Effectiveness of Vasopressin Against Cardiac Arrest: A Systematic Review of Systematic Reviews.

PURPOSE: This systematic review (SR) of SRs evaluates the effectiveness of vasopressin alone or in combination with other drugs in improving the outcomes of cardiac arrest (CA). METHODS: Using a three-step approach, we searched five databases to identify all relevant SRs. Two reviewers independently selected suitable studies, assessed study quality, and extracted relevant data. If an outcome was reported by multiple SRs, a re-meta-analysis was conducted as needed; otherwise, a narrative analysis was performed. RESULTS: Twelve SRs covering 16 original studies were included in this review. The meta-analysis results revealed a significant increase in survival to hospital admission for patients with in-hospital CA (IHCA) or out-of-hospital CA (OHCA) receiving vasopressin alone compared with that for those receiving epinephrine alone. Furthermore, the return of spontaneous circulation (ROSC) was significantly increased in patients with OHCA receiving vasopressin with epinephrine compared with that in those receiving epinephrine alone. Compared with patients with IHCA receiving epinephrine with placebo, those receiving vasopressin, steroids, and epinephrine (VSE) exhibited significant increases in ROSC, survival to hospital discharge, favorable neurological outcomes, mean arterial pressure, renal failure-free days, coagulation failure-free days, and insulin requirement. CONCLUSION: VSE is the most effective drug combination for improving the short- and long-term outcomes of IHCA. It is recommended to use VSE in patients with IHCA. Future studies should investigate the effectiveness of VSE against OHCA and CA of various etiologies, the types and standard dosages of steroids for cardiac resuscitation, and the effectiveness of vasopressin-steroid in improving CA outcomes.

Evaluation and Management of Hyponatremia in Heart Failure.

PURPOSE OF REVIEW: To provide a contemporary overview of the pathophysiology, evaluation, and treatment of hyponatremia in heart failure (HF). RECENT FINDINGS: Potassium and magnesium losses due to poor nutritional intake and treatment with diuretics cause an intracellular sodium shift in HF that may contribute to hyponatremia. Impaired renal blood flow leading to a lower glomerular filtration rate and increased proximal tubular reabsorption lead to an impaired tubular flux through diluting distal segments of the nephron, compromising electrolyte-free water excretion. Hyponatremia in HF is typically a condition of impaired water excretion by the kidneys on a background of potassium and magnesium depletion. While those cations can and should be easily repleted, further treatment should mainly focus on improving the underlying HF and hemodynamics, while addressing congestion. For decongestive treatment, proximally acting diuretics such as sodium-glucose co-transporter-2 inhibitors, acetazolamide, and loop diuretics are the preferred options.

Adjunctive Vasopressors in Patients with Septic Shock: Protocol for a Systematic Review and Meta-Analysis.

Background: Over one-third of patients with septic shock have adjunctive vasopressors added to first-line vasopressors. However, no randomized trial has detected improved mortality with adjunctive vasopressors. Published systematic reviews and meta-analysis have sought to inform the use of adjunctive vasopressors, yet each published review has limitations that hinder its interpretation. This review aims to overcome the limitations of previous reviews by systematically synthesizing the direct evidence for adjunctive vasopressor therapy use in adult patients with septic shock. Methods: We will conduct a systematic review and meta-analysis of randomized controlled trials evaluating adjunctive vasopressors (vasopressin analogues, angiotensin II, hydroxocobalamin, methylene blue, and catecholamine analogues) in adult patients with septic shock. Relevant studies will be identified through comprehensive searches of MEDLINE, Embase, CENTRAL, and reference lists of previous systematic reviews. Only randomized trials comparing adjunctive vasopressors (>75% of subjects on vasopressors at enrollment) to standard care vasopressors in adults with septic shock (>75% of subjects having septic shock) will be included. Titles and abstracts will be screened, full-text articles assessed for eligibility, and data extracted from included studies. Outcomes of interest include short-term mortality, intermediate-term mortality, kidney replacement therapy, digital/peripheral ischemia, and venous thromboembolism. Pairwise meta-analysis using a random-effects model will be utilized to estimate the risk ratio for the outcomes. Risk of bias will be adjudicated with the Cochrane Risk of Bias 2 tool, and GRADE will be used to rate the certainty of the body of evidence. Discussion: Although adjunctive vasopressors are commonly used in patients with septic shock their effect on patient-important outcomes is unclear. This study is planned to use rigorous systematic review methodology, including strict adhere to established guidelines, in order to overcome limitations of previously-published reviews and inform clinical practice and treatment guidelines for the use of adjunctive vasopressors in adults with septic shock. Systematic review registration: PROSPERO CRD4202327984.

