Method
Results
Summary
Author: Benjamin J. Ciliberti, Nathan B. Eddy
Pages: 1 to 8
Creation Date: 1961/01/01
Differences of opinion exist at present as to the type of drug to be used for pre-operative medication [ 2] , 6) though the basic concepts of premedication remain virtually unaltered. Primarily, the purpose is to obtain psychic sedation so that the patient is tranquil and relieved of his anxiety, but the purpose may also be reduction of respiratory tract secretions, smoother induction and maintenance of anaesthesia by minimizing autonomic reflex activity, fortifying anaesthetic agents or relief of pain (4). Newer and better drugs continue to be sought and assessed clinically, but narcotic analgesics, often in conjunction with belladonna alkaloids, continue to be used widely and remain reliable agents for premedication even when pain is not present. Naturally, therefore, new narcotic analgesics will be tried in this field to determine their relative usefulness.
Our purpose in the present study was to establish a procedure for the evaluation on a double blind basis of the satisfactoriness of pre-anaesthetic agents and to compare new agents with morphine and a placebo.
Observations were made by the anaesthesia staff of the Veterans Administration Hospital, Bronx, New York - mostly first- and second-year residents. There were 23 participants, 13 of whom were involved to the extent of carrying out the study on at least 20 patients. The patients used were unselected except that they were usually the first cases of the day on the operative schedule. This permitted sufficient time to complete and record observations prior to anaesthesia and surgery. There were 670 males and 9 females, with ages ranging from 20 to 85 years; 36 per cent were in the 60 or above age group. They were being prepared for the usual major (mostly) and minor surgical procedures of a large hospital. Approximately two-thirds of the anaesthetics were general and one-third spinal or regional.
All observations were made and recorded in the operating room. They included preliminary evaluation of the patient's mental and physical state and were repeated 10, 20, 30, 45 and 60 minutes after administration of the pre-anaesthetic medication. The points noted were degree of sedation, whether or not the patient was asleep, alert, excited, restless or euphoric, relief of pain, and measurement of blood pressure, heart and respiratory rates. Any side effects occurring during the pre-anaesthetic period were recorded.
1 Chief, Anaesthesia Section, Veterans Administration Hospital, Bronx, New York, U.S.A.
2 Consultant (formerly Chief, Section on Analgesics, Laboratory of Chemistry, National Institute of Arthritis and Metabolic Diseases), National Institutes of Health, Public Health Service, Department of Health, Education and Welfare, Bethesda, Maryland, U.S.A.
Notation was also made as to whether induction was smooth or stormy, whether maintenance was smooth or complicated, and whether respiratory tract secretions were minimal, moderate or marked. The type of anaesthesia and the anaesthetic agents used, including supplementation, especially for induction, were recorded. The awakening time after general anaesthesia was noted, and the time after surgery when the first analgesic medication was needed. The anaesthetist completed the record with his estimation of the premedication as satisfactory or unsatisfactory for the specific case and was urged to state the reason for his judgement. A typical record form is shown.
Three series of patients were reported upon, each series comprising more than 50 cases per medication. The medications were placebo (normal saline), morphine sulphate, oxymorphone 3 hydrochloride and anileridine 4 hydrochloride. These were supplied in multiple dose vials, identical in appearance. Each medication was represented by two code letters in each series, and the code letters were assigned in random sequence. The coding was different for each series.
The dose per unit weight was, for morphine, 5 8 mg in series I and 10 mg in series II and III; for oxymorphone 1.0 mg in series I and II and 1.33 mg in series III and for anileridine 25 mg in series I and II and 33 mg in series III. Concentration was such that the dose administered was 0.5 ml/60 kg body weight in the first and second series and 0.01 ml/2 lb body weight in the third series - a simpler calculation, since the patients were weighed in pounds. The selection of doses initially was based upon those which had been found previously to produce equi-analgesic effects [ 3] , [ 5] , [ 7] - [ 11] ). The doses of oxymorphone and anileridine were increased by a third in series III.
