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Home , Paralysis, Respiratory arrest

33434ournal ofNeurology, , and 1993;56:334-343

NEUROLOGICAL EMERGENCY J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.4.334 on 1 April 1993. Downloaded from Acute neuromuscular respiratory paralysis

R A C Hughes, D Bihari

This article reviews the recognition, diagnosis The severity of is related and management of respiratory failure in primarily to the number and nature of the acute . Respiratory muscle groups disabled by the primary dis- failure requiring occurs in ease. Weakness of the diaphragm has differ- about 14% of patients with Guillain-Barre ent effects from weakness of the intercostal syndrome (GBS),' a small percentage of and abdominal muscles. The diaphragm is patients with and inserted at an acute angle into the lower bor- polymyositis, and also in acute rhabdomyoly- der of the ribcage, pulls the ribcage upwards sis and a wide range of other less common and enlarges the cross-sectional area of the disorders (tables 1-3). Neuromuscular disor- thorax. At the same time the dome of the ders are responsible for only a tiny proportion diaphragm moves caudally and elongates the of admissions to most intensive care units, 23 thoracic cavity. As the diaphragm descends (1 1 %) of 2097 consecutive admissions to our the anterior abdominal wall is forced own unit in the last two years. Of those cases, anteriorly. Thus the action of the diaphragm 15 (60%) required mechanical ventilation is to move both the ribcage and the abdomen and two (8 7) died in hospital. The APACHE outwards. During quiet and III study in North America2 documented nearly all the work of breathing is performed neuromuscular disease as the cause of inten- by the diaphragm. sive care unit admission in only 45 patients When the diaphragm is paralysed, expan- (026%) of the cohort of 17 440 patients with sion of the ribcage is performed by the acces- a 15-6% unadjusted hospital mortality rate. sory muscles of respiration. When the ribcage These figures exclude those patients who expands, the fall in intrapleural pressure were admitted to the intensive care unit moves the flaccid diaphragm cephalad into because of operation or systemic disease and the thorax and the anterior abdominal wall, then developed neuromuscular disease which being coupled to the diaphragm movement caused respiratory failure or delayed weaning through the abdominal contents, moves off the ventilator. Respiratory failure occur- passively inwards during inspiration. This ring in the setting of chronic progressive neu- "paradoxical abdominal movement" is most romuscular disease, such as, Duchenne marked in the supine posture since gravity muscular dystrophy and motor neuron dis- assists the cephalad movement of the abdom- ease, presents a challenging management inal contents. The change in volume of the http://jnnp.bmj.com/ problem which is outside the scope of this ribcage is partly absorbed by the cephalad review. movement of the abdominal contents and the volume of air inspired is reduced. In the upright posture gravity partially counteracts Pathophysiology the upward movement of the abdominal con- Respiratory failure is particularly dangerous tents and improves the efficiency of the acces- when it is caused by neuromuscular rather sory muscles producing inspiration. on September 27, 2021 by guest. Protected copyright. than lung disease because its development Consequently, in diaphragmatic paralysis, may be insidious and unrecognised until sud- patients use the accessory muscles of respira- den decompensation causes life threatening tion, become distressed when supine and . The arterial hypoxaemia of these have smaller supine than erect vital capaci- patients is the result of both ties. Furthermore, the majority of neural and also microatelactasis arising from the drive to the muscles Acute neuromuscular respiratory during sleep respiratory paralysis retention of secretions.3 occurs is directed to the phrenic nerves, so that R A C Hughes only as a late feature in this form of respirato- patients with diaphragm paralysis are particu- D Bihari ry failure and usually heralds an impending larly prone to hypoventilation during sleep. Department of respiratory arrest. Bulbar involvement in the Patients with intact diaphragms but , UMDS, Guy's Hospital, primary disease process may prevent clearing impaired intercostal and abdominal muscle London of secretions and cause upper airway obstruc- function show paradoxical ribcage movement. R A C Hughes tion and significant pulmonary aspiration. As the diaphragm lowers intrapleural pressure Intensive Care Infection of the lower may during inspiration the intercostal spaces and Department, Guy's supervene at any stage and contribute to a the upper move inwards because of Hospital, London ribcage D Bihari further deterioration in pulmonary gas the lack of intercostal muscle tone. In the Correspondence to exchange. Underlying these changes is the upright posture, gravity pulls the abdominal Professor R AC Hughes, profound respiratory muscle dysfunction contents caudally and the flaccid anterior Department of Neurology, UMDS, Guy's Hospital, which interferes with the usual process of abdominal wall bulges anteriorly. The London SEI 9RT, UK. spontaneous breathing.4 diaphragm is thus flattened and shortened Acute neuromuscular respiratory paralysis 335

