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The Clinical Spectrum of Critical Illness Polyneuropathy
w
mayo
The Clinical Spectrum of Critical Illness Polyneuropathy EELCO F. M. WUDICKS, M.D., AND DOUGLAS R. GRACEY,
WILLIAM J. LITCHY, M.D.,
BARRY A. HARRISON,
• Objective: To describe the entity of critical illness polyneuropathy and review our experience with six cases. • Design: We present case reports of six patients with polyneuropathy associated with critical illness, who received medical care at the Mayo Clinic between 1992 and 1994, and discuss similar cases from the literature. • Results: Critical illness may damage peripheral nerves. In previous studies, sepsis and multiorgan failure have been found to trigger a peripheral neuropathy. Of our six patients with critical illness polyneuropathy, all had a preceding severe bacterial infection or septic shock. In one patient who had longterm administration of vecuronium bromide and had received massive intravenous doses of corticosteroids,
Critically ill patients with sepsis and multiorgan failure are at risk for peripheral nerve damage.13 The cause of this polyneuropathy is unclear, and few advances have been achieved in attempts to understand it. A recent report4 indicated that long-term exposure to vecuronium bromide may result in a polyneuropathy; thus, this finding suggested a mechanism other than the presumed final common pathway of sepsis and multiorgan failure. When prospectively investigated, 50% of the patients admitted with sepsis to the intensive-care unit (ICU) have electrodiagnostic features of an axonal neuropathy.1 Herein we report our experience with such patients encountered between 1992 and 1994 at the Mayo Clinic. REPORT OF CASES From 1992 to 1994, six patients with a polyneuropathy associated with critical illness were examined by one of us (E.F.M.W.). Results of electrodiagnostic tests were reviewed, and nerve and muscle biopsy specimens were available from one patient. In addition, we retrospectively reFrom the Department of Neurology (E.F.M.W.), Division of Clinical Neurophysiology (W.J.L.), Critical Care Service (B.A.H.), and Division of Pulmonary and Critical Care Medicine and Internal Medicine (D.R.G.), Mayo Clinic Rochester, Rochester, Minnesota. Address reprint requests to Dr. E. F. M. Wijdicks, Department of Neurology, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN 55905. Mayo Clin Proc 1994; 69:955-959
M.D.,
M.D.
sural nerve and quadriceps muscle biopsy specimens were available; they revealed axonal neuropathy and notable myopathie changes, respectively. The outcome was good in patients who survived the critical illness. • Conclusion: Polyneuropathy in critically ill patients may be a cause of severe generalized limb weakness and occurs in the setting of a sepsis syndrome. The long-term outcome is good in patients who recover from the underlying critical illness. Compression neuropathies may be a cause of permanent sequelae. (Mayo Clin Proc 1994; 69:955-959) GBS = Guillain-Barré syndrome; ICU = intensive-care unit
viewed the medical records of 497 patients admitted to the ICU between 1987 and 1992 who underwent at least one electrodiagnostic study while in the ICU. Although we attempted to identify those with a polyneuropathy, all patients had other neurologic disorders. No patient had severe prolonged generalized weakness. Case 1.—A 70-year-old man was admitted to a local hospital because of fever and respiratory distress. After intubation, performance of an open-lung biopsy revealed bronchiolitis obliterans and organizing pneumonia. Subsequently, he was treated with corticosteroids. He remained on a mechanical ventilator for 1 month before being transferred to the chronic ventilator unit. An intercurrent Staphylococcus pneumonia and bacteremia were treated with intravenously administered antibiotics. Throughout the patient's illness, no neuromuscular blocking agents were used. Two months after occurrence of the sepsis syndrome, neurologic examination at a Mayo Clinic-affiliated hospital showed normal strength in facial, bulbar, and neck muscles and normal extraocular movements. Severe generalized limb weakness and pronounced atrophy in distal limb musculature were noted. The deep tendon reflexes were hypoactive. Results of a sensory examination were normal. The nerve conduction and electromyographic findings were consistent with an axonal polyneuropathy (Table 1). On reexamination 955
© 1994 Mayo Foundation for Medical Education and Research
956
CRITICAL ILLNESS POLYNEUROPATHY
Mayo Clin Proc, October 1994, Vol 69
Table 1.—Summary of Neuroelectrophysiologic Data in Six Patients With Critical Illness Polyneuropathy* Nerve conduction and EMG studies
Casef
Normal values
1
2
3
4
5
6
Median motor Amplitude (mV) Velocity (m/s)
>4.0 >48
1.2 49
6.1 58
ND ND
2.6 43
0 ND
0.9 44
Ulnar motor Amplitude (mV) Velocity (m/s)
>6.0 >51
0.6 40
6.8 65
3.2 57
5.1 53
0.1 46
ND ND
>2.0 >41
1.6 49
4.0 47
0.1 36
0.5 44
0.3 33
0 ND
>4.0 >40 <58
ND ND ND
6.2 45 NR
0.7 37 66
1.5 52 63
ND ND ND
5.1 41 50
>6 >44
ND ND
ND ND
ND ND
ND ND
2 ND
7 41
>15 >55
4 49
10 58
8 54
6 ND
13 30
11 57
Fibrillation potentials Proximal Distal
+
+ +
+ +
ND +
+ +
+
Motor unit potentials Proximal Distal
+ +
-
-
ND +
+ +
+ +
Poor
None
None
Poor
Poor
Poor
