Heparin Syringes Research Articles

Comparison of Liquid Sodium Heparin Syringe and Preheparinised Syringe for Sample Rejection in Arterial Blood Gas Analysis: A Cross-sectional Study

Introduction: In hospital settings, Arterial Blood Gas (ABG) analysis is a routine investigation. Many errors can arise in the process, with 70% of errors in ABG analysis occurring during the preanalytical phase. Liquid heparin is commonly used as an anticoagulant in sample collection devices for Blood Gas (BG) analysis; however, inadequate heparin concentration and improper mixing of blood samples after collection often lead to incorrect results. This can be prevented by using syringes preloaded with lyophilised heparin. Aim: To monitor the prevalence of sample rejection collected by the device using liquid sodium heparin and calcium-balanced dried lithium heparin. Materials and Methods: This cross-sectional study was conducted at the ABG laboratory, Department of Biochemistry, Amrita Institute of Medical Sciences and Research Centre, Amrita Viswavidyapeetham University, Kochi, Kerala, India over a 4-month period from December 2022 to March 2023. ABG samples collected using either of the techniques were included, while venous BG samples were excluded. The sample size was 10,957 for each of the two groups- Group A and Group B. Group A included samples collected using liquid sodium heparin, and group B included spray-dried, calcium-balanced lithium heparin from different departments. The incidence of blood clots, air bubbles, and inadequate volume was studied. For all categorical variables, the results were expressed as the frequency and percentage of errors. An unpaired t-test (two-tailed) was used for data analysis. Results: In comparison with liquid sodium heparin collection, errors in the quality of the specimen such as blood clots (1.7% to 1.1%), air bubbles (0.04% to 0%), and inadequate volume (0.2% to 0.03%) were significantly reduced (p-value=0.002) with spray-dried, calcium-balanced lithium heparin (BD Preset™ Safety BG Syringe). Conclusion: The present study found that using calcium- balanced lithium heparin syringes over manually flushed liquid sodium heparin syringes reduces the risk of clots, thus preventing equipment malfunction and maintenance costs. With the introduction of preset syringes, the chance of air bubbles and insufficient volume can also be overcomed.

Comparison of arterial blood gas results obtained using two types of Heparinized Syringes

Objective: The objective of this study was to compare the arterial blood gas results obtained using syringes heparinized with liquid heparin and syringes containing lyophilized balanced heparin. Study Design: Comparative cross sectional. Place and Duration: This study was conducted in the Chemical Pathology department at Combined Military Hospital, Lahore for a period of six months from November 2022 to March 2023. Methodology: A total of 100 arterial blood samples were taken from 50 patients admitted in ICU using a regular plastic syringe flushed with 5000 IU/ mL liquid heparin and another containing lyophilized heparin. Samples were analyzed immediately after collection on Roche Cobas b121 ABG analyzer. Three of the measured parameters (pH, pCO2 and pO2) were then compared among both syringe groups. pH, pO2 and pCO2 were compared using mean difference. Results: The difference of means for pH was insignificant (p- Value >0.05). But pCO2 and pO2 showed significant difference in means with p- Values <0.05 (0.007 and 0.037, respectively). Bland Altman plots were also plotted for all three parameters. 12% of the pH values, 8% pco2 and 6% pO2 values exceeded the total allowable error. Conclusion: Arterial blood pH was comparable between the two types of syringes used. The pCO2 and pO2 differed significantly and where found to be lower in blood samples collected in the liquid heparin syringes. Keywords: Liquid Heparin, Lyophilized Heparin, Arterial Blood Gas, pH, pO2, pCO2. How to Cite This: Mahmood A, Sattar A, Shaheen S, Ahmad S, Hafeez A. Comparison of arterial blood gas results obtained using two types of Heparinized Syringes. Isra Med J. 2022; 14(4): 161-164. DOI: https://doi.org/10.55282/imj.oa1379

Production of Modified Autologous Conditioned Serum and Ex Vivo Assessment of Its Healing Potential in Murine Corneal Epithelium.

