Weaning failure due to acute neuromuscular disease.
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Biomedical subjects
Publications and source records attributed to C F Bolton.
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Five patients with a clinical diagnosis of acute Guillain-Barré polyneuropathy (GBP) had electrically inexcitable motor nerves. All were quadriplegic. One patient died and 3 of the 4 survivors showed poor recovery. Autopsy studies on the patient who died showed severe axonal degeneration in nerve roots and distal nerves without inflammation or demyelination. Electrophysiological studies in these patients suggested that the predominant process was axonal degeneration. These cases may represent a separate clinicopathological entity, and constitute a variant of GBP characterized by an acute axonal neuropathy.
A polyneuropathy of varying severity has been observed in association with sepsis and critical illness in 15 patients. Since clinical evaluation is often difficult, electrophysiological studies provided definitive evidence for polyneuropathy. These revealed reductions in the amplitudes of compound muscle and sensory nerve action potentials, the most marked abnormality. Near-nerve recordings confirmed such reductions for sensory fibres. Needle electromyography revealed signs of denervation of limb muscles. Phrenic nerve conduction and needle electromyographic studies of chest wall muscles suggested that the polyneuropathy partially explained difficulties in weaning patients from the ventilator, an early clinical sign. No defect in neuromuscular transmission was demonstrated, despite the use of aminoglycoside antibiotics in some patients. In those who survived the critical illness, clinical and electrophysiological improvement occurred. The 15 critically ill polyneuropathy patients were compared with 16 Guillain-Barré syndrome patients observed during the same period. The analysis showed that the two polyneuropathies are likely to be separate entities that can be distinguished in most instances by the predisposing illness, electrophysiological features and cerebrospinal fluid results.
Twelve fatal cases of encephalopathy associated with sepsis were examined in a ten-year retrospective study. The sources of infection and organisms isolated were variable. Six of the patients had focal neurologic signs; five had seizures. The level of consciousness varied from drowsiness to deep coma, and electroencephalograms revealed diffuse or multifocal abnormalities. Computed tomographic head scans and cerebrospinal fluid examinations were usually unremarkable. Eight patients had disseminated microabscesses in the brain at autopsy. Four patients had proliferation of astrocytes and microglia in the cerebral cortex, a feature associated with metabolic encephalopathies. Additional findings included cerebral infarcts, brain purpura, multiple small white matter hemorrhages, and central pontine myelinolysis. Although sepsis may cause encephalopathy by producing disturbances in cerebral synaptic transmission and cerebral energy production through a toxic mechanism, bacterial invasion of the brain with the formation of disseminated microabscesses is also an important cause.
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Five patients developed a severe motor and sensory polyneuropathy at the peak of critical illness (sepsis and multiorgan dysfunction complicating a variety of primary illnesses). Difficulties in weaning from the ventilator as the critical illness subsided and the development of flaccid and areflexic limbs were early clinical signs. However, electrophysiological studies, especially needle electrode examination of skeletal muscle, provided the definite evidence of polyneuropathy. The cause is uncertain, but the electrophysiological and morphological features indicate a primary axonal polyneuropathy with sparing of the central nervous system. Nutritional factors may have played a role, since the polyneuropathy improved in all five patients after total parenteral nutrition had been started, including the three patients who later died of unrelated causes. The features allow diagnosis during life, and encourage continued intensive management since recovery from the polyneuropathy may occur.
A 54-year-old patient with fracturing dialysis osteomalacia and dementia demonstrated rapid deterioration following parathyroidectomy which was performed for sustained hypercalcemia. Reduction of the total body aluminum burden was attempted using desferrioxamine (DFO) as a chelating agent. After 6 months, DFO infusion resulted in sustained clinical remission of both neurological and skeletal symptoms, associated with an improvement in the EEG and improved mineralization of bone. A reduction in total body aluminum burden was reflected by reduced skeletal aluminum content, quantitated histochemically in iliac crest bone biopsies before and after DFO therapy. Dramatic increases in serum aluminum levels were documented in the initial weeks of DFO therapy leading to increased removal of aluminum during dialysis; in vitro studies indicated that the ultrafiltrable fraction of serum aluminum increased from 17 to more than 60% after initiating DFO treatment. However, after 6 months of therapy, serum aluminum levels remained unchanged after DFO infusion. These findings suggest that the serum aluminum response to DFO infusion might be a useful reflection of the total-body aluminum burden and also a reflection of the adequacy of a chelation program designed to reduce whole-body aluminum content.
