Safety & Tolerability of Hypertonic Saline Administration Via Intraosseous Access

Intraosseous Administration of Hypertonic Saline in Acute Brain-injured Patients: A Prospective Case Series and Literature Review

Hypertonic saline is used to treat elevated intracranial pressure. Intraosseous vascular access has been used to administer fluids and medications. This study combines these to administer 3% hypertonic saline via IO.

Study Overview

• Status: Completed
• Conditions: Stroke; Intracranial Hypotension; Cerebral Edema
• Intervention / Treatment: Device: Intraosseous; Drug: Hypertonic saline

Detailed Description

HTS is used to mitigate and temporize intracranial pressure (ICP) elevations and cerebral edema by creating an osmotic gradient across the cell wall. HTS is part of the elevated ICP algorithm in the emergency neurologic life support protocols HTS is superior to mannitol which is the alternate osmotherapy agent . HTS is typically administered via central vascular access due to the concern that if extravasation of the infusion occurs, tissue damage from cell implosion can occur

The IO route is generally accepted in resuscitation environments including the emergency department, EMS, and military settings with some authors recommending the IO as a primary method of obtaining emergency vascular access The adult advanced cardiac life support (ACLS) guidelines recommend either intravenous or IO access.

A number of studies have established the safety of IO administration of hypertonic solutions. Randomized adult pigs to IO 7.5% HTS, IO 3% HTS, and 0.9% isotonic saline and found regular tissue morphology, no necrosis or microscopic ischemic changes in the HTS groups. Several studies conducted to evaluate the efficacy of hypertonic solutions on resuscitation for hemorrhagic shock used the IO route and did not make note of problems arising from the administration of IO HTS. Another study using a canine model of hemorrhagic shock briefly mentioned transient lameness in the IO HTS group, but this resolved by 48 hours . While the majority of studies using hypertonic saline solutions did not make note of complications, one study induced hemorrhagic shock in dehydrated swine and resuscitated one group with 7.5% HTS and noted a high rate of local complications from soft tissue and bone marrow necrosis .

One study noted a subgroup of patients in which IO access was obtained on conscious patients. None of the patients received local anesthetic and none reported pain during insertion. Eighteen of the 22 conscious patients reported pain during fluid administration. Central venous catheter (CVC) placement is the current standard of care; even with local anesthesia it can be painful. Most of the potential subjects, due to the nature of their severe neurologic injury, may not be affected by the pain associated with IO fluid administration. Manufacturer literature suggests the use of lidocaine to anesthetize the bone before infusing if possible (Teleflex).

It is expected that utilizing IO for vascular access in the ICU will be safe and tolerable. If this study confirms the anticipated results, there are numerous implications. First, neurologically injured patients requiring emergent HTS may have faster access to this therapy. A study comparing IO to CVC access undergoing resuscitation in the emergency department found IO to be faster to insert (2.3 vs. 9.9 minutes) and had fewer failures to access on the first attempt. Second, serious complications from IO were absent compared with severe to life-threatening mechanical complications from CVC including pneumothorax, damage to the carotid artery, and bleeding which were cited at 0.7%-2.1% depending on site. And thirdly, central line associated blood stream infections (CLABSI) are a leading cause of hospital acquired infections in the ICU and are associated with higher mortality. CLABSI rates are measured by number of infections per 1,000 catheter days and shorter CVC dwell time is prudent. If a reliable and rapid source of vascular access could postpone or eliminate CVC insertion, risk of CLABSI may be reduced. These potential benefits outweigh the minimal expected risk.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• NCCU patients in which osmotherapy with HTS is planned (standard of care
• Does not already have a CVC or PICC.

Exclusion Criteria:

• <18 years old
• Known pregnancy
• Long bone fracture in the targeted site
• Proximity to prosthetic joint
• Excessive tissue/absence of anatomical landmarks
• History of osteopetrosis
• Previous significant orthopedic procedure at site
• Prosthetic limb or joint
• IO catheter use in the past 48 hours of the target bone
• Infection at the area of insertion
• Hypersensitivity to lidocaine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Intraosseous; Administration of intraosseous hypertonic saline	Device: Intraosseous; Intraosseous administration of hypertonic saline; Drug: Hypertonic saline; Intraosseous administration of hypertonic saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Tissue Damage	Number of subjects with tissue damage (e.g. Myonecrosis, Skin necrosis, Extravasation, Compartment syndrome, Osteomyelitis). These data points will be determined by clinician assessment.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Scale	Pain (CPOT-critical care pain observation tool). All non-verbal subjects have pain assessed with a CPOT score, as observed by clinicians. The CPOT is a validated pain score for nonverbal patients. This tool assesses pain with nonverbal indicators, adding 1-2 points for several nonverbal indicators of pain, 0 if the nonverbal indicator is absent, and is reported as a total summed score. It ranges from 0-8, with 0 indicating no pain and 8 indicating high pain. No patients were verbal, so the numeric pain rating scale was not used for any patients.	24 hours

Collaborators and Investigators

• Sponsor: Ohio State University

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2017
• Primary Completion (Actual): April 21, 2018
• Study Completion (Actual): April 21, 2018

Study Registration Dates

• First Submitted: June 29, 2017
• First Submitted That Met QC Criteria: September 7, 2017
• First Posted (Actual): September 8, 2017

Study Record Updates

• Last Update Posted (Actual): July 9, 2019
• Last Update Submitted That Met QC Criteria: June 18, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypotension; Brain Edema; Intracranial Hypotension
• Other Study ID Numbers: 2017H0067

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: manuscript on the case series has been submitted
• IPD Sharing Supporting Information Type: Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes