Intravenous diltiazem versus metoprolol for atrial fibrillation with rapid ventricular rate: A meta-analysis.

BACKGROUND: Intravenous diltiazem and metoprolol are both commonly used to treat atrial fibrillation (AF) with rapid ventricular rate (RVR) in the emergency department (ED), but the advantages and disadvantages of these drugs cannot be verified. This meta-analysis aimed to assess the efficacy and safety of intravenous diltiazem versus metoprolol for AF with RVR. METHOD: We systematically searched PubMed, Web of Science, Embase, Cochrane library, the China National Knowledge Infrastructure (CNKI), Wanfang, China Biology Medicine disc (CBM) and the WeiPu (VIP). Meta-analysis was performed using weighted mean difference (WMD), relative risk (RR) and 95% confidence interval (CI). Statistical analysis was performed using Review Manager 5.4.1. RESULTS: Seventeen studies involving 1214 patients in nine randomized controlled trials (RCTs) and eight cohort studies were included in meta-analysis, including 643 patients in the intravenous diltiazem group and 571 patients group in the intravenous metoprolol. The results of the meta-analysis showed that compared with intravenous metoprolol, intravenous diltiazem was found higher efficacy (RR =1.11; 95% CI = 1.06 to 1.16, p < 0.00001), shorter average onset time (RR = -1.13; 95% CI = -1.97 to -0.28, p = 0.009), lower ventricular rate (RR = -9.48; 95% CI = -12.13 to -6.82, p<0.00001), less impact on systolic blood pressure (WMD = 3.76; 95% CI: 0.20 to 7.33, P = 0.04), and no significant difference in adverse events (RR = 0.80, 95% CI = 0.55 to 1.14, P = 0.22) and diastolic blood pressure (WMD = -1.20; 95% CI: -3.43 to 1.04, P = 0.29) was found between intravenous diltiazem and metoprolol. CONCLUSION: Intravenous diltiazem has higher efficacy, shorter average onset time, lower ventricular rate, less impact on blood pressure, and with no increase in adverse events compared to intravenous metoprolol.

Botulinum Toxin Injection Plus Topical Diltiazem for Chronic Anal Fissure: A Randomized Double-Blind Clinical Trial and Long-term Outcome.

