Withdrawal of Invasive Home Mechanical Ventilation in Patients with Advanced Amyotrophic Lateral Sclerosis: Ten Years of Danish Experience

Abstract

Background:

Due to the growing use of home mechanical ventilation in amyotrophic lateral sclerosis (ALS), physicians are increasingly confronted with patients seeking discontinuation of therapy. Yet there are few systematic investigations of the withdrawal of invasive home mechanical ventilation (IHMV). This article aims to describe the medical and patient-related aspects of terminating IHMV in patients with advanced stage ALS.

Methods:

A retrospective, descriptive study was made of all ALS patients cared for at our center from 2002 to 2009 who decided to withdraw their consent for IHMV.

Results:

All 12 ALS patients (4 females) received continuous IHMV. They had a median age of 61 years (range, 39–69 years). In all cases advance directives for end of life care, particularly concerning withdrawal of treatment, were discussed before the initiation of IHMV. The median time from initiation of IHMV to the decision to terminate treatment was 22 months (range, 1–35 months). The reasons for requests were for all patients a general loss of “meaning in life.” Deep sedation was achieved with high dose morphine and diazepam before disconnecting the ventilator.

Conclusion:

Patients' requests for the withdrawal of IHMV in advanced stage ALS was related to a perceived “loss of meaning in life.” Termination of treatment was performed under deep sedation as a medically, legally, and ethically justified procedure.

Introduction

The management of patients with amyotrophic lateral sclerosis (ALS) has developed rapidly over the past 20 years and although ALS is incurable, it is treatable.^1,2 The role of the physician is to provide comfort and optimize quality of life and the medical management of patients with ALS. This is a process extending over months or years, beginning with informing the patient of the diagnosis and continuing through to the terminal phase.¹ Regarding the diagnosis and management of ALS many articles have suggested that evidence is still weak and have commented that curative therapy is lacking. Even a review categorized by the authors as evidence-based lacks evidence and consists mostly of good practice points.³ The use of home mechanical ventilation (HMV) in ALS varies greatly between centers and countries, probably as a result of cultural and ethical differences,³ the clinician's attitudes, and the lack of evidence-based guidelines regarding HMV and withdrawal of treatment. Although there is a wide acceptance that advance directives for palliative end-of-life care are important and should be discussed at an early stage,³ there is a lack of guidelines for and descriptions of care and treatment of ALS patients.

In recent years, a growth in the use of HMV in ALS has been observed. In western Denmark, the prevalence of this group of patients has increased from 0.24 per 100,000 to 5.44 per 100,000 between 1998 and 2009 (Fig. 1).

FIG. 1.

Amyotrophic lateral sclerosis patients (ALS) on home mechanical ventilation (HMV) from 1998 to 2009 at Respiratory Centre West in Denmark.

Patients suffering from ALS have been offered noninvasive ventilation by mask (NIV) and invasive home mechanical ventilation via tracheostomy (IHMV) in western Denmark since 1998. Furthermore, an increasing proportion of ALS patients use IHMV, currently 32% of all treated patients in western Denmark. This high incidence is partly explained by the Danish welfare model providing interdisciplinary care and treatment, personal assistance in the home 24 hour a day, personal cars, and technical equipment, all paid for by the local authority. In addition, there is an active ALS patient group working to inform fellow sufferers of their options and rights. The patient's wishes and instructions regarding treatment and withdrawal thereof, together with a clear plan for management of respiratory failure should be established in advance.

Although Danish legislation (Table 1) addresses the question of termination of therapy, the decision to terminate ventilatory support is nevertheless difficult.³ When planning care and treatment, the autonomy of the patient should be respected,² especially in relation to advance directives for end-of-life care. When offering IHMV it is therefore important to acknowledge the risk of the patient developing a totally locked-in state (TLS) in the advanced stage of ALS, defined as no voluntary and emotional motor function or communication.⁴ Consequently, due to the growing use of HMV in advanced stages of ALS, physicians are increasingly confronted with patients seeking discontinuation of therapy. Yet there are few systematic investigations regarding the withdrawal of IHMV, and, for example, very few case reports have mentioned that parenteral diamorphine, a benzodiazepine and an antiemetic may be appropriate when the patient decides that ventilatory support should be withdrawn.³ Timing, legislation, and the family are often not mentioned and, if so, commonly only discussed in the context of treatment with noninvasive ventilation.

