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Curare Akinesia in Cataract Operations*
CURARE AKINESIA IN CATARACT OPERATIONS only large differences. A s the mean score increases in relation to standard error, smaller differences can be detected without using an impractical number of animals. Table 2 shows the estimated sample size necessary to give the significant percent change (a = 0.05 B = 0.95), 7 if it exists, for each specified score for the control
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( B A L - t r e a t e d ) eyes, when the standard er ror ( S ) = 14. SUMMARY
1. Hyaluronidase has no effect on the sev erity of lewisite burns in the rabbit eye, and does not influence the treatment of these burns with B A L .
REFERENCES
1. Meyer, K., and Chaffee, E.: Mucopolysaccharide acid of cornea and its enzymatic hydrolysis. Am. J. Ophth., 23 :1320-132S (Dec.) 1940. 2. Wislocki, G. B., Bunting, H., Dempsey, E. W.: Metachromasia in mammalian tissues and its relationship to mucopolysaccarides. Am. J. Anat., 81 :l-37 (July) 1947. (Quoted by Woodin.) 3. Woodin, A. M.: Hyaluronidase as a spreading factor in the cornea. Brit. J. Ophth., 34:37S-379 (June) 1950. 4. Lillie, R. D., Emmart, E. W., and Lasky, A. M.: Chondromucinase from bovine testis and chondromucin of the umbilical cord. Arch. Path., 52:363-368 (Oct.) 1952. 5. Woodin, A. M.: The corneal mucopolysaccharide. Biochem. J., 51:319-330 (June) 1952. 6. Military Specification BAL, M.L.B. 988A, 13 March 1951. 7. Harris, M., Horvitz, D. G., and Mood, A. M.: On the determination of sample size in designing experiments. J. Am. Statistical A., 43 :391-402, 1948.
CURARE AKINESIA IN CATARACT OPERATIONS* J O H N W.
HENDERSON,
M.D.
Rochester, Minnesota Although it has been known for some years that ptosis and diplopia were early manifesta tions of intoxication from curare, it has only been recently that such ocular difficulties were regarded as of any clinical importance. O n completion of the pharmacologic re searches by M c l n t y r e and co-workers, 1 in 1939, and Wintersteiner and Dutcher, 2 in 1943, the active principle of curare became available for clinical application. This brought about a change in the status of curare from a "curiosity poison" to an alka loid that had therapeutic possibilities because its dosage could be controlled. O P H T H A L M I C USE OF CURARE
As an addition to medical therapeutics the drug was first used in a large series of cases by Bennett 3 as an antispasmodic in individu als undergoing shock therapy with penty* From the Section of Ophthalmology, Mayo Clinic.
lenetetrazole (metrazole). Curare was next used in anesthesiology; the temporary mus cular paralysis or akinesia produced by curare was widely utilized as an adjuvant to anesthesia. In the combined fields of anes thesiology and ophthalmology, mention is made of enucleation of an eye in a patient who was anesthetized by a mixture of curare and thiopental sodium in a report by Baird and associates, 4 in 1948. T h e first extensive study of the application of curare to an ophthalmologic problem ap pears to have been done by Kirby, 5 in 1949. In this report, Kirby gave his personal im pressions of the use of curare in certain se lected cases in which the extraction of cata racts was required. H e gave "relaxing" doses of curare to his patients and was favorably impressed with the ophthalmic akinesia that was produced. Since Kirby's report, an increased inter est in the ophthalmologic aspects of curare has been evidenced. T h e literature on this
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subject, however, is still not large. Clark,6 Roche,7 Farquharson, 8 and Cordes and Mul len9 have reported on the specific use of curare in operations for cataract. Clark was of the opinion that use of this drug reduced the incidence of loss of vitre ous in the 44 cases in which it was used. Roche determined that the minimal dose of curare required to perform intraocular op erations in a group of SO cases averaged 45 units (equivalent to about 6.7 mg. of d-tubocurarine chloride). In Farquharson's series of 70 patients, curare was used as a supplementary drug to akinesia obtained by a combination of Van Lint infiltration and retrobulbar injections of two-percent solution of procaine contain ing epinephrine. Cordes and Mullen, after using the drug in 85 cases, were so favorably impressed with its relaxing effect that they stated, "We are now coming to the conclusion that curare should be used in every case of cataract extraction." More recently, Drucker, Sadove, and Unna10 carried out experiments with curare on normal volunteers. Notable among their findings was the fact that the extraocular muscles, as a group, were the last to recover from and the first to be affected by general ized akinesia induced by administration of curare. In a still more recent report, Kirby 11 sum marized his experiences over a five-year span with the administration of curare in nearly 600 patients undergoing operations for cata ract. As the result of further experiences with this drug, Kirby is convinced that curare in combination with local anesthesia promotes the "expedition, delicacy, and pre cision" of removal of cataracts and is re sponsible for "the absence or diminution of complications, particularly of extrusion and loss of viscid vitreous." My interest in the use of curare as an agent for the production of akinesia in cata ract operations was stimulated by Kirby's initial report in 1949. As a result, it was de
cided to administer curare to successive pa tients undergoing operations for cataract be cause it was deemed that a study of succes sive cases would supplement the knowledge already accumulated concerning the safety and behavior of curare in selected cases such as characterized Kirby's study. METHODS
One hundred and thirty-eight successive operations for cataract, performed during 1950 and 1951, form the basis from which the data of this study were obtained. To be included in this study, it was required only that the patient be an adult and that an op eration for cataract be required according to the usual indications. Curare in the form of d-tubocurarine chloride (1.0 cc. of the preparation used throughout this study was equal to 3.0 mg. of d-tubocurarine chloride) was admin istered intravenously to all patients under the supervision of an anesthesiologist. Curare was the sole agent employed for the purpose of akinesia; no local anesthetic agents were injected into any of the soft tissues of the eyeball or orbit or into the parotid plexus of the facial nerve. A 10percent solution of cocaine was applied topi cally to the eye to induce anesthesia. Secobarbital sodium (seconal) in doses of 1.5 gr. (0.1 gm.) was given preoperatively. Atropine, in doses of 1/150 of a grain (0.00043 gm.), was also administered pre operatively to combat the excessive secretion in the respiratory passages that sometimes occurs in patients receiving curare. The intravenous administration of curare was commenced 10 minutes before the start of the operation. To allow such an interval for induction of akinesia permitted slower administration than if the drug was given in one injection just prior to the corneal section or preplacement of sutures. The anesthesiologist may use this interval of in duction to observe the patient for any idio syncrasies to the drug or undue respiratory distress such as might occur in a patient who
