Intravascular Volume Depletion Research Articles

CT-pro-AVP as a tool for assessment of intravascular volume depletion in severe hyponatremia

BackgroundAssessment of volume status is essential to best manage hyponatremic patients but is not always accurate in clinical practice. The aim of this study was to evaluate the reliability of C-terminal portion of pro-arginine-vasopressin (CT-pro-AVP), a surrogate biomarker of vasopressin release, in assessing intravascular volume (IVV) depletion in hypoosmolar hyponatremic patients. MethodsPlasma CT-pro-AVP and urea-to-creatinine ratio (Ur/Cr) were performed in 131 hospitalized patients presenting chronic severe hypoosmolar hyponatremia. At hospital discharge, their IVV was evaluated regardless of CT-pro-AVP concentrations. All patients were then classified as decreased or as normal/expanded IVV group. ResultsPlasma CT-pro-AVP levels were higher in patients with decreased IVV (34.6 vs. 11.3 pmol/L, p<0.001) and exhibited a reliable performance for assessment of decreased IVV (ROC AUC at 0.717 [95% CI 0.629–0.805]). The combination of CT-pro-AVP and Ur/Cr resulted in an improved ROC AUC up to 0.787 (95% CI 0.709–0.866). ConclusionsOur findings support the hypothesis that CT-pro-AVP plasma level may reflect IVV and would be a tool for its assessment. This performance has been magnified by its combination with Ur/Cr. A dual-marker strategy may help clinicians to optimize the management of severe hyponatremia especially in case of confusing clinical presentations.

Acute kidney injury in children in Nigeria.

To highlight the epidemiologic characteristics and therapeutic challenges of childhood acute kidney injury (AKI) in Nigeria. A review of AKI publications on Nigerian children between January 1990 and December 2012 was carried out. Mean age at presentation varied between 3.1 ± 2.6 and 6.28 ± 4 (0.05 - 16) years. Male/female ratio ranged between 1.38 and 2.5 to 1. Hospital-acquired AKI (hAKI) and community-acquired AKI (cAKI) accounted for 17.1 - 27.2% and 72.8 - 82.9% of all AKI cases, respectively. 12 - 35 new AKI cases are seen per year. A single-center study puts cAKI and hAKI incidences at 9.8 per million children population (pmcp)/year (0.46%) and 3.7 pmcp/ year (0.17%), respectively; cAKI and hAKI prevalence rates were 49.2 pmcp (2.23%) and 18.3 pmcp (0.84%), respectively. Leading causes of AKI, accounting for 80.0% of all etiologies, were nephrotoxins (29.0%), infection (20.0%), intravascular volume depletion (17.9%), and glomerular disease (13.1%). Financial constraints, late presentation, presence of ≥ 2 comorbidities, need for dialysis, non-dialysis when indicated, severe hypertension, white cell count > 15 000/mm3, and platelet count < 100 000/mm3 are significant mortality risk factors in childhood AKI in our environment. Mean all-cause mortality rate from pooled data was 50.4 ± 25.2% (range: 28.4 - 86.5%). AKI incidence and its leading causes, in Nigerian children, can be significantly reduced if attention is paid to public health education, enforcement of environmental sanitation laws, and prompt utilization of healthcare services during sickness.

Abstract W P332: Ratio of Blood Urea Nitrogen to Serum Creatinine Predicts Primary Intracerebral Hemorrhage Volume

