Correlation Between Intraoperative Tourniquet Use and Limb pH, Functional Measures and Patient-reported Outcomes After Ankle Fracture Surgery
Phase: NA
Conditions: Ankle Fractures, Ankle Fracture - Lateral Malleolus, Ankle Fracture, Bimalleolar, Ankle Fracture, Trimalleolar, Ankle Fracture - Medial Malleolus, Maisonneuve's Fracture, Syndesmotic Injuries, Fibula Fracture
Sponsor: Oregon Health and Science University

 
 
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Correlation between intraoperative tourniquet use and limb pH, functional 
measures and patient-reported outcomes after ankle fracture surgery 
3/14/2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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Protocol 
1) 
Protocol Title 
Correlation between intraoperative tourniquet use and limb pH, functional measures and patient-
reported outcomes after ankle fracture surgery 
 
2) 
Objectives 
This study aims to 1) characterize skeletal muscle pH during/after tourniquet use and 2) 
investigate any relationship between intraoperative tourniquet use and postoperative 
functional measures/patient-reported outcomes.  
 
3) 
Background 
Cushing first described a pneumatic tourniquet 1904, normalizing its use in optimizing 
intraoperative visualization and decreasing blood loss.1 Tourniquets are widely accepted as “safe” 
for up to two hours of continued use, despite known risks and a paucity of literature supporting this 
duration. The two-hour limit comes from a 1971 paper by Shaw Wilgis using pH, PO2, and PCO2, 
in which he suggested that tourniquet ischemia longer than two hours approached a “critical point” 
where the fatiguability of muscle and further acidosis “produce irreversible changes” (pH  7.0).2 
Complications of tourniquets include tourniquet site pain, increased surgical site pain and swelling 
from reperfusion, neuropraxia, vascular injury, functional weakness, and decreased muscle 
endurance. Similar to compartment syndrome, tourniquets eliminate the tissue perfusion gradient 
necessary for oxygen, glucose, and lactic acid exchange. Lack of molecular exchange within the 
tissue is thought to result in tissue anoxia and acidosis, leading to cellular death of skeletal muscle 
and nerves.  
 
The clinical outcomes of tourniquet use have been studied more recently, but these studies were 
small and did not use robust physical exam measures or patient reported outcomes. In 1997, 
Ömeroĝlu et al. randomized 32 patients undergoing ankle fracture surgery to no-tourniquet and 
tourniquet groups and found increased pain scores in the tourniquet cohort at 24 and 48 hours 
postoperatively.3 More recently, a 2004 randomized, controlled study by Konrad et al. assigned 54 
patients with operative ankle fractures to no-tourniquet and tourniquet groups; findings included 
no difference in intraoperative time between the groups and significantly increased postoperative 
swelling and pain (measured via malleolar circumference and VAS) in the tourniquet cohort at 5 
days and 6 weeks postoperatively.4  
 
Surveys of foot and ankle surgeons in the US and Canada in 2005 revealed that tourniquet inflation 
pressure and duration of use has wide variability as there are currently few evidence-backed 
recommendations informing proper tourniquet use.5 We found no available literature synthesizing 
clinical outcomes of tourniquet use with its metabolic effects, particularly intramuscular pH. The 
use of intraoperative tissue pH monitoring remains experimental but is already being utilized at 
OHSU by our trauma surgeons, who insert a pH catheter into leg musculature to measure real-time 
tissue metabolism during reamed intramedullary nailing for tibia fractures in order to understand 
metabolic markers of compartment syndrome.  

 
 
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4) 
Study Design  
This randomized, prospective study will include ankle fracture patients undergoing surgical 
treatment at Oregon Health and Science University. The study includes only two arms, tourniquet 
and no-tourniquet (control). 
 
This study will utilize the same research material and process as current IRB approved protocol 
STUDY00017959 “Correlation of compartment syndrome diagnosis and pH measurement” under 
PI, Jung Yoo.  
 
