1. NEUROMUSCULAR BLOCKADE REVERSAL PRACTICE
Julia lienesch & carrie mcmahon
Gonzaga university
PROVIDENCE SACRED HEART MEDICAL CENTER
MARCH 20, 2014

2. STATEMENT OF THE PROBLEM
Residual neuromuscular blockade and its management are well-established topics in current literature
The incidence of residual blockade has not significantly declined even with the introduction of intermediate acting paralytics
From , 15 studies revealed 20-65% of postoperative incidence TOFR <0.9
Associated with hypoxia, weakness, aspiration, impairment of the hypoxic ventilatory drive, and respiratory failure

3. RESIDUAL BLOCKADE DEFINITION
TOFR of < 0.9
Clinical signs and symptoms of muscle weakness in the postoperative period
Evolution of TOFR standard for extubation
0.70.8currently 0.9
Increased respiratory events, pharyngeal dysfunction, and aspiration risk with TOFR <0.9 (Eriksson et al, 1997)

4. PURPOSE STATEMENT
“The purpose of this study was to assess, through survey, current practices among CRNAs in states from various regions regarding the use of reversal agents after pharmacologic neuromuscular blockade.”

5. RESEARCH QUESTIONS
To what degree are reversal agents being given by CRNAs after the administration of neuromuscular blocking agents?
What are the benefits and risks of neuromuscular blockade reversal?
What factors influence CRNAs’ management of neuromuscular blockade reversal?
How is the dose of reversal agent determined?

6. REVIEW OF LITERATURE MONITORING
Acceleromyography monitoring gold standard
Tactile fade lost at TOFR
5-second head lift possible at TOFR of <0.6
Pharyngeal tissue and upper esophageal sphincter dysfunction at TOFR  aspiration risk
Murphy et al. (2008)
Compared acceleromyography to conventional tactile TOF
TOFR ≤0.9 in PACU: 4.5% acceleromyography vs 30% conventional, P <0.0001
TOFR <0.7 in PACU: 0% acceleromyography vs 13.3% conventional, P<0.001
Acceleromyography had less respiratory events in PACU

7. REVIEW OF LITERATURE MONITORING
Clinical Tests
Tidal Volume: recovery of spontaneous breathing
Not reliable. Unchanged even when peripheral muscles are fully paralyzed.
Vital Capacity: ability to take deep breaths
Not sensitive enough. Unchanged with significant levels of paralysis at peripheral muscles.
Head or leg lift test >5 s
Not sensitive enough. Corresponds to TOFR >0.4. Useful to determine the optimal timing of reversal.
Tongue depressor test
Probably the most reliable clinical test. Corresponds to TOFR > Difficult to implement routinely.
(Plaud et al, 2010)

8. REVIEW OF LITERATURE MONITORING
Ulnar nerve superior site for planning emergence:
Less likelihood of direct muscle stimulation
Increased margin of safety as slower recovery vs diaphragm
5-fold increased risk of residual block when monitoring at eye
Placement
Electrode placement 2-6cm apart

9. REVIEW OF LITERATURE TIMING
Debaene, Plaud, Dilly, & Donati (2003)
Single dose of intermediate acting paralytic to 526 patients
No reversal and > two hours post-administration
16% TOFR of <0.7 and 45% TOFR <0.9 in PACU
Fuchs-Buder et al. (2010)
Addressed neostigmine dose for shallow levels of paralysis
Normal doses of neostigmine can produce paradoxical weakness at shallow residual paralysis (Caldwell, 1995)
Groups with TOFR 0.4 and 0.6 given neostigmine 0.01, 0.02, mg/kg, or none
Reversal at TOFR with neostigmine 0.02 mg/kg produced successful reversal within 10 minutes

10. REVIEW OF LITERATURE TIMING
Kim et al. (2004)
Administered neostigmine 0.07 mg/kg to surgical patients at a TOF of 1,2,3,4
Median times from neostigmine reversal administration until a TOFR of 0.9
TOF count 1 – 28.6minutes
TOF count 2 – 22.6 minutes
TOF count 3 – 15.6 minutes
TOF count 4 – 9.7 minutes
Authors recommend a TOF count of 4 for adequate reversal from rocuronium within 15 minutes
Thilen et al. (2012)
Every 10 minutes since paralytic dose = 10% less residual block

11. REVIEW OF LITERATURE NEOSTIGMINE DOSING
TOF 4/4 with minimal fade: mg/kg
TOF 2-3/4: mg/kg
Dosing >0.07 mg/kg unlikely to achieve additional effect (Kopman & Eikermann, 2009)
Avoiding blanket full reversal of light paralysis will minimize paradoxical weakness effect, risk for cholinergic crisis, and side effects
Most effective reversal when given >15-20 minutes prior to extubation (Brull & Murphy, 2010)

