Where to go for OB Anesthesia Research · Where to go for OB Anesthesia Research ? Conflicts of Interest ... Why Obst et ri c Anest hesi o l o gy i s t he Next F ron tier in Med ic

Marc Van de Velde, MD, PhD, EDRA.

Professor of Anaesthesia, Department Cardiovascular Sciences, Catholic University Leuven (KUL)

Chair, Department of Anaesthesiology, University Hospitals Leuven (UZL), Leuven, Belgium

OAA Committee member 2017-2020

President of the Society of Anesthesia and Resuscitation of Belgium 2016-2019 (SARB)

[email protected]

Where to go for OB Anesthesia Research ?

Conflicts of Interest

• Holder of the “Baxter UZLeuven Anaesthesia Research Chair 2012 – 2014”

• Co-Holder of the “Noble Gas research fund” supported by Air Liquide.

• Received financial support of the following companies for either research, consultancy or lectures

(Active = current or within the last 3 years):

– Smiths Medical (active).

– Sintetica (active).

– Grunenthal (active).

– Nordic Pharma (active).

– MSD (active).

– Janssens Pharmaceutics (active).

– Heron (active).

– Halyard (active).

– Aquettant (active).

– Aspen (active).

– AstraZeneca.

– Glaxo Smith Kline.

– BBraun.

– Abbvie.

– Fresenius.

– GE.

Chapter 20

Neuraxial Anaesthesia for Caesarean delivery

Armstrong, Walters, Cheesman and O’Sullivan

Lecture Outline.

• General ideas:

– Big Data/electronic record keeping.

– International, multicenter trials & OB Anesthesia Societies.

– Meta-Analyses, statistics and (personal) interpretation.

• Specifics:

– Alternatives for neuraxial anesthesia.

– PDPH.

– Maintenance of Analgesia: CI-PCEA, PIEB, adjuvants.

– Use of US in OB Anesthesia.

– Postoperative analgesia after C-section: new drugs.

– GA and neurologic development of the fetus/neonate.

– ………

Lecture Outline.

• General ideas:




• Specifics:


– PDPH.





– ………

The problems of OB anesthesia research.

• The infrequency of problems.

• Ethics.

• Funding.

• “Recipe” medicine.

• Cultural influence.

• The absence of OB anesthesia subspecialty medicine

in many areas of the world – The lack of focus.

• Good research often limited to certain countries.

– Thus not relative to other areas !

• Focus on “soft” parameters.

Lecture Outline.

• General ideas:




• Specifics:


– PDPH.





– ………

Big Data / Electronic Record Keeping

• (OB) Anesthesia is safe.

• But imperfect.

• OB anesthesia carries complications.

• We need better record keeping.

• We need big data – multicenter information.

• A role for OB anesthesia societies such as SOAP, OAA,

etc…. !!

• Examples: NAP – project in UK; KK women’s hospital

labour ward; …..

If You ask me how ?

I haven’t got a clue

I’m an IT nerd ……

But I believe we should initiate this

Lecture Outline.

• General ideas:




• Specifics:


– PDPH.





– ………

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Welcome to SOAP!

Celebrating Over 150 Years of Obstetric Anesthesia

The Society for Obstetric Anesthesia and Perinatology (SOAP)

was founded in 1968 to provide a forum for discussion of

problems unique to the peripartum period. SOAP is comprised

of anesthesiologists, obstetricians, pediatricians, and basic

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A membership in SOAP is an opportunity to meet people who

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BELGIAN ASSOCIATIONFOR REGIONAL ANESTHESIA

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BARA

The Belgian Association for Regional Anesthesia is the official Belgian representative of

the European Society of Regional Anesthesia.

Since its founding by a group of dedicated anesthesiologists in 2001, the BARA has

quickly become one of the largest anesthesia organizations in Belgium.

On this website you will find all information on our association.

2 members of our BARA Board are ESRA representative of Belgium:

Philippe Gautier ([email protected])

Luc Sermeus ([email protected])

CHECK OUT AND ORDER OUR LATEST BARA DVD !!

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ALBERT VAN STEENBERGE LECTURES 18TH BARA ANNUAL MEETING

ABOUT BARAACTIVITIES

2018 Obstetric Anaesthesia SIG Meeting

(/documents/obstetrics-anaesthesia_program_v5.pdf)

(https://waldronsmith.eventsair.com/anzca-asm-

2018/regpage)

Join us in Sydney on May 5 and 6 for the 2018 Obstetric Anaesthesia special interest group (SIG) meeting.“Obstetric anaesthesia… delivering what matters” is being held as a satellite meeting to the ANZCA AnnualScientific Meeting (https://asm.anzca.edu.au/) (ASM) at the brand new Sydney International Convention Centre.

Scientific program

The scientific program is broad ranging and will include new techniques for delivering epidural analgesia, airwayissues in obstetric anaesthesia, anaesthesia care for caesarean sections and care of critically ill women andthose with high risk pregnancies.

Workshops

In addition to lectures there will be a number of emergency response workshops conducted, and the opportunityfor participation in hospital based simulation centres covering key skills and scenarios in obstetric anaesthesia. Please note: The workshops are now full. Please contact Sarah Chezan (mailto:[email protected])to be placed on a waitlist.

Michael Paech Research Prize session

For the first time, the Obstetric Anaesthesia SIG will conduct a research prize session and the organisingcommittee calls for all researchers to submit an abstract. Please click here (/fellows/special-interest-groups/obstetric-anaesthesia/call-for-abstract-guidelines) for further information.

Invited speakers

Dr Marc Van de Velde (http://medevents.ro/arar/wp-content/uploads/2016/10/Short-CV-2015Marc.pdf) is head of the Department of Anesthesiology at the Catholic University inLeuven, Belgium and Full Professor at Leuven University Hospital. His primary clinicalinterest focuses on obstetric anaesthesia and anaesthesia for children and adults withcongenital heart disease undergoing non-cardiac surgery. Most of his current researchfocuses on obstetric anaesthesia.

