Polyneuropathy in the critical ill patient: a common diagnosis in intensive care medicine?

BACKGROUND AND OBJECTIVES: The diffuse axonal polyneuropathy, more commonly known as Critical Illness Polyneuropathy (CIP), has been discussed by authors by decades; however, it has only been deeply studied over the last thirty years, becoming more important as an important cause of long term dependence on mechanical ventilation by seriously ill patients in intensive care medicine. CONTENTS: A significant reason for such interest is due to the importance of the CIP as complication of the septic shock and in patients with multiple organ failure, as much as responsible for the prolonging hospitalization in the Intensive Care Unit, as for the gradual reduction of the chance of survival. It has been suggested that the polyneuropathy is related with cytokines and other mediators which would increase the permeability of the vases, resulting in endoneural edema and causing the axonal injury. It is difficult to do the initial diagnostic, which, in general, are only possibly recognized when the sepsis complications or the multiple organs failure have been satisfactorily controlled. The diagnosis is made through the eletroneuromiography exam, and although there is still no effective drug treatment other than the control of the basic illness, it is consensus among multidisciplinary team that the development of the CIP does not have to be understood as a way to reduce the intensity of treatment. CONCLUSIONS: Spit of your prevalence, it is still unknown the mainly factors which are physiopathology associated as soon as your correct therapy.JUSTIFICATIVA E OBJETIVOS: A polineuropatia axonal difusa, hoje mais conhecida como polineuropatia do paciente crítico (PPC), tem sido relatada por autores há décadas, porém, apenas nos últimos 30 anos, ocupa maior importância como causa de dependência prolongada de ventilação mecânica, em pacientes gravemente enfermos internados em Unidades de Terapia Intensiva. Esta revisão teve por objetivo apresentar os princípios tópicos que norteiam a fisiopatologia, diagnóstico e tratamento desta doença em Medicina intensiva. CONTEÚDO: A importância da PPC como complicação inicial do choque séptico e em pacientes com disfunção de múltiplos de órgãos e sistemas (DMOS) está claramente descrita como responsável pelo prolongamento da permanência na UTI e, também pela redução gradativa da probabilidade de sobrevida. Sugere-se que a polineuropatia esteja relacionada com as citocinas envolvidas na sepse, além de outros mediadores que aumentariam a permeabilidade dos vasos, resultando em edema endoneural e lesão axonal. Seu início é de difícil diagnóstico, geralmente sendo possível apenas quando as complicações da sepse ou falência de múltiplos órgãos tenham sido adequadamente controladas. O diagnóstico é feito através da eletroneuromiografia. Apesar de ainda não haver nenhum tratamento medicamentoso efetivo, além do controle da doença de base, é censo comum, entre equipes multidisciplinares que o desenvolvimento da PPC não deve ser entendido como forma de reduzir os esforços do tratamento. CONLUSÕES: A despeito de sua prevalência, ainda permanecem desconhecidos os fatores claramente associados à sua fisiopatologia, bem como adequada terapia para o manuseio desta condição.UNIFESP-EPMAMIB AMBUNIFESP, EPMSciEL

Propentofylline Prevents Sickness Behavior and Depressive-Like Behavior Induced by Lipopolysaccharide in Rats via Neuroinflammatory Pathway

<div><p>Recent studies have demonstrated the intimate relationship between depression and immune disturbances. Aware of the efficacy limits of existing antidepressant drugs and the potential anti-inflammatory properties of propentofylline, we sought to evaluate the use of propentofylline as a depression treatment. We used a rat model of depression induced by repetitive lipopolysaccharide (LPS) administrations. We have studied sickness behavior, by assessing daily body weight, open field behavior, and TNF-α plasmatic levels. Anxiety-like behavior (light-dark test), depressive-like behavior (forced swim test), plasmatic levels of the brain-derived neurotrophic factor (BDNF, depression biomarker), and central glial fibrillary acidic protein (GFAP) expression (an astrocyte biomarker) were also evaluated. LPS induced body weight loss, open field behavior impairments (decreased locomotion and rearing, and increased immobility), and increased TNF-α levels in rats, compared with control group. Thus, LPS induced sickness behavior. LPS also increased the immobility and reduced climbing in the forced swim test, when compared with the control group, i.e., LPS induced depressive-like behavior in rats. Propentofylline prevented sickness behavior after four days of consecutive treatment, as well as prevented the depressive-like behavior after five days of consecutive treatments. Propentofylline also prevented the increase in GFAP expression induced by LPS. Neither LPS nor propentofylline has influenced the anxiety and BDNF levels of rats. In conclusion, repetitive LPS administrations induced sickness behavior and depressive-like behavior in rats. Propentofylline prevented both sickness behavior and depressive-like behavior via neuroinflammatory pathway. The present findings may contribute to a better understanding and treatment of depression and associated diseases.</p></div

Body weight.

<p>Effects of LPS (1 mg/kg/day) and propentofylline (12.5 mg/kg/day) on the body weight of adult male rats. SAL+SAL, saline injection at days 1–5 and another saline injection 1 h later at days 3–4; SAL+LPS, saline injection at days 1–5 and LPS injection 1 h later at days 3–4; PPF+LPS, propentofylline injection at days 1–5 and LPS injection 1 h later at days 3–4; PPF+SAL, propentofylline injection at days 1–5 and saline injection 1 h later at days 3–4 (<i>n</i> = 10 per group). *<i>p</i> < 0.05 and **<i>p</i> < 0.01, SAL+LPS vs. SAL+SAL; ^#<i>p</i> < 0.05, SAL+LPS vs. PPF+LPS; ⁺<i>p</i> < 0.05, SAL+SAL vs. PPF+SAL (two-way ANOVA followed by the Newman-Keuls test). The data are expressed as the mean ± SEM.</p

Anxiety-like behavior.

