Diaphragm Neurostimulation Assisted Ventilation in Critically Ill Patients.

Diaphragm neurostimulation consists of placing electrodes directly on or in proximity to the phrenic nerve(s) to elicit diaphragmatic contractions. Since its initial description in the 18th century, indications have shifted from cardiopulmonary resuscitation to long-term ventilatory support. Recently, the technical development of devices for temporary diaphragm neurostimulation has opened up the possibility of a new era for the management of mechanically ventilated patients. Combining positive pressure ventilation with diaphragm neurostimulation offers a potentially promising new approach to the delivery of mechanical ventilation which may benefit multiple organ systems. Maintaining diaphragm contractions during ventilation may attenuate diaphragm atrophy and accelerate weaning from mechanical ventilation. Preventing atelectasis and preserving lung volume can reduce lung stress and strain and improve homogeneity of ventilation, potentially mitigating ventilator-induced lung injury. Furthermore, restoring the thoracoabdominal pressure gradient generated by diaphragm contractions may attenuate the drop in cardiac output induced by positive pressure ventilation. Experimental evidence suggests diaphragm neurostimulation may prevent neuroinflammation associated with mechanical ventilation. This review describes the historical development and evolving approaches to diaphragm neurostimulation during mechanical ventilation and surveys the potential mechanisms of benefit. The review proposes a research agenda and offers perspectives for the future of diaphragm neurostimulation assisted mechanical ventilation for critically ill patients.

Efficacy of aerobic training and resistance training combined with external diaphragm pacing in patients with chronic obstructive pulmonary disease: A randomized controlled study.

OBJECTIVE: To evaluate the efficacy of aerobic training, resistance training combined with external diaphragm pacing in patients with chronic obstructive pulmonary disease. DESIGN: Randomized controlled trial. SETTING: The Fourth Rehabilitation Hospital of Shanghai, China. PARTICIPANTS: 82 (67.0 ± 6.5 years, 59.8% male) patients with stable chronic obstructive pulmonary disease were randomized to intervention group 1 (n = 27), intervention group 2 (n = 28), and control group (n = 27). INTERVENTION: Intervention group 1 received aerobic and resistance training, while intervention group 2 received additional external diaphragm pacing. Control group received aerobic training only. MAIN MEASURES: 1-year follow-up of physical activity, body composition, respiratory function and diaphragm function. RESULTS: Intervention groups 1 and 2 showed statistically improvements in the difference value compared with control group in terms of 6-min walk distance (-95.28 ± 20.09 and -101.92 ± 34.91 vs -63.58 ± 23.38), forced expiratory volume in 1 s (-0.042 ± 0.027 and -0.130 ± 0.050 vs -0.005 ± 0.068), fat-free mass (-2.11 ± 3.74 and -3.82 ± 3.74vs 0.28 ± 1.49) and chronic obstructive pulmonary disease assessment test value (2.16 ± 0.85 and 2.38 ± 1.02 vs 1.50 ± 0.93). Intervention group 2 showed significant difference in arterial oxygen pressure (-4.46 ± 3.22 vs -1.92 ± 3.45), diaphragm excursion during deep breaths (-0.82 ± 0.74 vs -0.38 ± 0.29), and diaphragm thickness fraction (-8.77 ± 3.22 vs -4.88 ± 2.69) compared with control group. CONCLUSION: The combination of aerobic training, resistance training, and external diaphragm pacing obtained significant improvements in physical activity, respiratory function, body composition, arterial oxygen pressure, and diaphragm function in patients with chronic obstructive pulmonary disease. TRIAL REGISTRATION: ChiCTR1800020257, www.chictr.org.cn/index.aspx.

Diaphragm Pacing: A Safety, Appropriateness, Financial Neutrality, and Efficacy Analysis of Treating Chronic Respiratory Insufficiency.

