Monitoring of neuromuscular block in operative room and ICU

Josep Rodiera M.D. Ph.D. MsC

Marrakech 2016

Anesthesia DepartmentCentro Medico Teknon

Barcelona

Conflict of interest

Creator of the TOFCuff Concept

• Do you think that postoperative residual paralysis represents a

significant public health problem?

• Do you think that the routine use of neuromuscular monitoring

devices could decrease the incidence of postoperative residual

paralysis?

Europe n= 739USA n= 1792

Monitorization of NMB:Current situation

Monitorization of NMB:Current situation

Monitorization of NMB:Current situation

Europe n= 739USA n= 1792

EU USA

1. 70% TOF enough for extubate?

2. 80% TOF enough for extubate?

3. 90% TOF enough for extubate?

º

T.O.F. And Receptor occupancy

C. Thompson et al.

Current monitoring systems & devices

Twitch1

(T1) Twitch2

(T2) Twitch3

(T3) Twitch4

(T4)

Peripheral Nerve StimulatorsVisual or Tactile

Assessment

The absence of observed or tactile fade in response to TOFstimulation does not indicate adequacy of recovery fromneuromuscular blockade.Rodney G, Raju PKBC, Ball DR. Not just monitoring; a strategy for managing neuromuscular blockade.Anaesthesia 2015; 70: 1105–118.

Train-of-four fade is indistinguishable, even to experiencedobservers, once the TOF ratio exceeds 40%Viby-Mogenson J, Jenson NH, Engbaek J, Ording H, Skovgaard LT, Chaemmmer-Jorgensen B. Tactile andvisual evaluation of the response to train of four nerve stimulation. Anesthesiology 1985; 63: 440–3.

Stimulating Electrodes

Manual installation needed

Specific polarity to be kept

Using fragile connecting wires

Sensing Device

Manual installation needed

Sensitive to motionartifacts

Force Transducer-based Inertial Sensor-based

The hand needs to be strapped

Inertial Sensor-based

81% 80% 74% 71% 87% 75% 80% 81% 69% 76% 78% 71%

+ 16%

- 12% - 12%

Monitoring Neuromuscular Transmission with TOFCuff

Traditional Method

Como Funciona el TOFCuff?

Neuro Stimulation for Regional Anesthesia

Traditional MethodNeuro Stimulation the motor Nerve

How TOF Cuff work’s?

Flow Diagram

Cuff With Stimulating Electrodes(Qualitative Monitorization)

Muscle ContractionCuff Inflation Impedance OK

Stimulation Visual / Tactile Method

-0,6

-0,4

-0,2

0

0,2

0,4

0,6

0,8

1

1,2

1,4

10:15 AM

10:16 AM

10:17 AM

Pressure Changes in the Cuff during the Stimulation at Humeral level

T1 T2 T3 T4TOF

T1 T2 T3 T4TOF

-0,2

-0,1

0

0,1

0,2

0,3

0,4

0,5

1 88 175 262 349 436 523 610 697 784 871 958

31/03/1998 1:18 PM31/03/1998 1:19 PM31/03/1998 1:20 PM31/03/1998 1:21 PM

Pressure Changes in the Cuff during the Stimulation at Humeral level

Flow Diagram

Monitoring Neuromuscular Blockade with the Cuff(Quantitative Monitoring)

Muscle ContractionCuff Inflation Impedance OK

Stimulation Recording EvokedTOFCuff Pressure

Changes

By means of processing the cuff pressure, it is possible to obtain a quantitative measurement

-0,2

-0,1

0

0,1

0,2

0,3

0,4

0,5

1 86 171 256 341 426 511 596 681 766 851 936

31/03/98 1:18 PM

31/03/98 1:19 PM

31/03/98 1:20 PM

31/03/98 1:21 PM

Brachial plexus stimulation / Evaluation of the evoked response During Recovery

TOF-Cuff vs Mechanomyography

Recovery strategy

Giving time to spontaneous/neostigmine reversal

The average reversal time is approximately 12 minutes, as reported in recent studies.However, a large inter-individual variability exists. 10% of patients might need more than60 minutes to reach a TOF ratio of 0.9.

E.Dubois and J.P. Mulier. A review of the interest of Sugammadex for deep neuromuscular blockade management in Belgium. Acta AnesthesiologicaBelgica, 2013, 64, 49-60.

Fuchs-Buder T., Ziegenfuss T., Lysakowski K., Tassonyi E., Antagonism of vecuronium-induced neuromuscular block in patients pretreated withmagnesium sulphate : dose-effect relationship of neostigmine, b r . J. a naesth ., 82, 61-5, 1999.

Reid J. E., Breslin D. S., Mirakhur R. K., Hayes A. H., Neostigmine antagonism of rocuronium block during anesthesia with sevoflurane,isoflurane or propofol . c an . J. a naesth ., 48, 351-5, 2002.

