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Perioperative fluid therapy and associated outcomes of patients undergoing major elective open gastrointestinal surgery are poorly understood. This study measured perioperative fluid therapy, complication rates and outcomes for major elective open gastrointestinal surgery in a tertiary care hospital. We obtained demographic data, operative details, fluid prescription, complications and outcomes in 100 patients. Patients were elderly and had multiple comorbidities. Median delivered intraoperative fluid volume was 4.2 litres, followed by 6.3 litres over the subsequent 24 hours. Perioperative fluid prescription was associated with a positive fluid balance. Complications occurred in 57% of patients with 32% experiencing at least one major complication. Serious complications were substantially more frequent in patients having non-colorectal operations. The most common adverse events were pulmonary oedema (21%), ileus (18%), serious sepsis (17%), pneumonia (17%), arrhythmias (14%), delirium (14%) and wound healing problems (infections 13%, anastomotic leaks 12%). Mortality at 30 days was 2%. This study provides planning data for future interventional studies. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are a new mechanism of cellular communication, by delivering their cargo into target cells to modulate molecular pathways. EV-mediated crosstalk contributes to tumor survival and resistance to cellular stress. However, the role of EVs in B-cell Acute Lymphoblastic Leukaemia (B-ALL) awaits to be thoroughly investigated. We recently published that ActivinA increases intracellular calcium levels and promotes actin polymerization in B-ALL cells. These biological processes guide cytoskeleton reorganization, which is a crucial event for EV secretion and internalization. Hence, we investigated the role of EVs in the context of B-ALL and the impact of ActivinA on this phenomenon. We demonstrated that leukemic cells release a higher number of EVs in response to ActivinA treatment, and they can actively uptake EVs released by other B-ALL cells. Under culture-induced stress conditions, EVs coculture promoted cell survival in B-ALL cells in a dose-dependent manner. Direct stimulation of B-ALL cells with ActivinA or with EVs isolated from ActivinA-stimulated cells was even more effective in preventing cell death. This effect can be possibly ascribed to the increase of vesiculation and modifications of EV-associated microRNAs induced by ActivinA. These data demonstrate that ActivinA boosts EV-mediated B-ALL crosstalk, improving leukemia survival in stress conditions., (© 2024. The Author(s).)

Objectives: To identify the best population, design of the intervention, and to assess between-group biochemical separation, in preparation for a future phase III trial., Design: Investigator-initiated, parallel-group, pilot randomized double-blind trial., Setting: Eight ICUs in Australia, New Zealand, and Japan, with participants recruited from April 2021 to August 2022., Patients: Thirty patients greater than or equal to 18 years, within 48 hours of admission to the ICU, receiving a vasopressor, and with metabolic acidosis (pH < 7.30, base excess [BE] < -4 mEq/L, and Pa co2 < 45 mm Hg)., Interventions: Sodium bicarbonate or placebo (5% dextrose)., Measurements and Main Result: The primary feasibility aim was to assess eligibility, recruitment rate, protocol compliance, and acid-base group separation. The primary clinical outcome was the number of hours alive and free of vasopressors on day 7. The recruitment rate and the enrollment-to-screening ratio were 1.9 patients per month and 0.13 patients, respectively. Time until BE correction (median difference, -45.86 [95% CI, -63.11 to -28.61] hr; p < 0.001) and pH correction (median difference, -10.69 [95% CI, -19.16 to -2.22] hr; p = 0.020) were shorter in the sodium bicarbonate group, and mean bicarbonate levels in the first 24 hours were higher (median difference, 6.50 [95% CI, 4.18 to 8.82] mmol/L; p < 0.001). Seven days after randomization, patients in the sodium bicarbonate and placebo group had a median of 132.2 (85.6-139.1) and 97.1 (69.3-132.4) hours alive and free of vasopressor, respectively (median difference, 35.07 [95% CI, -9.14 to 79.28]; p = 0.131). Recurrence of metabolic acidosis in the first 7 days of follow-up was lower in the sodium bicarbonate group (3 [20.0%] vs. 15 [100.0%]; p < 0.001). No adverse events were reported., Conclusions: The findings confirm the feasibility of a larger phase III sodium bicarbonate trial; eligibility criteria may require modification to facilitate recruitment., Competing Interests: Dr. Higgins’ institution received funding from the National Health and Medical Research Council (NHMRC) investigator grant. Dr. Young disclosed government work. Dr. Maeda disclosed work for hire. Dr. French disclosed the off-label product use of Sodium bicarbonate in critical illness. Dr. Cooper’s institution received funding from the NHMRC of Australia and Eustralis Pharmaceuticals Pty Ltd (Pressura Neuro). Dr. Udy disclosed that he received trial consumables from Integra Lifesciences. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

