Characterization of Venous Thromboembolism Risk in Medical Inpatients Using Different Clinical Risk Assessment Models.

BACKGROUND: Symptomatic venous thromboembolism (VTE) occurs in about 1% of patients within 3 months after admission to a medical unit. Recent evidence for thromboprophylaxis in an unselected medical inpatient population has suggested only a modest net benefit. Consequently, guidelines recommend careful risk stratification to guide thromboprophylaxis. OBJECTIVES: To compare candidacy for thromboprophylaxis according to 4 risk stratification models: a regional preprinted order (PPO) set used in the study institution, the Padua Prediction Score, and the IMPROVE predictive and associative risk assessment models. METHODS: A retrospective review of health records was undertaken for patients with no contraindication to pharmacologic thromboprophylaxis who were admitted to the internal medicine service of a teaching hospital between April and July 2013. RESULTS: Of the 298 patients in the study cohort, 238 (80.0%) received pharmacologic thromboprophylaxis on admission, ordered according to the regional PPO. However, according to the Padua and the IMPROVE predictive risk assessment models, only 64 (21.5%) and 21 (7.0%) of the patients, respectively, were eligible for thromboprophylaxis at the time of admission. On the basis of risk factors identified during the subsequent hospital stay, 54 (18.1%) of the patients were eligible for thromboprophylaxis according to the IMPROVE associative model. Chance-corrected agreement between the PPO and the published risk assessment models was generally poor, with kappa coefficients of 0.109 for the PPO compared with the Padua Prediction Score and 0.013 for the PPO compared with the IMPROVE predictive model. CONCLUSIONS: These data suggest that quantitative models such as the Padua Prediction Score and the IMPROVE models identify more patients at low risk of venous thromboembolism than do in-hospital qualitative risk assessment models. Adoption of these guideline-based risk assessment models for predicting thromboembolic risk in medical inpatients could reduce the use of pharmacologic thromboprophylaxis from 80% to as low as 7%. Further external prognostic validation of risk assessment models and impact analysis studies may show improvements in safety and resource utilization.

La thromboembolie veineuse symptomatique se produit chez environ 1 % des patients dans les trois mois suivant leur admission à un service médical. Des données récentes portant sur la thromboprophylaxie chez une population non sélectionnée de patients hospitalisés ne suggéraient qu'un modeste avantage. Par conséquent, les lignes directrices recommandent une stratification du risque rigoureuse pour guider l'emploi d'une thromboprophylaxie.

Effectiveness of Sodium Polystyrene Sulfonate for Short-Term Treatment of Hyperkalemia.

BACKGROUND: Sodium polystyrene sulfonate (SPS) is a potassium-binding resin that is commonly used to treat mild hyperkalemia. However, there is limited evidence supporting its effectiveness in the short-term management of hyperkalemia. OBJECTIVE: To determine whether SPS is effective in reducing serum potassium in general medical patients after a single oral dose. METHODS: A retrospective observational study was conducted for patients admitted to the internal medicine service of a tertiary care hospital between January 2011 and May 2012 with documentation of a serum potassium level between 5.0 and 5.9 mmol/L during the hospital stay. Patients eligible for inclusion were adults without chronic or acute renal failure or recent changes in medication or diet that would affect serum potassium level. Propensity score matching was performed to minimize differences between the control group (no treatment) and the treatment group (treatment with oral SPS). Follow-up serum potassium levels (at 6-24 h) were compared with index potassium levels. RESULTS: A total of 138 patients met the inclusion criteria, 72 in the control group and 66 in the treatment group. For most patients in the treatment group, the dose was 15 or 30 g of SPS orally. The difference between the control and treatment groups in terms of mean change in serum potassium at 6 to 24 h after the index potassium measurement was statistically significant (by paired t test) in both an unmatched analysis (-0.41 ± 0.50 and -0.58 ± 0.39 mmol/L, respectively; p = 0.039) and a matched analysis (-0.44 ± 0.29 and -0.58 ± 0.39 mmol/L, respectively; p = 0.026). No difference was observed in terms of mean change in serum potassium between patients who received 15 and 30 g of SPS (-0.51 ± 0.38 and -0.66 ± 0.40 mmol/L, respectively; p = 0.13). CONCLUSIONS: In patients with mild hyperkalemia, oral SPS therapy reduced serum potassium by 0.14 mmol/L more than control. Although this difference was statistically significant, the small treatment effect observed in this study may not be clinically important. Furthermore, the cost and potential adverse effects of treatment suggest that routine use of SPS may be inappropriate for patients with mild hyperkalemia. Prospective randomized controlled trials would help in further evaluating the effectiveness and safety of SPS.

