[12] The Use of Promethazine for Premedication* Elaine A. Stuebner, D.D.S.** Max S. Sadove, M.D.***

* In the last decade there have was started to evaluate prometha- been important contributions in the zine. search for tranquilizing drugs that would be useful as adjuncts to local Action of Promethazine and general anesthesia. The reser- Promethazine ((N-(2'dimethyl pine drugs were among the first to amino-2'-methyl) ethyl phenothia- be used for premedicating agents. zine HCl)) has been reported by It was found that sedation, poten- Baxter3 "to act as a spasmolytic, tiation of anesthesia, and alleviation anti-convulsant, anti-emetic and to of nausea and vomiting proved lower the basal metabolic rate." It helpful in general anesthesia.' Ideal- has potentially all the basic proper- ly, there should be no depression ties of other tranquilizing drugs plus of the vital centers-respiratory and longer antihistaminic and anti-ana- circulatory functions-with the use phylactic actions.4 of the tranquilizing drugs. Central nervous system depres- Recently a phenothiazine deriva- sion was observed by Baxter5 with tive, promethazine (Phenergan®), marked action on the sympathetic has received favorable comments nervous system, like that of a potent and was found worthy of further adrenolytic agent. Its effect on the clinical evaluation. This drug has parasympathetic division was sim- been used extensively in general sur- ilar to that of the vagolytic sub- gery (over 1,000 cases) at this hos- stances. pital2, and it was realized that its Peripheral action of promethazine properties could be used in am- was found to be an antihistamine bulatory and hospital oral surgery effect and a quinidine-like action patients. Therefore, a clinical study on the heart. Winter6 explains this peripheral action by the depression * Presented to the American Dental Society of Anesthesiology, Miami Beach, of the local tissue hormones-acetyl- Florida, November 2, 1957. choline, histamine and adrenaline. ** Resident in the Department of Anes- thesiology, University of Illinois Re- Laborit7 and others have shown, search and Educational Hospital. after extensive studies with prome- *** Head of the Department of Anes- thesiology, University of Illinois Re- thazine, that it will potentiate the search and Educational Hospital. action of anesthetic agents, produce [13] sedation and alleviate nausea and Group IV consisted of 34 adults, vomiting. Halperns reports that ranging in age from 17 to 62 years, promethazine is one of the most who required exodontia on an am- useful antihistaminic drugs and has bulatory basis. Promethazine was shown its antianaphylactic actions given orally along with scopol- in the guinea pig. Howarth9 and amine. Owen have shown by direct cathete- rization procedures that prometha- Results zine has no significant effect on cir- Group I was given /2 mg. of culatory functions. promethazine per pound of body along with adequate sco- Physical Properties weight, polamine, 45 minutes prior to sur- Promethazine is soluble in water, gery. In this group, which con- chloroform and alcohol."0 A 5 per sisted of 46 children, sedation and cent solution in water has a pH of tranquility were satisfactory in all 4.0-6.5 and, therefore, is incom- but nine patients. Sadovell suggests patible with thiopentone sodium the use of meperidine along with solutions.10 promethazine and scopolamine for Purpose of Studying Promethazine the most effective premedication. This clinical study was under- It is possible that had these nine taken to evaluate the use of prome- children received meperidine along thazine as a premedicating agent with the promethazine and scopol- for ambulatory and hospital patients amine, sedation and tranquility who required exodontia and oral would have resulted. In the 37 chil- surgery. dren that were definitely sedated In this study four groups of pa- by the use of promethazine, a pat- tients were used to evaluate the best tern of complete unconcern with technic for using promethazine as their surrounding environment was a premedicating agent. evident. Most children were easily Group I consisted of 48 children, aroused from a light sleep by the aged 4 to 12, who required hospi- sound of the normal voice. talization for oral surgery pro- Respiratory depression and peri- cedures. In this group promethazine pheral cyanosis of the nail beds were was given intramuscularly along not observed clinically. with scopolamine. Postoperative vomiting was found Group II consisted of 52 children, in five of the cases. Vinethene® and aged 3 to 10, who required exo- ether plus oxygen were the anesthe- dontia or oral surgery procedures. tic agents used for the intubation 14] of the patient. After the intubation Postoperative vomiting and nau- procedure nitrous oxide-oxygen and sea were found in only three cases trichlorethylene were used for main- and this occured while the patients tenance. In the recovery room, post- were in the recovery room. Post- operative sedation prevailed and the operatively, the children who were normal voice could arouse the chil- asleep when they entered the oper- dren from sleep. From clinical ob- ating room were still dozing inter- servation, intramuscular prometha- mittently in the recovery room. zine has a duration of about three It is evident, for children six and one-half hours from onset of years and older, that 1 mg. per action. pound of body weight, orally, is not Group II consisted of 52 ambu- enough for complete sedation; how- latory children who required rou- ever, it is possible to give scopol- tine extractions. Dosage was 1 mg. amine along with Phenergan® to of promethazine per pound of body get the desired effect of sedation. weight (no scopolamine was