Diuretic Strategies in Acute Decompensated Heart Failure: A Narrative Review.

Background: Heart failure is a common condition with considerable associated costs, morbidity, and mortality. Patients often present to hospital with dyspnea and edema. Inadequate inpatient decongestion is an important contributor to high readmission rates. There is little evidence concerning diuresis to guide clinicians in caring for patients with acute decompensated heart failure. Contemporary diuretic strategies have been defined by expert opinion and older landmark clinical trials. Objective: To present a narrative review of contemporary recommendations, along with their underlying evidence and pharmacologic rationale, for diuretic strategies in inpatients with acute decompensated heart failure. Data Sources: PubMed, OVID, and Embase databases were searched from inception to December 22, 2022, with the following search terms: heart failure, acute heart failure, decompensated heart failure, furosemide, bumetanide, ethacrynic acid, hydrochlorothiazide, indapamide, metolazone, chlorthalidone, spironolactone, eplerenone, and acetazolamide. Study Selection: Randomized controlled trials and systematic reviews involving at least 100 adult patients (> 18 years) were included. Trials involving torsemide, chlorothiazide, and tolvaptan were excluded. Data Synthesis: Early, aggressive administration of a loop diuretic has been associated with expedited symptom resolution, shorter length of stay, and possibly reduced mortality. Guidelines make recommendations about dose and frequency but do not recommend any particular loop diuretic over another; however, furosemide is most commonly used. Guidelines recommend that the initial furosemide dose (on admission) be 2-2.5 times the patient's home dose. A satisfactory diuretic response can be defined as spot urine sodium content greater than 50-70 mmol/L at 2 hours; urine output greater than 100-150 mL/h in the first 6 hours or 3-5 L in 24 hours; or a change in weight of 0.5-1.5 kg in 24 hours. If congestion persists after the maximization of loop diuretic therapy over the first 24-48 hours, an adjunctive diuretic such as thiazide or acetazolamide should be added. If decongestion targets are not met, continuous infusion of furosemide may be considered. Conclusions: Heart failure with congestion can be managed with careful administration of high-dose loop diuretics, supported by thiazides and acetazolamide when necessary. Clinical trials are underway to further evaluate this strategy.

Contexte: L'insuffisance cardiaque est une maladie courante entraînant des coûts, une morbidité et une mortalité considérables. Les patients se présentent souvent à l'hôpital avec une dyspnée et un oedème. Une décongestion inadéquate des patients hospitalisés contribue largement aux taux élevés de réadmission. Il existe peu de données probantes concernant la diurèse pour guider les cliniciens dans la prise en charge des patients atteints d'insuffisance cardiaque aiguë décompensée. Les stratégies diurétiques contemporaines ont été définies par l'opinion d'experts et des essais cliniques de référence plus anciens. Objectif: Présenter une revue narrative des recommandations contemporaines, ainsi que leurs données probantes sous-jacentes et leur justification pharmacologique, pour les stratégies diurétiques chez les patients hospitalisés souffrant d'insuffisance cardiaque aiguë décompensée. Sources des données: Les bases de données PubMed, OVID et Embase ont été consultées depuis leur création jusqu'au 22 décembre 2022, avec les termes de recherche suivants: insuffisance cardiaque, insuffisance cardiaque aiguë, insuffisance cardiaque décompensée, furosémide, bumétanide, acide éthacrynique, hydrochlorothiazide, indapamide, métolazone, chlorthalidone, spironolactone, éplérénone et acétazolamide. Choix de l'étude: Les essais contrôlés randomisés et les revues systématiques portant sur au moins 100 patients adultes (plus de 18 ans) ont été inclus. Les essais impliquant le torsémide, le chlorothiazide et le tolvaptan ont été exclus. Synthèse des données: L'administration précoce et agressive d'un diurétique de l'anse a été associée à une résolution accélérée des symptômes, à une durée de séjour plus courte et éventuellement à une mortalité réduite. Les lignes directrices font des recommandations sur la dose et la fréquence, mais ne recommandent pas un diurétique de l'anse particulier plutôt qu'un autre; cependant, le furosémide est le plus couramment utilisé. Les lignes directrices recommandent que la dose initiale de furosémide à l'admission soit de 2 à 2,5 fois la dose à domicile du patient. Une réponse diurétique satisfaisante peut être définie comme une teneur ponctuelle en sodium dans l'urine supérieure à 50 à 70 mmol/L après 2 heures; débit urinaire supérieur à 100 à 150 mL/h au cours des 6 premières heures ou à 3 à 5 L en 24 heures; ou un changement de poids de 0,5 à 1,5 kg en 24 heures. Si la congestion persiste après la maximisation du traitement par diurétique de l'anse au cours des premières 24 à 48 heures, un diurétique d'appoint tel que le thiazidique ou l'acétazolamide doivent être ajoutés. Si les objectifs de décongestion ne sont pas atteints, une perfusion continue de furosémide peut être envisagée. Conclusions: L'insuffisance cardiaque accompagnée de congestion peut être gérée par l'administration prudente de diurétiques de l'anse à haute dose, appuyés par des thiazidiques et de l'acétazolamide si nécessaire. Des essais cliniques sont en cours pour évaluer davantage cette stratégie.