CONTEXTE: Le sulfonate de polystyrène sodique (SPS), une résine qui fixe le potassium, est fréquemment employé pour traiter l'hyperkaliémie légère. Or, peu de données appuient son efficacité réelle dans le traitement à court terme de ce trouble. OBJECTIF: Déterminer si le SPS permet de réduire les taux sériques de potassium chez les patients traités en médecine générale après administration d'une seule dose par voie orale. MÉTHODES: Une étude d'observation rétrospective a porté sur des patients hospitalisés au service de médecine interne d'un centre hospitalier de soins tertiaires entre janvier 2011 et mai 2012 qui ont présenté des taux sériques de potassium entre 5,0 et 5,9 mmol/L durant leur séjour. Seuls étaient admissibles à l'étude les patients adultes sans insuffisance rénale chronique ou aiguë et sans changement récent à leur pharmacothérapie ou à leur diète qui pourrait influencer leur taux de potassium sérique. Un appariement par scores de propension a été réalisé afin de réduire au minimum les différences entre le groupe témoin (sans traitement) et le groupe traité (administration de SPS par voie orale). Les kaliémies de contrôle (de 6 heures à 24 heures plus tard) ont été comparées aux indices d'hyperkaliémie. RÉSULTATS: En tout, 138 patients ont satisfait aux critères d'inclusion; 72 ont été placés dans le groupe témoin et 66 dans le groupe traité. La dose de SPS administrée aux patients du groupe traité était généralement de 15 g ou de 30 g par voie orale. En ce qui concerne le changement moyen des taux sériques de potassium mesurés de 6 à 24 heures suivant les indices d'hyperkaliémie, la différence entre le groupe témoin et le groupe traité était statistiquement significative (selon un test t pour échantillons appariés), et ce, autant dans une analyse non appariée (respectivement −0,41 ± 0,50 et −0,58 ± 0,39 mmol/L; p = 0,039) que dans une analyse appariée (respectivement −0,44 ± 0,29 et −0,58 ± 0,39 mmol/L; p = 0,026). Aucune différence n'a été observée en ce qui a trait au changement moyen des taux sériques de potassium entre les patients ayant reçu 15 g de SPS et ceux en ayant reçu 30 g (respectivement −0,51 ± 0,38 et −0,66 ± 0,40 mmol/L; p = 0,13). CONCLUSIONS: Chez les patients présentant une hyperkaliémie légère traités à l'aide de SPS par voie orale, on a observé une baisse des taux sériques de potassium de 0,14 mmol/L de plus que chez ceux du groupe témoin. Bien que cette différence fût statistiquement significative, le faible effet thérapeutique relevé dans cette étude pourrait ne pas être cliniquement important. De plus, les coûts ainsi que les effets indésirables potentiels du traitement laissent croire que le recours systématique au SPS pourrait être inapproprié pour les patients atteints d'hyperkaliémie légère. Des essais cliniques comparatifs aléatoires prospectifs aideraient à évaluer plus en profondeur l'efficacité réelle et l'innocuité du SPS.

Pharmacological interventions for the acute management of hyperkalaemia in adults.