Background&amp;Purpose: Dehydration is associated with poor outcomes in stroke patients. A common marker of hydration status is the calculated blood urea nitrogen (BUN) to serum creatinine (SCr) ratio. Few studies in primary ICH patients have focused on intravascular volume depletion and ICH volume. We examined if dehydration (BUN/SCr &gt; 15) predicted admission ICH volume. Subjects&amp;Methods: Consecutive patients (2008 – 2013) who presented with a spontaneous ICH to our academic stroke center in the Southeast US were retrospectively analyzed. Demographics, initial lab values, ICH volumes, and ICH scores were recorded. Patients with INR &lt;= 1.5 were divided into two groups: BUN/SCr &lt;= 15 and &gt; 15. ICH volumes were compared between groups. Statistical significance was determined using linear regression adjusting for admission systolic blood pressure (SBP) and ICH score. Results: We identified 326 patients who met inclusion criteria (mean age 63; SD=15, 43% women, 45% black). Patients with ratio &gt;15 were older (68 vs.60 years, p&lt;0.001). In addition, a higher proportion were white (63% vs.40%, p &lt;0.001) and female (56% vs. 36%, p&lt;0.001). The average SBP on arrival was similar between groups (176 vs.181 mmHg, p=0.159). The average initial ICH volumes for those with BUN/SCr &gt; 15 were higher than patients with BUN/SCr &lt;= 15 (29.6 mL vs. 20.6 mL, p = 0.022). After adjusting for SBP and ICH score, patients with elevated BUN/SCr had an average of 9 mL larger ICH volumes on admission. Conclusions: Elevated BUN/SCr ratio is linked to larger initial ICH volumes even after controlling for ICH score and SBP. This simple ratio is an independent predictor of ICH volume, may reflect poor hydration status, and can potentially be used in the early evaluation and treatment of ICH patients. Future studies to determine if correction impacts functional outcomes are warranted.

Fluid resuscitation in severe sepsis and septic shock: Shifting goalposts.

Fluid resuscitation in severe sepsis and septic shock: Shifting goalposts.

Vasoactive Drugs for Septic Shock: Where are we now?

Sepsis develops in about 750,000 people annually and accounts for more than 210,000 deaths per year in the United States [1]. Pediatric severe sepsis is also a burdensome public health problem, with prevalence, morbidity, and mortality rates similar to reports from critically ill adult populations [2]. In sepsis inflammatory mediators lead to circulatory abnormalities including peripheral vasodilatation, reduced mean arterial pressure (MAP), myocardial depression, and intravascular volume depletion [3]. With increased awareness and the use of protocolized care in the emergency department and in the intensive care unit (ICU) the mortality associated with sepsis has decreased significantly in the last decade in some countries [4,5].

Acute Poststreptococcal Glomerulonephritis: The Most Common Acute Glomerulonephritis

Acute Poststreptococcal Glomerulonephritis: The Most Common Acute Glomerulonephritis

Clinical Care of Two Patients with Ebola Virus Disease in the United States

West Africa is currently experiencing the largest outbreak of Ebola virus disease (EVD) in history. Two patients with EVD were transferred from Liberia to our hospital in the United States for ongoing care. Malaria had also been diagnosed in one patient, who was treated for it early in the course of EVD. The two patients had substantial intravascular volume depletion and marked electrolyte abnormalities. We undertook aggressive supportive measures of hydration (typically, 3 to 5 liters of intravenous fluids per day early in the course of care) and electrolyte correction. As the patients' condition improved clinically, there was a concomitant decline in the amount of virus detected in plasma.

Ischemic Colitis After Routine Colonoscopy

Introduction: We report a case of ischemic colitis after a screening colonoscopy in a 70-year-old female patient with hypertension and hyperlipidemia, but no other known risk factors. Within 24 hours, she developed vague abdominal pain and rectal bleeding. Repeat colonoscopy showed diffuse inflammation and ulceration with friable mucosa extending from the rectosigmoid to the transverse colon including the splenic flexure (25 to 60cm from anal verge) with an appearance consistent with ischemic colitis (Figures 1 and 2). All other areas were normal. Biopsy specimens showed hemorrhagic lamina propria and focal glandular drop out confirming ischemic colitis. All enteric pathogens were ruled out. Her symptoms spontaneously resolved within hours after repeat colonoscopy and she went home without further complications. To date, there have been at least 24 cases reported from 1990 to 2014 worldwide. This is only the third reported case in the U.S. Review of the literature suggests that the most important causative factor for ischemia is barotrauma from excessive air insufflation of the bowel along with repeated mechanical trauma from torqueing of the endoscope. Other risk factors include prep for colonoscopy including glutaraldehyde as a disinfectant of equipment and polyethylene glycol causing diarrhea and intravascular volume depletion. Since the patient tolerated the repeat colonoscopy without complication, we believe the most likely explanation was transient ischemia caused by colonoscopy technique, instead of other potential underlying risk factors. Thus, we suggest that clinicians be more aware of their technique especially in patients who may have more marginal vascular supply, although ischemic colitis can occur in otherwise normal patients.Figure 1Figure 2

Caring for critically ill patients with ebola virus disease. Perspectives from West Africa.