BACKGROUND: Chemical sphincterotomy avoids the risk of permanent incontinence in the treatment of chronic anal fissure, but it does not reach the efficacy of surgery and recurrence is high. Drug combination has been proposed to overcome these drawbacks. OBJECTIVE: This study aimed to compare the clinical, morphological, and functional effects of combined therapy with botulinum toxin injection and topical diltiazem in chronic anal fissure and to assess the long-term outcome after healing. DESIGN: This is a randomized, controlled, double-blind, 2-arm, parallel-group trial with a long-term follow-up. SETTINGS: This study was conducted at a tertiary care center. PATIENTS: A total of 70 consecutive patients were referred to the gastroenterology department of a hospital in Valencia, Spain. INTERVENTION: After botulinum toxin injection (20 IU), patients were randomly assigned to local diltiazem (diltiazem group) or placebo gel (placebo group) for 12 weeks. MAIN OUTCOME MEASURES: The primary outcome was fissure healing (evaluated by video register by 3 independent physicians). Secondary outcomes included symptomatic relief (30-day diary), effect on anal sphincters (manometry), safety, and long-term recurrence (24 months and 10 years). RESULTS: Healing was achieved per protocol in 13 of 25 (52%) patients of the diltiazem group and 11 of 30 (36.7%) patients of the placebo group (p = 0.25); on an intention-to-treat basis in 37.1% and 31.4% (p = 0.61). Both groups displayed significant reduction of anal pressures. Thirty percent reported minor and transitory incontinence, without differences between groups. Nine (69.2%) of the diltiazem group and 6 (54.5%) of the placebo group experienced a relapse at 24 months (p = 0.67). The overall recurrence rate at 10 years was 83.3% (20/24 patients). LIMITATIONS: This study was limited by the loss of patients during the trial. The low healing rate led to a small cohort to assess recurrence. CONCLUSIONS: Combined botulinum toxin injection and topical diltiazem is not superior to botulinum toxin injection in the treatment of chronic anal fissure. Both options offer suboptimal healing rates. Long-term recurrence is high (>80% at 10 years) and might appear at any time after healing. See Video Abstract at http://links.lww.com/DCR/B527. INYECCIN DE TOXINA BOTULNICA MS DILTIAZEM TPICO EN FISURA ANAL CRNICA UN ENSAYO CLNICO ALEATORIZADO DOBLE CIEGO Y RESULTADOS A LARGO PLAZO: ANTECEDENTES:La esfinterotomía química evita el riesgo de incontinencia permanente en el tratamiento de la fisura anal crónica, pero no alcanza la eficacia de la cirugía y la recurrencia es alta. Se ha propuesto la combinación de fármacos para superar estos inconvenientes.OBJETIVO:Comparar los efectos clínicos, morfológicos y funcionales de la terapia combinada con inyección de toxina botulínica y diltiazem tópico en fisura anal crónica y evaluar el resultado a largo plazo después de la cicatrización.DISEÑO:Ensayo aleatorizado, controlado, doble ciego, de dos brazos, de grupos paralelos con un seguimiento a largo plazo.ESCENARIO:Estudio realizado en un centro de atención terciaria.PACIENTES:Un total de 70 pacientes consecutivos referidos al servicio de gastroenterología de un hospital de Valencia, España.INTERVENCIÓN:Después de la inyección de toxina botulínica (20UI), los pacientes fueron asignados al azar a diltiazem local (grupo de diltiazem) o gel de placebo (grupo de placebo) durante 12 semanas.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la cicatrización de la fisura (evaluado por registro de video por tres médicos independientes). Los resultados secundarios incluyeron alivio sintomático (diario de 30 días), efecto sobre los esfínteres anales (manometría), seguridad y recurrencia a largo plazo (24 meses y 10 años).RESULTADOS:La curación se logró por protocolo en 13/25 (52%) en el grupo de Diltiazem y 11/30 (36,7%) en el grupo de Placebo (p = 0.25); por intención de tratar en el 37.1% y el 31.4%, respectivamente (p = 0.61). Ambos grupos mostraron una reducción significativa de las presiones anales. El 30% refirió incontinencia leve y transitoria, sin diferencias entre grupos. 9 (69.2%) del grupo de Diltiazem y 6 (54.5%) del grupo de placebo recurrieron a los 24 meses (p = 0.67). La tasa global de recurrencia a los 10 años fue del 83.3% (20/24 pacientes).LIMITACIONES:La pérdida de pacientes a lo largo del ensayo. La baja tasa de curación llevó a una pequeña cohorte para evaluar la recurrencia.CONCLUSIONES:La inyección combinada de toxina botulínica y diltiazem tópico no es superior a la inyección de TB en el tratamiento de la fisura anal crónica. Ambas opciones ofrecen tasas de curación subóptimas. La recurrencia a largo plazo es alta (> 80% a los 10 años) y puede aparecer en cualquier momento después de la curación. Consulte Video Resumen en http://links.lww.com/DCR/B527.

Dose tailoring of tacrolimus based on a non-linear pharmacokinetic model in children with refractory nephrotic syndrome.

The population pharmacokinetics (PPK) of tacrolimus (TAC) in children with refractory nephrotic syndrome (RNS) have not been well-characterized. This study aimed to investigate the significant factors affecting the TAC PPK characteristics of children with RNS and to optimize the dosing regimen. A total of 494 concentrations from 108 children were obtained from routine therapeutic drug monitoring between 2016 and 2018. Information regarding the demographic features, laboratory test results, genetic polymorphisms of CYP3A5 (rs776746) and co-therapy medications were collected. PPK analysis was performed using the nonlinear mixed-effects modelling (NONMEM) software and two modelling strategies (the linear one-compartment model and nonlinear Michaelis-Menten model) were evaluated and compared. CYP3A5 genotype, weight, daily dose of TAC and daily dose of diltiazem were retained in the final linear model. The absorption rate constant (Ka) was set at 4.48 h-1 in the linear model, and the apparent clearance (CL/F) and volume of distribution (V/F) in the final linear model were 14.2 L/h and 172 L, respectively. CYP3A5 genotype, weight and daily dose of diltiazem were the significant factors retained in the final nonlinear model. The maximal dose rate (Vmax) and the average steady-state concentration at half-Vmax (Km) in the final nonlinear model were 2.15 mg/day and 0.845 ng/ml, respectively. The nonlinear model described the pharmacokinetic data of TAC better than the linear model in children with RNS. A dosing regimen was proposed based on weight, CYP3A5 genotype and daily dose of diltiazem according to the final nonlinear PK model, which may facilitate individualized drug therapy with TAC.

