Standardized direct oral anticoagulants prescription for treatment of acute venous thromboembolism in the emergency department: A quality improvement initiative.

INTRODUCTION: Direct oral anticoagulants (DOACs) are commonly used for the treatment and prevention of venous thromboembolism (VTE). However, prescription errors with DOACs can lead to patient dissatisfaction and harm. This study aimed to evaluate the impact of a standardized prescription for DOACs for VTE on prescription appropriateness. MATERIALS AND METHODS: The study included patients discharged from the Emergency Department (ED) with a DOAC prescription for an acute VTE. A standardized prescription tool was developed and implemented, and patients were divided into pre- and post-intervention groups. The appropriateness of prescriptions was assessed using the Medication Appropriateness Index (MAI). RESULTS: A total of 161 patients with VTE were included in the study. The post-intervention group showed a significant increase in prescriptions with an MAI rating of "appropriate" and a decrease in ratings of "inappropriate." Improvements were observed in loading dose duration, maintenance dose frequency and duration, and inclusion of necessary drug coverage codes. CONCLUSION: The implementation of a standardized prescription for DOACs in the management of VTE in the ED significantly improved medication appropriateness and reduced inappropriate prescriptions. Standardized prescriptions have the potential to enhance patient safety and optimize care by providing clear and uniform guidance to healthcare providers. Further research is needed to explore the effectiveness of medication prescription software systems in real-world clinical settings to improve prescribing practices.

Two-week pulsatile gonadotropin releasing hormone infusion unmasks dual (hypothalamic and Leydig cell) defects in the healthy aging male gonadotropic axis.

OBJECTIVE: To examine the possibility that lower serum bioavailable testosterone concentrations, without increased LH release, in healthy older men, reflects hypothalamic GnRH deficiency. DESIGN: We used a randomized, double-blind, placebo-controlled design. METHODS: We treated each of five young (ages 20-34 years) and five older (ages 60-78 years) men with 2 weeks of randomized infusions of saline or pulsatile GnRH (100 ng/kg i.v. every 90 min). RESULTS: At baseline (saline infusion), older men had more LH pulses (young compared with old, 10 +/- 0.6 compared with 15 +/- 1, P = 0.0026) per 24h, reduced fractional LH pulse amplitude (219 +/- 17% compared with 167 +/- 40%, P = 0.0376), and more disorderly hormone release as judged by approximate entropy (ApEn) (LH, P < or = 0.0001; testosterone, P < or = 0.0047). In response to pulsatile i.v. GnRH infusions, serum 24-h LH concentrations (measured by immunoradiometric assay (IRMA)), increased equivalently in young and older men (to 7.3 +/- 1.2 and 7.2 +/- 1.8 IU/l respectively). GnRH treatment also normalized LH pulse frequency and amplitude, ApEn, and plasma biologically active LH (pooled) concentrations. In contrast, 24-h testosterone concentrations failed to increase equivalently in older men (young compared with old, 869 +/- 88 compared with 517 +/- 38 ng/dl, P = 0.0061), reflecting lower testosterone peak maxima (995 +/- 108 compared with 583 +/- 48 ng/dl, P = 0.0083) and interpeak nadirs (750 +/- 87 compared with 427 +/- 26 ng/dl, P = 0.0073). CONCLUSIONS: We have demonstrated that, in older men, successful reconstitution of 24-h pituitary (bioactive) LH output and pulsatile (IRMA) LH release patterns could be achieved by a fixed exogenous GnRH pulse signal, thereby implicating altered endogenous hypothalamic GnRH release in the relative hypogonadotropism of aging. The failure of testosterone concentrations to increase concomitantly points to a simultaneous Leydig cell defect. We conclude that aging in men is marked by a dual defect in the central nervous system-pituitary-Leydig cell axis.

Use of different anticoagulants in test tubes for analysis of blood lactate concentrations: Part 2. Implications for the proper handling of blood specimens obtained from critically ill patients.

