Explainable machine learning model for predicting furosemide responsiveness in patients with oliguric acute kidney injury.

BACKGROUND: Although current guidelines didn't support the routine use of furosemide in oliguric acute kidney injury (AKI) management, some patients may benefit from furosemide administration at an early stage. We aimed to develop an explainable machine learning (ML) model to differentiate between furosemide-responsive (FR) and furosemide-unresponsive (FU) oliguric AKI. METHODS: From Medical Information Mart for Intensive Care-IV (MIMIC-IV) and eICU Collaborative Research Database (eICU-CRD), oliguric AKI patients with urine output (UO) < 0.5 ml/kg/h for the first 6 h after ICU admission and furosemide infusion ≥ 40 mg in the following 6 h were retrospectively selected. The MIMIC-IV cohort was used in training a XGBoost model to predict UO > 0.65 ml/kg/h during 6-24 h succeeding the initial 6 h for assessing oliguria, and it was validated in the eICU-CRD cohort. We compared the predictive performance of the XGBoost model with the traditional logistic regression and other ML models. RESULTS: 6897 patients were included in the MIMIC-IV training cohort, with 2235 patients in the eICU-CRD validation cohort. The XGBoost model showed an AUC of 0.97 (95% CI: 0.96-0.98) for differentiating FR and FU oliguric AKI. It outperformed the logistic regression and other ML models in correctly predicting furosemide diuretic response, achieved 92.43% sensitivity (95% CI: 90.88-93.73%) and 95.12% specificity (95% CI: 93.51-96.3%). CONCLUSION: A boosted ensemble algorithm can be used to accurately differentiate between patients who would and would not respond to furosemide in oliguric AKI. By making the model explainable, clinicians would be able to better understand the reasoning behind the prediction outcome and make individualized treatment.

Acute Kidney Injury and Renal Failure in Horses.

Nephrotoxic and hemodynamically mediated disorders are the most common causes of acute renal failure (ARF) in horses and foals. Leptospira spp. is the most common infectious cause of ARF. Initial treatments for ARF include elimination of nephrotoxic drugs, correction of predisposing disorders, and fluid therapy to promote diuresis. Horses and foals with polyuric ARF often have a good prognosis, while those with oliguric or anuric ARF have a guarded to poor prognosis. When fluid therapy is unsuccessful in improving urine production, various drugs treatments have been used in an attempt to increase urine production, but none are consistently effective in converting oliguria to polyuria.

Effect of losartan on the recoverability of renal function in anuric and oliguric patients with a solitary obstructed kidney: a double-blind randomized placebo-controlled trial.

OBJECTIVES: To assess the role of the angiotensin receptor blocker losartan on the recoverability of renal function after de-obstruction in patients with anuria and oliguria. MATERIALS AND METHODS: This was a double-blind randomized placebo-controlled trial in anuric or oliguric patients with calcular obstruction of solitary kidney. Patients with an anomalous kidney or those with an American Society of Anesthesiology score of >3 were excluded. After relief of obstruction, patients were allocated to receive either losartan potassium 25 mg or placebo for 3 months. Serum creatinine (sCr) and renographic glomerular filtration rate (GFR) were measured at nadir and after 3 months. Changes in sCr and renographic GFR were calculated by subtracting the values at nadir from those at 3 months. Improvement, stabilization or deterioration of sCr and renographic GFR were defined as percentage increase or decrease from nadir ≥10%, while changes <10% were considered as stabilization. RESULTS: A total of 76 patients completed 3 months of follow-up. Demographics and peri-operative data were comparable in the two groups. The median (range) sCr change was -1.05 (-1.8, 0.4) and -0.5 (-1.3, 0.1) mg/dL in the losartan and placebo, groups, respectively (P = 0.07). In the losartan group, renographic GFR had improved in 26 (59.1%) and deteriorated in six (13.6%) patients, while, in the placebo group, it had improved in eight (25%) and deteriorated in 10 patients (31.3%; P = 0.01). Losartan also enhanced renographic GFR improvement vs placebo by a median (range) of 6.9 (-9, 44) vs 1.4 (-10, 32) mL/min (P = 0.004). CONCLUSIONS: In patients with anuria and oliguria, losartan treatment contributes to renal function recoverability after relief of calcular obstruction of the solitary kidney.

