Ultrafiltration is Associated With Fewer Rehospitalizations than Continuous Diuretic Infusion in Patients With Decompensated Heart Failure: Results From UNLOAD

BackgroundCompare outcomes of ultrafiltration (UF) versus standard intravenous (IV) diuretics by continuous infusion or bolus injection in volume overloaded heart failure (HF) patients. In the Ultrafiltration versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated heart Failure (UNLOAD) study, UF produced greater fluid reduction and fewer HF rehospitalizations than IV diuretics in 200 hospitalized HF patients. Outcomes may be due to greater fluid removal, but UF removes more sodium/unit volume than diuretics.Methods and ResultsOutcomes of 100 patients randomized to UF were compared with those of patients randomized to standard IV diuretic therapy with continuous infusion (32) or bolus injections (68). Choice of diuretic therapy was by the treating physician. Forty-eight hour weight loss (kg): 5.0 ± 3.1 UF, 3.6 ± 3.5 continuous infusion, and 2.9 ± 3.5 bolus diuretics (P = .001 UF versus bolus diuretic; P > .05 for the other comparisons). Net fluid loss (L): 4.6 ± 2.6 UF, 3.9 ± 2.7 continuous infusion, and 3.1 ± 2.6 bolus diuretics (P < .001 UF versus bolus diuretic; P > .05 for the other comparisons). At 90 days, rehospitalizations plus unscheduled visits for HF/patient (rehospitalization equivalents) were fewer in UF group (0.65 ± 1.36) than in continuous infusion (2.29 ± 3.23; P = .016 versus UF) and bolus diuretics (1.31 ± 1.87; P = .050 versus UF) groups. No serum creatinine differences occurred between groups up to 90 days.ConclusionsDespite similar fluid loss with UF and continuous diuretic infusion, fewer HF rehospitalizations equivalents occurred only with UF. Removal of isotonic fluid by UF compared with hypotonic urine by diuretics more effectively reduces total body sodium in congested HF patients.     

Loop diuretics for chronic renal insufficiency: a continuous infusion is more efficacious than bolus therapy.

OBJECTIVE: To test the hypothesis that a continuous, low-dose infusion of a loop diuretic is more efficacious and better tolerated than conventional intermittent bolus therapy in patients with severe chronic renal insufficiency (CRI). DESIGN: Randomized, crossover clinical trial with subjects serving as their own controls. SETTING: The General Clinical Research Center of Indiana University Hospital, Indianapolis, Indiana. PATIENTS: Eight adult volunteers with severe stable CRI (mean creatinine clearance, 0.28 mL/s; range, 0.15 to 0.47 mL/s) were recruited from the outpatient nephrology clinics of Indiana University Medical Center. INTERVENTIONS: On admission, diuretic drugs were withdrawn and patients were equilibrated on an 80 mmol/d sodium, 60 mmol/d potassium metabolic diet. Patients were randomized to receive a 12-mg intravenous dose of bumetanide given either as two 6-mg bolus doses separated by 6 hours or as the same total dose administered as a 12-hour continuous infusion. When sodium balance was re-established, each patient was crossed over to the alternative study limb. All patients completed both phases of the study. MEASUREMENTS AND RESULTS: Comparable amounts of bumetanide appeared in the urine during the study period (infusion, 912 +/- 428 micrograms; bolus, 944 +/- 421 micrograms; difference, 32 micrograms; 95% CI, -16 micrograms to 80 micrograms, P = 0.16). The continuous infusion resulted in significantly greater net sodium excretion (infusion, 236 +/- 77 mmol; bolus, 188 +/- 50 mmol; difference, 48 mmol; CI, 16 mmol to 80 mmol, P = 0.01). No patient had episodes of drug-induced myalgias during the continuous infusion compared with 3 of 8 patients with bolus therapy. CONCLUSIONS: In patients with severe CRI, a continuous intravenous infusion of bumetanide is more effective and less toxic than conventional intermittent bolus therapy. Continuous administration will probably be useful in patients with severe CRI who have not achieved an adequate natriuresis or who show evidence of drug toxicity with standard diuretic dosing regimens. A similar benefit may occur in selected diuretic-resistant patients with cardiac or hepatic disease, and studies in these patients seem warranted.     