Table 1 Peripheral neuropathies which cause respiratory failure and a normal or reduced respiratory rate. All J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.4.334 on 1 April 1993. Downloaded from Condition Specific test Specific treatment such patients should be monitored from the outset, especially during sleep, by pulse GBS (demyelinating form) nerve conduction block PE IVIg? GBS (axonal form) small CMAPs PE IVIg? oximetry for the early detection of arterial relatively normal MCV desaturation. Clinical assessment however, is CIDP nerve conduction block PE IVIg? S Critical illness polyneuropathy'415 - better than blood gas analysis in assessing the Toxins: need for ventilatory support. As respiratory Organophosphates77 red cell cholinesterase atropine, pralidoxime plasma pseudo- failure worsens, the patient becomes increas- cholinesterase ingly anxious, and though exhausted, may be Thallium'° whole blood thallium Berlin blue Arsenic'7,779 24 hour urine arsenic dimercaprol, DMSA unable to sleep. Additional bulbar weakness Lead"9 8 whole blood lead sodium calcium or insensitivity with the attendant danger of edetate, DMSA Gold"' dimercaprol inhalation is particularly hazardous. Lithium82 plasma lithium haemodialysis Although the decision to intubate and start Drugs: vincristine2' withdrawal Lymphoma2' nerve biopsy cytototoxics artificial ventilation depends primarily on the Vasculitis: systemic lupus erythematosus8' nerve biopsy S cyclophosphamide overall clinical assessment, quantitative Metabolic: acute intermittent porphyria25 urine porphobilinogen avoidance of precipitants iv haematin assessment and monitoring of respiratory Hereditary tyrosinaemia28 urine d-ALA high calorie intake muscle function are helpful. The most conve- liver transplant Diphtheria84 throat swab culture antitoxin nient method is the measurement of vital Buckthorn neuropathy (central America)85 capacity. A common error is to measure peak Abbreviations: PE = plasma exchange expiratory flow because devices for its mea- IVIg = intravenous immunoglobulin surement have always been more readily CIDP = chronic idiopathic demyelinating polyradiculoneuropathy S = steroids available on a general medical ward. MCV = maximum conduction velocity Fortunately, small portable electronic devices d-ALA = delta-aminolaevulinic acid DMSA = 2,3 dimercaptosuccinic acid79 are now available for monitoring respiratory frequency, tidal volume and vital capacity at and is inefficient in lifting the ribcage and the bedside in the spontaneously breathing elongating the thorax. In this situation respi- patient. Care is needed to educate the patient ratory distress may be experienced in the to obtain a meaningful measurement since upright position. The resultant poor vital facial weakness may prevent an adequate lip capacity and inability to contribute to seal around a mouth piece. In such cases, a ventilatory failure. padded, tightly fitting face mask attached to the measuring device may help. As a rule of thumb ventilatory support of some form Clinical diagnosis ofneuromuscular should be considered when the vital capacity respiratory failure in an adult falls to less than one litre. The The danger of respiratory failure should be exact figure depends upon the predicted nor- considered in every patient with progressive mal vital capacity for the weight and age of weakness, especially if the upper limbs and the individual concerned. bulbar muscles are involved. The patient Maximal static respiratory pressures (maxi- complains of weakness and fatigue but, unlike mum inspiratory pressure, PMmax, measured at a patient with parenchymal lung disease or residual volume; maximum expiratory pres-

airways obstruction, does not appear wheezy sure, PEmax, measured at total lung capacity) http://jnnp.bmj.com/ or cyanosed. Instead, the patient prefers to sit obtained whilst breathing against an occluded or lie still in bed, becomes breathless on talk- mouthpiece are said to be more sensitive ing or swallowing, and uses the accessory indicators of respiratory muscle weakness.5 A muscles of respiration (pectoral, scalene, ster- PEmax of less than 40 cm H,O (adult normal = nocleidomastoid, and levators of the nostrils). 100 cm H,O) has been associated with an Diaphragm weakness may be detected by inability to cough and clear secretions ade- indrawing of the abdominal wall, that is, quately whereas a PImax > -20 cm H,O (adult paradoxical abdominal movement. Whilst the normal < -70 cm H,O) precludes effective on September 27, 2021 by guest. Protected copyright. respiratory rate may be rapid and shallow, ventilation with the maintenance of a normal and the observation chart may show an arterial CO, tension. Nevertheless, a falling increase in heart and respiratory rate over the vital capacity approximates these changes previous few hours, this is not invariable and with impaired clearance of secretions occur- some patients present with ventilatory failure ring at around a vital capacity of less than 30 ml/kg and frank ventilatory failure at less than 10 ml/kg. Further assessment can be obtained Table 2 Disorders of neuromuscular transmission which cause respiratory failure by the measurement of transdiaphragmatic pressure during tidal breathing and on maxi- Condition Specific test Specific treatment mal inspiration. Such studies may be coupled Myasthenia gravis27 edrophonium test PE S with the measurement of the diaphragm anti AChR antibody Anticholinesterase overdose negative edrophonium test drug withdrawal EMG, but this is not routinely performed Antibiotic-induced paralysis'0 _ drug withdrawal outside research centres. Hypermagnesaemia29 plasma Mg iv calcium EMG increment on 50 Hz stimulation Botulism32 injection of serum into mice antitoxin Snake, scorpion and spider bite'2 identifying the snake antitoxin Diagnosis of the cause Fish, shellfish, crab identifying the fish varies CENTRAL CAUSES poisoning32 33 86 '2 34 finding the tick removal Diseases of the nervous system can cause res- Eaton-Lambert syndrome27 EMG increment on PE S failure the stimulation piratory by damaging respiratory repetitive centre in the medulla or its connections with 336 Hughes, Bihari