Cardiovascular magnetic resonance image analysis and mechanism study for the changes after treatments for primary microvascular angina pectoris.

ABSTRACT: Most cases of primary microvascular angina pectoris (PMVA) are diagnosed clinically, but the etiology and pathological mechanisms are unknown. The effect of routine clinical medications is minimal, and PMVA can progress to serious cardiovascular events. To improve the diagnosis and effective treatment of this disease, this study was designed to diagnose PMVA via cardiovascular magnetic resonance (CMR) and the coronary angiography thrombolysis in myocardial infarction (TIMI) blood flow grade, as well as to analyze vascular endothelial function to elucidate the pathogenesis of PMVA and compare the effects of routine clinical medications.The present randomized controlled trial including a parallel control group will be conducted on 63 PMVA patients in our cardiovascular department. The patients will be selected and randomly divided into the control, diltiazem, and nicorandil groups. The control group will be administered routine drug treatments (aspirin, atorvastatin, betaloc ZOK, perindopril, and isosorbidemononitrate sustained-release tablets). The diltiazem group will be additionally treated with 90 mg qd diltiazem sustained-release capsules. The nicorandil group was additionally given 5 mg tid nicorandil tablets. Coronary angiography will be performed before treatment, the severity and frequency of chest pain will be evaluated before and after 9 months of treatment, and homocysteine and von Willebrand factor levels will be measured. Electrocardiography, echocardiography, dynamic electrocardiography, a treadmill exercise test, and CMR will be performed. Sex, age, body mass index, complications, smoking, and family history will also be recorded. The SPSS19.0 statistical software package will be used to analyze the data. The measurements will be expressed as the mean ±â€Šstandard deviation. Measurement data will be compared between the groups using Student's t-test. A relative number description will be used for the counting data, and the chi-squaretest will be used to compare the groups. A multivariate logistic regression analysis will be performed A P-value < .05 will be considered significant.The direct indices (CMR and coronary angiographic TIMI blood flow grade) may improve after adding diltiazem or nicorandil during routine drug treatments (such as aspirin, statins, and nitrates) in PMVA patients, and indirect indices (homocysteine and von Willebrand factor levels) may be reduced. TRIAL REGISTRATION: Chinese Clinical Trial Registry (http://www.chictr.org.cn/showprojen.aspx?proj=41894), No. CHiCTR1900025319, Registered on August 23, 2019; pre initiation.

Topical Diltiazem Ointment For Post- Hemorrhoidectomy Pain.

BACKGROUND: Hemorrhoids are one of the most common anal pathology affecting millions of people around the world. Milligan-Morgan open hemorrhoidectomy is the most effective hemorrhoidectomy method used as gold standard procedure. Post-operative pain is recognized as a distressing complication of hemorrhoidectomy leading to increase hospital stay and psychological stress to both patient and surgeon. This study is designed to determine the efficacy of diltiazem gel in relieving pain after hemorrhoidectomy caused by anal muscle spasm. This will lead to decreased hospital stay and save both patient and surgeon from stress in postoperative period. OBJECTIVE: To compare mean post-operative pain in patients undergoing hemorrhoidectomy with vs. without topical application of diltiazem gel. METHODS: Total 80 patients who were diagnosed with third- and fourth-degree hemorrhoids and undergo hemorrhoidectomy were included in the study. Patients were randomly allocated to two groups using opaque sealed envelope method. Group A and B both have 40 patients in each group. Pain score was measured on visual analogue scale (VAS) by asking the patients to fill a questionnaire or by the help of the doctor. RESULTS: The patient's average age was 39.98±7.98 years. At 24 hours, mean pain score was significantly high in group B than group A [7.23±0.95 vs. 5.38±1.06; p=0.0005]. At 3rd post-operative day, mean pain score was significantly high in group B than group A [5±0.78 vs. 3.08±0.99; p=0.0005]. Seventy percent cases were observed in group B which required rescue analgesia. CONCLUSIONS: It is concluded that application of diltiazem ointment at perianal area with standard treatment considerably decreases pain after haemorrhoidectomy.