Suzuki T., Masaki G., Ogawa S., Neostigmine-induced reversal of vecuronium in normal weight, overweight and obese female patients, b r . J. anaesth ., 97, 160-3, 2006.

Neostigmine reversal

Many studies have found a high incidence of residual neuromuscularblockade after anesthesia and surgery, with a range of 4-64%

Rodney G, Raju PKBC, Ball DR. Not just monitoring; a strategy for managing neuromuscular blockade. Anaesthesia 2015;70: 1105–118.

Naguib et al.’s meta-analysis of 24 studies demonstrated a pooledincidence of 41%

Naguib M, Kopman AF, Ensor JE. Neuromuscular monitoring and postoperative residual curarisation: a meta-analysis.British Journal of Anaesthesia 2007; 98: 302–16.

Baillard C, Gehan G, Rebou-Marty J, et al. Residual curarisation in the recovery room after vecuronium. British Journal ofAnaesthesia 2000; 84: 394–5.

Hayes AH, Mirakhur RK, Breslin DS, Reid JE, McCourt KC. Postoperative residual block after intermediate-actingneuromuscular blocking drugs. Anaes-thesia 2001; 56: 312–8.

Sugammadex vs Neostigmine action time

Sugammadex Reversal

Moderate Block

Deep Block

Intense Bloc

Neostigmines Sugammadex

Reversal TimeLong,

UnpredictableShort,

Predictable

Pulmonary Diseases(COPD, Asthma...)

Risk ofBronchospasm

Suitable 2

Cardiac Failureand Arrhythmias

QT prolongation,Brady/Tachycardia

Suitable 3

Renal Insufficiency Not Recommended Suitable 4

Elderly Patients(+75 years)

Risk PORC Unaffected 5

Obese PatientsDelay of Onset,

UnpredictableSuitable 6

Apnea SyndromeRisk of Upper

Airway ObstructionRisk of Upper

Airway Obstruction

Works with ‘Deep’ or ‘Intense’ Blocks?

No Yes1

Risk of PONV Yes No

Tramer M.R., Fuchs-Buder T., Omitting antagonism of neuromuscular block: effect on postoperativenausea and vomiting and risk of residual paralysis. A systematic review. br. J. anaesth., 82, 379-86, 1999.

Gaszynski T., Szewczyk T., Gaszynski W., Randomized comparison of sugammadex and neostigmine forreversal of rocuronium-induced muscle relaxation in morbidly obese undergoing general anaesthesia, br.J. anaesth., 108, 236-9, 2012.

Amao R., Zornow M.H., Cowan R.M., Cheng D.C., Morte J.B., Allard M.W., Use of sugammadex in patientswith a history of pulmonary disease, J.clin. anesth., 24, 289-97, 2012.

Caldwell J.E., Reversal of residual neuromuscular block with neostigmine at one to four hours after asingle intubating dose of vecuronium. anesth. analg., 80, 1168-74, 1995.

Lock G., Loureiro Fialho G., Castro Lima D., Simoes Almeida M.C., Electrocardiographic changes afterneostigmine-atropine mixture. J. anesth. clinic res., 3, 188, 2012.

Staals L.M., Snoeck M.M., Driessen J.J., Flockton E.A., Heeringa M., Hunter J.M., Multicentre, parallel-group, comparative trial evaluating the efficacy and safety of sugammadex in patients with end-stagerenal failure or normal renal function, br. J. anaesth., 101, 492-7, 2008.

Cammu G., Interactions of neuromuscular blocking drugs, acta anaesth. belg., 52, 357-363, 2001..

Suzuki T., Kitajima O., Ueda K., Kondo Y., Kato J., Ogawa S., Reversibility of rocuronium-induced profoundneuromuscular block with sugammadex in younger and older patients, br. J. anaesth., 106, 823-6, 2011.

Bartkowsky R. R., Incomplete reversal of pancuronium neuromuscular blockade by neostigmine,pyridostigmine and edrophonium, anesth. analg., 66, 594-598, 1987.

Eikermann M., Fassbender P., Malhotra A., Takahashi M., Kubo S., Jordan A. S., Gautam S., White D.P.,Chamberlin N. L., Unwarranted administration of acetylcholinesterase inhibitors can impair genioglossusand diaphragm muscle function, anesthesiology, 107, 621-9, 2007.

7

One then might ask oneself• No need to Monitor the NMT!!

• Sugammadex to everyone!!

POWER WITHOUT CONTROL IS NOTHING

Sugammadex – A reversal strategy

One then might ask oneself• No need to Monitor the NMT!!

• Sugammadex to everyone!!

• No need to Monitor the NMT!!