Dr Richard Smiley (https://www.anesthesiology.cumc.columbia.edu/research/clinical-education-research/dr-richard-smiley) is an anaesthetist in New York, and is affiliated withNew York Presbyterian Hospital. He received his medical degree from the University of MiamiMiller School of Medicine and has been in practice for more than 20 years. He is one of 194doctors at theHospital specialising in anaesthesiology.

Professor Warwick Ngan Kee (http://www.sidra.org/leadership-team/warwick-ngan-kee/) isthe Chair of Anesthesiology at Sidra Medical and Research Center in Doha, Qatar. Hisresearch interests are centred on obstetric anaesthesia and analgesia and includehaemodynamic management during regional anaesthesia for caesarean section, computer-controlled drug delivery, and pharmacodynamic modelling of neuraxial anaesthetic agents.

Local speakers include Professor Michael Paech, Associate Professor Alicia Dennis and Associate ProfessorNolan McDonnell.

Accommodation

We are delighted to offer delegates a wide variety of specially negotiated hotel and apartment accommodationchoices to suit a range of budgets - all within close proximity to the International Convention Centre, Sydney.Accommodation bookings can be made through the official Accommodation Manager, Corporate Blue by

A big research network ?

• Provide larger grants.

• Initiate research projects:

– Long term projects.

– Hard outcome data.

– Rare complications.

– …….

A big research network ?

Lecture Outline.

• General ideas:




• Specifics:


– PDPH.





– ………

Cochrane Databaseof SystematicReviews

Combined spinal-epidural versusepidural analgesia in labour

(Review)

SimmonsSW, Taghizadeh N, DennisAT, HughesD, Cyna AM

SimmonsSW, Taghizadeh N, DennisAT, Hughes D, Cyna AM.

Combined spinal-epidural versusepidural analgesia in labour.

CochraneDatabaseof SystematicReviews 2012, Issue 10. Art. No.: CD003401.

DOI: 10.1002/14651858.CD003401.pub3.

www.cochranelibrary.com

Combined spinal-epidural versus epidural analgesia in labour (Review)

Copyright © 2012The CochraneCollaboration. Published by John Wiley & Sons, Ltd.

Cochrane Databaseof SystematicReviews


(Review)

SimmonsSW, Taghizadeh N, DennisAT, HughesD, Cyna AM

SimmonsSW, Taghizadeh N, DennisAT, HughesD, Cyna AM.

Combined spinal-epidural versusepidural analgesia in labour.

CochraneDatabaseof SystematicReviews 2012, Issue10. Art. No.: CD003401.

DOI: 10.1002/14651858.CD003401.pub3.

www.cochranelibrary.com


Copyright © 2012The CochraneCollaboration. Published by John Wiley &Sons, Ltd.

(RR 0.86; 95% CI 0.79 to 0.95; onetrial, 704 women); and rateof instrumental delivery (RR 0.81; 95% CI 0.67 to 0.97; six trials,

1015 women). Traditional epidural wasmorefavourable in relation to umbilical venouspH (MD -0.03; 95% CI -0.06 to -0.00; one

trial, 55 women). Therewereno dataon maternal satisfaction, blood patch for post dural punctureheadache, respiratory depression,

umbilical cord pH, rareneurological complications, analgesia for caesarean section after analgesic intervention or any economic/use

of resourcesoutcomes for thiscomparison. No differencesbetween CSE and traditional epidural were identified for mobilisation in

labour, theneed for labour augmentation, therateof caesarean birth, incidenceof post dural punctureheadache, maternal hypotension,

neonatal Apgar scoresor umbilical arterial pH.

For CSEversuslow-doseepidurals, threeoutcomeswerestatistically significant. Two of thesereflectedafaster onset of effectiveanalgesia

from time of injection with CSE and the third was of more pruritus with CSE compared to low-dose epidural (average RR 1.80;

95% CI 1.22 to 2.65; 11 trials, 959 women; random-effects, T² = 0.26, I² = 84%). There wasno significant difference in maternal

satisfaction (averageRR1.01; 95% CI 0.98 to1.05; seven trials, 520 women; random-effects, T² =0.00, I² =45%). Therewereno data

on respiratory depression, maternal sedation or theneed for labour augmentation. No differencesbetween CSE and low-doseepidural

wereidentified for need for rescueanalgesia, mobilisation in labour, incidenceof post dural punctureheadache, known dural tap, blood

patch for post dural headache, urinary retention, nausea/vomiting, hypotension, headache, theneed for labour augmentation, mode

of delivery, umbilical pH, Apgar scoreor admissionsto theneonatal unit.

Authors’ conclusions

There appears to be little basis for offering CSE over epidurals in labour, with no difference in overall maternal satisfaction despite

aslightly faster onset with CSE and conversely lessprurituswith low-dose epidurals. There wasno difference in ability to mobilise,

maternal hypotension, rateof caesarean birth or neonatal outcome. However, thesignificantly higher incidence of urinary retention,

rescueinterventionsand instrumental deliverieswith traditional techniqueswould favour theuseof low-doseepidurals. It isnot possible

to draw any meaningful conclusionsregarding rarecomplicationssuch asnerveinjury and meningitis.

P L A I N L A N G U A G E S U M M A R Y


Regional analgesiahasbeen shown to beeffectivein providingpain relief in labour. Regional analgesiacan bean epidural, aspinal or a

combination of thetwo. An epidural iswhen thepain-relievingdrugsareinjected into thepart of thebody which surroundsthespinal

column (epidural space). It ismost common for thesedrugsto beinfused through avery finetube(catheter) positioned in theepidural

space. Traditionally, high concentrations of local anaesthetic drugswereused. Thesenumbed thewoman from thewaist downwards

givingpain relief for most women. However, it also caused legweakness, poor mobility and difficulty for themother givingbirth. This

led to increased instrumental vaginal birthswith subsequent increased bruising, pain and incontinence later on for themother. More

recently with epidurals, low-doselocal anaestheticdrugshavebeen used in combination with opioid drugs. Herethereislessnumbing

of thewoman’slegsbut theopioid drugscrosstheplacentaand may makethebaby sleepy.