Table 3 Disorders of muscle which cause acute respiratoryfailure ical substrate also includes an acute axonal J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.4.334 on 1 April 1993. Downloaded from Condition Specific test Specific treatment form which may have an explosively rapid onset and be associated with a particularly Hypokalaemial8 plasma K + K + Polymyositis40 plasma CK S slow and incomplete recovery." The neuro- EMG physiological diagnosis of the axonal form of muscle biopsy Acute rhabdomyolysis40 EMG urine alkalinisation GBS requires the demonstration of reduction muscle biopsy in evoked muscle and nerve action potentials Hypophosphataemia39 plasma phosphate phosphate Acid maltase deficiency" PAS stain ofblood film without marked slowing or conduction block. Combined neuromuscular muscle biopsy withdrawal If the nerves are already inexcitable by the blockade and steroids28 Barium intoxication88 plasma K + iv K + time of the first neurophysiological study, the oral magnesium sulphate distinction between demyelination and axonal haemodialysis degeneration may need to be made by biopsy, preferably of a motor nerve.'2 1' The other causes of neuropathy (table 1) can be ruled out by a careful history. Critical the cervical and thoracic . In prac- illness polyneuropathy occurs in the setting of tice the commonest causes are the secondary an extremely ill patient who is being ventilat- consequences of central nervous system ed, has had sepsis and multiorgan failure, and depression by drugs or metabolic abnormali- cannot be weaned from the ventilator. It is ties or of primary cerebral or brain stem dis- due to an axonal neuropathy and its distinc- ease. These are important in differential tion from the axonal form of GBS may be diagnosis but this review is confined to disor- merely semantic. The aetiology of critical ill- ders affecting the lower motor neuron, ness polyneuropathy is not known but may be peripheral nerves, multifactorial.'4 5 Careful enquiry about pos- and muscles. The localisation of the disease sible toxin exposure as a cause of polyneu- process to the brain stem or spinal cord does ropathy is always necessary. Poisoning with not usually present the neurologist with any organophosphates or heavy metals severe difficulty because of the presence of symp- enough to cause a neuropathy with respirato- toms and signs at the level of the lesion and ry failure has usually been preceded by an involvement of the long tracts. acute illness with vomiting and an altered Poliomyelitis remains a common problem level of consciousness. Prominent cutaneous in Eastern Europe, the Middle East and the and muscular pain, especially in the feet, and Indian subcontinent. It should still be consid- preservation of the reflexes in the early stages ered in the differential diagnosis of acute flac- should raise the suspicion of thallium poison- cid paralysis throughout the world, especially ing.16 Painful tingling and weakness begin when sensory deficit is absent, the onset is within one to five days from ingestion of thal- asymmetrical and the CSF shows a pleocyto- lium, before the characteristic hairfall. In sis.6 I The diagnosis may be confirmed by cul- arsenic poisoning the early clinical picture turing the stool, and sometimes a throat swab sometimes closely resembles GBS and neuro- or CSF, and by finding a rising titre of neu- physiological changes may initially show par- tralising antibody in the serum. tial conduction block and slowing of

conduction before giving way to changes sug- http://jnnp.bmj.com/ gestive of axonal degeneration.17 is Peripheral neuropathy causing respiratory extremely rare in developed countries but failure can usually be diagnosed clinically cases were recently reported from Sweden,'8 from the gradual evolution of ascending or and the diagnosis should be considered in sometimes descending weakness associated patients with a recent upper respiratory infec- with paraesthesiae and sensory deficit and tion, especially if there is prominent palatal reduced or absent tendon reflexes. involvement.19 Buckthorn neuropathy need Difficulties in diagnosis arise in rapidly evolv- only be suspected in those who have con- on September 27, 2021 by guest. Protected copyright. ing pure motor neuropathies, especially in the sumed berries in Mexico.20 Drugs usually earliest stages when the tendon reflexes may cause an insidiously progressive distal be preserved. Also paraesthesiae occur in axonopathy without respiratory involvement, occasional cases of toxic neuromuscular con- but acute paralysis with respiratory failure duction block, including .8 occurred in a patient being treated with vin- Guillain-Barre syndrome (GBS) is so cristine, possibly due to coincidental GBS.2' much more common than any of the other Both T and B cell lymphomas may cause causes of neuromuscular respiratory failure acute neoplastic infiltration of the peripheral that there is a danger that other causes and nervous system which closely resembles particularly other causes of neuropathy will GBS.22-24 Sometimes acute neuropathy is the be overlooked.' 9 The diagnosis of GBS can- presenting feature of the lymphoma. not be made by any diagnostic test but Vasculitic neuropathy rarely causes respirato- requires the exclusion of other causes. These ry failure and usually only does so in the set- are listed in table 1. In most cases the patho- ting of a systemic illness with cutaneous, logical process is inflammatory, demyelinat- renal and lung involvement. Acute neuropa- ing, and probably autoimmune.' The thy occurs in acute intermittent , presence of demyelination can be confirmed usually after abdominal pain and vomiting, by the neurophysiological demonstration of but sometimes as the presenting feature.25 It multifocal conduction block.'0 However, GBS may be diagnosed during attacks by detecting is a heterogeneous condition whose patholog- increased urine porphobilinogen excretion, a Acute neuromuscular respiratory paralysis 337

test which should be undertaken in every case depressed reflexes which are enhanced after J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.4.334 on 1 April 1993. Downloaded from of undiagnosed acute neuromuscular paraly- exercise, and confirmed by electrophysiologi- sis. Recurrent neuropathy in infants is a cal tests showing an increment in muscle feature of hereditary tyrosinaemia.26 amplitude following repeti- tive nerve stimulation.27 It may be associated NEUROMUSCULAR JUNCTION DISORDERS with a small cell lung carcinoma or autoim- Respiratory failure can herald disorders of the mune disease. neuromuscular junction, which can be distin- guished from neuropathic causes by the MYOPATHY absence of sensory deficit and preservation of Respiratory failure in muscle disease usually tendon reflexes. In myasthenia gravis respira- occurs insidiously following progressive prox- tory failure usually occurs in the setting of imal weakness, which has evolved over established disease which has failed to months or years, and presents with nocturnal respond to conventional treatment. Even in hypoventilation causing morning headache an acute case the diagnosis is usually evident and daytime sleepiness. This form of respira- because of , facial weakness and bulbar tory failure may develop in the advanced palsy with muscle fatigue. The diagnosis can stages of severe muscular dystrophy and also be confirmed by the injection of intravenous in polymyositis. Sometimes, especially in edrophonium, neurophysiogical tests, and a myotonic dystrophy, the respiratory failure is positive test for receptor anti- worsened by depression of central respiratory bodies in a reliable laboratory.27 In treated drive. When the ventilatory reserve has fallen myasthenia, weakness can be caused by over- so far that the vital capacity is less than 55% dosage of anticholinesterase drugs causing of its predicted normal, there is a grave dan- depolarisation cholinergic block. This will be ger that an intercurrent lung infection will accompanied by diarrhoea, colic, excessive precipitate respiratory failure.'5 In acid mal- salivation and small pupils and will be wors- tase deficiency the diaphragm is particularly ened rather than improved by intravenous severely affected and the patient may present edrophonium. with respiratory failure before consulting a Other causes of neuromuscular junction neurologist about weakness.'6 Acid maltase blockade are rare and the diagnosis is usually deficiency should be suspected if there is obvious from the clinical setting. Botulism proximal upper limb weakness and marked should be suspected when acute descending wasting of the paraspinal muscles, and con- paralysis has been heralded by autonomic fea- firmed by seeking glycogen-containing gran- tures, dry mouth, constipation, poorly reac- ules in the lymphocytes which stain red with tive pupils, and ptosis and bulbar palsy. periodic acid Schiffs reagent applied to a These symptoms have usually been immedi- blood film.37 ately preceded by nausea, vomiting, abdomi- When a patient presents with flaccid paral- nal pain and diarrhoea from eating foul ysis and respiratory failure over a few hours smelling food contaminated by Clostridium or days, a correctable electrolyte disturbance botulinum.28 Severe hypermagnesaemia can be should be sought immediately. The feature produced by magnesium-containing antacids which distinguishes muscle disease from neu- and aperients in patients with impaired renal ropathy is the preservation of the reflexes and http://jnnp.bmj.com/ function. The increased magnesium interferes the absence of sensory symptoms or signs. with the release of acetylcholine so as to cause Hypokalaemia induced by potassium loss weakness which may develop into respiratory from the gut or kidneys is the commonest failure.29 The aminoglycoside and polymyxin cause and is probably responsible for the antibiotics and some other drugs also cause muscle fibre necrosis in acute rhabdomyolysis neuromuscular blockade by interfering with which occurs following some drugs, such as

