Skip to main content

Parenteral Fluids at the End of Life

It is better to die dry than wet. At least that is the gist of traditional thinking in hospice and palliative care, where parenteral (IV or subcutaneous) fluids are often avoided at the very end of life to prevent fluid buildup in the lungs and other organs.

The problem is that delirium often complicates end of life care as well. It is one of the four most common emergency calls for individuals receiving palliative care in the home and a common reason for admissions into inpatient hospice units. Reduced oral intake, a part of the natural dying process, may result in dehydration in some but not all individuals at the end of life, and may be a factor in the development delirium. Studies in the geriatric literature suggest that early recognition of dehydration and volume repletion is an important component of delirium prevention.

So, how do we reconcile our desire to avoid the unintended consequences of IV hydration in those at the end of life with that of treating dehydration to prevent delirium?  Some argue for a greater use of parenteral fluids in these patients to improve quality of life, at the very least for those with some evidence of dehydration.  However, the question remains, does IV hydration improve quality of life and decrease incidence of delirium, or will it just worsen symptoms at the end of life?

Dr. Eduardo Bruera and colleagues from MD Anderson add some evidence to how best to manage fluids at the end of life thanks to a study recently published in the Journal of Clinical Oncology. The authors randomized 129 individuals with advanced cancer from 6 hospices to either parenteral subcutaneous hydration of 1 L per day of normal saline or placebo.  In order to maintain blinding for both patients and staff, the placebo was a 100ml a day of saline injected over a similar 4 hour period per day as the fluids in the intervention group.

Inclusion criteria included advanced cancer, reduced oral intake of fluids with evidence of mild or moderate dehydration, at least mild symptoms of fatigue, hallucinations, sedation, and myoclonus, a life expectancy of less than 1 week, , and a Memorial Delirium Assessment Scale (MDAS) score less than 13 (i.e not severe delirium). Those with severe dehydration were excluded as were individuals with renal failure, congestive heart failure, or a history or clinical evidence of bleeding disorders.

The primary outcome was change from baseline to day 4 for the sum of four dehydration symptoms (fatigue, myoclonus, sedation and hallucinations). They also included a rather complete amount of secondary outcomes including:

  • Individual items on a symptom assessment scale - the Edmonton Symptom Assessment Scale (ESAS)
  • Two dementia scales – the Memorial Delirium Assessment Scale (MDAS) and Nursing Delirium Screening Scale (NuDESC) – and one agitation scale
  • A quality of life scale – the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F)
  • Dehydration assessment scale (the Dehydration Assessment Scale)
  • Labs including creatinine, urea, and electolytes
  • Overall survival.

In the intention-to-treat analysis, there were no statistically significant differences between the IV hydration group and the placebo group at either 4 days or 7 days in regards to:
  • The sum of the four dehydration symptoms (-3.3 vs -2.8, P=0.77)
  • Individual symptom evaluation based on the ESAS
  • Overall delirium scores based on the MDAS
  • Quality of life scores
  • Dehydration assessment scores
  • Median survival

The authors did find some differences in some measures such as night-time delirium scores, which was worse in the placebo group. However, given the numerous secondary outcomes (47 of them), I wouldn't place much weight on this, as by pure chance at least two of these outcomes will be positive using a P of 0.05.

One big limitation of the study was that it was underpowered. The planned sample size was 150 patients, but funding issues required termination of the study after 129 patients. This was likely due to the strict inclusion and exclusion criteria. So, you can argue that the authors didn't find a difference because they didn't enroll enough patients (a Type II error). This may be a classic Type II error where no significant difference between groups are reported when in fact such a difference exists.  I would be surprised though if the authors enrolled another 21 patients that a clinically significant result would have materialized for the primary outcome since it didn't look like a trend was developing (-3.3 vs -2.8, P=0.77).

So in the end, we have some data to suggest that IV hydration of 1 liter is unlikely to provide a meaningful benefit to most hospice patients with advanced cancer with mild to moderate dehydration (but not severe).

by: Eric Widera (@ewidera)


Moshe said…
I have not yet had a chance to read the entire study, so forgive me if this is addressed there.

Why was only one liter of fluid given? Is it possible that the reason no difference was found is because both groups were dehydrated, and the degree of dehydration did not show a difference clinically?
Eric Widera said…
Great question. The study gave 1 Liter of fluids per day "until the patient was unresponsive, developed progressive coma, or died."

Per the authors "a volume of 1,000 mL per day was chosen on the basis of previous studies demonstrating that this amount was adequate to improve clinical outcomes in palliative care patients."

This still may not have been enough to completely reverse mild to moderate dehydration though.
Anonymous said…
I have come to believe that at the end of life the ethical dilemma is to "do no harm." when we know that there is nothing more that we can do medically for the patient. Isn't that what is imparted to the patient and family. Thus, it is more important than the one liter of fluid that is given to the patient. It is the number of IV initiations and sticks that cause pain, the number of times the patient has to be suctioned, or the breaks in the skin caused by incontinence of bowel or bladder. So why we debate IV hydration at the end of life it may need to be shrouded by "do no harm".

Popular posts from this blog

Dying without Dialysis

There is a terrific article in this weeks Journal of Pain and Symptom Management by Fliss Murtagh of King's College in London about the epidemiology of symptoms for patients with advanced renal failure who die without dialysis.  This study is important because while we know that patients with advanced renal failure have a limited life expectancy and the average age of initiation of hemodialysis is increasing, we know little about the alternatives to hemodialysis.  Specifically, we know nothing about symptoms affecting quality of life among patients who elect not to start dialysis (so called "conservative management" - is this the best label?).  This article provides a terrific counterpoint to the article in last years NEJM showing that nursing home residents who initiated hemodialysis tended to die and decline in function (see GeriPal write up here). 

The study authors followed patients with the most advanced form of chronic kidney disease (the new name for renal failu…

The Dangers of Fleet Enemas

The dangers of oral sodium phosphate preparations are fairly well known in the medical community. In 2006 the FDA issued it’s first warning that patients taking oral sodium phosphate preparations are at risk for potential for acute kidney injury. Two years later, over-the-counter preparations of these drugs were voluntarily withdrawn by the manufacturers.  Those agents still available by prescription were given black box warnings mainly due to acute phosphate nephropathy that can result in renal failure, especially in older adults. Despite all this talk of oral preparations, little was mentioned about a sodium phosphate preparation that is still available over-the-counter – the Fleet enema.

Why Oral Sodium Phosphate Preparations Are Dangerous 

Before we go into the risks of Fleet enemas, lets spend just a couple sentences on why oral sodium phosphate preparations carry significant risks. First, oral sodium phosphate preparations can cause significant fluid shifts within the colon …

Survival from severe sepsis: The infection is cured but all is not well

Severe sepsis is a syndrome marked by a severe infection that results in the failure of at least one major organ system: For example, pneumonia complicated by kidney failure. It is the most common non-cardiac cause of critical illness and is associated with a high mortality rate.

But what happens to those who survive their hospitalization for severe sepsis? An important study published in JAMA from Iwashyna and colleagues provides answers and tells us all is not well. When the patient leaves the hospital, the infection may be cured, but the patient and family will need to contend with a host of major new functional and cognitive deficits.

Iwashyna examined disability and cognitive outcomes among 516 survivors of severe sepsis. These subjects were Medicare enrollees who were participants in the Health and Retirement Study. The average age of patients was 77 years.

When interviewed after discharge, most survivors were left with major new deficits in their ability to live independently. …