The Use of Nesiritide in Children With Congenital Heart Disease.

OBJECTIVE: We evaluated the use of nesiritide in children with critical congenital heart disease, pulmonary congestion, and inadequate urine output despite conventional diuretic therapy. DESIGN: We conducted a retrospective analysis of 26 consecutive patients, comprising 37 infusions occurring during separate hospitalizations. Hemodynamic variables, urine output, and serum creatinine levels were monitored prior to and throughout the duration of therapy with nesiritide. In addition, the stage of acute kidney injury was determined prior to and throughout the duration of the therapy using a standardized definition of acute kidney injury-The Kidney Disease: Improving Global Outcomes criteria. SETTING: Cardiac ICU. PATIENTS: Pediatric patients with critical congenital heart disease, pulmonary congestion, and inadequate urinary output despite diuretic therapy. INTERVENTION: Nesiritide infusion. MEASUREMENTS AND MAIN RESULTS: The use of nesiritide was associated with a significant decrease in the central venous pressure and heart rate with a trend toward a significant increase in urine output. During the course of therapy with nesiritide, the serum creatinine and stage of acute kidney injury decreased significantly. The decrease in stage of acute kidney injury became significant by day 4 (p = 0.006) and became more significant with time (last day of therapy compared with baseline; p < 0.001). During 12 of the 37 infusions, the stage of acute kidney injury decreased by two or more (p < 0.001). CONCLUSIONS: Nesiritide had a favorable impact on hemodynamics and urine output in children with critical congenital heart disease and pulmonary congestion, and there was no worsening of renal function.

Comparison of Intraoperative Aminophylline Versus Furosemide in Treatment of Oliguria During Pediatric Cardiac Surgery.

OBJECTIVES: To determine if intraoperative aminophylline was superior to furosemide to prevent or attenuate postoperative cardiac surgery-associated acute kidney injury. DESIGN: Single-center, historical control, retrospective cohort study. SETTING: PICU, university-affiliated children's hospital. PATIENTS: Children with congenital heart disease in PICU who received furosemide or aminophylline to treat intraoperative oliguria. INTERVENTIONS: Intraoperative oliguria was treated either with furosemide (September 2007 to February 2012) or with aminophylline (February 2012 to June 2013). The postoperative 48 hours renal outcomes of the aminophylline group were compared with the furosemide group. The primary outcomes were acute kidney injury and renal replacement therapy use at 48 hours postoperatively. Surgical complexity was accounted for by the use of Risk Adjustment for Congenital Heart Surgery-1 score. MEASUREMENTS AND MAIN RESULTS: The study involves 69 months of observation. There were 200 cases younger than 21 years old reviewed for this study. Eighty-five cases (42.5%) developed acute kidney injury. The aminophylline group patients produced significantly more urine (mL/kg/hr) during the first 8 hours postoperatively than furosemide patients (5.1 vs 3.4 mL/kg/hr; p = 0.01). The urine output at 48 hours postoperatively was similar between the two groups. There was no difference in acute kidney injury incidence at 48 hours between the aminophylline and furosemide groups (38% vs 47%, respectively; p = 0.29). Fewer aminophylline group subjects required renal replacement therapy compared to the furosemide group subjects (n = 1 vs 7, respectively; p = 0.03). In the multi-variant predictive model, intraoperative aminophylline infusion was noted as a negative predictive factor for renal replacement therapy, but not for cardiac surgery-associated acute kidney injury. CONCLUSION: The intraoperative use of aminophylline was more effective than furosemide in reversal of oliguria in the early postoperative period. There were less renal replacement therapy-requiring acute kidney injury in children in the aminophylline group. Future prospective studies of intraoperative aminophylline to prevent cardiac surgery-associated acute kidney injury may be warranted.

Initial experience using aminophylline to improve renal dysfunction in the pediatric cardiovascular ICU.

