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PubMed2000

Redox regulation of AMP synthesis in yeast: a role of the Bas1p and Bas2p transcription factors.

Expression of yeast AMP synthesis genes (ADE genes) was severely affected when cells were grown under oxidative stress conditions. To get an insight into the molecular mechanisms of this new transcriptional regulation, the role of the Bas1p and Bas2p transcription factors, known to activate expression of the ADE genes, was investigated. In vitro, DNA-binding of Bas1p was sensitive to oxidation. However, this sensitivity could not account for the regulation of the ADE genes because we showed, using a BAS1-VP16 chimera, that Bas1p DNA-binding activity was not sensitive to oxidation in vivo. Consistently, a triple cysteine mutant of Bas1p (fully resistant to oxidation in vitro) was unable to restore transcription of the ADE genes under oxidative conditions. We then investigated the possibility that Bas2p could be the oxidative stress responsive factor. Interestingly, transcription of the PHO5 gene, which is dependent on Bas2p but not on Bas1p, was found to be severely impaired by oxidative stress. Nevertheless, a Bas2p cysteine-free mutant was not sufficient to confer resistance to oxidative stress. Finally, we found that a Bas1p-Bas2p fusion protein restored ADE gene expression under oxidative conditions, thus suggesting that redox sensitivity of ADE gene expression could be due to an impairment of Bas1p/Bas2p interaction. This hypothesis was further substantiated in a two hybrid experiment showing that Bas1p/Bas2p interaction is affected by oxidative stress.

Adenosine Monophosphate↗

PubMed2002

Adverse drug events in children during hospitalization and after discharge in a Norwegian university hospital.

UNLABELLED: The frequency and characteristics of adverse drug events (ADEs) in children hospitalized in the paediatric department of Ullevaal University Hospital, Norway, were determined using intensive monitoring. Of 579 children treated with drugs, 28% experienced ADEs; 7% at the time of admission, 18% during hospitalization and 9% after discharge. All children treated for cancer, 19% treated with anti-infective drugs, 15% treated with antiasthmatics and 10% treated with drugs affecting the nervous system experienced ADEs. The most frequent events were gastrointestinal, CNS- and skin reactions and 19% were considered as serious. ADEs caused 6% of the admissions and 44% required interventions. Most ADEs were found by screening patient records, where physicians mostly described adverse drug events requiring interventions and nurses described less serious events. Parents reported 14% of the events, of which a majority were CNS reactions. CNS reactions may be more common than expected and observations by parents are important when investigating such reactions in children. CONCLUSIONS: ADEs, mainly gastrointestinal, CNS and skin reactions related to drugs affecting the nervous system, anti-infectives and antiasthmatics, were seen in 28% of the patients. The reporting of events by parents was a useful supplement to the screening of patient records.

Adolescent↗

PubMed2001

Potential risks and prevention, Part 4: Reports of significant adverse drug events.

A summary analysis of three descriptive studies of significant adverse drug events (ADEs) was conducted. Case reports of ADEs published in Clin-Alert during 1976-97 were the source of information on ADEs, including drug-induced deaths, disabilities, and threats to life. The results of the three studies were compared, and recommendations were made. During the 21-year period, 1520 significant ADEs were reported (29% resulting in death, 15% in permanent disability, and 56% in life threats). Event types were distributed as adverse drug reactions (52%), allergic drug reactions (25%), medication errors (15%), and drug interactions (8%). Only 12% of the drug interactions were classified as having highest significance by one drug information reference, while 32% of the drug interactions were unclassified. Typically, patients were 40-69 years old and relatively healthy or only moderately ill and had received usual dosages. However, 29% of the patients with a drug-induced permanent disability were less than 10 years old. Only 17% of the drugs that could have been monitored by blood level tests were so monitored. The drug categories most commonly involved in ADEs were central-nervous-system agents, antimicrobials, antineoplastics, and cardiovascular agents. The nervous, hematopoietic, cardiovascular, and respiratory systems were affected the most. Faulty prescribing was the most common reason for medication error, and wrong dosage was the most common type of error. A lawsuit was reported in 13% of the cases. Overall, 52% of the cases were judged to have been preventable; of these, 50% could have been prevented by a pharmacist. Litigation was reported for 13% of the cases; settlements and judgments averaged $3.1 million. A summary analysis of more than 1500 published case reports of ADEs for 1976-97 yielded information on possible risk factors for drug-related deaths, disabilities, and life threats and on which events may have been preventable.