A spinal iswhen theanalgesicdrugsareinjecteddirectly into thefluid surroundingthenervesin thespinal column and isquicker to take

effect than an epidural. However, becauseasinglespinal injection isonly effectivefor ashort period of time, they arenot commonly

used on their own for pain relief in labour. Also, theuseof very finecatheters in thespinal space hasbeen associated with increased

injury to nerves. Hence, thecombination of asinglespinal injection combined with theuseof an epidural catheter for ongoing pain

relief wasdeveloped. Thiscombined spinal-epidural wasthought to havethebenefitsof being quicker to providepain relief but with

no changeto theincidenceor severity of sideeffectsfor themother or baby.

This review of trialscompared CSE with traditional and with low-doseepidurals. Therewere27 trials, involving 3274 women. The

datashowed nodifferencein themothers’ satisfaction between CSEand epidurals. However, CSEshad aslightly faster onset of effective

pain relief, but more women itched than with low-dose epidurals. There was no difference seen for mobility in labour, headaches,

caesarean section or adverse effects for the baby. Any differences for rare complications such as nerve injury and meningitis remain

unknown. Thereappearsto belittledifferenceoverall between thesetechniques.



(RR 0.86; 95% CI 0.79 to 0.95; onetrial, 704 women); and rateof instrumental delivery (RR 0.81; 95% CI 0.67 to 0.97; six trials,

1015 women). Traditional epidural wasmorefavourable in relation to umbilical venouspH (MD -0.03; 95% CI -0.06 to -0.00; one

trial, 55 women). Therewereno dataon maternal satisfaction, blood patch for post dural punctureheadache, respiratory depression,

umbilical cord pH, rareneurological complications, analgesia for caesarean section after analgesic intervention or any economic/use

of resourcesoutcomes for thiscomparison. No differencesbetween CSE and traditional epidural were identified for mobilisation in

labour, theneed for labour augmentation, therateof caesarean birth, incidenceof post dural punctureheadache, maternal hypotension,

neonatal Apgar scoresor umbilical arterial pH.

For CSEversuslow-doseepidurals, threeoutcomeswerestatisticallysignificant. Twoof thesereflectedafaster onset of effectiveanalgesia

from time of injection with CSE and the third was of more pruritus with CSE compared to low-dose epidural (average RR 1.80;

95% CI 1.22 to 2.65; 11 trials, 959 women; random-effects, T² = 0.26, I² = 84%). Therewasno significant difference in maternal

satisfaction (averageRR1.01; 95% CI 0.98 to1.05; seven trials, 520 women; random-effects, T² =0.00, I² =45%). Therewerenodata

on respiratory depression, maternal sedation or theneed for labour augmentation. No differencesbetween CSE and low-doseepidural

wereidentified for need for rescueanalgesia, mobilisation in labour, incidenceof post dural punctureheadache, known dural tap, blood

patch for post dural headache, urinary retention, nausea/vomiting, hypotension, headache, theneed for labour augmentation, mode

of delivery, umbilical pH, Apgar scoreor admissionsto theneonatal unit.

Authors’ conclusions

There appears to be little basis for offering CSE over epidurals in labour, with no difference in overall maternal satisfaction despite

aslightly faster onset with CSE and conversely lessprurituswith low-dose epidurals. Therewasno difference in ability to mobilise,

maternal hypotension, rateof caesarean birth or neonatal outcome. However, thesignificantly higher incidence of urinary retention,

rescueinterventionsand instrumental deliverieswith traditional techniqueswould favour theuseof low-doseepidurals. It isnot possible

to draw any meaningful conclusionsregarding rarecomplicationssuch asnerveinjury and meningitis.

P L A I N L A N G U A G E S U M M A R Y


Regional analgesiahasbeen shown to beeffectivein providingpain relief in labour. Regional analgesiacan bean epidural, aspinal or a

combination of thetwo. An epidural iswhen thepain-relievingdrugsareinjected into thepart of thebody which surroundsthespinal

column (epidural space). It ismost common for thesedrugsto beinfused through avery finetube(catheter) positioned in theepidural

space. Traditionally, high concentrations of local anaesthetic drugswereused. Thesenumbed thewoman from thewaist downwards

giving pain relief for most women. However, it also caused legweakness, poor mobility and difficulty for themother giving birth. This

led to increased instrumental vaginal birthswith subsequent increased bruising, pain and incontinence later on for themother. More

recently with epidurals, low-doselocal anaesthetic drugshavebeen used in combination with opioid drugs. Herethereislessnumbing

of thewoman’slegsbut theopioid drugscrosstheplacentaand may makethebaby sleepy.

A spinal iswhen theanalgesicdrugsareinjecteddirectly into thefluid surroundingthenervesin thespinal column and isquicker to take

effect than an epidural. However, becauseasinglespinal injection isonly effectivefor ashort period of time, they arenot commonly

used on their own for pain relief in labour. Also, theuseof very fine cathetersin thespinal space hasbeen associated with increased

injury to nerves. Hence, thecombination of asinglespinal injection combined with theuseof an epidural catheter for ongoing pain

relief wasdeveloped. Thiscombined spinal-epidural wasthought to havethebenefitsof being quicker to providepain relief but with

no changeto theincidenceor severity of sideeffectsfor themother or baby.

This review of trialscompared CSE with traditional and with low-doseepidurals. Therewere27 trials, involving 3274 women. The

datashowed nodifferencein themothers’ satisfaction between CSEand epidurals. However, CSEshad aslightly faster onset of effective

pain relief, but more women itched than with low-dose epidurals. There was no difference seen for mobility in labour, headaches,

caesarean section or adverse effects for the baby. Any differences for rare complications such as nerve injury and meningitis remain

unknown. Thereappearsto belittledifferenceoverall between thesetechniques.



LA consumption ?

Epidural catheter failure ?

Breakthrough Pain ?

Motor Block ?

