Objective: To describe the pharmacology, efficacy, and safety of stiripentol in the treatment of refractory seizures in patients with Dravet syndrome. Data Sources: A search of the English language ...literature was conducted using PubMed and MEDLINE (1978 to April 2019) with the search terms stiripentol, Dravet syndrome, and refractory epilepsy. Other resources included article bibliographies, prescribing information, and relevant trials at https://clinicaltrials.gov/. Study Selection and Data Extraction: All phase 1, 2, or 3 trials; observational studies; and retrospective studies were analyzed. Data Synthesis: In controlled studies, stiripentol has been shown to reduce seizure frequency by 50% or more in 40% to 70% of patients with Dravet syndrome. Reductions in seizure duration and episodes of status epilepticus have also been documented. Common adverse effects include somnolence and anorexia. Stiripentol inhibits the metabolism of clobazam and valproate, often requiring dose adjustment. Relevance to Patient Care and Clinical Practice: Stiripentol, a direct allosteric modulator of GABAA receptors, offers a novel approach to treatment in patients with Dravet syndrome, both with and without pathogenic variants of the sodium channel α-1 subunit gene, and potentially other refractory seizures. Although available outside the United States for a decade, it was only recently approved by the Food and Drug Administration for patients 2 years of age and older with Dravet syndrome taking clobazam. Conclusions: Stiripentol is an effective adjunctive therapy for reducing the frequency and duration of refractory seizures in patients with Dravet syndrome. Its role in the treatment of other refractory epilepsies requires further study.
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Nonoptimized medication regimens cost patients and payors in the United States more than $528 billion in additional health care expenses each year. Comprehensive medication management is a ...patient-centered approach to medication optimization delivered by a clinical pharmacist working with the patient, physicians, and other members of the health care team. Comprehensive medication management ensures medications are assessed for appropriateness, effectiveness, and safety given the patient's clinical status, comorbidities, and other medications, as well as the patient's ability to take the medications as intended and adhere to the regimen. This article reviews the growing body of literature demonstrating the value of comprehensive medication management in achieving the quadruple aim of health care: better care, reduced health care costs, an improved patient experience, and provider well-being.
Bivalirudin, a direct thrombin inhibitor, is a useful alternative to heparin for anticoagulation in infants and children. It has been found to be effective in patients requiring treatment of ...thrombosis, as well as those needing anticoagulation during cardiopulmonary bypass, extracorporeal life support, or with a ventricular assist device. While it has traditionally been used in patients who were unresponsive to heparin or who developed heparin-induced thrombocytopenia, it has recently been studied as a first-line agent. Bivalirudin, unlike heparin, does not require antithrombin to be effective, and as a result, has the potential to provide a more consistent anticoagulation. The case reports and clinical studies currently available suggest that bivalirudin is as effective as heparin at reaching target activated clotting times or activated partial thromboplastin times, with equivalent or the lower rates of bleeding or thromboembolic complications. It is more expensive than heparin, but the cost may be offset by reductions in the costs associated with heparin use, including anti-factor Xa testing and the need for administration of antithrombin. The most significant disadvantage of bivalirudin remains the lack of larger prospective studies demonstrating its efficacy and safety in the pediatric population.
Use of lidocaine as part of a multimodal approach to postoperative pain management has increased in adults; however, limited information is available regarding safety and tolerability in pediatrics. ...This study's primary objective was to evaluate the incidence of adverse effects related to lidocaine infusions in a sample of pediatric patients.
A retrospective analysis was conducted in pediatric patients receiving lidocaine infusion for the management of postoperative analgesia at the University of Virginia Health System.
A total of 50 patients with 51 infusions were included in the final analysis. The median patient age was 14 years (range, 2-17 years). The most frequent surgeries were spinal fusion (30%), Nuss procedure for pectus excavatum (16%), and nephrectomy (6%). The mean ± SD starting rate was 13.6 ± 6.5 mcg/kg/min. The mean infusion rate during administration was 15.2 ± 6.3 mcg/kg/min, with 14.4 ± 6.2 mcg/kg/min at discontinuation. The mean length of therapy was 30.6 ± 22 hours. A total of 12 infusions (24%) were associated with adverse effects, primarily neurologic ones, including paresthesias in the upper extremities (10%) and visual disturbances (4%). The average time to onset was 16.2 ± 15.2 hours. Seven infusions were discontinued, whereas the remaining infusions resulted in either dose reduction or continuation without further incident. No patients experienced toxicity requiring treatment with lipid emulsion.