The largest ever Ebola virus disease outbreak is ravaging West Africa. The constellation of little public health infrastructure, low levels of health literacy, limited acute care and infection prevention and control resources, densely populated areas, and a highly transmissible and lethal viral infection have led to thousands of confirmed, probable, or suspected cases thus far. Ebola virus disease is characterized by a febrile severe illness with profound gastrointestinal manifestations and is complicated by intravascular volume depletion, shock, profound electrolyte abnormalities, and organ dysfunction. Despite no proven Ebola virus-specific medical therapies, the potential effect of supportive care is great for a condition with high baseline mortality and one usually occurring in resource-constrained settings. With more personnel, basic monitoring, and supportive treatment, many of the sickest patients with Ebola virus disease do not need to die. Ebola virus disease represents an illness ready for a paradigm shift in care delivery and outcomes, and the profession of critical care medicine can and should be instrumental in helping this happen.

Colloids to improve diuresis in critically ill patients: a systematic review

BackgroundThe background of this study is to determine whether the addition of intravenous colloid to diuretic therapy, in comparison to diuretic therapy alone, improves diuresis and oxygenation and prevents intravascular volume depletion in intensive care unit (ICU) patients without shock.MethodsWe searched MEDLINE, Embase, Cochrane Register of Controlled Trials, Google Scholar, conference abstracts of ACCP, SCCM, ATS, and references of relevant articles. Randomized controlled trials (RCTs) of adult ICU patients, not in shock (defined as patients on low dose or no vasopressors, without need for IV fluid bolus or blood transfusion within 24 h), comparing intravenous colloid therapy (human albumin, plasma, synthetic starches, or gels) plus diuretic to control (diuretic alone, or diuretic plus placebo). Two reviewers independently applied eligibility criteria, assessed quality, and extracted data.ResultsSeven hundred fifty five studies were found in the initial search; 14 were deemed relevant; 2 were found to be eligible. There was good agreement between reviewers for study relevance (k = 0.869) and eligibility (k = 0.811). One study of heart failure patients showed no evidence of improved mean or hourly urine output in the group receiving albumin. The second studied patients hypoproteinemic with ARDS and demonstrated an improved fluid balance in 3 days, improved oxygenation status, and improved serum albumin level in patients treated with albumin. No significant differences were found for other outcomes. No studies evaluating colloids other than albumin were found.ConclusionsOur review is limited by the small number of high-quality RCTs available to study this clinical question, both of which only studied albumin. High-quality RCTs are required to evaluate the effect of albumin as well as other colloids as an adjunct to diuresis in a general ICU population.Electronic supplementary materialThe online version of this article (doi:10.1186/2052-0492-2-37) contains supplementary material, which is available to authorized users.

Anaphylaxis

BackgroundAnaphylaxis is the quintessential critical illness in emergency medicine. Symptoms are rapid in onset and death can occur within minutes. Approximately 1500 patients die annually in the United States from this deadly disorder. It is imperative, therefore, that emergency care providers be able to diagnose and appropriately treat patients with anaphylaxis. Any delays in recognition or initiation of therapy can result in unnecessary increases in patient morbidity and mortality. DiscussionRecent literature, including updated international anaphylaxis guidelines, has improved our understanding and management of this critical illness. Anaphylaxis is a multisystem disorder that can manifest signs and symptoms related to the cutaneous, respiratory, cardiovascular, and gastrointestinal systems. Epinephrine remains the drug of choice and should initially be administered intramuscularly, into the anterolateral thigh, as soon as the diagnosis is suspected. For patients unresponsive to repeated intramuscular injections, a continuous infusion of epinephrine should be started. Antihistamines and corticosteroids are second-line medications and should never be given in lieu of, or prior to, epinephrine. Aggressive fluid resuscitation should also be used to treat the intravascular volume depletion characteristic of anaphylaxis. Patient observation and disposition should be individualized, as there is no well-defined period of observation after resolution of signs and symptoms. ConclusionsFor patients with anaphylaxis, rapid and appropriate administration of epinephrine is critical for survival. Additional therapy, such as supplemental oxygen, intravenous fluids, antihistamines, and corticosteroids should not delay the administration of epinephrine.