In recent years considerable progress has been made in identifying the impact of mRNA translation in tumour progression. Cancer cells hijack the pre-existing translation machinery to thrive under the adverse conditions originating from intrinsic oncogenic programs, that increase their energetic demand, and from the hostile microenvironment. A key translation program frequently dysregulated in cancer is the Integrated Stress Response, that reprograms translation by attenuating global protein synthesis to decrease metabolic demand while increasing translation of specific mRNAs that support survival, migration, immune escape. In this review we provide an overview of the Integrated Stress Response, emphasise its dual role during tumorigenesis and cancer progression, and highlight the therapeutic strategies available to target it., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: We aimed to assess the biochemical and physiological effects, clinical efficacy, and safety, of intravenous NaHCO3 therapy in critically ill patients with acute metabolic acidosis., Methods: We conducted a scoping review concerning the biochemical and physiological effects of NaHCO3 (PART A), and a systematic review regarding clinical efficacy (PART B). We searched MEDLINE in Part A and MEDLINE, EMBASE, Cochrane, the National Institute of Health Clinical Trials Register, and the WHOICTRP for randomised controlled trials in Part B., Results: Twelve studies in Part A and two trials in Part B fulfilled the eligibility criteria. Intravenous NaHCO3 increased blood pH, base excess, serum bicarbonate, sodium, and PaCO2 during and after administration and decreased anion gap and potassium value. For clinical efficacy, only one study contributed to the effect estimate. The risk ratio (RR) for all-cause mortality was 0.83 (95% confidence interval, 0.68 to 1.02), and the risk of hypocalcaemia was increased in the bicarbonate group (RR 1.65, 95% confidence interval 1.09 to 2.50). There were inadequate data on hemodynamic indices., Conclusions: Given the lack of data on the effects of intravenous NaHCO3 therapy to support its clinical use and the frequency of bicarbonate therapy, a program of investigation appears justified., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To evaluate the prevalence of "likely overassistance" (categorised by respiratory rate [RR] ≤ 17 breaths/min or rapid shallow breathing index [RSBI] ≤ 37 breaths/min/L) during invasive pressure support ventilation (PSV), and the additional prevalence of fixed ventilator settings., Design: Multicentre prospective observational study of invasive PSV practice in six general Victorian intensive care units with blinding of staff members to data collection., Patients: At each hospital, investigators collected data between 11 am and 2 pm on all invasive PSV-treated patients on 60 sequential days, excluding weekends and public holidays, between 22 February and 30 August 2017. Each patient was included for maximum of 3 days., Main Results: We studied 231 patients, with a total of 379 observations episodes over the study period. There were 131 patients (56.7%) with at least one episode of RR ≤ 17 breaths/min; 146 patients (63.2%) with at least one episode of RSBI ≤ 37 breaths/min/L, and 85 patients (36.8%) with at least one episode of combined RR ≤ 17 breaths/min and RSBI ≤ 37 breaths/min/L. Moreover, the total number of observations with "likely overassistance" (RR ≤ 17 or RSBI ≤ 37 breaths/min/L) was 178 (47%) and 204 (53.8%), respectively; while for both combined criteria, it was 154 (40.6%). We also found that 10 cmH 2 O pressure support was delivered on 210 of the observations (55.4%) and adjusted in less than 25% of observations. Finally, less than half (179 observations) of all PSV-delivered tidal volumes (V T ) were at the recommended value of 6-8 mL/kg predicted body weight (PBW) and more than 20% (79 observations) were at ≥ 10 mL/kg PBW., Conclusion: In a cohort of Victorian hospitals in Australia, during invasive PSV, "likely overassistance" was common, and the pressure support level was delivered in a standardised and unadjusted manner at 10 cmH 2 O, resulting in the frequent delivery of potentially injurious V T .

