Pre-anaesthetic medication. Phenazocine and levo phenacylmorphan compared with morphine, pethidine and a placebo

Sections

Procedure
Results
Side Effects
Secretions
Changes in the Pupil
Changes in Vital Signs
Need for Postoperative Analgesic
Summary

Details

Author: Benjamin J. CILIBERTI ,, Phyllis SHROFF , , Nathan B. EDDY ,
Pages: 41 to 51
Creation Date: 1964/01/01

Pre-anaesthetic medication. Phenazocine and levo phenacylmorphan compared with morphine, pethidine and a placebo

M.D., Benjamin J. CILIBERTI [ 1] ,
M.D., Phyllis SHROFF [ 2] ,
M.D., Nathan B. EDDY [ 3] ,

In a previous report, Ciliberti & Eddy (3) described the use of anileridine, oxymorphone, morphine and placebo as pre-anaesthetic medication in a general hospital set-up. The conditions of administration were double blind, and the observers were the anaesthesia residents. While two dose-levels of each drug were employed, the purpose was not so much to establish a dose-effect relationship as to determine whether or not a difference between the drugs employed and placebo, between the several drugs, or definite advantage or disadvantage for any agent, could be recognized. It was noted that some anaesthetists tended to be generally pessimistic or optimistic in their evaluation of all preanaesthetic medication. Nevertheless, under the conditions of the study each narcotic was superior to the placebo in its satisfactory rating, but the three were not materially different when administered in equi-analgesic dose.

The study of pre-anaesthetic medication has been continued and extended to the surgical service of another Veterans Administration hospital, again comparing two new agents, phenazocine [ 4] and levophenacylmorphan, [ 5] with the usual standard, morphine, and with pethidine and a placebo. The procedure followed was essentially the same as in the earlier study. Anaesthesia residents again made the observations and the record form was very similar (see chart 1). The observations, as indicated on the chart, were made prior to the administration of the particular agent and at intervals through the period of an hour. Then the anaesthetist entered on the chart his judgement of the result and his reason for that judgement.

Procedure

Each agent was supplied to each hospital in 10-ml vials under 12 code numbers in such concentration that the desired dose was obtained by 0.01 ml for each two pounds body weight. The agents and concentrations were:

 
mg/ml
Phenazocine hydrobromide
3.0
Levophenacylmorphan methane sulfonate
1.5
Morphine sulfate
20.0
Pethidine hydrochloride
100.0
Placebo
[ 6]

Phenazocine and levophenacylmorphan have similar pharmacologic properties and similar analgesic potency, taking into account that the former is a racemate and that its analgesic effect is brought about by its levocomponent (Fraser & Isbell, 5; Sadove, Schiffrin & Heller, 11; and Lasagna [ 7] ). The dose of morphine was increased for comparison with the 10 mg optimal dose (Lasagna & Beecher, 7) of the previous study and the dose of pethidine was that shown to be equi-analgesic with I0 mg of morphine (Lasagna & Beecher, 8).

The drugs were used in random sequence except that when a coded vial was opened its contents were used in successive patients until exhausted. Since the anaesthetist did not give the injection, he was not aware when the doses for two patients were from the same vial. It was, in addition, unusual for the same anaesthetist to be concerned with two successive patients. All doses were given intramuscularly.

Full size image: 165 kB

Results

The results of the study are summarized in table 1 for the New York cases, and in table 2 for those observed in California, in percentage figures for satisfactoriness, reported sedation, etc. Other details will be given in subsequent tables.

TABLE 1

Percentage of satisfactoriness and of related factors with pre-anaesthetic medications, New York cases

 
Phenazocine
Levophenacyl morphan
Morphine
Pethidine
Placebo
Dose mg/ml (0.01 ml/2 lb)
3.0 1.5 20.0 100.0 1.0ml
Number of patients
124 121 122 124 123
Satisfactory
64.5 68.6 83.6 78.2 39.0
Sedation:
         