CURARE AKINESIA IN CATARACT OPERATIONS had latent myasthenia gravis, for example. The rate of administration of curare was governed by close observation of the respira tory status of the patient and by a deter mination of the depth of akinesia at any given moment. T o ascertain the latter, the patient was asked to perform some task that re quired muscular effort, such as squeezing the anesthesiologist's hand. Immediately prior to the operation, I examined the patient's abil ity to squeeze the eyelids and to rotate the eyes in various directions. No operation was commenced until the muscular response of the patient to a com mand to look u p was completely paralyzed or severely incapacitated. If insufficient curare had been administered in the 10minute period of induction to bring about this degree of akinesia, the operation was delayed until the desirable degree was ob tained. T h e ages of these patients represented a reasonably good cross section of the age distribution among adults on whom opera tion for cataract is ordinarily performed. In 64 percent of the 138 operations, the pa tients were between 60 and 80 years of age. The youngest patient was aged 32 years and the oldest 92 years. No attempt was made to select a type of cataract to be extracted under the plan of this study. In about 10 percent of the patients, the cataracts were of the type in which relatively poor surgical results might be anticipated from the standpoint of comple tion of the operation without accident or com plication and from the standpoint of restora tion of useful sight. Included were cataracts that complicated such diseases as uveitis, cataracts associated with atrophy of the iris and posterior synechias, hypermature and morgagnian cata racts, those associated with secondary glau coma, and cataracts extracted after previ ous operations for glaucoma. RESULTS
Early in the course of the study, it was
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found that some patients could not tolerate the curare as it was administered intra venously. Since one of the main objectives of this study was to evaluate the ability of curare to produce akinesia, the cases in which curare failed were carefully studied. A n y restlessness of the patient and any ocular movements during operation were considered to constitute poor akinesia. A n y difficulty during the period of induction that made it impossible to proceed with the op eration was also considered as unsatisfactory. Results in the following cases were con sidered to be unsatisfactory: R E P O R T OF CASES
Case 1. The patient was a 72-year-old woman; 4.0 cc. (12 mg.) of curare was given over a sixminute interval immediately preceding operation. The operation required 11 minutes. Akinesia was unsatisfactory throughout the sur gical procedure; respiratory distress was so pro nounced that 0.5 mg. of neostigmine was given in travenously on completion of the operation. Case 2. The patient was an 81-year-old woman; 3.0 cc. (9.0 mg.) of curare was given in a twominute period. Respiratory distress was so extensive that arti ficial respiration by forced oxygen pressure was required. When the patient was resuscitated, the operation was performed. Profound paresis of up ward and downward rotation of the eyes and of the orbicularis oculi was present at the beginning of the operation. Case 3. The patient was a 59-year-old woman; 5.0 cc. (15 mg.) of curare was administered in a period of five minutes. Good ocular akinesia was noted objectively, but the patient was apprehensive and restless. Case 4. The patient was a 61-year-old man; 4.0 cc. (12 mg.) of curare was administered in a period of five minutes. So much respiratory distress de veloped that it was necessary to administer neostig mine and artificial respiration by forced oxygen. The surgical procedure was completed but loss of vitreous occurred. Case 5. The patient was a 46-year-old woman; 3.0 cc. (9.0 mg.) of curare was administered in a period of five minutes. Great respiratory distress developed, but neostigmine or oxygen was not re quired. Case 6. The patient was a 69-year-old woman; 2.5 cc. (7.5 mg.) of curare was administered, re sulting in pronounced paresis of upward rotation of the eye and moderate paresis of downward rota tion. No weakness of the orbicularis oculi was noted. Objectively, the respirations appeared adequate but the patient complained so bitterly of inability
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to get her breath that administration of curare was discontinued. The patient's speech did not seem to be affected. A successful combined intracapsular extraction of the lens was then accomplished with the aid of an injection of procaine into the parotid plexus of the facial nerve (O'Brien's technique). A second operation for cataract was performed almost a year later. Again, after administration of 2.5 cc. of curare, the patient experienced so much respiratory distress that administration of the drug was discontinued and the operation was completed with the patient under thiopentol sodium anesthesia. Case 7. The patient was a 68-year-old woman; 1.5 cc. (4.5 mg.) of curare was administered over a period of five minutes. So much respiratory difficulty developed that administration of the drug was discontinued and the operation was completed with the aid of injections of procaine hydrochloride into the retrobulbar space and parotid plexus of the facial nerve. Case 8. The patient was a 77-year-old man; 3.0 cc. (9.0 mg.) of curare was administered over a period of nine minutes. Respiratory collapse oc curred, and the patient was revived by administra tion of oxygen under pressure and of neostigmine. The operation was completed with the aid of an injection of procaine into the retrobulbar space and the parotid plexus of the facial nerve. Preoperatively, the patient had been known to have atelectasis of one lung. Case 9. The patient was a 61-year-old woman; 3.0 cc. (9.0 mg.) of curare was administered slowly during a period of 10 minutes. Respiratory distress threatened and pronounced paresis of up ward rotation of the eye and moderate paresis of downward rotation were noted. No weakness of the orbicularis oculi was visible. Akinesia was supplemented with an injection ac cording to the technique of O'Brien. The patient was known to have asthmatic bronchitis. Case 10. The patient was a 69-year-old woman; 4.0 cc. (12 mg.) of curare was administered. Aki nesia was incomplete, for the patient moved the eye during the operation. Case 11. The patient was a 54-year-old man; 5.0 cc. (15 mg.) of curare was administered, but the patient was still able to squeeze the eyelids and akinesia was considered to be incomplete. Case 12. The patient was a 55-year-old woman; 4.0 cc. (12 mg.) of curare was administered, but akinesia of the eye and eyelids was incomplete. Analysis of the data in these 13 instances of unsatisfactory akinesia involving 12 pa tients points to several explanations for the failure of this method. I n the first five cases, it was considered that the patients received an overdose of curare. T h e drug was given either too rapidly or in too large an amount. I n three of these (Cases 1, 3, and 5 ) , a
second operation for cataract was performed with successful results using intravenously administered curare. This would indicate that the unsatisfactory akinesia was not caused by any peculiarity on the part of the patient. In Cases 1 and 3, a smaller amount of curare was given at the second operation than at the first. In Case 5, the same amount of curare was given on both occasions, but it was given at a slower rate during the sec ond operation. I n Cases 6 and 7, only small amounts of curare were administered yet difficulty oc curred ; these cases were classed as examples of undue sensitivity to the drug. Since flaccid paralysis was not extensive, it did not appear likely that latent myasthenia gravis was pres ent in these instances. Perhaps the curare had some effect on the central nervous sys tem in these individuals. In Cases 8 and 9, the patients were known to have respiratory difficulty prior to ocular operation. Curare apparently greatly ag gravated their respiratory embarrassment. In several other patients who had asthma, suc cessful operation for cataract was carried out when curare was administered intra venously. However, in these latter cases the drug was given with great caution and even then the patients were on the verge of respiratory distress. Cases 10, 11, and 12 apparently were ex amples of great tolerance to the drug. Satis factory akinesia of ocular rotation could not be accomplished with the dosage used in these cases. T h e anesthesiologists were reluctant to give more than 12 to 15 mg. of curare in the period of induction. They considered that the safe limits of administration were exceeded when doses larger than 9.0 to 12 mg. (3.0 to 4.0 cc.) were given initially. O n many occasions, it was noted that the patients had a sense of suffocation or a feel ing that they could not draw a breath during the period of induction. This phenomenon usually occurred even in the presence of ade quate respiratory excursions. I t was considered that this sensation must
