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Pantocain as a Local Anesthetic in Ophthalmology
PANTOCAIN AS A LOCAL ANESTHETIC IN OPHTHALMOLOGY W I L M E R , M.D., LL.D., Sc.D. AND RICHARD TOWNLEY PATON, M.D.
WILLIAM
H.
The action of this derivative of novocain was tested on ten normal eyes and subse quently used as a local anesthetic in a number of ophthalmological procedures, with good results. Its relative toxicity for human beings is less than that of cocain, and np idiosyn crasies have as yet been observed. The technic employed in its use is described fully. From the Wilmer Ophthalmological Institute of the Johns Hopkins University and Hos pital. Read before the American Ophthalmological Society, New London, June 27, 1932. than that of cocain (Fussgänger and Schaumann 5 , Schmidt 1 ). Pantocain has been used instead of 10 percent cocain, in many foreign laryngological clinics. Hirsch 7 sums up his results as follows: (1) it is less toxic; (2) it has no effect on the tis sue, and does not cause dilation of the vessels at the site of injection ; (3) it dissolves readily in water and with stands sterilization well; (4) it com bines well with adrenalin chloride ; (5) it infiltrates the tissues readily. In 1929, Schmidt reported the use of pantocain for infiltration and spinal an esthesia. In this country, Lundy and Essex 4 have used it intraspinously in 400 cases; but German investigators have studied its effect more exten sively. Singer 8 reports 1,300 cases in which a 2 percent solution of pantocain was used in various types of operations on the nose, throat, and sinuses. Tobeck 9 and Theissing 10 used a 1 percent solution of pantocain for a number of operations on the upper respiratory tract. The solution was always used in combination with adrenalin chloride. No toxic results were observed. Kies 11 used pantocain for conduc tion and infiltration anesthesia in over 500 cases. In no instance was there any toxic manifestation. The operative pro cedures included hernioplastic, ab dominal, urological, and gynecological operations. He also reported the use of 2 percent pantocain (two or three drops of adrenalin chloride to 20 c.c. of pan tocain) in operations for hemorrhoids and for cystoscopic examinations. His experience with spinal anesthesia was limited to seven cases. The results, however, were very satisfactory. Runge and Schmidt 12 used pantocain 106
Of local anesthetics there are many. One of the newest is pantocain, a derivative of novocain. Pantocain, or butylamino-benzoic-acid-B-dimethylamino ethylestermono-hydrochloride, is a white crystalline substance. It is odorless, quite stable when exposed to light and air, readily soluble in water, and withstands prolonged boiling with out decomposition. Its melting point is 146°-147° C. (Schmidt 1 , Wiedhopf 2 ). In a 1 percent normal salt solution, it has a pH of about 6.7 (Wiedhopf). In a .1 percent normal salt solution, it has a pH of 7 (Wiedhopf, Schmidt). Pantocain combines well with adrenal in chloride and may be used safely in conjunction with many other drugs. Reible 8 reports on its compatibility with homatropin, atropin, scopolamin, boric acid, eserin, pilocarpin, resorcin, zinc sulphate. This agrees with our own experience. Lundy and Essex*, Fussgänger and Schaumann®, Ernst 6 , and Schmidt 1 are in close agreement in regard to the toxicity of this substance. According to these observers, the subcutaneous ab solute toxicity of pantocain is ten times that of novocain ; but the effective dose of pantocain is only one tenth that of novocain. The relative toxicity is there fore 1:1. According to Schmidt, the relative toxicity of the 1 percent pan tocain compared with the 10 percent novocain, is 1:1 by subcutaneous injec tion; but 1:1.6 by intravenous admin istration. The toxicity of a 1 percent solution of pantocain is equal to that of 2 percent cocain. But because it is effective as a surface anesthetic (corneal) in 1:10,000, whereas cocain is first effective in 1:1000, the relative toxicity of pantocain is therefore less