Extended Stability of Vasopressin Injection in Polyvinyl Chloride Bags and Polypropylene Syringes and Its Impact on Critically Ill Patient Care and Medication Waste.

Background. Vasopressin is frequently utilized for a variety of shock states in critically ill patients. Short stability (≤24 hours) after intravenous admixture with current manufacturer labeling requires just in time preparation and may lead to delays in therapy and increased medication waste. We aimed to evaluate vasopressin stability in 0.9% sodium chloride stored in polyvinyl chloride bags and polypropylene syringes for up to 90 days. Additionally, we evaluated the impact of extended stability on the time to administration and cost savings from reduced medical waste at an academic medical center. Methods. Dilutions of vasopressin to concentrations of 0.4 and 1.0 unit/mL were performed under aseptic conditions. The bags and syringes were stored at room temperature (23°C-25°C) or under refrigeration (3°C-5°C). Three samples of each preparation and storage environment were analyzed on days 0, 2, 14, 30, 45, 60, and 90. Physical stability was performed by visual examination. The pH was assessed at each point and upon final degradation evaluation. Sterility of the samples was not assessed. Chemical stability of vasopressin was evaluated using liquid chromatography with tandem mass spectrometry. Samples were considered stable if there was <10% degradation of the initial concentration. Results. Vasopressin diluted to 0.4 and 1.0 unit/mL with 0.9% sodium chloride injection was physically stable throughout the study. No precipitation was observed. At days 2, 14, 30, 45, 60, and 90 all bags and syringes diluted to 0.4 units/mL had <10% degradation. Vasopressin diluted to 1 unit/mL and stored under refrigeration had <10% degradation at all measured days, but when stored under room temperature was found to have >10% degradation at day 30. Implementation of a batching process resulted in reduced waste ($185 300) and improved time to administration (26 vs 4 minutes). Conclusion. Vasopressin diluted to a concentration of 0.4 units/mL with 0.9% sodium chloride injection is stable for 90 days at room temperature and under refrigeration. When diluted to 1.0 unit/mL with 0.9% sodium chloride injection it is stable for 90 days under refrigeration. Use of extended stability and sterility testing to batch prepare infusions may lead to improved time to administration and cost savings from reduced medication waste.

Vasopressin in vasoplegic shock in surgical patients: systematic review and meta-analysis

Purpose: Vasoplegia, or vasoplegic shock, is a syndrome whose main characteristic is reducing blood pressure in the presence of a standard or high cardiac output. For the treatment, vasopressors are recommended, and the most used is norepinephrine. However, new drugs have been evaluated, and conflicting results exist in the literature. Methods: This is a systematic review of the literature with meta-analysis, written according to the recommendations of the PRISMA report. The SCOPUS, PubMed, and ScienceDirect databases were used to select the scientific articles included in the study. Searches were conducted in December 2022 using the terms "vasopressin," "norepinephrine," "vasoplegic shock," "postoperative," and "surgery." Meta-analysis was performed using Review Manager (RevMan) 5.4. The endpoint associated with the study was efficiency in treating vasoplegic shock and reduced risk of death. Results: In total, 2,090 articles were retrieved; after applying the inclusion and exclusion criteria, ten studies were selected to compose the present review. We found no significant difference when assessing the outcome mortality comparing vasopressin versus norepinephrine (odds ratio = 1.60; confidence interval 0.47-5.50), nor when comparing studies on vasopressin versus placebo. When we analyzed the length of hospital stay compared to the use of vasopressin and norepinephrine, we identified a shorter length of hospital stay in cases that used vasopressin; however, the meta-analysis did not demonstrate statistical significance. Conclusions: Considering the outcomes included in our study, it is worth noting that most studies showed that using vasopressin was safe and can be considered in managing postoperative vasoplegic shock.

Augmented-Medication CardioPulmonary Resuscitation (AMCPR) trial: a study protocol for a randomized controlled trial.

