4 03 2010 J P Mulier 1

1150 1850 1947 1977 2010

The place of Sugammadex The place of Sugammadex (Bridion(Bridion®®) )

in laparoscopic bariatric surgeryin laparoscopic bariatric surgery

Jan Paul Mulier, MD PhDJan Paul Mulier, MD PhDSint Jan Brugge-OostendeSint Jan Brugge-Oostende

4 03 2010 J P Mulier 2

OverviewOverview1.1. Current state of reversalCurrent state of reversal

Limitations / Potential risks with residual blockadeLimitations / Potential risks with residual blockade Techniques to reduce need for reversalTechniques to reduce need for reversal

2.2. Reversal with bridionReversal with bridion®® (Sugammadex) (Sugammadex) Mechanism of action / Pharmacokinetics, pharmacodynamicsMechanism of action / Pharmacokinetics, pharmacodynamics Efficacy / Safety - Practical dosageEfficacy / Safety - Practical dosage

3.3. Indications for bridion Indications for bridion ®® (Sugammadex)(Sugammadex)

““Can not intubate / can not ventilate”Can not intubate / can not ventilate” Rapid sequence induction for short proceduresRapid sequence induction for short procedures Continuous deep blockade till end of surgeryContinuous deep blockade till end of surgery Sudden / not predicted / need for awakeningSudden / not predicted / need for awakening Need for an amfetamine like arousal effectNeed for an amfetamine like arousal effect

4.4. Practical use in bariatric laparoscopyPractical use in bariatric laparoscopy Anaesthesia inductionAnaesthesia induction Anaesthesia maintenanceAnaesthesia maintenance Anaesthesia awakening ERAS technique of BrugesAnaesthesia awakening ERAS technique of Bruges

4 03 2010 J P Mulier 3

Limitations of Limitations of Cholinesterase InhibitorsCholinesterase Inhibitors

Relatively slow in reversing Relatively slow in reversing neuromuscular blockadeneuromuscular blockade

Insufficient or impossible to reverse Insufficient or impossible to reverse deep blockadedeep blockade

Require concomitant administration Require concomitant administration of anticholinergicsof anticholinergics

Well-known side effect profileWell-known side effect profile

Bartkowski RR. Anesth Analg. 1987;66:594-598.Kim KS et al. Anesth Analg. 2004;99:1080-1085.Kopman AF et al. J Clin Anesth. 2005;17:30-35.

4 03 2010 J P Mulier 4

Neostigmine (50 µg/kg) Neostigmine (50 µg/kg) Inadequately Reverses 95% Twitch Inadequately Reverses 95% Twitch

DepressionDepression

5 min5 min 10 min10 min 15 min15 min 20 min20 min

ROC ROC 0.6 0.6 mg/kgmg/kg

n = 20n = 20

TOF ratioTOF ratio 0.33 0.33 ±± 0.130.13

0.57 0.57 ±± 0.110.11

0.70 0.70 ±± 0.120.12

0.79 0.79 ±± 0.120.12

TOF < TOF < 0.90.9

100% (20)100% (20) 100% (20)100% (20) 95% (19)95% (19) 85% (17)85% (17)NEO, neostigmine; ROC, rocuronium; TOF, train-of-four. Kopman AF et al. J Clin Anesth. 2005;17:30-35.

NEO administered

10 min 20 min 30 min

T1 = 100%

T1 = 50%Solid area = height of T4

Hatched area = height of T1

Vecuronium ProtocolVecuronium Protocol

Rocuronium ProtocolRocuronium Protocol

4 03 2010 J P Mulier 5

Side Effects Associated With Side Effects Associated With Current Reversal AgentsCurrent Reversal Agents

ChE inhibitors in the reversal can cause ChE inhibitors in the reversal can cause Bradycardia / HypersalivationBradycardia / Hypersalivation Bronchospasm / Increased bronchial Bronchospasm / Increased bronchial

secretionssecretions Urinary frequency / Urinary frequency / NauseaNausea and vomiting and vomiting

Coadministration of antimuscarinic Coadministration of antimuscarinic agentsagents TachycardiaTachycardia Dryness of mouth and noseDryness of mouth and nose Mydriasis / Urinary retentionMydriasis / Urinary retention

Neostigmine Methylsulfate Injection [package insert]; 2002. Atropine Sulfate Injection, USP [package insert]; 2003.

Glycopyrrolate Injection, USP [package insert]; 2006.

ChE, cholinesterase. *Atropine use causes dose-dependent adverse effects.

4 03 2010 J P Mulier 6

Increased Risk AssociatedIncreased Risk AssociatedWith Residual BlockadeWith Residual Blockade

Increased risk of postoperative Increased risk of postoperative pulmonary complications pulmonary complications coughing, expectoration, pain when coughing, expectoration, pain when

breathing, increased risk of breathing, increased risk of aspirationaspiration; ; Hypoxemia, hypercapnia, the need for Hypoxemia, hypercapnia, the need for reintubation, non invasive reintubation, non invasive ventilationventilation

delaydelay in meeting PACU discharge in meeting PACU discharge criteria and achieving actual criteria and achieving actual dischargedischarge

Berg H et al. Acta Anaesthesiol Scand. 1997;41:1095-1103.Bissinger U et al. Physiol Res. 2000;49:455-462.

Eikermann M et al. Anesth Analg. 2006;102:937-942.Murphy GS. Minerva Anestesiol. 2006;72:97-109. PACU, post anaesthesiology care unit

4 03 2010 J P Mulier 7

What was our answer before What was our answer before Bridion?Bridion?

Waiting for reversal before awakening, Waiting for reversal before awakening, extubation and transfer to PACUextubation and transfer to PACU Turnover time increased or ventilation in PACUTurnover time increased or ventilation in PACU

Incomplete reversal at extubationIncomplete reversal at extubation If patient can breath it is oke?If patient can breath it is oke? If patient can lift head it is oke?If patient can lift head it is oke? Ad midazolam so patients are not aware?Ad midazolam so patients are not aware?

Earlier decurarisation Earlier decurarisation (spont or neostigmine)(spont or neostigmine) Is every surgeon happy?Is every surgeon happy?

