Pulmonol.

2019;25(4):223---235

www.journalpulmonology.org

REVIEW

Diaphragmatic dysfunction
J. Ricoy a,∗ , N. Rodríguez-Núñez a , J.M. Álvarez-Dobaño a,b , M.E. Toubes a , V. Riveiro a ,
L. Valdés a,b

a
Pneumology Service, University Hospital Complex of Santiago, Santiago de Compostela, Spain
b
Interdisciplinary Research Group in Pulmonology, Institute of Sanitary Research of Santiago de Compostela (IDIS), Santiago de
Compostela, Spain

KEYWORDS Abstract The diaphragm is the main breathing muscle and contraction of the diaphragm is
Diaphragm; vital for ventilation so any disease that interferes with diaphragmatic innervation, contractile
Diaphragmatic muscle function, or mechanical coupling to the chest wall can cause diaphragm dysfunction.
dysfunction; Diaphragm dysfunction is associated with dyspnoea, intolerance to exercise, sleep disturbances,
Diaphragmatic hypersomnia, with a potential impact on survival.
ultrasound; Diagnosis of diaphragm dysfunction is based on static and dynamic imaging tests (espe-
Mechanical cially ultrasound) and pulmonary function and phrenic nerve stimulation tests. Treatment will
ventilation; depend on the symptoms and causes of the disease. The management of diaphragm dysfunc-
Plication of the tion may include observation in asymptomatic patients with unilateral dysfunction, surgery
diaphragm; (i.e., plication of the diaphragm), placement of a diaphragmatic pacemaker or invasive and/or
Phrenic nerve non-invasive mechanical ventilation in symptomatic patients with bilateral paralysis of the
stimulation; diaphragm. This type of patient should be treated in experienced centres.
Phrenic pacing This review aims to provide an overview of the problem, with special emphasis on the dis-
eases that cause diaphragmatic dysfunction and the diagnostic and therapeutic procedures most
commonly employed in clinical practice. The ultimate goal is to establish a standard of care
for diaphragmatic dysfunction.
© 2018 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).

Abbreviations: MEP, maximal expiratory pressure; MIP, maximal inspiratory pressure; NPPV, non-invasive positive pressure ventilation;
Pdi, transdiaphragmatic pressure; Pes, esophageal pressure; Pga, gastric pressure; PN, phrenic nerve; Tdi, diaphragm thickness; TFdi,
inspiratory diaphragm thickening fraction.
∗ Corresponding author.

E-mail address: [email protected] (J. Ricoy).

https://doi.org/10.1016/j.pulmoe.2018.10.008
2531-0437/© 2018 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
224 J. Ricoy et al.

Introduction

The diaphragm separates the thoracic cavity from the

abdominal cavity. It is the main breathing muscle and is
innervated by the phrenic nerves (PN) that arise from nerve
roots C3---C5. Diseases that interfere with diaphragmatic
innervation, contractile muscle properties, or mechani-
cal coupling to the chest wall can cause diaphragmatic
dysfunction.1 Diaphragmatic dysfunction is associated with
the presence of respiratory symptoms, especially dyspnoea,
exercise intolerance, sleep disturbances, hypersomnia and,
in the most severe cases, a negative impact on survival.2
The purpose of this review was to identify the causes
of diaphragmatic dysfunction, determine signs of the dis-
ease, and set diagnostic criteria for the establishment of a
standard of care.

Structure and function

The diaphragm is the main breathing muscle.2 During quiet

inspiration, the dome shape of the diaphragm changes very
little and the muscular action causes a shortening of the
apposition zone (area in which the lower rib cage and the
diaphragm are in direct contact) that makes the diaphragm
to move caudally like a piston, thereby increasing abdominal
pressure and decreasing pleural pressure. The latter is trans-
mitted to the lung --- causing it to insufflate --- and the costal
wall, which will tend to collapse. This action is compen-
sated by an increase of abdominal pressure --- which causes
the thoracic cage to expand in the apposition area --- and the
contraction of the diaphragm in the lower ribs, which also
opens the thoracic cage2---4 (Fig. 1A and B).

