What is the deal with nitrous? Eric Deutsch MD Overview of Topics - - PowerPoint PPT Presentation

What is the deal with nitrous?

Eric Deutsch MD

Overview of Topics

• History of Nitrous Oxide
• Pharmacodynamics
• Pharmacokinetics
• How labor nitrous is packaged and administered
• Adverse Drug Reactions of Nitrous
• Environmental concerns
• Evidence of efficacy?
• Patient selection
• How SLH started their L&D nitrous service

Disclosure

• No corporate, financial contracts, or investments to

disclose

Introduction

• “Labor is a complex and highly individualized

process; not every woman wants or needs analgesic intervention for delivery”

Eltzschig HK, Lieberman ES, Camann WR. Regional anesthesia and analgesia for labor and

• delivery. The New England journal of medicine. 2003;348(4):319-32.

Anesthesiologists from Harvard’s Brigham and Woman’s Hospital

The perfect labor analgesic…

1. Would eliminate all pain (nociceptors) 2. Is noninvasive 3. Would not block sensation of body/limb movement and position (proprioception) 4. Would permit ambulation (not block motor function) 5. Would not alter cognition 6. Could be easily and quickly converted to a surgical anesthetic (national c-section rate is 32.8%)* 7. Is safe and has no complications or side effects 8. Can be quickly implemented and quickly discontinued by non-experts 9. Is inexpensive

*Martin, J. A., Hamilton, B. E., Ph, D., Ventura, S. J., Osterman, M. J. K., Wilson, E. C., Mathews, T. J., et al. (2012). National Vital Statistics Reports Births : Final Data for 2010, 61(1), 1990–2010.

Melzack R. The myth of painless childbirth (the John J. Bonica lecture). Pain. 1984;19(4):321–337.

Medical Interventions

Nitrous Oxide (N2O)

• Inhaled N2O was introduced in 1881 to provide pain

relief during labor

• its routine use for labor analgesia began after

introduction of an apparatus for self administration in 1934

• Used by 60% of laboring women in the UK
• Used ~ 50% of laboring women in Australia, Finland

and Canada.

• In the US, there appear to be a few institutions

where it is routinely available (UW, UCSF, Vanderbilt,

• St. Joseph’s in Lewiston Idaho, and St. Luke’s

Hospital)

Nitrous Oxide (N2O)

• Premixed 50:50 N2O:O2
• Connected through a

demand valve which opens with sufficient negative inspiratory pressure

• Very modest reduction in

labor pain

• Interestingly, some women

who report no benefit request to continue its use

• Safe for fetus (APGAR & cord

gases)

• ccupational exposure

risk(Inactivation of methionine synthase)

Rosen MA. Nitrous oxide for relief of labor pain: A systematic review. Am J Obstet gynecol 2002; 186: S110-126.

Pharmacodynamics & Pharmacokinetics

• Greatest relief when inhaled ~ 30 seconds prior to

contraction results in highest serum peak concentrations

• MOA
• Triggers endogenous opioid release
• N-methyl-d-aspartate receptor inhibition reduces hyperalgesia (similar to

ketamine)

• Anxiolysis mediated by central gamma-aminobutyric acid receptors may

enhance the euphoric properties (similar to benzodiazepines and ETOH)

• Stimulatory activity at dopaminergic, and α2 adrenergic receptors
• Nitrous oxide is eliminated unchanged from the

body

• Rooks JP. “Safety and risks of nitrous oxide labor analgesia: a review.” J Midwifery Womens Health

2011;56:557–65

• Maze M, Fujinaga M. “Recent advances in understanding the actions and toxicity of nitrous oxide.”
• Anaesthesia. 2000;55:311-314.

