Safety and Effectiveness of Ferumoxytol in Hemodialysis Patients at 3 Dialysis Chains in the United States Over a 12-Month Period

Background

Intravenous (IV) iron is the treatment of choice for iron-deficiency anemia (IDA) in patients with dialysis-dependent chronic kidney disease (DD-CKD). However, IV iron products have been associated with serious adverse events (SAEs), including anaphylactoid reactions. Ferumoxytol is an IV iron preparation that can be injected over a short period of time. Although randomized clinical trials support ferumoxytol’s efficacy and safety, additional insights may be drawn from the acquisition of long-term, repeat dosing efficacy and safety data in a real-world setting.

Objective

The goal of this study was to characterize the effectiveness and safety profile of ferumoxytol as administered to adult DD-CKD patients with IDA in a real-world setting. The ability of ferumoxytol to maintain hemoglobin (Hb), transferrin saturation (TSAT), and ferritin treatment targets established by the 2006 Kidney Disease Outcomes Quality Initiative guidelines was determined in 3 medium-sized US-based dialysis chains.

Methods

This retrospective, observational study was conducted to examine laboratory and dosing data for all patients who received any dose of ferumoxytol at 3 US-based dialysis chains over a 12-month period. Investigators and/or physicians from each of the chains also made independent determinations regarding the seriousness of any adverse event (AE). Special attention was paid to the incidence and types of AEs and SAEs that were potentially associated with ferumoxytol.

Results

Over the 12-month observation period, 8666 patients (mean [SD] age in chains A, B and C, 63.9 [14.8], 63.9 [14.9] and 63.6 [15.1], respectively), were treated with 33,358 doses of ferumoxytol across the 3 chains. Treatment with ferumoxytol corresponded to an increased mean monthly Hb level relative to baseline (0.13–0.69 g/dL) and led to an increase in the proportion of patients maintained within the target Hb range of 10 to 12 g/dL (61%–72%). Ferumoxytol was also associated with increases in TSAT and ferritin that stabilized throughout the observation period. Incidence of AEs was similar across the 3 chains; between 0.07% and 1.77% of all patients treated at each chain experienced an AE associated with ferumoxytol administration. SAEs were reported in 0.2% of patients. The most common AEs reported (≥6 patients) were nausea (0.37% of patients), pruritus (0.29%), vomiting (0.25%), hypotension (0.21%), and dyspnea (0.20%). Two patients (0.02%) experienced anaphylactoid reactions. The AE profile of ferumoxytol remained consistent with that reported from controlled clinical trials.

Conclusions

These long-term data, which include repeat dosing in a large number of DD-CKD patients with IDA in a real-world setting, confirm the effectiveness of ferumoxytol in increasing and maintaining Hb levels within the target range and with favorable assessments of long-term safety.     

Efficient monthly subcutaneous administration of darbepoetin in stable CAPD patients.

BACKGROUND: Although subcutaneous administration of recombinant human erythropoietin (rHuEPO) in continuous ambulatory peritoneal dialysis (CAPD) patients is a widely accepted recommendation, the lowest possible frequency of an efficient dosing regimen remains controversial. Darbepoetin alpha, a new erythropoiesis-stimulating protein with a threefold longer serum half-life compared with rHuEPO, has greater in vivo potency and can be administered less frequently to obtain the same biological response. This study assessed the efficacy of darbepoetin administered once monthly in the treatment of anemia in CAPD patients. PATIENTS AND METHODS: In this single-center, prospective cohort study, 11 stable CAPD patients (5 males, 6 females; mean age 68.8 +/- 14.1 years; mean duration on peritoneal dialysis 31.6 +/- 13 months) maintained average hemoglobin and hematocrit levels of 12.09 +/- 1.29 g/dL and 37.29% +/- 3.58%, respectively, while receiving a mean weekly maintenance dose of epoetin alfa of 129 IU/kg. These same patients were assigned to receive the equivalent weekly darbepoetin dose once monthly for 24 consecutive weeks. Hematological response, iron status (transferrin saturation, serum ferritin levels), C-reactive protein (CRP), and the patients' biochemical profiles were evaluated monthly. RESULTS: During the monthly administration of darbepoetin, mean serum levels of Hb and Hct were 12.17 +/- 1.28 g/dL and 37.1% +/- 1.19% respectively. No statistically significant difference was apparent between the previous and monthly dosing values (12.09 +/- 1.29 vs 12.17 +/- 1.28 g/dL, p = 0.769, and 37.29% +/- 3.58% vs 37.1% +/- 1.19%, p = 0.752). Transferrin saturation levels as well as serum ferritin levels also remained unchanged (30.4% +/- 8.6% vs 30.1% +/- 9.4%, NS, and 556 +/- 212 vs 621 +/- 234 ng/mL, respectively, NS). CONCLUSION: These results indicate that darbepoetin alfa can be effectively given subcutaneously at monthly intervals for the treatment of anemia in stable CAPD patients. However, more studies are needed to validate the long-term efficacy of this monthly subcutaneous administration.     

