Sodium-Glucose Cotransporter 2 Inhibitors Should Be Avoided for the Inpatient Management of Hyperglycemia.

OBJECTIVE: Hyperglycemia in patients with type 2 diabetes mellitus is frequently encountered in the hospital setting. The recent guidelines for the management of inpatient hyperglycemia have included the use of dipeptidyl peptidase 4 inhibitors as an alternative to standard insulin therapy in select patients. This raises the question of the inpatient use of sodium-glucose cotransporter 2 inhibitors (SGLT2i), which have gained increasing popularity in the outpatient setting because of beneficial cardiovascular and renal outcomes. This article describes the risks associated with the use of SGLT2i for the management of inpatient hyperglycemia. METHODS: A literature review was performed using PubMed and Google Scholar for studies assessing the inpatient use of SGLT2i. Search terms included "SGLT2 inhibitors," "euglycemic DKA," "inpatient hyperglycemia," "DPP4 inhibitors," "hypovolemia," and "urinary tract infections." Studies not written in English were excluded. Forty-eight articles were included. RESULTS: Review of the literature showed significant safety concerns with the use of SGLT2i for the inpatient management of hyperglycemia. Hospitalized patients treated with SGLT2i were at increased risk of diabetic ketoacidosis, euglycemic diabetic ketoacidosis, hypovolemia, and urinary tract infections. When compared head-to-head, SGLT2i were not more effective for inpatient glycemic control than dipeptidyl peptidase 4 inhibitors and did not reduce insulin requirements when used in combination with insulin. Although SGLT2i can be considered for the treatment of congestive heart failure, they should be started close to or at the time of discharge. CONCLUSION: Although SGLT2i are a preferred pharmacotherapy class for the outpatient management of type 2 diabetes mellitus, there are considerable safety concerns when using them in a hospital setting, and avoidance is recommended.

Management of Hyperosmolar Hyperglycaemic State (HHS) in Adults: An updated guideline from the Joint British Diabetes Societies (JBDS) for Inpatient Care Group.

Hyperosmolar Hyperglycaemic State (HHS) is a medical emergency associated with high mortality. It occurs less frequently than diabetic ketoacidosis (DKA), affects those with pre-existing/new type 2 diabetes mellitus and increasingly affecting children/younger adults. Mixed DKA/HHS may occur. The JBDS HHS care pathway consists of 3 themes (clinical assessment and monitoring, interventions, assessments and prevention of harm) and 5 phases of therapy (0-60 min, 1-6, 6-12, 12-24 and 24-72 h). Clinical features of HHS include marked hypovolaemia, osmolality ≥320 mOsm/kg using [(2×Na+ ) + glucose+urea], marked hyperglycaemia ≥30 mmol/L, without significant ketonaemia (≤3.0 mmol/L), without significant acidosis (pH >7.3) and bicarbonate ≥15 mmol/L. Aims of the therapy are to improve clinical status/replace fluid losses by 24 h, gradual decline in osmolality (3.0-8.0 mOsm/kg/h to minimise the risk of neurological complications), blood glucose 10-15 mmol/L in the first 24 h, prevent hypoglycaemia/hypokalaemia and prevent harm (VTE, osmotic demyelination, fluid overload, foot ulceration). Underlying precipitants must be identified and treated. Interventions include: (1) intravenous (IV) 0.9% sodium chloride to restore circulating volume (fluid losses 100-220 ml/kg, caution in elderly), (2) fixed rate intravenous insulin infusion (FRIII) should be commenced once osmolality stops falling with fluid replacement unless there is ketonaemia (FRIII should be commenced at the same time as IV fluids). (3) glucose infusion (5% or 10%) should be started once glucose <14 mmol/L and (4) potassium replacement according to potassium levels. HHS resolution criteria are: osmolality <300 mOsm/kg, hypovolaemia corrected (urine output ≥0.5 ml/kg/h), cognitive status returned to pre-morbid state and blood glucose <15 mmol/L.

A case of septic shock due to delayed diagnosis of Cryptosporidium infection after liver transplantation.

