Intravascular Volume Depletion Research Articles

Decreased Mortality in Acute Pancreatitis Related to Early Aggressive Hydration

Early aggressive intravenous hydration is believed to prevent morbidity and mortality by preventing intravascular volume depletion and maintaining perfusion of the pancreas possibly preventing pancreatic necrosis. The following study was initiated to determine the relationship between the observed decrease in mortality and the role of early aggressive hydration. A consecutive series of patients with acute pancreatitis from a single community hospital in 1998 were compared to a consecutive series of patients with acute pancreatitis from the same institution in 2008. Significantly more patients developed pancreatic necrosis; 26 (15%) of 173 patients in 1998 compared to 4 (4%) of 113 patients in 2008. The mean rate of hydration was significantly higher in 2008 compared with that in 1998 (P = 0.02). In 1998, hydration was provided at 184 mL/h during the first 6 hours and 188 mL/h during the first 12 hours compared with 284 mL/h during the first 6 hours and 221 mL/h during the first 12 hours in 2008. There was a significant decrease in mortality in 2008 compared with that in 1998 (3.5% vs 12%, P = 0.03). The decrease in mortality seen in patients with acute pancreatitis during the last decade may be related to the increased aggressive hydration preventing pancreatic necrosis.

234 Effect of Dialysate Baths on Serum Bicarbonate Levels in Hemodialysis Patients

HYPONATREMIA AFTER HEAD INJURY: A COMPLEX CEREBRORENAL CONNECTION BEYOND SIADH Uma Pakkivenkata, Kambhampati Ganesh, Gurjit Dhatt, Amir Kazory Division of Nephrology, University of Florida, Gainesville, Florida, USA A 76-year-old female who was admitted for subdural hematoma secondary to a fall presented with hyponatremia of 120 mmol/l. The blood pressure was 149/73, pulse 80, and she appeared euvolemic. The brain CT scan revealed a stable subdural hematoma which was managed conservatively. Since the lab data (urine Na 48meq/L, urine osm 401mosm/kg, and serum osm 250mosm/kg) was consistent with the diagnosis of SIADH in the context of recent head injury, the patient was placed on free water restriction. However, this was followed by worsening of hyponatremia to 117 mmol/l and alteration in mental status. A repeat brain CT scan showed worsening hematoma, and she underwent a surgical drainage. Review of the lab results revealed characteristics compatible with increased ADH release associated with features of renal proximal tubulopathy: persistent high urinary levels of electrolytes (e.g. K, Mg, and Phos) despite very low serum levels. Therefore the diagnosis of cerebral salt wasting (CSW) was made and the patient was started on hypertonic saline, which was followed by progressive improvement in serum sodium levels. Two days after resolution of hyponatremia, serum and urine studies were rechecked: serum uric acid remained very low (1.4 mg/dl) and fractional excretion of uric acid did not normalize; a finding that further supported the diagnosis of CSW, rather than SIADH. Other manifestations of proximal tubulopathy (e.g. hypokalemia and hypo-phosphatemia) gradually improved. Hyponatremia after head injury is possibly the manifestation of a complex cerebro-renal connection, with poorly understood underlying mechanisms. In CSW, an unidentified mediator released from the brain disrupts the function of the proximal tubules and leads to leakage of electrolytes into the urine. Interestingly, ADH levels are also increased in CSW; hyponatremia is related to “appropriate” ADH secretion in response to intravascular volume depletion secondary to excessive tubular sodium excretion. As such, CSW and SIADH share several features and represent the biological consequences of a primary insult to the brain that can either be predominant in the brain (SIADH) or in the kidney (CSW). It is of utmost importance to appreciate the subtle differences existing between CSW and SIADH in order to avoid instauration of potentially-harmful management strategies such as this case.