Unit dosing of darbepoetin alfa for thetreatment of anemia in patients with end-stage renal disease being switched from recombinant human erythropoietin: Results of a phase IIIb, 27-week, multicenter, open-label study in Greek patients

Background:

Darbepoetin alfa is an erythropoietis-stimulating glycoprotein with a ∼3-fold longer t1/2 and greater biological activity compared with recombinant human erythropoietin (rHuEPO).

Objective:

The objective of this study was to evaluate the efficacy andtolerability of long-term (24-week) darbepoetin alfa treatment in maintaining hemoglobin (Hb) concentrations in the target range of 10 to 13 g/dL in patients undergoing dialysis; the patients were switched from rHuEPO to a less-frequent dosing regimen of darbepoetin alfa without an increase in dose.

Methods:

In this Phase IIlb, open-label, multicenter study, patients withend-stage renal disease (ESRD) undergoing dialysis who were receiving rHuEPO BIW or TIW at baseline were switched to darbepoetin alfa QW; patients receiving rHuEPO QW were switched to darbepoetin alfa Q2W Administration of darbepoetin alfa was by the same route as previous rHuEPO administration (IV or SC). Patients received darbepoetin alfa for 24 weeks, including a 20-week drug titration period followed by a 4-week, stable-dose evaluation period. The mode, dose, and frequency of administration of darbepoetin alfa were compared with those of baseline rHuEPO. Tolerability assessment was based on spontaneous reporting and laboratory tests (hematology, vital sign measurement, iron status, and biochemistry).

Results:

The study comprised 173 patients who were divided into 2 groups by route of administration (IV group, n = 146; SC group, n = 27). Mean (SE) adjusted increases in Hb concentration from baseline to the evaluation period for patients receiving darbepoetin alfa QW were 0.94 (0.32) g/dL and 0.38 (0.30) g/dL for the IV or SC routes, respectively (P = 0.004 and NS, respectively). For patients receiving darbepoetin alfa Q2W the mean (SE) adjusted increases in Hb concentration were 0.08 (0.53) g/dL and 0.48 (0.35) g/dL for the IV and SC routes, respectively (both, P = NS). No significant differences in IV/SC dose ratio were observed between the 2 routes of administration. In addition, no increases in darbepoetin alfa dose were observed. The most commonly reported adverse events were hypertension (8 patients [5%]) and vascular access thrombosis (4 [2%]). The incidence of treatment-related adverse events was 6 (3%).

Conclusions:

Darbepoetin alfa effectively maintained Hb concentrations within the target range without an increase in dose, even at a reduced dosing frequency. Overall, darbepoetin alfa was well tolerated.     

