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Respiratory Care May 2023Mechanical ventilation is widely used in ICU patients as a lifesaving intervention. Diaphragmatic atrophy and thinning occur from lack of contractions of the diaphragm...
BACKGROUND
Mechanical ventilation is widely used in ICU patients as a lifesaving intervention. Diaphragmatic atrophy and thinning occur from lack of contractions of the diaphragm during mechanical ventilation. It may prolong weaning and increase the risk of respiratory complications. Noninvasive electromagnetic stimulation of the phrenic nerves may ameliorate the atrophy seen with ventilation. The objective of this study was to show that noninvasive repetitive electromagnetic stimulation is safe, feasible, and effective to stimulate the phrenic nerves in both awake individuals and anesthetized patients.
METHODS
A single-center study with 10 subjects overall, 5 awake volunteers and 5 anesthetized subjects. We used a prototype electromagnetic, noninvasive, simultaneous bilateral phrenic nerve stimulation device in both groups. In the awake volunteers, we assessed time-to-first capture of the phrenic nerves and safety measures, such as pain, discomfort, dental paresthesia, and skin irritation. In the anesthetized subjects, time-to-first capture as well as tidal volumes and airway pressures at 20%, 30%, and 40% stimulation intensity were assessed.
RESULTS
Diaphragmatic capture was achieved in all the subjects within a median (range) of 1 min (1 min to 9 min 21 s) for the awake subjects and 30 s (20 s to 1 min 15 s) for the anesthetized subjects. There were no adverse or severe adverse events in either group, nor any dental paresthesia, skin irritation, or subjective pain in the stimulated area. Tidal volumes increased in all the subjects in response to simultaneous bilateral phrenic nerve stimulation and increased gradually with increasing stimulation intensity. Airway pressures corresponded to spontaneous breathing of ∼2 cm HO.
CONCLUSIONS
Noninvasive phrenic nerve stimulation can be safely performed in awake and anesthetized individuals. It was feasible and effective in stimulating the diaphragm by induction of physiologic and scalable tidal volumes with minimum positive airway pressures.
Topics: Humans; Phrenic Nerve; Feasibility Studies; Paresthesia; Respiration, Artificial; Diaphragm; Pain
PubMed: 36878642
DOI: 10.4187/respcare.10568 -
ELife Dec 2022Breathing, and the motor circuits that control it, is essential for life. At the core of respiratory circuits are Dbx1-derived interneurons, which generate the rhythm...
Breathing, and the motor circuits that control it, is essential for life. At the core of respiratory circuits are Dbx1-derived interneurons, which generate the rhythm and pattern of breathing, and phrenic motor neurons (MNs), which provide the final motor output that drives diaphragm muscle contractions during inspiration. Despite their critical function, the principles that dictate how respiratory circuits assemble are unknown. Here, we show that coordinated activity of a type I cadherin (N-cadherin) and type II cadherins (Cadherin-6, -9, and -10) is required in both MNs and Dbx1-derived neurons to generate robust respiratory motor output. Both MN- and Dbx1-specific cadherin inactivation in mice during a critical developmental window results in perinatal lethality due to respiratory failure and a striking reduction in phrenic MN bursting activity. This combinatorial cadherin code is required to establish phrenic MN cell body and dendritic topography; surprisingly, however, cell body position appears to be dispensable for the targeting of phrenic MNs by descending respiratory inputs. Our findings demonstrate that type I and II cadherins function cooperatively throughout the respiratory circuit to generate a robust breathing output and reveal novel strategies that drive the assembly of motor circuits.
Topics: Animals; Mice; Motor Neurons; Respiration; Interneurons; Respiratory Rate; Cadherins; Phrenic Nerve; Homeodomain Proteins
PubMed: 36583530
DOI: 10.7554/eLife.82116 -
European Journal of Heart Failure Dec 2018The presence of central sleep apnoea (CSA) is associated with poor prognosis in patients with heart failure (HF). The aim of this analysis was to evaluate if using... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
The presence of central sleep apnoea (CSA) is associated with poor prognosis in patients with heart failure (HF). The aim of this analysis was to evaluate if using phrenic nerve stimulation to treat CSA in patients with CSA and HF was associated with changes in HF-specific metrics.