Medications were ordered by code letter, A to H, until the requisite number of cases per drug had been studied, and were administered almost always intramuscularly, in the operating room after the preliminary observations had been made. Fifty-six doses were given subcutaneously and seven doses intravenously. No other medication was given prior to the anaesthetic regimen except occasionally atropine at the end of the pre-anaesthetic period.
3Oxymorphone is the generic and proposed international non-proprietary name for 14-hydroxydihydromorphinone. It was supplied through the courtesy of Endo Products, Inc. Its trade name is Numorphan.
4Anileridine is the generic and proposed international non-proprietary name for ethyl 1-(p-aminophenylethyl)-4-phenyl-4-piperidinecarboxylate. It was supplied through the courtesy of Merck, Sharp & Dohme, Inc. Its trade name is Leritine.
5 It is to be understood throughout that all references to the drugs and their doses refer to the salts as administered, though for convenience the salt designation is omitted.
Table 1 summarizes the judgement of the anaesthetists on this point with respect to each agent. The degree of sedation
is not the only factor to be considered in classifying a drug as a satisfactory pre-anaesthetic medication. The technique to be employed, whether general or regional anaesthesia, the anaesthetic agents to be used, the method of induction and the type of surgery contemplated must all be taken into
account. Troublesome side effects of the premedicant and the presence or absence of a drying effect on secretions will affect judgement. Pain is not usually a factor pre-operatively, and was infrequent in the present study. When it is present, an analgesic effect will contribute to a satisfactory rating. Pre-operative physical status and the age of the patient may also alter evaluation when dosage administered is based on weight alone. The anaesthetist may prefer the patient to be heavily or lightly sedated, and his experience also is likely to be a factor in his judgement. Most of these factors were present and operated equally, we believe, with each drug in each series. A few will be discussed in some detail.
The placebo was rated as satisfactory premedication 51 times in the three series combined, or in 30.1 per cent of its trials, a result corresponding closely to that of placebo effect in other situations [ 2] , [ 5] , [ 7] . Each of the three drugs was rated as satisfactory in a definitely higher percentage of trials than placebo in each series, but neither oxymorphone nor anileridine was rated better than morphine when equi-analgesic doses were used. Increasing their dose by a third did increase the percentage of satisfactory reports, but this difference might be questioned because with oxymorphone at least it was not greater than the difference in the satisfactory results with morphine in series II and III.
Placebo |
Morphine |
Oxymorphone |
Anileridine |
|||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Series |
I |
II |
III |
I |
II |
III |
I |
II |
III |
I |
II |
III |
Dose, mg/60 kg
|
0.5 ml | 0.5 ml | 0.6 ml | 8 | 10 | 10 | 1.0 | 1.0 | 1.33 | 25 | 25 | 33 |
Satisfactory
|
13 | 23 | 15 | 29 | 38 | 30 | 29 | 32 | 34 | 32 | 32 | 40 |
Unsatisfactory
|
41 | 36 | 41 | 24 | 22 | 26 | 25 | 28 | 22 | 24 | 27 | 16 |
Percentage satisfactory
|
24.1 | 39.0 | 20.5 | 54.7 | 63.3 | 53.6 | 53.7 | 53.3 | 60.7 | 57.1 | 54.2 | 71.4 |
Placebo |
Morphine |
Oxymorphone |
Anileridine |
|||||
---|---|---|---|---|---|---|---|---|
Observer |
Sat. |
Unsat. |
Sat. |
Unsat. |
Sat. |
Unsat. |
Sat. |
Unsat. |
P
|
1 | 8 | 9 | 7 | 8 | 6 | 5 | 8 |
So
|
0 | 8 | 6 | 4 | 5 | 7 | 3 | 13 |
We
|
5 | 7 | 9 | 4 | 3 | 4 | 6 | 1 |
Wo
|
1 | 4 | 1 | 2 | 2 | 3 | 7 | 1 |
Gn
|
0 | 10 | 0 | 13 | 6 | 11 | 7 | 11 |
K
|
4 | 8 | 12 | 8 | 14 | 7 | 9 | 5 |
C
|
5 | 5 | 6 | 2 | 3 | 6 | 7 | 3 |
Do
|
0 | 5 | 11 | 1 | 5 | 3 | 6 | 1 |
M
|
5 | 14 | 9 | 4 | 14 | 3 | 16 | 6 |
De
|
8 | 9 | 8 | 3 | 7 | 3 | 11 | 5 |
Gr
|
1 | 9 | 5 | 10 | 1 | 3 | 2 | 6 |
Sm
|
4 | 4 | 8 | 4 | 13 | 4 | 8 | 1 |
Gu
|