Treatment of renal anemia with darbepoetin alfa: results of an Austrian multicenter study

Darbepoetin alfa is a unique erythropoetic protein whose half-life is 3 times longer than that of recombinant human erythropoetin (rHuEPO). It corrects and maintains haemoglobin (Hb) concentrations at increased dosing intervals as compared to rHuEPO. The aim of this study was to evaluate the efficacy and safety of darbepoetin alfa administered as fixed unit doses. Haemodialysis patients (n = 250) maintained on stable rHuEPO treatment 2-3 times weekly (n = 200) were switched to darbepoetin alfa once weekly (QW). Treatment for patients on rHuEPO QW (n = 50) was changed to darbepoetin alfa every other week (Q2W). The route of administration (i.v. or s.c.) was kept unchanged. The dose of darbepoetin alfa was titrated to maintain Hb levels at 10-13 g/dL between baseline and the evaluation period (weeks 21-24; primary endpoint). There was no clinically relevant change in mean Hb levels between baseline (11.69 g/dL) and evaluation (-0.28 g/dL (95% CI: -0.43; -0.13)). Mean weekly dose requirements of darbepoetin alfa decreased by 13.3% from 36.7 micrograms (95% CI: 33.9; 39.7) to 31.8 micrograms (95% CI: 28.7; 35.2). This decrease was more pronounced in patients receiving darbepoetin alfa i.v. (-18.4%) as compared to those receiving it s.c. (-6.4%). Darbepoetin alfa was well tolerated. Overall safety data were consistent with those observed in other studies. These data confirm that unit dosing with darbepoetin alfa at increased dosing intervals and reduced dose effectively and safely maintains Hb levels in haemodialysis patients.     

Factors associated with anemia in patients with cancer admitted to an intensive care unit

Purpose

The study aimed to evaluate the relative impact of clinical and demographic factors associated with the prevalence and incidence of anemia (hemoglobin [Hb] <12 g/dL) in critically ill patients with cancer.

Materials and Methods

We performed an electronic chart review for demographic and clinical data of adult patients with cancer with or without anemia admitted to the intensive care unit (ICU). Prevalence of anemia was determined at admission, and incidence determined if anemia developed during ICU stay. Anemia was classified as mild, moderate, or severe. The additive impact of clinical and demographic factors was evaluated by using a hierarchical linear regression model.

Results

A total of 4705 patients were included in the study. The prevalence and incidence of anemia were 68.0% and 46.6%, respectively. In prevalent cases, we found that the clinical covariates modified sequential organ failure assessment score, admission to the medical ICU, prior chemotherapy, diagnosis of hematologic cancer, and length of hospital stay before ICU admission explained 18.7% of the variance in the model, whereas the demographic covariates (age, sex, and race) explained only an additional 0.6%. The pattern was similar for incidence cases.

Conclusions

Clinical factors are more influential than demographic factors in the observed rates of prevalence and incidence of anemia in the ICU; thus, protocols are needed to identify subgroups of patients with cancer who could benefit from novel management strategies.     

Dosing intervals and hemoglobin control in patients with chronic kidney disease and anemia treated with epoetin alfa or darbepoetin alfa: a retrospective cohort study

BACKGROUND: Anemia is a common complication of chronic kidney disease (CKD). The approved dosing interval for currently available erythropoiesis-stimulating agents (ESAs) is 2 to 3 times weekly for epoetin alfa (EPO) and every 1 to 2 weeks for darbepoetin alfa (DARB). However, clinicians sometimes use less frequent dosing in the interest of convenience. OBJECTIVES: This study investigated patterns of actual ESA use (doses and dosing intervals) and hemoglo- bin (Hb) control in adult outpatients with CKD not requiring dialysis at the Cleveland Clinic Foundation anemia clinic. The distribution of and variability in Hb levels in these patients were also examined. METHODS: The clinical charts and electronic records of adult outpatients with CKD who initiated ESA therapy before March 2005 were reviewed to identify the initial, dominant (used for the longest consecutive period), and final dosing intervals and mean weekly doses of EPO and DARB. Hb control was examined in terms of maximum deviations >12 g/dL and <11 g/dL, and the proportions of measurements outside these values. RESULTS: The analysis included data from 111 outpatients (mean [SD] age, 65.9 [14.4] years; 53.2% male; 66.7% white, 29.7% black, 2.7% other, 0.9% unknown ethnicity). Twenty-one patients received EPO only, 74 received DARB only, and 16 switched ESAs. The mean duration of follow-up was 20.5 months. The most common initial dosing intervals were qwk for EPO (66.7%) and q2wk for DARB (90.5%). The dominant dosing intervals were q2wk in 61.9% of EPO patients and q3wk in 62.3% of DARB patients. However, 80.0% of those who received EPO q2wk and 63.2% of those who received DARB q3wk eventually returned to their initial dosing intervals. The largest proportions of Hb mea- surements <11 g/dL occurred at dominant dosing intervals of qwk for EPO and q2wk for DARB (both, 46.0%; 11 and 26 patients, respectively), whereas the largest proportions of measurements >12 g/dL occurred with EPO dosed at q2wk (44.0%; 5 patients) and DARB dosed at >q4wk (62.0%; 5 patients). CONCLUSIONS: The patterns of ESA usage in adult outpatients with CKD at this center indicated that clinicians extended dosing intervals beyond those in the approved prescribing information. However, variations in Hb concentrations occurred during maintenance therapy administered at extended dosing intervals, resulting in the resumption of shorter dosing intervals in the majority of patients.     