OBJECTIVES: a) To test the hypothesis that the measurement of the circulating lactate concentration is influenced by the anticoagulant in the test tube that contains the blood sample; b) to test the hypothesis that the measurement of the circulating lactate concentration is influenced by the tissue used for analysis. DESIGN: A prospective, controlled study. SETTING: A critical care research laboratory, a 20-bed intensive care unit (ICU), and the general wards. SUBJECTS: Twenty-three ICU and ward patients with hyperlactatemia and 19 healthy volunteers. INTERVENTIONS: Blood samples were collected for determination of blood lactate concentration. MEASUREMENTS AND MAIN RESULTS: Venous blood samples (12 mL) were obtained from each of the 19 normal subjects and each 12-mL specimen was evenly divided into six aliquot portions (six test tubes). Experiment 1: Of the six tubes, two tubes were set aside for experiment 2. The other four tubes were used to test four anticoagulants (one anticoagulant per tube). The anticoagulants tested were: sodium heparin; EDTA; lithium heparin; and sodium citrate. Lactate concentrations were analyzed using an ion-selective, amperometric electrode that we have previously validated. There were no statistically significant differences between the lactate concentrations derived from blood samples stored in sodium heparin, EDTA, or lithium heparin (p > .05; n = 19; Student-Newman-Keuls' multiple comparisons test). The lactate concentration of blood stored in sodium citrate, however, was lower than all other anticoagulants (p < .001; n = 19; Student-Newman-Keuls' multiple comparisons). Experiment 2: Of the remaining two test tube samples from each subject, one tube contained sodium heparin and the other tube did not contain an anticoagulant. Each of these two tubes was centrifuged at 50 degrees F (10 degrees C) for 15 mins to obtain plasma and serum samples. Lactate concentrations were measured in the serum and plasma and compared with those concentrations found in whole blood samples from the tube containing sodium heparin from experiment 1. The plasma and serum lactate concentrations were consistently higher than the whole blood lactate values from the same specimen (p < .05; n = 42; Student-Newman-Keuls' multiple comparisons test). Since experiment 1 involved the collection of blood from healthy volunteers with normal lactate concentrations, we chose to investigate whether this discordance between plasma or serum and whole blood was dependent on the lactate concentration. To answer this question, we studied 23 patients with known hyperlactatemia and found that in subjects with a lactate concentration of < 2.2 mmol/L, there was a difference of 0.11 mmol/L in the mean values between plasma and whole blood concentrations (p < .0004; n = 19; paired t-test). In subjects with a lactate concentration of > 2.2 mmol/L, there was a difference of 0.14 mmol/L (p < .0001; n = 23; paired t-test) in the mean values between plasma and whole blood. In all samples at all concentrations, there was no significant difference between serum vs. plasma samples (p > .05; Student-Newman-Keuls' test). CONCLUSIONS: a) Sodium citrate, as an anticoagulant, caused lower lactate concentrations to be measured as compared with heparin or EDTA; b) the measurement of lactate concentrations in plasma or serum samples yields a higher value than the concentration found in the original whole blood specimen.

Relationship between blood lactate concentrations and ionized calcium, glucose, and acid-base status in critically ill and noncritically ill patients.

