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This clinical trial is for subjects undergoing right upper extremity surgery. The aim of the study is to investigate the dose-response relationship between local anesthetic volume and ipsilateral hemidiaphragmatic paresis (HDP) in patients getting ultrasound-guided supraclavicular brachial plexus blocks in a blinded, prospective trial.
With traditional landmark-based or nerve-stimulator techniques, the incidence of HDP following supraclavicular blocks is approximately 50-67%. Ultrasound-guided techniques are thought to enhance precision while reducing the volume of anesthetic used, but even then HDP incidence is nearly 60%. To date, no trials have studied the dose-response relationship between local anesthetic volume and degree of HDP.
Patient Selection
30 eligible patients undergoing right upper extremity surgery and eligible for supraclavicular blocks will be recruited at NewYork-Presbyterian/Weill Cornell Medical Center.
Evaluation of HDP
Baseline M-mode recordings of diaphragm function will be made by an anesthesiologist. Patients will perform "voluntary sniff" (VS) tests, or forceful nasal inhales, immediately preceding the brachial plexus blockade, and again at 15 minutes and 30 minutes after the block.
Diaphragmatic excursion from baseline will be measured in centimeters; three measurements will be made and averaged. Hemidiaphragmatic paresis will be defined as greater than or equal to 60% reduction in diaphragmatic excursion, no movement, or paradoxical movement in the VS test.
Evaluation of Pulmonary Function
A bedside negative inspiratory force (NIF) meter will be used to measure negative inspiratory force prior to the block and 30 minutes after the block.
Evaluation of Supraclavicular Block
At the 15- and 30-minute marks, the investigators will assess sensory blockade and motor block in the axial, musculocutaneous, radial, median, and ulnar distributions. Both will be judged on 3-point scales. The investigators will also apply a 0-10 point verbal rating scale to assess dyspnea at 30 minutes. Oxygen saturation will be measured off of supplemental oxygen before the block and 30 minutes after the block.
Following the assessments, patients will have surgery using brachial plexus blockade as the primary anesthetic.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Cohort 7 | Other | 5 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine Ultrasound Imaging Bedside Negative Inspiratory Force Meter |
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| Dose Cohort 6 | Other | 10 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine Ultrasound Imaging Bedside Negative Inspiratory Force Meter |
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| Dose Cohort 5 | Other | 15 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine Ultrasound Imaging Bedside Negative Inspiratory Force Meter |
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| Dose Cohort 4 | Other | 20 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine Ultrasound Imaging Bedside Negative Inspiratory Force Meter |
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| Dose Cohort 3 | Other |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ultrasound Imaging | Diagnostic Test | M-mode tracings of right diaphragm motion will be made and recorded by a skilled anesthesiologist. Patients will be examined in the supine position and scanned from a low intercostal or subcostal approach using the liver as an acoustic window. Patients will be asked to perform a "voluntary sniff" (VS) test, for which they will be asked to forcefully inhale through the nose in a sniffing position. The above measurement will be performed immediately preceding the brachial plexus blockade, and then at 15 minute and 30 minutes after block. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects With Hemidiaphragmatic Paresis at Various Volumes of Local Anesthetic 15 Minutes After Supraclavicular Block | Diaphragm motion was recorded during voluntary sniffing fifteen minutes after supraclavicular block with the specified volume of local anesthetic. Blinded investigators reviewed the scans and determined whether the scans were indicative of hemidiaphragmatic paresis (HDP) or not (No HDP). This data was fit to a dose response curve. | 15 minutes |
| Number of Subjects With Hemidiaphragmatic Paresis at Various Volumes of Local Anesthetic 30 Minutes After Supraclavicular Block | Diaphragm motion was recorded during voluntary sniffing 30 minutes after supraclavicular block with the specified volume of local anesthetic. Blinded investigators reviewed the scans and determined whether the scans were indicative of hemidiaphragmatic paresis (HDP) or not (No HDP). This data was fit to a dose response curve. | 30 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Negative Inspiratory Force (NIF) at 30 Minutes | The change of the absolute value of NIF from the baseline measurement to that at 30 minutes after the block | 30 minutes |
| Dose Response Curve for Motor and Sensory Block 15 Minutes After Block |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Tiffany Tedore, MD | WCMC, NYP | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Weill Cornell Medical College | New York | New York | 10065 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19916254 | Background | Renes SH, Spoormans HH, Gielen MJ, Rettig HC, van Geffen GJ. Hemidiaphragmatic paresis can be avoided in ultrasound-guided supraclavicular brachial plexus block. Reg Anesth Pain Med. 2009 Nov-Dec;34(6):595-9. doi: 10.1097/aap.0b013e3181bfbd83. | |
| 25650633 | Background | Petrar SD, Seltenrich ME, Head SJ, Schwarz SK. Hemidiaphragmatic paralysis following ultrasound-guided supraclavicular versus infraclavicular brachial plexus blockade: a randomized clinical trial. Reg Anesth Pain Med. 2015 Mar-Apr;40(2):133-8. doi: 10.1097/AAP.0000000000000215. |
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3 of the 24 enrolled patients were excluded due to baseline abnormal diaphragm motion or inability to visualize the diaphragm on baseline ultrasound scan.
