Radical Resection of Pediatric Fibrosarcoma Is Not Associated With Survival Benefit: A Nationwide Database Analysis.

INTRODUCTION: Fibrosarcoma is one of the most common nonrhabdomyosarcoma soft tissue sarcomas in the pediatric population. Surgical resection is the cornerstone of treatment; however, optimal factors regarding the extent of fibrosarcoma resection in localized versus regional disease is poorly understood. METHODS: The Surveillance, Epidemiology, and End Results database was queried for patients who are 19 y old or younger with a diagnosis of fibrosarcoma from 1975 to 2016. Kaplan-Meier analyses were performed for disease-specific survival on clinical and pathologic variables. Multivariate analysis was performed based on significant predictors of disease-specific survival. RESULTS: There were 1290 patients (median age 13 [7-17] y) identified with fibrosarcoma. The overall survival rate at 20 y was 93%. Radical resection was performed on 22%, 40%, and 52% of patients with localized, regional, and distant Surveillance, Epidemiology, and End Results disease stage, respectively. Chemotherapy (P < 0.001), radiation (P < 0.001), histology (P < 0.001), and stage (P = 0.004) were significant predictors of increased mortality using univariate Kaplan-Meier analysis. Most patients (86%) with localized or regional stage who underwent radiation had fibrosarcomas of nondermatofibrosarcoma histology (P < 0.001). Dermatofibrosarcoma subtype comprised most radical resections (41%). Excluding distant stage, nondermatofibroma histology (hazard ratio 16.94, 95% confidence interval 3.77-76.01) and regional stage (hazard ratio 8.15, 95% confidence interval 2.93-22.69) were independent prognostic factors of mortality (both P < 0.001). Radical resection was not a significant independent prognostic indicator of survival. CONCLUSIONS: Nondermatofibrosarcoma subtype is independently associated with increased mortality. Although surgery remains the mainstay of treatment, the extent of resection is not a predictor of survival for patients with the localized and regional stage of disease.

Protocol-Driven Surgical Care of Necrotizing Enterocolitis and Spontaneous Intestinal Perforation.

BACKGROUND: There is no clear consensus on the optimal operative management of premature infants with surgical necrotizing enterocolitis (sNEC) or spontaneous intestinal perforation (SIP); thus, a protocol was developed to guide surgical decision making regarding initial peritoneal drainage (PD) versus initial laparotomy (LAP). We sought to evaluate outcomes after implementation of the protocol. METHODS: Pre-post study including multiple urban hospitals. Premature infants with sNEC/SIP were accrued after implementation of surgical protocol-directed care (June 2014-June 2019). Patients with a birth weight of <750 g and less than 2 wk of age without pneumatosis or portal venous gas were treated with PD on perforation. PD patients received subsequent LAP for clinical deterioration or continued meconium/bilious drainage. Postprotocol characteristics and outcomes were compared with institutional historical controls. Significance set at P < 0.05. RESULTS: Preprotocol and postprotocol cohorts comprise 35 and 73 patients, respectively. There was a statistically significant difference in age at intervention between historical control PD (14 ± 13 d) and postprotocol PD (9 ± 4 d) groups (P = 0.01), PD patient's birth weight (716 ± 212 g versus 610 ± 141 g, P = 0.02) and estimated gestational age of LAP patients (27 ± 1.7 wk versus 31 ± 4 wk, P = 0.002). PD was definitive surgery in 27% (12 of 44) of postprotocol patients compared with 13% (3 of 23) historical controls. A trend in improved survival postprotocol occurred in all PD infants (73% versus 65%), all LAP (75% versus 70%), and for initial PD and subsequent LAP (82% versus 67%). CONCLUSIONS: Utilization of a surgical protocol in sNEC/SIP is associated with improved success of PD as definitive surgery and improved survival.

Treatment patterns and outcomes for pancreatic tumors in children: an analysis of the National Cancer Database.