OBJECTIVES: This study aimed to evaluate the safety and applicability of treating chronic respiratory insufficiency with diaphragm pacing relative to mechanical ventilation. MATERIALS AND METHODS: A literature review and analysis were conducted using the safety, appropriateness, financial neutrality, and efficacy principles. RESULTS: Although mechanical ventilation is clearly indicated in acute respiratory failure, diaphragm pacing improves life expectancy, increases quality of life, and reduces complications in patients with chronic respiratory insufficiency. CONCLUSION: Diaphragm pacing should be given more consideration in appropriately selected patients with chronic respiratory insufficiency.

Diaphragm Pacing in Patients with Spinal Cord Injury: A European Experience.

BACKGROUND: Patients with high spinal cord injury (SCI) are unable to breathe on their own and require mechanical ventilation (MV). The long-term use of MV is associated with increased morbidity and mortality. In patients with intact phrenic nerve function, patients can be partially or completely removed from MV by directly stimulating the diaphragm motor points with a diaphragm pacing system (DPS). OBJECTIVES: We describe our multicenter European experience using DPS in SCI patients who required MV. METHODS: We conducted a retrospective study of patients who were evaluated for the implantation of DPS. Patients evaluated for DPS who met the prospectively defined criteria of being at least 1 year of age, and having cervical injury resulting in a complete or partial dependency on MV were included. Patients who received DPS implants were followed for up to 1 year for device usage and safety. RESULTS: Across 3 centers, 47 patients with high SCI were evaluated for DPS, and 34 were implanted. Twenty-one patients had 12 months of follow-up data with a median DPS use of 15 h/day (interquartile range 4, 24). Eight patients (38.1%) achieved complete MV weaning using DPS 24 h/day. Two DPS-related complications were surgical device revision and a wire eruption. No other major complications were associated with DPS use. CONCLUSIONS: Diaphragm pacing represents an attractive alternative stand-alone treatment or adjunctive therapy compared to MV in patients with high SCI. After a period of acclimation, the patients were able to reduce the daily use of MV, and many could be completely removed from MV.

Diaphragm pacing in spinal cord injury can significantly decrease mechanical ventilation in multicenter prospective evaluation.

BACKGROUND: Cervical spinal cord injury (SCI) can lead to dependence on mechanical ventilation (MV) with significant morbidity and mortality. The diaphragm pacing system (DPS) was developed as an alternative to MV. METHODS: We conducted a prospective single-arm study of DPS in MV-dependent patients with high SCI and intact phrenic nerves. Following device acclimation, pacing effectiveness to provide ventilation was evaluated. The primary endpoint was the number who could use DPS to breathe for 4 continuous hours without MV. Secondary endpoints included the number of patients that could use DPS 24 h/day free of MV and the ability of DPS to maintain clinically acceptable tidal volume (Vt). In addition, we conducted a meta-analysis that included the prospective study along with data from four recently published studies to evaluate DPS hourly use. RESULTS: Fifty-three patients were implanted in the prospective study. Most were male (77.4%) with a median time from injury to treatment of 28.3 (IQR: 12.1, 83.3) months. Four- and 24-h use occurred in 96.2% (95% CI: 87.0%, 99.5%) and 58.5% (95% CI: 44.1%, 74.9%), respectively. Four and 24-h results in the meta-analysis cohort (n = 196) exhibited similar results 92.2% (95% CI: 82.6%, 96.7%) and 52.7% (95% CI: 36.2%, 68.6%) using DPS for 4 and 24 h, respectively. DPS use significantly exceeded the calculated basal tidal volume requirements by a mean of 48.4% (95% CI: 37.0, 59.9%; p < 0.001). CONCLUSIONS: This study demonstrates that in most ventilator-dependent patients, diaphragm pacing can effectively supplement or completely replace the need for MV and support basal metabolic requirements.

Children with Congenital Central Hypoventilation Syndrome Do Not Wake up to Ventilator Alarms.

