Clinical trial NCT03710408: Subcutaneous vs Intravenous Hydration on Older Adults
Official title: Adverse Effects of Subcutaneous vs Intravenous Hydration on Older Acutely Admitted Patients: An Assessor-blinded, Non-inferiority RCT
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dehydration
Keywords: Hypodermoclysis
Older adults
Geriatric patient
Hydration therapy
Adverse effects
Subcutaneous hydration
Lead sponsor: Aalborg University Hospital
Sponsor class: OTHER
Collaborators: name: Aalborg University
First posted: 2018-10-18
Enrollment: 51
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the risk of adverse effects of intravenous hydration compared to subcutaneous hydration. Half of the patients will receive hydration by the subcutaneous route the other half by the intravenous route. In the subsequent 24 hours period the patients will be monitored for any sign of adverse effects.

Detailed description: Adequate hydration is essential to humans, and is tightly regulated in the healthy adult by in- and output (i.e. thirst and urine production). This regulation is often hampered in the geriatric patient due to a decreased sensation of thirst and impaired kidney function. The risk of dehydration increases rapidly in the acutely ill geriatric patient with the growing fluid demand of fever and reduced ability to self-hydrate due to fatigue. Dehydration will often aggravate an acute illness creating a vicious circle. External rehydration is essential to stop or even prevent this downward spiral. Adequate hydration can be maintained or achieved by two different routes: oral intake or parenteral infusion. When oral hydration is insufficient, intravenous (IV) fluid infusion is the commonly used route. However, subcutaneous (SC) infusion of fluid, also known as hypodermoclysis, is an alternative route.

Several studies have compared SC hydration to IV hydration with the main outcome being laboratory test of hydration or subjective assessment scores. They all found similar effects on laboratory markers of hydration, which align with the theory of mass conservation. They also found a similar incidence of side effects between IV and SC hydration as secondary outcomes. The main drawback of these studies is methodological shortcomings. The lack of blinding introduces a large risk of bias on subjective outcome such as assessment scores and grading of side effects. Furthermore, the largest of the studies had a third of their patients switch groups diluting the result. A recent Cochrane review on achieving parenteral hydration found that the quality of included trials was low and future trials should prospectively register, have secure allocation concealment, adequate sample sizes and should be reported according to established standard.

This study will examine if subcutaneous (SC) hydration is a safe alternative to intravenous (IV) hydration in the geriatric patient in the Emergency Department, Acute Assessment Unit or Orthopedic Ward of Aalborg University Hospital. This will be achived by preforming an assessor-blinded, non-inferior, randomized controlled trial.

Relevant participants (see Eligibility Criteria) arriving at Aalborg University Hospital will be enrolled after informed consent. Baseline measurements will be obtained, and the participants will be randomized (1:1) to either intravenous or subcutaneous hydration. A sham setup will be use so both an intravenous access and a subcutaneous access will be visible on the patient, but only one of them will be active. For the next 24 hours the participants will regularly be evaluated by a nurse blinded to infusion for the presence of adverse effects.

Eligibility criteria: Inclusion Criteria:

1. Medical patients admitted to Acute Assessment Unit (AAU). (All internal medicine patients are admitted here first, except highly specialized patients (e.g. ketoacidosis or severe cardiology conditions).
2. Orthopedic hip fracture patients admitted to the orthopedic ward.
3. Patients admitted to short term care.
4. Prescription of 0.5-2 liters of parenteral fluid over the next 24 hours.

Exclusion Criteria:

1. Red triage tag (severe ill patients)
2. Prescription of IV antibiotics or other treatment administrate intravenous
3. Severe dehydration (fluid requirements over 2 liters over 24 hours)
4. Known strict fluid restriction (cannot receive ½ liters of fluid infusion)
5. Severe general edema
6. Unable to give informed consent