Extra dose neostigmine Extra dose neostigmine has only little effect but could even worsen decurarisation. has only little effect but could even worsen decurarisation.

Inject water instead of NMB Inject water instead of NMB To make your surgeon happy?To make your surgeon happy?

Be a transdisciplinary team Be a transdisciplinary team do you really know what surgeons think?do you really know what surgeons think?

4 03 2010 J P Mulier 8

My technique My technique (before Bridion)(before Bridion) to to reduce the need for reversal in reduce the need for reversal in

laparoscopylaparoscopy

Measure Abdominal ComplianceMeasure Abdominal Compliance Measure abdominal compliance and Measure abdominal compliance and

give less relaxants if Compliance is give less relaxants if Compliance is large.large.

Or use 2 MAC deep inhalation Or use 2 MAC deep inhalation anaesthesia at end surgery.anaesthesia at end surgery.

Use pressure support ventilation to Use pressure support ventilation to prevent patient from breathing against prevent patient from breathing against ventilator.ventilator.

4 03 2010 J P Mulier 9

Are NMB needed ?Are NMB needed ? Gynecologic laparoscopy without Gynecologic laparoscopy without

curarecurare is possible. is possible. ChassardChassard D D. Ann Fr Anesth Reanim. 1996;15(7):1013-7. Ann Fr Anesth Reanim. 1996;15(7):1013-7

Only when compliance is very high?Only when compliance is very high? Or when surgeons do not complain?Or when surgeons do not complain?

4 03 2010 J P Mulier 10

APVR descriptionAPVR description

Measure pressure volume relationMeasure pressure volume relation Angle is compliance or elastance EAngle is compliance or elastance E Section with Y axis is PV0: Section with Y axis is PV0: pressure at zero pressure at zero

volvol

0

2

4

6

8

10

12

14

16

18

0 0,5 1 1,5 2 2,5

liter

mm

Hg

P = 3,30 V + 8,40 mmHgSquared R = 0,96

E : 3,3 mmHg/LPV0 : 8,4 mmHg

4 03 2010 J P Mulier 11

E en PV0 determined by ?E en PV0 determined by ?

factors PV0 PVO sig E E sig

Age Neg 0.828 Pos 0.003*

Length Neg 0.356 Neg 0.245

Body weigth Pos 0.012*

Pos 0.294

Bmi neg 0.054 Neg 0.272

Sex Neg 0.596 Neg 0.536

Gravidity Neg 0.305 Neg 0.049*

Prev abd operation Neg 0.191 Neg 0.009*

Muscle relaxation Neg 0.001*

Neg 0.376

* Sig p<0.05

Mulier Dillemans ESA 2007Mulier Dillemans ESA 2007

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Patient with no effect of NMBPatient with no effect of NMB

0

5

10

15

20

25

0 1 2 3 4 5

No muscles in abd wall, No muscles in abd wall, diaphragm ?diaphragm ?

Fully relaxed by other factors ?Fully relaxed by other factors ? TOF > 90%TOF > 90% TOF = ¼TOF = ¼ TOF 0/4 and PTC < 5TOF 0/4 and PTC < 5

4 03 2010 J P Mulier 13

Why NMB sometimes have no Why NMB sometimes have no effect on APVR? effect on APVR?

Muscle total relaxed before giving Muscle total relaxed before giving NMB.NMB. Deep anesthesia?Deep anesthesia? Volatile anesthetics?Volatile anesthetics?

Muscle very thin or non existentMuscle very thin or non existent Muscle fascia parallel Muscle fascia parallel

4 03 2010 J P Mulier 14

Pig: High dose desfl sevo Pig: High dose desfl sevo Zelfde spier relaxatie effect sevo en desflZelfde spier relaxatie effect sevo en desfl

data JPMulier 2009data JPMulier 2009

2A 2B 3A 3B 4 5geen pavulon meting 1geen pavulonna pavulon geplooide voet

vol control sevofl 2 M Desfl 2 M pav + sevo pav + desf0,1 3 6 2 2 2 20,2 4 5 2 2 2 30,3 4 4 2 3 2 30,4 4 5 3 3 3 30,5 4 4 3 3 3 30,6 4 5 3 3 3 40,7 5 5 3 3 3 40,8 5 5 3 4 3 40,9 5 5 3 4 3 4

1 5 5 3 4 3 41,1 5 5 4 4 4 41,2 5 5 4 4 4 41,3 5 5 4 4 4 51,4 5 5 4 4 4 51,5 6 6 4 4 4 51,6 6 5 4 4 4 51,7 6 6 4 5 4 51,8 7 6 4 5 4 5

05

101520253035

0 2 4 6 8

vol liter

mm

Hg

controlsevofl 2 MDesfl 2 Mpav + sevopav + desf

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Effect of valsalva: breathing Effect of valsalva: breathing against ventilatoragainst ventilator

PV loops with fit

0

10

20

30

40

-0,5 0 0,5 1 1,5 2 2,5

IAV liter

IAP

mm

Hg

IAP

Valsalva is an active muscle contraction Valsalva is an active muscle contraction different from breathing to increase the different from breathing to increase the abdominal pressureabdominal pressure

Happens when patient reacts on Happens when patient reacts on Controlled VentilationControlled Ventilation

0

5

10

15

20

25

30

35

40

45

0 500 1000 1500 2000 2500 3000

IAP

mm

hg

-0,5

0

0,5

1

1,5

2

2,5

IAV

lite

r

IAP

IAV

no relaxation valsalva contract relaxation

4 03 2010 J P Mulier 16

BMI effect on abdominal P/V BMI effect on abdominal P/V relationrelation

Effect of BMI on PV0

-4

-2

0

2

4

6

8

10

0 10 20 30 40 50 60

BMI

PV

0 in

mm

Hg

Effect of BMI on E

0

0,002

0,004

0,006

0,008

0,01

0,012

0 20 40 60

BMI

E in

mm

Hg

/l

J Mulier ISPUB 2009J Mulier ISPUB 2009 Pressure volume relation is linearPressure volume relation is linear PV0 and E define each patientPV0 and E define each patient

