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.

Effect of intraoperative hypovolemic phlebotomy on transfusion and clinical outcomes in patients undergoing hepatectomy: a retrospective cohort study.

BACKGROUND: There is no consensus on how to best achieve a low central venous pressure during hepatectomy for the purpose of reducing blood loss and red blood cell (RBC) transfusions. We analyzed the associations between intraoperative hypovolemic phlebotomy (IOHP), transfusions, and postoperative outcomes in cancer patients undergoing hepatectomy. METHODS: Using surgical and transfusion databases of patients who underwent hepatectomy for cancer at one institution (11 January 2011 to 22 June 2017), we retrospectively analyzed associations between IOHP and RBC transfusion on the day of surgery (primary outcome), and with total perioperative transfusions, intraoperative blood loss, and postoperative complications (secondary outcomes). We fitted logistic regression models by inverse probability of treatment weighting to adjust for confounders and reported adjusted odds ratio (aOR). RESULTS: There were 522 instances of IOHP performed during 683 hepatectomies, with a mean (standard deviation) volume of 396 (119) mL. The IOHP patients had a 6.9% transfusion risk on the day of surgery compared with 12.4% in non-IOHP patients (aOR, 0.53; 95% confidence interval [CI], 0.29 to 0.98; P = 0.04). Total perioperative RBC transfusion tended to be lower in IOHP patients compared with non-IOHP patients (14.9% vs 22.4%, respectively; aOR, 0.72; 95% CI, 0.44 to 1.16; P = 0.18). In patients with a predicted risk of ≥ 47.5% perioperative RBC transfusion, 24.6% were transfused when IOHP was used compared with 56.5% without IOHP. The incidence of severe postoperative complications (Clavien-Dindo scores ≥ 3) was similar in patients whether or not IOHP was performed (15% vs 16% respectively; aOR, 0.97; 95% CI, 0.53 to 1.54; P = 0.71). CONCLUSIONS: The use of IOHP during hepatectomy was associated with less RBCs transfused on the same day of surgery. Trials comparing IOHP with other techniques to reduce blood loss and transfusion are needed in liver surgery.

RéSUMé: CONTEXTE: Il n'existe pas de consensus quant à la meilleure façon d'obtenir une pression veineuse centrale basse pendant une hépatectomie dans le but de réduire les pertes et les transfusions sanguines. Nous avons analysé les associations entre la phlébotomie hypovolémique peropératoire, les transfusions, et les résultats cliniques postopératoires chez les patients qui subissent une hépatectomie pour cancer. MéTHODE: À l'aide de bases de données chirurgicales et transfusionnelles de patients ayant subi une hépatectomie pour cancer dans un seul établissement (du 11 janvier 2011 au 22 juin 2017), nous avons rétrospectivement analysé les associations entre la phlébotomie hypovolémique peropératoire et les transfusions érythrocytaires le jour de la chirurgie (critère d'évaluation principal) et avec les transfusions périopératoires totales, les pertes sanguines peropératoires, et les complications postopératoires (critères d'évaluation secondaires). Nous avons utilisé des modèles de régression logistique avec pondération de probabilité inverse de traitement afin de tenir compte des facteurs de confusion et rapporté les rapports de cotes ajustés (RCa). RéSULTATS: Il y a eu 522 phlébotomies hypovolémiques peropératoires exécutées au cours de 683 hépatectomies, avec un volume moyen (écart type) de 396 (119) mL. Les patients ayant eu une phlébotomie hypovolémique peropératoire avaient un risque transfusionnel de 6,9 % le jour de la chirurgie, comparativement à 12,4 % pour les patients sans phlébotomie (RCa, 0,53; intervalle de confiance [IC] de 95 %, 0,29 à 0,98; P = 0,04). Les transfusions périopératoires totales d'érythrocytes tendaient à être moins fréquentes chez les patients ayant subi une phlébotomie hypovolémique peropératoire par rapport aux patients sans phlébotomie (14,9 % vs 22,4 %, respectivement; RCa, 0,72; IC 95 %, 0,44 à 1,16; P = 0,18). Pour les patients présentant un risque prédit de transfusion périopératoire d'érythrocytes ≥ à 47,5 %, 24,6 % de ceux qui ont eu une phlébotomie hypovolémique peropératoire ont été transfusés, comparativement à 56,5 % sans phlébotomie. L'incidence des complications postopératoires graves (scores de Clavien-Dindo ≥ 3) était semblable chez tous les patients, avec ou sans phlébotomie hypovolémique peropératoire (15 % vs 16 % respectivement; RCa, 0,97; IC 95 %, 0,53 à 1,54; P = 0,71). CONCLUSIONS: L'utilisation de la phlébotomie hypovolémique peropératoire pendant une hépatectomie était associée à un moins grand nombre de transfusions érythrocytaires le jour de la chirurgie. Des études qui compareront la phlébotomie hypovolémique peropératoire à d'autres techniques visant à réduire les pertes et les transfusions sanguines sont nécessaires en chirurgie hépatique.