Rebleeding in Variceal and Nonvariceal Gastrointestinal Bleeds in Cirrhotic Patients Using Vitamin K1: The LIVER-K Study.

BACKGROUND: Gastroesophageal varices are the most common cause of upper gastrointestinal bleeding (UGIB) in patients with cirrhosis. Vitamin K1 is commonly administered to patients presenting with UGIB and elevated international normalized ratio, despite limited evidence to support this practice. OBJECTIVES: The primary objective was to describe the incidence of rebleeding within 30 days after vitamin K1 administration in patients with cirrhosis and UGIB. The secondary objective was to describe prescribing patterns for vitamin K1. METHODS: This retrospective, descriptive multicentre study involved patients with cirrhosis and UGIB who were admitted to any of the 4 adult acute care hospitals in Calgary, Alberta, from January 1, 2014, to December 31, 2016. Patients were divided into 2 groups: those who received vitamin K1 and those who did not. RESULTS: A total of 370 patients met the inclusion criteria, of whom 243 received vitamin K1 and 127 did not. Baseline characteristics were similar between the groups. Greater proportions of patients in the vitamin K1 group received transfusions of packed red blood cells, fresh frozen plasma, platelets, cryoprecipitate, or prothrombin concentrate during their admissions. There was no significant difference in the duration of octreotide and pantoprazole infusions. Among patients in the vitamin K1 group, there were more admissions to the intensive care unit and longer lengths of stay. More patients in the no vitamin K1 group had esophageal varices evident on endoscopy that required endoscopic treatment. Forty of the patients (16.5%) in the vitamin K1 group and 7 (5.5%) in the no vitamin K1 group had rebleeding within 30 days of the initial bleed. The median total vitamin K1 dose administered was 25 mg. CONCLUSIONS: The study results suggest that vitamin K1 does not reduce the incidence of rebleeding within 30 days of the initial bleed in patients with cirrhosis and UGIB.