J Mulier IFSO 2007J Mulier IFSO 2007

4 03 2010 J P Mulier 17

Android versus Gynoid fat Android versus Gynoid fat distribution has a different distribution has a different

ElastanceElastance

Abdominal pressure volume relation: Android vs Gynoid

0

5

10

15

20

25

0 1 2 3 4

IAV Liter

IAP

mm

Hg

android

gynoid

4 03 2010 J P Mulier 18

Waist to Hip ratio Waist to Hip ratio (WHR)(WHR)

Man normal WHR: 0,9Man normal WHR: 0,9 Woman normal WHR: 0,7Woman normal WHR: 0,7

Android fat distributionAndroid fat distribution WHR > 0,8WHR > 0,8

Gynoid fat distributionGynoid fat distribution WHR < 0,8WHR < 0,8

4 03 2010 J P Mulier 19

Remember:Patient type Remember:Patient type with a high mortality riskwith a high mortality risk

Elderly male diabetes patient Elderly male diabetes patient with hypertension and being with hypertension and being super obese, no weigth loss.super obese, no weigth loss. Buchwald 2007Buchwald 2007

Central abdominal fat, not Central abdominal fat, not stopped smoking, alcoholicstopped smoking, alcoholic General risk General risk

Asthma and coronary artery Asthma and coronary artery diseasedisease Cardio pulmonary risksCardio pulmonary risks

4 03 2010 J P Mulier 20

Two types of android Two types of android obesityobesity

Intra visceral adiposity Intra visceral adiposity Extra visceral Extra visceral adiposityadiposity

Subcutaneus fat is scant and Subcutaneus fat is thick and Subcutaneus fat is scant and Subcutaneus fat is thick and

intra abdominal fat is thick and intra abdominal fat is scant.intra abdominal fat is thick and intra abdominal fat is scant.

Subcutaneus FatSubcutaneus Fat Visceral fatVisceral fat

4 03 2010 J P Mulier 21

The obese patient is a challenge The obese patient is a challenge for anaesthesia for anaesthesia

if android shape with intra visceral if android shape with intra visceral fat.fat.

4 03 2010 J P Mulier 22

NMB effect on E - PV0NMB effect on E - PV0

E or Compliance unchangedE or Compliance unchanged E determined by fascia, size and shapeE determined by fascia, size and shape

PV0 drops =extra volume at same PV0 drops =extra volume at same pressurepressure

4 03 2010 J P Mulier 23

How to change PV0?How to change PV0?

Mulier Dillemans 2008Mulier Dillemans 2008 NMBNMB Inhalation anesthesia > 2 MACInhalation anesthesia > 2 MAC Table inclination: trendelenburgTable inclination: trendelenburg Smaller tidal volume ventilationSmaller tidal volume ventilation Lower peepLower peep

4 03 2010 J P Mulier 24

How to change E : hip flexionHow to change E : hip flexion

Mulier JP, Dillemans B Obes Surg Mulier JP, Dillemans B Obes Surg 20092009

4 03 2010 J P Mulier 25

Begin – End of first Begin – End of first laparoscopylaparoscopy

Abdominal compliance Abdominal compliance changes during changes during pneumoperitoneumpneumoperitoneum

Inflation volume rises Inflation volume rises more than 1 liter!more than 1 liter!

No NMB needed at No NMB needed at end of operation ?end of operation ?

Effect of 1 hour laparoscopy

0

5

10

15

20

25

0 0,5 1 1,5 2 2,5 3 3,5

IAV: liter

IAP

: m

mH

g

Begin laparoscopy

End laparoscopy

One Hour Laparoscopy at 15 mmHg Elongates the Abdominal Wall

Mulier IFSO 2009

4 03 2010 J P Mulier 26

Laparoscopy without muscle Laparoscopy without muscle relaxants ?relaxants ?

Laparoscopy is possible without Laparoscopy is possible without muscle relaxants or at reduced dose if muscle relaxants or at reduced dose if adominal compliance > 0,5 L/mmHgadominal compliance > 0,5 L/mmHg IAV > 4 L at 15 mmHg at start laparoscopyIAV > 4 L at 15 mmHg at start laparoscopy

Gravidity > 3Gravidity > 3 Previous multiple laparoscopies/laparotomiesPrevious multiple laparoscopies/laparotomies > 10 kg weight reduction> 10 kg weight reduction No man with android fat distributionNo man with android fat distribution

andand Sufficient deep sleep Sufficient deep sleep

As patient should not breath against ventilator.As patient should not breath against ventilator. Pressure support ventilationPressure support ventilation

Easier to prevent breathing against ventilatorEasier to prevent breathing against ventilator

4 03 2010 J P Mulier 27

Are NMB needed in Are NMB needed in laparoscopy?laparoscopy?

No if abdominal compliance is large No if abdominal compliance is large Yes as inflation pressure can be Yes as inflation pressure can be

lower lower Yes to prevent breathing agains Yes to prevent breathing agains

ventilatorventilator After one hour laparoscopy After one hour laparoscopy

compliance is rosencompliance is rosen

4 03 2010 J P Mulier 28

PSVPSV

PSV is not a PSV is not a valsalva valsalva effect: IAV is effect: IAV is not changing.not changing.

PSV is PSV is possible possible during deep during deep muscle muscle relaxation.relaxation.

PSVPro during esmeron infusion

-5

0

5

10

15

20

25

time

0

20

40

60

80

100

120

EtCO2

NMT count

RR(CO2)

PTCount

SpO2

PROFOUND MUSCLE RELAXATION DOES NOT DISTURB PROFOUND MUSCLE RELAXATION DOES NOT DISTURB PRESSURE SUPPORT VENTILATION. PRESSURE SUPPORT VENTILATION.

Mulier J, Blacoe D PGA 2009Mulier J, Blacoe D PGA 2009

4 03 2010 J P Mulier 29

Is deep relaxation needed and Is deep relaxation needed and possiblepossible??

Time between end Time between end pneumoperitoneum and end pneumoperitoneum and end operation is very short: in 5 min operation is very short: in 5 min from TOF 0/4 -¼ till 90% is not from TOF 0/4 -¼ till 90% is not possible with neostigmine.possible with neostigmine.