CURARE AKINESIA IN CATARACT OPERATIONS be produced by some effect of the curare on the central nervous system for, except in those cases listed previously, the difficulty disappeared when the patients were told that the drug was prone to produce such an effect and were assured that their respiratory status was satisfactory. Since this subjective dis tress did not interfere with the operation or cause restlessness on the part of the patient, it was not regarded as a manifestation of unsatisfactory akinesia. Vitreous was lost during eight of the 138 operations (six percent). In two (Cases 3 and 4 ) , it was considered that unsatisfac tory akinesia was responsible for this loss, because of the restlessness of the patient. In the remaining six cases, other factors were responsible. In an earlier paragraph it was pointed out that the operation was not commenced until a certain degree of akinesia of upward rota tion of the eye was attained. Thirty-eight percent of the patients were considered to have pronounced weakness of upward rota tion; in the remainder (62 percent), this function was completely lost in response to a command to look up. It soon became evident that ability to look downward and to squeeze the eyelids was not affected as much as upward gaze. Although this difference was not great, there appeared to be less effect on the orbicularis oculi than on downward gaze. In only two patients was total simultaneous paresis of all three func tions noted. The amount of curare and the rate of ad ministration required to bring about the de sired degree of akinesia were quite variable. The smallest dosage required to bring about satisfactory akinesia was 2.0 cc. (6.0 mg.). In 66 percent of the cases, between 3.0 cc. (9.0 mg.) and 4.0 cc. (12 mg.) was required. The average for the entire group was 3.5 cc. (10.5 mg.). In six cases, more than 5.0 cc. (15 mg.) was given but in these instances it was necessary to supplement the initial satis factory akinesia by additional small amounts of curare because of the length of the opera
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tion and the wearing away of the effect of curare. The rate of administration was so altered by the respiratory status of the patient at any given moment that it was nearly impos sible to formulate any set pattern by an an alysis of the data. Administration of curare in the amount of 0.5 cc. per minute until the desired effect is attained would most closely approach the average experience in this study. Although the degree of akinesia was not retested at the completion of the operation, the impression was garnered that the effect of an average dose (3.5 cc.) administered over a period of about seven minutes per sisted for approximately 20 minutes at near maximal degree. The effects would then subside in about 10 minutes, as determined by the ability of the patient to squeeze the examiner's hand. In general, 20 minutes of akinesia was usually adequate to permit completion of the operation and return of the patient to bed. COMMENT
Many of the articles about clinical aspects of curare refer to its early effects on the eye. Results of this study tend to confirm this. The extraocular muscles appear to be among the first to exhibit the paralyzing effect of curare. Not generally recognized, or at least not mentioned in the literature, is the fact that the sequence of paralysis induced by curare may be selective within the particular group of muscles concerned with ocular rotation. Thus, not all the skeletal muscles that con trol movements of the eye and eyelid are affected to a like degree. This was demonstrated in this study by the fact that the ability of the eyes to rotate up ward could be nearly paralyzed, yet the pa tient still retained some ability to look down ward and to squeeze the eyelids. This was a most interesting finding; its possible ex planation is intriguing. It seems easiest to explain the differential
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effect of curare on the function of ocular ro tation in a vertical plane and squeezing of the eyelids on the basis of a sequence of paralysis of muscles innervated by different cranial nerves. The seventh cranial nerve, which innervates the orbicularis oculi, ap parently was less affected by curare in the majority of patients than was the third cranial nerve and the muscles it innervates. To explain the differential effect on up ward and downward rotation of the eye on this basis is somewhat more difficult. Since the function of looking upward is performed chiefly by muscles (superior rectus and inferior oblique) innervated by the third cranial nerve, whereas the function of looking downward also includes innervation from the fourth cranial nerve (superior oblique muscle), a selective effect of curare between adjacent cranial nerves might be postulated. If this is true, it attributes to curare a fine peripheral gradient effect that may not really exist. Since the functions of upward and down ward rotation of the eye were judged on the basis of response to command, the difference in response might be caused by some central effect of curare. On the basis of known pharmacologic facts, the former explanation is more plausible. The tendency of the eyes to roll upward or the inability of the patient to look down ward at some crucial moment during opera tion for cataract is one of the main bugaboos of surgeons who perform such operations. Because it nearly eliminates the ability of the eye to roll upward, curare should be a great boon to operative techniques for removal of cataract. Lancaster,12 as well as others, has spoken at various times of the importance of akinesia of the extraocular muscles; yet I and many others had considered proper akinesia of the eyelids to be a greater factor in reduction of the incidence of loss of vitreous. As I have analyzed the results of this study and have watched many curarized pa tients attempt to squeeze the eyelids against
the speculum in the presence of a nearly immobile eye, I have changed my opinion as to the necessity of complete akinesia of the eyelids. Whenever the akinesia of the extraocular muscles was nearly complete, squeezing of the eyelids appeared to have little influence on the incidence of loss of vitreous. At the beginning of this study, some ques tion existed as to the selection of an ocular test that would properly reflect the degree of desired curarization. Since it was desirable to eliminate looking upward, this function was selected as one test of the degree of curarization. It proved to be a fortunate selection, for this function as a response to command could be nearly abolished. It was thought that, if the patient was unable to roll the eye up even when coaxed or commanded to do so at the beginning of the operation, it was unlikely that this annoy ing movement would occur during the crucial moments before and after the delivery of the lens. One of the puzzling features in this series of patients was a softening effect of the eyes that appeared evident clinically but was more difficult to prove objectively. The eyeball appeared more flaccid or to display loss of tonus in comparison to the eyes on which I had operated prior to this study. This soften ing effect has been noted by others. At first, operation on these softened eyes appeared more difficult because a greater amount of traction on the lens and counterpressure on the vitreous was required to bring about delivery of the lens. This ap parently was a drawback to use of curare in operations for cataract but, as familiarity was attained with this diminished ocular tonus and with the altered mechanics of ex traction, this difficulty was replaced by a feeling of security. At completion of this study, it was con cluded that surgical results were potentially better when the eye was softer. More varied manipulations can be carried out within rea sonable limits on such eyes without fear of