5 | 6 | 4 | 8 | 3 | 4 | 8 | 3 |
Of the 23 anaesthetist observers engaged in this study 13 reported upon at least 20 premedications. Among these the greatest number of cases studied was 71 by observer M and the least was 21 by WO. Two of the observers, Gn and Gr, seemed uniformly to underrate the effectiveness of all agents and So tended to do this. Sm appeared to overrate effectiveness. These individual differences are presented in chart II, where the satisfactory and the unsatisfactory reports of each of the 13 observers are plotted as percentages of all reports for each observer for each drug. The number of reports upon which chart II is based are shown in table 2. Some observers tended to be pessimistic or optimistic towards all pre-anaesthetic medication. We believe, nevertheless, that the double blind technique in this situation provided excellent experience for the residents and improved their observations and evaluations. It also afforded the supervisors some insight into the understanding and ability of the residents.
In the first series the word "sedation" was omitted from the record sheet. Factors such as sleep, alertness, excitability, restlessness, euphoria, and response to questioning were to be graded as unchanged, increased or decreased, respectively, from premedication observations made of these categories. At the end of the hour following injection of the drug, sedation was to be indicated as none, slight, moderate or deep. Apparently the anaesthetists found this difficult, and the record form was modified for the second and third series. The item "sedation" was inserted and was to be marked as none, slight, moderate or deep at each observation. Also at the end of the hour the patient was asked if he had felt any difference since receiving his injection. His reply was recorded and taken into account as one of the factors in evaluation.
The number of patients reported to be moderately, slightly or not sedated by each agent in each series is shown in table 3. On this basis both oxymorphone and anileridine appeared to produce more sedation; at the higher dose. However, morphine too was reported as producing more sedation; at least there were fewer patients in whom no sedation was noted in the third series.
An alternative method of comparing the sedation produced by the several agents is shown in table 4. Because of the difference noted above in the record sheets this method is applicable only to series II and III. The anaesthetist was asked to record the presence and degree of sedation of each patient on five successive occasions after each pre-anaesthetic injection. Summing these individual observations of none, slight or moderate sedation; as has been done in table 4, has the advantage of bringing into the picture the element of duration of a sedative effect, as well as its presence and degree per patient. Again we find that there was a difference in the amount of sedations reported in the third series. In the second series, morphine seemed to produce no more sedation than was noted after the placebo, whereas the sedative effect of oxymorphone and anileridine was greater than that of morphine or the placebo. In the third series, however, morphine, as well as the other two drugs, was distinctly better than the placebo in the production of sedation, but oxymorphone and anileridine were hardly better than morphine, even though the dose of oxymorphone and anileridine had been increased by a third.
Another indication of the similarity of the sedative effect of each of the three narcotics is shown in table 5. In most cases in which general anaesthesia was employed sodium pentothal was given intravenously in induction. Table 5 summarizes the data available with respect to the pentothal dosage. The average per patient was very nearly the same when morphine, oxymorphone or anileridine was the pre-anaesthetic medication and less than was required when a placebo had been given. Also the proportion of doses in excess of 500 mg was similar for each of the narcotics and again definitely less than for the placebo cases.