Sugammadex Sugammadex TOF 0/4 till end pneumoperitoneumTOF 0/4 till end pneumoperitoneum Very deep NMB PTC < 5 is possible till Very deep NMB PTC < 5 is possible till

the endthe end

4 03 2010 J P Mulier 30

Effect deep muscle relaxation Effect deep muscle relaxation on IAP with constant IAVon IAP with constant IAV

Gradual pressure drop until flat lineGradual pressure drop until flat line Max effect at TOF 0/4Max effect at TOF 0/4 At PTC 0 no extra pressure dropAt PTC 0 no extra pressure drop

effect of deeping relaxation with cst IAV

0

500

1000

1500

2000

2500

1 6 11 16 21 26 31 36 41 46 51 56 61 66 71 76

TO

F a

ns

we

r

0

2

4

6

8

10

12

14

16

IAP

NMT(R1)

NMT(R4)

IAP

TOF 4/4 TOF ¼ PTC 10 PTC 5 PTC 0 TOF 4/4 TOF ¼ PTC 10 PTC 5 PTC 0

4 03 2010 J P Mulier 31

Effect of deep muscle Effect of deep muscle relaxation on abdominal PV relaxation on abdominal PV

looploop

TOF > 90%TOF > 90% TOF = ¼ - 0/4TOF = ¼ - 0/4 TOF 0/4 and PTC < 5TOF 0/4 and PTC < 5

02468

101214161820

-1 -0,5 0 0,5 1 1,5 2 2,5

4 03 2010 J P Mulier 32

Conclusion: NMB neededConclusion: NMB needed

Yes Yes Larger surgical workvolume for lower Larger surgical workvolume for lower

pressurespressures At low pressures less structural damage and At low pressures less structural damage and

less post op pain?less post op pain? Sometimes no sufficient workspace and angry Sometimes no sufficient workspace and angry

surgeons: try to do everything.surgeons: try to do everything.

NoNo Abd Compliance sometimes large enoughAbd Compliance sometimes large enough Work at higher intra abd pressure?Work at higher intra abd pressure? 2 MAC inhalation has same effect? 2 MAC inhalation has same effect? Effect of position and of time?Effect of position and of time?

Meten is weten (Measuring is knowing!)Meten is weten (Measuring is knowing!)

4 03 2010 J P Mulier 33

If Yes -> decurarisation If Yes -> decurarisation neededneeded

Only Brideon is able to do so ?Only Brideon is able to do so ?

4 03 2010 J P Mulier 34

Bridion’s Mechanism of Action Bridion’s Mechanism of Action Is Unlike Traditional Reversal Is Unlike Traditional Reversal

AgentsAgents

Adam JM et al. J Med Chem. 2002;45:1806-1816.

NMBA

NMB

Choline+

acetate

AChE

ACh

nAChR

Conventional NMB Reversal

Choline+

acetate

AChE

AChNMBA

nAChR

ChE inhibitors(eg, neostigmine)

Reversal With Bridion

Choline+

acetate

AChE

ACh

NMBA

nAChR Hostmolecule

ACh, acetylcholine; AChE, acetylcholinesterase.ChE, cholinesterase; nAChR, nicotinic acetylcholine receptor;NMBA, neuromuscular blocking agent; NMB, neuromuscular blockade.

4 03 2010 J P Mulier 35

Cameron KS et al. Org Lett. 2002;4:3403-3406. Gijsenbergh F et al. Anesthesiology. 2005;103:695-703.

Encapsulation of Encapsulation of Rocuronium By BridionRocuronium By Bridion

4 03 2010 J P Mulier 36

What happens when Bridion is What happens when Bridion is injected?injected?

= Esmeron

4 03 2010 J P Mulier 37

What happens when Bridion is What happens when Bridion is injected?injected?

= Bridion

4 03 2010 J P Mulier 38

What happens when Bridion is What happens when Bridion is injected?injected?

= Bridion - Esmeron complex

4 03 2010 J P Mulier 39

What happens when Bridion is What happens when Bridion is injected?injected?

= Bridion - Esmeron complex

4 03 2010 J P Mulier 40

What happens when Bridion is What happens when Bridion is injected?injected?

= Bridion - Esmeron complex

4 03 2010 J P Mulier 41

Bridion Bridion PharmacokineticsPharmacokinetics

VVssss 11 to 14 L 11 to 14 L

TT½½ elimination 1.8 hours elimination 1.8 hours Cl estimated to be ~88 mL/minCl estimated to be ~88 mL/min Major route of elimination: renalMajor route of elimination: renal

96% of the dose excreted in urine, of 96% of the dose excreted in urine, of which which at least 95% could be attributed to at least 95% could be attributed to unchanged Bridionunchanged Bridion

Cl, clearance; T½, half-life; Vss, volume of distribution at steady state.

Data on file.Bridion® [summary of product characteristics]Organon, Europe; 2008.

4 03 2010 J P Mulier 42

Various Depths of Various Depths of Blockade Blockade

Intense block: no response to either TOF or PTC Intense block: no response to either TOF or PTC stimulationstimulation

Deep block: response to PTC but not to TOF stimulationDeep block: response to PTC but not to TOF stimulation Moderate block: reappearance of response to TOF Moderate block: reappearance of response to TOF

stimulationstimulation Superficial block: reappearance of T4 Superficial block: reappearance of T4 T4/T1 ratio > 1%T4/T1 ratio > 1% No block: T4/T1 ratio > 90 %No block: T4/T1 ratio > 90 %

PTC 0 PTC ≥1

Intense block Deep block Moderate block

TOF count 0 TOF count 0 TOF count 1-3

Level of block

Response to TOF

Response to PTC

PTC, posttetanic count; TOF, train-of-four. Fuchs-Buder T et al. Acta Anaesthesiol Scand. 2007;51:789-808.