Anesth Analg 2011; 112, 167 - 173.

that the correct hypothesis lies in the logical complement of the null hypothesis. However, unless there is a single

alternative to the null hypothesis, the rejection of null hypothesis does not tell us which of the alternatives might be

the correct one.

As a general example, if a null hypothesis is assumed to follow the standard normal distribution N(0,1), then the

rejection of this null hypothesis can either mean (i) the mean is not zero, or (ii) the variance is not unity, or (iii) the

distribution is not normal, depending on the type of test performed. However, supposing we manage to reject the zero

mean hypothesis, even if we know the distribution is normal and variance is unity, the null hypothesis test does not

tell us which non-zero value we should adopt as the new mean.

If is a random variable representing the observed data and is the statistical hypothesis under consideration, then

the notion of statistical significance can be naively quantified by the conditional probability , which gives the

likelihood of the observation if the hypothesis is assumed to be correct. However, if is a continuous random

variable and an instance is observed, Thus, this naive definition is inadequate and needs to be

changed so as to accommodate the continuous random variables.

Nonetheless, it helps to clarify that p-values should not be confused with probability on hypothesis (as is done in

Bayesian Hypothesis Testing) such as the probability of the hypothesis given the data, or the

probability of the hypothesis being true, or the probability of observing the given data.

The p-value is defined as the probability,

under the null hypothesis, here simply

denoted by (but is often denoted , as

opposed to , which is sometimes used

to represent the alternative hypothesis), of

obtaining a result equal to or more

extreme than what was actually observed.

Depending on how it is looked at, the

"more extreme than what was actually

observed" can mean (right-tail

event) or (left-tail event) or the

"smaller" of and

(double-tailed event). Thus, the p-value is

given by

for right tail event,

for left tail event,

for double tail event.

Definition and interpretation

Example of a p-value computation. The vertical coordinate is the

probability density of each outcome, computed under the null

hypothesis. The p-value is the area under the curve past the

observed data point.

Where is clinical relevance ?

Anesthesiologists:

Marc Van de Velde, Barrie Fisher, Francis Bonnet,

Narinder Rawal, Stephan Schug, Girish Joshi, Philipp Lirk,

Patricia Lavand’Homme, Helene Beloeil, Esther Pogatzki-

Zahn, Johan Raeder, Alain Delbos

Surgeons:

Henrik Kehlet, Andrew Hill

www.postoppain.org

Need for interpretation and guidance…..

http://www.postoppain.org/

Lecture Outline.

• General ideas:




• Specifics:


– PDPH.





– ………

When is an epidural not an option ?

Infection

Coagulation

problems

Back

SurgeryAS or MS

Cardiac Disease

Raised ICP AllergiesHypovolemia

What do we know ?

• Moderate analgesia, worse then epidural, similar then other opioids.

• High risk of respiratory problems:

• 25% reported incidence of hypoventilation, apnea, etc….

• Several case reports on CPR, perimortem C-section.

• High risk of medication errors.

27 apneas in remi-group

9 resulted in saturation < 90%

BACKGROUND:

METHODS:

RESULTS:

CONCLUSIONS:

Anesth Analg. 2016 Nov 18. [Epub ahead of print]

Analysis of Physiological Respiratory Variable Alarm Alerts AmongLaboring Women Receiving Remifentanil.

Weiniger CF , Carvalho B, Stocki D, Einav S.

Abstract

Remifentanil may be used by laboring women for analgesia, despite

controversy because of potential apneas. We evaluated candidate variables as early warning

alerts for apnea, based on prevalence, positive predictive rate, sensitivity for apnea event

detection, and early warning alert time intervals (lead time) for apnea.

We performed a secondary analysis of respiratory physiological data that had been

collected during a prospective IRB-approved study of laboring women receiving IV patient-

controlled boluses of remifentanil 20 to 60 µg every 1 to 2 minutes. Analyzed data included the

respiratory rate (RR), end-tidal CO2 (EtCO2), pulse oximetry (SpO2), heart rate (HR), and the

Integrated Pulmonary Index (IPI; Capnostream 20; Medtronic, Boulder, CO) that had been

recorded continuously throughout labor. We defined immediate early warning alerts as any drop

in a variable value below a prespecified threshold for 15 seconds: RR < 8 breaths per minute

(bpm), EtCO2 < 15 mm Hg, and SpO2 < 92%. We defined alerts as "sustained" when the value

remained below the threshold for ≥ 10 further seconds. The IPI value (1 to 10; 10 = healthy

patient, ≤4 = immediate attention required, 1 = dire condition) was generated from a proprietary

algorithm using RR, EtCO2, SpO2, and HR parameters. Apnea was defined as maximal CO2 <

5 mm Hg for at least 30 consecutive seconds.

We counted 62 apneas, among 10 of 19 (52.6%) women who received remifentanil

(total dose 1725 ± 1392 µg, administered over 160 ± 132 minutes). We counted 331 immediate

early warning alerts for the variables; 271 (82%) alerts were sustained for ≥10 seconds. The

positive predictive value of alerts for apnea was 35.8% (99% confidence interval [CI]: 27.1-45.6),

28.9% (99% CI: 20.8-38.7), 4.3% (99% CI: 1.9-9.6), and 24.6% (99% CI: 18.3-32.2) for RR,

EtCO2, SpO2, and IPI, respectively. The sensitivity for apnea event detection was 100% (99%

CI: 90.3-100) for RR (<8 bpm) and IPI (≤4); 75.8% (99% CI: 59.8-86.9) for EtCO2 <15 mm Hg;

and 14.5% (99% CI: 6.5-29.4) for SpO2 <92%. We found a statistically significant difference in

the timing of RR, EtCO2, SpO2, and IPI alerts for apnea; Friedman's Q = 33.53; P < .0001. The

EtCO2 had a median (interquartile range) lead time of -0.2 (-12.2 to 0.7) seconds, and SpO2

had a median (interquartile range) lead time of 40.0 (40.0 to 40.0) seconds.