Peroneal motor Amplitude (mV) Velocity (m/s) Tibial motor Amplitude (mV) Velocity (m/s) F wave (ms) Sural sensory Amplitude (μν) Velocity (m/s) Median sensory Amplitude (μν) Velocity (m/s)
Recruitment
*EMG = electromyographic; ND = not done; NR = no response; + = present; - = absent. tSee text for detailed case reports. 2 months later, he was clinically unchanged. Subsequently, he died of septic shock, and an autopsy was not performed. Case 2.—A 46-year-old man had sudden onset of severe acute pancreatitis followed by the adult respiratory distress syndrome. A computed tomographic scan of the abdomen confirmed the presence of acute necrotizing pancreatitis and phlegmon, but no evidence of abscess was noted. He was treated with broad-spectrum antibiotics, and blood cultures remained negative. Subsequently, acute renal failure developed as a result of acute tubular necrosis. No neuromuscular blocking agents or corticosteroids were administered during the course of the disease. Six weeks after onset of the illness, neurologic examination showed severe proximal and distal muscle weakness; the patient was unable to lift his arms or legs from the bed. Atrophy was most prominent in the hand muscles. The deep tendon reflexes were absent. Electrodiagnostic evaluation showed nerve conduction velocities and amplitudes within normal limits but absent F waves. Needle electromyography revealed dense fibrillation poten-
tials, but no motor unit potentials could be activated (Table 1). Gradual improvement ensued, and he was weaned from the ventilator; he was ambulatory 2'/2 months after onset of the illness. Four months later, he was able to golf without assistance. Case 3.—A 78-year-old man was admitted to the surgical ICU because of sepsis after an aortobifemoral bypass surgical procedure. The patient had been transferred to the Mayo Clinic after surgical repair of an abdominal aortic aneurysm elsewhere was complicated by an abdominal abscess, pneumonia, and renal failure. The initial neurologic examination revealed normal cranial nerves but a complete flaccid quadriplegia and areflexia. Results of sensory testing were normal. Electrophysiologic findings were consistent with an axonal polyneuropathy (Table 1). The patient died of cardiac arrest before motor function improved, and no autopsy was performed. Case 4.—A 68-year-old woman was admitted to the ICU after surgical repair of a perforated duodenal diverticulum
Mayo Clin Proc, October 1994, Vol 69
associated with peritonitis. The postoperative course was complicated by septic shock and respiratory failure that necessitated tracheostomy and ventilator support. No neuromuscular blocking agents or corticosteroids were administered. On neurologic examination, severe proximal and distal weakness was evident, but the cranial nerves were normal, as were findings on sensory examination. The electrophysiologic studies showed evidence of an axonal sensorimotor polyneuropathy (Table 1). With successful treatment of the sepsis, gradual improvement was noted. After 6 months, the patient could walk unassisted. Case 5.—A 51-year-old man, who had a communityacquired pneumonia complicated by the adult respiratory distress syndrome, was admitted to a local hospital. He required mechanical ventilation, and vecuronium was used. Subsequent treatment consisted of intravenous administration of antibiotics and large amounts of corticosteroids and the use of bronchodilators. His clinical course was complicated by septic shock, gastrointestinal bleeding, and spontaneous bilateral pneumothoraces. With appropriate treatment, the patient was successfully weaned from mechanical ventilation. Neurologic examination at a Mayo Clinicaffiliated hospital showed normal cranial nerves but quadriplegia and areflexia. Electrodiagnostic studies disclosed a severe axonal polyneuropathy. A sural nerve biopsy showed early axonal degeneration (Dyck PJ. Personal communication). A quadriceps muscle biopsy showed type 2 fiber atrophy and numerous regenerating fibers. The atrophie type 2 fibers may represent the results of corticosteroid treatment or disuse. The regenerating fibers were at a similar stage, a finding that suggested a monophasic insult (EmslieSmith AM. Personal communication). After successful treatment of the sepsis, the patient experienced continuous clinical improvement and was able to ambulate with canes by 6 months. Case 6.—A 55-year-old woman with a history of chronic obstructive pulmonary disease was admitted to the ICU because of a Klebsiella pneumonia and the adult respiratory distress syndrome. She was given multiple antibiotics, sedated with propofol, and treated with pancuronium bromide for 10 days. After 3 months, improvement in her condition allowed weaning from the ventilator. Neurologic examination showed profound distal limb weakness and hyporeflexia. Of note was disproportionately severe weakness of the anterior tibial muscle, extensor hallucis longus, and peroneus longus and brevis muscles, suggesting bilateral peroneal palsies. Electrodiagnostic studies revealed an axonal polyneuropathy and bilateral focal peroneal neuropathies localized at the head of the fibula. Subsequently, she required a cane for walking and bilateral foot and ankle orthoses. The strength in her arms completely recovered.