NitronoxTM

Porter Instruments, Hatfield, PA ~$5,500

ENTONOX TM

Not available in the United States

Pin index safety system

Medical gas line Safety Systems

Oxygen vs Nitrous e-cylinder

“If it cannot be measured, it cannot be studied”

• A common academic saying

Comparison of N2O efficacy with other analgesic methods

• NOTE - Studies that evaluate the efficacy of techniques

used for labor analgesia are difficult to design

• There are numerous studies, but most are done prior to

2000

• Summary – Nitrous is approximately as efficacious as
• pioids

Analgesic method VAPS reduction (scale 0-10) Sedation (scale 0-3) Epidural

• 5

Remifentanil

• 1.5

2 Nitrous

• 0.5

0.5

• Westling F, Milsom I, Zetterström H, Ekström-Jodal B. “Effects of nitrous oxide/oxygen inhalation on the

maternal circulation during vaginal delivery.” Acta Anaesthesiol Scand. 1992;36:175-181

• Douma MR, Verwey RA, Kam-Endtz CE, et al. “Obstetric analgesia: a comparison of patient-controlled

meperidine, remifentanil, and fentanyl in labour.” Br J Anaesth. 2010;104:209-215.

Epidural vs Nitrous

Epidural Nitrous Dense/significant pain relief Variable and modest pain reduction No effect on anxiety* Significant anxiolysis Invasive Noninvasive expert personnel required No special skills required Monitoring required No monitoring required Serious side effects are uncommon No serious side effects when used in labor Restricted to bed Unrestricted ambulation Needs IV access and urinary catheter Does not require either Able to convert to surgical anesthesia Not possible as MAC of 104%

* Debated Collins et al. “Nitrous Oxide for Labor Analgesia: Expanding Analgesic options for Women in the United States.” Rev Obstet Gynecol. 2012; 5(314)

Most common ADR with Nitrous Oxide….

• Mild respiratory

depression/hypoxia (debated)

• Drowsiness
• Vertigo
• Nausea (debated)
• No effects on uterine

activity

• No increase in

maternal nausea or vomiting during labor.

• Lucas DN, Siemaszko O, Yentis SM. “Maternal hypoxaemia associated with the use of Entonox in labour”. Int J Obstet
• Anesth. 2000;9:270-272.
• Rosen MA. Nitrous oxide for relief of labor pain: A systematic review. Am J Obstet gynecol 2002; 186: S110-126.

Candidates for Nitrous…

• Parturients who are not NAA candidates
• Parturients who are rapidly progressing
• Parturients who want to ambulate, avoid bladder

catheterization, or avoid IV access.

• Vaginal repairs
• Retained placental products

Non-Candidates…

• Parturients with “at risk*” fetuses
• Persons in the labor room who are 1st trimester or

wish to become pregnant (nurses and visitors).

• *Non-reassuring fetal strips or parturients requiring oxygen

Nitrous Cost

• St. Joseph in Lewiston charges flat fee of $107
• Labor epidural cost is dynamic. Approximately

$1000 to $1400 at SLH

• Cost roughly equates to efficacy and complexity of

management.

Occupational exposure limits

OSHA* Not currently regulated NIOSH** 25 ppm time weighted average for duration of use (for exposure to “waste” gas.) ACGIH*** 50 ppm time weighted average for an 8-hr use * Occupational Safety and Health Administration ** National Institute for Occupational Safety and Health *** American Conference of Governmental Industrial Hygienists

Spontaneous Abortions and Scavenging

• Spontaneous abortions in rats at ≥ 1000 ppm
• Vertebral and rib defects in rats after days of exposure

to >45% concentration of nitrous

• NIOSH reports concentration of ≥ 1000 ppm in

nonscavenged settings

• “Scavenging equipment can make large differences in

exposure levels at moderate cost and appears to be important in protecting the reproductive health of women who work with nitrous oxide”

• There have been multiple epidemiological studies that

both support and refute a cause an effect relationship

More elephants…

• There is accumulating evidence that anesthetic agents

result in neurodegeneration of the developing brain (rat and primate).

• However, Nitrous oxide at subanesthetic concentrations,

reportedlytriggers little or no neuroapoptosis

• Creeley CE, Olney JW. The young: neuroapoptosis induced by anesthetics and what to do about it.
• Anesth. Analg. 2010;110(2):442–8.
• Jevtovic-Todorovic V et al. Early exposure to common anesthetic agents causes widespread

neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci 2003;23:876– 82

• Ma D, Williamson P et al. Xenon mitigates isofluraneinduced neuronal apoptosis in the developing

rodent brain. Anesthesiology 2007;106:746–53

Occupational exposure references

• Viera, E., Kleaton-Jones, P., Austin, J.C., Moyes, D.G., and Shaw, R. 1980. Effects of

Low Concentrations of Nitrous Oxide on Rat Fetuses. Anesth Analg 59: 175-177.

