Neuromuscular Disorders in the ICU

Published on 22/03/2015 by admin

Filed under Critical Care Medicine

Last modified 22/03/2015

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 1027 times

37 Neuromuscular Disorders in the ICU

Abnormal neuromuscular function may precipitate a patient’s admission to an intensive care unit (ICU) or may develop as a consequence of another critical illness and its treatment. This chapter focuses primarily on respiratory failure due to neuromuscular disease but also addresses autonomic dysfunction occurring in this setting. To facilitate understanding of the concepts involved, a brief review of the motor unit and its physiology is provided and specific muscles critical to ventilation are identified.

image The Motor Unit and Its Physiology

Central nervous system activity designated for motor output is ultimately conducted to lower motor neurons, also known as alpha motor neurons. A motor unit is composed of a lower motor neuron and its distal ramifications, its neuromuscular junctions, and the muscle fibers it innervates. The cell bodies of the lower motor neurons are located in the brainstem for cranial musculature and in the anterior horn of the spinal cord for somatic muscles. At the level of the brainstem or spinal cord, the motor neurons receive various excitatory and inhibitory inputs. Motor axons project through the subarachnoid space and penetrate the dura mater as nerve roots. They may join with other motor axons and with sensory and autonomic fibers in a plexus and then travel in peripheral nerves to the muscles they innervate. Alpha motor neurons are myelinated, a feature that accelerates nerve impulse propagation. The multiple terminal ramifications of the motor neuron synapse on individual muscle fibers.

The motor axon communicates with muscle via a specialized area termed the neuromuscular junction. On the presynaptic side of the neuromuscular junction, the neurotransmitter acetylcholine is synthesized, packaged in vesicles, and stored for release. Depolarization of the axon opens presynaptic voltage-gated calcium channels, which activate the molecular machinery responsible for drawing the vesicles to the presynaptic membrane. The vesicles then fuse with the membrane and release acetylcholine into the synaptic cleft. Acetylcholine molecules bind to receptors on the postsynaptic membrane and cause an influx of sodium, which in turn increases the muscle end-plate potential. When the end-plate potential exceeds the threshold level, the muscle membrane becomes depolarized. This depolarization releases calcium ions from the sarcoplasmic reticulum, and muscle contraction occurs through a process known as excitation-contraction coupling. After activating the acetylcholine receptor complex, the acetylcholine molecule is degraded by cholinesterase; the choline released by this reaction is then recycled by the presynaptic neuron.

image Muscles of Respiration

Three muscle groups may be defined based on their importance for respiration (Figure 37-1):1


Figure 37-1 Major respiratory muscles.

Inspiratory muscles are indicated on the left and expiratory muscles are indicated on the right.

(From Garrity ER. Respiratory failure due to disorders of the chest wall and respiratory muscles. In: MacDonnell KF, Fahey PJ, Segal MS, editors. Respiratory Intensive Care. Boston: Little, Brown; 1987, p. 313.)

The upper airway muscles receive their innervation from the lower cranial nerves. Sternomastoid innervation arrives predominantly from cranial nerve XI, with a small contribution from C2. The phrenic nerve originates from cell bodies located between C3 and C5, with a maximum contribution from C4, and innervates the diaphragm. Innervation to the scalenes arises from C4 to C8, whereas that of the parasternal intercostals is from T1 to T7. The intercostal muscles receive innervation from T1 to T12, and the abdominal musculature receives it from T7 to L1. Reference to this innervation scheme is important in understanding the effects of spinal cord and nerve root injuries on respiration and for the differential diagnosis of disorders producing apparently diffuse weakness.

Clinical Presentation of Neuromuscular Respiratory Failure

Patients experiencing respiratory dysfunction due to neuromuscular disease typically present with a combination of upper airway dysfunction and diminished tidal volume (VT). Difficulty with swallowing liquids, including respiratory secretions, is the most typical presentation of pharyngeal weakness, although some patients have an equal or greater degree of difficulty with solid food. A hoarse or nasal voice may also signal problems with the upper airway. These conditions are noted in patients who are at risk for aspiration and present with difficulty with attempts at negative-pressure ventilation (cuirass or iron lung), because the weakened muscles may not be able to keep the airway open as the pressure falls.2 Paradoxical abdominal movement (inward movement of the abdomen during inspiration) is an important sign of diaphragmatic weakness.3

Loss of VT occurs most dramatically with diaphragmatic weakness but also follows insults that affect the ability of the parasternal intercostals to keep the chest wall expanded against negative intrapleural pressure. This is most apparent in lower cervical spinal cord injuries where atelectasis commonly develops despite preserved phrenic nerve function. This problem usually diminishes over weeks as the parasternal intercostal muscles develop spasticity.

