Nitrous Oxide for Labor
Analgesia
Laurey Munch BSN, RN, IBCLC
East Carolina University
Nurse-Midwifery Concentration
Presentation Outline
 Current
Options for Labor Analgesia
 Nitrous Oxide- Then and Now
 Physiology
 Utilization for Labor Analgesia
 Advantages/Disadvantages
 Indications/Contraindications
 Policy and Protocol Development at UNC
 Points to Consider/Safety Concerns
 Billing and Reimbursement.
“It is a fact that women in
the United States have fewer
options for childbirth pain
management than women
in Canada, Australia, and
most of Western Europe.”
“Women in the United States
need alternative ways to
relieve labor pain.”
(Leeman et al., 2003; Marmor and Krol, 2002; Rooks,
2011)
Many women in the United States lack access to a reasonably affective method of labor analgesia when needed. (? Rooks article: 61% of women who had singleton vaginal births in the U.S.
received regional anesthesia for labor pain (from data collected in 2008 ). Some women do not need or want regional anesthesia and for those who do are often denied accessibility to this
modality due to lack of or competing needs for the services of anesthesia professionals. This is especially true for women living in rural areas and delivering in institutions where anesthesia may not
staff 24/7.
61% of women who have singleton vaginal births in
the U.S. receive regional anesthesia for labor pain.
All women do not need or want regional anesthesia.
Those who do are often denied accessibility due to
lack of or competing needs for the services of
anesthesia professionals. This is especially true for
women living in rural areas and delivering in
institutions where anesthesia may not staff 24/7.
(Rooks, 2007)
Current U.S. options considered to be “Very
helpful”
Epidural/spinal anesthesia: 81%
hydrotherapy in tub: 48%
Massage/therapeutic touch:40%
Opioids: 40%
Application of heat: 31%
Environmental/Position changes: 23%
Breathing techniques: 21%
(Declerq, E.R., 2006)
According to ACNM… “Women should have
access to a variety of approaches to promote
comfort and reduce pain throughout labor” -(Position
Statement on Nitrous Oxide 2010)
Welcome NITROUS Oxide!
History of Nitrous Oxide


Sir Humphrey Davy (17781829) first discovered N20’s
anesthetic properties as
ideal for surgery
1880 Stanislaw Klikowicz
studied the use of N20 for
labor analgesia on 25
subjects…
(Richards, W., Parbrook, G.D., & Wilson, D.
1976)
N20 was found to:
 Be harmless to
mom/fetus
 Not affect labor
progress
 Not result in loss of
consciousness
 Be effective at
relieving pain
related to labor and
birth
 Not require MD
supervision
Nitrous Oxide at the Present
•
•
•
•
•
•
•
•
Most utilized gaseous anesthetic worldwide
#1 utilized modality for labor analgesia worldwide
UK- 60% of laboring women utilize N20
Australia- 50% utilization
Norway- offered at 85% of birthing centers
Finland- 48% utilization
More common than regional anesthesia
worldwide
(Rooks, 2007; STAKES 2006; NSW
department of Health, 2005)
& in the United States…
Utilized and offered at two
major medical centers and
one small private hospital
 UCSF (over three decades)
 Vanderbilt (over two years)
 Small rural hospital in
Lewiston, ID
 Growing consumer
interest…. LOTS of
CNM/CPM practices
showing interest…

So Why NOT the United States???
 ???????
 Epidural anesthesia monoculture
 “Nitrous oxide is like an “orphan”
drug- little
known outside of dentistry, lacking pizzazz,
no companies/or influential groups that
stand to profit by its greater use.”
 Fear of potential/un-substantiated safety
risks…
(Rooks, 2007)
What is Nitrous Oxide??
Simple molecule
2 nitrogen atoms, 1
oxygen atom
 Colorless, tasteless
 Non-flammable
 Liquid at room
temperature
 When used for labor
analgesia…Fixed blend
of 50%nitrous oxide;
50%oxygen (Bishop, 2007; Rosen,