Continuous infusion

There is evidence, albeit scientifically weak, for improved cost/benefit with administration of factor concentrates by continuous infusion when high-dose replacement is necessary, as several studies have shown a reduced requirement for the concentrate. There is evidence from only one study for fewer bleeding complications with continuous infusion. There is evidence from two studies that additional therapy with tranexamic acid reduces the risk of bleeding complications in patients receiving continuous infusion. Future studies should address the question of minimum steady-state levels required for haemostasis, comparisons with bolus injection using a randomized design and investigate the risk of inhibitor formation.     

Efficacy and safety of loop diuretic therapy in acute decompensated heart failure: a clinical review

Intravenous loop diuretics are widely used to treat the symptoms and signs of fluid overload in acute heart failure (AHF). Although diuretic therapy is widely used and strongly recommended by most recent clinical guidelines, prospective studies and randomized clinical trials are lacking and so reliable evidence is missing about the best therapy in terms of doses and methods of administration. In addition, clinical efficacy and safety outcomes are often affected by the presence of contrasting evidence. The efficacy of loop diuretics is impaired by diuretic resistance characterized by a decreased diuretic and natriuretic effect. This review focuses on the current management of AHF with diuretic therapy. Continuous diuretic infusion seems to be a good choice, from a pharmacokinetic point of view, when fluid overload is refractory to conventional therapy. Some available evidence comparing bolus injection to continuous infusion of loop diuretics proved the latter to be an effective and safe method of administration. Continuous infusion seems to produce a constant plasmatic concentration of drug with a more uniform daily diuretic and natriuretic effect and a greater safety profile (fewer adverse events such as worsening renal failure, electrolyte imbalances, ototoxicity). The analyses of the published studies did not provide conclusive data about the effects on clinical outcomes (mortality, rate of hospital readmissions, length of hospital stay and adverse events). Furthermore, recent studies focus their attention on alternative strategies of fluid removal, such as vasopressin antagonists, adenosine antagonists and ultrafiltration but available data are often inconclusive.     

持续静脉滴注速尿治疗充血性心力衰竭随机对照研究

目的　探讨持续静脉滴注速尿治疗充血性心力衰竭 (CHF)的药效学及对生理平衡的影响是否优于一次性注射治疗。方法　采用随机对照方法将 70例 NYHA心功能 — 级 CHF患者分为持续静脉滴注组 (静滴组 ,35例 )和一次性静脉注射组 (静注组 ,35例 ) ,静滴组在注射 10 mg负荷剂量速尿后持续静滴 30 m g,静注组一次性注射 4 0 mg,均持续 3日。治疗前后分别评价心功能及血生化指标 ,并计算每日尿量和尿 K+、Na+、Cl-排泄量。结果　静滴组每日尿量及尿K+、Na+、Cl-排泄量均明显大于静注组 ,尤其在治疗的第二日、第三日 ,治疗后静注组除血脂浓度升高比静滴组更显著外 ,其他生化指标两组无显著差异。结论　持续静脉滴注速尿治疗 CHF在药效学方面明显优于静脉注射方式 ,并可提高肾脏对速尿的敏感性 ,延缓耐受性的产生。对生理平衡的影响也可能优于一次性静脉注射 ,值得进一步探讨。     

Twice-daily intravenous bolus tacrolimus infusion: A safe and effective regimen for graft-versus-host disease prophylaxis