BACKGROUND: Hyperkalaemia is a potentially life-threatening electrolyte disturbance which may lead to cardiac arrhythmias and death. Renal replacement therapy is known to be effective in treating hyperkalaemia, but safe and effective pharmacological interventions are needed to prevent dialysis or avoid the complications of hyperkalaemia until dialysis is performed. OBJECTIVES: This review looked at the benefits and harms of pharmacological treatments used in the acute management of hyperkalaemia in adults. This review evaluated the therapies that reduce serum potassium as well as those that prevent complications of hyperkalaemia. SEARCH METHODS: We searched Cochrane Kidney and Transplant's Specialised Register to 18 August 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs looking at any pharmacological intervention for the acute management of hyperkalaemia in adults were included in this review. Non-standard study designs such as cross-over studies were also included. Eligible studies enrolled adults (aged 18 years and over) with hyperkalaemia, defined as serum potassium concentration ≥ 4.9 mmol/L, to receive pharmacological therapy to reduce serum potassium or to prevent arrhythmias. Patients with artificially induced hyperkalaemia were excluded from this review. DATA COLLECTION AND ANALYSIS: All three authors screened titles and abstracts, and data extraction and risk of bias assessment was performed independently by at least two authors. Studies reported in non-English language journals were translated before assessment. Authors were contacted when information about results or study methodology was missing from the original publication. Although we planned to group all studies of a particular pharmacological therapy regardless of administration route or dose for analysis, we were unable to conduct meta-analyses because of the small numbers of studies evaluating any given treatment. For continuous data we reported mean difference (MD) and 95% confidence intervals (CI). MAIN RESULTS: We included seven studies (241 participants) in this review. Meta-analysis of these seven included studies was not possible due to heterogeneity of the treatments and because many of the studies did not provide sufficient statistical information with their results. Allocation and blinding methodology was poorly described in most studies. No study evaluated the efficacy of pharmacological interventions for preventing clinically relevant outcomes such as mortality and cardiac arrhythmias; however there is evidence that several commonly used therapies effectively reduce serum potassium levels. Salbutamol administered via either nebulizer or metered-dose inhaler (MDI) significantly reduced serum potassium compared with placebo. The peak effect of 10 mg nebulised salbutamol was seen at 120 minutes (MD -1.29 mmol/L, 95% CI -1.64 to -0.94) and at 90 minutes for 20 mg nebulised salbutamol (1 study: MD -1.18 mmol/L, 95% CI -1.54 to -0.82). One study reported 1.2 mg salbutamol via MDI 1.2 mg produced a significant decrease in serum potassium beginning at 10 minutes (MD -0.20 mmol/L, P < 0.05) and a maximal decrease at 60 minutes (MD -0.34 mmol/L, P < 0.0001). Intravenous (IV) and nebulised salbutamol produced comparable effects (2 studies). When compared to other interventions, salbutamol had similar effect to insulin-dextrose (2 studies) but was more effective than bicarbonate at 60 minutes (MD -0.46 mmol/L, 95% CI -0.82 to -0.10; 1 study). Insulin-dextrose was more effective than IV bicarbonate (1 study) and aminophylline (1 study). Insulin-dextrose, bicarbonate and aminophylline were not studied in any placebo-controlled studies. None of the included studies evaluated the effect of IV calcium or potassium binding resins in the treatment of hyperkalaemia. AUTHORS' CONCLUSIONS: Evidence for the acute pharmacological management of hyperkalaemia is limited, with no clinical studies demonstrating a reduction in adverse patient outcomes. Of the studied agents, salbutamol via any route and IV insulin-dextrose appear to be most effective at reducing serum potassium. There is limited evidence to support the use of other interventions, such as IV sodium bicarbonate or aminophylline. The effectiveness of potassium binding resins and IV calcium salts has not been tested in RCTs and requires further study before firm recommendations for clinical practice can be made.