Renal insufficiency: Management prior to transplantation

KEY POINTS (1) In cirrhosis, acute kidney injury (AKI) is mainly due to prerenal factors [including type 1 hepatorenal syndrome (HRS)] and ischemic acute tubular necrosis (ATN). (2) IN cirrhosis, chronic kidney disease (CKD) may be due to type 2 HRS, immunoglobulin A (IgA) nephropathy, or membranoproliferative glomerulonephritis. Some patients have acute-on-chronic kidney injury. (3) In patients with cirrhosis and CKD waiting for liver transplantation, renal biopsy may be indicated because histopathological analysis of renal biopsy specimens provides diagnostic and prognostic information. In these patients, the transjugular route can be safely used. (4) Treatments of AKI should target the cause of renal hypoperfusion (eg, fluid replacement to treat intravascular volume depletion or vasoconstrictor therapy for type 1 HRS). There is no specific treatment for ATN; renal replacement therapy may be used. (5) Treatments of CKD depend on the cause. There is no established therapy for type 2 HRS or IgA nephropathy; patients with chronic hepatitis C and membranoproliferative glomerulonephritis may benefit from antiviral therapy. (6) Combined liver and kidney transplantation may be used in some patients with cirrhosis and CKD. The decision is based on the value of the glomerular filtration rate (ideally one should use the measured value and not the estimated value) and the results of renal biopsy. Liver Transpl 16:S72-S76, 2010. © 2010 AASLD.

The Conundrum of Worsening Renal Function and Optimal Volume Status in Patients with Acute Decompensated Heart Failure

Management strategies to treat advanced decompensated heart failure include alleviation of congestion in an attempt to decrease filling pressures and achieve a near euvolemic state. Aggressive diuresis leading to intravascular volume depletion often is associated with worsening renal function (WRF). Moreover, when diuresis proceeds at a rate greater than the plasma refill rate, the plasma becomes concentrated, leading to increases in levels of hemoglobin and plasma proteins. The investigators of this study postulated that hemoconcentration may represent the aggressiveness of diuresis more directly than other goals such as changes in filling pressures or deterioration of renal function. Aims

Hemoconcentration, Heart Failure, and Survival

Background: Overly aggressive diuresis leading to intravascular volume depletion has been proposed as a cause for worsening renal function during the treatment of decompensated heart failure .I f diuresis occurs at ar ate greater than extravascular fluid can refill the intravascular space, the concentration of such intravascular substances as hemoglobin and plasma proteins increases. We hypothesized that hemoconcentration would be associated with worsening renal function and possibly would provide insight into the relationship between aggressive decongestion and outcomes. Methods and Results: Subjects in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial limited data set with a baseline/ discharge pair of hematocrit, albumin, or total protein values were included (336 patients). Baseline-to-discharge increases in these parameters were evaluated, and patients with ≥2 in the top tertile were considered to have evidence of hemoconcentration. The group experiencing hemoconcentration received higher doses of loop diuretics, lost more weight/fluid, and had greater reductions in filling pressures (P<0.05 for all). Hemoconcentration was strongly associated with worsening renal function (odds ratio, 5.3; P<0.001), whereas changes in right atrial pressure (P=0.36) and pulmonary capillary wedge pressure (P=0.53) were not. Patients with hemoconcentration had significantly lower 180-day mortality (hazard ratio, 0.31; P=0.013). This relationship persisted after adjustment for baseline characteristics (hazard ratio, 0.16; P=0.001). Conclusion: Hemoconcentration is significantly associated with measures of aggressive fluid removal and deterioration in renal function. Despite this relationship, hemoconcentration is associated with substantially improved survival. These observations raise the question of whether aggressive decongestion, even in the setting of worsening renal function, can positively affect survival.