Study subjects were recruited from August 2018 to July 2019. Fifty-nine subjects were assessed for eligibility. Fourteen subjects were excluded or refused to participate, and 21 were eligible but not approached due to the anticipation of insufficient time to complete assessments. Twenty-four patients consented to enrollment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dose Cohort 7 | Supraclavicular block performed with 5 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
| FG001 | Dose Cohort 6 | Supraclavicular block performed with 10 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 5, 2017 |
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A modified "3+3" dose escalation design, modeled after Phase I dose-finding trials, was used to define the dose response curve for local anesthetic volume in the supraclavicular block and resulting hemidiaphragmatic paresis in patients undergoing right upper extremity surgery with supraclavicular block as the primary anesthetic. Possible dosing levels of 5, 10, 15, 20, 25, 30, 35 and 40 mL of local anesthetic were pre-specified with a cohort of three subjects per dose. Diaphragm function was determined by a blinded assessor with M-mode tracings of the right diaphragm before and after supraclavicular block. Secondary objectives included the assessment of respiratory function via negative inspiratory force, oxygen saturation and subjective dyspnea, as well as the extent of sensory and motor blockade.
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The physician reviewing the ultrasound images and determining the presence/absence of diaphragm paralysis is masked to treatment assignment.
Supraclavicular Block: 25 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine Ultrasound Imaging Bedside Negative Inspiratory Force Meter |
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| Dose Cohort 2 | Other | 30 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine Ultrasound Imaging Bedside Negative Inspiratory Force Meter |
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| Dose Cohort 1 | Other | 35 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine Ultrasound Imaging Bedside Negative Inspiratory Force Meter |
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| Supraclavicular Block | Drug | The patient will be positioned supine with the head turned to the contralateral side. The ultrasound will be placed in the supraclavicular fossa, and the skin and subcutaneous tissues will be infiltrated lateral to the probe with 2% lidocaine. The anesthesiologist can redirect the needle and perform additional injections for complete coverage of the brachial plexus. The local anesthetic will be a 2:1 mix of 1.5% mepivacaine and 0.5% bupivacaine. |
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| Bedside Negative Inspiratory Force Meter | Other | A bedside negative inspiratory force (NIF) meter will be used to measure negative inspiratory force prior to the block and 30 minutes after the block. |
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As described in the protocol, each subject's block was assessed via motor and sensory exam at 15 minutes and given a score (0-20), with 20 being a perfect block and any score less than 10 indicating an ineffective block. A dose response curve was generated for block score with different volumes of local anesthetic administered.
