Patricio Downey

Sublingual microcirculatory changes during high-volume hemofiltration in hyperdynamic septic shock patients

IntroductionPrevious studies have suggested that high volume hemofiltration (HVHF) may contribute to revert hypotension in severe hyperdynamic septic shock patients. However, arterial pressure stabilization occurs due to an increase in systemic vascular resistance, which could eventually compromise microcirculatory blood flow and perfusion. The goal of this study was to determine if HVHF deteriorates sublingual microcirculation in severe hyperdynamic septic shock patients.MethodsThis was a prospective, non-randomized study at a 16-bed, medical-surgical intensive care unit of a university hospital. We included 12 severe hyperdynamic septic shock patients (norepinephrine requirements > 0.3 μg/kg/min and cardiac index > 3.0 L/min/m2) who underwent a 12-hour HVHF as a rescue therapy according to a predefined algorithm. Sublingual microcirculation (Microscan for NTSC, Microvision Medical), systemic hemodynamics and perfusion parameters were assessed at baseline, at 12 hours of HVHF, and 6 hours after stopping HVHF.ResultsMicrocirculatory flow index increased after 12 hours of HVHF and this increase persisted 6 hours after stopping HVHF. A similar trend was observed for the proportion of perfused microvessels. The increase in microcirculatory blood flow was inversely correlated with baseline levels. There was no significant change in microvascular density or heterogeneity during or after HVHF. Mean arterial pressure and systemic vascular resistance increased while lactate levels decreased after the 12-hour HVHF.ConclusionsThe use of HVHF as a rescue therapy in patients with severe hyperdynamic septic shock does not deteriorate sublingual microcirculatory blood flow despite the increase in systemic vascular resistance.

Increased activation of protein C, but lower plasma levels of free, activated protein C in uraemic patients: relationship with systemic inflammation and haemostatic activation

Chronic renal failure (CRF) courses with both systemic inflammatory reaction and haemostatic activation. We explored the relationship of these processes with plasma levels of free, activated protein C (APC) and complexes of APC with its inhibitors in patients with CRF under conservative treatment. Plasma concentrations of inflammatory cytokines [tumour necrosis factor alpha (TNFα) and interleukin 8], acute‐phase proteins (C‐reactive protein, fibrinogen, α1‐anti‐trypsin and von Willebrand factor), and markers of haemostatic activation (thrombin–anti‐thrombin complexes, plasmin–anti‐plasmin complexes, and fibrin and fibrinogen degradation products) were higher in patients than in controls. Inflammatory and haemostatic markers were significantly and positively correlated. Total plasma APC and APC:α1‐anti‐trypsin (α1AT) complexes were 44% and 75% higher in patients than in controls (P = 0·0001), whereas free APC was 20% lower (P < 0·015). No significant difference was observed in APC:protein C inhibitor (PCI) complexes between both groups. The free/total APC ratio was significantly lower in patients than in controls (P < 0·0001). Total plasma APC and APC:α1AT were positively correlated with activation markers of haemostasis and acute‐phase proteins, whereas free APC was inversely correlated with plasma levels of creatinine, acute‐phase proteins and fibrin degradation products (FnDP). Systemic inflammation and activation of haemostasis are interrelated processes in CRF. APC generation was increased in response to elevated thrombin production, but the inflammatory reaction, associated with increased synthesis of α1AT, reduced its anticoagulant effect. Lower free plasma APC in CRF may be pathogenically associated with atherothrombosis, a major cause of death in this disease.

Pregnant Rats Treated With a Serotonin Precursor Have Reduced Fetal Weight and Lower Plasma Volume and Kallikrein Levels

Pregnant women with preeclampsia have increased serotonin levels, suggesting a possible role of this amine in abnormal pregnancy. With the hypothesis that an increase in serotonin would reduce volume expansion and cause fetal growth restriction, we evaluated the maternal and fetal effects of the administration of the serotonin precursor 5-hidroxytryptophan (5-HTP) to Sprague-Dawley rats. At pregnancy day 13 (n=19) or in random cycle nonpregnant rats (n=10), animals were assigned to a single injection of 5-HTP (100 mg/kg IP) or to a control group. Animals were studied at day 21, after overnight urinary collection. Additional pregnant rats received ketanserin (1 mg/kg), a 5-HT2 receptor antagonist, 1 hour before 5-HTP injection. In pregnant rats, 5-HTP lowered plasma volume (control: 22±1.1; 5-HTP: 17±0.7 mL; P<0.001) and creatinine clearance, whereas serum creatinine and urinary protein excretion were increased; no changes were observed in nonpregnant rats. Systolic blood pressure did not change significantly. Urinary kallikrein activity and plasma aldosterone levels decreased only in pregnant animals. Fetal (control: 5.5±0.1; 5-HTP: 4.2±0.2 g; P<0.001) and placental weights were reduced. In nonpregnant and pregnant animals, 5-HTP caused profound renal morphological alterations and decreased kallikrein immunostaining. Preadministration of ketanserin abolished all of the changes associated with the use of 5-HTP. These data indicate that the administration of a serotonin precursor to pregnant rats limits plasma volume expansion and fetal growth via 5-HT2 receptors, suggesting a possible role for serotonin in abnormal pregnancy. We postulate that an increased vascular resistance, both at the placental and renal levels, mediates these effects.