given Group III consisted of adults who in this group) which was given required hospitalization for oral sur- orally 45 minutes before the time gery procedures. In all 56 cases pro- of extractions. Of this group of 52 methazine was given intramuscular- children, 19 were sedated and asleep ly one and one-half hours prior to when they came to the operat- surgery and the dosage was de- ing room. It is important to note termined on a weight basis of ¼ mg. that all but four of the group were per pound of body weight. In the six years or under in age. Twenty older age groups 8 mg. per pound of the remaining 33 children were was found sufficient to produce the awake but said that they felt sleepy. desired sedation. Meperidine was They did not object to the face given on an equal basis with pro- mask or appear frightened during methazine, along with scopolamine, the induction stage of anesthesia. intramuscularly, 45 minutes before Of the remaining 13 children, none surgery. felt sleepy and eight were unco- As the patients arrived in the operative in accepting the mask dur- operating room a definite attitude ing the induction procedure. of unconcern was evident. Only 20 The anesthetic given was nitrous patients were definitely asleep. The oxide-oxygen-trichlorethylene, and patients stated, when questioned, induction appeared slightly more that they felt sleepy and relaxed. rapid and definitely smoother with Each was asked to give his name, the use of promethazine. address, and telephone number. [15 ] Definite slowness in speech when were easily aroused from a light answering made evident the fact sleep. Some were awake but would that cerebral cortical depression doze on and off in the recovery was present. room. In five cases, where the pa- Blood pressure, respiration and tients tried to get out of bed after pulse were taken upon arrival in minor surgery, definite postural the operating room, prior to induc- hypotension was present. It is inte- tion, during surgery and postoper- resting to note that in cases that atively in the recovery room. There had been given promethazine intra- were no significant respiratory or muscularly for extractions under circulatory complications involved local anesthesia, no postural hypo- preoperatively, during surgery or tension was observed. This finding postoperatively with the dosage that could be interpreted to mean that was planned for these patients. promethazine when given alone In one case meperidine was given does not predispose to hypotension, in double the dosage and the res- but with the addition of meperi- piratory rate was decreased to 12 dine, thiopental sodium and anes- per minute. Because of the de- thetic agents, postural hypotension creased respirations, 1 mg. of Lor- can result. phan® was given; however, peri- One interesting feature of this pheral nail bed cyanosis was not premedicating technic is that the evident at the time of administering majority of these patients did not the Lorphan®. remember going to the operating It is apparent that promethazine room or being asked any questions will potentiate meperidine and de- before surgery. A definite pattern of crease the amount of mineperidine sedation, loss of memory and un- that otherwise would be needed for concern with their surroundings premedication. Thus, the desired were the prominent features. No sedation is produced without res- postoperative vomiting was found piratory or circulatory depression. in this group. All of these patients were in- When promethazine was given tubated by utilizing 2.5 per cent intramuscularly, eight patients com- thiopental sodium and succinyl- plained of a definite burning sensa- choline hydrochloride. Anesthesia tion at the site of the injection was maintained by small intrave- which lasted a few seconds. nous doses of meperidine along with Group IV consisted of adult pa- nitrous oxide and oxygen. tients who were given 50 to 75 mg. Postoperatively, most patients of promethazine, orally, 45 minutes [161 prior to extractions. None in the the recovery room. There were two group was asleep from the pre- cases of nausea but no actual vomit- medicating dosage. The majority ing occurred. appeared to be slightly sedated and stated that they felt relaxed. Twelve Evaluation and Summary patients stated that there was no Table 1 will help to clarify change after taking the tablets. the results obtained from this Clinical observation revealed no clinical study. After reviewing these respiratory or circulatory depression. findings and comparing them The anesthesia used was nitrous with promethazine as used in gen- oxide-oxygen-trichlorethylene. The eral surgery, we conclude it expe- average anesthetic tirme was 11 min- ditious to submit these evaluations utes, and there was no increase in on an individual group basis, as fol- pulse rate or deviation in blood lows: pressure. Group. I. Promethazine with sco- Induction time was shorter, and polamine given by intramuscular a surgical plane was easily main- injection in children under six tained. All patients were anesthe- years of age gave an ideal sedating tized and extractions could be done effect; however, over the age of without the patient moving during six, a definite advantage is obtained anesthesia. Two patients fought the by using meperidine along with induction but were then carried to promethazine for ideal sedation of an anesthetic plane. the patient. The smoothness of in- Recovery was slightly prolonged, duction, potentiation of anesthesia and the patient gradually awoke a and alleviation of nausea and vom- few minutes after the anesthetic iting that have been attributed to agents were withdrawn. All were this drug are substantiated in these able to walk with an assistant to findings.