BACKGROUND: Cryptosporidium is recognized as a significant pathogen of diarrhea disease in immunocompromised hosts, and studies have shown that Cryptosporidium infection is high in solid organ transplantation (SOT) patients and often has serious consequences. Because of the lack of specificity of diarrheasymptoms cased by Cryptosporidium infection, it is rarely reported in patients undergoing liver transplantation (LT). It frequently delays diagnosis, coming with severe consequences. In clinical work, diagnosing Cryptosporidium infection in LT patients is also complex but single, and the corresponding anti-infective treatment regimen has not yet been standardized. A rare case of septic shock due to a delayed diagnosis of Cryptosporidium infection after LT and relevant literature are discussed in the passage. CASE PRESENTATION: A patient who had received LT for two years was admitted to the hospital with diarrhea more than 20 days after eating an unclean diet. After failing treatment at a local hospital, he was admitted to Intensive Care Unit after going into septic shock. The patient presented hypovolemia due to diarrhea, which progressed to septic shock. The patient's sepsis shock was controlled after receiving multiple antibiotic combinations and fluid resuscitation. However, the persistent diarrhea, as the culprit of the patient's electrolyte disturbance, hypovolemia, and malnutrition, was unsolved. The causative agent of diarrhea, Cryptosporidium infection, was identified by colonoscopy, faecal antacid staining, and blood high-throughput sequencing (NGS). The patient was treated by reducing immunosuppression and Nitazoxanide (NTZ), which proved effective in this case. CONCLUSION: When LT patients present with diarrhea, clinicians should consider the possibility of Cryptosporidium infection, in addition to screening for conventional pathogens. Tests such as colonoscopy, stool antacid staining and blood NGS sequencing can help diagnose and treat of Cryptosporidium infection early and avoid serious consequences of delayed diagnosis. In treating Cryptosporidium infection in LT patients, the focus should be on the patient's immunosuppressive therapy, striking a balance between anti-immunorejection and anti-infection should be sought. Based on practical experience, NTZ therapy in combination with controlled CD4 + T cells at 100-300/mm3 was highly effective against Cryptosporidium without inducing immunorejection.

Orthostatic intolerance after acute mild hypovolemia: incidence, pathophysiologic hemodynamics, and heart-rate variability analysis-a prospective observational cohort study.

PURPOSE: Early postoperative mobilization can be hindered by orthostatic intolerance (OI). Postoperative OI has multifactorial pathogenesis, possibly involving both postoperative hypovolemia and autonomic dysfunction. We aimed to investigate the effect of mild acute blood loss from blood donation simulating postoperative hypovolemia, on both autonomic function and OI, thus eliminating confounding perioperative factors such as inflammation, residual anesthesia, pain, and opioids. METHODS: This prospective observational cohort study included 26 blood donors. Continuous electrocardiogram data were collected during mobilization and night sleep, both before and after blood donation. A Valsalva maneuver and a standardized mobilization procedure were performed immediately before and after blood donation, during which cardiovascular and tissue oxygenation variables were continuously measured by LiDCOrapid™ and Massimo Root™, respectively. The incidence of OI, hemodynamic responses during mobilization and Valsalva maneuver, as well as heart rate variability (HRV) responses during mobilization and sleep were compared before and 15 min after blood donation. RESULTS: Prior to blood donation, no donors experienced OI during mobilization. After blood donation, 6/26 (23%; 95% CI, 9 to 44) donors experienced at least one OI symptom. Three out of 26 donors (12%; 95% CI, 2 to 30) terminated the mobilization procedure prematurely because of severe OI symptoms. Cardiovascular and cerebral tissue oxygenation responses were reduced in patients with severe OI. After blood loss, HRV indices of total autonomic power remained unchanged but increased sympathetic and decreased parasympathetic outflow was observed during mobilization, but also during sleep, indicating a prolonged autonomic effect of hypovolemia. CONCLUSION: We describe a specific hypovolemic component of postoperative OI, independent of postoperative autonomic dysfunction, inflammation, opioids, and pain. STUDY REGISTRATION: ClinicalTrials.gov (NCT04499664); registered 5 August 2020.

RéSUMé: OBJECTIF: La mobilisation postopératoire précoce peut être entravée par une intolérance orthostatique (IO). L'IO postopératoire a une pathogenèse multifactorielle, impliquant peut-être à la fois une hypovolémie postopératoire et un dysfonctionnement autonome. Notre objectif était d'étudier l'effet d'une légère perte de sang aiguë due au don de sang simulant une hypovolémie postopératoire, à la fois sur la fonction autonome et sur l'IO, éliminant ainsi les facteurs périopératoires confondants tels que l'inflammation, l'anesthésie résiduelle, la douleur et les opioïdes. MéTHODE: Cette étude de cohorte observationnelle prospective comprenait 26 personnes ayant donné leur sang. Des données d'électrocardiogramme continu ont été recueillies pendant la mobilisation et le sommeil nocturne, avant et après le don de sang. Une manœuvre de Valsalva et une procédure de mobilisation standardisée ont été réalisées immédiatement avant et après le don de sang, au cours desquelles les variables d'oxygénation cardiovasculaire et tissulaire ont été mesurées en continu avec les moniteurs LiDCOrapid™ et Massimo Root™, respectivement. L'incidence d'IO, les réponses hémodynamiques pendant la mobilisation et la manœuvre de Valsalva, ainsi que les réponses de variabilité de la fréquence cardiaque (VFC) pendant la mobilisation et le sommeil ont été comparées avant et 15 minutes après le don de sang. RéSULTATS: Avant le don de sang, aucune personne ayant fait un don de sang n'a ressenti d'IO pendant la mobilisation. Après le don de sang, 6/26 (23 %; IC 95 %, 9 à 44) des donneurs et donneuses ont manifesté au moins un symptôme d'IO. Trois personnes sur 26 (12 %; IC 95 %, 2 à 30) ont interrompu prématurément la procédure de mobilisation en raison de symptômes graves d'IO. Les réponses d'oxygénation des tissus cardiovasculaires et cérébraux ont été réduites chez les personnes atteintes d'IO sévère. Après la perte de sang, les indices de VFC de la puissance totale autonome sont demeurés inchangés, mais une augmentation du flux sympathique et une diminution du flux parasympathique ont été observées pendant la mobilisation, mais également pendant le sommeil, indiquant un effet autonome prolongé de l'hypovolémie. CONCLUSION: Nous décrivons une composante spécifique hypovolémique de l'IO postopératoire, indépendante du dysfonctionnement autonome postopératoire, de l'inflammation, des opioïdes et de la douleur. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT04499664); enregistrée le 5 août 2020.

