Surgery

Summary

Phenytoin has been reported useful prior to, during and after surgery. Among its uses are relief of apprehension and anxiety, prevention and treatment of cardiac arrhythmias, prevention of ischemic brain damage and relief of pain. PHT, in therapeutic doses, does not depress respiration or cerebral function, thus optimizing preoperative state and post-operative recovery. PHT’s ability to relieve pain, without sedation, reduces the need for narcotics.

Jaffe, Personal Communication (1966),747 found PHT useful in the pre-operative and postoperative periods and during the course of cataract surgery. PHT replaced large doses of barbiturates previously used pre-operatively to combat apprehension. PHT replaced Demerol and opiates preoperatively and was especially useful in cases where unpredictable or aggressive behavior was anticipated. During the course of surgery where intravenous Demerol had previously been required to control violent outbursts in the operating room, intravenous PHT was successfully substituted.

747. Jaffe, N. S., Use of diphenylhydantoin in ophthalmic surgery, Personal conmunication, 1966.

Mercer and Osborne, Annals of Internal Medicine (1967),248 reported on the use of intravenous PHT in the treatment of 259 patients who developed arrhythmias during and after cardiac surgery. With PHT, complete control of the arrhythmias was achieved in 164 patients and partial response (at least 50% reduction of arrhythmias) was observed in sixty-five patients.

248. Mercer, E. N. and Osborne, J. A., The current status of diphenylhydantoin in heart disease, Ann. Intern. Med., 67: 1084-1107, 1967.

Seuffert, Helfant, Dana and Urbach, Anesthesia and Analgesia (1968),409 report on the use of PHT, prophylactically and therapeutically, in the treatment of arrhythmias which develop and persist during surgery. Twenty patients undergoing elective surgery, scheduled to receive cyclopropane anesthesia, were divided into two groups: eleven were pretreated with PHT (5 mg/kg) intravenously, and nine received an equivalent amount of lactated Ringer's solution with or without propylene glycol solvent for PHT, serving as controls. Eight of the nine patients in the control group developed arrhythmias, whereas only three of the eleven patients pretreated with PHT developed arrhythmias during the entire anesthesia procedure. During “maintenance,” eight of the nine in the control group developed arrhythmias, in contrast to only one of eleven pretreated with PHT. The authors pointed out that this difference was statistically significant. PHT was also given to ten other patients under general anesthesia, who developed arrhythmias which did not respond to standard treatment. PHT promptly restored regular sinus rhythm in eight patients who developed ventricular arrhythmias. It was not effective in two of the patients who developed supraventricular arrhythmias. (See also Ref. 720).

409. Scuffert, G. W., Helfant, R. H., Dana, J. F., and Urbach, K. F., Use of diphenylhydantoin in prevention and treatment of cardiac arrhythmias during general anesthesia. Anesth. Analg., 47: 334-339,1968.
720. Helfant, R. H., Seuffert, G. W., Patton, R. D., Stein, E., and Damato, A. N., The clinical use of diphenylhydantoin (Dilantin) in the treatment and prevention of cardiac arrhythmias, Amer. Heart J., 77: 315-323, 1969.

Gautam, British Heart Journal (1969),721 reported on the use of intravenous and oral PHT in treating a variety of cardiac arrhythmias following open heart surgery (thirteen Starr-Edwards prosthetic valve replacement s and one atrial septal defect closure). The arrhythmias, which included multiple ventricular extrasystoles, recurrent ventricular tachycardia and nodal tachycardia, appeared within two to thirty hours after surgery. PHT was rapidly and highly effective in abolishing the arrhythmias in thirteen patients. The author states that the rapidity of its action and the relative paucity of side effects make PHT an effective antiarrhythmic agent.

721. Gautam, H. P., Phenytoin in post-operative cardiac arrhythrnias, Brit. Heart J., 31: 641-644, 1969.

Barasch, Baras and Galin, Personal Communication (1970),732 found that PHT replaced all preoperative and postoperative medication in cataract surgery other than the local anesthetic. The authors previously had used barbiturates, Demerol, Compazine, codeine and aspirin. Because PHT does not impair normal function, its use instead of narcotics and sedatives permitted the prompt ambulation of patients. For this reason the use of PHT enabled the discharge of patients within twenty-four hours, in a series of 100 consecutive uncomplicated cases of cataract surgery. The authors state that since this study, they now use PHT routinely in cataract surgery.

732. Barasch, K., Baras, I., and Galin, M. A., Early ambulation after cataract surgery, Personal communication, 1970.

Chamberlain, Personal Communication (1970),744 reported on the therapeutic value of PHT in a series of 200 surgical cases. The ages of the patients varied from six months to ninety years. Dosage of PHT: 25 mg to 600 mg depending on age of patient and severity of symptoms and surgical procedure used. PHT was successfully employed as follows:

1        As pre-operative medication for anxiety.
2        As post-operative medication for anxiety and pain.
3        In the agitated, depressed and alcoholic surgical patient.
4        In long-term treatment of both the operable and inoperable patient with malignant disease.

