Sodium bicarbonate versus isotonic saline solution to prevent contrast-induced nephropathy: a systematic review and meta-analysis

Introduction: Contrast-induced nephropathy is one of the main causes of acute kidney injury and increased hospital-acquired morbidity and mortality. The use of sodium bicarbonate for nephroprotection has emerged as a preventative strategy; however, its efficacy is controversial compared to other strategies, such as hydration using 0.9% saline solution. Objective: To compare the effectiveness of sodium bicarbonate vs. hydration using 0.9% saline solution to prevent contrast-induced acute kidney injury. Methods: A systematic review of studies registered in the COCHRANE, PUBMED, MEDLINE, LILACS, SCIELO and EMBASE databases was conducted. Randomized controlled studies that evaluated the use of 0.9% saline solution vs. sodium bicarbonate to prevent contrast-induced nephropathy were included. Results: A total of 22 studies (5,686 patients) were included. Sodium bicarbonate did not decrease the risk of contrast-induced nephropathy (RD= 0.00; 95% CI= -0.02 to 0.03; p= 0.83; I2= 0%). No significant differences were found in the demand for renal replacement therapy (RD= 0.00; 95% CI= -0.01 to 0-01; I2= 0%; p= 0.99) or in mortality (RD= -0.00; 95% CI= -0.001 to 0.001; I2= 0%; p= 0.51). Conclusions: Sodium bicarbonate administration is not superior to the use of 0.9% saline solution for preventing contrast-induced nephropathy in patients with risk factors, nor is it better at reducing mortality or the need for renal replacement therapy.

Treatment of hemorrhagic shock with hypertonic saline solution modulates the inflammatory response to live bacteria in lungs

Shock and resuscitation render patients more susceptible to acute lung injury due to an exacerbated immune response to subsequent inflammatory stimuli. To study the role of innate immunity in this situation, we investigated acute lung injury in an experimental model of ischemia-reperfusion (I-R) followed by an early challenge with live bacteria. Conscious rats (N = 8 in each group) were submitted to controlled hemorrhage and resuscitated with isotonic saline (SS, 0.9% NaCl) or hypertonic saline (HS, 7.5% NaCl) solution, followed by intratracheal or intraperitoneal inoculation of Escherichia coli. After infection, toll-like receptor (TLR) 2 and 4 mRNA expression was monitored by RT-PCR in infected tissues. Plasma levels of tumor necrosis factor α and interleukins 6 and 10 were determined by ELISA. All animals showed similar hemodynamic variables, with mean arterial pressure decreasing to nearly 40 mmHg after bleeding. HS or SS used as resuscitation fluid yielded equal hemodynamic results. Intratracheal E. coli inoculation per se induced a marked neutrophil infiltration in septa and inside the alveoli, while intraperitoneal inoculation-associated neutrophils and edema were restricted to the interseptal space. Previous I-R enhanced lung neutrophil infiltration upon bacterial challenge when SS was used as reperfusion fluid, whereas neutrophil influx was unchanged in HS-treated animals. No difference in TLR expression or cytokine secretion was detected between groups receiving HS or SS. We conclude that HS is effective in reducing the early inflammatory response to infection after I-R, and that this phenomenon is achieved by modulation of factors other than expression of innate immunity components.

Essai clinique randomisé visant à évaluer l’efficacité du lavage des cavités nasales à l’aide d’une solution saline dans la prévention des otites moyennes aiguës à répétition

Introduction: Les instillations nasales de solution saline isotonique (INSS) chez les enfants sont recommandées par les pédiatres et des oto-rhino-laryngologistes de notre institution dans le but de prévenir les otites moyennes aigues à répétition (OMAr). Cependant, aucune étude dans la littérature ne vient corroborer ou infirmer cette pratique. Objectifs: Déterminer l’efficacité des INSS dans la prévention des OMAr. Méthode: Projet pilote d’un essai clinique randomisé. Les enfants diagnostiqués avec des OMAr étaient éligibles. Les patients recrutés ont été randomisés en 2 groupes. Seul le groupe traitement procède aux INSS. L’issue primaire est l’incidence d’OMAr pendant une période de 3 mois. Résultats: Vingt-neuf patients satisfaisant les critères d’inclusion et d’exclusion ont consenti à participer. Le taux d’OMAr était inférieur dans le groupe traitement (p=0.03, chi-carré) Conclusion: Les INSS semblent efficaces dans la prévention des OMAr. Une étude multicentrique est indiquée pour vérifier la validité externe et confirmer la sécurité.

Median preoptic nucleus mediates the cardiovascular recovery induced by hypertonic saline in hemorrhagic shock

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Renal sodium handling in acute and chronic salt loading/depletion protocols: the confounding influence of acute water loading.