Impact of diuretic treatment and sodium intake on plasma volume in patients with compensated systolic heart failure

In patients with heart failure (HF), the use of diuretics may be a double-edged sword that can alleviate symptoms of congestion, but also result in over-diuresis and intravascular volume depletion. The purpose of the present study was to examine plasma volume (PV) in HF patients receiving from 0 to 160 mg of furosemide and to investigate whether determination of plasma N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) concentrations can predict PV-status. Plasma volume, extracellular volume, glomerular filtration rate, NT-proBNP, and daily renal sodium excretion were measured in 18 patients with medically treated, compensated HF and in 27 healthy volunteers. Cardiac function was examined by non-invasive cardiac output determination and echocardiography. Exercise capacity was evaluated by 6 min walk test. There was a borderline significant difference in PV between patients with HF and control subjects (37.3 +/- 6.0 and 40.2 +/- 5.8 mL/kg, respectively, P = 0.092) with a significant tendency towards a contraction of PV with increasing use of diuretics (P = 0.031). There was no difference in extracellular volume between patients with HF and control subjects (P = 0.844). NT-proBNP plasma concentrations had no correlation to either sodium excretion (P = 0.193) or PV (P = 0.471) in patients with HF. Plasma volume in patients with HF was within normal limits, but patients treated with high doses of loop-diuretics tended to have subnormal PV. Single measurement of NT-proBNP plasma concentration could not be used to estimate intravascular volume status in patients with HF.

Cardiorenal Syndrome: Diagnosis, Treatment, and Clinical Outcomes

The pathophysiologic interactions that link the heart and kidney are multiple and complex, and have been grouped under the umbrella term "cardiorenal syndrome." In the setting of acute decompensated heart failure, worsening renal function has been directly associated with poor clinical prognosis and complicates treatment. However, the pathophysiology underlying acute cardiorenal syndrome remains incompletely understood and treatment options remain limited. Traditionally, the development of worsening renal function in acute decompensated heart failure has been attributed to renal arterial underfilling due to reduced cardiac output or intravascular volume depletion. However, increasing data have expanded our understanding of the roles that venous congestion and intra-abdominal pressure play in driving renal injury, with important implications for therapeutic management and the development of novel renal-sparing therapies.

Potential Effects of Aggressive Decongestion during the Treatment of Decompensated Heart Failure on Renal Function and Survival: Insights from the ESCAPE Trial Limited Dataset

Background: Overly aggressive diuresis leading to intravascular volume depletion has been proposed as a cause for worsening renal function (WRF) during the treatment of decompensated heart failure. If diuresis occurs at a rate greater than extravascular fluid can refill the intravascular space, intravascular substances such as hemoglobin and plasma proteins increase in concentration. We hypothesized that hemoconcentration would be associated with WRF and possibly provide insight into the relationship between aggressive decongestion and outcomes. Methods: Subjects in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial limited dataset with a baseline/discharge pair of hematocrit, albumin, or total protein values were included (336 patients). Baseline to discharge increases in these parameters were evaluated and patients with ≥2 in the top tertile were considered to have evidence of hemoconcentration. Results: The group experiencing hemoconcentration received higher doses of loop diuretics, lost more weight/fluid, and had greater reductions in filling pressures (p < 0.05 for all). Hemoconcentration was strongly associated with WRF (OR = 5.3, p < 0.001) whereas change in right atrial pressure (p = 0.36) and change in pulmonary capillary wedge pressure (p = 0.53) were not. Patients with hemoconcentration had significantly lower 180 day mortality (HR = 0.31, p = 0.013). This relationship persisted after adjustment for baseline characteristics (HR = 0.16, p = 0.001). Conclusion: Hemoconcentration is significantly associated with measures of aggressive fluid removal and deterioration in renal function. Despite this relationship, hemoconcentration is associated with substantially improved survival. These observations raise the question whether aggressive decongestion, even in the setting of WRF, can positively impact survival.