None
24.2 24.8 10.6 12.9 43.1
Slight
43.5 43.0 36.1 47.6 39.0
Moderate
32.3 32.2 53.3 39.5 17.9
Time of onset, min
28.2 29.2 27.4 27.8 29.3
Sleep and/or drow- siness
51.6 50.4 62.3 62.9 26.0
Relaxation
46.0 46.4 54.1 52.4 37.4
Preoperative pain:
         
Incidence
15.3 16.5 13.1 14.5 13.8
Relieved
86.6 90.0 93.7 66.6 52.9

TABLE 2

Percentage of satisfactoriness and of related factors with pre-anaesthetic medications, California cases

 
Phenazocine
Levophenacyl morphan
Morphine
Pethidine
Placebo
Dose mg/ml (0.01 ml/2 lb)
3.0 1.5 20.0 100.0 1.0ml
Number of patients
123 129 123 121 129
Satisfactory
58.5 60.0 70.7 64.6 21.7
Sedation:
         
None
21.1 29.4 13.8 15.7 69.8
Slight
66.6 62.2 77.2 66.1 28.7
Moderate
12.2 8.4 9.0 18.2 1.5
Time of onset, min
44.0 46.0 47.3 40.3 49.4
Sleep and/or drowsiness
29.3 62.8 67.4 71.9 24.8
Relaxation
52.0 48.1 52.8 52.9 37.2
Preoperative pain:
         
Incidence
29.3 25.6 28.4 21.6 23.2
Relieved
100.0 87.8 100.0 88.5 39.6

For all medications, satisfactoriness was rated higher by the New York than by the California observers, and for both groups all narcotics were rated better than the placebo. Also for both groups the percentage satisfactoriness was a little less for phenazocine and levophenacylmorphan than for morphine or pethidine. The difference is less, however, than between any narcotic and the placebo. The satisfactoriness of the narcotics compared with the placebo and compared with each other was paralleled by the sedation, drowsiness and relaxation reported, except that in the California cases phenazocine produced as much drowsiness and relaxation as morphine or pethidine. At the New York hospital the larger dose of morphine used in the present series produced more sedation and was rated more satisfactory (83.6 vs. 58.6%) than the dose used in the previous series (Ciliberti & Eddy, 3). A higher incidence of side effects with the larger dose of morphine offset its apparent advantage.

The number of patients receiving each medication was very nearly the same in New York and in California. The diagnoses, or operative procedures undertaken, were similar per hospital and per drug, except that in California more prostatectomies and more orthopaedic procedures (except laminectomies) were carried out and in New York more abdominal and chest surgery and a greater number of laminectomies (see table 3). A significant difference at the two hospitals was a higher incidence of spinal anaesthesias in California, 60.4%, than in New York, 30.3%. However, a similar degree of satisfactoriness was reported generally for premedication for spinal and for general anaesthesia, with the same difference between the two hospitals previously noted for both types of anaesthesia (see table 4).

TABLE 3

Diagnosis or operative procedure per drug group. New York cases (col. 1); California cases (col. 2)

 
Phenazocine
Levophenacyl morphan
Morphine
Pethidine
Placebo
Hernia
19-32
27-40
29-26
25-31
23-28
Prostatectomy
6-35
5-32
6-25
6-24
8-32
Other genitourinary
5-10
3-5
8-10
11-15
5-17
Laparotomy:
         
Gastrectomy and/or vagotomy
14-2
13-0
15-2
19-2
11-1
Cholecystectomy
10-1
14-2
8-6
6-5
11-2
Other
18-7
14-3
7-3
13-3
16-0
Chest surgery
6-0
9-1
3-0
2-1
7-1
Neurosurgery
         
Central nervous system
3-0
1-0
2-0
1-0
5-0
Sympathectomy
5-1
5-2
3-5
2-1
3-1
Peripheral nerve repair
2-1
4-0
3-0
3-1
0-0
Laminectomy
10-1
7-0
8-1
14-1
8-1
Orthopaedic
0-6
1-11
1-11
0-9
3-6
Plastic surgery
2-4
0-3
1-5
0-1
0-4
Tumors, miscellaneous
2-0
1-4
2-0
0-2
0-2
Varicose veins
5-2
1-2
7-5
3-2
2-2
Haemorrhoidectomy
4-11
5-6
7-6
1-6
7-6
Carcinoma of rectum
4-0
1-0
2-1
0-0
1-0
Face and neck dissection
2-0
2-1
4-1
4-0
5-0
Mastoidectomy
0-2
0-4
0-1
0-4
0-2
Thyroidectomy
2-0
3-1
1-0
2-0
0-0
Vascular surgery
2-0
2-0
1-0
5-1
1-0
Miscellaneous minor procedures
1-3
2-2
2-6
3-4
4-7
Surgery cancelled after premedication period
2-5
1-10
2-9
4-8
3-17