Índices de shock prehospitalario y hospitalario como predictores de transfusión masiva en la atención inicial del paciente politraumático / Prehospital and hospital shock indices as predictors of massive blood transfusion during the initial treatment of polytrauma patients

OBJETIVOS: Establecer la posible relación entre el Índice de Shock (IS) con los requerimientos de transfusión masiva, estancia hospitalaria y en unidad de críticos, y mortalidad. MÉTODO: Estudio observacional de los pacientes mayores de 18 años con traumatismos de alta energía del registro TraumCat atendidos en el Hospital Universitario de Bellvitge entre 2012 y 2016. Se recogió el IS prehospitalario (PH), a la llegada al hospital (H) y en la unidad de reanimación (IS-C), y la cantidad de transfusión las primeras 24 horas. RESULTADOS: Se recogieron 184 pacientes y 75 (41%) recibieron transfusión sanguínea. Las medianas de los IS para todos los pacientes del estudio fueron: IS-PH 0,77 (Q1-Q3; 0,61-1,01), IS-H 0,78 (Q1-Q3; 0,64-1), IS-C 0,92 (Q1-Q3;0,76-1,13). Fallecieron 46 pacientes (25%). El IS-PH y el IS-H fueron los que diferenciaron de manera significativa la cantidad de transfusión. El valor 0,9 mostró una especificidad/sensibilidad del 73%/66% para el IS-PH y del 74%/80%para el IS-H. El área bajo la curva ROC para el IS-PH y el IS-H fue del 68% (IC 95% 61-75) y del 72% (IC 95% 65-79) respectivamente. No hubo relación significativa de los IS con la mortalidad y la estancia hospitalaria. CONCLUSIÓN: El IS es una herramienta útil y accesible para identificar pacientes politraumatizados con requerimientos transfusionales de manera temprana y optimizar el tratamiento. Para evaluar estancias hospitalarias o mortalidad, podrían ser más útiles otros índices

OBJECTIVES: To explore a possible association between the shock index and a need for massive blood transfusion, duration of hospital stay in the critical care unit, and mortality. METHODS: Observational study of data for all patients over the age of 18 years with multiple high-energy injuries included in the TraumCat Registry who were treated in Hospital Universitario de Bellvitge between 2012 and 2016.We calculated shock index values before hospital emergency department arrival, on arrival at the hospital, and on admission to the critical care unit for resuscitation. The amount of blood transfused in the first 24 hours was also obtained from the registry. RESULTS: Of 184 polytrauma patients, 75 (41%) received blood transfusions. Median (interquartile range) shock indices were as follows: prehospital, 0.77 (0.61-1.01); on hospital arrival, 0.78 (0.64-1); and on critical care admission, 0.92 (0.76-1.13). Forty-six patients (25%) died. A prehospital shock index of 0.9 was significant, differentiating the amount of blood transfused. The specificity and sensitivity of the cut off were 73% and 66%,respectively, at the prehospital recording and 74% and 80% on hospital arrival. The areas under the receiver operating characteristic curve and 95% CIs were as follows for prehospital and on-arrival shock indices: 68% (61%-75%) and 72% (65%-79%). Mortality and hospital stay were not significantly associated with shock indices. CONCLUSIONS: The shock index is a useful, easy-to-obtain predictor to identify polytrauma patients who need early blood transfusion for optimal treatment. Hospital stay and mortality might be better predicted by other indicators

Mechanisms and management of gastrointestinal symptoms in postural orthostatic tachycardia syndrome.

