Dose-Response Relationships for Hemidiaphragmatic Paresis Following Ultrasound-Guided Supraclavicular Block

NCT ID: NCT03138577

Last Updated: 2020-05-13

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-02-12

Study Completion Date

2019-07-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Surgery of Right Upper Extremity

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
The physician reviewing the ultrasound images and determining the presence/absence of diaphragm paralysis is masked to treatment assignment.

Study Groups

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Dose Cohort 7

5 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine Ultrasound Imaging Bedside Negative Inspiratory Force Meter

Group Type OTHER

Ultrasound Imaging

Intervention Type 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.

Supraclavicular Block

Intervention Type 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.

Bedside Negative Inspiratory Force Meter

Intervention Type 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.

Dose Cohort 6

10 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine Ultrasound Imaging Bedside Negative Inspiratory Force Meter

Group Type OTHER

Ultrasound Imaging

Intervention Type 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.

Supraclavicular Block

Intervention Type 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.

Bedside Negative Inspiratory Force Meter

Intervention Type 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.

Dose Cohort 5

15 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine Ultrasound Imaging Bedside Negative Inspiratory Force Meter

Group Type OTHER

Ultrasound Imaging

Intervention Type 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.

Supraclavicular Block

Intervention Type 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.

Bedside Negative Inspiratory Force Meter

Intervention Type 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.

Dose Cohort 4

20 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine Ultrasound Imaging Bedside Negative Inspiratory Force Meter

Group Type OTHER

Ultrasound Imaging

Intervention Type 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.

Supraclavicular Block

Intervention Type 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.

Bedside Negative Inspiratory Force Meter

Intervention Type 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.

Dose Cohort 3

Supraclavicular Block: 25 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine Ultrasound Imaging Bedside Negative Inspiratory Force Meter

Group Type OTHER

Ultrasound Imaging

Intervention Type 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.

Supraclavicular Block

Intervention Type 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.

Bedside Negative Inspiratory Force Meter

Intervention Type 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.

Dose Cohort 2

30 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine Ultrasound Imaging Bedside Negative Inspiratory Force Meter

Group Type OTHER

Ultrasound Imaging

Intervention Type 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.

Supraclavicular Block

Intervention Type 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.

Bedside Negative Inspiratory Force Meter

Intervention Type 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.

Dose Cohort 1

35 mL of 2:1 mixture of 1.5% mepivacaine and 0.5% bupivacaine Ultrasound Imaging Bedside Negative Inspiratory Force Meter

Group Type OTHER

Ultrasound Imaging

Intervention Type 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.

Supraclavicular Block

Intervention Type 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.

Bedside Negative Inspiratory Force Meter

Intervention Type 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.

Interventions

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Ultrasound Imaging

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.

Intervention Type DIAGNOSTIC_TEST

Supraclavicular Block

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.

Intervention Type DRUG

Bedside Negative Inspiratory Force Meter

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.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Undergoing right upper extremity surgery with supraclavicular block as the primary anesthetic
* Age greater than or equal to 18 years of age
* American Society of Anesthesiologists (ASA) physical status 1 to 3
* Able to give informed consent

Exclusion Criteria

* Patient refusal for supraclavicular block
* Inability to give informed consent
* Allergy to local anesthetics
* Hemidiaphragmatic dysfunction, suspected or known pulmonary disease
* Neuromuscular disease
* Obstructive or restrictive pulmonary disease
* Medical or anatomic contraindication to supraclavicular blockade as judged by clinician
* Pregnancy
Minimum Eligible Age

18 Years

Maximum Eligible Age

105 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Weill Medical College of Cornell University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tiffany Tedore, MD

Role: PRINCIPAL_INVESTIGATOR

WCMC, NYP

Locations

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Weill Cornell Medical College

New York, New York, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 19916254 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25650633 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23648519 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19017880 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3354995 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17196502 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19574870 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 2350571 (View on PubMed)

Garrett-Mayer E. The continual reassessment method for dose-finding studies: a tutorial. Clin Trials. 2006;3(1):57-71. doi: 10.1191/1740774506cn134oa.

Reference Type BACKGROUND
PMID: 16539090 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26695877 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33004656 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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1609017547

Identifier Type: -

Identifier Source: org_study_id

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