Posttetaniccount

Twitchresponse

Twitchpercentage

Superficial block

TOF count 4T1/T4 %

4 03 2010 J P Mulier 43

Increased Flexibility in the Increased Flexibility in the Time of ReversalTime of Reversal

Immediate Reversal*Immediate Reversal* Within 3 min following administration of Within 3 min following administration of

rocuronium, rocuronium, 16 mg/kg16 mg/kg Routine ReversalRoutine Reversal

4 mg/kg4 mg/kg if recovery has reached 1 if recovery has reached 1––2 PTC 2 PTC (deep blockade)(deep blockade)

2 mg/kg2 mg/kg if spontaneous recovery has reached if spontaneous recovery has reached the reappearance of Tthe reappearance of T22 (moderate blockade) (moderate blockade)

Bridion allows full relaxation until Bridion allows full relaxation until the end of surgical proceduresthe end of surgical procedures

*Only recommended with rocuronium-induced blockade.PTC, posttetanic count.

Data on file.Bridion® [summary of product characteristics]. Organon, Europe; 2008.

4 03 2010 J P Mulier 44

Recommended dosageRecommended dosage

16 mg/kg16 mg/kg intense blockintense block 4 mg/kg4 mg/kg deep blockdeep block 2 mg/kg2 mg/kg all other blocksall other blocks

Maximum safety: Maximum safety: overloading t1/2 longer than rocoverloading t1/2 longer than roc Fastest reversalFastest reversal Never recurarisationNever recurarisation Individual variation coveredIndividual variation covered

Less? Less? No studies yetNo studies yet Re-occurrence of relaxationRe-occurrence of relaxation

TBW or IBW ?TBW or IBW ? No studies yet but as rocuronium is dosed according No studies yet but as rocuronium is dosed according

to IBW and has the same water solubility ???to IBW and has the same water solubility ??? Combination with neostigmine is possible but Combination with neostigmine is possible but

you get the side effects back.you get the side effects back.

4 03 2010 J P Mulier 45

Practical bridion usePractical bridion use

Vial 2 ml, 100 mg/ml 200 mg per Vial 2 ml, 100 mg/ml 200 mg per vialvial

2 mg/kg in a 70 kg person: 2 mg/kg in a 70 kg person: 140 mg one vial140 mg one vial

2 mg/kg in a 200 kg person:2 mg/kg in a 200 kg person: 400 mg or two vials or IBW 140 mg?400 mg or two vials or IBW 140 mg?

Is the patient, willing to pay for it?Is the patient, willing to pay for it? Yes ifYes if

previous history of rest curarisationprevious history of rest curarisation you explain that procedure you explain that procedure

is otherwise not safeis otherwise not safe might take longermight take longer Is not possibleIs not possible

You prevent post op complications?You prevent post op complications?

4 03 2010 J P Mulier 46

Measure Depth of Measure Depth of Blockade Blockade

Intense block: 16 mg/kgIntense block: 16 mg/kg Deep block: 4 mg/kgDeep block: 4 mg/kg Moderate block: 2 mg/kgModerate block: 2 mg/kg + Neostigmine?+ Neostigmine? Superficial block: 1 mg/kgSuperficial block: 1 mg/kg + Neostigmine? + Neostigmine? No block: 0 mg/kgNo block: 0 mg/kg

PTC 0 PTC ≥1

Intense block Deep block Moderate block

TOF count 0 TOF count 0 TOF count 1-3

Level of block

Response to TOF

Response to PTC

PTC, posttetanic count; TOF, train-of-four. Fuchs-Buder T et al. Acta Anaesthesiol Scand. 2007;51:789-808.

Posttetaniccount

Twitchresponse

Twitchpercentage

Superficial block

TOF count 4T1/T4 %

4 03 2010 J P Mulier 47

More Rapid Recovery With Bridion More Rapid Recovery With Bridion From From

TT2 2 Following RocuroniumFollowing Rocuronium

Rocuronium 0.6 mg/kg Neostigmine 50 µg/kg(%)

100

50

7:49:34 7:59:34 8:09:34 8:19:34 8:29:49 8:39:49 8:50:03 9:00:19 9:10:19 9:20:34 9:30:49 9:41:04

Rocuronium 0.6 mg/kg Bridion 2 mg/kg(%)

100

50

10:21:06 10:32:38 10:44:08 10:55:38 11:07:08 11:18:53 11:30:38 11:42:08 11:53:53 12:04:39 12:13:56

Data from Aurora trial.

TOF ratioTwitch height

TOF, train-of-four.

4 03 2010 J P Mulier 48

Faster Reversal from Rocuronium at Faster Reversal from Rocuronium at reappearance of 2 Countsreappearance of 2 Counts

Recovery of TOF Ratio to 0.9

2,7

49

0

10

20

30

40

50

60

Med

ian

Tim

e t

o R

eco

very

(m

in)

CI, confidence interval, NEO, neostigmine. Data from Signal trial.

n = 37NEO 70 µg/kg

95% CI (35.7–59.5 min)

Bridion 4 mg/kg

95% CI (2.3–3.3 min)n = 37

4 03 2010 J P Mulier 49

Time From TTime From T11 10% to 90% 10% to 90% Within SubjectWithin Subject

T1=10% T1=90% T1=10% T1=90%Rocuronium 1.2 mg/kg +

Bridion 16 mg/kgSuccinylcholine 1.0 mg/kg

0

5

10

15

20

Min

ute

s

Data from Spectrum trial.

n = 56 n = 54

4 03 2010 J P Mulier 50

Immediate Reversal Immediate Reversal of Intense Blockadeof Intense Blockade

0

2

4

6

8

10

12

14

Me

an

(2

*SE

M)

Tim

e (

min

)

Rocuronium 1.2 mg/kg Bridion 16 mg/kg Succinylcholine 1 mg/kg

*P < 0.0001 versus succinylcholine treatment group; results based on intent-to-treat population.SEM, standard error of mean. Data from Spectrum trial.