Postural orthostatic tachycardia syndrome (POTS) is a disorder of orthostatic intolerance associated with many GI manifestations that can be broadly classified into two different categories: those present all the time (non-positional) and those that occur with orthostatic position change. There are also many conditions that can co-exist with POTS such as mast cell activation syndrome and the hypermobile form of Ehlers-Danlos syndrome (hEDS) that are also oftentimes associated with GI symptoms. In the current issue of Neurogastroenterology and Motility, Tai et al. explored the relationship between functional GI disorders among hEDS patients with and without concomitant POTS and showed that the hEDS-POTS cohort was more likely to have more than one GI organ involved compared to the cohort with hEDS alone, and certain GI symptoms were also more common in the hEDS-POTS cohort. In this review article, we will briefly review the literature surrounding putative mechanisms responsible for GI symptoms in POTS with an emphasis on the contributory role of concomitant hEDS and then discuss management strategies for GI symptoms in POTS.

Diabetes prevalence and outcomes in hospitalized cardiorenal-syndrome patients with and without hyponatremia.

BACKGROUND: Hyponatremia is known to be associated with a worse patient outcome in heart failure. In cardiorenal syndrome (CRS), the prognostic role of concomitant hyponatremia is unclear. We sought to evaluate potential risk factors for hyponatremia in patients with CRS presenting with or without hyponatremia on hospital admission. METHODS: In a retrospective study, we investigated 262 CRS patients without sepsis admitted to the University Hospital Halle over a course of 4 years. CRS diagnosis was derived from an electronic search of concomitant diagnoses of acute or chronic (NYHA 3-4) heart failure and acute kidney injury (AKIN 1-3) or chronic kidney disease (KDIGO G3-G5nonD). A verification of CRS diagnosis was done based on patient records. Depending on the presence (Na < 135 mmol/L) or absence (Na ≥ 135 mmol/L) of hyponatremia on admission, the CRS patients were analyzed for comorbidities such as diabetes, presence of hypovolemia on admission, need for renal replacement therapy and prognostic factors such as in-hospital and one-year mortality. RESULTS: Two hundred sixty-two CRS patients were included in this study, thereof, 90 CRS patients (34.4%) with hyponatremia (Na < 135 mmol/L). The diabetes prevalence among CRS patients was high (> 65%) and not related to the serum sodium concentration on admission. In comparison to non-hyponatremic CRS patients, the hyponatremic patients had a lower serum osmolality, hypovolemia was more prevalent (41.1% versus 16.3%, p < 0.001). As possible causes of hypovolemia, diarrhea, a higher number of diuretic drug classes and higher diuretic dosages were found. Hyponatremic and non-hyponatremic CRS patients had a comparable need for renal-replacement therapy (36.7% versus 31.4%) during the hospital stay. However, after discharge, relatively more hyponatremic CRS patients on renal replacement therapy switched to a non-dialysis therapy regimen (50.0% versus 22.2%). Hyponatremic CRS patients showed a trend for a higher in-hospital mortality (15.6% versus 7.6%, p = 0.054), but no difference in the one-year mortality (43.3% versus 40.1%, p = 0.692). CONCLUSIONS: All CRS patients showed a high prevalence of diabetes mellitus and a high one-year mortality. In comparison to non-hyponatremic CRS patients, hyponatremic ones were more likely to have hypovolemia, and had a higher likelihood for temporary renal replacement therapy.

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.

Novel Insights into the Pathogenesis and Prevention of Intradialytic Hypotension.

BACKGROUND: Intradialytic hypotension (IDH) is a common complication of haemodialysis (HD) and associated with adverse outcomes, especially when a nadir definition (systolic blood pressure <90 mm Hg) is used. The pathogenesis of IDH is directly linked to the discontinuous nature of the HD treatment, in combination with patient-related factors such as age, diabetes mellitus and cardiac failure. SUMMARY: Although the decline in blood volume due to removal of fluid by ultrafiltration is the prime mover, thermally induced reflex vasodilation compromises the haemodynamic response to hypovolemia. Recent studies have stressed the relevance of changes in tissue perfusion during HD, which may translate in long-term organ damage. Monitoring changes in tissue perfusion, for which emerging evidence becomes available, appears to have great promise in the fine-tuning of the dialysis procedure. Key Messages: While it is unlikely that IDH can be completely prevented, reduction in inter-dialytic weight gain, prevention of an increase in core temperature by adjusting the dialysate temperature and more frequent or prolonged dialysis treatment remain cornerstones in providing a more comfortable and safe treatment.