Diaphragmatic dysfunction

The term diaphragmatic dysfunction includes eventration,

weakness and diaphragmatic paralysis.5 Eventration is a
permanent elevation of all or part of the hemidiaphragm
Figure 1 (A) Normal contraction of the diaphragm during
caused by thinning.5,6 Diaphragmatic weakness would be the
quiet inspiration: the muscular action causes the diaphragm
partial loss of muscle strength to generate the necessary
to move together like a piston in the caudal direction (direc-
pressure for adequate ventilation,6,7 while paralysis means
tion of the arrows), thereby increasing abdominal pressure and
the total absence of this capacity. This disorder, depend-
decreasing pleural pressure. The latter is transmitted to the
ing on the cause, can be unilateral or bilateral, temporary
lung, causing it to be insufflated. (B) In supine position, it can
or permanent.8 The hernia is the protrusion of an abdom-
be seen that both the rib cage and the abdomen move outwards.
inal organ or tissue through a diaphragmatic defect. The
(C) When there is paralysis of the diaphragm (right side), the
most frequent congenital hernias are those of Bochdalek and
negative intrathoracic pressure drags the diaphragm and the
Morgani6 and, of those acquired, the hiatus hernia.9 On chest
abdominal viscera towards the thorax (direction of the arrows),
X-ray they will be observed as a localized elevation of the
which generates a negative abdominal pressure. (D) In supine
diaphragm.
position, it is observed how this negative abdominal pressure
Another rare form of diaphragmatic dysfunction is
causes a paradoxical movement during inspiration: the abdomen
diaphragmatic flutter. This dysfunction is characterized by
moves inwards.
the occurrence of repeated, variable-duration episodes of
regular involuntary contractions. Signs of diaphragmatic
flutter include pulsations in the epigastrium, dyspnoea and Aetiology
thoraco-abdominal pain. The aetiology of this condition is
not well understood, and a standard of care has not been The incidence of diaphragmatic dysfunction is unknown,
established yet. A set of trials have been performed with given the multiple diseases that cause it. The level of
different agents, surgical ablation of the phrenic nerve and severity of this complication is determined either by
non-invasive ventilatory support, with varying results.10,11 the level of anatomical involvement or one-sidedness or
Diaphragmatic dysfunction 225

Vascular accident

Vascular accident
Arnold-Chiari disease
Multiple sclerosis

Post-polio syndrome
Amyotrophic lateral sclerosis
Syringomyelia
Paraneoplastic neuropathy
associated with antibodies-HU
Trauma Phrenic nerve Post-irradiation
Compresion/Infiltration Spinal muscular atrophy
Guillain-Barré syndrome
Infection
Amyotrophic neuralgia
Thoracic surgeries

Chronic obstructive pulmonary disease

Asthma

Myastenia gravis
Lambert-Eaton syndrome Muscular dystrophies
Botulism Steroid myopathy
Pompe disease
Mechanical ventilation

Figure 2 Causes of diaphragmatic dysfunction according to the level of involvement.

bilaterality.2,7,12 Fig. 2 shows by anatomical site the diseases and possible dullness to percussion.56 Paradoxical thoraco-
that can cause diaphragmatic dysfunction from the cerebral abdominal movement during sleep occurs occasionally. Some
cortex, through the internal capsule, the central nervous studies have revealed that these patients tend to sleep with
system, the spinal cord, the brachial plexus, the motor neu- the healthy hemidiaphragm in the lower part.57
rons and the PN, until reaching the neuromuscular synapse When there is bilateral involvement, patients usually
and the muscles themselves.1,13---46 Table 1 shows its most show symptoms of orthopnoea. Dyspnoea --- which may
relevant characteristics. occur at rest --- becomes evident during immersion in
Alterations such as hypokalemia, hypophosphatemia, water.58 Patients usually show cyanosis, bilateral diminu-
hypomagnesemia or metabolic alkalosis; some connec- tion of breathing sounds, rapid and superficial respiration,
tive tissue diseases, such as Shrinking lung syndrome or paradoxical movement of the abdominal wall,7,59 espe-
(rare presentation of systemic lupus erythematosus that cially when the patient is in decubitus;2,60 this is due to the
presents with respiratory distress and restrictive functional ‘‘passive’’ behaviour of the diaphragm during inspiration.
impairment); percutaneous punctures of veins (subclavian When the diaphragm is paralyzed, inspiration is obtained
and internal jugular); placement of intercostal drainages; thanks to the contraction of the external intercostal muscles
radiofrequency ablation; or chronic sclerosing mediastinitis, and accessory muscles (sternocleidomastoids, scalenes),
may also co-occur with diaphragmatic dysfunction.2,7,42,47---52 which will expand the rib cage and generate intrathoracic
negative pressure. This pressure will ‘‘drag’’ the diaphragm
and abdominal viscera towards the thorax, which will gen-
Clinical presentation erate a negative abdominal pressure and, therefore, a
decrease in the anterior abdominal wall60 (Fig. 1C and D).
Unilateral diaphragmatic dysfunction may be Most patients with diaphragmatic involvement have sleep
asymptomatic,53 which explains why it is often diag- disorders and significant hypoventilation, especially during
nosed incidentally5 when an elevation is observed in a REM sleep, with its related symptoms.61,62 Table 2 shows the
hemidiaphragm on chest X-ray performed for another rea- most relevant differences between unilateral or bilateral
son. Symptoms are usually more severe in obese patients diaphragmatic paralysis.
or patients with an associated cardiac or pulmonary Patients with unilateral diaphragmatic dysfunction usu-
pathology.2,7 The most frequent symptoms are dyspnoea on ally exhibit respiratory sleep disorders (fatigue, daytime
exertion and orthopnea,53,54 but there may also be symp- sleepiness, snoring and apnea). Thus, some authors recom-
toms of nocturnal hypoventilation and gastroesophageal mend that all patients with eventration or diaphragmatic
reflux.55 paralysis undergo a full-night polysomnography.63 Respira-
Physical examination is non-specific: decreased respi- tory events generally include central hypopneas during REM
ratory sounds at the base of the affected hemithorax sleep. These events often coincide with repeated episodes
226 J. Ricoy et al.