CURARE AKINESIA IN CATARACT OPERATIONS
loss of vitreous than can be done on the eyes of patients who have not been curarized. On the basis of experience prior to this study, it was scarcely possible to maneuver a vectis inside the eye without fear of loss of vitreous. In this series, it was surprising to find that five cases occurred in which de livery of the lens was completed with the vectis without loss of vitreous. In any evaluation of the practical applica tion of curare to operations for cataract, it must be kept in mind that nearly paralyzing doses, so far as the extraocular muscles were concerned, were utilized in this study, whereas other investigators have recom mended "relaxing" rather than paralyzing doses. Farquharson, reporting on his series of 70 extractions of cataracts during which curare had been administered, found that it required between 20 and 60 units (3.0 to 9.0 mg. of d-tubocurarine chloride) with an average of 44 units (6.6 mg.). These data agree closely with those noted by Roche, who found that 45 units of curare was the minimal dose necessary to obtain a quiet eye for intraocular operations. Such dosage is less than the average amount (10.5 mg. or 70 units) utilized in the study being reported. In 15 patients who did not have premedication, Roche found that the paralyz ing dose was 76 units (11.4 mg. of d-tubo curarine chloride). Although a paralyzing dose might not be deemed necessary, its use still appears to be practical since it was administered in 138 successive cases without undue complication. A smaller dose, such as permits only relaxa tion, might have but little more effect than the usually administered local anesthetics. As already mentioned, the rate of ad ministration of curare varied extensively in different patients and the rate was altered greatly according to the respiratory status of the patient at any moment; these variations make statistical analysis impossible. Never theless, the impression was gained that it was not the amount of drug given but rather
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the rate of its injection that was the most important factor in safety. This fact was learned chiefly by means of trial and error; had it been possible to apply the experience of the last half of the study to some of the initial patients, the incidence of cases of unsatisfactory akinesia probably would have been less. As a rough guide to those who might try the drug, I propose that it be administered intravenously at a rate not to exceed 0.5 cc. (1.5 mg.) per minute after an initial injec tion of 1.0 cc. (3.0 mg.). Contraindications to administration of curare to patients who have cataracts are few but definite. Even though several asthmatic patients were successfully operated on, pa tients who had difficulties in respiratory ex change were, as a whole, extremely hard to handle. I have discontinued administration of curare to any individual who has chronic bronchitis, atelectasis, bronchiectasis, asthma, or pneumothorax. On the other hand, curare was given with out complication to patients who had all varieties of cardiac and vascular difficulties. Such conditions as auricular fibrillation, severe hypertension, cardiac enlargement, generalized arteriosclerosis, angina pectoris, disease of the coronary arteries, and valvular cardiac disease did not prove to be contra indications to administration of curare. One of the obvious drawbacks from a practical standpoint to use of curare in opera tions for cataract is the need for someone to supervise the injection of the solution. In this study, an anesthesiologist supervised this phase of the procedure; however, once an ophthalmologist becomes familiar with the use and behavior of curare anyone should be able to administer the drug intravenously under the direction of the ophthalmic sur geon. i Still, this need for another person to supervise administration of the drug is a factor that may prevent general utilization of this method of akinesia by ophthalmol ogists. Any procedure concerning surgical
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technique in removal of cataracts that is not under direct control of the surgeon is a de finite drawback in the opinion of many oph thalmologists. Several publications concerning akinesia induced by curare include statements that a discussion of antidotes has no place because, if the drug is administered correctly, no need for antagonists of curare exists. No matter how skillfully a drug may be administered, instances of undue sensitivity to even small amounts will be encountered when it is given to a large enough group of patients. I n this study one patient experienced respiratory embarrassment after receiving 1.5 cc. (4.5 mg.) ; in several patients, it seemed advisable to administer neostigmine. T h e neostigmine was given in conjunction with artificial respiration by means of posi tive pressure. Until recently, neostigmine was the drug most widely used as an antago nist of curare, although from a pharmacologic standpoint it was known to have several drawbacks as to its specificity and reliability for such purpose. N o w a commercial preparation, N-ethylN - ( m - hydroxyphenyl) - N , N - dimethylam -
monium bromide (tensilon), is available that, by preliminary clinical trial, appears to have a more specific and faster effect against paralysis of peripheral muscles than any other drug at present. Although it has not been necessary to use tensilon in this study, it is another safety factor that insures safer use of curare and is of reassurance to the surgeon in time of need. Although this study was begun with some skepticism as to the practical value of curare as an aid to akinesia during operation for cataract, it is now considered that the drug is of great help in this particular phase of ophthalmology. Since the conclusion of this study, I have continued to use curare in all extractions of cataracts except when the drug is contraindicated. Lancaster, 1 2 in a paper on operation for cataract, once said, " M y aim is to receive a patient who cannot feel, does not want to move, and could not move if he tried." Curare bids fair to solve the third factor of Lancaster's dictum for the successful prep aration of patients who are to undergo re moval of cataracts. The Mayo Clinic.
REFERENCES
1. Mclntyre, A. R.: Curare: Its History, Nature, and Clinical Use. Chicago, Univ. Chicago Press, 1947. 2. Wintersteiner, O., and Dutcher, J. D.: Curare alkaloids from chondodendron tomentosum. Science, 97-.467-470(May) 1943. 3. Bennett, A. E.: Curare: A preventive of traumatic complications in convulsive shock therapy. (Including a preliminary report on a synthetic curare-like drug.) Am. J. Psychiat., 97:1040-1060 (Mar.) 1941. 4. Baird, J. W., Johnson, W. R., and Van Bergen, F. H.: Pentothal-curare solution: A preliminary report and analysis of its use in 160 cases. Anesthesiology, 9:141-1S8 (Mar.) 1948. 5. Kirby, D. B.: Use of curare in cataract surgery. Tr. Sect. Ophth., A.M.A., 1949, pp. 279-293. 6. Clark, W. B.: Use of curare as an adjuvant in cataract surgery. Watson-Gailey Eye Foundation Quart., 1:34, 1949. 7. Roche, J. R.: Research in the use of curare for ocular surgery. Am. J. Ophth., 33:91-94 (Jan.) 1950. 8. Farquharson, H.: Curare with local anesthesia in cataract surgery. Am. J. Opth., 34:554-556 (Apr.) 1951. 9. Cordes, F. C, and Mullen, R. S.: The use of curare in cataract surgery. Am. J. Ophth., 34:557564 (Apr.) 1951. 10. Drucker, A. P., Sadove, M. S., and Unna, K. R.: Ophthalmic studies of curare and curarelike drugs in man. Am. J. Ophth., 34 :543-553 (Apr.) 1951. 11. Kirby, D. B.: Curare in cataract surgery: Five years' experience. Sec. Ophth., A.M.A., June, 1952. 12. Lancaster, W. B.: The cataract operation: A study of details. Surg., Gynec. & Obst., 52:452-461 (Feb.) 1931.
