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Hormonal hyperthermia: endocrinologic causes of fever
not. Virtually all the patients had extensive pulmonary infiltrates and low lung compliance contributing to their respiratory failure, and t h e r e were roughly comparable associated medical conditions in the two groups. P E E P increased the length of survival from 4.2 to 9.2 days, but overall survival, defined as hospital discharge, was similar at 31% with and 26% without PEEP. Patients in the P E E P group with an improvement in PaO2 and decrease in shunt fraction following a trial of P E E P had a more favorable outcome. In both survival related more to the maintenance of adequate tissue oxygenation as manifested by PaO2 than to improved gas exchange as reflected by an increase in PaO=. Survival was related to the extent of hypoxemia prior to the use of PEEP rather t h a n its subsequent continued use. In light of the fact that P E E P can reduce cardiac output and net oxygen delivery to tissues, and can adversely affect hepatic, renal and splanchnic blood flow, PEEP should be used selectively in patients in whom benefits outweigh risks. Greater selectivity by criteria not yet determined, survival in those patients who show improvement in PvO2 as well as PaO2 after a trial of PEEP, and overall care of the patient should be directed at improving tissue oxygen delivery rather than pulmonary gas exchange alone. Frederick K. Seydel, MD
positive end expiratory pressure, respiratory failure; respiratory failure, positive end expiratory pressure Hormonal hyperthermia: endocrinologic causes of fever. Simon HB, Daniels GH, Am J Med 66:257-263, (Feb) 1979. Endocrine disturbances may be associated with fever, but it is uncommon for fever alone to be the presenting manifestation. Of seven patients studied, six presented with fever as their major manifestation of hormonal disturbance. In all, the admitting diagnosis was infection, with tuberculosis suspected in three, gram-negative bacterimia in two, and endocarditis in one. Infection was ruled out in all patients. Fever was a t t r i b u t e d to otherwise clinically i n a p p a r e n t thyrotoxicosis, triiodothyronine, Ta toxicosis, subacute thyr0iditis, primary adrenal insufficiency, pheochromocytoma, and thyroid storm. The patient with pheochromocytoma presented with fever, abdominal distress and hypotension. The mechanisms of fever in these disorders is reviewed. The calorigenic effects of thyroid hormone, probably in association with a poorly characterized thermoregulatory disturbance, are well known. In thyroiditis, fever probably results from actual inflammation of the thyroid gland and usually responds well to anti-inflammatory drugs. (Editor's note: As mentioned in this article hypoglycemia may present with hypothermia and this diagnosis is far more likely to be encountered in the field or ED.) Frederick K. Seydel, MD
fever, endocrinologic causes; hyperthermia, hormonal Rapid metabolism of phenytoin: a method of calculating proper dosage. Hawkins DW, Ludden TM, Hoffman SF, et al, Arch Neurol 36:109-110, (Feb) 1979. Despite apparently adequate dosage of phenytoin, there is considerable variation in therapeutic blood levels, making adjustment of dosage difficult, frequently due to fear of overdosage in the individual p a t i e n t . Application of classic Michaelis-Menten pharmacokinetics permit s adjustment of dosage based on individual variations of the maximum rate of metabolism (V-max) and the apparent plasma clearance rate. Calculations can be made from steady-state data using a nomogram. They have been applied successfully with a resultant daily dosage of phenytoin, for example, in the case reported here of 650 rag/day. After eliminating poor patient compliance and malabsorption as causes of inadequate dosage, the calculation may be applied as follows: Two steady state serum phenytoin concentrations (Cp) are obtained at different daily doses (Ro). The ratio Ro/Cp is plotted agains~ Ro on the nomogram to obtain estimated V-max for the indi-
9:4 (April) 1980
vidual patient at the Y-intercept of the line extended from the values of Cp; the slope of the line is Km. The average V-max from the literature is 6.1 mg/kg/day. The desired daily dose is Ro in the formula Ro = V-max x Cp/Km + Cp. Of importance theoretically and practically is the fact t h a t phenobarbital has no influence on the relationships of phenytoin metabolism parameters used here. (Editar's note: The significance of this article for most EDs is that there may be a reason for a patient's seizures other'than noncompliance. In this instance increased metabolism was the cause but malabsorption can also occur. The ED is more likely than the neurology clinic to be the locus of increased seizure activity, and this phenomenon should be sought as explanation.)