Preliminary data was collected to determine the accuracy of our intended pH catheter, the 
VersaFlex® pH catheter, in recording muscle tissue pH. The catheter’s measurements were 
compared to a standard USDA approved meat pH meter, the HANNA Instruments meat pH meter, 
and found to be 99.7% accurate at measuring the pH of living and dead (to simulate compartment 
syndrome) rat muscle tissue. The preliminary results suggest the VersaFlex® pH catheter as an 
appropriate choice for this study. To date, we have performed pH recording using protocol from 
STUDY0017959 on 20 patients without any complications or adverse effects.   
 
We propose a randomized, prospective trial to further characterize muscular pH and postoperative 
characteristics in patients undergoing ankle fracture surgery with or without use of intraoperative 
tourniquet. Participants will be randomized prospectively to a tourniquet versus no-tourniquet 
group. All participants will have a continuous intramuscular pH probe placed in the anterior 
compartment of the leg prior to start of surgery. Intraoperatively and for two hours postoperatively, 
we will continuously measure intramuscular pH. We will measure tourniquet duration, as well as 
lactate and venous blood gas pre-tourniquet and at the time of tourniquet release. We will collect 
functional outcomes including postoperative pain, range of motion, swelling, and 
strength/fatiguability; patient reported outcomes via validated surveys; as well as adverse 
outcomes including falls and venous thrombosis. We hypothesize that tourniquet use results in 
altered metabolic markers including intramuscular pH and poorer patient reported and functional 
outcomes measured at our follow-up periods of 2 hours, 2 days, 3 weeks, 6 weeks and 3 months. 
We plan to assess our patient reported outcomes by utilizing the Foot and Ankle Ability Measure 
(FAAM) and PROMIS physical function (PF) and pain interference (PI) modules, as these are 
validated and widely used measures of patient reported outcomes.6 Information gleaned from this 
study will help us further understand the relationship between tourniquet use, intramuscular and 
venous pH and patient outcomes after ankle fracture surgery, and may help formulate evidence-
based guidelines for duration and use of tourniquets intraoperatively. 
 
Patients will be screened in the emergency department, clinic or preop area day of surgery. Patients 
can also be screened/recruited via telephone but consent for all patients will occur via email in 
REDCap or on paper. Following consent of subjects via email or on paper, REDCap, a secure web 
application designed for research use and for building and maintaining clinical databases, will be 
used to document data..  
 

 
 
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PROMIS surveys and VAS pain scale will be administered at postoperative follow-up 
appointments to track participants over time. The follow-up appointments will take place: 
 New patient 
 3 weeks 
 6 weeks 
 3 months 
VAS pain scale will also be asked at 2 hours and 2 days postoperatively.  
 
Determining tissue pH and understanding its relationship to tourniquet use, the patient’s physical 
function, clinical outcome, and physiologic changes will provide important information about the 
relationship between tissue pH and tourniquet use and current determinants of tissue protection and 
function. 
 
5) 
Study Population 
a) Number of Subjects 
We estimate that 290 patients will meet the eligibility criteria to be included in our study over a 
three-year period.   
 
 
Inclusion and Exclusion Criteria 
Adult patients (18 years to 89 years) undergoing surgical ankle fracture fixation at OHSU will be 
eligible for this study. Patients with sepsis, other significant long bone or internal injuries will be 
excluded from the study (including ipsilateral limb injuries). Patient medical records and specific 
procedural information will be pre-reviewed by the research staff to determine eligibility. In the 
event of a screen failure, all data already collected will be destroyed immediately.  
 
b) Vulnerable Populations 
We will not include children, pregnant women, neonates, decisionally impaired adults, or 
prisoners in this study. 
 