Patients with progressive generalized weakness (e.g., Guillain-Barré syndrome) commonly begin to lose VT before developing upper airway weakness. To maintain minute ventilation, and therefore carbon dioxide excretion, a patient’s respiratory rate increases. Respiratory rate is thus one of the most important clinical parameters to monitor. As the vital capacity falls from the norm of about 65 to 30 mL/kg, a patient’s cough weakens, and clearing secretions becomes difficult. A further decrease of vital capacity to 20 to 25 mL/kg results in an impaired ability to sigh with progressive atelectasis. At this point, hypoxemia may be present because of ventilation-perfusion mismatching and because an increasing percentage of VT is used to ventilate dead space. Before the vital capacity reaches 18 mL/kg, a patient should be in an ICU, because respiratory failure is imminent and endotracheal intubation should be considered. The precise point at which mechanical ventilation is necessary varies with the patient, the underlying condition, and especially with the likelihood of a rapid response to treatment.

Regardless of the vital capacity, however, indications for intubation and mechanical ventilation include evidence of fatigue, hypoxemia despite supplemental oxygen administration, difficulty with secretions, and a rising PaCO2. In the absence of hypercapnia, occasional patients (e.g., those with myasthenia gravis) can be managed under very close observation in an ICU with less invasive techniques (e.g., bilevel positive airway pressure [BiPAP]).4

In addition to vital capacity, trended measurements of the maximum inspiratory pressure (PImax, more typically recorded as negative inspiratory force [NIF]), are useful indicators of ventilatory capacity. Inability to maintain a PImax greater than 20 to 25 cm H2O usually indicates a need for mechanical ventilation. Although the maximum expiratory pressure (PEmax) is a more sensitive indicator of weakness,5 it has not proved to be as useful as an indicator of the need for mechanical ventilation. A more detailed discussion of these variables and their use may be found elsewhere.6,7

Because a patient with neuromuscular respiratory failure has intact ventilatory drive,8 the fall in VT is initially matched by an increase in respiratory rate, keeping the PaCO2 normal or low until the vital capacity becomes dangerously reduced. Many patients initially maintain their PaCO2 in the range of 35 mm Hg because of either (1) a subjective sense of dyspnea at low VT or (2) hypoxia from atelectasis and increasing dead space. When the PaCO2 begins to rise in this circumstance, abrupt respiratory failure may be imminent.

The modest degree of hypoxia in most of these patients worsens when the PaCO2 begins to rise, displacing more oxygen from the alveolar gas. However, aspiration pneumonia and pulmonary embolism are also frequent causes of hypoxemia in these patients. To determine the relative contributions of these conditions to a patient’s hypoxemia, one can use a simplified version of the alveolar gas equation as follows (derived elsewhere)6,7:

where PAO2 is the alveolar partial pressure of oxygen, PIO2 is the partial pressure of inspired oxygen (in room air, 150 mm Hg), and R is the respiratory quotient (on most diets, about 0.8). This allows estimation of the alveolar-arterial oxygen difference (PAO2 − PaO2). Under ideal circumstances in young people breathing room air, this value is about 10 mm Hg, but it rises to about 100 mm Hg when the fraction of inspired oxygen (FIO2) is 1.0. The alveolar air equation allows one to factor out the contribution of hypercarbia to the decrease in arterial partial pressure of oxygen (PaO2); it should be used to determine whether there is a cause of significant hypoxemia in addition to the displacement of oxygen by carbon dioxide.

Patients with orbicularis oris weakness may have artifactually low vital capacity and NIF measurements because they cannot form a tight seal around the spirometer mouthpiece. The need for nursing and respiratory therapy personnel who are experienced in the care of these patients is thus underscored. It is also important for physicians to observe these patients directly rather than relying solely on reported measurements. The physical findings associated with neuromuscular respiratory failure are reviewed elsewhere.6,7 Among the most important findings are rapid, shallow breathing,9 the recruitment of accessory muscles, and paradoxical movement of the abdomen during the respiratory cycle. Fluoroscopy of the diaphragm is occasionally valuable for the diagnosis of diaphragmatic dysfunction.10

Autonomic dysfunction commonly accompanies some of the neuromuscular disorders requiring critical care, such as Guillain-Barré syndrome, botulism, and porphyria (Table 37-1). In Guillain-Barré syndrome (discussed later) dysautonomia is common and may arise in parallel with weakness or may follow the onset of the motor disorder after one week or more.

