Medical Arts and Sciences: A Scientific oJ urnal of the College of Medical Evangelists
Volume 2 | Number 4 Article 5
10-1948 A Resume of Intravenous Procaine Therapy Fred B. Moor College of Medical Evangelists
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Recommended Citation Moor, Fred B. (1948) "A Resume of Intravenous Procaine Therapy," Medical Arts and Sciences: A Scientific oJ urnal of the College of Medical Evangelists: Vol. 2: No. 4, Article 5. Available at: http://scholarsrepository.llu.edu/medartssciences/vol2/iss4/5
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A RESUME OF INTRAVENOUS PROCAINE THERAPY* FRED B. MOOR, M.D.
The most surpnsmg development among may be recovered in ten to twelve hours from new uses for old drugs is the intravenous in the urine as ·para-aminobenzoic acid, para jection of procaine for a variety of clinical aminohippuric acid, para-aminobenzoyl gly conditions. This drug was synthesized by Ein curonate, diethylaminoethanol, and traces of horn in 1905. In 1909 Bier produced anes procaine. Graubard et al.b found that twenty thesia in the extremities by injecting procaine minutes after the' intravenous injection of 20 intravenously distal to a tourniquet. On ac mg. of procaine per kilogram of body weight count of the occasional fatal outcome from in the rabbit, only traces could be found in . the use of procaine for local anesthesia, how the blood stream of the animal. On the basis ever, it has, until recently, been considered of this study these authors evolved a dosage unsafe to inject the drug into the venous method based on body weight for the human . circulation. Now that it has been shown that as follows: procaine can, with comparative safety, be ad 4 mg/kilogram of body weight ministered intravenously, its clinical use is = I procaine unit expanding rapidly. in 20 minutes.
CHEMISTRY AND PHARMACOLOGY It was recommended that this be given in a Procaine hydrochloride is para-aminoben 0.1 per cent solution, so that I mil contained zyl-diehylaminoethanol hydrochloride: 1 mg. of the drug. From clinical experience, the authors found this dosage to give optimal results with a minimum of toxic reactions. Mautz showed that the local application of procaine to the heart reduced the irritability of the myocardium so that a considerably Procaine hydrochloride occurs as colorless stronger stimulus was needed to produce ven crystals which are soluble in 0.6 part of water tricular fib9llation. Burstein et aI.c demon and 30 parts of alcohol. It is stable to tempera strated that ventricular fibrillation could be tures as high as I 00 C. produced in the experimental animal by the Goldberg, Koster, and Warsaw have shown intravenous injection of epinephrine during that when procaine is injected, it is hydrolyzed cyclopropane anesthesia. It was possible to in the liver by an esterase into para-amino prevent the occurrence of fibrillation, if the benzoic acid and diethylaminoethanol. The injection of epinephrine was preceded by an para-aminobenzoic acid is then acetylated. In intravenous injection of procaine. 1919, Eggleston and Hatcher demonstrated One of the surprising effects of the intra that nearly 95 per cent of injected procaine venous administration of procaine is the clear ing up of urticaria! skin manifestations in • From the Department or Therapeutia, Colleae or Medical E\'IUl plista. serum sickness and other allergic conditions.
129 130 Moor-Intravenous Procaine Therapy
Graubard et al.c believe that p~ocaine has a procaine during local anesthesia may have twofold action in traumatized and inflamed been due to its combination with epinephrine tissues: (1) direct action on irritated nerve rather than to the procaine alone, since epine fibers; (2) indirect action of diethylamino phrine increases the toxicity of procaine about ethanol on the endothelium of blood vessels threefold. With the too rapid intravenous in and capillary walls to lessen fluid loss from the jection of the 1 per cent solution of procaine blood to the tissues. The latter idea is based hydrochloride convulsions may occasionally on the structural similarity of diethylamino occur, but these are controlled by stopping the ethanol to benadryl which has well-known flow or by the intravenous injection of a bar- antihistamine activity. Most investigators biturate. agree that procaine is concentrated in trauma Since the burden of the destruction of pro tized or inflamed tissues because of the exuda caine in the body falls upon the liver, one tion which occurs there. might expect evidence of damage to this organ. The concentration employed and the ad Jacoby et al. however, have recently demon ministration of procaine has varied consider strated that repeated massive doses of procaine ably with different investigators and with the hydrochloride adininistered to rats and dogs purposes for which the drug has been given. in acute and subacute experiments produce This will become apparent when the clinical no hi~tologic evidence of damage in the liver, application of intravenously administered pro the spleen, the heart, or the kidney. Liver caine is discussed. function tests done on human beings after the · The subjective manifestations of intrave administration of procaine intravenously gave nous procaine injection in the conscious pa no indication of impaired hepatic function. tient are usually not unpleasant. In five to Richards has shown that starvation and a seven minutes after the injection is started deficiency of vitamin C markedly increase the there is a sensation