Treatment of arterial hypertension in children

Hypertension in children is divided in 2 groups: primary hypertension and the secondary forms which are more severe and mostly due to kidney diseases. The medical management of hypertension includes non pharmacological intervention (diet, exercise, life-style) and pharmacological agents. The children with primary and mild hypertension may need only non pharmacological strategies. The main pharmacological agents used are: diuretics, vasodilators, sympathetic blockers, centrally acting agents, converting enzyme inhibitors. Except for hypertensive emergencies, the management of children with hypertension is facilitated by a stepped-care titration approach. Step 1: beta adrenergic blockers or vaso-dilators; step 2: combine beta adrenergic blockers with vaso-dilators or with diuretics or converting enzyme inhibitors alone; step 3: combine converting enzyme inhibitors with vaso-dilators and/or diuretics and/or beta adrenergic blockers; step 4: drugs include minoxidil, prazosin, labetalol.     

Adjunctive pharmacotherapy in neonates with respiratory failure

Whereas oxygen, continuous positive airway pressure (CPAP) and mechanical ventilation are the mainstays of treatment of pulmonary conditions in newborns, there are a number of adjunctive therapies that may improve the pulmonary function of these infants. These include the use of bronchodilators and diuretics given either systemically or through the inhaled route, mucolytic agents, and anti-inflammatory agents. This chapter gives an overview of the use of the most-studied agents including aerosolized bronchodilators, systemic and inhaled diuretics, and systemic and inhaled corticosteroids in the treatment and prevention of, where appropriate, respiratory distress syndrome, bronchopulmonary dysplasia, and meconium aspiration syndrome. Evidence on the use of mucolytic agents including acetylcysteine and deoxyribonuclease, and the anti-inflammatory agents including the macrolide antibiotics, cromolyn, pentoxyfylline, and recombinant human Clara cell protein are also reviewed.     

Myocarditis in infants and children: A review for the paediatrician

Clinical myocarditis is uncommon in infants and children. The most common pathogen is Coxsackievirus B. The offending agent triggers an immune response, which results in myocardial edema with subsequent impairment of systolic and diastolic function. Newborns and infants are more severely affected because the immature myocardium has limited ways of adapting to an acute insult. Children typically present with sinus tachycardia and gallop on auscultation, cardiomegaly on chest x-ray and small voltages on electrocardiogram. The echocardiogram shows reduced ventricular function. Viral studies can isolate the pathogen. Myocardial biopsy is useful diagnostically, but carries a significant risk for the sick infant. The first line of treatment includes measures such as rest, oxygen and diuretics. Inotropic agents are useful in moderate to severe heart failure. The role of immunosuppressive therapy is not yet clearly established in the paediatric age group. Prognosis is guarded in newborns but more favourable in older children.     

Nesiritide in a pediatric oncology patient with renal insufficiency and myocardial dysfunction following septic shock

Nesiritide is a recombinant formulation of B-type natriuretic peptide used most commonly in the treatment of adults with decompensated congestive heart failure. The physiologic effects of BNP include natriuresis, diuresis, and smooth muscle relaxation. These physiologic effects result in its beneficial therapeutic effects, including a decrease in afterload, resulting in increased cardiac output with improved peripheral perfusion. The authors report on a 17-year-old with acute myelogenous leukemia who was admitted to the Pediatric ICU for treatment of septic shock, respiratory failure, myocardial dysfunction, and renal insufficiency. After the initial stabilization of his hemodynamic status, nesiritide was started and resulted in a stable balance of fluid intake versus output without the use of diuretics, improvement in myocardial function, and recovery of renal function manifested by a decrease of blood urea nitrogen and creatinine back to baseline values. The end-organ effects of nesiritide, previous reports regarding its use in the pediatric population, and its potential applications in the ICU setting are discussed.     

急性肺损伤和急性呼吸窘迫综合征的预后评估指标

急性肺损伤、急性呼吸窘迫时机体发生一系列的病理生理变化,研究者通过对相关临床、生化指标进行研究发现其中一些指标与预后密切相关.临床指标包括年龄、病因、器官功能不全、免疫抑制等.生化指标包括心功能指标氨基末端脑钠肽前体、心肌酶;凝血纤溶相关指标蛋白C;肺表面活性物质;氧化应激产物:一氧化氮、血管假性血友病因子、炎症因子等.利用这些指标可以判断疾病进展,为指导后续治疗提供依据.     