TABLE37-1 Neuromuscular Causes of Acute Respiratory Failure

Location Disorder Associated Autonomic Dysfunction?
Spinal cord Tetanus112 Frequent
Anterior horn cell Amyotrophic lateral sclerosis113 No
  Poliomyelitis No
  Rabies Frequent
  West Nile virus flaccid paralysis No
Peripheral nerve Guillain-Barré syndrome Frequent
  Critical illness polyneuropathy No
  Diphtheria No, but cardiomyopathy and arrhythmias may occur
  Porphyria Occasional
  Ciguatoxin (ciguatera poisoning) Occasional
  Saxitoxin (paralytic shellfish poisoning) No
  Tetrodotoxin (pufferfish poisoning) No
  Thallium intoxication No
  Arsenic intoxication114,115 No
  Lead intoxication No
  Buckthorn neuropathy No
Neuromuscular junction Myasthenia gravis No
  Botulism116 Frequent
  Lambert-Eaton myasthenic syndrome117 Yes, frequent dry mouth and postural hypotension
  Hypermagnesemia118 No
  Organophosphate poisoning No
  Tick paralysis No
  Snake bite No
Muscle Polymyositis/dermatomyositis No
  Acute quadriplegic myopathy No
  Eosinophilia-myalgia syndrome119 No
  Muscular dystrophies120 No, but cardiac rhythm disturbances may occur
  Carnitine palmitoyl transferase deficiency No
  Nemaline myopathy121 No
  Acid maltase deficiency122 No
  Mitochondrial myopathy123 No
  Acute hypokalemic paralysis No
  Stonefish myotoxin poisoning No
  Rhabdomyolysis No
  Hypophosphatemia124 No

image Neuromuscular Disorders

Many chronic neuromuscular disorders and other central nervous system conditions affecting the suprasegmental innervation and control of respiratory muscles eventually compromise ventilation. In this chapter, however, we emphasize the more common acute and subacute neuromuscular disorders that precipitate or prolong critical illness due to ventilatory failure and autonomic dysfunction. A more complete listing of neuromuscular diseases appears in Table 37-1; reviews of this subject11,12 or the references listed in Table 37-1 may be consulted for details of the more rare disorders. Some of the diseases listed (e.g., Lambert-Eaton myasthenic syndrome) rarely cause respiratory failure in isolation but may be contributing causes in the presence of other conditions13 such as neuromuscular junction blockade intended only for the duration of a surgical procedure.14

Neuromuscular Diseases Precipitating Critical Illness

Guillain-Barré Syndrome

Guillain-Barré syndrome, or acute inflammatory demyelinating polyradiculoneuropathy, is typically a motor greater than sensory peripheral neuropathy with subacute onset, monophasic course, and nadir within 4 weeks. Although the precise etiology is unknown, Guillain-Barré syndrome is immune mediated and related to antibodies directed against peripheral nerve components. Approximately 1.7 cases occur per 100,000 population per year.15 Most patients suffer a demyelinating neuropathy, but in about 5% of cases the condition is a primary axonopathy.16 Numerous antecedents have been implicated17; the more frequent ones are listed in Box 37-1. The association with antecedent infections suggests that certain agents may elicit immune responses involving antibodies that cross-react with peripheral nerve gangliosides. In particular, the development of ganglioside antibodies has been observed in Guillain-Barré syndrome after Campylobacter jejuni infections, such as GM1 antibodies in axonal forms of Guillain-Barré syndrome18 and GQ1b antibodies in the Miller-Fisher variant of Guillain-Barré syndrome.19

The initial findings of patients with Guillain-Barré syndrome are subacute and progressive weakness, usually most marked in the legs, associated with sensory complaints but without objective signs of sensory dysfunction.20 Deep tendon reflexes are often significantly reduced or absent at presentation, though this finding may take several days to develop. The cerebrospinal fluid (CSF) typically reveals an albuminocytologic dissociation or elevated protein content without pleocytosis; this may not evolve until the second week of illness. The major reason to examine the CSF is to preclude other diagnoses. Although mild CSF lymphocytic pleocytosis (10-20 cells/mm3) may suggest the possibility of associated human immunodeficiency virus (HIV) infection, in most patients, the nucleated cell count is less than 10 cells/mm3.21 Although they may be normal initially, results of electrodiagnostic studies (motor and sensory nerve conduction studies and needle electromyography) often reflect segmental nerve demyelination with multifocal conduction blocks, temporally dispersed compound muscle action potentials, slowed conduction velocity, and prolonged or absent F waves.22 Differential diagnostic considerations for patients with suspected Guillain-Barré syndrome are primarily those listed in the “Peripheral Nerve” section of Table 37-1.

The components of treatment for patients with Guillain-Barré syndrome are as follows:

Patients with Guillain-Barré syndrome with evolving respiratory failure should generally be intubated when the vital capacity falls to about 15 mL/kg or when difficulty with secretions begins, because the response to treatment is slow. If a patient has been immobile for several days before intubation and neuromuscular junction blockade is needed, a nondepolarizing agent should be used to avoid transient hyperkalemia. Oral intubation is again being viewed as preferable to the nasal route, because the endotracheal tube is frequently required for a week or longer, raising the risk of sinusitis with nasal intubation.