Potential Effects of Aggressive Decongestion During the Treatment of Decompensated Heart Failure on Renal Function and Survival

Overly aggressive diuresis leading to intravascular volume depletion has been proposed as a cause for worsening renal function during the treatment of decompensated heart failure. If diuresis occurs at a rate greater than extravascular fluid can refill the intravascular space, the concentration of such intravascular substances as hemoglobin and plasma proteins increases. We hypothesized that hemoconcentration would be associated with worsening renal function and possibly would provide insight into the relationship between aggressive decongestion and outcomes. Subjects in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial limited data set with a baseline/discharge pair of hematocrit, albumin, or total protein values were included (336 patients). Baseline-to-discharge increases in these parameters were evaluated, and patients with >or=2 in the top tertile were considered to have evidence of hemoconcentration. The group experiencing hemoconcentration received higher doses of loop diuretics, lost more weight/fluid, and had greater reductions in filling pressures (P<0.05 for all). Hemoconcentration was strongly associated with worsening renal function (odds ratio, 5.3; P<0.001), whereas changes in right atrial pressure (P=0.36) and pulmonary capillary wedge pressure (P=0.53) were not. Patients with hemoconcentration had significantly lower 180-day mortality (hazard ratio, 0.31; P=0.013). This relationship persisted after adjustment for baseline characteristics (hazard ratio, 0.16; P=0.001). Hemoconcentration is significantly associated with measures of aggressive fluid removal and deterioration in renal function. Despite this relationship, hemoconcentration is associated with substantially improved survival. These observations raise the question of whether aggressive decongestion, even in the setting of worsening renal function, can positively affect survival.

Incidence and Prognosis of Different Types of Functional Renal Failure in Cirrhotic Patients With Ascites

Hepatorenal syndrome is a well-characterized type of terminal renal failure that occurs in patients with cirrhosis with ascites. Information about other types of functional renal failure in these patients is scarce. We assessed the incidence and prognosis of different types of functional renal failure in cirrhotic patients with ascites and investigated prognostic factors for these disorders. Consecutive cirrhotic patients (n = 263) were followed for 41 +/- 3 months after their first incidence of ascites. Three types of functional renal failure were considered: pre-renal failure (when renal failure was associated with a depletion of intravascular volume), renal failure induced by infection that did not result in hepatorenal syndrome, and hepatorenal syndrome. During the follow-up period, 129 (49%) patients developed some type of functional renal failure. The most frequent was pre-renal failure (27.4%), followed by renal failure induced by infection (14.1%), and then hepatorenal syndrome (7.6%). The 1-year probability of developing the first episode of any functional renal failure was 23.6%. The independent predictors of functional renal failure development were baseline age, Child-Pugh score, and serum creatinine. Although the 1-year probability of survival was 91% in patients without renal failure, it decreased to 46.9% in those patients who developed any functional renal failure (P = .0001). Approximately 50% of the cirrhotic patients with ascites developed some type of functional renal failure during the follow-up period; renal failure was associated with worse prognosis. Efforts should be made to prevent renal failure in cirrhotic patients with ascites.

Hepatorenal Syndrome

Critical care nurses occasionally confront patient conditions that are not common. One such condition is hepatorenal syndrome (HRS). Three primary processes contribute to regional alterations in circulation in the renal and splanchnic beds. These processes include effective hypovolemia from the massive release of vasoactive mediators, thereby underfilling circulation, systemic and splanchnic vasodilation along with renal vasoconstriction, and hyperdynamic circulation. A “second-hit” hypothesis, whereby a triggering event causes intravascular volume depletion, likely initiates the development of HRS. The idea of a second hit focuses the attention of the health care team on surveillance strategies to prevent or limit HRS in patients with advanced cirrhosis and ascites. The treatment goal is to restore systemic and splanchnic vasoconstriction, while promoting renal vasodilation, balance sodium, and achieve euvolemia. The critical care nurse must maintain ongoing education to care for the patient with this complex syndrome in order to prevent complications and death.

