What is the deal with nitrous? Eric Deutsch MD

Transcription

1 What is the deal with nitrous? Eric Deutsch MD

2 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

3 Disclosure No corporate, financial contracts, or investments to disclose

4 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): Anesthesiologists from Harvard s Brigham and Woman s Hospital

5 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),

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

7 Medical Interventions

8 Nitrous Oxide (N 2 O) Inhaled N 2 O 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)

9 Nitrous Oxide (N 2 O) Premixed 50:50 N 2 O:O 2 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) occupational exposure risk(inactivation of methionine synthase) Rosen MA. Nitrous oxide for relief of labor pain: A systematic review. Am J Obstet gynecol 2002; 186: S

10 Pharmacodynamics & Pharmacokinetics Greatest relief when inhaled ~ 30 seconds prior to contraction results in highest serum peak concentrations MOA o o o o 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 α 2 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: Maze M, Fujinaga M. Recent advances in understanding the actions and toxicity of nitrous oxide. Anaesthesia. 2000;55:

11 Nitronox TM Porter Instruments, Hatfield, PA ~$5,500

12 ENTONOX TM Not available in the United States

13 Pin index safety system

14 Medical gas line Safety Systems

15 Oxygen vs Nitrous e-cylinder

16 If it cannot be measured, it cannot be studied - A common academic saying

17 Comparison of N 2 O 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 opioids Analgesic method VAPS reduction (scale 0-10) Sedation (scale 0-3) Epidural -5 0 Remifentanil Nitrous 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: 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:

18 Epidural Epidural vs Nitrous Dense/significant pain relief No effect on anxiety* Invasive expert personnel required Monitoring required Serious side effects are uncommon Restricted to bed Needs IV access and urinary catheter Nitrous Variable and modest pain reduction Significant anxiolysis Noninvasive No special skills required No monitoring required No serious side effects when used in labor Unrestricted ambulation 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)

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

20 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

21 Non-Candidates Parturients with at risk* fetuses Persons in the labor room who are 1 st trimester or wish to become pregnant (nurses and visitors). *Non-reassuring fetal strips or parturients requiring oxygen

22 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.

23 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

24 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

25 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): 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: Ma D, Williamson P et al. Xenon mitigates isofluraneinduced neuronal apoptosis in the developing rodent brain. Anesthesiology 2007;106:746 53

26 Occupational exposure references Viera, E., Kleaton-Jones, P., Austin, J.C., Moyes, D.G., and Shaw, R Effects of Low Concentrations of Nitrous Oxide on Rat Fetuses. Anesth Analg 59: Control of Nitrous Oxide in Dental Operatories 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 Rowland, A.S., Baird, D.D., Weinberg, C.R., Shore, D.L., Shy, C.M., and Wilcox, A.J Reduced Fertility Among Women Employed as Dental Assistants exposed to High Levels of Nitrous Oxide. N Engl J Med 327: Rowland, A.S., Baird, D.D., Shore, D.L., Weinberg, C.R., Savitz, D.A., and Wilcox, A.J Nitrous Oxide and Spontaneous Abortion in Female Dental Assistants. Am J Epidemiol 141: Tannenbaum, T.N., and Goldberg, R.J Exposure to Anesthetic Gases and Reproductive Outcome. J Occ Med 27: Fink, B.R., Shepard, T.H., and Blandau, R.J Teratogenic Activity of Nitrous Oxide. Nature 214: Purdham, J.T Anesthetic Gases and Vapors (p86-21e). Hamilton, ON: Canadian Centre for Occupational Health and Safety. Kestenberg, S.H., and Young, E.R Potential Problems Associated with Occupational Exposure to Nitrous Oxide. J Can Dent Assoc 54: Quarnstrom F. Nitrous oxide analgesia. What is a safe level of exposure for the dental staff? Dent Today Apr;21(4):104-9.

27 Proposed SAB mechanism

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

29 How Nitrous was implemented at SLH

30 SLH Nitrous Policy

31 Other pharmacological options 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.

32 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 or baby. Nitrous has an 80 year safety record in labor decks around the world

33 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. Wong C a. Advances in labor analgesia. Int. J. Womens Health. 2010;1: 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):e 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 Jan;118(1): Quarnstrom F. Nitrous oxide analgesia. What is a safe level of exposure for the dental staff? Dent Today Apr;21(4):104-9

34 Thank you!

35 Questions? Comments?