Another difference should be noted, which may account in part for the lower percent of statisfactoriness reported for the California cases. Because of difficulties in operating room scheduling there was a greater lapse of time between the giving of the premedication and the beginning of the anaesthesia in the California cases (see table 5). The anaesthetist was expected to make his judgement of the satisfactoriness of the premedication an hour after it had been given, but where there was considerable delay he must lack the responsiveness of the patient and the smoothness of induction of anaesthesia as parameters for his judgement. He sometimes commented on waning of the effect of the premedicant when anaesthesia was started. The differences in pre- medication time at the two hospitals occurred similarly with all premedications.

TABLE 4

Incidence of spinal and general anaesthesias and percentage of satisfactoriness of premedication for each

 

New York patients

California patients

Medication and anaesthesia
Sat.
Unsat.
% sat
Sat
Unsat.
% sat.
Phenazocine
           
Spinal
22 13 62.9 54 30 63.3
General
55 26 67.9 15 9 62.5
Levophenacylmor-
           
phan
           
Spinal
18 16 52.9 46 35 56.8
General
62 20 75.6 16 14 53.3
Morphine
           
Spinal
35 7 83.3 50 14 78.1
General
59 13 81.9 25 12 67.6
Pethidine
           
Spinal
28 8 77.7 44 27 62.0
General
65 16 80.2 22 12 64.7
Placebo
           
Spinal
16 23 41.0 24 54 30.8
General
28 49 36.8 3 20 13.0

TABLE 5

Time elapsing between giving of premedication and beginning of anaesthesia

 

90 minutes or less Average incidence

90-150 minutes Average incidence

>150 minutes Average incidence

Total Average

 
Minutes
%
Minutes
%
Minutes
%
Minutes
New York cases
             
Phenazocine
74 73.5 105 24.8 205 1.6 84
Levophenacylmorphan
74 75.4 109 23.0 167 1.6 84
Morphine
75 68.9 110 30.7 170 0.8 87
Pethidine
75 75.9 105 22.3 165 1.8 84
Placebo
75 79.3 106 20.0 170 0.8 82
Total
74 74.6 107 24.0 177 1.8 84
California cases
             
Phenazocine
80 26.5 118 59.0 182 14.5 117
Levophenacylmorphan
73 29.1 117 43.3 184 27.5 122
Morphine
77 31.0 109 54.3 191 14.7 111
Pethidine
79 26.7 118 48.2 200 25.0 128
Placebo
77 37.8 118 50.4 171 11.7 109
Total
77 30.2 116 51.0 178 18.7 116

Pre-anaesthetic medication 45

The age distribution of the patients in this study and the per cent satisfactoriness of the several agents for the four age groups are shown in table 6. The figures do not suggest a difference in effectiveness with age.

As in the previous study, there is indication that some anaesthetists tended to be over-enthusiastic and others over-pessimistic in their judgement of the satisfactoriness of the various medications in comparison with the judgement of the group as a whole. The records of all anaesthetists who participated in the study of each agent are presented in table 7. In the New York group, J. G. always, and A. S. for three of the five medications, overestimated, while Gi and B. C. tended to underestimate satisfactoriness. The number of patients observed that the last two are small, and the result may be coloured accordingly. For the California group, J. C. over-estimated for all agents except morphine, and H. K. under-estimated for all except pethidine. Both of these investigators were among those who saw a fair number of patients with each agent.

