Clinical trial NCT03564886
Conditions: Arthroscopic Knee Surgery
Sponsor: University of Missouri-Columbia
Start date: 2019-01-01; Completion date: 2019-09-05
Enrollment: 48 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
An isotonic solution, such as saline (0.9%, 300mOsm/L) or lactated ringer's (273 mOsm/L), is commonly used and safely proven for joint irrigation during arthroscopy. Arthroscopic fluid is usually pressurized to enable visualization through dilation of the joint or bursa and prevent bleeding from the microvasculature. It has been recommended that this pressure be maintained at 49mmHg or less below the systolic blood pressure to preserve the clarity of view. The combination of large amounts of pressurized irrigation solution and lengthy arthroscopic procedures may cause substantial tissue fluid retention. Thus, extravasation of irrigation fluid into the periarticular tissues is inevitable and may create technical difficulties as well as patient morbidity and complications. Previous investigators have reported complications including tracheal obstruction, post-operative airway edema and compromise leading to prolonged intubation, excess weight gain, neurologic injuries, skin necrosis, and fluid overload associated with excessive fluid extravasation and tissue retention. Furthermore, it has been shown that fluid accumulated during the operation is slowly released back into the systemic circulation. Although there is not a rapid change in circulating volume, there may be implications for elderly patients and those with multiple comorbidities during prolonged arthroscopic surgery. Therefore the investigators seek to determine if a hyperosmolar solution, similar to what is used in head trauma patients, can reduce the degree of fluid extravasation in knee arthroscopy. The investigators also seek to determine if a hyperosmolar solution has any effect on post-operative knee pain compared to the standard isotonic solution. The third objective is to determine if a hyperosmolar solution has any effect on post-operative pain medicine consumption compared to the standard isotonic solution.

Detailed description:

Arms: arm 1: The hyperosmolar solution will be created by adding 120cc of 23.4% NS solution to a 3L bag of LR. arm 2: Lactate Ringer's (LR, 273mOsm/L) is commonly used at our facility as our isotonic standard irrigation solution and will serve as the control to be evaluated against a hyperosmolar (1.9%, 600mOsm) solution.
Interventions: intervention 1: Hyperosmolar Saline intervention 2: Normal saline
Intervention descriptions: intervention 1: The hyperosmolar solution will be created by adding 120cc of 23.4% NS solution to a 3L bag of LR. intervention 2: Lactate Ringer's (LR, 273mOsm/L)

Protocol documents:
Prot_001.pdf: 
Safety and Efficacy of Hyperosmolar Saline Irrigation Fluid in 
Arthroscopic Knee Surgery 
 
 
IRB Project #: 2011296  
 
PROTOCOL VERSION NUMBER: 3.0 
 
DATE: 03 APR 2019  
 
 
 
 
 
Principal Investigator: James P. Stannard, MD  
 
Co-Investigators: James L. Cook, DVM, PHD; Seth L. Sherman, MD; Nathan Skelley, MD 
 
 
 
 
 
Study Sites: University of Missouri Health System 
 
 
 
 


TABLE OF CONTENTS 
1. Background Information & Significance 
2. Objectives, Contribution, & Hypothesis  
3. Selection of Subjects 
4. Study Procedure 
5. Confidentiality of Data 
6. Assessment of Risks & Benefits  
7. Payment and Remuneration, and Costs 
8. References 
 
