A New Surface Technique for Phrenic Nerve Conduction Study.

Objective: To report a new patient friendly and convenient technique for phrenic nerve conduction with alternative sites of stimulation and recording. Methods: Phrenic nerve conduction was performed in forty volunteers and ten patients of peripheral neuropathy. Active recording electrode was placed in tenth intercostal space 2.5 cm away from para-spinal muscles (mid-scapular line), reference electrode in eighth intercostal space just medial to subcostal margin with ground between stimulating and recording electrode. Stimulation was done at the level of crico-thyroid space near or under the posterior margin of sternocleidomastoid muscle. This new method was compared with existing ones. Analysis: Data was analysed using SPSS 23 version. Correlation between height, weight, body mass index, age, and chest expansion was done using bi-variate correlation. Mean latency and amplitude of the study method were compared with other methods using MANNOVA test. Results: Total of forty subjects were studied. Thirty-seven were male subjects. Mean age was 28.03 ± 9.63 years, height 168.0 ± 9.60 cm and chest expansion 3.53 ± 0.64 cm. Right sided phrenic nerve mean latency was 5.99 ± 0.629 ms and amplitude 1.088 ± 0.178 mV. Left sided phrenic nerve conductions showed mean latency of 6.02 ± 1.82 ms, amplitude of 1.092 ± 0.2912 mV. These standard deviations were smaller than what were observed with other methods suggesting increased consistency of our results. There was no correlation between phrenic nerve conduction with age, height, gender or chest expansion. Conclusion: This study method gave a better as well as consistent morphology, higher amplitude and required lower amount of current strength. It was superior to previously reported methods in consistency of normative data.

Investigation of vascular endothelial growth factor receptor-dependent neuroplasticity on rat nucleus tractus solitarius and phrenic nerve after chronic sustained hypoxia.

The neuronal system that controls respiration creates plasticity in response to physiological changes. Chronic sustained hypoxia causes neuroplasticity that contributes to ventilatory acclimatization to hypoxia (VAH). The purpose of this study is to explain the potential roles of the VAH mechanism developing because of chronic sustained hypoxia on respiratory neuroplasticity of vascular endothelial growth factor (VEGF) receptor activation on the nucleus tractus solitarius (NTS) and phrenic nerve. In this study 24 adult male Sprague-Dawley rats were used. Subjects were separated into four groups, a moderate-sham (mSHAM), severed-sham (sSHAM), moderate chronic sustained hypoxia (mCSH), and severed chronic sustained hypoxia (sCSH). Normoxic group (mSHAM and sSHAM) rats were exposed to 21% O2 level (7 days) in the normobaric room while hypoxia group (mCSH and sCSH) rats were exposed to 13% and 10% O2 level (7 days). Different protocols were applied for normoxic and hypoxia groups and ventilation, respiratory frequency, and tidal volume measurements were made with whole-body plethysmography. After the test HIF-1α, erythropoietin (EPO), and VEGFR-2 expressions on the NTS region in the medulla oblongata and phrenic nerve motor neurons in spinal cord tissue were analyzed using the immunohistochemical stain method. Examinations on the medulla oblongata and spinal cord tissues revealed that HIF-1α, EPO, and VEGFR-2 expressions increased in hypoxia groups compared to normoxic groups while a similar increase was also seen when respiratory parameters were assessed. Consequently, learning about VAH-related neuroplasticity mechanisms developed as a result of chronic continuous hypoxia will contribute to developing new therapeutical approaches to various diseases causing respiratory failure using brain plasticity without recourse to medicines.

Assessment of magnetic flux density properties of electromagnetic noninvasive phrenic nerve stimulations for environmental safety in an ICU environment.

Diaphragm weakness affects up to 60% of ventilated patients leading to muscle atrophy, reduction of muscle fiber force via muscle fiber injuries and prolonged weaning from mechanical ventilation. Electromagnetic stimulation of the phrenic nerve can induce contractions of the diaphragm and potentially prevent and treat loss of muscular function. Recommended safety distance of electromagnetic coils is 1 m. The aim of this study was to investigate the magnetic flux density in a typical intensive care unit (ICU) setting. Simulation of magnetic flux density generated by a butterfly coil was performed in a Berlin ICU training center with testing of potential disturbance and heating of medical equipment. Approximate safety distances to surrounding medical ICU equipment were additionally measured in an ICU training center in Bern. Magnetic flux density declined exponentially with advancing distance from the stimulation coil. Above a coil distance of 300 mm with stimulation of 100% power the signal could not be distinguished from the surrounding magnetic background noise. Electromagnetic stimulation of the phrenic nerve for diaphragm contraction in an intensive care unit setting seems to be safe and feasible from a technical point of view with a distance above 300 mm to ICU equipment from the stimulation coil.

