2018/08/08 by J. G. Bilmen, Jonathan G. Bilmen, P. M. Hopkins +1 · 5 citations
Neuroscience · Medicine · #Anesthesia and Neurotoxicity Research #Anesthesia and Sedative Agents #Inhalation and Respiratory Drug Delivery
paper · doi:10.1111/anae.14407
Malignant hyperthermia (MH) is a potentially fatal condition caused by exposure of genetically predisposed individuals to potent inhalational anaesthetic agents. It has been promulgated that exposure to agents at a concentration above 5 parts per million (ppm) may be sufficient to trigger a crisis in MH-susceptible individuals. This is based on a publication of work performed in MH-susceptible swine 1. Although 5 ppm probably affords a large safety margin, subsequent research has focused on reducing anaesthetic agent residue in inspired gases delivered by workstations to under 5 ppm when they are used in the anaesthetic management of MH-susceptible patients 2. The evolution of anaesthetic workstations has led to incorporation of more and more internal non-metal pipework. As a result, there is now a significant increase in anaesthetic vapour residue after stopping inhalational agents for more than 60 min. A comparison of newer anaesthetic workstations has shown that inhalational agents can be measured above 5 ppm for up to 144 min following cessation of delivery of anaesthetic agents and application of high-flow oxygen through the system 3. In the days of less complex (and cheaper) anaesthetic machines, many hospitals stored a vapour-free machine that could be used when a patient at increased risk of developing MH needed surgery; this is no longer a financially viable solution. Therefore, there was great interest in the commercial production and marketing (in 2010 in the USA and 2015 in Europe) of activated charcoal filters (ACFs) that were designed to rapidly eliminate inhalational anaesthetics from anaesthesia workstations. It has long been suggested that activated charcoal could serve as an excellent adsorbent to remove inhalational anaesthetic agents as both a pollutant in operating theatres and from anaesthetic circuits 4, 5. Activated charcoal is carbon, purified from wood and other organic sources, which has been treated to create an extremely porous structure. The treatment used is either of the following: chemical, by addition of an acid, strong base or salt, followed by heat treatment; or, physical, by heating the charcoal in an inert gas (nitrogen or argon) to between 900 and 1200 K and then exposing it to oxygen to create the porous state. The highly porous structure creates a huge surface area of exposed carbon atoms that are readily available to bond to any organic matter that passes over them. Hence, when volatile anaesthetic agents pass through activated charcoal, they bind to these exposed carbon atoms and are held within the charcoal (the process of adsorption). This effect makes activated charcoal an ideal substance to filter out volatile anaesthetic agents in our workstations. As early as 1992, groups have been experimenting with activated charcoal as a method to reverse inhalational anaesthesia 6. Activated charcoal is used in many day-to-day products, including toothpaste, skincare products, water purifiers, and as an aid to digestion as an oral tablet. It is also used in healthcare, as an adsorbent for ingested toxins and in facial gas mask filters to help clean air in contaminated atmospheres. It is considered a very safe substance in terms of human exposure (either through contact or ingestion) with almost no side-effects, very occasionally vomiting or constipation with excessive ingestion 7. Studies performed by Krivoy et al. in 2005 studied the use of activated charcoal in respiratory systems containing supplemental oxygen to demonstrate its safety in use with high oxygen-containing systems 8. They found no increased risk whatsoever in exposing activated charcoal to high partial pressures of oxygen (up to 100% oxygen) at ambient temperatures, demonstrating its safety in breathing circuits. Following the introduction of ACFs, there have been several studies regarding efficacy and also debate about whether it should be compulsory for them to be stocked at locations where inhalational anaesthesia is administered. As noted in recent correspondence in Anaesthesia the currently available Association of Anaesthetists guidelines for the management of a MH crisis pre-date the availability of ACFs in Europe 9. The Association of Anaesthetists has convened a Working Party tasked with producing a new comprehensive guideline for the management of MH-susceptible patients, but this may not report until early 2019. The early research on the use of the commercially available ACFs, unsurprisingly perhaps, involved authors who were instrumental in the product coming to market and therefore with a financial interest (albeit appropriately declared) in the product. In 2011, Birgenheier et al. described the successful integration of charcoal filters into an anaesthetic circuit and proposed that they could be used for preparing an anaesthetic workstation for use in MH-susceptible patients 10. These experiments involved bench testing an Apollo (Drager, Luebeck, Germany) anaesthetic workstation, using contaminated parts and determining the most expedient method of ACF placement and disposable pipework replacement to reduce volatile agents to safe levels (< 5 ppm). In addition, as part of their marketing in Europe, Dynaesthetics LLC (the manufacturers of the ACFs) successfully obtained the CE (Conformité Européene) marking, meaning that the ACFs met the necessary standards of health and safety to be used as described in anaesthetic workstations. Subsequent work undertaken by Kern et al. 11 has shown that ACFs can be employed successfully with a wide variety of anaesthetic workstations. In numerous tests, this group found that the filters, when applied according to manufacturer guidelines, successfully reduced vapour concentrations to < 5 ppm in all but one anaesthetic workstation (the Leon +) and even here, the rise only occurred