OBJECTIVE: To determine if aminophylline administration is associated with improved creatinine clearance and greater urine output in children with acute kidney injury in the cardiovascular ICU. DESIGN: Single-center retrospective cohort study. SETTING: Pediatric cardiovascular ICU, university-affiliated children's hospital. PATIENTS: Children with congenital or acquired heart disease in the cardiovascular ICU who received aminophylline to treat oliguric acute kidney injury and fluid overload. INTERVENTIONS: Patients received aminophylline after consultation with a pediatric nephrologist. Data were collected retrospectively over 7 days to assess if aminophylline was associated with improvement in creatinine clearance, urine output, and fluid overload. MEASUREMENTS AND MAIN RESULTS: Thirty-one patients received 52 aminophylline courses. Over the 7-day study period, serum creatinine decreased from a mean of 1.13 ± 0.91 to 0.87 ± 0.83 mg/dL (-0.05 mg/dL/d, p < 0.001). A concomitant increase was seen in estimated glomerular filtration rate from a mean of 50.0 ± 30.0 to 70.6 ± 58.1 mL/min/1.73 m (+3.66 mL/min/1.73 m/d, p < 0.001). Average daily urine output increased by 0.22 mL/kg/hr (p < 0.001), and fluid overload decreased on average by 0.42% per day in the 7-day study period (p = 0.005). Although mean furosemide dose increased slightly (0.12 mg/kg/d, p = 0.01), hydrochlorothiazide dosing did not significantly change over the study period. There were no complications related to aminophylline administration. CONCLUSIONS: Our study suggests that aminophylline therapy may be associated with significantly improved renal excretory function and may augment urine output in children who experience oliguric acute kidney injury in the cardiovascular ICU. Additionally, we did not identify any aminophylline-related side effects in this high-risk cardiac population. Future prospective studies are necessary to confirm the safety profile and to ensure that the beneficial effects are independent of other clinical interventions.

[Low-dose of furosemide to correct oliguria in gynecological surgery].

OBJECTIVE: To investigate the safety and efficay of low-dose furosemide in the correction of oliguria in the patients undergoing gynecologic surgery. METHODS: A total of 120 patients, aged between 20 to 50 years old, who were scheduled to receive elective gynecological open surgery under general anesthesia, were randomly divided into 3 groups: the control group, furosemide 0. 05 mg/kg (F0.5) group and furosemide 0. 1 mg/kg (F1) group (n=40). During surgery, blood volume and blood pressure was maintained in the normal range. The urine volume was recorded every 30 minutes. Oliguria was defined as the urine volume less than 0. 5 mL/(kg . h), When oliguria was observed, flurosemide or saline was given to the patients based on the enrollment status. If the patients were still oliguric 30 min later, the treatment was repeated. The total time of surgery, net fluid infusion volume, urine volume per unit time per body weight at the completion of surgery, the incidence of intraoperative oliguria, the total amount of furosemide and the average specific gravity of urine were recorded. RESULTS: There was no statistically significant difference in sex, age, fasting time, the total time of surgery and intraoperative net fluid infusion volume among the three groups (P>0. 05). The urine volume per unit time per body weight in control group was significantly lower than that of the other two groups (P<0. 01). The incidence of intraoperative oliguria in the three groups (control, low dose, high dose groups) were 52. 5%, 12. 5% and 0%, respectively (P<0. 01). CONCLUSION: Low-dose of furosemide could maintain normal urine volume and specific gravity of urine during gynecological surgery.

[Diuretics in pregnancy can do harm]. / Diureettien käyttöön liittyy vaaroja loppuraskauden aikana.

We describe a case with severe pre-eclampsia with poor obstetric outcome. This patient developed oliguria and received multiple doses of furosemide which probably contributed to the poor outcome. This case presentation reminds of the risks associated with pre-eclampsia in which both blood volume and utero-placental blood flow are already decreased. This condition was further worsened by diuretics.

Effect of eplerenone on blood pressure and the renin-angiotensin-aldosterone system in oligo-anuric chronic hemodialysis patients - a pilot study.

