Subcutaneous vs Intravenous Hydration on Older Adults

Study Overview
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Brief Summary
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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
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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.

Official Title
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Adverse Effects of Subcutaneous vs Intravenous Hydration on Older Acutely Admitted Patients: An Assessor-blinded, Non-inferiority RCT

Conditions
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Dehydration

Intervention / Treatment
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* Other: Intravenous hydration
* Other: Subcutaneous hydration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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). Orthopedic hip fracture patients admitted to the orthopedic ward. Patients admitted to short term care. Prescription of 0.5-2 liters of parenteral fluid over the next 24 hours. Exclusion Criteria: Red triage tag (severe ill patients) Prescription of IV antibiotics or other treatment administrate intravenous Severe dehydration (fluid requirements over 2 liters over 24 hours) Known strict fluid restriction (cannot receive ½ liters of fluid infusion) Severe general edema Unable to give informed consent

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subcutaneous hydration<br> | Other: Subcutaneous hydration<br>* Participants assigned to the subcutaneous hydration arm will receive their hydration therapy through a subcutaneous access. This access will be achieved by placing a BD Saf-T-Intima™ Integrated Safety Catheter System on the abdomen or, alternatively if the participants is suspected of becoming delirious and at risk of removing the needle, it will be placed on the back at the scapular region. Furthermore, a sham IV access device BD VenflonTM Pro Safety - 22G will be placed on the dorsal side of the hand without piercing the skin.<br>* Other names: BD Saf-T-Intima™ Integrated Safety Catheter System;|
| Active Comparator: Intravenous hydration<br> | Other: Intravenous hydration<br>* Participants assigned to the intravenous hydration arm will receive their hydration therapy through an intravenous access. This access will be achieved by inserting a BD VenflonTM Pro Safety - 22G in a vein in the dorsal side of the hand or further up the forearm. If the participants is suspected of becoming delirious and at risk of removing the cannula from the hand/forearm, it may be inserted at the dorsal side of the foot. The clinical staff judge this risk and decide site of placement. Furthermore, a sham subcutaneous access device BD Saf-T-Intima™ Integrated Safety Catheter System will be placed on the abdomen without piercing the skin.<br>* Other names: BD VenflonTM Pro Safety - 22G;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse effects (dichotomous variable, blinded, non-inferior) | The incidence of adverse effects of hydration therapy (both serious and minor adverse effects) is the primary outcome measure of this study. Serious adverse effects will be defined as any consequence of infusion requiring treatment(e.g. diuretics, analgesic and antibiotics) Minor adverse effects will be defined as any of the following: Reddening of the skin at infusion site larger than what is covered by dressing. Painful swelling at infusion site. Prolonged swelling at infusion site (more than two hours after end of infusion). Itching. Phlebitis without needing treatment. Patient complaining of infusion related pain. Failure of infusion. Need of reinserting the infusion needle. Accidental catheter removal by the patient. Need for reducing of flow speed due to complaint from the patient. Swelling at infusion site, without discomfort or need for action, will not be evaluated as an adverse effect. | The participants will be observed for 24 hours after the start of infusion. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of serious adverse effects (total number of serious adverse effects (discrete variable, blinded) | A sensitivity analysis of the primary outcome comparing only the serious adverse effects. | The participants will be observed for 24 hours after the start of infusion | 
| Incidence of adverse effects (dichotomous variable, blinded, superiority calculation) | Same description as primary outcome, but this calculation will only be performed if non-inferiority is found. | The participants will be observed for 24 hours after the start of infusion. | 
| Incidence of adverse effects (total number of adverse effects (discrete variable, not blinded) | Same as description primary outcome but this is a comparison of the number of adverse effects the average patient experience. | The participants will be observed for 24 hours after the start of infusion. | 
| Personal graded time spend on insertion of active device (ordered categorical variable, non-blinded). | Nurses will estimate the time of insertion of the active device into the following categories: 1) less than 3 min., 2) 3-5 min, 3) 5-10 min, 4) 10-20 min. If the primary nurse cannot achieve access it will be noted if 5) another ER nurse or an 6) anesthesiological nurse is needed. Lower is better. | During procedure. | 
| Participants evaluation of pain during inserting the active device (continuous variable, non-blinded). | Participants will evaluate the pain of having the active access device inserted on a Visual Analog Scale (VAS) 0-100 mm. Lower is better. | During procedure. | 
| Participants evaluation of pain during fluid infusion through the active device (continuous variable, non-blinded) | Participants will evaluate the pain during infusion (24 hours) on a Visual Analog Scale (VAS) 0-100 mm. Lower is better. This will be done for both the active and sham device. | Participants will evaluate this at the end of observation (24 hours after inclusion) | 
| Presence of delirium (dichotomous variable, blinded) | Number of delirious participants at end of observation adjusted for number of delirious participants at inclusion. The presence of delirium will be evaluated using Confusion Assessment Method (CAM). | Duration of observation (24 hours) | 
| Death during hospitalization (dichotomous variable, blinded) | Compare death during hospitalization between groups. Both deaths during the observation period and after the end of observation but still during the same admission. | From inclusion to end of current admission. Cutoff is one month after inclusion. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypodermoclysis, Older adults, Geriatric patient, Hydration therapy, Adverse effects, Subcutaneous hydration