PANTOCAIN AS A LOCAL ANESTHETIC in fifty-five cases for infiltration anes thesia, and in 167 cases intraspinously. The results were good. Schmidt stated it had been used in over 8000 cases in the Urological and Laryngological Clinics of the University of HamburgEppendorf with good results. Pfitzner 18 used .5 percent pantocain for conduction and infiltration anesthe sia in 185 cases. There was no tissue disturbance. The anesthesia produced was better than that obtained with novocain. The types of operative pro cedures included hernioplasty, removal of small tumors, vasectomy, phrenicectomy, thoracotomy, and various ab dominal operations. Gastrostomy, ap pendectomy, and laporotomy were per formed under the local anesthesia of pantocain with a few ounces of supple mental ether. For infiltration anesthe sia, he used five drops of adrenalin to every 100 c.c. of 1 percent pantocain. He also reported eighty-five cases which received pantocain intraspin ously. These cases included general surgical and gynecological operations. Schülein1"* recommends the use of pantocain as a substitute for novocain because of its prolonged action and cheapness. H e does not mention the types of cases, but gives an example of a patient whose fingernail had to be re moved. The duration of anesthesia with pantocain was from 4 to 6 hours ; with novocain from 1-1/2 to 1-3/4 hours. Payr 18 reports the favorable results obtained from the local injection of pantocain into the omental bursa as a method of anesthesia for operations on the upper abdomen. Very little mention has been made of the advantages of pantocain in oph thalmology. Only two references could be found in the German literature (Glees1*, Reible 3 ) and none in the Eng lish. Preparation: Pantocain comes in tablets (0.1 gm.), in powder, and in so lution in hermetically sealed ampules. The distributor in this country is the Winthrop Chemical Company in New York. The required amount of pantocain is dissolved in physiologic sodium chlo ride solution, and sterilized by boiling
107
for a short period of time. After the so lution has cooled, adrenalin chloride may be added if desired. It is important to prepare the solution in normal salt solution ; for pantocain has a powerful hypotonie action in an aqueous solu tion; but prepared in physiological sa line, it is free from traumatic dis turbances and hemolysis (Fussgänger and Schaumann 8 , Schmidt 1 ). Sterilization of pantocain is con ducted by placing the solution in the autoclave for 15 minutes, at 15 pounds pressure. Bacteriological investigations of these solutions show that after six days' use, no pathogenic organisms have been found, although the pipette has been frequently removed and re placed during that period. Pantocain has been used in the Wilmer Ophthalmological Institute in more than 500 cases with gratifying re sults. It has shown certain definite ad vantages over other forms of local an esthesia. Ten Normal Eyes. In each case, two drops of a 1/2 percent solution of pan tocain were instilled in the lower culde-sac. When the eyelids were kept closed, there was practically no smart ing from the drug; but when the eye lids were opened every few seconds to test the smarting, the longest duration of stinging was 47 seconds, the short est 25 seconds, the average 34.3 sec onds. The second instillation was made by dropping the solution on the cornea. Anesthesia was complete immediately after the second application, and lasted from 9 to 30 minutes, with an average of 20 minutes. Slight lacrimation oc curred in all cases upon opening the eyes; but there was no hyperemia. In no instance was there any disturbance of the corneal epithelium. The personal experience of one ob server (Wilmer) indicates the useful ness of this drug. A cinder under the upper eyelid and a fragment on the cornea, rendered the eye very uncom fortable. After the instillation of two drops of a 1/2 percent solution of pantocain, there was no stinging sen sation while the eyelids remained closed; but there was a slight smart ing when the eyes were opened. This
108
WILLIAM H. WILMER AND RICHARD TOWNLEY PATON