of warmth over the entire toxicity of procaine. He postulated that vita body. There is comfortable relaxation as pain min C may be part of an enzyme system con is relieved. There is _some dryness of the mouth cerned with the destruction of procaine. He and a metallic taste. There is likely to be suggested the administration of large doses of transient lightheadedness. The operator may vitamin C and glucose before the use of pro observe flushing of the face and neck, tearing caine in poorly nourished patients. of the eyes, and dilatation of the pupils. More A few, but by no means all, of the investi severe responses are marked dizziness, appre gators who have done the pioneer work on hension, sensation of trembling, sleepiness be the intravenous use of procaine recommend yond comfortable relaxation, and momentary · a preliminary skin test to determine the sensi loss of consciousness. tivity of the patient to the drug. It is suggested that 1 cc. of the 0.1 per cent solution be in TOXICOLOGY jected intradermally. If the patient is sensi The minimal lethal dose of procaine hydro tive, the reaction is apparent in about ten chloride for the rabbit is 40 to 60 mg. per minutes. Another wise precaution is the pre kilogram of body weight, 40 to 45 mg. per liminary administration of a therapeutic dose kilogram for the guinea pig, and 45 to 75 mg. of a barbiturate. When procaine is to be in per kilogram for the dog. The minimal lethal jected intravenously, an injectable barbiturate dose for man is unknown. It has been sug should be·available for immediate intravenous. gested that many of the deaths attributed to administration. Medical Arts and Sciences 131
CLINICAL APPLICATION caine hydrochloride in a large number of Procaine has been used successfully by the patients with acute cardiac arrhythmias dur intravenous route for the relief of various pru ing intrathoracic surgery. The drug was given ritic conditions. Lundy, in 1940, used 20 cc. in dosages ranging from 30 to 70 mg. in 1 per of 0.1 per cent procaine intravenously for the cent solution injected rapidly by vein with treatment of pruritis in jaundiced patients. uniformly good results. State and Wangensteen encountered delayed Bittrich and Powers have recently reported serum sickness following the injection of crys their experience in 17 cases with intravenous tallized bovine albumin as a blood substitute. procaine in thoracic surgery. They employed In order to relieve the severe joint pain which a continuous intravenous drip of I per cent their patients suffered, they gave I gm. of procaine hydrochloride at the rate of 65 to procaine hydrochloride in 500 cc. of physio I 00 drops per minute during the operative logical saline solution during a period of two procedure. In spite of the procaine, 5 of the hours. To their surprise, all the manifestations 17 patients developed cardiac arrhythmias. It of serum sickness subsided almost immedi was the authors' impression that their patients ately. Appelbaum et al. observed rapid dis tolerated thoracic surgery better and made appearance of the urticaria} rash and the joint easier recoveries with the use of intravenous symptoms of serum sickness, resulting from a procaine. prophylactic dose of tetanus antitoxin, follow Graubard et aI.c reported the intravenous ing the intravenous injection of I gm. of pro injection of procaine hydrochloride in a dos caine hydrochloride in 500 cc. of physiological age of 4 mg. ~r kilogram of body weight in saline solution. Dressler and Dwork have re 0.1 per cent solution in the treatment of ported the almost immediate subsidence of the osteoarthritis. The results were exceedingly arthralgia and the urticaria} rash produced by good with the relief 'of pain with increased penicillin in a sensitive patient. Their dosage mobility for prolonged periods of time. of procaine was I gm. in 500 cc. of physio Gordon found the use of intravenously ad logical saline by the intravenous route. ministered procaine of great value for the Graubard et al.•·c employed a 0.1 per cent control of pain in 10 patients during the dress solution of procaine hydrochloride in a dosage ing of severe burns. He gave a liter of 0.1 per of 4 mg. per kilogram of body weight with cent solution of procaine hydrochloride over gratifying results in the treatm~nt of traumatic a period of one and a half hours. Pain was conditions. This dosage should not be ad relieved without the simultaneous use of ministered in less than twenty minutes. morphine. Among the conditions successfully treated McLachlin found the intravenous use of were sprains, fractures, and traumatic arthritis. procaine hydrochloride superior to morphine The intravenous injection of procaine has for the control of postoperative pain. In a proved to be of definite value for the pre series of ten cases he injected 1.0 gm. of pro vention of cardiac irritability during thoracic caine hydrochloride in 500 cc. of physiological surgery. Mautz, as mentioned previously, in saline solution in one to one and a half hours. 