Objective Clinical trials on demodynamic-directed cardiopulmonary resuscitation have been limited. The aim of this study is to investigate whether Augmented-Medication CardioPulmonary Resuscitation (AMCPR) would improve the odds of return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest. Methods This is a double-blind, single-center, randomized placebo-controlled trial that will be conducted in the emergency department of a tertiary, university-affiliated hospital in Seoul, Korea. A total of 148 adult patients with nontraumatic, nonshockable, out-of-hospital cardiac arrest who have an initial diastolic blood pressure above 20 mmHg will be randomly assigned to two groups of 74 patients (a 1:1 ratio). Patients will receive an intravenous dose of 40 IU of vasopressin with epinephrine, or a placebo with epinephrine. The primary endpoint is a sustained ROSC (over 20 minutes). Secondary endpoints are enhanced diastolic blood pressure, end-tidal carbon dioxide levels, acidosis, and lactate levels during resuscitation. Discussion AMCPR is a trial about tailored medication for select patients during resuscitation. This is the first randomized control trial to identify patients who would benefit from vasopressin for achieving ROSC. This study will provide evidence about the effect of administration of vasopressin with epinephrine to increase ROSC rate. Trial registration ClinicalTrials.gov identifier: NCT03191240. Registered on June 19, 2017.

Cross talk of vasopressin conditioned cell therapy in ischemic heart disease: Role of oxidative stress markers.

Objectives: Background: Impaired coronary blood flow causes cardiac ischemia. Cellular therapy is a new approach to the treatment of myocardial ischemia. This study aimed to investigate the effect of adipose tissue-derived mesenchymal stem cells (AD-MSCs) conditioned with vasopressin on oxidative stress, perivascular collagen, and angiogenesis caused by myocardial infarction (MI) in rats. Materials and Methods: We divided 40 male albino Wistar rats into 4 groups; Control group; No intervention; in experimental groups, after it generated induced MI on models, it divided into three groups: Vehicle group (150 µl of cell-free culture medium received); ASC-MI group (6× 106 AD-MSC received) and AVP-ASC-MI group (received 6 × 106 AD-MSC conditioned with 10 nM vasopressin). Then, histologic parameters and anti-oxidant enzymes were evaluated 7 days post-MI cell injection. Results: Arterial muscle diameter improved and collagen deposition around the coronary arteries decreased in cell-received groups compared with the vehicle group. Malondialdehyde (MDA), catalase (CAT), (GSH) Glutathione, and Total Anti-oxidant Capacity (TAC) parameters were not significantly different between the cells received groups compared with the vehicle group. But the Catalase (CAT) parameter in the ASC-MI group had a significant increase from the control group. Conclusion: We prepared direct evidence that intramyocardial injection of AD-MSCs reveals the positive cardiac remodeling post-MI in rats, and these useful effects can be more enhanced by administrating injection of conditioned ADSCs with vasopressin.

Effects of vasopressin administration in the oral cavity on cardiac function and hemodynamics in rats.

BACKGROUND: The vasoconstrictive effect of epinephrine in local anesthetics affects the heart, which leads to hesitation among dentists in injecting local anesthetics into patients with cardiovascular disease. Due to its vasoconstrictive effects, the present study investigated the effects of vasopressin administration on cardiac function in rats. METHODS: Experiment 1 aimed to determine the vasopressin concentration that could affect cardiac function. An arterial catheter was inserted into the male Wistar rats. Next, 0.03, 0.3, and 3.0 U/mL arginine vasopressin (AVP) (0.03V, 0.3V, and 3.0V) was injected into the tongue, and the blood pressure was measured. The control group received normal saline only. In Experiment 2, following anesthesia infiltration, a pressure-volume catheter was placed in the left ventricle. Baseline values of end-systolic elastance, end-diastolic volume, end-systolic pressure, stroke work, stroke volume, and end-systolic elastance were recorded. Next, normal saline and 3.0V AVP were injected into the tongue to measure their effect on hemodynamic and cardiac function. RESULTS: After 3.0V administration, systolic blood pressures at 10 and 15 min were higher than those of the control group; they increased at 10 min compared with those at baseline. The diastolic blood pressures at 5-15 min were higher than those of the control group; they increased at 5 and 10 min compared with those at baseline. The preload decreased at 5 and 10 min compared to that at baseline. However, the afterload increased from 5 to 15 min compared with that of the control group; it increased at 10 min compared with that at baseline. Stroke volume decreased at 10 and 15 min compared with that of the control group; it decreased from 5 to 15 min compared with that at baseline. Stroke work decreased from 5 to 15 min compared with that of the control group; it decreased from 5 to 15 min compared with that at baseline. CONCLUSION: Our results showed that 3.0 U/mL concentration of vasopressin resulted in increased blood pressure, decreased stroke volume and stoke work, decreased preload and increased afterload, without any effect on myocardial contractility.