None of the patients in this study were considered to be deeply or oversedated. Drowsiness was noted occasionally (see table 6) but the patients remained co-operative.
Table 6 lists the side effects noted with the four agents during the pre-anaesthetic hour of observation. Each of the narcotics caused significantly more side effects than the placebo, and a few differences among them are noteworthy. Local reactions, a wheal erythema or flare, at the site of injection were seen most often after morphine. Dizziness was reported 11 times after oxymorphone, 9 times after anileridine and 5 times after morphine. A feeling of euphoria was noted 10 times after oxymorphone, 4 times after morphine and only once after anileridine. Respiratory depression of a degree to cause the anaesthetist some concern was noted ten times, 6 times after oxymorphone and 4 times after anileridine. Also, hypotension of rather marked degree, apparently associated with drug action, was reported twice, once after morphine and once after anileridine.
Placebo |
Morphine |
Oxymorphone |
Anileridine |
|||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Series |
I |
II |
III |
I |
II |
III |
I |
II |
III |
I |
II |
III |
Dose, mg/60 kg
|
8 | 10 | 10 | 1.0 | 1.0 |
1..33
|
25 | 25 | 33 | |||
Number of patients
|
54 | 59 | 56 | 53 | 60 | 56 | 54 | 60 | 56 | 56 | 59 | 56 |
None
|
27 | 35 | 35 | 15 | 34 | 16 | 9 | 21 | 16 | 13 | 26 | 7 |
Slight
|
6 | 18 | 16 | 5 | 17 | 26 | 11 | 24 | 20 | 11 | 23 | 27 |
Moderate
|
4 | 6 | 5 | 7 | 9 | 14 | 9 | 15 | 20 | 6 | 10 | 22 |
Not reported
|
17 | 0 | 0 | 26 | 0 | 0 | 25 | 0 | 0 | 26 | 0 | 0 |
Percentage not sedated
|
73.0 | 59.3 | 62.5 | 55.6 | 56.7 | 28.6 | 31.0 | 35.0 | 28.6 | 43.3 | 44.1 | 12.5 |
Placebo |
Morphine |
Oxymorphone |
Anileridine |
|||||
---|---|---|---|---|---|---|---|---|
Series |
II |
III |
II |
III |
II |
III |
II |
III |
None
|
237=75.2%
|
224=80.0%
|
210=75.0%
|
153=54.6%
|
183=61.6%
|
145=51.8%
|
200=67.8%
|
132=47.1%
|
Slight
|
56 = 17.7%
|
48 = 17.1%
|
61 = 21.8%
|
93 = 33.2%
|
87 = 29.0%
|
89 = 31.8%
|
72 = 24.4%
|
108 = 38.6%
|
Moderate
|
22= 6.9%
|
8= 2.8%
|
9= 3.2%
|
34=12.1%
|
30=10.0%
|
46=16.4%
|
23= 7.8%
|
40=14.3%
|
Placebo |
Morphine |
Oxymorphone |
Anileridine |
|
---|---|---|---|---|
Number of patients
|
53 | 54 | 40 | 42 |
Average dose, mg
|
481 | 408 | 400 | 412 |
Range of dosage
|
100-1,160
|
80-1,200
|
100-1,000
|
100-1,400
|
Number of doses:
|
||||
200 mg or less
|
12 | 18 | 13 | 12 |
500 mg or less
|
22 | 16 | 13 | 11 |
The over-all incidence of side effects, excluding drowsiness - which in this situation probably should be considered advantageous - was least after anileridine and slightly greater after oxymorphone than after morphine. The number of patients for whom no side effects were reported was greatest after morphine and least after oxymorphone. In both respects the differences were not great.