Certain trends presented themselves with the use of PHT:

(a)    In children, PHT (25 mg q.i.d. to 100 mg t.i.d.) reduced or eliminated the use of pre-and post-operative narcotics.
(b)   In adults, 200 mg of PHT prior to surgery reduced the need for pre-operative narcotics.
(c)    In adults, post-operative use of PHT (500-600 mg daily) relieved pain, making it possible to do away with practically all post-operative narcotics. PHT also decreased anxiety and promoted a general feeling of well-being in most cases.
(d)   Elderly agitated and difficult patients became much calmer with PHT.
(e)    In the inoperable malignant cases, PHT in doses up to 600 mg daily relieved pain, making it possible to greatly cut down on the amount of narcotics used. PHT definitely improved the mental outlook of these forlorn patients.
(f)     In postoperative malignant cases undergoing radiation and other forms of treatment, the use of PHT, 400-600 mg daily, relieved pain and allowed for a marked decrease or elimination of the need for narcotics.

The author notes that, in general, there was marked improvement of mental outlook in patients receiving PHT.

744. Chamberlain, W., Use of diphenylhydantoin in surgery, Personal communication, 1970.

Winter, International Surgery (1972),1692 presents a detailed study on surgery in patients with asthma and emphysema. In this study the author says that severe respiratory problems require careful preoperative and post-operative medical treatment. He states that in patients with severe respiratory problems he does not use narcotics and that, in his opinion, they should never be used in such cases. He further says that barbiturates and tranquilizers should only be used in small doses. The author states that he has found PHT of considerable value in severe respiratory problems, both pre-operatively and post-operatively. He notes that PHT appears to have special value in patients with bronchospastic problems. (See also Refs. 341, 401, 1535, and Anti-anoxic Effects of PHT.)

1692. Winter, B., Bilateral carotid body resection for asthma and emphysema, Int. Surg., 57: 458-466, 1972.
341. Shulman, M. H., The use of Dilantin sodium in bronchial asthma: a preliminary report, New Eng. J. Med., 226: 260-264, 1942.
401. Sayar, B. and Polvan, O., Epilepsy and bronchial asthma, Lancet, 1: 1038, 1968.
1535. Shah, J. R., Vora, G., Karkhanis, A. V., and Talwalkar, C. V., The effect of diphenylhydantoin on ventilation tests in airway obstruction, Indian J.. Chest. Dis., 12: 10-14, 1970.

Landolt, Acta Endocrinologica (1974),1256 reported a patient who developed the syndrome of inappropriate ADH secretion following surgery for craniopharyngioma. Intravenous PHT, during two such episodes, promptly increased urine output. Serum sodium values returned to normal and the patient became more alert. (See Inappropriate ADH Syndrome).

1256. Landolt, A. M., Treatment of acute post-operative inappropriate antidiuretic hormone secretion with diphenylhydantoin, Acta Endocr., 76: 625-628, 1974.

Aldrete and Franatovic, Archives of Surgery (1980),1717 studied the effects of PHT on changes of arterial blood pressure and heart rate occurring during anesthesia and in the immediate postoperative period. In a controlled study, ninety hypertensive patients were separated into three groups. One group was untreated. One group received 100 mg of PHT, and another group received 200 mg, the evening before and the morning of surgery. Both groups receiving PHT had better hemodynamic stability than the non-treated group. The group receiving 200 mg had statistically significant improvement.

1717. Aldrete, J. A. and Franatovic, Y., Postponement of operations-its prevention in patients found to be mildly hypertensive, Arch. Surg., II 5: 1204-6, 1980.

Aldrete, Romo-Salas, Mazzia and Tan, Critical Care Medicine (1981),2142 studied the effect of intravenous PHT in ten patients who suffered cardiac arrest during or after anesthesia. PHT was given after spontaneous heartbeat and systolic blood pressure greater than 100 mm Hg had been restored and the diagnosis of neurological deficit had been established on the basis of unconsciousness, dilated and areflexic pupils and rigid and/or decerebrate posture. With PHT (7 mg/kg) nine of the ten patients recovered nearly complete neurological function. The other patient had partial recovery but succumbed to other complications.

2142. Aldrete, J.A., Romo-Salas, F., Mazzia, V.D.B. and Tan, S.L., Phenytoin for brain resuscitation after cardiac arrest, Critical Care Medicine, 9(6): 474-7, 1981

Garson and Gillette, PACE (1981),2528 reported the use of oral and intravenous PHT for the treatment of chronic ventricular dysrhythmias in fifty-one young patients, thirty-five of whom had previously undergone corrective surgery for cardiac mal-formations including ventricular septal defect, tetralogy of Fallot, and valvular insufficiency. Overall, PHT was the most effective drug, controlling the arrhythmias in thirty-nine of the fifty-one patients. The authors conclude that PHT is the drug of choice for children with ventricular dysrhythmias, especially those with abnormal hemodynamics. (See also Ref. 1847.)