BISAP-eGFR could improve prediction of severity and mortality in acute pancreatitis. eGFR ? play the trump card.

Introduction: Early prediction of severity of acute pancreatitis (AP) by a simple system which includes clinical features would be very helpful as it may direct management and improve outcome. Certain components of different scores reflecting severe intravascular volume depletion can play an important role in accuracy of the method (but sensitivity and specificity of these scores are not at the desired level yet). Low eGFR (estimated glomerular filtration rate) is already known to be unfavorable prognostic parameter in AP, however it was never assessed as an element of multifactor score. Aim: The aim of this study is to determine whether replacing urea nitrogen (BUN) in bedside index of severity in acute pancreatitis (BISAP) score by eGFR (BISAP-eGFR score) improves prediction of severity and mortality in patients with AP. Methods: Cohort of 100 patients with AP were prospectively enrolled in the study. The BISAP and eGFR (abbreviated Modification of Diet in Renal Disease equation) were calculated using data from the first 24 h from admission. Severe AP was defined as the persistence of organ failure exceeding 48 hours. The predictive accuracy of the BISAP and BISAP-eGFR score was measured as the area under the receiver operating characteristic curve (AUC). Results: We evaluated a total of 100 consecutive patients with AP. Twenty of the 100 patients (20%) were considered severe AP. The best cutoff value of eGFR was 80 ml/min/1,73 m2. All 20 patients with severe pancreatitis had eGFR 25 mg/dL (BISAP score cut-off for BUN). Overall, 16% of the 100 evaluated patients had a BISAP score ≥3 while BISAP-eGFR score ≥ 3 was reported for 23% patients. A BISAP score ≥ 3 had a sensitivity, specificity, positive and negative predictive value of 65%, 96.1%, 81.2% and 91.3% respectively, with an accuracy of 87% comparing to 95.2%, 96.2%, 86.9% and 98.7% respectively for BISAP-eGFR score with an accuracy of 96%. The AUC for severity predicted by BISAP was 0.762 and by BISAP-eGFR score was 0.942. There were statistically significant trends for increasing severity (P<0.001) and mortality (P<0.001) with increasing BISAPeGFR score. Ten out of ten (100%) patients with fatal AP had BISAP-eGFR ≥3, 6 of them (60%) reported BISAP≥3. Conclusion: BISAP-eGFR score is a simple method to identify patients at risk of increased mortality and allows predicting the severity of the AP. eGFR replacing BUN in BISAP score provides higher sensitivity, specificity and diagnostic accuracy comparing to traditional BISAP score. In addition, eGFR component may be helpful in planning fluid therapy, particularly in the acute phase of the AP. This finding may have important clinical implications, however further studies are required to validate the BISAPeGFR score in predicting severity and mortality in AP.

Dengue human infection model performance parameters.

Dengue is a global health problem and of concern to travelers and deploying military personnel with development and licensure of an effective tetravalent dengue vaccine a public health priority. The dengue viruses (DENVs) are mosquito-borne flaviviruses transmitted by infected Aedes mosquitoes. Illness manifests across a clinical spectrum with severe disease characterized by intravascular volume depletion and hemorrhage. DENV illness results from a complex interaction of viral properties and host immune responses. Dengue vaccine development efforts are challenged by immunologic complexity, lack of an adequate animal model of disease, absence of an immune correlate of protection, and only partially informative immunogenicity assays. A dengue human infection model (DHIM) will be an essential tool in developing potential dengue vaccines or antivirals. The potential performance parameters needed for a DHIM to support vaccine or antiviral candidates are discussed.

