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Acute treatment of hypertension with slow infusion of diazoxide
. 470
?C ?HRONIC PROTRACTED DIARRHEA OF INFANCY: A NUTRITIONAL DISEASE, Lo CW, Walker WA. Pediatrics 1983; 72:786-800. Diarrhea1 disease is an extremely common cause of morbidity in infancy. Although its impact is especially severe in children of underdeveloped countries, in industrialized countries the mortality for infants hospitalized with diarrhea still exceeds 1%. Stool weight, consistency, and frequency are not reliable guides to etiology. Clinical findings of dehydration, malabsorption, and failure to thrive are easily recognized and require careful management. The majority of cases of intractable diarrhea seen in this country are due to postinfectious diarrhea, cow’s milk allergy, giardia and parasites, and celiac sprue. Chronic nonspecific diarrhea is easily distinguished from intractable diarrhea by the absence of malabsorption characteristics and dehydration. More common in the first 30 months of life, it is thought to be the childhood counterpart of irritable bowel syndrome and has psychologic overlay. Postinfectious and viral diarrhea are probably the most common causes of intractable diarrhea. Rotavirus has been found in 40% to 70% of infants with gastroenteritis. Bacterial pathogens (Shigelia, Salmonella, Escherichia coil) are found in 4% to 33Vo; the virulence of these agents is due to their invasiveness of the bowel mucosa. Cow’s milk allergy usually occurs before the age of 6 months and is felt to be due to an antigenic response to the milk protein, leading to villous atrophy. Symptoms resolve on milk-free formulas. Giardiasis occurs frequently in some parts of the United States. Most infections are asymptomatic. The degree of malabsorption and steatorrhea does not correlate with the number of parasites or severity of mucosal injury. Entamoeba histolytica, Strongyloides, and Ascaris are other causes of parasitic diarrhea. Celiac sprue, a toxic reaction to gluten, causes mucosal atrophy, crypt hyperplasia, and malabsorption. Gluten-free diets are . essential to prevent growth failure. Treatment. of diarrhea includes glucose and electrolyte repletion. The inherent danger of standard electrolyte solutions is calorie and protein starvation after several days. Dehydration and failure to thrive require hospitalization and electrolyte replacement to break the cycle of malabsorption, failure to heal mucosal damage, and further wasting. [Ramon Pabalan, MD] Editor’s Note: Although not emphasizing emergency department diagnosis and treatment,
The Journal of Emergency Medicine
this article is an excellent review of the etiology and pathogenesis of chronic diarrhea in infancy.
?ACUTE ? CHEST SYNDROME IN SICKLECELL DISEASE. Davies SC, Win AA, Lute J, et al. Lancet Jan 7, 1984; 36-38. The acute chest syndrome is a relatively common and potentially fatal complication of acute sickle-cell crisis. This restrospective study examines 25 admissions of 13 adult patients with sickle-cell disease having acute chest syndrome. The most common symptom was chest pain, occurring in 23 episodes. Cough, usually nonproductive, occurred in 9. Abnormal chest findings, crackles, and diminished breath sounds occurred in 11. Radiographs revealed abnormal findings in 9 of 25 cases on presentation but appeared in all 25 at some time during hospitalization. These findings included patchy infiltrates, florid consolidations, linear atelectasis, and small pleural effusions. Patients with bilateral changes appeared more severely ill. Infection was rarely the cause of acute chest syndrome in adults. In one case mycoplasma was isolated, and Escherichia coli was identified in another. Clinical deterioration occurred in 12 patients who received rehydration alone. Patients receiving exchange transfusions showed improvement within 48 hours of the exchange. Two patients died. It has been suggested that the etiology of acute chest syndrome is secondary to intravascular sickling and pulmonary infarction. The authors cite a previous study that demonstrated postmortem evidence of pulmonary thromboembolism in two thirds of patients with sickle-cell disease. Rapid response to exchange transfusions has further alluded to this etiology. [Larry Hobbs, MD]
?IACUTE ? TREATMENT OF HYPERTENSION WITH SLOW INFUSION OF DIAZOXIDE. Huysmans FT, Thien T, Koene RA. Arch Intern Med 1983; 143:882-884. Diazoxide has long been recommended for the treatment of hypertensive emergencies. Serious complications related to a precipitous fall in blood pressure, however, have frequently been reported. This steep fall in blood pressure is felt to be due to the rapid intravenous bolus injection previously believed necessary to saturate albumin binding sites and elicit an antihypertensive effect. To evaluate the efficacy of slow intravenous infusion of d&oxide, the au-