OBJECTIVES: Renal tubular sodium handling was measured in healthy subjects submitted to acute and chronic salt-repletion/salt-depletion protocols. The goal was to compare the changes in proximal and distal sodium handling induced by the two procedures using the lithium clearance technique. METHODS: In nine subjects, acute salt loading was obtained with a 2 h infusion of isotonic saline, and salt depletion was induced with a low-salt diet and furosemide. In the chronic protocol, 15 subjects randomly received a low-, a regular- and a high-sodium diet for 1 week. In both protocols, renal and systemic haemodynamics and urinary electrolyte excretion were measured after an acute water load. In the chronic study, sodium handling was also determined, based on 12 h day- and night-time urine collections. RESULTS: The acute and chronic protocols induced comparable changes in sodium excretion, renal haemodynamics and hormonal responses. Yet, the relative contribution of the proximal and distal nephrons to sodium excretion in response to salt loading and depletion differed in the two protocols. Acutely, subjects appeared to regulate sodium balance mainly by the distal nephron, with little contribution of the proximal tubule. In contrast, in the chronic protocol, changes in sodium reabsorption could be measured both in the proximal and distal nephrons. Acute water loading was an important confounding factor which increased sodium excretion by reducing proximal sodium reabsorption. This interference of water was particularly marked in salt-depleted subjects. CONCLUSION: Acute and chronic salt loading/salt depletion protocols investigate different renal mechanisms of control of sodium balance. The endogenous lithium clearance technique is a reliable method to assess proximal sodium reabsorption in humans. However, to investigate sodium handling in diseases such as hypertension, lithium should be measured preferably on 24 h or overnight urine collections to avoid the confounding influence of water.

L-canavanine, an inhibitor of inducible nitric oxide synthase, improves venous return in endotoxemic rats.

OBJECTIVE: To investigate the hemodynamic effects of L-canavanine (an inhibitor of inducible, but not of constitutive, nitric oxide synthase) in endotoxic shock. DESIGN: Controlled, randomized, experimental study. SETTING: Animal laboratory. SUBJECTS: Wistar rats. INTERVENTIONS: Rats were anesthetized with pentobarbital, and hemodynamically monitored. One hour after an intravenous challenge with 5 mg/kg of Escherichia coli endotoxin, the rats were randomized to receive a continuous infusion of either L-canavanine (20 mg/kg/hr; n = 8) or vehicle only (isotonic saline, n = 11). In all animals, the infusion was given over 5 hrs at a rate of 2 mL/kg/hr. These experiments were repeated in additional rats challenged with isotonic saline instead of endotoxin (sham experiments). MEASUREMENTS AND MAIN RESULTS: Arterial blood pressure, heart rate, thermodilution cardiac output, central venous pressure, mean systemic filling pressure, urine output, arterial blood gases, blood lactate concentration, and hematocrit were measured. In sham experiments, hemodynamic stability was maintained throughout and L-canavanine had no detectable effect. Animals challenged with endotoxin and not treated with L-canavanine developed progressive hypotension and low cardiac output. After 6 hrs of endotoxemia, both central venous pressure and mean systemic filling pressure were significantly below their baseline values, indicating relative hypovolemia as the main determinant of reduced cardiac output. In endotoxemic animals treated with L-canavanine, hypotension was less marked, while cardiac output, central venous pressure, and mean systemic filling pressure were maintained throughout the experiment. L-canavanine had no effect on the time-course of hematocrit. L-canavanine significantly increased urine output and reduced the severity of lactic acidosis. CONCLUSIONS: Six hours after an endotoxin challenge in rats, low cardiac output develops, which appears to be primarily related to relative hypovolemia. L-canavanine, a selective inhibitor of the inducible nitric oxide synthase, increases the mean systemic filling pressure, thereby improving venous return, under these conditions.

Assessment of changes in body water by bioimpedance in acutely ill surgical patients.