12. REVIEW OF LITERATURE PONV SIDE EFFECT
King et al. (1988) said Yes to PONV
38 orthopedic patients: Neostigmine 2.5mg/Atropine 1.2mg, 68% PONV compared with 32% at 24hr postop, (P<0.01)
Joshi et al. (1999) said No difference
100 ambulatory surgery, Neostigmine 2.5mg/Robinul 0.5mg, (P<0.05)
Hovorka et al. (1997) said No difference
DB*, 162 hysterectomy cases. Neostigmine 2mg/Robinul 0.4mg (P<0.05)
Cheng et al. (2005) said No difference
Lit review, 933 patients, compared Neostigmine 2.5 vs 1.5mg doses and Robinul vs Atropine (P=0.08)
Lovstad et al. (2001) said Yes to nausea
DB, 90 lap-gyn cases, Mivacurium, Neostigmine 0.05mg/kg + Robinul 0.01mg/kg. (P=0.03). First 6hrs, 30% vs 11% nausea. No difference in vomiting.
*(DB=double blind)

13. METHODOLOGY Qualitative study Online survey utilizing SurveyMonkey
Survey distributed via state CRNA organizations
Participants
289 CRNA survey participants
Participating states: WA, AZ, NC, MD

14. FINDINGS REVERSAL AND TIME

15. FINDINGS REVERSAL AND TIME

16. FINDINGS REVERSAL AND TIME

17. FINDINGS REVERSAL AND TIME

18. FINDINGS TOP 3 FACTORS

19. FINDINGS PATIENT FACTORS

20. FINDINGS SIDE EFFECTS

21. FINDINGS MONITORING

22. RECOMMENDATIONS
Time from last paralytic dose is not an adequate determinant of residual blockade
Monitoring of blockade should be standard practice
Acceleromyography superior as tactile fade lost at TOFR of 0.4
Not all patients need a full reversal dose
Risk for paradoxical weakness and increased side effects
Majority can benefit from a partial reversal dose
Increased PONV is inconclusive and appears to be dose-dependent
Faster recovery after reversal with increasing TOF count
Allow minutes after reversal for maximal effect

23. REFERENCES
Brull, S.J., & Murphy, G.S. (2010). Residual neuromuscular block: lessons unlearned. Part II: methods to reduce the risk of residual weakness. Anesthesia and Analgesia, 111(1),
Cheng, C., Sessler, D. I., & Apfel, C. C. (2005). Does neostigmine administration produce a clinically important increase in postoperative nausea and vomiting? Anesthesia & Analgesia, 101,
Debaene, B., Plaud, B., Dilly, M., & Donati, F. (2003). Residual paralysis in the PACU after a single intubating dose of nondepolarizing muscle relaxant with an intermediate duration of action. Anesthesiology, 98(5), Retrieved from
Eriksson, L. I., Sundman, E., Olsson, R., Nilsson, L., Witt, H., Ekberg, O., & Kuylenstierna, R. (1997). Functional assessment of the pharynx at rest and during swallowing in partially paralyzed humans: Simultaneous videomanometry and mechanomyography of awake human volunteers. Anesthesiology, 87(5), Retrieved from
Fuchs-Buder, T., Meistelman, C., Alla, F., Grandjean, A., Wuthrich, Y., & Donati, F. (2010). Antagonism of low degrees of Atracurium-induced neuromuscular blockade. Anesthesiology, 112(1),

24. REFERENCES
Hovorka, J., Korttila, K., Nelskyla, K., Soikkeli, A., Sarvela, J., Paatero, H., ... Yli-Hankala, A. (1997). Reversal of neuromuscular blockade with neostigmine has no effect on the incidence or severity of postoperative nausea and vomiting. Anesthesia & Analgesia, 85,
Joshi, G. P., Garg, S. A., Hailey, A., & Yu, S. Y. (1999). The effects of antagonizing residual neuromuscular blockade by neostigmine and glycopyrrolate on nausea and vomiting after ambulatory surgery. Anesthesia & Analgesia, 89,
Kim, K., Cheong, M., Lee, H., Lee, J. (2004) Tactile assessment for the reversibility of rocuronium induced neuromuscular blockade during propofol or sevoflurane anesthesia. Anesthesia Analgesia, 99,
King, M. T., Milazkiewicz, R., Carli, F., & Deacock, A. R. (1988). Influence of neostigmine on postoperative vomiting. British Journal of Anaesthesia, 61,
Kopman, A.F., & Eikermann, M. (2009). Antagonism of non-depolarising neuromuscular block: current practice. Anaesthesia, 64,

25. REFERENCES
Lovstad, R. Z., Thagaard, K. S., Berner, N. S., & Raeder, J. C. (2001). Neostigmine 5mcg/kg with glycopyrrolate increases postoperative nausea in women after laparoscopic gynaecological surgery. Acta Anaesthesiologica, 45,
Murphy, G. S., Szokol, J. W., Marymont, J. H., Greenberg, S. B., Avram, M. J., Vender, J. S., & Nisman, M. (2008). Intraoperative Acceleromyographic Monitoring Reduces the Risk of Residual Neuromuscular Blockade and Adverse Respiratory Events in the Postanesthesia Care Unit. Anesthesiology, 109,
Plaud, B., Debane, B., Donati, F., Marty, J. (2010) Residual paralysis after emergence from anesthesia. Anesthesiology, 112(4),
Thilen, S. R., Hansen, B. E., Ramaiah, R., Kent, C. D., Treggiari, M. M., & Bhananker, S. M. (2012). Intraoperative neuromuscular monitoring site and residual paralysis. Anesthesiology, 117,