Table 1 Causes that can cause diaphragmatic dysfunction.

Location of the Disease Comment
lesion
Cerebral cortex Vascular accident The respiratory motor neurons of the pyramidal tract (corticospinal)
are scattered throughout a wide area of the cortex, so they rarely
affect the diaphragm.
Internal capsule Vascular accident Vascular accidents located in the brain stem can cause
Arnold---Chiari disease hypoventilation due to involvement of the bulbospinal tract,
affecting the automatic control of respiration.1,13
Central nervous Multiple sclerosis Uncommon cause of diaphragmatic involvement. The main
system implication occurs in the expiratory musculature. It usually appears
in patients in very advanced stages with severe alteration of
mobility. The initial clinical presentation as isolated diaphragmatic
paralysis is rare and is usually bilateral.14---18
Spinal cord Traumatic degenerative (severe If the lesion is at the level of C3---C5, in addition to the
spondylosis) diaphragmatic involvement, other major muscles of inspiration may
be affected. When the injury affects the C2 level or higher, the need
for ventilatory support is almost inevitable and, as we move away
from this level, the probability decreases and is rarely needed in
lesions below C5.19---21
Motor neurons Post-polio syndrome The post-polio syndrome can manifest itself years after its recovery
Amyotrophic lateral sclerosis and affect the same muscle groups as new ones.1,22
Syringomyelia Amyotrophic lateral sclerosis produces secondarily atrophy and
Paraneoplastic neuropathy weakness of the respiratory muscles. Diaphragmatic involvement
associated with antibodies-HU may be the first manifestation or develop throughout the disease. It
Radiation post-irradiation is bilateral and its involvement could be valuable even before the
Spinal muscular atrophy respiratory symptoms begin.23---25
Brachial plexus Traumatic All of these can cause diaphragmatic paralysis.26---29
Iatrogenic (anaesthetic blockages,
obstetric procedures, chiropractic
manipulations of the neck,
radiotherapy)
Idiopathic
Phrenic Trauma30 Guillain---Barré disease is the most frequent cause of acute
Compression/infiltration respiratory muscle paralysis. More than 25% of patients will need
(mediastinal neoplasms) non-invasive ventilation.
Guillain---Barré31 Infection with Herpes---Zoster virus produces diaphragmatic paralysis
Infection (Herpes---Zoster virus, if it affects the cervical territory and is usually ipsilateral and usually
pneumonias,32 Lyme disease,33 permanent.
HIV infection34 ) Amyotrophic neuralgia presents pain and flaccid paralysis of the
Amyotrophic neuralgia shoulder muscles. It is associated with both uni and bilateral
(Parsonage-Turner)35 diaphragmatic involvement.
Thoracic surgeries36 In idiopathic causes the paralysis can be unilateral or bilateral.
Others [malnutrition,37
diabetes,38 hypothyroidism,23
benign thyroid hypertrophy,39
porphyria, vasculitis,
Charcot-Marie-Toot41 disease]
Idiopathic46
Lung Asthma and chronic obstructive The existing pulmonary hyperinflation can deteriorate the
pulmonary disease diaphragmatic function since the diaphragm does not have an
optimal length for its normal functioning.1
Neuromuscular Myasthenia gravis, botulism,40 During an acute myasthenic crisis there may be acute respiratory
junction Lambert---Eaton syndrome20 failure that will require invasive ventilation.
Muscular Muscular dystrophies, steroid In the presence of a diaphragmatic paralysis, acid alfa-glucosidase
myopathy,42 Pompe disease,43 enzyme levels should be determined to discard late-onset Pompe
myositis, mechanical ventilation45 disease (16.7%) prevalence).44
Mechanical ventilation, both invasive and non-invasive, can produce
atrophy of the diaphragm due to disuse.
Diaphragmatic dysfunction 227

Table 2 Comparison of the clinical history, diagnostic tests and treatments according to diaphragmatic paralysis, either
unilateral or bilateral (modified by McCool and Tzelepis)7

