The recent update by the French High Authority for Health (“HAS”) on continuous deep sedation until death coupled with the announcement that Midazolam will soon be available on prescription in French pharmacies creates great confusion on the way to use this drug in a home setting for individuals at the end-of-life.
Measures Taken by the “HAS”
After the “Claeys-Leonetti” end-of-life law was voted in 2016, the French National Authority for Health (HAS) began evaluating the guidelines for pain relief, including those for the rare cases for “implementing continuous deep sedation until death (CDSUD)”. Their “care pathway guide” for CDSUD was published in 2018 to assist in the decision-making process on implementing this sedation.
This text has now been updated to specify the modalities for administering drugs, including off-label* drugs, to sedate patients at the end-of-life by “appropriate, deep, transient or continuous sedation until death”. No drug in France has an officially approved indication for use in sedative practices. Thus, by publishing “analgesia for unbearable, resistant pain and sedation in adults: drug use in palliative care until the end-of-life” the “HAS” is basically endorsing specific drugs for sedation as well as recommending their methods of use.
The Midazolam which is currently restricted for use in hospitals, is the recommended first-line drug for sedation.
On February 10, 2020 in a press release issued by the “HAS”, and based on its recommendations, it requested that the government authorize pharmacies to dispense these drugs to general practitioners who care for patients at the end-of-life in their homes.
* Marketing Authorization (MA) refers to the properties of a drug and its use. It is issued with a Summary of Product Characteristics (SmPC) and an informational leaflet for the patient.
What is Midazolam?
Midazolam, more frequently referred to as Hypnovel®, its old trade name, is the only benzodiazepine currently available on the market with an extremely short duration of action. Benzodiazepines are prescribed in psychiatry, mainly for its anti-anxiety effect, in neurology for epilepsy, in anesthesia-resuscitation for sedation, in addictology for alcohol withdrawal … Well-known drugs in this class of benzodiazepines include Lexomil®, Xanax®, Valium®, Rivotril®…However one of the drawbacks for these drugs is their duration of action, with elimination half-lives ranging from 7 to 10 days. Midazolam has the advantage of being eliminated rapidly, with a half-life of approximately 2 hours, thereby minimizing the risk of accumulating the doses. This is an important advantage for balancing drug dosage and treatment, especially in elderly patients, or those with major organ deficiencies (cardiac, respiratory, hepatic, renal…) symptoms which often occur at the end-of-life. In these situations, it is appropriate to prescribe Midazolam. It could even be recommended, whether at the end-of-life or not, to treat anxiety, or to alleviate various anxiety disorders. Thus from a pharmacological point of view, general practitioners should be able to prescribe Midazolam. Up until April 30, 2013 it was dispensed in pharmacies under the name of Versed®.
In addition to analgesic treatment, based on professional agreement, the French National Safety Agency for Medicine and Health Products (“ANSM”) recommends the off-label use of Midazolam for its effect of amnesia, when undergoing painful procedures which may provoke anxiety.
Today, this product has only received marketing authorization for anesthesia. However, the Health Ministry has announced that it intends to approve Midazolam for sedation, which will create an amalgam between this product and deep continual sedation until death.
Continuous deep sedation until death, an exceptional last resort measure
Before the law was voted, “deep and continuous sedation until death” had been previously practiced by professionals in rare cases, for circumstances of unbearable, resistant suffering which could not be relieved by any other means, and when faced with a short-term vital prognosis. Basically, sedation alters the patient’s consciousness and thus severs any further relationship. The sedative doses may be proportional to the intensity of the symptoms and reversible. Professionals prefer to use, when it is possible, painkillers which allow patients to remain conscious. On the contrary, sedating a patient whom we know will not wake up is difficult both for close relatives and caregivers. The official French National Authority for Health “HAS” text rightly points this out and recommends a specific support for the various participants concerned to ensure that these situations are not trivialized, and must remain a rare practice.
The law provided that sedation request could be initiated by the patient himself. When stopping or restricting care, including nutrition and hydration, there is a risk that this practice could veer towards euthanasia. Alliance VITA takes part in the movement “Relieve Suffering without Killing” which also brings together health professionals, and together they denounced this gray zone during debates for revising the law. Some ambiguities still persist despite the recommendations by the “HAS”.
What the Law Stipulates
France passed a law on April 22, 2005 which allowed families and doctors of terminally-ill patients to withhold life-sustaining treatment. However in 2008, following the case of Chantal Sébire, suffering from an incurable facial tumor, and who requested assisted suicide, this law was revised and the Code of Ethics was modified. Thus article 37, (§III) of this law concerning patient rights at the end-of-life states: “(…), even if the patient’s suffering cannot be assessed due to his cerebral state, the doctor may implement treatment to relieve the pain of the person, in particular analgesics and sedatives (…). He also ensures that the patient’s relatives are informed of his situation and receive the necessary support. The principle of maintaining sedation and this article of the Code of Ethics were not explicitly included in the law of April 22, 2005.
The law of February 2, 2016 allows “continuous deep sedation until death” under very specific conditions: at the patient’s request to avoid all suffering and unreasonable obstinacy. According to the law on unreasonable obstinacy, acts of prevention, investigation, treatment or care must not be performed or continued if they are unnecessary, disproportionate or have no other effect than the artificial maintenance of life”. In February, 2018, two years after this law was enacted, the “HAS” issued recommendations concerning continuous deep sedation until death. The two-year time lapse prior to the “HAS” publication testifies to how difficult it is to evaluate these cases before implementing sedation, which must remain exceptional and cannot be trivialized.
Where does the confusion come from?
1 / In her letter addressed to the French Union of Liberal Doctors, the Health Minister, Agnès Buzyn equated administering Midazolam with deep and continuous sedation. This threatens to conceal its real usefulness and to use it as an “ordinary” medicine, whereas this type of sedation must remain exceptional. Due to the Claeys-Leonetti law of 2016, if Midazolam becomes more widely available today, we risk to be confronted with even more cases of hidden euthanasia.
2 / Already last December, a general practitioner from the Seine-Maritime region was accused of having involuntarily put 5 of his elderly patients to death with Midazolam, which was labeled as a powerful sedative reserved for hospital use. The product was obtained illegally from his wife who is an anesthesiologist. This legal case is difficult to assess, as the trial is still ongoing. The doctor stated that he wanted to alleviate his patients with this anxiolytic, not kill them. He explained that: “by using this drug, the intention was neither to accelerate the patients’ death nor unnecessarily prolong their lives. Strictly speaking, it was meant to help the patients to remain at home and for their families to remain as serene as possible, since this is always a difficult period.”
Will hidden euthanasia increase when Midazolam is dispensed to general practitioners?
There should be no cause and effect relationship; unless end-of-life support is reduced and sedation until death is practised. As long as the drug is used correctly, there should be an improved quality of care. However for patients experiencing pain, augmented by severe anxiety, the appropriate use of Midazolam may decrease the number of requests to end life, which are very rare and often associated with inadequate care.
The challenge is rather that of training doctors to use this product, and relying on genuine collegiality when establishing conditions for using it for sedation. It is the context of the Claeys-Leonetti law that is unclear and leads to confusion.