Serum selenium and zinc levels in critically ill surgical patients

Purpose

The authors designed this study to determine how serum selenium and zinc affect the outcomes of critically ill surgical patients.

Methods

The medical records of 162 patients admitted to a surgical intensive care unit (ICU) from October 2010 to July 2012 and managed for more than 3 days were retrospectively investigated.

Results

Overall, the mean patient age was 61.2 ± 15.0 years, and the median ICU stay was 5 (3-115) days. The mean Acute Physiologic and Chronic Health Evaluation II score was 18.0 ± 8.0. Eighteen (11.1%) of the study subjects died in ICU. mean selenium levels were 83.5 ± 23.8 ng/dL in the survivor group and 83.3 ± 29.6 ng/dL in the nonsurvivor group, and corresponding mean zinc levels were 46.3 ± 21.7 and 65.6 ± 41.6 μg/dL, respectively. Mean selenium concentrations were significantly different in patients with and without shock (77.9 ± 25.4 and 87.2 ± 23.1 ng/dL, P = .017). Furthermore, mean serum selenium was lower in patients with sepsis than in traumatic or simply postoperative patients (P < .001 and P = .038). Serum Zn was significantly lower in patients with sepsis than in patients with trauma (43.4 ± 25.4 μg/dL vs 54.8 ± 28.1 μg/dL, P = .038).

Conclusions

To determine the effects of serum selenium and zinc levels on critically ill surgical patients, a large-scale prospective study is needed.     

Effect of darbepoetin alfa administered once monthly on maintaining hemoglobin levels in older patients with chronic kidney disease

Background: The anemia of chronic kidney disease (CKD) is associated with increased hospitalizations, increased cardiovascular morbidity and mortality, and diminished quality of life in the elderly. Darbepoetin alfa is an erythropoiesis-stimulating agent that has been shown to be effective in treating anemia in patients with CKD (but not on dialysis) when administered using extended-dosing regimens.Objective: The purpose of this post hoc analysis was to examine the efficacy and safety profile of once-monthly (QM) darbepoetin alfa in study patients stratified according to age (ie, <65, 65–74, and ≥75 years).Methods: Patients with CKD but not on dialysis, receiving darbepoetin alfa every other week (Q2W), and with stable hemoglobin (Hb) levels between 11 and 13 g/dL, inclusive, were enrolled in this 33-week, multicenter, open-label, single-arm study. The study was carried out at 36 US centers and consisted of a 24-week QM darbepoetin alfa dose-titration period followed by an 8-week evaluation period. Hb levels were measured Q2W. Study results were stratified according to patient age (<65, 65–74, and ≥75 years).Results: A total of 152 patients (79 women, 73 men) were enrolled; 55 patients (36%) were <65 years of age, 46 (30%) were 65 to 74 years of age, and 51 (34%) were ≥75 years of age. In patients who received ≥1 dose of darbepoetin alfa, Hb levels ≥11 g/dL were maintained in 76%, 80%, and 71% of patients aged <65, 65 to 74, and ≥75 years, respectively. For patients who completed the study, the proportions who maintained Hb levels ≥11 g/dL were 83%, 88%, and 85%, respectively, for the 3 age groups. The safety profile of QM darbepoetin alfa in this study was consistent with that expected in patients with CKD not receiving dialysis.Conclusions: Darbepoetin alfa administered QM maintained Hb levels ≥11 g/dL in patients with CKD (not on dialysis) aged <65, 65 to 74, and ≥75 years. This treatment regimen may help optimize anemia management for older community-dwelling and long-term care patients.     