disappeared at the end of 24 seconds. As in the case of the other local anes After a second instillation of pantocain, thetics previously used, in very nervous the foreign bodies were quickly re subjects it is the custom to give the moved without any discomfort. The ap injection of morphine, 16 mgm., and plication of pantocain was not followed scopolamin, 0.3 mgm., half an hour be by any later smarting, lacrimation, hy- fore the operation. In sclerocorneal peremia, or blurring of vision ; and trephining, in addition to the use of there was no interference in the use of pantocain, the injection of novocain and the eyes for the ophthalmoscope or the adrenalin chloride is made at the site slitlamp. Anesthesia disappeared at the of the conjunctival flap. It is the inten tion later to substitute a smaller dose end of 23 minutes. In addition to the normal eyes men of a .1 percent solution of pantocain tioned above, pantocain has been used with adrenalin for the novocain.* Com for many ophthalmological procedures plete anesthesia was produced in all where a local anesthetic was necessary cases. No corneal disturbances have —tonometry; application of contact been noted except the usual tendency to glasses; subconjunctival injections of drying of the cornea from prolonged ex salt solutions ; dilation of the tear duct ; posure in muscle operations. This is less treatment of conjunctival inflamma than in the case of other local anes tions; removal of foreign bodies; thetics. No postoperative complications diathermy ; use of the thermaphore ; have been observed. transillumination ; for obtaining epithe At our suggestion, the Dental De lial scrapings ; and for ophthalmoscopy partment of the Johns Hopkins Hospi and biomicroscopy, where the eyes tal has been using pantocain as a con were inflamed and sensitive. duction anesthetic for dental extrac Pantocain has also been used in the tions with such favorable results that following operative procedures : extrac the dental surgeons are inclined to be tion of cataract; discission of capsular lieve that .1 percent solution is of suf cataract ; sclerocorneal trephining ; pos ficient strength to produce a satisfac terior sclerotomy ; iridectomy ; removal tory anesthesia. of chalazia; ignipuncture ; tenotomy; Disadvantages: The toxicity of this recession and advancement of the ex- drug for human beings is not definitely traocular muscles ; and tatooing of the known; so far it has been determined cornea. only through animal experimentation. In the case of minor procedures, such Idiosyncrasies have not yet been ob as the use of the tonometer, two drops served, and our experience is not suf of a 1/2 percent solution of pantocain ficiently large to permit a report upon are instilled in the lower lid while the this phase. No definite antiseptic prop patient looks up. The eyes are then erty of this drug has yet been demon closed ; but every few seconds they are strated. opened to note the disappearance of the Advantages : Quickness of action ; stinging. As soon as this occurs, two depth of penetration ; freedom from more drops of the same solution are smarting and irritation ; well tolerated ; dropped on the cornea while the patient very little tendency to drying of cor looks down. As a rule, within 2 min nea ; does not dilate pupil ; does not in utes after the first application, anesthe crease intraocular tension ; acts well in sia is complete. In major operations, one-half-percent solution ; combines two drops of a 1/2 percent solution of. readily with adrenalin and other drugs ; pantocain are put in the eye 5 minutes is inexpensive. before the patient is brought to the op Conclusions erating suite. The remaining instilla The advantages already enumerated tions are made in quick succession just preceding the operation. For cataract will secure for pantocain a permanent extraction, usually four applications are place in the examining and the operatmade ; for sclerocorneal trephining, * Since writing the above, this substitution four ; for operations on the muscles, six. has been made with satisfactory results.
PANTOCAIN AS A LOCAL A N E S T H E T I C
ing rooms ; and in spite of the many local anesthetics now in use, pantocain
109
is a very valuable addition to the armamentarium of the ophthalmologist.