PURPOSE: Pancreatic tumors are rare in children and limited data are available regarding incidence, treatment, and outcomes. We aim to describe patient and tumor characteristics and to report on survival of these diseases. METHODS: Children with pancreatic tumors were queried from the National Cancer Database (2004-2014). The association between treatment and hazard of death was assessed using Kaplan-Meier method and Cox regression model. RESULTS: We identified 109 children with pancreatic tumors; 52% were male and median age at diagnosis was 14 years. Tumors were distributed as follows: pseudopapillary neoplasm (30%), endocrine tumors (27%), pancreatoblastoma (16%), pancreatic adenocarcinoma (16%), sarcoma (6%) and neuroblastoma (5%). Seventy-nine patients underwent surgery, of which 76% achieved R0 resection. Most patients (85%) had lymph nodes examined, of which 22% had positive nodes. Five-year overall survival by tumor histology was 95% (pseudopapillary neoplasm), 75% (neuroblastoma), 70% (pancreatoblastoma), 51% (endocrine tumors), 43% (sarcoma), and 34% (adenocarcinoma). On multivariable analysis, surgical resection was the strongest predictor of survival (HR 0.26, 95% CI 0.10-0.68, p < 0.01). CONCLUSION: Overall survival of children with pancreatic tumors is grim, with varying survival rates among different tumors. Surgical resection is associated with improved long-term survival.

Increased lymph node ratio predicts poor survival in pediatric rhabdomyosarcoma.

BACKGROUND/PURPOSE: Lymph Node Ratio (LNR) is defined as the number of positive lymph nodes (pLN) divided by total lymph nodes (LN) examined. LNR correlates with recurrence and/or overall survival in many adult cancers but has not previously been described in pediatric oncologic disease. We hypothesized that LNR correlates with worse disease specific survival (DSS) in pediatric rhabdomyosarcoma (RMS). METHODS: Patients <20 years who underwent surgery for RMS between 1988 and 2013 in the SEER database were analyzed. RESULTS: 188 patients with a mean age at diagnosis of 8.8 ±â€¯6 years and a mean LNR of 0.13 ±â€¯0.27 were identified. Univariate analysis found that alveolar type, positive lymph node (pLN), stage, site, LNR, and age had significantly worse survival. Cox regression analysis identified LNR > 0.75 (HR 4.32, P = 0.015), alveolar histology (HR 4.797, P < 0.003), age < 1 year (HR 4.402, P = 0.004), and distant disease (HR 5.738, P < 0.001), as independent determinants of worse DSS. pLN and site were not statistically significant determinant of DSS on multivariate analysis. DSS for the entire cohort was 83% at 5 and 78% at 10 and 15 years. DSS at 5, 10, and 15 year for LNR ≤ 0.75 was 79% while patients with LNR > 0.75 had a 22% 5 year and 0% 10 year survival (P <0.001). CONCLUSIONS: LNR is superior to pLN status as an independent prognostic indicator of DSS in pediatric RMS. LEVEL OF EVIDENCE: Level III.

Fatal gastrointestinal bleeding in a case report of Coat's plus syndrome.

INTRODUCTION: Coat's plus syndrome is an extremely rare genetic syndrome that leads to a variety of symptoms. We are reporting a case of Coat's plus syndrome that had persistent GI bleeding and review of current literature. PRESENTATION OF CASE: The patient is a female in her 40 s with a history of coat's disease and end stage renal failure on dialysis. The etiology of renal failure was not discovered, and the patient was being worked up for a kidney transplant. The patient required admission after deterioration of nutritional status with a BMI of 14.3. During admission the patient initially had intermittent GI bleeding requiring weekly blood transfusions. On work up of the GI bleed, no etiology was identified either. As a result persistent negative GI bleed work up, we pursued alternative diagnoses. The history of Coat's disease prompted us to work up the patient for Coat's plus syndrome. A genetic test confirmed the presence of CTC-1 gene mutation, which results in Coat's plus syndrome. With no treatment available as of yet, the patient continued to deteriorate into multi-organ failure. DISCUSSION: We present an example of GI bleeding in Coat's plus syndrome, only identified thru genetic testing, that is very rare and complex in nature. Despite numerous workups, no specific etiology was identified for the GI bleeding. CONCLUSION: Previous reports have not investigated cause of GI bleeding, since it is extremely rare in the literature. Further investigation is warranted to understand cause and effects of GI bleeding in this rare genetic disease.