CRITICAL ILLNESS POLYNEUROPATHY
957
DISCUSSION From this study, three important observations can be emphasized. First, the absence of critical illness polyneuropathy in a large series of patients in the ICU reviewed retrospectively and the observation of a relatively large series within a 2year period suggest that this syndrome, although infrequent, may be more common than previously appreciated. Second, the outcome of patients with critical illness polyneuropathy is good, even in those with severe quadriplegia, if the underlying disease is successfully treated. Studies of long-term outcome in these patients, however, have not been done. Third, meticulous attention to compression points in these patients with quadriplegia may minimize neurologic sequelae from compression neuropathy. Polyneuropathy should be considered in patients with generalized muscle weakness after any type of critical illness. It has frequently been found in patients with sepsis and multiorgan failure. Since the original description of critical illness polyneuropathy reported by Bolton and associates57 and Op de Coul and colleagues,8 widespread interest in this syndrome has become evident. Although polyneuropathy in critically ill patients has been increasingly recognized, only recently has it been described in major critical-care texts. Our series of patients, albeit seemingly small, is one of the largest personally observed series of cases of critical illness polyneuropathy. Previous studies have presented similar clinical descriptions of critical illness polyneuropathy. Frequently, as the critically ill patient recovers, a major problem is respiratory failure from a neuromuscular rather than a primary pulmonary cause, which results in difficulty in weaning from the mechanical ventilator.9 Severe limb weakness and muscle wasting are invariably noted in these patients. Before critical-care physicians recognized the limb weakness and wasting as an axonal polyneuropathy, failure to wean from mechanical ventilation was often the initially noted neurologic symptom.2 Frequently, patients with longterm ventilatory problems are difficult to wean from mechanical ventilation; poor nutrition and chronic lung disease can be contributory factors. With increased vigilance, critical illness polyneuropathy can be diagnosed earlier. Our identification of six patients in 2 years and the absence of any cases in a retrospective survey of the previous 5 years suggest that clinical recognition of the syndrome is important for identifying affected patients. This factor was also noted in a report by Zochodne and associates,2 who found 5 patients with critical illness polyneuropathy in a 4-year period and 14 patients during the subsequent 2 years. Surprisingly, in two recent prospective studies of neurologic complications associated with critical illness, no patients with critical illness polyneuropathy were noted.10" The reasons remain unclear, but such patients may not have been encountered by
958
CRITICAL ILLNESS POLYNEUROPATHY
physicians with a specific interest or expertise in newly acquired neuromuscular weakness or may have been in the ICU for only a brief period. Generalized weakness in patients in the ICU is most common with prolonged mechanical ventilation. The differential diagnosis of new-onset weakness from polyneuropathy in this setting may be limited but should include acute porphyria, vasculitis, effects of medication, and a previously undiagnosed neurologic disorder. The Guillain-Barré syndrome (GBS) has reportedly occurred after any type of surgical intervention, epidural anesthesia, administration of fibrinolytic agents, and use of high doses of methylprednisolone for asthma.12 In addition, generalized muscle weakness may occur in the setting of acute spinal cord injury, myopathy, motor neuron disorder, or disorder of the neuromuscular junction. To our knowledge, prospective studies of causes of weakness in patients in the ICU have not been conducted. On the basis of our observations in the ICU setting, critical illness polyneuropathy should be considered in patients with generalized weakness and prolonged mechanical ventilation (Fig. 1). Recently, some investigators have also noted that sepsis and multiorgan failure are not essential factors in the occurrence of critical illness polyneuropathy. In a series of 10 patients with status asthmaticus treated with vecuronium, polyneuropathy developed in 5; however, it was not found in a case-control series of patients with exacerbation of asthma who did not receive infusions of vecuronium.4 Another explanation for generalized weakness in patients in the ICU was reported by Wokke and coworkers,13 who found struc-