Predicting the development of anemia by measuring the diameter of the inferior vena cava of patients with spinal cord injury

Purpose and Methods

We retrospectively investigated whether measurement of the diameter of the inferior vena cava (IVC) is useful in predicting the development of anemia in 12 patients with spinal cord injury. Measurement of the IVC was performed in conjunction with computed tomography scan upon arrival. The subjects were divided into two groups: those with a minimum (Min) hemoglobin (Hb) of less than 10 g/dL, and those with a Min Hb greater than 10 g/dL during hospitalization.

Results

The average diameter of IVC in the Hb<10 g/dL group was smaller that that in the Hb>10g/dL group. Blood pressure was not significantly different between the two groups. The difference between the Min and initial Hb value and incidence of blood transfusion in the Hb<10g/dL group was significantly greater than that in the Hb>10g/dL group.

Conclusion

To predict the development of anemia, measurement of the IVC of patients with spinal cord injury may therefore be useful.     

Hemoglobin Stability and Patient Compliance With Darbepoetin Alfa in Peritoneal Dialysis Patients After the Implementation of the Prospective Payment System

PurposeSince the Centers for Medicare & Medicaid Services implemented the End-Stage Renal Disease Prospective Payment System, dialysis providers have increasingly focused on balancing resource utilization and quality outcomes for the treatment of anemia in patients undergoing peritoneal dialysis. Limited data exist regarding anemia management outcomes for these patients in US-based dialysis centers after the implementation of the new payment system.MethodsThis was a retrospective, observational, cohort study of stable PD patients with end-stage renal disease who received darbepoetin alfa for anemia management over a 15-month period (April 1, 2011–June 29, 2012). The medication was administered by staff in the home-training unit instead of being self-administered at home. The primary end point was mean quarterly hemoglobin (Hb) levels. Variability in Hb levels was assessed over the 5 quarters by using repeated measures ANOVA to test for differences in the observed mean SDs.FindingsIn the 139 adult patients on stable peritoneal dialysis and meeting the eligibility criteria, mean (SD) Hb level by quarter was 10.8 (1.2) g/dL in quarters 2 and 3 of 2011, 10.5 (1.1) g/dL in quarter 4 of 2011, and 10.4 (1.1) g/dL in quarters 1 and 2 of 2012. Hb levels were stable (mean SDs, 0.58–0.72) over the 5 quarters of the study. Patient compliance with attendance for all scheduled home training unit visits was 84%.ImplicationsPD patients who underwent darbepoetin alfa administration and twice-monthly laboratory testing in the home-training unit had stable Hb levels. Despite more frequent center visits compared with a home-administered approach, patient compliance was high.     

Epoetin alfa reduces blood transfusion requirements in patients with intertrochanteric fracture

Purpose

The purpose of this study is to identify the potential benefits or complications from the use of epoetin alfa in patients with intertrochanteric fracture.

Materials and Methods

Seventy-nine patients who sustained an intertrochanteric fracture were divided into 2 groups. One group received 10 daily doses of 20?000 IU of epoetin alfa beginning from the day of trauma, whereas the control group received placebo.

Results

We found a statistically significant difference in the required units of allogenic blood used between the 2 groups (P = .034). The group that received epoetin alfa also showed an elevation of hematocrit and hemoglobin values, which was statistically significant at the seventh postoperative day (P = .019 and .015, respectively) compared to the control group. No complications were evident during our study.

Conclusions

Patients with intertrochanteric fractures seem to benefit from the use of epoetin alfa because it is safe and reduces the need for blood transfusions.     

