Bilateral Diaphragm Paralysis: A Challenging Diagnosis

Martha E Billings MD, Moira L Aitken MD, and Joshua O Benditt MD

Introduction

Bilateral diaphragm paralysis is a rare cause of unex-plained respiratory failure. Although it is a known com-plication of cardiothoracic surgery, it is often under-rec-ognized and diagnosis is frequently delayed.1 It should beconsidered in patients with low lung volumes on imaging,progressive hypercapnia, and pronounced dyspnea in thesupine position.2 Pulmonary function tests reveal a restric-tive process; the maximum inspiratory pressure (MIP) isreduced. It can be very challenging to definitively diag-nose. Fluoroscopic sniff test, which is 90% sensitive forthe diagnosis of unilateral diaphragm paralysis, can pro-vide misleading results when bilateral diaphragm paralysisis present. Measurement of transdiaphragmatic pressurewith gastric and esophageal balloon placement is the onlyreliable method to accurately diagnose this disorder.3 Wereport a case of recurrent hypercapnia, supine dyspnea,and respiratory failure for 2 months prior to diagnosis andtreatment of bilateral diaphragm paralysis.

Case Summary

A 22-year-old woman with congenital aortic stenosisdeveloped persistent dyspnea and inability to wean frommechanical ventilation after surgical repair of an ascend-ing aortic aneurysm. She had undergone multiple repairsof her aortic stenosis, beginning in infancy with valvulot-omy. She underwent aortic valve replacement at age 5. Atage 20 she required the Konno procedure (aortic valvereplacement and enlargement of the aortic annulus, as-cending aorta, and left-ventricular outflow tract to treat

subaortic stenosis) with placement of a St Jude valve. TheKonno procedure resulted in the development of a dilatedascending aortic aneurysm.

Prior to her aneurysm repair she had no dyspnea, chestpain, orthopnea, or exercise limitations, and could walk up15 flights of stairs. She underwent a modified Bentallprocedure, in which the aortic root and ascending aorta arereplaced with a Dacron graft. The surgery was compli-cated by hemorrhage with associated hypotension prior toinitiation of cardiopulmonary bypass. She had multiplepostoperative complications, including stroke, seizures, andacute renal failure. She underwent tracheostomy 2 weeksafter surgery because of persistent respiratory failure.

While on the surgical service she was unable to weanfrom the ventilator, despite multiple trials over 6 weeks.She reported dyspnea that worsened to the feeling of suf-focation with lying flat. She complained that she was un-able to sleep because of shortness of breath. She deniedchest pain but noted difficulty with taking deep breathsand the feeling that her chest was tight. She had no lower-extremity swelling. She denied cough, difficulty swallow-ing or speaking, or aspiration. She reported difficulty withdeep coughing and clearing secretions.

She had no other medical history. She was taking war-farin, epopoetin alfa, aspirin, lansoprazole, labetalol, cita-lopram, and levetiracetam, as well as oxycodone and zol-pidem as needed. She was married but had no children.She rarely drank alcohol and never smoked. She had nofamily history of congenital heart disease or lung disease.

Her examination was notable for tachypnea with rapid,shallow breathing. She was an obese young woman whoappeared very anxious. Cardiac examination revealedtachycardia and mechanical valve sounds, but no murmursor gallops. She had normal jugular venous pressure. Onauscultation her upper lobes were bilaterally clear, butlung sounds were diminished one-third up posteriorly, withassociated dullness to percussion. This did not change withinspiration. She had no lower-extremity edema.

Her bedside MIP was �16 cm H2O. Her arterial bloodgas values while receiving oxygen (4 L/min via nasal can-nula) were pH 7.35, PCO2

63 mm Hg, PO2121 mm Hg, and

bicarbonate 34 mEq/L. She had a normal thyroid stimu-lating hormone level. Chest radiograph showed low lung

Martha E Billings MD, Moira L Aitken MD, and Joshua O Benditt MDare affiliated with the Division of Pulmonary and Critical Care Medicine,Department of Medicine, University of Washington, Seattle, Washing-ton.