Mayo Clin Proc, October 1994, Vol 69
tural alterations of the neuromuscular junction in intercostal muscles in two patients who had had prolonged neuromuscular blockade. Further confirmation of this finding will be necessary. In our patients, the general pattern was prolonged mechanical ventilation for pneumonia or acute respiratory disease in association with sepsis. Usually, the clinical features of critical illness polyneuropathy include severe generalized weakness without bulbar involvement. Compression neuropathies may also be noted clinically or detected during electrophysiologic testing. Resolution of the disorder yields improved strength in the proximal muscles of the upper and lower limbs, successful weaning from mechanical ventilation, and subsequent improvement in distal lower limb strength. Electrodiagnostic studies confirm the presence of an axonal neuropathy and show reduced or absent compound muscle action potentials in conjunction with fibrillation potentials and a decreased number of motor unit potentials on needle electromyography. A sural nerve biopsy specimen from one of our patients (case 5) substantiated the presence of axonal degeneration as well. A controversial issue in critical illness polyneuropathy is whether a myopathy can be detected in this clinical syndrome. Previous studies have shown either neurogenic changes or abnormalities in the soleus muscle; however, pressure necrosis in the soleus muscle could be a contributing factor.3 In one of our patients (case 5), a biopsy specimen from the quadriceps muscle showed appreciable myopathie changes and numerous regenerating fibers of similar stage,
Critical illness polyneuropathy
Prolonged mechanical ventilation Neuromuscular blocking agents
Fig. 1. Diagram showing interrelationship between sepsis and neuromuscular blocking agents in the population of critically ill patients who have generalized weakness and require prolonged mechanical ventilation.
Mayo Clin Proc, October 1994, Vol 69
indications of a recent monophasic disorder. Whether a myopathy exists in addition to a polyneuropathy in patients with critical illness2-3 remains unresolved. Previous studies have shown electrophysiologic evidence of a myopathy on electromyography. Moreover, a recent study of percutaneous biopsy specimens from 15 anterior tibial muscles in critically ill patients showed evidence of necrotizing myopathy.14 The role of rhabdomyolysis, however, was unclear. In addition, substantial intravenous doses of corticosteroids in association with neuromuscular blockade may cause a necrotic myopathy, usually in the setting of acute status asthmaticus.4 Therefore, use of corticosteroids in our patient from whom a muscle biopsy was obtained may have been a confounding factor. Critical illness polyneuropathy can mimic axonal GBS, but several clinical differences are apparent.1215 In severe GBS, most patients have pronounced facial weakness, ophthalmoplegia, and dysautonomia. Orthostatic hypotension may be noted in any patient after a critical illness, but the well-described dramatic labile blood pressure, sustained tachycardia, and profuse sweating are infrequently present in patients with critical illness polyneuropathy, observations that oppose GBS preceded by sepsis as an alternative diagnosis.1215 The long-term outcome in patients with critical illness polyneuropathy is good, but the most important predictive factor for improvement is the successful treatment of the underlying critical illness. Indeed, a substantial number of patients die of the critical illness rather than of complications associated with immobilization and prolonged mechanical ventilation because of neuromuscular failure. ADDENDUM Since submission of this article, we have encountered five additional patients with critical illness polyneuropathy, all of which cases were associated with sepsis and use of neuromuscular blocking agents. In all five patients, recovery was virtually complete.
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959