PURPOSE: Congenital Central Hypoventilation Syndrome (CCHS) requires lifelong ventilatory support during sleep. Subjects with CCHS are vulnerable to sleep disturbances associated with treatments, monitoring alarms, and care they receive. We hypothesized that sleep would be disrupted in patients  with CCHS due to ventilatory support and other treatments at night. METHODS: An anonymous survey of patients with CCHS, age up to 17 years was conducted through REDCAP. Subjects were recruited in person, by flyer, email, and social media. Data collected included demographics, PHOX2B genotype, ventilatory support, treatments, nursing, and sleep parameters. RESULTS: We received 23 responses (35% female, 8.1 years ± 5.6). PHOX2B genotypes were 20/24 PARM (2), 20/25 PARM (4), 20/26 PARM (2), 20/27 PARM (9), ≥ 20/28 PARM (2), and NPARM (2). Two subjects did not indicate the PHOX2B genotype. 13/23 were ventilated by PPV via tracheostomy, 7 by NIPPV, 2 by diaphragm pacing, and 1 did not indicate. Additional treatments received at night included suctioning (9), aerosol (1), G-tube feeding (2), and none (11). Only 9 received nursing at night. 13 used pulse oximetry for monitoring, and 9 used both pulse oximetry and end tidal CO2 monitor. 17/23 rarely woke up due to ventilator or monitor alarms. 11/23 usually or sometimes woke up at least once a night; only 2/11 woke up due to alarms. 5/17 who rarely woke up to the alarms had night nursing. CONCLUSION: Most subjects with CCHS did not awaken to ventilator or monitoring alarms and a majority of these patients did not have nighttime nursing. (Mathur et al. in Sleep 43(Supplement_1):A333, 2020).

Model-Based Optimization of Spinal Cord Stimulation for Inspiratory Muscle Activation.

OBJECTIVE: High-frequency spinal cord stimulation (HF-SCS) is a potential method to provide natural and effective inspiratory muscle pacing in patients with ventilator-dependent spinal cord injuries. Experimental data have demonstrated that HF-SCS elicits physiological activation of the diaphragm and inspiratory intercostal muscles via spinal cord pathways. However, the activation thresholds, extent of activation, and optimal electrode configurations (i.e., lead separation, contact spacing, and contact length) to activate these neural elements remain unknown. Therefore, the goal of this study was to use a computational modeling approach to investigate the direct effects of HF-SCS on the spinal cord and to optimize electrode design and stimulation parameters. MATERIALS AND METHODS: We developed a computer model of HF-SCS that consisted of two main components: 1) finite element models of the electric field generated during HF-SCS, and 2) multicompartment cable models of axons and motoneurons within the spinal cord. We systematically evaluated the neural recruitment during HF-SCS for several unique electrode designs and stimulation configurations to optimize activation of these neural elements. We then evaluated our predictions by testing two of these lead designs with in vivo canine experiments. RESULTS: Our model results suggested that within physiological stimulation amplitudes, HF-SCS activates both axons in the ventrolateral funiculi (VLF) and inspiratory intercostal motoneurons. We used our model to predict a lead design to maximize HF-SCS activation of these neural targets. We evaluated this lead design via in vivo experiments, and our computational model predictions demonstrated excellent agreement with our experimental testing. CONCLUSIONS: Our computational modeling and experimental results support the potential advantages of a lead design with longer contacts and larger edge-to-edge contact spacing to maximize inspiratory muscle activation during HF-SCS at the T2 spinal level. While these results need to be further validated in future studies, we believe that the results of this study will help improve the efficacy of HF-SCS technologies for inspiratory muscle pacing.

Airway Obstruction during Sleep due to Diaphragm Pacing Precludes Decannulation in Young Children with CCHS.