Objective/BackgroundAmong patients undergoing allogeneic hematopoietic cell transplant, continuous intravenous (IV) tacrolimus infusion is frequently used for graft-versus-host disease (GvHD) prophylaxis. Twice-daily intermittent IV tacrolimus dosing may confer safety and convenience benefits.MethodsWe performed a retrospective chart review of 66 patients who received twice-daily IV bolus tacrolimus for GvHD prophylaxis. The primary end point of the study was safety, as measured by renal toxicity. The secondary end points included mean tacrolimus serum concentrations, incidence of grades II–IV acute GvHD, electrolyte abnormalities, hyperglycemia, hypertension, and neurologic toxicity.ResultsThere was acceptable, possibly favorable, incidence of renal toxicity (42%) and no significant difference in grades II–IV GvHD (37%), compared with published data. Mean tacrolimus blood concentrations were not affected by occurrence of renal toxicity.ConclusionWe conclude that administration of IV tacrolimus twice daily over 4 h may be safe and effective in preventing GvHD in allogeneic hematopoietic cell transplant.     

Intermittent administration of furosemide vs continuous infusion preceded by a loading dose for congestive heart failure.

Several reports have suggested that continuous intravenous administration of loop diuretics may be superior to intermittent administration. We performed a prospective randomized crossover study comparing intermittent intravenous administration (IA) of furosemide with continuous infusion following a single loading dose (LDCI) in nine patients with severe congestive heart failure. At the time of hospital admission, patients were randomly assigned to one of two treatment groups. One group (four patients) received an IV bolus injection of furosemide followed immediately by a continuous infusion for 48 h. The second group (five patients) was treated with three IV bolus injections a day for 48 h. Total doses of furosemide were equivalent in the two groups. After 48 h, each patient was crossed over to the other method and treated for an additional 48 h. LDCI produced significantly greater diuresis and natriuresis than IA (total urine output increased by 12 to 26 percent, total sodium excretion increased by 11 to 33 percent) (p less than 0.01). There were no significant differences in side effects between the two methods. These results indicate that LDCI may be a preferred method for administration of furosemide in patients with congestive heart failure.     

Randomized Comparison of Gastric pH Control with Intermittent and Continuous Intravenous Infusion of Famotidine in ICU Patients

Objective : To compare gastric pH control using intravenous famotidine as a primed, continuous infusion versus intermittent infusion. Methods : In a prospective, double-blind study, 40 ICU patients at risk for stress ulceration were randomly assigned to receive either famotidine 20 mg intravenous bolus followed by 1.67 mg/h infusion or famotidine 20 mg intravenously every 12 h. Intraluminal gastric pH was recorded at baseline and every 4 h using a glass electrode. Clinical outcome indicators were also monitored. Subjects were studied for a minimum of 24 h and a maximum of 6 days. Continuous variables were analyzed by ANOVA and nominal variables by Fisher's exact test (α= 0.05). Results : Nineteen patients were randomized to the continuous infusion group, and 21 were randomized to the intermittent group. Using gastric pH greater than 4.0 as an endpoint, the continuous group exhibited better pH control, both in terms of percentage of total measurements (83% versus 63%, p < 0.001) and time spent above pH 4.0 (91% versus 76%, p < 0.01). Similar results were found at pH greater than 5.0 (78% versus 56% for all measurements for the continuous and bolus groups, respectively ( p < 0.001), and 88% versus 72% for the time spent above pH 5.0 ( p < 0.01). Clinical outcomes, including evidence for gastrointestinal bleeding and hospital mortality, did not differ significantly between groups. Conclusion : Famotidine infusion at 1.67 mg/h, when preceded by a bolus dose of 20 mg, provides a greater and more sustained increase in gastric pH than intermittent administration of famotidine 20 mg every 12 h.     