2002)
 Enters
body through
inhalation, exits through
exhalation
 Onset is <60 seconds
 Dose dependent for onset
and effect
 Very weak accumulation in
fat/tissues (metabolism is
0.004%)
 Elimination half-life is 5 minutes
(Gabbe, Niebyl, & Simpson, 2006; Rosen, 2002)
Physiology
So… How Does N20 Work??
 Exact
mechanism is unknown
 Increases the release of endogenous
endorphins, corticotropins and dopamine
 Anxiolysis-mediated by GABA
 Basically… N20 affects the brain which
modulates pain stimuli by way of
descending spinal cord nerve
pathways.
(Gabbe, Niebyl, & Simpson, 2006; Rosen, 2002)
Utilization for Labor





Weak anesthetic at high doses; anxiolytic
and moderate analgesic at low doses
when utilized for labor
N20 for analgesia NOT anesthesia
Intermittent utilization
Responsiveness is normal response to
verbal stimulation
Airway and spontaneous
ventilation is unaffected
(ASA policy statement on Nitrous for Labor Analgesia
Rosen, 2002)
Nitrous Oxide for Labor Analgesia
Self-administered by inhalation
Fixed 50% nitrous 50% oxygen blend
“Nitronox”
 Efficacy is titrated by frequency and
intensity of inhalation
 Reduces pain without loss of sensation


Nitrous Oxide for Labor Analgesia
According to results from a pilot study evaluating
the benefits of N20 on labor pain and satisfaction:





P

N=126 (50% adolescent population) all low-income
Pain significantly decreased by 56.2% on average
(p=0.0001)-as assessed by Visual Analog Scale 1 hr after
initiating N20
96% would recommend N20 for labor pain; 92.9% graded
the procedure as good/excellent.
Maternal hemodynamic parameters were unaltered
Neonatal outcome favorable (no Apgar <7 at 5 minutes)
NVB rates were 96.9%
Adverse effects: dizziness (43%); sleepiness (25%); emesis
(7%)
(Pita et al., 2012)


Nitrous Oxide for Labor Analgesia
According to Mark Rosen, MD
Director of Obstetric Anesthesia at UCSF:
“I have found it particularly wonderful for
women especially toward the end of the
first stage or in the pushing stage.”
 “One reason for its success is the
element of control it gives to women
during their labor.”

(Personal communication, 2013)

P
Advantages
Equipment: Nitronox
Two portable tanks (N20 and 02)
or may use wall O2
• Blender device mixes 02 and N20 to
deliver a set 50:50% concentration
• Face mask self-applied by client
• Demand valve preventing continuous
flow of gas unless woman is inhaling
• Scavenging system diverts exhaled
gas to hospital suction, so it is not
exhaled into room air
• Rolling cart allows for client mobility
•
Advantages
 Extensive
record of safe use (quality data since 1970’s)
 Ease of use – self administered; may be initiated by RN
 Low cost- Pregnancy currently tied with CAD for most
expensive “conditions” contributing to over $790 billion in annual
hospital costs.
 Rapid
onset and offset
 Laboring woman remains awake and responsive
 Provides an element of control- increases selfconfidence and satisfaction
 Does not require routine IP interventions
(AHRQ, 2004; Bishop, 2007; Holdcroft & Morgan, 1974;Rosen, 2002)
Advantages
 No
effect on labor progress or diminished sensation
to push
 N20
does NOT reduce the release or effectiveness
of endogenous oxytocin thus has no effect of
decreasing uterine contractility.
 RCT
of 1300 Chinese randomized to inhalation of
50%N20 versus none- women who utilized N20 had
shorter active phase (153 vs. 187 p<0.05) and fewer
cesarean births (11.6% vs. 19.3% P<0.05)
(Su, R., Wei, X., Chen, X., Hu, Z, Hu, H., 2002)
Advantages

No associated neonatal morbidity (no affect on
FHR/APAGR’s)- **NO studies or published observations
have identified adverse effects in the neonate.

Crosses the placenta: concentration in fetal blood is
80% within 15 minutes

Large Chinese RCT (N=1300)- no significance among
women using 50% N20/02 in labor for incidence of
meconium staining/ APGAR scores or umbilical blood
gas levels.