Daily acute intermittent hypoxia enhances phrenic motor output and stimulus-evoked phrenic responses in rats.

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.NEW & NOTEWORTHY 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.

Case Studies in Neuroscience: Neuropathology and diaphragm dysfunction in ventilatory failure from late-onset Pompe disease.

Pompe disease (PD) is a neuromuscular disorder caused by a mutation in the acid alpha-glucosidase (GAA) gene. Patients with late-onset PD retain some GAA activity and present symptoms later in life, with fatality mainly associated with respiratory failure. This case study presents diaphragm electrophysiology and a histological analysis of the brainstem, spinal cord, and diaphragm, from a male PD patient diagnosed with late-onset PD at age 35. The patient was wheelchair dependent by age 38, required nocturnal ventilation at age 40, 24-h noninvasive ventilation by age 43, and passed away from respiratory failure at age 54. Diaphragm electromyography recorded using indwelling "pacing" wires showed asynchronous bursting between the left and right diaphragm during brief periods of independent breathing. The synchrony declined over a 4-yr period preceding respiratory failure. Histological assessment indicated motoneuron atrophy in the medulla and rostral spinal cord. Hypoglossal (soma size: 421 ± 159 µm2) and cervical motoneurons (soma size: 487 ± 189 µm2) had an atrophied, elongated appearance. In contrast, lumbar (soma size: 1,363 ± 677 µm2) and sacral motoneurons (soma size: 1,411 ± 633 µm2) had the ballooned morphology typical of early-onset PD. Diaphragm histology indicated loss of myofibers. These results are consistent with neuromuscular degeneration and the concept that effective PD therapy will need to target the central nervous system, in addition to skeletal and cardiac muscle.NEW & NOTEWORTHY This case study offered a unique opportunity to investigate longitudinal changes in phrenic neurophysiology in an individual with severe, ventilator-dependent, late-onset Pompe disease. Additional diaphragm and neural tissue histology upon autopsy confirmed significant neuromuscular degeneration, and it provided novel insights regarding rostral to caudal variability in the neuropathology. These findings suggest that a successful treatment approach for ventilator-dependent Pompe disease should target the central nervous system, in addition to skeletal muscle.

Serotonergic innervation of respiratory motor nuclei after cervical spinal injury: Impact of intermittent hypoxia.

Although cervical spinal cord injury (cSCI) disrupts bulbo-spinal serotonergic projections, partial recovery of spinal serotonergic innervation below the injury site is observed after incomplete cSCI. Since serotonin contributes to functional recovery post-injury, treatments to restore or accelerate serotonergic reinnervation are of considerable interest. Intermittent hypoxia (IH) was reported to increase serotonin innervation near respiratory motor neurons in spinal intact rats, and to improve function after cSCI. Here, we tested the hypotheses that spontaneous serotonergic reinnervation of key respiratory (phrenic and intercostal) motor nuclei: 1) is partially restored 12 weeks post C2 hemisection (C2Hx); 2) is enhanced by IH; and 3) results from sprouting of spared crossed-spinal serotonergic projections below the site of injury. Serotonin was assessed via immunofluorescence in male Sprague Dawley rats with and without C2Hx (12 wks post-injury); individual groups were exposed to 28 days of: 1) normoxia; 2) daily acute IH (dAIH28: 10, 5 min 10.5% O2 episodes per day; 5 min normoxic intervals); 3) mild chronic IH (IH28-5/5: 5 min 10.5% O2 episodes; 5 min intervals; 8 h/day); or 4) moderate chronic IH (IH28-2/2: 2 min 10.5% O2 episodes; 2 min intervals; 8 h/day), simulating IH experienced during moderate sleep apnea. After C2Hx, the number of ipsilateral serotonergic structures was decreased in both motor nuclei, regardless of IH protocol. However, serotonergic structures were larger after C2Hx in both motor nuclei, and total serotonin immunolabeling area was increased in the phrenic motor nucleus but reduced in the intercostal motor nucleus. Both chronic IH protocols increased serotonin structure size and total area in the phrenic motor nuclei of uninjured rats, but had no detectable effects after C2Hx. Although the functional implications of fewer but larger serotonergic structures are unclear, we confirm that serotonergic reinnervation is substantial following injury, but IH does not affect the extent of reinnervation.

