Abstract
Patients suffering from critical illness are at risk to develop critical illness neuromyopathy (CINM). The underlying pathophysiology is complex and controversial. A central question is whether soluble serum factors are involved in the pathogenesis of CINM. In this study, smooth muscle preparations obtained from the colon of patients undergoing elective surgery were used to investigate the effects of serum from critically ill patients. At the time of blood draw, CINM was assessed by clinical rating and electrophysiology. Muscle strips were incubated with serum of healthy controls or patients in organ baths and isometric force was measured. Fifteen samples from healthy controls and 98 from patients were studied. Ratios of responses to electric field stimulation (EFS) before and after incubation were 118% for serum from controls and 51% and 62% with serum from critically ill patients obtained at day 3 and 10 of critical illness, respectively (p = 0.003, One-Way-ANOVA). Responses to carbachol and high-K+ were equal between these groups. Ratios of post/pre-EFS responses correlated with less severe CINM. These results support the existence of pathogenic, i.e. neurotoxic factors in the serum of critically ill patients. Using human colon smooth muscle as a bioassay may facilitate their future molecular identification.
Highlights
Patients suffering from critical illness are at risk to develop critical illness neuromyopathy (CINM)
A sequential organ failure assessment (SOFA) score of ≥ 8 had been stated on ≥ 3 days after admission to the intensive care unit (ICU)
A major point of discussion in the pathophysiology of generalized neuromuscular dysfunction in critically ill patients is whether alterations of nerves and skeletal muscles are caused by soluble humoral factors or by cellular cytotoxicity[2,49]
Summary
Patients suffering from critical illness are at risk to develop critical illness neuromyopathy (CINM). Ratios of responses to electric field stimulation (EFS) before and after incubation were 118% for serum from controls and 51% and 62% with serum from critically ill patients obtained at day 3 and 10 of critical illness, respectively (p = 0.003, One-Way-ANOVA). Ratios of post/pre-EFS responses correlated with less severe CINM These results support the existence of pathogenic, i.e. neurotoxic factors in the serum of critically ill patients. Abbreviations ADM Musculus abductor digiti minimi ANOVA Analysis of variance CCh Carbachol CINM Critical illness neuromyopathy CMAP Compound muscle action potential EDB Musculus extensor digitorum brevis EFS Electric field stimulation ENG Electroneurography ICC Interstitial cells of Cajal ICU Intensive care unit ICUA-AW Intensive care unit acquired weakness K+ Potassium ions KHB Krebs–Henseleit-buffer MRC-SS Muscle research council sum score SMC Smooth muscle cell SNAP Sensory nerve action potential SOFA Sequential organ failure assessment TTX Tetrodotoxin. Most of them, e.g. cytokines and hormones, rather reflect the severity of critical illness itself and are of limited use for identifying individual patients that are prone to developing CINM or ICU-AW2
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