INTRODUCTION AND AIMS: Recent studies have suggested that aldosterone has many effects in addition to its ability to cause the kidney to retain sodium. To test the hypothesis that aldosterone can cause hypertension in a manner that does not involve renal sodium retention, we administered eplerenone, a specific aldosterone antagonist, to oligo-anuric chronic hemodialysis patients who had HTN. METHODS: 220 chronic hemodialysis patients underwent initial screening. Of these, 8 patients were followed for 8 weeks and their blood pressure, weight, plasma potassium, aldosterone levels and plasma renin activity were recorded. After a 4 week run in period, each patient received eplerenone 25 mg twice daily for another 4 weeks. RESULTS: Administration of eplerenone for 4 weeks decreased predialysis systolic blood pressure from 166 ± 14 to 153 ± 10 mmHg (p < 0.05). Eplerenone had no effect on diastolic blood pressure, potassium, predialysis weight, intradialytic weight gain, plasma aldosterone or PRA. CONCLUSION: Eplerenone significantly reduces systolic blood pressure in oligo-anuric hypertensive hemodialysis patients without effect on plasma aldosterone concentrations or plasma renin activity. Plasma potassium increases minimally after 4 weeks of therapy, a finding that raises some concern for long-term eplerenone use in chronic hemodialysis.

Desensitization Regimen Consisting of High-Dose Intravenous Immunoglobulin, Plasmapheresis, and Rituximab (an Anti-CD20 Antibody), Without Eculizumab and/or Bortezomib, in 41 Highly Sensitized Kidney Transplant Recipients.

OBJECTIVES: Antibody-mediated rejection in patients with positive crossmatches can be severe and result in sudden onset of oliguria, leading to graft loss. In an attempt to prevent posttransplant oliguria, we adopted a preoperative desensitization protocol involving the use of high-dose intravenous immunoglobulin/plasmapheresis and the anti-CD20 antibody, rituximab, in 41 transplant recipients with positive crossmatch test results. MATERIALS AND METHODS: We retrospectively examined the clinical courses of the 41 kidney transplant recipients, paying special attention to renal graft function, urine volume, and changes in the titers of donor-specific antibodies. RESULTS: Four grafts were lost during an average of 4.5-year follow-up. Average graft function was excellent, with a serum creatinine level of 1.3 ± 0.4 mg/dL. Sufficient urine output, with no oliguria or anuria, was achieved postoperatively in 40 of the 41 patients. However, among the 34 patients who underwent graft biopsies, the biopsies revealed acute antibody-mediated rejection in 21 patients (62%), and chronic antibodymediated rejection in 10 patients (30%). CONCLUSIONS: The high-dose intravenous immunoglobulin treatment included in our desensitization protocol was shown to be safe and effective for achieving successful transplant outcomes and allowed the avoidance of more aggressive B-cell-targeted treatments, such as C5 inhibitors and/or proteosome inhibitors, for preventing posttransplant oliguria and anuria.

Severe neonatal Marfan syndrome with a novel mutation in the intron of the FBN1 gene: A case report.

RATIONALE: Marfan syndrome (MFS) has been defined as a genetic disorder that affects various systems such as the musculoskeletal, orbital, and cardiovascular systems. Neonatal MFS is considered rare and the most severe form of MFS is characterized by rapidly progressive atrioventricular valve dysfunction, often leading to death during early childhood due to congestive heart failure. PATIENT CONCERNS: A newborn with neonatal MFS and severe cardiac involvement. He presented various severe clinical features such as arachnodactyly, camptodactyly, elbow and knee joint contracture, senile facial appearance, and deep settling with down-slanting palpebral fissure, hypoplastic ear cartilage, sagging mouth, brachycephaly, and ectopia lentis. DIAGNOSIS: Genetic analysis revealed a novel mutation at nucleotide 3964 (c.3964 + 1 G > T) in intron 32 of the fibrillin-1 gene. This mutation is identified to be in the so-called neonatal region of fibrillin-1 exon 24 to 32, as reported previously. INTERVENTIONS: The patient was managed medically for improving the low cardiac output according to severe mitral regurgitation and aortic regurgitation. Afterload reduction, full sedation, and use of diuretic were attempted to improve the oliguria and heart failure. OUTCOMES: Despite the medical management, aortic regurgitation, mitral regurgitation, pulmonary hypertension, and cardiac contractility got worse. Surgical treatment is essential to prolong the patient's life, however, considerations for the grave progression of the disease make families decide to continue palliative care instead of surgical treatment. A few months after birth, he presented with rapidly progressive aortic regurgitation, mitral regurgitation, and congestive heart failure leading to death. CONCLUSIONS: This review demonstrated the prominent characteristics of neonatal MFS mutations, it would be helpful for the recognition of novel neonatal MFS variants and valuable for the understanding of the genotype-phenotype correlations and using the plans for managements and counseling in neonatal MFS.

