Sources of off-target effects of vagus nerve stimulation using the helical clinical lead in domestic pigs.

Objective: Clinical data suggest that efficacious vagus nerve stimulation (VNS) is limited by side effects such as cough and dyspnea that have stimulation thresholds lower than those for therapeutic outcomes. VNS side effects are putatively caused by activation of nearby muscles within the neck, via direct muscle activation or activation of nerve fibers innervating those muscles. Our goal was to determine the thresholds at which various VNS-evoked effects occur in the domestic pig­an animal model with vagus anatomy similar to human­using the bipolar helical lead deployed clinically. Approach: Intrafascicular electrodes were placed within the vagus nerve to record electroneurographic (ENG) responses, and needle electrodes were placed in the vagal-innervated neck muscles to record electromyographic (EMG) responses. Main results: Contraction of the cricoarytenoid muscle occurred at low amplitudes (~0.3 mA) and resulted from activation of motor nerve fibers in the cervical vagus trunk within the electrode cuff which bifurcate into the recurrent laryngeal branch of the vagus. At higher amplitudes (~1.4 mA), contraction of the cricoarytenoid and cricothyroid muscles was generated by current leakage outside the cuff to activate motor nerve fibers running within the nearby superior laryngeal branch of the vagus. Activation of these muscles generated artifacts in the ENG recordings that may be mistaken for compound action potentials representing slowly conducting Aδ-, B-, and C-fibers. Significance: Our data resolve conflicting reports of the stimulation amplitudes required for C-fiber activation in large animal studies (>10 mA) and human studies (<250 µA). After removing muscle-generated artifacts, ENG signals with post-stimulus latencies consistent with Aδ- and B-fibers occurred in only a small subset of animals, and these signals had similar thresholds to those that caused bradycardia. By identifying specific neuroanatomical pathways that cause off-target effects and characterizing the stimulation dose-response curves for on- and off-target effects, we hope to guide interpretation and optimization of clinical VNS.

Functional vagotopy in the cervical vagus nerve of the domestic pig: implications for the study of vagus nerve stimulation.

OBJECTIVE: Given current clinical interest in vagus nerve stimulation (VNS), there are surprisingly few studies characterizing the anatomy of the vagus nerve in large animal models as it pertains to on-and off-target engagement of local fibers. We sought to address this gap by evaluating vagal anatomy in the pig, whose vagus nerve organization and size approximates the human vagus nerve. APPROACH: Here we combined microdissection, histology, and immunohistochemistry to provide data on key features across the cervical vagus nerve in a swine model, and compare our results to other animal models (mouse, rat, dog, non-human primate) and humans. MAIN RESULTS: In a swine model we quantified the nerve diameter, number and diameter of fascicles, and distance of fascicles from the epineural surface where stimulating electrodes are placed. We also characterized the relative locations of the superior and recurrent laryngeal branches of the vagus nerve that have been implicated in therapy limiting side effects with common electrode placement. We identified key variants across the cohort that may be important for VNS with respect to changing sympathetic/parasympathetic tone, such as cross-connections to the sympathetic trunk. We discovered that cell bodies of pseudo-unipolar cells aggregate together to form a very distinct grouping within the nodose ganglion. This distinct grouping gives rise to a larger number of smaller fascicles as one moves caudally down the vagus nerve. This often leads to a distinct bimodal organization, or 'vagotopy'. This vagotopy was supported by immunohistochemistry where approximately half of the fascicles were immunoreactive for choline acetyltransferase, and reactive fascicles were generally grouped in one half of the nerve. SIGNIFICANCE: The vagotopy observed via histology may be advantageous to exploit in design of electrodes/stimulation paradigms. We also placed our data in context of historic and recent histology spanning multiple models, thus providing a comprehensive resource to understand similarities and differences across species.

An Injectable Neural Stimulation Electrode Made from an In-Body Curing Polymer/Metal Composite.

