Although this is not a chapter on muscle disease, there are some disease states which have enhanced the understanding of the physiology of the neuromuscular junction. Moreover, there are also some disease states that impact the safety and effectiveness of neuromuscular blocker use. Most of the diseases which are directly related to the neuromuscular junction, such as myasthenia gravis and Eaton-Lambert syndrome, are rare in the pediatric population.
Myasthenia gravis is caused by antibodies to the acetylcholine receptor at the neuromuscular junction, and is characterized by rapid fatigue of muscles, demonstrated by inability to per- form such tasks as sustained upward gaze or sustained head lift. Children with myasthenia gravis will be exquisitely sensitive to neuromuscular blockers. The Eaton-Lambert syn- drome is also an immune-mediated disorder of neuromuscular transmission associated with muscle weakness. In contrast to myasthenia gravis, however, it is associated with impaired release of acetylcholine as autoantibodies are formed against the presynaptic voltage-gated calcium channels. In this syndrome, there tends to be improved muscle function with activity as the result of accumulation of presynaptic calcium and improved release of acetylcholine.
Conditions which can lead to the proliferation of acetylcholine receptors are not uncom- mon in children. Such conditions include denervation injuries, burns, major trauma, immo- bility, and intracranial disorders. A decrease in acetylcholine release or prolonged inhibition can lead to increased acetylcholine receptor density at the motor end-plate. In addition, severe injury can also lead to the proliferation of extrajunctional acetylcholine receptors found along the muscle membrane. This proliferation of receptors makes the patient more sensitive to the depolarizing neuromuscular blockers (and all of the potential adverse effects, especially hyperkalemia), and less sensitive to the non-depolarizing agents. This prolifera- tion of receptors is evident within several hours of lower motor neuron injury, and the effects
Conditions such as denervation injuries, burns, major trauma, immobility, and intracranial disorders can lead to the prolif- eration of acetylcholine receptors in children. This proliferation of receptors makes the patient more sensitive to the depolarizing neuromuscular blockers (and all of the potential adverse effects, especially hyperkalemia), and less sensitive to the non-depolarizing agents.
last for at least several months. The onset of these effects after upper motor neuron injury is somewhat slower, and high risk has been documented out to 6 months.
The muscular dystrophies may also lead to abnormalities in the acetylcholine receptors.
Although innervations are relatively normal in these conditions, post-synaptic acetylcholine receptors are a mixture of fetal- and adult-type receptors. The preponderance of fetal acetyl- choline receptors in the dystrophic muscle likely represents the effect of muscle regeneration rather than dystrophic muscle. Although fetal-type receptors are less sensitive to neuromus- cular blocking agents than the adult-type, the patient response to blockade and reversal is unpredictable. In fact, patients with muscular dystrophy may be unusually sensitive to non- depolarizing agents. Finally, hyperkalemia and cardiac arrest have been clearly documented following succinylcholine administration in patients with undiagnosed muscular dystrophies.
REVIEW QUESTIONS
1. Which of the following statements is true regarding non-depo- larizing neuromuscular inhibition?
A. Acetylcholinesterase inhibitors are not site specifi c and cause increased concentration of acetylcholine at all receptor sites, including muscarinic receptors.
B. Both of the acetylcholine receptor binding sites must be bound by an antagonist to prevent channel opening, but only one site needs to be occupied by acetylcholine in order to open the channel.
C. Reversal of a non-depolarizing neuromuscular blockade using a pharmacologic reversal agent is independent of the concen- tration of the neuromuscular blocking medication.
D. The degree of neuromuscular inhibition is independent of the ratio of the concentrations of acetylcholine and antagonist.
E. When a reversal agent is administered, activation of acetyl- cholinesterase produces an increased concentration of acetyl- choline which fosters binding of acetylcholine to the acetylcholine receptors and neuromuscular activation.
2. Transmission through the acetylcholine receptor may be infl u- enced by mechanisms that change receptor function without af- fecting the receptor binding site. The three most common mech- anisms by which this occurs includes receptor desensitization, channel blockade, and the phase II block. Which of the following most accurately describes the process of desensitization?
A. Desensitization occurs at neuromuscular junctions continu- ously in contact with depolarizing agents when the membrane potential returns to normal, but the depolarizing agent is still present.
B. Desensitization occurs when a conformational change within the acetylcholine receptor subunits maintains the receptor in an inactive state such that attachment of an agonist does not lead to opening of the channel.
C. Desensitization only occurs when both sites of the acetylcho- line receptor are bound by neuromuscular antagonists.
D. Desensitization results from a structural change in the acetyl- choline receptor subunits, but does not alter the dynamic func- tion of the receptor.
E. Desensitization results from the inhibition of the fl ow of ions at the level of the acetylcholine receptor by a variety of medi- cations at dosages clinically used.