Phrenic nerve conduction study to diagnose unilateral diaphragmatic paralysis.

BACKGROUND: Unilateral diaphragmatic paralysis (UDP) has major clinical and etiological implications and, therefore, is important to diagnose. Lung function tests and invasive transdiaphragmatic pressure (Pdi) measurements are widely used to this end but, contrary to phrenic nerve conduction study (NCS), they require volitional maneuvers and/or may be poorly tolerated by patients. The purpose of this study was to compare the diagnostic accuracy of Pdi and phrenic NCS for UDP. METHODS: We retrospectively reviewed 28 patients with suspected UDP. The diagnosis established during a multidisciplinary meeting was the reference standard. RESULTS: Phrenic NCS correlated well with Pdi (r = 0.82, P < .005), and the two tests showed good agreement (κ = 0.82, P < .005). Phrenic NCS and Pdi measurements both had 95% sensitivity, 87.5% specificity, 95% positive predictive, and 87.5% negative predictive values. CONCLUSIONS: Both tests were highly sensitive and specific. Phrenic NCS measurement is a simple, reproducible, noninvasive method whose results correlate well with Pdi and provide insight into the UDP mechanism. In the most difficult cases, combining lung function tests, respiratory muscle assessments, and phrenic NCS can help to establish the diagnosis.

Association of chest tube position with phrenic nerve palsy after neonatal and infant cardiac surgery.

BACKGROUND: Diaphragm paralysis (DP) complicates the postoperative course of neonates and infants undergoing cardiac surgery. Events causing DP remain poorly understood, and preventive strategies remain elusive. This retrospective cohort analysis aims to test the hypothesis that chest tubes in contact with the phrenic nerve in the pleural apex may cause pressure palsy. METHODS: In late 2018, the chest tube positioning strategy was changed so as to avoid a putative "danger zone" configuration, defined as (1) the chest tube looping apicomedially at the level of the second right intercostal space, and (2) wedging of chest tube tip against pericardium. A preintervention and postintervention analysis of 531 patients from 2012 to 2019 was performed to evaluate any association of chest tube position or duration in place with DP. Univariable and multivariable analyses were carried out, with significance set a priori at P < .05. RESULTS: The preintervention group comprised 488 patients, of whom 32 (6.6%) had RDP. The postintervention group comprised 43 patients, none of whom had DP. Multivariable analysis of the entire cohort revealed chest tube positioning in the danger zone as the only significant association with RDP (odds ratio, 4.22; 95% confidence interval, 1.57-11.33; P < .05). CONCLUSIONS: Chest tubes that occupy the right superior pleural space are associated with increased risk of DP.

Spinal cord injury level and Phrenic Nerve Conduction Studies do not predict diaphragm pacing success or failure- all patients should undergo diagnostic laparoscopy.

BACKGROUND: Diaphragm Pacing(DP) demonstrates benefits over mechanical ventilation(MV) for spinal cord injured(SCI) patients. The hypothesis of this report is that phrenic nerve conduction study(PNCS) results cannot differentiate success or failure in selection of patients for DP. Direct surgical evaluation of the diaphragm should be performed. METHODS: Observational report of prospective databases of patients undergoing laparoscopic evaluation of their diaphragms to assess for ability to stimulate to cause contraction for ventilation. RESULTS: In 50 SCI patients who could not be weaned from MV, PNCS results showed latencies in stimulated patients (n = 44) and non-stimulated(n = 6) overlapped (7.8 ± 2.5 ms vs 9.4 ± 2.8 ms) and the null hypothesis cannot be rejected (p-value>0.05). Amplitudes overlapped (0.4 ± 0.2 mV vs 0.2 ± 0.2 mV) and the null hypotheses cannot be rejected (P-value >0.05). In 125 non SCI patients with diaphragm paralysis, there were 78(62.4%) with false negative PNCS. CONCLUSION: PNCS are inadequate pre-operative studies. Direct laparoscopic evaluation should be offered for all SCI patients to receive the benefit of DP.