Hepatorenal Syndrome

Critical care nurses occasionally confront patient conditions that are not common. One such condition is hepatorenal syndrome (HRS). Three primary processes contribute to regional alterations in circulation in the renal and splanchnic beds. These processes include effective hypovolemia from the massive release of vasoactive mediators, thereby underfilling circulation, systemic and splanchnic vasodilation along with renal vasoconstriction, and hyperdynamic circulation. A "second-hit" hypothesis, whereby a triggering event causes intravascular volume depletion, likely initiates the development of HRS. The idea of a second hit focuses the attention of the health care team on surveillance strategies to prevent or limit HRS in patients with advanced cirrhosis and ascites. The treatment goal is to restore systemic and splanchnic vasoconstriction, while promoting renal vasodilation, balance sodium, and achieve euvolemia. The critical care nurse must maintain ongoing education to care for the patient with this complex syndrome in order to prevent complications and death.

Pulmonary edema and blood volume after aneurysmal subarachnoid hemorrhage: a prospective observational study

IntroductionPulmonary edema (PED) is a severe complication after aneurysmal subarachnoid hemorrhage (SAH). PED is often treated with diuretics and a reduction in fluid intake, but this may cause intravascular volume depletion, which is associated with secondary ischemia after SAH. We prospectively studied intravascular volume in SAH patients with and without PED.MethodsCirculating blood volume (CBV) was determined daily during the first 10 days after SAH by means of pulse dye densitometry. CBV of 60-80 ml/kg was considered normal. PED was diagnosed from clinical signs and characteristic bilateral pulmonary infiltrates on the chest radiograph. We compared CBV, cardiac index, and fluid balance between patients with and without PED with weighted linear regression, taking into account only measurements from the first day after SAH through to the day on which PED was diagnosed. Differences were adjusted for age, bodyweight, and clinical condition.ResultsIn total, 102 patients were included, 17 of whom developed PED after a mean of 4 days after SAH. Patients developing PED had lower mean CBV (56.6 ml/kg) than did those without PED (66.8 ml/kg). The mean difference in CBV was -11.3 ml/kg (95% CI, -16.5 to -6.1); adjusted mean difference, -8.0 ml/kg (95% CI, -14.0 to -2.0). After adjusting, no differences were found in cardiac index or fluid balance between patients with and without PED.ConclusionsSAH patients developing pulmonary edema have a lower blood volume than do those without PED and are hypovolemic. Measures taken to counteract pulmonary edema must be balanced against the risk of worsening hypovolemia.Trial registrationNTR1255.

Scleroderma Renal Crisis: A Rare but Severe Complication of Systemic Sclerosis

Scleroderma renal crisis (SRC) is a major complication in patients with systemic sclerosis (SSc). It is characterized by malignant hypertension and oligo/anuric acute renal failure. SRC occurs in 5% of patients with SSc, particularly in the first years of disease evolution and in the diffuse form. The occurrence of SRC is more common in patients treated with glucocorticoids, the risk increasing with increasing dose. Left ventricular insufficiency and hypertensive encephalopathy are typical clinical features. Thrombotic microangiopathy is detected in 43% of the cases. Anti-RNA-polymerase III antibodies are present in one third of patients who develop SRC. Renal biopsy is not necessary if SRC presents with classical features. However, it can help to define prognosis and guide treatment in atypical forms. The prognosis of SRC has dramatically improved with the introduction of angiotensin-converting enzyme inhibitors (ACEi). However, 5 years survival in SSc patients who develop the full picture of SRC remains low (65%). SRC is often triggered by nephrotoxic drugs and/or intravascular volume depletion. The treatment of SRC relies on aggressive control of blood pressure with ACEi, if needed in combination with other types of antihypertensive drugs. Dialysis is frequently indicated, but can be stopped in approximately half of patients, mainly in those for whom a perfect control of blood pressure is obtained. Patients who need dialysis for more than 2 years qualify for renal transplantation.