Management and outcome of hepatocellular adenoma with massive bleeding at presentation.

AIM: To evaluate outcome of acute management and risk of rebleeding in patients with massive hemorrhage due to hepatocellular adenoma (HCA). METHODS: This retrospective cohort study included all consecutive patients who presented to our hospital with massive hemorrhage (grade II or III) due to ruptured HCA and were admitted for observation and/or intervention between 1999-2016. The diagnosis of HCA was based on radiological findings from contrast-enhanced magnetic resonance imaging (MRI) or pathological findings from biopsy or resection of the HCA. Hemorrhage was diagnosed based on findings from computed tomography or MRI. Medical records were reviewed for demographic features, clinical presentation, tumor features, initial and subsequent management, short- and long-term complications and patient and lesion follow-up. RESULTS: All patients were female (n = 23). Treatment in the acute phase consisted of embolization (n = 9, 39.1%), conservative therapy (n = 13, 56.5%), and other intervention (n = 1, 4.3%). Median hemoglobin level decreased significantly more on days 0-3 in the intervention group than in the patients initially treated conservatively (0.9 mmol/L vs 2.4 mmol/L respectively, P = 0.006). In total, 4 patients suffered severe short-term complications, which included hypovolemic shock, acute liver failure and abscess formation. After a median follow-up of 36 mo, tumor regression in non-surgically treated patients occurred with a median reduction of 76 mm down to 25 mm. Four patients underwent secondary (elective) treatment (i.e., tumor resection) to address HCA size of > 5 cm and/or desire for future pregnancy. One case of rebleeding was documented (4.3%). None of the patients experienced long-term complication (mean follow-up time: 36 mo). CONCLUSION: With a 4.3% risk of rebleeding, secondary (elective) treatment of HCA after massive hemorrhage may only be considered in patients with persistent HCA > 5 cm.

Global end-diastolic volume could be more appropiate to reduce intraoperative bleeding than central venous pressure during major liver transection.

BACKGROUND: Central venous pressure often fails to identify the true value of cardiac preload. Our purpose is to investigate whether Global End-Diastolic Volume (GEDV) values can control hemodynamic parameters for the measurement of fluid volume, cardiac preload and blood loss during liver transection. METHODS: This was a prospective clinical study that included patients undergoing liver resection. All patients were monitored by means of PiCCO technology and 222 hemodynamic measurements were performed in 74 patients. Fluid restriction was used. Transpulmonary thermodilutions were performed at different times of surgery, namely: 1. at the beginning of surgery; 2. before hepatectomy and after selective vascular exclusion (Time 1); 3. approximately half way through the liver transection (Time 2); and 4. after liver resection (Time 3). RESULTS: One hundred and twenty-nine of the 222 GEDV values were decreased (prevalence of hypovolemia of 58.1%). However, twenty two of the 222 CVP values were decreased (prevalence of 10.8%). Sensitivity of CVP with regard to volume depletion (GEDV > 650 mL m-2) on the times (1, 2 and 3) were 16.28 (4.08-28.48, 95% CI), 18.18 (5.65-30.75, 95% CI) and 21.43 (7.83-35.03, 95% CI), respectively. There was no correlation between CVP and GEDV. CONCLUSIONS: GEDV values may be more appropriate for monitoring cardiac preload during liver transection.

Experience in the use of non-pneumatic anti-shock garment (NASG) in the management of postpartum haemorrhage with hypovolemic shock in the Fundación Valle Del Lili, Cali, Colombia.