Diagnosis and Management of Sodium Disorders: Hyponatremia and Hypernatremia.

Hyponatremia and hypernatremia are electrolyte disorders that can be associated with poor outcomes. Hyponatremia is considered mild when the sodium concentration is 130 to 134 mEq per L, moderate when 125 to 129 mEq per L, and severe when less than 125 mEq per L. Mild symptoms include nausea, vomiting, weakness, headache, and mild neurocognitive deficits. Severe symptoms of hyponatremia include delirium, confusion, impaired consciousness, ataxia, seizures, and, rarely, brain herniation and death. Patients with a sodium concentration of less than 125 mEq per L and severe symptoms require emergency infusions with 3% hypertonic saline. Using calculators to guide fluid replacement helps avoid overly rapid correction of sodium concentration, which can cause osmotic demyelination syndrome. Physicians should identify the cause of a patient's hyponatremia, if possible; however, treatment should not be delayed while a diagnosis is pursued. Common causes include certain medications, excessive alcohol consumption, very low-salt diets, and excessive free water intake during exercise. Management to correct sodium concentration is based on whether the patient is hypovolemic, euvolemic, or hypervolemic. Hypovolemic hyponatremia is treated with normal saline infusions. Treating euvolemic hyponatremia includes restricting free water consumption or using salt tablets or intravenous vaptans. Hypervolemic hyponatremia is treated primarily by managing the underlying cause (e.g., heart failure, cirrhosis) and free water restriction. Hypernatremia is less common than hyponatremia. Mild hypernatremia is often caused by dehydration resulting from an impaired thirst mechanism or lack of access to water; however, other causes, such as diabetes insipidus, are possible. Treatment starts with addressing the underlying etiology and correcting the fluid deficit. When sodium is severely elevated, patients are symptomatic, or intravenous fluids are required, hypotonic fluid replacement is necessary.

Imaging in crush injury: a spectrum of findings in survivors of the twin earthquakes on February 6, 2023.

On February 6, two major earthquakes with magnitudes of 7.8 and 7.7 on the Richter scale hit Turkey and Northern Syria causing more than 50,000 deaths. In the immediate aftermath of the earthquakes, our major tertiary medical referral center received dozens of cases of crush syndrome, presenting with a variety of imaging findings. Crush syndrome is characterized by hypovolemia, hyperkalemia, and myoglobinuria that can lead to rapid death of victims, despite their survival of staying under wreckage for days. The typical triad of crush syndrome consists of the acute tubular necrosis, paralytic ileus, and third-space edema. In this article, we focus primarily on characteristic imaging findings of earthquake-related crush syndrome and divided them into two distinct subsections: myonecrosis, rapid hypovolemia, excessive third-space edema, acute tubular necrosis, and paralytic ileus, which are directly related to crush syndrome, and typical accompanying findings of earthquake-related crush syndrome. Lower extremity compression in earthquake survivors results in the typical third-space edema. In addition to the lower extremities, other skeletal muscle regions are also affected, especially rotator muscles, trapezius, and pectoral muscles. Although it may be relatively easy to better detect myonecrosis with contrast-enhanced CT scans, changing the windowing of the images may be helpful.

Diagnosis and Management of Hyponatremia: A Review.