Waardenburg Syndrome Type IV De Novo SOX10 Variant Causing Chronic Intestinal Pseudo-Obstruction.

Waardenburg syndrome (WS) type IV is characterized by pigmentary abnormalities, deafness and Hirschsprung's disease. This syndrome can be triggered by dysregulation of the SOX10 gene, which belongs to the SOX (SRY-related high-mobility group-box) family of genes. We discuss the first known case of a SOX10 frameshift mutation variant defined as c.895delC causing WS type IV without Hirschsprung's disease. This female patient of unrelated Kuwaiti parents, who tested negative for cystic fibrosis and Hirschsprung's disease, was born with meconium ileus and malrotation and had multiple surgical complications likely due to chronic intestinal pseudo-obstruction. These complications included small intestinal necrosis requiring resection, development of a spontaneous fistula between the duodenum and jejunum after being left in discontinuity, and short gut syndrome. This case and previously reported cases demonstrate that SOX10 gene sequencing is a consideration in WS patients without aganglionosis but with intestinal dysfunction.

Disparities in pediatric gonadal torsion: Does gender, race and insurance status affect outcomes?

PURPOSE: Ovarian and testicular torsions are emergencies requiring prompt surgical treatment to preserve gonadal function. However, diagnosis in females is often delayed owing to nonspecific symptoms. We sought to assess disparities in management and outcomes between males and females with torsion. METHODS: The National Inpatient Sample was queried for pediatric patients with "emergent", "urgent", or "trauma center" admission and ICD-9 codes for ovarian torsion and testicular torsion. Demographic data, operative procedure, gonadal loss, length of stay (LOS), total charges (TC), and mortality were recorded. RESULTS: There were 2254 unweighted encounters. The average age was 11.56±5.30years for males and 12.55±3.72years for females (p<0.001). Among males, 90% underwent surgery (p<0.001), of which 40% required orchiectomy. Conversely, 73% of females had surgery (p<0.001), of which 78% had oophorectomy. Subsequent analysis with only patients who underwent surgery showed that insurance status (p=0.012), race (p<0.001), and U.S. region (p<0.001) were significantly different between males and females. Gender specific analyses showed that hospital control, hospital location/teaching status, and treatment year were also significant. As such, these six factors in addition to age and gender were used for propensity score matching (PSM). PSM produced two gender cohorts of 755 encounters each. Females had longer LOS (2.44±1.84days vs. 1.28±2.27days for males, p<0.001) and had higher TC ($20,058.44±13,420.82) compared to males ($12,386.58±12,793.34), p<0.001. Logistic regression revealed that males (OR 0.163 [0.130-0.206]) and older patients (age OR 0.924 [0.903-0.946]) were less likely to undergo gonadal loss. Compared to those with private insurance, those with Medicare/Medicaid were more likely to have gonadal loss (1.401 [1.101-1.783]). CONCLUSION: Disparities exist in the management of torsion based on gender. Overall, females had higher charges, had longer hospitalization, and were more likely to have gonadal loss despite current data supporting gonadal preservation for nearly all cases of ovarian torsion. CLINICAL STUDY: Level III Evidence.

Incidence and Operative Factors Associated With Discretional Postoperative Mechanical Ventilation After General Surgery.