Human blood-derived topical therapies have been a boon to clinicians in recent decades. Autologous serum (AS) and platelet-rich plasma (PRP) are enriched in epitheliotropic growth factors that are essential in corneal wound healing. Unlike AS, PRP is based on a differential centrifugation system, yielding more platelet-derived growth factors. Autologous conditioned serum (ACS) not only preserves the preparation of AS and PRP, but also focuses on immune-modulating properties, which are important in inflammatory diseases. The lack of standardized protocols and high preparation costs are limitations for the clinical application of ACS. This video experiment demonstrates a standard operating procedure for preparing modified autologous conditioned serum (mACS) eye drops. First, glycerol was added into heparin syringes as the blood cell stabilizer during hypoxic incubation. To activate the blood cells, a 4 h incubation at 37 °C was initiated. Then, the blood samples were centrifuged at 3,500 × g for 10 min at room temperature. After filtration of the supernatant through a 0.22 µm filter, the mACS eye drops were fully prepared. A tentative try-out of the therapeutic effect of mACS showed that it may have competitive advantages over conventional AS in the corneal wound healing in ex vivo mouse eyes. The AS used in this study was prepared according to published studies and the clinical practice in our hospital. Therefore, the efficacy of mACS on ocular surface diseases could be evaluated in future research through in vivo animal studies and clinical trials.

Sample stability and heparin interference in ionized calcium and ionized magnesium measurements in horses using the Stat Profile Prime Plus co-oximetry electrolyte analyzer.

The determination of iCa and iMg is important in veterinary medicine, but their immediate determination in whole blood is not always possible. Their stability in other sample types and the existence of interferences must be evaluated before its use. We aimed to analyze the effects of storage time on the stability of iCa, iMg, and other analytes in whole blood, plasma, and serum samples in horses and assess the interference of heparin in these measurements. Whole blood, heparin-plasma, and serum samples from 10 horses were stored at 4°C and analyzed 1, 2, 3, 4, 5, 6, 7, 8, 24, 48, and 168 hours after sample collection using the Stat Profile Prime Plus Vet equipment (Nova Biomedical, Waltham, MA, USA). Results were analyzed by ANOVA or mixed-effect models. The concentration of iCa, iMg, total calcium (tCa), total magnesium (tMg), and the ratios iCa/tCa and iMg/tMg did not differ up to 168 hours when compared to the initial time. Total Ca, iMg, and tMg were not significantly different among sample types, but iCa concentrations were slightly but significantly lower in plasma. Freezing at -20°C did not affect iCa, iMg, tCa, and tMg. The pH increased in serum and plasma after 8 hours, and a mild negative correlation existed between plasma iCa concentration and pH. A negative correlation was observed also between the ratios iCa/tCa or iMg/tMg and pH in plasma and serum. A significant decrease in iCa and iMg was detected when comparing homemade syringes at high heparin concentration (~200-300 U heparin/mL) and commercial lithium-heparin tubes (20-30 U/mL). Samples stored at 4°C can be used to determine iCa and iMg concentrations up to 7 days after collection. Other metabolites are stable for up to 8 hours; heparin interference should be taken into account if using homemade heparin syringes.

Using Residual Blood from the Arterial Blood Gas Test to Perform Therapeutic Drug Monitoring of Vancomycin: An Example of Good Clinical Practice Moving towards a Sustainable Intensive Care Unit.

Regarding sustainability in the intensive care unit (ICU), there is increasing interest in reducing material waste and avoiding unnecessary procedures. Therapeutic drug monitoring (TDM) of vancomycin, using a dedicated tube, is standard clinical care during treatment with vancomycin. Furthermore, in the ICU, on a daily basis, arterial blood gas (ABG) tests are frequently performed throughout the day. After analysis, a variable volume of blood is discarded. Lithium heparin (LiHep) syringes for ABG tests differ from normally used dipotassium ethylenediaminetetraacetic acid (K2EDTA) tubes. The primary objective was to compare both containers and validate the use of LiHep syringes. Secondary objectives were to evaluate the potential impact on saving materials, nursing time, and costs when implementing vancomycin TDM via LiHep syringes. Vancomycin analysis from sampling in lithium heparin (LiHep) syringes for ABG tests was validated and compared with the concentrations from conventional sampling in K2EDTA tubes. For method comparison, a Bland-Altman plot and Deming regression analysis were performed. The method was validated for inter- and intra-day precision and accuracy. Vancomycin was analyzed by means of the validated method using a particle-enhanced turbidimetric inhibition immunoassay (PETINIA) autoanalyzer. Furthermore, an analysis was conducted to evaluate the potential impact of implementing vancomycin sampling via ABG tests on savings in materials, nursing time, and costs. From 18 patients, 24 plasma samples in both K2EDTA tubes and LiHep syringes were obtained and compared. The mean relative difference between the two containers was -2.0% (-3.0 to -0.93%). Both the Deming regression analysis and the Bland-Altman plot met the acceptance criteria. Potentially, over 1000 blood draws and accompanying materials and packaging can be saved when vancomycin samples are obtained by means of scavenged LiHep syringes. The vancomycin analysis for LiHep syringes showed a total interday precision of 1.95% and an accuracy of 99.7%. The total intraday precision was 2.22%, and the accuracy was 99.2%. Accuracy and precision values were within the acceptance criteria of recovery 85 to 115% and ≤15%, respectively. No significant differences were found in vancomycin concentration between the two analyses, and the LiHep analysis was validated for further implementation in clinical care. Residual blood from ABG test samples can be used for TDM of vancomycin, resulting in a potential reduction of materials used and the number of blood draws. These results will contribute to a more sustainable TDM process with benefits for the patient.