Attempts at the identification of specific uremic toxins have, to date, been unrewarding and yet there is vogue for the measurement of, and the control by devices of hypothetical levels of, "middle molecular weight" toxins. In an attempt to elucidate whether small or middle molecular weight retention products are responsible for uremic platelet and peripheral nerve conduction defects, 14 patients with end-stage renal disease established on hemodialysis were studied using a conventional hemodialyzer and an experimental device which combined hemodialysis and hemoperfusion and which has enhanced in vitro vitamin B12 clearances. With the latter device reduced BUN and creatinine clearances were encountered and over a 2-month treatment period patient's serum BUN rose. In spite of this, there was improvement in the velocity of platelet aggregation to 10 microM adenosine diphosphate and to a standard collagen preparation associated with treatment by the experimental device. There was not, however, any demonstrable influence made on nerve conduction studies. The study suggests that different uremic retention products influence platelet and peripheral nerve function and that further efforts into studying the function of living cells or systems, in uremia might have better yield in the future guidance of the adequacy of dialysis than will the biochemical measurements of various waste products.
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The upper limbs of 10 healthy subjects were cooled and then warmed over physiological temperature ranges. The compound action potentials of median digital nerves, median sensory nerve at the wrist, radial sensory nerve at the wrist, and median thenar muscle, all showed progressive reduction in latency, amplitude, duration and area during rising temperature. Our studies suggest that the sensory compound action potential changes occur predominantly because of the summated effects of reduction in the duration of the action potentials of single myelinated fibres, although disproportionate increase in the conduction velocity of larger myelinated fibres also plays a role.
Two patients with previous cerebral damage and seizures and three patients with acute inflammatory cerebral lesions developed status epilepticus. They were unresponsive to standard anticonvulsants, but anesthetic barbiturates (thiopental and pentobarbital) stopped the seizures promptly.
A variety of peripheral nerve disorders may be associated with chronic renal failure. The polyneuropathy due to uremic toxins is a distal, motor and sensory polyneuropathy in which there is segmental demyelination, axonal degeneration, and segmental remyelination. The nature of the uremic toxin and the underly mechanism of these changes is unknown. The incidence in patients with "end-stage" renal disease has fallen in recent years, severe cases now being rare, perhaps due to refinements in chronic hemodialysis, transplantation, and other therapies. However, while chronic hemodialysis stabilizes uremic neuropathy, manipulation of hemodialysis schedules may not alter its course, according to current assessment. Successful renal transplantation improves both the clinical and electrophysiological signs, even in severe uremic neuropathy.
The amplitude of human, antidromic, sensory compound action potentials (CAP) recorded from median and ulnar digital nerves is greater in females than males. This sex difference is probably due entirely to females having digits of smaller circumference, resulting in digital nerves being closer to the recording ring electrode enclosing the digit. The negative linear correlation between CAP amplitude and circumference holds true for persons of the same sex.
A bovine shunt, inserted between the radial artery and cephalic vein in the upper arm for access during chronic haemodialysis, caused a distal, ischaemic neuropathy in two patients. There were electrophysiological signs of axonal degeneration of motor and sensory nerve fibres in the patient with severe ischaemia, and, of only sensory fibres in the patient with mild ischaemia. Thenar muscle blood flow studies using 133Xe were a useful measure of altered tissue perfusion. Recovery was incomplete in both cases, despite banding of the graft and improved tissue perfusion in the severe case.