2528. Garson, A., Gillette, P. C., Treatment of chronic ventricular dysrhythmias in the young, Pace, 4: 658-69, 1981.
1847. Garson, A., Kugler, J. D., Gillette, P. C., Simonelli, A. and McNamara, D. G., Control of late postoperative ventricular arrhythmias with phenytoin in young patients, Am. J. Cardiol., 46(2): 290-4, 1980.

Rocchini, Chun and Dick, American Journal of Cardiology (1981),2251  reported the elimination of ventricular tachycardia by PHT in four children who had undergone repair of the tetralogy of Fallot. The authors state that PHT appears to be the antiarrhythmic agent of choice after repair of the tetralogy of Fallot.

2251. Rocchini, A. P., Chun, P. O., and Dick, M., Ventricular tachyeardia in children, Am. J. Cardiol., 47: 1091-7,1981.

Kavey, Blackman and Sondheimer, American Heart Journal (1982),2654 reported the effects of oral PHT in nineteen patients, seen consecutively, who developed ventricular premature complexes (VPCS) late after surgery for congenital heart disease. Arrhythmias included ventricular tachycardia, couplets and frequent multiform or uniform VPCS, documented by twenty-four hour ambulatory ECG. Sixteen had undergone previous repair of the tetralogy of Fallot and three had had aortic valve surgery. Nine of these children had been unresponsive to previous treatment. PHT decreased ventricular dysrhythmias in all nineteen patients. The arrhythmias were completely suppressed in fifteen, and in four they were reduced to uniform VPCS. The authors state that the high rate of success in treating these patients, who are at particular risk for sudden death, and the relative lack of side effects suggests that PHT is the drug of choice for this patient group.

2654. Kavey, R. E., Blackman, M. S., Sondheimer, H. M., Phenytoin therapy for ventricular arrhythmias occurring late after surgery for congenital heart disease, Am. Heart J., 104: 794-8,1982.

Massei, DeSilva, Grosso, Robbiati, Infuso, Ravagnati and Altamura, Neurosurgical Science (1983), 2768 reported on the use of PHT for cerebral metabolic protection during carotid thromboendoarterectomy (TEA). PHT was chosen because of its known therapeutic properties in reducing cerebral metabolic oxygen consumption, preserving energy compounds, increasing cerebral blood flow, and in regulating intra-and extracellular cerebral ion content. Twelve patients undergoing TEA were given intravenous PHT (15-17 mg/kg), fifteen minutes before clamping. EEG and PHT blood levels were monitored during and after surgery at fixed intervals over a twenty-four-hour period. The authors stated that patients awakened promptly and did not require intensive care. This was in contrast to their experience with other methods of cerebral protection, including barbiturates. Also, with PHT, no postoperative neurological complications were observed.

2768. Massei, R., DeSilva, E., Grosso, P., Robbiati, B. R., Infuso, L., Ravagnati, L., Altamura, C. A., Cerebral protection with diphenylhydantoin during disobliterating surgery of the sovra-aortic branches, J. Neurosurg. Sci., 27(2): 107-10, 1983.

Perez-Ruvalcaba, Quintero-Perez, Campa-Uribe, Chapa-Alvarez, Rodriguez-Noriega, European Journal of Clinical Investigation (1984),2858 reviewed the multiple uses of PHT in their general hospital. Their review included the use of 100 mg of PHT, as sole preoperative medication the evening before surgery, in fifty patients. Treatment with PHT resulted in excellent control of apprehension and sleep disturbances usually encountered preoperatively. The authors state that these beneficial effects of PHT were achieved without the undesirable sedative effects experienced with many commonly used sedatives and/or tranquilizers.

2858. Perez-Ruvalcabaga, J. A., Quintero-Perez, N. P., Campa-Uribe, G., Chapa-Alvarez, R., Rodriquez-Noriega, E., The multiple uses of phenytoin in a general hospital setting, Eur. J. Clin. Invest., 14: 37, 1984

Kuo, Ho, Hu, Li and Hwing, Anaesthesiologica Sinica (1990), evaluated the effects of pre-treatment with phenytoin or tubocurarine (d-TC) on the adverse effects of succinylcholine, a muscle relaxant widely used for surgical anesthesia. Adverse effects of succinylcholine include muscle fasciculations, postoperative myalgia, and elevated serum levels of potassium and creatine phosphokinase. Four minutes before injection of succinylcholine, three groups of eighteen patients each received either normal saline (Group A-control); 2.5 mg/kg phenytoin (Group B); or 50 µg/kg d-TC (Group C). The authors found that pre-treatment with PHT or d-TC significantly decreased the incidence of succinylcholine-induced fasciculations. The pre-treatment did not improve postoperative myalgia or decrease creatine phosphokinase levels.

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