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Heparin errors continue despite prior fatal events

[black small square] As many as 17 infants in a Texas hospital neonatal intensive care unit (NICU) recently received heparin overdoses. Two infants-premature twins-have since died, although their deaths haven't been definitively linked to the errors. The other infants are in stable condition or have been discharged to home.


The erroneously prepared heparin products were administered to infants in the NICU. Nurses discovered the error after investigating unexpected abnormalities during routine blood testing on several infants.


Families with infants involved were informed about the error. Although the hospital's press releases note that the error was unrelated to product labeling or packaging, it appears that the infants received as much as 100 times more heparin than intended. Based on an analysis of neonatal heparin dosing errors in other facilities, a potential causative factor for this type of error could be a failed verification process. These errors have been attributed to: 1) inadequate staffing, training, or documentation of compounding, 2) environmental factors, or 3) simple human error, which could have been detected if bar code technology had been employed.


Studies on the use of heparin to maintain patency of venous and arterial lines in neonates yield conflict ing data. Without definitive data about the safest and most efficacious practice for maintaining line patency, various protocols are currently being utilized for otherwise similar neonatal patients. Moreover, without a standard protocol, few manufacturers have been willing to offer premixed neonatal heparin products. More recently, preservative-free prefilled heparin flush syringes have been made available in 1 unit/mL, 2 units/mL, 10 units/mL, and 100 units/mL concentrations, which should help reduce the risk of pharmacy or nursing compounding errors when syringes are needed. To reduce the risk of confusion between various concentrations of heparin in similar-looking vials, some hospitals use a prefilled syringe of preservative-free heparin 100 units/mL (500 units/5 mL) to prepare flushes. Heparin is also administered to neonates via continuous infusion through an umbilical vein or artery, but no premixed solutions with low concentrations of heparin are commercially available for this use.


Source: Institute for Safe Medication Practices. Heparin errors continue despite prior, high-profile, fatal eve nts. Available at: Accessed August 20, 2008.


Epidural-I.V. route mix-ups: Reducing the risk of deadly errors

[black small square] A number of risks have been associated with epidural injections and infusions. One of the most significant risks involves erroneous infusions of epidural medications-particularly epidural infusions containing bupivacaine-by I.V. route of administration. I.V. bupivacaine can quickly lead to cardiotoxicity. A Black Box warning for bupivacaine notes that the drug can cause profound disturbances in cardiac rhythm and contractility that are resistant to typical resuscitation efforts, making these mix-ups particularly deadly. Likewise, medications intended for I.V. administration-particularly morphine and vincristine-have been administered via the epidural or intrathecal route, also leading to fatal outcomes.


The National Patient Safety Agency and British news media recently published information about a young woman who died after receiving I.V. bupivacaine. In this case, the woman should have received normal saline I.V., but a nurse accidentally selected a virtually identical bag of bupivacaine located in the same unlocked drawer as the saline. Because the nurse thought she was hanging a bag of normal saline, she had no reason to consider asking another nurse to double-check the solution before administering it. The patient developed seizures and cardiac arrest.


Unfortunately, these cases are not isolated events. Between 2000 and 2004, three additional deaths were reported in the United Kingdom following I.V. administration of epidural bupivacaine. Between 2005 and 2006, another six events were reported in which epidural medications were given I.V. In the United States, three additional cases between 2004 and 2007 resulted in one fatality and two near fatalities. In one of the near-fatal cases, the patient received a small I.V. loading dose of bupivacaine and morphine intended for epidural patient-controlled analgesia. Multiple cases in which I.V. medications, such as vincristine, were accidentally administered by the intrathecal route, again leading to fatalities, were also published.


Unlike many threats to patient safety, those involving epidural-I.V. mix-ups are well understood and can be prevented by industry changes to make I.V. and epidural syringe and tubing connections incompatible with each other. Institute for Safe Medication Practices and other safety agencies, both in the United States and internationally, continue to work toward that goal.


Source: Institute for Safe Medication Practices. Epidural-IV route mix-ups: Reducing the risk of deadly errors. Available at: Accessed August 20, 2008.


Vasopressin added to epinephrine doesn't improve CPR outcome

[black small square] Physicians in France report that the combination of vasopressin and epinephrine is no more effective than epinephrine alone during advanced cardiac life support for out-of-hospital cardiac arrest.


Investigators conducted a prospective, multicenter clinical trial comparing the two treatment regimens. The study cohort included adult patients with out-of-hospital cardiac arrest presenting with ventricular fibrillation, pulseless electrical activity, or asystole requiring vasopressor therapy during CPR. Settings included small and large cities and rural areas.


According to their report in The New England Journal of Medicine, patients were randomly assigned "to receive successive injections of either 1 mg of epinephrine and 40 international units of vasopressin or 1 mg of epinephrine and saline, followed by administration of the same combination of study drugs if spontaneous circulation wasn't restored and subsequently by additional epinephrine if needed."