BACKGROUND: Mechanical ventilation after general surgery is associated with worse outcomes, prolonged hospital stay, and increased health care cost. Postoperatively, patients admitted to the intensive care unit (ICU) may be categorized into 1 of 3 groups: extubated patients (EXT), patients with objective medical indications to remain ventilated (MED), and patients not meeting these criteria, called "discretional postoperative mechanical ventilation" (DPMV). The objectives of this study were to determine the incidence of DPMV in general surgery patients and identify the associated operative factors. METHODS: At a large, tertiary medical center, we reviewed all surgical cases performed under general anesthesia from April 1, 2008 to February 28, 2015 and admitted to the ICU postoperatively. Patients were categorized into 1 of 3 cohorts: EXT, MED, or DPMV. Operative factors related to the American Society of Anesthesiologists Physical Status (ASA PS), duration of surgery, surgery end time, difficult airway management, intraoperative blood and fluid administration, vasopressor infusions, intraoperative arterial blood gasses, and ventilation data were collected. Additionally, anesthesia records were reviewed for notes indicating a reason or rationale for postoperative ventilation. Categorical variables were compared by χ test, and continuous variables by analysis of variance or Kruskal-Wallis H test. Categorical variables are presented as n (%), and continuous variables as mean ± standard deviation or median (interquartile range) as appropriate. Significance level was set at P≤ .05. RESULTS: Sixteen percent of the 3555 patients were categorized as DPMV and 12.2% as MED. Compared to EXT patients, those classified as DPMV had received significantly less fluid (2757 ± 2728 mL vs 3868 ± 1885 mL; P < .001), lost less blood during surgery (150 [20-625] mL vs 300 [150-600] mL; P< .001), underwent a shorter surgery (199 ± 215 minutes vs 276 ± 143 minutes; P< .001), but received more blood products, 900 (600-1800) mL vs 600 (300-900) mL. The DPMV group had more patients with high ASA PS (ASA III-V) than the EXT group: 508 (90.4%) vs 1934 (75.6%); P< .001. Emergency surgery (ASA E modifier) was more common in the DPMV group than the EXT group: 145 (25.8%) vs 306 (12%), P< .001, respectively. Surgery end after regular working hours was not significantly higher with DPMV status compared to EXT. DPMV cohort had fewer cases with difficult airway when compared to EXT or MED. When compared to MED patients, those classified as DPMV received less fluid (2757 ± 2728 mL vs 4499 ± 2830 mL; P< .001), lost less blood (150 [20-625] mL vs 500 [200-1350] mL; P < .001), but did not differ in blood products transfused or duration of surgery. CONCLUSIONS: In our tertiary medical center, patients often admitted to the ICU on mechanical ventilation without an objective medical indication. When compared to patients admitted to the ICU extubated, those mechanically ventilated but without an objective indication had a higher ASA PS class and were more likely to have an ASA E modifier. A surgery end time after regular working hours or difficult airway management was not associated with higher incidence of DPMV.

Beta blockers in critically ill patients with traumatic brain injury: Results from a multicenter, prospective, observational American Association for the Surgery of Trauma study.

BACKGROUND: Beta blockers, a class of medications that inhibit endogenous catecholamines interaction with beta adrenergic receptors, are often administered to patients hospitalized after traumatic brain injury (TBI). We tested the hypothesis that beta blocker use after TBI is associated with lower mortality, and secondarily compared propranolol to other beta blockers. METHODS: The American Association for the Surgery of Trauma Clinical Trial Group conducted a multi-institutional, prospective, observational trial in which adult TBI patients who required intensive care unit admission were compared based on beta blocker administration. RESULTS: From January 2015 to January 2017, 2,252 patients were analyzed from 15 trauma centers in the United States and Canada with 49.7% receiving beta blockers. Most patients (56.3%) received the first beta blocker dose by hospital day 1. Those patients who received beta blockers were older (56.7 years vs. 48.6 years, p < 0.001) and had higher head Abbreviated Injury Scale scores (3.6 vs. 3.4, p < 0.001). Similarities were noted when comparing sex, admission hypotension, mean Injury Severity Score, and mean Glasgow Coma Scale. Unadjusted mortality was lower for patients receiving beta blockers (13.8% vs. 17.7%, p = 0.013). Multivariable regression determined that beta blockers were associated with lower mortality (adjusted odds ratio, 0.35; p < 0.001), and propranolol was superior to other beta blockers (adjusted odds ratio, 0.51, p = 0.010). A Cox-regression model using a time-dependent variable demonstrated a survival benefit for patients receiving beta blockers (adjusted hazard ratio, 0.42, p < 0.001) and propranolol was superior to other beta blockers (adjusted hazard ratio, 0.50, p = 0.003). CONCLUSION: Administration of beta blockers after TBI was associated with improved survival, before and after adjusting for the more severe injuries observed in the treatment cohort. This study provides a robust evaluation of the effects of beta blockers on TBI outcomes that supports the initiation of a multi-institutional randomized control trial. LEVEL OF EVIDENCE: Therapeutic/care management, level III.

