As we administered IVIG only after the first clinical evidence of CIPNM at median five (three to seven) days after the start of the respective SIRS/sepsis episode, these two studies are selleckchem not entirely comparable.Rationale for the treatment strategyThe pathophysiologic rationale for using IVIG to treat CIPNM in the present study is based on the association of CIPNM with pro-inflammatory cytokines, such as TNF-��, IFN-��, IL-1, and IL-12 accompanied by increased E-selection expression [3,17]. This is suggested to promote the adhesion of leukocytes to endothelial-cells and extravasation of activated leukocytes within the endoneurial space. The increased cytokine production leads to enhanced vascular permeability favoring the passage of neurotoxic factors into the endoneurium causing neuron damage [18].

Furthermore, elevated cytokine levels directly induce muscle protein damage via activation of calpain and ubiquitine-proteasome [14]. The anti-inflammatory and immunomodulating properties of IVIG are mediated by regulating the production, release and function of pro-inflammatory cytokines and have been successfully used in numerous autoimmune and inflammatory diseases [16,21,22].The use of IgM-enriched IVIG was based on the potential superiority over standard IVIG as seen in sepsis treatment and on the analysis of Mohr et al., who suggested a beneficial effect of IgM-enriched IVIG in the prevention of CIPNM [15,23].Standard IVIG has been safely administered intravenously at daily doses of 0.40 g/kg body weight over five days in patients with Guillain-Barr�� syndrome [24].

Mohr et al. administered IgM-enriched IVIG at doses of 0.3 g/kg body weight daily over three days [15]. However, the manufacturer recommends that IgM-enriched IVIG be administered at a maximum dose of 0.25 g/kg body weight daily for three consecutive days, which is also the common dosage for the treatment of severe sepsis [25]. Therefore, we decided to administer IgM-enriched IVIG at a dose of 0.25 g/kg body weight daily for three consecutive days. Nevertheless, we cannot rule out a potential benefit with higher doses of IgM-enriched IVIG regarding the treatment of CIPNM.Strengths and limitationsIt is desirable to have a clinical endpoint like the Medical Research Council (MRC) scale for muscle strength to assess the course of CIPNM.

However, the MRC scale assessment depends on patient’s cooperation and cannot be performed in patients who are not fully awake [26]. Patients in our study were severely ill, represented by MOF, SIRS/sepsis and high SOFA/APACHE III scores. The vast majority was fully or partly sedated (87% at baseline; 50% on Day 14) and/or intubated/tracheotomized (95% Carfilzomib at baseline; 84% on Day 14). Therefore, clinical assessment of the muscle weakness using the MRC scale was not feasible in the majority of our patients.