Outcomes didn't differ significantly between the 1,442 patients who received the combination treatment and the 1,452 who received epinephrine alone.


Specifically, the two groups had a similar percentage of patients who survived to hospital admission or to hospital discharge. Moreover, return of spontaneous circulation, 1-year survival, and neurologic recovery weren't affected by treatment group.


Even among patients with a better prognosis-those with witnessed cardiac arrest, immediate CPR, initial ventricular fibrillation, or return of spontaneous circulation after a single administration of study drugs-combination treatment wasn't superior to monotherapy with epinephrine.


Source: Reuters Health. Vasopressin added to epinephrine doesn't improve CPR outcome. Available at: Accessed August 20, 2008.


Intravenous quercetin significantly reduces mortality in STEMI

[black small square] Intravenous quercetin reduces infarct size, improves left ventricular function, and significantly lowers cardiac mortality in patients with ST-segment elevation myocardial infarction (STEMI), according to a prospective, randomized study presented at the Heart Failure 2008 Congress.


The main inclusion criteria for this study were patients aged 21 years or older who were admitted to the hospital within 12 hours of onset of STEMI symptoms and who had Killip ranking of class II or III and a left ventricular ejection fraction (LVEF) <=40%. The main exclusion criteria were for standard comorbidities, including decompensated diabetes and severe renal insufficiency (serum creatinine >=265 mcmol/L).


Nearly all 57 patients enrolled were receiving antiplatelet (100%), heparin (99%), and beta-blocker (98%) therapy, with 76% also on acetylcholine esterase inhibitors. Patients were randomized to receive either placebo (n = 32; mean age, 55.5 years; men, 93.7%) or the quercetin I.V. infusion (n = 25; mean age, 57.3 years; men, 96.0%) over 5 days, with quercetin started at least 30 minutes before reperfusion.


There were no significant differences in baseline clinical characteristics across the treatment groups, including echocardiography. Patients exhibited similar peak levels of creatine kinase (CK), muscle and brain (MB), and time to peak of CK-MB; the treatment groups were thus similar for baseline infarct size.


Following calculations for mass of myocardial necrosis, there was a significant 25% reduction seen between control and quercetin-treated patients. This was seen as a significant shortening of the CK-MB normalization times (43.1 hours versus 30.2 hours; P < 0.05).


From a median baseline LVEF of 34.5% across all patients, by day 10 the quercetin group saw a significant 21.8% increase in LVEF (P < 0.01); the increase in the placebo group of 11.3% didn't reach significance over this baseline. Similarly, at median follow-up of 6.7 years, the patients in the quercetin group showed a significantly reduced primary end point of cardiovascular death at 120 months (P = 0.04 versus placebo).


Source: Berrie C. Intravenous Quercetin Significantly Reduces Mortality in STEMI: Presented at HF2008. Available at: Accessed August 20, 2008.


Rolofylline reduces congestion, improves renal function

[black small square] Researchers report that infusions of the adenosine A1 receptor antagonist rolofylline are safe and can provide significantly improved renal function and reduced death and rehospitalization of patients hospitalized for acute heart failure (AHF) requiring diuretics.


Researchers conducted a pilot phase study of an ongoing study to assess the treatment effect on congestion and renal function. The study enrolled patients who were 18 years or older, had at least a 14-day history of AHF, and continued to require I.V. diuretics. Patients had impaired renal function (creatinine clearance 20 to 80 mL/min) and systolic blood pressure more than 95 mm Hg.


Among 301 patients with AHF with renal impairment and volume overload, 78 patients were randomized to receive placebo (mean age, 70 years; men, 72%), 74 patients to rolofylline 10 mg (mean age, 69 years; men, 58%), 75 patients to rolofylline 20 mg (mean age, 72 years; men, 53%), and 74 patients to receive rolofylline 30 mg (mean age, 72 years; men, 54%). The patients' clinical and medication baselines were similar across the four treatment groups.


For the primary end point, increasing success was associated with increasing rolofylline dose (nominal P < 0.05 for dose-related trend at day 14). At 24 hours, dyspnea improved by 51% in the placebo group and in the rolofylline groups by 62% (10 mg), 63% (20 mg), and 66% (30 mg). Serum creatinine changes to day 14 also reached significant benefit: +0.21, +0.13, +0.03, and -0.04 mg, respectively (placebo versus rolofylline 30 mg, P < 0.05). Failure rates were 33%, 32%, 24%, and 19%, respectively, providing a trend in the placebo versus rolofylline 30 mg hazard ratio of 0.55 (95% confidence interval, 0.28 to 1.04).


For safety, the rates of adverse reactions were similar across the treatment groups, and no seizures occurred.


Source: Berrie C. Rolofylline Reduces Congestion and Improves Renal Function for Patients Hospitalised With Acute Heart Failure and Volume Overload: Presented at HF2008. Available at:, Accessed August 20, 2008.