Implanted neural stimulation and recording devices hold vast potential to treat a variety of neurological conditions, but the invasiveness, complexity, and cost of the implantation procedure greatly reduce access to an otherwise promising therapeutic approach. To address this need, a novel electrode that begins as an uncured, flowable prepolymer that can be injected around a neuroanatomical target to minimize surgical manipulation is developed. Referred to as the Injectrode, the electrode conforms to target structures forming an electrically conductive interface which is orders of magnitude less stiff than conventional neuromodulation electrodes. To validate the Injectrode, detailed electrochemical and microscopy characterization of its material properties is performed and the feasibility of using it to stimulate the nervous system electrically in rats and swine is validated. The silicone-metal-particle composite performs very similarly to pure wire of the same metal (silver) in all measures, including exhibiting a favorable cathodic charge storage capacity (CSCC ) and charge injection limits compared to the clinical LivaNova stimulation electrode and silver wire electrodes. By virtue of its simplicity, the Injectrode has the potential to be less invasive, more robust, and more cost-effective than traditional electrode designs, which could increase the adoption of neuromodulation therapies for existing and new indications.

Surgical team workload comparison for 4-port and single-port laparoscopic cholecystectomy procedures.

Advanced minimally invasive procedures may cause postural constraints and increased workload and stress for providers. This study compared workload and stress across surgical team roles for 48 laparoscopic cholecystectomies (4-port vs single-port) using a task load index (NASA-TLX), a procedural difficulty question, and salivary stress hormones. Statistical analyses were performed based on the presence intra-cluster correlation within team roles, at α=0.05. The single-port technique resulted in an 89% increase in physical workload for the surgeon and 63% increase for the assistant (both p<0.05). The surgeon had significantly higher salivary stress hormones during single-port surgeries. The degree of procedural difficulty was positively correlated between the surgeon and most roles: resident (r=0.67), assistant (r=0.81), and technician (r=0.81). There was a statistically significant positive correlation between the surgeon and assistant for all selfreported workload measures (p<0.05). The single-port technique requires further improvement to balance surgical team workload for optimal patient safety and satisfaction.

Impact of single-incision laparoscopic cholecystectomy (SILC) versus conventional laparoscopic cholecystectomy (CLC) procedures on surgeon stress and workload: a randomized controlled trial.

INTRODUCTION: Single-incision laparoscopic cholecystectomy (SILC) may lead to higher patient satisfaction; however, SILC may expose the surgeon to increased workload. The goal of this study was to compare surgeon stress and workload between SILC and conventional laparoscopic cholecystectomy (CLC). METHODS: During a double-blind randomized controlled trial comparing patient outcomes for SILC versus CLC (NCT0148943), surgeon workload was assessed by four measures: surgery task load index questionnaire (Surg-TLX), maximum heart rate, salivary cortisol level, and instruments usability survey. The maximum heart rate and salivary cortisol levels were sampled from the surgeon before the random assignment of the surgical procedure, intraoperatively after the cystic duct was clipped, and at skin closure. After each procedure, the surgeon completed the Surg-TLX and an instrument usability survey. Student's t tests, Wilcoxon rank sum test, and Kruskal-Wallis nonparametric ANOVAs on the dependent variables by the technique (SILC vs. CLC) were performed with α = 0.05. RESULTS: Twenty-three SILC and 25 CLC procedures were included in the intent-to-treat analysis. No significant differences were observed between SILC and CLC for patient demographics and procedure duration. SILC had significantly higher post-surgery surgeon maximum heart rates than CLC (p < 0.05). SILC also had significantly higher mean change in the maximum heart rate between during and post-procedure (p < 0.05) than CLC. Salivary cortisol level was significantly higher during SILC than CLC (p < 0.01). Awkward manipulation of the instruments and limited fine motions were reported significantly more frequently with SILC than CLC (p < 0.01). In the surgeon-reported Surg-TLX, subscale of physical demand was significantly more demanding for SILC than CLC (p < 0.05). CONCLUSIONS: Surgeon heart rate, salivary cortisol level, instrument usability, and Surg-TLX ratings indicate that SILC is significantly more stressful and physically demanding than the CLC. Surgeon stress and workload may impact patients' outcomes; thus, ergonomic improvement on SILC is necessary.

PROMIS for Laparoscopy.