Adverse Drug Reaction Reporting Systems↗

PubMed1998

Assessment of energy expenditure in overweight women.

PURPOSE: To compare field measures of average daily energy expenditure (ADEE) against criterion data by the doubly labeled water method (DLW) in overweight women. METHODS: The subject were 20 overweight (BMI 29.9 +a- 3.0 kg.m-2) premenopausal women. Energy expenditure was measured by DLW and by the factorial method (activity diary, two techniques differing by method to obtain resting energy expenditure, REE), heart-rate monitoring (HR, two techniques differing by the FLEX-point to discriminate sedentary and activity HR), accelerometer, and pedometer. RESULTS: The ADEE(DLW) was 10.26 +a- 1.1 MJ.d-1. The mean bias (ADEE by the alternative minus ADEE(DLW) was smallest for the accelerometer (+ 0.08 +a- 1.63 MJ) and HR-FLEX10 (+ 0.11 +a- 1.67 MJ). The HR-FLEX(0) technique (lower FLEX-point) overestimated ADEE by + 1.18 (+a- 1.97 MJ). However, the random error (SD of bias) was smaller for both factorial techniques (REE measured: -0.48 +2- 0.81 MJ; REE calculated from the WHO equation: -0.22 +2- 0.88 MJ). CONCLUSION: The results show that simple factorial methods may assess ADEE with small random errors in population with a rather narrow range of physical activity. The accelerometer and HR with the higher FLEX-point have comparable results with smaller bias but larger random error compared with the factorial techniques.

Adult↗

PubMed2004

An evaluation of the adequacy of outpatient monitoring of thyroid replacement therapy.

OBJECTIVES: Hypothyroid patients managed with excessive or insufficient thyroid replacement therapy are often difficult to clinically recognize. Monitoring may prevent or minimize the consequences of adverse drug events (ADEs). We sought to develop an explicit model of medication monitoring and to evaluate monitoring processes and ADEs in patients taking levothyroxine. METHODS: A retrospective chart review of 400 outpatients receiving levothyroxine therapy between 1 January 2000 and 1 January 2001 at a large North American tertiary care hospital. We measured the proportion of patients satisfying minimum monitoring criteria, experiencing specific monitoring errors and having levothyroxine-related ADEs. Explicit monitoring criteria were derived from the literature and through expert opinion. Adverse drug events were identified using structured implicit reviews. RESULTS: Overall, only 56% (95% confidence interval [95% CI] 51-62%) of the patients prescribed levothyroxine received the minimal recommended monitoring. Errors were identified at all stages of the monitoring model. Patients who received the recommended monitoring had fewer levothyroxine-related ADEs (1% vs. 6%, P=0.013) than those who did not. Minority status (white people 2% vs. black people 4% vs. Hispanics 14%, P=0.023) and primary language (English 3% vs. Non-English 20%, P=0.002) were the patient characteristics associated with levothyroxine-related ADEs. CONCLUSION: Only half of outpatients taking levothyroxine at one tertiary care hospital received the recommended monitoring during one year of follow-up. Levothyroxine-related ADEs were more frequent in patients with lower-quality monitoring and in minorities and non-English speakers.

Ambulatory Care↗

PubMed2006

Small hepatic nodules (< or =2 cm) in cirrhosis patients: characterization with contrast-enhanced ultrasonography.