Importance: Hyponatremia is the most common electrolyte disorder and it affects approximately 5% of adults and 35% of hospitalized patients. Hyponatremia is defined by a serum sodium level of less than 135 mEq/L and most commonly results from water retention. Even mild hyponatremia is associated with increased hospital stay and mortality. Observations: Symptoms and signs of hyponatremia range from mild and nonspecific (such as weakness or nausea) to severe and life-threatening (such as seizures or coma). Symptom severity depends on the rapidity of development, duration, and severity of hyponatremia. Mild chronic hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures. In a prospective study, patients with hyponatremia more frequently reported a history of falling compared with people with normal serum sodium levels (23.8% vs 16.4%, respectively; P < .01) and had a higher rate of new fractures over a mean follow-up of 7.4 years (23.3% vs 17.3%; P < .004). Hyponatremia is a secondary cause of osteoporosis. When evaluating patients, clinicians should categorize them according to their fluid volume status (hypovolemic hyponatremia, euvolemic hyponatremia, or hypervolemic hyponatremia). For most patients, the approach to managing hyponatremia should consist of treating the underlying cause. Urea and vaptans can be effective treatments for the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure, but have adverse effects (eg, poor palatability and gastric intolerance with urea; and overly rapid correction of hyponatremia and increased thirst with vaptans). Severely symptomatic hyponatremia (with signs of somnolence, obtundation, coma, seizures, or cardiorespiratory distress) is a medical emergency. US and European guidelines recommend treating severely symptomatic hyponatremia with bolus hypertonic saline to reverse hyponatremic encephalopathy by increasing the serum sodium level by 4 mEq/L to 6 mEq/L within 1 to 2 hours but by no more than 10 mEq/L (correction limit) within the first 24 hours. This treatment approach exceeds the correction limit in about 4.5% to 28% of people. Overly rapid correction of chronic hyponatremia may cause osmotic demyelination, a rare but severe neurological condition, which can result in parkinsonism, quadriparesis, or even death. Conclusions and Relevance: Hyponatremia affects approximately 5% of adults and 35% of patients who are hospitalized. Most patients should be managed by treating their underlying disease and according to whether they have hypovolemic, euvolemic, or hypervolemic hyponatremia. Urea and vaptans can be effective in managing the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure; hypertonic saline is reserved for patients with severely symptomatic hyponatremia.

Sudden death due to acute hemoabdomen and hypovolemia from a ruptured splenic hemangiosarcoma in a German shepherd dog.

A 12-year-old neutered male German shepherd dog was evaluated after dying suddenly at home. A few hours prior to the unexpected death the dog displayed anorexia and lethargy. Post-mortem examination and histopathology led to a diagnosis of marked hemoabdomen and hypovolemia due to a single ruptured splenic hemangiosarcoma.

Mort subite due à un hémo-adomen aigu et une hypovolémie à la suite de la rupture d'un hémangiosarcome splénique chez un chien berger allemand. Un chien berger allemand mâle castré âgé de 12 ans fut évalué à la suite de son décès soudain à la maison. Quelques heures avant ce décès inattendu, le chien montra des signes d'anorexie et de léthargie. L'examen post-mortem et histopathologique ont mené à un diagnostic d'hémoabdomen marqué et d'hypovolémie due à la rupture unique d'un hémangiosarcome splénique.(Traduit par Dr Serge Messier).

Hyponatraemia in patients with community-acquired pneumonia; prevalence and aetiology, and natural history of SIAD.

OBJECTIVE: Hyponatraemia is common in community-acquired pneumonia (CAP) and is associated with increased mortality. The mechanism of hyponatraemia in CAP is not completely understood and treatment is therefore ill-defined. We aimed to define the causation of hyponatraemia in CAP. DESIGN: Prospective, single-centre, observational study of all patients with CAP and hyponatraemia (≤ 130 mmol/L) during a 9-month period. PATIENTS: The prevalence of each subtype of hyponatraemia, and the associated mortality, was determined in 143 admissions with CAP (Study 1). A sub-cohort of patients with SIAD (n = 10) was prospectively followed, to document the natural history of SIAD associated with CAP (Study 2). MEASUREMENTS: In Study 2, blood and urine were collected on day 1, 3, 5 and 7 following admission for measurement of plasma vasopressin, sodium, osmolality and urine osmolality. RESULTS: In study 1, 143/1723(8.3%) of CAP patients had hyponatraemia (≤130 mmol/L). About 66 had SIAD (46%), 60(42%) had hypovolaemic hyponatraemia (HON), 13(9%) had hypervolaemic hyponatraemia (HEN) and 4(3%) patients had hyponatraemia due to glucocorticoid hormone deficiency. Mortality was higher in the HEN than in the HON, SIAD or normonatraemic groups (P < 0.01). In Study 2, plasma sodium concentration normalized in 8/10 (80%) by day 7. Two patients with persistent hyponatraemia were discovered to have underlying bronchiectasis. CONCLUSIONS: Hyponatraemia in CAP is most commonly secondary to SIAD or hypovolaemia. HEN is less common, but has worse prognosis. Prospective observation demonstrates that in SIAD, plasma AVP and sodium concentrations normalize with antimicrobials; failure of reversal of suggests underlying lung disease, such as bronchiectasis.