The authors report no conflicts of interest related to the content of thispaper.

Correspondence: Martha E Billings MD, Division of Pulmonary CriticalCare, Box 359762, Harborview Medical Center, 325 9th Avenue, SeattleWA 98104. E-mail: mebillin@u.washington.edu.

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Joshua O Benditt MD, Section Editor Teaching Case of the Month

volumes and bibasilar opacification (Fig. 1). Her echocar-diogram showed normal left-ventricular function and nosubstantial valvular insufficiency. Computed tomogram re-vealed bilateral linear atelectasis of the bases, but no pleu-ral effusions. Diaphragm fluoroscopy via the sniff test wasinterpreted as normal by an experienced chest radiologist.

Two months into the hospital course, her providers re-quested a pulmonary consultation for evaluation of dys-pnea and persistent mechanical ventilation requirement.Suspicion for bilateral diaphragm paralysis was high, givenher history of new-onset orthopnea, low lung volumes,very low MIP, and absence of valvular or ventricular heartfailure to explain her dyspnea. Esophageal and gastric bal-loon pressure measurements revealed a transdiaphragmaticpressure of zero with tidal breathing and the maximal in-spiratory maneuver. The gastric pressure (Pga), whichshould become more positive during inspiration, showed anegative deflection parallel to the esophageal pressure (Pes),which confirmed bilateral diaphragm paralysis (Fig. 2).

The patient was started on noninvasive ventilation (NIV)the following night, with immediate results; with NIV shewas able to sleep and no longer had the sensation of severedyspnea when flat. She was transferred from the intensivecare unit the next day and was quickly transitioned torehabilitation, where her tracheostomy was removed. Sev-eral months later she continued to have evidence of dia-phragm dysfunction. In clinic, her MIP was –40 cm H2O.Spirometry revealed an upright forced vital capacity of1.27 L (38% of predicted), which decreased to 0.68 L(17% of predicted) when supine, which is a decrease of46%, consistent with persistent bilateral diaphragm paral-ysis. Her end-tidal CO2 was 38 mm Hg in clinic, whichwas down from 63 mm Hg on initial evaluation. The pa-

tient is currently home, walking daily around her neigh-borhood, and using NIV when she sleeps.

Discussion

Bilateral diaphragm paralysis develops after injury tothe phrenic nerve and certain other neuropathies and my-opathies (Table 1). Most commonly the etiology is neverfound.2 Phrenic-nerve paralysis can develop after bluntcervical trauma, neck manipulation, cardiothoracic surgeryor radiation. Some idiopathic cases are due to neuralgicamyotrophy, associated with brachial plexus neuropathy(Parsonage-Turner syndrome) or possibly a post-viral neu-ropathy such as herpes zoster. Diaphragm paralysis mayalso result from myopathies, such as dermatomyositis, limb-girdle muscular dystrophy, mixed connective tissue dis-ease, acid maltase deficiency, malnutrition, or amyloid-osis. Neuropathic diseases such as poliomyelitis, multiplesclerosis, amyotrophic lateral sclerosis, and Guillain-Barresyndrome may also lead to diaphragm paralysis.4 In thispatient the injury occurred during her thoracic surgery; themechanism was probably phrenic-nerve injury due to ster-nal retraction or hypothermia injury with cardioplegia.5

Bilateral diaphragm paralysis has a unique presentationof dyspnea, orthopnea, and reduced MIP, but is challeng-

Fig. 1. Chest radiograph reveals low lung volumes and basilaratelectasis.

Fig. 2. A: Normal esophageal pressure (Pes) and gastric pressure(Pga) measurements. The dashed line indicates inspiration. Notethe deflection in opposite directions of Pes and Pga during inspi-ration. B: Pes and Pga measurements in a patient with diaphragmparalysis. The dashed line indicates inspiration. Note the deflec-tion in the same direction of Pes and Pga during inspiration. In thiscase the transdiaphragmatic pressure (Pga – Pes) is zero becausethe pressure deflections are moving in the same direction.