An evaluation of off-label fenoldopam use in the neonatal intensive care unit.

We analyzed the effect of off-label fenoldopam (FDM) therapy on electrolyte balance, renal function, blood pressure, and urinary output in neonatal patients. We performed a retrospective review of 22 neonates treated with FDM in two neonatal intensive care units. Primary outcome compared physiological status 24 hours before FDM therapy to the first 24 hours of FDM therapy. Electrolytes, blood urea nitrogen (BUN), creatinine, fluid intake, respiratory support, blood pressure, and heart rate were also compared. FDM was used to treat oliguria and anasarca. Seven infants were supported with extracorporeal membrane oxygenation. Gestation ranged 24 to 39 weeks (median 37) and postnatal age, 1 to 89 days (median 10). FDM dose increased over time (median initial dose 0.10 microg/kg/min versus 0.20 at 48 hours). FDM therapy had no effect on serum creatinine, electrolytes, or cardiopulmonary function but was associated with a significant increase in BUN ( P = 0.008). Urine output did not increase significantly for the group as a whole (paired T test) but did significantly increase during the initial 24-hour infusion among oliguric infants. Low-dose FDM did not improve urine output in critically ill neonates as a whole. There were no apparent adverse cardiopulmonary or metabolic effects from FDM use in this limited population. Future FDM use in the context of a randomized prospective trial appears warranted in the early management of infants with oliguria.

Effect of Furosemide under Hyperchloremic Acidosis on Intraoperative Oliguria and Acute Kidney Injury in Patients with Normal Renal Function.

BACKGROUND: Renal function tends to deteriorate in a hyperchloremic acidifying environment, which is reflected by a decrease in the difference between sodium and chloride. OBJECTIVES: To examine the effect of furosemide administered under hyperchloremic acidosis on intraoperative oliguria and acute kidney injury in patients with preoperatively normal renal function. METHODS: In patients undergoing abdominal or orthopedic surgeries (April 2010-November 2018), we retrospectively identified patients who preoperatively had a normal renal function but experienced intraoperative oliguria under hyperchloremic acidosis (a sodium-chloride difference < 30 mEq/L) without dehydration. We compared the perioperative urine output and the incidence of postoperative acute kidney injury between patients who intraoperatively received an initial dose of 5 mg of furosemide (the furosemide group) and patients who did not intraoperatively receive furosemide (the control group). RESULTS: We identified 62 patients in the furosemide group and 48 patients in the control group. The furosemide group intraoperatively received 0.11 ± 0.06 mg/kg of furosemide (range 0.06-0.39 mg/kg). Compared to the control group, the furosemide group had greater urine output (mL/kg/h) in the operating room (1.1 ± 0.7 vs. 0.3 ± 0.1, p < 0.01) and on postoperative day 1 (1.2 ± 0.5 vs. 1.1 ± 0.4, p = 0.02). The incidence of postoperative acute kidney injury was lesser in the furosemide group than that in the control group (8.0 vs. 27.0%, p < 0.01; multivariate OR 0.18; 95% CI 0.05-0.61; p < 0.01). CONCLUSIONS: In surgery patients under hyperchloremic acidosis, furosemide (0.1 mg/kg) resolved intraoperative oliguria and reduced the incidence of postoperative acute kidney injury.

Late renal vein thrombosis associated with recurrence of membranous nephropathy in a renal allograft: a case report.

