NITROUS OXIDE: SHOULD WE USE IT?

When I was training, we used nitrous oxide on just about every anesthetic. It was easy to use. It was inexpensive. It didn’t tend to effect hemodynamics so it was useful in less stable patients when combined with an opioid. It helped speed induction through the second gas effect. It was not metabolized so renal and liver insufficiency were of less concern.

However, with all of the more recent investigation into reasons for cognitive dysfunction or decline in infants and the elderly following anesthesia, a lot more is now known about the pharmacologic disadvantages of nitrous oxide (1, 2, 3).

Nitrous oxide irreversibly oxidizes the cobalt atom of vitamin B12, transferring it from the active Co(I) state to the inactive Co(II or III) state, inactivating it, somewhat analogous to the reduction of hemoglobin to methemoglobin (4).

Methionine is an essential amino acid that serves as a methyl donor (via its activated form S-adenosylmethionine) in hundreds of biologic reactions. The end product of methionine demethylation is homocysteine, whose remethylation is catalyzed by the vitamin B12 dependent enzyme methionine synthase (synthetase). Inhibition of methionine synthetase by nitrous is irreversible. New enzyme must be produced to replace that which has been inactivated, which can take 2-7 days.

Ninety minutes of exposure to 50% nitrous is enough to halve function of the folate pathway, raising homocysteine levels. Duration of exposure is important.
Elevated homocysteine is associated with vascular events and prolonged recovery.
So far there is no proof in the literature of increased cardiac risk.  Pretreatment with B6 does not change cardiac outcome — even those with mutated folate pathways

HOWEVER, what about CNS risk? Provision of B6 in the stroke literature shows it does help preservation and recovery in the acute stroke patient Elevated homocysteine levels are a risk factor for dementia and Alzheimer’s. Four hours of nitrous in elderly rats causes long lasting (2 wk) memory impairment. Obviously rats are not humans, however it does give one pause before turning that nitrous dial. ten to Twenty percent of adults have folate and B12 deficiency, perhaps predisposing them to injury.

What about some the other issues with nitrous oxide.

  • Nitrous methylates DNA — which may mean that it can have an epigenetic effect to future offspring. That means that methylation of DNA eggs and sperm could potentially cause changes in genetic expression in our sons and daughters, conceived years after the parent’s (or the grandparent’s) anesthetic.
  • N2O is an NMDA receptor antagonist
  • DNA methylation is involved with long term memory storage. Could interference with this process this be the mechanism effecting memory in elderly rats (5)?
  • N2O is a potent green house gas. It remains in the upper atmosphere about 114 years and promotes depletion of the  ozone layer (5,6,7). Click here for a prior discussion of greenhouse effects of nitrous and our other anesthetic agents.

There are times when limited use of nitrous can be useful. I still use it occasionally to speed mask induction of pediatric inhalational anesthetic in the uncooperative child, for instance. I then turn the nitrous off and switch to air/oxygen. I might turn it on at the very end of a case to smooth the wakeup.

My current practice is to avoid use of nitrous

  • serial anesthetics over a short period (less than time frame for regeneration of methionine synthetase)
  • really long cases
  • patient  with known folate and B12 deficiency
  • malnutrition
  • first trimester pregnancy
  • in vitro fertilization
  • renal failure
  • those with inborn errors of metabolism (or untested family members) homocytineuria, an autosomal recessive disease, is the second most common disease of amino acid metabolism. Associated with elevated homocysteine levels and impaired folate pathway
  • patient with hypotonia
  • megaloblastic anemias
  • during anti-folate chemotherapy
  • hypercoagulability or a prothrombotic state

I consider avoiding or limiting exposure to nitrous in:

  • bone marrow harvesting
  • L&D/C-section ( avoiding interference with neurogenesis)
  • Advanced peripheral vascular disease CAD with at risk phenotypes
  • Demyelinating conditions
  • Stroke and CNS surgery
  • Young children and infants during time of major synaptic formation except for short periods during induction and emergence

Finally, one must consider the effects of waste anesthetic gases on health care personnel exposed during the anesthetic (8).

You can correctly infer from that list that I personally don’t use nitrous much at all these days,. If I do it’s not for very long. While it is certainly true that research has not yet shown clear evidence one way or the other that any specific anesthetic causes neurotoxic effects in our patients. Research is ongoing in infants and in the elderly (9, 10).

Nitrous has it’s uses. But consider use only in those patients with minimum risk of harm.

  1. Use of anesthetic agents in neonates and young children.Mellon RD, Simone AF, Rappaport BA. Anesth Analg. 2007 Mar; 104(3):509-20.
  2. Bittner EA, Yue Y, Xie Z. Brief review: Anesthetic neurotoxicity in the elderly, cognitive dysfunction and Alzheimer’s disease. Canadian journal of anaesthesia = Journal canadien d’anesthesie. 2011;58(2):216-223. doi:10.1007/s12630-010-9418-x.
  3. Pinyavat T, Warner DO, Flick RP, et al. Summary of the update session on clinical neurotoxicity studies. J Neurosurg Anesthesiol 2016;28:356-360https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5077165/
  4. Baum V: When Nitrous Oxide Is No Laughing Matter. http://www2.pedsanesthesia.org/meetings/2007winter/pdfs/Baum-Friday3-9-07-1050am.pdf
  5. Jevtovic-Todorovic V, Beals J, Benshoff N, Olney JW. Prolonged exposure to inhalational anesthetic nitrous oxide kills neurons in adult rat brain. Neuroscience 2003;122:609-16
  6. Ishizawa Y: General Anesthetic Gases and the Global Environment. Anesth Analg 2011;112:213–7
  7. Sherman J ; Le C; Lamers, V; Eckelman, M: Life Cycle Greenhouse Gas Emissions of Anesthetic Drug. Anesthesia & Analgesia: May 2012 – Volume 114 – Issue 5 – p 1086–1090
  8. Health Effects Associated With Exposure to Anesthetic Gas Nitrous Oxide-N<sub>2</sub>O in Clinical Hospital – Shtip Personel.Eftimova B, Sholjakova M, Mirakovski D, Hadzi-Nikolova M. Open Access Maced J Med Sci. 2017 Oct 15; 5(6):800-804. Epub 2017 Oct 10.

