The Biomechanical Effects of Flaccid Paralysis Induced by Botulinum Toxin a After Damage Control Laparotomy

The Biomechanical Effects of Flaccid Paralysis Induced by Botulinum Toxin a After Damage Control Laparotomy: A Pilot Study

Damage control laparotomy (DCL) is a life saving maneuver used with success in trauma and acute general surgery patients. The technique involves source control of sepsis and hemorrhage with an abbreviated laparotomy. In other words, the surgical procedure is cut short to allow for resuscitation in the ICU after the immediately life threatening pathology is treated. Planned re-exploration is then performed within 24-48 hours. It is at this procedure that the injuries are reconstructed. This technique, unfortunately, has several complications implicit with its use including wound infection, enterocutaneous fistula formation, and intra-abdominal abscess development.[1] Additionally, in patients whom primary fascial closure is not achieved, extensive abdominal wall reconstruction will be required in 6-12 months. The key for preventing these complications is definitive closure of the abdominal fascia, however, 10-50% of patients will have a planned ventral hernia with an open abdominal wound at dismissal [1,2] Proven methods for decreasing the rate of planned ventral hernia utilize tension in the midline to counter the effects of lateral abdominal muscular retraction.[3,4,5] Despite these improvements, however, the planned ventral hernia rate continues to be substantial.[2] Botulinum toxin a (BTX) is an FDA approved neuron modulating agent which has been used extensively in cosmetic, motor and pain disorders over the past 20 years [6,7]. The toxin blocks acetylcholine and pain modulator release (calcitonin gene related peptide and substance P) from the pre-synaptic cholinergic nerve terminal. The peptides are unable to bind at their motor end plate receptors through a process that cleaves proteins involved in the transport protein cascade. This results in flaccid paralysis and neuromodulation of the abdominal wall muscles resulting in reduced lateral tension and pain. Theoretically, this could increase the rates of primary fascial closure, improve pain sensation, decrease the rate of complications associated with open abdomens all while lowering the costs and need for future abdominal wall reconstruction.

Study Overview

• Status: Completed
• Conditions: Wound; Abdomen, Abdominal Wall
• Intervention / Treatment: Drug: Botulinum Toxin Type A; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
    • St. Paul, Minnesota, United States, 55101
      • Regions Hosptial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• male or female, aged ≥ 18 years or older
• signed Informed Consent form by appropriate patient representative
• undergone a DCL for trauma or acute general surgery

Exclusion Criteria

• death prior to BTX injection
• failure to achieve hemodynamic stability within 24 hours (stable or decreasing vasopressor support within 6 hours in combination with a stable or improving base deficit or lactate level)
• Viable pregnancy
• At risk populations (<18 years of age, prisoners)
• BMI > 50
• Pre-existing pareses (Amyotrophic Lateral Sclerosis, myopathies, motor polyneuropathies
• impaired neuromuscular transmission (Myasthenia Gravis, Lambert-Eaton Syndrome)
• concurrent aminoglycoside use
• chronic obstructive pulmonary disease
• known metastatic malignancy
• pre-existing cirrhosis
• necrotizing fasciitis of the trunk
• hypocoagulable state (INR >1.5)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Botulinum Toxin A injection	Drug: Botulinum Toxin Type A; Six 25 cc injection of Botulinum Toxin A
PLACEBO_COMPARATOR: Placebo (Normal Saline) injection	Drug: Placebo; Placebo (Normal Saline)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary objective of this study is to determine whether BTX will facilitate primary fascial closure after DCL.	The primary endpoint is the rate of delayed primary fascial closure. Delayed primary fascial closure will be considered when the rectus abdominus fascia is directly approximated in the midline during the same hospitalization as the initial DCL without the use of mesh.	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Mortality	2 years
Non-invasive biomechanical testing results (surface wave elastography, traction index and durometry)	2 years
Duration of mechanical ventilation	2 years
Complications (wound infection, fascial dehiscence, enterocutaneous fistula formation, acute renal failure, pneumonia)	2 years
Overall hospital cost	2 years
Total narcotic use (morphine equivalents)	2 years
ABPS score	2 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Martin D Zielinski, M.D., Mayo Clinic; Principal Investigator: David Dries, MD, Regions Hospital

Publications and helpful links

General Publications

• Zielinski MD, Kuntz M, Zhang X, Zagar AE, Khasawneh MA, Zendejas B, Polites SF, Ferrara M, Harmsen WS, Ballman KS, Park MS, Schiller HJ, Dries D, Jenkins DH. Botulinum toxin A-induced paralysis of the lateral abdominal wall after damage-control laparotomy: A multi-institutional, prospective, randomized, placebo-controlled pilot study. J Trauma Acute Care Surg. 2016 Feb;80(2):237-42. doi: 10.1097/TA.0000000000000917.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ACTUAL): August 1, 2014
• Study Completion (ACTUAL): June 1, 2015

Study Registration Dates

• First Submitted: November 15, 2011
• First Submitted That Met QC Criteria: December 16, 2011
• First Posted (ESTIMATE): December 20, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): April 27, 2016
• Last Update Submitted That Met QC Criteria: April 25, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Botulinum Toxin A; Open Abdomen; Damage Control Laparotomy; Primary Fascial Closure
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Wounds and Injuries; Paralysis; Abdominal Injuries; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: 10-008404