470 THIAMINE 



noted on many thousands of injections by either the subcutaneous, intra- 

 muscular, intraspinal, or intravenous route in doses which in many cases 

 were from one hundred to two hundred times larger than the daily main- 

 tenance dose. These excessive amounts have been well tolerated apparently 

 without any noticeable or measurable effects on circulation, respiration, or 

 other organ systems. A nut-like taste has been reported on injection of 

 large amounts of thiamine; this taste sensation has been used as criterion 

 for the measurement of circulation time by intravenous injection of 300 mg. 

 of thiamine.^^ 



In relatively rare instances, thiamine has caused reactions resembling 

 anaphylactic shock in man. Such reactions have been recorded in over two 

 hundred cases in the world literature (for extensive case references, see 

 Jaros et al.^). All reactions have occurred exclusively on parenteral adminis- 

 tration. They consist in their milder form of a feeling of burning and 

 warmth, urticaria, weakness, restlessness, sweating, nausea, tightness of 

 the throat and chest, dyspnea, hypotension, and tachycardia. In more 

 severe cases the symptoms may rapidly progress to angioneurotic edema, 

 cyanosis, pulmonary edema, hemorrhage into the gastrointestinal tract, 

 and collapse. Five cases of sudden death following intravenous or intra- 

 muscular injection of thiamine have been reported. ^^"^^ The signs and 

 symptoms of these reactions^- are those of anaphylactic shock. Their onset 

 follows the injection within minutes. The patient may, in milder cases, 

 recover quickly. Treatment directed against the symptoms generally con- 

 sists in injection of epinephrine, artificial respiration, administration of 

 oxygen, and analeptics such as caffeine. The occurrence of these reactions 

 and their severity is not related to the dose of thiamine injected, which has 

 varied between 5 and 100 mg. The great majority of patients in which 

 these reactions have been observed had previously tolerated parenteral 

 injection of equal amounts of thiamine without any untoward effects. Thus, 

 they apparently developed a hypersensitivity to thiamine. Only in rare 

 instances^^' ^* have such reactions been observed on the first known injection 

 of thiamine. Most of the reactions have been reported after four to ten or 

 more preceding injections. 



These reactions are caused by thiamine and not by other solutes, sol- 

 vents, or preservatives in the solutions which were injected, since they 



38 C. A. Mills, /. Am. Med. Assoc. 117, 1501 (1941). 



39 I. M. Reingold and F. R. Webb, /. Am. Med. Assoc. 130, 491 (1946). 

 ^0 Fornara, cited by F. Dotti, Minerva med. 1, 720 (1949). 



" J. Arias, Rev. Med. Peruana 22, 160 (1951). 

 « C. G. Weigand, Geriatrics 5, 274 (1950). 

 « M. M. Mitrani,' /. Allergy 15, 150 (1944). 

 ^* J. Seusing, Klin. Wochschr. 29, 394 (1951). 