Objectives: In critically ill patients with acute kidney injury receiving vasopressors, high cytokine levels may sustain the shock state. High cutoff hemofiltration achieves greater cytokine removal in ex vivo and in animal models and may reduce the duration of shock but may also increase albumin losses., Design: This was a single-center double-blind randomized controlled trial comparing continuous venovenous hemofiltration-high cutoff to continuous venovenous hemofiltration-standard., Setting: Tertiary care hospital in Australia., Patients: Vasopressor-dependent patients in acute kidney injury who were admitted to the ICU., Interventions: Norepinephrine-free time were calculated in critically ill vasopressor-dependent patients in acute kidney injury, randomized to either continuous venovenous hemofiltration-high cutoff or continuous venovenous hemofiltration-standard., Measurement and Main Results: A total of 76 patients were randomized with the following characteristics (continuous venovenous hemofiltration-high cutoff vs continuous venovenous hemofiltration-standard); median age of 65 versus 70 year, percentage of males 47% versus 68%, and median Acute Physiology and Chronic Health Evaluation scores of 25 versus 23.5. The median hours of norepinephrine-free time at day 7 were 32 (0-110.8) for continuous venovenous hemofiltration-high cutoff and 56 hours (0-109.3 hr) (p = 0.520) for continuous venovenous hemofiltration-standard. Inhospital mortality was 55.6% with continuous venovenous hemofiltration-high cutoff versus 34.2% with continuous venovenous hemofiltration-standard (adjusted odds ratio, 2.49; 95% CI, 0.81-7.66; p = 0.191). There was no significant difference in time to cessation of norepinephrine (p = 0.358), time to cessation of hemofiltration (p = 0.563), and filter life (p = 0.21). Serum albumin levels (p = 0.192) were similar and the median dose of IV albumin given was 90 grams (20-212 g) for continuous venovenous hemofiltration-high cutoff and 80 grams (15-132 g) for continuous venovenous hemofiltration-standard (p = 0.252)., Conclusions: In critically ill patients with acute kidney injury, continuous venovenous hemofiltration-high cutoff did not reduce the duration of vasopressor support or mortality or change albumin levels compared with continuous venovenous hemofiltration-standard.