BACKGROUND: The aim of this case series is to describe the experience of using the non-pneumatic anti-shock garment (NASG) in the management of severe Postpartum hemorrhage (PPH) and shock, and the value of implementing this concept in high-complexity obstetric hospitals. METHODS: Descriptive case series of 77 women that received NASG in the management of PPH with severe hypovolemic shock from June 2014 to December 2015. Vital signs, shock index (SI), the lactic acid value and the base deficit were compared before and after NASG application. RESULTS: Fifty-six (77%) women had an SI > 1.1 at the time shock management was initiated; 96% had uterine atony. All women received standard does of uterotonics. The average time between the birth and NASG applications was 20 min. Forty-eight percent of women recovered haemodynamic variables in the first hour and 100% within the first 6 h; 100% had a SI < 1.0 in the first hour. The NASG was not removed until definitive control of bleeding was achieved, with an average time of use of 24 h. There were no mortalities. CONCLUSIONS: In this case series of women in severe shock, the NASG was an effective management device for the control of severe hypovolemic shock. It should be considered a first-line option for shock management.

Dehydration Status is Associated With More Severe Hemispatial Neglect After Stroke.

BACKGROUND: Many stroke patients are clinically dehydrated at the time of hospital presentation, which could lead to an increase in blood viscosity and alteration in cerebral perfusion. Impaired cerebral perfusion can cause hemispheric dysfunction, which can be rapidly quantified with bedside tests of hemispatial neglect. We hypothesized that hospitalized patients with laboratory markers consistent with dehydration or a volume contracted state (VCS) would have more severe cerebral dysfunction defined by greater degree of neglect. METHODS: Subjects were a consecutive series of right-handed patients with acute right hemispheric stroke admitted within the Johns Hopkins Health System. All participants had clinical syndrome and magnetic resonance imaging consistent with acute infarction. The primary definition of a VCS was a urea/creatinine ratio >15, with secondary definition including urine specific gravity over 1.010. Acute infarct volume was measured on magnetic resonance imaging. Neglect was evaluated using a standardized battery of bedside tests. RESULTS: Of 201 patients meeting inclusion criteria, 131/201 (65%) had elevated BUN/creatinine ratios at admission. Approximately 61% (122/201) had some degree of neglect. Elevated BUN/creatinine ratio was associated with an increased odds of severe neglect in unadjusted models (OR=4.1; 95% CI, 1.2, 14.4), with loss of significance in adjusted models (OR=4.43; 95% CI, 0.99, 19.8) after adjustment for age, infarct volume, sex, and NIHSS score. CONCLUSIONS: Our data suggest that patients who are in a VCS at the time of stroke may have more frequent and severe neglect, with attenuation of results after adjustment for factors related to stroke size and age. If proven clinically relevant, a formalized rehydration strategy based on objective lab markers may represent an opportunity for improvement in outcome with low-cost, broadly available treatment for acute stroke patients.

Osmotic diuresis with SGLT2 inhibition: analysis of events related to volume reduction in dapagliflozin clinical trials.

OBJECTIVE: Dapagliflozin reduces hyperglycemia in type 2 diabetes mellitus (T2DM) and lowers blood pressure, at least in part, secondary to mild diuresis consequent to dapagliflozin-induced glucosuria. While blood-pressure lowering may contribute to cardiovascular risk reduction, dapagliflozin-induced diuresis may potentially contribute to adverse events (AEs) of volume reduction. The present analysis compared the frequency of AEs of volume reduction between dapagliflozin and placebo. METHODS: Pooled data were assessed from 13 placebo-controlled dapagliflozin clinical trials ≤24 weeks in patients with T2DM, overall, and in those at risk (aged ≥65y, estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m(2), or on antihypertensive therapy). Longer-term (≤104 weeks) data were available for 9 of these trials. RESULTS: The frequency of patients experiencing ≥1 AE of volume reduction over 24 weeks was low overall; 27/2360 (1.1%) with dapagliflozin 10 mg and 17/2295 (0.7%) with placebo; and slightly more frequent in patients ≥65 years (11/665 [1.7%] and 6/711 [0.8%], respectively) and in patients receiving loop diuretics (6/236 [2.5%] and 4/267 [1.5%], respectively). Over 104 weeks, AEs of volume reduction occurred in 38/2026 (1.9%) with dapagliflozin 10 mg and in 27/1956 (1.4%) with placebo; serious AEs of volume reduction in 4/2026 (0.2%) and 6/1956 (0.3%), respectively; and 2 patients in each group discontinued therapy due to these AEs. Dapagliflozin versus placebo incidence rate ratios did not suggest any meaningful increase in frequency of these AEs with dapagliflozin 10 mg, either overall or in those at risk. Although mean eGFR declined by 4.2 ml/min/1.73 m(2) within the first week of dapagliflozin therapy, thereafter eGFR gradually recovered to baseline levels by 104 weeks (mean change from baseline +0.02 mL/min/1.73 m(2); 95%CI: -0.9, 1.0). CONCLUSION: No meaningful increase in frequency of AEs of volume reduction occurred with dapagliflozin 10 mg in patients with T2DM, either overall, or in those at increased risk of these events. However, caution should nevertheless be exercised when prescribing dapagliflozin to elderly patients, those with reduced eGFR, and those receiving antihypertensive medication.