The majority of women receiving IV remifentanil for labor analgesia

experienced apneas. Alerts for EtCO2 (<15 mm Hg), RR (<8 bpm), and IPI (≤4) detected most

Format: Abstract

1

Author information

Full text links

PubMed

• Secondary analysis of the 2014 paper.

• Analysis of RR, etCO2, Pulseoximetry, heart rate and the

IPI (integrated pulmonary index: score from 1 - 10).

• Ability to predict apnea !!

• Immediate Early Warning Alerts:

Value below a predetermined threshold >15 seconds.

RR < 8 bpm

etCO2 < 15 mmHg

Saturation < 92 %

• Sustained Early Warning Alerts: if value remained below

for a further 10 seconds.

• IPI < or = 4: Immediate attention required.

IPI = 1: dire condition.

• Apnea: etCO2 < 5 mmHg for 30 seconds.

BACKGROUND:

METHODS:

RESULTS:

CONCLUSIONS:

Anesth Analg. 2016 Nov 18. [Epub ahead of print]

Analysis of Physiological Respiratory Variable Alarm Alerts AmongLaboring Women Receiving Remifentanil.

Weiniger CF , Carvalho B, Stocki D, Einav S.

Abstract

Remifentanil may be used by laboring women for analgesia, despite

controversy because of potential apneas. We evaluated candidate variables as early warning

alerts for apnea, based on prevalence, positive predictive rate, sensitivity for apnea event

detection, and early warning alert time intervals (lead time) for apnea.

We performed a secondary analysis of respiratory physiological data that had been

collected during a prospective IRB-approved study of laboring women receiving IV patient-

controlled boluses of remifentanil 20 to 60 µg every 1 to 2 minutes. Analyzed data included the

respiratory rate (RR), end-tidal CO2 (EtCO2), pulse oximetry (SpO2), heart rate (HR), and the

Integrated Pulmonary Index (IPI; Capnostream 20; Medtronic, Boulder, CO) that had been

recorded continuously throughout labor. We defined immediate early warning alerts as any drop

in a variable value below a prespecified threshold for 15 seconds: RR < 8 breaths per minute

(bpm), EtCO2 < 15 mm Hg, and SpO2 < 92%. We defined alerts as "sustained" when the value

remained below the threshold for ≥ 10 further seconds. The IPI value (1 to 10; 10 = healthy

patient, ≤4 = immediate attention required, 1 = dire condition) was generated from a proprietary

algorithm using RR, EtCO2, SpO2, and HR parameters. Apnea was defined as maximal CO2 <

5 mm Hg for at least 30 consecutive seconds.

We counted 62 apneas, among 10 of 19 (52.6%) women who received remifentanil

(total dose 1725 ± 1392 µg, administered over 160 ± 132 minutes). We counted 331 immediate

early warning alerts for the variables; 271 (82%) alerts were sustained for ≥10 seconds. The

positive predictive value of alerts for apnea was 35.8% (99% confidence interval [CI]: 27.1-45.6),

28.9% (99% CI: 20.8-38.7), 4.3% (99% CI: 1.9-9.6), and 24.6% (99% CI: 18.3-32.2) for RR,

EtCO2, SpO2, and IPI, respectively. The sensitivity for apnea event detection was 100% (99%

CI: 90.3-100) for RR (<8 bpm) and IPI (≤4); 75.8% (99% CI: 59.8-86.9) for EtCO2 <15 mm Hg;

and 14.5% (99% CI: 6.5-29.4) for SpO2 <92%. We found a statistically significant difference in

the timing of RR, EtCO2, SpO2, and IPI alerts for apnea; Friedman's Q = 33.53; P < .0001. The

EtCO2 had a median (interquartile range) lead time of -0.2 (-12.2 to 0.7) seconds, and SpO2

had a median (interquartile range) lead time of 40.0 (40.0 to 40.0) seconds.

The majority of women receiving IV remifentanil for labor analgesia

experienced apneas. Alerts for EtCO2 (<15 mm Hg), RR (<8 bpm), and IPI (≤4) detected most

Format: Abstract

1

Author information

Full text links

PubMed

• 19 women; 160 ± 132 minutes.

• 62 apneas !!!!

• 331 immediate alerts.

• 271 sustained alerts.

• Low positive predictive value for all parameters:

MANY FALSE POSITIVES

• High sensitivity (100%) of RR and IPI to detect apnea.

• Good sensitivity (75%) of etCO2 to detect apnea.

• LOW sensitivity (15%) of pulseoximetry to detect apnea.

Closed loop systems ?

Lecture Outline.

• General ideas:




• Specifics:


– PDPH.





– ………

Clinical Trial Network

EPiMAP Obstetrics

EPiMAP Obstetrics: European Practices in the Management of Accidental dural Puncture in Obstetrics:European prospective multicentre observational audit to MAP out current practices in the management ofpatients who had accidental dural puncture during EPIdural insertionAbout EPiMAPObjectivesTimelineJoin the studyDocuments: Protocol and AppendicesDocuments: Validated Patient Documents & TranslationsNews: Centre Status and info lettersEthicsFAQ & GuidanceeCRFSteering CommitteeSponsorEndorsementsContact usStudy is registered on ClinicalTrials.gov website: NCT02362828

Copyright 2014 © European Society of Anaesthesiology. All rights reserved. | Privacy Policy | Terms and Conditions

Lecture Outline.

• General ideas:




• Specifics:


– PDPH.





– ………

Computer Integrated PCEA (CI-PCEA)

Programmed Intermittent or

Automated Mandatory Epidural

Boluses (PIEB-PCEA or AMB-PCEA)

Sia et al. Singapore Med J 2006; 47, 951 - 956.

Lim et al. Anaesthesia 2006; 61, 339 – 344.

Sng et al. Anaesth Intens Care 2009; 37, 46 – 53.

BACKGROUND:

OBJECTIVES:

DESIGN:

SETTING:

PARTICIPANTS:

INTERVENTION:

MAIN OUTCOME MEASURES:

RESULTS:

CONCLUSION:

Eur J Anaesthesiol. 2014 Apr;31(4):190-6. doi: 10.1097/EJA.0b013e32836249e9.