ANTECEDENTES: La hiperpotasemia es un trastorno de los electrólitos potencialmente mortal que puede provocar arritmias cardíacas y muerte. Se sabe que el tratamiento de reemplazo renal es efectivo para tratar la hiperpotasemia, pero se necesitan intervenciones farmacológicas seguras y eficaces para prevenir la diálisis o evitar las complicaciones de la hiperpotasemia hasta que se realice la diálisis. OBJETIVOS: Esta revisión analizó los efectos beneficiosos y perjudiciales de los tratamientos farmacológicos utilizados en el tratamiento agudo de la hiperpotasemia en adultos. Esta revisión evaluó los tratamientos que reducen el potasio sérico, así como los que previenen las complicaciones de la hiperpotasemia. MÉTODOS DE BÚSQUEDA: Se realizaron búsquedas en el registro especializado del Grupo Cochrane de Riñón y Trasplantes (Cochrane Kidney and Transplant Group) hasta el 18 de agosto de 2015 mediante contacto con el coordinador de búsqueda de ensayos y se utilizaron términos de búsqueda relevantes para esta revisión. CRITERIOS DE SELECCIÓN: En esta revisión se incluyeron todos los ensayos controlados aleatorios (ECA) y cuasialeatorios que analizaron cualquier intervención farmacológica para el tratamiento agudo de la hiperpotasemia en adultos. También se incluyeron los diseños no estándar de estudios como los estudios cruzados (crossover). Los estudios elegibles reclutaron adultos (18 años de edad o más) con hiperpotasemia, definida como una concentración de potasio sérico ≥ 4,9 mmol/l, para recibir tratamiento farmacológico con el objetivo de reducir el potasio sérico o prevenir las arritmias. Los pacientes con hiperpotasemia artificialmente inducida se excluyeron de esta revisión. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Los tres revisores examinaron los títulos y los resúmenes, y la extracción de los datos y al menos dos revisores realizaron la evaluación del riesgo de sesgo de forma independiente. Los estudios informados en revistas de idiomas diferentes al inglés se tradujeron antes de la evaluación. Se estableció contacto con los autores cuando faltó información acerca de los resultados o la metodología del estudio en la publicación original. Aunque se planificó agrupar todos los estudios de un tratamiento farmacológico particular independientemente de la vía de administración o la dosis para el análisis, no fue posible realizar los metanálisis debido al escaso número de estudios que evaluaron cualquier tratamiento administrado. Para los datos continuos se informó la diferencia de medias (DM) y los intervalos de confianza (IC) del 95%. RESULTADOS PRINCIPALES: Se incluyeron siete estudios (241 participantes) en esta revisión. El metanálisis de estos siete estudios incluidos no fue posible debido a la heterogeneidad de los tratamientos y a que muchos de los estudios no proporcionaron información estadística suficiente con sus resultados. La metodología de asignación y del cegamiento se describió de forma deficiente en la mayoría de los estudios. Ningún estudio evaluó la eficacia de las intervenciones farmacológicas para la prevención de resultados clínicamente relevantes como la mortalidad y las arritmias cardíacas; sin embargo, hay pruebas de que varios tratamientos de uso habitual reducen eficazmente los niveles de potasio sérico. El salbutamol administrado vía nebulizador o inhalador de dosis fija (IDF) redujo significativamente el potasio sérico en comparación con placebo. El efecto máximo de 10 mg de salbutamol nebulizado se observó a los 120 minutos (DM ­1,29 mmol/l; IC del 95%: ­1,64 a ­0,94) y a los 90 minutos para 20 mg de salbutamol nebulizado (un estudio: DM ­1,18 mmol/l; IC del 95%: ­1,54 a ­0,82). Un estudio informó que 1,2 mg de salbutamol vía IDF produjo una disminución significativa en el potasio sérico que comenzó a los diez minutos (DM ­0,20 mmol/l; p < 0,05) y una disminución máxima a los 60 minutos (DM ­0,34 mmol/l; p < 0,0001). El salbutamol intravenoso (IV) y nebulizado produjo efectos equivalentes (dos estudios). En comparación con otras intervenciones el salbutamol tuvo un efecto similar a la insulina­dextrosa (dos estudios), pero fue más eficaz que el bicarbonato a los 60 minutos (DM ­0,46 mmol/l; IC del 95%: ­0,82 a ­0,10; un estudio). La insulina­dextrosa fue más eficaz que el bicarbonato IV (un estudio) y la aminofilina (un estudio). La insulina­dextrosa, el bicarbonato y la aminofilina no se analizaron en estudios controlados con placebo. Ninguno de los estudios incluidos evaluó el efecto del calcio IV o las resinas quelantes de potasio en el tratamiento de la hiperpotasemia. CONCLUSIONES DE LOS AUTORES: Las pruebas para el tratamiento farmacológico agudo de la hiperpotasemia son limitadas, y no hay estudios clínicos que demuestren una reducción en los resultados adversos de los pacientes. De los agentes estudiados, el salbutamol por cualquier vía y la insulina­dextrosa IV parecen ser más eficaces en la reducción del potasio sérico. Hay pruebas limitadas para apoyar la administración de otras intervenciones como bicarbonato de sodio IV o aminofilina. La efectividad de las resinas quelantes de potasio y las sales de calcio IV no se ha probado en ECA y requiere estudios adicionales antes de poder hacer recomendaciones sólidas para la práctica clínica.

Development and validation of a novel vancomycin dosing nomogram for achieving high-target trough levels at 2 canadian teaching hospitals.