In this sample, lidocaine was a well-tolerated addition to multimodal postoperative pain management in the pediatric population. Although adverse effects were common, they were mild and resolved with either dose reduction or discontinuation.
Extracorporeal membrane oxygenation (ECMO) is a prolonged form of cardiopulmonary bypass used to support patients with life-threatening respiratory or cardiac failure. In neonates, ECMO is used for a ...variety of indications, including sepsis and pulmonary diseases such as meconium aspiration syndrome, persistent pulmonary hypertension or congenital diaphragmatic hernia. In recent years, ECMO has been increasingly used after surgery to correct congenital cardiac defects. Despite the need for numerous drugs to maintain the ECMO circuit and treat the patient's underlying illness, relatively little is known of the disposition of drugs in this patient population. To date, the largest number of pharmacokinetic studies have been conducted with gentamicin and vancomycin. Both drugs have been found to have an increased volume of distribution, probably as a result of the addition of a large exogenous blood volume for circuit priming. Elimination half-lives for both drugs are prolonged during ECMO, with several studies demonstrating a return to expected values after decannulation. The reason for this prolonged elimination is probably multifactorial, with a reduction in renal function as the primary determinant. This same pattern of an increased volume of distribution and prolonged elimination has been found for several other drugs, including tobramycin, bumetanide and ranitidine. Other factors that affect drug disposition during ECMO include loss of the drug from adhesion to the circuit components and loss in the circulating blood volume during changes in the equipment. The benzodiazepines and propofol are largely sequestered within the circuit. Serum concentrations of heparin, morphine, fentanyl, furosemide, phenytoin and phenobarbital are also reduced by these mechanisms. The addition of haemofiltration or dialysis in up to a quarter of ECMO patients further complicates the determination of population pharmacokinetic parameters. The literature published to date on the pharmacokinetic changes associated with ECMO provide preliminary support for dosage adjustment; however, more research is needed to identify optimal administration strategies for this patient population.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objective:
To review and assess the available literature on the use of intraosseous (IO) drug administration during cardiopulmonary resuscitation, addressing the benefits and risks of using this ...method of drug delivery in children and adults.
Data Sources:
The MEDLINE (1950–July 2007) database was searched for pertinent abstracts, using the key term intraosseous infusions. Additional references were obtained from the bibliographies of the articles reviewed. Manufacturer Web sites were used to obtain information about IO insertion devices.
Study Selection and Data Extraction:
All available English-language clinical trials, retrospective studies, and review articles describing IO drug administration were reviewed. Studies conducted in animal models to evaluate the effectiveness and safety of IO drug administration were also included.
Data Synthesis:
IO access uses the highly vascularized bone marrow to deliver fluids and medications during cardiopulmonary resuscitation. This route, developed in the 1940s, has been revived In the past decade as a means of achieving rapid vascular access when intravenous access cannot be obtained. The primary advantage of IO access is the high success rate (approximately 80%). Most trained providers can place an IO line within 1–2 minutes. A number of small-scale studies and retrospective reviews have established the usefulness of this route for the delivery of many commonly used resuscitation drugs. In addition, animal models have demonstrated rapid drug delivery to the systemic circulation. While all resuscitation drugs can be given by the IO route, administration of ceftriaxone, chloramphenicol, Phenytoin, tobramycin, and vancomycin may result in lower peak serum concentrations. The most common adverse effect seen with IO use, extravasation, has been reported in 12% of patients. Compartment syndrome, osteomyelitis, and tibial fracture are rare, but have also been reported.
Conclusions:
IO administration is a safe and effective method for delivering drugs during cardiopulmonary resuscitation. It should be considered whenever intravenous access cannot be rapidly obtained.
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To evaluate the incidence of apnea and requirement for positive pressure ventilation in patients who received caffeine for prevention while receiving alprostadil compared with those who did not ...receive caffeine.