OBJECTIVE: To evaluate the relationship between changes in body bioelectrical impedance (BI) at 0.5, 50 and kHz and the changes in body weight, as an index of total body water changes, in acutely ill surgical patients during the rapid infusion of isotonic saline solution. DESIGN: Prospective clinical study. SETTING: Multidisciplinary surgical ICU in a university hospital. PATIENTS: Twelve male patients treated for acute surgical illness (multiple trauma n = 5, major surgery n = 7). Selection criteria: stable cardiovascular parameters, normal cardiac function, signs of hypovolemia (CVP < or = 5 mmHg, urine output < 1 ml/kg x h). INTERVENTIONS: After baseline measurements, a 60 min fluid challenge test was performed with normal saline solution, 0.25 ml/kg/min [corrected]. MEASUREMENTS AND RESULTS: Body weight (platform digital scale), total body impedance (four-surface electrode technique; measurements at 0.5, 50 and 100 kHz) and urine output. Fluid retention induced a progressive decrease in BI at 0.5, 50 and 100 kHz, but the changes were significant for BI 0.5 and BI 100 only, from 40 min after the beginning of the fluid therapy onwards. There was a significant negative correlation between changes in water retention and BI 0.5, with individual correlation coefficients ranging from -0.72 to 0.95 (p < 0.01-0.0001). The slopes of the regression lines indicated that for each kg of water change, there was a mean decrease in BI of 18 ohm, but a substantial inter-individual variability was noted. CONCLUSION: BI measured at low frequency can represent a valuable index of acute changes in body water in a group of surgical patients but not in a given individual.

Effects of intranasal administration of synthetic (4-28)human atrial natriuretic peptide to normal volunteers.

The effects of intranasal administration of increasing doses of synthetic human natriuretic peptide (4-28 hANP) were studied in six healthy volunteers. The peptide was administered as a nasal spray at doses of 50, 100, 200, and 500 micrograms in ascending order at 48-h intervals. Vehicle was administered by the same route randomly between any two of the doses. Intranasal hANP administration had no effect on either blood pressure, heart rate (HR), or hematocrit. Diuresis did not change consistently, whereas natriuresis tended to rise with vehicle as well as with hANP administration. This was attributed to the infusion of isotonic saline during the experiment. There was no significant increase in plasma ANP levels after intranasal administration of any of the different doses. Thus, no evidence that the atrial natriuretic peptide tested (4-28 hANP) can cross the nasal mucosal barrier was found.

Eficàcia de la teràpia amb aigua de mar isitònica nebulitzada en pacients amb MPOC. Beneficis respecte a l'ús del sèrum fisiològic convencional

Objectius: Establir l’eficàcia del tractament, en quant a la millora de la qualitat de vida relacionada amb la salut (CVRS) que podem obtenir, efectuant nebulitzacions amb aigua de mar isotònica versus el sèrum fisiològic, en pacients crònics respiratoris amb MPOC. Secundàriament vol determinar si hi ha una millora subjectiva de la tolerància a l’exercici físic, una reducció significativa dels símptomes, de les aguditzacions amb els conseqüents ingressos hospitalaris i una reducció de la despesa farmacèutica. - Metodologia: Assaig clínic aleatoritzat a doble cec sobre 3 grups (aigua de mar, sèrum fisiològic i placebo) de 60 pacients d’atenció primària diagnosticats de MPOC moderada segons els criteris GOLD que hagin superat els criteris d’inclusió i exclusió. Les teràpies s’autoadministraran al propi domicili. Els resultats seran avaluats mitjançant els següents instruments: el CRQ (Chronic Respiratory Questionnaire), l’escala de dispnea del British Medical Research Council (MRC), la prova de la marxa de 6 minuts, espirometria, analítica, gasometria arterial i pulsioximetria. - Limitacions de l’estudi: Manca de participació, incompliment terapèutic, abandonament de l’hàbit tabàquic durant el tractament i pèrdues per temporalitat.

Moderate hypercapnia exerts beneficial effects on splanchnic energy metabolism during endotoxemia.

PURPOSE: Low tidal volume ventilation and permissive hypercapnia are required in patients with sepsis complicated by ARDS. The effects of hypercapnia on tissue oxidative metabolism in this setting are unknown. We therefore determined the effects of moderate hypercapnia on markers of systemic and splanchnic oxidative metabolism in an animal model of endotoxemia. METHODS: Anesthetized rats maintained at a PaCO(2) of 30, 40 or 60 mmHg were challenged with endotoxin. A control group (PaCO(2) 40 mmHg) received isotonic saline. Hemodynamic variables, arterial lactate, pyruvate, and ketone bodies were measured at baseline and after 4 h. Tissue adenosine triphosphate (ATP) and lactate were measured in the small intestine and the liver after 4 h. RESULTS: Endotoxin resulted in low cardiac output, increased lactate/pyruvate ratio and decreased ketone body ratio. These changes were not influenced by hypercapnia, but were more severe with hypocapnia. In the liver, ATP decreased and lactate increased independently from PaCO(2) after endotoxin. In contrast, the drop of ATP and the rise in lactate triggered by endotoxin in the intestine were prevented by hypercapnia. CONCLUSIONS: During endotoxemia in rats, moderate hypercapnia prevents the deterioration of tissue energetics in the intestine.