Children with congenital central hypoventilation syndrome (CCHS) have a PHOX2B mutation-induced control of breathing deficit necessitating artificial ventilation as life support. A subset of CCHS families seek phrenic nerve-diaphragm pacing (DP) during sleep with the goal of tracheal decannulation. Published data regarding DP during sleep as life support in the decannulated child with CCHS and related airway dynamics in young children are limited. We report a series of 3 children, ages 3.3-4.3 years, who underwent decannulation. Sleep endoscopy performed during DP revealed varied (oropharynx, supraglottic, glottic, etc.) levels of complete airway obstruction despite modification of pacer settings. Real-time analysis of end tidal CO2 and SpO2 confirmed inadequate gas exchange. Because the families declined re-tracheostomy, all 3 patients rely on noninvasive mask ventilation as a means of life support while asleep. These results emphasize the need for extreme caution in proceeding with tracheal decannulation in young children with CCHS who expect to use DP during sleep as life support. Parents and patients should anticipate that they will depend on noninvasive mask ventilation (rather than DP) during sleep after undergoing decannulation. This information may improve management and guide expectations regarding potential decannulation in young paced children with CCHS.

A practical technique in laparoscopic diaphragm pacing surgery: Retrospective analyse of 43 patients.

INTRODUCTION: Diaphragm pacing stimulation (DPS) is a treatment method used in respiratory failure occurs in diseases such as high-level cervical spinal cord injury, central hypoventilation syndrome and amyotrophic lateral sclerosis. MATERIALS AND METHODS: A total of 43 patients, who had undergone DPS implantation surgery were evaluated retrospectively. The patients were divided into two groups according to the surgical technique (Group 1: classical surgical technic and Group 2: modified surgical technic) applied. The patients with previous abdominal surgery or percutaneous endoscopic gastrostomy were excluded from the study. RESULTS: The mean operation duration was significantly shorter in modified DPS implantation technic (105.1 min in Group 1 and 87.4 min in Group 2) (P < 0.001). Capnothorax is seen 11% of the cases in classical surgery procedure. In the modified group, capnothorax was not observed. Pneumothorax rate was found similar in both groups. Post-operative atelectasis was determined 16% of the cases in classical surgery procedure and also in the modified group atelectasis was not observed. The complications were higher in classical surgery procedure group but not differed statistically in this study. Total hospitalisation duration was significantly shorter in the modified surgical technique group compared to the other group (8.0 days in Group 1 and 6.0 days in Group 2) (P = 0.03). CONCLUSION: With modification in DPS implantation surgery, shorter operation and hospitalisation durations, and less complications may be achieved.

Importance of diaphragm thickness in amyotrophic lateral sclerosis patients with diaphragm pacing system implantation.

INTRODUCTION: Severe respiratory failure develops as a result of the involvement of the respiratory muscles in patients with amyotrophic lateral sclerosis (ALS). Implantation of diaphragm pacing system (DPS) has been carried out on ALS patients since 2005 to avoid these situations, but the importance of diaphragm thickness has not yet been established clearly. MATERIAL AND METHOD: We retrospectively evaluated 34 ALS patients who had previously implanted DPS to detect the importance of diaphragm thickness. We investigated the effect of diaphragm thickness, which was measured by preoperative thorax computerized tomography on preoperative respiratory function tests (RFT), arterial blood gas (ABG) analysis, postoperative 3- and 6-month oxygen saturations and mortality. RESULTS: The right diaphragm thickness was calculated as 4.60 (2.95-6.00) mm, while the left diaphragm thickness was 4.10 (2.77-6.00) mm. Six patients died during the follow-up period. We did not detect a significant relationship between ABG parameters, RFT and diaphragm thickness. However, according to our observations, the diaphragm thickness was significantly related to mortality. The right diaphragm was significantly thinner in cases that required preoperative respiratory support and had percutaneous endoscopic gastrostomy. When the cut-off values for the diaphragm thickness were accepted as 3.50 mm, significantly higher mortality among patients below this was observed. CONCLUSION: Diaphragm thickness is an important criterion in cases for which DPS implantation is planned. We consider that avoidance of DPS implantation is more suitable for cases with a diaphragm thickness below 3.50 mm because of mortality.

Diaphragmatic pacing for respiratory failure in children.