Predicting fluid responsiveness: A review of literature and a guide for the clinician.

Volume resuscitation is of utmost importance in the treatment of shock. It is imperative that this resuscitation be guided using a reliable method of ascertaining volume status to avoid the ill-effects of hypovolemia while also avoiding those of over-resuscitation. There are numerous tools and methods available in this era to aid the bedside physician in guiding volume resuscitation, many of which will be described in this review of literature. The methods to assess preload responsiveness are broadly divided into static and dynamic measurements. Static measurements involve 'snapshot' estimations of preload. Dynamic measurements rely on fluctuations in heart-lung interactions or a simulated volume challenge to predict whether increasing preload by volume loading will be beneficial. Dynamic measurements are favored over static measurements, however the conditions to be met for most dynamic measurements to be valid leave these methods to be used reliably in a very discrete critically-ill population. This issue is overcome by utilizing maneuvers that have been developed to assess fluid responsiveness that liberalize the conditions required for most dynamic measurements, such as passive leg raising, end expiratory occlusion, and mini-fluid boluses. This review of literature highlights the differences between static and dynamic measurements of fluid responsiveness, and proposes a guide to choosing the most reliable methods of ascertaining volume responsiveness individualized to each patient.

The Right Ventricle Is Dilated During Resuscitation From Cardiac Arrest Caused by Hypovolemia: A Porcine Ultrasound Study.

OBJECTIVES: Dilation of the right ventricle during cardiac arrest and resuscitation may be inherent to cardiac arrest rather than being associated with certain causes of arrest such as pulmonary embolism. This study aimed to compare right ventricle diameter during resuscitation from cardiac arrest caused by hypovolemia, hyperkalemia, or primary arrhythmia (i.e., ventricular fibrillation). DESIGN: Thirty pigs were anesthetized and then randomized to cardiac arrest induced by three diffrent methods. Seven minutes of untreated arrest was followed by resuscitation. Cardiac ultrasonographic images were obtained during induction of cardiac arrest, untreated cardiac arrest, and resuscitation. The right ventricle diameter was measured. Primary endpoint was the right ventricular diameter at the third rhythm analysis. SETTING: University hospital animal laboratory. SUBJECTS: Female crossbred Landrace/Yorkshire/Duroc pigs (27-32 kg). INTERVENTIONS: Pigs were randomly assigned to cardiac arrest caused by either hypovolemia, hyperkalemia, or primary arrhythmia. MEASUREMENTS AND MAIN RESULTS: At the third rhythm analysis during resuscitation, the right ventricle diameter was 32 mm (95% CI, 29-35) in the hypovolemia group, 29 mm (95% CI, 26-32) in the hyperkalemia group, and 25 mm (95% CI, 22-28) in the primary arrhythmia group. This was larger than baseline for all groups (p = 0.03). When comparing groups at the third rhythm analysis, the right ventricle was larger for hypovolemia than for primary arrhythmia (p < 0.001). CONCLUSIONS: The right ventricle was dilated during resuscitation from cardiac arrest caused by hypovolemia, hyperkalemia, and primary arrhythmia. These findings indicate that right ventricle dilation may be inherent to cardiac arrest, rather than being associated with certain causes of arrest. This contradicts a widespread clinical assumption that in hypovolemic cardiac arrest, the ventricles are collapsed rather than dilated.

Reduced compensatory responses to maintain central blood volume during hypovolemic stress in women with vasovagal syncope.

Although vasovagal syncope (VVS) is a common clinical condition, the underlying pathophysiology is not fully understood. A decrease in cardiac output has recently been suggested as a factor in orthostatic VVS. The aim was to investigate compensatory mechanisms to maintain central blood volume and venous return during hypovolemic stress in women with VVS. Fourteen VVS women (25.7 ± 5.0 yr) and 15 matched controls (22.8 ± 3.2 yr) were investigated. Single-step and graded lower body negative pressure (LBNP) to presyncope were used to create hypovolemic stress. Peripheral mobilization of venous blood from the arm (capacitance response and net capillary fluid absorption) and lower limb blood pooling (calf capacitance response) were evaluated using a volumetric technique. Cardiovascular responses and plasma norepinephrine (P-NE) were measured. Resting P-NE was elevated in VVS women (P < 0.01). Despite a similar hypovolemic stimulus, the increase in P-NE was blunted (P < 0.01) and the maximal percent increase in total peripheral resistance was reduced (P < 0.05) during graded LBNP in VVS women. The arm capacitance response was slower (P < 0.05) and reduced in VVS women at higher levels of LBNP (P < 0.05). Capillary fluid absorption from extra- to intravascular space was reduced by ∼40% in VVS women (P < 0.05). Accordingly, the reduction in cardiac output was more pronounced (P < 0.05). In conclusion, in VVS women, mobilization of peripheral venous blood and net fluid absorption from tissue to blood during hypovolemic stress were decreased partly as a result of an attenuated vasoconstrictor response. This may seriously impede maintenance of cardiac output during hypovolemic stress and could contribute to the pathogenesis of VVS.