Use of raw Euphorbia tirucalli extract for inhibition of ascitic Ehrlich tumor

Objective: to evaluate the effect of the Euphorbia tirucalli hydroalcoholic extract (ETHE) on the development of Ehrlich Tumor, in its ascitic form. Methods: we intraperitoneally inoculated 15 Swiss mice with 10.44 x 107 cells of Ehrlich Tumor and divided them in two groups one day after: ETHE Group (eight mice), treated with a dosage of 125 mg/kg/day of EHTE for five days; and Control Group (seven mice), treated only with 0.9% isotonic saline solution over the same period. The treatment was done by gavage. Ten days after inoculation, four mice from each group were sacrificed for quantification of tumor cell number, ascitic fluid volume and bone marrow cell number. The remaining animals were maintained to evaluate survival. Results: The ascitic fluid volume and the tumor cell number were decreased in the ETHE group when compared with the control group, but with no statistical significance. On the other hand, survival was higher in the ETHE group, as well as the number of bone marrow cells. Conclusion: Treatment with ETHE after inoculation of Ehrlich Tumor decreases its development and increases survival and the bone marrow cellularity, thus reducing the myelosuppression present in the Ehrlich Tumor bearing mice.

Complement activation-related pseudoallergy in dogs following intravenous administration of a liposomal formulation of meglumine antimoniate

The increasing use of nanotechnologies in advanced therapies has allowed the observation of specific adverse reactions related to nanostructures. The toxicity of a novel liposome formulation of meglumine antimoniate in dogs with visceral leishmaniasis after single dose has been investigated. Groups of 12 animals received by the intravenous route a single dose of liposomal meglumine antimoniate (group I [GI], 6.5 mg Sb/kg), empty liposomes (GII) or isotonic saline (GIII). Evaluation of hematological and biochemical parameters showed no significant changes 4 days after administration. No undesired effects were registered in the GIII. However, adverse reactions were observed in 67.7% of dogs from both groups that received liposomal formulations. The side effects began moments after bolus administration and disappeared during the first 15 minutes after treatment. Prostation, sialorrhea and defecation were the most frequent clinical signs, registered in 33.3% and 41.6 % of animals from the groups GI and GII, respectively. Tachypnea, mydriasis, miosis, vomiting and cyanosis were also registered in both groups. The adverse reactions observed in this study were attributed to the activation of the complement system by lipid vesicles in a phenomenon known as Complement Activation-Related Pseudoallergy (CARPA). The influence of the physical-chemical characteristics of liposomal formulation in the triggering of CARPA is discussed.

The cardiopulmonary reflexes of spontaneously hypertensive rats are normalized after regression of left ventricular hypertrophy and hypertension

Cardiopulmonary reflexes are activated via changes in cardiac filling pressure (volume-sensitive reflex) and chemical stimulation (chemosensitive reflex). The sensitivity of the cardiopulmonary reflexes to these stimuli is impaired in the spontaneously hypertensive rat (SHR) and other models of hypertension and is thought to be associated with cardiac hypertrophy. The present study investigated whether the sensitivity of the cardiopulmonary reflexes in SHR is restored when cardiac hypertrophy and hypertension are reduced by enalapril treatment. Untreated SHR and WKY rats were fed a normal diet. Another groups of rats were treated with enalapril (10 mg kg-1 day-1, mixed in the diet; SHRE or WKYE) for one month. After treatment, the volume-sensitive reflex was evaluated in each group by determining the decrease in magnitude of the efferent renal sympathetic nerve activity (RSNA) produced by acute isotonic saline volume expansion. Chemoreflex sensitivity was evaluated by examining the bradycardia response elicited by phenyldiguanide administration. Cardiac hypertrophy was determined from the left ventricular/body weight (LV/BW) ratio. Volume expansion produced an attenuated renal sympathoinhibitory response in SHR as compared to WKY rats. As compared to the levels observed in normotensive WKY rats, however, enalapril treatment restored the volume expansion-induced decrease in RSNA in SHRE. SHR with established hypertension had a higher LV/BW ratio (45%) as compared to normotensive WKY rats. With enalapril treatment, the LV/BW ratio was reduced to 19% in SHRE. Finally, the reflex-induced bradycardia response produced by phenyldiguanide was significantly attenuated in SHR compared to WKY rats. Unlike the effects on the volume reflex, the sensitivity of the cardiac chemosensitive reflex to phenyldiguanide was not restored by enalapril treatment in SHRE. Taken together, these results indicate that the impairment of the volume-sensitive, but not the chemosensitive, reflex can be restored by treatment of SHR with enalapril. It is possible that by augmenting the gain of the volume-sensitive reflex control of RSNA, enalapril contributed to the reversal of cardiac hypertrophy and normalization of arterial blood pressure in SHR.