the release of acetylcholine.30 This is usually carbenoxolone.'8 Severe hypophosphataemia on September 27, 2021 by guest. Protected copyright. only significant when weaning infected can also cause paralysis requiring respiratory patients off ventilation." Physicians practising failure. It is usually precipitated by parenteral in the tropics have to cope with a much wider glucose infusions in alcoholic patients.'9 range of toxic causes of neuromuscular con- Acute rhabdomyolysis is a rare condition in duction blockade whose diagnosis will be which acute muscle necrosis causes the very obvious from the history (table 2).32 Fish or rapid onset of muscle pain, tenderness, shellfish toxin poisoning (usually Caribbean swelling and weakness sometimes severe or Pacific fish) causes a gastrointestinal upset enough to cause respiratory failure. The mus- before the development of weakness.'2" In cle enzyme concentrations, including creatine North America paralysis is sometimes caused kinase, are markedly increased in the plasma, by the bite of a female tick whose saliva con- and the EMG shows myopathic changes and tains an unidentified toxin which probably spontaneous . A muscle biopsy is also interferes with neuromuscular conduc- necessary to confirm the diagnosis and will tion.'234 The tick may be difficult to find but show massive muscle fibre necrosis and often its removal is reported to be curative. numerous regenerating fibres but relatively Respiratory failure occurs in the Lambert- little inflammation. The neurological picture Eaton myasthenic syndrome, but only rarely is overshadowed by the development of myo- and then usually in the setting of gradually globinuria and acute renal failure. Causes of progressive weakness. The diagnosis may be acute rhabdomyolysis are alcohol abuse, suggested clinically by autonomic symptoms, viruses (influenza, Coxsackie B5, ECHO 9, including a dry mouth, the finding of adenovirus 21, Epstein-Barr), mycoplasma,40 338 Hughes, Bihani

and a wide variety of drugs, especially potas- cheal intubation is especially harmful during J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.4.334 on 1 April 1993. Downloaded from sium-lowering drugs, amphetamine-like the weaning period when a weak patient is agents, barbiturates, and the combination of asked to make some effort whilst receiving the pancuronium and corti- graded reductions in ventilatory support. costeroids.3041 If the causative agent is with- Following pre-oxygenation, etomidate, pro- drawn and the patient can be nursed through pofol or a benzodiazepine () may the period of respiratory and renal failure, be used to render the patient unconscious regeneration of the necrotic muscle and full and this on its own-in the presence of recovery are usual. cricoid pressure-may be sufficient for the Respiratory muscle involvement was a pre- experienced operator to perform the neces- senting feature in 4% of 118 patients with sary laryngoscopy and intubation. A non- polymyositis. More commonly it developed depolarising muscle relaxant (atracurium, later, contributing to in 14%.42 vecuronium) in adequate doses will abolish Neuromuscular respiratory failure may be all remaining muscular tone and can improve worsened by simultaneous interstitial infiltra- the inexperienced operator's ability to visu- tion and fibrosis of the lungs.40 Inflammatory alise the . Suxamethonium should changes in muscle are usually so extensive never be used in this setting because of that the diagnosis can be readily confirmed by reports of ventricular tachycardia and asystole the increased plasma creatine kinase concen- caused by a sudden rise in serum potassium tration, myopathic EMG with additional in patients with denervated muscles.4445 spontaneous discharges, and inflammatory Cricoid pressure should always be used since changes in a muscle biopsy. although patients may not have eaten for some time before the induction of anaesthe- sia, gastric stasis and ileus are common par- Institution of mechanical ventilation ticularly in the early stages of the GBS. The decision to institute respiratory support Following successful tracheal intubation, a depends much more on the clinical state of nasogastric tube (if not already present) the patient than on any physiological mea- should be placed to facilitate the initiation of surement. Arterial blood gas analysis is not enteral nutrition. particularly helpful. Intervention is required to prevent the development of arterial hypox- aemia and carbon dioxide retention before Management during mechanical they become life threatening. Continuous ventilation administered by face GENERAL PRINCIPLES mask may be useful in the temporary correc- The principles which govern management tion of arterial hypoxaemia but is uncomfort- during mechanical ventilation centre upon able and poorly tolerated for prolonged three primary concerns-access to the airway periods of time. It has little effect on CO2 with the provision of adequate pulmonary gas retention although it may reduce the work of exchange, the maintenance of nutrition and breathing by correcting any reduction in the prevention of nosocomial infection. Other functional residual capacity in patients with issues, very often taken for granted but which retention and atelectasis. require special attention, include the need for http://jnnp.bmj.com/ Nevertheless, it is only a "stop-gap" measure scrupulous nursing care to avoid nerve com- used to avoid tracheal intubation in a small pression syndromes and bed sores; physio- minority of cases in whom some basic treat- therapy with the provision of splints to ment, for example, drug therapy or plasma prevent irreversible contractures and joint exchange, will reverse the primary disease immobilisation; subcutaneous heparin for the process. On the whole, it is safer to proceed prophylaxis of deep venous thrombosis; pre- rapidly to tracheal intubation to ensure con-