MEBO versus topical Diltiazem versus a combination of both ointments in the treatment of acute anal fissure: a randomized clinical trial protocol.

BACKGROUND: Anal fissure is a common complication of the anorectal region and one of the most reported causes of anal pain. Acute anal fissure can be cured by surgery or medical treatment. There is an increase in the use of topical therapy for the treatment of anal fissures. A common topical drug used is Diltiazem (DTZ), a calcium-channel blocker, which relaxes the anal sphincter and thus promotes healing of the anal fissure. Moist exposed burn ointment (MEBO) is an ointment that is effective for the treatment of burns and wound healing and is becoming popular in the treatment of anal fissures. METHODS: This is a 1:1:1 randomized, controlled, parallel design, with endpoint measures of change in pain score, wound healing, defecation strain score and patient's global impression of improvement. The study will be conducted at AUBMC over a 10-week period. Patients will be randomized to three treatment arms: MEBO, Diltiazem, and a combination of MEBO and Diltiazem ointments. DISCUSSION: The results of this study will allow physicians to assess the efficacy and safety of MEBO in the treatment of acute anal fissure, and also in comparison to Diltiazem. This trial will generate evidence-based conclusions regarding the use of a herbal/natural-based product (MEBO ointment) for the treatment of anal fissures. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04153032 . Clinical Trial Registration Date: 06-NOVEMBER-2019.

Comparison of sustained rate control in atrial fibrillation with rapid ventricular rate: Metoprolol vs. Diltiazem.

OBJECTIVE: The objective of this study was to compare sustained rate control with intravenous (IV) diltiazem vs. IV metoprolol in acute treatment of atrial fibrillation (AF) with rapid ventricular rate (RVR) in the emergency department (ED). METHODS: This retrospective chart review at a large, academic medical center identified patients with AF with RVR diagnosis who received IV diltiazem or IV metoprolol in the ED. The primary outcome was sustained rate control defined as heart rate (HR) < 100 beats per minute without need for rescue IV medication for 3 h following initial rate control attainment. Secondary outcomes included time to initial rate control, HR at initial control and 3 h, time to oral dose, admission rates, and safety outcomes. RESULTS: Between January 1, 2016 and November 1, 2018, 51 patients met inclusion criteria (diltiazem n = 32, metoprolol n = 19). No difference in sustained rate control was found (diltiazem 87.5% vs. metoprolol 78.9%, p = 0.45). Time to rate control was significantly shorter with diltiazem compared to metoprolol (15 min vs. 30 min, respectively, p = 0.04). Neither hypotension nor bradycardia were significantly different between groups. CONCLUSIONS: Choice of rate control agent for acute management of AF with RVR did not significantly influence sustained rate control success. Safety outcomes did not differ between treatment groups.

Diltiazem-loaded electrospun nanofibers as a new wound dressing: fabrication, characterization, and experimental wound healing.