Suppression of phrenic nerve activity as a potential predictor of imminent sudden unexpected death in epilepsy (SUDEP).

Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death in patients with refractory epilepsy. Centrally-mediated respiratory dysfunction has been identified as one of the principal mechanisms responsible for SUDEP. Seizures generate a surge in adenosine release. Elevated adenosine levels suppress breathing. Insufficient metabolic clearance of a seizure-induced adenosine surge might be a precipitating factor in SUDEP. In order to deliver targeted therapies to prevent SUDEP, reliable biomarkers must be identified to enable prompt intervention. Because of the integral role of the phrenic nerve in breathing, we hypothesized that suppression of phrenic nerve activity could be utilized as predictive biomarker for imminent SUDEP. We used a rat model of kainic acid-induced seizures in combination with pharmacological suppression of metabolic adenosine clearance to trigger seizure-induced death in tracheostomized rats. Recordings of EEG, blood pressure, and phrenic nerve activity were made concomitant to the seizure. We found suppression of phrenic nerve burst frequency to 58.9% of baseline (p < 0.001, one-way ANOVA) which preceded seizure-induced death; importantly, irregularities of phrenic nerve activity were partly reversible by the adenosine receptor antagonist caffeine. Suppression of phrenic nerve activity may be a useful biomarker for imminent SUDEP. The ability to reliably detect the onset of SUDEP may be instrumental in the timely administration of potentially lifesaving interventions.

Permanent diaphragmatic deficits and spontaneous respiratory plasticity in a mouse model of incomplete cervical spinal cord injury.

High spinal cord injuries (SCI) lead to permanent respiratory insufficiency, and the search for new therapeutics to restore this function is essential. To date, the most documented preclinical model for high SCI is the rat cervical C2 hemisection. However, molecular studies with this SCI model are limited due to the poor availability of genetically modified specimens. The aim of this work was to evaluate the pathophysiology of respiratory activity following a cervical C2 injury at different times post-injury in a C57BL/6 mouse model. No significant spontaneous recovery of diaphragmatic activity was observed up to 30 days post-injury in eupneic condition. However, during a respiratory challenge, i.e. mild asphyxia, a partial restoration of the injured diaphragm was observed at 7 days post-injury, corresponding to the crossed phrenic phenomenon. Interestingly, the diaphragmatic recording between 2 respiratory bursts on the injured side showed an amplitude increase between 1-7 days post-injury, reflecting a change in phrenic motoneuronal excitability. This increase in inter-burst excitability returned to pre-injured values when the crossed phrenic phenomenon started to be effective at 7 days post-injury. Taken together, these results demonstrate the ability of the mouse respiratory system to express long-lasting plasticity following a C2 cervical hemisection and genetically modified animals can be used to study the pathophysiological effects on these plasticity phenomena.

Phrenic Nerve Involvement in Neuralgic Amyotrophy (Parsonage-Turner Syndrome).

Neuralgic amyotrophy is a poorly understood neuromuscular disorder affecting peripheral nerves mostly within the brachial plexus distribution but can also involve other sites including the phrenic nerve. In the classic form of the syndrome it causes proximal upper limb and neck pain on the affected side with subsequent muscle weakness that can be highly heterogeneous. Nocturnal noninvasive ventilation support is a first-line treatment after phrenic mononeuropathy. The regular monitoring of diaphragm function with spirometry and diaphragm ultrasound can help determine prognosis and inform decision-making.

Hypoxia-induced hypotension elicits adenosine-dependent phrenic long-term facilitation after carotid denervation.

Moderate acute intermittent hypoxia (AIH) elicits a persistent, serotonin-dependent increase in phrenic amplitude, known as phrenic long-term facilitation (pLTF). Although pLTF was originally demonstrated by carotid sinus nerve stimulation, AIH still elicits residual pLTF in carotid denervated (CBX) rats via a distinct, but unknown mechanism. We hypothesized that exaggerated hypoxia-induced hypotension after carotid denervation leads to greater spinal tissue hypoxia and extracellular adenosine accumulation, thereby triggering adenosine 2A receptor (A2A)-dependent pLTF. Phrenic activity, arterial pressure and spinal tissue oxygen pressure were measured in anesthetized CBX rats. Exaggerated hypoxia-induced hypotension after CBX was prevented via intravenous phenylephrine; without the hypotension, spinal tissue hypoxia during AIH was normalized, and residual pLTF was no longer observed. Spinal A2A (MSX-3), but not serotonin 2 receptor (5-HT2) inhibition (ketanserin), abolished residual pLTF in CBX rats. Thus, pLTF regulation may be altered in conditions impairing sympathetic activity and arterial pressure regulation, such as spinal cord injury.