3 minBridion administered

T1 to 10% T1 to 90%

*

*

1.4

3.27.1

10.9

n = 56 n = 54 n = 56 n = 54

4 03 2010 J P Mulier 51

Rapid Dose-Dependent Reversal FromRapid Dose-Dependent Reversal FromTT22 in Children and Adolescents in Children and Adolescents

Following Rocuronium 0.6 mg/kgFollowing Rocuronium 0.6 mg/kg

Recovery of TOF Ratio to 0.9

1,2 1,1 1,2

0,61,1

1,4

0

1

2

3

4

5

Children Adolescents Adults

Med

ian

Tim

e t

o R

eco

very

(m

in)

Bridion 2 mg/kg*

Bridion 4 mg/kg

TOF, train-of-four.*Approved dose in children and adolescents. Data from Libra trial.

4 03 2010 J P Mulier 52

No Dose Adjustment Required No Dose Adjustment Required With Increasing AgeWith Increasing Age

Recovery of TOF ratio to 0.9*

2,22,6

3,6

0

1

2

3

4

5

18–64 65–74 75+

Me

dia

n T

ime

to

Re

co

ve

ry (

min

)

TOF, train-of-four. *Reversal from T2 following rocuronium 0.6 mg/kg

Data from Diamond trial.Bridion® [summary of product characteristics].

Organon, Europe; 2008.

n = 48 n = 62 n = 40

Age, yr

4 03 2010 J P Mulier 53

Bridion Has a Demonstrated Bridion Has a Demonstrated Safety Profile Safety Profile

Bridion has been studied in >2000 clinical Bridion has been studied in >2000 clinical trial subjects trial subjects

Safety has been demonstrated in patients Safety has been demonstrated in patients with cardiac and pulmonary disease with cardiac and pulmonary disease

Bridion is not recommended in patients Bridion is not recommended in patients with severe renal failure (CrCl <30 ml/min)with severe renal failure (CrCl <30 ml/min)

Great caution should be taken in patients Great caution should be taken in patients with severe hepatic diseasewith severe hepatic diseaseDedicated studies in this population have not Dedicated studies in this population have not

taken placetaken place

CrCl, creatinine clearance. Data on file.

Bridion® [summary of product characteristics]. Organon, Europe; 2008.

4 03 2010 J P Mulier 54

Drug-Drug Interactions Drug-Drug Interactions Affecting the Efficacy of Affecting the Efficacy of

BridionBridion No clinically relevant drug interactions have been No clinically relevant drug interactions have been

reported with Bridionreported with Bridion Pharmacokinetic-pharmacodynamic simulations Pharmacokinetic-pharmacodynamic simulations

show that the following show that the following displacementdisplacement interactions interactions are possible:are possible: ToremifeneToremifene

The recovery to TThe recovery to T44/T/T11 ratio of 0.9 could be delayed in patients who ratio of 0.9 could be delayed in patients who have received toremifene on the same day of surgery have received toremifene on the same day of surgery

Intravenous administration of high-dose flucloxacillin* Intravenous administration of high-dose flucloxacillin*

and fusidic acidand fusidic acid The recovery to TThe recovery to T44/T/T11 ratio of 0.9 could be delayed in patients who ratio of 0.9 could be delayed in patients who

receive these products in the preoperative phase receive these products in the preoperative phase Administration of these products in the postoperative phase Administration of these products in the postoperative phase

(6 hours) is to be avoided (6 hours) is to be avoided *Infusion of 500 mg or more.

Data on file.Bridion® [summary of product characteristics]. Organon, Europe; 2008.

4 03 2010 J P Mulier 55

Drug-Drug Interactions Drug-Drug Interactions Affecting the Efficacy of Other Affecting the Efficacy of Other

DrugsDrugs

Pharmacokinetic-pharmacodynamic Pharmacokinetic-pharmacodynamic simulations show that the following simulations show that the following capturingcapturing interaction is possible: interaction is possible: Hormonal contraceptives Hormonal contraceptives

An interaction between 4 mg/kg Bridion An interaction between 4 mg/kg Bridion and a progestogen could lead to a and a progestogen could lead to a decrease in progestogen exposure, 34% of decrease in progestogen exposure, 34% of AUC, which is similar to that of a missed AUC, which is similar to that of a missed dose of oral contraceptive dose of oral contraceptive

AUC, area under the curve.Data on file.

Bridion® [summary of product characteristics]. Organon, Europe; 2008.

4 03 2010 J P Mulier 56

““Can not intubate / can not Can not intubate / can not ventilate”ventilate”

How frequently ?How frequently ? Did you ever awakened your patient Did you ever awakened your patient

immediately within the first 30 immediately within the first 30 minutes?minutes?

Conclusion:Conclusion: It feels safe to have a drug available to It feels safe to have a drug available to

bring patient immediately back to bring patient immediately back to spontaneous breathing and to cancel the spontaneous breathing and to cancel the surgery. surgery.

Always have it never use it?Always have it never use it?

4 03 2010 J P Mulier 57

Rapid sequence / Crush inductionRapid sequence / Crush induction

Who is at Risk for aspiration?Who is at Risk for aspiration? Food or drank recentlyFood or drank recently ObstructionObstruction PregnantPregnant Super obeseSuper obese Previous bariatric surgeryPrevious bariatric surgery

Long procedure: high dose of NMBLong procedure: high dose of NMB No need for bridion or succinylcholineNo need for bridion or succinylcholine

Short procedure: high dose Short procedure: high dose Rocuronium and bridionRocuronium and bridion Esmeron 1,2 mg/kg IBW measure TOF: Esmeron 1,2 mg/kg IBW measure TOF:

bridionbridion

4 03 2010 J P Mulier 58

Very short and superficial Very short and superficial blockadeblockade

Superficial blockade is sufficient for Superficial blockade is sufficient for ECTECT

Succinylcholine: 0,5 mg/kg (normal: 2 Succinylcholine: 0,5 mg/kg (normal: 2 mg/kg) is sufficientmg/kg) is sufficient Relative rapid onset, within 2 minutesRelative rapid onset, within 2 minutes Spontaneous recovery within 5 minutes possible Spontaneous recovery within 5 minutes possible

Rocuronium 0,15 mg/kg (normal: 0,6 Rocuronium 0,15 mg/kg (normal: 0,6 mg/kg) slower onset, longer durationmg/kg) slower onset, longer duration Dose of bridion dependent on TOFDose of bridion dependent on TOF Neostigmine possible but side effectsNeostigmine possible but side effects