 
 
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c) Setting 
All procedures will be performed at OHSU by OHSU personnel. Determination of eligibility will 
occur in Sam Jackson Hall. Study surgical procedures will take place in the South OR or Center 
for Health and Healing outpatient surgery center (participants will be either inpatients or 
outpatients). Consent will take place in the emergency room, the Orthopaedic clinic, or in 
inpatient areas. Patients can be contacted by telephone for recruitment and collection of email 
address but all consents will be obtained on paper or electronically via email in REDCap. 
Research administrative tasks along with data management and analysis will be conducted in 
Sam Jackson Hall at OHSU using the web application, REDCap. PROMIS Surveys will be 
collected in REDCap and administered via email. 
 
d) Recruitment Methods 
Patient medical records and specific procedural information will be pre-reviewed by the research 
staff to determine eligibility. No additional advertising or recruitment will be conducted. 
Subjects will not receive compensation. 
 
e) Consent Process 
Once identified by the pre-review discussed above, which can include a telephone conversation 
to discuss the study, patients will be consented via RedCap. Research staff and/or the care team 
will emphasize that participating in this study is optional and that patients can continue their care 
without participation. This fact will be reiterated throughout the consent discussion. Research 
staff and/or the care team will also emphasize that patients can withdraw their consent at any 
time. Participants will be continuously reminded of their ability to withdraw consent throughout 
the consent discussion and treatment period. They can also elect to not participate in the pH 
probe portion of the study and just have their outcomes tracked as a randomized tourniquet or 
non-tourniquet patient.  
 
Modifications to the Consent Process  
Patient medical records and specific procedural information will be pre-reviewed by the research 
staff to determine eligibility. This information is necessary to identify potential subjects. Every 
effort will be taken to protect subject privacy both before and after consent. 
 
Non-English Speaking Subjects 
Non-English speaking subjects will be enrolled in this study. Short forms will be used with the 
use of an interpreter. The interpreter will assist with the initial consent process and subsequent 
study visits. The interpreter may be in person or on the phone. If using a short consent form, an 
interpreter present by phone may sign the interpreter box on the full English form via secure 
email, fax or mail. The interpreter may not be the subject’s friend or family member except in 
urgent circumstances. A subject who chooses to use his or her own interpreter must sign a 
waiver. OHSU Interpreter services will be contacted to obtain this document.  
 

 
 
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6) 
Procedures 
Patient medical records and specific procedural information will be reviewed by the research staff. 
Participants will be subject to retrospective evaluation of their charts. We will collect the following 
information from our chart review: age, sex, comorbidities, current medications, substance use, 
occupation, height, weight, BMI, physical examination results, fracture type, and nature of the 
surgical procedure. Standard preoperative laboratory evaluation will take place with basic 
metabolic panel, complete blood count, 25(OH)D level and hemoglobin A1c. Preoperative 
radiographic evaluation includes x-rays of the ankle and tibia/fibula. Co-morbidities will be 
assessed with American Society of Anesthesiologists (ASA) Physical Status Classification System. 
Fractures will be categorized into three groups: isolated fibular, bimalleolar and bimalleolar 
equivalent, and trimalleolar and trimalleolar equivalent fractures. All study data is to be uploaded 
to REDCap data managed by the coordinating site.  
 
The patient will be randomized to tourniquet or no tourniquet based on a computerized 
randomization with a random number generator, which will be queried and communicated to the 
surgeon by the research assistant. For each patient, calf girth will be measured at its greatest 
dimension bilaterally. A pneumatic tourniquet will be placed with the center of the tourniquet 
halfway between the ASIS and the patella for all patients, but only the participants randomized to 
the "tourniquet" group will have the tourniquet inflated. The tourniquet will be deflated after the 
splint is complete or at the 2 hour mark, whichever is sooner. Length of surgery will be recorded, 
in addition to length of tourniquet use (and elevation/deflation times relative to surgery stop/start 
times). The surgeons’ current practice of using/not using regional anesthesia will not change and 
methods will be documented. However, surgeons’ preferred practice of using/not using tourniquets 
will be randomized to control for surgeon skill level and average surgical time.  