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ing to diagnose. Patients typically note symptoms of in-tense dyspnea when recumbent. Pulmonary function testsreveal a restrictive pattern, with a reduced vital capacity ofapproximately 55% of predicted and residual volume of45% of predicted (Table 2).6 Characteristically, patientshave a supine decrease in forced vital capacity of up to40%, caused by displacement of the abdominal contentsbecause gravity shifts the diaphragm cephalad.4 A uniquesymptom is dyspnea with immersion in water. Chest com-pliance is decreased and the elastic work of breathing in-creases with increased hydrostatic pressure on the chestand abdomen. With immersion there is a mean vital ca-pacity decrease of 34% in patients with bilateral diaphragmparalysis, compared to less than 10% in normals.7 Patientsalso typically have an abnormal MIP, to greater than�60 cm H2O, often near �20 cm H2O. Patients also haveprofound sleep disturbances from worsening supine respi-ratory dysfunction, and loss of thoracic muscle tone duringrapid-eye-movement sleep.6 This leads to nocturnal hyp-oxia, hypercapnia, and symptoms of daytime somnolence,morning headaches, and anxiety, all of which were seen inthis patient.

Fluoroscopic sniff test, although sensitive and specificfor unilateral diaphragm paralysis, is not sensitive for, andis frequently misinterpreted as bilateral diaphragm paral-ysis. The cephalad movement of the ribs as the accessorymuscles contract can give the false appearance of caudaddisplacement of the diaphragm. Thus, as in this case, itmay appear as if the diaphragm is moving with respiratoryeffort and produces a false negative result.

Transdiaphragmatic pressure measurements with bal-loon-tipped esophageal and stomach catheters is the ac-cepted standard test for diagnosis of diaphragm paralysis.The catheters are placed transnasally into the stomach andesophagus (Fig. 3). A catheter in the stomach measuresPga. Transducers in the lower third of the esophagus mea-sure Pes, which reflects pleural pressure (transdiaphrag-matic pressure � Pga � Pes).3 During normal inspiration,Pes becomes more negative as pleural pressure drops,whereas Pga rises as abdominal contents are compressedwith the diaphragm descending. The pressure tracingsshould move in opposite directions (Fig. 2A). With com-plete diaphragm paralysis, the Pes and Pga move in thesame directions and transdiaphragmatic pressure is zero(Fig. 2B). Maneuvers such as sniff can increase the sen-sitivity of this test.

Electromyography of the diaphragm and phrenic-nerve-conduction-velocity testing are also diagnostic of diaphragmparalysis.1 Electromyography and nerve-conduction stud-ies are more useful in distinguishing the etiology of theparalysis (eg, myogenic vs neurogenic, demyelinating vsdenervation).6 Electromyography and nerve-conductionstudies are often used early for initial diagnosis, but theseare more invasive than diaphragm pressure measurementsand require a skilled operator.

Recovery can occur over months to years, depending onthe cause of paralysis. Hypothermia injury to the phrenicnerve is reversible, usually over several months.5 Idiopathicneuralgic amyotrophy or viral neuropathy may recoverover years. Many cases of idiopathic phrenic-nerve paral-ysis never resolve.8 Neuromuscular causes of diaphragm

Table 2. Pulmonary Function Test Abnormalities in BilateralDiaphragm Paralysis

Forced expiratory volume in the first second(% predicted)

50

Vital capacity (% predicted) 45Supine vital capacity (%) Decrease � 40Total lung capacity (% predicted) 55Residual volume (% predicted) 55Functional residual capacity (% predicted) 60Maximum inspiratory pressure (cm H2O) �10 to �20Transdiaphragmatic pressure (cm H2O) 40–10

(Adapted from Reference 6.)