Improvement of Umbilical Cord Blood Gas Analysis with Implementation of Clot Catchers.

Umbilical cord blood gas testing is a key component of objective pre- and perinatal evaluation of fetal acid base status to determine presence of intrapartum asphyxia and risk of neonatal encephalopathy. Heparinized cord blood is more likely to form small clots than other blood sources, which can interfere with, or preclude, sample analysis. Cord blood samples are irreplaceable and cannot be recollected, thereby compromising clinical decision-making when analysis is not possible. We evaluated processes to prevent excessive rates of cord blood clotting and quantified their impact on successful testing of blood gas specimens. Verified result and cancellation data were obtained retrospectively from the laboratory information system. Clot catchers were evaluated using noncord remnant specimens. Collection syringes were compared via collection from remnant cord sections. Prior to implementation of any interventions, retrospective analysis indicated a cancellation rate of 18.6% for umbilical cord blood gas specimens (arterial and venous) and 0.7% for noncord blood arterial and venous samples. Clot catchers were validated for clinical use, with a bias of <±4% for all analytes. After clot catchers were implemented for all cord specimens, cancellation rate decreased approximately 5-fold in the first month and remained <5% a year after implementation. A limited comparison of two heparin syringe types revealed a small difference in the overall rate of specimen clotting. Implementation of clot catchers was acceptable for analysis of cord blood samples, and when implemented resulted in a sustained 5-fold decrease in the rate of cord blood gas order cancellation.

Evaluation of heparinized syringes for measuring newborn metabolites in neonates with a central arterial line

Newborn metabolic screening is emerging as a novel method for predicting neonatal morbidity and mortality in neonates born very preterm (<32 weeks gestation). The purpose of our study was to determine if blood collected by an electrolyte-balanced dry lithium heparin syringe, as is routine for blood gas measurements, affects targeted metabolite and biomarker levels. Two blood samples (one collected with a heparinized syringe and the other with a non-heparinized syringe) were obtained at the same time from 20 infants with a central arterial line and tested for 49 metabolites and biomarkers using standard procedures for newborn screening. Overall, the median metabolite levels did not significantly differ by syringe type. However, there was wide variability, particularly for amino acids and immunoreactive trypsinogen, for individual paired samples and therefore, consideration should be given to sample collection when using these metabolites in prediction models of neonatal morbidity and mortality.

Comparing the Liquid Heparin Syringe with Dry Bound Heparin Syringe for Blood Gas Analysis

Abstract Background Blood gas (BG) analysis is routine today for patient management in intensive care units. Accurate analysis of different parameters in the BG is essential for managing critical patients. Errors in BG analysis can happen at many levels, with one of them being at sampling and heparinization. We compared self-prepared heparinized syringes rinsed with liquid heparin (LH) and the standard commercially available syringes with dry bound heparin (DBH) for arterial BG analysis of postoperative cardiac surgical patients. Methods This prospective observational study was conducted in 100 consecutive adult cardiac surgical patients in the cardiac surgical intensive care unit. Paired samples were collected, analyzed immediately, and statistically compared for pH, partial pressure of arterial oxygen (pO2), partial pressure of arterial carbon dioxide (pCO2), oxyhemoglobin saturation (SaO2), HCO, Na+, K+, Cl–, Ca2+, Mg2+, base excess (BE), hemoglobin (Hb), hematocrit, glucose, and lactate. Paired parameters were compared and agreement was evaluated using Bland–Altman difference plots. The 95% limits of absolute agreement (LOA) were compared with total allowable error (TEa). Results The BG parameters analyzed by two types of heparinized (LH and DBH) syringes were found to be comparable with a negligible mean difference and had an agreement outside the TEa of 8% for pO2, pCO2, and hematocrit, 7% for BE, 6% for Mg2+, 5% for K+, Ca2+, and lactate, 4% for HCOand Na+, 3% for pH, Cl–, Hb, and glucose, and zero for SaO2. The two types of syringes did not show clinically relevant discrepancies among many different parameters as per LOA and TEa limits. Conclusion In this study, we found that the BG parameters—respiratory, metabolic, and electrolytes—were comparable between the two types of syringes used for sampling. Unlike some previous studies, we did not find statistically significant differences among these analytes, which might have been due to appropriate self-preparation of heparin syringes.