References 1
Schmidt, H. Ein neues Lokalanaestheticum der Novacainreihe (Pantocain). Chirurg., 1931, Feb., v. 3, pp. 97-105. Wiedhopf, O. Pantokain, ein neues Lokalanästhetikum. Deutsche med. Wchnschr., 1931, v. 57, pp. 13-14. * Reible, R. Pantokain, ein neues Oberflächenanästhetikum. Deutsche med. Wchnschr., 1931, July, v. 57, pp. 1327-1328. 4 Lundy, J. S. and Essex, H. E. Experiments for anesthetics—Laboratory and clinical ob servations. Proc. Staff Meeting, Mayo Clinic, 1931, June, v. 6, pp. 376-380. 5 Fussgänger, R. and Schaumann, O. Ueber ein neues Lokalanästhetikum der Novakainreihe (Pantokain). Arch. f. exper. Path u. Pharm., 1931, Jan. v. 160, pp. 53-65. " Ernst, M. Erfahrungen mit dem neuen Lokalanästhetikum Pantocain. Münch. med. Wchnschr., 1931, Jan., v. 57, p. 15. 'Hirsch, C. Pantokain (2593), ein neues Oberflächenanästhetikum. Deutsche med. Wchnschr., 1931, Jan., v. 57, p. 15. " Singer, R. Pantocain als Oberflächenanästhetikum. Wien. med. Wchnschr., 1931, Nov., v. 81, p. 1593. * Tobeck, A. Unsere Erfahrungen mit dem neuen Lokalanästhetikum Pantocain als Schleimhautanästhetikum. Med. Klin., 1931, Jan., v. 27, p. 21. " Theissing, G. Unsere Erfahrungen mit dem neuen Lokalanästhetikum Pantocain bei der Oberflächenanästhesie. Ztschr. f. Laryng. Rhin., 1931, Aug., v. 21, pp. 462-464. II Kies, T. Erfahrungen mit einem neuen Mittel zur örtlichen Betäubung. Zentralbl. f. Chir., 1930, Dec, v. 57, pp. 3090-3095. " Runge, H. G. and Schmidt, H. Pantocain, ein vollwertiger Kokainersatz. Arch. f. Ohren-Nasen- u. Kehlkopfe, 1931, Apr., v. 128, pp. 232-243. " Pfitzner, H. Klinische Erfahrungen mit Pantokain. Zentralbl. f. Chir., 1931, May, v. 58, pp. 1116-1120. 14 Schülein, M. Pantocain an Stelle von Novokain für den praktischen Arzt. München. med. Wchnschr., 1931, Aug., v. 78, p. 1475. " Payr, E. Anästhesie für Oberbauchoperationen durch Pantocainfüllung der Bursa omentalis. Deutsche Ztschr. f. Chir., 1931, Nov., v. 234, pp. 130-136. " Glees, M. Ueber die Wirkung des Pantokains auf das Auge. Klin. Monats, f. Augenh., 1931, Dec, v. 87, pp. 755-760. I
WILLIAM
H.
The action of this derivative of novocain was tested on ten normal eyes and subse quently used as a local anesthetic in a number of ophthalmological procedures, with good results. Its relative toxicity for human beings is less than that of cocain, and np idiosyn crasies have as yet been observed. The technic employed in its use is described fully. From the Wilmer Ophthalmological Institute of the Johns Hopkins University and Hos pital. Read before the American Ophthalmological Society, New London, June 27, 1932. than that of cocain (Fussgänger and Schaumann 5 , Schmidt 1 ). Pantocain has been used instead of 10 percent cocain, in many foreign laryngological clinics. Hirsch 7 sums up his results as follows: (1) it is less toxic; (2) it has no effect on the tis sue, and does not cause dilation of the vessels at the site of injection ; (3) it dissolves readily in water and with stands sterilization well; (4) it com bines well with adrenalin chloride ; (5) it infiltrates the tissues readily. In 1929, Schmidt reported the use of pantocain for infiltration and spinal an esthesia. In this country, Lundy and Essex 4 have used it intraspinously in 400 cases; but German investigators have studied its effect more exten sively. Singer 8 reports 1,300 cases in which a 2 percent solution of pantocain was used in various types of operations on the nose, throat, and sinuses. Tobeck 9 and Theissing 10 used a 1 percent solution of pantocain for a number of operations on the upper respiratory tract. The solution was always used in combination with adrenalin chloride. No toxic results were observed. Kies 11 used pantocain for conduc tion and infiltration anesthesia in over 500 cases. In no instance was there any toxic manifestation. The operative pro cedures included hernioplastic, ab dominal, urological, and gynecological operations. He also reported the use of 2 percent pantocain (two or three drops of adrenalin chloride to 20 c.c. of pan tocain) in operations for hemorrhoids and for cystoscopic examinations. His experience with spinal anesthesia was limited to seven cases. The results, however, were very satisfactory. Runge and Schmidt 12 used pantocain 106