Table 1. Causes of Diaphragmatic Paralysis

NeuropathiesCentral nervous system lesion

Amyotrophic lateral sclerosisMultiple sclerosisSpinal cord transectionPoliomyelitisCervical spondylosis

Peripheral nervous system lesionParsonage-Turner brachial plexus neuropathyGuillain-Barré syndromeIdiopathic neuralgic amyotrophyPeripheral neuropathy secondary to diabetesChronic inflammatory demyelinating polyneuropathy

Phrenic nerve dysfunctionCardiac surgery hypothermia injury and stretchingBlunt traumaTumor, aneurysm, or goiter compressionPost-viral phrenic neuropathyIdiopathic phrenic neuropathyCervical chiropractic manipulation

MyopathiesLimb-girdle muscular dystrophyAcid maltase deficiencyHypothyroidism or hyperthyroidismDermatomyositisSystemic lupus erythematosusMixed connective-tissue diseaseMalnutritionVitamin B6 and B12 deficiencyAmyloidosisIdiopathic myopathy

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paralysis are most often permanent. The median delay indiagnosis is reportedly 2 years (range 6 wk to 10 y).1

Delay is more common in ventilator-dependent patients.Treatment is supportive while awaiting recovery. Pa-

tients often develop progressive hypercapnia and hypoxiadue to atelectasis and reduced vital capacity.4 Nocturnalhypoventilation is treated via positive-pressure ventilation.With isolated diaphragm paralysis and no other neuromus-cular impairment, NIV is preferred to invasive mechanicalventilation. Nocturnal bi-level NIV via nasal or face maskwithout tracheostomy was recently adopted.1 This preservespatient independence and improves quality of life. Phrenic-nerve pacing requires a functional nerve, so it cannot beused if the cause of diaphragm paralysis is phrenic-nerve

injury. The procedure has had some success in patientswith spinal-cord injury but requires an invasive thoracot-omy. Recently, surgeons developed a laparoscopic ap-proach to placement of intramuscular electrodes in thediaphragm, with early encouraging results. In one inves-tigational series, 3 of 5 tetraplegics were able to achieveventilator independence.9

Bilateral diaphragm paralysis should be considered incases of new-onset dyspnea that is most severe in thesupine position. The diagnosis should be suspected in pa-tients with neuropathic and myopathic diseases, recenttrauma or surgery to the neck or chest, and in patientswithout apparent risks. Clues to prompt transdiaphragm-atic pressure measurement are low lung volumes, reducedMIP, and a supine drop in vital capacity. Although dia-phragm paralysis may be permanent, treatment with noc-turnal NIV may restore patients to near-normal functionalstatus and improve quality of life.

REFERENCES

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2. Schram DJ, Vosik W, Cantral D. Diaphragmatic paralysis followingcervical chiropractic manipulation: case report and review. Chest2001;119(2):638-640.

3. Benditt JO. Esophageal and gastric pressure measurements. RespirCare 2005;50(1):68-75.

4. Celli BR. Respiratory management of diaphragm paralysis. SeminRespir Crit Care Med 2002;23(3):275-281.

5. Tokuda Y, Matsumoto M, Sugita T, Nishizawa J, Matsuyama K,Yoshida K, Matsuo T. Bilateral diaphragmatic paralysis after aorticsurgery with topical hypothermia: ventilatory assistance by means ofnasal mask bilevel positive pressure. J Thorac Cardiovasc Surg 2003;125(5):1158-1159.

6. Aldrich TK, Tso R. The lungs and neuromuscular diseases. In: Mur-ray JF, Nadel JA, editors. Murray and Nadel’s textbook of respira-tory medicine, 4th edition. Philadelphia: Saunders; 2005:2285-2290.

7. Schoenhofer B, Koehler D, Polkey MI. Influence of immersion inwater on muscle function and breathing pattern in patients withsevere diaphragm weakness. Chest 2004;125(6):2069-2074.

8. Lin PT, Andersson PB, Distad BJ, Barohn RJ, Cho SC, So YT, et al.Bilateral isolated phrenic neuropathy causing painless bilateral dia-phragmatic paralysis. Neurology 2005;65(9):1499-1501.

9. DiMarco AF, Onders RP, Ignagni A, Kowalski KE, Mortimer JT.Phrenic nerve pacing via intramuscular diaphragm electrodes in tet-raplegic subjects. Chest 2005;127(2):671-678.

Fig. 3. Schematic of setup and placement of sensors to measureesophageal, gastric, and transdiaphragmatic pressures.

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