Association between systemic hemodynamics and septic acute kidney injury in critically ill patients: a retrospective observational study

Introduction

The role of systemic hemodynamics in the pathogenesis of septic acute kidney injury (AKI) has received little attention. The purpose of this study was to investigate the association between systemic hemodynamics and new or persistent of AKI in severe sepsis.

Methods

A retrospective study between 2006 and 2010 was performed in a surgical ICU in a teaching hospital. AKI was defined as development (new AKI) or persistent AKI during the five days following admission based on the Acute Kidney Injury Network (AKIN) criteria. We studied the association between the following hemodynamic targets within 24 hours of admission and AKI: central venous pressure (CVP), cardiac output (CO), mean arterial pressure (MAP), diastolic arterial pressure (DAP), central venous oxygen saturation (ScvO₂) or mixed venous oxygen saturation (SvO₂).

Results

This study included 137 ICU septic patients. Of these, 69 had new or persistent AKI. AKI patients had a higher Simplified Acute Physiology Score (SAPS II) (57 (46 to 67) vs. 45 (33 to 52), P < 0.001) and higher mortality (38% vs. 15%, P = 0.003) than those with no AKI or improving AKI. MAP, ScvO₂ and CO were not significantly different between groups. Patients with AKI had lower DAP and higher CVP (P = 0.0003). The CVP value was associated with the risk of developing new or persistent AKI even after adjustment for fluid balance and positive end-expiratory pressure (PEEP) level (OR = 1.22 (1.08 to 1.39), P = 0.002). A linear relationship between CVP and the risk of new or persistent AKI was observed.

Conclusions

We observed no association between most systemic hemodynamic parameters and AKI in septic patients. Association between elevated CVP and AKI suggests a role of venous congestion in the development of AKI. The paradigm that targeting high CVP may reduce occurrence of AKI should probably be revised. Furthermore, DAP should be considered as a potential important hemodynamic target for the kidney.     

Vasculitis associated with large granular lymphocyte (LGL) leukemia: Presentation and treatment outcomes of 11 cases

Objective

The association between vasculitis and large granular lymphocyte (LGL) leukemia has rarely been reported or investigated. Thus, we assessed the clinical and biological phenotypes of LGL leukemia associated with vasculitis.

Results

We studied a series of 11 patients displaying LGL leukemia associated with vasculitis (LAV). The mean age at diagnosis of LGL leukemia was 60.3 years; there were nine women and two men. The mean follow-up period was 45 months. The main LGL lineage was T-LGL (10 patients), and only one NK-LGL was identified. Clinical and biological features of T-LGL leukemia were compared with those from the 2009 French T-LGL registry. We did not find any relevant differences except that patients with LAV were predominantly female (p < 0.05). The most frequently observed vasculitis was cryoglobulinemia (n = 5). Three patients presented with cutaneous leukocytoclastic angiitis, two patients had ANCA-negative microscopic polyangiitis, and one patient had giant cell arteritis. The main clinical features involved the skin, e.g., purpura (91%), arthralgia (37%), peripheral neuritis (27%), and renal glomerulonephritis (18%). The most frequent histologic finding was leucocytoclastic vasculitis (54%). The rate of complete remission was high; i.e., 80%. A minority of patients had a vasculitis relapse (27%). Three patients (27%) died; one death was related to LGL leukemia (acute infection) and the two other deaths were related to vasculitis (both with heart failure).

Conclusion

We conclude that vasculitis is overrepresented in the population of LGL patients, LAV predominantly affects women, vasculitis preferentially affects the small vessels, and LAV has high rate of complete response.     

Functional study, in man, of congestive gastropathy in cirrhosis by measurement of potential difference

