Ultrasonographic Identification of the Proximal Humerus Landmarks for Intra-Osseous Vascular Access Across Different Body Habitus
Conditions: Proximal Humerus Interosseous Venous Access, Anatomic Landmark, Ultrasonography
Sponsor: The Cleveland Clinic

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NCT 03121794 
Ultrasonographic Identification of the Proximal 
Humerus Landmarks for Intra-Osseous Vascular 
Access across Different Body Habitus 
 
 
An observational study to determine if there is consistency in ultrasonographic landmark 
identification of the proximal humerus across various body habitus  
 
                                 Original Date: July 11, 2016 (version 1.0) 
 
 
         Final version Date:  12/01/2016 
 
 
Names and Addresses of: 
 
Principal Investigator 
Name: 
Sergio Bustamante, MD 
Address: Cleveland Clinic 
Department of Cardiothoracic Anesthesiology 
9500 Euclid Avenue  
Cleveland, OH 44195 
 
Tel: 
216-444-4488 
Email: 
bustams@ccf.org  
Co-investigator 
Name: 
Negmeldeen Mamoun, MD  
Address: Cleveland Clinic 
Department of General Anesthesiology 
9500 Euclid Avenue  
Cleveland, OH 44195 
 
Tel: 
216-444-7783 
Email: 
mamounn@ccf.org  
Co-investigator 
Name: 
Shravan Cheruku, MD 

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Address: Cleveland Clinic 
Department of Cardiothoracic Anesthesiology 
9500 Euclid Avenue  
Cleveland, OH 44195 
 
Tel: 
347-387-0039    
Email: 
cheruks2@ccf.org 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Study Summary 
 
Title 
Ultrasonographic identification of the proximal humerus landmarks for 
Intraosseous Vascular access across different body habitus 
Short Title 
Ultrasonographic landmark identification of the proximal humerus  
Principal Investigator 
Sergio Bustamante, MD 
Primary Objectives 
Evaluate whether discrete landmarks of the proximal humerus can be 
identified using ultrasound in patients with various body habitus and BMI.  
Primary Endpoints 
Ability to identify the following 6 anatomical landmarks for proximal 
humerus interosseous venous access with ultrasound:  1.  Humeral shaft, 
2, Surgical neck of the humerus, 3. Lesser tubercle, 4. Greater tubercle, 5.  
Intertubercular sulcus 6. Target site for needle insertion in the greater 
tubercle. 
Secondary Objectives 
- 
Evaluate the time used to identify all 6 anatomical landmarks 
using ultrasound. 
- 
Evaluate the depth of each landmark from skin under ultrasound. 
- 
Correlate the Arm thickness with the depth of the anatomical 
structures. 
- 
Correlate the BMI with the depth of the anatomical structures.  
 
Secondary Objectives 
Measures 
- 
Time used to identify all 6 anatomical landmarks in seconds. 
- 
Depth of each anatomical landmark from skin in centimeters.  
Study Design 
A single institution observational study 
Inclusion Criteria 
1- Males or females 18 years of age or older. 
2- BMI > 18.5 
 
Exclusion Criteria 
1. Limited mobility/ range of motion of arms 
2. Prior surgical intervention on shoulder or humerus  
3. History of arm dislocation with internal rotation 
4. History of arm fracture  
5. BMI in ranges: 25.1 – 29.9, 35.1 – 39.9 
 
Expected Sample Size 
30 Patients (60 exams) 
Statistical Methodology 
We will summarize the total number of correctly identified landmarks per 
patient overall and by BMI category. We will also estimate the incidence 
of correctly identifying all landmarks per patient with a 95% bootstrap 
confidence interval.  
 
 
 
 
 
 
 

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List of Abbreviations 
 
 
 
Abbreviation                    
Definition 
BMI 
 
 
 
Body Mass Index 
CFD  
 
 
Color Flow Doppler 
CV 
 
 
 
Central Venous 
IO 
 
 
 
Intraosseous  
PH 
 
 
 
Proximal Humerus 
PHIO  
 
 
Proximal Humerus Intraosseous  
PHIOVA 
 
 
Proximal Humerus Intraosseous Vascular Access 
PIV 
 
 
 
Peripheral Intravenous 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1 Introduction 
    This document is a protocol for a human research study. This study is to be conducted 
according to US and international standards of Good Clinical Practice (FDA Title 21 and 
International Conference on Harmonization guidelines), applicable government regulations and 
Cleveland Clinic research policies and procedures.  
 
