Nitrous Oxide for Labor Analgesia

1. Nitrous Oxide for Labor Analgesia Laurey Munch BSN, RN, IBCLC East Carolina University Nurse-Midwifery Concentration

2. 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.

3. “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.” (Leemanet al., 2003; Marmor and Krol, 2002; Rooks, 2011)

4. 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)

5. 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)

6. 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)

7. Welcome NITROUS Oxide!

8. History of Nitrous Oxide • Sir Humphrey Davy (1778- 1829) 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

9. 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)

10. & 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…

11. 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)

12. 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)

13. Physiology • 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)

14. 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)

15. 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)

16. 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

17. Nitrous Oxide for Labor Analgesia • P According to results from a pilot study evaluating the benefits of N20 on labor pain and satisfaction: 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)

18. Nitrous Oxide for Labor Analgesia • P 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)

19. Advantages

20. 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

21. 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 self-confidence and satisfaction • Does not require routine IP interventions (AHRQ, 2004; Bishop, 2007; Holdcroft & Morgan, 1974;Rosen, 2002)

22. 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)

23. 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)

24. 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)

25. 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)

26. 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

27. 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)

28. 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)

29. 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.

30. Conjuring “interest” and “buy-in” for this “new” modality…

31. 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

32. Points to Consider… whendeveloping 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 Non-Anesthesiologists”

33. 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

34. 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)

35. Apotosis: aka programmed cellular death ** Apoptosis also applies to potential SE of sedatives, Potential neurotoxicity of anesthetic agents has become recent topic of “interest”; also applies to potential SE of sedatives, hypnotics, narcotics and other Inhalation anesthetics…

36. 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)

37. 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)(

38. 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)

39. 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.

40. 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 badges- periodic monitoring will be performed by Environmental Safety Division and Machine safety/maintenance will be performed by anesthesia department/provider prior to each use

41. 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

42. Client Education…

43. 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

44. Billing and Reimbursement … …an unfortunate reality in contemporary health care.

45. 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: $4986NOX-55072H Nitronox Wall Mount Package: Retail $4352 Sales Price: $3482NOX-5042H Nitronox Mobile Cart Package: Retail $4476 Sales Price: $3581Pricing includes the new 2013 Medical Device Tax of 2.3%

46. 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) .

47. 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 .

48. In Conclusion… • Self-administered Nitrous oxide for labor analgesia is • Simple • Safe and effective • Inexpensive • Accessible • Popular • Desired • and……. SHOULD BE AVAILABLE AS AN OPTION TO WOMEN IN North Carolina AND THE U.S.!!! .

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50. Thank You .