Comparison of blood gas results collected in a ‘low heparin’ and ‘electrolyte balanced’ syringe with samples collected in a ‘plain syringe’

Introduction: Blood gas samples require heparin to prevent clotting of samples prior to analysis on a blood gas analyser. Heparin binds cations, decreasing Results for free calcium and sodium. There are two approaches: minimising the amount of heparin used, a ‘low heparin syringe’; or adding electrolytes to compensate for the heparin binding, ‘electrolyte balanced syringe’.

The effect of different forms of heparin on point-of-care blood gas analysis

Background. Point-of-care blood gas analysis plays an integral role in the management of critically ill and injured patients presenting to the emergency department (ED). While the use of specially manufactured syringes containing electrolyte-balanced dried heparin is recommended when processing these specimens, alternatives including manually self-prepared syringes washed with liquid heparin or heparin vacutainers are still often used. Objectives. To assess the effect of two concentrations of liquid heparin and the use of heparin vacutainers on the reliability of blood gas analysis results compared with the recommended standard of dried heparin syringes in the ED setting. Methods. Blood samples were drawn from 54 patients attending a tertiary-level hospital ED. Individual samples were distributed equally among each of four different collection devices: a dried heparin syringe, self-prepared syringes washed separately with 1 000 IU/mL and 5 000 IU/mL liquid heparin, and a heparin vacutainer. Results obtained from the standard dried heparin syringes were compared with those from the other three methods. Results. For both the liquid heparin cohorts, partial pressure of carbon dioxide (pCO2), potassium (K + ), sodium (Na + ), ionised calcium (iCa 2+ ) and haemoglobin had &gt;20% of results falling beyond the total allowable error. iCa 2+ and K + results were most affected in the 5 000 IU/mL cohort and iCa 2+ and Na + in the 1 000 IU/ml cohort. pCO2, pH and iCa 2+ were the most significantly affected in the heparin vacutainer cohort. Conclusions. Use of liquid heparin can result in significant negative bias in the majority of blood gas analytes, especially electrolytes. Heparin vacutainer use can result in unacceptable variations in the respiratory analytes. While standard dried heparin syringes may not always be available, it is of vital importance that practitioners be aware of these biases and limitations when using substitutes.

The effect of different forms of heparin on point-of-care blood gas analysis.

Point-of-care blood gas analysis plays an integral role in the management of critically ill and injured patients presenting to the emergency department (ED). While the use of specially manufactured syringes containing electrolyte-balanced dried heparin is recommended when processing these specimens, alternatives including manually self-prepared syringes washed with liquid heparin or heparin vacutainers are still often used. To assess the effect of two concentrations of liquid heparin and the use of heparin vacutainers on the reliability of blood gas analysis results compared with the recommended standard of dried heparin syringes in the ED setting. Blood samples were drawn from 54 patients attending a tertiary-level hospital ED. Individual samples were distributed equally among each of four different collection devices: a dried heparin syringe, self-prepared syringes washed separately with 1 000 IU/mL and 5000 IU/mL liquid heparin, and a heparin vacutainer. Results obtained from the standard dried heparin syringes were compared with those from the other three methods. For both the liquid heparin cohorts, partial pressure of carbon dioxide (pCO2), potassium (K+), sodium (Na+), ionised calcium (iCa2+) and haemoglobin had &gt;20% of results falling beyond the total allowable error. iCa2+ and K+ results were most affected in the 5 000 IU/mL cohort and iCa2+ and Na+ in the 1 000 IU/ml cohort. pCO2, pH and iCa2+ were the most significantly affected in the heparin vacutainer cohort. Use of liquid heparin can result in significant negative bias in the majority of blood gas analytes, especially electrolytes. Heparin vacutainer use can result in unacceptable variations in the respiratory analytes. While standard dried heparin syringes may not always be available, it is of vital importance that practitioners be aware of these biases and limitations when using substitutes.