The knowledge about the vector-borne infections in domestic dogs has been increasing worldwide. However no studies have been done on hard tick infestation and tick-borne pathogens (TBPs) of dogs present in Malta. Therefore, a total of 99 dogs was selected and inspected between March and July 2013 in 18 urban and 17 rural areas on the islands of Malta and Gozo. All ticks were removed from the dogs and identified. Blood samples were taken and tested for protozoa (Babesia spp. and Hepatozoon spp.) and bacteria (Anaplasma spp., Ehrlichia spp., Rickettsia spp.) by conventional PCR. All of the ticks collected from 34 (34.3%; 95% CI: 26-44) dogs belong to the species Rhipicephalus sanguineus sensu lato. Tick infestation on the farm dogs was significantly higher than that of dogs kept outdoors as pets (OR: 15.19, 95% CI: 2.72-118.92, p<0.001) or in a sanctuary (OR: 35.11, 95% CI: 3.20-1986.67, p<0.001). Altogether 22 animals were infected with one or two TBPs, most of them with Hepatozoon canis (16/22; 72.7%). Anaplasma platys and Babesia vogeli were detected in 5 and 4 dogs, respectively. Three dogs had co-infections caused by H. canis and A. platys. To the best of our knowledge, this is the first report on tick infestation and TBPs of dogs in Malta., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Novel acute kidney injury (AKI) biomarkers offer promise of earlier diagnosis and risk stratification, but have yet to find widespread clinical application. We measured urinary α and π glutathione S-transferases (α-GST and π-GST), urinary l-type fatty acid-binding protein (l-FABP), urinary neutrophil gelatinase-associated lipocalin (NGAL), urinary hepcidin and serum cystatin c (CysC) before surgery, post-operatively and at 24 h after surgery in 93 high risk patient undergoing cardiopulmonary bypass (CPB) and assessed the ability of these biomarkers alone and in combination to predict RIFLE-R defined AKI in the first 5 post-operative days. Twenty-five patients developed AKI. π-GST (ROCAUC = 0.75), lower urine Hepcidin:Creatine ratio at 24 h (0.77), greater urine NGAL:Cr ratio post-op (0.73) and greater serum CysC at 24 h (0.72) best predicted AKI. Linear combinations with significant improvement in AUC were: Hepcidin:Cr 24 h + post-operative π-GST (AUC = 0.86, p = 0.01), Hepcidin:Cr 24 h + NGAL:Cr post-op (0.84, p = 0.03) and CysC 24 h + post-operative π-GST (0.83, p = 0.03), notably these significant biomarkers combinations all involved a tubular injury and a glomerular filtration biomarker. Despite statistical significance in receiver-operator characteristic (ROC) analysis, when assessed by ability to define patients to two groups at high and low risk of AKI, combinations failed to significantly improve classification of risk compared to the best single biomarkers. In an alternative approach using Classification and Regression Tree (CART) analysis a model involving NGAL:Cr measurement post-op followed by Hepcidin:Cr at 24 h was developed which identified high, intermediate and low risk groups for AKI. Regression tree analysis has the potential produce models with greater clinical utility than single combined scores.

Purpose: In acute kidney injury patients, metabolic acidosis is common. Its severity, duration, and associated changes in mean arterial pressure (MAP) and vasopressor therapy may be affected by the intensity of continuous renal replacement therapy (CRRT). We aimed to compare key aspects of acidosis and MAP and vasopressor therapy in patients treated with two different CRRT intensities., Methods: We studied a nested cohort of 115 patients from two tertiary intensive care units (ICUs) within a large multicenter randomized controlled trial treated with lower intensity (LI) or higher intensity (HI) CRRT., Results: Levels of metabolic acidosis at randomization were similar [base excess (BE) of -8 ± 8 vs. -8 ± 7 mEq/l; p = 0.76]. Speed of BE correction did not differ between the two groups. However, the HI group had a greater increase in MAP from baseline to 24 h (7 ± 3 vs. 0 ± 3 mmHg; p < 0.01) and a greater decrease in norepinephrine dose (from 12.5 to 3.5 vs. 5 to 2.5 μg/min; p < 0.05). The correlation (r) coefficients between absolute change in MAP and norepinephrine (NE) dose versus change in BE were 0.05 and -0.37, respectively., Conclusions: Overall, LI and HI CRRT have similar acid-base effects in patients with acidosis. However, HI was associated with greater improvements in MAP and vasopressor requirements (clinical trial no. NCT00221013).