vention of deep vein thrombosis; and finally, on September 27, 2021 by guest. Protected copyright. trol of the airway, adequate oxygenation, ven- extensive psychological support throughout tilation and tracheal toilet (especially in the period of their illness when an individual patients with an inadequate cough reflex) and patient with neuromuscular disease is entirely the prevention of pulmonary aspiration. dependent upon his attendants and the Intubation is best performed by a skilled mechanical ventilator. Keeping a paralysed operator in the setting of an intensive care but conscious patient comfortable requires unit. This requires referral and involvement careful positioning and frequent gentle repo- of the intensive care medical staff at an early sitioning: sitting up, expecially out of bed, stage to prevent any emergency intervention may help and is good for morale. A particular on a general medical ward. Intubation is best problem in patients with GBS is the manage- achieved by the oral route following adequate ment of autonomic dysfunction which can intravenous sedation in combination with result in wide fluctuations in pulse and blood muscle relaxation. Whilst it is often said that pressure as well as a wide variety of atrial and nasotracheal tubes are a well tolerated alter- ventricular arrhythmias.' 45 native, we have found them to be unsuitable because they carry a high risk of sinusitis,43 AIRWAY ACCESS AND MECHANICAL and their extra length with the narrow inter- VENTILATION nal diameter makes them more difficult to Most patients who develop respiratory failure aspirate adequately and increases the resis- as a consequence of neuromuscular dysfunc- tance of the ventilatory circuit. Any increase tion will require a tracheostomy. Whilst in work of breathing associated with nasotra- mechanical ventilation via an orotracheal tube Acute neuromuscular respiratory paralysis 339

can be performed for a limited period of time tures of ileus. In our experience these features J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.4.334 on 1 April 1993. Downloaded from (usually for 5-7 days in our unit), a tra- have usually.been related to the excessive use cheostomy simplifies management consider- of sedatives, especially opiates. Early tra- ably and allows the withdrawal of all cheostomy and the subsequent withdrawal of sedation.46 The tracheostomy tube is well tol- all sedation (other than simple night sedation erated, gives excellent access for tracheal toi- to ensure an appropriate sleep pattern) will let and chest physiotherapy and since the reduce the incidence of ileus. Diarrhoea usu- patient can be placed on and off different ally reflects the administration of broad spec- forms of respiratory support at will, permits trum antimicrobials rather than any effect of easier "weaning". Tracheostomy can now be enteral nutrition. It should be treated sympto- performed at the bedside, using a percuta- matically and every effort made to withdraw neous Seldinger technique, and this appears the offending antibiotics. to be the preferred technique.47 Nevertheless, tracheostomy by whatever method is not PREVENTION OF NOSOCOMIAL INFECTION without risk (infection of the stoma; primary The prevention of hospital acquired infection and secondary haemorrhage). is at the heart of good intensive care prac- In the absence of severe pulmonary aspira- tice.54 It is especially important in patients tion or infection, it is not difficult to achieve requiring prolonged mechanical ventilation adequate pulmonary in these since uncontrolled nosocomial sepsis is likely patients. Initially, most patients are too weak to be an important cause of death in those to generate an adequate negative pressure. to cases who die in the intensive care unit. "trigger" the ventilator and so require "con- Several studies have demonstrated an associa- trolled ventilation". More modem ventilators, tion between the likelihood of developing a for example, the Siemens Servo 300, have a nosocomial and the number of different method of triggering which requires days of mechanical ventilation.55 Prevalence the patient to change a baseline flow within rates vary enormously from unit to unit and the machine rather than to reduce a pressure. reflect local practices and resources. Every These machines are much more sensitive to intensive care unit should have a written the respiratory efforts of a patient and should infection control policy developed in conjunc- theoretically be beneficial in management. In tion with local microbiological experts. fact, no particular kind of ventilation or venti- Central issues are local practices of hand- lator has been shown to be superior in sup- washing, nursing numbers, strict intravenous porting these patients and most intensivists line/urinary catheter and antimicrobial poli- rely on pressure support or some combination cies, the avoidance of gastric alkalinization of intermittent mandatory ventilation with with H, antagonists and antacids, and an pressure support to provide an adequate tidal infection surveillance programme. These volume and minute ventilation. Positive end- aspects concerning the organisation of inten- expiratory pressure (with a pressure of 3-6 sive care are fundamental in the prevention of cm H,0) together with physiotherapy is infection in individual cases. used in the often vain attempt to prevent Recently, the practice of "selective decont- atelectasis. amination of the digestive tract" has been proposed as another means of reducing the http://jnnp.bmj.com/ PROVISION OF NUTRITION incidence of unit-acquired gram negative Every effort should be made to feed these infections.56 This method requires the appli- patients early via the enteral route.48 Whilst it cation of a paste of nonabsorbable antimicro- is impossible to prevent muscle wasting relat- bials (most commonly the combination of ed to denervation, loss of muscle bulk will tobramycin, polymyxin and amphotericin) to only be more exaggerated if an external the oropharynx and via the nasogastric tube,