Frederick K. Seydel, MD
phenytoin, dosage Pathogenesis of transient ischemic attacks within the vertebrobasilar arterial system. Naritomi H, Sakai F, Meyer JS, Arch Neurol 36:121-128, (Mar) 1979. The syndrome of transient neurologic deficits attributed to v e r t e b r o b a s i l a r a r t e r i a l i n s u f f i c i e n c y (VBI) i n c l u d e s symptoms usually seen in older patients, including vertigo, transient visual impairment, intermittent deafness, ataxia, syncope and drop attacks, often accompafiied by occipital headache. The pathogenesis of this syndrome was studied using measurement of regional cerebral blood flow by xenon 133 inhalation in 36 patients with VBI, 15 controls, and three patients with brainstem infarction, before and after induction of pastural hypotension using a tilt table. Two types of cerebral ischemia t h a t may contribute to VBI symptoms were found: 1) cerebral ischemia persistent for about three weeks after the onset of VBI symptoms, probably due to thromboembolism; and 2) cerebral ischemia induced by ort h o s t a t i c h y p o t e n s i o n , a n d r e l a t e d to c e r e b r a l a r t e r i a l dysautoregulation, ie, inability to adjust regional cerebral blood flow to maintain perfusion. Taken together, the results suggest t h a t VBI may be initiated by a thromboembolic event with subsequent cerebral dysautoregulation and postural hypotension resulting from the initial event. The patient would thereafter be predisposed to repeated episodes of ischemia due to alterations in perfusion pressure, progressing with time to be more severe and widespread. (Editor's note: An interesting article since it suggests that while the initial problem is thromboembolic, subsequent pathophysiology is deranged autoregulation. Therefore, anticoagulation may not be effective unless combined with efforts to maintain cerebral perfusion.) Frederick K. Seydel, MD
ischemia, vertebrobasilar arterial system Evaluation and treatment of penetrating cervical injuries. Roon AJ, Christensen N, J Trauma 19:391-397, (Jun) 1979. Underestimation of the seriousness of penetrating cervical trauma based on physical examination frequently leads to delay in definitive therapy. It is reported in prior studies that almost 33% of patients with normal examination excluding the entry wound have major occult injury and that delay in definitive care leads to an increase in mortality of 20%. In a prospective study including 189 patients (49 gunshot wounds and 140 stab wounds) with penetrating cervical trauma, the authors address the controversy of early exploration versus observation. The protocol mandated exploration if the wound penetrated the platysma. One hundred fifty-four patients allowed exploration and 35 were not explored due to nonmedical reasons. The authors report hemorrhage, hematoma, shock, or neurologic deficit to be present alone or in combination in 74% of the series. Neurologic deficit had a 100% correlation with major deep structure injury while the others were less predictive. In the 26% of patients without clinical abnormality only 6% were found to have occult serious injury. This statistic differs greatly from prior studies reporting an incidence of major occult injury of about 33%. Of the 154
Ann Emerg Med
236/97
positive end expiratory pressure, respiratory failure; respiratory failure, positive end expiratory pressure Hormonal hyperthermia: endocrinologic causes of fever. Simon HB, Daniels GH, Am J Med 66:257-263, (Feb) 1979. Endocrine disturbances may be associated with fever, but it is uncommon for fever alone to be the presenting manifestation. Of seven patients studied, six presented with fever as their major manifestation of hormonal disturbance. In all, the admitting diagnosis was infection, with tuberculosis suspected in three, gram-negative bacterimia in two, and endocarditis in one. Infection was ruled out in all patients. Fever was a t t r i b u t e d to otherwise clinically i n a p p a r e n t thyrotoxicosis, triiodothyronine, Ta toxicosis, subacute thyr0iditis, primary adrenal insufficiency, pheochromocytoma, and thyroid storm. The patient with pheochromocytoma presented with fever, abdominal distress and hypotension. The mechanisms of fever in these disorders is reviewed. The calorigenic effects of thyroid hormone, probably in association with a poorly characterized thermoregulatory disturbance, are well known. In thyroiditis, fever probably results from actual inflammation of the thyroid gland and usually responds well to anti-inflammatory drugs. (Editor's note: As mentioned in this article hypoglycemia may present with hypothermia and this diagnosis is far more likely to be encountered in the field or ED.) Frederick K. Seydel, MD