CONTEXTE: Les varices oesophagiennes sont la cause la plus fréquente de l'hémorragie gastro-intestinale supérieure (HGIS) parmi les patients atteints de cirrhose. On administre communément de la vitamine K1 aux patients présentant une HGIS et dont la mesure du rapport international normalisé (RIN) est élevée, malgré le manque de preuves soutenant cette pratique. OBJECTIFS: L'objectif principal consistait à décrire la fréquence de la reprise du saignement dans les 30 jours après l'administration de la vitamine K1 à des patients atteints de cirrhose et de HGIS. L'objectif secondaire consistait à décrire les schémas de prescription de la vitamine K1. MÉTHODE: Cette étude multicentrique, descriptive et rétrospective comprenait des patients atteints de cirrhose et de HGIS, ayant été admis à n'importe lesquels des quatre hôpitaux de soins actifs pour adultes de Calgary, Alberta, du 1er janvier 2014 au 31 décembre 2016. Les patients étaient répartis en deux groupes : ceux ayant reçu de la vitamine K1 et ceux n'en ayant pas reçu. RÉSULTATS: Le nombre total de 370 patients correspondait aux critères d'inclusion. Parmi ceux-ci, 243 avaient reçu de la vitamine K1 et 127 n'en n'avaient pas reçu. Les caractéristiques de base étaient similaires entre les groupes. Un plus grand nombre de patients du groupe « Vitamine K1 "avaient reçu une transfusion d'un concentré de globules rouges, de plasma frais congelé, de plaquettes, de cryoprécipité ou de concentré de prothrombine au cours de leur séjour hospitalier. On n'a noté aucune différence significative dans la durée des injections de pantoprazole et d'octréotide. Le nombre d'admissions de patients du groupe « Vitamine K1 ¼ à l'unité de soins intensifs était plus élevé et le séjour de ceux-ci était plus long. L'endoscopie a montré qu'un plus grand nombre de patients du groupe « Sans vitamine K1 ¼ présentaient des varices oesophagiennes nécessitant un traitement endoscopique. Dans les 30 jours après le saignement initial, quarante (16,5 %) patients du groupe « Vitamine K1 ¼ et 7 (5,5 %) du groupe « Sans vitamine K1 ¼ ont subi une nouvelle hémorragie. La dose moyenne totale de vitamine K1 administrée était de 25 mg. CONCLUSIONS: Les résultats de l'étude tendent à démontrer que la vitamine K1 ne réduit pas la fréquence de la reprise du saignement dans les 30 jours qui suivent le saignement initial parmi les patients atteints de cirrhose et de HGIS.

PHArmacists' perspective oN the Take hOme naloxone prograM (The PHANTOM Study).

OBJECTIVE: To evaluate pharmacists' attitudes toward the Take Home Naloxone (THN) program and identify areas that could be improved to support pharmacists' involvement. METHODS: Pharmacists on the Alberta College of Pharmacists' directory were invited to complete an online survey between July 10 and August 8, 2016. The survey consisted of 19 questions. Descriptive statistics were used to analyze the data. RESULTS: Four hundred seventy pharmacists completed the survey (response rate = 11.2%). A total of 76.8% of respondents strongly agreed or agreed that pharmacists should be screening patients to identify those at risk of opioid overdose. Full-time pharmacists were more likely to agree (p = 0.02). A total of 79.8% of respondents strongly agreed or agreed that pharmacists should be recommending THN kits. Pharmacists working in large population centres (p = 0.008) and full-time pharmacists (p = 0.02) were more likely to agree with this statement. Furthermore, 60.6% of pharmacists were extremely willing or very willing to participate in the THN program. Pharmacists in practice for ≤15 years were more willing to participate in the THN program than pharmacists in practice >15 years (p = 0.03). The most common perceived barriers to implementation of the THN program were lack of time in pharmacists' current work environment and education about the program. CONCLUSIONS: Overall, pharmacists had positive attitudes toward screening patients to identify those at risk of opioid overdose, recommending THN kits and willingness to participate in the program. Factors that may facilitate increased participation in the program include addressing time issues and improving education about the THN program.

Thiamine Prescribing Practices for Adult Patients Admitted to an Internal Medicine Service.