source of calories and nitrogen is not forth- to the stomach. It has been best studied in on September 27, 2021 by guest. Protected copyright. coming.49 Muscle wasting is particularly patients following multiple trauma and major marked in those cases who develop nosoco- surgery. Whilst several studies have demon- mial sepsis and may contribute to a prolonga- strated reductions in the incidence of infec- tion of the period of dependence on tion using this technique, no influence on mechanical ventilation.50 Use of the enteral survival has been observed. Many believe that route ensures that the gastrointestinal mucosa selective decomtamination only works well in does not atrophy and the integrity of gut bar- the setting of a high nosocomial infection rate rier is maintained. Theoretically this should and we do not use it. contribute to the prevention of nosocomial infection by reducing the likelihood of AUTONOMIC DYSFUNCTION translocation of bacteria and endotoxin from In respiratory paralysis due to acute neuropa- the lumen of the gut into the portal venous thy, and especially in GBS, autonomic dys- circulation and lymphatic system.51 Parenteral function is common.'4557-59 Tachycardia with nutrition on the other hand, especially that loss of sinus arrhythmia are usual. Rapid fluc- containing large amounts of intravenous fat, tuations of pulse and blood pressure and may contribute to an increased risk of sepsis sweating may occur and are sometimes the and is best avoided.525' It may be difficult to harbingers of asystole. In particular tracheal establish enteral nutrition in occasional suction may cause bradycardia and asystole. patients with an ileus. A distended abdomen This can usually be prevented by hyperoxy- and large nasogastric aspirates with the genation beforehand but if it persists it may absence of bowel sounds are the usual fea- be necessary to use atropine and even an 340 Hughes, Bihani

endocardial pacemaker. Serious arrhythmias expensive, it is not usually more expensive usually only occur in patients who need venti- than PE and it is more widely available and J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.4.334 on 1 April 1993. Downloaded from lation but we have had a patient with early simpler to give. Because GBS has such a vari- GBS who developed asystole before needing able prognosis and results are available from ventilation. We monitor the ECG from the only one relatively small "open label" trial,68 time of admission in all patients with GBS it would be premature to replace PE with who have any sign of respiratory or bulbar IVIg as the preferred treatment for GBS and involvement. Although the bladder is spared we await the outcome of an international trial in the early stages of GBS, it may be affected which is comparing PE alone with IVIg alone in severe cases and bladder catheterisation is and PE followed by IVIg. In the meantime we often needed as part of the intensive care of recommend IVIg whenever PE is impractical. the ventilated patient. Postural is common when the patient is being mobilised MYASTHENIA GRAVIS so that the blood pressure should be moni- After establishing with an edrophonium test tored. This is best done with the aid of a tilt that a patient has respiratory failure due to table. myasthenia gravis the dose of anti- cholinesterase drugs should be optimised. The vital capacity should be monitored Specific interventions before and after small (2 mg) doses of intra- GUILLAIN-BARRE SYNDROME venous edrophonium. Swallowing is usually In two large randomised trials, patients with impaired and a nasogastric tube is often GBS who received plasma exchange (PE) needed. Pyridostigmine should be given oral- recovered more quickly than those not so ly or via the nasogastric tube, but when enter- treated.6"6' PE should therefore be offered to al fluids cannot be absorbed, neostigmine all patients with GBS who have such severe should be given intramuscularly, substituting disease that they require assistance to walk. It each 60 mg of pyridostigmine with 1 mg of seems logical to give it as early as possible, neostigmine. preferably during the first week, and its value Patients with myasthenia gravis respond so after the second week is doubtful, although so dramatically in the short term to PE that a long as the disease is still progressing it would controlled trial has never been undertaken. be worth using PE. In the North American We use 50 ml/kg exchanges on alternate days trial continuous flow PE appeared more until an adequate response has been effective than intermittent flow although achieved, usually after two to five exchanges. intermittent flow was better than none.62 Improvement is usually noticeable after the There is no information concerning the rela- second exchange and lasts for about four to tive merits of filtration compared with cen- six weeks. Similar clinical benefit and falls in trifugation systems. Albumin is the preferred anti-acetylcholine receptor antibody have exchange fluid since fresh frozen plasma been reported following IVIg. The largest caused more reactions and was no more published experience is that of Cosi et at9 effective.6' The North American trial who reported clinical improvement 12 days exchanged 200-250 ml/kg body weight (four after a standard course of 0'4 g/kg in 70% of

to five plasma volumes) over seven to 14 37 patients treated which lasted for 60 days in http://jnnp.bmj.com/ days, and the French trial two plasma vol- 57%. Arsura et al70 reported improvement in umes on alternate days for a total of four 11 of 12 patients beginning 3-6 days after exchanges. It is not known whether more IVIg treatment began, reaching a maximum exchanges would be more effective, but after 8 6 days and lasting an average of 52 10-25% of patients show a limited relapse days. Sustained improvement has been main- after one to six weeks and usually respond to tained with repeated courses in a small num- a further PE.6364 We space five 50 ml/kg PEs ber of cases.7' Judgement of the relative over 14 days and add further exchanges if merits of PE and IVIg must await compara- on September 27, 2021 by guest. Protected copyright. there is a subsequent relapse; tive trials. In the meantime it would be rea- Although steroids might have been expect- sonable to try IVIg to treat a myasthenic crisis ed to be beneficial in GBS, neither a small if PE is not available. trial of oral prednisolone nor a large double- Since PE provides only temporary relief, masked trial of intravenous methyl- immunosuppressive treatment should be prednisolone 500 mg daily for 5 days started, or increased, at the same time. We demonstrated any benefit.6566 follow the practice of Newsom-Davis27 and Much interest surrounds the possible use use prednisolone 120 mg on alternate days. of intravenous immunoglobulin (IVIg) as an In patients with early respiratory failure alternative to PE. A recent Dutch trial steroids should be introduced slowly and cau- showed that the rate of recovery was similar tiously because of the danger of a transient or possibly slightly faster in patients treated worsening during the first week or two of the with IVIg 0.4 g/kg daily for 5 days compared course. In patients with established respirato- with those treated with PE. The median time ry failure on artificial ventilation, this cautious to walk unaided was 55 days in 75 patients approach is superfluous and a full dose of treated with IVIg and 69 days in the same steroids can be started immediately. Very number treated with PE (p = 0-07 two- large doses of steroids, including boluses of tailed). Lung and circulatory complications intravenous methylprednisolone, should be were more common in the PE treated group avoided because of the danger of inducing than the IVIg group.67 Although IVIg is necrotic myopathy.7' For patients who are Acute neuromuscular respiratory paralysis 341