1.1 
Background and Rationale 
 
Establishing vascular access is of vital importance during resuscitation of cardiac arrest, 
trauma and during various intraoperative scenarios. During cardiac arrest minimizing time 
wasted without performing chest compression is vital to successful resuscitation, therefore, being 
able to establish vascular access quickly can save lives[1]. Intraoperatively, the ability to rapidly 
obtain vascular access is crucial to maintain hemodynamic stability. Similarly, having adequate 
vascular access is the cornerstone for resuscitation in trauma patients.  
 
Three main forms of vascular access are used in the scenarios above: peripheral 
intravenous (PIV), Central venous (CV) and intraosseous (IO). Of the different types of vascular 
access PIV and CV access have drawbacks when used during resuscitation[2], because they can 
be difficult to obtain when patients are volume depleted as in cases of trauma. Attempting CV 
access has numerous risks with complications occurring in up to 33% of attempts. These include 
failed placement (22%), arterial puncture (5%), catheter malposition (4%), pneumothorax (1%) 
and asystolic cardiac arrest (<1%)[3]. Attempting to obtain CV access may also disrupt chest 
compressions in cases of cardiac arrest. Intraosseous access has been used in scenarios where 
PIV and CV access is difficult or impossible to obtain. Pharmacokinetic studies and standard 
practice support the bioequivalence of intraosseous and intravenous administration of common 

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medications[4]. Intravascular depletion does not hinder attempts at IO access, and as the 
insertion sites are peripheral to the heart, insertion can be done avoiding interruptions in chest 
compressions. Obtaining proximal humerus interosseous (PHIO) access may also be faster than 
obtaining both PIV and CV access with a relatively low complication rate[2]. In one survey of 
Scandinavian users, complications of IO included difficulty in identifying correct anatomical site 
(3%), extravasation (3.7%), displacement after insertion (8.5%), and very rarely late 
complications including compartment syndrome (0.6%), osteomyelitis (0.4%) and skin infection 
(0.3%)[5]. 
 
The site that has been used most commonly for IO access has been the proximal anterior 
tibia because of ease of landmark identification and provider familiarity. The proximal humerus 
(PH) has recently gained more attention and is a viable alternative to the anterior tibia because of 
decreased pain with initial bolus, decreased medullary pressure resulting in more rapid fluid 
delivery and is in closer proximity to the heart[6]. 
Proximal humerus interosseous access relies on landmark identification of the greater 
tubercle via palpation of the surgical neck of the humerus. This method can be especially 
difficult in patients with prominent deltoid musculature or adipose tissue overlying these 
landmarks. Failure to identify landmarks is an absolute contraindication to IO access[1]. Success 
rates for PHIO needle insertion have been cited as low as 76% in one study compared to 92% for 
proximal tibial insertion[7]. Moreover, a failed IO needle insertion precludes the immediate use 
of the same site for another trial.  

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Ultrasound identification of PH structures on cadavers has recently been described in the 
literature and has the promise of increasing the success rate of what is now considered a blind 
procedure[8] 
 
1.2 
Clinical Data to Date 
Ultrasound identification of proximal humeral structures is a novel concept with no 
current case reports or clinical trials demonstrating its use in clinical practice.  
A correspondence letter by Bustamante et al.[8] demonstrated the use of ultrasound to 
identify PH structures on a cadaver model. Structures identified were the greater and lesser 
tubercles, intertubercular groove and surgical neck. Identification of these structures are 
necessary for PHIO needle placement. A 13-6 MHz ultrasound linear probe (SonoSite Inc; 
Bothell, Washington, USA) was used to identify these structures on 5 cadavers with body max 
indexes (BMI) ranging from 20 – 35. All structures were relatively superficial, within 3cm from 
the skin. Once landmarks and target site were identified, an IO needle was inserted and 
placement was confirmed with color flow doppler (CFD).   
Failure to identify proximal humeral structures is considered an absolute contraindication 
to attempting PHIO placement. Prominent deltoid musculature and adipose tissue overlying 
proximal humeral landmarks can make identifying proximal humeral structures by palpation 
difficult if not impossible. As failed PHIO access of one arm precludes the use of the same arm 
for subsequent trials the first attempt must be optimized to allow for the greatest chance for 
success. If ultrasound is found to successfully identify all landmarks, even in patients with higher 
BMI’s, failure to identify landmarks by palpation will no longer be considered an absolute 
contraindication.  

