CCIDENTAL drug overdosage, a 1 ways A troublesome, is perhaps never so dramatic as when the drug is epinephrine. The case report and discussion to follow are concerned with the accidental subcutaneous injection of about 10 ml. of a 1:2OOO solution of epinephrine (5 mg.) and its degradation and urinary excretion. REPORT OF A CASEA 41-year-old obese and mentally-retarded woman with a basal-cell nevus syndrome was admitted to the University of Virginia Hospital for excision of numerous basal-cell carcinomas, with split thickness skin grafts to follow. She gave a history of multiple surgical procedures over the preceding 10 years, including amputation of the right forearm for an invasive basal-cell carcinoma, bilateral oophorectomy for multinodular ovarian fibromas, bilateral subtotal thyroidectomy for follicular adenoma, and multiple excisions of basal-cell carcinomas of the lower abdomen and sacral region.Admission temperature was 36.6" C. (97" F.) , pulse 84, respirations 20, blood pressure 130/110, and hematocrit 41 percent. Except for right lenticular opacity and numerous basal-cell carcinomas covering the face and trunk, the admission examination was unremarkable.On the morning of surgical operation, she was premedicated intramuscularly with 10 mg. of morphine sulfate and 0.4 mg. of scopolamine hydrobromide. On arrival in the
Watts( 1) showed that bleeding dogs to a mean arterial pressure of 38 mm Hg increased the peripheral arterial blood epinephrine (as the base) from 0.9 to 20.5 pgJ1. Several investigators (2-5) have substantiated this observation and have also shown that there is a significant increase in arterial norepinephrine in dogs during shock. These results from different laboratories obtained by several methods for catecholamine determination show there is a 5-10-fold increase in norepinephrine and a 50-100-fold increase in epinephrine during hemorrhagic shock in dogs. In the present experiments peripheral blood catecholamines in dogs have been determined under a variety of conditions, to establish more precisely the origin and physiological role of these vasopressor agents during hemorrhagic shock. These studies include:( 1 ) Comparison of values obtained by simultaneous determinations of arterial epinephrine levels by bioassay and fluorimetry.(2 ) Arterial epinephrine-norepinephrine levels at decreasing increments of arterial pressure.(3) Effect of pentobarbital, chloralose and local anesthesia on arterial blood epinephrine levels during shock. (4) Simultaneous estimation of epinephrine in blood from the inferior vena cava above the adrenals, the femoral artery and the femoral vein, to obtain information on the secretion and disappearance of epinephrine during hemorrhagic shock.Methods. Dogs of both sexes weighing *This investigation was supported by a PHS research grant, from Nat. Heart Inst., P.H.S. from 8.2 to 15.9 kg were anesthetized with pentobarbital (30 mg/kg), chloralose (80 mgJkg), by infiltration of 1% procaine in the area to be cannulated. The dogs were bled from the femoral artery into a pressure compensator to a mean blood pressure of 40 mm Hg either by 30 mm Hg increments or by 50 ml increments at 10-minute intervals. Carotid blood pressure was monitored by means of a Sanborn 150 M recorder with a Statham transducer. Control arterial blood samples for bioassay were collected at the beginning of each experiment and after each bleeding. The method of Gaddum and Lembeck( 6) as modified by Franko et aZ ( 7) was used for bioassay of epinephrine in 0.5 ml plasma or whole blood samples. To compare the bioassay method with the fluorimetric method four to eight 50 ml blood samples corresponding to the samples for bioassay were collected in chilled polyethylene centrifuge tubes containing 50 mg ethylenediaminetetraacetic acid disodium salt (Eastman) and immediately centrifuged a t 4OC and 2500 rpm for 2 5 minutes. The plasma was decanted, the volume measured and stored a t 4OC until assayed. The fluorimetric method of Vendsalu( 8) was used until it was found that catecholamine adsorption on aluminum oxide according to the procedure of Goldfien et aZ(9) followed by the trihydroxyindole procedure of von Euler and Lishajko ( lo) was just as adequate and less time consuming. In several experiments the epinephrine levels in blood from the superior vena cava, femoral artery and femoral vein were compared. The samples were...
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