Table 1.

The Danish Health Law No. 546 of June 24, 2005

Chapter 5, § 15.

Paragraph. 1: No treatment should be initiated or continued without the patient's informed consent.

Paragraph. 2: The patient can at any time withdraw his consent.

Chapter 6, § 25.

Paragraph. 1: A terminally ill patient may refuse treatment which will only postpone death.

Paragraph. 2: If a terminally ill patient is unable to express his own right of self-determination, a professional person may not start or continue life-prolonging treatment.

Paragraph. 3: An irreversible dying patient may receive analgesics, sedatives, or similar measures which are necessary to relieve the patient's suffering, even though this may lead o acceleration of death.

One of the controversial aspects of IHMV is the issue of withdrawal of life-support. According to Danish legislation (Table 1), patients must not only give informed consent to any therapy, they can also withdraw consent at any time.

There are few systematic studies concerning the withdrawal of IHMV and in clinical practice this is an issue of great concern for clinicians, patients, and relatives.⁵ A palliative care approach to the care of ALS patients and their caregivers from the time of diagnosis is therefore necessary.⁶ Since 1998, IHMV has been offered to patients suffering from ALS in Denmark and throughout this period, patient and care-centered clinical guidelines have been developed. These guidelines may be regarded as a consensus of good clinical practice, particularly in respect of when and how to withdrawal IHMV treatment. In West Denmark around 300 patients have been offered both invasive and noninvasive HMV and 12 patients have decided to withdraw their consent for IHMV. In this article we describe and discuss the medical and patient-related aspects and circumstances of terminating IHMV in these 12 patient cases in advanced stage ALS.

Method

A retrospective, descriptive study of ALS patients cared for at Respiratory Centre West in Denmark from 2002 to 2009 who decided to withdraw their consent for IHMV. The times from initiation of IHMV to decision of termination for each patient were recorded. The reasons for the request and the circumstances of the procedure of termination were obtained. One case example will be described.

Results

Twelve ALS patients (4 females) median age 61 years (range, 39–69 years) were included in the study. All patients were cared for in their own homes primarily by informal caregivers 24 hours a day and they all had percutaneous endoscopic gastrostomy feeding tubes (Table 2). In all cases, advance directives for end-of-life care concerning withdrawal of treatment were discussed with the patient before the initiation of IHMV. All patients gave in advance their informed consent to withdrawal treatment with IHMV in the event that they should develop a TLS. In 2 cases, the patients developed TLS and were examined by the physician twice, with an interval of 10 days, to ensure the durability of the diagnosis. Withdraw of IHMV was then carried out with the agreement of the close relatives.

Table 2.

Clinical Features of the Twelve Patients Terminated from IHMV

N	Age at death/years/gender	Bulbar(b), spinal(s), or mixed(m) onset	Time on NIV before IHMV/months	Time on 24 hours IHMV/months	TLS +/−
1	42/M	s	2	14	−
2	69/M	s	2	30	−
3	60/F	m	14	34	−
4	39/F	b	0	24	−
5	61/F	s	15	14	−
6	53/F	b	8	35	−
7	66/M	m	0	21	−
8	65/M	m	0	23	−
9	61/M	s	7	4	+
10	47/M	b	1	22	+
11	61/M	m	11	6	−
12	63/M	m	8	1	−

NIV, noninvasive ventilation; IHMV, invasive home mechanical ventilation; TLS, totally locked-in state.

In all cases the median times from initiation of IHMV to termination were 22 months (range, 1–35 months). The reasons for requests were mostly a general loss of the will to live, but for 3 patients crucial factors were, respectively, recurrent infections, inability to speak, and bleeding from colorectal cancer. In only 2 cases was treatment withdrawn after the patient developed a TLS; the remaining 10 patients requested termination of treatment before TLS became an issue. The final decision to withdraw IHMV was taken after median two meetings with the patients (range, 1–3) with median 10 days (range, 1–87 days) interval, to ensure the durability of the decision. The procedure was carried out in the home in 10 cases and at the hospital in 2 cases, according to the patients' wishes. Deep sedation was achieved with high-dose morphine (median,100 mg; range, 60–400 mg) and diazepam (median, 100 mg; range, 20–120 mg) before the ventilator was disconnected. No suffering was observed in any of the patients after this procedure. Median time from discontinuation to apnoea was 15 minutes (range, 0–18 hours) and to death 28 minutes (range, 5 minutes to 18 hours). In all cases follow-up interviews with relatives were offered after 1 month and carried out in 10 of the 12 cases. The relatives stated in all cases that they had been apprehensive regarding the death scenario but they were also in agreement in describing how the discontinuation of treatment passed off peacefully and in a dignified way in accordance with their relative's wishes.