Abstracts
471
thors treated 81 patients who had severe hypertension with an infusion of diazoxide at a rate of 15 mg/min, in a total dose of 5 mg/kg of body weight, with a minimal dose of 300 mg. Blood pressure was effectively reduced both in patients with a hypertensive crisis (n = 34) and in patients with severe hypertension (n =40). The decrease in mean arterial pressure was 19.7%*1.5% and 17.0%~1.2% in the two groups, respectively. Drop in mean arterial pressure was significantly greater in patients with preclampsia (26.0% f 3.0%). In all cases, blood pressure fell gradually and then decreased only slightly after discontinuation of the infusion. There was no steep or hazardous fall in blood pressure. Two patients experienced ECG findings of myocardial ischemia; no other serious side effects were reported. The authors conclude that slow infusion of d&oxide is a safe and effective procedure for the reduction of blood pressure in patients with severe hypertension. [Ted Szymanski, MD] Editor’s Note: This study adds to the increasing body of literature supporting the use of slow infusion of diazoxide in patients with a hypertensive emergency; and further adds another drug besides nitroprusside which is not all or none in effect. Moreover, diazoxide is easier to use clinically because it is not photosensitive.
begun and continued throughout hospitalization. Cumulative creatine kinase release and continuous vectorcardiography were utilized to assess infarct evolution. Of the 144 patients studied, 73 were assigned to the timolol group and 71 to placebo. Treatment with timolol reduced heart rate, blood pressure, and pain within one hour after the first dose. The timolol group had reduced myocardial ischemia and infarct size as measured by an accelerated reduction of ST vector magnitude, a significant reduction of maximal cumulative creatine kinase release, and significantly smaller changes in QRS vector variables. Timolol was also associated with a significant reduction in pain and need for analgesics. The authors conclude that this study supports the use of timolol as acute intervention early in the process of MI. [Richard G. Lyons, MD] Editor’s Note: This is a well-designed clinical trial that supports the concept of early 0 blockade for acute uncomplicated MI, raising the possibility of its use in the initial emergency department management of MI. It remains yet to be elaborated which group of patients should be acutely revascularized with streptokinase, coronary angioplasty, or acute coronary artery bypass and what role fl blockers will play if any of these procedures are to be utilized.
?R ?EDUCTION OF INFARCT SIZE WITH THE EARLY USE OF TIMOLOL IN ACUTE MYOCARDLAL INFARCTION. The International Collaborative Study Group. N Engl J Med 1984; 310:9-15. To assess the benefits of timely intervention with intravenous fi blockers in myocardial infarction (MI) a randomized, double-blind, placebo-controlled, multicenter study was performed using intravenous timolol within five hours of the onset of symptoms. Patients between the ages of 21 and 70 years not already being treated with a fi blocker, calcium antagonist, digitalis, or other antiarrhythmic agent were included. Patients with bradycardia, hypotension, severe left ventricular failure, and conduction delay were excluded. Treatment was begun with a bolus injection of 1 mg timolol maleate or normal saline and repeated in ten minutes. A constant infusion of timolol 0.6 mg/hr or normal saline was begun ten minutes later. After 24 hours of intravenous infusion, oral therapy of 10 mg timolol bid or placebo was
? l? DOUBLE-BLIND RANDOMIZED CROSSOVER TRIAL OF VERAPAMIL AND PROPRANOLOL IN CHRONIC STABLE ANGINA. Bowles MJ, Subramanian VB, Davies AB, Raftery EB. Am Heart J 1983; 106:12971306. Propranolol (240 mg daily) and verapamil (360 mg daily) were compared in a randomized placebo-controlled, double-blind crossover study in 22 patients with chronic stable angina pectoris. Exercise treadmill testing with computer-assisted ECG analysis was performed after 2 weeks on placebo and at the end of each 4-week period of active drug treatment. The mean exercise time to produce angina in the placebo group was 5.5 ~0.4 minutes, which increased to 7.8 •t 0.5 minutes on propranolol and 9.1+0.5 minutes on verapamil. The improvement in exercise time of verapamil over propranolol was statistically significant. Propranolol had a much more profound effect on both resting and maximal heart rate than did verapamil. ST segment changes showed improvement with both drugs