Table 1 Results of Premedication with Promethazine in the Four Group Studies No. of Relaxation or Patients Sedation Tranquility No effect Vomiting Nausea Group I 46 37 - 9 5 Group II 52 19 20 13 3 Group III 56 20 36 - Group IV 34 - 22 12 - 2 [ 17] Grou/p II. Oral p)romethazine bination of anesthetic agents, such produced adequate sedation in chil- as nitrous oxide and trichlorethylene drcn under six years of age; how- is used. However, with the use of ever, for the older age groups the promethazine dcfinite case of induc- addition of scopolamine rnay pro- tion and maintenance of anesthesia duce the desired sedation. Since the was found. None of these patients procedures are relatively short for was actually asleep with the use of dental extractions in children, there proinethazine, but the tranquility is little need for the potentiation that prevailed was pleasant to the of anesthesia: however, sedation patient and his cooperativeness was and tranquilitv are definitelv indi- evident to the ancsthetist. Although cated for the uncooperative, ner- one third of the patients stated they vous, imientally disturbed or asthmia- felt no relaxation or tranquility, the tic child, aind even the cooperative anesthetic induction and imiain- (hild imiay henefit froiim sedation. tenance was, for all intents and pur- When the nitrous oxide-oxygen-tri- poses, the same for those who said chlorethvlene technic is used in con- they were relaxed with the drug. junction with p)rolnlethazine, vonmit- Again, there was no vomniting. Two ing is reduced. wonmen comlplained of nausea in the Group III. Patients who require recovery roonm. hospitalization for oral surgery pro- Summary cedurcs definitely bencfit fromn the As a premiedicating agent for the usc of promiiethazine from the stand- uncooperativc and nervous child, l)oint of sedation, tranquility, poten- tiation of anesthesia and the alle- promethazine has definite advan- viation of vomiting and nausea. tages. The cooperativeness that re- There is a definite advantage in a sults from the usc of this drug may remcedicating agent that docs not bc beneficial to all children. lproduce respiratory or circulatory In adults who require anesthcsia depression, and creates an ainnesia on an ambulatory basis, it definitely effect. The decreasc in post-oper- can be useful for induction and ative nausea and vomiiting is an- maintenance when nitrous oxide other factor to consider when se- and trichlorethylene are used. How- lecting a premedicating agent. ever, the choice of the best pre- Group IV. Anesthesia for extrac- miedicating agent for the patient tions and mninor oral surgery pro- should be determined on an indi- cedures can be difficult when a com- vidual basis. [18] In patients who require hospitali- 2. SADovEi, MAX S., "Promietliazine in Surgery',, J./.l.M.Al. 162:712 (Oct. zation, the advantages in prome- 20) 1956. thazine for premcdication are very 3. BAXTER, \\I.,R. et al, "Thllree Plheno- encouraging. There are many pre- tlhiazine D)erivatives in Antesthesia," .lnesthlcsi(a 9:79-87 (April) 1954. mnedication technics, but the advan- 4. HALPERN, B. N., "Recent A(lvances tages of using a tranquilizer for hos- ill thle I)Domain otf the Alltillistamine patients makes this technic an Subl)stances: tlle Plenotlliazine Deri- pital vatives," Bu-ll. Afew 'York Acad. Med. imiiportant one for the oral surgeon. 25 :323-330. The accompanying dosage chart, 5. BAXTER, R. \\., ct al, Op. cit. which is used at the University of 6. \\INTER., C. A., "Antihistamine Ac- tion of P'rometlhazine," J. Phar. 94 :7- Illinois Research and Educational 1948. Hospital, is recommended when 7. Lx:\ORIT,-I H., LEGERI, L., Op. cit. is used for premedica- 8. tHALPERN, B13. N., Op. cit. promethazine H.}OWARTH, S., OWEN, S. G., "Action tion (Table 2). of Pronmethlazine on Systemic Blood 1)ressure, I 'ulmonary Artery Pres- References suire, and IPulmonary 13loo(1 Flow," 1. LABORIT, H., LEGER, L. "Use of a Brit. 1. .J. 2:1266-1267 (Nov. 27) SvNtlietic Antilhistamine in l're- 'er- 1954. at(l I'ost-Operative Therapeutics", 10. I\AXTER, R. W\., et al, Op. cit. Presse ,,ied. 58:492 (April 29) 1950. 11. SA)ovE., MAX S., ().) Cit.

Table 2 1)osagc Chart for Preanesthetic Medication lPatientt A gt Weighlt l'rotiethaziate i\1 eperiuli tie Scopolalmi ne lbs. tag. IM. g. I M1 gr. I M. 12-18 ilmos. 22-25 12 - 1/450 18-24 25-27 15 1/400 2-3 vrs. 27-3() 15-20 -- 1/300 3- 30)-40 20-25 1/300 6-8 40-55 25 25 1/200 8-10 5 -65 25 35 1/150 10-14 65-(O 25 50 1/15o .\(hilts lilore tlhan 90 30-50 50-75 1/150-1/100 tlug. 1P.(). 2-5 vrs. 27-40 15-25 - 6-8 43-60 25 1/250 9-12 60-80 3 - 1/150 12-14 80-90 50 25 1/s150 A(ults tilmore than ()0 50-75 50 1/100 Department of Anesthesiologqy University of Illinois Research and Educatiohal Hospital Chicago, Illinois