Cost per Patient Low

Neostigmines(Prostigmine®)

Sugammadex(BRIDION®)

Sales Formulation

High

Moderate Block (2 mg/Kg)

Deep Block (4 mg/Kg)

76,96 €

153,92 €

0,44-0,88 €

0,44-0,88 €

Emergency Rev. (16 mg/Kg) 461,76 €Not Applicable

So, an administration rationale needs to be stablished

Sugammadex-mandatory

0,5 mg/ml Vial5 ml (0,44€ per Vial)

200 mg and 500 mg Vials(76,96 € and 192,4 €)

Neostigmine-suitable

1

2 Eikermann M., Fassbender P., Malhotra A., Takahashi M., Kubo S., JordanA. S., Gautam S., White D.P., Chamberlin N. L., Unwarrantedadministration of acetylcholinesterase inhibitors can impair genioglossusand diaphragm muscle function, anesthesiology, 107, 621-9, 2007.

1 Assessment Committee for the uptake of new Hospital-use Drugs.OSAKIDETZA - Health & Consumer Department of the Basque CountryGovernment (Spain).

2 Bartkowsky R. R., Incomplete reversal of pancuronium neuromuscularblockade by neostigmine, pyridostigmine and edrophonium, anesth.analg., 66, 594-598, 1987.

3 4

Cost per Treatment (VAT not included), for an average patient of 70 Kg.

Moderate Block

Deep Block

Intense Bloc

2

Sugammadex-mandatory(no room for saving)

3 Ph. E. Dubois, J.P. Mulier, A review of the interest of Sugammadex fordeep neuromuscular blockade management in Belgium. Acta Anaesth.Belgica, 2013, 64, 49-60.

4 G. Rodney, P.K.B.C. Raju, D.R. Ball, Not just monitoring; a strategy formanaging neuromuscular blockade. Anaesthesia, 2015, 70, 1105-1118.

Reversal Strategy

Neostigmines(Prostigmine®)

Sugammadex(BRIDION®)

Sales Formulation

Moderate Block (2 mg/Kg)

Deep Block (4 mg/Kg)

76,96 €

153,92 €

0,44-0,88 €

0,44-0,88 €

Emergency Rev. (16 mg/Kg) 461,76 €Not Applicable

0,5 mg/ml Vial5 ml (0,44€ per Vial)

200 mg and 500 mg Vials(76,96 € and 192,4 €)

So, an administration rationale needs to be stablished

Sugammadex-mandatory Neostigmine-suitable

1

1

G.

Ro

dn

ey,

P.K

.B.C

.R

aju

,D

.R.

Bal

l,N

ot

just

mo

nit

ori

ng;

ast

rate

gyfo

rm

anag

ing

neu

rom

usc

ula

rb

lock

ade.

An

aest

hes

ia,

20

15

,70

,11

05

-11

18.

Saving 76 € per patient

Moderate Block

Deep Block

Intense Bloc

Saving 153 € per patient

Saving 76 €per patient

Saving 153 € per patient

Ph. E. Dubois, J.P. Mulier, A review of the interest ofSugammadex for deep neuromuscular blockade managementin Belgium. Acta Anaesth. Belgica, 2013, 64, 49-60.

TOFRATIO > 90%

ROCURONIUMInduction 0,6 mg/Kg.

ROCURONIUM(for levelling the patient at TOF COUNT = 1)

Infusion Pump (100 mg/250mL) 5-10µg/Kg/min

Bolus 0,15 mg/Kg

TOF COUNT = 0Post-Tetanic COUNT = 1-2

TOF COUNT = 1-3 TOF COUNT = 4

HIGH-RiskPatient

Surgery

EXTUBATION TOF RATIO > 90%

SUGAMMADEX4 mg/Kg

SUGAMMADEX2 mg/Kg

TOF RATIO < 40%

NEOSTIGMINE 40 µg/KgATROPINE 1 mg

TOF RATIO > 40%

NEOSTIGMINE 20 µg/Kg

ATROPINE 0,7 mg

NEOSTIGMINE 50 µg/KgATROPINE 1 mg

LOW-RiskPatient

Surgery

Wait for TOF COUNT = 3

HIG

H-R

isk

Pat

ien

t

Pulmonary Diseases (COPD, asthma…)

Sleep Apnea Syndrome

Cardiac failure and arrhythmias

Increased Age (+75 years)

Obesity (BMI >30)

Renal Insufficiency

Thoracotomy

Supraumbilical Laparotomy

Lumbotomy

Hypothermia

HIG

H-R

isk

Surg

erie

s

Reversal Strategy

Conclusions

• Residual paralysis is considered a important problem

• Neuromuscular monitoring could avoid the residual paralysis.

• There are consensus : Nueromuscular Monitoring should be

routine

• The TOFCuff concept has a clear clinical use

•A reversal strategy is recommended