INTRODUCTION: We tested the responsiveness of the National Institutes of Health-sponsored Patient-Reported Outcomes Measures Information System (PROMIS) global health short form and a linear analog self-assessment for laparoscopy. METHODS: From May 2011 through December 2013, patients undergoing laparoscopy responded to patient reported outcome questionnaires perioperatively. Composite and single item scores were compared. RESULTS: One hundred fifteen patients, mean age 55 years, 58 % female, were enrolled. Visual analog pain scores differed significantly from baseline (mean 1.7 ± 2.3) to postoperative day 1 (mean 4.8 ± 2.6) and 7 (mean 2.5 ± 2.1) (p<0.0001). PROMIS physical subscale and total physical component subscore differed significantly from baseline (14.4 ± 3.0/47.4 ± 8.3) to postoperative day 1 (12.7 ± 3.2/42.1 ± 8.8) (p=0.0007/0.0003), due to everyday physical activities (p=0.0001). Linear analog self-assessment scores differed from baseline for pain frequency (p<0.0001), pain severity (p<0.0001), and social activity (p=0.0052); 40 % of subjects reported worsening in PROMIS physical T-score to postoperative day 1 and 25 % to postoperative day 7. Linear analog self-assessment mental well-being scores were worse in 32 % of patients at postoperative day 7, emotional well-being in 28 %, social activity in 24 %, and fatigue in 20 % of patients. CONCLUSION: Single items and change from baseline are responsive perioperative quality of life assessments for laparoscopy.

Natural orifice transluminal endoscopic surgery for patients with perforated peptic ulcer.

BACKGROUND: Perforation accounts for 70% of deaths attributed to peptic ulcers. Laparoscopic repair is effective but infrequently used. Our aim was to assess how many patients with perforated peptic ulcer could be candidates for a transluminal endoscopic omental patch closure. METHODS: This retrospective study reviewed patients with perforated peptic ulcer from 2005 to 2010. Demographics, ulcer characteristics, operative procedure, and outcomes were recorded. Candidates for endoscopic transluminal repair were defined as those having undergone omental patch closure of an ulcer of appropriate size and no contraindications to laparoscopy or endoscopy. RESULTS: In the retrospective review, a total of 104 patients were identified; 62% female, mean age = 68 years, mean ASA of 3, and 63% medication-related ulcers. Fifty-nine (63%) had an omental patch (80% open), and 35 (37%) had other procedures. Ten patients had nonoperative management. Thirty-day mortality was 14% and 1 year mortality was 35%. Forty-nine patients (52%) were considered potential candidates for transluminal repair. CONCLUSION: Sixty-three percent of our patients sustained a medication-related perforation with 1 year mortality of 35%. The majority of patients were treated using open omental patch repair. Transluminal endoscopic repair may provide an additional situation for a minimally invasive approach for a number of these patients.

Natural orifice translumenal endoscopic surgery used for perforated viscus repair is feasible using lower peritoneal pressures than laparoscopy in a porcine model.

BACKGROUND: Procedure-related complications contribute to 1-year mortality in patients with perforated ulcers. Natural orifice translumenal endoscopic surgery (NOTES) might offer a new repair approach. STUDY DESIGN: Swine were randomized to laparoscopic or NOTES repair. Laparoscopic gastrotomy creation (1 cm) was followed by 4 hours soilage time. After peritoneal cavity irrigation (per group assignment), repair proceeded with a laparoscopic or NOTES approach. For NOTES repair, omentum was endoscopically grasped, pulled into the gastric lumen, and fixed with metallic clips. Feasibility; time to complete procedures; pneumoperitoneal pressures; and clinical parameters, including necropsy and peritoneal culture at 2 weeks, were recorded. RESULTS: NOTES repair failed in 1 animal (technical); repair was completed laparoscopically, and data were analyzed as intention to treat. Specific NOTES repair time (minutes) was comparable with laparoscopy (36 versus 46; p = 0.2). Mean abdominal pressure (mmHg) required to complete NOTES repair was lower than in laparoscopy (4 versus 12; p < 0.001). Nineteen of 23 animals thrived until necropsy at 2 weeks. Three animals succumbed to airway compromise in recovery; 1 NOTES animal failed to thrive on postoperative day 7. No intra-abdominal cause for these deaths was found. At necropsy all repairs were intact, and peritoneal cultures revealed a small and equivalent amount of colony-forming units in each group. CONCLUSIONS: Endoscopic ulcer repair appears technically feasible with similar clinical and infectious outcomes to laparoscopy. The lower required pneumoperitoneal pressures used in these NOTES techniques are recognizable different outcomes from laparoscopy and can be advantageous in critically ill patients.