1. Background Information & Significance 
An isotonic solution, such as saline (0.9%, 300mOsm/L) or lactated ringer’s (273 mOsm/L), is 
commonly used and safely proven for joint irrigation during arthroscopy. Arthroscopic fluid is 
usually pressurized to enable visualization through dilation of the joint or bursa and prevent 
bleeding from the microvasculature. It has been recommended that this pressure be maintained at 
49mmHg or less below the systolic blood pressure to preserve the clarity of view. The combination 
of large amounts of pressurized irrigation solution and lengthy arthroscopic procedures may cause 
substantial tissue fluid retention. Thus, extravasation of irrigation fluid into the periarticular tissues 
is inevitable and may create technical difficulties as well as patient morbidity and complications. 
Previous investigators have reported complications including tracheal obstruction, post-operative 
airway edema and compromise leading to prolonged intubation, excess weight gain, neurologic 
injuries, skin necrosis, and fluid overload associated with excessive fluid extravasation and tissue 
retention.  Furthermore, it has been shown that fluid accumulated during the operation is slowly 
released back into the systemic circulation. Although there is not a rapid change in circulating 
volume, there may be implications for elderly patients and those with multiple comorbidities 
during prolonged arthroscopic surgery. Our research team and other groups have reported that 
hyperosmolar solutions (up to 600 mOsm/L) are chondroprotective in vitro, and safe and effective 
clinically when used as the irrigation solution for arthroscopic shoulder surgeries in a prospective 
controlled randomized clinical trial. 
 
2. Objectives, Contribution, & Hypothesis  
Objectives: To determine if a hyperosmolar solution, similar to what is used in head trauma 
patients, can reduce the degree of fluid extravasation in knee arthroscopy. To determine if a 
hyperosmolar solution has any effect on post-operative knee pain compared to the standard 
isotonic solution. To determine if a hyperosmolar solution has any effect on post-operative pain 
medicine consumption compared to the standard isotonic solution. 
Contribution: The potential benefits of this study lie in determining the differences noted in our 
shoulder arthroscopy clinical trial extend to arthroscopic knee procedures. 
Hypothesis: A hyperosmolar irrigation solution used in knee arthroscopy will reduce the extent 
of fluid extravasation to surrounding tissue, decrease perioperative pain, and result in diminished 
utilization of perioperative pain medication. 
3. Selection of Subjects  


Inclusion Criteria: Adult patients (18 years of age or greater) undergoing arthroscopic knee 
surgery who are willing and able to consent. 
Exclusion Criteria: Current pregnancy or breastfeeding; Unable to give consent; Prisoner; 
Mentally Disabled.  
 
Sample Size: We anticipate enrolling up to 100 patients to complete the study. Patients will be 
evenly randomized to either hyperosmolar or standard irrigation solution. 
 
4. Study Procedure  
Timeline: 12-24 months of data collection 
Protocol: Study candidates will be identified as they present to the clinic at the Missouri 
Orthopaedic Institute at the University of Missouri, and will be evaluated by one of our three 
sports orthopaedic surgeon co-investigators. Informed consent will be obtained as per IRB 
protocol. Enrollees will receive a copy of the study protocol, consent, and HIPAA form. 
Background patient information will be collected including age, sex, BMI and co-morbidities. 
American Society of Anesthesiologist (ASA) classification will be assigned by the involved 
anesthesiologist.  
 
Lactate Ringer’s (LR, 273mOsm/L) is commonly used at our facility as our isotonic standard 
irrigation solution and will serve as the control to be evaluated against a hyperosmolar (1.9%, 
600mOsm) solution. The hyperosmolar solution will be created by adding 120cc of 23.4% NS 
solution to a 3L bag of LR. The patient will be randomized before surgery by a research team 
member by obtaining a sealed envelope that designates the type of irrigation solution to be used 
in the surgery. If randomized to the hyperosmolar group, an OR staff member will make the 
solution prior to the start of the case. The surgeon and patient will be blinded to the type of 
irrigation solution used in surgery. 
 
Quantitative variables that will be recorded include, pre and post-operative blood pressure, the 
type and amount (mL) of irrigation fluid used, amount of intravenous fluid used (mL), pre and 
post-operative weight (lb), procedures performed, number of portals, arthroscopic surgical time 
(minutes), pre and post-operative knee girth measurements (cm), and amount of perioperative 
opioid medication. We will also document any immediate, post-operative adverse effects (ie, 
airway comprise, prolonged intubation, etc.).  
 