Side Effects

Side effects reported with the five medications in the two groups of cases are listed with their incidence in table 8. A few points are worth noting. A local reaction as a wheal and/or flare occurred most frequently with morphine. Curiously burning or stinging at the site of injection was noted very frequently in 104 of 129 patients in California, who received the placebo injection and very infrequently otherwise in any group, a finding for which we have no explanation, especially since the solution which was used as a placebo was the solvent for each of the narcotics. Nausea was noted with about equal frequency for each of the narcotics, but vomiting occurred four times after morphine, three times after pethidine, twice after levophenacylmorphan, and not at all after phenazocine. Nausea present before premedication was said to have been relieved within twenty minutes after injection in seven patients, three times after morphine, twice after pethidine and once each after phenazocine and levophenacylmorphan. Side effects as a whole occurred less frequently after phenazocine and levophenacylmorphan than after morphine and pethidine. Hypotension as a side effect will be discussed in connexion with observed changes in vital signs.

TABLE 6

Age distribution and satisfactoriness of premedication per age group

Age group
Phenazocine
Levo-phenacyl-morphan
Morphine
Pethidine
Placebo
Age incidence
 
S/U
S/U
S/U
S/U
S/U
Per cent
30 or under
           
New York
1/3
7/3
8/2
5/1
4/2
5.9
California
2/3
4/5
4/2
5/5
1/2
5.3
Total
3/6
11/8
12/4
10/6
5/4
5.6
Per cent satisfactory
33.3 57.9 75.0 62.5 55.6  
31-50
           
New York
29/19
29/8
43/10
40/8
23/36
39.9
California
22/20
18/12
26/14
19/13
6/35
30.0
Total
51/39
47/30
69/24
59/21
29/71
34.9
Per cent satisfactory
56.6 61.0 74.2 73.8 29.0  
51-70
           
New York
44/28
44/25
46/7
33/20
17/31
48.6
California
31/22
40/32
49/15
43/24
16/47
51.4
Total
75/50
84/57
95/22
76/44
33/78
50.0
Per cent satisfactory
60.0 59.5 81.2 63.3 30.0  
Over 70
           
New York
6/4
3/2
5/1
3/3
4/6
6.0
California
15/6
15/3
8/5
10/0
5/16
13.4
Total
21/10
18/5
13/6
13/3
9/22
9.7
Per cent satisfactory
67.7 78.3 68 4 81.3 29.0  
Per cent satisfactory, all cases
58.7 61.2 77.1 77.6 30.3  

TABLE 7

Judgement of the satisfactoriness of premedications as reported by individual anaesthetists,

 

Phenazocine

Levo-phenacyl-morphan

Morphine

Pethidine

Placebo

Anaesthetist
Sat.
Unsat.
%sat.
Sat.
Unsat.
%sat.
Sat.
Unsat.
%sat
Sat.
Unsat.
%sat.
Sat.
Unsat.
% sat.
New York group
                             
