Lower Thoracic Spinal Cord Stimulation to Restore Cough in Patients With Spinal Cord Injury: Results of a National Institutes of Health–Sponsored Clinical Trial. Part I: Methodology and Effectiveness of Expiratory Muscle Activation

Abstract

Objective-Evaluation of the capacity of lower thoracic spinal cord stimulation (SCS) to activate the expiratory muscles and generate large airway pressures and high peak airflows characteristic of cough, in subjects with tetraplegia. Design-Clinical trial.Setting-In-patient hospital setting for electrode insertion; out-patient setting for measurement of respiratory pressures; home setting for application of SCS. Disclosure:We certify that we have affiliations with or financial involvement (eg, employment, consultancies, honoraria, stock ownership or options, expert testimony, grants and patents received or pending, royalties) with an organization or entity with a financial interest in, or financial conflict with, the subject matter or materials discussed in the manuscript AND all such affiliations and involvements are disclosed on the title page of the manuscript. Explanation of Disclosure:Dr. DiMarco is a Founder of and has a significant financial interest in Synapse BioMedical, Inc, a manufacturer of diaphragm pacing systems. Participants-Subjects (N = 9; 8 men, 1 woman) with cervical spinal cord injury and weak cough. Clinical Trial Registration Number: NCT00116337 Suppliers NIH Public AccessIntervention(s)-A fully implantable electrical stimulation system was surgically placed in each subject. Partial hemilaminectomies were made to place single-disc electrodes in the epidural space at the T9, T11 and L1 spinal levels. A radiofrequency receiver was placed in the subcutaneous pocket over the anterior portion of the chest wall. Electrode wires were tunneled subcutaneously and connected to the receiver. Stimulation was applied by activating a small portable external stimulus controller box powered by a rechargeable battery to each electrode lead alone and in combination.Main Outcome Measure(s)-Airway pressure and peak airflow generation achieved with SCS.Results-Supramaximal SCS resulted in large airway pressures and high peak airflow rates during stimulation at each electrode lead. Maximum airway pressures and peak airflow rates were achieved with combined stimulation of any 2 leads. At total lung capacity, mean maximum airway pressure generation and peak airflow rates were 137 ± 30 cmH 2 O (mean ± SE) and 8.6 ± 1.8 (mean ± SE) L/ s, respectively.Conclusions-Lower thoracic SCS results in near maximum activation of the expiratory muscles and the generation of high positive airway pressures and peak airflow rates in the range of those observed with maximum cough efforts in normal individuals.

Comparison of wire and disc leads to activate the expiratory muscles in dogs

“…[23][24][25][26] Importantly, the results of these studies translated well into clinical trials in which SCS resulted in near maximum expiratory muscle activation and was successful in restoring an effective cough mechanism in subjects with SCI. [20][21][22] Airway pressures generated with the disc leads, therefore, represented our gold standard with which other leads could be compared. The results of the present study demonstrate that the application of electrical stimulation with wire leads at the same spinal cord levels also results in substantial positive airway pressures.…”

“…A remote ground electrode was positioned in the back musculature. Since we have previously demonstrated, both in animal 24,25 and human 20,21 studies, that any combination of two of the three spinal cord levels tested (T9, T11, and L1) resulted in maximum pressure generation, we focused our evaluation to stimulation of each site individually and the simultaneous stimulation of various combinations of two sites. The effects of both monopolar and bipolar stimulation were also evaluated.…”

“…Since monopolar SCS with the disc leads, when applied in clinical trials, 20,21 resulted in airway pressure generation that approximated pressures generated with a normal maximum cough, airway pressure generation achieved during SCS with these leads served as our gold standard to which all comparisons were made. Data are reported as mean ± SE.…”

“…This method is successful in achieving an effective means of secretion clearance, as demonstrated by the generation of large airway pressures and peak expiratory airflow rates, which approximate values observed during maximum cough efforts in normal people. 20,21 Importantly, this technique significantly facilitates airway clearance, reduces the difficulty in raising secretions, reduces the need for caregiver support for secretion management, reduces the incidence of respiratory tract infections, and improves life quality. 20,22 While successful in restoring an effective cough in each subject, this technique requires an invasive procedure for disc lead placement (typically, 4-6 hours of operating room time) and 2-3-day hospital admission.…”

“…In recent human studies, we demonstrated that an effective cough can be restored in subjects with SCI via stimulation of electrodes positioned on the lower thoracic and upper lumbar spinal cord. [20][21][22] This procedure involves the placement of disc leads at the T9, T11, and L1 spinal cord levels on the dorsal epidural surface via laminotomy incisions, and a ground electrode positioned in the subcutaneous tissue. This method is successful in achieving an effective means of secretion clearance, as demonstrated by the generation of large airway pressures and peak expiratory airflow rates, which approximate values observed during maximum cough efforts in normal people.…”