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Efficacy of a 12-hour sustained-released preparation in maintaining therapeutic serum theophylline levels in asthmatic children
gonococcal disease. ESR elevation is variably present. A negative cervical Gram's stain does not exclude gonococcal disease, but can be quite specific if vaginal flora is eliminated and a pure endocervical specimen obtained. When GC is seen, a presumptive diagnosis of GC salpingitis may be made. Culdocentesis recovers turbid fluid and leukocytes in 80% of those with moderate or severe symptoms, but may also be positive in other types of intra-abdominal pathology. When pelvic abscess is suspected, ultrasonography is a highly accurate means of diagnosis. (Editor's note: The high incidence of false positive diagnoses and their nature, namely missed appendicitis and ectopic pregnancy, is of great concern. While laparoscopy will reduce this, it is not practical to laparoscope all patients with non-classic presentations, negative cervical Gram's stains, and negative culdocenteses as indicated.) Carla Janson, MD
pelvic inflammatory disease
Efficacy of a 12-hour sustained-released preparation in maintaining therapeutic serum theophyiline levels in asthmatic children. Kelly HW, Murphy S, Pediatrics 66:97-102, (Jul) 1980. This study was done to evaluate Theodur, a sustained-release theophylline preparation, in children aged 6 to 18, with respect to serum theophylline levels and a q 12 hour versus q 8 hour dosage. It is well known t h a t children metabolize theophylline faster than do adults, and it was believed that they required q 8 h dosage of even SR preparations, whereas adequate blood levels in adults could be maintained with q 12 h administration. The difficulty of keeping therapeutic levels with q 4 or 6 h doses of rapid-release theophylline preparations, combined with demonstrated 11% compliance at a q 6 h schedule, makes this study important. Twenty children were studied, approximately 50% under 10 years and the other half 10 to 18 years. Each child's dose was adjusted so that 6 hours after administration of Theodur, his blood level of theophylline was between 10 and 20 mg/ml. The patients were kept on this dose for five days, then q 3 hourly levels were drawn. Significant difference occurred between only two times, ie, 8 am and 8 pm, with 8 pm being lower. Even at 8 pm only two children had levels below 10 mg/kg dose given q 12 hour. There was only a slight difference in the average dose for those under age 10 compared to those over 10. (Editor's note: This study is of considerable importance in decreasing emergency department visits by children with frequently recurring bronchospasm because patient noncompliance is a major factor in both pediatric and adult patients.) Constance Greene, MD
asthma, theophylline
Corticosteroids in the treatment of acute exacerbations of asthma. Loren ML, Chai H, Leung P, et al, Ann A/lergy 45:67-71, (Aug) 1980. A double-blind study examining the role of steroids in the acute therapy of asthma was performed on 16 moderately to severely asthmatic children already on continuous regular medication. The latter included daily theophylline and in some cases alternate day corticosteroids, oral beta adrenergic agonists, cromolyn sodium, and inhaled beclomethasone. Entry into the study was made by demonstration of a sudden exacerbation of asthma, typically including dyspnea, wheezing, decreased exercise tolerance, and increased medication requirement. Children receiving daily steroid therapy, those receiving IV therapy, and those with a past hisory of respira-
10:3 (March) 1981
tory failure or with suspected adrenal insufficiency were excluded from the study. All subjects were randomized to a group receiving either a placebo or prednisone 2 mg/kg/day each divided doses every 6 hours for a total of 72 hours. Medications being taken before entry were continued unchanged, and the use of beta adrenergic agonist therapy, either inhaled or injected, was administered as needed. Peak expiratory flow rates (PERF - - expressed as a percentage of predicted value) were measured three times daily and the results averaged into a mean for the 24-hour period before the study and four consecutive 12-hour periods after it began. Beginning at the 1- to 12-hour period and continuing through the 25- to 36-hour period, the steroid-treated group showed a significantly greater improvement in the PERF than did the placebo group; this increase in the steroid-treated group was