BACKGROUND: Thiamine (vitamin B1) is an essential cofactor responsible for the breakdown of glucose, and its deficiency is associated with Wernicke encephalopathy (WE). There is a lack of evidence from systematic studies on the optimal dosing of thiamine for WE. Objectives: The primary objective was to describe the prescribing patterns for IV thiamine in adult patients admitted to a large teaching hospital. The secondary objective was to evaluate the clinical resolution of WE symptoms (confusion, ataxia, and/or ocular motor abnormalities) in relation to the dose of IV thiamine prescribed. METHODS: A retrospective design was used to review data for adult patients admitted to an internal medicine service from June 1, 2014, to June 30, 2015. All patients included in the study received IV thiamine: low-dose therapy was defined as 100 mg IV daily and high-dose therapy was defined as dosage greater than 100 mg IV daily. RESULTS: A total of 141 patients were included; low-dose thiamine was prescribed for 115 (81.6%) and high-dose thiamine for 26 (18.4%). Patients for whom high-dose thiamine was prescribed were more likely to be those in whom a diagnosis of WE was being considered (12/26 [46.2%] versus 5/115 [4.3%], p < 0.001). Of the total 219 IV thiamine doses ordered, 180 (82.2%) were for 100 mg, and 143 (65.3%) were prescribed for once-daily administration. There was no statistically significant difference in the time to resolution of WE symptoms for patients receiving high-dose versus low-dose thiamine. CONCLUSIONS: A wide variety of thiamine prescribing patterns were noted. This study did not show a difference in time to resolution of WE symptoms in relation to the dose of IV thiamine. Additional large-scale studies are required to determine the optimal dosing of thiamine for WE.

CONTEXTE: La thiamine (vitamine B1) est un cofacteur essentiel responsable du métabolisme du glucose. Une carence en thiamine est associée à l'encéphalopathie de Wernicke (EW). Or, on observe une absence de données probantes provenant d'analyses systématiques portant sur la posologie optimale de thiamine dans le traitement de l'EW. OBJECTIFS: L'objectif principal était de décrire les habitudes de prescription de thiamine à administrer par voie intraveineuse chez les patients adultes admis dans un important hôpital universitaire. L'objectif secondaire était d'évaluer la disparition clinique des symptômes de l'EW (confusion, ataxie ou troubles moteurs oculaires) en fonction de la dose prescrite de thiamine à administrer par voie intraveineuse. MÉTHODES: Un plan d'étude rétrospectif a été utilisé pour étudier les données concernant les patients adultes admis à un service de médecine interne entre le 1er juin 2014 et le 30 juin 2015. Tous les patients à l'étude ont reçu de la thiamine par voie intraveineuse : le traitement à faible dose était de 100 mg par jour et le traitement à dose élevée excédait 100 mg par jour. RÉSULTATS: Au total, 141 patients ont été admis à l'étude; l'on a prescrit une faible dose de thiamine à 115 (81,6 %) d'entre eux et une dose élevée aux 26 (18,4 %) autres. Les patients qui se sont vus prescrire une dose élevée de thiamine étaient vraisemblablement ceux pour qui l'on envisageait un diagnostic d'EW (12/26 [46,2 %] contre 5/115 [4,3 %], p < 0,001). Pour l'ensemble des 219 doses prescrites de thiamine à administrer par voie intraveineuse, 180 (82,2 %) étaient de 100 mg et 143 (65,3 %) devaient être injectées à une fréquence uniquotidienne. On n'a relevé aucune différence statistiquement significative quant au temps de disparition des symptômes de l'EW entre les patients ayant reçu une dose élevée de thiamine et ceux en ayant reçu une faible dose. CONCLUSIONS: On a noté une grande variété d'habitudes de prescription de la thiamine. La présente étude n'a pas montré que la dose de thiamine administrée par voie intraveineuse changeait le temps nécessaire à la disparition des symptômes de l'EW. Il est nécessaire de mener de plus amples études à grande échelle afin de déterminer quelle est la posologie optimale de thiamine dans le traitement de l'EW.

Supravenous Hyperpigmentation in an HIV-Infected Patient.

A 47-year-old African American man was seen for routine follow-up for his human immunodeficiency virus (HIV). The patient's medical history included insomnia, gastroesophageal reflux disease, pulmonary embolism, right shoulder musculoskeletal pain, latent tuberculosis infection, sickle cell trait (hemoglobin S variant), and HIV of 24 years' duration.

Thiamine prescribing practices within university-affiliated hospitals: a multicenter retrospective review.