Test Unilateral diaphragmatic paralysis Bilateral diaphragmatic paralysis

Background Pain in the neck or shoulder; Pain in the neck or shoulder; thoracic or neck
thoracic or neck surgery; surgery; manipulation of the cervical spine;
manipulation of the cervical neuromuscular disease
spine; neuromuscular disease
Symptomatology It can be asymptomatic; dyspnoea Dyspnoea at rest; dyspnoea not explained;
not explained; limitation to limitation to exercise; orthopnoea; dyspnoea on
exercise; casual radiological immersion in water; respiratory insufficiency;
finding prolonged mechanical ventilation
Physical exploration No paradoxical abdominal Paradoxical abdominal movement
movement
Diagnostic tests
Vital capacity >70% of the theoretical <50% of the theoretical
Vital capacity in supine Descent greater than 15% Descent greater than 30%
MIP <60% of the theoretical <40% of the theoretical
Fluoroscopy Positive sniff test Not useful
Pdi max >70 cm H2 O <40 cm H2 O
TwichPdi <10 cm H2 O <20 cm H2 O
Complications Occasional hypoventilation during Frequent hypoventilation during sleep,
sleep atelectasis, pneumonia, acute respiratory
failure
Treatment
Observation period for 1.5---3 years 1.5---3 years
recovery
Treatment of Yes Yes
comorbidities
Reversal of metabolic Yes Yes
alteration
NIV Usually not indicated. Use if Normally indicated
sleep-disordered breathing or
nocturnal hypoventilation
Diaphragm plication Can be useful Not indicated
Phrenic pacemaker Not a therapeutic option Yes, in patients with severe spinal cord damage
MIP, maximum inspiratory pressure; NIV, non-invasive ventilation; Pdi max, transdiaphragmatic pressure after maximum inspiratory effort
with closed glottis; TwichPdi, transdiaphragmatic pressure after transcutaneous electrical or magnetic stimulation of the phrenic nerve.

of desaturation that can be observed by pulse oximetry and related mechanical alterations (inappropriate length-
and are related to diaphragmatic weakness and paradoxical tension relationship66 ). In the hypoventilation-obesity
breathing. Desaturation is more frequent and severe when syndrome, the mechanisms that cause hypoventilation are
the patient is in lateral decubitus on the affected side.64 complex and multifactorial. The role of diaphragmatic
Patients with bilateral diaphragmatic dysfunction show weakness in hypoventilation in obese patients is not well-
the same symptoms and desaturation events, although they understood; however, obesity seems to add an additional
are more likely to experience orthopnea.62 The standard load to the respiratory system.67
of treatment for patients with (unilateral or bilateral)
diaphragmatic dysfunction and respiratory sleep disorders is
continuous positive airway pressure or non-invasive mechan- Diagnosis
ical ventilation. Yet, continuous positive airway pressure is
more likely to fail in patients with bilateral diaphragmatic Suspicion of diaphragmatic dysfunction may arise from the
dysfunction, who will ultimately require non-invasive venti- study of unexplained dyspnoea or, occasionally, after the
lation. Therefore, pressure titration should be performed in casual finding of a diaphragmatic elevation in an imaging test
a sleep laboratory.65 performed for another purpose. Whatever it is, diagnosis is
There is a range of potential pathophysiological mecha- usually based on imaging tests --- both static and dynamic
nisms of hypercapnic respiratory failure in obese patients. --- including radiography, fluoroscopy and chest ultrasound.
Some of these mechanisms include diaphragmatic dys- Table 2 summarizes the most relevant diagnostic tests for
function secondary to the accumulation of adipose tissue unilateral and bilateral diaphragmatic paralysis.
228 J. Ricoy et al.