fever, endocrinologic causes; hyperthermia, hormonal Rapid metabolism of phenytoin: a method of calculating proper dosage. Hawkins DW, Ludden TM, Hoffman SF, et al, Arch Neurol 36:109-110, (Feb) 1979. Despite apparently adequate dosage of phenytoin, there is considerable variation in therapeutic blood levels, making adjustment of dosage difficult, frequently due to fear of overdosage in the individual p a t i e n t . Application of classic Michaelis-Menten pharmacokinetics permit s adjustment of dosage based on individual variations of the maximum rate of metabolism (V-max) and the apparent plasma clearance rate. Calculations can be made from steady-state data using a nomogram. They have been applied successfully with a resultant daily dosage of phenytoin, for example, in the case reported here of 650 rag/day. After eliminating poor patient compliance and malabsorption as causes of inadequate dosage, the calculation may be applied as follows: Two steady state serum phenytoin concentrations (Cp) are obtained at different daily doses (Ro). The ratio Ro/Cp is plotted agains~ Ro on the nomogram to obtain estimated V-max for the indi-
9:4 (April) 1980
vidual patient at the Y-intercept of the line extended from the values of Cp; the slope of the line is Km. The average V-max from the literature is 6.1 mg/kg/day. The desired daily dose is Ro in the formula Ro = V-max x Cp/Km + Cp. Of importance theoretically and practically is the fact t h a t phenobarbital has no influence on the relationships of phenytoin metabolism parameters used here. (Editar's note: The significance of this article for most EDs is that there may be a reason for a patient's seizures other'than noncompliance. In this instance increased metabolism was the cause but malabsorption can also occur. The ED is more likely than the neurology clinic to be the locus of increased seizure activity, and this phenomenon should be sought as explanation.)
Frederick K. Seydel, MD
phenytoin, dosage Pathogenesis of transient ischemic attacks within the vertebrobasilar arterial system. Naritomi H, Sakai F, Meyer JS, Arch Neurol 36:121-128, (Mar) 1979. The syndrome of transient neurologic deficits attributed to v e r t e b r o b a s i l a r a r t e r i a l i n s u f f i c i e n c y (VBI) i n c l u d e s symptoms usually seen in older patients, including vertigo, transient visual impairment, intermittent deafness, ataxia, syncope and drop attacks, often accompafiied by occipital headache. The pathogenesis of this syndrome was studied using measurement of regional cerebral blood flow by xenon 133 inhalation in 36 patients with VBI, 15 controls, and three patients with brainstem infarction, before and after induction of pastural hypotension using a tilt table. Two types of cerebral ischemia t h a t may contribute to VBI symptoms were found: 1) cerebral ischemia persistent for about three weeks after the onset of VBI symptoms, probably due to thromboembolism; and 2) cerebral ischemia induced by ort h o s t a t i c h y p o t e n s i o n , a n d r e l a t e d to c e r e b r a l a r t e r i a l dysautoregulation, ie, inability to adjust regional cerebral blood flow to maintain perfusion. Taken together, the results suggest t h a t VBI may be initiated by a thromboembolic event with subsequent cerebral dysautoregulation and postural hypotension resulting from the initial event. The patient would thereafter be predisposed to repeated episodes of ischemia due to alterations in perfusion pressure, progressing with time to be more severe and widespread. (Editor's note: An interesting article since it suggests that while the initial problem is thromboembolic, subsequent pathophysiology is deranged autoregulation. Therefore, anticoagulation may not be effective unless combined with efforts to maintain cerebral perfusion.) Frederick K. Seydel, MD
ischemia, vertebrobasilar arterial system Evaluation and treatment of penetrating cervical injuries. Roon AJ, Christensen N, J Trauma 19:391-397, (Jun) 1979. Underestimation of the seriousness of penetrating cervical trauma based on physical examination frequently leads to delay in definitive therapy. It is reported in prior studies that almost 33% of patients with normal examination excluding the entry wound have major occult injury and that delay in definitive care leads to an increase in mortality of 20%. In a prospective study including 189 patients (49 gunshot wounds and 140 stab wounds) with penetrating cervical trauma, the authors address the controversy of early exploration versus observation. The protocol mandated exploration if the wound penetrated the platysma. One hundred fifty-four patients allowed exploration and 35 were not explored due to nonmedical reasons. The authors report hemorrhage, hematoma, shock, or neurologic deficit to be present alone or in combination in 74% of the series. Neurologic deficit had a 100% correlation with major deep structure injury while the others were less predictive. In the 26% of patients without clinical abnormality only 6% were found to have occult serious injury. This statistic differs greatly from prior studies reporting an incidence of major occult injury of about 33%. Of the 154
Ann Emerg Med
236/97