B. C.
3 3 50.0 3 4 42.8 5 1 83.3 8 2 80.0 0 6 0.0
G. T.
4 2 66.6 10 5 66.6 12 2 85.7 7 1 87.5 2 7 22.2
R. G.
11 6 64.7 8 5 61.5 10 5 66.6 9 2 81.8 5 8 38.2
E. M.
4 2 66.6 5 1 83.3 8 3 72.7 6 4 60.0 6 2 75.0
H. G.
8 7 53.3 8 2 80.0 9 0 100.0 6 3 66.6 2 8 20.0
A. S.
12 7 63.2 19 5 79.2 14 3 82.3 17 1 94.4 12 6 66.6
D. L.
3 0 100.0 6 1 85.7 3 0 100.0 3 1 75.0 1 2 33.3
O. S.
9 4 69.2 7 3 70.0 15 2 88.2 13 5 72.2 6 5 54.5
J. G.
14 3 82.3 15 1 93.8 15 0 100.0 16 1 94.1 7 7 50.0
S. F.
4 5 44.4 2 6 25.0 9 0 100.0 6 1 85.7 5 9 35.7
Gi.
2 3 40.0 0 4 0.0 1 3 25.0 3 3 50.0 0 6 0.0
E. F.
6 3 66.6 5 2 71.4 5 1 83.3 3 2 60.0 3 4 42.8
Sm.
7 2 77.7 2 4 33.3 5 0 100.0 5 1 83.3 3 5 37.5
All cases
    64.5     68.6     83.6     78.2     39.0
California group
      6 11 35.3 9 5 64.3 12 2 71.4 1 17 5.5
H. K .
10 8 55.5 13 2 86.6 8 3 72.7 22 2 91.6 11 9 55.0
J. C.
24 2 92.3 5 4 55.5 1 3 25.0 0 4 0.0 2 4 33.3
G. S.
8 2 80.0 8 4 66.6 8 4 66.6 3 6 33.3 1 10 9.0
J. V.
3 3 50.0 4 2 66.6 4 1 80.0 3 6 33.3 0 5 0.0
E. C.
4 6 40.0 0 3 0.0 1 3 25.0 2 5 28.6 0 5 0.0
J. B.
1 6 14.6 5 4 55.5 13 3 81.2 13 3 81.2 5 7 41.6
R. S.
7 10 41.2 5 10 33.3 9 3 75.0 5 3 62.5 3 11 21.4
R. V.
7 5 58.3 10 6 62.5 8 4 66.6 6 2 75.0 1 20 4.8
J. M.
1 4 25.0 3 1 75.0 7 1 87.5 6 3 66.6 1 3 25.0
R. F.
4 2 66.6 5 0 100.0 11 1 91.6 5 3 62.5 1 3 25.0
D. C.
1 1 50.0                        
All cases
    58.5     60.0     70.7     64.6     21.7

Secretions

The anaesthetists were asked to judge the secretions in mouth and throat as minimal (less than normal), moderate (normal or greater than normal, but not troublesome), or marked (excessive and troublesome to the anaesthetist). They reported accordingly for the majority of patients, failing to do so for some of the cases of spinal anaesthesia where secretions were of no concern. The results are summarized in table 9. Pethidine and morphine appear to have had some drying effect, probably a little greater for the former, consistent with the incidence of dry mouth noted after pethidine in the listing of side effects. Levophenacylmorphan probably had some drying effect also, about like that of morphine, but phenazocine did not differ from placebo in this respect. Atropine was administered to check secretions in some cases after all premedications and the frequency of its use was not entirely consistent with the reported incidence of marked (troublesome) secretions. The former exceeded the latter with all premedications except phenazocine, and the discrepancy was greatest for pethidine and morphine.

Changes in the Pupil

The pupil-size was measured at each observation against a pupilometer, a card with a series of black dots differing in diameter by 0.5 mm. The results are shown in table 10. The unusual finding is the degree of pupillary constriction noted when only a placebo had been given. Otherwise morphine caused the most, phenazocine and levophenacylmorphan similar butsomewhat less, and pethidine the least constriction.

Pre-anaesthetic medication 47

TABLE 8

Side effects

 

Phenazocine

Levo-phenacyl-morphan

Morphine

Pethidine

Placebo

 
N.Y.
Cal.
N.Y.
Cal.
N.Y.
Cal.
N.Y.
Cal.
N.Y.
Cal.
Number of patients
124 123 121 129 122 123 124 121 123 129
None
67 75 70 86 32 69 51 71 79 25
Local reaction:
                   
Wheal and/or flare
3 2 4 2 30 5 7 5    
Burning or stinging
  4     8 13   2   104
Nausea
1 9 1 7 2 8 2 10    
Vomiting
    1 1   4   3    
Dizziness
4 9 1 13 3 9 6 18   1
Lightheaded
  1   1 1          
Drymouth
45 3 43 4 37 7 65 5 39 1
Euphoria.
3 9 2 2 4 6 4 8    
Grogginess
1 2   8   4 2 6 3  
Tiredness
        3   1      
Heaviness
1   1   1   1 1    
Numbness
                1  
Sweating.
5 12 3 5 4 10 1 22 1 1
Feeling of warmth
  8   8   6   16   2
Hot flashes
1 1           1    
Itching
2 2     2 2 1      
Headache
1 4   1 2         3
Hiccup
    1              
Conjunctival injection
                   
Visual disturbance
1 1                
Nystagmus
              1    
Confused
              2    
Abdominal pain
                   