Allograft renal vein thrombosis (RVT) is an uncommon but potentially catastrophic complication. Although it usually occurs in the early posttransplant period and is associated with surgical complications or vascular rejection, it may develop later, when it is generally related with a hypercoagulable state. Typical clinical presentation is sudden oligoanuric acute renal failure, and hematuria, with a painful and swollen renal allograft. Confirmation of the diagnosis requires Doppler ultrasound and computed tomography. Herein we have reported a successfully treated case of late RVT that developed in an allograft with recurrent membranous nephropathy associated with the nephrotic syndrome. The patient fully recovered renal graft function a few days after presentation, which was related to anticoagulant therapy. We demonstrated complete recanalization of the venous thrombosis.

Tolvaptan rescue contrast-induced acute kidney injury: A case report.

RATIONALE: Contrast-induced acute kidney injury is one of the most serious adverse effects of contrast media and is related to three distinct but interacting mechanisms: medullary ischemia, formation of reactive oxygen species and direct tubular cell toxicity, especially in the patients with chronic kidney disease. The strategies of treatment, including stabilization of hemodynamic parameters and maintenance of normal fluid and electrolyte balance, were similar to the management of other types of acute kidney injury. PATIENT CONCERNS: A 58-year-old woman experienced acute oligouria after complex percutaneous coronary intervention for multiple vessel coronary artery disease. DIAGNOSES: Chest radiography showed pulmonary congestion and hyponatremia was noted after fluid hydration for suspicious contrast-induced nephropathy. INTERVENTIONS: Oral tolvaptan, at 15mg per day, was used for three days. OUTCOMES: Urine output increased gradually and symptoms relieved one day later after using tolvaptan. Serum creatinine also improved to baseline level one week later after this event. LESSONS: Here, we reported an interesting case about contrast-induced acute kidney injury and hypervolemic hyponatremia, where tolvaptan was used to rescue the oliguric phase. Tolvaptan could be considered to use for contrast-induced acute kidney injury and had possibility of prevention from hemodialysis. Larger studies are still needed to investigate the role of tolvaptan in rescuing the oliguric phase in contrast-induced acute kidney injury.

[Blackwater fever in children during cerebral malaria: 3 case reports in Bamako]. / La fièvre bilieuse hémoglobinurique chez l'enfant: à propos de 3 observations à Bamako.

BACKGROUND: Blackwater fever is a rare but serious form of malaria in children. Diagnosis relies on clinical symptoms and on the color of the urines. OBJECTIVES: To describe blackwater fever in children, a disease whose prevalence seems to be increasing. METHOD: We report 3 cases of blackwater fever observed in our institution. RESULTS: In 2 cases, acute renal insufficiency with oligoanuria was observed. In all the 3 cases, treatment with quinine was stopped and replaced by injectable artemether. Evolution was dependent on renal function, and included in 1 patient neurological sequels consisting in aphasia. CONCLUSION: Blackwater fever is a severe affection whose diagnosis should be evoked using the color of urine. Evolution is usually favorable in the pediatric population, when adequate care can be provided.

Effect of high-dose furosemide on the prognosis of critically ill patients.

PURPOSE: Diuretics are used frequently in critically ill patients. We investigated the effects of furosemide on the prognosis. MATERIALS AND METHODS: Following a retrospective review of patients admitted to the medical intensive care unit (ICU), we analyzed risk factors with variables including initial furosemide dose for ICU mortality. RESULTS: A total of 448 patients were included. Total furosemide dose during the first three days of the ICU stay (odds ratio (OR) 2.35, 95% confidence interval (CI) 1.01-5.02) and fluid balance during the same period (OR 3.04, 95% CI 1.46-6.31) were associated with ICU mortality, as were malignancy, chronic furosemide use, and APACHE II score. However, in oliguric patients, positive fluid balance was associated with ICU mortality (OR 22.33, 95% CI 1.82-273.72) but the high-dose furosemide was not. In contrast, in non-oliguric patients, high-dose furosemide was associated with ICU mortality (OR 2.47, 95% CI 1.01-5.68); however, the positive fluid balance showed only a trend for high ICU mortality. CONCLUSION: Early high-dose furosemide use is associated with ICU mortality, particularly in non-oliguric patients. We suggest that furosemide should be used with caution even in non-oliguric critically ill patients until the safety is confirmed in powered study.