Population pharmacokinetics and dose simulation of vancomycin in critically ill patients during high-volume haemofiltration.

This study aimed to describe the population pharmacokinetics of vancomycin in critically ill patients with refractory septic shock undergoing continuous venovenous high-volume haemofiltration (HVHF) and to define appropriate dosing for these patients. This was a prospective pharmacokinetic study in the ICU of a university hospital. Eight blood samples were taken over one vancomycin dosing interval. Samples were analysed by a validated liquid chromatography-tandem mass spectrometry assay. Non-linear mixed-effects modelling was used to describe the population pharmacokinetics. Dosing simulations were used to define therapeutic vancomycin doses for different HVHF settings. Nine patients were included (five male). The mean weight and SOFA score were 70 kg and 11, respectively. Mean HVHF settings were: blood flow rate, 240 mL/min; and haemofiltration exchange rate, 100 mL/kg/h. A linear two-compartment model with zero-order input adequately described the data. Mean parameter estimates were: clearance, 2.9 L/h; volume of distribution of central compartment (V(1)), 11.8L; volume of distribution of peripheral compartment (V(2)), 18.0 L; and intercompartmental clearance, 9.3 L/h. HVHF intensity was strongly associated with vancomycin clearance (P < 0.05) and was a covariate in the final model. Simulations indicate that after a loading dose, vancomycin doses required for different HVHF intensities would be 750 mg every 12h (q12h) for 69 mL/kg/h, 1000 mg q12h for 100 mL/kg/h and 1500 mg q12h for 123 mL/kg/h. Continuous infusion would also be a valuable administration strategy. In conclusion, variable and much higher than standard vancomycin doses are required to achieve therapeutic concentrations during different HVHF settings.

Resolution of early stage diabetic nephropathy in an obese diabetic patient after gastric bypass

Epidemiological studies have proven that obesity is a significant risk factor for type 2 diabetes. Long-term progression of diabetes leads to various microvascular complications, of which diabetic nephropathy has become of increasing importance, and is the main cause of end-stage renal failure in occidental countries. Microalbuminuria is the first marker of incipient diabetic nephropathy, an early stage glomerulopathy which can progress to renal failure and which historically has been treated with angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists. We report a severely obese diabetic patient on treatment for diabetic nephropathy with ACE-inhibitors and poor results, which resolved after Roux-en-Y gastric bypass.

Fisiopatología de la insuficiencia renal aguda durante la sepsis

Acute renal failure (ARF) is an independent risk factor associated with increased mortality during sepsis. Recent consensus definitions have allowed the standardization of research on the subject. The understanding of the physiopathology of ARF during sepsis is limited by the scarcity of histological studies and the inability to measure renal microcirculatory flows. Historically, ARF during sepsis has been considered to be a consequence of diminished renal blood flow (RBF). Indeed, in early stages of sepsis or in sepsis associated to cardiogenic shock, RBF may decrease. However, recent studies have shown that in resuscitated sepsis, in which cardiac output is characteristically normal or even elevated and there is systemic vasodilatation, RBF is normal or even increased, with no associated histological evidence of significant tubular necrosis. Thus, other factors may participate in the genesis of ARF in sepsis. These include apoptosis, glomerular and medullary microcirculatory disorders, cell changes in response to the pro-inflammatory cascade characteristic of sepsis, oxidative stress, mitochondrial dysfunction and damage induced by mechanical ventilation, among others. Sepsis associated ARF treatment is supportive. In general, renal replacement therapies can be grouped as intermittent or continuous, and as those whose primary objective is the replacement of impaired renal function, versus those whose main objective is to secure hemodynamic stability through the clearing of pro-inflammatory mediators.

Shock cardiogénico por infarto agudo del miocardio manejado con hemofiltración de alto volumen: Caso clínico

Cardiogenic shock secondary to acute myocardial infarction unveils a systemic inflammatory response with elevation of cytokines that contribute to hypoperfusion. High volume hemofiltration may remove cytokines in patients with septic shock resulting in hemodynamic improvement and reducing the requirements of norepinephrine. We report a 48 year-old male with cardiogenic shock secondary to acute myocardial infarction who presented a systemic inflammatory response characterized by fever and hemodynamic collapse, without evidence of infection. Its hemodynamic profile was stabilized with high volume hemofiltration.