Weight: On the day of surgery, the patient’s weight will be measured to the closest one tenth of a 
pound (lb) before and after surgery on the same calibrated, digital weighing scale. Patients will 
be weighed while wearing the same attire and hospital gown for each measurement. After 
surgery, patients will be weighed before discharge and before voiding or eating to ensure that the 
maximal amount of weight gain attributable to shoulder arthroscopy can be documented. A 
standard amount of dressing will be applied for each procedure that is surgeon specific and will 
be accounted for during the calculation of weight gain. Intraoperatively, we will record the 


amount of intravenous fluid given during the case (mL).  
 
Knee Girth: Change in knee size (girth) will be evaluated based on change in surface area. Prior 
to start of the surgery, a sterile measuring tape will be used to record knee girth. Following the 
surgical procedure the operating surgeon will perform a repeat measuring of the knee girth.  
During the assessment, the patients will lay supine with the tester aiming to  maintain  the  hip  in  
neutral  position.  The knee will be relaxed and extended as much as possible. If the knee extends 
below 0°, a cylinder firm back roll will be placed under the heel of the foot. The tester will stand 
closest to the examined leg and place a small dot with a  pen  1  cm  proximal  to  the  base  of  
the  patella  using  a  non-elastic   tape   measure. The mark  will be  removed  between  
measurements.  The  tape  measure  will be  placed  carefully  and  snug  above  the  dot,  and  
the  tester will measured the knee joint circumference. The tape measure will be blinded on the 
side facing the tester. When the  tester  is  satisfied  with  the  alignment  of  the  tape  measure,  
the  unblinded  scale  will be  revealed  to  the  data  recorder. The value will be recorded to the 
nearest 0.1 cm and the measurement  will be repeated.  The  highest  value  of  the  two  knee  
circumference  recordings  will be used  in  the data analysis 
 
Prior to departure from the hospital, the patient will be given the option to either receive a paper 
copy of the Pain Evaluation form or have an electronic version sent to them (through Patient IQ) 
each day. The patient will be instructed to write down their pain level (based on the Visual 
Analog Score, 0-10) and amount of pain medication taken during each day from the day of 
surgery to post-operative day 3. If given the paper form, the patient will return this form at 
his/her first post-operative clinic visit. 
 
Approximately 1 year after surgery, patients will be contacted via telephone by a member of the 
research team. A telephone questionnaire will be conducted to gain additional information about 
their recovery and current functional status. The phone interview will include questions 
pertaining to three outcome measures: 1) KOOS Jr, 2) Single Assessment Numeric Evaluation 
(SANE) score for their knee, and 3) Data collection regarding any additional surgeries involving 
the affected shoulder.    
 
5. Confidentiality of Data 
Patient confidentiality during the course of this study will be protected in compliance with 
HIPAA requirements as well as the requirements of the University of Missouri Health-Sciences 
IRB.  
 
All subjects will be assigned a study identification number that requires the use of a key in order 
to decipher a subject’s personal identification information. The key will be kept in the Cerner 
Power Trials database, which is password protected. The study identification number will be 
used to label all paper data collection instruments.  
 
All subject information in electronic format will be kept in password-protected storage. All 
subject information in paper format will be kept in locked cabinets in a secured suite at the 


Missouri Orthopedic Institute, and otherwise will be archived in a secure storage facility, or 
destroyed.  
 
6. Assessment of Risks & Benefits 
Risks: Risks for breach of confidentiality does exist but will be limited with tight control and 
limited access to the investigators.     
 
Benefits: The potential benefits of this study lie in determining the differences noted in our 
shoulder arthroscopy clinical trial extend to arthroscopic knee procedures.  
 
Data Safety Monitoring Plan: Subject safety will be ensured through standard of care 
perioperative monitoring by the anesthesia staff.   
7. Payment and Remuneration, and Costs 
Payment and Remuneration: Participants will not receive payment for participating in this study.  
 
Costs: Subjects will be responsible for the cost of any surgical and clinic follow up costs. The treatment 
arm does not in any way effect the costs that patients are experiencing. 
 
8. References 
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3. 
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