Study on Role of Oral Clonidine in Laparoscopic Cholecystectomy Surgery – A Comparative Study

Laparoscopic surgical techniques have been rapidly accepted by the surgeon worldwide e.g. especially laparoscopic cholecystectomy, with published reports describing the benefits of less postoperative pain, reduced hospital stay and an earlier return to work. The hall mark of laparoscopic surgery is the creation of pneumoperitoneum with pressurized CO2. The high solubility of CO2 increases systemic absorption by the vasculature of the peritoneum. This, combined with smaller tidal volumes because of poor lung complication, leads to increased arterial CO2 levels which is known as hypercarbia. If hypercarbia allowed to develop, will stimulate the sympathetic nervous system and thus increase heart rate, blood pressure, and the risk of dysrhythmias. These effects can prove especially challenging in patients with restrictive lung disease, impaired cardiac function, or intravascular volume depletion . The present study was to evaluate the role of oral clonidine and atenolol in controlling tachycardia and hypertension associated with pneumoperitoneum with CO2 during laparoscopic cholecystectomy under general anaesthesia and also to find out the best premedicant in controlling heamodynamic instability in laparo-scopic cholecystomy. 75 patients schedule for laparoscopic cholecystectomy were randomly selected by blind envelop method. Patients were divided equally into three groups, which were Group-I: Oral clonidine(150ìgm), Group-II: oral atenolol(25mg) and Group-III: placebo (vitamin-c tablet), twenty five patients were in each group The mean difference of pulse rate at different times was significant (p&lt;0.05), however just before induction, just after skin incision and just after insufflations CO2 were not significant (p&gt;0.05). The mean differences of systolic, diastolic BP at different times were not significant (p&gt;0.05), however BP was almost stable just before induction to the end of the operation in group I patients. The mean difference of SPO2 at different times was not significant(p&gt;0.05) but just after intubations (99.6%±0.5% in group I, 99.3% ±0.5% in group II and 98.7%±1.1% in group III) and just after skin incision (99.5%±0.6% in group I, 98.9%± 0.6% in group II and 98.3% ±0.9 % in group III) was significant (p&lt;0.05). The mean difference of ETCO2 at different times was not significant (p&gt;0.05) however after 5 minutes insufflations (35.8±0.8 mmHg in group I, 36.5±0.5 mmHg in group II and 35.5±0.8 mmHg in group III) was significant (p&lt;0.05). The mean (±SD) halothane intake of group I patients was 0.49±0.06%, 0.56±0.10% in group II and 0.66±0.09% in group III. The mean (±SD) duration of first analegesic demand of the patents was 90.8±8.5 minutes in group I, 74.0±8.5 minutes in group II and 72.2±8.7 minutes in group III. The mean difference of halothane requirement &amp; duration of first analegesic demand were significant (p&lt;0.05). The aldrete recovery status of original criteria were almost similar in three groups (p&gt;0.05). We can conclude that oral clonidine and atenolol to control heart rate &amp; haemodynamic instability in laparoscopic cholecystectomy under general anaesthesia is better than placebo. Journal of BSA, Vol. 21, No. 1, January 2008 12-20

Provider Knowledge of Contrast-Induced Acute Kidney Injury

BackgroundAlthough past research has elucidated the principal risk factors and efficacy of preventive interventions for contrast-induced acute kidney injury (CIAKI), provider awareness of this empiric evidence base is largely unknown. We sought to assess provider knowledge of the risk factors and preventive interventions for CIAKI. MethodsWe asked medical providers caring for patients undergoing procedures with intravascular iodinated contrast to complete a survey designed to assess their knowledge of the risk factors and preventive interventions for CIAKI. ResultsOf the 87 participating providers, nearly all (n = 85; 98%) recognized chronic kidney disease and intravascular volume depletion as risk factors. However, 35 (41%) incorrectly identified allergy to contrast media as a risk factor and 8 (10%) incorrectly identified intravenous (IV) water as an effective preventive intervention. Compared with those with little or no prior training on CIAKI, those with substantial prior training correctly reported that peripheral vascular disease and atrial fibrillation are not risk factors and that fenoldopam and IV water are ineffective preventive interventions (P<0.05). Trainees were more likely than those who had completed their postgraduate medical training to correctly report that IV saline and sodium bicarbonate are effective preventive interventions and that fenoldopam, dopamine, mannitol, and IV water are ineffective measures (P<0.05). ConclusionsThere is wide variability in providers’ knowledge of CIAKI. Providers with more training on CIAKI and trainees had greater knowledge of the risk factors and preventive interventions for CIAKI. These findings underscore the need to standardize and intensify provider education of this costly and preventable iatrogenic condition.

