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UCSF
October 27th, 2016
Mark Rollins, MD, PhDProfessor & Director Obstetric Anesthesia
UCSF Department of Anesthesia
2016 UCSF OB/GYN
Update
1) Discuss the efficacy and safety for the use of nitrous oxide in labor
2) Discuss the efficacy and safety for the use of remifentanil in labor
3) Describe current protocols and provide guidance for implementation
At the conclusion of this activity, participants should be able to:
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First to use nitrous oxide as a labor anesthetic in 1881
Canada 40-45%Finland 60%Sweden 65%United Kingdom 50-75%
Rosen 2002; Am J Obstet Gynec 186:S110-27Likis 2012; AHRQ Publication No. 12-EHC071-EFRooks 2007; Birth 34:3-5
Odorless
Colorless
Lack of Flammability
Low blood solubility
Minimal metabolism
Low Anesthetic Potency
Endorphins
Corticotropins
Dopamine
Alpha 2 Adrenoreceptors
NMDA receptors
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Conclusions: The literature addressing nitrous oxide for the management of labor pain includes few studies of good or fair quality. Further research is needed across all of the areas examined: effectiveness satisfaction and adverse events.
(A&A 2014; 118:153-67)
Nitrous oxide
Patients (n=265):11% Complete61% Considerable28% Slight or None
Midwives:7% Excellent35% Good49% Adequate9% inadequate
Rosen 1969 BMJ, Vol3:263
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Carstinou. Anesthesiology 1994; 80:30-5
However, most women chose to continue using nitrous despite the fact there was no difference in VAS in comparison to compressed air.
N=26
Method %Using
VeryHelpful
SomeHelpful
Not VeryHelpful
NotHelpful
Epidural 63 78 15 3 4Tub Immersion 6 49 41 10 1Shower 8 32 52 13 2Birth Ball 5 32 52 13 2Nitrous Oxide 2 30 22 21 26Massage 32 30 52 13 6Opioids 30 24 42 20 9Mental Strategy 30 22 52 18 5Compress 15 21 62 14 3Breathing 61 21 48 21 10Position Change 60 19 60 16 5
Maternity Center Association: Listening to Mothers Survey 2002
Anesth Analg 2015;121:974–80
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Women and Birth (2013) 26, 33—40
• Labor analgesia
• Vacuum assisted delivery
• Forceps assisted delivery
• Manual placenta removal
• Bedside D&C
• Laceration repair
• IV placement
• Primary outcome pain assessment (n=100)
• 2nd Degree (32%), Episiotomy (29%)
Vaginal Tear(31%), Labial Tear (20%)
• 50% Nitrous vs 1%Prilocaine
• No difference in pain scores
• 77% Nitrous and 90% Prilocaine satisfied
Berlit S. Eur Jou of Obstet & Gyn and Repro Bio 2013; 170:329-32 Rosen 2002; Am J Obstet Gynec 186:S110-27Likis F. A&A 2014; 118:153-67
• Nausea 5% - 13%
• Dizziness 3% - 5%
• Dysphoria 5%
• Drowsiness 0 - 4%
• Transient unconsciousness < 0.5%
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Rooks 2011; J Midwifery Health; 56:557-65Rosen 2002; Am J Obstet Gynec 186:S110-27Likis F. A&A 2014; 118:153-67
• No effect on fetal heart rate
• No effect on cord gases
• No effect on APGAR scores
• No effect on newborn respiration
• No effect on neonatal behavioral scores
• No effect on duration of labor
• No effect on mode of delivery
“… it may be almost impossible to perform human studies addressing whether in utero exposure of nitrous during labor has adverse affects on the infant central nervous system… Thus women who ask to use N2O/O2 during labor should be informed of that we lack data about this outcome.”
A&A 2014: 118(1):12-14
Eur J Anaesthesiol 2015; 32:1–4
Conclusions:“An extensive amount of clinical evidence indicates that N2O can be used safely for procedural pain management (in the emergency room, in the normal ward or in a prehospital situation), for the management of labour pain, and for anxiolysis and sedation”
Eur J Anaesthesiol 2015; 32:1–4
Conclusions:• “ There is currently no clinically relevant evidence for the withdrawal of N2O from the armamentarium of anaesthesia practice”
• “There is no evidence indicating that the use of N2O in a modern clinically relevant setting increases health risk in patients or providers”
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• Set at 50/50 blend with oxygen
• Patient controlled with facemask
• Patient education
• Sole agent
• Breathing prior to contraction onset
• Wall or portable devices
• Scavenging system present
• Family Members
“… the story of how nitrous oxide is being reintroduced for the benefit of women in the United States is significant. Rediscovery can be as important, if not more important, than the original discovery.
Tekoa L. King, CNM, MPH, FACNM
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Remifentanil Objectives
• Review Use of Remifentanil in Labor
– Alternative to Other Narcotics or Epidural Analgesia
– Maternal and Fetal Safety
• Discuss Remifentanil PCA Implementation
Remifentanil Pharmacokinetics:Ultra-Short Acting (mu-1 opioid receptor agonist)
• Rapid onset (onset = 30-60 sec; Peak = 2.5 min)
• Inactive metabolites (plasma esterases)
• Short Context-Sensitive half-life (3.5 min)
• ““““Respiratory Depression”””” half-life (2.5 min) Hinova et al. Systemic Remifentanil for Labor Analgesia. Anesthesia & Analgesia. 2009; 109(6): 1925-9. Babenco et al. The pharmacodynamic effect of a remifentanil bolus on ventilatory control. Anesthesiology 2000; 92:393-8.