METHODS AND RESULTS
All patients randomized in the remedē System Pivotal Trial and identified at baseline with HF were included (n = 96). Effectiveness data from treatment and former control groups were pooled based on months since therapy activation. Changes from baseline to 6 and 12 months in sleep metrics, Epworth Sleepiness Scale, patient global assessment health-related quality of life, Minnesota Living with Heart Failure Questionnaire (MLHFQ), and echocardiographic parameters are reported. HF hospitalization, cardiovascular death, and the composite of HF hospitalization or cardiovascular death within 6 months are reported by the original randomized group assignment for safety assessment. Sleep metrics and quality of life improved from baseline to 6 and 12 months. At 12 months, MLHFQ scores changed by -6.8 ± 20.0 (P = 0.005). The 6-month rate of HF hospitalization was 4.7% in treatment patients (standard error = 3.3) and 17.0% in control patients (standard error = 5.5) (P = 0.065). Reported adverse events were as expected for a transvenous implantable system.
CONCLUSIONS
Phrenic nerve stimulation reduces CSA severity in patients with HF. In parallel, this CSA treatment was associated with benefits on HF quality of life.
Topics: Aged; Electric Stimulation Therapy; Female; Follow-Up Studies; Heart Failure; Humans; Male; Phrenic Nerve; Polysomnography; Prospective Studies; Quality of Life; Sleep Apnea, Central; Treatment Outcome
PubMed: 30303611
DOI: 10.1002/ejhf.1312 -
Journal of Thoracic Disease Aug 2019There is a lack of consensus in the literature regarding phrenic nerve proximity to thoracic structures at the level of the diaphragm. This study was undertaken to...
BACKGROUND
There is a lack of consensus in the literature regarding phrenic nerve proximity to thoracic structures at the level of the diaphragm. This study was undertaken to provide thoracic surgeons data on phrenic nerve location in order to reduce iatrogenic injury during invasive surgery.
METHODS
Bilateral thoracic dissection was performed on 43 embalmed human cadavers (25 males; 18 females) and data was obtained from 33 left and 40 right phrenic nerves. The site of phrenic nerve penetration into the diaphragm was identified. Calipers were used to measure the distance from each phrenic nerve to the: inferior vena cava (IVC), descending aorta, esophagus, lateral thoracic wall and anterior thoracic wall.
RESULTS
Mean thoracic diameter of male cadavers was significantly greater than that of female cadavers (P value <0.0001). There was no statistically significant difference between the distances from each phrenic nerve to visceral structures between males and females, except regarding the distance from the right phrenic nerve to the anterior thoracic wall where males exhibited significantly greater distances (P value =0.0234).
CONCLUSIONS
This study provides important data on phrenic nerve proximity to intrathoracic structures in an effort to help reduce iatrogenic injury during procedures within the thoracic cavity. Although males had a significantly larger thoracic diameter than females, the only statistically significant difference showed that the right phrenic nerve is deeper in the thoracic cavity in males. As this nerve passes closer to visceral structures it may be more susceptible to damage from pathology in surrounding vessels. This may explain the increased incidence of right phrenic nerve damage due to aortic aneurysm in males reported in the literature.
PubMed: 31559049
DOI: 10.21037/jtd.2019.07.75 -
Respiratory Physiology & Neurobiology Apr 2023We hypothesized that activation of phrenic afferents induces diaphragm motor plasticity. In anesthetized and spontaneously breathing rats we delivered 40 Hz, low...
We hypothesized that activation of phrenic afferents induces diaphragm motor plasticity. In anesthetized and spontaneously breathing rats we delivered 40 Hz, low threshold (twitch and 1.5X twitch threshold), inspiratory-triggered stimulation to the left hemidiaphragm for 30 min to activate ipsilateral phrenic afferents. Diaphragm amplitude ipsilateral and contralateral to stimulation were increased for 60 min following both currents compared to time controls not receiving stimulation. Diaphragm stimulation was repeated in laminectomy controls or following a unilateral C3-C6 dorsal rhizotomy to eliminate phrenic afferent volleys. Laminectomy controls expressed neuromuscular plasticity post-stimulation. In contrast, ipsilateral and contralateral diaphragm amplitude following dorsal rhizotomy was lower than laminectomy controls and no different than time controls, suggesting diaphragm motor plasticity was not induced post-rhizotomy. Our results indicate that diaphragm stimulation induces a novel form of plasticity in the phrenic motor system which requires phrenic afferent activation. Respiratory motor plasticity elicited by diaphragm stimulation may have value as a therapeutic strategy to improve diaphragm output in neuromuscular conditions.