[Postural orthostatic tachycardia syndrome (POTS)--pathophysiology, diagnostics, and treatment]. / Zespól posturalnej tachykardii ortostatycznej (POTS)--patofizjologia, rozpoznanie i leczenie.

Postural orthostatic tachycardia syndrome (POTS) is one of the most common presentation of orthostatic intolerance. The syndrome is described as a multifactorial affliction. Main symptoms consist of persistent orthostatic tachycardia (heart rate increase at least 30 beats/min, lasting at least 10 min after assumic vertical position) with high noradrenalin serum concentration (measured in stand-up position). Additionally patients with POTS tend to have lover total blood volume. POTS is generally classified into dysatonomia disorders Symptoms in patients affected with POTS are chronic. The syndrome occurs predominantly in young women (approximately 80%). Due to complexity and variable intensity of symptoms POTS can severely impair daily activity and quality of life in otherwise healthy people. The correct diagnosis and identification of potential pathophysiological mechanisms of POTS is necessary before treatment administration. Adequate therapy can significantly reduce symptoms giving the patients a chance for a normal life.

Hypovolaemia was associated with clustering of major cardiovascular risk factors in general population.

BACKGROUND: Previous studies indicated that the clustering of major cardiovascular disease (CVD) risk factors is common, and multiple unhealthy lifestyles are responsible for the clustering of CVD risk factors. However, little is known about the direct association between the volume load and the clustering of CVD risk factors in general population. METHODS: We investigated the association of the clustering of CVD risk factors (defined as two or more of the following factors: hypertension, diabetes, dyslipidemia and overweight) with volume load, which was evaluated by bioelectrical impedance analysis. Hypovolaemia was defined as extracellular water/total body water (ECW/TBW) at and under the 10th percentile for the normal population. RESULTS: Among the 7900 adults, only 29.3% were free of any pre-defined CVD risk factors and 40.8% had clustering of CVD risk factors. Hypovolaemia in clustering group was statistically higher than that either in the single or in the none risk factor group, which was 23.7% vs. 17.0% and 10.0%, respectively (P <0.001). As a categorical outcome, the percentage of the lowest quartiles of ECW/TBW and TBW/TBWwatson in clustering group were statistically higher than either those in the single or in the none risk factor group, which were 44.9% vs. 36.9% and 25.1% (P <0.001), 36.2% vs. 32.2% and 25.0%, respectively (P <0.001). After adjusting of potential confounders, hypovolaemia was significantly associated with clustering of CVD risk factors, with an OR of 1.66 (95% CI, 1.45-1.90). CONCLUSIONS: Hypovolaemia was associated with clustering of major CVD risk factors, which further confirms the importance of lifestyle for the development of CVD.

Renal failure in patients with end stage liver disease and its impact on clinical outcome.