OBJECTIVE: To determine the relationships between circulating blood lactate concentrations and several biochemical variables including ionized calcium, glucose, pH, and acid-base status in critically ill and noncritically ill patients. DESIGN: A prospective, cohort study. SETTING: The critical care research laboratory, intensive care unit (ICU), emergency room (ER), and general ward of a 466 bed university-affiliated hospital. PATIENTS: Three-hundred thirty-four critically ill and noncritically ill patients. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Circulating blood lactate concentrations, ionized calcium concentrations, blood glucose, pH, and base deficit values were simultaneously determined in blood samples from various patient populations. Descriptive data and physiologic parameters were also recorded. Circulating lactate and ionized calcium determinations were performed simultaneously in 334 whole blood samples from 334 subjects. There was neither a statistically significant nor clinically relevant correlation between circulating lactate concentrations and ionized calcium concentrations when lactate values were < or = 2 mmol/L (p = 0.8962, r2 = .01) or when lactate values were > 2 mmol/L (p = .3697, r2 = .09) in a heterogeneous patient population. Our study populations included five subject groups: a) nonhypotensive ICU patients (n = 93), b) nonhypotensive ER patients (n = 85), c) nonhypotensive general ward patients (n = 44), d) hypotensive patients from the ICU, ER, and general wards (n = 39), and e) normal controls (n = 73). There was neither a statistically significant nor clinically relevant correlation between circulating lactate concentrations and ionized calcium concentrations in each of the five populations studied for lactate values either < or = 2 mmol/L or > 2 mmol/L. We studied the relationship between circulating lactate concentrations and blood glucose concentrations (n = 334 patients), arterial pH and base deficit (n = 163 patients), and venous pH and base deficit (n = 171 patients). Statistically significant, but perhaps not clinically relevant correlations were observed when comparing circulating lactate values with blood glucose values (p = .0330, r2 = .12), arterial pH (p = .0007, r2 = .26) and base deficit from arterial specimens (p = .0014, r2 = .25). There were neither statistically significant nor clinically relevant correlations when comparing circulating lactate concentrations with venous pH (p = .9098, r2 = .01) or base deficit determined from venous blood specimens (p = .1365, r2 = .11). CONCLUSIONS: a) There is neither a statistically significant nor clinically relevant relationship between whole blood lactate concentrations and ionized calcium concentrations when studying patients with or without hyperlactatemia. b) Although there is a statistically significant correlation between circulating lactate concentrations and blood glucose concentrations, arterial pH or arterial base deficit, such associations do not appear to be clinically important.

Effects of crystalloid solutions on circulating lactate concentrations: Part 1. Implications for the proper handling of blood specimens obtained from critically ill patients.

OBJECTIVES: a) To test the hypothesis that circulating lactate concentrations are the same in simultaneously collected arterial and central venous blood specimens; b) to test the hypothesis that even small amounts of crystalloid solutions, which are inadequately "cleared" from these indwelling arterial and venous catheters, can lead to clinically important and misleading changes in the measured lactate values. DESIGN: A prospective, multiexperiment study. SETTING: A critical care research laboratory and a 20-bed intensive care unit (ICU). PATIENTS: Three hundred fifty-five patients. INTERVENTIONS: Blood samples were collected. MEASUREMENTS AND MAIN RESULTS: Experiment 1: Simultaneously collected arterial and central venous blood specimens were obtained on 148 occasions from 48 medical ICU patients receiving no lactated Ringer's solution (RL). Arterial and central venous lactate values were nearly identical in these patients. The correlation between the arterial and central venous lactate concentrations was excellent (r2 = .85; p < .0001) and the agreement between the arterial and central venous lactate concentrations was also excellent (bias and precision = 0.04 mmol/L and +/- 0.38 mmol/L, respectively). Experiment 2: Arterial and mixed venous blood samples were obtained from 100 percutaneous transluminal coronary angioplasty (PTCA) and 75 cardiac surgical patients immediately before the performance of these cardiac procedures. We found the central venous lactate concentrations to be higher than arterial lactate values in the cardiac surgical group, and there was a very poor correlation (r2 = .07) between arterial and central venous lactate values in the cardiac surgical group. The correlation between central venous and arterial lactate concentrations in the PTCA patients was excellent (r2 = .84) and similar to the findings of experiment 1. Since the cardiac surgical patients received RL and the PTCA patients received no RL, we speculated that the intravenous infusion of RL in the cardiac surgical group accounted for these discordant findings. To test this speculation, we performed experiments 3 and 4. Experiment 3: In a large bench study, blood specimens were divided into multiple 1-mL aliquot portions, to which 0.01, 0.05, 0.10, 0.50, or 1.0 mL of various crystalloid solutions, containing or not containing RL, were added. In a volume-dependent and linear manner, solutions containing RL increased the circulating lactate concentration from 10% to > 400% of the baseline lactate value. In a volume-dependent and linear fashion, the non-RL crystalloid solutions decreased the lactate concentration by 0 to 66% of the baseline nondiluted lactate concentration. Experiment 4: In 30 different cardiac surgical patients, we simultaneously obtained central venous and arterial blood specimens. Patients this time received no RL, and catheter lines were adequately cleared (removal > 5 mL) of crystalloid solutions. We found a correlation (r2 = .82; p < .0001) that was virtually identical to the findings of experiment 1 and to the findings in the PTCA group of experiment 2. CONCLUSIONS: a) Arterial and central venous lactate concentrations are similar in hemodynamically stable critically ill patients, b) Even small amounts of RL-containing solutions in catheters used for blood sampling may cause false increases in the circulating lactate concentration. c) Even small amounts of non-RL crystalloid solutions in catheters used for blood sampling may falsely decrease circulating lactate values. d) When blood specimens are drawn from indwelling catheters, all crystalloid solutions must be cleared from the line.