Intubation During Cardiac Resuscitation

Intubating patients during cardiac resuscitation is often challenging because of the circumstances surrounding the intubation. Excitement and apprehension accompany this life saving effort. If you don’t intubate often, you’re likely to be nervous. Even experienced intubators get excited in emergency situations, but we control our excitement and let the adrenaline work for us, rather than against us.

Step one, therefore, is to remain in control of your own sense of alarm. The leaders, which includes the person in control of the airway, must stay calm. If you appear panicked, the rest of your team will follow your lead.

Step two is to quickly assess the situation. Is the patient being ventilated? Ventilation takes priority over intubation. Is there suction available? Without suction you many not be able to see the glottis, and you won’t be able to manage emesis. What help do you have? The intubator almost always needs some assistance in having someone hand equipment, or assist with cricoid pressure, among other tasks. As I tell my students, intubation is a team sport.

Finally you need to assess what position the patient is in, and how can you optimize that position. The patient is often in a less than optimal position while chest compressions are in progress. You usually find the patient in one of two awkward positions: on the ground or in a bed. This article discusses techniques to better manage intubation during cardiac resuscitation, especially with the patient in an awkward position. Illustrations are copyright from Anyone Can Intubate, 5th Edition.  Continue reading

When Learning Intubation Is Hard

Learning to intubate is easier for some people than for others. Sometimes, no matter how knowledgeable you are about the theory of the technique, the novice can still struggle to bring it all together to pass the endotracheal tube. The anatomy can be confusing. Understanding how to place the laryngoscope blade and manipulate that anatomy can be challenging. And all the while you must be ever vigilant to protect those precious front teeth, avoid hypertension and tachycardia, and breathe for the patient at regular intervals.

I believe there are 4 chief barriers that inhibit learning how to intubate:

  1. Failure to visualize how the outside anatomy links with the inside anatomy makes it hard to predict how deeply to insert the blade.
  2. A mistaken belief that placing the laryngoscope blade itself is all that is needed to align the axes of the airway and reveal the larynx.
  3. Failure to grasp the dynamic nature of the larynx, and the need to actively manipulate it during intubation.
  4. A lack of understanding that intubation is not a sequence of isolated steps, but is instead a complex dance of interacting steps, each setting the stage for the next.

This discussion is going to assume some knowledge of the basic technique of intubation. If you’d like to review those basics you can find links for multiple prior in depth discussions at the end of this article. (Illustrations and animation from Anyone Can Intubate, 5th edition, C Whitten MD.) Continue reading

Respiratory Depression In A Child: A Case Demonstrating Excellent Communication Skills

When I’m teaching airway management to my Perioperative/OR nurses, I often recount the story of what happened during one particular child’s recovery years ago. This case, involving a 2 year old child who developed respiratory depression in the recovery room, demonstrates how good communication, including the ability to challenge an authority figure, can improve patient safety and allow collaborative teamwork in a crisis management situation. Continue reading

In Airway Emergencies Always Start With The Basics of Airway Management

We have just finished another round of Critical Event Training for my hospital’s Anesthesia and OR staff. One of the scenarios we ran was how to manage a failed airway: the dreaded “can’t intubate-can’t ventilate” scenario.

As an instructor, it’s important for me to set the stage realistically. The more real the scenario, the more the providers will learn and be able to apply the information should they ever find themselves in a comparable situation. I must observe as the trainees respond to the emergency, and then help the trainees self-analyze what went well — or not so well — during the scenario. Of course, discussion of how things went during a training scenario always leads to sharing of examples from past real life scenarios. And after 37 years of practice I’ve had a lot of sharable experiences.

One past case we discussed is particularly appropriate for those students around the country who are just beginning to learn airway management because the solution rested in basic airway management techniques. This case, involving an intubation in an ICU patient that turned into a “can’t intubate/can’t ventilate” emergency demonstrates how returning to the basics of airway management can sometimes be the way to save your patient from harm. All illustrations from Anyone Can Intubate 5th Edition. Continue reading

Close Call In Honduras With A Nosebleed

I recently visited Honduras with a Head and Neck surgical team where we had a close call with a potential airway obstruction due to a blood clot. The case illustrates how a provider should never make assumptions, because if those assumptions are wrong, you can endanger your patient.

After a long day in the OR, while we were packing up to leave, a nurse from the ward ran in and said that one of the patient’s who had had a septoplasty that day for chronic sinusitis was bleeding. I immediately started setting up the OR again while our surgeon went over to the ward. Continue reading

Finding PEEP In a Bottle (of Water): Thinking Outside The Box

As you read this I am flying to Honduras with International Relief Team on a head and neck surgery medical mission. I will attempt to post mission updates from the hospital compound, pending internet connections. Participating in a medical mission to the developing world is never easy.

Medical personnel trained in a high tech environment take for granted the complex monitoring devices, multiple choices of drugs, and plentiful support peronnel which simplify our job. When medical volunteers travel to the developing world they are often unprepared for the potential hazards produced by outdated technology, unfamiliar and sometimes poorly maintained equipment, poor sanitation, limited supplies, and a malnourished, often poorly educated population.

Let me give you an example of one rather exciting case from early in my volunteer experience. Continue reading