Stefania Bianzina

The Syndrome of Inappropriate Antidiuresis: Pathophysiology, Clinical Management and New Therapeutic Options

Hyponatremia is a marker of different underlying diseases and it can be a cause of morbidity itself; this implies the importance of a correct approach to the problem. The syndrome of inappropriate antidiuresis (SIAD) is one of the most common causes of hyponatremia: it is a disorder of sodium and water balance characterized by urinary dilution impairment and hypotonic hyponatremia, in the absence of renal disease or any identifiable non-osmotic stimulus able to induce antidiuretic hormone (ADH) release; according to its definition, it is diagnosed through an exclusion algorithm. SIAD is usually observed in hospitalized patients and its prevalence may be as high as 35%. The understanding of the syndrome has notably evolved over the last years, as reflected by the significant change in the name, once the syndrome of inappropriate secretion of ADH (SIADH), today SIAD. This review is up to date and it analyses the newest notions about pathophysiological mechanisms, classification, management and therapy of SIAD, including vaptans.

In vivo calibration of esophageal pressure in the mechanically ventilated patient makes measurements reliable.

BackgroundEsophageal pressure (Pes) can provide information to guide mechanical ventilation in acute respiratory failure. However, both relative changes and absolute values of Pes can be affected by inappropriate filling of the esophageal balloon and by the elastance of the esophagus wall. We evaluated the feasibility and effectiveness of a calibration procedure consisting in optimization of balloon filling and subtraction of the pressure generated by the esophagus wall (Pew).MethodsAn esophageal balloon was progressively filled in 36 patients under controlled mechanical ventilation. VBEST was the filling volume associated with the largest tidal increase of Pes. Esophageal wall elastance was quantified and Pew was computed at each filling volume. Different filling strategies were compared by performing a validation occlusion test.ResultsFifty series of measurements were performed. VBEST was 3.5 ± 1.9 ml (range 0.5–6.0). Esophagus elastance was 1.1 ± 0.5 cmH2O/ml (0.3–3.1). Both Pew and the result of the occlusion test differed among filling strategies. At filling volumes of 0.5, VBEST and 4.0 ml respectively, Pew was 0.0 ± 0.1, 2.0 ± 1.9, and 3.0 ± 1.7 cmH2O (p < 0.0001), whereas the occlusion test was satisfactory in 22 %, 98 %, and 88 % of cases (p < 0.0001).ConclusionsUnder mechanical ventilation, an increase of balloon filling above the conventionally recommended low volumes warrants complete transmission of Pes swings, but is associated with significant elevation of baseline. A simple calibration procedure allows finding the filling volume associated with the best transmission of tidal Pes change and subtracting the associated baseline artifact, thus making measurement of absolute values of Pes reliable.

Mechanisms underlying sCD40 production in hemodialysis patients.

CD40 and its ligand (CD40L) regulate several cellular functions, including T and B-cell activation. The soluble form of CD40 (sCD40) antagonizes CD40/CD40L interaction. Patients undergoing hemodialysis (HD) present elevated sCD40 serum levels, which underlying molecular mechanisms are unknown. We studied sCD40 serum and urinary levels, CD40 membrane and gene expression and membrane shedding in HD, uremic not-HD patients (UR) and healthy subjects (N). We found that in HD sCD40 serum levels were higher than UR and N, being significantly elevated in anuric patients, and that sCD40 correlated to renal function in UR subjects, who presented also a reduced sCD40 urinary excretion rate. HD and UR presented reduced CD40 membrane and gene expression. The concentration of TNF-α converting enzyme (TACE), responsible for CD40 cleavage was not different between HD and N. Therefore the reduced renal clearance is the main cause of elevated sCD40 levels in HD. This finding could have relevant clinical implications.

CD40/SCD40 imbalance in hemodialysis patients.