The incidence of changes in blood pressure, both systolic and diastolic, after the pre-anaesthetic medications is summarized in table 7. The differences in systolic pressure were slightly greater for oxymorphone than for morphine or anileridine, but for each of the narcotics the changes were not greatly different from those after placebo, except for the less frequent occurrence with the latter of decreases in pressure of 20 mm Hg or more. Very likely a great part of the apparent decreases in blood pressure recorded occurred because the initial readings were above usual levels for the individuals in the quiet state accompanying the exciting effect of the operating room situation. This should diminish as the patient became accustomed to the new situation, assisted by the quieting effect of the drugs. For example, after placebo a fall in systolic pressure of 20 mm Hg or more was reported 21 times - average fall 22 mm. In 13 of these cases premedication was judged to be unsatisfactory with no or inadequate sedation. After oxymorphone a fall of 20 mm or more was reported 45 times, average fall 25 mm. In 17 of these cases the rating was unsatisfactory with no or inadequate sedation. The slightly greater effect of oxymorphone on systolic pressure might be due to its quieting effect. The same could be said of the effect of morphine and anileridine. However, the anaesthetists complained twice of a hypotensive effect, once after 8 mg of morphine and once after 25 mg of anileridine. A hypotensive effect beyond what might be expected from a quieting effect alone was apparent from the blood pressure readings in a number of other cases, although not commented upon specifically by the anaesthetist (see table 8). In some, but not all of these cases, the pressures were probably not basal initially.
The changes in diastolic blood pressure were much alike in incidence and degree after each of the three narcotics and differed only slightly from the changes seen when a placebo was given (see table 7).
Placebo |
Morphine |
Oxymorphone |
Anileridine |
||||
---|---|---|---|---|---|---|---|
Dose, mg/60 kg
|
8 | 10 | 1.0 | 1.33 | 25 | 33 | |
Number of patients
|
169 | 53 | 116 | 114 | 56 | 115 | 56 |
None
|
155=91.7%
|
31=58.5%
|
81=78.4%
|
77=67.5%
|
24=42.9%
|
77=67.0%
|
31 =55.3%
|
Drowsiness
|
12 | 12 | 15 | 22 | 16 | 24 | 18 |
Dizziness
|
0 | 2 | 3 | 5 | 6 | 6 | 3 |
Itching
|
0 | 4 | 4 | 3 | 0 | 3 | 0 |
Euphoria
|
0 | 3 | 1 | 8 | 2 | 1 | 0 |
Local reaction
|
0 | 8 | 11 | 3 | 1 | 2 | 1 |
Nausea
|
1 | 4 | 2 | 1 | 2 | 1 | 1 |
Vomiting
|
0 | 0 | 1 | 0 | 1 | 0 | 1 |
Sweating
|
0 | 1 | 2 | 1 | 4 | 1 | 0 |
Dry mouth
|
0 | 1 | 3 | 3 | 3 | 3 | 2 |
Headache
|
1 | 2 | 0 | 1 | 1 | 2 | 1 |
Grogginess
|
0 | 1 | 0 | 4 | 1 | 1 | 3 |
Difficulty in focusing eyes
|
0 | 0 | 0 | 0 | 0 | 1 | 0 |
Numbness or feeling of heaviness
|
0 | 0 | 0 | 0 | 1 | 0 | 1 |
Paraesthesia
|
0 | 0 | 0 | 0 | 0 | 0 | 1 |
Respiratory depression
|
0 | 0 | 0 | 1 | 5 | 1 | 3 |
Hypotension
|
0 | 1 | 0 | 0 | 0 | 1 | 0 |
TOTAL
|
14 | 39 | 42 | 52 | 43 | 47 | 36 |
Placebo |
Morphine |
Oxymorphone |
Anileridine |
|
---|---|---|---|---|
Number of patients
|
169 | 169 | 169 | 171 |
Systolic pressure
|
||||
No change or a variation of
|
||||
less than 10 mm Hg
|
49 | 44 | 38 | 42 |
Variation of 10 mm Hg Inc
|
35 | 38 | 32 | 44 |
or more Dec.
|
85 | 87 | 99 | 85 |
Variation of 20 mm Hg Inc.