Epidural neostigmine and clonidine improves the quality of

combined spinal epidural analgesia in labour: a randomised,

double-blind controlled trial.

Boogmans T , Vertommen J, Valkenborgh T, Devroe S, Roofthooft E, Van de Velde M.

Abstract

In labour analgesia, the combination of epidural clonidine and neostigmine as

adjuvants to local anaesthetics and opioids is under investigation to provide a longer duration of

initial spinal analgesia with local anaesthetics and/or opioids.

To evaluate the quality of analgesia with epidural neostigmine and clonidine,

added to initial spinal analgesia, and to test the hypothesis that the incidence of breakthrough

pain could be reduced and patient satisfaction improved.

Randomised double-blind controlled trial.

University Hospital of Leuven in Belgium.

One hundred healthy, term (≥37 weeks) parturients.

All patients received initial spinal analgesia with ropivacaine and sufentanil.

Fifteen minutes after spinal injection, 10 ml of a solution containing neostigmine 500 µg and

clonidine 75 µg, or 10 ml physiological saline alone was injected epidurally. Patient-controlled

analgesia with ropivacaine and sufentanil was then made available.

The incidence of breakthrough pain, patient satisfaction and

hourly ropivacaine use.

Ropivacaine use decreased significantly by 32.6% in the neostigmine/clonidine

(NC) group [11.6 ± 4.2 vs. 17.2 ± 5.3 mg h in the NC group and placebo (P) group, respectively]

and a significant difference in breakthrough pain was noted; only 3% in group NC had

breakthrough pain compared with 36% in group P. Patient satisfaction was better after 1 h in

group NC compared with group P (P <0.05) but not different after 24 h (visual analogue scale

score 97 ± 5 vs. 88 ± 11 mm after 1 h; 92 ± 10 vs. 90 ± 14 mm after 24 h).

The administration of epidural clonidine and neostigmine as adjuvants,

following spinal injection of local anaesthetic, improves the quality of analgesia with less

ropivacaine consumption, higher patient satisfaction 1 h after administration and a decrease in

breakthrough pain compared to standard combined spinal and epidural analgesia and patient-

Format: Abstract

1

Author information

Full text links

PubMed

Lecture Outline.

• General ideas:




• Specifics:


– PDPH.





– ………

Gastric

UltraSoundA Point-of-care tool for aspiration risk

assessment

EDITORS

Peter Van de Putte, MD

Anesthesiologist • AZ Monica, campus Deurne • Deurne, Belgium

Anahi Perlas, MD

Anesthesiologist • Toronto Western Hospital • Toronto, Canada

.

DISCLAIMER

HOME INTRODUCTION INDICATIONS IMAGE ACQUISITION

IMAGE INTERPRETATION SPECIAL PATIENTS ADDITIONAL MATERIAL

Lecture Outline.

• General ideas:




• Specifics:


– PDPH.





– ………

HTX-011HTX-011, which utilizes our proprietary Biochronomer drug delivery technology

(our-technologies), is under investigation in Phase 3 clinical studies as a long-acting

formulation of the local anesthetic bupivacaine in a Dxed-dose combination with the

anti-inFammatory meloxicam for the prevention of post-operative pain (pain-

management). By delivering sustained levels of both a potent anesthetic and an anti-

in7ammatory agent directly to the site of tissue injury, HTX-011 was designed to

deliver superior pain relief while potentially reducing the need for systemically

administered pain medications such as opioids, which carry the risks of harmful side

effects, abuse, and addiction.

HTX-011 is the Drst long-acting anesthetic that is designed to address both post-

operative pain and accompanying inFammation by combining the local anesthetic

bupivacaine and the anti-inFammatory meloxicam in a single administration.

®

(/ )

Lecture Outline.

• General ideas:




• Specifics:


– PDPH.





– ………

Sanders et al. Brit J Anaesth 2013; 110, i53-i72.

Mechanisms.Masterthesis KUL 2014 Van Biesen, Rex

MechanismsMasterthesis KUL 2014 Van Biesen, Rex

Recent new data in humans.

- Observer blinded, randomized trial

- GA versus Awake Regional (spinal, caudal or

combined)

- Inguinal Hernia Repair.

- Infants younger then 60 w postmenstrual age

- IQ score at 5 years (not reported now)

- Composite Cognitive score at Age 2 (planned

- Interim analysis)

- 238 Awake Regional cases

- 294 GA cases

- Anesthetists not blinded.

- Parents and observers blinded to group.

- Hospital and gestational age at birth were

used to stratify randomisation.

It is a secondary outcome

for which study was not

powered

- Sibling matched cohort.

- One single anesthetic for inguinal hernia repair before age 3 y

- All children were born at 36 weeks or more.

- Control group: siblings without anesthesia before age 3 y.

- IQ testing at age 10 approximately.

- 105 sibling pairs.

- NO difference in IQ !!!

FETAL BRAIN

NEONATAL BRAIN

Differences neonatal versus fetal brain.

• Timing synaptogenesis.

• Neurogenesis and neuroregeneration:

– Trophic effects from glutamate and GABA.

• The presence of maternal hormones.

• Plasma increases in oxytocin: effects on GABA

signalling.

• Trimester specific effects ???

Is the fetal brain vulnerable ?

• Easy transplacental passage of anesthestic

agents animal data: measurable

concentrations of isoflurane in the fetal brain.

• Sometimes exposure relatively long.

• In animals, minor procedures distrupt brain

development.

• Human brain more complex, hence even more

vulnerable.

Animal data: fetal exposure !

Pitfalls: animal to human data !!!

• Longer exposure in animal studies (1 – 6 hours) +

relative to animal gestation (22 days in rodents).

• Lack of cardiorespiratory stability.

– However, more recent animal studies reaffirm this even with good

stability.

• Interspecies differences in neurodevelopment.

• Do we know animal behavior well enough ?