The following case description is intended to illustrate the process in greater detail:

Case example

In 2001 a 56-year-old man was diagnosed with ALS with nonbulbar involvement. In April 2004 the patient was for the first time informed of the various respiratory treatment options. Also at this interview, he was informed of the risk of developing TLS and of the need to make a decision regarding the eventual termination of ventilatory treatment in advance of this. The patient was at that time fully able to communicate but was wheelchair-dependent. He agreed to receive noninvasive and invasive ventilation if needed and would discuss with his wife whether treatment should be terminated if he developed TLS.

One month later, in May 2004, noninvasive ventilation was initiated following an episode of acute respiratory insufficiency. Treatment with noninvasive ventilation was initially only necessary during sleep but over the following few months the need for ventilatory support increased to nearly 24 hours a day. The patient reasserted his wish to start invasive ventilation and had agreed with his wife that invasive ventilator therapy should be terminated if he were to develop TLS. In preparation for invasive ventilator therapy, he should assemble a team of helpers to carry out 24-hour care. The helpers would then be trained in the care of the tracheostomy and the ventilator. When the team was ready, the patient would receive a tracheostomy and invasive ventilator treatment would commence.

In October 2004 the patient was hospitalized with acute respiratory insufficiency. A tracheotomy was performed, invasive treatment was initiated, and the helper team was trained. Thereafter he attended the center as an outpatient every month and as an in-patient once a year, where among other things advance directives where discussed. Over the following 6 years he developed total dependency and communication was possible only by means of eye movements.

In March 2010 the patient was hospitalized with acute pneumonia complicated by sepsis. The pneumonia and related sepsis did not respond to treatment and the patient was furthermore diagnosed with TLS. The patient's wife maintained her husband's wish that ventilation therapy should be terminated should he develop TLS and that withdrawal of treatment should be carried out in such a way as to maintain his dignity. The decision to discontinue ventilator therapy was made in accordance with both his previously stated wishes and relevant legislation. The patient's wife was present at this meeting and she restated her husband's expressed wishes and decision regarding termination of treatment. She was also present when the patient was informed of the plan to induce deep sedation and then discontinue the ventilator. The date for cessation of treatment was agreed with the patient's wife and the patient was again informed in order to ensure as far as possible that he was aware of the decision. Withdrawal of ventilator therapy was carried out in hospital. The patient's wife and two sons were present. The patient was again informed of the procedure. A venous cannula was inserted and 50 mg of morphine and 50 mg of diazepam were given intravenously. When the patient was judged to be adequately sedated the ventilator was switched off. There was no spontaneous ventilation and after 10 minutes the patient was pronounced dead.

The patient's wife was contacted after 1 month. She stated that the withdrawal of ventilator therapy was carried out in a quiet and calm way and she was satisfied that death occurred in a peaceful and dignified manner in accordance with her husband's wishes.

Discussion

In this study we have described our experience and presented some empirical data regarding the process of dying in ALS patients with IHMV. As Albert and colleagues⁷ state, it is a challenging task for clinicians to provide appropriate expectations for life after tracheostomy while recognizing the ALS patients' strong will to live. Many studies emphasis the need for the early establishment of advance directives for end-of-life care^8–10 and the terminal phase of the disease should be discussed before the patient experiences symptoms of dyspnea, in order to prevent unwarranted fears of “choking to death.”^7,11 In spite of the description of the concept of advance directives for end-of-life care and decision making, a recent French study¹² found that in 80% of cases, the physician had to make a treatment decision in the absence of any prior instructions from the patient. Furthermore, the emergence of mechanical ventilation as a treatment option for terminal respiratory insufficiency has introduced further dilemmas.¹³ As described in our study, such dilemmas can be resolved only with repeated discussion with the patients and their relatives and a tool for multi-disciplinary documentation of treatment and care is essential. This documentation tool facilitates communication and the sharing of information and knowledge necessary to carry out end-of-life decisions and end-of-life care related to withdrawal of IHMV. Dialogue and discussion regarding treatment and care is ongoing from the initial planning of HMV until death and special emphasis must be placed on the patient's autonomy and the particular dilemmas involved.

