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OBJECTIVE: To determine if initial fluid resuscitation with balanced crystalloid (e.g., multiple electrolytes solution [MES]) or 0.9% saline adversely affects kidney function in children with septic shock. DESIGN: Parallel-group, blinded multicenter trial. SETTING: PICUs of four tertiary care centers in India from 2017 to 2020. PATIENTS: Children up to 15 years of age with septic shock. METHODS: Children were randomized to receive fluid boluses of either MES (PlasmaLyte A) or 0.9% saline at the time of identification of shock. All children were managed as per standard protocols and monitored until discharge/death. The primary outcome was new and/or progressive acute kidney injury (AKI), at any time within the first 7 days of fluid resuscitation. Key secondary outcomes included hyperchloremia, any adverse event (AE), at 24, 48, and 72 hours, and all-cause ICU mortality. INTERVENTIONS: MES solution (n = 351) versus 0.9% saline (n = 357) for bolus fluid resuscitation during the first 7 days. MEASUREMENTS AND MAIN RESULTS: The median age was 5 years (interquartile range, 1.3-9); 302 (43%) were girls. The relative risk (RR) for meeting the criteria for new and/or progressive AKI was 0.62 (95% CI, 0.49-0.80; p < 0.001), favoring the MES (21%) versus the saline (33%) group. The proportions of children with hyperchloremia were lower in the MES versus the saline group at 24, 48, and 72 hours. There was no difference in the ICU mortality (33% in the MES vs 34% in the saline group). There was no difference with regard to infusionrelated AEs such as fever, thrombophlebitis, or fluid overload between the groups. CONCLUSIONS: Among children presenting with septic shock, fluid resuscitation with MES (balanced crystalloid) as compared with 0.9% saline resulted in a significantly lower incidence of new and/or progressive AKI during the first 7 days of hospitalization. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the dynamics of the pituitary-adrenal interaction during the course of coronary artery bypass grafting both on and off pump. Since our data pointed to a major change in adrenal responsiveness to adrenocorticotropic hormone, we used a reverse translation approach to investigate the molecular mechanisms underlying this change in a rat model of critical illness. Design: Clinical studies: Prospective observational study. Animal studies: Controlled experimental study. Setting: Clinical studies: Cardiac surgery operating rooms and critical care units. Animal studies: University research laboratory. Subjects: Clinical studies: Twenty, male patients. Animal studies: Adult, male Sprague-Dawley rats. Interventions: Clinical studies: Coronary artery bypass graft-both on and off pump. Animal studies: Injection of either lipopolysaccharide or saline (controls) via a jugular vein cannula. Measurements and Main Results: Clinical studies: Blood samples were taken for 24 hours from placement of the first venous access. Cortisol and adrenocorticotropic hormone were measured every 10 and 60 minutes, respectively, and corticosteroid-binding globulin was measured at the beginning and end of the 24-hour period and at the end of operation. There was an initial rise in both levels of adrenocorticotropic hormone and cortisol to supranormal values at around the end of surgery. Adrenocorticotropic hormone levels then returned toward preoperative values. Ultradian pulsatility of both adrenocorticotropic hormone and cortisol was maintained throughout the perioperative period in all individuals. The sensitivity of the adrenal gland to adrenocorticotropic hormone increased markedly at around 8 hours after surgery maintaining very high levels of cortisol in the face of "basal" levels of adrenocorticotropic hormone. This sensitivity began to return toward preoperative values at the end of the 24-hour sampling period. Animal studies: Adult, male Sprague-Dawley rats were given either lipopolysaccharide or sterile saline via a jugular vein cannula. Hourly blood samples were subsequently collected for adrenocorticotropic hormone and corticosterone measurement. Rats were killed 6 hours after the injection, and the adrenal glands were collected for measurement of steroidogenic acute regulatory protein, steroidogenic factor 1, and dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 messenger RNAs and protein using real-time quantitative polymerase chain reaction and Western immunoblotting, respectively. Adrenal levels of the adrenocorticotropic hormone receptor (melanocortin type 2 receptor) messenger RNA and its accessory protein (melanocortin type 2 receptor accessory protein) were also measured by real-time quantitative polymerase chain reaction. In response to lipopolysaccharide, rats showed a pattern of adrenocorticotropic hormone and corticosterone that was similar to patients undergoing coronary artery bypass grafting. We were also able to demonstrate increased intra-adrenal corticosterone levels and an increase in steroidogenic acute regulatory protein, steroidogenic factor 1, and melanocortin type 2 receptor accessory protein messenger RNAs and steroidogenic acute regulatory protein, and a reduction in dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 and melanocortin type 2 receptor messenger RNAs, 6 hours after lipopolysaccharide injection. Conclusions: Severe inflammatory stimuli activate the hypothalamic- pituitary-adrenal axis resulting in increased steroidogenic activity in the adrenal cortex and an elevation of cortisol levels in the blood. Following coronary artery bypass grafting, there is a massive increase in both adrenocorticotropic hormone and cortisol secretion. Despite a subsequent fall of adrenocorticotropic hormone to basal levels, cortisol remains elevated and coordinated adrenocorticotropic hormone-cortisol pulsatility is maintained. This suggested that there is an increase in adrenal sensitivity to adrenocorticotropic hormone, which we confirmed in our animal model of immune activation of the hypothalamic-pituitary- adrenal axis. Using this model, we were able to show that this increased adrenal sensitivity results from changes in the regulation of both stimulatory and inhibitory intra-adrenal signaling pathways. Increased understanding of the dynamics of normal hypothalamicpituitary- adrenal responses to major surgery will provide us with a more rational approach to glucocorticoid therapy in critically ill patients. [ABSTRACT FROM AUTHOR]