BACKGROUND: Recent guidelines recommend a vancomycin trough (predose) level between 15 and 20 mg/L in the treatment of invasive gram-positive infections, but most initial dosing nomograms are designed to achieve lower targets (5-15 mg/L). Clinicians need guidance about appropriate initial dosing to achieve the higher target. OBJECTIVE: To develop and validate a high-target vancomycin dosing nomogram to achieve trough levels of 15-20 mg/L. METHODS: A retrospective study was conducted at 2 teaching hospitals, St Paul's Hospital and Vancouver General Hospital in Vancouver, British Columbia. Patients who were treated with vancomycin between January 2008 and June 2010 and who had achieved a trough level of 14.5-20.5 mg/L were identified. Demographic and clinical data were collected. Multiple linear regression was used to develop a vancomycin dosing nomogram for each hospital site. An integrated nomogram was constructed by merging the data from the 2 hospitals. A unique set of patients at each institution was used for validating their respective nomograms and a pooled group of patients for validating the integrated nomogram. Predictive success was evaluated, and a nomogram was deemed significantly different from another nomogram if p < 0.05 via "χ(2) testing. RESULTS: Data from 78 patients at one hospital and 91 patients at the other were used in developing the respective institutional nomograms. For each hospital's data set, both age and initial serum creatinine were significantly associated with the predicted dosing interval (p < 0.001). Validation in a total of 105 test patients showed that the integrated nomogram had a predictive success rate of 56%. CONCLUSIONS: A novel vancomycin dosing nomogram was developed and validated at 2 Canadian teaching hospitals. This integrated nomogram is a tool that clinicians can use in selecting appropriate initial vancomycin regimens on the basis of age and serum creatinine, to achieve high-target levels of 15-20 mg/L. The nomogram should not replace clinical judgment for patients with unstable and/or reduced renal function.

Spironolactone for hypertension.

BACKGROUND: Spironolactone is an aldosterone antagonist, considered fourth line therapy for hypertension in patients already treated with multiple medications. OBJECTIVES: Primary: to determine the effect of spironolactone on patient mortality, morbidity, and to quantify the magnitude of blood pressure lowering effect of spironolactone monotherapy.Secondary: to determine the prevalence of adverse reactions observed with spironolactone monotherapy and to determine if there is a blood-pressure lowering dose response with spironolactone. SEARCH STRATEGY: We searched the following databases: Cochrane Central Register of Controlled Trials (3rd Quarter 2009), MEDLINE (2005 - Sept. 2009), and EMBASE (2007 - Sept. 2009). References from retrieved studies were reviewed to identify any studies missed in the initial search. No language restrictions were applied. SELECTION CRITERIA: We selected RCTs studying patients with primary hypertension. We excluded studies of patients with secondary or gestational hypertension, and studies where patients were receiving multiple antihypertensives. DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed the search results for studies meeting our criteria. Three reviewers extracted data and assessed trial quality using a standardized data extraction form. Data synthesis and analysis was performed using RevMan 5. MAIN RESULTS: Meta-analysis of the 5 cross-over studies found a reduction in SBP of 20.09 mmHg (95%CI:16.58-23.06,p<0.00001) and a 6.75 mmHg (95%CI:4.8-8.69,p<0.00001) reduction in DBP. These results were statistically significant and there was no evidence of heterogeneity between the studies. There may be a dose response effect with spironolactone up to 50 mg/day, but the confidence intervals around the mean end-of-study blood pressure for doses ranging 25-500 mg/day all overlapped. In other words, it appears that doses >50mg/day do not produce further reductions in either SBP or DBP. One cross-over study found that spironolactone 25 mg/day did not statistically significantly change SBP or DBP compared to placebo, SBP: -9.9 (95%CI:-21.15,1.35); DBP -2.34 (95%CI:-7.92,3.06). AUTHORS' CONCLUSIONS: From the limited available evidence, spironolactone appears to lower blood pressure compared to placebo to a similar degree in patients with primary (essential) hypertension when doses of 100-500 mg/day are given. A dose of 25 mg/day did not statistically significantly reduce systolic or diastolic blood pressure, compared to placebo. Given the lack of a dose-response, coupled with a possible increased risk in adverse events with higher doses, doses of 25 to 100 mg/day are reasonable. There is no evidence of the effect of spironolactone on clinical outcomes in hypertensive patients.