Scleroderma renal crisis.

Scleroderma renal crisis (SRC) is characterized by malignant hypertension and oligo-anuric acute renal failure. It occurs in 5% of patients with systemic sclerosis (SSc), particularly in patients with diffuse disease during the first years. SRC is more common in patients receiving corticosteroids, the risk increasing with increasing dose. The disease is sometimes triggered by use of nephrotoxic drugs and/or intravascular volume depletion. Left ventricular insufficiency and hypertensive encephalopathy are typical clinical features. Thrombotic microangiopathy is detected in 43% of cases, and anti-RNA-polymerase III antibodies are present in one-third of patients. Renal biopsy is not necessary if SRC presents classical features. However, biopsy may help to define the prognosis and guide treatment in atypical forms. The prognosis of SRC has greatly improved with the introduction of angiotensin-converting enzyme (ACE) inhibitors. However, the 5-year survival for SSc patients with full SRC remains low (65%). The treatment of SRC relies on aggressive blood pressure control with an ACE inhibitor, combined with other antihypertensive drugs if needed. Dialysis is frequently indicated but can be stopped in about half of patients, mainly those with good blood pressure control. Patients who need dialysis for more than 2 years qualify for renal transplantation.

Defining the role of albumin infusion in cirrhosis-associated hyponatremia.

The presence of negatively charged, impermeant proteins in the plasma space alters the distribution of diffusible ions in the plasma and interstitial fluid (ISF) compartments to preserve electroneutrality and is known as Gibbs-Donnan equilibrium. In patients with hypoalbuminemia due to underlying cirrhosis, the decrease in the plasma water albumin concentration ([Alb-]pw) would be expected to result in a decrease in the plasma water sodium concentration ([Na+]pw) due to an alteration in the distribution of Na+ between the plasma and ISF. In addition, cirrhosis-associated hyponatremia may be due to the renal diluting defect resulting from the intravascular volume depletion due to gastrointestinal losses and overdiuresis and/or decreased effective circulatory volume secondary to splanchnic vasodilatation. Therefore, albumin infusion may result in correction of the hyponatremia in cirrhotic patients either by modulating the Gibbs-Donnan effect due to hypoalbuminemia or by restoring intravascular volume in patients with intravascular volume depletion due to gastrointestinal losses and overdiuresis. However, the differential role of albumin infusion in modulating the [Na+]pw in these patients has not previously been analyzed quantitatively. In the present study, we developed an in vitro assay system to examine for the first time the quantitative effect of changes in albumin concentration on the distribution of Na+ between two compartments separated by a membrane that allows the free diffusion of Na+. Our findings demonstrated that changes in [Alb-]pw are linearly related to changes in [Na+]pw as predicted by Gibbs-Donnan equilibrium. However, based on our findings, we predict that the improvement in cirrhosis-associated hyponatremia due to intravascular volume depletion results predominantly from the restoration of intravascular volume rather than alterations in Gibbs-Donnan equilibrium.

Mo1327 Early Oral Feeding and Selection of Initial Diet in Mild Acute Pancreatitis

