Isosorbide aerosol: an option for the treatment of hypertensive crises

In this study the authors assessed the effectiveness and safety of isosorbide dinitrate aerosol administered through the oral mucosa in 30 adult patients who presented with a hypertensive crisis (mean arterial pressure > 130 mm Hg and evidence of target organ damage). The patients were given a first dose of 1.25 mg of aerosol when they were admitted to the hospital; a second dose was administered 15 minutes later if the mean arterial pressure had not decreased by > 15%. An electrocardiogram (ECG) was obtained for every patient immediately prior to and 30 minutes after administration of the medication. Nine patients (30%) had a good response with one dose, whereas 21 patients (70%) required a second dose. All 30 patients had a significant reduction of the arterial blood pressure (187+/-13 / 121+/-6.6 to 153+/-15.3 / 92.3+/-7.6 mm Hg; p<0.005) as well as of the mean arterial pressure (136.6+/-8 to 109.5+/-7 mm Hg; p<0.005) in a period of 30 minutes. No adverse effects, rebound hypertension, or severe hypotension were observed. These figures remained under control for 6 hours. Two of the patients had angina pectoris at admission and their ECG showed subepicardial ischemia, both of which disappeared with the medication. A second ECG appeared normal. A reduction of 14% in heart rate was obtained (95+/-15 to 82+/-14 beats per minute; p<0.005). These observations suggest that isosorbide dinitrate aerosol is an effective and safe alternative for the treatment of patients with hypertensive crises.     

Intravenous sildenafil lowers pulmonary vascular resistance in a model of neonatal pulmonary hypertension

Persistent pulmonary hypertension secondary to meconium aspiration syndrome is an important cause of morbidity and mortality in the neonatal population. We investigated the use of the phosphodiesterase-5 inhibitor sildenafil, in its intravenous form, as a pulmonary vasodilator in a model of meconium aspiration syndrome. Pulmonary hypertension was induced in 18 piglets, by endotracheal instillation of human meconium, 6 piglets subsequently received an infusion of intravenous sildenafil for 2 hours, 6 received inhaled nitric oxide for 2 hours, and 6 control animals received no additional intervention. Meconium aspiration increased pulmonary vascular resistance by 70%, and increased oxygenation index by over 100%. Pulmonary vascular resistance remained elevated for the remainder of the study period in control animals. Inhaled nitric oxide reduced the pulmonary vascular resistance by 40% after 2 hours of treatment; intravenous sildenafil completely reversed the increase in pulmonary vascular resistance within 1 hour of commencing the infusion. Neither agent had an effect on systemic hemodynamics. Sildenafil also increased cardiac output by 30%, but while doing so did not adversely influence oxygenation. Intravenous sildenafil is a selective and highly effective pulmonary vasodilator, which is at least as effective as inhaled nitric oxide, in this model of neonatal persistent pulmonary hypertension.     

Intravenous gamma globulin is effective as an urgent treatment in Brucella-induced severe thrombocytopenic purpura

Severe thrombocytopenia is a rare hematologic manifestation of brucellosis, which can occasionally be associated with bleeding into the skin and from mucosal sites. Prompt recognition of this brucellosis complication and aggressive therapy is vital because the mortality rate associated with bleeding into the central nervous system is high. We report a case of a patient infected with Brucella melitensis who was admitted with a severe case of thrombocytopenic purpura. The patient responded well to intravenous gamma globulin (IVIg) treatment with platelet recovery within 2-3 days. For cases of Brucella-induced thrombocytopenic purpura, IVIg may be administered as an urgent therapy until the microbial therapy takes effect.     

Diagnosis and treatment of intestinal malabsorption in cystic fibrosis

Intestinal malabsorption is severe and of early onset in virtually all people who have cystic fibrosis. The main cause is deficiency of pancreatic enzymes. Bicarbonate deficiency, abnormal bile salts, mucosal transport problems, motility differences, and anatomical structural changes are other contributory factors. Effective treatment should allow a normal to high-fat diet to be taken, control symptoms, correct malabsorption, and achieve a normal nutritional state and growth. Appropriate pancreatic enzyme replacement therapy will achieve normal or near-normal absorption in most people with cystic fibrosis. Early identification and treatment of intestinal malabsorption is critical to achieving optimal nutritional status. The occurrence of fibrosing colonopathy in a few patients on very high doses of those enzymes which have the copolymer Eudragit L30 D55 in their covering resulted in guidelines in the UK to avoid doses equivalent to more than 10,000 IU lipase per kg per day, and also to avoid preparations containing this copolymer in children and adolescents. For patients not responding to 10,000 IU lipase per kg per day review of adherence to treatment, change of enzyme preparation, variation in time of administration, and reduction in gastric acid may improve absorption. The importance of early investigation to exclude other gastrointestinal disorders as a cause of the patient's symptoms, rather than merely increasing the dose of enzymes, is stressed. With modern pancreatic enzymes in doses up to or only slightly in excess of 10,000 IU lipase per kg per day, adequate control of gastrointestinal symptoms and absorption can be achieved, and a normal nutritional state and growth rate maintained in most people with cystic fibrosis.     