inadequately controlled with steroids we add tion to be placed on a spontaneous mode of J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.4.334 on 1 April 1993. Downloaded from azathioprine. If azathioprine is not tolerated, ventilation. At this stage, lung compliance other immunosuppressive agents, such as and spontaneous minute ventilation should cyclophosphamide or methotrexate, and as a be relatively normal with a stable cardiovas- last resort, low dose total body irradiation can cular system. We prefer pressure support as a be tried. When the respiratory failure due to weaning mode and it is our practice to reduce myasthenic crisis has been controlled younger gradually the amount of pressure support patients and those with thymoma should be while monitoring the clinical appearance of assessed for thymectomy. the patient, respiratory rate, tidal volume, and arterial saturation by pulse oximetry. Daily POLYMYOSITIS measurements of vital capacity are also per- Treatment of polymyositis with large doses of formed but it is not clear how helpful these steroids is universally recommended and so are in the assessment of the recovery of respi- clearly helpful, at least in the short term, that ratory muscle function. One study has clearly a controlled trial has never been considered demonstrated that tidal volume rather than necessary. A typical regime, recommended by vital capacity is more closely related to recov- Mastaglia and Ojeda,40 is prednisone 60 to 80 ering diaphragm function.76 However, we mg/kg daily for 6 to 8 weeks followed by have not found the more complex assess- gradual withdrawal at the rate of 5 mg of the ments of diaphragmatic performance such as daily dose per week. After the dose has maximum transdiaphragmatic pressure reached 30 mg daily further reductions (PDjimax) or inspiratory time fraction (T[/Tt.) should be made at 2-5 mg per week. useful in the withdrawal of ventilatory sup- However, a wide range of doses are used: port in these cases. some prefer an alternate day dose but others As respiratory muscle strength increases, it feel that this is not so effective.40 It is impor- is possible to ask the patient to breathe for tant to bring the disease under control before longer periods off the ventilator, either on beginning the reduction and then to monitor continuous positive airways pressure or a T- the course of the disease closely with serial piece. A relatively low level of pressure sup- measurements of muscle strength and plasma port (10 cm H,O) is usually maintained creatine kinase concentrations. Although PE overnight to allow a patient to rest and to pre- combined with cyclophosphamide has been vent nocturnal hypoxaemia. Many patients reported beneficial in polymyositis,73 the use- find that this period of ventilator withdrawal fulness of PE alone was not confirmed in a provokes extreme anxiety because of psycho- controlled trial in which three groups of 13 logical dependence on the presence and the patients were treated with leukopheresis, PE, sound of the ventilator. Careful assessment of or sham PE.74 The authors of that trial claim respiratory function and extensive psychologi- an 80% power of detecting a minimal cal support are required to meet the physical improvement in functional capacity. The trial and emotional needs of the patient. did not answer the question whether PE fol- lowed by immunosuppression would provide a more rapid response than immunosuppres- The aftermath sion alone. Further exploration of this possi- Prevention of death from respiratory failure is http://jnnp.bmj.com/ bility would be worthwhile since the PE merely the first stage in treatment of an illness group had a highly significant fall in plasma such as GBS. Maintenance of morale and creatine kinase concentration compared with recognition and treatment of depression are the sham PE group. Intravenous important and difficult tasks which call on all immunoglobulin was dramatically effective in the resources of the intensive care team. For two cases resistant to steroids and immuno- some conditions patient support groups exist

suppressive drugs,75 but its usefulness which offer counselling services (for example, on September 27, 2021 by guest. Protected copyright. requires more study. Immunosuppressive Guillain-Barre Syndrome Support Group treatment with azathioprine, cyclophos- International, PO Box 262, Wynnewood, Pa phamide or methotrexate have often been 19096, USA; Guillain-Barre Syndrome tried when steroids have failed,40 but they Support Group, Foxley, Holdingham, probably do not have the rapid effect neces- Sleaford, Lincs NG34 8NR, UK). There are sary to prevent or reverse the acute onset of no easy guidelines. The patient and the fami- respiratory failure. In desperation, total body ly need clear information about what is hap- low dose irradiation has sometimes been used pening" and what may be expected. and remissions have occurred in those cases Over-optimistic prognoses may be greeted which have been published.40 eagerly at first but reap a grim harvest of dashed hopes later. Above all, a conscious patient festooned with monitoring equipment Withdrawal ofmechanical ventilation in a modern intensive care unit needs a sym- The course of respiratory failure related to pathetic caring approach tailored to his or her neuromuscular disease is extremely variable. own needs. Various factors such as the primary diagnosis, chronic health status, treatment and the pres- We thank our colleagues and the nursing staff of Russell Brock and Starling Wards for their help, Dr L Loh, Radcliffe ence or absence of supervening complications Infirmary, Oxford, Dr D F Moore, Guy's Hospital Poisons dictate the rate of recovery. It eventually Information Service, and Professor CM Wiles, University of Wales, Cardiff for advice, and the Medical Research Council becomes evident that an individual patient and Guillain-Barr6 Syndrome Support Group for financial has regained adequate neuromuscular func- support. 342 Hughes, Bihari