Blood Urea Nitrogen (BUN) for the Early Prediction of Mortality in Acute Pancreatitis

Purpose: We previously identified BUN as the most accurate routine laboratory test for prediction of mortality in acute pancreatitis (AP) in a large multi-center retrospective cohort study. The purpose of this study was to: 1) confirm accuracy of BUN during first 24 hours for prediction of mortality in a rigorously defined prospective AP cohort and; 2) identify factors associated with increased BUN. Methods: Prospective cohort study of consecutive AP patients treated in a tertiary care hospital from June 2005-May 2007. AP was defined as 2 or more of the following: characteristic abdominal pain, amylase/lipase elevation >3 times upper limit normal and/or confirmatory imaging findings. Routine laboratory tests were monitored throughout hospitalization. Accuracy of BUN for prediction of in-hospital mortality was evaluated using logistic regression including admission BUN and change in BUN at 24 hours as discreet variables. Logistic regression was also used to determine the extent to which hydration (cc/kg first 24 hours), renal insufficiency (serum creatinine) or systemic inflammation (SIRS) contributed to increases in BUN. Results: We enrolled a total of 397 AP cases during the study period. Among these, 17% were hospital transfers. There were 15 (3.7%) deaths. A logistic regression model incorporating admission BUN and change in BUN at 24 hours produced an AUC of 0.91 for mortality. Both admission BUN and change in BUN were independent predictors of mortality (p<0.0001) after adjusting for age, gender, Charlson comorbidity score and hospital transfer status. Reduced fluid resuscitation (p=0.03), worsened renal insufficiency (p<0.0001) and SIRS (p=0.03) were independently associated with rise in BUN. Conclusion: We have prospectively confirmed the accuracy of early rise in BUN for prediction of mortality in AP. Rise in BUN is multi-factorial, reflecting intravascular volume depletion, renal insufficiency and systemic inflammation.

The Renal Pathophysiological Changes in Advanced Cirrhosis Accounting for the Development of Diuretic Resistant Ascites; Literature Review

Purpose: The development of ascites marks the transition from compensated to decompensated cirrhosis. In most cases, cirrhotic ascites is resolved through dietary sodium restriction and/or the use of diuretics. In 10-20% of cases, however, ascites becomes refractory to diuretics and sodium restriction. The aim of this review is to evaluate the renal pathophysiological changes that occur in advanced cirrhosis and promote the transition to a diuretic resistant stage. Methods: An extensive literature review was conducted of studies about renal pathophysiological changes in cirrhosis. Results: In the earliest stages of ascites, urinary sodium excretion is plentiful and negative salt balance can be achieved by salt restriction. As the disease advances, neurohumoral effects become more activated resulting in more intense renal salt retention. At this stage, adding spironolactone will be effective in increasing urinary sodium excretion by inhibiting salt reabsorption at the collecting duct level. With further disease progression, much of the filtered salt will be reabsorbed proximal to the collecting duct and at this stage thiazides and loop diuretics will have to be added to spironolactone to increase urinary sodium excretion. Eventually, the majority of the filtered load is reabsorbed at the proximal tubular level making ascites at this point diuretic resistant. The enhanced salt reabsorption by the proximal tubular cells has been shown to be secondary to angiotensin II and norepinephrine which stimulate (Na/K)-ATPase and apical Na-H exchanger in proximal tubular cells (keeping in mind that these endogenous substances, angiotensin II and norepinephrine, are overproduced in cirrhosis). In addition, effective intravascular volume depletion in cirrhosis results in efferent arteriolar constriction trying to increase the intraglomerular pressure to maintain filtration. The net effect of increasing the filtration fraction in the glomerulus is that the concentration of plasma proteins in the glomerular capillaries increases and as a result the oncotic pressure in these capillaries increases which is transmitted to the first branches of peritubular capillaries at the level of proximal tubule and favors more sodium reabsorption by passive starling forces thus further increasing fluid absorption at the proximal tubules. Conclusion: The main pathophysiological changes observed in advanced cirrhosis lead to increased proximal tubular absorption and this explains why these patients progress into a diuretic resistant stage, simply because the conventional diuretics used to treat ascites (lasix and spironolactone) are more effective at distal nephron segments where sodium delivery is markedly decreased.