Progressive Pulmonary Hypertension and Lung Nodules Related to Intravenous Promethazine and Heparin Incompatibility.

SESSION TITLE: Miscellaneous SESSION TYPE: Global Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: This case describes a patient who had progressive embolic pulmonary hypertension and nodular lung disease related to intravenous heparin and promethazine drug incompatibility. CASE PRESENTATION: A 46-year-old woman with chronic relapsing pancreatitis under the supervision of a pain management specialist used self-administered promethazine injections through an implanted mediport at home. She presented to the hospital with abdominal pain, slowly progressive dyspnea on exertion, and a dry cough. Lab work demonstrated elevated liver function tests and CRP. Her chest x-ray showed borderline cardiomegaly and increased interstitial markings with reticular nodular opacities. CT angiography of the chest was negative for PE, but did confirm widespread poorly marginated small nodular densities as well as mild adenopathy. Bronchoscopy with BAL and wash was non-diagnostic. Her echo demonstrated an RVSP of 64 and a right heart catheter later confirmed moderate pulmonary HTN. Further lab workup for pulmonary HTN was negative. Pulmonary function testing showed restrictive disease with a reactive component. She required oxygen with exertion at discharge and was seen in close outpatient follow up for additional workup. Ten weeks later she was readmitted for symptom management of her severe abdominal pain. She denied any shortness of air or cough at that point in time. Repeat CT of the abdomen prompted chest imaging that demonstrated progressive widespread milliary nodular pattern of both lungs with progressive adenopathy. Echo demonstrated slight worsening of pulmonary hypertension. VATS was completed for surgical lung biopsy and pathology demonstrated an exuberant foreign body type reaction to polarizable amorphous foreign material associated with acute inflammation as well as focal microabscess formation. Cultures and stains for infectious organisms were negative. She denied illicit drug use and careful review of her outpatient medications revealed an in-line incompatibility of her IV heparin flushes and promethazine injections. MicroMedex IV compatibility listed the incompatibility as causing an increase in measured haze or turbidity, particulates and/or color change.1 Additional history was obtained and due to lack of readily available normal saline flushes, she had been using prefilled heparin syringes to flush her mediport after injecting promethazine. She was started on high dose prednisone that was slowly tapered over several months with normalization of her pulmonary hypertension on follow up echo. Follow up CT imaging demonstrated resolution of her adenopathy and improvement but incomplete resolution of her nodular airspace disease. DISCUSSION: The patient had been self-administering IV promethazine for nausea via an implanted port often several times per day. Her insurance company had only authorized a small allotment of prefilled saline syringes per month, but had provided a much larger allotment of prefilled heparin syringes for her to use for line maintenance. Due to this discrepancy, she would often use the more readily available heparin syringes as opposed to saline to flush her line after a promethazine dose. Incompatibility between IV promethazine and heparin led to precipitate formation that then embolized in the pulmonary circulation causing progressive pulmonary hypertension as well as diffuse micronodular airspace disease noted on CT. A progressive inflammatory reaction likely potentiated the progressive nodule growth. Treating the patient with steroids was successful in halting the inflammation and partial reversal of the disease process. Proper education about line maintenance and use of saline flushes prevented ongoing embolization. CONCLUSIONS: This case demonstrated the in-line incompatibility of IV promethazine and heparin had significant embolic effects on the pulmonary circulation. Obtaining a thorough history regarding utilization of home medications ultimately led to the diagnosis. Detailed attention as well as appropriate education and monitoring should be given to patients who self-administer IV medications via mediports. Reference #1: Truven Health Analytics MicroMedex IV compatability checker DISCLOSURE: The following authors have nothing to disclose: David Hasselbacher, Rebecca Parrish, Emma Coronel No Product/Research Disclosure Information

