Administration of opioids, sufficient to counteract pain and/or DARD should be established before ventilator withdrawal. Since many patients already receive benzodiazepines/opioids before the decision to withdraw treatment, the strategy is based on the existing dose and the prediction of the degree of DARD after withdrawal [
14]. There is always the risk of under-medicating for pain, based on the assumption that ‘no-pain’ is associated with neuromuscular blockade during therapeutic ventilation [
18,
19]. Lying in bed, sedated and with severe organ failure, can cause severe pain in muscles and ligaments, especially in elderly patients. This is the main reason for the administration of opioids for pain in end-of-life care on the ICU. Sometimes opiods are proposed for use in ‘sedation’ [
20]. Opioids are inadequate for sedation because they simply do not induce and maintain sleep [
21], but can induce hallucinations, delirium, and restlessness [
22]. One of the reasons to sedate a terminal patient is to relieve terminal stress. The dying ‘organism’ experiences stress due to organ and systemic failure, leading to irreversible destruction of homeostasis and physical death. An increase in endogenous cortisol is presumed to be a protective reflex against these fatal threats. It was hypothesized that if the extent of the terminal stress reaction was high, high-dose morphine administration would suppress a rise in cortisol levels. However, results indicate that cortisol levels are not suppressed by high-dose morphine [
23]. Thus, administering morphine to moribund patients for relief of terminal stress is
not effective. The only valid reason for morphine administration is the relief from (suspected) pain or the prevention and treatment of DARD, which is an observable corollary to subjective dyspnea. For patients and relatives, the sensation of breathlessness is one of the most terrifying symptoms during the dying process. Relatives fear the patient is undergoing excessive suffering due to suffocation. Opioids are often recommended agents for managing DARD [
9,
24‐
26]. Several mechanisms may be responsible for the observed effects. Ventilatory insufficiency and failure at the end of life results from a number of causes including reduced respiratory neuromuscular capacity, increased load by airway obstruction, diminished lung and chest wall compliance, and suppression of the cerebral ventilatory drive in response to high CO
2 levels. Several intercurrent stresses such as anxiety, fever, bronchoconstriction, or stridor may increase fatigue by further increasing drive, effort, and load. Augmented drive by increase in ventilatory effort can result in fatigue, which is clinically significant as shallow breathing occurs, leading to death [
26]. Morphine reduces the work load of breathing, thereby protecting against premature death from fatigue [
26].
Unfortunately, palliative administration of opioids is perceived as hastening of death [
27]. Several studies have shown, however, that it does not effect survival in palliative [
28‐
30] and ICU patients [
2,
26,
31‐
33]. Doses exceeding the required amount necessary to achieve the desired effect of symptom relief should not be used. Much attention is given to physicians’ intentions, but distinguishing between intent to provide palliative comfort or to hasten death is an impossible task. Indirect or hidden intentions cannot be completely determined. The administered dose and choice of medication in the individual patient, rather than intent, should be the determinant as to whether the physician is acting in accordance with normal standards. The often-mentioned risk of ‘serious respiratory depression’ is very rare [
21,
34]. Among 1,524 post-operative patients treated with systemic or neuraxial morphine, a respiratory rate of less than 10 breaths/min was recorded in only 18 (1.2%) patients [
35]. The term ‘respiratory depression’ has no clear definition [
34], but in most cases it refers to low respiratory rate (<10 breaths/min), but are of no concern to dying patients, or at times, even desired. Death of an ICU patient is usually related to fatigue and dysfunction in multiple organs after withdrawal of ventilatory support and is not due to the administration of opioids.