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.

We observed no adverse effects (e.g., hypoglycemia) that could be attributed to recombinant human IGF-I therapy.

Sepsis is characterized by a severe shift in metabolism, characterized by low IGF-I levels. We have studied the influence of caecal ligation and puncture (CLP) on the levels of circulating IGF-I and hepatic IGF-I and IGF-binding protein (IGFBP)-1, -2 and -3 mRNA in adult male Wistar rats (n = 12) and compared it with sham-operated rats (n = 6). In order to exclude anorexia-induced changes we also studied animals pair-fed to both groups. IGF-I levels were measured by RIA. Steady-state hepatic IGF-I, IGFBP-1, IGFBP-2 and IGFBP-3 mRNA levels were measured by Northern blot analysis using specific rat cDNA probes. Food intake averaged 13.0 +/- 2.0 g/day in the sham-operated rats fed ad libitum during the study period, with a sharp decline in food intake in the CLP animals (2.3 +/- 1.3 g/day). After CLP, there was a significant reduction in circulating IGF-I levels (467.2 +/- 50.9 micrograms/l) compared with sham-operated animals (924.0 +/- 75.3 micrograms/l; P = 0.04) or those pair-fed to the CLP rats (612.5 +/- 52.9 micrograms/l; P = 0.04). Total hepatic IGF-I mRNA levels were significantly reduced (2.57 +/- 0.05 densitometric units (DU) after CLP compared with the sham-operated group (2.71 +/- 0.04); P = 0.04), or their pair-fed controls (2.75 +/- 0.08 DU; P < 0.05). Hepatic IGFBP-3 mRNA levels were lower after CLP (0.37 +/- 0.04 DU) than in the sham-operated animals (0.66 +/- 0.09 DU; P = 0.04) or their pair-fed controls (0.61 +/- 0.05 DU; P = 0.04). On the other hand, hepatic IGFBP-2 mRNA levels were increased after CLP (0.91 +/- 0.11 DU) compared with sham-operated animals (0.28 +/- 0.06 DU; P = 0.01) or with their pair-fed controls (0.22 +/- 0.02; P = 0.01), as were hepatic IGFBP-1 mRNA levels (CLP animals 0.95 +/- 0.11 DU; sham-operated 0.30 +/- 0.04 DU, P = 0.01; pair-fed 0.30 +/- 0.02 DU, P = 0.01). No significant difference between sham-operated animals and their pair-fed controls was observed in circulating IGF-I levels (888.0 +/- 109.3 micrograms/l; P = not significant (N.S.)), hepatic mRNA levels for IGF-I (2.72 +/- 0.06 DU; P = N.S), IGFBP-3 (0.71 +/- 0.07 DU; P = N.S.), IGFBP-2 (0.25 +/- 0.07 DU; P = N.S.) or IGFBP-1 (0.27 +/- 0.06 DU; P = N.S.). In summary, after CLP there was a reduction in both circulating and hepatic IGF-I mRNA levels associated with a specific and differential regulation of hepatic IGFBP-1, -2 and -3 mRNA levels. Although we cannot eliminate a possible effect of surgical stress combined with malnutrition, our results suggest that these changes are a specific effect of sepsis rather than simply a result of surgical stress or poor nutrition alone.

No abstract