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( B A L - t r e a t e d ) eyes, when the standard er ror ( S ) = 14. SUMMARY
1. Hyaluronidase has no effect on the sev erity of lewisite burns in the rabbit eye, and does not influence the treatment of these burns with B A L .
REFERENCES
1. Meyer, K., and Chaffee, E.: Mucopolysaccharide acid of cornea and its enzymatic hydrolysis. Am. J. Ophth., 23 :1320-132S (Dec.) 1940. 2. Wislocki, G. B., Bunting, H., Dempsey, E. W.: Metachromasia in mammalian tissues and its relationship to mucopolysaccarides. Am. J. Anat., 81 :l-37 (July) 1947. (Quoted by Woodin.) 3. Woodin, A. M.: Hyaluronidase as a spreading factor in the cornea. Brit. J. Ophth., 34:37S-379 (June) 1950. 4. Lillie, R. D., Emmart, E. W., and Lasky, A. M.: Chondromucinase from bovine testis and chondromucin of the umbilical cord. Arch. Path., 52:363-368 (Oct.) 1952. 5. Woodin, A. M.: The corneal mucopolysaccharide. Biochem. J., 51:319-330 (June) 1952. 6. Military Specification BAL, M.L.B. 988A, 13 March 1951. 7. Harris, M., Horvitz, D. G., and Mood, A. M.: On the determination of sample size in designing experiments. J. Am. Statistical A., 43 :391-402, 1948.
CURARE AKINESIA IN CATARACT OPERATIONS* J O H N W.
HENDERSON,
M.D.
Rochester, Minnesota Although it has been known for some years that ptosis and diplopia were early manifesta tions of intoxication from curare, it has only been recently that such ocular difficulties were regarded as of any clinical importance. O n completion of the pharmacologic re searches by M c l n t y r e and co-workers, 1 in 1939, and Wintersteiner and Dutcher, 2 in 1943, the active principle of curare became available for clinical application. This brought about a change in the status of curare from a "curiosity poison" to an alka loid that had therapeutic possibilities because its dosage could be controlled. O P H T H A L M I C USE OF CURARE
As an addition to medical therapeutics the drug was first used in a large series of cases by Bennett 3 as an antispasmodic in individu als undergoing shock therapy with penty* From the Section of Ophthalmology, Mayo Clinic.
lenetetrazole (metrazole). Curare was next used in anesthesiology; the temporary mus cular paralysis or akinesia produced by curare was widely utilized as an adjuvant to anesthesia. In the combined fields of anes thesiology and ophthalmology, mention is made of enucleation of an eye in a patient who was anesthetized by a mixture of curare and thiopental sodium in a report by Baird and associates, 4 in 1948. T h e first extensive study of the application of curare to an ophthalmologic problem ap pears to have been done by Kirby, 5 in 1949. In this report, Kirby gave his personal im pressions of the use of curare in certain se lected cases in which the extraction of cata racts was required. H e gave "relaxing" doses of curare to his patients and was favorably impressed with the ophthalmic akinesia that was produced. Since Kirby's report, an increased inter est in the ophthalmologic aspects of curare has been evidenced. T h e literature on this
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subject, however, is still not large. Clark,6 Roche,7 Farquharson, 8 and Cordes and Mul len9 have reported on the specific use of curare in operations for cataract. Clark was of the opinion that use of this drug reduced the incidence of loss of vitre ous in the 44 cases in which it was used. Roche determined that the minimal dose of curare required to perform intraocular op erations in a group of SO cases averaged 45 units (equivalent to about 6.7 mg. of d-tubocurarine chloride). In Farquharson's series of 70 patients, curare was used as a supplementary drug to akinesia obtained by a combination of Van Lint infiltration and retrobulbar injections of two-percent solution of procaine contain ing epinephrine. Cordes and Mullen, after using the drug in 85 cases, were so favorably impressed with its relaxing effect that they stated, "We are now coming to the conclusion that curare should be used in every case of cataract extraction." More recently, Drucker, Sadove, and Unna10 carried out experiments with curare on normal volunteers. Notable among their findings was the fact that the extraocular muscles, as a group, were the last to recover from and the first to be affected by general ized akinesia induced by administration of curare. In a still more recent report, Kirby 11 sum marized his experiences over a five-year span with the administration of curare in nearly 600 patients undergoing operations for cata ract. As the result of further experiences with this drug, Kirby is convinced that curare in combination with local anesthesia promotes the "expedition, delicacy, and pre cision" of removal of cataracts and is re sponsible for "the absence or diminution of complications, particularly of extrusion and loss of viscid vitreous." My interest in the use of curare as an agent for the production of akinesia in cata ract operations was stimulated by Kirby's initial report in 1949. As a result, it was de
cided to administer curare to successive pa tients undergoing operations for cataract be cause it was deemed that a study of succes sive cases would supplement the knowledge already accumulated concerning the safety and behavior of curare in selected cases such as characterized Kirby's study. METHODS
One hundred and thirty-eight successive operations for cataract, performed during 1950 and 1951, form the basis from which the data of this study were obtained. To be included in this study, it was required only that the patient be an adult and that an op eration for cataract be required according to the usual indications. Curare in the form of d-tubocurarine chloride (1.0 cc. of the preparation used throughout this study was equal to 3.0 mg. of d-tubocurarine chloride) was admin istered intravenously to all patients under the supervision of an anesthesiologist. Curare was the sole agent employed for the purpose of akinesia; no local anesthetic agents were injected into any of the soft tissues of the eyeball or orbit or into the parotid plexus of the facial nerve. A 10percent solution of cocaine was applied topi cally to the eye to induce anesthesia. Secobarbital sodium (seconal) in doses of 1.5 gr. (0.1 gm.) was given preoperatively. Atropine, in doses of 1/150 of a grain (0.00043 gm.), was also administered pre operatively to combat the excessive secretion in the respiratory passages that sometimes occurs in patients receiving curare. The intravenous administration of curare was commenced 10 minutes before the start of the operation. To allow such an interval for induction of akinesia permitted slower administration than if the drug was given in one injection just prior to the corneal section or preplacement of sutures. The anesthesiologist may use this interval of in duction to observe the patient for any idio syncrasies to the drug or undue respiratory distress such as might occur in a patient who
CURARE AKINESIA IN CATARACT OPERATIONS had latent myasthenia gravis, for example. The rate of administration of curare was governed by close observation of the respira tory status of the patient and by a deter mination of the depth of akinesia at any given moment. T o ascertain the latter, the patient was asked to perform some task that re quired muscular effort, such as squeezing the anesthesiologist's hand. Immediately prior to the operation, I examined the patient's abil ity to squeeze the eyelids and to rotate the eyes in various directions. No operation was commenced until the muscular response of the patient to a com mand to look u p was completely paralyzed or severely incapacitated. If insufficient curare had been administered in the 10minute period of induction to bring about this degree of akinesia, the operation was delayed until the desirable degree was ob tained. T h e ages of these patients represented a reasonably good cross section of the age distribution among adults on whom opera tion for cataract is ordinarily performed. In 64 percent of the 138 operations, the pa tients were between 60 and 80 years of age. The youngest patient was aged 32 years and the oldest 92 years. No attempt was made to select a type of cataract to be extracted under the plan of this study. In about 10 percent of the patients, the cataracts were of the type in which relatively poor surgical results might be anticipated from the standpoint of comple tion of the operation without accident or com plication and from the standpoint of restora tion of useful sight. Included were cataracts that complicated such diseases as uveitis, cataracts associated with atrophy of the iris and posterior synechias, hypermature and morgagnian cata racts, those associated with secondary glau coma, and cataracts extracted after previ ous operations for glaucoma. RESULTS