Of local anesthetics there are many. One of the newest is pantocain, a derivative of novocain. Pantocain, or butylamino-benzoic-acid-B-dimethylamino ethylestermono-hydrochloride, is a white crystalline substance. It is odorless, quite stable when exposed to light and air, readily soluble in water, and withstands prolonged boiling with out decomposition. Its melting point is 146°-147° C. (Schmidt 1 , Wiedhopf 2 ). In a 1 percent normal salt solution, it has a pH of about 6.7 (Wiedhopf). In a .1 percent normal salt solution, it has a pH of 7 (Wiedhopf, Schmidt). Pantocain combines well with adrenal in chloride and may be used safely in conjunction with many other drugs. Reible 8 reports on its compatibility with homatropin, atropin, scopolamin, boric acid, eserin, pilocarpin, resorcin, zinc sulphate. This agrees with our own experience. Lundy and Essex*, Fussgänger and Schaumann®, Ernst 6 , and Schmidt 1 are in close agreement in regard to the toxicity of this substance. According to these observers, the subcutaneous ab solute toxicity of pantocain is ten times that of novocain ; but the effective dose of pantocain is only one tenth that of novocain. The relative toxicity is there fore 1:1. According to Schmidt, the relative toxicity of the 1 percent pan tocain compared with the 10 percent novocain, is 1:1 by subcutaneous injec tion; but 1:1.6 by intravenous admin istration. The toxicity of a 1 percent solution of pantocain is equal to that of 2 percent cocain. But because it is effective as a surface anesthetic (corneal) in 1:10,000, whereas cocain is first effective in 1:1000, the relative toxicity of pantocain is therefore less
PANTOCAIN AS A LOCAL ANESTHETIC in fifty-five cases for infiltration anes thesia, and in 167 cases intraspinously. The results were good. Schmidt stated it had been used in over 8000 cases in the Urological and Laryngological Clinics of the University of HamburgEppendorf with good results. Pfitzner 18 used .5 percent pantocain for conduction and infiltration anesthe sia in 185 cases. There was no tissue disturbance. The anesthesia produced was better than that obtained with novocain. The types of operative pro cedures included hernioplasty, removal of small tumors, vasectomy, phrenicectomy, thoracotomy, and various ab dominal operations. Gastrostomy, ap pendectomy, and laporotomy were per formed under the local anesthesia of pantocain with a few ounces of supple mental ether. For infiltration anesthe sia, he used five drops of adrenalin to every 100 c.c. of 1 percent pantocain. He also reported eighty-five cases which received pantocain intraspin ously. These cases included general surgical and gynecological operations. Schülein1"* recommends the use of pantocain as a substitute for novocain because of its prolonged action and cheapness. H e does not mention the types of cases, but gives an example of a patient whose fingernail had to be re moved. The duration of anesthesia with pantocain was from 4 to 6 hours ; with novocain from 1-1/2 to 1-3/4 hours. Payr 18 reports the favorable results obtained from the local injection of pantocain into the omental bursa as a method of anesthesia for operations on the upper abdomen. Very little mention has been made of the advantages of pantocain in oph thalmology. Only two references could be found in the German literature (Glees1*, Reible 3 ) and none in the Eng lish. Preparation: Pantocain comes in tablets (0.1 gm.), in powder, and in so lution in hermetically sealed ampules. The distributor in this country is the Winthrop Chemical Company in New York. The required amount of pantocain is dissolved in physiologic sodium chlo ride solution, and sterilized by boiling
107
for a short period of time. After the so lution has cooled, adrenalin chloride may be added if desired. It is important to prepare the solution in normal salt solution ; for pantocain has a powerful hypotonie action in an aqueous solu tion; but prepared in physiological sa line, it is free from traumatic dis turbances and hemolysis (Fussgänger and Schaumann 8 , Schmidt 1 ). Sterilization of pantocain is con ducted by placing the solution in the autoclave for 15 minutes, at 15 pounds pressure. Bacteriological investigations of these solutions show that after six days' use, no pathogenic organisms have been found, although the pipette has been frequently removed and re placed during that period. Pantocain has been used in the Wilmer Ophthalmological Institute in more than 500 cases with gratifying re sults. It has shown certain definite ad vantages over other forms of local an esthesia. Ten Normal Eyes. In each case, two drops of a 1/2 percent solution of pan tocain were instilled in the lower culde-sac. When the eyelids were kept closed, there was practically no smart ing from the drug; but when the eye lids were opened every few seconds to test the smarting, the longest duration of stinging was 47 seconds, the short est 25 seconds, the average 34.3 sec onds. The second instillation was made by dropping the solution on the cornea. Anesthesia was complete immediately after the second application, and lasted from 9 to 30 minutes, with an average of 20 minutes. Slight lacrimation oc curred in all cases upon opening the eyes; but there was no hyperemia. In no instance was there any disturbance of the corneal epithelium. The personal experience of one ob server (Wilmer) indicates the useful ness of this drug. A cinder under the upper eyelid and a fragment on the cornea, rendered the eye very uncom fortable. After the instillation of two drops of a 1/2 percent solution of pantocain, there was no stinging sen sation while the eyelids remained closed; but there was a slight smart ing when the eyes were opened. This