A bolus calculator is an effective means of controlling postprandial glycemia in patients on insulin pump therapy

Accurate bolus insulin doses require calculations based on (1) current blood glucose, (2) target blood glucose, (3) carbohydrate-to-insulin ratios, (4) total grams of carbohydrate in meals, and (5) insulin sensitivity factors. Patients may often forego these calculations for insulin doses based on empirical estimates. A bolus calculator (Medtronic MiniMed) uses these five parameters to generate a recommended bolus insulin dose. This study provides the evidence that a hand-held bolus calculator is effective in controlling postprandial blood glucose. Subjects (n = 49) with Type 1 diabetes and experienced with continuous subcutaneous insulin infusion therapy were randomized to begin one of two bolus dosing methods. After 7 days, subjects crossed over to the alternate method. Prior to entering the Bolus Calculator period, physicians established patients' bolus parameters and programmed them into a personal digital assistant (PDA). Subjects used the PDA to obtain recommended pre-meal insulin bolus doses. During the Standard Bolus period, significantly more correction boluses were administered to curtail postprandial hyperglycemia (p = 0.008) and more supplemental carbohydrate was consumed to raise low blood glucose (p = 0.046). Similar values were observed between the two bolus dosing methods in average deviation of 2-h postprandial blood glucose. Subjects reported that the bolus calculator was easy to use and that they were confident in the bolus doses suggested by the device. These results confirm that bolus insulin doses computed by a bolus calculator, compared with standard bolus techniques, achieve target postprandial blood glucose but with fewer correction boluses and supplemental carbohydrate. A bolus calculator, which can be integrated into insulin pump software, may help patients to more accurately meet prandial insulin dosage requirements, improve postprandial glycemic excursions, and achieve optimal glycemic control.     

Sustained hemodynamic effects of an infusion of nesiritide (human b-type natriuretic peptide) in heart failure: a randomized, double-blind, placebo-controlled clinical trial. Natrecor Study Group.

OBJECTIVES: The goal of this study was to further define the role of nesiritide (human b-type natriuretic peptide) in the therapy of decompensated heart failure (HF) by assessing the hemodynamic effects of three doses (0.015, 0.03 and 0.06 microg/kg/min) administered by continuous intravenous (IV) infusion over 24 h as compared with placebo. BACKGROUND: Previous studies have shown beneficial hemodynamic, neurohormonal and renal effects of bolus dose and 6-h infusion administration of nesiritide in HF patients. Longer term safety and efficacy have not been studied. METHODS: This randomized, double-blind, placebo-controlled multicenter trial enrolled subjects with symptomatic HF and systolic dysfunction (left ventricular ejection fraction < or =35%). Central hemodynamics were assessed at baseline, during a 24-h IV infusion and for 4 h postinfusion. RESULTS: One hundred three subjects with New York Heart Association class II (6%), III (61%) or IV (33%) HF were enrolled. Nesiritide produced significant reductions in pulmonary wedge pressure (27% to 39% decrease by 6 h), mean right atrial pressure and systemic vascular resistance, along with significant increases in cardiac index and stroke volume index, with no significant effect on heart rate. Beneficial effects were evident at 1 h and were sustained throughout the 24-h infusion. CONCLUSIONS: The rapid and sustained beneficial hemodynamic effects of nesiritide observed in this study support its use as a first-line IV therapy for patients with symptomatic decompensated HF.     

Aggressive diuresis for severe heart failure in the elderly

STUDY OBJECTIVE: To determine the efficacy, safety, and economic benefit of continuous IV infusion of furosemide as a treatment modality for elderly patients with class IV heart failure. DESIGN: Prospective trial of consecutively admitted elderly patients > 65 years old with class IV heart failure. SETTING: A single cardiovascular service in a university medical center. PATIENTS: Seventeen male and female patients > 65 years old consecutively admitted to a cardiovascular service. RESULTS: High-dose, continuous IV infusion of furosemide was successful in providing a 9- to 20-L diuresis in an average of 3.5 days without causing clinical complications or aberrations in blood chemistry. The length of stay was 2.3 days shorter than a contemporary group of class III and class IV elderly patients with heart failure managed on other medical services. The Medicare reimbursement for heart failure was $6,047. Patients receiving IV bolus diuretic therapy incurred billing charges of $10,193, or a loss of $4,146 per patient to the hospital. Patients receiving diuretic infusion therapy incurred billing charges of $4,944. This was a difference of $5,249 per patient treated by continuous IV infusion compared to bolus therapy and a profit per Medicare patient of $1,103. Therefore, a $4,146 billing loss was converted to $1,103 profit. CONCLUSION: IV furosemide infusion therapy for class IV heart failure in the elderly is a safe, effective, and economic mode of therapy.     