Radiography has shown to be useful for the detection of diaphragmatic

dysfunction,77 with a high sensitivity (93%) and speci-
Chest X-ray is a simple effective test to evaluate the pul- ficity (100%) for diaphragmatic neuromuscular disease.78 At
monary parenchyma in search of other potential causes present, many authors consider ultrasound the method of
of dyspnoea.12 X-ray allows physicians to see the struc- choice for the evaluation of diaphragmatic movement.72,74,79
ture, morphology and elevation of the diaphragm, has Hemidiaphragm visualization by ultrasound is achieved
moderate interobserver reliability, and shows slightly more from an anterior approach, with the patient in supine
elevated values for the right hemidiaphragm.68 Its sensitiv- position performing different breathing manoeuvres (quiet,
ity, specificity, positive and negative predictive value for deep breathing and sniff). Examination must start with the
the diagnosis of unilateral diaphragmatic paralysis are 90%, patient lying on the ‘‘healthy’’ side if unilateral paralysis is
44%, 33% and 93%, respectively.68 However, in other studies, suspected.56,69,75
its sensitivity has not reached 70%.69 In bilateral diaphrag- The thickening of the diaphragm (Tdi) indicates a short-
matic paralysis, the typical finding is the elevation of the two ening of the diaphragm. Its absence during inspiration
hemidiaphragms, which is associated with small pulmonary confirms diaphragmatic paralysis. If there is muscle atrophy,
volumes and bibasal atelectasis.58 Although the presence thickness decreases and the diaphragm does not contract
of a diaphragmatic elevation is not necessarily a sign of during inspiration.73,80 The lower limit of normal diaphrag-
dysfunction, its absence makes diaphragmatic dysfunction matic thickness at rest (at the end of an unforced expiration)
unlikely.68 in most patients is 1.5 mm.81 The two indexes usually used
for the diagnosis of diaphragmatic paralysis include a Tdi
value <2 mm and a diaphragm thickening fraction (TFdi)
Fluoroscopy
value <20% [TFdi: (thickness at the end of the inspira-
tion − thickness at the end of expiration)/thickness at the
It is a test that allows us to visualize the diaphragm continu-
end of expiration (in %)].80 The normal lower limit accepted
ously throughout the normal respiratory cycle and during the
for the TFdi is 20%.
execution of forced inspiratory manoeuvres. It is an easy-
The normal movement of the diaphragm during inspira-
to-use and -interpret technique5 with good inter-observer
tion is caudal, so the line corresponding to the diaphragm
reliability70 and, for years, it has been the gold standard
(echogenic line located between the liver or spleen and the
for the diagnosis of diaphragmatic paralysis.69 However, in
lung) moves downward (approaching the transducer), pre-
some patients with bilateral diaphragmatic weakness, flu-
ceded by a pause. Diaphragmatic paralysis shows an absence
oroscopy findings can be misinterpreted, as some patients
of caudal movement of the diaphragm during normal inspi-
in the standing position may adopt an unusual respiratory
ration, or a paradoxical movement of the diaphragm during
pattern to compensate for their lack of mobility.2,58 This
the sniff test and occasionally with deep inspiration.5,69,82
mechanism of compensation may be misinterpreted in the
Diaphragmatic weakness is determined where there is
fluoroscopy as a diaphragmatic contraction.60 This situation
decreased amplitude of movement during deep breathing
can be prevented if the patient is in recumbent position,
--- with or without paradoxical movement during the sniff
which is why some authors recommend that fluoroscopy is
manoeuvre.
performed in this position. Therefore, fluoroscopy is a use-
ful test for the diagnosis of unilateral hemidiaphragmatic
paralysis. Conversely, fluoroscopy is not as useful for bilat-
eral dysfunction, as findings can be misinterpreted. It should Pulmonary function tests
be performed with the patient in upright position (frontal
and lateral) or in decubitus by an expert radiologist.
Pulmonary function tests are relevant to the diagnosis of
diaphragmatic dysfunction. In general, weakness of the
Ultrasound inspiratory muscles usually leads to a restrictive pattern,
with a decrease in the total pulmonary, vital and functional
Diaphragmatic ultrasound is a non-invasive, portable, quick residual capacities, keeping the CO diffusion and the resid-
to perform, simple and well-tolerated test with a lin- ual volume preserved. The FEV1 /FVC ratio is also relatively
ear relationship between diaphragmatic movement and preserved.54,57 The measurement of vital capacity is of great
inspired volume, which allows quantitative and qualitative value. On the one hand, when vital capacity is normal, rele-
assessment of diaphragmatic movement.71 Thus, ultrasound vant inspiratory muscle weakness is unlikely.83 On the other
been suggested as the technique of choice for assessing hand, a more severe decrease of 15---30% when going from
diaphragmatic movement on suspicion of malfunctioning.72 the sitting position to decubitus --- depending on whether
In addition, there is no exposure to ionizing radiation and paralysis is unilateral or bilateral --- suggests some degree of
intense patient cooperation is not essential.69 In expert diaphragmatic weakness and requires further examination.2
hands, and following the appropriate methodology,73 it One way of estimating the strength of respiratory mus-
is a very reproducible technique, with good inter and cles is by measuring the pressures they generate at different
intra-observer reliability and good reproducibility.71---74 The points in the airway. To do this, two types of tests can be
thickness of the diaphragm can be determined in more than used: (a) non-invasive tests, which determine the pressures
85% of measurements, with a low coefficient of variation generated in the mouth, nose or endotracheal tube;84 and
(0.09---0.14).73 Variability of diaphragmatic movement can (b) invasive tests, which require the placement of pressure
also be determined in virtually all measurements, with a probes in the stomach and/or oesophagus that will serve as
good intra- and inter-observer correlation.75,76 Ultrasound a reflex of abdominal and pleural pressure, respectively.
Diaphragmatic dysfunction 229