Syndrome of inappropriate anti-diuresis induces volume-dependent hypercalciuria.

Hyponatremia is associated with bone demineralization. We hypothesized that, during hyponatremia, calciuria and calcium balance depend on volemic status. We evaluated calciuria in patients with hyponatremia, secondary to SIAD or hypovolemia. Patients with SIAD exhibited a volemic expansion that was associated with hypercalciuria. Calciuria was proportional to markers of volemia. INTRODUCTION: Chronic mild hyponatremia has been associated with bone demineralization of unknown mechanisms. During chronic hyponatremia, arginine-vasopressin secretion can result from hypovolemia or from syndrome of inappropriate anti-diuresis (SIAD) that leads to a slightly volemic expansion. Since volemia determines renal calcium excretion and balance, we evaluated calcium homeostasis in patients with chronic hyponatremia, related to SIAD or to hypovolemia. METHODS: We retrospectively included all patients referred to our Department between May 2006 and May 2014 for hyponatremia, resulting from SIAD or chronic hypovolemia. None had edema, cirrhosis, cardiac, or renal insufficiency. Exploration included estimation of volemia, extracellular fluid volume (ECFV) measurement with inulin, and calcium homeostasis. RESULTS: In total, the SIAD and hypovolemic groups included 22 and 7 patients, respectively. The SIAD group exhibited signs of increased volemia: higher glomerular filtration rate, higher fractional excretion of uric acid, and lower plasma renin. ECFV exceeded that of the hypovolemic group and was above usual values. There was no difference between the two groups regarding plasma calcium, PTH, and vitamin D. However, in the SIAD group, calciuria was higher than in the hypovolemic group, reaching levels of hypercalciuria. Furthermore, there was a positive correlation between calciuria and markers of volemia. CONCLUSIONS: Our results show that SIAD results in a volemic expansion tendency that is associated with a decrease in renal calcium reabsorption and thus hypercalciuria, whereas in the hypovolemic group, calciuria was not increased. Therefore, renal loss of calcium and bone demineralization in SIAD patients could be partly induced by volemic expansion.

Incidence, aetiology and outcome of community-acquired acute kidney injury in medical admissions in Malawi.

BACKGROUND: Epidemiological data on Acute Kidney Injury (AKI) from low-income countries is sparse. The aim of this study was to establish the incidence, severity, aetiology, and outcomes of community-acquired AKI in Malawi. METHODS: We conducted a prospective observational study of general medical admissions to a tertiary hospital in Blantyre between 27th April and 17th July 2015. All patients were screened on admission with a serum creatinine; those with creatinine above laboratory reference range were managed by the nephrology team. Hospital outcome was recorded in all patients. RESULTS: Eight hundred ninety-two patients were included; 188 (21 · 1%) had kidney disease on admission, including 153 (17 · 2%) with AKI (median age 41 years; 58 · 8% HIV seropositive). 60 · 8% of AKI was stage 3. The primary causes of AKI were sepsis and hypovolaemia in 133 (86 · 9%) cases, most commonly gastroenteritis (n = 29; 19 · 0%) and tuberculosis (n = 18; 11 · 8%). AKI was multifactorial in 117 (76 · 5%) patients; nephrotoxins were implicated in 110 (71 · 9%). Inpatient mortality was 44 · 4% in patients with AKI and 13 · 9% if no kidney disease (p <0.0001). 63 · 2% of patients who recovered kidney function left hospital with persistent kidney injury. CONCLUSION: AKI incidence is 17 · 2% in medical admissions in Malawi, the majority is severe, and AKI leads to significantly increased in-hospital mortality. The predominant causes are infection and toxin related, both potentially avoidable and treatable relatively simply. Effective interventions are urgently required to reduce preventable young deaths from AKI in this part of the world.

Pathogenesis of Hepatorenal Syndrome: Implications for Therapy.

Patients with cirrhosis are prone to develop acute kidney injury (AKI) due to a number of causes, including bacterial infections with or without septic shock, hypovolemia, administration of nephrotoxic drugs, and intrinsic kidney diseases, among others. Most importantly, patients with advanced cirrhosis develop a distinctive cause of AKI, characterized by rapidly progressive glomerular filtration rate loss associated with marked disturbances in circulatory function in the absence of obvious pathologic abnormalities in the kidneys, known as hepatorenal syndrome (HRS). Decreased kidney function results from intense renal vasoconstriction secondary to the complex circulatory changes of cirrhosis with splanchnic vasodilatation and effective hypovolemia. Beyond activation of vasoactive systems, factors including impaired renal blood flow autoregulation and systemic inflammation may play a role in the development of HRS. Most patients improve with albumin and vasopressors; however, the prognosis of HRS remains very poor. Novel biomarkers may be helpful in distinguishing HRS from other causes of AKI in patients with cirrhosis.