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2 
Objectives 
2.1      Primary Objectives: 
Estimate the ability to successfully identify each of the six proximal humerus anatomical 
landmarks required for proximal humerus interosseous vascular access (PHIOVA), using 
ultrasound in patients with different body habitus: BMI 18.5-25 kg/m2, BMI 30-35 kg/m2, and 
BMI > 40 kg/m2. 
 
2.2       Secondary Objectives:  
- 
Estimate the time used (in seconds) to identify all 6 anatomical landmarks using 
ultrasound in patients with different body habitus. 
 
- 
Estimate the depth of each landmark (in centimeters) from the skin using ultrasound in 
patients with different body habitus.  
 
- 
Estimate the correlation between upper arm thickness and the depth of the anatomical 
structures.  
 
- 
Estimate the correlation between BMI and the depth of the anatomical structures.  
 
 
 
 
 
 
 
 
 

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3 
Primary hypothesis 
We will test the hypothesis that all 6 anatomical landmarks for proximal humerus 
interosseous venous access can be identified using ultrasound in all patients irrespective of their 
BMI, or mid upper arm circumference. 
 
4 
Study Design 
4.1 General Design 
- 
An observational study performed on adult patients undergoing general, cardiac, thoracic 
or vascular surgery.  
- 
Demographic data collected include age, sex, weight (kg), Height (cm)  
- 
BMI, and mid upper arm circumference will be measured or calculated for all subjects. 
The study procedure will be performed on each patient by two out of three investigators 
trained on performing an ultrasonographic exam of the proximal humerus using a linear 
probe. All investigators have at least one year of experience in ultrasonography with the 
linear probe and have participated in at least three (3) PHIO access workshops.  (Sergio 
Bustamante, MD, Negmeldeen Mamoun, MD, and Shravan Cheruku, MD). Two 
investigators will perform an ultrasonographic exam on each patient, with one investigator 
examining each side. Investigator A will perform the exam and identify all 6 landmarks with 
ultrasound, while investigator B will time the exam starting from when the ultrasound probe 
is handled till all landmarks are identified. Investigator B’s role is also to verify that 
landmarks are identified and document how many of the landmarks were seen from zero to 
six out of six per arm. After the exam is complete, the roles of investigator A and B are then 

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switched to perform an exam on the contralateral humerus, where investigator B identifies 
landmarks on the opposite side and investigator A times the exam.  
After the conclusion of the exam on each arm the depth of each landmark under 
ultrasound will be noted, and the mid upper arm circumference will be measured.  
4.2        Primary Study Endpoints 
- 
Ultrasound evaluation of the proximal humerus will aim at identifying 6 anatomical 
landmarks for PIHOVA with ultrasound:   
1. The humeral shaft,  
2. The surgical neck of the humerus,  
3. The lesser tubercle,  
4. The greater tubercle,  
5. The intertubercular sulcus   
6. The target site in the greater tubercle for needle insertion.  
Each arm will receive a score that ranges from zero to six out of six depending on how 
many landmarks were identified successfully.  
4.3        Secondary Study Endpoints 
- 
Time used to identify all 6 anatomical landmarks using ultrasound in seconds. 
 
- 
Depth of each landmark from the skin using ultrasound in centimeters. 
 
- 
Correlation between upper arm thickness and the depth of the anatomical structures. 
- 
Correlation between BMI and the depth of the anatomical structures 
 
 
 

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5 
Subject Selection and Withdrawal 
5.1 
 Inclusion Criteria 
1- Males or females, 18 years of age or older. 
2- BMI > 18.5 
5.2 
Exclusion Criteria 
1. Limited mobility/ range of motion of any of the upper extremities.  
 
2. Prior surgical intervention on shoulder or humerus in any of the upper extremities. 
 
3. History of arm dislocation with internal rotation in any of the upper extremities. 
 
4. History of arm fracture in any of the upper extremities.  
 
5. BMI in ranges: 25.1 – 29.9, 35.1 – 39.9 
 
5.3 
Subject Recruitment and Screening 
Participants will be selected after chart review of current patients undergoing general, 
cardiac, thoracic, or vascular surgery.  Patients will be approached in the preoperative clinic or 
during their hospitalization (preoperatively or postoperatively). Informed consent will be 
obtained on the same day of performing the ultrasound exam. 
Participants will be separated into 3 cohorts based on BMI. The number of participants in 
each cohort is as follows: 10 patients with BMI 18.5 – 25 kg/m2; 10 patients with BMI 30-35 
kg/m2, 10 patients with BMI > 40 kg/m2.  
 