 
 
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For all patients, a VersaFlex® pH catheter from the Covidien pH monitoring kit will be placed in 
the anterior compartment of the operative leg via small incision and the Digitrapper® Recorder 
will measure and record continuous intramuscular pH. Recording will start immediately after 
placement of the probe and will continue intraoperatively and for 2 hours postoperatively. The 
probe will be removed in PACU prior to patient discharge.  
 
In the tourniquet arm, the operative limb will be exsanguinated with esmarch bandage and all 
tourniquets will be inflated to 250 mm Hg. The tourniquet will be inflated from prior to incision 
through wound closure and placement of sterile dressings, or up to, and never longer than, 120 
minutes intraoperatively. For all patients, venous blood gas and lactate will be collected after 
induction of anesthesia and at the time of tourniquet release for the tourniquet arm and at the 
conclusion of surgery for the no-tourniquet arm. If a surgeon determines that use of a tourniquet is 
required for optimal fracture reduction in the "no tourniquet" group, then the limb will be 
exsanguinated and the tourniquet will be inflated intraoperatively. The patient will remain in their 
assigned arm of the study and an intention to treat analysis will be done. 
 
Malleolar circumference (swelling), calf girth, quadricep strength (via timed up and go), ankle 
range of motion, fatigability (via biodex), proximal and distal lower extremity strength (via 
handheld dynamometer), and balance measures (single-limb stance time and Y-balance test scores) 
will be measured by blinded physical therapists at 6 weeks and 12 weeks. VAS pain score will be 
collected electronically prior to surgery, 2 hours after procedure stop time, 2 days after surgery, 
and then at each visit using the aforementioned schedule. The FAAM and PROMIS PI and PF 
modules will be collected at the time of 3-week, 6-week, and 3-month postoperative followup 
appointments electronically via Redcap. Other relevant variables including number of 
postoperative PT sessions and adverse events, including number of postoperative falls, DVT or PE 
and wound complications, will be collected at postoperative PT and clinic visits.  
 
7) 
Data and Specimens 
a) Handling of Data and Specimens 
We will collect the following information from our chart review: age, sex, comorbidities, current 
medications, height, weight, BMI, physical examination results, fracture type, nature of the 
surgical procedure, and results of lab draws, including comprehensive metabolic panel, blood gas 
and complete blood count. We will also collect fracture classification information from CT 
and/or X-ray radiographs. A VersaFlex® pH catheter from the Covidien pH monitoring kit will 
be placed in the anterior compartment of the leg. Intramuscular pH will be measured and 
recorded using the Digitrapper® Recorder for the duration of surgery and for 2 hours 
postoperatively, then deidentified and uploaded to a secure location on the OHSU x:drive. Data 
will be coded with unique identifiers and stored in a secure, password protected location on the 
OHSU x:drive. Data will be stored indefinitely. 
b) Sharing of Results with Subjects 
Results will not be shared with subjects. 

 
 
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c) Data and Specimen Banking 
Data to be collected from study subjects by OHSU research personnel and entered into REDCap 
data registry. PROMIS surveys will be administered electronically via email, and will be entered 
directly into REDCap database. All other data to be collected by study coordinator directly from 
subject’s medical record via Epic. 
 
HIPAA identifiers will only be visible to the site that contributed them. In other words, HIPAA 
identifiers of OHSU subjects will only be visible to OHSU study personnel and the data 
administrator at the primary site. These identifiers are not for the purpose of research but simply 
to ease data collection at each site. Identifiers will be flagged in the REDcap database so that 
they cannot be exported. De-identified data will be available to other members of the consortium 
after an application process with a proposed study. 
 