This was a single-center, retrospective study of patients who received alprostadil over a 7-year time frame. Patients were divided into 2 groups based on whether they received caffeine for prevention of apnea while receiving alprostadil. The incidence of apnea and requirements for positive pressure ventilation were recorded.
A total of 64 patients who received alprostadil were included for review. Thirty-two patients received caffeine for the prevention of apnea, and 32 patients received alprostadil only. Alprostadil doses were similar between the 2 groups (0.04-0.05 mcg/kg/min). Seven patients had a documented apneic event; 3 in the group given caffeine and 4 in the control group. One patient in each group required intubation because of apnea. All patients with documented apnea were on low-dose alprostadil therapy (<0.05 mcg/kg/min). Three patients had apnea after dose reductions had been made. Six out of the seven patients experienced apnea within the first 24 hours after the infusion. Only 1 patient experienced multiple apneic events.
In this small sample, there was no difference in incidence of apnea between patients on low-dose alprostadil who received caffeine for prevention and those who did not. Despite the use of low-dose alprostadil therapy and dose reductions, the incidence of apnea remains low, and most patients did not have repeated apneic events or require intubation.
BACKGROUND
Activation and consumption of platelets (PLT) and clotting factors along with hemolysis occurs when blood contacts the extracorporeal life support (ECLS) circuit and its components.
STUDY ...DESIGN AND METHODS
The objective was to examine the effects of reducing ECLS circuit volume by decreasing tubing length and changing components on blood product usage in neonatal and pediatric patients. Blood product administration was analyzed in 40 consecutive patients who required ECLS for respiratory or cardiac failure before (PRE) and after (POST) changes in circuit design and components.
RESULTS
The total circuit volume was reduced from 500 mL (PRE) to 275 mL (POST). In the POST group, total blood product volume usage was 58% lower compared to the PRE group (81 mL/kg/day vs. 191 mL/kg/day, p = 0.003), 65% lower for fresh‐frozen plasma (FFP; 15 mL/kg/day vs. 43 mL/kg/day, p = 0.001), and PLT volumes trended lower. In the subgroup of infants with respiratory or cardiac failure, there was a 55% reduction of a total blood product replacement (61 mL/kg/day vs. 136 mL/kg/day, p = 0.008), red blood cell (RBC) use was 61% lower (28 mL/kg/day vs. 71 mL/kg/day, p < 0.049), and there was a 73% reduction in FFP use (11 mL/kg/day vs. 41 mL/kg/day, p < 0.001). In the subgroup of postoperative infants, there was a 25% decrease in RBC use (86 mL/kg/day vs. 115 mL/kg/day, p = 0.03).
CONCLUSION
Decreasing the ECLS circuit volume by reducing the tubing length and changing the components was associated with a significant reduction in blood product usage.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The American College of Clinical Pharmacy and other stakeholder organizations seek to advance clinical pharmacist practitioners, educators, and researchers. Unfortunately, there remains an inadequate ...supply of residency‐trained clinical specialists to meet the needs of our health care system, and nonspecialists often are called on to fill open specialist positions. The impact of clinical pharmacy specialists on pharmacotherapy outcomes in both acute care and primary care settings demonstrates the value of these specialists. This commentary articulates the need for postgraduate year two (PGY2)‐trained clinical specialists within the health care system by discussing various clinical and policy rationales, interprofessional support, economic justifications, and their impact on quality of care and drug safety. The integrated practice model that has grown out of the American Society of Health‐System Pharmacists Pharmacy Practice Model Initiative (PPMI) could threaten the growth and development of future clinical specialists. Therefore, the ways in which PGY2‐trained clinical pharmacist specialists are deployed in the PPMI require further consideration. PGY2 residencies provide education and training opportunities that cannot be achieved in traditional professional degree programs or postgraduate year one residencies. These specialists are needed to provide direct patient care to complex patient populations and to educate and train pharmacy students and postgraduate residents. Limitations to training and hiring PGY2‐trained clinical pharmacy specialists include site capacity limitations and lack of funding. A gap analysis is needed to define the extent of the mismatch between the demand for specialists by health care systems and educational institutions versus the capacity to train clinical pharmacists at the specialty level.
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