REFERENCES 1. Witt NJ, Zochodne DW, Bolton CF, Grand'Maison F, Wells G, Young GB, et al. Peripheral nerve function in sepsis and multiple organ failure. Chest 1991;99:176-184 2. Zochodne DW, Bolton CF, Wells GA, Gilbert JJ, Hahn AF, Brown JD, et al. Critical illness polyneuropathy: a complication of sepsis and multiple organ failure. Brain 1987;110:819-841 3. Op de Coul AA, Verheul GA, Leyten AC, Schellens RL, Teepen JL. Critical illness polyneuromyopathy after artificial respiration. Clin Neurol Neurosurg 1991 ; 93:27-33 4. Kupfer Y, Namba T, Kaldawi E, Tessler S. Prolonged weakness after long-term infusion of vecuronium bromide. Ann Intern Med 1992; 117:484-486 5. Bolton CF, Gilbert JJ, Hahn AF, Sibbald WJ. Polyneuropathy in critically ill patients. J Neurol Neurosurg Psychiatry 1984; 47:12231231 6. Bolton CF, Laverty DA, Brown JD, Witt NJ, Hahn AF, Sibbald WJ. Critically ill polyneuropathy: electrophysiological studies and differentiation from Guillain-Barré syndrome. J Neurol Neurosurg Psychiatry 1986;49:563-573 7. Bolton CF. Electrophysiologic studies of critically ill patients. Muscle Nerve 1987;10:129-135 8. Op de Coul AA, Lambregts PC, Koeman J, van Puyenbroek MJ, Ter Laak HJ, Gabreels-Festen AA. Neuromuscular complications in patients given Pavulon (pancuronium bromide) during artificial ventilation. Clin Neurol Neurosurg 1985;87:17-22 9. Gorson KC, Ropper AH. Acute respiratory failure neuropathy: a variant of critical illness polyneuropathy. Crit Care Med 1993; 21:267-271 10. Bleck TP, Smith MC, Pierre-Louis SJ, Jares JJ, Murray J, Hansen CA. Neurologic complications of critical medical illnesses. Crit Care Med 1993;21:98-103 11. Kelly BJ, Matthay MA. Prevalence and severity of neurologic dysfunction in critically ill patients: influence on need for continued mechanical ventilation. Chest 1993;104:1818-1824 12. Ropper AH, Wijdicks EFM, Truax BT. Guillain-Barré Syndrome. Philadelphia: FA Davis, 1991:73-105 13. Wokke JH, Jennekens FG, van den Oord CJ, Veldman H, van Gijn J. Histological investigations of muscle atrophy and end plates in two critically ill patients with generalized weakness. J Neurol Sci 1988; 88:95-106 14. Helliwell TR, Coakley JH, Wagenmakers AJ, Griffiths RD, Campbell ΓΤ, Green CJ, et al. Necrotizing myopathy in critically-ill patients. JPathol 1991;164:307-314 15. Feasby TE, Gilbert JJ, Brown WF, Bolton CF, Hahn AF, Koopman WF, et al. An acute axonal form of Guillain-Barré polyneuropathy. Brain 1986; 109:1115-1126
mayo
The Clinical Spectrum of Critical Illness Polyneuropathy EELCO F. M. WUDICKS, M.D., AND DOUGLAS R. GRACEY,
WILLIAM J. LITCHY, M.D.,
BARRY A. HARRISON,
• Objective: To describe the entity of critical illness polyneuropathy and review our experience with six cases. • Design: We present case reports of six patients with polyneuropathy associated with critical illness, who received medical care at the Mayo Clinic between 1992 and 1994, and discuss similar cases from the literature. • Results: Critical illness may damage peripheral nerves. In previous studies, sepsis and multiorgan failure have been found to trigger a peripheral neuropathy. Of our six patients with critical illness polyneuropathy, all had a preceding severe bacterial infection or septic shock. In one patient who had longterm administration of vecuronium bromide and had received massive intravenous doses of corticosteroids,
Critically ill patients with sepsis and multiorgan failure are at risk for peripheral nerve damage.13 The cause of this polyneuropathy is unclear, and few advances have been achieved in attempts to understand it. A recent report4 indicated that long-term exposure to vecuronium bromide may result in a polyneuropathy; thus, this finding suggested a mechanism other than the presumed final common pathway of sepsis and multiorgan failure. When prospectively investigated, 50% of the patients admitted with sepsis to the intensive-care unit (ICU) have electrodiagnostic features of an axonal neuropathy.1 Herein we report our experience with such patients encountered between 1992 and 1994 at the Mayo Clinic. REPORT OF CASES From 1992 to 1994, six patients with a polyneuropathy associated with critical illness were examined by one of us (E.F.M.W.). Results of electrodiagnostic tests were reviewed, and nerve and muscle biopsy specimens were available from one patient. In addition, we retrospectively reFrom the Department of Neurology (E.F.M.W.), Division of Clinical Neurophysiology (W.J.L.), Critical Care Service (B.A.H.), and Division of Pulmonary and Critical Care Medicine and Internal Medicine (D.R.G.), Mayo Clinic Rochester, Rochester, Minnesota. Address reprint requests to Dr. E. F. M. Wijdicks, Department of Neurology, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN 55905. Mayo Clin Proc 1994; 69:955-959
M.D.,
M.D.