脓毒症心功能障碍机制的研究进展

脓毒症心功能障碍是脓毒症多器官功能障碍的表现之一.脓毒症心功能障碍的临床和基础研究已超过50年,但其具体病理生理机制还不完全明确.现阶段的研究认为:线粒体功能障碍、循环中各种心肌抑制物、心肌细胞内钙稳态失调等共同作用促进了脓毒症时心功能障碍的发生.     

Unexpected extra-renal effects of loop diuretics in the preterm neonate

The loop diuretics furosemide and bumetanide are commonly used in neonatal intensive care units (NICUs). Furosemide, because of its actions on the ubiquitous Na(+) -K(+) -2Cl(-) isoform cotransporter and its promotion of prostanoid production and release, also has non-diuretic effects on vascular smooth muscle, airways, the ductus arteriosus and theoretically the gastrointestinal tract. Loop diuretics also affect the central nervous system through modulation of the GABA-A chloride channel. Conclusion: The loop diuretics have a variety of biological effects that are potentially harmful as well as beneficial. Care should be taken with the use of these agents because the range of their effects may be broader than the single action sought by the prescribing physician.     

Adverse effects of hormone preparations and related medications used to treat disorders of bone and mineral metabolism

Disorders of bone and mineral metabolism can be effectively treated by a relatively small number of preparations which include minerals, vitamin D metabolites, other hormones, bisphosphonates, and diuretics. In addition to achieving the treatment goals, management of these patients must include close monitoring for potential adverse effects of the medications. The following chapter addresses the currently available treatment modalities of bone and mineral disorders and their potential side effects. Careful attention to recommended precautions, means of monitoring for potential adverse effects, and consequent adjustment of therapy play a key role in protecting the patient from development of serious adverse effects.     

Reflux gastro-œsophagien chez l'enfant

The clinical manifestations of gastroesophageal reflux (GER) in infancy and childhood include vomiting dysphagia, abdominal pain and substernal pain, oesophagitis and respiratory disorders. Diagnostic approaches consist of history and physical examination, oesophageal pH monitoring, endoscopy, biopsy and sometimes an empiric medical therapy. Treatment options in infancy include prone position, diet change with milk thickening agents, and if necessary with a new formula without cow milk proteins. Lifestyle changes are recommended. In case of oesophagitis, acid suppressor therapy with proton pump inhibitors are used. Prokinetic therapy reduces the frequency of symptoms. Surgical therapy (fundoplication) generally results in favourable outcomes in case of prolonged medical therapy failure.     

Chronic afterload reduction in infants and children with primary myocardial disease

The purpose of this study was to determine the long-term effects of chronic afterload reduction with oral hydralazine therapy in patients with primary myocardial disease (PMD). Twenty-six children aged 3 to 48 months with the diagnosis confirmed by M-mode and two-dimensional echocardiograms and angiograms were given digitalis and diuretics. Fourteen of these patients also received hydralazine orally in doses up to 4.0 mg/kg/day in four divided doses. Echocardiograms were initially repeated at 1- to 3-month intervals and subsequently at 6-month intervals. Long-term follow-up data were available in 10 patients given hydralazine and eight control patients; the follow-up interval ranged from 3 to 48 months. In the hydralazine group the shortening fraction rose from 14.5 +/- 4.9 to 23.2 +/- 7.5 (P less than 0.01), and the ratio of pre-ejection period to ejection time (0.52 +/- 0.05 to 0.35 +/- 0.06, P less than 0.001) and left ventricular size, normalized to body surface area (116 +/- 7 to 87 +/- 21, P less than 0.01), decreased. Significant improvement was demonstrated by echocardiography after 12 months of hydralazine therapy. There was no significant change in any of these values in the control group. We conclude that hydralazine therapy is a useful adjunct in the management of primary myocardial disease in infancy and childhood.     

Therapeutic applications and uses of inhalational anesthesia in the pediatric intensive care unit.