Hemodynamic Response to Vasopressin Dosage of 0.03 Units/Min vs. 0.04 Units/Min in Patients With Septic Shock.

BACKGROUND: Arginine vasopressin (AVP) is suggested as an adjunct to norepinephrine in patients with septic shock. Guidelines recommend an AVP dosage up to 0.03 units/min, but 0.04 units/min is commonly used in practice based on initial studies. This study was designed to compare the incidence of hemodynamic response between initial fixed-dosage AVP 0.03 units/min and AVP 0.04 units/min. METHODS: This retrospective, multi-hospital health system, cohort study included adult patients with septic shock receiving AVP as an adjunct to catecholamine vasopressors. Patients were excluded if they received an initial dosage other than 0.03 units/min or 0.04 units/min, or AVP was titrated within the first 6 hours of therapy. The primary outcome was hemodynamic response, defined as a mean arterial pressure ≥65 mm Hg and a decrease in catecholamine dosage at 6 hours after AVP initiation. Inverse probability of treatment weighting (IPTW) based on the propensity score for initial AVP dosage receipt was utilized to estimate adjusted exposure effects. RESULTS: Of the 1536 patients included in the observed data, there was a nearly even split between initial AVP dosage of 0.03 units/min (n = 842 [54.8%]) and 0.04 units/min (n = 694 [45.2%]). Observed patients receiving AVP 0.03 units/min were more frequently treated at the main campus academic medical center (96.3% vs. 52.2%, p < 0.01) and in a medical intensive care unit (87.4% vs. 39.8%, p < 0.01). The IPTW analysis included 1379 patients with achievement of baseline covariate balance. There was no evidence for a difference between groups in the incidence of hemodynamic response (0.03 units/min 50.0% vs. 0.04 units/min 53.1%, adjusted relative risk 1.06 [95% CI 0.94, 1.20]). CONCLUSIONS: Initial AVP dosing varied by hospital and unit type. Although commonly used, an initial AVP dosage of 0.04 units/min was not associated with a higher incidence of early hemodynamic response to AVP in patients with septic shock.

Vasopressin for persistent hypotension due to amlodipine and olmesartan overdose: A case report.

BACKGROUND: While there are consensus recommendations for managing calcium channel blocker (CCB) toxicity, reports on angiotensin II receptor blocker (ARB) toxicity and management are limited. Herein, we report a case of catecholamine-refractory hypotension due to CCB and ARB overdose. CASE PRESENTATION: A 54-year-old woman with underlying hypertension was brought to the emergency department after she attempted suicide by ingesting 345 mg of amlodipine, a CCB, and 340 mg of olmesartan, an ARB. She was hypotensive, which was considered vasodilatory because of high cardiac and low systemic vascular resistance indices. Hypotension persisted despite the administration of norepinephrine and epinephrine. Intravenous calcium gluconate, glucagon, and high-dose insulin euglycemia therapy, which were initiated because CCB toxicity was suspected, failed to raise her blood pressure. The presence of normal anion-gap metabolic acidosis and the fact that the patient remained hypotensive suggested that the hypotension might have been due to the effect of ARB. Vasopressin was finally administered, which improved her hemodynamic status. She was weaned off all vasopressors on day 3. DISCUSSION: There is no consensus recommendation for ARB toxicity. Since chronic use of ARBs at conventional doses can block the sympathetic nervous and renin-angiotensin systems, catecholamines may not effectively increase blood pressure in cases of hypotension due to ARB overdose, for which vasopressin could be indicated. CONCLUSIONS: Vasopressin could be an option for treating hypotension secondary to ARB and CCB toxicity when catecholamines and treatment for CCB toxicity fail.