sural nerve and quadriceps muscle biopsy specimens were available; they revealed axonal neuropathy and notable myopathie changes, respectively. The outcome was good in patients who survived the critical illness. • Conclusion: Polyneuropathy in critically ill patients may be a cause of severe generalized limb weakness and occurs in the setting of a sepsis syndrome. The long-term outcome is good in patients who recover from the underlying critical illness. Compression neuropathies may be a cause of permanent sequelae. (Mayo Clin Proc 1994; 69:955-959) GBS = Guillain-Barré syndrome; ICU = intensive-care unit
viewed the medical records of 497 patients admitted to the ICU between 1987 and 1992 who underwent at least one electrodiagnostic study while in the ICU. Although we attempted to identify those with a polyneuropathy, all patients had other neurologic disorders. No patient had severe prolonged generalized weakness. Case 1.—A 70-year-old man was admitted to a local hospital because of fever and respiratory distress. After intubation, performance of an open-lung biopsy revealed bronchiolitis obliterans and organizing pneumonia. Subsequently, he was treated with corticosteroids. He remained on a mechanical ventilator for 1 month before being transferred to the chronic ventilator unit. An intercurrent Staphylococcus pneumonia and bacteremia were treated with intravenously administered antibiotics. Throughout the patient's illness, no neuromuscular blocking agents were used. Two months after occurrence of the sepsis syndrome, neurologic examination at a Mayo Clinic-affiliated hospital showed normal strength in facial, bulbar, and neck muscles and normal extraocular movements. Severe generalized limb weakness and pronounced atrophy in distal limb musculature were noted. The deep tendon reflexes were hypoactive. Results of a sensory examination were normal. The nerve conduction and electromyographic findings were consistent with an axonal polyneuropathy (Table 1). On reexamination 955
© 1994 Mayo Foundation for Medical Education and Research
956
CRITICAL ILLNESS POLYNEUROPATHY
Mayo Clin Proc, October 1994, Vol 69
Table 1.—Summary of Neuroelectrophysiologic Data in Six Patients With Critical Illness Polyneuropathy* Nerve conduction and EMG studies
Casef
Normal values
1
2
3
4
5
6
Median motor Amplitude (mV) Velocity (m/s)
>4.0 >48
1.2 49
6.1 58
ND ND
2.6 43
0 ND
0.9 44
Ulnar motor Amplitude (mV) Velocity (m/s)
>6.0 >51
0.6 40
6.8 65
3.2 57
5.1 53
0.1 46
ND ND
>2.0 >41
1.6 49
4.0 47
0.1 36
0.5 44
0.3 33
0 ND
>4.0 >40 <58
ND ND ND
6.2 45 NR
0.7 37 66
1.5 52 63
ND ND ND
5.1 41 50
>6 >44
ND ND
ND ND
ND ND
ND ND
2 ND
7 41
>15 >55
4 49
10 58
8 54
6 ND
13 30
11 57
Fibrillation potentials Proximal Distal
+
+ +
+ +
ND +
+ +
+
Motor unit potentials Proximal Distal
+ +
-
-
ND +
+ +
+ +
Poor
None
None
Poor
Poor
Poor
Peroneal motor Amplitude (mV) Velocity (m/s) Tibial motor Amplitude (mV) Velocity (m/s) F wave (ms) Sural sensory Amplitude (μν) Velocity (m/s) Median sensory Amplitude (μν) Velocity (m/s)
Recruitment
*EMG = electromyographic; ND = not done; NR = no response; + = present; - = absent. tSee text for detailed case reports. 2 months later, he was clinically unchanged. Subsequently, he died of septic shock, and an autopsy was not performed. Case 2.—A 46-year-old man had sudden onset of severe acute pancreatitis followed by the adult respiratory distress syndrome. A computed tomographic scan of the abdomen confirmed the presence of acute necrotizing pancreatitis and phlegmon, but no evidence of abscess was noted. He was treated with broad-spectrum antibiotics, and blood cultures remained negative. Subsequently, acute renal failure developed as a result of acute tubular necrosis. No neuromuscular blocking agents or corticosteroids were administered during the course of the disease. Six weeks after onset of the illness, neurologic examination showed severe proximal and distal muscle weakness; the patient was unable to lift his arms or legs from the bed. Atrophy was most prominent in the hand muscles. The deep tendon reflexes were absent. Electrodiagnostic evaluation showed nerve conduction velocities and amplitudes within normal limits but absent F waves. Needle electromyography revealed dense fibrillation poten-
tials, but no motor unit potentials could be activated (Table 1). Gradual improvement ensued, and he was weaned from the ventilator; he was ambulatory 2'/2 months after onset of the illness. Four months later, he was able to golf without assistance. Case 3.—A 78-year-old man was admitted to the surgical ICU because of sepsis after an aortobifemoral bypass surgical procedure. The patient had been transferred to the Mayo Clinic after surgical repair of an abdominal aortic aneurysm elsewhere was complicated by an abdominal abscess, pneumonia, and renal failure. The initial neurologic examination revealed normal cranial nerves but a complete flaccid quadriplegia and areflexia. Results of sensory testing were normal. Electrophysiologic findings were consistent with an axonal polyneuropathy (Table 1). The patient died of cardiac arrest before motor function improved, and no autopsy was performed. Case 4.—A 68-year-old woman was admitted to the ICU after surgical repair of a perforated duodenal diverticulum
Mayo Clin Proc, October 1994, Vol 69