AIM: We evaluated the efficacy of contrast-enhanced ultrasonography (CEUS) for the characterization of small hepatic nodules (< or =2 cm) in cirrhosis patients. PATIENTS AND METHODS: Thirty cirrhosis patients with 30 hepatic nodules (1-2 cm) were enrolled in this study. Eighteen hepatic nodules were hepatocellular carcinomas (HCC) and 12 were benign lesions. CEUS was performed using microbubble contrast (Levovist). With surrounding hepatic parenchyma as a reference, two characteristics of hepatic nodules, including arterial phase enhancement (AE) and the absence of delayed phase enhancement (ADE), were evaluated as criteria for the diagnosis of HCC. A radiologist independently reviewed the dynamic computed tomographies (CT) of 26 hepatic nodules. RESULTS: CEUS showed AE in 15 nodules (13 HCC and two benign) and ADE in 17 lesions (14 HCC and three benign). For HCC, the coincidental AE of both CEUS and dynamic CT was 40%. Using both AE and ADE for HCC diagnosis, the sensitivity, specificity, accuracy, positive predictive value and negative predictive values were 55.6%, 91.7%, 70%, 90.9% and 57.9%, respectively. When using either AE or ADE for HCC diagnosis, the same parameters were 94.4%, 66.7%, 83.3%, 81% and 88.9%, respectively. One benign hepatic nodule with both AE and ADE was diagnosed as HCC 29 months after the CEUS study. CONCLUSIONS: A combination of characteristics of AE and ADE as determined by CEUS was highly specific for small HCCs in cirrhosis patients. Concurrent delayed phase imaging is useful in the diagnosis of small hypovascular HCCs.

Adult↗

PubMed2005

Outpatient prescribing errors and the impact of computerized prescribing.

BACKGROUND: Medication errors are common among inpatients and many are preventable with computerized prescribing. Relatively little is known about outpatient prescribing errors or the impact of computerized prescribing in this setting. OBJECTIVE: To assess the rates, types, and severity of outpatient prescribing errors and understand the potential impact of computerized prescribing. DESIGN: Prospective cohort study in 4 adult primary care practices in Boston using prescription review, patient survey, and chart review to identify medication errors, potential adverse drug events (ADEs) and preventable ADEs. PARTICIPANTS: Outpatients over age 18 who received a prescription from 24 participating physicians. RESULTS: We screened 1879 prescriptions from 1202 patients, and completed 661 surveys (response rate 55%). Of the prescriptions, 143 (7.6%; 95% confidence interval (CI) 6.4% to 8.8%) contained a prescribing error. Three errors led to preventable ADEs and 62 (43%; 3% of all prescriptions) had potential for patient injury (potential ADEs); 1 was potentially life-threatening (2%) and 15 were serious (24%). Errors in frequency (n=77, 54%) and dose (n=26, 18%) were common. The rates of medication errors and potential ADEs were not significantly different at basic computerized prescribing sites (4.3% vs 11.0%, P=.31; 2.6% vs 4.0%, P=.16) compared to handwritten sites. Advanced checks (including dose and frequency checking) could have prevented 95% of potential ADEs. CONCLUSIONS: Prescribing errors occurred in 7.6% of outpatient prescriptions and many could have harmed patients. Basic computerized prescribing systems may not be adequate to reduce errors. More advanced systems with dose and frequency checking are likely needed to prevent potentially harmful errors.

Adult↗

PubMed2007

Risk factors for adverse drug events in older adults with mobility limitations in the community setting.

OBJECTIVES: To investigate risk factors for self-reported adverse drug events (ADEs) in a cohort of annually surveyed Iowa Medicare beneficiaries with mobility limitations. DESIGN: Prospective cohort study with baseline and two annual follow-up questionnaires. SETTING: Population-based sample of Iowa Medicare beneficiaries with mobility limitations. PARTICIPANTS: Members of the cohort with complete follow-up questionnaires and prescription dispensing data (N=689). MEASUREMENTS: The questionnaires asked about self-reported ADEs in the previous 12 months, sociodemographic data, smoking, alcohol use, number of mobility limitations, and history of chronic disease. Pharmacy dispensing records were the source of number and classes of prescription drug use. Linked Medicare claims provided additional comorbidity data. RESULTS: Of the 689 subjects, 151 (21.9%) reported an ADE, 83% of which resulted in physician contact and 56% of which resulted in discontinuing the medication. Number of different medications dispensed during the prior year was an independent predictor of a self-reported ADE. Neither age, extent of mobility limitation, nor number of chronic conditions was independently associated with reporting an ADE. CONCLUSION: Excess ADE risk observed with increasing mobility limitations is mediated through greater medication use.