Remifentanil Pharmacokinetics:
Fox A J , Rowbotham D J BMJ 1999;319:557-560©1999 by British Medical Journal Publishing Group
Remifentanil Pharmacokinetics:
Fox A J , Rowbotham D J BMJ 1999;319:557-560©1999 by British Medical Journal Publishing Group
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Remifentanil and Pregnancy• The placenta contains nonspecific esterases• Fetal esterases nearly fully developed at birth• Within 5-10 minutes of turning off an infusion
there is virtually no residual effect.• Remifentanil can be turned off minutes before
delivery without fetal respiratory depression
Remifentanil and Pregnancy
• Plasma concentrations in pregnancy are ½ of non-pregnancy due to a larger volume of distribution and higher clearance
• Crosses the placenta, but rapidly metabolized and redistributed in fetus
Hinova et al. Anesthesia & Analgesia. 2009; 109(6): 1925-9.
Maternal-Fetal Transfer
Kan, R, et al.. Anesthesiology; 1998;88:1467-74
Maternal-Fetal Transfer
Kan, R, et al.. Anesthesiology; 1998;88:1467-74
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Marwah et al. Can J Anesth (2012); 59:246-54
• Remifentanil
• Bolus 0.25 mcg/kg q 2min
• Infusion .025 -.05 mcg/kg/min, 4hr limit 3mg
• Fentanyl
• Bolus 25 - 50 mcg q 3 to 6 min
• No Infusion, 4hr limit up to 1.5mg
Marwah et al. Can J Anesth (2012); 59:246-54
• No difference in pain scores between groups
• Moderate decrease in pain from baseline
• More transient desaturation with remi 13% vs 2%
• More neonates in the fentanyl group required
resuscitation 59% vs 25%
Remifentanil and Labor:
Van de Velde et al. Int J Obstet Anesth 2016; 25: 66-74.
Side Effects of Remifentanil:• Mild transient maternal desaturation• Mild sedation• Nausea and vomiting (0% to 60%)• No notable neonatal effects (APGARS and cord
gases all WNL)• Low incidence of FHR abnormalities (no
intervention)
Hinova et al. Anesthesia & Analgesia. 2009; 109(6): 1925-9.Devabhakthuni. Clinical Medicine Insights: Women’s Health 2013
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RCT Remifentanil vs. Epidural
Volmanen et al. Acta Anesthesiol Scand 2008; 52: 249-55.
N=45 Total
RCT Remifentanil vs. Epidural
Volmanen et al. Acta Anesthesiol Scand 2008; 52: 249-55.
N=45 Total
(Anesth Analg 2011;113:818 –25)
• Initial & stepwise boluses 0.15�g/kg (lean body mass)• 2-min lock-out• Conversion to epidural 3 of 41 (7%)• Mean 0.38 �g/kg (1-hr) and 0.68 �g/kg (end 1st stage) • Highest dose 1.05 �g/kg• 37/41 (93%) were satisfied or very satisfied • 36/41 (88%) would choose same analgesia again• 27% received supplemental oxygen (sat< 92%)
IJOA (2013) 22:19-25Anesth & Analg. 118(3) 2014
Remi PCA (n=19) Epidural (n=20)
Satisfaction 8.6 ± 1.4 9.1 ± 1.5
Pain (30min) 3.7 ± 2.8 1.5 ± 2.2* p<.01
RR (bpm) 18.2 ± 4.1 21.1 ± 3.9* p<.05
Sat (%) 96.8% 98.4%* p<.001
Apnea (>20sec) n=5 n=0 p<.05
No Difference in APGARS or Cord Gases
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• Multicenter RCT (15 centers) – 1414 women• Pain relief during labor between 32 and 42 weeks• Women randomized to receive epidural analgesia according to
local protocol or remifentanil PCA according to study protocol• Lower satisfaction scores, higher pain scores with remifentanil• 13% conversion remifentanil to epidural• Oxygen saturation lower in remifentanil group• Maternal and neonatal outcomes were comparable
Remifentanil patient controlled AnalgesiaVersus Epidural analgesia during Labor
Freeman et al. BMJ 2015;350:846
Evidence based recommendations: • Remifentanil provides modest labor analgesia
(Class IIb, Level B)
• Remifentanil provides more effective analgesia
than nitrous oxide (Class IIa, Level B)
• Neuraxial analgesia provides significantly more
effective labor analgesia than remifentanil PCIA (Class I, A)
Van de Velde et al. Int J Obstet Anesth 2016; 25: 66-74.
Evidence based recommendations:
• Remifentanil has less effect on the fetus than othe r
parenteral opioids (Class IIb, Level B).
• Remifentanil increases risk of significant respir atory
depression compared to neuraxial analgesia (Class I; Level A)
Van de Velde et al. Int J Obstet Anesth 2016; 25: 66-74.
Monitoring Recommendations: • Continuous uninterrupted one-to-one
midwifery/nursing care and surveillance
• Monitoring for adequate ventilation: apnea monito ring
or capnography
• Continuous maternal oxygen saturation monitoring
Van de Velde et al. Int J Obstet Anesth 2016; 25: 66-74.
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Implementation: • Remifentanil in standard concentration• Have a standardized order set • Initial patient dose increased to effect (example
0.25mcg/kg & increases of 10mcg)
• Lockout of PCA q2 minutes, no/minimal basal rate• All patients need Sat/Sedation monitoring and
supplemental O2 , 1:1 nursing• Pediatricians present at delivery
Summary:• Literature supports the use of remifentanil when
neuraxial block is contraindicated • Literature supports neonatal outcomes similar with
epidural and remifentanil• Possibly more effective than other current
alternatives to neuraxial analgesia• Comparable satisfaction scores to epidural• Prior to implementation, providers should undergo
training and a protocol developed