Aim: To test whether short-term perioperative administration of oral atorvastatin could reduce incidence of postoperative acute kidney injury (AKI) in cardiac surgical patients., Methods: We conducted a double-blind, randomized controlled trial in 100 cardiac surgical patients at increased risk of postoperative AKI. Patients were randomized to atorvastatin (40 mg once daily for 4 days starting preoperatively) or identical placebo capsule. Primary outcome was to detect a smaller absolute rise in postoperative creatinine with statin therapy. Secondary outcomes included AKI defined by the creatinine criteria of RIFLE consensus classification (RIFLE R, I or F), change in urinary neutrophil gelatinase-associated lipocalin (NGAL) concentration, requirement for renal replacement therapy, length of stay in intensive care, length of stay in hospital and hospital mortality., Results: Study groups were well matched. For each patient maximal increase in creatinine during the 5 days after surgery was assessed; median maximal increase was 28 µmol/L in the atorvastatin group and 29.5 µmol/L in the placebo group (P = 0.62). RIFLE R or greater occurred in 26% of patients with atorvastatin and 32% with placebo (P = 0.65). Postoperatively urine NGAL changes were similar (median NGAL : creatinine ratio at intensive care unit admission: atorvastatin group 1503 ng/mg, placebo group 1101 ng/mg; P = 0.22). Treatment was well tolerated and adverse events were similar between groups., Conclusion: Short-term perioperative atorvastatin use was not associated with a reduced incidence of postoperative AKI or smaller increases in urinary NGAL. (ClinicalTrials.gov NCT00910221)., (© 2011 The Authors. Nephrology © 2011 Asian Pacific Society of Nephrology.)

Background: Acute kidney injury (AKI) is a common and serious complication of cardiopulmonary bypass (CPB) surgery. Hepcidin, a peptide hormone that regulates iron homeostasis, is a potential biomarker of AKI following CPB., Methods: We investigated the association between post-operative changes in serum and urinary hepcidin and AKI in 93 patients undergoing CPB., Results: Twenty-five patients developed AKI based on the Risk, Injury, Failure, Loss, End-stage kidney disease (RIFLE) criteria in the first 5 days. Serum hepcidin, urine hepcidin concentration, the urinary hepcidin:creatinine ratio and fractional excretion of hepcidin in urine rose significantly after surgery. However, urine hepcidin concentration and urinary hepcidin:creatinine ratio were significantly lower at 24 h in patients with RIFLE-Risk, Injury or Failure compared to those without AKI (P = 0.0009 and P < 0.0001, respectively). Receiver operator characteristic analysis showed that lower 24-h urine hepcidin concentration and urinary hepcidin:creatinine ratio were sensitive and specific predictors of AKI. The urinary hepcidin:creatinine ratio had an area under the curve for the diagnosis of RIFLE ≥ risk at 24 h of 0.77 and of 0.84 for RIFLE ≥ injury. Urinary hepcidin had similar predictive accuracy. Such predictive ability remained when patients with early creatinine increases were excluded., Conclusions: Urinary hepcidin and hepcidin:creatinine ratio are biomarkers of AKI after CPB, with an inverse association between its increase at 24 h and risk of AKI in the first five post-operative days. Measuring hepcidin in the urine on the first day following surgery may deliver earlier diagnosis and interventions.

Objective: To test the precision and limits of agreement of point-of-care testing (POCT)-based measurement of serum creatinine (Cr) in critically ill patients., Methods: We studied 250 paired blood samples from 82 critically ill patients from a general intensive care unit by simultaneous POCT and central laboratory testing (Jaffé method). Correlation, precision, bias, and limits of agreement were assessed. Possible confounders for interference of noncreatinine chromogens were evaluated by multivariate linear regression analysis., Results: The mean difference in serum Cr measured by central laboratory and POCT was +9.6 μmol/L (95% limits of agreement: -11.2 to +30.4 μmol/L). The mean percentage difference between the two techniques was 8.7% (95% limits of agreement -7.8% to +25.1%). On multivariate regression, the difference in serum Cr was increased with greater hemoglobin and lactate levels but decreased with greater bilirubin, albumin, and calcium levels., Conclusions: Compared with the central laboratory testing, POCT-based measurement of serum Cr in critically ill patients carried a small negative bias. This difference appeared affected by the blood levels of biochemical variables known to affect the Jaffé method. POCT-based Cr measurement appears sufficiently accurate for clinical use.

