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Is Nitrous Oxide Safe for use in Pneumothorax?

Three Part Question

In [adults with simple pneumothorax] is [administration of equal part nitrous oxide and oxygen gas] [safe]?

Clinical Scenario

A twenty year old male dials 999 for an ambulance complaining of acute onset shortness of breath and severe chest pain. The plain is pleuritic in nature, being worse on inspiration and limiting his ability to take a deep breath. His pain score is seven out of ten. He has no past medical history, but smokes ten cigarettes per day.
On examination, his observations are normal, including an oxygen saturation of 97%. He has slightly decreased chest expansion on the left. There are no signs of mediastinal shift. There is hyper-resonance to percussion along the left chest. Breath sounds are decreased on the left with decreased air entry.
The paramedic makes a provisional diagnosis of primary spontaneous pneumothorax and wonders whether a nitrous oxide and oxygen gas combination would be a safe analgesic choice in this patient.

Search Strategy

OvidSP interface - MEDLINE 1950 to April 2010
[exp pneumothorax OR] AND [exp nitrous or Nitrous Oxide/ OR exp or Analgesia, Obstetrical/ OR exp] LIMIT to english language

Search Outcome

38 papers, of which 34 were irrelevant and one was of insufficient quality

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Eger & Saidman
Three dogsExperimental Research - Animal StudyChange in volume of pneumothoraxVolume increased by 100% over 10 minutes and almost 300% by 60 minutes.No correlation to clinical outcome, change in observations, etc. Subjects anesthetized and undergoing positive pressure ventilation
VariousSystematic Review of Experimental Studies & Case ReportsMovement of nitrous oxide gas into various air filled body cavitiesNitrous oxide freely and rapidly moves into both artificial and native air filled cavitiesOnly reviews experiments and various case studies. Limited information on pneumothoraces
Seaberg et al
Five female pigsExperimental Animal CrossoverChange in pneumothorax sizeStatistically significant increases in size were produced in subjects with small and medium pneumothoraces after thirsty minutes No measurement of nitrous oxide in pleural gas
Hemodynamic compromiseNone of the subjects developed any hemodynamic complications or deteriorations, nor any clinical signs of tension pneumothorax


These papers all elaborate on one known truth about inhaled nitrous oxygen gas – it will diffuse into air filled cavities. Nitrous oxide gas’ ability to permeate body air spaces is largely to do with its high solubility. However, the clinical implications of this are what are of interest to determine whether it is safe for clinical use. The concentration of nitrogenous gas plays an important part in determining the quantity of volume expansion that will occur. Analgesic mixtures used commercially contain a 50% solution mixed with 50% oxygen gas, and are demand-activated by spontaneous breaths of the patient, which was artificially replicated in the study by Seaberg et al. Positive pressure ventilation with concentrations higher than 50% is used in the anesthetic setting, and therefore outcomes are only loosely analogous to real life emergency department and prehospital scenarios. Based on the results of these studies, it is difficult to make pneumothorax an absolute contraindication to administration of N2O and O2 mixtures. While there was no evidence that increasing size of pneumothoraces led to tension pneumothorax or hemodynamic instability, caution should be used and the patient kept under close observation if nitrous oxide is to be administered. None of the studies replicated a true pneumothorax, however, as damage to the parietal pleura was always used to introduce the air, as opposed to the visceral pleura as in a real pneumothorax. The effect this might have on volume changes is unknown. Further study into the area is warranted, although carrying out such investigations on human patients would be both ethically and theoretically difficult.

Clinical Bottom Line

While equal part nitrous oxide and oxygen gas mixtures, e.g. Entonox®, may not lead to deterioration of patient condition, it does lead to increase in size of pneumothorax. Therefore, its use in patients with known or suspected pneumothorax should be cautioned against, making it a relative contraindication.

Level of Evidence

Level 3 - Small numbers of small studies or great heterogeneity or very different population.


  1. Eger, E I; Saidman, L J Hazards of Nitrous Oxide Anesthesia in Bowel Obstruction and Pneumothorax Anaesthesiology 1965; 61-6
  2. Munson, E S Transfer of nitrous oxide into body air cavities British Jounral of Anaesthesia 1974; 202-9
  3. Seaberg, D C; Yealh, D M; Ilkhanipour, K Effect of nitrous oxide analgesia on pneumothorax Academic Emergency Medicine 1995; 287-92