Determination of maximum static pressures in the mouth Transcutaneous electrical phrenic stimulation can be per-
during inspiration (MIP) and expiration (MEP) with the air- formed at the level of the neck unilaterally or bilaterally.
way closed is considered a reasonable method for measuring However, this technique causes the patient discomfort and
the force generated jointly by the inspiratory and expira- is technically more difficult in obese patients or in patients
tory muscles. In addition, it is one of the most widely used with anatomical alterations. The magnetic stimulation of
techniques in clinical practice. This technique is easy to per- PNs is usually applied bilaterally at the level of the cervical
form and well tolerated.85 Its greatest disadvantage is that spine90 ; it is reproducible, easy to perform and well toler-
it is highly dependent on the cooperation and effort of the ated by patients. A Twitch Pdi < 10---20 cm H2 O (depending on
patient.86 In general, absolute values of MIP above 80 cm H2 O whether involvement is unilateral or bilateral) is generally
in men and 70 cm H2 O in women exclude clinically relevant suggestive of diaphragmatic dysfunction.91 Measuring Sniff
inspiratory muscle weakness.83 Normal MEP combined with Pdi and Twitch Pdi allows differential diagnosis of diaphrag-
low MIP suggests the existence of isolated weakness of the matic paralysis caused either by first or second motor neuron
diaphragm.85 Finally, the concomitant reduction of MIP and involvement, a central cause, or lack of cooperation.92
MEP suggests that diaphragmatic involvement may be due Although electromyography and the stimulation test must
to a generalized process, with simultaneous involvement of be performed by experienced operators, they are very accu-
the inspiratory and expiratory muscles.7 In percentage val- rate in the assessment of neural and muscular disorders.
ues, MIP is around 60% of the predicted value (on average) Electromyography is performed by the insertion of a nee-
in unilateral affectation87 vs. 40% in bilateral dysfunction.88 dle electrode. This test can show abnormal spontaneous
Nonetheless, a diminished MIP is not exclusive to muscu- activity of the diaphragm, and it can also show differ-
lar weakness and can be observed in patients with chronic ent characteristics of motor unit potential, like amplitude,
obstructive pulmonary disease.89 shape or recruitment.93 The uses of electromyography in the
The nasal sniff manoeuvre is used do determine inspira- examination of respiratory muscles are described in specific
tory pressures in the nose and involves the performance of guides.85
a rapid voluntary inspiratory effort through the nasal pas- Findings in electromyography are supported by evidence
sages. It is a useful test for evaluating the strength of the obtained in other functional tests --- such as PN conduc-
diaphragm in clinical practice.85 A pressure, in absolute val- tion studies. Electromyography is a very useful method for
ues, greater than 70 mm Hg in men and 60 mm Hg in women is determining the diagnosis, evolution and prognosis of PN
unlikely to be associated with significant inspiratory muscle disorders. Although electromyography is associated with
weakness.85 potential complications, it has been demonstrated to be
The most widely used invasive tests include oesophageal safe.94
pressure (Pes) and transdiaphragmatic pressure (Pdi) mea- Stimulation tests measure the efficacy of neural and
surement by estimating the difference between Pes neuromuscular transmission. They can be performed using
(intrathoracic pressure) and gastric pressure (Pga) (intra- electrical or magnetic stimulators. Electrical stimulators are
abdominal pressure) [Pdi = Pes − Pga]. Pes and Pdi can be less expensive and relatively selective but they cause the
obtained during maximum voluntary efforts, the most fre- patients discomfort and the technique is complex. Magnetic
quent being the sniff test (Sniff Pdi). Pdi is specific to stimulators are easy to use and cause less discomfort, but
diaphragm contraction and is the gold standard method for they are less selective and more expensive.
the evaluation of diaphragm function. Also, Pdi is the only PN is stimulated at the level of the neck, and the elec-
reliable diagnostic method for bilateral paralysis.89 If an tromyographic activity of the diaphragm is registered to
inspiratory effort is made with the paralyzed diaphragm, measure PN latencies and amplitudes of muscle compound
Pes and Pga will be negative and, therefore, the Pdi will action potentials. In some neuromuscular disorders (i.e.,
not change.85 In clinical practice, Sniff Pes and Sniff Pdi demyelinating polyneuropathies), latencies are delayed due
are the two most reproducible voluntary tests for assess- to slow PN conduction (6---8 ms in healthy adults). In other
ing overall respiratory and diaphragmatic force.83 A value settings (PN trauma) the amplitude of muscle action poten-
of Sniff Pdi > 100 cm H2 O in men and 80 cm H2 O in women tials can be decreased (normal amplitude values average
make the existence of clinically significant diaphragmatic 500---800 mV). A lack of muscle action potential after phrenic
weakness unlikely.85 A Pdi of 0 confirms bilateral diaphrag- stimulation is suggestive of diaphragmatic paralysis with a
matic paralysis89 although some authors have established lesion near or at the neuromuscular junction. Cortical stim-
the cut-off point at <10 mm Hg. ulation is usually performed using a magnetic stimulator to
measure response time of the diaphragm. This time is com-
pared with latency after direct stimulation of the PN, which
Stimulation of the phrenic nerve yields central conduction time. Cortical stimulation is not
selective and its application to the respiratory system is
The gold standard method for the quantification of the difficult.85
mechanical function of the diaphragm is by measuring the
negative pressure generated by its contraction in response
to the stimulation of the PN.85 This method offers the Treatment
possibility of activating and studying the diaphragm sep-
arately without the activation and concomitant action of The treatment of diaphragmatic paralysis depends mainly on
other muscle groups. During stimulation, negative pres- its cause and the symptomatology of the patient. In general,
sure can be monitored by calculating the difference patients with asymptomatic unilateral involvement do not
between oesophageal and gastric pressures (Twitch Pdi). require treatment. Initially, all associated factors must be
230 J. Ricoy et al.

