Authors:

Dr. Benjamin Thomas, Staff Specialist in Palliative Medicine, Illawarra Shoalhaven Local Health District, NSW, Australia. bluesky: andiyar.bsky.social

Dr. Greg Barclay, Senior Staff Specialist in Palliative Medicine, Illawarra Shoalhaven Local Health District, NSW, Australia

 

 

 

Introduction:

Voluntary assisted dying (VAD) is becoming more widespread in multiple jurisdictions around the world. Legislation is currently being considered in parliament in England and Wales. This is being followed with some interest in Australia, where assisted dying is accessible under certain preconditions in all state jurisdictions, with services introduced between 2019 to 2023. Implementation has required new processes and procedures for referral pathways, for instance, and access issues have needed to be addressed. In the Australian context there have been funding implications for clinical services and for state governments.

Background:

It is notable that the different jurisdictions in Australia have different criteria for administration of drugs for the purpose of VAD, with all states having an intravenous (IV) and oral (PO) option available. These options vary slightly from state to state, and there are limitations on discussing specifics, due to Australian Federal Law which can lead to criminal charges. International experience however of medical aid in dying in Canada (MAID) and reviews of the agents used there, reveal similar practices, with similar agent groups like paralytics, barbiturates and anaesthetic agents available¹.

There is a significant paucity, however, in the literature about the effect and process these agents have upon the not-imminently-dying patient when they are administered, whether by the PO or the IV route.

Patients who are in the terminal phase of life will often have medication provided that can be sedative, with an apparent relief of consciousness and comfort provision, however recent studies in palliative medicine have demonstrated that apparent comfort does not necessarily translate to deep sedation, with responsiveness to almost the point of awareness, and reaction to breakthrough medication evident even when patients look externally comfortable². This leads to the question around the dying process in relation to VAD – the efficacy of the agents utilised may be there in theory, but is the process for the patient dying via VAD drug regimens as comfortable as it can be?

Agents

Barbiturates have been utilised in lethal injection protocols, notably in the United States, until recently due to ethical concerns around supply by manufacturers. There have been numerous reports of patients suffering at the point of death, which is potentially dose-dependent. There was an autopsy series conducted on capital punishment prisoners who were executed with barbiturates that revealed, concerningly, a high incidence of acute (flash) pulmonary oedema (APO) post-mortem³, also associated with benzodiazepines. The occurrence of APO in settings such as VAD has not been studied, but could be potentially concerning due to the symptoms of respiratory distress and suffocation from APO, which a high enough dose of barbiturate, might externally mask from the external observer. The individual would be unable to move a muscle to show any signs of distress, and may even look peaceful.

IV regimens described in MAID jurisdictions often use propofol for sedation and a neuromuscular blockade agent to ensure diaphragm paralysis and death^1,4. These regimens should be highly effective at achieving death. It is important to note that patients under anaesthesia can have awareness, despite them appearing in deep sleep, and this can approach 1%^5,6. Neuromuscular blockers work by antagonising acetylcholine at the post-synaptic receptors of the neuromuscular junction, resulting in total muscle relaxation. This effect begins preferentially at smaller muscles and moves to larger muscles of the trunk and finally the diaphragm, causing respiratory failure. In combination, using an anaesthetic agent with a neuromuscular blocker would in theory be efficacious, but if there was any preservation of awareness despite lack of external responsiveness, a patient would be at risk of awakeness during paralysis and eventual suffocation.

Reflection

There is a lack of information in the medical literature around VAD and the underlying processes. The agents utilised eventually have the desired effect of achieving death, but it is the process by which they do so, that may result in a patient suffering, whilst appearing externally calm due to sedatives taking away control potentially without fully diminishing awareness. Our concern is that these issues may have been inadequately considered in the implementation of VAD. Practitioners should consider the side effect profiles of these agents even in the dying – just because someone may look comfortable clinically, there is no evidence regarding what is happening to a patient neurophysiologically, given that unresponsiveness does not equate to unconsciousness⁷. In providing assisted dying, clinicians of course have a clinical duty of care to ensure this is a comfortable process, without distress to the patient.

We would caution against assuming pharmacotherapeutics with known mechanisms of action have a consistently predictable activity. The history of medicine contains multiple examples of arrogant paternalistic assumptions in pharmacology and “best practice”, that ended up reversed when proper independent and randomised controlled studies were performed. ⁸  Areas of medicine that over-rely on anecdotal experience and expert opinion due to potential fear of consequence, or even litigation, are at much higher risk ending up as subject of national inquiries. This is a particularly delicate situation and we owe it to patients and their loved ones to make sure the care we are providing is the best possible – and that if this is a clinicians role, then like all medicine it should be evidence based and appropriately governed and regulated.

We would therefore caution that we do not know what best practice is, and that the current situation, although effective, may be leaving some patients aware and in potential distress. Dosing practices vary considerably in the anaesthetic realm, and there should be cause for concern and consideration of potential harm, even if it is only for a very small percentage of patients – how many potentially aware patients would be considered too many?

We cannot simply assume that they are going gently, because they appear so based on the rather blunt tool of an external observer assessment for signs of distress or discomfort.

 

References

 

1. Stukalin I, Olaiya OR, Naik V, Wiebe E, Kekewich M, Kelly M, et al. Medications and dosages used in medical assistance in dying: a cross-sectional study. CMAJ Open. 2022;10(1):E19-26.
2. Barbato M, Barclay G, Potter J, Yeo W. Breakthrough Medication in Unresponsive Palliative Care Patients: Indications, Practice, and Efficacy. J Pain Symptom Manage. 2018;56(6):944-50.
3. Zivot JB, Edgar MA, Lubarsky DA. Execution by lethal injection: Autopsy findings of pulmonary edema. medRxiv [Preprint]. 2022 [cited 2024 Feb 10]. Available from: https://doi.org/10.1101/2022.08.24.22279183
4. Martin H. Euthanasia referendum: What drugs are used in assisted dying and how do they work. Stuff [Internet]. 2020 Aug 14 [cited 2024 Feb 10]. Available from: https://www.stuff.co.nz/national/health/euthanasia-debate/300073069/euthanasia-referendum-what-drugs-are-used-in-assisted-dying-and-how-do-they-work
5. Ghoneim MM. Awareness during anesthesia. Anesthesiology. 2000;92(2):597-602.
6. Pandit JJ, Andrade J, Bogod DG, Hitchman JM, Jonker WR, Lucas N, et al. The 5th National Audit Project (NAP5) on accidental awareness during general anaesthesia: summary of main findings and risk factors. Anaesthesia. 2014;69:1089-101.
7. Prasad V, Gall V, Cifu A. The frequency of medical reversal. Arch Intern Med. 2011;171(18):1675-6.

Sanders RD, Tononi G, Laureys S, Sleigh JW. Unresponsiveness ≠