 
 

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6 
Statistical methods 
 
We will summarize the study population on baseline characteristics using appropriate 
summary statistics (e.g., mean ± standard deviation, median [Q1, Q3], or N (%)).  
 
6.1 
Primary Analysis 
 
We will summarize the success of landmark identification overall and by BMI category. 
Landmark identification is considered successful if all 6 landmarks are identified correctly. We 
will estimate the incidence of correct identification of all landmarks with a 95% bootstrap 
confidence interval. We will use bootstrap confidence intervals instead of binomial confidence 
intervals to account for intra-subject correlation because landmark identification will be 
performed twice per subject.  
We will also report the median [Q1, Q3] of the mean number of landmarks identified 
correctly per patient overall and by BMI category. Results will be presented in tables and 
appropriate graphs. Descriptively, we will summarize the percent of correct identification by 
landmark location.  
 
6.2 
Secondary Analyses 
 
We will estimate the median [Q1, Q3] of the mean time in seconds to identify all 
landmarks using ultrasound overall per patient overall and by BMI category.  
 
Depth of each landmark will be summarized overall and by BMI category using 
appropriate summary statistics (e.g., mean ± standard deviation and median [Q1, Q3]). 
 
We will estimate the correlations between the following measures using Pearson 
correlation with 95% confidence intervals: 

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- Arm thickness with depth of anatomical structures 
- BMI with depth of anatomical structures 
Arm thickness, depth of anatomical structures, and BMI are only measured once per patient so 
standard methods are applicable (i.e., no repeated measures).  
 
6.2 
Sample Size Considerations 
We will enroll 30 patients, with 10 patients in each BMI category: BMI 18.5-25 kg/m2, 
BMI 30-35 kg/m2, and BMI > 40 kg/m2. Given that investigators will be highly trained, we 
conservatively assume all landmarks will be identified 80% of the time. We expect very weak 
intra-subject correlation. Ignoring intra-subject correlation, we expect 95% confidence interval 
widths as small as 0.22 for overall incidence of correct identification and 0.38 within each BMI 
category. Confidence intervals will be somewhat larger depending on the strength of intra-
subject correlation. Confidence interval widths will be narrower if investigators are more than 
80% successful at identifying landmarks.  
Study enrollment will start with 3 pilot patients with different BMI, but they will not be 
included in the statistical analysis. Thereby, a total of 33 patients will be enrolled in our study  
 
 
 
 
 
 
 

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References  
 
1. 
Anson, J.A., Vascular Access in Resuscitation. Is There a Role for the Intraosseous 
Route? Anesthesiology, April 2014. 120(4): p. 1015-31. 
2. 
Paxton JH, K.T., Klausner HA Proximal Humerus Intraosseous Infusion: A Preferred 
Emergency Venous Access. The Journal of Trauma, September 2009. 67(3): p. 606-11. 
3. 
Eisen LA, N.M., Berger JS et al., Mechanical complications of central venous catheters. 
Journal of Intensive Care Mericine, 2006. 21(40). 
4. 
VonHoff DD., K.J., Burris HA. III, Miller LJ., Does intraosseous equal intravenous? A 
pharmacokinetic study. American Journal of Emergency Medicine, 2008. 26: p. 31-8. 
5. 
Hallas P, B.M., Folkestad L, Complications With Intraosseous Access. Western J Emerg 
Med, 2013. 15(5): p. 440-43. 
6. 
Philbeck T, M.L., Montez D, Puga T. , Hurts So Good. Journal of Emergency Medical 
Services. , September 2010: p. 58 - 69. 
7. 
Kovar J, G.L., Alternate route: the humerus bone – a viable option for IO access. Journal 
of Emergency Medical Services, August 2010. 35(8): p. 52-9. 
8. 
Bustamante S, C.S., Ultrasound to Improve Target Site Identification for Proximal 
Humerus Intraosseous Vascular Access. In press Anesth Analg, 2016.