• Animal studies and brain protection= proved not to work

in humans !

Neuroprotective strategies.

• Lithium

• Xenon

• Magnesium

• Dexmetedomidine

• Remifentanil

Am J Transl Res 2017;9(10):4521-4533

www.ajtr.org /ISSN:1943-8141/AJTR0059129

Original ArticleThe neuroprotective effects of remifentanil on isoflu

rane- induced apopt osis in the neonatal rat brain

Bo Pan, Shaoqiang Huang, Shen Sun, Tingting Wang

Department of Anesthesiology, Obstetrics and Genecology Hospital, Fudan University, Shanghai, China

Received June 10, 2017; Accepted August 28, 2017; Epub October 15, 2017; Published October 30, 2017

Abstract: Remifentanil is one of the most frequently prescribed opioids used in combination with inhalation anes-

thetics in clinical practice, but the effects of such combinations on the developing rat brain are unknown. In our

study, we investigated first the potential neurotoxic effects of remifentanil on the developing brain and then the

effects of remifentanil on isoflur ane- induced apoptosis in the neonatal rat brain following exposure to a nociceptive

stimulus. In the first experiment, postnatal day (P) 7 rats were randomly exposed to 30% oxygen, 1.5% isoflur ane

alone, 1.5% isoflurane and a plantar incision, normal saline, or remifentanil at a low (5 µg·kg-1·h-1), moderate (20

µg·kg-1·h-1) or high (80 µg·kg-1·h-1) dose for 4 h. In the second 4-h experiment, P7 rats were randomly exposed to 1.5%

isoflu

r

ane, infused with different doses of remifentanil (5, 10, and 20 µg·kg-1·h-1), and subjected to a plantar incision.

In both experiments, the number of apoptotic neurons in the cortex, hippocampus, and thalamus was assessed af-

ter two hours by cleaved caspase-3 or TUNEL staining. Our data showed that unlike 1.5% isoflur ane, remifentanil at

any dose did not cause signific

a

nt neuronal apoptosis in any brain section. In addition, in response to a nociceptive

stimulus, the infusion of 10 µg·kg-1·h-1 remifentanil reduced isoflur ane- induced apoptosis in the hippocampus (P =

0.003 in CA1, P = 0.002 in CA3) but not in the cortex or thalamus. Our find i ngs suggest that remifentanil does not

induce apoptosis and reduces isoflu

r

ane- induced apopt osis in the developing brain.

Keywords: Opioid effect, neurotoxicity, developing brain, remifentanil

Introduction

Commonly used general anesthetics, including

inhaled and intravenous anesthetics, are asso-

ciated with neurotoxic effects on the develop-

ing brain. These consequences include neuro-

nal apoptosis [1-4] and impaired neurogenesis

[5-7], reduced synapse formation [8-10] and

damaged glial cell development [11, 12].

Anesthetic-induced neurotoxicity is associated

with neuroinflammation, and inhaled anesthet-

ics stimulate the inflammatory response by

increasing intracellular calcium ion levels and

thereby activating the transcription factor

NF-κB, which recognizes DNA sequences in the

nucleus and subsequently induces the tran-

scription of the proinflammatory cytokine IL-6

[13].

Recent studies have primarily focused on the

effects of a single anesthetic on the developing

brain, which is not consistent with clinical prac-

tice, where inhalation anesthetics are typically

used in combination with opioids under condi-

tions of a nociceptive stimulus. Both a single

inhaled anesthetic and the combination of opi-

oids and nociceptive stimuli are associated

with neurotoxic effects on the developing brain.

However, unlike general anesthetics, the neuro-

toxic effects of opioid analgesics on the devel-

oping brain are controversial. Different opioids

may have different effects on the developing

brain. Remifentanil is frequently prescribed due

to its fast onset of action, rapid metabolism and

controllable profile. In addition, the use of remi-

fentanil in children and pregnant women has

increased. However, few studies have investi-

gated the effects of remifentanil on the devel-

oping brain. Remifentanil exerts its anti-inflam-

matory action by down-regulating the NF-κB

pathway in lung injury models [14] and liver

ischemia-reperfusion injury models [15]. Thus,

we hypothesized that remifentanil reduces iso-

flurane-induced apoptosis in the brain of neo-

natal rats subjected to a nociceptive stimulus.

The neuroprotective effects of remifentanil

4531 Am J Transl Res 2017;9(10):4521-4533

anil exerted neuroprotective effects. Isoflurane

also induced thalamic neuron apoptosis. The

thalamus is the most important sensory con-

duction station, and various regions, excepting

the olfactory sensory pathway, project neurons

into the thalamus, which subsequently projects

them into the cerebral cortex. The thalamus is

also associated with emotion [39], Wernicke-

Korsakoff syndrome and amnesia, suggesting

that this brain region is involved in memory and

attention [40, 41]. However, remifentanil did

not reduce isoflurane-induced apoptosis in the

thalamus in the present study. Briefly, remifent-

anil exerted a neuroprotective effect on the hip-

pocampus but not on the cortex or thalamus,

likely for three reasons. 1: The neurotoxic effect

of isoflurane varies among different brain

regions. The number of apoptotic cells in each

brain region was highest in the hippocampus

(200.8 cells/mm2 in CA1 and 727.9 cells/mm2

in CA3), followed by the thalamus (49.6 cells/

mm2) and cortex (1.0 cells/mm2). Thus, the

neuroprotective effect of remifentanil may be

more apparent in more important regions. 2:

The sample size was small (n = 10). 3: Because

of the limitations of the present study, a higher

dose of remifentanil, which may have exerted

an anti-apoptotic effect on the thalamus or cor-

tex, could not be used.

Based on our observation that the combination

of isoflurane with 10 µg·kg-1·h-1 remifentanil

reduced isoflurane-induced apoptosis in the

hippocampus, the neurotoxic effect of a single

dose of remifentanil in the presence of a noci-

ceptive stimulus was observed. However, remi-

fentanil did not exert a neurotoxic effect on the

developing brain.