| 15 minutes |
| Dose Response Curve for Motor and Sensory Block Score 30 Minutes After Block | As described in the protocol, each subject's block was assessed via motor and sensory exam at 30 minutes and given a score (0-20), with 20 being a perfect block and any score less than 10 indicating an ineffective block. A dose response curve was generated for block score with different volumes of local anesthetic administered. | 30 minutes |
| Change in Room Air Oxygen Saturation at 30 Minutes. | The change in room air oxygen saturation from baseline to 30 minutes after the block was calculated. | 30 minutes |
| Subjective Dyspnea 30 Minutes After Block | 30 minutes after the block, patients were asked to rate any symptoms of dyspnea on a scale of 0 (no trouble breathing) to 10 (extreme trouble breathing). | 30 minutes |
| 23648519 | Background | Kant A, Gupta PK, Zohar S, Chevret S, Hopkins PM. Application of the continual reassessment method to dose-finding studies in regional anesthesia: an estimate of the ED95 dose for 0.5% bupivacaine for ultrasound-guided supraclavicular block. Anesthesiology. 2013 Jul;119(1):29-35. doi: 10.1097/ALN.0b013e31829764cf. |
| 19017880 | Background | Boussuges A, Gole Y, Blanc P. Diaphragmatic motion studied by m-mode ultrasonography: methods, reproducibility, and normal values. Chest. 2009 Feb;135(2):391-400. doi: 10.1378/chest.08-1541. Epub 2008 Nov 18. |
| 3354995 | Background | Mier-Jedrzejowicz A, Brophy C, Moxham J, Green M. Assessment of diaphragm weakness. Am Rev Respir Dis. 1988 Apr;137(4):877-83. doi: 10.1164/ajrccm/137.4.877. |
| 17196502 | Background | Soares LG, Brull R, Lai J, Chan VW. Eight ball, corner pocket: the optimal needle position for ultrasound-guided supraclavicular block. Reg Anesth Pain Med. 2007 Jan-Feb;32(1):94-5. doi: 10.1016/j.rapm.2006.10.007. No abstract available. |
| 19574870 | Background | Tedore TR, YaDeau JT, Maalouf DB, Weiland AJ, Tong-Ngork S, Wukovits B, Paroli L, Urban MK, Zayas VM, Wu A, Gordon MA. Comparison of the transarterial axillary block and the ultrasound-guided infraclavicular block for upper extremity surgery: a prospective randomized trial. Reg Anesth Pain Med. 2009 Jul-Aug;34(4):361-5. doi: 10.1097/AAP.0b013e3181ac9e2d. |
| 2350571 | Background | O'Quigley J, Pepe M, Fisher L. Continual reassessment method: a practical design for phase 1 clinical trials in cancer. Biometrics. 1990 Mar;46(1):33-48. |
| 16539090 | Background | Garrett-Mayer E. The continual reassessment method for dose-finding studies: a tutorial. Clin Trials. 2006;3(1):57-71. doi: 10.1191/1740774506cn134oa. |
| 26695877 | Background | Neal JM. Ultrasound-Guided Regional Anesthesia and Patient Safety: Update of an Evidence-Based Analysis. Reg Anesth Pain Med. 2016 Mar-Apr;41(2):195-204. doi: 10.1097/AAP.0000000000000295. |
| 33004656 | Derived | Tedore TR, Lin HX, Pryor KO, Tangel VE, Pak DJ, Akerman M, Wellman DS, Oden-Brunson H. Dose-response relationship between local anesthetic volume and hemidiaphragmatic paresis following ultrasound-guided supraclavicular brachial plexus blockade. Reg Anesth Pain Med. 2020 Dec;45(12):979-984. doi: 10.1136/rapm-2020-101728. Epub 2020 Oct 1. |
| FG002 | Dose Cohort 5 | Supraclavicular block performed with 15 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
| FG003 | Dose Cohort 4 | Supraclavicular block performed with 20 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
| FG004 | Dose Cohort 3 | Supraclavicular block performed with 25 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
| FG005 | Dose Cohort 2 | Supraclavicular block performed with 30 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
| FG006 | Dose Cohort 1 | Supraclavicular block performed with 35 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 5 mL | 5 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
| BG001 | 10 mL | 10 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
| BG002 | 15 mL | 15 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
| BG003 | 20 mL | 20 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
| BG004 | 25 mL | 25 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
| BG005 | 30 mL | 30 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
| BG006 | 35 mL | 35 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
| BG007 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| ASA Classification | American Society of Anesthesiologists (ASA) Classification: I: Normal, healthy patient II: Patient with mild systemic disease III: Patient with severe systemic disease | Count of Participants | Participants |
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| Upper Extremity Surgery Location | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Subjects With Hemidiaphragmatic Paresis at Various Volumes of Local Anesthetic 15 Minutes After Supraclavicular Block | Diaphragm motion was recorded during voluntary sniffing fifteen minutes after supraclavicular block with the specified volume of local anesthetic. Blinded investigators reviewed the scans and determined whether the scans were indicative of hemidiaphragmatic paresis (HDP) or not (No HDP). This data was fit to a dose response curve. | Posted | Count of Participants | Participants | 15 minutes |