Calcium channel blockers such as diltiazem have recently been investigated for their wound-healing potential. The aims of this study were to fabricate diltiazem-loaded nanofibers for a new wound dressing and investigate their beneficial properties for wound healing. Nanofibers were electrospun using polyvinyl alcohol solution containing 0, 2 or 4% diltiazem. Fibers were characterized in terms of physicochemical properties, drug release and fibroblast viability, and in animal wound healing assays. Compared to other formulations, nanofibers containing 4% diltiazem showed thin fiber size (152.7 nm), high porosity (88.4%), high swelling (110.4%), low water contact angle (29.1°) and little weight loss (17.3%). Drug release from 4%-diltiazem nanofibers showed good fit to a Korsmeyer-Peppas model, suggesting a non-Fickian release mechanism (R 2 = 96%, n = 0.52). In vitro, 4%-diltiazem mats were not cytotoxic and enhanced fibroblast proliferation by 263% after 5 days of treatment compared to control. In vivo, wounds treated with this mat for 14 days showed the smallest size (14.7%) and better histopathologic characteristics compared to other wounds. The 4%-diltiazem mat also demonstrated significant antioxidant activity by reducing tissue MDA and nitrite levels by 63 and 59% compared to normal saline. The findings support the eligibility of this novel wound dressing for additional clinical research.

Diltiazem on tacrolimus exposure and dose sparing in Chinese pediatric primary nephrotic syndrome: impact of CYP3A4, CYP3A5, ABCB1, and SLCO1B3 polymorphisms.

PURPOSE: To evaluate the role of diltiazem on tacrolimus sparing in pediatric primary nephrotic syndrome (PNS) and its relation to CYP3A4, CYP3A5, ABCB1, and SLCO1B3 polymorphisms. METHODS: The PNS children treated with tacrolimus and with steady-state trough concentration (C0) were retrospectively collected. The impacts of diltiazem on tacrolimus dose-adjusted C0 (C0/D), target concentration achievement, and required dose were evaluated. Meanwhile, the relationship between the polymorphisms (including CYP3A4*1G, CYP3A5*3, ABCB1-C3435T, and SCLO1B3) and dose-sparing effect were investigated. RESULTS: A total of 71 children with 535 concentrations, including 16 children with concomitant diltiazem, were involved. Significantly increased C0/D (94.0 vs 83.8 ng/mL per mg/kg, p = 0.038) and lower required daily dose of tacrolimus (0.056 vs 0.064 mg/kg, p = 0.003) were observed in patients co-administered with diltiazem. Subpopulation carrying CYP3A4*1G, CYP3A5*1, ABCB1-3435TT, or SLCO1B3-699AA was presented with enhanced increment in tacrolimus C0/D by 38.8-102.9%. CONCLUSION: Moderate effect of diltiazem on tacrolimus sparing, which might relate to the polymorphisms of CYP3A4, CYP3A5, ABCB1, and SLCO1B3, was documented.

Diltiazem potentiates the cytotoxicity of gemcitabine and 5-fluorouracil in PANC-1 human pancreatic cancer cells through inhibition of P-glycoprotein.

AIM: Pancreatic cancer (PC) is one of the most aggressive tumors with dismal survival and a high death rate due to chemotherapeutic failure. P-glycoprotein (P-gp) plays a pivotal role in PC response to gemcitabine and 5-fluorouracil (5-FU). Diltiazem, a calcium channel blocker, is a P-gp inhibitor. In the current study, we investigated the hypothesis that targeting of P-gp by diltiazem can enhance the cytotoxicity of gemcitabine and 5-FU against human pancreatic cancer cells. MAIN METHODS: The cytotoxic effect of diltiazem, gemcitabine, and 5-FU in single and combined forms against PANC-1 and AsPC-1 cells were assayed by MTT. Flow cytometric analysis was used for the determination of cell cycle, apoptosis, and stemness markers in PC cells. Besides, immunoblotting was used for assessment of Bax, caspase 3, cyclin D1, and P-gp expressions. KEY FINDINGS: Diltiazem co-treatment, either with gemcitabine or 5-FU, synergistically reduced cell viability, induced apoptosis, and caused cell cycle arrest. In addition, diltiazem co-treatment decreased the expressions of stem cell markers CD24 and CD44, increased the expressions of Bax and cleaved caspase 3, enhanced DNA fragmentation, and attenuated cyclin D1 and P-gp expressions as compared to cells treated with either gemcitabine or 5-FU alone. SIGNIFICANCE: Our findings suggest that diltiazem may be potential neoadjuvant therapy to enhance the response of PC to gemcitabine or 5-FU treatment.