Rapid Sequence Intubation: A Review of Recent Evidences

Rapid sequence intubation is an essential bullet in the maintenance of patency of the airway during intubation in emergency. It is a valid method in all those situations where you can not determine whether the patient is fasting or not. But RSI is not applicable in all critically ill patients. The presence of severe acidosis, depletion of intravascular volume, heart failure and severe pulmonary disease may complicate the pre-induction period as the induction, leading to the onset of vasodilatation and hypotension. Another complication is represented by Hypoxemia during the manoeuvre. The algorithm of RSI consists in six steps: pre-oxygenation, premedication, myo-relaxation and induction, intubation, primary and secondary confirmation, post-intubation patient management. Propofol has replaced Thiopental as the most common intravenous ipnotic. In hypotensive patients Ketamine represents a viable alternative. Succinylcholine is the most common neuromuscular relaxant used in the RSI. The not depolarizing NMBAs are an alternative to Succinylcholine. Among these, the most important is the Rocuronium. This drug is characterized by a fairly rapid onset (1-2 min) and an intermediate half-life (45-70 min). The onset depends on the dosage used. The problem that limits the use of Rocuronium is the fact that its duration of action is much longer than that of Succinylcholine, especially when used at higher doses. This problem can be solved through the use of Sugammadex. As a muscle relaxant chelating Sugammadex antagonizes the effects induced by Rocuronium on muscle tissue and quickly resolve the blockade.

Src family protein tyrosine kinase (PTK) modulates the effect of SGK1 and WNK4 on ROMK channels

WNK4 (with no lysine kinase 4) inhibits ROMK channel activity in the distal nephron by stimulating clathrin-dependent endocytosis, an effect attenuated by SGK1 (serum-glucocorticoids-induced kinase)-mediated phosphorylation. It has been suggested that increased ROMK activity because of SGK1-mediated inhibition of WNK4 plays a role in promoting renal K secretion in response to elevated serum K or high K (HK) intake. In contrast, intravascular volume depletion also increases SGK1 activity but fails to stimulate ROMK channels and K secretion. Because HK intake decreases Src family protein tyrosine kinase (PTK) activity an inhibitor of ROMK channels, it is possible that Src family PTK may modulate the effects of SGK1 on WNK4. Here, we show that c-Src prevents SGK1 from attenuating WNK4's inhibition of ROMK activity. This effect of c-Src was WNK4-dependent because c-Src had no effect on ROMK harboring mutation at the site of c-Src phosphorylation (R1Y337A) in the absence of WNK4. Moreover, expression c-Src diminished the SGK1-mediated increase in serine phosphorylation of WNK4, suggesting that c-Src enhances WNK4-mediated inhibition of ROMK channels by suppressing the SGK1-induced phosphorylation. This notion is also supported by the observation that c-Src was not able to modulate the interaction between SGK1 and WNK4 mutants (WNK4(S1169A) or WNK4(S1169D)) in which an SGK1-phosphorylation site (serine 1169) was mutated by alanine or aspartate. We conclude that c-Src inhibits SGK1-mediated phosphorylation hereby restoring the WNK4-mediated inhibition of ROMK channels thus suppressing K secretion.