Introduction: Early prediction of severity of acute pancreatitis (AP) by a simple system which includes clinical features would be very helpful as it may direct management and improve outcome. Certain components of different scores reflecting severe intravascular volume depletion can play an important role in accuracy of the method (but sensitivity and specificity of these scores are not at the desired level yet). Low eGFR (estimated glomerular filtration rate) is already known to be unfavorable prognostic parameter in AP, however it was never assessed as an element of multifactor score. Aim: The aim of this study is to determine whether replacing urea nitrogen (BUN) in bedside index of severity in acute pancreatitis (BISAP) score by eGFR (BISAP-eGFR score) improves prediction of severity and mortality in patients with AP. Methods: Cohort of 100 patients with AP were prospectively enrolled in the study. The BISAP and eGFR (abbreviated Modification of Diet in Renal Disease equation) were calculated using data from the first 24 h from admission. Severe AP was defined as the persistence of organ failure exceeding 48 hours. The predictive accuracy of the BISAP and BISAP-eGFR score was measured as the area under the receiver operating characteristic curve (AUC). Results: We evaluated a total of 100 consecutive patients with AP. Twenty of the 100 patients (20%) were considered severe AP. The best cutoff value of eGFR was 80 ml/min/1,73 m2. All 20 patients with severe pancreatitis had eGFR 25 mg/dL (BISAP score cut-off for BUN). Overall, 16% of the 100 evaluated patients had a BISAP score ≥3 while BISAP-eGFR score ≥ 3 was reported for 23% patients. A BISAP score ≥ 3 had a sensitivity, specificity, positive and negative predictive value of 65%, 96.1%, 81.2% and 91.3% respectively, with an accuracy of 87% comparing to 95.2%, 96.2%, 86.9% and 98.7% respectively for BISAP-eGFR score with an accuracy of 96%. The AUC for severity predicted by BISAP was 0.762 and by BISAP-eGFR score was 0.942. There were statistically significant trends for increasing severity (P<0.001) and mortality (P<0.001) with increasing BISAPeGFR score. Ten out of ten (100%) patients with fatal AP had BISAP-eGFR ≥3, 6 of them (60%) reported BISAP≥3. Conclusion: BISAP-eGFR score is a simple method to identify patients at risk of increased mortality and allows predicting the severity of the AP. eGFR replacing BUN in BISAP score provides higher sensitivity, specificity and diagnostic accuracy comparing to traditional BISAP score. In addition, eGFR component may be helpful in planning fluid therapy, particularly in the acute phase of the AP. This finding may have important clinical implications, however further studies are required to validate the BISAPeGFR score in predicting severity and mortality in AP.

Prospective evaluation of intravascular volume status in critically ill patients

In search of a standardized noninvasive assessment of intravascular volume status, we prospectively compared the sonographic inferior vena cava collapsibility index (IVC-CI) and central venous pressures (CVPs). Our goals included the determination of CVP behavior across clinically relevant IVC-CI ranges, examination of unitary behavior of IVC-CI with changes in CVP, and estimation of the effect of positive end-expiratory pressure (PEEP) on the IVC-CI/CVP relationship. Prospective, observational study was performed in surgical/medical intensive care unit patients between October 2009 and July 2013. Patients underwent repeated sonographic evaluations of IVC-CI. Demographics, illness severity, ventilatory support, CVP, and patient positioning were recorded. Correlations were made between CVP groupings (<7, 7-12, 12-18, 19+) and IVC-CI ranges (<25, 25-49, 50-74, 75+). Comparison of CVP (2-unit quanta) and IVC-CI (5-unit quanta) was performed, followed by assessment of per-unit ΔIVC-CI/ΔCVP behavior as well as examination of the effect of PEEP on the IVC-CI/CVP relationship. We analyzed 320 IVC-CI/CVP measurement pairs from 79 patients (mean [SD] age, 55.8 [16.8] years; 64.6% male; mean [SD] Acute Physiology and Chronic Health Evaluation II, 11.7 [6.21]). Continuous data for IVC-CI/CVP correlated poorly (R = 0.177, p < 0.01) and were inversely proportional, with CVP less than 7 noted in approximately 10% of the patients for IVC-CIs less than 25% and CVP less than 7 observed in approximately 85% of patients for IVC-CIs greater than or equal to 75%. Median ΔIVC-CI per unit CVP was 3.25%. Most measurements (361 of 320) were collected in mechanically ventilated patients (mean [SD] PEEP, 7.76 [4.11] cm H2O). PEEP-related CVP increase was approximately 2 mm Hg to 2.5 mm Hg for IVC-CIs greater than 60% and approximately 3 mm Hg to 3.5 mm Hg for IVC-CIs less than 30%. PEEP also resulted in lower IVC-CIs at low CVPs, which reversed with increasing CVPs. When IVC-CI was examined across increasing PEEP ranges, we noted an inverse relationship between the two variables, but this failed to reach statistical significance. IVC-CI and CVP correlate inversely, with each 1 mm Hg of CVP corresponding to 3.3% median ΔIVC-CI. Low IVC-CI (<25%) is consistent with euvolemia/hypervolemia, while IVC-CI greater than 75% suggests intravascular volume depletion. The presence of PEEP results in 2 mm Hg to 3.5 mm Hg of CVP increase across the IVC-CI spectrum and lower collapsibility at low CVPs. Although IVC-CI decreased with increasing degrees of PEEP, this failed to reach statistical significance. While this study represents a step forward in the area of intravascular volume estimation using IVC-CI, our findings must be applied with caution owing to some methodologic limitations. Diagnostic study, level III. Prognostic study, level III.