No affect on lactation or early bonding
(Su, R., Wei, X., Chen, X., Hu, Z, Hu, H., 2002)
Advantages
 May
be utilized for procedural analgesia (i.e
extensive laceration repair, manual placental
extraction, manual occiput rotation, intra-cervical
balloon placement)
 May
allow for postponement/avoidance of narcotics
or regional anesthesia and their associated adverse
effects
(Bishop 2007; Rosen, 2002)
Disadvantages
 May
cause nausea and ,
dizziness and/or dysphoria
 Mobility may be constrained by
machine tubing
 May not provide desired level of analgesic
efficacy… at Vanderbilt approx. 50% of women using N20 go
on to receive regional anesthesia.
 **Main
disadvantage is the unavailability
in the U.S. and unfamiliarity among U.S.
providers
(Bishop 2007; Rosen, 2002)
Candidates for Use…
 In
labor, any stage.
 No time is too early or late!
 Intrapartum/Postpartum Procedures
 ** If used in combination w/ other IV narcotics,
this is considered conscious sedation NOT
analgesia and should be administered only in
the presence of anesthesia
Contraindication for Use…
 Cannot/unwilling
to hold a face mask
 Have a documented B12 deficiency or
 Any condition that reduces cobalamin function:
Crohn's disease, celiac disease, gluten
intolerance, pernicious anemia, long-term
recreational abuse of N20, chronic malnutrition,
strict vegan diet.
 Are acutely intoxicated or have impaired LOC
 Have received IV opioids within the last 2 hours
(Rooks, 2011)
Contraindication for Use…
 Clients
w/ a pneumothorax, bowel obstruction,
increased intro-ocular pressure, recent ear surgery
(NITROUS ACCUMULATES in CLOSED SPACES).
 Clients
w/ URI, allergic rhinitis and severe sinusitis
should use N20 with caution- Nitrous oxide may
cause emesis in part by pressure changes in the
middle ear
(Rooks, 2011)
Protocol development and Utilization of
Nitrous Oxide for Labor Analgesia at UNC
Health Care
 Present
and Achieve “Buy in” from key leaders…
aka the “cool kids” + OB ANESTHESIA!!!!!
 Also, program directors OB, FM, CNM, NBN/NICU,
Lactation
 Develop an institutional protocol
 Approval from Pharmacy/Therapeutics & Sedation
 Approval from Safety/Biomedical Engineering
 Nursing management and Education
 Institutional Practice/Policy committee.
Conjuring “interest” and “buy-in” for this
“new” modality…
Share what other “good” institutions are
doing…




UCSF- Policy appears in full JMWH (2007) Title:
“Administration of Nitrous Oxide in Labor:
Expanding the Options for Women”
Vanderbilt
UNC… very soon
AHRQ and Cochrane Review
Points to Consider… when
developing a institutional protocol




Laboring woman administers N20
Initiation could occur by anesthesia
provider, OB, CNM, FM, or RN (this will
ABSOLUTELY affect accessibility!!)
FHM should be determined by underlying condition
NOT based on concurrent utilization of N20
REGULATIONS- No regulations currently exist for use
of 50% (or less) Nitrous; best source is American
Society of Anesthesiologists (ASA) “Practice
Guidelines for Sedation and Analgesia by NonAnesthesiologists”
Safety Concerns…
 NO
implications of harm with ANALGESIC
levels, when used intermittently and with:
Use of scavenging equipment
Use of demand valve
Proper instruction to and use by user
*** all of which limits exposure of others in the room
Safety Concerns…
50% N20/02 is SAFE!!
 4 yr prospective survey of >35,000 administrations of
50% n20/02 in 191 French adult and pediatric
hospitals reported only 27 “serious adverse events”
 These included 2 incidences of emesis; 1 each of:
decreased consciousness, bradycardia, vertigo,
headache, nightmares, sweating, and somnolence

(Onody, Gil, & Hennequin, 2006)
Apotosis: aka programmed cellular death
Potential neurotoxicity of anesthetic agents has
become recent topic of “interest”; also applies to
potential SE of sedatives, hypnotics, narcotics and other
Inhalation anesthetics…
Safety Concerns for Apoptosis…




Dose is the critical determinant of risk from
occupational exposure to N20
“Apoptosis”…ONLY in animal studies when exposed
to extreme amount over long periods of time.
FDA has investigated the issue: “We have no
evidence that supports detrimental CNS effect in
pediatric patients/staff who have been exposed.”
FDA clearly articulates that NO changes are
recommended for any anesthetic practice
(including utilization of N20) at this time. (FDA, 2007)
Safety Concerns-effects of N20 on
Cobalamin…