Pharmacokinetics and pharmacodynamics of once-weekly subcutaneous epoetin alfa in critically ill patients: results of a randomized, double-blind, placebo-controlled trial

OBJECTIVE: To describe the erythropoietin pharmacokinetic profile after once-weekly epoetin alfa treatment in critically ill patients. Secondary objectives were to compare pharmacodynamic and safety profiles between active treatment and placebo in these patients. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Medical, surgical, or mixed medical/surgical intensive care units. PATIENTS: A total of 73 anemic critically ill adults with an expected stay of >3 days and a hematocrit value of <38%. INTERVENTIONS: Patients were randomized 2:1 to epoetin alfa, 40,000 IU, administered subcutaneously once weekly (n=48) or matching placebo (n=25) for up to 4 wks. MEASUREMENTS AND MAIN RESULTS: Serum erythropoietin concentration and hematologic variables (percentage reticulocytes [RETI], hemoglobin [Hb], and total red blood cell [RBC] counts) were measured, and area under the serum concentration-time curve from time 0 to the last blood sampling time at time t (t: 120, 144, or 168 hrs) postdose (AUC0-Tlast) for these three variables was determined. Mean serum erythropoietin concentrations in placebo patients were slightly higher than typical physiologic levels of erythropoietin in healthy subjects, although not appropriate for the degree of anemia in these patients. Overall, exposure of endogenous erythropoietin in the placebo group (in terms of AUC0-Tlast) was only about 20% of exposure to exogenous erythropoietin in the epoetin alfa group. Baseline hemoglobin levels were the same in both groups (9.9 g/dL). Mean change in hemoglobin level from baseline through day 29 was 1.9 g/dL and 1.6 g/dL in the epoetin alfa and placebo groups, respectively. Mean AUC(RETI)0-Tlast was higher with epoetin alfa than with placebo and was related to the AUC of erythropoietin. There were no apparent differences in AUC(Hb)0-Tlast and AUC(RBC)0-Tlast between epoetin alfa and placebo groups, which was most likely due to bleeding and transfusion events. Epoetin alfa was safe and well tolerated, with a rate of treatment-emergent complications similar to that seen with placebo. CONCLUSION: Epoetin alfa, once weekly, augmented the erythropoietic response in critically ill patients as indicated by the increased erythropoietin levels and larger AUC(RETI)0-Tlast in treated patients.     

Acute Alcohol Intoxication in Adolescents: Frequency of Respiratory Depression

Background

Adolescents and young adults are frequent users of alcohol. Younger patients may be more sensitive to the effects of alcohol than their adult counterparts, and toxicity has been known to occur at lower doses. Respiratory depression is a serious adverse effect of alcohol intoxication; however, current monitoring practices may not adequately detect respiratory depression.

Objective

Our objective was to determine the frequency of hypoventilation as measured by capnography among adolescents with acute alcohol intoxication. Our secondary objective was to determine if an association exists between alcohol levels and incidence of hypoventilation.

Methods

This was a prospective observational pilot study of patients 14–20 years of age with acute alcohol intoxication. Blood or breath alcohol measurements were obtained on arrival. Hourly measurements of vital signs including capnography were recorded.

Results

Sixty-five subjects were analyzed. Mean alcohol level was 185 mg/dL. Twenty-eight percent of subjects had episodes of hypoventilation. Episodes occurred in similar proportions on arrival and during the first 5 h of measurements. There was no difference in alcohol levels between subjects who did and did not hypoventilate (185 mg/dL vs. 186 mg/dL; 95% confidence interval −29 to 25). Oxygen desaturations occurred in 14 subjects and were associated with hypoventilation (p = 0.015).

Conclusions

Hypoventilation is common among adolescents who are acutely intoxicated with alcohol. It is independent of alcohol level and occurs at a steady rate during the first several hours of intoxication. Capnography should be considered as an additional monitoring device to detect these episodes and enhance patient safety.     

Prescribing Habits of Vancomycin in the Emergency Department: Are We Dosing Appropriately?