<p>Effects of LPS (1 mg/kg/day) and propentofylline (12.5 mg/kg/day) on the light-dark test in adult male rats. SAL+SAL, saline injection at days 1–5 and another saline injection 1 h later at days 3–4; SAL+LPS, saline injection at days 1–5 and LPS injection 1 h later at days 3–4; PPF+LPS, propentofylline injection at days 1–5 and LPS injection 1 h later at days 3–4; PPF+SAL, propentofylline injection at days 1–5 and saline injection 1 h later at days 3–4 (<i>n</i> = 10 per group). **<i>p</i> < 0.01 (one-way ANOVA followed by the Newman-Keuls test). The data are expressed as the mean ± SEM.</p

GFAP photomicrographs.

<p>Effects of LPS (1 mg/kg/day) and propentofylline (12.5 mg/kg/day) on central glial fibrillary acidic protein (GFAP) expression. Photomicrographs of the medial prefrontal cortex, nucleus accumbens, and hippocampus analyzed by immunohistochemistry in adult male rats. SAL+SAL, saline injection at days 1–5 and another saline injection 1 h later at days 3–4; SAL+LPS, saline injection at days 1–5 and LPS injection 1 h later at days 3–4; PPF+LPS, propentofylline injection at days 1–5 and LPS injection 1 h later at days 3–4; PPF+SAL, propentofylline injection at days 1–5 and saline injection 1 h later at days 3–4.</p

TNF-α and BDNF.

<p>Effects of LPS (1 mg/kg/day) and propentofylline (12.5 mg/kg/day) on TNF-α and BDNF plasma levels in adult male rats. SAL+SAL, saline injection at days 1–5 and another saline injection 1 h later at days 3–4; SAL+LPS, saline injection at days 1–5 and LPS injection 1 h later at days 3–4; PPF+LPS, propentofylline injection at days 1–5 and LPS injection 1 h later at days 3–4; PPF+SAL, propentofylline injection at days 1–5 and saline injection 1 h later at days 3–4 (<i>n</i> = 10 per group). **<i>p</i> < 0.01 (one-way ANOVA followed by the Newman-Keuls test). The data are expressed as the mean ± SEM.</p

Open-field behavior.

<p>Effects of LPS (1 mg/kg/day) and propentofylline (12.5 mg/kg/day) on the open-field behaviors in adult male rats. SAL+SAL, saline injection at days 1–5 and another saline injection 1 h later at days 3–4; SAL+LPS, saline injection at days 1–5 and LPS injection 1 h later at days 3–4; PPF+LPS, propentofylline injection at days 1–5 and LPS injection 1 h later at days 3–4; PPF+SAL, propentofylline injection at days 1–5 and saline injection 1 h later at days 3–4 (<i>n</i> = 10 per group). ***<i>p</i> < 0.001, SAL+LPS vs. SAL+SAL; ^#<i>p</i> < 0.05 and ^##<i>p</i> < 0.01, SAL+LPS vs. PPF+LPS; ⁺⁺<i>p</i> < 0.01, SAL+SAL vs. PPF+SAL (two-way ANOVA followed by the Newman-Keuls test). The data are expressed as the mean ± SEM.</p

GFAP expression.

<p>Effects of LPS (1 mg/kg/day) and propentofylline (12.5 mg/kg/day) on glial fibrillary acidic protein (GFAP) expression in the medial prefrontal cortex, nucleus accumbens, and hippocampus, analyzed by immunohistochemistry in adult male rats. SAL+SAL, saline injection at days 1–5 and another saline injection 1 h later at days 3–4; SAL+LPS, saline injection at days 1–5 and LPS injection 1 h later at days 3–4; PPF+LPS, propentofylline injection at days 1–5 and LPS injection 1 h later at days 3–4; PPF+SAL, propentofylline injection at days 1–5 and saline injection 1 h later at days 3–4 (<i>n</i> = 10 per group). *<i>p</i> < 0.05 and ***<i>p</i> < 0.0001 (one-way ANOVA followed by the Newman-Keuls test). The data are expressed as the mean ± SEM.</p

Depressive-like behavior.

<p>Effects of LPS (1 mg/kg/day) and propentofylline (12.5 mg/kg/day) on the forced-swim test in adult male rats. SAL+SAL, saline injection at days 1–5 and another saline injection 1 h later at days 3–4; SAL+LPS, saline injection at days 1–5 and LPS injection 1 h later at days 3–4; PPF+LPS, propentofylline injection at days 1–5 and LPS injection 1 h later at days 3–4; PPF+SAL, propentofylline injection at days 1–5 and saline injection 1 h later at days 3–4 (<i>n</i> = 10 per group). *<i>p</i> < 0.05, **<i>p</i> < 0.01, ***<i>p</i> < 0.001 (one-way ANOVA followed by the Newman-Keuls test). The data are expressed as the mean ± SEM.</p