when the workstation was switched from spontaneous to controlled ventilation 11. Furthermore, the rise in concentration of anaesthetic vapour did not exceed 10 ppm, a concentration that is likely to be a safe level of exposure in an MH-susceptible patient 2. Meanwhile, other groups have conducted further bench studies to examine the optimal use of ACFs. It has been demonstrated, for example, that only one ACF is needed when preparing an anaesthetic workstation, provided that it is placed on the inspiratory limb of the anaesthetic circuit 12, 13. The manufacturer still recommends using two filters and this will avoid the potential to put a single filter on the expiratory limb by mistake. The manufacturer also recommends changing the filters for a new pair should a case last longer than 12 h. However, we cannot find any reasonable justification for not just simply removing them after this time period, while maintaining a fresh gas flow of 10 l.min−1, as evidenced by Bilmen and Gillies 12. Contrary to the assumptions of some, the incidence of MH reactions from inhalational agents in the UK has remained remarkably constant over the past 30 years and the mortality remains approximately 4% 14. Indeed, in the USA, mortality from MH increased in the past decade 15. In our experience, a poor outcome is invariably related to the interval between the onset of the reaction and institution of effective treatment. The diagnosis of MH can be challenging, for example, in a septic patient undergoing surgery, and so there is an imperative to be able to institute a multifaceted treatment as soon as possible after the diagnosis has been made. The initial treatment includes elimination of the triggering inhalational anaesthetics; administration of an effective dose of dantrolene and promotion of heat loss. Actions that can be implemented immediately in all cases are turning off the vaporiser; increasing fresh gas flows to maximum; mechanical hyperventilation of the lungs; switching off warming devices; and exposing as much of the patient's body as possible. All other measures are tasks that ideally should be allocated to theatre team members while the anaesthetist leads and coordinates the patient's management. When the emergency is first called, the number of staff available to help is likely to be limited and there will be competing priorities. However, there should be no delay in retrieving dantrolene from its stored location and, ideally, two dedicated team members should begin preparing dantrolene for administration, as well as switching to a non-volatile-based anaesthetic, essentially propofol-based total intravenous anaesthesia (TIVA). The evolution of modern anaesthetic workstations has not only made it more difficult to eliminate the volatile agent but also made it impractical to rapidly substitute with an alternative ‘clean’ machine or replace components that adsorb the anaesthetic. The immediate alternatives available before the introduction of ACFs were essentially either to manually hyperventilate the patient's lungs, using a non-rebreathing circuit to bypass the workstation circuit, or to accept that it would take some time for the volatile agent to be eliminated. Further arrangements could then be made, such as procuring an ICU ventilator, although this takes time to practically arrange, as well as personnel, which may be crucially needed to perform more immediate tasks such as mixing the necessary doses of dantrolene. Even then, an ICU ventilator carries risk of contamination with inhalational anaesthetics, as they are often used to transfer patients from theatres to ICU, which in itself poses a risk to MH-susceptible patients. In situations where a known MH-susceptible patient is undergoing elective surgery, appropriate precautions can be made that do not involve the use of ACFs, such as flushing the workstation to reduce vapour levels to safe margins or to utilise a clean ICU ventilator, although this can be time consuming. In such cases, TIVA would be required. The availability of ACFs provides an effective solution to the quandary of balancing the need to eliminate the triggering anaesthetic and the alternative actions that the available manpower might need to prioritise. We recommend that a pair of ACFs is kept with each box of dantrolene at locations where triggering anaesthetics are used. The application of a pair of charcoal filters into the anaesthetic breathing circuit is straightforward: it merely requires placement of ACFs on the inspiratory and expiratory limb. The manufacturer recommends that the breathing circuit and reservoir bag should be changed at the same time. This requirement during the height of an MH crisis may, however, lead to errors (tubing not placed correctly or connected properly) and a delay in undertaking other interventions. We are hopeful that the next iteration of the Association of Anaesthetists guidelines will address the use of ACFs in the emergency management of MH reactions as well as the anaesthetic management of MH-susceptible patients undergoing elective surgery. Activated charcoal filters are very useful in preparing anaesthetic workstations in situations where time is a critical factor. Furthermore, ACFs may play a critical role in patients who have an ‘on-table’ suspected MH reaction, by removing all trigger agents from the circuit and hence reducing perpetuation of the potential MH crisis. Therefore, we would recommend their storage in all areas where volatile agents are used. Recently, an endowment to the University of Leeds has been used to form the UK MH Registry based within the Malignant Hyperthermia Unit at St James's University Hospital in Leeds. One of the main purposes of the Registry is to be a resource for patients, members of the public and healthcare professionals on all aspects of MH. Details of this can be found at www.ukmhr.ac.uk. Included on this site is a freely downloadable up-to-date guideline for the management of an MH reaction that includes our advice on ACFs. No funding or competing interests declared.