4 03 2010 J P Mulier 59

Tof monitoringTof monitoring

TOF measurement is neededTOF measurement is needed To justify use of bridionTo justify use of bridion To lower dose of bridionTo lower dose of bridion

4 03 2010 J P Mulier 60

Immediate effects in Immediate effects in morbid obese morbid obese

patients patients Deep breaths possibleDeep breaths possible

Less collapsLess collaps

Aurosal effectAurosal effect Like Amfetamine awakeningLike Amfetamine awakening Sudden muscle fiber stimulation gives Sudden muscle fiber stimulation gives

aurosalaurosal

Patient transfers him/her self in bedPatient transfers him/her self in bed 50 % of cases instead of only10% 50 % of cases instead of only10%

Spontaneous movements easierSpontaneous movements easier Deep venous trombosis preventionDeep venous trombosis prevention

4 03 2010 J P Mulier 61

Our Results in lap RNYOur Results in lap RNY

4 03 2010 J P Mulier 62

Adjustable Gastric band Adjustable Gastric band Biliary pancreatic div Biliary pancreatic div DuodenalSwitchDuodenalSwitch

Jejuno ileal bypassJejuno ileal bypass

Vertical banded gastroplasty Vertical banded gastroplasty Roux & Y Gastric bypass Sleeve Roux & Y Gastric bypass Sleeve GastrectomyGastrectomy

4 03 2010 J P Mulier 63

Andere vragen in de Andere vragen in de anesthesie bij morbide anesthesie bij morbide

obesitasobesitas Pre operatieve voorbereidingPre operatieve voorbereiding Inductie en intubatieInductie en intubatie Patient positioneringPatient positionering Medicatie doseringMedicatie dosering Extubatie en postoperatief beleidExtubatie en postoperatief beleid Post op pijn behandelingPost op pijn behandeling

Enkele items nu belichtenEnkele items nu belichten

4 03 2010 J P Mulier 64

Waarom onvoldoende Waarom onvoldoende spierrelaxatie geven?spierrelaxatie geven?

Restcurarisatie is zeer beangstigend, Restcurarisatie is zeer beangstigend, slecht ademen post op, lage saturatie, slecht ademen post op, lage saturatie, hoge CO2hoge CO2

Liever geen neostigmine gebruiken omdatLiever geen neostigmine gebruiken omdat Bradycardie tot totaal AV blockBradycardie tot totaal AV block Bronchospasme bij asthma patientenBronchospasme bij asthma patienten Braken en onwel gevoel post opBraken en onwel gevoel post op

Relaxatie moet voldoende uitgewerkt zijn Relaxatie moet voldoende uitgewerkt zijn om te decurariseren met neostigmineom te decurariseren met neostigmine TOF minimum één antwoordTOF minimum één antwoord

4 03 2010 J P Mulier 65

Continuous deep blockade Continuous deep blockade till end of surgery.till end of surgery.

3. Laparoscopy3. Laparoscopy Rapid awakeningRapid awakening Keep your surgeon in Keep your surgeon in

the ORthe OR Quality surgery = Quality surgery =

short surgical timeshort surgical time High volumesHigh volumes

Quality anaesthesia = Quality anaesthesia = short turn overshort turn over High volumesHigh volumes

4 03 2010 J P Mulier 66

Our Results in lap RNY Our Results in lap RNY gastric bypassgastric bypass

4 03 2010 J P Mulier 67

ERAS 1 ERAS 1 (early recovery after (early recovery after surgery)surgery)

Halfway surgery (last 30 min)Halfway surgery (last 30 min) Large abdomen stop esmeron infusion, Large abdomen stop esmeron infusion, Small abd keep esmeron infusion till Small abd keep esmeron infusion till

end of operation.end of operation. Last staplerLast stapler

Reduce/stop remifentanyl infusion Reduce/stop remifentanyl infusion Start pressure support ventilationStart pressure support ventilation

Hypercapnic PSV increases CO and BPHypercapnic PSV increases CO and BP Keep inhalation conc high if small Keep inhalation conc high if small

abd till end of pneumoperitoneum.abd till end of pneumoperitoneum.

4 03 2010 J P Mulier 68

PSV voorkomt tegenademen PSV voorkomt tegenademen bij onvoldoende relaxatiebij onvoldoende relaxatie

PSV is not a PSV is not a valsalva valsalva effect: IAV is effect: IAV is not changing.not changing.

PSV is PSV is possible possible during deep during deep muscle muscle relaxation.relaxation.

PSVPro during esmeron infusion

-5

0

5

10

15

20

25

time

0

20

40

60

80

100

120

EtCO2

NMT count

RR(CO2)

PTCount

SpO2

PROFOUND MUSCLE RELAXATION DOES NOT DISTURB PROFOUND MUSCLE RELAXATION DOES NOT DISTURB PRESSURE SUPPORT VENTILATION. PRESSURE SUPPORT VENTILATION.

Mulier J, Blacoe D PGA 2009Mulier J, Blacoe D PGA 2009

4 03 2010 J P Mulier 69

Hypercapnia / Pressure Hypercapnia / Pressure supportsupport

TableTable normocapnynormocapny hypercapnyhypercapny

Minute vol *Minute vol *

L/minL/min11,6 +/- 1,711,6 +/- 1,7 7,1 +/- 1,17,1 +/- 1,1

Airw pres *Airw pres *

cmH20cmH2032 +/- 532 +/- 5 26 +/- 326 +/- 3

Et PCO2 *Et PCO2 *

mmHgmmHg38 +/- 638 +/- 6 56 +/- 856 +/- 8

O2 sat %O2 sat % 96 +/- 396 +/- 3 97 +/- 297 +/- 2

Ephedrine * mgEphedrine * mg 30 +/- 1530 +/- 15 5 +/- 85 +/- 8

Breathing *Breathing *

minmin4 +/- 44 +/- 4 2 +/- 42 +/- 4

Extubation *Extubation *

minmin8 +/- 48 +/- 4 4 +/- 54 +/- 5

TableTable PCVPCV PSVPSV

Number of Number of TOF *TOF *

0,60,6 1,41,4

Cisatracurium Cisatracurium mg *mg *

32 +/- 432 +/- 4 23 +/-223 +/-2

etPCO2etPCO2

mmHgmmHg44 +/- 644 +/- 6 54 +/- 1054 +/- 10

ExtubationExtubation

minmin5 +/- 65 +/- 6 3 +/- 23 +/- 2

J P Mulier, B Dillemans, Use of pressure support ventilation during laparoscopic bariatric surgery is possible and facilitates weaning and extubation. In:Obes Surg 2008; 18:444 J P Mulier, B Dillemans, Hypercapnic lung ventilation reduces airway pressure during laparoscopic surgery. In:Eur J Anesth 2008; 25, S44:78