Many patients are too weak to trigger the ventilator; in such cases, the assist/control or intermittent mandatory ventilation mode is initiated. Weaning patients with Guillain-Barré syndrome from mechanical ventilation must wait for adequate improvement in strength. We usually shift to pressure support ventilation for weaning, although evidence of its superiority over intermittent mandatory ventilation or synchronized intermittent mandatory ventilation modes is only anecdotal. Although the majority of patients require mechanical ventilation for less than 4 weeks, as many as one-fifth need 2 or more months of support before they can breathe without assistance. Improvement in vital capacity to greater than 15 mL/kg and in NIF to greater than 25 cm H2O suggests that a patient has improved enough to begin weaning from the ventilator. A formula using a combination of ventilatory and gas exchange variables may allow more accurate determination of a patient’s ability to be weaned.23

Autonomic dysfunction related to Guillain-Barré syndrome most typically presents as a hypersympathetic state and is often heralded by unexplained sinus tachycardia. The blood pressure may fluctuate wildly. Patients may rarely experience bradycardic episodes, which may require temporary pacing. Autonomic surges during tracheal suctioning or due to a distended viscus may be very dramatic and should be minimized. Autonomic failure and pulmonary embolism are now the major causes of mortality in Guillain-Barré syndrome.

Nursing care for patients with Guillain-Barré syndrome is similar to that for other paralyzed and mechanically ventilated patients, but special care must be taken to remember that patients with Guillain-Barré syndrome are completely lucid. In addition to explaining any procedures carefully, arranging for distractions during the daytime (e.g., television, movies, conversation, visitors) and adequate sleep at right is very important. For the most severely affected patients, sedation should be considered. In concert with physical and occupational therapists, passive exercise should be performed frequently throughout the day.

Deep venous thrombosis is a significant danger for patients with Guillain-Barré syndrome. Episodic arterial desaturation is a common event, presumably owing to transient mucus plugging; submassive pulmonary emboli may therefore be overlooked. Adjusted-dose heparin (to slightly prolong the partial thromboplastin time) should be given, and sequential compression devices should be used on the legs; therapeutic anticoagulation may be considered. The risk of fatal pulmonary embolism extends through the initial period of improvement until patients are ambulatory.

Nutritional support should begin as soon as a patient is admitted, with appropriate concern for the risk of aspiration.24 Most mechanically ventilated patients with Guillain-Barré syndrome can be fed via soft, small-caliber feeding tubes; autonomic dysfunction affecting the gut occasionally requires total parenteral nutrition.

Immunotherapy for Guillain-Barré syndrome includes removal of autoantibodies with plasma exchange or immune modulation with high-dose intravenous immunoglobulin (IVIg). The efficacy of plasma exchange has been evaluated in a Cochrane systematic review of six class II trials comparing plasma exchange alone with supportive care.25 Most of the trials employed up to 5 plasma exchanges of 50 mL/kg over 2 weeks. In a large North American trial,25 the time needed to improve one clinical grade (being weaned from the ventilator or being able to walk) was reduced by 50% in the plasma exchange group by comparison with the control group. There was no significant benefit when plasma exchange was begun later than 2 weeks after symptom onset. A meta-analysis demonstrated more rapid recovery in ventilated patients treated with plasma exchange within 4 weeks of onset.26 The optimal number of plasma exchanges has been assessed in patients with mild (unable to run), moderate (unable to stand without assistance), and severe (requiring mechanical ventilation) Guillain-Barré syndrome by the French Cooperative Group.27 On the basis of this trial, two exchanges are better than none in mild Guillain-Barré syndrome; four are better than two in moderate Guillain-Barré syndrome; and six are no better than four in severe Guillain-Barré syndrome. Albumin is the preferred replacement solution.28 Treatment with IVIg for Guillain-Barré syndrome has also been examined in a Cochrane systematic review. Three randomized controlled trials demonstrated class I evidence that IVIg (2 g/kg over 2-5 days) is as effective as plasma exchange in Guillain-Barré syndrome patients with impaired walking.29 Complication rates were somewhat higher in the plasma exchange groups. A large international multicenter randomized trial compared plasma exchange (50 mL/kg × 5 exchanges over 8-13 days), IVIg (0.4 g/kg × 5 days), and plasma exchange followed by IVIg.30 No significant outcome differences between these therapies were found with respect to functional improvement at 4 weeks or at 48 weeks.

Buy Membership for Critical Care Medicine Category to continue reading. Learn more here