statistically significant by 12 hours and maximal by 24 hours, while the increase in the placebo-treated group was not significant in any period. The authors note that the placebo-treated group required a significantly increased number of nebulization treatments compared to the steroidtreated group. It was concluded that oral prednisone can be an effective adjunct in controlling acute asthma. (Editor's n o t e : No explanation is given for including alternate-day steroid patients in the study while excluding those taking daily steroids. Nevertheless, the use of prednisone, a relatively longacting steroid [half life 24 to 36 h~urs] which is orally absorbed and hepatically metabolized to its active component prednisolone, is supported. A comparison with parenterally injected active steroid, such as hydrocortisone or methyl prednisolone, would be of interest.) John D. Patrick, MD
asthma, corticosteroids
*
Pitfalls in the recognition of subarachnoid hemorrhage. Adams HP, Jergenson DD, Kassell NF, et al, JAMA 244:794-796, (Aug) 1980. One hundred eighty-two patients were admitted to the University of Iowa Hospitals for t r e a t m e n t of subarachnoid hemorrhage (SAH) secondary to a ruptured aneurysm. The correct diagnosis was delayed in 41 patients from i to 27 days. The incidence of SAH is 8% of all acute CVAs, with 20,000 ocurring annually (10.3/100,000). The incidence of SAH has been stable the last 15 years, while that for other CVAs has decreased. Severe headache, nuchal rigidity, nausea, vomiting, focal neurological signs, and stupor are the classic presenting symptoms and signs of SAH. The article emphasizes other presentations, such as chest pain, confusion, ataxia, sudden hearing loss and photophobia, as less common symptoms. The most common misdiagnosis was systemic infection, migraine headache, and hypertensive encephalopathy. Other less common misdiagnoses were neck trouble, meningitis, MI, intoxication, and malingering. SAH occurred most frequently during work and activities. The diagnosis was made without the use of CAT scan. Lumbar puncture and cerebral angiography were the diagnostic procedures of choice. Rebleeding within the first two weeks had a 40% mortality rate. Cerebral infarction was associated with cerebral vasospasm occurring 7 to 10 days after SAH. One must have a high index of suspicion when diagnosing SAH that presents with atypical symptoms and signs. Early recognition and treatment has been shown to reduce the mortality of SAH significantly. (Editor's note: In hospitals with CAT scanners, this study should be done before the lumbar puncture, since it may be diagnostic and will obviate the need for a lumbar puncture, which is hazardous in patients with increased CSR pressure.) Richard Karrel, MD
hemorrhage, subarachnoid
Ann Emerg Med
171/77
pelvic inflammatory disease
Efficacy of a 12-hour sustained-released preparation in maintaining therapeutic serum theophyiline levels in asthmatic children. Kelly HW, Murphy S, Pediatrics 66:97-102, (Jul) 1980. This study was done to evaluate Theodur, a sustained-release theophylline preparation, in children aged 6 to 18, with respect to serum theophylline levels and a q 12 hour versus q 8 hour dosage. It is well known t h a t children metabolize theophylline faster than do adults, and it was believed that they required q 8 h dosage of even SR preparations, whereas adequate blood levels in adults could be maintained with q 12 h administration. The difficulty of keeping therapeutic levels with q 4 or 6 h doses of rapid-release theophylline preparations, combined with demonstrated 11% compliance at a q 6 h schedule, makes this study important. Twenty children were studied, approximately 50% under 10 years and the other half 10 to 18 years. Each child's dose was adjusted so that 6 hours after administration of Theodur, his blood level of theophylline was between 10 and 20 mg/ml. The patients were kept on this dose for five days, then q 3 hourly levels were drawn. Significant difference occurred between only two times, ie, 8 am and 8 pm, with 8 pm being lower. Even at 8 pm only two children had levels below 10 mg/kg dose given q 12 hour. There was only a slight difference in the average dose for those under age 10 compared to those over 10. (Editor's note: This study is of considerable importance in decreasing emergency department visits by children with frequently recurring bronchospasm because patient noncompliance is a major factor in both pediatric and adult patients.) Constance Greene, MD