Effects of Chronic and Acute Pulmonary Hyperinflation on Phrenic Nerve Conduction in Patients with COPD.

In patients with moderate-to-severe Chronic Obstructive Pulmonary Disorder (COPD), pulmonary hyperinflation can occur at rest and increase during episodes of exacerbation. Among other mechanical constraints, changes in position and configuration of the diaphragm are also induced by increased end-expiratory lung volume. Both descent and flattening of diaphragm might damage the phrenic nerves by stretching their fibers. The study aimed to investigate the phrenic nerve conduction in COPD patients in stable conditions and during COPD exacerbation. In a group of 11 COPD patients without relevant comorbidities in stable conditions and subsequently in another group of 10 COPD patients during in-hospital COPD exacerbation and recovery, measurements of functional respiratory parameters and assessment of phrenic nerves motor conduction by bilateral electric stimulation were performed concurrently. Significant increase in phrenic nerves latency (p < 0.05), but similar amplitude of motor compound muscle action potential (cMAP) was observed in stable COPD patients vs. matched controls (p < 0.05). However, in COPD patients with resting pulmonary hyperinflation as reliably detected by substantial Inspiratory Capacity reduction (<80% pred.), the mean bilateral latency was longer vs. COPD patients without pulmonary hyperinflation (p < 0.02). During COPD exacerbation, in contrast with mean latency, the mean amplitude of phrenic nerves cMAP improved at discharge when compared with in-hospital admission (p < 0.05). In stable COPD patients the velocity of phrenic nerve conduction was impaired mostly in the presence of pulmonary hyperinflation, while during COPD exacerbation where dynamic pulmonary hyperinflation abruptly occurs, the reversible decrease of cMAP amplitude does suggest a temporary, acute axonal damage of phrenic nerves, potentially contributing to diaphragmatic dysfunction in these circumstances.

Contemporary analysis of phrenic nerve injuries following cryoballoon-based pulmonary vein isolation: A single-centre experience with the systematic use of compound motor action potential monitoring.

BACKGROUND: Phrenic nerve injury (PNI) remains one of the most frequent complications during cryoballoon-based pulmonary vein isolation (CB-PVI). Since its introduction in 2013, the use of compound motor action potential (CMAP) for the prevention of PNI during CB-PVI is increasing; however, systematic outcome data are sparse. METHODS: The CMAP technique was applied in conjunction with abdominal palpation during pacing manoeuvres (10 mV, 2 ms) from the superior vena cava for 388 consecutive patients undergoing CB-PVI between January 2015 and May 2017 at our tertiary arrhythmia centre. Cryoablation was immediately terminated when CMAP amplitude was reduced by 30%. RESULTS: Reductions in CMAP amplitude were observed in 16 (4%) of 388 patients during isolation of the right veins. Of these, 11 (69%) patients did not manifest a reduction in diaphragmatic excursions. The drop in CMAP amplitude was observed in 10 (63%) patients during ablation of the right superior pulmonary veins (PVs) and in 7 (44%) patients during ablation of the right inferior PVs. Postprocedural persistent PNI was observed in three of four patients for a duration of 6 months, with one of these patients remaining symptomatic at the 24-month follow-up. One of the four patients was lost to long-term follow-up. CONCLUSIONS: All PNIs occurred during right-sided CB-PVI and were preceded by a reduction in CMAP amplitude. Thus, the standardized use of CMAP surveillance during CB-PVI is easily applicable, reliable and compared with other studies, results in a lower number of PNIs.

Activation of µ-opioid receptors differentially affects the preBötzinger Complex and neighbouring regions of the respiratory network in the adult rabbit.