Age Factors↗

PubMed1969

Defective Bacteriophage PBSH in Bacillus subtilis: III. Properties of Adenine-16 Marker in Purified Bacteriophage Deoxyribonucleic Acid.

The adenine-16 (ade-16) marker (the marker nearest the chromosomal origin of Bacillus subtilis) in purified PBSH deoxyribonucleic acid (DNA) renatured more rapidly and to a greater extent than any other marker in the phage DNA, and more rapidly and to a greater extent than all markers, including ade-16, in bacterial DNA. The renaturation of the phage DNA ade-16 marker followed a first-order reaction, whereas renaturation of bacterial markers was initially a second-order reaction. No cross-linkages were detected in DNA molecules containing the ade-16 marker. Buoyant density measurements and inactivation by heat and micrococcal deoxyribonuclease of the ade-16 marker did not reveal large segments of clusters of the individual bases in these molecules. Alternative mechanisms for the unique renaturation behavior of the ade-16 marker are discussed.

Journal Article↗

PubMed2005

Medication safety program reduces adverse drug events in a community hospital.

BACKGROUND: There is widespread interest in improving medication safety, particularly in the hospital setting. Numerous suggestions have been made as to how this should be done, but there is a paucity of data demonstrating the effectiveness of any of the interventions that have been proposed. OBJECTIVES: To assess the impact of a wide ranging, community hospital based patient safety program on patient harm as measured by the rate of adverse drug events. DESIGN: An audit of discharged hospital patients was conducted from January 2001 to December 2003. Baseline data were collected for the first 6 months and multiple drug protocols and other interventions were instituted on the nursing units and in the pharmacy department over the subsequent 9 months (transition period). These interventions were largely based on information about medication risks acquired from internal medication event reporting. Each month of the study adverse drug events (ADE) were sought from a random sample of inpatient charts. A trigger tool was used to detect clues to ADEs, the presence of which was confirmed or excluded by detailed manual chart review. The severity of these events was categorized using the classification system of the National Coordinating Council for Medication Error and Reporting and Prevention. MAIN OUTCOME MEASURES AND RESULTS: Median ADEs per 1000 doses of medication dispensed declined significantly from 2.04 to 0.65 (p<0.001). Median ADEs per 100 patient days declined significantly from 5.07 to 1.30 (p<0.001). The proportion of inpatients with one or more ADE in the baseline period was 31% and declined threefold (p<0.001). The severity of reported medication events also declined. The number of ADEs associated conclusively with patient harm was 1.67 per total doses delivered in the baseline period and declined eightfold (p<0.001). CONCLUSION: The implementation of a carefully planned series of low cost interventions focused on high risk medications, driven by information largely from internal event reporting, and designed to improve a hospital's medication safety leads to a significant decrease in patient harm.

Adverse Drug Reaction Reporting Systems↗

PubMedDate not supplied

Evaluating the capability of information technology to prevent adverse drug events: a computer simulation approach.