N20 oxidizes a physiologically active from of cobalamin (vit
B12); inactivating it.
Extremely high doses of N20 and/or long term exposure (dose
= concentration x duration of exposure) can cause adverse
effects incl. bone-marrow depression, macrocytic anemia,
and neuropsychiatric disorders.
Effects reverse with time; Royston et al. research concluded
that surgical (receiving anesthetic doses) are at risk when
receiving N20 >70%, for >6 hours.
Conditions that reduce cobalamin fct (Chron’s dx, Celiac dx,
gluten intolerance, pernicious anemia, strict adherence to
vegan diet, etc.) increase risks with N20 exposure.
(Rooks, 2011)
(
Safety Concerns… Swedish study:
A large study (N = 3347) analyzed associations between
several reproductive problems and exposure to N2O and
other occupational risks among Swedish midwives in the
1980s. Approximately half of the midwives had some
occupational exposure to N2O during their most recent
pregnancy, although most Swedish women use it for
relatively short periods during labor. Scavenging and
forced ventilation were not used in Swedish hospitals
during the 1980s.
Results: There was no relationship between fertility and
N2O/O2 exposure except among 41 midwives who
attended greater than 30 births per month in which N2O
was being used without scavenging devices. No effect
was seen among midwives with less exposure to N2O/O2
(Rooks, 2011)
Safety Concerns…
 Potential
for abuse: Low abuse potential for Nitronox
equipment…. demand valve, scavenger, 50/50 N20/02 is not
lethal or unsafe!!!!
 This
has NOT EVER been a reported problem
 Some institutions are considering to have family
members in room sign consent forms…. Advise against
this as this implies they are at risk- THEY ARE NOT AT
RISK
 It is safe for children and support persons to remain at
the bedside when nitrous oxide is in use… they should
be told that they cannot touch the equipment
because self-administration is essential for safety.
N20 Monitoring exposure



Occupational exposure guidelines
NIOSH set standard exposure limit: <25ppm 8hr
UCSF yearly evaluation in 2010 (Dosimeter badges
worn by three RN’s: <1-2.0ppm/yr.
L&D staff at UNC will NOT wear dosimeter badgesperiodic monitoring will be performed by
Environmental Safety Division and Machine
safety/maintenance will be performed by
anesthesia department/provider prior to each use
Assuring Safety…
Pre-anesthesia evaluation to determine suitability
• H&P
• Informed consent
• Equipment check and proper device set up
• Initial patient education
• No additional opioid can be given w/o direct
anesthesia supervision
• May initiate N20 once 2 hours after IV narcotics has
passed
• May receive IV narcotic dose 15 minutes after
discontinuation of N20
•
Client Education…
Client Education…
•
•
•
•
•
•
Proper mask placement to create a good
seal around the face
Time breaths to contractions- must begin
deep breathing at least 30 seconds before
onset of contraction
Client MUST be able to hold own mask w/o
assistance
Client cannot let others use the mask.
SE: nausea, dizziness, dysphoria
Requires assistance with ambulation
Billing and Reimbursement …
…an unfortunate reality in contemporary health care.
Equipment & Costs
FINALLY AVAILABLE IN THE U.S.!!!
Mike Civitello, Medical Product Manager:
Michael.Civitello@Parker.com
888-723-4001, ext. 8224
www.PorterInstrument.com/Medical
NOX-5445H Nitronox E-Stand Package:
Retail $6233 Sales Price: $4986
NOX-55072H Nitronox Wall Mount Package:
Retail $4352 Sales Price: $3482
NOX-5042H Nitronox Mobile Cart Package:
Retail $4476 Sales Price: $3581
Pricing includes the new 2013 Medical Device Tax of 2.3%
Billing and Reimbursement …$$$
…an unfortunate reality in contemporary health care.