1936 called attention to the reduction in car This was repeated as needed in some of the diac irritability produced by the epicardial patients. The surgical convalescence of these and intravenous administration of procaine. patients was unusually comfortable. Allen, Burstein•, and Burstein and Alexander,b and Crossman et al.b have actually performed later reported the intravenous use of pro- major surgical procedures using a continuous 132 Moor-Intravenous Procaine Therapy intravenous infusion of I per cent procaine died carefully so that this useful new method hydrochloride given at rates up to 20 cc. per may not be discredited by accidents and un minute. They did not, however, recommend necessary danger to patients. this method for general use. Allen • in 1945 reported the use of intra REFERENCES venous procaine for the production of anes Allen, F. M.: (a) Intravenous obstetrical anesthesia, Am. thesia in 12 obstetrical cases at the City Hos J. Surg. 70:285 (Dec.) 1945. pital, Welfare Island, New York. For this pur --, Crossman, L. W., and Lyons, L. V.: (b) Intra pose, a I per cent solution of procaine hydro venous procaine analgesia, Anesth. and Analg. 25: 1 Oan. Feb.) 1946. chloride was given at the rate of 0.5 to 13 cc. Appelbaum, E.; Abraham, A., and Sinton, W.: A case of per minute depending upon the degree of serum sickness treated with procaine inttavenously, J. A. analgesia or anesthesia reqqired. M. A. 151: (Aug. 17) 1946. Johnson and Gilbert, also of the City Hos Bier, A.: Ueber eine neue Methods der lokalen Anas thesie, Miinchen med. Wchnschr. 1:589, 1909. pital, Welfare Island, reported 20 obstetrical Bittrich, N . M., and Powen, W. F.: Intravenous procaine cases in which· I per cent procaine hydro in thoracic surgery, Anesth. and Analg. 27:181 Ouly-Aug.) chloride was used intravenously as the anal 1948. gesic and anesthetic agent. The only compli Burstein, C. L.: (a) Treatment of acute arrhythmias dur ing anesthesia by intravenous procaine, Anesthesiology cation occurring in the 32 cases covered in 7: 115 (Mar.) 1946. these two reports was the occurrence of mild --, and Alexander, F. A. D.: (b) Anesthesia for convulsions, which were easily controlled and thoracic surgery. Management in an Army general hospital overseas, Anesthesiology 8:56 Oan.) 1947. apparently harmless. The authors, although --Marangoni, B. A.; DeGraff, A. C., and Roven they admitted that their series was small, be stine, E. A.: (c) Laboratory studies on the prophylaxis and lieved that the method was simple and safe treatment of ventricular fibrillation induced by epine phrine during cyclopropane anesthesia, Anesthesiology 1: for both mother and child. 167 (Sept.) 1940. Dressler, S., and Dwork, R. E.: Reactions to penicillin: SUMMARY procaine hydr
Lundy, J. S.: Clinical anesthesia. Philadelphia, W. B. tection in cardiac surgery, J. Thoracic Surg. 5:612 (Aug.) Saunders Co. 1942, pp. 392 and 583. 1936. McLachlin, J. A.: The intravenous use of novocaine as Richards, R. K.: Effects of vitamin C deficiency and a substitute for morphine in postoperative care, Canad. starvation upon the toxicity of procaine, Anesth. and Analg. 26:22 (Jan.·Feb.) 1947. Med. Ass. J. 52:383 (Apr.) 1945. State, D ., and Wangensteen, 0. H.: Procaine intrave· Mautz, F. R.: Reduction of cardiac irritability by the nously in treatment of delayed serum sickness, J. A. M. A. epicardial and systemic administration of drugs as a pro· 130:990 (Apr. U) 1946.
INTRA VENOUS PROCAINE DURING THORACIC SURGERY* FORREST E. LEFFINGWELL, M.D.
With increasing boldness and skill surgeons thus preventing fibrillations which would or are probing into hitherto inaccessible areas, dinarily occur under the conditions of the altering and remodeling tissues of some of experiment. In many instances procaine re our most vital organs and effecting surgical established a normal rhythm even after fibril cures for conditions which a decade ago were lation had been induced. accepted as unfortunate but incurable mala The recent war produced a large number dies. Among the most recent beneficiaries of of cases in which operative procedures were such surgical intrepidity are those successfully carried out on the heart. These provided an undergoing surgery of the heart and great excellent clinical test of the above mentioned vessels. As a result of such surgery many chil principles. Burstein reports 14 cases in which dren, once in hopeless invalidism because of dysrhythmias were corrected during surgery some congenital cardiovascular defect, now by intravenous injection of 1 per cent pro lead normal lives, with a greatly extended life caine. These occurred in a series of 121 opera expectancy. tions in which shell fragments or other foreign Surgery on the heart and paracardial struc bodies were removed from the pericardium, tures or traction on the hilus of the lung may myocardium, or from within or in close re initiate serious arrhythmias which can result lation to the great vessels. in death if not promptly contr.olled. Proce Disturbances of rhythm and shifting of the dures involving the pericardium are particu pacemaker may result either from direct larly apt to be followed by severe derange stimulation of cardiac muscle or reflexly ments of rhythm. Thus anesthesiology is faced through the well-known vago-vagal mechan with another challenge. ism. In the laboratory, cardiac arrhythmias Various investigators, Mautz (1936), Shen can be produced almost at will in animals and Simon ( 1938), and Burstein and Maran under cyclopropane anesthesia by injections goni ( 1940), have shown that irritability of of epinephrine in doses which are no more the myocardium and conduction system of than double the amount which may be ex the heart may be reduced by topical applica pected to be secreted during an average emo tion or intravascular injection of procaine, tional strain. Vago-vagal reflexes may be initi ated by stimulation of the perica{dium or by • From the Department or Anesthesiology, College or Medical Evanseliata. traction on the hilus. These impulses which