Comparison of nebivolol versus diltiazem in improving coronary artery spasm and quality of life in patients with hypertension and vasospastic angina: A prospective, randomized, double-blind pilot study.

BACKGROUND: Beta-blockers are often not the preferred treatment for patients with vasospastic angina. However, nebivolol, beta-blocker with nitric oxide-releasing effect, could theoretically improve coronary vasospasm. We compared nebivolol versus diltiazem in improving coronary vasospasm and quality of life in patients with hypertensive vasospastic angina during a 12-week follow-up. METHODS: Fifty-one hypertensive patients with documented coronary vasospasm were randomly allocated into 3 treatment groups: (1) Nebivolol Group (5mg for 2 weeks/10mg for 10 weeks); (2) Diltiazem Group (90mg for 2 weeks/180mg for 10 weeks); (3) Low-dose Combination Group (2.5mg + 45mg for 2 weeks/5mg + 90mg for 10 weeks). The primary endpoint was to compare the percent changes in coronary vasospasm at 12 weeks from baseline among the 3 groups. The secondary endpoints included changes in quality of life based on the Seattle Angina Questionnaire and changes in blood pressure at 12 weeks from baseline. RESULTS: Significant improvements in coronary vasospasm were found in all groups; however, the improvement in percent changes in coronary artery spasm was greatest in the Diltiazem Group (50.4±8.8% vs. 67.8±12.8% vs. 46.8±12.3%, Nebivolol Group vs. Diltiazem Group p = 0.008; Nebivolol Group vs. Low-dose Combination Group p = 0.999; Diltiazem Group vs. Low-dose Combination Group p = 0.017). The overall Seattle Angina Questionnaire scores were significantly elevated at 12 weeks compared to the baseline in entire study population. There were no significant differences between the three groups in the overall Seattle Angina Questionnaire score changes and blood pressure changes. CONCLUSIONS: Both nebivolol and diltiazem showed significant coronary vasospasm reduction effect, but the effect was greater for diltiazem.

A case of vasospastic angina. Vasospasm physiopathology: a new therapeutic role for ranolazine?

We report the case of a 40-year-old man, transferred from another hospital to our ICU because of acute coronary syndrome. Coronarography did not show coronary stenosis. Twenty-four hours monitoring EKG allowed diagnosis of Prinzmetal angina and appropriate therapy was administered. Six months after discharge due recurrence of symptoms, ranolazine was added to therapy. After one year the patient is symptoms free.

Engineering of Nanospheres Dispersed Microneedle System for Antihypertensive Action.

BACKGROUND: A combinational therapy is mostly preferred in hypertension treatment because of low-dose and less side effects like pretibial edema, and gastrointestinal bleeding. OBJECTIVE: So the objective of the present work was to formulate an advanced drug delivery system in the form of bio-responsive microneedles by incorporating nifedipine, a cardiodepressant and diltiazem, a vasodilator for effective synergism in the treatment of hypertension. METHODS: The pH-responsive PLGA nanospheres of diltiazem were formulated using Water-in-Oil-in- Water (W/O/W) double emulsion and solvent-diffusion-evaporation technique. These nanospheres were added to nifedipine-PVP mixture and then incorporated into mold to develop microneedles. RESULTS: The microneedles showed the release of nifedipine almost 96.93± 2.31% for 24 h due to high PVP solubilization. The nanospheres of diltiazem on contact with acidic pH of skin managed to form of CO2 bubbles and increase the internal pressure to burst PLGA shell due to pore formation. The mean blood pressure observed for the normal group was 89.58 ± 3.603 mmHg, whereas the treatment with the new formulation significantly reduced the mean blood pressure up to 84.11 ± 2.98 mmHg in comparison to the disease control group (109.9 ± 1.825 mm Hg). CONCLUSION: This system co-delivers the drugs nifedipine and diltiazem in hypertension and shows an advance alternative approach over conventional drug delivery system.

Hemodynamic comparison of intravenous push diltiazem versus metoprolol for atrial fibrillation rate control.