8) 
Data Analysis 
Use of tourniquet and tourniquet time will be our independent variables. Intramuscular pH, venous 
blood gas and lactate are dependent physiologic variables. Objective functional outcomes will be 
malleolar circumference (swelling), calf girth, quadricep strength (via timed up and go), ankle 
range of motion, fatigability/total work (via biodex), proximal and distal lower extremity strength 
(via biodex), balance measures (single-limb stance time and Y-balance test scores), and fall 
frequency. Patient-reported outcomes will be assessed via validated PROMIS and FAAM surveys. 
Covariates, including age, sex, comorbidities, current medications, height, weight, BMI, physical 
examination results, fracture type, lab values, and nature of the surgical procedure, as well as our 
dependent variables will be compared, using chi-squared, fisher’s exact, ANOVAs, and t-tests, 
between patients that did and did not use a tourniquet. Regression analysis will be conducted to 
determine the relationship between the dependent and independent variables. All analyses will be 
completed using SAS statistical software (SAS Institute, Cary NC).   
 
9) 
Privacy, Confidentiality and Data Security 
Only IRB approved research staff will be collecting data from the chart review. Access to data will 
be restricted to the principal investigator and the study team with password protection. Every effort 
will be taken to protect subject privacy. After complete collection, data will be completely 
unidentified and stored on OHSU’s x:drive, a secure, password protected location. and/or 
REDCap. During collection, data will be password protected and stored on OHSU’s x:drive. 
Standard institutional practices will be followed as described in the OHSU Information Security 
and Research Data Resource Guide (http://ozone.ohsu.edu/cc/sec/isg/res_sec.pdf) to maintain the 
confidentiality and security of data collected in this study. Study staff will be trained with regard to 
these procedures. 
 
Data Security is ensured. 

 
 
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1. Project Level Security in REDCap: Data groups will be created in REDCap to restrict the data 
access. Sites can only see the data entered by personnel that belongs to the specific site. Cross 
site data access is restricted.  
2. Data Storage Security: All the REDCap data is stored on an Oregon Health and Science 
University server that is protected inside a firewall. The access to the server is restricted and 
tightly controlled by the server administrators. 
 
10) Risks and Benefits  
a) Risks to Subjects 
This study presents only minimal risk to subjects as tourniquet use for duration under 2 hours is 
considered “safe.” There will be minimal risk of loss of confidentiality to subjects. Only IRB 
approved research staff and the care team will be able to contact patients and collect data from the 
chart review.  Every effort will be taken to protect subject privacy.  
 
b) Potential Benefits to Subjects 
Potential benefits are limited to the generation of data that could help care of future patients.  
                                              
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2 Wilgis ES. Observations on the effects of tourniquet ischemia. J Bone Joint Surg. 1971; 53(7):1343-6 
3 Ömeroĝlu H, Günel U, Biçimoĝlu A, Tabak AY, Uçaner A, Güney Ö. The Relationship Between the Use of Tourniquet and 
the Intensity of Postoperative Pain in Surgically Treated Malleolar Fractures. Foot Ankle Int. 1997;18(12):798-802. 
doi:10.1177/107110079701801208 
4 Konrad G, Markmiller M, Lenich A, Mayr E, Ruter A. Tourniquets May Increase Postoperative Swelling and Pain after 
Internal Fixation of Ankle Fractures: Clinical Orthopaedics and Related Research. 2005;NA;(433):189-194. 
doi:10.1097/01.blo.0000151849.37260.0a 
5 Younger ASE, Kalla TP, McEwen JA, Inkpen K. Survey of Tourniquet Use in Orthopaedic Foot and Ankle Surgery. Foot 
Ankle Int. 2005;26(3):208-217. doi:10.1177/107110070502600305+ 
6 Hung M, Baumhauer JF, Licari FW, Voss MW, Bounsanga J, Saltzman CL. PROMIS and FAAM Minimal Clinically 
Important Differences in Foot and Ankle Orthopedics. Foot Ankle Int. 2019;40(1):65-73. doi:10.1177/1071100718800304