|
7 | 9 | 11 | 9 |
or more Dec.
|
32 | 35 | 43 | 31 |
Variation of 30 mm Hg Inc
|
0 | 3 | 3 | 1 |
or more Dec.
|
7 | 13 | 14 | 8 |
Diastolic pressure
|
||||
No change or a variation of
|
||||
less than 10 mm Hg
|
82 | 71 | 69 | 75 |
Variation of 10 mm Hg Inc
|
30 | 31 | 32 | 24 |
or more Dec.
|
57 | 67 | 68 | 72 |
Variation of 20 mm Hg Inc.
|
5 | 3 | 5 | 6 |
or more Dec.
|
11 | 13 | 13 | 11 |
Drug and dose |
Initial blood pressure |
Maximal fall |
Time of maximal change (minutes) |
Pressure 60 minutes after injection |
Degree of sedation reported |
---|---|---|---|---|---|
Placebo
|
160/100
|
140/70
|
10 |
140/80
|
None
|
Placebo
|
160/70
|
140/40
|
30 |
150/50
|
None
|
Placebo
|
180/70
|
135/68
|
45 |
140/70
|
None
|
Morphine, 8 mg
|
120/70
|
50/40
|
10 |
100/70
|
Satisfactory
|
Morphine, 8 mg
|
220/110
|
174/100
|
30 |
185/100
|
Unsatisfactory
|
Morphine, 10 mg
|
185/95
|
140/75
|
20 |
140/75
|
None
|
Oxymorphone, 1.0 mg
|
160/60
|
115/55
|
60 |
115/55
|
Satisfactory
|
Oxymorphone, 1.0 mg
|
165/100
|
130/84
|
30 |
150/100
|
Satisfactory
|
Oxymorphone, 1.0 mg
|
138/70
|
100/64
|
60 |
100/64
|
Unsatisfactory
|
Oxymorphone, 1.0 mg
|
180/80
|
135/80
|
60 |
135/80
|
Moderate
|
Oxymorphone, 1.33 mg
|
126/74
|
84/54
|
20 |
110/70
|
Moderate
|
Oxymorphone, 1.33 mg
|
176/100
|
144/88
|
45 |
172/92
|
Slight, satisfactory
|
Oxymorphone, 1.33 mg
|
130/70
|
90/50
|
60 |
90/50
|
None
|
Anileridine, 25 mg
|
120/80
|
80/50
|
60 |
80/50
|
Slight, satisfactory
|
Anileridine, 25 mg
|
170/70
|
130/60
|
45 |
140/70
|
None
|
Anileridine, 25 mg
|
150/70
|
110/70
|
60 |
110/70
|
None
|
Anileridine, 25 mg
|
130/80
|
95/65
|
60 |
95/65
|
Slight, satisfactory
|
Anileridine, 25 mg
|
210/90
|
100/50
|
20 |
130/70
|
Slight, satisfactory
|
With all premedications a decrease in heart rate was noted more often than an increase (see table 9). The changes after morphine were very similar to those after a placebo, bur the incidence of a decrease in rate was slightly greater afteoxymorphone or anileridine. In one case who received morr phine the heart rate declined briefly to 50. In several other cases with each of the narcotics the anaesthetist commented on a bradycardia and said that this was the indication for the administration of atropine, but in none of these patientt was the reported rate during the hour of pre-anaesthetic observation below 60.