OBJECTIVE: Intravenous push (IVP) diltiazem and metoprolol are commonly used for management of atrial fibrillation (AF) with rapid ventricular rate (RVR) in the emergency department (ED). This study's objective was to determine if there was a significant difference in blood pressure reduction between agents. METHODS: This was a single-center, retrospective study of adult patients initially treated with IVP diltiazem or metoprolol in the ED from 2008 to 2018. Primary endpoint was mean reduction in systolic blood pressure (SBP) from baseline to nadir during the study period. Study period was defined as time from first dose of IVP intervention to 30 min after last dose of IVP intervention or first dose of maintenance therapy, whichever came first. RESULTS: A total of 63 diltiazem patients and 45 metoprolol patients met eligibility criteria. Baseline characteristics were similar except for initial ventricular rate (VR) and home beta-blocker use. Median dose of initial intervention was 10 [10-20] mg and 5 [5-5] mg for diltiazem and metoprolol respectively. Mean SBP reduction was 18 ± 22 mmHg for diltiazem compared to 14 ± 15 mmHg for metoprolol (p = .33). Clinically relevant hypotension was similar between groups 14% vs. 16% (p = .86). Rate control was achieved in 35 (56%) of the diltiazem group and 16 (36%) of the metoprolol group (p = .04). CONCLUSION: IVP diltiazem and metoprolol caused similar SBP reduction and hypotension when used for initial management of AF with RVR in the ED. However, rate control was achieved more often with diltiazem.

Diltiazem-associated Photodistributed Hyperpigmentation.

Diltiazem is a calcium-channel blocker commonly used for the treatment of hypertension. Common adverse effects include dizziness, headache, and edema. Fewer than 20 cases of diltiazem-associated photodistributed hyperpigmentation have been reported in the literature. Here, we present the case of a 71-year-old woman with new-onset facial hyperpigmentation 6 months after initiating treatment with diltiazem.

A prospective, double-blind, randomized, placebo-controlled trial comparing the efficacy of polyethylene glycol versus polyethylene glycol combined with topical diltiazem for treating anal fissure in children.

BACKGROUND: Anal fissure (AF) in children is usually treated with laxatives and/or topical agents such as calcium channel blockers. We hypothesize that owing to the superior efficacy of Polyethylene glycol (PEG) in treating constipation in children, adding diltiazem (DTZ) might not improve healing of AF. METHODS: Children ≤14 years with anal fissure presented to the pediatric surgery clinic between November 2014 and March 2016 were recruited. Randomization was performed to either PEG with DTZ or PEG with placebo. Study personnel, patients, and their families were blinded. Primary outcome was resolution of symptoms. Secondary outcomes were constipation and treatment complications at 12-week follow up. RESULTS: 48 patients were randomized: 24 to PEG + DTZ and 24 to PEG + placebo. Both groups were similar in their baseline characteristics. At week 12, majority of patients' symptoms have improved without significant difference between groups; painful defecation at week 12: 20.8% and 8.3% (p-value 0.41), blood per rectum at week 12: 4.2% and 8.3% (p value 0.58) in the DTZ and placebo groups, respectively. Additionally, there was similar improvement in constipation in both groups. CONCLUSION: PEG alone was associated with similar improvement in anal fissure symptoms in children compared to PEG and topical diltiazem combined. LEVEL OF EVIDENCE: I.

Improving Appropriate Dosing of Intravenous dilTIAZem in Patients With Atrial Fibrillation or Flutter With Rapid Ventricular Response in the Emergency Department.

INTRODUCTION: Atrial fibrillation and atrial flutter are common supraventricular arrhythmias in patients who present to the emergency department. Under the American Heart Association guidelines, dilTIAZem is the calcium channel blocker frequently used by many practitioners for rate control. Currently, institution-specific data have identified that many patients receiving dilTIAZem for atrial fibrillation or atrial flutter are given initial doses that exceed the recommended dose by more than 10%, resulting in hypotension in some patients. METHODS: ED personnel were surveyed to determine their current knowledge of appropriate intravenous dilTIAZem dosing and methods of prescribing intravenous dilTIAZem to determine the causes of higher dosing. Based on the baseline data, an intervention of adding a text alert when withdrawing dilTIAZem from the automated medication dispensing cabinet was implemented. RESULTS: Following the intervention, 29 patients received intravenous dilTIAZem for rate control of atrial fibrillation or flutter with rapid ventricular response. For the primary outcome, the incidence of high-dose dilTIAZem decreased by 19% (P = 0.03). There was no change in the secondary outcome of a reduction in hypotension (P = 0.3). DISCUSSION: The interventions of education and medication alerts resulted in a significant increase in the percentage of patients receiving appropriate doses of dilTIAZem and a nonsignificant decrease in the incidence of hypotension. This process-oriented intervention resulted in an improvement in appropriate dilTIAZem doses at our site. Rate control was not statistically significantly different between the 2 groups. Long-term sustainability of this intervention requires further study.