The role of the different components of the respiratory network in the mediation of opioid-induced respiratory depression is still unclear. We investigated the contribution of the preBötzinger Complex (preBötC) and the neighbouring Bötzinger Complex (BötC) and inspiratory portion of the ventral respiratory group (iVRG) in anesthetized, vagotomized, paralyzed and artificially ventilated adult rabbits making use of bilateral microinjections (30-50 nl) of the µ-opioid receptor agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO). Dose-dependent effects were observed. In the preBötC and the BötC 0.1 mM DAMGO microinjections caused mainly reductions in peak phrenic amplitude associated with tonic phrenic activity and irregular (ataxic) patterns of breathing that were more pronounced in the preBötC. Apneic effects developed at 0.5 mM. In the iVRG DAMGO provoked decreases in amplitude and frequency of phrenic bursts at 0.1 mM and apnea at 0.5 mM. Local 5 mM naloxone reversed the apneic effects. The results imply that different components of the respiratory network may contribute to opioid-induced respiratory disorders.

Motor axonopathies in a mouse model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease caused by deleterious mutations in the DMD gene which encodes the dystrophin protein. Skeletal muscle weakness and eventual muscle degradation due to loss of dystrophin are well-documented pathological hallmarks of DMD. In contrast, the neuropathology of this disease remains understudied despite the emerging evidence of neurological abnormalities induced by dystrophin loss. Using quantitative morphological analysis of nerve sections, we characterize axonopathies in the phrenic and hypoglossal (XII) nerves of mdx mice. We observe dysfunction in these nerves - which innervate the diaphragm and genioglossus respectively - that we propose contributes to respiratory failure, the most common cause of death in DMD. These observations highlight the importance in the further characterization of the neuropathology of DMD. Additionally, these observations underscore the necessity in correcting both the nervous system pathology in addition to skeletal muscle deficits to ameliorate this disease.

The impaired diaphragmatic function after bilateral lung transplantation: A multifactorial longitudinal study.

BACKGROUND: Lung transplantation is a complex but effective treatment of end-stage pulmonary disease. Among the post-operative complications, phrenic nerve injury, and consequent diaphragmatic dysfunction are known to occur but are hitherto poorly described. We aimed to investigate the effect of lung transplantation on diaphragmatic function with a multimodal approach. METHODS: A total of 30 patients were studied at 4 time points: pre-operatively, at discharge after surgery, and after approximately 6 and subsequently 12 months post surgery. The diaphragmatic function was studied in terms of geometry (assessed by the radius of the diaphragmatic curvature delineated on chest X-ray), weakness (considering changes in forced vital capacity when the patient shifted from upright to supine position), force (maximal pressure during sniff), mobility (excursion of the dome of the diaphragm delineated by ultrasound), contractility (thickening fraction assessed by ultrasound), electrical activity (latency and area of compound muscle action potential during electrical stimulation of phrenic nerve), and kinematics (relative contribution of the abdominal compartment to tidal volume). RESULTS: Despite good clinical recovery (indicated by spirometry and 6 minutes walking test), a reduction of the diaphragmatic function was detected at discharge; it persisted 6 months later to recover fully 1 year after transplantation. Diaphragmatic dysfunction was demonstrated in terms of force, weakness, electrical activity, and kinematics. Our data suggest that the dysfunction was caused by phrenic nerve neurapraxia or moderate axonotmesis, potentially as a consequence of the surgical procedure (i.e., the use of ice and pericardium manipulation). CONCLUSIONS: The occurrence of diaphragmatic dysfunction in patients with a good clinical recovery indicates that the evaluation of diaphragmatic function should be included in the post-operative assessment after lung transplantation.

Respiratory Neurophysiology in Intensive Care Unit.

Patients with intensive care unit-acquired weakness have an increased risk of prolonged mechanical ventilation, which is a risk factor for prolonged stay and mortality. The most common cause of this problem is weakness of the diaphragm, which can derive from phrenic nerve injury associated with critical neuropathy, or with the complex multiorgan failure/systemic respiratory response syndrome causing muscle fiber lesion. Two conventional neurophysiological techniques are useful to investigate the respiratory muscles, phrenic nerve conduction, and needle electromyography of the accessory respiratory muscles and diaphragm. Phrenic nerve stimulation is a standard noninvasive technique; amplitude of the motor response can be reduced because of muscle fiber inexcitability or axonal loss. Electromyography of the diaphragm is an invasive method but is safe if performed as indicated. It can reveal neurogenic or myopathic motor units. Although these neurophysiological methods have limitations in the investigation of intensive care unit patients with severe respiratory involvement, normal phrenic nerve responses should exclude marked axonal loss and indicate a better prognosis.