108
WILLIAM H. WILMER AND RICHARD TOWNLEY PATON
disappeared at the end of 24 seconds. As in the case of the other local anes After a second instillation of pantocain, thetics previously used, in very nervous the foreign bodies were quickly re subjects it is the custom to give the moved without any discomfort. The ap injection of morphine, 16 mgm., and plication of pantocain was not followed scopolamin, 0.3 mgm., half an hour be by any later smarting, lacrimation, hy- fore the operation. In sclerocorneal peremia, or blurring of vision ; and trephining, in addition to the use of there was no interference in the use of pantocain, the injection of novocain and the eyes for the ophthalmoscope or the adrenalin chloride is made at the site slitlamp. Anesthesia disappeared at the of the conjunctival flap. It is the inten tion later to substitute a smaller dose end of 23 minutes. In addition to the normal eyes men of a .1 percent solution of pantocain tioned above, pantocain has been used with adrenalin for the novocain.* Com for many ophthalmological procedures plete anesthesia was produced in all where a local anesthetic was necessary cases. No corneal disturbances have —tonometry; application of contact been noted except the usual tendency to glasses; subconjunctival injections of drying of the cornea from prolonged ex salt solutions ; dilation of the tear duct ; posure in muscle operations. This is less treatment of conjunctival inflamma than in the case of other local anes tions; removal of foreign bodies; thetics. No postoperative complications diathermy ; use of the thermaphore ; have been observed. transillumination ; for obtaining epithe At our suggestion, the Dental De lial scrapings ; and for ophthalmoscopy partment of the Johns Hopkins Hospi and biomicroscopy, where the eyes tal has been using pantocain as a con were inflamed and sensitive. duction anesthetic for dental extrac Pantocain has also been used in the tions with such favorable results that following operative procedures : extrac the dental surgeons are inclined to be tion of cataract; discission of capsular lieve that .1 percent solution is of suf cataract ; sclerocorneal trephining ; pos ficient strength to produce a satisfac terior sclerotomy ; iridectomy ; removal tory anesthesia. of chalazia; ignipuncture ; tenotomy; Disadvantages: The toxicity of this recession and advancement of the ex- drug for human beings is not definitely traocular muscles ; and tatooing of the known; so far it has been determined cornea. only through animal experimentation. In the case of minor procedures, such Idiosyncrasies have not yet been ob as the use of the tonometer, two drops served, and our experience is not suf of a 1/2 percent solution of pantocain ficiently large to permit a report upon are instilled in the lower lid while the this phase. No definite antiseptic prop patient looks up. The eyes are then erty of this drug has yet been demon closed ; but every few seconds they are strated. opened to note the disappearance of the Advantages : Quickness of action ; stinging. As soon as this occurs, two depth of penetration ; freedom from more drops of the same solution are smarting and irritation ; well tolerated ; dropped on the cornea while the patient very little tendency to drying of cor looks down. As a rule, within 2 min nea ; does not dilate pupil ; does not in utes after the first application, anesthe crease intraocular tension ; acts well in sia is complete. In major operations, one-half-percent solution ; combines two drops of a 1/2 percent solution of. readily with adrenalin and other drugs ; pantocain are put in the eye 5 minutes is inexpensive. before the patient is brought to the op Conclusions erating suite. The remaining instilla The advantages already enumerated tions are made in quick succession just preceding the operation. For cataract will secure for pantocain a permanent extraction, usually four applications are place in the examining and the operatmade ; for sclerocorneal trephining, * Since writing the above, this substitution four ; for operations on the muscles, six. has been made with satisfactory results.