TABLE 9

Effect of premedications on secretions

 

New York

California

Total

New York

California

Total

New York

California

Total

 
Incidence
%
Incidence
%
Incidence
%
Incidence
%
Incidence
%
Incidence
%
Incidence
%
Incidence
%
Incidence
%
 
Phena-zocine
         
Levo-phenacyl-morphan
         
Morphine
         
Minimal
39 36.1 80 72.7 119 54.6 66 70.2 78 67.2 144 68.6 72 77.4 65 57.5 137 66.5
Moderate
51 47.2 26 23.6 77 35.3 21 22.3 26 22.4 47 22.4 19 20.4 38 33.6 57 27.6
Marked
18 16.7 4 3.6 22 10.1 7 7.4 12 10.3 19 9.0
+2
2.2 10 8.8 12 5.8
Not reported
16   13       27   13   40   29   10   39  
Atropine given for excessive secretion
        18           26           20  
 
Pethidine
         
Placebo
                     
Minimal
63 61.2 87 79.8 150 75.0 50 51.6 62 58.5 112 55.1            
Moderate
22 21.3 13 11.9 35 17.5 34 35.1 33 31.1 67 33.0            
Marked
6 5.8 9 8.2 15 7.5 13 13.4 11 10.4 24 11.8            
Not reported
33   12   45   26   23   49              
Atropine given for excessive secretion
        26           29              

TABLE 10

Changes in the size of the pupil

 

New York

California

Total

     

%

   

%

   

%

 
Phena-zocine
Reported
124     123     247    
Constricted
96   77.4 89   72.3 185   75.3
Constricted by: 1.0 mm. or more.
78   62.9 43   35.0 121   49.0
Initial diameter, mm
  3.34     3.17     3.26  
Minimal diameter, mm
  2.26     2.52     2.39  
Degree of constriction, per cent
  32.2     20.5     26.7  
 
Levo-phenacyl-morphan
Reported
120     128     248    
Constricted
98   81.6 89   69.5 187   75.4
Constricted by: 1.0 mm. or more
78   65.0 37   28.9 115   46.4
Initial diameter, mm
  3.22     3.05     3.13  
Minimal diameter, mm
  2.01     2.47     2.25  
Degree of constriction, per cent
  37.5     19.0     28.1  
 
Morphine
Reported
122     120     242    
Constricted
105   86.1 94   78.3 199   82.2
Constricted by: 1.0 mm. or more
98   80.3 45   37.5 143   59.1
Initial diameter, mm
  3.38     3.13     3.25  
Minimal diameter, mm
  3.08     2.45     2.26  
Degree of constriction, per cent
  38.5     21.7     30.5  
 
Pethidine
Reported
123     118     242    
Constricted
90   73.2 69   58.5 159   65.7
Constricted by: 1.0 mm. or more
71   57.7 23   19.5 94   38.8
Initial diameter, mm
  3.24     3.03     3.14  
Minimal diameter, mm
  2.26     2.58     2.41  
Degree of constriction, per cent
  30.3     14.8     23.2  
 
Placebo
Reported
122     127     249    
Constricted
74   66.5 47   37.0 121   48.6
Constricted by: 1.0 mm. or more
48   39.3 8   6.3 56   22.5
Initial diameter, mm
  3.17     3.07     3.11  
Minimal diameter, mm
  2.56     2.94     2.74  
Degree of constriction, per cent
  19.2     4.2     11.9  

Changes in Vital Signs

Blood pressure (table 11).- With any of the parameters examined phenazocine did not differ from placebo, and morphine and levophenacylmorphan were alike in their effect. Both were credited with producing more effect on systolic and diastolic blood pressure in incidence and degree than phenazocine or placebo, and each was reported to have produced a drop in blood pressure described-as a hypotensive episode in two cases. Pethidine had a greater effect on blood pressure, especially on diastolic blood pressure and in the production of hypotensive episodes (seven) than any of the other agents: The lack of effect of phenazocine on blood pressure in these cases is in accord with the findings of others on this point (Stephen & Macmillan, 12; Eckenhoff & Prevoznik, 4).