A placebo-controlled trial of continuous intravenous diltiazem infusion for 24-hour heart rate control during atrial fibrillation and atrial flutter: a multicenter study

The safety and efficacy of a 10- to 15-mg/h continuous infusion of intravenous diltiazem were evaluated in 47 patients with atrial fibrillation or flutter who first responded to 20 mg or 20 mg followed by one or more 25-mg bolus doses of open label intravenous diltiazem. Of the 47 patients, 44 responded to the bolus injection and were randomized under double-blind conditions to receive either a continuous infusion of intravenous diltiazem (10 to 15 mg/h) (23 patients) or placebo (21 patients) for up to 24 h. Seventeen (74%) of the 23 patients receiving diltiazem infusion and none of the 21 with placebo infusion maintained a therapeutic response for 24 h (p less than 0.001). Over 24 h, patients receiving diltiazem infusion lost response significantly more slowly than did those receiving placebo infusion (p less than 0.001). Nonresponders to the double-blind infusion were given an additional bolus injection of open label intravenous diltiazem and administered an open label 24-h intravenous diltiazem infusion. The overall proportion of patients maintaining a response to a 24-h infusion of intravenous diltiazem under double-blind or open label conditions combined was 83% (34 of 41). Efficacy of the 24-h infusion of intravenous diltiazem was similar in elderly versus young patients, those who did versus those who did not receive digoxin and those weighing less than 84 versus greater than or equal to 84 kg. However, intravenous diltiazem appeared to be more effective in atrial fibrillation than in atrial flutter. No significant untoward effects were noted.(ABSTRACT TRUNCATED AT 250 WORDS)     

A dosing nomogram for continuous infusion intravenous naloxone

Naloxone hydrochloride is extremely valuable for diagnosing and managing the opioid overdose. Due to naloxone's short half life and a long duration of action of most opioids, repeated naloxone dosing often is required to prevent the recurrence of respiratory depression. An alternative to repeated bolus administration is a continuous IV infusion. We conducted a two-phase study to determine the pharmacokinetics of naloxone and to develop a continuous dosing nomogram. In the first phase seven patients were given an IV bolus dose alone and serial plasma naloxone levels were determined. Naloxone elimination was found to be biexponential with the mean beta half life equal to 0.023 +/- 0.002 reciprocal minutes in two patients and 0.015 +/- 0.02 reciprocal minutes in five patients. In the second phase ten volunteers were given either a 2-mg or a 4-mg bolus dose followed by a 1.5-mg/hr or a 3-mg/hr continuous infusion. The mean volume of distribution of the central compartment was found to be 0.806 +/- 0.408 L/kg. The mean beta rate constant of elimination was found to be 0.036 +/- 0.027 reciprocal minutes. A computer simulation of the pharmacokinetic parameters determined in our study found that a continuous infusion of two-thirds of the bolus dose that resulted in reversal each hour will maintain the plasma naloxone levels equal to or greater than the naloxone levels that would have existed 30 minutes following the bolus dose.     