Weight-based versus non-weight-based diltiazem dosing in the setting of atrial fibrillation with rapid ventricular response.

PURPOSE: There is conflicting evidence to support the superiority of weight-based (WB) dosing of intravenous (IV) diltiazem over non-weight-based (NWB) dosing strategies in the management of atrial fibrillation (AFib) with rapid ventricular response (RVR). METHODS: A retrospective review evaluated patients presenting to the emergency department (ED) in AFib with RVR and receiving IV diltiazem from 2015 to 2018. Those receiving a NWB dose were compared with those receiving a WB dose based on actual body weight (ABW). Secondary analyses evaluated safety profiles of the regimens and compared response in groups defined by ABW or ideal body weight (IBW). RESULTS: A total of 371 patients were included in the analysis. No significant difference was observed in achieving a therapeutic response (66.5% vs. 73.1%, p = 0.18) or adverse events between the groups. Patients receiving a WB dose were significantly more likely to have a HR < 100 bpm than those receiving a NWB dose (40.9% vs. 53.5%, p = 0.01). When groups were defined by IBW, WB dosing was associated with a significantly higher incidence of achieving a therapeutic response (62.7% vs. 74.3%, p = 0.02). CONCLUSION: In patients presenting with AF with RVR, there was no significant difference in achieving a therapeutic response between the two strategies. A WB dosing approach did result in a greater proportion of patients with a HR < 100 bpm. The utilization of IBW for WB dosing may result in an increased achievement of a therapeutic response.

Management of paroxysmal atrial flutter that occurred in an outpatient prior to dental surgery: a case report.

BACKGROUND: It is essential to accomplish the appropriate emergency care particularly in patients undergoing stressful dento-oral surgical procedures. Atrial flutter may be induced by sympathetic hypertonia due to excessive mental and physical stress. There is no report regarding dental care in patients with atrial flutter. Herein, we describe a rare case of the antiarrhythmic management in an outpatient who presented with an electrocardiographic finding of paroxysmal atrial flutter before the initiation of the dento-oral surgical procedure. CASE PRESENTATION: A 60-year-old male patient was scheduled for a dental extraction. He had a history of angina pectoris, diabetes mellitus, and paroxysmal atrial fibrillation with medication. The preoperative electrocardiogram (ECG) revealed left ventricular hypertrophy and ST-T segment abnormality. Immediately before the dental extraction, II-lead ECG revealed atrial flutter; however, he complained of few subjective symptoms, such as precordial discomfort or palpitation. Observing the vital signs, ECG findings, and the general condition of the patient, low dose diltiazem was immediately administered by continuous infusion in order to control the heart rate and prevent atrial flutter-induced supraventricular tachyarrhythmia. Special attention was paid to prevent any critical cardiovascular condition under a preparation of intravenous disopyramide and verapamil and a defibrillator. The intravenous administration of diltiazem progressively restored the sinus rhythm after converting atrial flutter into atrial fibrillation, resulting in the prevention of tachycardia, and then was found to be appropriate as a prophylactic therapy of tachyarrhythmia. CONCLUSIONS: The present case suggests that it is possible to successfully manage some of such patients using our method during dento-oral surgery which is likely to be associated with mental and physical stress. Therefore, it is essential to accomplish an initial emergency care in parallel to the differential diagnosis of unforeseen serious medical conditions or paroxysmal arrhythmia such as atrial flutter.