The use and clinical importance of a substrate-specific electrode for rapid determination of blood lactate concentrations.

OBJECTIVE: To determine the validity and clinical importance of a newly developed amperometric, enzymatic, substrate-specific electrode for the rapid measurement of circulating lactate concentrations. DESIGN: A prospective multiexperiment study. SETTING: The critical care medicine research laboratory, intensive care unit (ICU), emergency department (ED), and general wards of a university-affiliated hospital. PATIENTS: A total of 1218 patients and control subjects were studied on one or more occasions. INTERVENTIONS: Blood lactate concentrations, descriptive data, physiological parameters, and outcome results were determined in various patient populations. MAIN OUTCOME MEASURES AND RESULTS: Experiment 1: Lactate determinations performed with the new substrate-specific electrode were compared with two laboratory reference methods. Blood samples from 80 ICU patients and 165 ED patients formed the basis of this first experiment. There was excellent agreement between the test instrument and the two reference methods as reflected by bias (with reference method 1, 0.19 mmol/L; reference method 2, 0.09 mmol/L), precision (with reference method 1, +/- 0.47 mmol/L; reference method 2, +/- 0.34 mmol/L), and correlation data (with reference method 1, r = .92; reference method 2, r = .98). Experiment 2: The new test microchemistry instrument was used to analyze blood samples from 927 patients. The mean (SE) blood lactate concentrations in the various patient populations were 1.26 (0.04) mmol/L for control subjects (n = 85), 1.52 (0.03) mmol/L for general ward patients (n = 489; P < .001 vs normal subjects), 2.34 (0.15) mmol/L for ICU patients (n = 180; P < .001 vs normal subjects and general ward patients), and 2.44 (0.15) mmol/L for ED patients (n = 173; P < .001 vs normal subjects and general ward patients). None of the normal subjects and only one (0.2%) of 489 nonhypotensive general ward patients had a blood lactate value greater than 4 mmol/L. Circulating lactate concentrations greater than 4 mmol/L were 98.2% specific in predicting the need for hospital admission in patients presenting to the ED. Furthermore, lactate concentrations greater than 4 mmol/L were 96% specific in predicting mortality in hospitalized nonhypotensive patients. Experiment 3: Blood samples from 46 hypotensive ICU and ED patients and from 353 nonhypotensive ICU and ED patients (the latter samples were derived from experiment 2) were analyzed. A statistically significant difference was noted between the mean (SE) lactate concentration in hypotensive patients in the ICU and ED (4.75 [0.75] mmol/L) when compared with nonhypotensive ICU and ED patients (2.28 [0.10] mmol/L; P < .001). Furthermore, blood lactate values greater than 4 mmol/L were 87.5% specific in predicting mortality in hypotensive patients. CONCLUSIONS: Lactate determinations performed using the new test instrument are precise and accurate. Blood lactate concentrations greater than 4 mmol/L are unusual in normal and noncritically ill hospitalized patients and warrant concern. In hospitalized (non-ICU) nonhypotensive subjects, as well as in critically ill patients, a blood lactate concentration greater than 4 mmol/L may portend a poor prognosis.