BACKGROUND: The annual cost of morbidity and mortality due to medication errors in the U.S. has been estimated at $76.6 billion. Information technology implemented systematically has the potential to significantly reduce medication errors that result in adverse drug events (ADEs). OBJECTIVE: To develop a computer simulation model that can be used to evaluate the effectiveness of information technology applications designed to detect and prevent medication errors that result in adverse drug effects. METHODS: A computer simulation model was constructed representing the medication delivery system in a hospital. STELLA, a continuous simulation software package, was used to construct the model. Parameters of the model were estimated from a study of prescription errors on two hospital medical/surgical units and used in the baseline simulation. Five prevention strategies were simulated based on information obtained from the literature. RESULTS: The model simulates the four stages of the medication delivery system: prescribing, transcribing, dispensing, and administering drugs. We simulated interventions that have been demonstrated in prior studies to decrease error rates. The results suggest that an integrated medication delivery system can save up to 1,226 days of excess hospitalization and $1.4 million in associated costs annually in a large hospital. The results of the analyses regarding the effects of the interventions on the additional hospital costs associated with ADEs are somewhat sensitive to the distribution of errors in the hospital, more sensitive to the costs of an ADE, and most sensitive to the proportion of medication errors resulting in ADEs. CONCLUSIONS: The results suggest that clinical information systems are potentially a cost-effective means of preventing ADEs in hospitals and demonstrate the importance of viewing medication errors from a systems perspective. Prevention efforts that focus on a single stage of the process had limited impact on the overall error rate. This study suggests that system-wide changes to the medication delivery system are required to drastically reduce mediation errors that may result in ADEs in a hospital setting.

Clinical Pharmacy Information Systems↗

PubMed2004

Characteristics and consequences of drug allergy alert overrides in a computerized physician order entry system.

OBJECTIVE: The aim of this study was to determine characteristics of drug allergy alert overrides, assess how often they lead to preventable adverse drug events (ADEs), and suggest methods for improving the allergy-alerting system. DESIGN: Chart review was performed on a stratified random subset of all allergy alerts occurring during a 3-month period (August through October 2002) at a large academic hospital. MEASUREMENTS: Factors that were measured were drug/allergy combinations that triggered alerts, frequency of specific override reasons, characteristics of ADEs, and completeness of allergy documentation. RESULTS: A total of 6,182 (80%) of 7,761 alerts were overridden in 1,150 patients. In this sample, only 10% of alerts were triggered by an exact match between the drug ordered and allergy listed. Physicians' most common reasons for overriding alerts were "Aware/Will monitor" (55%), "Patient does not have this allergy/tolerates" (33%), and "Patient taking already" (10%). In a stratified random subset of 320 patients (28% of 1,150) on chart review, 19 (6%) experienced ADEs attributed to the overridden drug; of these, 9 (47%) were serious. None of the ADEs was considered preventable, because the overrides were deemed clinically justifiable. The degree of completeness of patients' allergy lists was highly variable and generally low in both paper charts and the CPOE system. CONCLUSION: Overrides of drug-allergy alerts were common and about 1 in 20 resulted in ADEs, but all of the overrides resulting in ADEs appeared clinically justifiable. The high rate of alert overrides was attributable to frequent nonexact match alerts and infrequent updating of allergy lists. Based on these findings, we have made specific recommendations for increasing the specificity of alerting and thereby improving the clinical utility of the drug allergy alerting system.

Decision Support Systems, Clinical↗

PubMed2000

2-hydroxyadenine in DNA is a very poor substrate of the Escherichia coli MutY protein.

To test the possibility that the Escherichia coli MutY or MutM protein acts as a 2-hydroxyadenine (2-OH-Ade) glycosylase, we treated double-stranded oligodeoxyribonucleotides containing 2-OH-Ade with the E. coli MutY or MutM protein in vitro. We found that a strand with 2-OH-Ade was a very poor substrate of MutY, irrespective of the base in the complementary strand. Moreover, a strand containing adenine or guanine opposite 2-OH-Ade was also rarely cleaved by MutY. The cleavage of oligonucleotides with 2-OH-Ade by MutM was not observed. These results indicate that neither MutY nor MutM plays an important role in the removal of 2-OH-Ade from DNA.

DNA Glycosylases↗

PubMed2005

Risk factors for adverse drug events: a 10-year analysis.