Early in the course of the study, it was
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found that some patients could not tolerate the curare as it was administered intra venously. Since one of the main objectives of this study was to evaluate the ability of curare to produce akinesia, the cases in which curare failed were carefully studied. A n y restlessness of the patient and any ocular movements during operation were considered to constitute poor akinesia. A n y difficulty during the period of induction that made it impossible to proceed with the op eration was also considered as unsatisfactory. Results in the following cases were con sidered to be unsatisfactory: R E P O R T OF CASES
Case 1. The patient was a 72-year-old woman; 4.0 cc. (12 mg.) of curare was given over a sixminute interval immediately preceding operation. The operation required 11 minutes. Akinesia was unsatisfactory throughout the sur gical procedure; respiratory distress was so pro nounced that 0.5 mg. of neostigmine was given in travenously on completion of the operation. Case 2. The patient was an 81-year-old woman; 3.0 cc. (9.0 mg.) of curare was given in a twominute period. Respiratory distress was so extensive that arti ficial respiration by forced oxygen pressure was required. When the patient was resuscitated, the operation was performed. Profound paresis of up ward and downward rotation of the eyes and of the orbicularis oculi was present at the beginning of the operation. Case 3. The patient was a 59-year-old woman; 5.0 cc. (15 mg.) of curare was administered in a period of five minutes. Good ocular akinesia was noted objectively, but the patient was apprehensive and restless. Case 4. The patient was a 61-year-old man; 4.0 cc. (12 mg.) of curare was administered in a period of five minutes. So much respiratory distress de veloped that it was necessary to administer neostig mine and artificial respiration by forced oxygen. The surgical procedure was completed but loss of vitreous occurred. Case 5. The patient was a 46-year-old woman; 3.0 cc. (9.0 mg.) of curare was administered in a period of five minutes. Great respiratory distress developed, but neostigmine or oxygen was not re quired. Case 6. The patient was a 69-year-old woman; 2.5 cc. (7.5 mg.) of curare was administered, re sulting in pronounced paresis of upward rotation of the eye and moderate paresis of downward rota tion. No weakness of the orbicularis oculi was noted. Objectively, the respirations appeared adequate but the patient complained so bitterly of inability
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to get her breath that administration of curare was discontinued. The patient's speech did not seem to be affected. A successful combined intracapsular extraction of the lens was then accomplished with the aid of an injection of procaine into the parotid plexus of the facial nerve (O'Brien's technique). A second operation for cataract was performed almost a year later. Again, after administration of 2.5 cc. of curare, the patient experienced so much respiratory distress that administration of the drug was discontinued and the operation was completed with the patient under thiopentol sodium anesthesia. Case 7. The patient was a 68-year-old woman; 1.5 cc. (4.5 mg.) of curare was administered over a period of five minutes. So much respiratory difficulty developed that administration of the drug was discontinued and the operation was completed with the aid of injections of procaine hydrochloride into the retrobulbar space and parotid plexus of the facial nerve. Case 8. The patient was a 77-year-old man; 3.0 cc. (9.0 mg.) of curare was administered over a period of nine minutes. Respiratory collapse oc curred, and the patient was revived by administra tion of oxygen under pressure and of neostigmine. The operation was completed with the aid of an injection of procaine into the retrobulbar space and the parotid plexus of the facial nerve. Preoperatively, the patient had been known to have atelectasis of one lung. Case 9. The patient was a 61-year-old woman; 3.0 cc. (9.0 mg.) of curare was administered slowly during a period of 10 minutes. Respiratory distress threatened and pronounced paresis of up ward rotation of the eye and moderate paresis of downward rotation were noted. No weakness of the orbicularis oculi was visible. Akinesia was supplemented with an injection ac cording to the technique of O'Brien. The patient was known to have asthmatic bronchitis. Case 10. The patient was a 69-year-old woman; 4.0 cc. (12 mg.) of curare was administered. Aki nesia was incomplete, for the patient moved the eye during the operation. Case 11. The patient was a 54-year-old man; 5.0 cc. (15 mg.) of curare was administered, but the patient was still able to squeeze the eyelids and akinesia was considered to be incomplete. Case 12. The patient was a 55-year-old woman; 4.0 cc. (12 mg.) of curare was administered, but akinesia of the eye and eyelids was incomplete. Analysis of the data in these 13 instances of unsatisfactory akinesia involving 12 pa tients points to several explanations for the failure of this method. I n the first five cases, it was considered that the patients received an overdose of curare. T h e drug was given either too rapidly or in too large an amount. I n three of these (Cases 1, 3, and 5 ) , a
second operation for cataract was performed with successful results using intravenously administered curare. This would indicate that the unsatisfactory akinesia was not caused by any peculiarity on the part of the patient. In Cases 1 and 3, a smaller amount of curare was given at the second operation than at the first. In Case 5, the same amount of curare was given on both occasions, but it was given at a slower rate during the sec ond operation. I n Cases 6 and 7, only small amounts of curare were administered yet difficulty oc curred ; these cases were classed as examples of undue sensitivity to the drug. Since flaccid paralysis was not extensive, it did not appear likely that latent myasthenia gravis was pres ent in these instances. Perhaps the curare had some effect on the central nervous sys tem in these individuals. In Cases 8 and 9, the patients were known to have respiratory difficulty prior to ocular operation. Curare apparently greatly ag gravated their respiratory embarrassment. In several other patients who had asthma, suc cessful operation for cataract was carried out when curare was administered intra venously. However, in these latter cases the drug was given with great caution and even then the patients were on the verge of respiratory distress. Cases 10, 11, and 12 apparently were ex amples of great tolerance to the drug. Satis factory akinesia of ocular rotation could not be accomplished with the dosage used in these cases. T h e anesthesiologists were reluctant to give more than 12 to 15 mg. of curare in the period of induction. They considered that the safe limits of administration were exceeded when doses larger than 9.0 to 12 mg. (3.0 to 4.0 cc.) were given initially. O n many occasions, it was noted that the patients had a sense of suffocation or a feel ing that they could not draw a breath during the period of induction. This phenomenon usually occurred even in the presence of ade quate respiratory excursions. I t was considered that this sensation must