Optimal dose of intravenous pantoprazole in patients with peptic ulcer bleeding requiring endoscopic hemostasis in Korea

Background and Aim:  The lowest effective dose of proton pump inhibitors (PPI) for prevention of peptic ulcer rebleeding remains unclear. The objective of the present study was to evaluate whether low-dose PPI has a similar efficacy to high-dose i.v. administration for maintaining intragastric pH above 6.
Methods:  Sixty-one patients with bleeding ulcers were randomized into one of three groups after endoscopic hemostasis: pantoprazole 80 mg bolus followed by 8 mg/h; 40 mg, 4 mg/h infusion; and bolus injection of 40 mg every 24 h. Intragastric pH values and rebleeding rates were measured. In addition, pharmacokinetic parameters and association with CYP2C19 polymorphisms and H. pylori infection were assessed.
Results:  Mean percentage of time with intragastric pH > 6, and the proportion of patients with pH > 6 for more than 60% of the time were significantly higher in the 40 mg, 4 mg/h infusion group compared to the 40 mg bolus injection. There was no significant difference between the 80 mg, 8 mg/h and the 40 mg, 4 mg/h groups. In the H. pylori (−) group, only 40% of patients that received continuous infusion reached the target pH > 6 for more than 60% of the time; this was significantly lower than the H. pylori (+) group, 87.5% ( P  = 0.026).
Conclusions:  A continuous infusion, regardless of high or low dose, was more effective for acid suppression than a 40 mg bolus PPI injection in Korea. H. pylori infection was an important factor for the maintenance of an intragastric pH > 6.     

How to use diuretics in heart failure

Systemic and pulmonary congestion is a central aspect of both acute and chronic heart failure and directly leads to many of the clinical manifestations of these syndromes. Therefore, diuretic therapy to treat congestion plays a fundamental role in heart failure management. However, although diuretics are the most common drugs prescribed for heart failure, there is limited quality evidence to guide their use. Unlike other components of the heart failure armamentarium, such as β-blockers and angiotensin-converting enzyme inhibitors, diuretics (with the exception of aldosterone antagonists) have not been shown to decrease heart failure progression or improve mortality. Additionally, some observational data suggest that diuretics may actually be harmful in heart failure, contributing to neurohormonal activation, renal dysfunction, and potentially mortality. Despite these concerns, diuretics remain ubiquitous in heart failure management because of the need to address symptoms of congestion and the lack of alternative strategies. Recently, the development of a variety of potential adjuncts or alternatives to diuretic therapy has suggested the need for an active reappraisal of diuretic therapy for heart failure. The main classes of diuretics are the loop diuretics, potassium-sparing diuretics, and thiazides. Loop diuretics, the mainstay of acute and chronic therapy for heart failure, are “threshold drugs”; therefore, an adequate dose to achieve a pharmacodynamic effect (ie, to increase urine output) must be prescribed for effective therapy. The minimum dose to achieve diuresis and manage congestion should be used to minimize adverse effects. For patients refractory to initial dosing of intravenous diuretics, options include dose escalation, use of continuous infusion rather than intermittent boluses, or combination therapy with the addition of a thiazide or thiazide-like diuretic (eg, metolazone). Management of chronic heart failure often includes patient-directed titration of diuretics based on changes in symptoms or body weight in an attempt to decrease hospitalizations, although the efficacy of this strategy has not been tested in well-designed trials. Aldosterone antagonists, which are used primarily as neurohormonal agents rather than for their diuretic effects, are indicated for patients with systolic failure and moderate to severe symptoms, as long as renal function and serum potassium are stable and monitored closely. All diuretic therapy requires careful monitoring of electrolytes and renal function. Whether newer modalities for managing congestion (vasopressin antagonists, adenosine A1 antagonists, and ultrafiltration therapy) will be an improvement over diuretic therapy will be determined by the results of multiple ongoing clinical trials.     

