of residual paralysis.
• Better reversal from paralysis may be associated with a shorter PACU length of stay.
• A high percentage of patients continued to exhibit postoperative residual neuromuscular block at the time of extubation and on arrival in recovery.
• Most beneficial factors from the protocol were most likely:
  • Delaying neostigmine administration until the TOF count had returned for four palpable responses at the thumb.
  • Dosing neostigmine based on the presence or absence of fade using ideal body weight with dose adjustments for female gender and age, which may have led to more appropriate doses for reversal and reduced neostigmine-induced muscle weakness.

Stated Limitations from the Study

• Small sample size – failure to demonstrate significance in primary outcome is likely a Type 2 Statistical error due to an underpowered study.
• A bundled intervention: we do not know which component contributed most to improved outcomes.
• Clinicians were under observation by research assistants in both arms of the study, which may have biased practice.
• Not all anaesthetic providers agreed to participate in the protocol arm of the study, which may have biased practice.
• This was not a randomised controlled trial with a concurrent control group.
• Did not fully calibrate the TOF-Watch SX for baseline signal stabilisation

Discussion from Journal Club Meeting

• The risk of postoperative residual neuromuscular block can be reduced but not eliminated through the routine use of a peripheral nerve stimulator and neostigmine.
• Despite best practice a high percentage of patients continued to exhibit severe postoperative residual neuromuscular block at the time of extubation and on arrival in recovery.
• Is it time to move to Quantitative Neuromuscular Monitoring, particularly in at risk patient groups?

Summary by Dr P Daum. Journal Club Meeting 26 September 2018.