Heart rate (table 12).-The averages for degrees of change in heart rate after phenazocine or placebo on the one hand are very similar and those for the other three agents on the other hand are similar, and indicate a greater decrease in rate following the drug. The lowest individual rates were seen after morphine.

TABLE 11

Blood pressure changes after premedication

   
Phenazocine
Levo-phenacyl-morphan
Morphine
Pethidine
Placebo
Decrease in systolic B.P. a
Number
82 105 103 109 87
 
Per cent
33.2 42.0 42.0 44.5 34.5
Decrease in diastolic B.P b
Number
69 87 88 110 65
 
Per cent
23.0 34.8 35.9 44.9 25.8
Simultaneous decrease in systolic and
Number
33 57 55 70 35
diastolic pressures
Per cent
13.3 22.8 22.4 28.6 13.9
Peak decrease in systolic pressure of
Number
26 45 50 57 27
20 mm or more
Per cent
10.5 18.0 20.4 23.3 10.7
Peak decrease in systolic pressure of
Number
5 12 11 15 7
30 mm or more
Per cent
2.0 4.8 4.5 6.1 2.4

Details of cases described as hypotensive after premedication c

Patient number
Degree of sedation
Initial
10'
20'
30'
45'
60'
   
Phenazocine
         
None
             
   
Levo-phenacyl-morphan
         
265
Slight
230/130/72
168/110/68
160/110/68
220/130/68
210/130/68
192/120/60
573
Slight
120/ 80/78
110/ 70/74
74/ 48/84
80/ 50/54
74/ 48/84
84/ 50/84
   
Morphine
         
433
Slight
132/ 84/69
132/ 84/69
132/ 84/70
88/ 60/55
112/ 78/55
124/ 80/60
492
None
160/ 80/77
120/ 70/74
120/ 70/74
76/ 42/56
110/ 70/76
120/ 80/74
   
Pethidine
         
93
Moderate
190/100/72
190/100/72
160/ 80/68
130/ 80/66
126/ 84/66
134/ 90/70
330
Moderate
125/ 60/92
120/ 60/84
110/ 60/80
90/ 50/76
100/ 60/78
100/ 60/68
434
None
160/ 70/76
130/ 60/76
120/ 50/72
120/ 50/72
104/ 50/72
110/ 60/68
438
Slight
110/ 70/76
105/ 60/78
80/ 50/72
82/ 50/72
88/ 60/68
92/ 60/76
608
Slight
152/ 90/90
135/ 75/90
110/ 70/70
110/ 60/74
110/ 60/74
105/ 55/82
201
Moderate
134/ 84/84
120/ 80/90
124/ 84/92
60/ ? /70
80/ ? /65
94/ 64/78
543
Slight
164/ 94/78
140/ 90/50
110/ 60/50
134/ 68/54
132/ 70/61
134/ 70/59
   
Placebo
         
None
             

aDecrease of 8 mm or more for two or more consecutive observations.

bDecrease of 5 mm or more for two or more consecutive observations.

cFirst figure systolic blood pressure, second figure diastolic blood pressure, third figure heart rate.

Atropine was given because of the low heart rate, in a small number of cases, consistent with the statement just made about changes in rate (with one exception); it was used most often after pethidine.

Respiratory rate (table 13).-Respiratory depression, or a trend towards it, in so far as it is indicated by a decrease in respiratory rate, was greater after each of the narcotics than after placebo. It was greatest with morphine, least with pethidine. On this point phenazocine was not free of adverse effect.In one case the rate fell to 5, lower than with any of the other agents. The similarity of respiratory effect of phenazocine indicated by these figures again is in accord with the observations of others (Bellville et al., 1; Greisheimer et al., 6; Berkowitz et al., 2; and Papadopoulos & Keats, 10).