OBJECTIVE: To review the physical properties, end-organ effects, therapeutic applications, and delivery techniques of inhalational anesthetic agents in the pediatric intensive care unit. DATA SOURCE: A computerized, bibliographic search regarding intensive care unit applications of inhalational anesthetic agents. MAIN RESULTS: Although the end-organ effects of inhalational anesthetic agents vary depending on the agent, general effects include a dose-related depression of ventilatory and cardiovascular function. With increasing anesthetic depth, there is a decrease in alveolar ventilation with a reduction in tidal volume and an increase in PaCO2 in spontaneously breathing patients. The potent inhalational anesthetic agents decrease mean arterial pressure and myocardial contractility. The decrease in mean arterial pressure reduces renal and hepatic blood flow. Secondary effects on end-organ function may result from the metabolism of these agents and the release of inorganic fluoride. Beneficial effects include sedation, amnesia, and anxiolysis, making these agents effective for sedation during mechanical ventilation. Bronchodilatory and anticonvulsant properties have led to their use as therapeutic agents in patients with refractory status asthmaticus and epilepticus. Issues regarding their delivery in the intensive care unit include equipment for their delivery, scavenging, and monitoring. CONCLUSIONS: The literature contains reports of the therapeutic use of the potent inhalational anesthetic agents in the pediatric intensive care unit. Potential applications include sedation during mechanical ventilation as well as therapeutic use for the treatment of status asthmaticus and epilepticus.     

儿童右心衰的病因与治疗

儿童疾病谱与成人不同,导致右心衰的原因也不尽相同.压力或容量过负荷、心肌病变、心律失常等均可引起右心衰竭.在成人研究的基础上,儿童需结合自身疾病特点选择适合的诊疗方案.     

Anthracycline toxicity

Anthracycline compounds are useful agents in cancer therapy. Major toxicities include mucositis and other gastrointestinal complications, myelodepression and cardiotoxicity. With the current multimodal cancer therapy, anthracycline toxicities may be potentiated by radiation treatment or other chemotherapeutic agents. The choice of anthracycline, drug combination, and drug schedule should be carefully evaluated to minimize toxicity.     

Pharmacology of inotropic agents in infants and children

Inotropic agents are drugs which increase the stroke work of the heart at a given pre-load and after-load. All of these agents work through a final common pathway involving the modulation of calcium interactions with various myocardial contractile proteins. The agents employed with pediatric patients include the cardial glycosides, catecholamine beta-agonists and the selective phosphodiesterase III inhibitors. Digoxin is the prototypic cardiac glycoside which has a long history of safe and effective use in infants and children. Its utility in improving right ventricular dysfunction in patients with cor pulmonale leading to biventricular dysfunction makes it ideally suited to the pediatric population. Monitoring digoxin pharmacokinetics in infants is confounded by the presence of an endogenous digoxin-like substance. Nevertheless, the drug is well suited for subacute and chronic myocardial support. In contrast, the catecholamines are the drugs of choice for acute intervention. Their pharmacokinetics permit rapid dosing titration. In infants and children the greatest experience has been accrued with dopamine, a mixed alpha- and beta-agonist but both epinephreine and norepinephrine are being used with increasing frequency as the need for drugs with increased potency and pressor activity becomes more common. The phosphodiesterase inhibitors amrinone and milrinone are the newest additions to our therapeutic armamentarium. In addition to their modest inotropic effects, amrinone and to a greater extent, milrinone offer significant pulmonary vasodilatation as part of their therapeutic package. These effects occur with little or any impact on myocardial oxygen consumpton while their lusitropic effects enhance relaxation in hypertrophied ventricular muscle. Of the two agents milrinone is probably preferred due to its greater therapeutic index and shorter elimination half-life. All of these agents remain important tools in the care of critically ill infants and children. The rational use of these drugs based upon their pharmacokinetic and pharmacodynamic properties is essential to achieve their optimal effects.     

Steroid-refractory graft-vs.-host disease: past,present and future

Despite current standard preventive strategies that include optimizing donor selection and the combination of methorexate and a calcineurine inhibitor, acute and chronic GVHD remains a major barrier to successful hematopoietic cell transplantation for a sizeable proportion of patients. When acute and chronic GVHD become manifest a standard primary therapy approach has been the addition of glucocorticoid therapy to a background of calcineurine inhibition. When this approach fails patients with GVHD require secondary therapy. Ideally, second-line agents should promote transplantation tolerance so that the morbidity associated with prolonged use of glucocorticoids and other immunosuppressive agents can be minimized. Promising new agents or strategies which warrant further controlled clinical trials include: mycophenolate mofetil, sirolimus, humanized or chimeric monoclonal antibodies such as visilizumab, daclizumab and infliximab, and extracorporeal photopheresis. Co-operative studies are necessary to hasten the process of evaluating novel treatment strategies for acute and chronic GVHD.     