Topics: Rats; Animals; Diaphragm; Thorax; Respiration; Phrenic Nerve; Electric Stimulation
PubMed: 36642318
DOI: 10.1016/j.resp.2023.104014 -
Respiratory Medicine Case Reports 2019Bilateral phrenic nerve paralysis is a rare potentially life-threatening condition which is usually due to trauma (including surgery) or neurologic disease. We present a...
Bilateral phrenic nerve paralysis is a rare potentially life-threatening condition which is usually due to trauma (including surgery) or neurologic disease. We present a patient with apparent rapid onset bilateral phrenic nerve paralysis whose primary symptom was severe positional (supine) dyspnea with profound supine oxygen desaturation. Nerve conduction study abnormalities of the phrenic nerves and some left brachial plexus nerves suggested a diagnosis of ALS. He was treated with supportive night time ventilatory assistance (BiPAP) and over 4 years his condition recovered essentially completely. In retrospect the most likely diagnosis was a rare brachial plexopathy referred to as neuralgic amyotrophy.
PubMed: 31681533
DOI: 10.1016/j.rmcr.2019.100953 -
Journal of Neurophysiology Sep 2021Plasticity is a hallmark of the respiratory neural control system. Phrenic long-term facilitation (pLTF) is one form of respiratory plasticity characterized by...
Plasticity is a hallmark of the respiratory neural control system. Phrenic long-term facilitation (pLTF) is one form of respiratory plasticity characterized by persistent increases in phrenic nerve activity following acute intermittent hypoxia (AIH). Although there is evidence that key steps in the cellular pathway giving rise to pLTF are localized within phrenic motor neurons (PMNs), the impact of AIH on the strength of breathing-related synaptic inputs to PMNs remains unclear. Furthermore, the functional impact of AIH is enhanced by repeated/daily exposure to AIH (dAIH). Here, we explored the effects of AIH versus 2 wk of dAIH preconditioning on spontaneous and evoked phrenic responses in anesthetized, paralyzed, and mechanically ventilated rats. Evoked phrenic potentials were elicited by respiratory cycle-triggered lateral funiculus stimulation at the C2 spinal level delivered before and 60 min post-AIH (or the equivalent in time controls). Charge-balanced biphasic pulses (100 μs/phase) of progressively increasing intensity (100-700 μA) were delivered during the inspiratory and expiratory phases of the respiratory cycle. Although robust pLTF (∼60% from baseline) was observed after a single exposure to moderate AIH (3 × 5 min; 5-min intervals), there was no effect on evoked phrenic responses, contrary to our initial hypothesis. However, in rats preconditioned with dAIH, baseline phrenic nerve activity and evoked responses were increased, suggesting that repeated exposure to AIH enhances functional synaptic strength when assessed using this technique. The impact of daily AIH preconditioning on synaptic inputs to PMNs raises interesting questions that require further exploration. Two weeks of daily acute intermittent hypoxia (dAIH) preconditioning enhanced stimulus-evoked phrenic responses to lateral funiculus stimulation (targeting respiratory bulbospinal projection to phrenic motor neurons). Furthermore, dAIH preconditioning enhanced baseline phrenic motor output responses to maximal chemoreflex activation in intact rats.
Topics: Animals; Evoked Potentials; Hypoxia; Male; Motor Neurons; Neuronal Plasticity; Phrenic Nerve; Rats; Rats, Sprague-Dawley
PubMed: 34260289
DOI: 10.1152/jn.00112.2021 -
Journal of Cancer Research and... Dec 2022This study aimed to analyze the cases of phrenic nerve injury caused by the percutaneous microwave ablation of lung tumors conducted at our center and to explore the...
OBJECTIVE
This study aimed to analyze the cases of phrenic nerve injury caused by the percutaneous microwave ablation of lung tumors conducted at our center and to explore the risk factors.
MATERIALS AND METHODS
The data of 455 patients who underwent the percutaneous microwave ablation of lung tumors at the Department of Interventional Radiology, First Affiliated Hospital of Fujian Medical University from July 2017 to October 2021, were retrospectively analyzed. The cases of phrenic nerve injury after the percutaneous ablation were reported to analyze the risk factors involved, such as the shortest distance between tumor margin and phrenic nerve, tumor size, and ablation energy. The groups were divided based on the shortest distance between the tumor edge and the phrenic nerve into group 1, d ≤ l cm; group 2, 1 < d ≤2 cm; and group 3, d >2 cm. Lesions with a distance ≤2 cm were compared in terms of tumor size and ablation energy.