associated with peritonitis. The postoperative course was complicated by septic shock and respiratory failure that necessitated tracheostomy and ventilator support. No neuromuscular blocking agents or corticosteroids were administered. On neurologic examination, severe proximal and distal weakness was evident, but the cranial nerves were normal, as were findings on sensory examination. The electrophysiologic studies showed evidence of an axonal sensorimotor polyneuropathy (Table 1). With successful treatment of the sepsis, gradual improvement was noted. After 6 months, the patient could walk unassisted. Case 5.—A 51-year-old man, who had a communityacquired pneumonia complicated by the adult respiratory distress syndrome, was admitted to a local hospital. He required mechanical ventilation, and vecuronium was used. Subsequent treatment consisted of intravenous administration of antibiotics and large amounts of corticosteroids and the use of bronchodilators. His clinical course was complicated by septic shock, gastrointestinal bleeding, and spontaneous bilateral pneumothoraces. With appropriate treatment, the patient was successfully weaned from mechanical ventilation. Neurologic examination at a Mayo Clinicaffiliated hospital showed normal cranial nerves but quadriplegia and areflexia. Electrodiagnostic studies disclosed a severe axonal polyneuropathy. A sural nerve biopsy showed early axonal degeneration (Dyck PJ. Personal communication). A quadriceps muscle biopsy showed type 2 fiber atrophy and numerous regenerating fibers. The atrophie type 2 fibers may represent the results of corticosteroid treatment or disuse. The regenerating fibers were at a similar stage, a finding that suggested a monophasic insult (EmslieSmith AM. Personal communication). After successful treatment of the sepsis, the patient experienced continuous clinical improvement and was able to ambulate with canes by 6 months. Case 6.—A 55-year-old woman with a history of chronic obstructive pulmonary disease was admitted to the ICU because of a Klebsiella pneumonia and the adult respiratory distress syndrome. She was given multiple antibiotics, sedated with propofol, and treated with pancuronium bromide for 10 days. After 3 months, improvement in her condition allowed weaning from the ventilator. Neurologic examination showed profound distal limb weakness and hyporeflexia. Of note was disproportionately severe weakness of the anterior tibial muscle, extensor hallucis longus, and peroneus longus and brevis muscles, suggesting bilateral peroneal palsies. Electrodiagnostic studies revealed an axonal polyneuropathy and bilateral focal peroneal neuropathies localized at the head of the fibula. Subsequently, she required a cane for walking and bilateral foot and ankle orthoses. The strength in her arms completely recovered.
CRITICAL ILLNESS POLYNEUROPATHY
957
DISCUSSION From this study, three important observations can be emphasized. First, the absence of critical illness polyneuropathy in a large series of patients in the ICU reviewed retrospectively and the observation of a relatively large series within a 2year period suggest that this syndrome, although infrequent, may be more common than previously appreciated. Second, the outcome of patients with critical illness polyneuropathy is good, even in those with severe quadriplegia, if the underlying disease is successfully treated. Studies of long-term outcome in these patients, however, have not been done. Third, meticulous attention to compression points in these patients with quadriplegia may minimize neurologic sequelae from compression neuropathy. Polyneuropathy should be considered in patients with generalized muscle weakness after any type of critical illness. It has frequently been found in patients with sepsis and multiorgan failure. Since the original description of critical illness polyneuropathy reported by Bolton and associates57 and Op de Coul and colleagues,8 widespread interest in this syndrome has become evident. Although polyneuropathy in critically ill patients has been increasingly recognized, only recently has it been described in major critical-care texts. Our series of patients, albeit seemingly small, is one of the largest personally observed series of cases of critical illness polyneuropathy. Previous studies have presented similar clinical descriptions of critical illness polyneuropathy. Frequently, as the critically ill patient recovers, a major problem is respiratory failure from a neuromuscular rather than a primary pulmonary cause, which results in difficulty in weaning from the mechanical ventilator.9 Severe limb weakness and muscle wasting are invariably noted in these patients. Before critical-care physicians recognized the limb weakness and wasting as an axonal polyneuropathy, failure to wean from mechanical ventilation was often the initially noted neurologic symptom.2 Frequently, patients with longterm ventilatory problems are difficult to wean from mechanical ventilation; poor nutrition and chronic lung disease can be contributory factors. With increased vigilance, critical illness polyneuropathy can be diagnosed earlier. Our identification of six patients in 2 years and the absence of any cases in a retrospective survey of the previous 5 years suggest that clinical recognition of the syndrome is important for identifying affected patients. This factor was also noted in a report by Zochodne and associates,2 who found 5 patients with critical illness polyneuropathy in a 4-year period and 14 patients during the subsequent 2 years. Surprisingly, in two recent prospective studies of neurologic complications associated with critical illness, no patients with critical illness polyneuropathy were noted.10" The reasons remain unclear, but such patients may not have been encountered by
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CRITICAL ILLNESS POLYNEUROPATHY