Clinical characteristics of congenital nephrogenic diabetes insipidus / 中华内科杂志

The purpose of this study was to improve the ability to visualize and diagnose congenital nephrogenic diabetes insipidus (CNDI). The clinical manifestations, laboratory examination findings, imaging features and treatment outcomes of 22 patients with CNDI admitted to the First Affiliated Hospital of Zhengzhou University from May 2013 to May 2020 were retrospectively analyzed. Among the 22 patients with CNDI, 86.4% (19 cases) were male. The age of the 22 patients ranged from 2 months to 47 years old, in which 20 cases were younger than 30 years old and 2 cases were older than 30 years old. The clinical manifestations were polydipsia and polyuria, accompanied with various degrees of fever, defects in growth and development, and increased serum creatinine in some patients. Fifteen patients (68.2%) had different degrees of bilateral kidney and ureteral hydronephrosis, and increased residual urine volume in the bladder. Pituitary magnetic resonance imaging (MRI) enhanced scan showed that the high signal intensity in the posterior pituitary lobe was not detectable in 5 cases (22.7%), and blurred in 6 cases (27.3%). Seven tested patients were all found AVPR2 gene mutation. For patients with suspected CNDI, water-inhibiting vasopressin test and genetic testing should be performed in time so as to confirm diagnosis and treat as early as possible.

Intraoperative vasopressor use during emergency surgery on injured meth users.

BACKGROUND: Methamphetamine is a growing drug of abuse in America. Patients with recent methamphetamine use pose potential complications to general anesthesia due to changes in hemodynamics and arrhythmias. Limited data exists on the incidence of intraoperative complications on methamphetamine-intoxicated patients requiring urgent or emergent trauma surgery. This study aims to describe intraoperative complications observed in methamphetamine and amphetamine-intoxicated patients requiring emergent surgery. METHODS: Using the Trauma Registry at our ACS-verified level I trauma center, we completed a single-center, descriptive, retrospective cohort review between July 1, 2012 and June 30, 2016, of adult patients requiring emergent surgery with a positive urine-drug screen for methamphetamines or amphetamines. The objective was to evaluate vasopressor utilization during surgical operation. RESULTS: A total of 92 patients were identified with a positive UDS for amphetamine and/or methamphetamine who went to the operating room within 24 hours of admission. Thirty-two (34%) patients received one or more (≥1) doses of vasopressor, while 60 patients (66%) received no vasopressor. Changes in mean arterial pressure (MAP) were noted in 64%, while only 3% experienced an EKG change. A binomial logistic regression showed age, base deficit and change in MAP to be predictive of vasopressor use (p<0.002). No intraoperative cardiac events or anesthetic complications were seen. DISCUSSION: Hemodynamic instability in the amphetamine and methamphetamine-intoxicated population may be more directly related to degree of resuscitation required, than the presence of a positive UDS. LEVEL OF EVIDENCE: IV.

Vasopressin in vasoplegic shock: A systematic review.

BACKGROUND: Vasoplegic shock is a challenging complication of cardiac surgery and is often resistant to conventional therapies for shock. Norepinephrine and epinephrine are standards of care for vasoplegic shock, but vasopressin has increasingly been used as a primary pressor in vasoplegic shock because of its unique pharmacology and lack of inotropic activity. It remains unclear whether vasopressin has distinct benefits over standard of care for patients with vasoplegic shock. AIM: To summarize the available literature evaluating vasopressin vs non-vasopressin alternatives on the clinical and patient-centered outcomes of vasoplegic shock in adult intensive care unit (ICU) patients. METHODS: This was a systematic review of vasopressin in adults (≥ 18 years) with vasoplegic shock after cardiac surgery. Randomized controlled trials, prospective cohorts, and retrospective cohorts comparing vasopressin to norepinephrine, epinephrine, methylene blue, hydroxocobalamin, or other pressors were included. The primary outcomes of interest were 30-d mortality, atrial/ventricular arrhythmias, stroke, ICU length of stay, duration of vasopressor therapy, incidence of acute kidney injury stage II-III, and mechanical ventilation for greater than 48 h. RESULTS: A total of 1161 studies were screened for inclusion with 3 meeting inclusion criteria with a total of 708 patients. Two studies were randomized controlled trials and one was a retrospective cohort study. Primary outcomes of 30-d mortality, stroke, ventricular arrhythmias, and duration of mechanical ventilation were similar between groups. Conflicting results were observed for acute kidney injury stage II-III, atrial arrhythmias, duration of vasopressors, and ICU length of stay with higher certainty of evidence in favor of vasopressin serving a protective role for these outcomes. CONCLUSION: Vasopressin was not found to be superior to alternative pressor therapy for any of the included outcomes. Results are limited by mixed methodologies, small overall sample size, and heterogenous populations.