.
In dentistry, N20 administration is touted has having
“economic benefit” for a practice
Fees of $50-$150 are added to the bill for nitrous
Dental (ADA ) code= D9230 (anxiolysis, analgesia,
inhalation of N20)
No current CPT/ICD-9 codes specifically for inhalation of
nitrous for labor analgesia- may assign ICD-9 CM
procedure code 00.12 (administration of inhaled nitric
oxide)
UNC plans to charge set amount with additional charges
per unit of time (sliding scale based on time of
utilization)- approximately $150 up to $300 (plus
disposable parts including mask and tubing)
N20 for Labor Analgesia… What’s
happening…
 Lots
of interest from media: Associated Press,
ABC, Slate, Newsweek, Wall St. Journal, etc.
 “No Laughing Matter” You Tube
 “Gas and Air” recently aired on Call of the
Midwife
 Lots of interest from private practices and
CNM/CPM owned/operated birthing centers
 UNC will be up and running late summer 2013
 DHMC is probably about 9 months behind
.
In Conclusion…
 Self-administered
analgesia is
Nitrous oxide for labor
Simple
Safe and effective
Inexpensive
Accessible
Popular
Desired
and…….
SHOULD BE AVAILABLE AS AN OPTION TO
WOMEN IN North Carolina AND THE U.S.!!!
.
For Additional Information…
Join the listserv:
N20duringlabor.subscribe@yahoogroups
.com
.
Thank You
.
References
American College of Nurse-Midwives Position Statement: Nitrous Oxide for Labor Analgesia. (2010).
Journal of Midwifery and Women’s Health, 55(3), 292-296.
Bishop, J.T. (2007). Administration of nitrous oxide in labor: Expanding the options for women.
Journal of Midwifery and Women’s Health, 52(3), 308-309.
Declerq, E.R., Sakala, C., Cory, M.P. & Applebaum, S. (2006). Listening to mothers II: Report of the
second national U.S. survey of women’s childbearing experiences. NY, NY: Childbirth Connection.
Holdcroft, A. & Morgan, M. (1974). An assessment of the analgesic effect in labour of pethidine and
50 percent nitrous oxide in oxygen (Entonox). BJOG, 81, 603-607.
Leeman, L., Fontaine, P., King, V., Klein, M.C., & Ratcliffe, S. (2003). The nature and management of
labor pain: Part II. Pharmacologic pain relief. American Family Physician, 68, 1115-1120.
Marmor, T.R., & Krol, D.M. (2002). Labor pain management in the United States: Understanding
patterns and the issue of choice. American Journal of Obstetrics and Gynecology, 186S 173-180.
STAKES. (2006). Official Statistics of Finland, Health 2006: Statistical Summary. Retrieved from
References
NSW Department of Health. (2005). New South Wales Mothers and Babies. Retrieved from
http://www.health.nsw.gov.au/public-health/phbsup/mdc04.pdf.
Onody, P., Gil, P., Hennequin, M. (2006). Safety of inhalation of a 50% nitrous oxide/oxygen
premix: A prospective survey of 35, 828 administrations . Drug Safety, 29(7), 633-640.
Pita, C.P., Pazmino, S. , Vallejo, M., Salazar-Pousada, D., Hidalgo, L., et al. (2012). Inhaled
intrapartum analgesia using a 50-50% mixture of nitrous oxide-oxygen in a low-income
hospital setting. Archives of Gynecology and Obstetrics, 286, 627-631.
Rooks, J.P. (2007). Nitrous oxide for pain in labor-Why not in the United States? Birth, 34(1), 3-5.
Rooks, J.P. (2011). Safety and risks of nitrous oxide in labor analgesia: A review. Journal of
Midwifery & Women’s Health, 56(6), 557-564.
Rosen, M. A. (2002). Nitrous oxide for relief of labor pain: A systematic review. American
Journal of Obstetrics and Gynecology, 186S, S131-59. doi: 10.1067/mob.2002.121259.
References
Royston, B.D., Nunn, J.F., Weinbren, H.K., Royston, D., Cormack, R.S. et al. (1988). Rate of
inactivation of human and rodent hepatic methionine synthase by nitrous oxide,
Anesthesiology, 68(2), 213-216.
Su, R., Wei, X., Chen, X., Hu, Z, Hu, H. (2002). Clinical study on efficacy and safety of labor
analgesia with inhalation of nitrous oxide in oxygen. Zhonghua Fu Chan Ke Za Zhi, 37(10),
584-587
U.S. Agency for Healthcare Research and Quality (2004). HCUP Statistical Brief #13. The
National Hospital Bill: The Most Expensive Conditions. Retrieved from http://www.hcupus.ahrq.gov/reports/statbriefs/sb13.pdf.