Primary outcomes:
measure: Incidence of adverse effects (dichotomous variable, blinded, non-inferior)
timeFrame: The participants will be observed for 24 hours after the start of infusion.
Secondary outcomes:
measure: Incidence of serious adverse effects (total number of serious adverse effects (discrete variable, blinded)
timeFrame: The participants will be observed for 24 hours after the start of infusion
measure: Incidence of adverse effects (dichotomous variable, blinded, superiority calculation)
timeFrame: The participants will be observed for 24 hours after the start of infusion.
measure: Incidence of adverse effects (total number of adverse effects (discrete variable, not blinded)
timeFrame: The participants will be observed for 24 hours after the start of infusion.
measure: Personal graded time spend on insertion of active device (ordered categorical variable, non-blinded).
timeFrame: During procedure.
measure: Participants evaluation of pain during inserting the active device (continuous variable, non-blinded).
timeFrame: During procedure.
measure: Participants evaluation of pain during fluid infusion through the active device (continuous variable, non-blinded)
timeFrame: Participants will evaluate this at the end of observation (24 hours after inclusion)
measure: Presence of delirium (dichotomous variable, blinded)
timeFrame: Duration of observation (24 hours)
measure: Death during hospitalization (dichotomous variable, blinded)
timeFrame: From inclusion to end of current admission. Cutoff is one month after inclusion.
Other outcomes:
measure: Effect of infusion method on hydration status, evaluated by P-albumin (continuous variables)
timeFrame: Changes from inclusion to end of observation (24 hours)
measure: Effect of infusion method on hydration status, evaluated by P-creatinine (continuous variables)
timeFrame: Changes from inclusion to end of observation (24 hours)
measure: Effect of infusion method on hydration status, evaluated by eGFR (continuous variables)
timeFrame: Changes from inclusion to end of observation (24 hours)
measure: Effect of infusion method on hydration status, evaluated by P-urea (continuous variables)
timeFrame: Changes from inclusion to end of observation (24 hours)
measure: Effect of infusion method on hydration status, evaluated by P-osmolality (continuous variables)
timeFrame: Changes from inclusion to end of observation (24 hours)
measure: Effect of infusion method on hydration status, evaluated by hemoglobin (continuous variables)
timeFrame: Changes from inclusion to end of observation (24 hours)
measure: Effect of infusion method on hydration status, evaluated by P-sodium (continuous variables)
timeFrame: Changes from inclusion to end of observation (24 hours)
measure: Effect of infusion method on hydration status, evaluated by P-potassium (continuous variables)
timeFrame: Changes from inclusion to end of observation (24 hours)
measure: Effect of infusion method on hydration status, evaluated by blood pressure (both systolic and diastolic will be measured and compared) (continuous variables).
timeFrame: Changes from inclusion to end of observation (24 hours)
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
Study officials:
affiliation: Aalborg University Hospital
name: Mathias B Danielsen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: O'Keeffe ST, Lavan JN. Subcutaneous fluids in elderly hospital patients with cognitive impairment. Gerontology. 1996;42(1):36-9. doi: 10.1159/000213768.
citation: Challiner YC, Jarrett D, Hayward MJ, al-Jubouri MA, Julious SA. A comparison of intravenous and subcutaneous hydration in elderly acute stroke patients. Postgrad Med J. 1994 Mar;70(821):195-7. doi: 10.1136/pgmj.70.821.195.
citation: Slesak G, Schnurle JW, Kinzel E, Jakob J, Dietz PK. Comparison of subcutaneous and intravenous rehydration in geriatric patients: a randomized trial. J Am Geriatr Soc. 2003 Feb;51(2):155-60. doi: 10.1046/j.1532-5415.2003.51052.x.
citation: Ker K, Tansley G, Beecher D, Perner A, Shakur H, Harris T, Roberts I. Comparison of routes for achieving parenteral access with a focus on the management of patients with Ebola virus disease. Cochrane Database Syst Rev. 2015 Feb 26;2015(2):CD011386. doi: 10.1002/14651858.CD011386.pub2.
citation: Danielsen MB, Worthington E, Karmisholt JS, Moller JM, Jorgensen MG, Andersen S. Adverse effects of subcutaneous vs intravenous hydration in older adults: An assessor-blinded randomised controlled trial (RCT). Age Ageing. 2022 Jan 6;51(1):afab193. doi: 10.1093/ageing/afab193.