• Control of Nitrous Oxide in Dental Operatories. 1994. Cincinnati, OH:

U.S.Department of Health and Human Services. Public Health Service. Centers for Disease Control and Prevention. National Institute for Occupational Safety and

• Health. DHHS (NIOSH) Publication No. 94-129
• Rowland, A.S., Baird, D.D., Weinberg, C.R., Shore, D.L., Shy, C.M., and Wilcox, A.J.
• 1992. Reduced Fertility Among Women Employed as Dental Assistants exposed to

High Levels of Nitrous Oxide. N Engl J Med 327: 993-997

• Rowland, A.S., Baird, D.D., Shore, D.L., Weinberg, C.R., Savitz, D.A., and Wilcox, A.J.
• 1995. Nitrous Oxide and Spontaneous Abortion in Female Dental Assistants. Am J

Epidemiol 141: 531-38

• Tannenbaum, T.N., and Goldberg, R.J. 1985. Exposure to Anesthetic Gases and

Reproductive Outcome. J Occ Med 27: 659-668.

• Fink, B.R., Shepard, T.H., and Blandau, R.J. 1967. Teratogenic Activity of Nitrous
• Oxide. Nature 214: 146-148.
• Purdham , J.T. 1986. Anesthetic Gases and Vapors (p86-21E). Hamilton, ON:

Canadian Centre for Occupational Health and Safety.

• Kestenberg, S.H., and Young, E.R. 1988. Potential Problems Associated with

Occupational Exposure to Nitrous Oxide. J Can Dent Assoc 54: 277-286

• Quarnstrom F. Nitrous oxide analgesia. What is a safe level of exposure for the

dental staff? Dent Today. 2002 Apr;21(4):104-9.

Proposed SAB mechanism

Implementation models

• Anesthesia Model
• Anesthesia is comfortable with Nitrous and gas blenders.
• Unfortunately, there is no “code” for nitrous administration.
• Nursing/Hospital Model
• Analgesic modality that is controlled by L&D
• Nitrous has a better safety profile than IV or IM narcotics
• Nitrous is commonly used for dental procedures without monitoring.
• There are billing and implementation models already in place

How Nitrous was implemented at SLH

SLH Nitrous Policy

Other pharmacological

• ptions
• Narcotics (Ex; Remifentanil PCA)
• Ketamine
• Dexmedetomidine

All three may be moderately more effective than inhaled nitrous, but have more ADR’s and more complicated setup.

Summary

• Nitrous oxide, although providing only a modest

reduction of pain, gives laboring women an inexpensive, non-invasive, and easily implemented pharmacological option for labor analgesia with essentially no serious adverse reactions for mother

• r baby.
• Nitrous has an 80 year safety record in labor decks

around the world

Good Review Reading

• Rosen M. Nitrous oxide for relief of labor pain: A systematic review.
• Am. J. Obstet. Gynecol. 2002;186(5):S110–S126.
• Baysinger C. Nitrous Oxide for Labor Analgesia.

http://www.asahq.org/resources/resources-from-asa- committees/nitrous-oxide

• Wong C a. Advances in labor analgesia. Int. J. Womens Health.

2010;1:139–54.

• Collins MR, Starr SA, Bishop JT, Baysinger CL. Nitrous oxide for labor

analgesia: expanding analgesic options for women in the United

• States. Rev Obstet Gynecol. 2012;5(3-4):e126-31.
• Likis FE, Andrews JC, Collins MR, Lewis RM, Seroogy JJ, Starr SA,

Walden RR, McPheeters ML. Nitrous oxide for the management of labor pain: a systematic review. Anesth Analg. 2014 Jan;118(1):153-67.

• Quarnstrom F. Nitrous oxide analgesia. What is a safe level of

exposure for the dental staff? Dent Today. 2002 Apr;21(4):104-9

Thank you!

Questions? Comments?