treated, including obesity, respiratory or chronic heart dis- phrenic involvement of a mainly iatrogenic or traumatic
eases, which could influence and increase the symptoms of origin who have not shown any clinical or radiological
paralysis. There are specific treatments when the aetiology improvement in a reasonable period of time. It is necessary
of the paralysis is known and is potentially reversible, as in to previously demonstrate the continuity of the nerve and
infectious processes,34,91 metabolic, endocrinological (such the viability of the neuromuscular plate through PN conduc-
as diabetes94 or hypothyroidism95 ) or systemic erythemato- tion studies and electromyography.110
sus lupus (shrinking lung syndrome).47 We must also bear
in mind that paralyzes of idiopathic cause --- such as amy-
otrophic neuralgia --- can resolve spontaneously.26,44 Other Diaphragmatic pacemaker
studies have shown that diaphragmatic paralysis of poten-
tially reversible aetiology (surgical, paraneoplastic, diabetic It can be placed in patients with impaired bilateral mobility
neuropathy, etc.) can improve spontaneously the strength of of the diaphragm who wish to delay the initiation of ventila-
the diaphragm and respiratory muscles by 40---60% of cases tion --- both invasive and non-invasive --- or who have started
over time,96---98 suggesting the convenience of delaying any it but do not wish to continue or were not able to tolerate
surgical approach. it. These patients generally exhibit cervical involvement at
During the observation period, the patient can be a level above C3, or with central alterations different from
included in a specific respiratory rehabilitation plan.99 It has cervical involvement, --- mainly congenital or acquired cen-
been shown that one-year inspiratory muscle training after tral hypoventilation. It can also be seen in patients with
cardiac surgery improves diaphragmatic mobility and the lower motor neuron involvement for a reason other than
inspiratory muscle strength of patients with diaphragmatic amyotrophic lateral sclerosis111 and in traumatological or
dysfunction.100 idiopathic etiologies.112
The most relevant studies published so far on the use
of a diaphragmatic pacemaker in amyotrophic lateral scle-
Surgical diaphragmatic plication
rosis have not confirmed its expected benefits, with higher
mortality rates in patients using a pacemaker. Therefore, at
This is the main surgical correction treatment available to
present, it is not indicated for this type of patients.113,114
control dyspnoea in patients with diaphragmatic paralysis.
The patients to whom this treatment is offered must be
It consists of folding the paralyzed diaphragm so that it is
strictly selected and studied in institutions with experience;
immobilized in a position of maximum inspiration, thereby
the presence of severe nocturnal hypoventilation must be
relieving compression of the lung parenchyma and allow-
confirmed and PN, diaphragm, and lung function must be
ing lung reexpansion. It can be done through a thoracic
shown to be ideal.111
(with thoracoscopy)99 or abdominal approach.101 It is pri-
marily indicated for symptomatic patients with unilateral
diaphragmatic dysfunction that --- based on clinical, radi-
Ventilatory support
ological and functional tests --- has not resolved after a
period of observation of 6---12 months and is therefore con-
It has been used successfully both in patients with unilateral
sidered permanent and irreversible.99,102 Plication has also
and bilateral diaphragmatic paralysis, either permanently in
been successfully performed in some patients with bilateral
the latter,115 or temporally in the former, until complete
involvement.102,103 In the series of patients operated on, the
recovery of diaphragmatic function. Ventilatory support
main causes of paralysis were traumatism, cardiac surgery
can be applied by invasive mechanical ventilation or
and iatrogenic.99,104
non-invasive positive pressure ventilation (NPPV). NPPV is
Plication has been shown to be effective, safe and
actually considered the tool of choice mainly in symp-
cause few complications,99,104---106 inducing an improvement
tomatic patients with bilateral diaphragmatic paralysis.
of symptoms and dyspnoea.100,105 The beneficial effects of
Tolerance is good,116 and it has been shown to provide
plication are not only visible on radiological scans101,104 but
both clinical and blood gas improvement in the long
also in improved pulmonary function parameters.99,102,104,105
term.117 The indication of non-invasive ventilation would
After surgery, improvements occur in the tidal volume of
be similar to that for other neuromuscular or restrictive
both hemidiaphragms (the operated and the healthy, prob-
pathologies.118,119
ably related to a significant improvement in the expansion
Patients with acute respiratory failure may need intu-
of the abdominal compartments of the rib cage),107 exercise
bation and mechanical ventilation, which can continue
capacity,108 daily activity and quality of life, with a reduction
over time as a result of respiratory muscle paralysis.
of up to 20 points in the score on Saint George’s Respira-
A study in 152 patients with spinal cord injury (50%
tory Questionnaire.99,101,108 All this allows many patients to
with affectation at C3---C5 level) revealed that early tra-
return to normal life. Morbid obesity, calcification of the
cheostomy reduces the duration of invasive ventilation
diaphragm and certain neuromuscular diseases are relative
and length of stay in the ICU; in addition, it decreases
contraindications.109
the incidence of complications associated with orotracheal
intubation, except for ventilation-associated pneumonia.120
Phrenic nerve repair by microsurgery However, non invasive ventilation has been proposed as
a weaning method prior to tracheostomy in collabora-
This surgical approach --- which includes modalities such tive patients with bilateral diaphragmatic paralysis, a
as local decompression, transposition or interposition of a small volume of secretions and an appropriate inspiratory
nerve graft --- can be indicated for patients with unilateral flow.115
Diaphragmatic dysfunction 231

Figure 3 Suggestions for diagnostic and therapeutic algorithms in unilateral (A) and bilateral (B) diaphragmatic paralysis (modified
from Dubé and Dres12 ). CPAP, continuous positive pressure in the airway; CT, computed tomography; GSA, arterial blood gases; MIP,
maximum inspiratory pressure; NIV, non-invasive ventilation; Pdi, transdiaphragmatic pressure; NPSG, nocturnal polysomnography;
SaO2 , arterial oxygen saturation; TFdi, fraction of thickening of the diaphragm; VC, vital capacity.