?C ?HRONIC PROTRACTED DIARRHEA OF INFANCY: A NUTRITIONAL DISEASE, Lo CW, Walker WA. Pediatrics 1983; 72:786-800. Diarrhea1 disease is an extremely common cause of morbidity in infancy. Although its impact is especially severe in children of underdeveloped countries, in industrialized countries the mortality for infants hospitalized with diarrhea still exceeds 1%. Stool weight, consistency, and frequency are not reliable guides to etiology. Clinical findings of dehydration, malabsorption, and failure to thrive are easily recognized and require careful management. The majority of cases of intractable diarrhea seen in this country are due to postinfectious diarrhea, cow’s milk allergy, giardia and parasites, and celiac sprue. Chronic nonspecific diarrhea is easily distinguished from intractable diarrhea by the absence of malabsorption characteristics and dehydration. More common in the first 30 months of life, it is thought to be the childhood counterpart of irritable bowel syndrome and has psychologic overlay. Postinfectious and viral diarrhea are probably the most common causes of intractable diarrhea. Rotavirus has been found in 40% to 70% of infants with gastroenteritis. Bacterial pathogens (Shigelia, Salmonella, Escherichia coil) are found in 4% to 33Vo; the virulence of these agents is due to their invasiveness of the bowel mucosa. Cow’s milk allergy usually occurs before the age of 6 months and is felt to be due to an antigenic response to the milk protein, leading to villous atrophy. Symptoms resolve on milk-free formulas. Giardiasis occurs frequently in some parts of the United States. Most infections are asymptomatic. The degree of malabsorption and steatorrhea does not correlate with the number of parasites or severity of mucosal injury. Entamoeba histolytica, Strongyloides, and Ascaris are other causes of parasitic diarrhea. Celiac sprue, a toxic reaction to gluten, causes mucosal atrophy, crypt hyperplasia, and malabsorption. Gluten-free diets are . essential to prevent growth failure. Treatment. of diarrhea includes glucose and electrolyte repletion. The inherent danger of standard electrolyte solutions is calorie and protein starvation after several days. Dehydration and failure to thrive require hospitalization and electrolyte replacement to break the cycle of malabsorption, failure to heal mucosal damage, and further wasting. [Ramon Pabalan, MD] Editor’s Note: Although not emphasizing emergency department diagnosis and treatment,
The Journal of Emergency Medicine
this article is an excellent review of the etiology and pathogenesis of chronic diarrhea in infancy.
?ACUTE ? CHEST SYNDROME IN SICKLECELL DISEASE. Davies SC, Win AA, Lute J, et al. Lancet Jan 7, 1984; 36-38. The acute chest syndrome is a relatively common and potentially fatal complication of acute sickle-cell crisis. This restrospective study examines 25 admissions of 13 adult patients with sickle-cell disease having acute chest syndrome. The most common symptom was chest pain, occurring in 23 episodes. Cough, usually nonproductive, occurred in 9. Abnormal chest findings, crackles, and diminished breath sounds occurred in 11. Radiographs revealed abnormal findings in 9 of 25 cases on presentation but appeared in all 25 at some time during hospitalization. These findings included patchy infiltrates, florid consolidations, linear atelectasis, and small pleural effusions. Patients with bilateral changes appeared more severely ill. Infection was rarely the cause of acute chest syndrome in adults. In one case mycoplasma was isolated, and Escherichia coli was identified in another. Clinical deterioration occurred in 12 patients who received rehydration alone. Patients receiving exchange transfusions showed improvement within 48 hours of the exchange. Two patients died. It has been suggested that the etiology of acute chest syndrome is secondary to intravascular sickling and pulmonary infarction. The authors cite a previous study that demonstrated postmortem evidence of pulmonary thromboembolism in two thirds of patients with sickle-cell disease. Rapid response to exchange transfusions has further alluded to this etiology. [Larry Hobbs, MD]
?IACUTE ? TREATMENT OF HYPERTENSION WITH SLOW INFUSION OF DIAZOXIDE. Huysmans FT, Thien T, Koene RA. Arch Intern Med 1983; 143:882-884. Diazoxide has long been recommended for the treatment of hypertensive emergencies. Serious complications related to a precipitous fall in blood pressure, however, have frequently been reported. This steep fall in blood pressure is felt to be due to the rapid intravenous bolus injection previously believed necessary to saturate albumin binding sites and elicit an antihypertensive effect. To evaluate the efficacy of slow intravenous infusion of d&oxide, the au-
