[Weak respiratory muscles as a first sign of ALS: symptoms may put the physician on the wrong track]. / Zwakke ademhalingsspieren als eerste teken van ALS.

BACKGROUND: Patients with decreased exercise tolerance and orthopnoea are often referred to an internist, a cardiologist or a pulmonologist. These symptoms can also be caused by weakness of the respiratory muscles, as an indication of a neuromuscular disease. If these symptoms are not recognized as such, this may result in a delay in timely diagnosis. CASE DESCRIPTION: An 82-year-old man had suffered from decreased exercise tolerance for 18 months. For the last months he had been sleeping upright and had lost 20 kg in weight. Analyses by the cardiologist and the internist had not led to a definitive diagnosis. He was finally brought to the emergency department with loss of consciousness and hypercapnic respiratory insufficiency. Neurological examination was suggestive of motor neuron disease such as progressive spinal muscular atrophy or amyotrophic lateral sclerosis. The patient died within 24 hours of admission. CONCLUSION: Patients with symptoms resulting from respiratory muscle weakness are commonly referred to non-neurological specialists, leading to a delay in diagnosis and treatment of an underlying neuromuscular disease.

[No glucocorticoids for treatment of sepsis; unless ]. / Geen glucocorticoïden bij sepsis, tenzij .

Steroids influence the immune response and blood pressure in patients with septic shock. Many trials have evaluated a putative positive effect of steroids as an adjuvant therapy in patients with sepsis and septic shock, with contradictory outcomes. As a consequence, the use of steroids in sepsis patients varies widely. A recently published randomized clinical trial has demonstrated that treatment with hydrocortisone does not delay or prevent progress to septic shock in patients with sepsis. Based on the current available data, the use of steroids in sepsis should be reserved for those patients who remain severely hemodynamic unstable after fluid resuscitation and vasopressor therapy, or those with a separate indication for steroid therapy. A corticotropin stimulation test to evaluate adrenal insufficiency is not useful.

Characterization of a model of systemic inflammation in humans in vivo elicited by continuous infusion of endotoxin.

Investigating the systemic inflammatory response in patients with critical illness such as sepsis, trauma and burns is complicated due to uncertainties about the onset, duration and severity of the insult. Therefore, in vivo models of inflammation are essential to study the pathophysiology and to evaluate immunomodulatory therapies. Intravenous bolus administration of endotoxin to healthy volunteers is a well-established model of a short-lived systemic inflammatory response, characterized by increased plasma cytokine levels, flu-like symptoms and fever. In contrast, patients suffering from systemic inflammation are often exposed to inflammatory stimuli for an extended period of time. Therefore, continuous infusion of endotoxin may better reflect the kinetics of the inflammatory response encountered in these patients. Herein, we characterize a novel model of systemic inflammation elicited by a bolus infusion of 1 ng/kg, followed by a 3hr continuous infusion of 1 ng/kg/h of endotoxin in healthy volunteers, and compared it with models of bolus administrations of 1 and 2 ng/kg of endotoxin. The novel model was well-tolerated and resulted in a more pronounced increase in plasma cytokine levels with different kinetics and more prolonged symptoms and fever compared with the bolus-only models. Therefore, the continuous endotoxin infusion model provides novel insights into kinetics of the inflammatory response during continuous inflammatory stimuli and accommodates a larger time window to evaluate immunomodulating therapies.