Bronchopulmonary dysplasia: Myths of pharmacologic management

Bronchopulmonary dysplasia (BPD) is the leading cause of long-term respiratory morbidity in newborns who require respiratory support at birth. BPD is a multifactorial disorder, and infants are frequently subjected to treatment with multiple pharmacologic agents of dubious efficacy and questionable safety, including diuretics, bronchodilators, corticosteroids, anti-reflux medications, and pulmonary vasodilators. These agents, with narrow therapeutic indices, are widely used despite the lack of an evidence base, and some may do more harm than good. It is incumbent on the clinician to establish a risk:benefit ratio and to avoid drugs that have little efficacy and a high rate of toxicity.     

Molecular pathogenesis of myocardial remodeling and new potential therapeutic targets in chronic heart failure

ABSTRACT: It is well known that the natural history of chronic heart failure (CHF),regardless of age and aetiology,is characterized by progressive cardiac dysfunction refractory to conventional cardiokinetic, diuretic and peripheral vasodilator therapy. Several previous studies, both in animals and humans, showed that the key pathogenetic element of CHF negative clinical evolution is constituted by myocardial remodeling. This is a complex pathologic process of ultrastructural rearrangement of the heart induced by various neuro-humoral factors released by cardiac fibrocells in response to biomechanical stress connected to chronic haemodynamic overload. Typical features of myocardial remodeling are represented by cardiomyocytes hypertrophy and apoptosis, extracellular matrix alterations, mesenchymal fibrotic and phlogistic processes and by cardiac gene expression modifications with fetal genetic program reactivation. In the last years, increasing knowledge of subtle molecular and cellular mechanisms involved in myocardial remodeling has led to the discovery of some new potential therapeutic targets capable of inducing its regression. In this paper our attention is focused on the possible use of antiapoptotic and antifibrotic agents, and on the fascinating perspectives offered by the development of myocardial gene therapy and, in particular, by myocardial regenerative therapy.     

Nonpharmacologic treatment of acute heart failure

Acute heart failure is unusual in the pediatric population, but in many situations it justifies aggressive therapy. For example, children with lymphocytic myocarditis have an overall survival rate of nearly 90%, with complete myocardial recovery for the majority. Pharmacologic agents traditionally have been the mainstay of medical therapy for acute heart failure, but, in recent years, there has been increasing interest in using measures that reduce the myocardial workload. This article highlights nonpharmacologic approaches to the management of severe heart failure in the critically ill child. It also concentrates on physiologic approaches that address the balance between oxygen demand and delivery; the manipulation of cardiopulmonary interactions to optimize ventricular function; and the use of mechanical circulatory support as a method of achieving ultimate myocardial rest.     

Otitis media

There is a high rate of use of antimicrobial drugs for otitis media in children. This article reviews the diagnostic considerations for acute otitis media. An extensive review of literature on this subject has been carried out in order to address the issues of indications, choice, appropriate doses of antimicrobial agents and the duration for which they should be used. It is important to distinguish acute otitis media from otitis media with effusion because antibiotics are seldom indicated for the latter condition. Oral amoxicillin remains first-line therapy for uncomplicated acute otitis media, a short course of antimicrobial therapy (five to seven days) may be appropriate in children two years of age or older with uncomplicated presentations. For clinical treatment failures after 3 days of amoxicillin, recommended antimicrobial agents include oral amoxicillin/clavulanate, cefuroxime axetil, cefprozil, cefpodoxime proxetil, and intramuscular (i.m.) ceftriaxone. Tympanocentesis for identification of pathogens and susceptibility to antimicrobial agents is recommended for selection of third-line agents.     

Contraception and pregnancy in the young female hypertensive patient

Aspects of primary or secondary hypertension in relation to oral contraceptive use and pregnancy are discussed. Possible mechanisms of oral contraceptive-induced secondary hypertension and contraindications to the pill are listed. Hypertension as a contraindication to pregnancy is weighed in relation to sterilization and cases of term pregnancies in hypertensive patients are cited. Misdiagnosis of secondary hypertension as toxemia in most pregnant patients with elevated blood pressure is characterized in a review of a clinical study involving 4273 patients (Table 1). A method for differential diagnosis of hypertension in pregnancy which includes ophthalmoscopic examination and urinalysis is outlined (Figure 1). Suggested treatment for the pregnant patient with hypertension is a low sodium diet for the first 20 weeks of pregnancy followed by the stepped care program (Figure 2). The most desirable therapy for pregnant women with toxemia are diuretics during the early pathological phase (sodium retention and edema) with edema in the periorbital areas and hands as diagnostic indicators for this phase. The efficacy of diuretics (alone or combined with hypotensive agents) in hypertensive patients is evaluated with regard to maternal and fetal risks. Indications for termination of pregnancy or induction of labor in hypertensive or toxemic women are summarized.