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70 Arsura EL, Bick A, Brunner NG, Namba T, Grob D. 80 Watt G, Theakston RDG, Hayes CG, et al Positive J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.4.334 on 1 April 1993. Downloaded from High dose intravenous immunoglobulin in the manage- response to edrophonium in patients with neurotoxic ment of myasthenia gravis. Arch Intern Med 1986; envenoming by cobras (Naja Naja Philippinensis) A 146:1365-8. placebo controlled study. N Etngl _7 Afed 1986; 71 Arsura E, Bick A, Brunner NG, Grob D. Effects of 315:1444-8. repeated doses of intravenous immunoglobulin in myas- 81 Vernay D, Dubost JJ, Thevent JP, Sauvezie B, Rampon S. thenia gravis. An, J Med Sci 1988;295:438-43. "Choree fibrillaire de Morvan" followed by Guillain- 72 Panegyres P, Squier M, Mills KR, Newsom-Davis J. Barre syndrome in a patient receiving gold therapy. Acute myopathy associated with large parenteral corti- Arthritis Rheunm 1986;29:1413-14. costeroid dosage in myasthenia gravis. J Neuerol 82 Brust JCM, Hammer JS, Challenor Y, Healton EB, Lesser Neurosurg Psychiatry 1993;56:(in press). R. Acute generalized polyneuropathy accompanying 73 Dau PC. Plasmapheresis in idiopathic inflammatory lithium poisoning. Ann Neurol 1979;6:360-2. myopathy. Experience with 35 patients. Arch Neurol 83 Hughes RAC, Cameron JS, Hall SM, Heaton J, Payan JA, 1981 ;38:544-52. Teoh R. Multiple mononeuropathy as the initial presen- 74 Miller FW, Leitman SF, Cronin ME, et al Controlled trial tation of systemic lupus erythematosus-nerve biopsy of plasma exchange and leukapheresis in polymyositis and response to plasma exchange. _7 Neuirol 1982; and dermatomyositis. New Engl Jf Med 1992;326: 228:239-47. 1380-4. 84 Christie AB. Diphtheria. In: Weatherall DJ, et al, eds. 75 Jann S, Beretta S, Moggio M, Adobbati L, Pellegrini G. Oxford textbook of medicine. Oxford: Oxford University High-dose intravenous human immunoglobulin in Press, 1987;5:164-5. polymyositis resistant to treatment. 7 Neurol Neurosurg 85 Calderon-Gonzalez R, Gonzalez-Cantu N, Rissi- Psychiatry 1992;55:60-62. Hernandez H. Recurrent polyneuropathy with pregnan- 76 Borel CO. Diaphragmatic performance during recovery cy and oral contraceptives. N Engl _7 Mvfed 1970;282: from acute ventilatory failure in Guillain-Barre syn- 1307-8. drome and Myasthenia Gravis. Chest 1991;99:444-5 1. 86 Senanayake N, Roman GC. Toxic neuropathies in the 77 Senanayave N, Johnson MK. Acute polyneuropathy after tropics. Journal of Tropical and Geographic Neuirology poisoning by a new organophosphate insecticide. New 1991;1:3-15. Englj Med 1982;306: 155-7. 87 Danon MJ, Carpenter S. Myopathy with thick filament 78 Greenberg C, Davies S, McGowan T, Schorer A, Drage (myosin) loss following prolonged paralysis with vecuro- C. Acute respiratory failure following severe arsenic nium during steroid treatment. Afluscle Nerve poisoning. Chest 1979;76:596-8. 1991;14:1131-9. 79 Graziano JH. 2,3-dimercaptosuccinic acid (DMSA). In: 88 Gould DB, Sorrell MR, Lupariello AD. Barium sulfide Goldfranks LR, et al, eds. Toxicological Enmergencies. poisoning. Arch Intern Med 1973;132:891-4. Norwalk, Ct: Appleton and Lange, 1990:638-40.

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Emanuel Swedenborg (1688-1772) Swedenborg, best known for his mystic and religious beliefs, also made important contributions to science. He received his formal education in Uppsala, where his father Jesper Svedberg) was Professor of Theology. Soon after Swedenborg's death, his devoted followers created Swedenborgian societies dedicated to the study of his work. He produced a new design for a dry dock, machinery for working salt springs and a system for moving large boats overland. He devised a method of calculating longitude at sea by the stars, invented an ear trumpet, began the science of crysallography, drew up plans for a http://jnnp.bmj.com/ machine gun, a submarine and an aeroplane. As assessor for the Royal Bureau of Mines he also devoted himself to the improvement of the Swedish metal mining industry. His concepts of representation of the cerebral cortex were astonishingly modern. He observed that the muscles of the extremities were controlled by the upper frontal convolutions, those of the abdomen and thorax by the on September 27, 2021 by guest. Protected copyright. middle frontal convolutions, and those of the head and neck by the lower frontal convolutions. Swedenborg also studied the cerebrospinal fluid, the pituitary gland (which he called the arch gland) and proposed the concept of upper and lower motor neuron. He constructed a type of Cathedral at Uppsala, not far from that of Linnaeus. He neuron theory based on the observations of Malpighi and was initially reburied with the wrong skull which had, Leeuwenhoek. until then, remained in England. In 1936 Swedenborg Swedenborg died on 29 March 1772 in London and was honoured with this stamp to mark the 250th anniver- was buried there in the Swedish Lutheran church. In sary of his birth (Stanley Gibbons 201, 202; Scott 266, 1908 the Swedish Government brought his remains back 267). to Sweden, and they now lie in a large tomb in the L F HAAS