Number of patients |
Decreased heart rate |
Increased heart rate |
|
---|---|---|---|
Placebo
|
169 |
57 (33.7%)
|
30 (17.8%)
|
Morphine
|
169 |
54 (32.0%)
|
31 (18.4%)
|
Oxymorphone
|
169 |
75 (44.2%)
|
40 (23.5%)
|
Anilcridine
|
171 |
70 (40.9 %)
|
38 (22.2 %)
|
A decrease of four or more per minute was recorded in some cases after the placebo, more frequently after morphine and anileridine and most frequently after oxymorphone (see table 10). The rate decreased to 12, never below that figure, in five cases to whom a placebo was given. It decreased to 12 or lower in 18 cases and to 10 or lower in 4 cases (once to 6, once to 8 per minute) when morphine was given. It decreased to 12 or lower in 10 cases and to 10 or lower in 4 cases (once to 7 and once to 9) after anileridine. It decreased to 12 or lower in 22 cases and to 10 or lower in 9 cases (4 times to 8 per minute) after oxymorphone. The effect on repiratory rate was definitely greater after the larger doses of anileridine and oxymorphone. The anaesthetists characterized the effects as respiratory depression ten times, in six to whom the drug given was oxymorphone, in four when anileridine had been given. The depression was not judged severe enough in any case to require an antagonist during the pre-anaesthetic period, but in two patients apnea occurred during induction, in both instances attributed to the preanaesthetic drug (oxymorphone).
Placebo |
Morphine |
Oxymorphone |
Anileridine |
||||
---|---|---|---|---|---|---|---|
Dose, mg/60 kg
|
8 | 10 | 1.0 | 1.33 | 25 | 33 | |
Number of cases
|
169 | 53 | 116 | 114 | 56 | 115 | 56 |
Cases showing decrease of 4 or more/min
|
27 | 12 | 30 |
.36
|
30 | 22 | 22 |
Percentage of cases showing decrease
|
16.0 | 22.6 | 25.8 | 31.4 | 53.4 | 18.2 | 39.2 |
Cases showing decrease to 12/min. or below .
|
5 | 9 | 9 | 6 | 16 | 3 | 7 |
Cases showing decrease to 10/min. or below
|
0 | 1 | 3 | 3 | 5 | 1 | 3 |
The incidence of minimal secretion (drying effect) was greater for each of the narcotics than for placebo, and anileridine was slightly better than morphine or oxymorphone in this respect (see table 11). Some of the patients were given atropine at the end of the pre-anaesthetic period most commonly because secretions were excessive and troublesome. This occurred 33 times after placebo, 29 times after morphine, 32 times after oxymorphone and 27 times after anileridine.
TABLE 11 Effect of pre-anaesthetic medications on respiratory tract secretions
Placebo |
Morphine |
Oxymorphone |
Anileridine |
|||||
---|---|---|---|---|---|---|---|---|
Secretions |
Number of patients |
Percentage |
Number of patients |
Percentage |
Number of patients |
Percentage |
Number of patients |
Percentage |
Minimal
|
54 | 40.3 | 72 | 54.9 | 69 | 57.0 | 83 | 62.9 |
Moderate
|
41 | 30.6 | 39 | 29.0 | 34 | 28.1 | 34 | 25.8 |
Marked
|
39 | 29.1 | 20 | 15.2 | 18 | 14.8 | 15 | 11.3 |
Not reported
a
|
35 | 38 | 49 | 39 |
a Most of the cases not reported received regional or spinal anaesthesia.
The nature of the premedication appeared to have little influence on the need for postoperative analgesic medication or on the time when this was required. Such differences as were noted favoured morphine slightly, since the number of patients to whom analgesic medication was given within three hours after operation was less and the average time to such medication was slightly greater with morphine than with the other agents (see table 12).
Placebo |
Morphine |
Oxymorphone |
Anileridine |
||||
---|---|---|---|---|---|---|---|
Dose, mg/60 kg
|
8 | 10 | 1.0 | 1.33 | 25 | 33 | |
None needed within 24 hours
|
26 | 4 | 21 | 18 | 12 | 14 | 11 |
Patients given analgesic in 3 hours or less after surgery
|
57 | 15 | 28 | 36 | 16 | 42 | 18 |
Average postoperative time to first dose of analgesic (minutes)
|
279 | 324 | 307 | 304 | 235 | 275 | 315 |
Not reported
|
15 | 6 | 1 | 4 | 0 | 4 | 1 |
Many factors can of course affect postoperative awakening time, and perhaps pre-anaesthetic medication is the least important. It could presumably play a role in so far as it reduced the amount of induction medication (pentothal) or the amount of anaesthetic agent, or both. It has been shown previously (table 5) that the amount of pentothal used was less when one of the narcotics was used as premedication than when this was a placebo. A parallel difference was shown in the postoperative awakening time (see table 13).