Tracheostomy and invasive ventilation can also be The diagnostic and therapeutic algorithms for unilateral
required by patients with neuromuscular disease when non- and bilateral diaphragmatic paralysis are shown in Fig. 3A
invasive ventilation has failed or invasive interventions are and B, respectively.
ineffective.121 In summary, diaphragmatic dysfunction can be associated
Non-invasive ventilation is associated with some with important clinical consequences. Identifying its origin
complications. Mild or transient complications are related and treating its symptoms and effects on sleep structure
to the use of masks. Severe complications can be caused and exercise capacity requires thorough examination. Ultra-
by: (1) ventilation failure, which can be minimized by the sound is a simple and effective means of routinely assessing
strict selection of patients and the appropriate control of diaphragm function which guides clinicians in their thera-
ventilation; (2) ventilation-associated pneumonia, with a peutic choice. Diaphragmatic dysfunctions should be treated
lower risk in patients on invasive ventilation; (3) barotrau- in experienced centres, with access to diaphragmatic ultra-
mas, with a lower incidence than in patients on invasive sonography, phrenic stimulation, pacemaker placement, and
ventilation; and (4) hypotension.122 surgical experience in diaphragmatic plication.
232 J. Ricoy et al.

Author’s contribution 12. Dubé BP, Dres M. Diaphragm dysfunction: diagnostic

approaches and management strategies. J Clin Med.
Jorge Ricoy. Author. Conception and design. Writing of the 2016;5:113.
13. Monserrat JM, Picado C, Agustí-Vidal A. Arnold---Chiari: mal-
article presented. Approval of the final version.
formation and paralysis of the diaphragm. Respiration.
Nuria Rodríguez-Núñez. Co-author. Review of the submit- 1988;53:128---31.
ted article. Approval of the final version. 14. Levy J, Bensmail D, Brotier-Comienne A, Butel S, Joussain C,
José Manuel Álvarez-Dobaño. Co-author. Review of the Hugeron C, et al. Respiratory impairment in multiple sclerosis:
submitted article. Approval of the final version. a study of a respiratory function in wheelchair-bound patients.
María E. Toubes. Co-author. Review of the submitted arti- Eur J Neurol. 2017;24:497---502.
cle. Approval of the final version. 15. Tzelepis GE, McCool FD. Respiratory dysfunction in multiple
Vanessa Riveiro. Co-author. Review of the submitted arti- sclerosis. Respir Med. 2015;109:671---9.
cle. Approval of the final version. 16. Cooper CB, Trend PJ, Viles CM. Severe diaphragm weakness in
Luis Valdés. Author. Responsible. Conception and design. multiple sclerosis. Thorax. 1958;40:633---4.
17. Aisen M, Alt G, Foster S. Diaphragmatic paralysis with-
Writing of the article presented. Approval of the final ver-
out bulbar or limb paralysis in multiple sclerosis. Chest.
sion. 1990;98:499---501.
18. Balbierz JM, Ellenberg M, Honet JC. Complete hemidiaphrag-
matic paralysis in a patient with multiple sclerosis. Am J Phys
Funding Med Rehabil. 1988;67:161---5.
19. Winslow C, Rozovsky J. Effect of spinal cord injury on
The authors declare the non-existence of external financing the respiratory system. Am J Phys Med Rehabil. 2003;82:
of this article. 803---14.
20. Benditt JO, Boitano LJ. Pulmonary issues in patients with
chronic neuromuscular disease. Am J Respir Crit Care Med.
Conflict of interests 2013;187:1046---55.
21. Wicks AB, Menter RR. Long-term outlook in quadriplegic
We wish to confirm that are no known conflicts of inter- patients with initial ventilator dependency. Chest.
est associated with this publication and there has been no 1986;90:406---10.
financial support for this work that could have influenced its 22. Chai T, Aseff JN, Halstead LS. Diaphragm dysfunction due to
outcome. remote poliomyelitis in a patient with unexplained dyspnoea.
PM&R. 2011;3:179---82.
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Acknowledgement ment of respiratory functions by spirometry and phrenic nerve
studies in patients of amyotrophic lateral sclerosis. J Neurol
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The authors would like to thank José Ángel Novo-Platas for 24. Khan Z, Arafeh A, Blaivas A, Jafary A, Meehan T. Amyotrophic
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