Patterns of neurophysiological abnormality in prolonged critical illness.

OBJECTIVE: To describe the various patterns of neurophysiological abnormalities which may complicate prolonged critical illness and identify possible aetiological factors. DESIGN: Prospective case series of neurophysiological studies, severity of illness scores, organ failures, drug therapy and hospital outcome. Some patients also had muscle biopsies. SETTING: General intensive care unit (ICU) in a University Hospital. PATIENTS: Forty-four patients requiring intensive care unit stay of more than 7 days. The median age was 60 (range 27-84 years), APACHE II score 19 (range 8-33), organ failures 3 (range 1-6), and mortality was 23%. RESULTS: Seven patients had normal neurophysiology (group I), 4 had a predominantly sensory axonal neuropathy (group II), 11 had motor syndromes characterised by markedly reduced compound muscle action potentials and sensory action potentials in the normal range (group III) and 19 had combinations of motor and sensory abnormalities (group IV). Three patients had abnormal studies but could not be classified into the above groups (group V). All patients had normal nerve conduction velocities. Electromyography revealed evidence of denervation in five patients in group III and five in group IV. There was no obvious relationship between the pattern of neurophysiological abnormality and the APACHE II score, organ failure score, the presence of sepsis or the administration of muscle relaxants and steroids. A wide range of histological abnormalities was seen in the 24 patients who had a muscle biopsy; there was no clear relationship between these changes and the neurophysiological abnormalities, although histologically normal muscle was only found in patients with normal neurophysiology. Only three of the eight patients from group III in whom muscle biopsy was performed had histological changes compatible with myopathy. CONCLUSIONS: Neurophysiological abnormalities complicating critical illness can be broadly divided into three types -- sensory abnormalities alone, a pure motor syndrome and a mixed motor and sensory disturbance. The motor syndrome could be explained by an abnormality in the most distal portion of the motor axon, at the neuromuscular junction or the motor end plate and, in some cases, by inexcitable muscle membranes or extreme loss of muscle bulk. The mixed motor and sensory disturbance which is characteristic of 'critical illness polyneuropathy' could be explained by a combination of the pure motor syndrome and the mild sensory neuropathy. More precise identification of the various neurophysiological abnormalities and aetiological factors may lead to further insights into the causes of neuromuscular weakness in the critically ill and ultimately to measures for their prevention and treatment.

Administration of human recombinant insulin-like growth factor-I in critically ill patients.

OBJECTIVES: To study the pharmacokinetics of a single subcutaneous dose of recombinant human insulin-like growth factor-I (IGF-I) in patients with systemic inflammatory response syndrome in the intensive care unit (ICU). To evaluate the effects of exogenous recombinant human IGF-I on circulating concentrations of IGF-I binding protein-1 (IGFBP-1), IGF-I binding protein-3 (IGFBP-3), and growth hormone in the critically ill patient; to assess the safety of the subcutaneous administration of 40 microg/kg of recombinant human IGF-I in these patients; and to investigate any effect this dose might have on nitrogen balance, creatinine clearance, and serum electrolyte and lipid concentrations. DESIGN: Open-labeled, noncontrolled, prospective, single-dose study of eight fully evaluable ICU patients with systemic inflammatory response syndrome. SETTING: ICUs in a teaching hospital and a linked district general hospital in England. PATIENTS: Nine patients were examined, eight of whom were fully evaluable. INTERVENTIONS: Subcutaneous administration of 40 microg/kg of recombinant human IGF-I. MEASUREMENTS AND MAIN RESULTS: Blood samples were taken 24 hrs before the subcutaneous injection of 40 microg/kg of recombinant human IGF-I, and for 48 hrs thereafter. Urine was collected throughout this period. Serum concentrations of IGF-I, IGFBP-1, IGFBP-3, growth hormone, and insulin were measured by radioimmunoassay. IGF-I concentrations (median and range) increased significantly above baseline values (35 ng/mL [20 to 144]) from 15 mins (p < .02) until 10 hrs (p < .02) after injection of recombinant human IGF-I. Peak IGF-I concentrations were sustained from 2 hrs (90.5 ng/mL [23 to 228]) to 5 hrs (88.5 ng/mL [29 to 300]). By 24 hrs, circulating IGF-I concentrations had returned to baseline values. Baseline IGF-I concentrations were extremely low, and although peak values were three times greater, these values only approached the fifth percentile of defined reference ranges for normal values. Compared with values in less seriously ill patients, maximum IGF-I concentrations were reached earlier, the elimination half-life was shorter, clearance was more rapid, and the apparent volume of distribution was similar. IGFBP-3 concentrations also increased after recombinant human IGF-I injection, and at 3 to 4 hrs were significantly elevated, from 30 mins (p = .04) to 8 hrs (p = .04). There was marked between-patient variability in changes in circulating IGF-I, and IGFBP-1, and IGFBP-3 concentrations. More severely ill patients had the lowest circulating IGF-I concentrations and the least response to exogenous recombinant human IGF-I. Elevated baseline circulating growth hormone concentrations (2.3 ng/mL, range 0.8 to 4 [5.1 mU/L, 1.5 to 8]) were significantly depressed from 4 hrs (0.5 ng/mL, 0.5 to 1.5 [1 mU/L, 1 to 3], p = .01) to 6 hrs (0.8 ng/mL, 0.5 to 4 [1.5 mU/L, 1 to 8], p = .02) after recombinant human IGF-I administration. CONCLUSION: We observed no adverse effects (e.g., hypoglycemia) that could be attributed to recombinant human IGF-I therapy.