To heparinize or not to heparinize: Effect on arterial blood gas measurements

The most useful of investigations should be rapid and easy to perform, give reliable results and influence management decisions. The arterial blood gas goes a long way toward fulfilling the above needs. The utility of the arterial blood gas has been enhanced by the additional information provided by modern analyzers, including the plasma electrolytes, anion gap, ionized calcium and plasma lactate.[1] Its continuing reliability is dependent upon recognition of changes in the normal values with changes in the methods and technology employed for measurement. Samples not analyzed at the point of care require anticoagulation albeit in very small quantities, viz heparin 1 U/ml. The ideal anticoagulant would be dry, free of interference in laboratory tests, inexpensive and completely reliable as an anticoagulant.[2] The International Federation of Clinical Chemistry recommend for blood gas sampling, filling up of the dead space of the syringe with heparin, to lubricate the inner wall of the syringe, to expel the excess anticoagulant and to collect at least 20 times the dead space volume of blood.[3] In actual fact preanalytical sample handling is estimated to account for 75% of the errors in blood gas analysis.[4] In the study by Chhapola et al.[5] in this issue of the Journal examines an important aspect of arterial blood gas measurement, namely the influence on the various parameters of the type of heparin, dry balanced vs. liquid in the preparation of the sample. Dry balanced heparin is “electrolyte balanced,” (containing Lithium and Zinc rather than sodium or calcium) to prevent interference with the numerous electrolytes and other parameters estimated.[4] Heparin has two different effects on blood gas samples based on its intrinsic chemical properties and a dilution of the sample. As heparin dilutes mainly the plasma phase of the blood sample the magnitude of the dilution of a 1 ml blood sample by 0.05 ml of liquid heparin may be around 10%.[4] The authors have painstakingly prepared liquid heparin syringes with meticulous attention to detail regarding the pH, Na + and pO2 content of the heparin available in an attempt to standardize the technique. Further strengths of the study include a single needle prick for sampling with both syringes that minimized sampling differences. duplicate analysis of each sample giving a coefficient of variation of 1%, point of care analysis and achieving a sample size larger than calculated for pCO2. The authors however as stated did not measure ionized calcium a parameter previously shown to be influenced by various preparations of heparin.[2]

Use of liquid heparin for blood gas sampling in pediatric intensive care unit: A comparative study of effects of varying volumes of heparin on blood gas parameters

Background and Aims:Pre-analytical errors in sample collection affect the reliability of blood gas (BG) analysis. Amount of liquid heparin as anticoagulant in samples for BG can affect results by its dilutional direct binding and compositional effects. The aim of this study was to examine the effect of varying amounts of heparin in blood samples on results.Materials and Methods:The prospective study was conducted on 15 children at a pediatric intensive care unit (PICU). Three different heparinized syringes were used containing minimal, 60 IU and 120 IU of heparin. A total volume of 1 ml blood in each syringe was taken and was analyzed by blood gas analyzer. Statistical analysis used related samples Friedman's test and Wilcoxon signed ranks test for paired comparisons. The observed bias was also compared with the desirable bias according to specifications by Ricos et al.Results:There was a significant difference (P < 0.05) in values of pH, pCO2, HCO3−, Hb and Na+ in the three syringes. The pCO2, HCO3− and Na+ levels decreased with the increasing amount of heparin. The observed percentage bias was more than desirable percentage bias specifications for pCO2, HCO3−, Hb, Na+, K+ and Cl− levels.Conclusions:Syringes with minimal liquid heparin are most appropriate for studying BG parameters as they have the least effect on these parameters. There is a need to standardize the procedure of syringe preparation for BG analysis. Further studies are needed to compare minimal amounts of heparin with commercially available dry balanced heparin syringes.

Association of Plasma Cell-Free Hemoglobin with Physiological Measures of Nitric Oxide Responsiveness and Estimated Pulmonary Artery Systolic Pressure: Requirement for Rigorously Optimized Blood Processing Variables