The article presents a study which determined the effects of compression of the lungs due to thoracoabdominal constriction in acute lung injury on ventilator-induced lung injury and lung function in rats. Saline lavage was used to induce acute lung injury. It was found that chest wall constriction worsens hypoxemia, decreases lung volume, proinflammatory mediator release, mechanical abnormalities, and increases pulmonary edema.

The article presents a study which identifies whether circadian clock gene expression in the human peripheral blood leukocytes is altered dramatically and possibly uncoupled from the central clock's activity during periods of acute systemic inflammation. It says that a standard dose of endotoxin or saline was administered to human subjects and collected blood samples at selected pre- and postinfusion periods. The results showed that the melatonin secretory rhythm was not perturb by endotoxin.

The article presents a study which aims to determine whether elevation of plasma cortisol enhances human systemic inflammatory response to Escherichia coli endotoxin. In this study, total plasma and salivary-free cortisol of research subjects who received intravenous injection of bacterial endotoxin following intravenous infusion of saline or hydrocortisone were measured. Results show that interleukin-6 response to endotoxemia was increased following subject's exposure to cortisol.

The article evaluates the correlation between pulmonary artery and aortic transpulmonary thermodilution (TPTD) for monitoring of cardiac output (CO) in patients with severe left ventricular dysfunction. According to the authors, the two methods were compared by simultaneously recording the results of pulmonary artery and TPTD after injection of a cold saline bolus. They add that mean CO of both methods was 4.4 L/min with a basis of 0.45 L/min, resulting in a percentage error of 27.3%.

B Learning Objectives: b The use of non-buffered 0.9% normal saline (NS) for resuscitation contributes to metabolic disturbances, kidney injury and increased mortality. In this study, a porcine model of controlled hemorrhage and volume overload resuscitation was used to characterize the effects of NS compared to a balanced buffered electrolyte solution [PlasmaLyte (PL)] on acid base status and endothelial function. [Extracted from the article]

The author comments on a study published within the issue that described the effects of bolus injection of saline and hydroxyethyl starch (HHS) on functional neurological recovery after successful restoration of circulation in a rat model of cardiac arrest. Findings showed that neurological assessments of the animals did not reveal benefits from HHS treatment. He also noted that the superiority of hypertonic resuscitation in traumatic brain injury could neither be aptly demonstrated.

The author expresses his views on the impact of hypertonic saline over mannitol on attenuating cerebral edema in a rabbit bacterial meningitis model in relation to a study conducted by researcher S. Liu and colleagues, published in a 2011 issue of the journal "Critical Care Medicine." The aim of the researchers was to identify a treatment for elevated intracranial pressure (ICP). The author also offers information on hypertonic saline as an osmotic agent.