Introduction: During critical illness, oliguria is often used as a biomarker of acute kidney injury (AKI). However, its relationship with the subsequent development of AKI has not been prospectively evaluated., Methods: We documented urine output and daily serum creatinine concentration in patients admitted for more than 24 hours in seven intensive care units (ICUs) from six countries over a period of two to four weeks. Oliguria was defined by a urine output < 0.5 ml/kg/hr. Data were collected until the occurrence of creatinine-defined AKI (AKI-Cr), designated by RIFLE-Injury class or greater using creatinine criteria (RIFLE-I[Cr]), or until ICU discharge. Episodes of oliguria were classified by longest duration of consecutive oliguria during each day were correlated with new AKI-Cr the next day, examining cut-offs for oliguria of greater than 1,2,3,4,5,6, or 12 hr duration,, Results: We studied 239 patients during 723 days. Overall, 32 patients had AKI on ICU admission, while in 23, AKI-Cr developed in ICU. Oliguria of greater than one hour was significantly associated with AKI-Cr the next day. On receiver-operator characteristic area under the curve (ROCAUC) analysis, oliguria showed fair predictive ability for AKI-Cr (ROCAUC = 0.75; CI:0.64-0.85). The presence of 4 hrs or more oliguria provided the best discrimination (sensitivity 52% (0.31-0.73%), specificity 86% (0.84-0.89%), positive likelihood ratio 3.8 (2.2-5.6), P < 0.0001) with negative predictive value of 98% (0.97-0.99). Oliguria preceding AKI-Cr was more likely to be associated with lower blood pressure, higher heart rate and use of vasopressors or inotropes and was more likely to prompt clinical intervention. However, only 30 of 487 individual episodes of oliguria preceded the new occurrence of AKI-Cr the next day., Conclusions: Oliguria was significantly associated with the occurrence of new AKI-Cr, however oliguria occurred frequently compared to the small number of patients (~10%) developing AKI-Cr in the ICU, so that most episodes of oliguria were not followed by renal injury. Consequently, the occurrence of short periods (1-6 hr) of oliguria lacked utility in discriminating patients with incipient AKI-Cr (positive likelihood ratios of 2-4, with > 10 considered indicative of a useful screening test). However, oliguria accompanied by hemodynamic compromise or increasing vasopressor dose may represent a clinically useful trigger for other early biomarkers of renal injury.

Background and Objectives: There is no information on the clinical features and outcome of patients receiving multiple Medical Emergency Team (MET) reviews. Accordingly, we studied the characteristics and outcome of patients receiving one MET call and compared them with those receiving multiple MET reviews., Design: Retrospective observational study using prospectively collected data., Setting: Tertiary hospital., Patients: Cohort of 1664 patients receiving 2237 MET reviews over a 2-year period., Measurements and Main Results: We retrieved information about patient demographics, reasons for MET review, procedures performed by the MET and hospital outcome. We found that 1290 (77.5%) patients received a single MET review and 374 (22.5%) received multiple MET reviews (mean 2.5 reviews, median 2.0). Multiple MET reviews were more likely to be in surgical patients (p < 0.001) and to be due to arrhythmias (p = 0.016). Multiple MET review patients were more likely to be admitted for gastrointestinal diseases (p < 0.001), had a 50% longer hospital stay (p < 0.001) and a 34.6% increase in hospital mortality (p < 0.001) compared to single MET review patients. Their odds ratio (OR) for mortality was 2.14 (95% C.I.: 1.62-2.83; p < 0.001). After exclusion of patients with not for resuscitation (NFR) orders, the OR for mortality was 2.92 (95% C.I.: 2.10-4.06; p < 0.001). The in-hospital mortality of patients subject to multiple MET reviews who were not designated NFR was 34.1%, but only 9.7% of these deaths occurred within 48 h of the initial MET review., Conclusion: In our hospital, one fifth of patients receiving MET calls are subject to multiple MET calls. Such patients have identifiable features and have an increased risk of morbidity and mortality. Within any rapid response system, such patients should be recognized as a higher risk group and receive specific additional attention., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Point of care technology makes it possible to measure blood and urine creatinine and electrolytes within the intensive care unit. We tested whether such point of care technology can accurately measure urine creatinine and electrolytes. We obtained urine from 28 patients for a total of 77 paired samples and measured creatinine and electrolytes using central laboratory technology and point of care technology. The mean difference in urine creatinine was 74 mcmol/L with 95% limits of agreement of -673 to 821 mcmol/L. The mean difference in urinary sodium was 0.282 mmol/L with 95% limits of agreement of -14 to 15 mmol/L. Significantly greater biases and wider limits of agreement were seen for potassium and chloride. We conclude that, despite the limited bias, due to wide limits of agreement, urinary creatinine and sodium cannot be estimated with point of care technology. Even greater inaccuracies make the estimation of potassium and chloride in urine by point of care technology not usable for clinical purposes.

