From nucleus - summer 2018 - mythbusters:opioids and hydration in palliative care
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Daniella Osaghae explores the evidence
You've heard of evidence based medicine — practising medicine backed up by reliable, critically appraised research. Let me introduce you to evidence based ethics! Christian medical ethics shouldn't shy away from engaging with scientific evidence. Here I hope to show you through logic and critical appraisal, how some myths around palliative care can be dispelled by peer-reviewed research.
Critical appraisal is 'the process of carefully and systematically examining research to judge its trustworthiness and its value and relevance in a particular context' (1)
introduction to logical fallacies
Examples of fallacies used to support myths include:
This is post hoc fallacy as the two events running chronologically are presented as causally related.
'We have to choose between treating the pain and distress knowing it will shorten life OR leaving the patient suffering unnecessarily.'
This is a false dilemma — giving the false impression that the choice is only between the essay and sleep in the first example (one can in fact write a great essay without sleep deprivation). Similarly, suffering can be relieved without shortening life.
Doctors believe that morphine kills and 'experience proves' that those on morphine die.
This is circular reasoning, where the original premise (that my university is best or that morphine kills) assumes the conclusion.
With these fallacies in mind, let's now look at the evidence for two common myths...
Myth 1: Doctors regularly kill their patients with morphine as a 'double-effect'
Estfan et al (3) explore this premise by seeking to determine if there is an association between opioid titration and hypoventilation for cancer pain in the palliative setting. It is an observational study in the US. Patients were selected based on strict inclusion criteria such as: age over 18 and cancer pain necessitating continuous opioid infusion via syringe driver; exclusion criteria included inability to consent and previous parenteral (intravenous or subcutaneous) opioid use.
Baseline data was collected including pain characteristics, vital signs and end-tidal carbon dioxide. End-tidal carbon dioxide, oxygen saturation and respiratory rate were then monitored at the same time each day as measures of respiratory function. End-tidal carbon dioxide was used as the primary variable as it is directly influenced by alveolar gas exchange, so a good marker of respiratory depression.
results & discussion
The mean increase in end-tidal carbon dioxide following opioid titration was not statistically significant, with all subjects maintaining oxygen saturations greater than 92%.This finding was in spite of equianalgesic opioid dosage (ie high enough dose to be effective in pain relief) being given to the patients. The discussion notes that pain is a known antagonist to respiratory depression, making it very difficult to induce respiratory depression if opioid is only given when the patient is in pain.
So were there any limitations? This was a small cohort study at one centre, and was not blinded. Many participants were withdrawn due to changes in clinical condition including delirium (not carbon dioxide-induced, as the study checks), withdrawal of consent and out-of-hours admission; of the 129 recruited, only 30 completed the study reflecting the inherent difficulties in recruiting palliative patients.
Opioids for relief of moderate cancer pain are not associated with respiratory depression and thus they do not hasten death in end of life patients. As few studies of this nature had been done previously, further studies need to be done in different centres — although, notably there was a randomised controlled trial from Switzerland showing similar results to those presented here. (4)
Myth 2: Doctors regularly allow their patients to die by withholding fluids at the end of life
This observational study recruited patients from a variety of hospital and community palliative and oncology settings in Japan. Inclusion criteria included life expectancy of three months or less, age over 20 and incurable malignancy of lung or abdominal origin. Patients with conditions predisposing to fluid overload, such as liver cirrhosis and renal failure, and those using artificial enteral nutrition were excluded. Patients were examined for clinical signs of dehydration and fluid retention. Fluid balance was monitored with recording of fluid input (parenteral fluids) and output (urine, fluid draining, vomiting and insensible body loss). For this part of the study, only patients whose oral fluid intake happened to be less than 500ml/day in the previous three weeks were chosen for simplicity and ethical reasons. Therefore, oral fluid intake was not strictly monitored and oral fluids were not withheld from patients at any time. Sodium, potassium, urea, creatinine and albumin levels on blood tests that happened to be done in the previous week were analysed and patients divided into hydration (so given supplemental parenteral fluids) and non-hydration groups. All of this data was gathered prospectively.
results & discussion
The study had several interesting findings. Mean albumin levels were significantly lower (hypoalbuminaemia) in the hydration group compared to the non-hydration group. This demonstrates that giving parenteral fluids can cause measurable harm as hypoalbuminaemia is linked with fluid retention. On the other hand, there was no significant difference between the hydration and non-hydration groups in their sodium, potassium, urea and creatinine levels (these markers would be expected to go up with dehydration).
The calculated fluid balance was not significantly different between those who had clinical signs of dehydration and fluid retention and those who did not. This may be because terminally ill patients have different physiology, where there is fluid shift from intravascular to interstitial spaces rather than total body dehydration, as shown by the same study group in another paper. (6)
Being an observational study leaves it open to treatment bias. It also focused on abdominal and lung malignancies. Insensible body loss was estimated at 500ml per day per patient, as this is very hard to measure in practice. Patients withdrew for various reasons, but the study helpfully performs analysis to show that there was no significant difference in demographics and cancer type between those excluded and included in the fluid balance part of the study.
Active artificial hydration is associated with hypoalbuminaemia. There are no clear benefits in giving artificial hydration to normalise urea, creatinine, sodium and potassium. Calculated fluid balance does not correlate with clinical signs of fluid retention or dehydration. So, when withholding parenteral fluids, doctors are not dehydrating patients. This begs the question of whether there is any need for performing blood tests and monitoring fluid balance when patients are in their final days.
In summary, we've dispelled two myths of death causation in palliative care. Doctors do not expedite death by prescribing opioids nor do they cause dehydration by withholding parenteral fluids in dying patients. The more studies that are done in this area, the greater the evidence base will become to support the findings here.
I hope this encourages you to explore how research can be directly applied to the way you engage with ethics in your future clinical practice. Evidence based ethics can help as you approach discussions around end of life issues, including sensitively clarifying what is fact or myth. As well as demonstrating integrity as a healthcare professional by dispelling myths, you can also empower patients and their families to make informed decisions about their care, based on evidence.
1. Burls A. What is critical appraisal? Oxford University 18 April 2018. bit.ly/2k2nYuM
2. George & Regnard. Commentary - Lethal opioids or dangerous prescribers? Palliative Medicine 2007;21:77-80
3. Estfan et al. Respiratory function during parenteral opioid titration for cancer pain. Palliative Medicine 2007;21: 81-86
4. Mazzocato et al. The effects of morphine on dyspnea and ventilatory function in elderly patients with advanced cancer: a randomized double-blind controlled trial. Annals of Oncology 1999;10(12): 1511-4
5. Morita et al. Artificial Hydration Therapy, Laboratory Findings and Fluid Balance in Terminally Ill Patients with Abdominal Malignancies. Journal of Pain and Symptom Management 2006;31(2): 130-9
6. Morita et al. Fluid status of terminally ill cancer patients with intestinal obstruction: an exploratory observational. Support Care Cancer 2002;10: 474-479