Gastroduodenal artery coiling to curb upper gastrointestinal bleeding.

BACKGROUND: Peptic ulcers in pediatric populations are uncommon and can present with upper gastrointestinal bleeding and shock on presentation. An endoscopy is done initially to identify bleeding source. However, definitive treatment is achieved with angiography. The use of coiling is effective in achieving hemorrhagic control in duodenal ulcers or gastric ulcers, particularly in adults. However, the use in pediatric populations is unknown. We present a case of peptic ulcer disease treated with a gastroduodenal artery coil in a pediatric patient that has never been reported in the literature. CASE PRESENTATION: A 15-year-old male with a five-year history of peptic ulcer disease was admitted with an upper gastrointestinal bleed. Angiographic imaging was done to isolate and locate the bleeding, and coil embolization of the gastroduodenal artery was performed. Coils eroded into intestinal lumen but bleeding was controlled. CONCLUSION: Peptic ulcers in pediatric populations are rare and complex in nature. Besides aggressive resuscitation and endoscopy, other methods to control bleeding such as coil embolization can be performed. Further investigations are needed to understand long-term effects of coil embolization in pediatric peptic ulcer patients. LEVEL OF EVIDENCE: 5/Case Report/.

Effectiveness of a Perioperative Transthoracic Ultrasound Training Program for Students and Residents.

OBJECTIVE: Focused ultrasound (US) is being incorporated across all levels of medical education. Although many comprehensive US courses exist, their scope is broad, requiring expert instructors, access to simulation, and extensive time commitment by the learner. We aim to compare learning across levels of training and specialties using a goal-directed, web-based course without live skills training. DESIGN: A prospective observational study of students and residents from medicine, surgery, and anesthesiology. Analysis compared pretests and posttests assessing 3 competencies. Individual mean score improvement (MSI) was compared by paired-sample t-tests and MSI among cohorts by analysis of variance, with significance set at p ≤ 0.05. McNemar test compared those who agreed or strongly agreed with survey items with those who did not before and after intervention. SETTING: Jackson Memorial Hospital, Miami, FL residency training programs in Medicine, Surgery, and Anesthesiology. RESULTS: A total of 180 trainees participated. A significant MSI was noted in each of 3 competencies in all 3 cohorts. Students' (S) MSI was significantly higher than residents' (R) and interns' (I) in US "knobology" and window recognition [S = 2.28 ± 1.29/5 vs R = 1.63 ± 1.21/5 (p = 0.014); vs I = 1.59 ± 1.12/5 (p = 0.032)]; students' total score MSI was significantly higher than residents [7.60 ± 3.43/20 vs 5.78 ± 3.08/20 (p < 0.008)]. All cohorts reported improved comfort in using transthoracic US and improved ability to recognize indications for use. More than 81% of all participants reported improved confidence in performing transthoracic US; more than 91% reported interest in additional training; and more than 88% believed course length was appropriate. CONCLUSIONS: Learners across levels of medical training and specialties can benefit from a brief, goal-directed, web-based training with early incorporation producing maximal yield.

The characteristics and prognostic importance of NT-ProBNP concentrations in critically ill patients.