OBJECTIVE: To evaluate the prevalence of renal failure (RF) in the patients of end stage liver disease (ESLD), to determine the causes of RF in these patients and its impact on patient's outcome. STUDY DESIGN: Descriptive, analytical study. PLACE AND DURATION OF STUDY: Shifa International Hospital, Islamabad, Pakistan, from May 2011 to March 2013. METHODOLOGY: A total of 523 patients with end stage liver disease (ESLD) were evaluated, renal failure (RF) and its causes were recognized in these patients according to established criteria. Outcome of these patients was assigned as reversal of RF or mortality. Data was analyzed using SPSS version 16. Chi-square test was used for comparing proportions and t-test was used for comparing mean values. P < 0.05 was considered significant. RESULTS: Out of 523 patients, 261 (49.9%) had RF. Acute kidney injury (AKI) was the most common presentation seen in 160 (61%) patients. Hypovolemia and infections were the most frequent causes of RF. Mortality was significantly higher in the patients with RF, when compared to the patients without RF (31% vs. 4.5%, p < 0.001). Reversal of RF was seen in 98 (37%) of the affected patients. Reversal was more common in the patients with hypovolemia. The mortality was higher in the patients with hepatorenal syndrome (HRS) and infections. CONCLUSION: Renal failure in the end stage liver disease is an important prognostic factor. Etiology of RF is the key factor in patients' outcome. Patients of ESLD with RF had higher mortality. Majority of the cases of RF were reversible in patients of ESLD coming in the setup.

Clinical evaluation of hyponatremia and hypovolemia in critically ill adult neurologic patients: contribution of the use of cumulative balance of sodium.

PURPOSE: Knowledge of the cumulative balance of sodium (CBS) is important for the diagnosis of salt disorders and water homeostasis and has the potential to predict hypovolemic status in acute neurological patients. However, an extensive application of the use of CBS is still lacking in the intensive care setting, where salt and water homeostasis represents a priority. METHODS: Records of consecutive series of acute neurological patients admitted to a neurointensive care unit over a 6-month period were retrospectively reviewed. CBS was calculated at the admission to the Emergency Department. Discrimination between cerebral salt-wasting syndrome (CSWS) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was performed on the basis of the classical criteria. Additionally, we used the findings of a negative CBS exceeding 2 mEq/kg for the diagnosis of CSWS. Two independent clinicians who were blinded to the CBS results performed diagnosis of the causes of hyponatremia and estimated the daily volemic status of the patients on the basis of clinical parameters. Logistic regression analysis was used to determine the independent prognostic factors of hypovolemia. RESULTS: Thirty-five patients were studied for a total of 418 days. Four patients (11.4%) fitted the criteria of CSWS and three patients (8.5%) had SIADH. The unavailability of the CBS led to a wrong diagnosis in three of the eight hyponatremic patients (37.5%). The risk of developing hypovolemia in patients with negative CBS was 7.1 times higher (CI 3.86-13.06; p < 0.001). Multivariate analysis revealed that negative cumulative fluid balance, negative CBS >2 mEq/kg, and CVP ≤5 cmH2O were independent prognostic factors for hypovolemia. CONCLUSIONS: CBS is likely to be a useful parameter in the diagnosis of CSWS and a surrogate parameter for estimating hypovolemia in acute neurological patients.

Impact of the 2009 Melbourne heatwave on a major public hospital.

In the week following the onset of the 2009 heatwave in Melbourne, Australia, The Alfred Hospital observed a significant increase in total hospital admissions (adjusted incidence rate ratio (IRR) 1.11, P = 0.046), emergency department presentations (IRR 1.15, P < 0.01) and general medical admissions (IRR 1.81, P < 0.01). Under the general medical unit there was a rise in the number of deaths (IRR 3.9, P < 0.01), and patients with a broad range of disorders, particularly of the endocrine/metabolic (IRR 2.2, P < 0.01), circulatory (IRR 1.9, P < 0.01) and genitourinary (IRR 2.6, P < 0.01) systems.

Cardiac remodeling induced by 13-cis retinoic acid treatment in acne patients.

BACKGROUND: Currently, 13-cis-retinoic acid (13-cis-RA) is the most effective therapy for acne. Isotretinoin, a first-generation synthetic 13-cis-RA compound, is associated with numerous adverse effects. To investigate the cardiac effects of 13-cis-RA, acne patients receiving 13-cis-RA were studied. METHODS: Twenty male patients with acne were enrolled in the study. Patients were treated with a dose of 0.5 mg/kg/d of isotretinoin. All participants were assessed prior to treatment and after 10 weeks of therapy with Doppler-echocardiogram. RESULTS: Patients showed reductions in right atrium vertical diameter, left atrium longitudinal diameter, left atrium volume and left ventricular diastolic diameter over the course of treatment. Significant increases in interventricular septum diastolic thickness, posterior wall diastolic thickness, relative wall relative thickness and left ventricle (LV) mass were observed. The LV mass index showed an increase in ventricular mass and a decrease in the cavity size. Examining LV systolic function, a decrease was observed for the cardiac index. CONCLUSION: In this study, 10 weeks of 13-cis-RA therapy at a dose of 0.5 mg/kg/d was found to promote concentric-type heart remodeling due to the occurrence of two associated events: heart hypertrophy and hypovolemia.

