The odorless, the colorless, the tasteless and the complacent

Abstract

In this issue of the Acta Anaesthesiologica Belgica, Chakupurakal et al describe a case series of acute CO₂ overexposure in patients undergoing general anesthesia, caused by CO₂ delivery instead of N₂O¹. Because the thread of the fittings between the N₂O and CO₂ cylinders in Belgium differ by only 0.2 mm, N₂O and CO₂ cylinders could easily be misconnected. The case series illustrates that despite all existing precautions (reviewed in some detail by the authors) deadly mixtures of odorless, colorless, and tasteless gases can still be delivered to the lungs of our patients.

CO₂ can kill. It is used to provide euthanasia in animals². Death is caused by its toxic effects, not necessarily by hypoxic mixtures per se (although hypoxemia may contribute). In humans, low concentrations have little, if any, toxicological effects. At higher concentrations (>5%), hypercapnia and respiratory acidosis ensue. Concentrations above 10% may cause convulsions, coma, and death³. CO₂ levels of more than 30% rapidly lead to loss of consciousness within seconds. The effects in humans are illustrated in Table 1^4-6.

In the reports by Chakupural et al., the dialed gas mixture was 50% O₂ and 50% “N₂O”. The CO₂ concentration at the common gas outlet was 297 mmHg or approximately 40% because CO₂ was delivered via a N₂O flow meter. While the viscosity of CO₂ and N₂O are identical at room temperature, the density of CO₂ (1.87 kg/m3) is higher than that of N₂O (1.977 kg/m3), causing the flow of CO₂ to be lower than dialed. Even so, this was a potentially lethal CO₂ concentration. The only line of defense left between the wrong connection and the patient was, fortunately, a properly functioning multigas analyzer with active alarm and discoloration of the sodalime which rapidly alerted the anesthesiologists to the problem. Swift action prevented patient harm: administering 100% O₂, increasing fresh gas flows, and confirming delivery of O₂.

But what about other lines of defense for other gases we co-administer with O₂? Even when the correct gas cylinder is attached, hypoxic mixtures can form when O₂/N₂O and O₂/air are administered in a circle breathing system. N₂O is not acutely toxic per se but can kill by becoming part of an inspired hypoxic mixture. This risk is supposed to be minimized not only by gas analysis but also by the obligatory O₂/N₂O proportioning device. This device increases the relative proportion of O₂ in the O₂/N₂O mixture as the total FGF is lowered. Halas, the system does not work: inspired hypoxic mixtures can still form, especially within the 1 – 2 L/min FGF range⁷. The system will fail altogether when a CO₂ cylinder is wrongly attached instead of the N₂O cylinder because even non-hypoxic CO₂ mixtures can be toxic! End-expired gas analysis with properly set alarm limits remains essential.

And what about the plain good air we breath? Air/O₂ mixtures can also cause the formation of inspired hypoxic mixtures when an improper mixture of O₂/air is delivered into a circle breathing system. In a sense, N₂ is worse than N₂O. First, we do not measure N₂ concentrations because it is a symmetrical molecule (and thus cannot be measured by infrared gas analysis) and because it has no paramagnetic properties (and thus cannot be measured by a paramagnetic analyzer, used to measure O₂). Second, there is no proportioning system such as the O₂/N₂O proportioning device. Third, N₂ is far less soluble than N₂O (total body stores are only 3 L in the average adult). When air is delivered at a FGF below minute ventilation hypoxic inspired mixtures will form^7-9. The low FiO₂ alarm will go off, but if no appropriate action is taken, the FiO₂ will decrease to lethal levels. Even though an active inspired hypoxic guard exists that automatically increases O₂ delivery if this should occur, the response by the anesthesia community to its availability has been lackluster: its adaptation in modern anesthesia workstations is rather slow. An active inspired hypoxic guard would also be activated when inspired hypoxic mixtures form when the wrong O₂/N₂O mixture is dialed. Target controlled delivery (where the clinician would demand a target inspired or end-expired O₂ concentration) would minimize the risk of improper carrier gas mixing by the anesthesia provider.

To summarize, it is appalling that no uniform standard exists for cylinder fittings in Europe. And it is even more appalling that two nearly identical fittings can be used to connect both N₂O and CO₂ cylinders. N₂O and N₂ can kill. It is dreadful that active inspired hypoxic guards are not becoming an obligatory requirement for future anesthesia workstations. Why are we, the anesthesia community, not more aggressive at closing these safety loopholes? Complacency reigns, it seems. Complacency is defined as overconfidence, self- satisfaction, or smugness that’s bred from success and makes us unaware of potential dangers or threats. The success is patient safety. Anesthesiology has obtained a very commendable track record when it comes to reducing anesthesia related mortality and morbidity. But, as this case series illustrates, loopholes still exist. Therefore, we should not become complacent but instead continue actively closing as many as we can. There is no room for complacency when we are delivering odorless, colorless, and invisible gases and drugs to our patients.

References

1. Chakupurakal S, Gamela G, Ghosez Y, Van Der Linden P. Severe and acute hypercapnia, subsequent to the mistaken connection of a carbon dioxide cylinder to the nitrous oxide manifold: a report of three simultaneous cases. Acta Anaesth Belg 2023; xx:xx – xx.
2. Guidelines for Euthanasia of Rodents Using Carbon Dioxide https://oacu.oir.nih.gov/system/files/media/ file/2021-06/b5_euthanasia_of_rodents_using_carbon_ dioxide.pdf. Accessed October 26, 2023.
3. Permentier K, Vercammen S, Soetaert S, Schellemans C. Carbon dioxide poisoning: a literature review of an often forgotten cause of intoxication in the emergency department. Int J Emerg Med 2017;10:14 doi: 10.1186/s12245-017-0142-y
4. https://ntrs.nasa.gov/api/citations/20200002093/downloads/20200002093.pdf, page 85. Accessed October 26, 2023.
5. https://taskbook.nasaprs.com/tbp/index.cfm?action=public_query_taskbook_ content&TASKID=11247. Accessed October 26, 2023.
6. https://www.nasa.gov/wp-content/uploads/2023/03/CO2-technical-brief-ochmo.pdf Accessed October 26, 2023
7. De Cooman S, Schollaert C, Hendrickx J, Peyton PJ, Van Zundert T, De Wolf AM. Hypoxic guard systems do not prevent rapid hypoxic inspired mixture formation. J Clin Monit Comput 2014; 29:491-7.
8. Ghijselings EI, De Cooman S, Carette R, Hendrickx JFA, Peyton P, De Wolf AM. Performance of an Active Inspired Hypoxic Guard. J Clin Monit Comput 2016; 30:63-8.
9. Hendrickx JF, De Wolf AM, De Hert S. O2, Anybody? Eur J Anaesthesiol 2015; 32:371-3.