CURARE AKINESIA IN CATARACT OPERATIONS be produced by some effect of the curare on the central nervous system for, except in those cases listed previously, the difficulty disappeared when the patients were told that the drug was prone to produce such an effect and were assured that their respiratory status was satisfactory. Since this subjective dis tress did not interfere with the operation or cause restlessness on the part of the patient, it was not regarded as a manifestation of unsatisfactory akinesia. Vitreous was lost during eight of the 138 operations (six percent). In two (Cases 3 and 4 ) , it was considered that unsatisfac tory akinesia was responsible for this loss, because of the restlessness of the patient. In the remaining six cases, other factors were responsible. In an earlier paragraph it was pointed out that the operation was not commenced until a certain degree of akinesia of upward rota tion of the eye was attained. Thirty-eight percent of the patients were considered to have pronounced weakness of upward rota tion; in the remainder (62 percent), this function was completely lost in response to a command to look up. It soon became evident that ability to look downward and to squeeze the eyelids was not affected as much as upward gaze. Although this difference was not great, there appeared to be less effect on the orbicularis oculi than on downward gaze. In only two patients was total simultaneous paresis of all three func tions noted. The amount of curare and the rate of ad ministration required to bring about the de sired degree of akinesia were quite variable. The smallest dosage required to bring about satisfactory akinesia was 2.0 cc. (6.0 mg.). In 66 percent of the cases, between 3.0 cc. (9.0 mg.) and 4.0 cc. (12 mg.) was required. The average for the entire group was 3.5 cc. (10.5 mg.). In six cases, more than 5.0 cc. (15 mg.) was given but in these instances it was necessary to supplement the initial satis factory akinesia by additional small amounts of curare because of the length of the opera
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tion and the wearing away of the effect of curare. The rate of administration was so altered by the respiratory status of the patient at any given moment that it was nearly impos sible to formulate any set pattern by an an alysis of the data. Administration of curare in the amount of 0.5 cc. per minute until the desired effect is attained would most closely approach the average experience in this study. Although the degree of akinesia was not retested at the completion of the operation, the impression was garnered that the effect of an average dose (3.5 cc.) administered over a period of about seven minutes per sisted for approximately 20 minutes at near maximal degree. The effects would then subside in about 10 minutes, as determined by the ability of the patient to squeeze the examiner's hand. In general, 20 minutes of akinesia was usually adequate to permit completion of the operation and return of the patient to bed. COMMENT
Many of the articles about clinical aspects of curare refer to its early effects on the eye. Results of this study tend to confirm this. The extraocular muscles appear to be among the first to exhibit the paralyzing effect of curare. Not generally recognized, or at least not mentioned in the literature, is the fact that the sequence of paralysis induced by curare may be selective within the particular group of muscles concerned with ocular rotation. Thus, not all the skeletal muscles that con trol movements of the eye and eyelid are affected to a like degree. This was demonstrated in this study by the fact that the ability of the eyes to rotate up ward could be nearly paralyzed, yet the pa tient still retained some ability to look down ward and to squeeze the eyelids. This was a most interesting finding; its possible ex planation is intriguing. It seems easiest to explain the differential
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effect of curare on the function of ocular ro tation in a vertical plane and squeezing of the eyelids on the basis of a sequence of paralysis of muscles innervated by different cranial nerves. The seventh cranial nerve, which innervates the orbicularis oculi, ap parently was less affected by curare in the majority of patients than was the third cranial nerve and the muscles it innervates. To explain the differential effect on up ward and downward rotation of the eye on this basis is somewhat more difficult. Since the function of looking upward is performed chiefly by muscles (superior rectus and inferior oblique) innervated by the third cranial nerve, whereas the function of looking downward also includes innervation from the fourth cranial nerve (superior oblique muscle), a selective effect of curare between adjacent cranial nerves might be postulated. If this is true, it attributes to curare a fine peripheral gradient effect that may not really exist. Since the functions of upward and down ward rotation of the eye were judged on the basis of response to command, the difference in response might be caused by some central effect of curare. On the basis of known pharmacologic facts, the former explanation is more plausible. The tendency of the eyes to roll upward or the inability of the patient to look down ward at some crucial moment during opera tion for cataract is one of the main bugaboos of surgeons who perform such operations. Because it nearly eliminates the ability of the eye to roll upward, curare should be a great boon to operative techniques for removal of cataract. Lancaster,12 as well as others, has spoken at various times of the importance of akinesia of the extraocular muscles; yet I and many others had considered proper akinesia of the eyelids to be a greater factor in reduction of the incidence of loss of vitreous. As I have analyzed the results of this study and have watched many curarized pa tients attempt to squeeze the eyelids against
the speculum in the presence of a nearly immobile eye, I have changed my opinion as to the necessity of complete akinesia of the eyelids. Whenever the akinesia of the extraocular muscles was nearly complete, squeezing of the eyelids appeared to have little influence on the incidence of loss of vitreous. At the beginning of this study, some ques tion existed as to the selection of an ocular test that would properly reflect the degree of desired curarization. Since it was desirable to eliminate looking upward, this function was selected as one test of the degree of curarization. It proved to be a fortunate selection, for this function as a response to command could be nearly abolished. It was thought that, if the patient was unable to roll the eye up even when coaxed or commanded to do so at the beginning of the operation, it was unlikely that this annoy ing movement would occur during the crucial moments before and after the delivery of the lens. One of the puzzling features in this series of patients was a softening effect of the eyes that appeared evident clinically but was more difficult to prove objectively. The eyeball appeared more flaccid or to display loss of tonus in comparison to the eyes on which I had operated prior to this study. This soften ing effect has been noted by others. At first, operation on these softened eyes appeared more difficult because a greater amount of traction on the lens and counterpressure on the vitreous was required to bring about delivery of the lens. This ap parently was a drawback to use of curare in operations for cataract but, as familiarity was attained with this diminished ocular tonus and with the altered mechanics of ex traction, this difficulty was replaced by a feeling of security. At completion of this study, it was con cluded that surgical results were potentially better when the eye was softer. More varied manipulations can be carried out within rea sonable limits on such eyes without fear of