BACKGROUND: Patients with suspected thiamine deficiency should receive treatment with parenteral thiamine to achieve the high serum thiamine levels necessary to reverse the effects of deficiency and to circumvent problems with absorption common in the medically ill. OBJECTIVE: To quantify rates of parenteral administration of thiamine across university-affiliated hospitals and to identify factors associated with higher rates of parenteral prescribing. DESIGN: Multicenter, retrospective observational study of thiamine prescriptions. METHODS: Prescriptions for thiamine were captured from computerized pharmacy information systems across participating centers, providing information concerning dose, route, frequency, and duration of thiamine prescribed from January 2010 to December 2011. SETTING: Fourteen university-affiliated tertiary care hospitals geographically distributed across Canada, including 48,806 prescriptions for thiamine provided to 32,213 hospitalized patients. RESULTS: Parenteral thiamine accounted for a statistically significant majority of thiamine prescriptions (57.6%, P < 0.001); however, oral thiamine constituted a significant majority of the total doses prescribed (68.4%, z = 168.9; P < 0.001). Protocols prioritizing parenteral administration were associated with higher rates of parenteral prescribing (61.3% with protocol, 45.8% without protocol; P < 0.001). Patients admitted under psychiatry services were significantly more likely to be prescribed oral thiamine (P < 0.001). CONCLUSIONS: Although parenteral thiamine accounted for a statistically significant majority of prescriptions, oral thiamine was commonly prescribed within academic hospitals. Additional strategies are needed to promote parenteral thiamine prescribing to patients with suspected thiamine deficiency.

Vascular protection in patients with diabetes admitted for vascular surgery in a canadian tertiary care hospital: pilot study.

BACKGROUND: Patients with peripheral artery disease are 6 times as likely as healthy individuals to die of cardiovascular causes within 10 years after diagnosis. Combination therapy with a statin, an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB), and an antiplatelet agent is recommended to reduce cardiovascular events in patients with peripheral artery disease, especially those with concomitant diabetes mellitus and those who have undergone vascular surgery. OBJECTIVES: The primary objective was to determine the proportion of patients with concurrent diabetes and peripheral artery disease who were receiving therapy with a statin, ACE inhibitor or ARB, and antiplatelet agent (acetylsalicylic acid or clopidogrel) at the time of discharge after vascular surgery. The secondary objectives were to determine if target blood pressure was achieved and if smoking cessation therapy was offered and/or provided. METHODS: This pilot study was a retrospective, cross-sectional chart analysis. The health records database for Alberta Health Services was searched to identify patients with diabetes who underwent vascular surgery at the Foothills Hospital in Calgary with discharge between January 1 and June 30, 2010. In addition to baseline demographic characteristics, blood pressure values at the time of admission and discharge were collected. Discharge medications, including cardiovascular medications such as statins, ACE inhibitor or ARB, and antiplatelet agents, were recorded. Descriptive analysis of the data was performed. RESULTS: Of the 42 patients for whom charts were obtained, 25 (60%) had prescriptions for cardiovascular triple therapy (statin, ACE inhibitor or ARB, antiplatelet agent). Just over half of the patients (23 [55%]) had achieved target blood pressure (< 130/80 mm Hg) at the time of discharge. Of the 14 current smokers, 9 (64%) had documented evidence in the chart that smoking cessation counselling was offered and/or drug therapy was provided. CONCLUSION: Only about half of the patients in this study were receiving cardiovascular triple therapy, which suggests that many patients were not receiving optimal vascular protection. A larger study is needed to review prescribing patterns for patients with peripheral artery disease.