We read with great interest the paper by Pawlak et al. [1] recently published in Clinical Biochemistry. The authors demonstrated that the serum levels of soluble CD40 (sCD40), a natural antagonist of CD40/ CD40L system, are high in patients on hemodialysis (HD) and are strictly related to renal residual function (RRF). Elevated sCD40 serum levels have been reported in the clinical setting of chronic kidney disease, peritoneal dialysis, and HD and have been related to the deficient response to hepatitis B vaccination found in those patients [2,3]. In addition, it has been recently described that, in HD patients, the reduction of sCD40 levels by a treatment with a high permeability dialytic membrane is associated to a significant increase of anti-HBs antibody titer [4]. Therefore, a role for sCD40 in uremic immunodeficiency has been hypothesized and it is currently under investigation. In order to evaluate the CD40/sCD40 balance in HD patients, we performed an observational study comparing CD40 B-cell membrane expression and sCD40 serum levels among HD patients, uremic patients not on HD (UR) and, also, healthy subjects (HS). Fourteen stable patients (mean±SD; age, 65.1±13.6 years) on regular thrice-weekly bicarbonate HD for at least 6 months were enrolled. Patients affected by conditions influencing the immune response, such as acute infections, active immunological diseases, immunosuppressive therapy, previous transplantation, or history of malignancies, were excluded from the study. Control samples were taken from7UR(age, 68.8±8.5 years) and8HS(age, 47.9±11.5 years).

Renal involvement in mushroom poisoning: The case of Orellanus syndrome

Although mushroom poisoning is a rare cause of acute renal injury, in some cases it may lead to the development of a severe and irreversible renal failure. Orellanus syndrome is the most important example of organic renal damage related to mushroom consumption. It is caused by the ingestion of orellanine, the main toxin of different types of Cortinarius mushrooms (Cortinarius speciosissimus, C. orellanus, C. orellanoides, etc.), and it is characterized by progressive clinical phases with a predominant kidney involvement, finally requiring renal replacement therapy in about 10% of cases. Renal damage is often late and associated with a histological picture of interstitial nephritis. Diagnosis is essentially clinical and no specific therapy has been shown to be effective in preventing and treating renal damage. Here, we describe the case of a patient with mixed wild mushroom poisoning, presenting the typical clinical signs and course of the Orellanus syndrome. This case offers us the opportunity to review the main clinical features of this severe and little‐known intoxication.

Multiple electrolyte disorders in a neurosurgical patient: solving the rebus

BackgroundIt is important to ensure an adequate sodium and volume balance in neurosurgical patients in order to avoid the worsening of brain injury.Indeed, hyponatremia and polyuria, that are frequent in this patient population, are potentially harmful, especially if not promptly recognized.Differential diagnosis is often challenging, including disorders, which, in view of similar clinical pictures, present very different pathophysiological bases, such as syndrome of inappropriate antidiuresis, cerebral/renal salt wasting syndrome and diabetes insipidus.Case presentationHere we present the clinical report of a 67-year-old man with a recent episode of acute subarachnoid haemorrhage, admitted to our ward because of severe hyponatremia, hypokalemia and huge polyuria.We performed a complete workup to identify the underlying causes of these alterations and found a complex picture of salt wasting syndrome associated to primary polydipsia. The appropriate diagnosis allowed us to correct the patient hydro-electrolyte balance.ConclusionThe comprehension of the pathophysiological mechanisms is essential to adequately recognize and treat hydro-electrolyte disorders, also solving the most complex clinical problems.

Automatic monitoring of plateau and driving pressure during pressure and volume controlled ventilation

Plateau pressure (Pplat) limitation is routinely used to avoid ventilator-induced lung injury. Recently, driving pressure (ΔP) was strongly associated with survival in ARDS patients [1].

Artificial Lung Gas Exchanges Depend On Ecmo Settings

Artificial membrane lung (AL) gas exchanges are usually evaluated according to PaO2/FiO2 ratio. in addition, dead space ventilation and shunt fraction can be measured by the same equations used for native lungs [1].