asthma, theophylline
Corticosteroids in the treatment of acute exacerbations of asthma. Loren ML, Chai H, Leung P, et al, Ann A/lergy 45:67-71, (Aug) 1980. A double-blind study examining the role of steroids in the acute therapy of asthma was performed on 16 moderately to severely asthmatic children already on continuous regular medication. The latter included daily theophylline and in some cases alternate day corticosteroids, oral beta adrenergic agonists, cromolyn sodium, and inhaled beclomethasone. Entry into the study was made by demonstration of a sudden exacerbation of asthma, typically including dyspnea, wheezing, decreased exercise tolerance, and increased medication requirement. Children receiving daily steroid therapy, those receiving IV therapy, and those with a past hisory of respira-
10:3 (March) 1981
tory failure or with suspected adrenal insufficiency were excluded from the study. All subjects were randomized to a group receiving either a placebo or prednisone 2 mg/kg/day each divided doses every 6 hours for a total of 72 hours. Medications being taken before entry were continued unchanged, and the use of beta adrenergic agonist therapy, either inhaled or injected, was administered as needed. Peak expiratory flow rates (PERF - - expressed as a percentage of predicted value) were measured three times daily and the results averaged into a mean for the 24-hour period before the study and four consecutive 12-hour periods after it began. Beginning at the 1- to 12-hour period and continuing through the 25- to 36-hour period, the steroid-treated group showed a significantly greater improvement in the PERF than did the placebo group; this increase in the steroid-treated group was statistically significant by 12 hours and maximal by 24 hours, while the increase in the placebo-treated group was not significant in any period. The authors note that the placebo-treated group required a significantly increased number of nebulization treatments compared to the steroidtreated group. It was concluded that oral prednisone can be an effective adjunct in controlling acute asthma. (Editor's n o t e : No explanation is given for including alternate-day steroid patients in the study while excluding those taking daily steroids. Nevertheless, the use of prednisone, a relatively longacting steroid [half life 24 to 36 h~urs] which is orally absorbed and hepatically metabolized to its active component prednisolone, is supported. A comparison with parenterally injected active steroid, such as hydrocortisone or methyl prednisolone, would be of interest.) John D. Patrick, MD
asthma, corticosteroids
*
Pitfalls in the recognition of subarachnoid hemorrhage. Adams HP, Jergenson DD, Kassell NF, et al, JAMA 244:794-796, (Aug) 1980. One hundred eighty-two patients were admitted to the University of Iowa Hospitals for t r e a t m e n t of subarachnoid hemorrhage (SAH) secondary to a ruptured aneurysm. The correct diagnosis was delayed in 41 patients from i to 27 days. The incidence of SAH is 8% of all acute CVAs, with 20,000 ocurring annually (10.3/100,000). The incidence of SAH has been stable the last 15 years, while that for other CVAs has decreased. Severe headache, nuchal rigidity, nausea, vomiting, focal neurological signs, and stupor are the classic presenting symptoms and signs of SAH. The article emphasizes other presentations, such as chest pain, confusion, ataxia, sudden hearing loss and photophobia, as less common symptoms. The most common misdiagnosis was systemic infection, migraine headache, and hypertensive encephalopathy. Other less common misdiagnoses were neck trouble, meningitis, MI, intoxication, and malingering. SAH occurred most frequently during work and activities. The diagnosis was made without the use of CAT scan. Lumbar puncture and cerebral angiography were the diagnostic procedures of choice. Rebleeding within the first two weeks had a 40% mortality rate. Cerebral infarction was associated with cerebral vasospasm occurring 7 to 10 days after SAH. One must have a high index of suspicion when diagnosing SAH that presents with atypical symptoms and signs. Early recognition and treatment has been shown to reduce the mortality of SAH significantly. (Editor's note: In hospitals with CAT scanners, this study should be done before the lumbar puncture, since it may be diagnostic and will obviate the need for a lumbar puncture, which is hazardous in patients with increased CSR pressure.) Richard Karrel, MD
hemorrhage, subarachnoid
Ann Emerg Med
171/77