physicians with a specific interest or expertise in newly acquired neuromuscular weakness or may have been in the ICU for only a brief period. Generalized weakness in patients in the ICU is most common with prolonged mechanical ventilation. The differential diagnosis of new-onset weakness from polyneuropathy in this setting may be limited but should include acute porphyria, vasculitis, effects of medication, and a previously undiagnosed neurologic disorder. The Guillain-Barré syndrome (GBS) has reportedly occurred after any type of surgical intervention, epidural anesthesia, administration of fibrinolytic agents, and use of high doses of methylprednisolone for asthma.12 In addition, generalized muscle weakness may occur in the setting of acute spinal cord injury, myopathy, motor neuron disorder, or disorder of the neuromuscular junction. To our knowledge, prospective studies of causes of weakness in patients in the ICU have not been conducted. On the basis of our observations in the ICU setting, critical illness polyneuropathy should be considered in patients with generalized weakness and prolonged mechanical ventilation (Fig. 1). Recently, some investigators have also noted that sepsis and multiorgan failure are not essential factors in the occurrence of critical illness polyneuropathy. In a series of 10 patients with status asthmaticus treated with vecuronium, polyneuropathy developed in 5; however, it was not found in a case-control series of patients with exacerbation of asthma who did not receive infusions of vecuronium.4 Another explanation for generalized weakness in patients in the ICU was reported by Wokke and coworkers,13 who found struc-
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tural alterations of the neuromuscular junction in intercostal muscles in two patients who had had prolonged neuromuscular blockade. Further confirmation of this finding will be necessary. In our patients, the general pattern was prolonged mechanical ventilation for pneumonia or acute respiratory disease in association with sepsis. Usually, the clinical features of critical illness polyneuropathy include severe generalized weakness without bulbar involvement. Compression neuropathies may also be noted clinically or detected during electrophysiologic testing. Resolution of the disorder yields improved strength in the proximal muscles of the upper and lower limbs, successful weaning from mechanical ventilation, and subsequent improvement in distal lower limb strength. Electrodiagnostic studies confirm the presence of an axonal neuropathy and show reduced or absent compound muscle action potentials in conjunction with fibrillation potentials and a decreased number of motor unit potentials on needle electromyography. A sural nerve biopsy specimen from one of our patients (case 5) substantiated the presence of axonal degeneration as well. A controversial issue in critical illness polyneuropathy is whether a myopathy can be detected in this clinical syndrome. Previous studies have shown either neurogenic changes or abnormalities in the soleus muscle; however, pressure necrosis in the soleus muscle could be a contributing factor.3 In one of our patients (case 5), a biopsy specimen from the quadriceps muscle showed appreciable myopathie changes and numerous regenerating fibers of similar stage,
Critical illness polyneuropathy
Prolonged mechanical ventilation Neuromuscular blocking agents
Fig. 1. Diagram showing interrelationship between sepsis and neuromuscular blocking agents in the population of critically ill patients who have generalized weakness and require prolonged mechanical ventilation.
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indications of a recent monophasic disorder. Whether a myopathy exists in addition to a polyneuropathy in patients with critical illness2-3 remains unresolved. Previous studies have shown electrophysiologic evidence of a myopathy on electromyography. Moreover, a recent study of percutaneous biopsy specimens from 15 anterior tibial muscles in critically ill patients showed evidence of necrotizing myopathy.14 The role of rhabdomyolysis, however, was unclear. In addition, substantial intravenous doses of corticosteroids in association with neuromuscular blockade may cause a necrotic myopathy, usually in the setting of acute status asthmaticus.4 Therefore, use of corticosteroids in our patient from whom a muscle biopsy was obtained may have been a confounding factor. Critical illness polyneuropathy can mimic axonal GBS, but several clinical differences are apparent.1215 In severe GBS, most patients have pronounced facial weakness, ophthalmoplegia, and dysautonomia. Orthostatic hypotension may be noted in any patient after a critical illness, but the well-described dramatic labile blood pressure, sustained tachycardia, and profuse sweating are infrequently present in patients with critical illness polyneuropathy, observations that oppose GBS preceded by sepsis as an alternative diagnosis.1215 The long-term outcome in patients with critical illness polyneuropathy is good, but the most important predictive factor for improvement is the successful treatment of the underlying critical illness. Indeed, a substantial number of patients die of the critical illness rather than of complications associated with immobilization and prolonged mechanical ventilation because of neuromuscular failure. ADDENDUM Since submission of this article, we have encountered five additional patients with critical illness polyneuropathy, all of which cases were associated with sepsis and use of neuromuscular blocking agents. In all five patients, recovery was virtually complete.
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