BACKGROUND: There are limited data for prognostic and diagnostic use of natriuretic peptides in intensive care unit (ICU) patients. We evaluate amino-terminal brain natriuretic peptide (NT-proBNP) in the medical ICU, specifically its correlation with noncardiac admission diagnosis and prognosis of critically ill patients. METHODS: NT-proBNP (pg/mL) was measured in 179 ICU patients without acute decompensated heart failure or acute coronary syndrome. Death during hospitalization (mortality), APACHE II score, laboratory data, echocardiograms, medical history, and demographics were assessed. NT-proBNP concentrations were compared with established cutoffs for congestive heart failure (>450 pg/mL for patients <50 years of age, >900 pg/mL for patients 50-70 years of age, and >1800 pg/mL for patients >70 years of age). Predictors of mortality and of NT-proBNP were analyzed by regression analysis. Tertiles were compared by analysis of variance and chi-squared test. RESULTS: NT-proBNP was elevated in these ICU patients (median 2139 pg/mL, 25th percentile 540 pg/mL, 75% percentile 7389 pg/mL). Severity of illness and renal dysfunction (APACHE II score and serum creatinine) increased with rising NT-proBNP. The incidence of acute respiratory distress syndrome, sepsis, death, history of coronary artery disease (CAD) or congestive heart failure (all P <.05) increased with each tertile. Independent predictors of increased NT-proBNP were creatinine (P <.001), CAD (P <.001), APACHE II score (P <.05), and sepsis (P < or =.001). Overall hospital mortality was 26%, and log NT-proBNP (P <.05), APACHE II (P < or =.001), and CAD (P <.05) were independent predictors of mortality. CONCLUSIONS: For patients admitted to the ICU without decompensated heart failure or acute coronary syndrome, NT-proBNP concentrations are markedly elevated, especially in patients with sepsis. NT-proBNP strongly and independently predicts mortality. However, NT-proBNP should not be used to direct volume management in critically ill patients.

Effect of chronic changes in heart rate on congestive heart failure.

BACKGROUND: Heart rate can affect cardiac function, but the importance of rates lower than 100 paced beats per minute is unknown. We therefore sought to evaluate the impact of different heart rates on ejection fraction, 6-minute walk, and peak oxygen consumption (VO2) in heart failure patients. METHODS AND RESULTS: We studied 13 pacemaker-dependent New York Heart Association Class III patients with ejection fraction <40%, age 66 +/- 13. Eligible patients included those pacing at least 75% of the time at a lower set rate of 60 ppm. This was a 3-period randomized blinded crossover study. Patients were assigned to pace at 60, 75, or 90 ppm (with rate responsivity to 20 ppm above the lower rate) for 2 months at each setting. At the end of each period, ejection fraction (by nuclear ventriculography) and exercise tolerance (by peak VO2 and 6-minute walk) were assessed. Ejection fraction, peak VO2, and 6-minute walk distance were significantly different among the 3 heart rates. All 3 were depressed at 90 ppm. A heart rate of 90 also led to more clinical deterioration and premature discontinuation from that period. CONCLUSIONS: Pacing at a heart rate of 90 led to lower ejection fraction, VO2, 6-minute walk distance and clinical evidence of worsening heart failure as compared with slower heart rates.

B-type natriuretic peptide and N-terminal pro B-type natriuretic peptide are depressed in obesity despite higher left ventricular end diastolic pressures.

BACKGROUND: B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are frequently used in diagnosing and monitoring patients with heart failure. Recent studies have demonstrated that concentrations of these peptides are decreased in obese patients, but whether lower natriuretic peptide concentrations are really due to different hemodynamics is unknown. The relationship between these markers and left ventricular end diastolic pressure (LVEDP) in obesity has not been elucidated. METHODS: We examined patients undergoing cardiac catheterization who had creatinine of < 2.0, no evidence of myocardial infarction or pulmonary embolism, and no cardiac transplant. Body mass index and LVEDP were determined, and BNP and NT-proBNP obtained at the start of each case. Obesity was defined as body mass index of > or = 30 kg/m2. RESULTS: Of 203 patients enrolled, 101 were obese. The groups were similar in respect to race, creatinine, cholesterol, and history of dyslipidemia and cardiomyopathy. The obese patients tended to be younger, were more likely to have diabetes and hypertension, and were less likely to have coronary artery disease. The obese patients had higher LVEDP but reduced BNP and NT-pro-BNP. The relationship between the natriuretic peptides and LVEDP was poor, with r values of < 0.1. CONCLUSIONS: Obese patients have reduced concentrations of BNP and NT-proBNP compared to nonobese patients despite having elevated LVEDP. This suggests that factors other than cardiac status impact on BNP and NT-proBNP concentrations. The poor relationship between natriuretic peptide concentrations and LVEDP also suggests that these concentrations should not be considered surrogates for cardiac filling pressures or volumes.