Background

To prevent the development of bacterial resistance, current guidelines recommend vancomycin dosages of 15–20 mg/kg based on actual body weight.

Objective

Our aim was to determine if two community teaching Emergency Departments followed the new recommendations for a weight-based dosing regimen for vancomycin.

Methods

A retrospective cohort study was conducted on the prescribing habits of vancomycin in the Emergency Department. During a 6-month time period, 1,734 doses of vancomycin were dispensed and a subsequent random sample of 240 doses was reviewed. Data collection included age, gender, weight, creatinine clearance, vancomycin dose, and indication for vancomycin therapy. Mean values, standard deviations, and ranges were computed to illustrate current prescribing practices.

Results

The mean vancomycin dose was 1,117 ± 325 mg. Based on actual body weight, the calculated mean dose was 14.6 ± 5.7 mg/kg. Only 19.6% (47 of 240) of all patients received an appropriate dose based on the recommended 15–20 mg/kg vancomycin dose.

Conclusions

Our Emergency Department is inappropriately dosing vancomycin in the majority of patients. Educating clinicians regarding appropriate vancomycin dosing is recommended to achieve compliance with the latest consensus guidelines.     

Erythropoietin claims monitoring policy: implications of the October 2006 update continuing.

The Centers for Medicare and Medicaid Services issued a revised erythropoietin claims monitoring policy that governs reimbursement for Epoetin alfa and darbepoetin alfa in patients on dialysis effective October 1, 2006. The new policy reinforces the upper Hb target level of 12.0 g/dL. However, the new provisions also allow increased latitude for making timely dose adjustments in response to the variability in Hb levels that occurs due to changes in patient status.     

Evaluation of a dosing regimen for continuous vancomycin infusion in critically ill patients: An observational study in intensive care unit patients

Purpose

We aimed to evaluate a dosing algorithm for continuous vancomycin administration in intensive care unit patients.

Materials and Methods

This observational study was conducted in a medical intensive care unit (German university hospital; June 2012-February 2013). Following a loading dose of 20 mg per kg actual body weight, vancomycin was administered continuously (20 or 30 mg of vancomycin per kg actual body weight over 24 hours depending on renal function). The vancomycin infusion rate was adjusted to achieve a target serum vancomycin concentration of 20-30 mg/L.

Results

Vancomycin was administered for a median (interquartile range) of 7 (5-9) days. The median vancomycin dose given as an initial bolus was 1750 (1400-2000) mg. The median daily vancomycin dose ranged from 480 (180–960) mg (day 6) to 3.120 (2596-3980) mg (day 1). Altogether, the achieved median serum vancomycin concentration was 29.0 (25.2-33.2) mg/L. On treatment days 1 to 7, we observed target serum vancomycin levels (20-30 mg/L) in 48%, 39%, 33%, 26%, 43%, 57%, and 69% of patients. Supra-therapeutic serum vancomycin concentrations (> 30 mg/L) were observed in 36%, 52%, 61%, 63%, 39%, 19%, and 15% of patients on treatment days 1 to 7.

Conclusions

The evaluated vancomycin dosing regimen for continuous infusion allowed rapid achievement of sufficient vancomycin serum levels. However, we frequently observed supra-therapeutic serum vancomycin concentrations in the first days of vancomycin treatment.     

A carbohydrate-restrictive strategy is safer and as efficient as intensive insulin therapy in critically ill patients

Purpose

The aim of this study is to compare the safety and efficacy of 2 different strategies for glycemic control in critically ill adult patients.

Materials and Methods

A total of 337 patients were randomly assigned to a carbohydrate-restrictive strategy (group 1) through glucose-free venous hydration, hypoglycidic nutritional formula, and subcutaneous insulin if blood glucose level was higher than 180 mg/dL or to strict normalization of blood glucose levels (80-120 mg/dL) with the use of insulin infusion (group 2).