Method Based on the β-Lactamase PenPC Fluorescent Labeled for β-Lactam Antibiotic Quantification in Human Plasma.

Recently, Wong et al. have successfully developed a fluorescent biosensor based on the PenPC β-lactamase which changes its intrinsic fluorescence in presence of β-lactam antibiotics (BLAs). Here, we studied systematically this correlation among the fluorescence change of the biosensor and the concentration of different BLAs aimed at developing a novel method for estimating the concentration of a wide range of BLAs. This method showed high precision and specificity and very low interference from clinically relevant samples. We were able to monitor the pharmacokinetics of meropenem in healthy volunteers as well as in an ill animal model too, indicating that the implemented method could be suitable for clinical practice.

Creación del Comité de Nefrología Diagnóstica e Intervencionista de la Sociedad Chilena de Nefrología

Sr. Editor: El desarrollo dentro de la Nefrologia de un area dedicada tanto a procedimientos diagnosticos como terapeuticos es una aspiracion legitima. En las ultimas decadas los centros de salud han incorporado procedimientos que aportan valiosa informacion diagnostica y permiten implementar medidas terapeuticas efectivas. Complementando el cuidado de los pacientes hipertensos arteriales o insuficientes renales cronicos, creemos que podemos colaborar a su cuidado mediante estas acciones. Esta tendencia se ha reflejado en un incremento en la actividad asistencial asi como en cantidad de publicaciones que han aparecido en relacion a procedimientos invasivos o no invasivos realizados por distintos grupos nefrologicos (1,2). En nuestro medio se han realizado cursos de nefrologia intervencionista con buena acogida de publico y en congresos de la especialidad los trabajos presentados tambien tienden a incrementarse ano a ano. (Libro de resumenes 29o Congreso Conjunto de las Sociedades Chilenas de Nefrologia, Hipertension y trasplante, Pucon Septiembre 2012). leer mas...

Incidencia e importancia pronóstica del deterioro de la función renal en pacientes hospitalizados con insuficiencia cardiaca

Background: Acute deterioration of kidney function among patients admitted to the hospital for cardiac failure is associated with an increased mortality. Aim: To investigate the association between deterioration of kidney function and mortality among patients hospitalized for cardiac failure. Material and Methods: Patients admitted for decompensated cardiac failure to 14 Chilean hospitals between 2002 and 2009 were incorporated to the study. Clinical and laboratory features were registered. Serum creatinine values on admission and discharge were determined. Hospital and long term mortality was determined requesting death certificates to the National Identification Service at the end of follow up, lasting 635 ± 581 days. Results: One thousand sixty four patients were incorporated and 1100, aged 68 ± 13 years (45% females) had information about renal function. Seventy seven percent were hypertensive and 36% were diabetic. Mean ejection fraction was 41 ± 18% and 34% had an ejection fraction over 50%. Mean admission creatinine was 1.7 ± 1.6 mg/dl and 19% had a creatinine over 2 mg/dl. Serum creatinine increased more than 0.5 mg/dl during hospitalization in 9% of general patients and in 11% of diabetics. The increase in creatinine was associated with a higher risk of hospital mortality (odds ratio (OR) 12.9, 95% confidence intervals (CI) 6.7-27.6) and long term mortality (OR 2.1, 95% CI 1.6-3). Conclusions: The deterioration of renal function during hospitalization of patients with heart failure is a risk factor for hospital and long term mortality.BACKGROUND Acute deterioration of kidney function among patients admitted to the hospital for cardiac failure is associated with an increased mortality. AIM To investigate the association between deterioration of kidney function and mortality among patients hospitalized for cardiac failure. MATERIAL AND METHODS Patients admitted for decompensated cardiac failure to 14 Chilean hospitals between 2002 and 2009 were incorporated to the study. Clinical and laboratory features were registered. Serum creatinine values on admission and discharge were determined. Hospital and long term mortality was determined requesting death certificates to the National Identification Service at the end of follow up, lasting 635 ± 581 days. RESULTS One thousand sixty four patients were incorporated and 1100, aged 68 ± 13 years (45% females) had information about renal function. Seventy seven percent were hypertensive and 36% were diabetic. Mean ejection fraction was 41 ± 18% and 34% had an ejection fraction over 50%. Mean admission creatinine was 1.7 ± 1.6 mg/dl and 19% had a creatinine over 2 mg/dl. Serum creatinine increased more than 0.5 mg/dl during hospitalization in 9% of general patients and in 11% of diabetics. The increase in creatinine was associated with a higher risk of hospital mortality (odds ratio (OR) 12.9, 95% confidence intervals (CI) 6.7-27.6) and long term mortality (OR 2.1, 95% CI 1.6-3). CONCLUSIONS The deterioration of renal function during hospitalization of patients with heart failure is a risk factor for hospital and long term mortality.