Improved anticoagulation with a weight-adjusted heparin nomogram in patients with acute coronary syndromes: A randomized trial

The optimal heparin dosing schedule to achieve rapid and therapeutic anticoagulation has not been established. The objective of this study is to determine whether an intravenous heparin dosing nomogram based on body weight achieves adequate anticoagulation more rapidly than a standard-care nomogram. Sixty-four patients requiring intravenous heparin treatment for acute coronary syndromes, but who did not receive thrombolytic therapy, were randomized to a standard-care nomogram in which heparin was given as a 5000 unit IV bolus followed by 1000 U/hr, or a weight adjusted nomogram in which heparin was given as an 80 U/ kg IV bolus and 18 U/kg/hr. Activated partial thromboplastin time (APTT) values were checked at 6,12,18, 24, and 48 hours and adjusted either by 100–200 U/hr (standard-care nomogram) or by 2–4 U/kg/hr (weight-based nomogram). Activated partial thromboplastin times were measured using a widely generalizable laboratory method. The primary goal was to achieve and maintain the APTT between 60 and 90 seconds. The median APTT values were higher in the weight adjusted group compared with the standard-care group at 6, 12, 18, 24, and 48 hours: 150 versus 83 (p=0.001), 100 versus 79 (p=0.09), 66 versus 61 (p=0.005), 63 versus 56 (p = 0.09), and 64 versus 56 (p=0.11). At 18 hours only 11% of patients in the weight-adjusted group had an APTT <61 compared with 26% in the standard-care nomogram (p=0.007). No major bleeding complications were noted in either group. A weight-adjusted heparin nomogram offers improved anticoagulation in the first 24 hours after heparin initiation compared with a standard-care nomogram in patients with acute coronary artery syndromes.     

Infection risk and stability of a continuous 8‐h 250 mL rFVIII infusion

This study seeks to identify the delivery method of continuous infusion using a 250 cc IV bag via pump, change every 8 h. Additionally, the study will examine the infection risk with the use of 8 h infusions. Ten hemophilia A patients were identified for the study. Each patient received a bolus factorVIII (FVIII) infusion with a pre FVIII level and 1 h post FVIII level to determine recovery levels for optimal dosing. On the day of 8‐h continuous infusion, the pt received a bolus VIII (Kogenate FS ^?) for correction to 100% followed by individually calculated continuous infusion (Kogenate FS ^?) FVIII. FVIII levels were drawn from the IV bag and peripherally from the patient in the opposite arm at time points: pre infusion, 1, 2, 3, 4, 5, 6 and 8 h. Additionally, blood cultures were drawn from the IV bag and from the IV tubing at time points pre infusion, 4 and 8 h. Fourteen subjects agreed to participate in the study; 4 failed to follow up, hence 10 subjects were included in the analysis of data; 7 severe, 2 moderate, and 1 mild hemophilia A. Age range was 26–62 years. Ethnic breakdown included 5 African American, 4 Caucasian, 1 Hispanic. With all infusions, the range of FVIII was 65–135% (blood) and 62–200% (bag). After the start of infusion, there were no significant differences noted between the hourly FVIII levels in the subjects and the IV values (P‐value range 0.36–0.9). Additionally, given three time points with six cultures per patient, totaling 60 points of cultures drawn for the study, all cultures from the IV bag and patient were negative. The effective delivery method and safety of an 8‐h continuous infusion of FVIII (Kogenate FS ^?) has been confirmed. This method can be helpful given that many hospitals may not carry the required mini‐pumps, allowing a standard safe delivery of FVIII (Kogenate FS ^?) continuous infusion by available means.     

Effect of inositol-trisphosphate on fluid transport and protein extravasation in the obstructed small bowel