BACKGROUND: Many adverse drug events (ADEs) are the result of known pharmacologic properties, and some result from medication errors. However, some are the result of patient-specific risk factors. OBJECTIVE: To identify inpatient risk factors for ADEs. METHODS: Conditional logistic regression was used to analyze all pharmacist-verified ADEs by therapeutic class of drugs and severity during a 10-year study period. All inpatients > or = 18 years of age from a 520-bed tertiary teaching hospital were included. Each case patient was matched with up to 16 control patients. Odds ratios for patient factors associated with ADEs were calculated from different therapeutic classes of drugs. RESULTS: Odds ratios for numerous risk factors were identified for 4376 ADEs and were found to vary depending on therapeutic classification. The risk factors for the different classifications were grouped by (1) patient characteristics--female (OR 1.5-1.7), age (0.7-0.9), weight (1.2-1.4), creatinine clearance (0.8-4.7), and number of comorbidities (1.1-12.6); (2) drug administration--dosage (1.2-3.7), administration route (1.4-149.9), and number of concomitant drugs (1.2-2.4); and (3) patient type--service (1.2-4.9), nursing division (1.5-3.8), and diagnosis-related group (1.5-5.7). CONCLUSIONS: Some risk factors are consistent for all ADEs and across multiple therapeutic classes of drugs, while others are class specific. High-risk agents should be closely monitored based on patient characteristics (gender, age, weight, creatinine clearance, number of comorbidities) and drug administration (dosage, administration route, number of concomitant drugs).

Adolescent↗

PubMed2006

Alterations in anti-oxidative defence enzymes in erythrocytes from sporadic amyotrophic lateral sclerosis (SALS) and familial ALS patients.

BACKGROUND: Overproduction of nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) may be an important factor in the pathogenesis of amyotrophic lateral sclerosis (ALS). Owing to their ability to permeate through biological membranes, excess NO and H(2)O(2) may be present in the media surrounding motor neurones. Anti-oxidative defence enzymes (ADEs) in erythrocytes are capable of detoxifying reactive oxygen species (produced endogenously or exogenously), but may also be structurally modified and inactivated by reactive oxygen and nitrogen species. Both balanced and coordinated ADE activities are of utmost importance for their correct physiological function. METHODS: We determined activity of the following ADEs: copper-zinc superoxide dismutase (CuZn SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) in erythrocytes from sporadic ALS patients [SALS (-/+)], familial ALS patients with the Leu144Phe mutation in the SOD1 gene [FALS (+/+)], asymptomatic carriers with the Leu144Phe mutation in the SOD1 gene (+/-), and control subjects (-/-). We also examined the in vitro effect of diethyldithiocarbamate (DDC) on CuZn SOD activity in erythrocytes from FALS patients, SALS patients and control subjects. RESULTS: The influence of the Leu144Phe mutation and/or disease was apparent for ADE activities measured in all three patient groups. The SOD1 gene mutation decreased CuZn SOD and GSH-Px activity (two-way ANOVA, significant mutation effect). We noted that the disease also contributed to decreased CuZn SOD activity in SALS patients in comparison with the control group (two-way ANOVA, mutation and disease effect). The disease also influenced CAT and GR activity. CAT activity was decreased in both SALS and FALS patients. In all three patient groups, GR activity was higher than in the control group. Finally, DDC inhibited CuZn SOD activity in erythrocytes from control subjects, FALS (Leu144Phe) patients and SALS patients; however, its effect was more pronounced and significant in FALS patients. CONCLUSIONS: Changes in erythrocyte ADE activities suggest that oxidative stress, involved in the motor neurone pathogenesis of SALS and FALS, also has systemic effects. Differences in ADE systems between the study groups revealed the presence of different types of oxidative pressure, indicating the potential additional benefit of individually designed anti-oxidant cocktail therapies.

Amyotrophic Lateral Sclerosis↗

PubMed2004

Information technology for detecting medication errors and adverse drug events.

It is estimated that over three-quarters of a million people are injured or die in hospitals each year from adverse drug events (ADEs). The majority of medical errors result from poorly designed healthcare systems rather than from negligence on the part of healthcare providers. In general, healthcare systems rely on voluntary reporting, which seriously underestimates the number of medication errors and ADEs by as much as 90%. This paper reviews the causes and impact of medication errors and ADEs. It also reports studies that have used information technology (IT) to detect and prevent medication errors and ADEs. Significant reduction of medication errors and ADEs requires systemic implementation of IT, improvements in the reporting of errors, and integration of the components of the healthcare systems' information systems. At the present time, most healthcare systems should be able to use IT to detect and prevent ADEs.