3. Which of the following muscle groups is MOST resistant to neuromuscular blockade?
A. The adductor pollicis B. The diaphragm C. The masseter D. The orbicularis oculi E. The quadriceps femoris
4. A 3 year old child has required intermittent neuromuscular blockade to facilitate effective mechanical ventilation for acute lung injury. From a pulmonary standpoint, he is ready to be extubated. You wish to confi rm that he has no residual neuro- muscular blockade. In addition to your clinical exam, you per- form a train of four peripheral nerve stimulation. Which of the following train of four responses is most indicative of a patient without residual neuromuscular blockade?
A. A decrease in the amplitude of the muscle contraction of only the fi rst response (T1).
B. A decrease of muscle contraction that is observed only in the height of the fourth response (T4).
C. A steady decrease in the amplitude of the muscle contractions over the four responses, but with some documented response to the fourth stimuli.
D. A train-of-four ratio greater than 0.5 with other clinical vari- ables and risk factors suggestive of no residual neuromuscular weakness.
E. Four muscle contractions of equal strength in response to four supramaximal stimuli given at 2 Hz.
5. A 16 year old male with a spinal cord injury is being re-ad- mitted to the pediatric intensive care unit from the rehabilita- tion unit for intubation and mechanical ventilation secondary to nosocomial pneumonia. In preparing for the intubation, the bedside nurse asks if you would like her to draw up succinyl- choline. Which of the following would be your best response to her suggestion?
A. Denervation injuries can lead to an increased acetylcholine receptor density at the motor end-plate, and thus, twice the dose of succinylcholine will be needed.
B. Denervation injuries can lead to an increased acetylcholine receptor density at the motor end-plate, but only after years
of decreased acetylcholine release or prolonged inhibi- tion, and thus, the usual dose of succinylcholine may be administered.
C. Denervation injuries can lead to an increased acetylcholine receptor density at the motor end-plate making the adolescent more sensitive to the effects of succinylcholine, and thus, its use should be avoided.
D. Denervation injuries can result in a decrease in acetylcholine receptor density at the motor end-plate, and thus, only half the dose of succinylcholine will be required.
E. Denervation injuries should not affect the acetylcholine recep- tor density at the motor end-plate, and thus, the usual dose of succinylcholine may be administered.
ANSWERS
1. A 2. B 3. B
4. E 5. C
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Saunders Elsevier; 2007. p. 2554–9. Chapter 611.
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SUGGESTED READINGS
178
Assessment of Neurologic Function
LEARNING OBJECTIVES
Describe examination techniques important in the
■
assessment of neurologic function. Include cortical, brain stem and spinal examinations of the child with altered mental status.
Differentiate upper motor neuron pathology from
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lower motor neuron pathology.
Understand the utility and limitations of the Glasgow
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coma scale.
Appreciate dermatomal distribution of peripheral
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nerves.
Describe fi ndings in herniation syndromes.
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Describe spinal syndromes and their unique physical
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examination fi ndings.
Describe the components of a brain death
■
examination.
Describe the technique, clinical applications and
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limitations of intracranial pressure monitoring in the child with intracranial hypertension.
Understand the differences between intracranial
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monitoring devices.
Understand indications, contraindications and analysis
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of cerebrospinal fl uid and opening pressure measurement.
Understand the indications for the use of
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electroencephalography and evoked potentials in the neurologically compromised child.
Review indications and limitations of neuroimaging
■
techniques.
CHAPTER OUTLINE
Learning Objectives Introduction Examination
Consciousness Brainstem Spinal Cord
Neuromuscular Junction
Assessment of Cerebral Blood Flow Intracranial Pressure Monitoring Evaluation of Cerebral Spinal Fluid Neurophysiologic Monitoring
Electroencephalogram Evoked Potentials Train of Four Neuroimaging Biomarkers Conclusion Review Questions Answers
Suggested Readings
INTRODUCTION
Despite multiple advances in neuroimaging, monitoring of intracranial hemodynamics, and electrodiagnosis, serial neurological examinations remains the primary method to detect clinical changes in the child with potential or ongoing neurologic impairment. Neurologic dysfunction must be discriminated from sedation, residual anesthesia, neuromuscular block- ade and psychological adjustment to the pediatric intensive care unit (PICU) environment.
Toxins, infections, metabolic diseases and hypoxia tend to cause generalized cerebral dys- function with relative sparing of the brainstem structures. Tumors, trauma and focal isch- emia tend to cause localized lesions that can manifest as neurologic dysfunction involving the cerebral hemispheres, brainstem or both.
E LIZABETH E . S CARLETT , B RANDI N . P EACHEY, AND J ILL M . G OTOFF
The most important component of neurologic assessment of the patient in the PICU is serial evaluation of level of consciousness .
This chapter will explore the various modalities for the neurologic assessment of the critically ill pediatric patient using physical examination, ICP monitoring, CSF analysis, neurophysiologic monitoring, imaging modalities and biomarkers.