Results

Patients in group 1 (n = 169) received 2 (0-6.5) units of regular insulin per day, whereas patients in group 2 (n = 168) received 52 (35-74.5) units per day (P < .001). The median blood glucose level was 144 mg/dL in group 1 and 133.6 mg/dL in group 2 (P = .003). Hypoglycemia occurred in 6 (3.5%) patients in group 1 and 27 (16%) in group 2 (P < .001) and was an independent risk factor for neurological dysfunction and mortality.

Conclusions

A carbohydrate-restrictive strategy reduced significantly the incidence of hypoglycemia in critically ill patients compared to intensive insulin therapy. Mortality and morbidity were comparable between the 2 groups.     

Emergency Department Vancomycin Use: Dosing Practices and Associated Outcomes

Background

Emergency Department (ED) dosing of vancomycin and its effect on outcomes has not been examined.

Study Objective

To describe current vancomycin dosing practices for ED patients, focusing on patient factors associated with administration, dosing accuracy based on patient body weight, and clinical outcomes.

Methods

Single-center, retrospective cohort study of vancomycin administered in the ED over 18 months in an academic, tertiary care ED. Data were collected on 4656 patients. Data were analyzed using a generalized estimating equations model to account for multiple doses being administered to the same patient.

Results

The ED dose was continued, unchanged, in 2560 admitted patients (83.8%). The correct dose was given 980 times (22.1%), 3143 doses (70.7%) were underdosed, and 318 were overdosed (7.2%). Increasing weight was associated with underdosing (adjusted odds ratio 1.52 per 10 kg body weight, p < 0.001). Patients who received doses of vancomycin > 20 mg/kg had longer hospital length of stay (p = 0.005); were more likely to spend ≥ 3 days in the hospital (odds ratio [OR] 1.49; 95% confidence interval [CI] 1.12–1.98, p = 0.006); and more likely to die (OR 1.88; 95% CI 1.22–2.90, p = 0.004).

Conclusion

In this largest study to date examining ED vancomycin dosing, vancomycin was commonly given. Dosing outside the recommended range was frequent, and especially prevalent in patients with a higher body weight. The ED dose of vancomycin was frequently continued as an inpatient, regardless of dosing accuracy. There is significant room for improvement in dosing accuracy and indication. Vancomycin dosing in the ED may also affect clinical outcomes.     

Relation of uric acid and contrast-induced nephropathy in patients undergoing primary percutaneous coronary intervention in the ED

Objectives

To investigate the predictive role of serum uric acid (SUA) levels measured in the emergency department (ED) to monitor contrast-induced nephropathy (CIN) and correlation with severity of nephropathy in patients undergoing primary percutaneous coronary intervention (PCI).

Method

The patients who were admitted to our ED and underwent primary PCI were enrolled retrospectively. Their baseline characteristics including SUA and creatinine levels in the ED and their creatinine levels 48 hours after PCI were noted. Nephropathy was graded as follows: grade 0, ΔCr ≤ 25% and ≤ 0.5 mg/dL; grade 1, ΔCr > 25% but ≤ 0.5 mg/dL; and grade 2, ΔCr > 0.5 mg/dL. A multiple logistic regression analysis was used to define the independent predictors of CIN.

Results

Of a total of 744 patients, CIN was observed in 12.5% (n = 93). Serum uric acid levels were significantly higher in the CIN (+) group compared with the CIN (−) group (6.09 ± 2.01 mg/dL vs 4.89 ± 1.32 mg/dL, respectively; P < .001). Patients with grade 0 CIN had significantly lower SUA levels than did those with grades 1 and 2 (4.89 ± 1.32 mg/dL vs 5.88 ± 1.99 and 6.41 ± 2.02 mg/dL, respectively; P < .001), but there was no significant difference between grade 1 and grade 2 CIN cases in terms of SUA levels (5.88 ± 1.99 mg/dL vs 6.41 ± 2.02 mg/dL, P = .10). The cutoff value for SUA was 5.05 mg/dL for the prediction of CIN (area under the curve, 0.685; P < .001; sensitivity, 66%; specificity, 60%) in the population.

Conclusions

The SUA level is a simple independent early predictor of CIN in patients who underwent primary PCI, and early detection may help prevent the progression of CIN.