Miracle cure?

In 1989, happy-go-lucky teenager Anthony Bland went to support Liverpool, his favourite football team. Tragically that day he was crushed in the Hillsborough disaster, suffering such a severe chest injury that it caused profound hypoxic brain damage. He was in a permanent vegetative state (PVS) with no prospect of recovery. This condition means that a patient requires 24-hour care. They will be doubly incontinent and, due to their absent swallow/gag reflex, they will require artificial feeding, usually by a percutaneous endoscopic gastrostomy (PEG) tube. While the condition is characterised by a sleep/wake cycle, a spontaneous breathing ability and stable circulation, patients are not considered to be conscious of themselves or their environment.

When Bland's landmark case reached the House of Lords (Airedale NHS Trust v Bland [1993] AC 789), the decision was unanimous that the declaration sought by the hospital to withdraw all life-sustaining medical treatment measures should be granted. Lord Goff observed (at 870) that his condition was 'in reality no more than a living death, and for whom such treatment or care would, in medical terms, be futile'.

High Court application

Following Airedale, where the treating clinician of a patient in a PVS and his hospital staff (or indeed the patient's family) believe that continuing treatment is futile and should cease, an application must be made to the Family Division of the High Court. (When the Mental Capacity Act 2005 comes into force in October 2007, applications for declaratory relief will be made to the Court of Protection.) Such applications protect the Trust and its staff from criminal and civil liability over any future omission of treatment. The family of such a patient frequently supports the application, considering that, had they the ability to decide for themselves, they would not wish to live a life without meaning or awareness. On the grant of declaratory relief, the withdrawal of treatment permits the patient to pass away peacefully.

An apparently unresponsive patient clearly lacks capacity to make decisions about their own medical treatment, and so in such cases an initial declaration will be made by the court to that effect, with the Official Solicitor appointed as their Litigation Friend. When Airedale reached the Court of Appeal, referring to Bland's incapacity, Hoffmann LJ held as follows (at 827-828):

'It would'¦ be in accordance with the English approach to resolving the conflict between the right of self-determination and the sanctity of life that if Anthony Bland were to be momentarily restored to consciousness with full knowledge that he would shortly revert to his persistent vegetative state, and if he were to instruct those caring for him that he no longer wanted artificially to be kept alive, the doctors and nurses would be obliged to respect his wishes. If he were to give such an instruction, I think that many would feel that his wishes be obeyed, not only because they were his wishes, but because (unlike the case of a person who for religious reasons refuses treatment which could restore him to vigorous health) his wishes were entirely understandable. The horror of his situation is such that few would not think it perfectly reasonable for him to decide that, as he had already lost all sense and consciousness, he would prefer to die.

'In this case, however, Anthony Bland has not made such a decision and never will.'

This part of the judgment has proved hauntingly prophetic in the light of new research into treatment for PVS which recently led to a high-profile application to court (B NHS Trust v J, unreported). Mrs J had suffered severe anoxic brain damage. Her family disagreed with the hospital's decision to undertake a trial of medication which might improve her vegetative state.

A South African study had found that Zolpidem '“ ironically, a sleeping pill '“ remarkably had the reverse of its intended effect in patients with an apparent diagnosis of PVS ('Drug induced arousal from the permanent vegetative state', Clauss & Nel, NeuroRehabilitation 21 (2006), 23-26). The ongoing study found that three apparently non-sentient PVS victims of road traffic accidents with resulting brain damage to whom the sleeping pill was administered once daily developed rapid awareness within around 20 minutes. Once 'awake', they were able to communicate with their loved ones for the first time in years (two of the patients had diagnoses of PVS for three years, and the third for six years). Patient L was able to state the name of his favourite rugby player when asked, perform basic arithmetic, put food in his mouth and swallow it, speak on the telephone, and make jokes. On administration of the drug to patient N, he became able to state his name and age, and to watch television, reacting appropriately to comedy with laughter. Patient G had almost drowned following his road traffic accident. Zolpidem restored his ability to lift his hand, smile and count to five on request. Patients L and G also benefited from a marked decrease in their spasticity '“ a common problem for brain-damaged patients.

When the effects of the drug wore off around four hours after its administration, the patients' awareness 'disappeared' until the following day when the medication was repeated. The drug produced no apparent side-effects. Furthermore, while it would appear that the dosage could only be administered once per day, there was no evidence of tolerance necessitating its increase. Each patient had been treated with Zolpidem for between three and six years.