Diaphragm pacing is a ventilation strategy in respiratory failure. Most of the literature on pacing involves adults with common indications being spinal cord injury and amyotrophic lateral sclerosis (ALS). Previous reports in pediatric patients consist of case reports or small series; most describe direct phrenic nerve stimulation for central hypoventilation syndrome. This differs from adult reports that focus most commonly on spinal cord injuries and the rehabilitative nature of diaphragm pacing. This review describes the current state of diaphragm pacing in pediatric patients. Indications, current available technologies, surgical techniques, advantages, and pitfalls/problems are discussed.

An Implantable Self-Driven Diaphragm Pacing System Based on a Microvibration Triboelectric Nanogenerator for Phrenic Nerve Stimulation.

Spinal cord injury poses considerable challenges, particularly in diaphragm paralysis. To address limitations in existing diaphragm pacing technologies, we report an implantable, self-driven diaphragm pacing system based on a microvibration triboelectric nanogenerator (MV-TENG). Leveraging the efficient MV-TENG, the system harvests micromechanical energy and converts this energy into pulses for phrenic nerve stimulation. In vitro tests confirm a stable MV-TENG output, while subcutaneous implantation of the device in rats results in a constant amplitude over 4 weeks with remarkable energy-harvesting efficacy. The system effectively induces diaphragmatic motor-evoked potentials, triggering contractions of the diaphragm. This proof-of-concept system has potential clinical applications in implantable phrenic nerve stimulation, presenting a novel strategy for advancing next-generation diaphragm pacing devices.

Temporary diaphragm pacing for patients at risk of prolonged mechanical ventilation after extensive aortic repair.

Objective: Prolonged mechanical ventilation (MV) after extensive aortic reconstructive surgery is common. Studies have demonstrated that diaphragm pacing (DP) improves lung function in patients with unilateral diaphragm paralysis. The goal of this study is to determine whether this technology can be applied to complex aortic repair to reduce prolonged MV and other respiratory sequelae. Methods: A retrospective review was performed of patients who underwent temporary DP after extensive aortic reconstructive surgery between 2019 and 2022. The primary end point was prolonged MV incidence. Other measured end points included diaphragm electromyography improvement, length of hospitalization, duration of intensive care unit stay, and reintubation rates. Results: Fourteen patients deemed at high risk of prolonged MV based on their smoking and respiratory history underwent DP after extensive aortic repair. The mean age was 70.2 years. The indications for aortic repair were a thoracoabdominal aortic aneurysm (n = 8, including 2 ruptured, 2 symptomatic, and 1 mycotic), a perivisceral aneurysm (n = 4), and a perivisceral coral reef aorta (n = 2). All patients had a significant smoking history (active or former) or other risk factors for ventilator-induced diaphragmatic dysfunction and prolonged MV. The mean total duration of MV postoperatively was 31.9 hours (range, 8.1-76.5 hours). The total average pacing duration was 4.4 days. Two patients required prolonged MV, with an average of 75.4 hours. Two patients required reintubation. No complications related to DP wire placement or removal occurred. Conclusions: DP is safe and feasible for patients at high risk of pulmonary insufficiency after extensive aortic reconstructive surgery.