Outbreak of epidemic dropsy in Ethiopia: the clinical and therapeutic observation.

INTRODUCTION: Epidemic dropsy results from ingestion of argemone oil contaminated food staffs. The oil from Argemone Mexican seeds contains toxic alkaloids called sanguinarine and dehydrosangunarine. These cause wide spread capillary dilatation, proliferation and leakages. This leads to oedema, hypovolemia and hypotension. OBJECTIVE: To describe the socio-demographic and clinical manifestations of the patients affected with epidemic dropsy in Tikur Anbessa specialized Hospital (TASH). METHODS: A case series study was conducted in an outbreak with unusual cases which was later diagnosed to be epidemic dropsy. Clinical evaluation of suspects was done and optimal therapy given for the complications detected and information was filled in structured format by medical residents and medial chart records review was made for occurrence of new complications in the end of 9 months. RESULTS: A total of 164 patients were seen at TASH from 26 households, in 8 sub-cities of Addis Ababa. A wide range of age group was affected with 70% from 16 to 40 years of age. There was no case among less than 5 years of age. Females were affected more than threefold as compared to males. All the patients manifested with bilateral leg swelling and pitting oedema. It was tender in 50 (30.4%) of them while 43 (26.2%) had erythema. Tachycardia was the next common manifestation occurring in 135 (82.3%), followed by cough in 123 (75%), anaemia in 59 (36%), headache in 58 (35.4%), shortness of breathing in 52 (31.2%), hair loss in 44 (26.8%) and respiratory distress in 35 (21.3%). Abdominal pain, hepatomegally, nausea and vomiting were also seen. There was abnormality in the chest X-ray of 31 (27.2%). Hair loss, tingling and burning extremities, difficulty of standing, hyperpigmentation, pruritic rash and eye symptoms were observed lately during follow up. Five of the patients died while in hospital care due to acute respiratory distress syndrome (ARDS). CONCLUSIONS: The commonest clinical manifestation in our patients is bilateral leg swelling which is similar to other outbreaks of epidemic dropsy elsewhere. The mortality rate is also comparable with other series but all cases died by ARDS in our series which is unusual in other reports. As this is the first reported epidemics in Ethiopia the findings will create awareness of clinical features of epidemic dropsy among clinicians, and therefore, helps for diagnoses of similar problems in the future.

Fractional excretion of uric acid as a predictor for saline responsiveness in long-term kidney transplant patients.

BACKGROUND/AIMS: Subclinical hypovolemia may contribute to allograft dysfunction in long-term kidney transplant (KT) patients. In order to predict responsiveness to saline hydration, indices for tubular transport were investigated. METHODS: Fifty-four clinically euvolemic long-term KT patients with recently aggravated azotemia were given intravenous hydration as follows: 0.9% saline 5 ml/kg over 1 h, followed by 0.9% saline 1 ml/kg/h over 12 h and 1 liter of 0.45% saline over the next 24 h. Serum and urine data were collected and analyzed to assess responses. RESULTS: In all patients, saline hydration relieved azotemia, as shown by blood urea nitrogen (46.9 ± 17.2 vs. 39.3 ± 15.4 mg/dl; p < 0.01) and serum creatinine levels (2.9 ± 1.1 vs. 2.5 ± 1.1 mg/dl; p < 0.01) on day 0 versus day 2. In 38 patients, serum creatinine did not increase in the following month (70% responders). Compared with the nonresponders, the responders had a higher urine-to-plasma creatinine ratio and lower fractional excretion of sodium, uric acid and urea at admission. Multivariate logistic regression analysis revealed that responsiveness to saline hydration was independently associated with lower fractional excretion of uric acid. CONCLUSION: Subclinical hypovolemia should be considered in long-term KT patients with azotemia of unexplainable causes. Fractional excretion of uric acid may predict responsiveness to saline hydration.