4 03 2010 J P Mulier 70

ERAS 2ERAS 2 LeaktestLeaktest

High volume loadHigh volume load SAP > 140 mmHgSAP > 140 mmHg

Et CO2 to 60; PSV give extra suf if tachypnoeEt CO2 to 60; PSV give extra suf if tachypnoe Ephedrine/phenylephrine bolusEphedrine/phenylephrine bolus

dose sufenta till RR < 16dose sufenta till RR < 16 Last surgical stichLast surgical stich

Lower PSV further, keep peepLower PSV further, keep peep Stop inhalationStop inhalation TOF 4/4 <50% neostigmineTOF 4/4 <50% neostigmine TOF < 2/4TOF < 2/4 bridion dose according to TOF bridion dose according to TOF

and IBWand IBW give bridion after patient is secured on the tablegive bridion after patient is secured on the table

4 03 2010 J P Mulier 71

PSV pain therapy PSV pain therapy optimalisationoptimalisation

Before Before after extra suf after extra suf bolusbolus

4 03 2010 J P Mulier 72

Hypercapnic pressure Hypercapnic pressure support: easier SAP risesupport: easier SAP rise

TableTable NormocapnicNormocapnic HypercapnicHypercapnic

SAP mmHgSAP mmHg 143 +/- 25143 +/- 25 148 +/- 13148 +/- 13

Et P CO2 mmHgEt P CO2 mmHg 39 +/- 739 +/- 7 53 * +/-653 * +/-6

CO L/minCO L/min 6,2 +/- 1,86,2 +/- 1,8 14,3 * +/- 2,914,3 * +/- 2,9

Min Vol L:minMin Vol L:min 9 +/- 1,39 +/- 1,3 7,6 *+/- 1,27,6 *+/- 1,2

Ephedrine mgEphedrine mg 11 +/- 711 +/- 7 3 * +/- 33 * +/- 3

J P Mulier (2008) Hypercapnic support ventilation during laparoscopic gastric bypass increases the cardiac output. Anesthesiology 2008 A174

4 03 2010 J P Mulier 73

Can anesthesiology help to Can anesthesiology help to prevent post op bleeding? prevent post op bleeding?

yesyes

110/57 145/78110/57 145/78

J.P.Mulier, B Dillemans, G Vandrogenbroek, F Akin J.P.Mulier, B Dillemans, G Vandrogenbroek, F Akin The effect of systolic arterial pressure on bleeding of the gastric stapling during laparoscopic gastric The effect of systolic arterial pressure on bleeding of the gastric stapling during laparoscopic gastric

bypass surgery. bypass surgery. Obes Surg 2007; 17: 1051 Obes Surg 2007; 17: 1051

4 03 2010 J P Mulier 74

Hypercapnic pressure support Hypercapnic pressure support ventilationventilation

Increases cardiac outputIncreases cardiac output Less wound infectionsLess wound infections

Lowers airway pressuresLowers airway pressures Resp freq: morfine if too low stop PSVResp freq: morfine if too low stop PSV TV: curarisation corrected by support TV: curarisation corrected by support

levellevel Improves saturation per op if lowImproves saturation per op if low Rapid awakening and spontaneous Rapid awakening and spontaneous

breathingbreathing Non surgical time between OP < 20 minNon surgical time between OP < 20 min

Less pain when awakeningLess pain when awakening Extra doses given during end of surgeryExtra doses given during end of surgery

Better post op breathingBetter post op breathing less post ventilationless post ventilation

4 03 2010 J P Mulier 75

ERAS 3ERAS 3

Reversed induction technique ?Reversed induction technique ? 50 à 100 mg propofol in bolus50 à 100 mg propofol in bolus

Gastric tube suction, oral cavity Gastric tube suction, oral cavity clean?clean?

PSV to Spontaneous, TV > 200 mlPSV to Spontaneous, TV > 200 ml Extubation beach chair if possibleExtubation beach chair if possible

Diep ademen, benen bewegenDiep ademen, benen bewegen Nooit sedativa, benzodiazepines,…Nooit sedativa, benzodiazepines,… Voldoende pijn medicatie perop startenVoldoende pijn medicatie perop starten

Test: patient moet zich zelf Test: patient moet zich zelf verbedden 3 minuten na extubatie!verbedden 3 minuten na extubatie!

Turnover time between end surgery - Turnover time between end surgery - incision next patient < 20 minuten.incision next patient < 20 minuten.

4 03 2010 J P Mulier 76

ConclusionConclusion

Always have Bridion available.Always have Bridion available. Decide when long and deep Decide when long and deep

relaxation is needed till end.relaxation is needed till end. Measure TOF ctu or at endMeasure TOF ctu or at end

Never believe without control clinical Never believe without control clinical relaxationrelaxation

According to TOF at end operation.According to TOF at end operation. (Nothing)(Nothing) (Neostigmine)(Neostigmine) BridionBridion

4 03 2010 J P Mulier 77

Second Second ESPCOP ESPCOP Scientific Scientific meeting meeting

MultidisciplinarMultidisciplinarityity

Pordenone, Pordenone, Italy 18 sept Italy 18 sept

20102010

4 03 2010 J P Mulier 78

More infoMore info www.publicationslist.com/jan.mulierwww.publicationslist.com/jan.mulier www.espcop.orgwww.espcop.org