Objectives: To describe two identical cases of severe sodium valproate overdose treated with two different approaches., Design: Case report and review of the literature., Patients: Two cases of identical life-threatening valproate (VPA) overdose with high VPA blood levels, markedly elevated ammonia levels and coma., Interventions: One patient was treated with supportive therapy alone until the development of cerebral edema and seizures; the other was treated with immediate extended hemodialysis followed by high-volume hemodiafiltration., Measurements and Main Results: The first patient remained critically ill with elevated VPA and ammonia levels until the development of seizures and life-threatening cerebral edema. After the delayed application of hemofiltration, the patient slowly recovered to be discharged from intensive care on day 11. In contrast, the second patient's VPA and ammonia levels rapidly declined with hemodialysis and hemodiafiltration with rapid clinical improvement and intensive care discharge on day 3., Conclusions: In severe VPA overdose, early intervention with blood purification of suitable intensity was associated with a rapid reduction in VPA and ammonia levels and clinical improvement. This improvement was not seen with supportive therapy alone.

Background: Blood pressure is an important determinant of renal perfusion and acute kidney injury (AKI) is common in hospital patients. However, there is limited knowledge concerning the incidence of relative hypotension prior to its development in general wards., Methods: We compared blood pressure recordings in a cohort of consecutive patients with no change in renal function to a cohort of patients with acute changes in renal function according to RIFLE classes R, I and F for AKI. We assessed blood pressure over a 3-day period before the development of AKI in index patients and a similar 3-day period in controls. We excluded patients with absolute hypotension [systolic blood pressure (SBP) <90 mmHg]., Results: Patients were old (mean age 76.1 +/- 15.1) and mostly female (57.1%). Those who developed AKI had a lower diastolic blood pressure (P = 0.01), a trend towards lower mean arterial pressure (P = 0.077) and a greater decrease in mean systolic (P < 0.0001), mean diastolic (P < 0.0001) and mean arterial pressure (P < 0.0001) compared to controls. On multivariate logistic regression analysis, a decrease in SBP relative to pre-morbid value was a significant independent predictor of the development of AKI and of RIFLE classes I and F (odds ratio 1.084 for every -1 mmHg change in SBP)., Conclusions: Relative hypotension is more common in ward patients who develop nosocomial AKI than in controls. In these patients, a decrease in SBP relative to pre-morbid value is a significant independent predictor of the development of severe AKI.

Objective: To identify factors that predict outcome in patients receiving a Medical Emergency Team review., Design: Prospective observational study., Setting: Tertiary hospital., Patients: Cohort of 228 patients receiving one or more Medical Emergency Team reviews during daytime hours over a 1-year-period. Control cohort of all patients (n = 900) receiving a Medical Emergency Team review in the same period., Measurements and Results: We prospectively collected information from patients receiving a Medical Emergency Team review during daytime hours from Monday to Friday (audit group) including the clinical cause of deterioration and timing of call in relation to the first documented Medical Emergency Team call criterion (activation delay). We also collected information from the hospital Medical Emergency Team database regarding all patients visited by the Medical Emergency Team during the same period (complete cohort). Audit group patients had several similar characteristics to complete cohort patients but were less likely to be not-for-resuscitation before Medical Emergency Team review and more likely to receive a Medical Emergency Team review because of hypotension, change in neurological status and oliguria. Delayed Medical Emergency Team activation and not-for resuscitation orders were the only factors to show an independent statistical association with mortality (OR 2.53, 95% CI: 1.2-5.31, P = 0.01 and OR 5.63, 95% CI: 2.81-11.28, P < 0.01, respectively)., Conclusion: Delayed Medical Emergency Team activation and NFR orders are the strongest independent predictors of mortality in patients receiving a Medical Emergency Team review. Avoidance of delayed Medical Emergency Team activation should be a priority for hospitals operating rapid response systems.