The adequacy of laboratory monitoring in patients treated with spironolactone for congestive heart failure.

OBJECTIVES: This study was designed to determine the adequacy of monitoring patients receiving spironolactone as well as spironolactone's relationship to hyperkalemia. BACKGROUND: After the Randomized Aldactone Evaluation Study (RALES) demonstrated a 30% mortality benefit for treating severe heart failure patients with spironolactone, acceptance of this drug was overwhelming. Hyperkalemia and worsening renal function were rare in RALES, but laboratory monitoring was frequent. In clinical practice, the incidence of hyperkalemia and worsening renal function and adequacy of follow-up is unknown. METHODS: We reviewed the monitoring of congestive heart failure (CHF) patients with spironolactone initiation after publication of RALES. All potassium and creatinine determinations at baseline and within three months following therapy initiation were assessed. Increased potassium was defined as any [K] > or = 5.5 mEq/l and severe hyperkalemia as any [K] > or = 6.0. RESULTS: A total of 840 patients had new prescriptions for spironolactone. Of these, 91% had baseline laboratory values, and 34% did not have any serum potassium or creatinine determined within three months. Patients seen in the cardiology clinic were more likely to have appropriate follow-up (p < or = 0.001). Of 551 patients with follow-up laboratory values determined, 15% developed hyperkalemia and 6% developed severe hyperkalemia. Fifty-one patients (9%) developed renal dysfunction, of whom 25 developed hyperkalemia within three months. Hyperkalemia developed in 48 of 138 (35%) patients with baseline creatinine > or = 1.5 mg/dl and 12 of 19 (63%) with baseline creatinine > or = 2.5 mg/dl. CONCLUSIONS: Many patients treated with spironolactone for CHF do not receive needed follow-up of potassium or creatinine concentrations, although hyperkalemia and renal dysfunction are common. Elevated baseline creatinine predicts patients at high risk. Physician education of the risks of spironolactone and the need for follow-up is essential.

Nesiritide does not improve renal function in patients with chronic heart failure and worsening serum creatinine.

BACKGROUND: Nesiritide (synthetic human brain natriuretic peptide) is approved for the treatment of symptomatic heart failure. However, studies of brain natriuretic peptide in patients with heart failure have come to conflicting conclusions about effects on glomerular filtration rate (GFR), effective renal plasma flow, natriuresis, and diuresis. METHODS AND RESULTS: To identify a population at high risk of renal dysfunction with conventional treatment, we selected patients with a creatinine level increased from baseline (within 6 months). We examined the effects of nesiritide on GFR (measured by iothalamate clearance), renal plasma flow (measured by para-amino hippurate clearance), urinary sodium excretion, and urine output in a double-blind, placebo-controlled, crossover study. Patients received nesiritide (2 microg/kg IV bolus followed by an infusion of 0.01 microg/kg per minute) or placebo for 24 hours on consecutive days. Nesiritide and placebo data were compared by repeated-measures analysis and Student t test. We studied 15 patients with a recent mean baseline creatinine of 1.5+/-0.4 mg/dL and serum creatinine of 1.8+/-0.8 mg/dL on admission to the study. There were no differences in GFR, effective renal plasma flow, urine output, or sodium excretion for any time interval or for the entire 24-hour period between the nesiritide and placebo study days. For 24 hours, urine output was 113+/-51 mL/h with placebo and 110+/-56 mL/h with nesiritide. GFR during placebo was 40.9+/-25.9 mL/min and with nesiritide was 40.9+/-25.8. CONCLUSIONS: Nesiritide did not improve renal function in patients with decompensated heart failure, mild chronic renal insufficiency, and renal function that had worsened compared with baseline. The lack of effect may be related to renal insufficiency, hemodynamic alterations, sodium balance, severity of heart failure, or drug dose. Understanding the importance of these issues will permit effective and appropriate use of nesiritide.