Analysis of influencing factors associated with responsiveness to terlipressin in septic shock patients / 中国基层医药

Objective To determine the relevant factors associated with the responsiveness of terlipressin inpatients with septic shock.Methods From June 2013 to June 2018,the clinical data of patients with septic shock in the intensive care unit ( ICU) of the Affiliated Hospital of Hangzhou Normal University who received catecholamine and treated with terlipressin for at least 6 h,were retrospectively analyzed .Then,the patients were categorized as either responders or non -responders according to their responsiveness to terlipressin .The potential associations between some clinical indicators before the addition of terlipressin and responsiveness to terlipressin were analyzed .Results A total of 132 patients with septic shock were included in this study,including 60cases(45.45％) responders and 72cases(54.54％) non -responders.Compared with responders , non -responders had significantly higher ICU mortality and hospital mortality (ICU mortality:20.00％ vs.72.22％,χ2 =35.734,P<0.001;hospital mortality:81.67％vs.94.44％,P=0.028) and higher median blood lactate (2.73 mmol/L vs.5.22 mmol/L,Z=3.181,P=0.001).Multivariate logistic regression analysis showed that blood lactate level before the addition of terlipressin was a risk factor for patients with no response to terlipressin (odds ratio 1.130,95％confidence interval 1.05-1.23,P=0.002).Receiver operating characteristic curve showed that the area under the curve of blood lactate before the addition of terlipressin was 0.661.Conclusion Blood lactate levels may be useful in predicting terlipressin responsiveness in patients with septic shock .

Analysis of influencing factors associated with responsiveness to terlipressin in septic shock patients / 中国基层医药

Objective@#To determine the relevant factors associated with the responsiveness of terlipressin in patients with septic shock.@*Methods@#From June 2013 to June 2018, the clinical data of patients with septic shock in the intensive care unit (ICU) of the Affiliated Hospital of Hangzhou Normal University who received catecholamine and treated with terlipressin for at least 6 h, were retrospectively analyzed.Then, the patients were categorized as either responders or non-responders according to their responsiveness to terlipressin.The potential associations between some clinical indicators before the addition of terlipressin and responsiveness to terlipressin were analyzed.@*Results@#A total of 132 patients with septic shock were included in this study, including 60cases(45.45%) responders and 72cases(54.54%) non-responders.Compared with responders, non-responders had significantly higher ICU mortality and hospital mortality (ICU mortality: 20.00% vs.72.22%, χ2=35.734, P<0.001; hospital mortality: 81.67% vs.94.44%, P=0.028) and higher median blood lactate (2.73 mmol/L vs.5.22 mmol/L, Z=3.181, P=0.001). Multivariate logistic regression analysis showed that blood lactate level before the addition of terlipressin was a risk factor for patients with no response to terlipressin (odds ratio 1.130, 95% confidence interval 1.05-1.23, P=0.002). Receiver operating characteristic curve showed that the area under the curve of blood lactate before the addition of terlipressin was 0.661.@*Conclusion@#Blood lactate levels may be useful in predicting terlipressin responsiveness in patients with septic shock.

Variation in renal responses to exercise in the heat with progressive acclimatisation.