AbstractAbstract 3253 Background:Accurate plasma hemoglobin (PHb) measurements are needed to investigate a model proposing a link between intravascular hemolysis and decreased nitric oxide (NO) bioavailability in sickle cell disease (SCD). Artifactual hemolysis hypothetically can produce excessive noise that might obscure the signal and lead to misinterpretation of data. We systematically studied possible blood processing variables that could cause artifactual hemolysis to obscure in vivo levels of free hemoglobin in adults with SCD. Methods:We systematically compared the effects on PHb measured by ELISA of anticoagulant type, Vacutainer materials and processing time on the same blood specimens from healthy controls and adults with SCD divided into aliquots that were then processed using a variety of in vitro conditions. We analyzed the results of PHb measurements from archived specimens from 467 SCD patients. We evaluated in greater detail plasma specimens collected and processed at bedside from 44 patients with SCD under optimal conditions: drawn from indwelling wide-bore brachial artery catheters by minimal negative pressure into heparinized syringes, gently transferred to tubes for centrifugation within 5 minutes, evaluating the associations of PHb levels from these optimally processed samples with relevant in vivo physiological measurements. Results:Analysis of specimens from healthy control subjects (n=10) and adults with SCD (n=10) for each experiment, split into aliquots to test each variable under defined conditions yielded significant evidence indicating that: (1) arterial catheter syringe specimens are superior to conventional Vacutainer venipuncture specimens; (2) heparin is superior to EDTA anticoagulant; (3) glass tubes are superior to plastic tubes; (4) processing in 2 hours or less is superior to longer processing times. Comparison of 467 archived EDTA plasma specimens processed under comparably variable conditions provided results consistent with the bench top results, confirming the importance of these processing variables on research specimens. Conventional venipuncture EDTA Vacutainer tubes with conventional processing yielded median PHb levels four-fold that of arterial catheter heparin syringe specimens processed at bedside, suggesting that on average 75% of the PHb in conventional specimens may represent background noise and only 25% of the PHb level may represent in vivo free hemoglobin.Blood specimens were collected and processed by the optimal conditioned defined by the preceding experiments from 44 adults with sickle cell anemia. This set of specimens yielded a median PHb level of 6.07μM (CI95=5.27–7.03μM). PHb correlated significantly with blunting of vasodilation in vivo after brachial artery infusion of each of three graded doses of the NO donor sodium nitroprusside (SNP), an indicator of vascular NO responsiveness; at doses of 0.8μg/min(r=−0.46 p=0.0022), 1.6μg/min (r=−0.41, p=0.0082), and 3.2μg/min (r=−0.46, p=0.0024). Quartile analysis revealed a significant difference in forearm blood flow response across all doses of SNP among the highest, middle, and lowest PHb quartiles (p=0.0386). PHb also correlated significantly with tricuspid regurgitant velocity (R=0.37, p=0.0147), suggesting a significant association with Doppler echocardiography estimates of pulmonary artery pressure. A limited number of patients from this specimen pool (n=7) subsequently underwent clinically indicated right heart catheterization. There was a trend in this small subset correlating PHb with mean pulmonary artery pressure (r=0.61, p=0.1482). Conclusions:Plasma hemoglobin levels collected and processed under optimal conditions show statistically significant associations with in vivo physiological measures of nitric oxide responsiveness and echocardiographically estimated pulmonary artery pressure, with supportive trends from right heart catheterization in a limited subgroup of patients with SCD. This supports a role for plasma hemoglobin as a biomarker of nitric oxide resistance and pulmonary hypertension in SCD. Conventional phlebotomy into Vacutainer tubes introduces a high background level of artifactual ex vivo hemolysis in SCD specimens that is capable of obscuring these associations, especially if processing is delayed 2 hours or more. Disclosures:No relevant conflicts of interest to declare.

Serratia marcescens bacteremia because of contaminated prefilled heparin and saline syringes: A multi-state report

A national outbreak of Serratia marcescens bacteremia because of contaminated prefilled heparin and saline syringes led to their recall. We evaluated the clinical impact of this outbreak in 57 patients at 3 centers. All patients were symptomatic and were treated with intravenous antibiotics with a fatal outcome in 1 patient.