RESULTS
Among the 455 patients included in this study, 348 had primary lung cancer, and 107 had oligometastatic cancer. A total of 579 lesions were detected, with maximum diameter of 1.27 ± 0.55 cm, and the ablation energy was 9,000 (4,800-72,000) J. Six patients developed phrenic nerve injury, with an incidence of 1.32%. For these six patients, the shortest distance from the lesion edge to the phrenic nerve was 0.75 ± 0.48 cm, and the ablation energy was 10,500 (8,400-34,650) J. There were statistically significant differences in phrenic nerve injury among groups 1, 2, and 3 (P < 0.05). In patients with a distance (d) ≤ 2 cm, there were no significant differences in tumor diameter and energy between the phrenic nerve injury group and the non-injury group (P = 0.80; P = 0.41). In five out of six patients, the diaphragm level completely recovered to the pre-procedure state, and the recovery time of the phrenic nerve was 9.60 ± 5.60 months. Another one was re-examined 11 months after the procedure, and the level of the diaphragm on the affected side had partially recovered.
CONCLUSIONS
Phrenic nerve injury is a rare but not negligible complication of thermal ablation and is more likely to occur in lesions with a distance ≤2 cm from the phrenic nerve.
Topics: Humans; Catheter Ablation; Phrenic Nerve; Retrospective Studies; Microwaves; Lung Neoplasms; Treatment Outcome
PubMed: 36647962
DOI: 10.4103/jcrt.jcrt_1254_22 -
Journal of Neurophysiology Jul 2019In aging Fischer 344 rats, phrenic motor neuron loss, neuromuscular junction abnormalities, and diaphragm muscle (DIAm) sarcopenia are present by 24 mo of age, with...
In aging Fischer 344 rats, phrenic motor neuron loss, neuromuscular junction abnormalities, and diaphragm muscle (DIAm) sarcopenia are present by 24 mo of age, with larger fast-twitch fatigue-intermediate (type FInt) and fast-twitch fatigable (type FF) motor units particularly vulnerable. We hypothesize that in old rats, DIAm neuromuscular transmission deficits are specific to type FInt and/or FF units. In phrenic nerve/DIAm preparations from rats at 6 and 24 mo of age, the phrenic nerve was supramaximally stimulated at 10, 40, or 75 Hz. Every 15 s, the DIAm was directly stimulated, and the difference in forces evoked by nerve and muscle stimulation was used to estimate neuromuscular transmission failure. Neuromuscular transmission failure in the DIAm was observed at each stimulation frequency. In the initial stimulus trains, the forces evoked by phrenic nerve stimulation at 40 and 75 Hz were significantly less than those evoked by direct muscle stimulation, and this difference was markedly greater in 24-mo-old rats. During repetitive nerve stimulation, neuromuscular transmission failure at 40 and 75 Hz worsened to a greater extent in 24-mo-old rats compared with younger animals. Because type IIx and/or IIb DIAm fibers (type FInt and/or FF motor units) display greater susceptibility to neuromuscular transmission failure at higher frequencies of stimulation, these data suggest that the age-related loss of larger phrenic motor neurons impacts nerve conduction to muscle at higher frequencies and may contribute to DIAm sarcopenia in old rats. Diaphragm muscle (DIAm) sarcopenia, phrenic motor neuron loss, and perturbations of neuromuscular junctions (NMJs) are well described in aged rodents and selectively affect FInt and FF motor units. Less attention has been paid to the motor unit-specific aspects of nerve-muscle conduction. In old rats, increased neuromuscular transmission failure occurred at stimulation frequencies where FInt and FF motor units exhibit conduction failures, along with decreased apposition of pre- and postsynaptic domains of DIAm NMJs of these units.
Topics: Aging; Animals; Diaphragm; Female; Male; Motor Neurons; Muscle Fatigue; Muscle Fibers, Fast-Twitch; Neuromuscular Junction; Phrenic Nerve; Rats; Rats, Inbred F344; Synaptic Potentials
PubMed: 31042426
DOI: 10.1152/jn.00061.2019 -
The Journal of Thoracic and... Nov 2017
Topics: Child; Diaphragm; Herniorrhaphy; Humans; Paresis; Phrenic Nerve; Respiration Disorders
PubMed: 28867382
DOI: 10.1016/j.jtcvs.2017.07.042