OBJECTIVES: To investigate changes in renal status from exercise in the heat with acclimatisation and to evaluate surrogates markers of Acute Kidney Injury. DESIGN: Prospective observational cohort study. METHODS: 20 male volunteers performed 60 min standardised exercise in the heat, at baseline and on four subsequent occasions during a 23-day acclimatisation regimen. Blood was sampled before and after exercise for serum creatinine, copeptin, interleukin-6, normetanephrine and cortisol. Fractional excretion of sodium was calculated for corresponding urine samples. Ratings of Perceived Exertion were reported every 5 min during exercise. Acute Kidney Injury was defined as serum creatinine rise ≥26.5 µmol L-1 or fall in estimated glomerular filtration rate >25%. Predictive values of each candidate marker for developing Acute Kidney Injury were determined by ROC analysis. RESULTS: From baseline to Day 23, serum creatinine did not vary at rest, but showed a significant (P<0.05) reduction post-exercise (120 [102, 139] versus 102 [91, 112] µmol L-1). Acute Kidney Injury was common (26/100 exposures) and occurred most frequently in the unacclimatised state. Log-normalised fractional excretion of sodium showed a significant interaction (exercise by acclimatization day), with post-exercise values tending to rise with acclimatisation. Ratings of Perceived Exertion predicted AKI (AUC 0.76, 95% confidence interval 0.65-0.88), performing at least as well as biochemical markers. CONCLUSIONS: Heat acclimatization is associated with reduced markers of renal stress and AKI incidence, perhaps due to improved regional perfusion. Acclimatisation and monitoring Ratings of Perceived Exertion are practical, non-invasive measures that could help to reduce renal injury from exercise in the heat.

Exposure to Stress-Dose Steroids and Lethal Septic Shock After In-Hospital Cardiac Arrest: Individual Patient Data Reanalysis of Two Prior Randomized Clinical Trials that Evaluated the Vasopressin-Steroids-Epinephrine Combination Versus Epinephrine Alone.

PURPOSE: Low-dose steroids may reduce the mortality of severely ill patients with septic shock. We sought to determine whether exposure to stress-dose steroids during and/or after cardiopulmonary resuscitation is associated with reduced risk of death due to postresuscitation septic shock. METHODS: We analyzed pooled, individual patient data from two prior, randomized clinical trials (RCTs). RCTs evaluated vasopressin, steroids, and epinephrine (VSE) during resuscitation and stress-dose steroids after resuscitation in vasopressor-requiring, in-hospital cardiac arrest. In the second RCT, 15 control group patients received open-label, stress-dose steroids. Patients with postresuscitation shock were assigned to a Steroids (n = 118) or No Steroids (n = 73) group according to an "as-treated" principle. We used cumulative incidence competing risks Cox regression to determine cause-specific hazard ratios (CSHRs) for pre-specified predictors of lethal septic shock (primary outcome). In sensitivity analyses, data were analyzed according to the intention-to-treat (ITT) principle (VSE group, n = 103; control group, n = 88). RESULTS: Lethal septic shock was less likely in Steroids versus No Steroids group, CSHR, 0.40, 95% confidence interval (CI), 0.20-0.82; p = 0.012. ITT analysis yielded similar results: VSE versus Control, CSHR, 0.44, 95% CI, 0.23-0.87; p = 0.019. Adjustment for significant, between-group baseline differences in composite cardiac arrest causes such as "hypotension and/or myocardial ischemia" did not appreciably affect the aforementioned CSHRs. CONCLUSIONS: In this reanalysis, exposure to stress-dose steroids (primarily in the context of a combined VSE intervention) was associated with lower risk of postresuscitation lethal septic shock.

Remote Left Ventricular Hemodynamic Monitoring Using a Novel Intracardiac Sensor.

BACKGROUND: Heart failure (HF) remains the most common reason for hospital admission in patients aged >65 years. Despite modern drug therapy, mortality and readmission rates for patients hospitalized with HF remain high. This necessitates further research to identify early patients at risk for readmission to limit hospitalization by timely adjustment of medical therapy. Implantable devices can monitor left ventricular (LV) hemodynamics and remotely and continuously detect the early signs of decompensation to trigger interventions and reduce the risk of hospitalization for HF. Here, we report the first preclinical study validating a new batteryless and easy to implant LV-microelectromechanical system to assess LV performance. METHODS AND RESULTS: A miniaturized implantable wireless pressure sensor was adapted for implantation in the LV apex. The LV-microelectromechanical system sensor was tested in a canine model of HF. The wireless pressure sensor measurements were compared with invasive left heart catheter-derived measurements at several time points. During different pharmacological challenge studies with dobutamine or vasopressin, the device was equally sensitive compared with invasive standard procedures. No adverse events or any observable reaction related to the implantation and application of the device for a period of 35 days was observed. CONCLUSIONS: Our miniaturized wireless pressure sensor placed in the LV (LV-microelectromechanical system) has the potential to become a new telemetric tool to earlier identify patients at risk for HF decompensation and to guide the treatment of patients with HF.