Adverse Drug Reaction Reporting Systems↗

PubMed2004

Computerized physician order entry and medication errors in a pediatric critical care unit.

OBJECTIVE: Medication errors are a major concern of health care professionals and medical institutions, especially errors involving children. Studies in adults have shown that computerized physician order entry (CPOE) systems reduce medication errors and adverse drug events (ADEs). The effect of CPOE implementation in a pediatric population has not been reported. The objective of this study was to evaluate the impact of CPOE on the frequency of errors in the medication ordering process in a pediatric critical care unit (PCCU). METHODS: A prospective trial was conducted of 514 pediatric patients who were admitted to a 20-bed PCCU in a tertiary-care children's hospital before and after implementation of CPOE. Medication errors were identified after review of all orders during the study period and then further classified as potential ADEs, medication prescribing errors (MPE), and rule violations (RV). RESULTS: A total of 13 828 medication orders were reviewed. Before implementation, potential ADEs occurred at a rate of 2.2 per 100 orders, MPEs at a rate of 30.1 per 100 orders, and RVs at a rate of 6.8 per 100 orders. After implementation, the rate of potential ADEs was reduced to 1.3 per 100 orders, MPEs to 0.2 per 100 orders, and RVs to 0.1 per 100 orders. The overall error reduction was 95.9%. Potential ADEs were reduced by 40.9%, and MPEs and RVs were reduced by 99.4% and 97.9%, respectively. CONCLUSIONS: The implementation of CPOE resulted in almost a complete elimination of MPEs and RVs and a significant but less dramatic effect on potential ADEs.

Child↗

PubMed2001

The effects of atropine and methotrimeprazine on the epinephrine-induced arrhythmias in halothane-anesthetized dogs.

The effects of atropine and methotrimeprazine on epinephrine-induced ventricular arrhythmias were evaluated in halothane-anesthetized dogs. Ten mixed-breed dogs were assigned to 3 treatments (saline, atropine, and methotrimeprazine) in a randomized complete block design. Anesthesia was induced and maintained with halothane (1.5 minimum alveolar concentration) in oxygen. Controlled ventilation was used throughout to maintain eucapnia. Saline, atropine (0.05 mg/kg, i.v.) or methotrimeprazine (0.5 mg/kg, i.v.) were administered and, 5 minutes later the arrhythmogenic dose of epinephrine (ADE) was measured by i.v. infusion of progressively increasing infusion rates of epinephrine, until the ventricular arrhythmia criterion was met (at least 4 ectopic ventricular contractions (EVCs) during a 15-second period). Data were analyzed using a student's t-test for ADE values and multivariate profile analysis for heart rate (HR), arterial blood pressure (ABP), and rate pressure product (RPP). The ADE increased in atropine- and methotrimeprazine-treated groups, whereas 1 and 4 animals from these groups did not develop any ventricular arrhythmia, respectively. Epinephrine induced multiform premature ventricular contractions (PVCs) in the atropine group, whereas ventricular escape beats were observed in the control and methotrimeprazine groups. Heart rate and RPP decreased, and ABP increased at the time of ADE observation in the control group. Epinephrine infusion in the atropine group caused marked increases in HR, ABP, and RPP, which were associated with pulsus alternans in 2 animals. It was concluded that 1) the presence of cholinergic blockade influences the type of ventricular arrhythmia induced by epinephrine; 2) increased ADE values recorded following atropine administration must be cautiously interpreted, since in this situation the PVCs were associated with signs of increased myocardial work and ventricular failure; and 3) the use of a broader arrhythmia criterion (EVCs instead of PVCs) may not allow a direct comparison between ADE values, since it includes ventricular arrhythmias mediated by different mechanisms.

Analgesics, Non-Narcotic↗