Risk factors in critical illness myopathy during the early course of critical illness: a prospective observational study

Abstract

Introduction: Non-excitable muscle membrane indicates critical illness myopathy (CIM) during early critical illness. We investigated predisposing risk factors for non-excitable muscle membrane at onset of critical illness.

Methods: We performed sequential measurements of muscle membrane excitability after direct muscle stimulation (dmCMAP) in 40 intensive care unit (ICU) patients selected upon a simplified acute physiology (SAPS-II) score >OR= 20 on 3 successive days within 1 week after ICU admission. We then investigated predisposing risk factors, including the insulin-like growth factor (IGF)-system, inflammatory, metabolic and hemodynamic parameters, as well as suspected medical treatment prior to first occurrence of abnormal dmCMAP. Nonparametric analysis of two-factorial longitudinal data and multivariate analysis were used for statistical analysis.

Results: 22 patients showed abnormal muscle membrane excitability during direct muscle stimulation within 7 (5 to 9.25) days after ICU admission. Significant risk factors for the development of impaired muscle membrane excitability in univariate analysis included inflammation, disease severity, catecholamine and sedation requirements, as well as IGF binding protein-1 (IGFBP-I), but did not include either adjunctive hydrocortisone treatment in septic shock, nor administration of neuromuscular blocking agents or aminoglycosides. In multivariate Cox regression analysis, interleukin-6 remained the significant risk factor for the development of impaired muscle membrane excitability (HR 1.006, 95%-CI (1.002 to 1.011), P = 0.002).

Conclusions: Systemic inflammation during early critical illness was found to be the main risk factor for development of CIM during early critical illness. Inflammation-induced impairment of growth-factor mediated insulin sensitivity may be involved in the development of CIM.

Figure 1

Critical illness myopathy and disease severity scores. Normal (≥3 mV) and abnormal (< 3 mV) direct muscle stimulation compound muscle action potentials (dmCMAP), (a) simplified acute physiology score-II (SAPS-II) and (B) sequential organ failure assessment (SOFA) score on the first eight days after ICU admission. Patients with impaired muscle membrane excitability had significantly higher SAPS-II and SOFA scores during the first eight days after ICU admission. Nonparametric analysis of longitudinal data in a two-factorial design (1st factor: dmCMAP normal versus dmCMAP abnormal, 2nd factor: repetitions in time. The statistical analysis was the same for Figures 1 to 6, either focusing on values from the first eight days after ICU admission (Figures 1, 2, 4 and 5) or referring to a first and second interval between days 3 and 7 after ICU admission and between days 8 and 10 after ICU admission, respectively (Figures 3 and 6).

Figure 2

Critical illness myopathy and hemodynamic variables. Normal (≥3 mV) and abnormal (< 3 mV) direct muscle stimulation compound muscle action potentials (dmCMAP), (a) mean shock index and (b) daily norepinephrine dosage on the first eight days after ICU admission. Patients with impaired muscle membrane excitability had significantly higher shock indices and required significantly higher daily norepinephrine dosages during the first eight days after ICU admission.

Figure 3

Critical illness myopathy and systemic inflammation. Normal (≥3 mV) and abnormal (< 3 mV) direct muscle stimulation compound muscle action potentials (dmCMAP), (a) IL-6 plasma levels, (b) IL-10 plasma levels at median day (25th/75th percentile) 5 (3 to 7) and median day 8 (6 to 10,25). Patients with impaired muscle membrane excitability had significantly higher IL-6 plasma levels but no significant differences of IL-10 plasma levels at both measurement intervals.

Figure 4

Critical illness myopathy and glycemic control. Normal (≥3 mV) and abnormal (< 3 mV) direct muscle stimulation compound muscle action potentials (dmCMAP), (a) mean blood glucose levels and (b) insulin in relation to daily carbohydrate intake on the first eight days after ICU admission. Mean blood glucose levels and insulin in relation to daily carbohydrate intake did not differ significantly in patients with impaired muscle membrane excitability compared with patients with normal membrane excitability.

Figure 5

Critical illness myopathy and plasma homeostasis. Normal (≥3 mV) and abnormal (< 3 mV) direct muscle stimulation compound muscle action potentials (dmCMAP), (a) plasma sodium, (b) plasma osmolarity, (c) plasma pH and (d) plasma urea (multiply by factor 0.46 for blood urea nitrogen (BUN) conversion) over the first eight days after ICU admission. Patients with impaired muscle membrane excitability had significantly higher plasma sodium, plasma osmolarity, plasma pH and plasma urea during the first eight days after ICU admission.

Figure 6

Critical illness myopathy and insulin sensitivity. Normal (≥3 mV) and abnormal (< 3 mV) direct muscle stimulation compound muscle action potentials (dmCMAP), (a) insulin-like growth factor binding protein (IGFBP)-1 plasma levels, (b) IGFBP-3 plasma levels at median day (25th/75th percentile) 5 (3 to 7) and median day 8 (6 to 10,25). Patients with impaired muscle membrane excitability had significantly higher IGFBP-1 plasma levels but no significant differences of IGFBP-3 plasma levels at both measurement intervals.

Figure 7

Multivariate Cox' proportional hazard regression after backward selection for variables, that were considered as risk factors impairing muscle membrane excitability (as dependent variable). For the particular parameter values from the day of first blood sampling for IL-6 were included in the analysis. Hazard ratios (HR) with (95% confidence intervals (CI) and P values for each variable. HC, adjunctive hydrocortisone treatment in septic shock; IGFBP, insulin-like growth factor-binding protein; IL-6, interleukin-6; SOFA, sequential organ failure assessment score.