Use of fenoldopam to increase urine output in a patient with renal insufficiency secondary to septic shock: A case report.

OBJECTIVE: We describe the use of fenoldopam to increase urine output in a pediatric patient with sepsis, heart failure, oliguria, and volume overload. DESIGN: Case report. SETTING: A tertiary pediatric intensive care unit. PATIENT: A 17-year-old male who was being treated for acute lymphoblastic leukemia and was admitted from outside the hospital to the pediatric intensive care unit, in septic shock, after a course of chemotherapy. INTERVENTIONS: A continuous fenoldopam infusion of 0.03 microg/kg/min was added to a regimen of multiple inotropic and vasopressor agents and a furosemide continuous infusion. MEASUREMENTS AND MAIN RESULTS: Urine output increased 586% 12 hrs after starting the fenoldopam infusion and 775% from baseline 24 hrs after starting the infusion. Diuretics were decreased while maintaining adequate urine output. No hypotension was noted. CONCLUSIONS: Fenoldopam increased urine output in a pediatric patient who was in septic shock and oliguria. The mechanism for this effect is unclear, and further trials are necessary to determine the role of fenoldopam in this patient population.

Continuous low-dose human atrial natriuretic peptide promotes diuresis in oliguric patients after living donor liver transplantation.

Human atrial natriuretic peptide (ANP) is beneficial for the prophylaxis of acute renal failure (ARF) after liver transplantation (OLT). We evaluated renal function in OLT patients with or without ARF, describing cases unresponsive to loop diuretics successfully treated with continuous low-dose ANP infusion without hemodialysis. Twenty-seven consecutive adult-to-adult living donor liver transplantations (LDLTs) were performed in 26 patients. One case was excluded due to the need for continuous hemodialysis (HD) during the operation. Of the 26 cases, 6 (23%, group 2) developed ARF in the first 30 days after LDLT; the other 20 were ARF-free (group 1). The median follow-up was 24 months. No patient required either continuous or intermittent HD. Only one patient died due to multiple liver abscesses. Mean preoperative serum creatinine (sCr) value and intraoperative blood loss in group 2 were significantly higher than those in group 1. Three cases in group 2 failed to improve on high-dose loop diuretics with low-dose dopamine, exhibiting fluid overload. The remaining three cases in group 2 responded to conventional diuretic treatments. Continuous low-dose ANP was started 2, 4, or 5 days after LDLT, and urine output significantly increased after ANP administration. The serum creatinine values were 1.1, 1.2, and 1.1 at 1 month and 1.0, 0.9, and 0.6 mg/dL at 6 months after LDLT. Massive blood loss during the operation caused ARF, but did not affect renal function after LDLT. Continuous low-dose ANP improved renal function and diuresis for oliguric ARF patients, preventing the need for HD or continuous venovenous hemodialysis.

Cardiovascular toxicity with levetiracetam overdose.

OBJECTIVE: To describe the cardiovascular toxicity and pharmacokinetics of levetiracetam in overdose. CASE REPORT: A 43-year-old female presented 8 h post ingestion of 60-80 g of levetiracetam with mild central nervous system depression, bradycardia, hypotension and oliguria. Her cardiovascular toxicity transiently responded to atropine and intravenous fluids. A bedside echocardiogram demonstrated normal left and right ventricular contractility. Despite her cardiovascular toxicity and oliguria, she had normal serial venous lactates and renal function; and made a complete recovery over 48 h. Her levetiracetam concentration was 463 mcg/ml 8 h post ingestion (therapeutic range 10-40 mcg/ml) and her concentration-time data best fitted a one-compartment model with first-order input and an elimination half-life of 10.4 h. DISCUSSION: Levetiracetam in large ingestions appears to cause bradycardia and hypotension that is potentially responsive to atropine and intravenous fluids. Based on a normal echocardiogram, the mechanism for this effect may be levetiracetam acting at muscarinic receptors at high concentration. The pharmacokinetics of levetiracetam in overdose appeared to be similar to therapeutic levetiracetam dosing.