CURARE AKINESIA IN CATARACT OPERATIONS
loss of vitreous than can be done on the eyes of patients who have not been curarized. On the basis of experience prior to this study, it was scarcely possible to maneuver a vectis inside the eye without fear of loss of vitreous. In this series, it was surprising to find that five cases occurred in which de livery of the lens was completed with the vectis without loss of vitreous. In any evaluation of the practical applica tion of curare to operations for cataract, it must be kept in mind that nearly paralyzing doses, so far as the extraocular muscles were concerned, were utilized in this study, whereas other investigators have recom mended "relaxing" rather than paralyzing doses. Farquharson, reporting on his series of 70 extractions of cataracts during which curare had been administered, found that it required between 20 and 60 units (3.0 to 9.0 mg. of d-tubocurarine chloride) with an average of 44 units (6.6 mg.). These data agree closely with those noted by Roche, who found that 45 units of curare was the minimal dose necessary to obtain a quiet eye for intraocular operations. Such dosage is less than the average amount (10.5 mg. or 70 units) utilized in the study being reported. In 15 patients who did not have premedication, Roche found that the paralyz ing dose was 76 units (11.4 mg. of d-tubo curarine chloride). Although a paralyzing dose might not be deemed necessary, its use still appears to be practical since it was administered in 138 successive cases without undue complication. A smaller dose, such as permits only relaxa tion, might have but little more effect than the usually administered local anesthetics. As already mentioned, the rate of ad ministration of curare varied extensively in different patients and the rate was altered greatly according to the respiratory status of the patient at any moment; these variations make statistical analysis impossible. Never theless, the impression was gained that it was not the amount of drug given but rather
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the rate of its injection that was the most important factor in safety. This fact was learned chiefly by means of trial and error; had it been possible to apply the experience of the last half of the study to some of the initial patients, the incidence of cases of unsatisfactory akinesia probably would have been less. As a rough guide to those who might try the drug, I propose that it be administered intravenously at a rate not to exceed 0.5 cc. (1.5 mg.) per minute after an initial injec tion of 1.0 cc. (3.0 mg.). Contraindications to administration of curare to patients who have cataracts are few but definite. Even though several asthmatic patients were successfully operated on, pa tients who had difficulties in respiratory ex change were, as a whole, extremely hard to handle. I have discontinued administration of curare to any individual who has chronic bronchitis, atelectasis, bronchiectasis, asthma, or pneumothorax. On the other hand, curare was given with out complication to patients who had all varieties of cardiac and vascular difficulties. Such conditions as auricular fibrillation, severe hypertension, cardiac enlargement, generalized arteriosclerosis, angina pectoris, disease of the coronary arteries, and valvular cardiac disease did not prove to be contra indications to administration of curare. One of the obvious drawbacks from a practical standpoint to use of curare in opera tions for cataract is the need for someone to supervise the injection of the solution. In this study, an anesthesiologist supervised this phase of the procedure; however, once an ophthalmologist becomes familiar with the use and behavior of curare anyone should be able to administer the drug intravenously under the direction of the ophthalmic sur geon. i Still, this need for another person to supervise administration of the drug is a factor that may prevent general utilization of this method of akinesia by ophthalmol ogists. Any procedure concerning surgical
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technique in removal of cataracts that is not under direct control of the surgeon is a de finite drawback in the opinion of many oph thalmologists. Several publications concerning akinesia induced by curare include statements that a discussion of antidotes has no place because, if the drug is administered correctly, no need for antagonists of curare exists. No matter how skillfully a drug may be administered, instances of undue sensitivity to even small amounts will be encountered when it is given to a large enough group of patients. I n this study one patient experienced respiratory embarrassment after receiving 1.5 cc. (4.5 mg.) ; in several patients, it seemed advisable to administer neostigmine. T h e neostigmine was given in conjunction with artificial respiration by means of posi tive pressure. Until recently, neostigmine was the drug most widely used as an antago nist of curare, although from a pharmacologic standpoint it was known to have several drawbacks as to its specificity and reliability for such purpose. N o w a commercial preparation, N-ethylN - ( m - hydroxyphenyl) - N , N - dimethylam -
monium bromide (tensilon), is available that, by preliminary clinical trial, appears to have a more specific and faster effect against paralysis of peripheral muscles than any other drug at present. Although it has not been necessary to use tensilon in this study, it is another safety factor that insures safer use of curare and is of reassurance to the surgeon in time of need. Although this study was begun with some skepticism as to the practical value of curare as an aid to akinesia during operation for cataract, it is now considered that the drug is of great help in this particular phase of ophthalmology. Since the conclusion of this study, I have continued to use curare in all extractions of cataracts except when the drug is contraindicated. Lancaster, 1 2 in a paper on operation for cataract, once said, " M y aim is to receive a patient who cannot feel, does not want to move, and could not move if he tried." Curare bids fair to solve the third factor of Lancaster's dictum for the successful prep aration of patients who are to undergo re moval of cataracts. The Mayo Clinic.
REFERENCES
1. Mclntyre, A. R.: Curare: Its History, Nature, and Clinical Use. Chicago, Univ. Chicago Press, 1947. 2. Wintersteiner, O., and Dutcher, J. D.: Curare alkaloids from chondodendron tomentosum. Science, 97-.467-470(May) 1943. 3. Bennett, A. E.: Curare: A preventive of traumatic complications in convulsive shock therapy. (Including a preliminary report on a synthetic curare-like drug.) Am. J. Psychiat., 97:1040-1060 (Mar.) 1941. 4. Baird, J. W., Johnson, W. R., and Van Bergen, F. H.: Pentothal-curare solution: A preliminary report and analysis of its use in 160 cases. Anesthesiology, 9:141-1S8 (Mar.) 1948. 5. Kirby, D. B.: Use of curare in cataract surgery. Tr. Sect. Ophth., A.M.A., 1949, pp. 279-293. 6. Clark, W. B.: Use of curare as an adjuvant in cataract surgery. Watson-Gailey Eye Foundation Quart., 1:34, 1949. 7. Roche, J. R.: Research in the use of curare for ocular surgery. Am. J. Ophth., 33:91-94 (Jan.) 1950. 8. Farquharson, H.: Curare with local anesthesia in cataract surgery. Am. J. Opth., 34:554-556 (Apr.) 1951. 9. Cordes, F. C, and Mullen, R. S.: The use of curare in cataract surgery. Am. J. Ophth., 34:557564 (Apr.) 1951. 10. Drucker, A. P., Sadove, M. S., and Unna, K. R.: Ophthalmic studies of curare and curarelike drugs in man. Am. J. Ophth., 34 :543-553 (Apr.) 1951. 11. Kirby, D. B.: Curare in cataract surgery: Five years' experience. Sec. Ophth., A.M.A., June, 1952. 12. Lancaster, W. B.: The cataract operation: A study of details. Surg., Gynec. & Obst., 52:452-461 (Feb.) 1931.