Perioperative fluid volume optimization following proximal femoral fracture.

BACKGROUND: Proximal femoral fracture (PFF) is a common orthopaedic emergency that affects mainly elderly people at high risk of complications. Advanced methods for managing fluid therapy during treatment for PFF are available, but their role in reducing risk is unclear. OBJECTIVES: To compare the safety and effectiveness of the following methods of perioperative fluid optimization in adult participants undergoing surgical repair of hip fracture: advanced invasive haemodynamic monitoring, such as transoesophageal Doppler and pulse contour analysis; a protocol using standard measures, such as blood pressure, urine output and central venous pressure; and usual care.Comparisons of fluid types (e.g. crystalloid vs colloid) and other methods of optimizing oxygen delivery, such as blood product therapies and pharmacological treatment with inotropes and vasoactive drugs, are considered in other reviews. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 9); MEDLINE (October 2012 to September 2015); and EMBASE (October 2012 to September 2015) without language restrictions. We ran forward and backward citation searches on identified trials. We searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform for unpublished trials. This is an updated version of a review published originally in 2004 and updated first in 2013 and again in 2015. Original searches were performed in October 2003 and October 2012. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in adult participants undergoing surgical treatment for PFF that compared any two of advanced haemodynamic monitoring, protocols using standard measures or usual care, irrespective of blinding, language or publication status. DATA COLLECTION AND ANALYSIS: Two review authors assessed the impact of fluid optimization interventions on outcomes of mortality, length of hospital stay, time to medical fitness, whether participants were able to return to pre-fracture accommodation at six months, participant mobility at six months and adverse events in-hospital. We pooled data using risk ratio (RR) or mean difference (MD) for dichotomous or continuous data, respectively, on the basis of random-effects models. MAIN RESULTS: We included in this updated review five RCTs with a total of 403 participants, and we added two new trials identified during the 2015 search. One of the included studies was found to have a high risk of bias; no trial featured all pre-specified outcomes. We found two trials for which data are awaited for classification and one ongoing trial.Three studies compared advanced haemodynamic monitoring with a protocol using standard measures; three compared advanced haemodynamic monitoring with usual care; and one compared a protocol using standard measures with usual care. Meta-analyses for the two advanced haemodynamic monitoring comparisons are consistent with both increased and decreased risk of mortality (RR Mantel-Haenszel (M-H) random-effects 0.41, 95% confidence interval (CI) 0.14 to 1.20; 280 participants; RR M-H random-effects 0.45, 95% CI 0.07 to 2.95; 213 participants, respectively). The study comparing a protocol with usual care found no difference between groups for this outcome.Three studies comparing advanced haemodynamic monitoring with usual care reported data for length of stay and time to medical fitness. There was no statistically significant difference between groups for these outcomes in the two studies that we were able to combine (MD IV fixed 0.63, 95% CI -1.70 to 2.96); MD IV fixed 0.01, 95% CI -1.74 to 1.71, respectively) and no statistically significant difference in the third study. One study reported reduced time to medical fitness when comparing advanced haemodynamic monitoring with a protocol, and when comparing protocol monitoring with usual care.The number of participants with one or more complications showed no statistically significant differences in each of the two advanced haemodynamic monitoring comparisons (RR M-H random-effects 0.83, 95% CI 0.59 to 1.17; 280 participants; RR M-H random-effects 0.72, 95% CI 0.40 to 1.31; 173 participants, respectively), nor any differences in the protocol and usual care comparison.Only one study reported the number of participants able to return to normal accommodation after discharge with no statistically significant difference between groups.There were few studies with a small number of participants, and by using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation Working Group) approach, we judged the quality of the outcome evidence as low. We had included one study with a high risk of bias, but upon applying GRADE, we downgraded the quality of this outcome evidence to very low. AUTHORS' CONCLUSIONS: Five studies including a total of 403 participants provided no evidence that fluid optimization strategies improve outcomes for participants undergoing surgery for PFF. Further research powered to test some of these outcomes is ongoing.

Clinical profile and outcome of patients with acute kidney injury requiring dialysis-an experience from a haemodialysis unit in a developing country.