Diagnosis and treatment of hypertensive crises in the elderly patients

Hypertension is a common clinical problem in the elderly worldwide and physicians of all types are likely to encounter patients with hypertensive urgencies and emergencies in these patients. Although various terms have been applied to these conditions, they are all characterized by acute elevations in blood pressure and evidence of end-organ injury. Prompt, but carefully considered therapy is necessary to limit morbidity and mortality. A wide range of pharmacologic alternatives are available to the practitioner to control blood pressure and treat complications in these patients. The management of the elderly patient with hypertensive crises needs to include close monitoring and a gentle decline in blood pressure to avoid catastrophic complications, exacerbation of ischemic myopathy, and vascular insufficiency.     

枸橼酸西地那非治疗妊娠合并肺动脉高压的临床效果观察

目的探讨枸橼酸西地那治疗妊娠合并肺动脉高压患者的临床疗效。方法将我院97例妊娠合并PAH的患者随机分为观察组47例及对照组50例,两组患者均给予常规治疗,观察组患者同时给予枸橼酸西地那非,观察两组患者的妊娠结局及各项指标变化情况,以及心功能及PAH转归情况。结果治疗后观察组患者的妊娠结局显著优于对照组,同时左室射血分数、氧分压、血氧饱和度显著优于对照组患者,差异均具有统计学意义(P0.05);并且对照组患者经过治疗PAH程度及心功能进展的例数显著高于观察组患者,差异具有统计学意义(P0.05)。结论枸橼酸西地那非治疗妊娠合并肺动脉高压效果理想,能够改善患者的各项指标及妊娠结局,阻止心功能及PAH的进一步加重。     

Management of hypertensive crises: the scientific basis for treatment decisions

The spectrum of disorders associated with an elevated blood pressure (BP) encompasses chronic uncomplicated hypertension and the hypertensive crises, including hypertensive urgencies and emergencies. Although these syndromes vary widely in their presentations, clinical courses, and outcomes they share pathophysiologic mechanisms and, consequently, therapeutic responses to specifically targeted antihypertensive drug types. Nevertheless, hypertensive crises are often treated with drugs which, in that setting are either unsafe or are of unsubstantiated efficacy. The purpose of this review is to examine the pathophysiology of commonly encountered hypertensive crises, including stroke, hypertensive encephalopathy, aortic dissection, acute pulmonary edema, and preeclampsia-eclampsia and to provide a rational approach to their treatment based upon relevant pathophysiologic and pharmacologic principles. Measurement of plasma renin activity (PRA) level often provides insight regarding pathophysiology and predicts efficacy of antihypertensive treatments in the individual patient. However, in hypertensive crises, drug therapy is initiated before the PRA level is known. Nevertheless, the renin-angiotensin dependence (R-type) or volume dependence (V-type) of hypertension can often be deduced by the BP response to drugs that interrupt the renin system (R-drugs) or that decrease body volume (V-drugs). Based upon these considerations, a treatment algorithm is provided to guide drug selection in patients presenting with a hypertensive crisis.     

Intravenous aminophylline in the treatment of acute bronchospastic exacerbations of chronic obstructive pulmonary disease

Often chronic obstructive pulmonary disease (COPD) patients treated for acute exacerbations receive intravenous (IV) aminophylline in addition to inhaled bronchodilators that may raise serum levels of theophylline into the toxic range. A double-blind, randomized study of 52 men with COPD who came to the emergency department for treatment of exacerbations was initiated to establish the efficacy and safety of this common practice. After history and physical examination, patients were treated with 28% oxygen by Venturi mask and 0.3 cc metaproterenol sulfate in 2.5 cc saline by nebulizer; an IV line was started and patients received either aminophylline or D5W. Measurements included baseline and two-hour serum theophylline levels, pulmonary function tests, and symptom questionnaires. Mean values from the entire group showed decreases in respiratory rate, cardiac rate, and pulsus paradoxus, and increases in forced expiratory volume in one second (FEV1) and vital capacity (VC) over a two-hour treatment period (P less than .01). Despite the increase in serum theophylline in the treatment group, the demographic, clinical, pulmonary function, and outcome data were found to have no statistically significant differences when compared to control patients. The data were then analyzed according to serum theophylline levels. Theophylline level greater than 20 micrograms/mL occurred in 15 patients with no untoward effects; premature ventricular contractions (PVCs) were no more frequent in this group than in those with lower serum theophylline levels. A theophylline level greater than 10 micrograms/mL after two hours of treatment resulted in the following differences, which were not statistically significant: mean FEV1 response less than or equal to 10 micrograms/mL vs greater than 10 micrograms/mL, 20% vs 28%; mean VC change, 17% vs 30%; or mean emergency department returns in one week, 0.1 vs 0.26. In our experience, oxygen and inhaled metaproterenol are effective treatment for exacerbations of COPD.     

Intravenous treatment of acute heart failure

Acute heart failure is a disease with various etiologies that is difficult to treat and has a poor prognosis. If causal treatment--revascularization, treatment of a hypertensive crisis--is not possible, symptomatic treatment takes over, based primarily on intravenous treatment with diuretics, vasodilators and/or positive inotropes. Despite undoubted progress in this form of treatment, large, randomised clinical studies have never proved the success of this treatment or confirmed an improvement in prognosis. For this reason most recommendations are based only on clinical experience and surrogate targets such as a reduction in BNP or shortening of the hospitalisation period. Great attention is directed in particular to natriuretic peptides (nesiritide, ularitide) and to levosimendan, which is a calcium sensitizer with a vasodilatory and positive inotropic effect. Nevertheless, even this medicine has not yet been shown to reduce mortality in large studies.