So how did Zolpidem have such an extraordinary effect in patients previously thought to be entirely lacking in consciousness with no prospect of recovery? Following anoxic brain injury, gamma-aminobutyric acid (GABA) receptors suppress cellular metabolism as a protective mechanism. This leads to the irreversible death of certain brain cells, but dormancy in others. This particular sleeping pill appears to stimulate the production of GABA, which switches off the abnormal cellular metabolism so that the dormant areas of the brain are temporarily reawakened.

Allowing the drug trial

In B NHS Trust v J, the family's objection to a Zolpidem trial was based on their belief that, should it have the desired effect, Mrs J would suffer distress at the realisation of the extent of her severe disabilities. However, the President of the Family Division, Sir Mark Potter, endorsed the Trust's application for declaratory relief that the drug trial would be lawful. This was not unsurprising, given the importance of the sanctity of life; all possible treatment options for a patient who lacks capacity must be explored prior to withdrawal of life-sustaining treatment measures '“ particularly where such treatment is unlikely to have adverse side-effects. Further, the court will have had in mind the words of the then president, Dame Elizabeth Butler-Sloss, in Re L (A Minor) [2005] 1 FLR 491 (at 12-13): 'Even very severely handicapped people find a quality of life rewarding which to the unhandicapped may seem manifestly intolerable. People have an amazing adaptability.'

To the family's great relief (but perhaps sadly for Mrs J), her trial of Zolpidem had no effect (B PCT v J [2006] EWHC 3128 (Fam)). Similarly, there was no response to the drug in another such case (An NHS Trust v SW [2007] (to be reported)) when it was administered to Mrs SW with the agreement of her family prior to an application to court being made for declaratory relief in respect of withdrawal of treatment. As there was no prospect of recovery for either of these patients, the court thereafter granted the declaratory relief sought that it should be lawful for life-sustaining treatment measures to be withdrawn.

Naturally, one has enormous sympathy for Mrs J's family and their wish not to cause her needless distress. Nonetheless, had Zolpidem had an effect, it is suggested that any restored communication between a patient who had previously failed to recognise or respond to their family, however, short-lived, would be liable to prove precious to all parties. This is likely to be so even if a patient remains profoundly disabled due to brain damage.

Work in progress

It is unclear at this stage what precise properties the drug possesses to cause the awakening of the patients in the study, and why it fails to have an effect in all PVS patients. The prevailing view of the medical experts who specialise in such cases in the UK is that the patients in the study had an incorrect diagnosis. Rather than being in a PVS, they suggest, the patients were in a minimally conscious state from which recovery was more likely. Indeed, it should be noted that the patients' diagnoses were made using the 1994 guidance of the Multi-Society Task Force on the Persistent Vegetative State, rather than the guidance of either the Royal College of Physicians or that of the International Working Party in force at the time, both of which were compiled later than the Task Force guidance. (After the diagnoses would have taken place, the Royal College of Physicians provided its 2003 updated guidance which is now the preferred tool for diagnosis of PVS in the UK.) A number of experts in the field have suggested that the patients in the study were the fortunate ones who were likely to recover and emerge from their states of apparent unconsciousness in any event, and Zolpidem merely confirmed a positive prognosis.

Despite the scepticism of the medical profession, and while the significance and efficacy of Zolpidem is unclear at present, the remarkable properties of this apparent 'miracle' pill provides a window of hope for patients with a diagnosis of PVS and their families. Since capacity may fluctuate, in the future it may be possible for a PVS patient who is unresponsive and apparently insensate to regain capacity, albeit temporarily. Had Zolpidem had the effect that Mrs. J's family so wished to avoid, the patient's capacity and autonomy could have been returned to her. As Hoffmann LJ stated in Airedale, if consciousness could be restored sufficiently, even 'momentarily', the conflict between the right of self-determination and the sanctity of life would be resolved. That would result in the decision as to further treatment once again resting with the patient. Given that the vast majority of
individuals in society are likely to want to have a say in their own medical treatment, the discovery of the remarkable properties of Zolpidem can only be welcomed.

Scepticism aside, this recent research in respect of the vegetative state is extremely exciting and encouraging to those who work with patients or know a loved one with this tragic diagnosis. No doubt further research will ensue. It is to be hoped that the unexpected properties of Zolpidem may lead to the development of other drugs which can have an effect in more (perhaps all) patients in a vegetative state, even those whose diagnosis is considered permanent. If this proves the case, the term 'PVS' in the future may become a misnomer, and the number of ethical cases of this nature reaching the courts will be radically reduced in number.

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