BACKGROUND: Small-bowel obstruction is characterized by accumulation of fluid in the obstructed intestine. A pronounced inflammation in the obstructed gut wall has been shown to play an important role in the pathogenesis of the profuse fluid losses. alpha-Trinositol (D-myo-inositol-1,2,6-trisphosphate; PP56) has potent anti-inflammatory as well as antisecretory properties. The effects of alpha-Trinositol on inflammation and fluid losses in the obstructed small intestine are examined. METHODS: A total obstruction of the proximal part of the rat jejunum was induced during 18 h by thread ligation. A small segment of the obstructed intestine, with intact vascular and nervous supply, was placed in a chamber suspended from a force displacement transducer allowing for continuous registration of net fluid transport on a Grass polygraph. Three groups were included. One group (n = 12) received low-dose alpha-Trinositol (bolus: 2 mg kg(-1); IV infusion: 10 mg kg(-1) min(-1)), a second group (n = 10) received high-dose alpha-Trinositol (bolus: 12 mg kg(-1); IV infusion: 60 mg kg(-1) min(-1)), while a control group (n = 9) received corresponding volumes of isotonic saline (bolus: 0.5 ml; IV infusions 15 microl min(-1)). Quantitative measurement of extra-vasated Evans blue albumin in the obstructed jejunum was used as a marker of inflammation. RESULTS: High-dose alpha-Trinositol induced a significant (P < 0.001) inhibition of net fluid secretion, while low-dose alpha-Trinositol had no significant effect versus saline. In contrast, both doses of alpha-Trinositol induced significant inhibition of EB-albumin leakage (P < 0.05). CONCLUSION: High-dose alpha-Trinositol is a potent inhibitor of fluid secretion in obstructive ileus, most probably involving an anti-inflammatory mechanism.     

Endothelial injury markers with high-dose intravenous iron therapy in renal failure.

Endothelial injury is prevalent in patients with chronic renal failure (CRF) and may be exacerbated by commonly used intravenous (IV) iron therapy. The effects of high-dose IV iron sucrose treatment (200 mg daily in 250 mL of 0.9% saline, administered over 1 hour, median treatment duration 5 days) on circulating endothelium and/or tissue injury markers such as hepatocyte growth factor, thrombomodulin, von Willebrand factor, and C-reactive protein levels were studied. The markers were determined in 24 anemic (mean hemoglobin 9.48 g/dL) pre-dialysis (median creatinine clearance 21.5 mL/min) patients with CRF and defined absolute and/or functional iron deficiency. The measurements were performed before iron administration and 24 hours after the last infusion. All the markers remained unchanged following the IV iron therapy (all p < 0.172); no thrombotic or other adverse effects were observed. In conclusion, the above high-dose IV iron sucrose supplementation does not cause evident endothelial or other tissue injury in patients with CRF, and is clinically safe.     

Effect of Inositol-Trisphosphate on Fluid Transport and Protein Extravasation in the Obstructed Small Bowel

Background: Small-bowel obstruction is characterized by accumulation of fluid in the obstructed intestine. A pronounced inflammation in the obstructed gut wall has been shown to play an important role in the pathogenesis of the profuse fluid losses. α -Trinositol (D-myo-inositol-1,2,6-trisphosphate; PP56) has potent anti-inflammatory as well as antisecretory properties. The effects of α -Trinositol on inflammation and fluid losses in the obstructed small intestine are examined. Methods: A total obstruction of the proximal part of the rat jejunum was induced during 18 h by thread ligation. A small segment of the obstructed intestine, with intact vascular and nervous supply, was placed in a chamber suspended from a force displacement transducer allowing for continuous registration of net fluid transport on a Grass polygraph. Three groups were included. One group ( n = 12) received low-dose α -Trinositol (bolus: 2 mg kg -1 ; IV infusion: 10 mg kg -1 min -1 ), a second group ( n = 10) received high-dose α -Trinositol (bolus: 12 mg kg -1 ; IV infusion: 60 mg kg -1 min -1 ), while a control group ( n = 9) received corresponding volumes of isotonic saline (bolus: 0.5 ml; IV infusions 15 μl min -1 ). Quantitative measurement of extravasated Evans blue albumin in the obstructed jejunum was used as a marker of inflammation. Results: High-dose α -Trinositol induced a significant ( P < 0.001) inhibition of net fluid secretion, while low-dose α -Trinositol had no significant effect versus saline. In contrast, both doses of α -Trinositol induced significant inhibition of EB-albumin leakage ( P < 0.05). Conclusion: High-dose α -Trinositol is a potent inhibitor of fluid secretion in obstructive ileus, most probably involving an anti-inflammatory mechanism.