A plantar incision (Brennan’s model) was used

as the pain stimulus in the present study.

Brennan’s model is typically used to simulate

the effect of pain stimuli on the neonatal ner-

vous system [42] and to examine remifentanil-

induced hyperalgesia [16, 17].

Our study has some limitations. First, we did

not measure vital signs, anesthesia depth and

injury severity in the pups in all groups to deter-

mine whether the anesthesia depth was con-

sistent with the injury severity. Second, without

tracheal intubation, respiratory depression and

hypercapnia readily occurred in pups treated

with inhaled isoflurane combined with the infu-

sion of moderate-dose remifentanil (Iso+Rf20+I

group), and the mice subjected to isoflurane

inhalation and 20 µg·kg-1·h-1 remifentanil infu-

sion had more apoptotic cells. Thus, we cannot

be certain whether the increased apoptosis

induced by hypercapnia or the 20 µg·kg-1·h-1

remifentanil infusion represents a neuroprotec-

tive effect. Further studies are required to

determine whether the effects in the high-dose

group would be different if the pups had

received tracheal intubation.

In conclusion, regardless of the presence of a

nociceptive stimulus, inhaled anesthetics were

associated with neuronal apoptosis in some

brain regions, particularly in the hippocampus.

However, remifentanil did not exert neurotoxic

effects on the developing brain, and it reduced

isoflurane-induced apoptosis. Thus, the anti-

apoptosis mechanism of remifentanil requires

further investigation.

Acknowledgements

Funded by the Municipal Natural Science

Foundation of Shanghai (15ZR1404600).

Yanqing Gao, PhD, State key Laboratory of

Medical Neurobiology, Fudan University, Sh-

anghai, China; Mingyue Xu, PhD, State key

Laboratory of Medical Neurobiology, Fudan

University, Shanghai, China; Hongfeng Mu, MD,

State key Laboratory of Medical Neurobiology,

Fudan University, Shanghai, China; Mengfei

Cai, MD, State key Laboratory of Medical Ne-

urobiology, Fudan University, Shanghai, China.

Disclosure of confli

c

t of int erest

None.

Address correspondence to: Dr. Shaoqiang Huang,

Department of Anesthesiology, Obstetrics and Ge-

necology Hospital, Fudan University, Shanghai,

China. 86-13918210787; E-mail: drhuangsq@163.

com

References

[1] Jevtovic-Todorovic V, Hartman RE, Izumi Y, Ben-

shoff ND, Dikranian K, Zorumski CF, Olney JW

and Wozniak DF. Early exposure to common

anesthetic agents causes widespread neuro-

degeneration in the developing rat brain and

persistent learning defici ts. J Neurosci 2003;

23: 876-882.

[2] Rizzi S, Carter LB, Ori C and Jevtovic-Todorovic

V. Clinical anesthesia causes permanent dam-

The neuroprotective effects of remifentanil

4528 Am J Transl Res 2017;9(10):4521-4533

nal and glial apoptosis [24]. Severe trauma or

pain per se may also cause neurotoxicity in the

brain [25]; however, in the presence of pain,

morphine usage is associated with protective

effects on the immature brain [26].

As a frequently used opioid analgesic, remifen-

tanil has an impressive pharmacokinetic profile

and is more frequently used in young children

and parturient/pregnant women exposed to su-

rgical anesthesia. In addition, intravenous remi-

fentanil infusion is an alternative for labour

analgesia [27-29] when neuraxial analgesia is

contraindicated. Similar to most anesthetics,

remifentanil may affect the foetus by easily cr-

ossing the placenta [30]; therefore, the effects

of remifentanil on the immature brain must be

considered. However, few studies have investi-

gated the neurotoxic effects of remifentanil on

the developing brain. The in vitro study by

Figure 3. A specific

remifentanil dose reduced isoflur ane- induced apoptosis in the hippocampus CA3 region. (A)

Representative images of immunofluo r escence staining for cleaved caspase-3 in the CA3. Red staining indicates apoptotic (cleaved caspase-3-positive) cells, and green staining indicates neurons in the CA3. Merge: cleaved cas-pase-3 and NeuN double-labelled neurons (apoptotic neurons). Scale bar = 50 µm. (B) Representative images of

TUNEL staining in the CA3. Green staining indicates apoptotic (TUNEL-positive) cells, and blue staining indicates DAPI-stained nuclei. Merge: TUNEL and DAPI double-labelled cells (apoptotic cells). Scale bar = 50 µm. (C, D) Quan-tific

at ion of the number of (C) cleaved caspase-3- and (D) TUNEL-positive cells in the CA3. Sham (n = 10): control

group; Iso+I (n = 10): inhaled 1.5% isoflur ane with a plantar incision; Iso+Rf5+I (n = 10): inhaled 1.5% isoflur ane

with a plantar incision and infusion of 5 µg·kg-1·h-1 remifentanil; Iso+Rf10+I (n = 10): inhaled 1.5% isoflur ane with a plantar incision and infusion of 10 µg·kg-1·h-1 remifentanil; Iso+Rf20+I (n = 10): inhaled 1.5% isoflur ane with a

plantar incision and infusion of 20 µg·kg-1·h-1 remifentanil. * P < 0.05 compared with the Sham group. # P < 0.05 compared with the Iso+I group.

Conclusions.

• General ideas:




• Specifics:


– PDPH.





– ………

Big data

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Obstetric Anaesthetists' AssociationPromoting the highest standards of anaesthetic practice in the care of mother and baby

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Obstetric Anaesthesia Annual Meeting

The OAA's Annual Scientific Meeting including:

Innovative programme with international speakers

Dedicated sessions for presentation of obstetric anaesthesia research

E-poster presentations

Lively social programme!

Parent and Baby room with live streaming

Eligible for CPD points and European Accreditation

Meeting Details:

Date 24 - 25 May 2018

Location/Venue Waterfront, Belfast

Programme Please click here

Workshops Please click here

Social Events Please click here

Accommodation Please click here

Registration Please click here

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