CONTEXTE: Les patients atteints d'une maladie artérielle périphérique ont un risque six fois plus élevé de mourir d'une maladie cardiovasculaire dans les 10 ans suivant le diagnostic que les personnes non atteintes d'une telle maladie artérielle. Les traitements associant une statine, un inhibiteur de l'enzyme de conversion de l'angiotensine (ECA) ou un antagoniste des récepteurs de l'angiotensine II (ARA), et un antiplaquettaire sont recommandés pour réduire le risque d'événements cardiovasculaires chez les patients atteints d'une maladie artérielle périphérique, particulièrement ceux présentant un diabète sucré concomitant ou ayant subi une chirurgie vasculaire. OBJECTIFS: Le principal objectif était de déterminer la proportion de patients présentant simultanément un diabète et une maladie artérielle périphérique qui recevaient un traitement associant une statine, un inhibiteur de l'ECA ou un ARA, et un antiplaquettaire (acide acétylsalicylique ou clopidogrel) au moment de leur congé de l'hôpital après une chirurgie vasculaire. Les objectifs secondaires étaient de déterminer si les chiffres tensionnels ciblés ont été atteints et si un traitement de cessation tabagique a été offert ou prodigué. MÉTHODES: Il s'agit d'une étude pilote menée au moyen de l'analyse transversale rétrospective de dossiers médicaux. Une recherche a été effectuée dans la base de données des dossiers médicaux des Services de santé de l'Alberta pour recenser les patients atteints de diabète qui avaient subi une chirurgie vasculaire à l'Hôpital Foothills de Calgary et reçu leur congé entre le 1er janvier et le 30 juin 2010. Les données démographiques de base ont été recueillies, de même que les chiffres tensionnels au moment de l'hospitalisation et du congé des patients. Les médicaments prescrits au congé du patient, dont les agents cardiovasculaires comme les statines, les inhibiteurs de l'ECA ou les ARA, et les antiplaquettaires, ont été relevés. Une analyse descriptive des données a été effectuée. RÉSULTATS: Des 42 patients dont les dossiers médicaux ont été obtenus, 25 (60 %) avaient reçu une prescription pour une trithérapie cardiovasculaire (statine, inhibiteur de l'ECA ou ARA, antiplaquettaire). Un peu plus de la moitié des patients (23 [55 %]) avaient atteint les chiffres tensionnels ciblés (< 130/80 mm Hg) au moment de leur congé de l'hôpital. Selon les dossiers médicaux, des 14 fumeurs, 9 (64 %) avaient eu une consultation ou reçu une pharmacothérapie pour la cessation tabagique. CONCLUSION: Environ seulement la moitié des patients de cette étude avaient reçu une trithérapie cardiovasculaire, ce qui suggère que plusieurs patients n'avaient pas reçu une prophylaxie vasculaire optimale. Une étude de plus grande envergure est nécessaire pour examiner les habitudes de prescription chez les patients atteints d'une maladie artérielle périphérique. [Traduction par l'éditeur].

Clinical experience with argatroban for heparin-induced thrombocytopenia in a large teaching hospital.

BACKGROUND: Argatroban is a direct thrombin inhibitor approved for the prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia (HIT). The product monograph does not guide clinicians beyond specifying the initial dose of 2 µg/kg per minute (or 0.5 µg/kg per minute for patients with hepatic impairment). Some authors have suggested that in the intensive care unit (ICU) and for patients with acute cardiac disease and those with renal or hepatic dysfunction, this dose may result in a supratherapeutic activated partial thromboplastin time (aPTT). OBJECTIVES: To evaluate the efficacy and safety of argatroban in adult patients with suspected HIT in a large teaching hospital, and to review dosing for patients in the ICU, patients with acute cardiac disease, and patients with renal or hepatic dysfunction. METHODS: Charts of patients with suspected HIT who had received argatroban for at least 24 h between October 1, 2005, and October 1, 2007, at the Foothills Medical Centre, Calgary, Alberta, were examined retrospectively. RESULTS: Thirty patients met the inclusion criteria, with charts available for review. Of these, 21 (70%) patients had an initial argatroban dose of 2 µg/kg per minute and 4 (13%) had an initial dose of 0.5 µg/kg per minute. The median duration of therapy was 6 days, and the mean dose was 2.14 µg/kg per minute. There were 122 dosage adjustments, the most common change being 0.5 µg/kg per minute, followed by adjustments of 1 and 0.1 µg/kg per minute. Six patients had supratherapeutic aPTT values (above 100 s), and none experienced major bleeding. CONCLUSIONS: The results of this study suggest that an initial argatroban dose of 2 µg/kg per minute is appropriate for patients with no hepatic dysfunction. Patients with acute cardiac disease and critically ill patients may require lower doses of argatroban; however no dosage adjustments are required for patients with renal dysfunction.