Functional coupling of renal K+ and Na+ handling causes high blood pressure in Na+ replete mice

A network of kinases, including WNKs, SPAK and Sgk1, is critical for the independent regulation of K+ and Na+ transport in the distal nephron. Angiotensin II is thought to act as a key hormone in orchestrating these kinases to switch from K+ secretion during hyperkalaemia to Na+ reabsorption during intravascular volume depletion, thus keeping disturbances in electrolyte and blood pressure homeostasis at a minimum. It remains unclear, however, how K+ and Na+ transport are regulated during a high Na+ intake, which is associated with suppressed angiotensin II levels and a high distal tubular Na+ load. We therefore investigated the integrated blood pressure, renal, hormonal and gene and protein expression responses to large changes of K+ intake in Na+ replete mice. Both low and high K+ intake increased blood pressure and caused Na+ retention. Low K+ intake was accompanied by an upregulation of the sodium-chloride cotransporter (NCC) and its activating kinase SPAK, and inhibition of NCC normalized blood pressure. Renal responses were unaffected by angiotensin AT1 receptor antagonism, indicating that low K+ intake activates the distal nephron by an angiotensin-independent mode of action. High K+ intake was associated with elevated plasma aldosterone concentrations and an upregulation of the epithelial sodium channel (ENaC) and its activating kinase Sgk1. Surprisingly, high K+ intake increased blood pressure even during ENaC or mineralocorticoid receptor antagonism, suggesting the contribution of aldosterone-independent mechanisms. These findings show that in a Na+ replete state, changes in K+ intake induce specific molecular and functional adaptations in the distal nephron that cause a functional coupling of renal K+ and Na+ handling, resulting in Na+ retention and high blood pressure when K+ intake is either restricted or excessively increased.

Aromatase Inhibitor for Prevention of Ovarian Hyperstimulation Syndrome(OHSS)

Aromatase Inhibitor for Prevention of Ovarian Hyperstimulation Syndrome(OHSS) Ovarian hyperstimulation syndrome (OHSS) was first described by Muller in 1962. Since then this iatrogenically originated malady has been reported to afflict high numbers of women who are in infertility treatment. The most serious and potentially lethal complication of controlled ovarian hyperstimulation (COH) is a severe form of OHSS. The incidence of OHSS is 5%-10% of all ovarian hyperstimulation for assisted reproduction treatment. It is characterized by ovarian enlargement with multiple follicular development, intravascular volume depletion and haemoconcentration.

Fluid resuscitation in sepsis: reexamining the paradigm.

Sepsis results in widespread inflammatory responses altering homeostasis. Associated circulatory abnormalities (peripheral vasodilation, intravascular volume depletion, increased cellular metabolism, and myocardial depression) lead to an imbalance between oxygen delivery and demand, triggering end organ injury and failure. Fluid resuscitation is a key part of treatment, but there is little agreement on choice, amount, and end points for fluid resuscitation. Over the past few years, the safety of some fluid preparations has been questioned. Our paper highlights current concerns, reviews the science behind current practices, and aims to clarify some of the controversies surrounding fluid resuscitation in sepsis.