BACKGROUND: The first government funded and sustainable dialysis unit was established in Ethiopia at Saint Paul's Hospital Millennium Medical College (SPHMMC). This has led to the development of a unique cohort of patients about which very little is known. This study was conducted to describe the clinical profile and outcome of adult Acute Kidney Injury (AKI) patients treated with intermittent haemodialysis at the dialysis center of SPHMMC. METHODS: A retrospective review of clinical records of cases of AKI who required haemodialysis support during the time period from August 1, 2013 to February 1, 2015 was conducted. RESULTS: A total of 151 cases AKI requiring dialysis were included for the study. Overall, the patients were generally younger with a mean age of 36.7 years and thus with few premorbid conditions. The most common causes of AKI were hypovolemia (22.5 %), acute glomerulonephritis (AGN) (21.9 %) and pregnancy related causes (18.5 %). Nearly a third (29.1 %) of patients succumbed to the AKI. CONCLUSION: Infections, AGN, obstetric causes and nephrotoxins were the primary causes of dialysis requiring AKI. Most of these causes can be prevented with simple interventions such as health education on oral rehydration, quality prenatal and emergency obstetric care, appropriate management of infections and taking appropriate precautions when prescribing potentially nephrotoxic medications.

Four decades without diagnosis: Sheehan's syndrome, a retrospective analysis.

AIM: Sheehan's syndrome (SS) remains a frequent cause of hypopituitarism in undeveloped and developing countries, but due to improvements in obstetric care, it is rare in developed countries. We aimed to share the results of a retrospective study analyzing the demographic, clinical, imaging, and hormonal characteristics of a large group of patients with SS, and also increase awareness of this syndrome especially in developed countries. METHODS: The medical records of 124 patients with SS patients who were followed up in the Endocrinology Department of Dicle University between 1995 and 2015 were assessed retrospectively. RESULTS: The mean period of diagnostic delay was 20.37 ± 8.34 years on average. 5.7% of patients with SS were literate; 62% of patients delivered at home. Anemia was identified in 64.5% of SS patients. Mean blood sodium levels were 129.8 ± 11.3 mEq/L. The mean urine densities were 1013 ± 6.5. Osteoporosis and osteopenia were found in 44 (35.4%) and 71 (57.2%) patients, respectively, According to pituitary magnetic resonance imaging (MRI) analyses, 92 (74.2%) patients with SS had completely empty sella, 29 (23.3%) had partially empty sella, and 1 patient had microadenoma, and 2 had normal pituitary MRI results. CONCLUSIONS: Improved obstetric care and effective interventions for postpartum hemorrhage have limited the prevalence of SS in developed countries. However, in developing countries like Turkey, SS due to postpartum bleeding remains common. Thus, physician's awareness of the symptoms of SS is urgently required to avoid the associated morbidity and mortality.

Effects of acute hemorrhage on intrapulmonary shunt in a pig model of acute respiratory distress-like syndrome.

BACKGROUND: In acute respiratory distress syndrome (ARDS), gas exchange and respiratory system mechanics (compliance) are severely impaired. Besides ventilatory parameters, the degree of respiratory abnormality can be influenced by the circulatory state. This study investigated the influence of acute hypovolemia on the respiratory system. METHODS: We performed a secondary analysis of a previous study including 8 pigs with ARDS-like syndrome induced by lung lavage and surfactant depletion method (ARDS group) and 10 mechanically ventilated pigs with no intervention (CTRL group). Animals of both groups were subjected to hemorrhage and retransfusion successively. We reanalyzed the effect of acute blood volume variations on intrapulmonary shunt (shunt), arterial oxygenation (PaO2:FiO2), global oxygen delivery (DO2) and respiratory system compliance (Crs). RESULTS: In the ARDS group, after hemorrhage, shunt decreased (-28 +/- 3.5 % (p < 0.001)), respiratory system compliance (Crs) increased (+5.1 +/- 1.0 ml/cm H2O (p < 0.001)) moreover, there was a concurrent increase in PaO2:FiO2 (+113 +/- 19.1 mmHg; p < 0.001) but this did not prevent a reduction in DO2 (-317 +/- 49.8 ml/min; p < 0.001). Following retransfusion, shunt and Crs return towards pre-hemorrhage values. Similar changes, but of smaller magnitude were observed in the CTRL group, except that no significant changes in oxygenation occurred. CONCLUSIONS: The present analysis suggests that an acute decrease in blood volume results in a decrease in shunt with a parallel improvement in arterial oxygenation and an increase in Crs during ARDS-like syndrome. Our results strengthen the importance to integrate the circulatory condition in the analysis of the state of the respiratory system. However, the translation of this physiological model in a clinical perspective is not straightforward because our model of acute and severe hemorrhage is not strictly equivalent to a progressive hypovolemia, as could be obtained in ICU by diuretic. Furthermore, the present model does not consider the impact of blood loss induced decrease of DO2 on other vital organs function. TRIAL REGISTRATION: 'Not applicable'.