The morphologic features of the gastric mucosa in patients with cirrhosis have been well investigated. The aim of this study was to evaluate its functional disruption by measuring the gastric potential difference. Forty patients were investigated, 12 control subjects and 28 consecutive cirrhotic patients with endoscopically proved congestive gastropathy. Potential difference was measured the morning, on an empty stomach, at least 3 days after endoscopy; the method used a double channel gastric perfused probe placed under fluoroscopy 10 cm above the cardia, and a subcutaneous reference, both connected to a millivoltimeter via gelose agar-KCl bridges. Potential difference was recorded in each case 20 min before (baseline) and after local instillation of lysine acetylsalicylate (500 mg) as a provocative test. Cirrhotic patients had significantly lower basal potential difference than controls (-28.3 +/- 1.5 mV vs -33.8 +/- 1.3mV, p = 0.007). Potential difference was significantly lower in patients with severe gastropathy than in patients with mild gastropathy (-20.5 +/- 2.1 and -28.9 +/- 1.6 mV, respectively, p less than 0.01). After stimulation with acetylsalicylate, the area under curve and the irritability index were greater in patients with gastropathy (81.4 +/- 12.8 vs 41.2 +/- 8.6 mV.min, p = 0.032 and 0.935 +/- 0.19 vs 0.290 +/- 0.07 mV.mV.min, p = 0.022, respectively). These differences were explained by a higher drop in potential difference (delta DPmax/baseline; 28.1 +/- 3 vs 16.1 +/- 3 p. 100, p = 0.006) whereas basal return time remained unchanged (16.2 +/- 2.1 vs 13.7 +/- 2.2 min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cachectine ou TNF (Tumor Necrosis Factor): implications cliniques

Septic shock remains an acute condition with a bad prognosis and a high mortality rate. This could be related to our incomplete understanding of the pathophysiological mechanisms involved, especially in the immunological field. Recently, several studies have stressed the key role of cytokines. Amongst these, the tumour necrosis factor (TNF) seems to be the most important. This peptide is a hormone secreted by monocytes and macrophages under the effect of various stimuli such as lipopolysaccharides or endotoxin. Giving TNF mimicks the clinical and biological patterns of septic shock. Moreover, high concentrations of TNF have been found in patients suffering from septic shock. Pretreatment with monoclonal antibodies against TNF prevents the occurrence of septic shock after endotoxin administration. TNF acts directly via ubiquitous specific receptors; this probably explains its diffuse activity. The therapeutic implications of these recent advances are not clear. It is not known, for the moment, whether TNF secretion is beneficial or deleterious for the patient.     

Plasma renin activity and prostaglandin E2 in hypotension induced by sodium nitroprusside

Sodium nitroprusside (SNP) is a potent, effective and readily reversible vasodilating agent frequently used in anaesthesia for deliberate hypotension. Moderate hypotension induced by SNP activated catecholamine and vasopressin secretions, and the renin-angiotensin system, resulting in partial antagonism of the hypotensive response to SNP. Furthermore, this increase in renin release was involved in the hypertensive rebound after SNP withdrawal. This activation of vasoconstrictor systems led to pharmacological associations aimed at reducing the risk of cyanide poisoning. The physiological interrelationship between prostaglandins and renin secretion has now been well established but, as far as we know, no paper existed concerning prostaglandins during SNP-induced hypotension. In such hypotension (Pa: -30%), monitored by invasive and non invasive haemodynamic techniques (pulsed Doppler), the variations in plasma renin activity (PRA) and in venous and arterial plasma PGE2 concentrations (V PGE2 and A PGE2), determined by radioimmunoassay, were studied in anaesthetized dogs. Invasive haemodynamic data were similar to previous reports. Common carotid diameter increased (p less than 0.05), with a constant common carotid blood flow. PRA (p less than 0.05), V PGE2 (p less than 0.05) and A PGE2 (p less than 0.05) increased. PRA and V PGE2 were highly correlated before and after SNP. SNP resulted in hypotension with reflex sympathetic activation and dilatation of large arteries. Carotid blood flow autoregulation was maintained. Whilst pulmonary removal of PGE2 remained unchanged, an increase in A PGE2 may have been involved in the vasodilator mechanisms.     

5-(2-bromoethyl)-2'-deoxyuridine: a selective inhibitor of herpes simplex viruses in vitro

A new pyrimidine analog, 5-(2-bromoethyl)-2'-deoxyuridine (BEUdR), was tested in vitro for antiviral activity on Herpes simplex virus types 1 and 2. As reference compounds, ACG, BVUdR and PAA were used. Compared to ACG and BVUdR, BEUdR resulted less potent on both HSV-1 and HSV-2. However, a 50% inhibition of the multiplication of uninfected cells could be obtained only at very high BEUdR concentration (ID50 = 8500 microM). This makes BEUdR the least toxic analog known and gives it a selective index comparable to, if not better, than of ACG and BVUdR.