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| Primary | Number of Subjects With Hemidiaphragmatic Paresis at Various Volumes of Local Anesthetic 30 Minutes After Supraclavicular Block | Diaphragm motion was recorded during voluntary sniffing 30 minutes after supraclavicular block with the specified volume of local anesthetic. Blinded investigators reviewed the scans and determined whether the scans were indicative of hemidiaphragmatic paresis (HDP) or not (No HDP). This data was fit to a dose response curve. | Posted | Count of Participants | Participants | 30 minutes |
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| Secondary | Change in Negative Inspiratory Force (NIF) at 30 Minutes | The change of the absolute value of NIF from the baseline measurement to that at 30 minutes after the block | Posted | Median | Inter-Quartile Range | cm H2O | 30 minutes |
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| Secondary | Dose Response Curve for Motor and Sensory Block 15 Minutes After Block | As described in the protocol, each subject's block was assessed via motor and sensory exam at 15 minutes and given a score (0-20), with 20 being a perfect block and any score less than 10 indicating an ineffective block. A dose response curve was generated for block score with different volumes of local anesthetic administered. | Posted | Number | score on a scale | 15 minutes |
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| Secondary | Dose Response Curve for Motor and Sensory Block Score 30 Minutes After Block | As described in the protocol, each subject's block was assessed via motor and sensory exam at 30 minutes and given a score (0-20), with 20 being a perfect block and any score less than 10 indicating an ineffective block. A dose response curve was generated for block score with different volumes of local anesthetic administered. | Posted | Number | score on a scale | 30 minutes |
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| Secondary | Change in Room Air Oxygen Saturation at 30 Minutes. | The change in room air oxygen saturation from baseline to 30 minutes after the block was calculated. | Posted | Median | Inter-Quartile Range | percent | 30 minutes |
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| Secondary | Subjective Dyspnea 30 Minutes After Block | 30 minutes after the block, patients were asked to rate any symptoms of dyspnea on a scale of 0 (no trouble breathing) to 10 (extreme trouble breathing). | Posted | Median | Inter-Quartile Range | score on a scale | 30 minutes |
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48 hours
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dose Cohort 7 (5 mL) | Supraclavicular block performed with 5 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine | 0 | 3 | 0 | 3 | 0 | 3 |
| EG001 | Dose Cohort 6 (10 mL) | Supraclavicular block performed with 10 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine | 0 | 3 | 0 | 3 | 0 | 3 |
| EG002 | Dose Cohort 5 (15 mL) | Supraclavicular block performed with 15 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine | 0 | 3 | 0 | 3 | 0 | 3 |
| EG003 | Dose Cohort 4 (20 mL) | Supraclavicular block performed with 20 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine | 0 | 3 | 0 | 3 | 0 | 3 |
| EG004 | Dose Cohort 3 (25 mL) | Supraclavicular block performed with 25 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine | 0 | 3 | 0 | 3 | 0 | 3 |
| EG005 | Dose Cohort 2 (30 mL) | Supraclavicular block performed with 30 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine | 0 | 3 | 0 | 3 | 0 | 3 |
| EG006 | Dose Cohort 1 (35 mL) | Supraclavicular block performed with 35 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine | 0 | 3 | 0 | 3 | 0 | 3 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Tiffany Tedore | Weill Cornell Medical College | 212-746-2725 | tft9001@med.cornell.edu |
| Apr 28, 2020 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D014463 | Ultrasonography |
| ID | Term |
|---|---|
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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| No HDP |
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| OG004 | Dose Cohort 3 (25 mL) | Supraclavicular block performed with 25 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
| OG005 | Dose Cohort 2 (30 mL) | Supraclavicular block performed with 30 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
| OG006 | Dose Cohort 1 (35 mL) | Supraclavicular block performed with 35 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
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| OG004 | Dose Cohort 3 (25 mL) | Supraclavicular block performed with 25 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
| OG005 | Dose Cohort 2 (30 mL) | Supraclavicular block performed with 30 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
| OG006 | Dose Cohort 1 (35 mL) | Supraclavicular block performed with 35 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
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| OG004 | Dose Cohort 3 (25 mL) | Supraclavicular block performed with 25 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
| OG005 | Dose Cohort 2 (30 mL) | Supraclavicular block performed with 30 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
| OG006 | Dose Cohort 1 (35 mL) | Supraclavicular block performed with 35 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine |
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