Abstracts
471
thors treated 81 patients who had severe hypertension with an infusion of diazoxide at a rate of 15 mg/min, in a total dose of 5 mg/kg of body weight, with a minimal dose of 300 mg. Blood pressure was effectively reduced both in patients with a hypertensive crisis (n = 34) and in patients with severe hypertension (n =40). The decrease in mean arterial pressure was 19.7%*1.5% and 17.0%~1.2% in the two groups, respectively. Drop in mean arterial pressure was significantly greater in patients with preclampsia (26.0% f 3.0%). In all cases, blood pressure fell gradually and then decreased only slightly after discontinuation of the infusion. There was no steep or hazardous fall in blood pressure. Two patients experienced ECG findings of myocardial ischemia; no other serious side effects were reported. The authors conclude that slow infusion of d&oxide is a safe and effective procedure for the reduction of blood pressure in patients with severe hypertension. [Ted Szymanski, MD] Editor’s Note: This study adds to the increasing body of literature supporting the use of slow infusion of diazoxide in patients with a hypertensive emergency; and further adds another drug besides nitroprusside which is not all or none in effect. Moreover, diazoxide is easier to use clinically because it is not photosensitive.
begun and continued throughout hospitalization. Cumulative creatine kinase release and continuous vectorcardiography were utilized to assess infarct evolution. Of the 144 patients studied, 73 were assigned to the timolol group and 71 to placebo. Treatment with timolol reduced heart rate, blood pressure, and pain within one hour after the first dose. The timolol group had reduced myocardial ischemia and infarct size as measured by an accelerated reduction of ST vector magnitude, a significant reduction of maximal cumulative creatine kinase release, and significantly smaller changes in QRS vector variables. Timolol was also associated with a significant reduction in pain and need for analgesics. The authors conclude that this study supports the use of timolol as acute intervention early in the process of MI. [Richard G. Lyons, MD] Editor’s Note: This is a well-designed clinical trial that supports the concept of early 0 blockade for acute uncomplicated MI, raising the possibility of its use in the initial emergency department management of MI. It remains yet to be elaborated which group of patients should be acutely revascularized with streptokinase, coronary angioplasty, or acute coronary artery bypass and what role fl blockers will play if any of these procedures are to be utilized.
?R ?EDUCTION OF INFARCT SIZE WITH THE EARLY USE OF TIMOLOL IN ACUTE MYOCARDLAL INFARCTION. The International Collaborative Study Group. N Engl J Med 1984; 310:9-15. To assess the benefits of timely intervention with intravenous fi blockers in myocardial infarction (MI) a randomized, double-blind, placebo-controlled, multicenter study was performed using intravenous timolol within five hours of the onset of symptoms. Patients between the ages of 21 and 70 years not already being treated with a fi blocker, calcium antagonist, digitalis, or other antiarrhythmic agent were included. Patients with bradycardia, hypotension, severe left ventricular failure, and conduction delay were excluded. Treatment was begun with a bolus injection of 1 mg timolol maleate or normal saline and repeated in ten minutes. A constant infusion of timolol 0.6 mg/hr or normal saline was begun ten minutes later. After 24 hours of intravenous infusion, oral therapy of 10 mg timolol bid or placebo was
? l? DOUBLE-BLIND RANDOMIZED CROSSOVER TRIAL OF VERAPAMIL AND PROPRANOLOL IN CHRONIC STABLE ANGINA. Bowles MJ, Subramanian VB, Davies AB, Raftery EB. Am Heart J 1983; 106:12971306. Propranolol (240 mg daily) and verapamil (360 mg daily) were compared in a randomized placebo-controlled, double-blind crossover study in 22 patients with chronic stable angina pectoris. Exercise treadmill testing with computer-assisted ECG analysis was performed after 2 weeks on placebo and at the end of each 4-week period of active drug treatment. The mean exercise time to produce angina in the placebo group was 5.5 ~0.4 minutes, which increased to 7.8 •t 0.5 minutes on propranolol and 9.1+0.5 minutes on verapamil. The improvement in exercise time of verapamil over propranolol was statistically significant. Propranolol had a much more profound effect on both resting and maximal heart rate than did verapamil. ST segment changes showed improvement with both drugs