Effects of external diaphragm pacing combined with conventional rehabilitation therapies in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: Numerous randomized controlled trials (RCTs) have reported the benefits of external diaphragm pacing combined with conventional rehabilitation therapies (EDP-CRTs) on pulmonary function and exercise capacity in patients with chronic obstructive pulmonary disease (COPD). However, evidence-based regarding its effects remains unclear. OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the effects of EDP-CRTs versus CRTs on patients with COPD. DESIGN: Systematic review and meta-analysis. DATA SOURCES AND METHODS: We performed a systematic review and meta-analysis, searching PubMed, Embase, Cochrane Central Register of Controlled Trials, Scopus, China Biology Medicine Disc, Chinese National Knowledge Infrastructure, Wan-Fang Database, and Chinese Scientific Journal Database from inception to 10 September 2023. RCTs investigating the effects of EDP-CRTs versus CRTs on COPD patients were included. The primary outcome was pulmonary function, including forced expiratory volume in 1 s (FEV1), the percentage of predicted values of FEV1 (FEV1%pred), and FEV1/forced vital capacity (FVC)%. Secondary outcomes included arterial blood gas analysis [the partial pressure of arterial oxygen (PaO2) and the partial pressure of arterial carbon dioxide (PaCO2)]; dyspnea [modified Medical Research Council Dyspnea Scale (mMRC)]; exercise capacity [6-min walking distance (6MWD)]; and quality of life [COPD assessment test (CAT)]. RevMan 5.3 software was used for meta-analysis. The quality of the included studies was assessed using the revised Cochrane Risk of Bias tool for randomized trials (RoB 2.0). The certainty of the evidence was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation system. RESULTS: In total, 13 studies/981 participants were included. The pooled results revealed significant benefits of EDP-CRTs versus CRTs on the FEV1 [standardized mean difference (SMD) = 1.07, 95% confidence interval (CI) = 0.58-1.56], FEV1%pred [weighted mean difference (WMD) = 6.67, 95% CI = 5.69-7.64], the FEV1/FVC% (SMD = 1.24, 95% CI = 0.48-2.00), PaO2 (SMD = 1.29, 95% CI = 0.74-1.84), PaCO2 (SMD = -1.88, 95% CI = -2.71 to -1.04), mMRC (WMD = -0.55, 95% CI = -0.65 to -0.45), 6MWD (SMD = 1.63, 95% CI = 0.85-2.42), and CAT (WMD = -1.75, 95% CI = -3.16 to -0.35), respectively. Planned subgroup analysis suggested that EDP-CRTs had a better effect on FEV1, FEV1/FVC%, 6MWD, and CAT in the duration of 2-4 weeks. CONCLUSION: EDP-CRTs have better effects on pulmonary function, PaCO2, dyspnea, exercise capacity, and quality of life in COPD patients than CRTs, and the duration to achieve the most effective treatment is 2-4 weeks. TRIAL REGISTRATION: This systematic review and meta-analysis protocol was prospectively registered with PROSPERO (No. CRD42022355964).

Congenital Central Hypoventilation Syndrome: Diagnosis and Long-Term Ventilatory Outcomes.

Background: Congenital central hypoventilation syndrome (CCHS), a rare disease caused by variants in the paired-like homeobox 2B (PHOX2B) gene, affects regulation of respiration necessitating lifelong assisted ventilation (AV). Most patients require full-time AV during infancy and some patients may sustain adequate spontaneous ventilation during wakefulness and change AV modalities at a later age. The aims of this study were to assess the changes in duration and modalities of AV, long-term respiratory outcomes, and to correlate them with PHOX2B genotypes. Methods: We conducted a retrospective study of patients with CCHS treated at our institution between January 1997 and May 2022. Results analyzed included: clinical presentation, PHOX2B genotype, modality and duration of AV at diagnosis and follow-up, survival, and transition to adult care. Results: We identified 30 patients with CCHS-8 with PHOX2B nonpolyalanine repeat mutations (NPARMs), 21 with polyalanine repeat mutations (PARMs), and 1 with unknown PHOX2B genotype. The median age at presentation was 0.25 months (IQR 0.1-0.7 months). At diagnosis of CCHS, 24 (80%) patients required continuous AV and 28 (93%) received AV via tracheostomy. Twenty-six patients required sleep-only AV at a median age of 9 months (IQR 6-14 months). Nine patients requiring sleep-only AV underwent tracheostomy decannulation at a median age of 11.2 years (IQR 5.9-15.7 years) and used noninvasive positive pressure ventilation or diaphragm pacing. There was insufficient evidence to conclude that patients with PARMs and NPARMs differed by age at presentation (P = .39), tracheostomy (P = .06), and transition to sleep-only AV (P = .9). Six patients transitioned to adult care, 23 continued receiving pediatric care, and 1 patient died due to complications from Hirschsprung's disease. Conclusion: Our study demonstrates prolonged survival and good long-term respiratory outcomes possibly related to the early diagnosis of CCHS, optimizing AV strategies, and multidisciplinary care. The increasing number of patients attaining adulthood highlights the necessity for multidisciplinary care for adults with CCHS.