Carbamazepine toxicity induced by lopinavir/ritonavir and nelfinavir.

OBJECTIVE: To present a case of carbamazepine toxicity induced by lopinavir/ritonavir and nelfinavir. CASE SUMMARY: A 50-year-old HIV-positive male developed excessive drowsiness secondary to carbamazepine when an antiretroviral regimen containing lopinavir/ritonavir was introduced. The carbamazepine serum concentration increased 46%. Subsequently, the patient developed a possible adverse skin reaction to his antiretrovirals and was hospitalized. The protease inhibitor was changed to nelfinavir. Within 3 days, the patient again developed excessive drowsiness and became unsteady on his feet. This time, the carbamazepine serum concentration had increased by 53%. In both instances, the carbamazepine dosage was decreased by 33%, which resulted in resolution of symptoms. DISCUSSION: Carbamazepine undergoes extensive hepatic metabolism. The major metabolic pathway involves oxidation of carbamazepine via CYP3A4 to an active metabolite, carbamazepine-10,11-epoxide. Protease inhibitors are well-known CYP3A4 inhibitors. Other cases of carbamazepine toxicity secondary to protease inhibitors are reviewed. A MEDLINE search (1966-May 2006) revealed 4 cases of carbamazepine toxicity secondary to antiretrovirals. Carbamazepine serum concentrations increased two- to threefold from baseline. Vertigo, drowsiness, disorientation, ataxia, and vomiting occurred within 12 hours to 2 months, which resolved with reduction of the carbamazepine dosage. CONCLUSIONS: An objective causality assessment suggests that our patient became drowsy and unsteady on his feet secondary to a carbamazepine-protease inhibitor interaction. Lopinavir/ritonavir and nelfinavir may decrease carbamazepine metabolism, causing an elevation in carbamazepine serum concentrations. Carbamazepine toxicity may be prevented by reducing the carbamazepine dosage by 25-50% when protease inhibitors are introduced. A carbamazepine serum concentration should be repeated 3-5 days after the protease inhibitors are started.

Inappropriate use of intravenous pantoprazole: extent of the problem and successful solutions.

BACKGROUND & AIMS: Indications for intravenous proton pump inhibitors (IV PPI) include upper gastrointestinal bleeding (UGIB) from peptic ulcer disease with high-risk stigmata and patients receiving nothing by mouth (NPO). The objectives were to assess the extent of errors in indications for IV PPI use and to determine whether multidisciplinary interventions could improve IV PPI use and costs. METHODS: Part 1: Patients prescribed IV PPI during a period of 4 months were divided into 2 settings, UGIB or non-UGIB. The setting-specific appropriateness of the IV PPI indication and dosing regimen was determined. Part 2: Patients prescribed IV PPI before and after multidisciplinary interventions (educating physicians, a computerized dose template, pharmacists altering IV PPI orders in non-UGIB patients who were not NPO, and recommending a GI consult when a continuous infusion was ordered) were studied. Incidence of prescribing errors, IV PPI costs, and potential confounders were compared. RESULTS: Part 1: Only 50% of UGIB (n = 145) patients received IV PPI for an appropriate indication. Both indication and dosing regimen were appropriate in 21%. In the non-UGIB group (n = 95), 33% were truly NPO; 51% had a correct dosing frequency. Part 2: The postintervention (n = 105) group (vs the preintervention group, n = 113) showed a significant absolute reduction in the degree of inappropriate indication in the UGIB (26%; 95% confidence interval [CI], 10%-42%; P < .0001) and in the non-UGIB (41%; 95% CI, 24%-58%; P < .0001) subgroups. However, a greater improvement in underspending than overspending meant that overall costs were unchanged. CONCLUSIONS: IV PPI was frequently prescribed inappropriately and incorrectly; simple maneuvers resulted in reductions in errors.