Studies of hospital performance highlight the problem of 'failure to rescue' in acutely ill patients. This is a deficiency strongly associated with serious adverse events, cardiac arrest, or death. Rapid response systems (RRSs) and their efferent arm, the medical emergency team (MET), provide early specialist critical care to patients affected by the 'MET syndrome': unequivocal physiological instability or significant hospital staff concern for patients in a non-critical care environment. This intervention aims to prevent serious adverse events, cardiac arrests, and unexpected deaths. Though clinically logical and relatively simple, its adoption poses major challenges. Furthermore, research about the effectiveness of RRS is difficult to conduct. Skeptics argue that inadequate evidence exists to support its widespread application. Indeed, supportive evidence is based on before-and-after studies, observational investigations, and inductive reasoning. However, implementing a complex intervention like RRS poses enormous logistic, political, cultural, and financial challenges. In addition, double-blinded randomised controlled trials of RRS are simply not possible. Instead, as in the case of cardiac arrest and trauma teams, change in practice may be slow and progressive, even in the absence of level I evidence. It appears likely that the accumulation of evidence from different settings and situations, though methodologically imperfect, will increase the rationale and logic of RRS. A conclusive randomised controlled trial is unlikely to occur.

Acute kidney injury (AKI) is a common complication of severe sepsis. Severe sepsis is the most common cause of AKI in ICU. The widely accepted and practiced initial cornerstone of treatment for septic AKI is fluid resuscitation. The biological rationale for fluid resuscitation in septic AKI is based on the assumption that septic AKI is an ischemic form of AKI and that increasing renal perfusion and oxygen delivery by means of fluid resuscitation will protect the kidney. Whether this is true, however, remains uncertain. In this paper, we discuss salient pathophysiological aspects of AKI, review the evidence available on the need for fluid resuscitation, the amount and the type of fluid that might be best suited to AKI and discuss all major aspects of fluid resuscitation for septic AKI in humans and experimental animals.

Aim: Protein C (PC) is a plasma glycoprotein implicated in modulating coagulation and inflammation. Its levels decrease in sepsis and related diseases, where it has also proved to be a prognostic indicator of outcome. Infusion of exogenous PC, although not able to decrease mortality in severe sepsis and septic shock, can safely resolve the coagulation imbalances related to these pathological states., Methods: A retrospective study was performed about utilisation of PC in severe sepsis and septic shock patients in three italian PICUs during a one-year period. Data from 29 patients were analysed. Age, PIM 2, mortality and length of stay were compared between treated and non treated patients. Treated patients were also analysed for PC dosage received, length of treatment, and modification of hemocoagulation parameters, before PC infusion and every 24 hours., Results: In treated patients, the activity of PC, PT and PTT activity and fibrinogen improved significantly from basal to day 5 (p<0.05). Diminution of d-dimer was not quite significant (p=0.0514). Rise in platelets count and antithrombin III activity was not significant. No adverse reactions related to Protein C concentrate were observed. No difference in mortality was observed between the two groups., Conclusions: Although PC is included in guidelines for management of severe sepsis and septic shock, only 38%, of observed patients received PC treatment. Even in the treated group, patients received a lower dosage of PC, and for a shorter period, than recommended. In accordance to previous studies, we did not observe differences in mortality between treated and untreated patients. Our results showed a significant increase in plasma PC activity, following infusion of PC concentrate. This increase in PC appeared sufficient to restore some, but not all, of the abnormalities in the coagulation system. A large randomized, phase 3, placebo-controlled trial in children with severe sepsis and septic shock is advisable to establish effective role of therapy with PC in reducing mortality of these patients.