Functional electrical stimulation in spinal cord injury respiratory care.

The management of chronic respiratory insufficiency and/or long-term inability to breathe independently has traditionally been via positive-pressure ventilation through a mechanical ventilator. Although life-sustaining, it is associated with limitations of function, lack of independence, decreased quality of life, sleep disturbance, and increased risk for infections. In addition, its mechanical and electronic complexity requires full understanding of the possible malfunctions by patients and caregivers. Ventilator-associated pneumonia, tracheal injury, and equipment malfunction account for common complications of prolonged ventilation, and respiratory infections are the most common cause of death in spinal cord-injured patients. The development of functional electric stimulation (FES) as an alternative to mechanical ventilation has been motivated by a goal to improve the quality of life of affected individuals. In this article, we will review the physiology, types, characteristics, risks and benefits, surgical techniques, and complications of the 2 commercially available FES strategies - phrenic nerve pacing (PNP) and diaphragm motor point pacing (DMPP).

An unusual cause of diaphragm pacer failure in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome is a rare genetic disorder affecting ventilatory response to hypercapnia and/or hypoxemia. We describe a case of diaphragm pacing (DP) failure in a 38-year-old woman with congenital central hypoventilation syndrome who used DP as ventilatory support only during sleep for 24 years. Diagnostic evaluation began with examination of external DP equipment, but adjustment did not elicit adequate diaphragm contractions. Clinical evaluation and transtelephonic monitoring showed absent function of the right pacer and diminished function of the left pacer. The patient had surgical exploration of her internal DP components. The operation revealed that the right pacer receiver had significant circumferential calcium accumulation. After replacement of the receivers in subcutaneous pockets closer to the skin surface, robust diaphragm contractions bilaterally occurred with stimulation. This case suggests DP failure can result from development of calcification and increased distance from the skin surface to the receivers due to weight gain. CITATION: Kwon A, Lodge M, McComb JG, et al. An unusual cause of diaphragm pacer failure in congenital central hypoventilation syndrome. J Clin Sleep Med. 2022;18(3):949-952.

The terminal segment of the human phrenic nerve as a novel implantation site for diaphragm pacing electrodes: Anatomical and clinical description.

BACKGROUND: Diaphragm pacing allows certain ventilator-dependent patients to achieve weaning from mechanical ventilation. The reference method consists in implanting intrathoracic contact electrodes around the phrenic nerve during video-assisted thoracic surgery, which involves time-consuming phrenic nerve dissection with a risk of nerve damage. Identifying a phrenic segment suitable for dissection-free implantation of electrodes would constitute progress. STUDY DESIGN: This study characterizes a free terminal phrenic segment never fully described before. We conducted a cadaver study (n = 14) and a clinical observational study during thoracic procedures (n = 54). RESULTS: A free terminal phrenic segment was observed on both sides in 100% of cases, "jumping" from the pericardium to the diaphragm and measuring 60 mm [95% confidence interval; 48-63] and 72.5 mm [65-82] (right left, respectively; p = 0.0038; cadaver study). This segment rolled up on itself at end-expiration and became unravelled and elongated with diaphragm descent (clinical study). Three categories of fat pads were defined (type 1: pericardiophrenic bundle free of surrounding fat; type 2: single fatty fringe leaving the phrenic nerve visible until diaphragmatic entry; type 3: multiple fatty fringes masking the site of penetration of the phrenic nerve) that depended on body mass index (p = 0.001, clinical study). Hematoxylin-eosin and toluidine blue staining (cadaver study) showed that all of the phrenic fibers in the distal, pre-branching part of the terminal segment were contained within a single epineurium containing a variable number of fascicles (right: 1 [95%CI 0.65-4.01]; left 5 [3.37-7.63]; p = 0.03). CONCLUSION: Diaphragm pacing through periphrenic electrodes positioned on the terminal phrenic segment should be tested.