Placebo |
Morphine |
Oxymorphone |
Anileridine |
|
---|---|---|---|---|
Cases reported
|
100 | 105 | 92 | 97 |
Average awakening time (minutes)
|
12.5 | 9.2 | 7.9 | 8.8 |
Awake immediately at end of procedure
|
34 = 34.0%
|
31 = 29.5%
|
33 = 35.9%
|
40 = 41.2%
|
Awake within 5 minutes
|
61 = 61.0%
|
69 = 65.5%
|
62 = 67.4%
|
70 = 72.2%
|
Awakening time 15 minutes or longer
|
25 = 25.0%
|
22 = 20.9%
|
16 = 17.3%
|
16 = 16.5%
|
Oxymorphone and anileridine were compared with morphine and a placebo. Each narcotic was superior to the placebo in its satisfactory rating, but the three were not materially different when administered in equi-analgesic dose. An increase of a third in the dosage of oxymorphone and anileridine increased their effectiveness, each having a greater sedative effect at the higher dose. The over-all incidence of side effects was least after anileridine and slightly greater after oxymorphone than after morphine. A reaction at the side of injection was seen most often after morphine. Euphoria and respiratory depression were reported most often after oxymorphone. A drying effect on secretions was slightly better with anileridine. An apparent mild hypotensive effect was reported after each of the narcotics and the placebo, probably owing in large part to initial pressures being elevated somewhat by the operating room situation, but contributed to by the quieting effect of the narcotics and in some instances representing specific drug action. As compared with placebo, the narcotics slightly reduced the amount of sodium pentothal required for induction and the average postoperative awakening time. Some anaesthetist observers tended to be generally pessimistic or optimistic in their evaluation of all preanaesthetic medications. The demonstration of this trend was a useful by-product of the investigation.
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002BEECHER, H. K.: The powerful placebo. J.A.M.A. 159: 1602-1606, 1955.
003COBLENTZ, A. & BIERMAN, H. R.: The analgesic properties of Numorphan (14-hydroxydihydromorphinone), New Eng. J. Med . 255: 694-698, 1956.
004DRIPPS, P,.. D., ECKENHOFF, J. E. & VANDAM, L. D.: Introduction to anesthesia: Principles of safe practice, Philadelphia, 1957, W.B.Saunders.
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006ECKENHOFF, J. E., HELRICH, M., HEDGE, M.J.O. & JONES, R. E.: Respiratory hazards of opiates and other narcotic analgesics. Surg. Gynec. Obstet . 101: 701-708, 1955.
007EDDY, N. B. & LEE, L. E. Jr.: The analgesic equivalence to morphine and relative side action liability of oxymorphone . J. Pharmacol Exp. Ther . 125: 116-121, 1959.
008EDDY, N.B.., LEE, L. E. Jr. & HARRIS, C. A.: The rate of development of physical dependence and tolerance to analgesic drugs in patients with chronic pain. Bull. Narcotics , XI: No. 1, 3-17, 1959.
009LASAGNA, L. & BEECHER, H. K.: The optimal dose of morphine, J.A.M.A. 156: 230-234, 1954.
010SAMUELS, M. L., STEHLIN, J. S., DALE, S. C. & HOWE, C. D.: A critical evaluation of Numorphan, Southern Med. J . 52: 207-210, 1959.
011THERIEN, R. C., LEE, L. W., MALASHOCK, E. M. & DAVIS, N. B.: Anileridine hydrochloride - its clinical use as an analgesic and sedative, J.A.M.A. 168: 2098-2100, 1958.