Preventing Outbreaks

Archives of Internal Medicine Multistate Outbreak of Serratia marcescens Bloodstream Infections Caused by Contamination of Prefilled Heparin and Isotonic Sodium Chloride Solution Syringes David Blossom, MD; Judith Noble-Wang, PhD; John Su, MD; Stacy Pur, RN, BSN; Roy Chemaly, MD, MPH; Alicia Shams; Bette Jensen, MMSc; Neil Pascoe, RN, CIC; Jessica Gullion, PhD; Eric Casey, BA; Mary Hayden, MD; Matthew Arduino, PhD; Daniel S. Budnitz, MD, MPH; Isaam Raad, MD; Gordon Trenholme, MD; Arjun Srinivasan, MD; for the Serratia in Prefilled Syringes Investigation Team Group Background To investigate clusters of Serratia marcescens (SM) bloodstream infections (BSIs) at health care facilities in several states and determine whether contaminated prefilled heparin and isotonic sodium chloride solution (hereinafter, saline) syringes from a single manufacturer (company X) were the likely cause, we performed an outbreak investigation of inpatient and outpatient health care facilities from October 2007 through February 2008. Methods Active case finding for clusters of SM BSIs. Information on SM BSIs was obtained, and SM blood isolates were sent to the Centers for Disease Control and Prevention (CDC). Culture specimens were taken from various lots of prefilled heparin and saline syringes by health care facilities and the CDC to test for the presence of SM. The SM isolates from syringes and blood were compared by pulsed-field gel electrophoresis. Results A total of 162 SM BSIs in 9 states were reported among patients at facilities using prefilled heparin and/or saline syringes made by company X. Cultures of unopened prefilled heparin and saline syringes manufactured by company X grew SM. Of 83 SM blood isolates submitted to the CDC from 7 states, 70 (84%) were genetically related to the SM strain isolated from prefilled syringes. A US Food and Drug Administration inspection revealed that company X was not in compliance with quality system regulations. Conclusions A multistate outbreak of SM BSIs was associated with intrinsic contamination of prefilled syringes. Our investigation highlights important issues in medication safety, including (1) the importance of pursuing possible product-associated outbreaks suggested by strong epidemiologic data even when initial cultures of the suspected product show no contamination and (2) the challenges of medical product recalls when production has been outsourced from one company to another.

Preanalytical variables in measurement of free (ionized) calcium in lithium heparin-containing blood collection tubes

Background Measurements of free (ionized) calcium (iCa) are increasingly requested in patient care locations where immediate analysis is unavailable. Evacuated blood collection tubes containing lithium heparin and gel separator material are widely used in clinical laboratories, but little information is available on the effects of these tubes or of delay prior to analysis on the concentration or stability of iCa. Methods We collected blood from volunteers into lithium-heparin tubes (PST, Vacutainer ® PST™, BD Pre-Analytic Systems) of multiple lots and into electrolyte-balanced heparin syringes (Portex ® Dry Heparin, Smiths Medical). iCa was measured (Siemens 1265 blood gas analyzers) immediately and, in PST, at 0–7 h with or without transportation of the tubes from remote sites. Results The mean difference of free calcium results in the PST tubes and electrolyte-balanced syringes was − 0.08 (95% confidence interval − 0.17 to 0.012) mmol/l, and the SD of the residuals (S y, x) of the regression was 0.03 mmol/l. There was no detectable lot-to-lot variation in results. Free calcium was stable in tubes at room temperature and at 4 °C for at least 7 h with or without transportation. Conclusion iCa measured in the examined blood collection tubes is stable and unaffected by lot-to-lot variation of tubes, but results are slightly lower than with special blood gas syringes.

Liquid Heparin Anticoagulant Produces More Negative Bias in the Determination of Ionized Magnesium than Ionized Calcium

The ionized calcium level in blood is known to be falsely decreased when self-prepared liquid heparin anticoagulant is used, due to dilution and binding effects. The effect of liquid heparin on the determination of ionized magnesium is not as well understood. We compared the effect of liquid sodium heparin on the determination of ionized calcium and magnesium in 44 clinical samples using two types of user-prepared heparin syringes which differed in the amount of residual heparin from the BD Preset™ reference syringe. With the type 1 syringe, the liquid heparin was expelled once or twice such that some heparin could be left in the dead space at the syringe hub, while the liquid sodium heparin was thoroughly expelled from the type 2 syringe. The ionized magnesium levels obtained with the type 1 syringe were significantly lower than the reference value (by 0.068 mmol/L) (p < 0.0001), while the value obtained with the type 2 syringe differed less from the reference, by only 0.014 mmol/L (p < 0.0001). The heparin binding effect resulted in more negative bias in ionized magnesium (- 0.026 ± 0.032 mmol/L) than in ionized calcium (- 0.009 ± 0.042 mmol/L, p < 0.0001). In conclusion, we recommend using lyophilized, calcium-balanced, heparinized syringes for the determination of ionized magnesium and ionized calcium due to the increased negative bias in ionized magnesium determinations. When user-prepared syringes are used, the thorough evacuation of heparin solution should be strictly prescribed.

Evaluation of lyophilized heparin syringes for the collection of arterial blood for acid base analysis.

The effects of liquid heparin on the analysis of acid/base status of arterial blood include a reduction in PCO2 and an increase in PO2. A study was performed to compare a lyophilised heparin syringe with a liquid heparin glass syringe for collection of blood for acid/base analysis. No significant difference between the variables measured in blood taken in the two syringes was demonstrated.