The care of people with ALS involves challenging ethical dilemmas and related decisions are often delayed in patients with ALS.^14–17 The need for careful forward planning and discussion must be emphasized so that decisions can be made in a timely manner as a result of careful consideration and not hurriedly in an emergency situation.¹⁵ As Silvers and colleagues¹⁸ found as long ago as 1991, ALS patients change their minds and decisions regarding life-sustaining therapy can vary during the course of the disease. As we found in our study, periodic reevaluation with the patients must be encouraged with regard to advance directives for end-of-life care. We have not commented specifically on the changing perspective in decision-making in our study. However, the fact that the patients are able to change their minds may be one of the reasons that our center has a high frequency of IHMV, but this needs further investigation. Another reason may be the publicly funded provision of 24-hour care and treatment in the home setting, as defined by the Danish welfare model. Furthermore, the existence of a high-profile and influential patient organization in Denmark, promoting sharing of experiences, discussion, and dialogue between patients and with health care professionals could be another reason for the high frequency of IHMV.

The introduction of IHMV as an option in the treatment of patients with ALS has drastically changed the course of the terminal phase of ALS and elective termination of ventilation requires differentiated pharmacological palliative care. In a retrospective investigation of nine German ALS patients, clinical data were recorded from the discontinuation of both noninvasive and invasive ventilation.⁵ The terminal phase in deep sedation was short (15–80 minutes).⁵ In our study we had a wider range of 5 minutes to 18 hours but still with no reported suffering. We furthermore had a wider range of doses of morphine and diazepam used than in the German study,⁵ perhaps reflecting national variations in clinical practice. All the patients in our study had minimal or absent spontaneous breathing.

Discontinuation of mechanical ventilation in these circumstances is expected to result in rapid onset of hypoxia. This implies a likelihood of dyspnea and anxiety, if it is not accompanied by deep sedation. We believe therefore that to be ethically the ethically justifiable, the termination of ventilatory treatment requires the induction of deep sedation, and this is consistent with a previous study.⁵

We have described our use of morphine and sedatives in the hope of inspiring others but as Kühnlein and colleagues¹⁹ argue it is important to find further empirical data about the process of dying in these patients.

The form and quality of end-of-life care varies greatly between ALS patients; the appropriate time to induce death by terminating ventilation is not easily defined, and decision making is hampered by logistical and financial barriers. More clinical evidence is needed regarding how to provide optimal end-of-life care, specifically in ALS.^20,21 In The Netherlands, 1 in 5 patients with ALS dies as a result of euthanasia or physician-assisted suicide.²² In other countries a wait-and-see policy toward end-of-life care is often pursued by both the patients and physicians.²³ In our study, early end-of-life decision-making and establishment of advance directives for end-of-life care before the start of IHMV were standard practice and our results were similar to Burchardi and colleague's²³ conclusion that an open and honest patient-physician dialogue is an important prerequisite for the discussion of living wills.²³ In a recent Cochrane review Radunovic²⁴ states that it is unlikely that there will be further randomized controlled trials in unselected cohorts of patients with ALS because of ethical issues. Good practice points and descriptive studies will therefore be of great importance in the future care and treatment of patients with ALS, especially the regarding withdrawal of IHMV in the terminal stage.

Conclusion

A majority of the patients decided in advance that life-prolonging treatment should be withdrawn in the event of them developing TLS. The reason cited for this decision was a general loss of meaning in life. Withdrawal of IHMV under deep sedation may be a medically, legally, and morally justified procedure to ensure a peaceful death in patients with advanced stage ALS and dependent on continuous IHMV.

Author Contributions

P.D. is the primary author and was responsible for the drafting of the manuscript. P.D. contributed the majority of the writing and analysis in this manuscript. The other author's contribution to the manuscript is reflected in the order of the authors on the title page. P.D. and M.F. were responsible for the study conception and design. P.D., M.F., C.S.K., and C.K.L. made critical revisions to the paper. M.F. supervised the study.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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