PANTOCAIN AS A LOCAL A N E S T H E T I C
ing rooms ; and in spite of the many local anesthetics now in use, pantocain
109
is a very valuable addition to the armamentarium of the ophthalmologist.
References 1
Schmidt, H. Ein neues Lokalanaestheticum der Novacainreihe (Pantocain). Chirurg., 1931, Feb., v. 3, pp. 97-105. Wiedhopf, O. Pantokain, ein neues Lokalanästhetikum. Deutsche med. Wchnschr., 1931, v. 57, pp. 13-14. * Reible, R. Pantokain, ein neues Oberflächenanästhetikum. Deutsche med. Wchnschr., 1931, July, v. 57, pp. 1327-1328. 4 Lundy, J. S. and Essex, H. E. Experiments for anesthetics—Laboratory and clinical ob servations. Proc. Staff Meeting, Mayo Clinic, 1931, June, v. 6, pp. 376-380. 5 Fussgänger, R. and Schaumann, O. Ueber ein neues Lokalanästhetikum der Novakainreihe (Pantokain). Arch. f. exper. Path u. Pharm., 1931, Jan. v. 160, pp. 53-65. " Ernst, M. Erfahrungen mit dem neuen Lokalanästhetikum Pantocain. Münch. med. Wchnschr., 1931, Jan., v. 57, p. 15. 'Hirsch, C. Pantokain (2593), ein neues Oberflächenanästhetikum. Deutsche med. Wchnschr., 1931, Jan., v. 57, p. 15. " Singer, R. Pantocain als Oberflächenanästhetikum. Wien. med. Wchnschr., 1931, Nov., v. 81, p. 1593. * Tobeck, A. Unsere Erfahrungen mit dem neuen Lokalanästhetikum Pantocain als Schleimhautanästhetikum. Med. Klin., 1931, Jan., v. 27, p. 21. " Theissing, G. Unsere Erfahrungen mit dem neuen Lokalanästhetikum Pantocain bei der Oberflächenanästhesie. Ztschr. f. Laryng. Rhin., 1931, Aug., v. 21, pp. 462-464. II Kies, T. Erfahrungen mit einem neuen Mittel zur örtlichen Betäubung. Zentralbl. f. Chir., 1930, Dec, v. 57, pp. 3090-3095. " Runge, H. G. and Schmidt, H. Pantocain, ein vollwertiger Kokainersatz. Arch. f. Ohren-Nasen- u. Kehlkopfe, 1931, Apr., v. 128, pp. 232-243. " Pfitzner, H. Klinische Erfahrungen mit Pantokain. Zentralbl. f. Chir., 1931, May, v. 58, pp. 1116-1120. 14 Schülein, M. Pantocain an Stelle von Novokain für den praktischen Arzt. München. med. Wchnschr., 1931, Aug., v. 78, p. 1475. " Payr, E. Anästhesie für Oberbauchoperationen durch Pantocainfüllung der Bursa omentalis. Deutsche Ztschr. f. Chir., 1931, Nov., v. 234, pp. 130-136. " Glees, M. Ueber die Wirkung des Pantokains auf das Auge. Klin. Monats, f. Augenh., 1931, Dec, v. 87, pp. 755-760. I