Need for Postoperative Analgesic

The figures for the incidence and time of giving a postoperative narcotic (analgesic) medication are very slightly in favour of an effect of morphine as premedication decreasing the need for postoperative analgesia. There is another point in this connexion which favours morphine and, to a lesser extent, pethidine. In many cases the first postoperative narcotic dose was pethidine 25 mg or morphine 5 or 6 mg given most often within the first two hours after the completion of surgery. These doses would be considered generally of little use for analgesia and presumably were given mainly for postoperative restlessness. Since these small doses were used least often when the premedication was morphine and almost as infrequently when the premedication was pethidine, it would seem that the effect of each of these drugs carried over to some extent to the postoperative period, helping to allay post operative discomfort.

TABLE 12

Changes in heart rate after premedication

 
Phenazocine
Levo-phenacyl-morphan
Morphine
Pethidine
Placebo
No consistent trend
188 = 76.4%
170 = 68.0%
157 = 64.1%
158 = 64.5 %
179 = 71.0%
Increase of 8/min. or more
18 = 6.5%
16 = 6.4%
26 = 10.6%
27 = 11.0%
19 = 7.5%
Decrease of 8/min. or more
41 = 16.6%
64 = 25.6%
62 = 25.3%
60 = 24.5%
54 = 21.0%
Change according to initial rate: a
         
Initially>80
18 (72) 31(78) 28 (80) 26 (81) 33 (92)
Decrease to<70
1 (84-66) b
3 (83-65)
1 (84-68)
5 (88-65)
None
Initially 70-80
19 (97) 22 (108) 26 (90) 27 (92) 18 (19)
Decrease to<60
None
1 (76-58)
1 (77-56)
6 (76-55)
None
Initially<70
4 (77) 11 (64) 8 (75) 7 (72) 3 (69)
Decrease to<60
3 (64-65)
6 (63-51)
7 (67-53)
6 (65-56)
3 (68-57)
Atropine or scopolamine given to increase heart rate
7 10 9 13 7

aFirst figure is number showing the minimal decrease indicated above; second figure is number of patients in drug group having that initial rate.

bFigures in parentheses are averages.

Summary

Two synthetic analgesics, phenazocine and levophenacylmorphan, have been used as pre-anaesthetic medication on a double-blind basis in comparison with morphine, pethidine and a placebo. Each of the narcotics was superior to the placebo in the anaesthetists' judgement of satisfactoriness and in the production of sedation, drowsiness and relaxation. The results with morphine were superior in these respects to those obtained in a previous study with the smaller dose of 10 mg per 60 kg body weight, but were obtained at the cost of a higher incidence of side effects. Phenazocine produced the fewest side effects among the narcotics and especially did not differ from the placebo in any apparent effect on the circulation. It was not, however, superior to the other narcotic agents in its effect on respiratory rate. Pethidine appeared to have the greatest disturbing effect on the circulation, lowering the blood pressure to an extent described as hypotensive episodes in seven cases. Such episodes occurred twice after morphine, twice after levophenacylmorphan, but not after phenazocine or placebo. It cannot be concluded that any one of the narcotics is outstandingly superior to the others or entirely free of disadvantage.

TABLE 13

Changes in respiratory rate after premedication

 
Phenazocine
Levo-phenacyl-morphan
Morphine
Pethidine
Placebo
No consistent trend
170 = 68.8%
178 = 71.2%
167 = 68.2%
168 = 68.6%
202 = 80.1%
Increase of 3/min. or more
6 = 2.4%
9 = 3.6%
8 = 3.3%
11 = 4.5%
19 = 7.5%
Decrease of 3/min. or more
71 = 28.7%
63 = 25.2%
70 = 28.6%
66 = 26.9%
21 = 8.3%
Minimal rate after drug of 12/min.
         
or less
18 (16-11)
16 (16-11)
23 (17-10)
22 (17-12)
4 (20-11)
Post-drug rate of<10
13-9
15-9
16-8
None
None
(Individual records)
20-5
13-7
14-9
   
   
12-8
19-8
   
   
14-8
14-8
   
     
20-9
   
01

1 Chief, Anaesthesia Section, Veterans Administration Hospital, Bronx, N.Y.

02

2Chief, Anaesthesia Section, Veterans Administration Hospital, Los Angeles, Calif.

03

3 Consultant, National Institutes of Health, Public Health Service, Department of Health, Education and Welfare, Bethesda, Md.

04

4 Phenazocine is the generic and proposed international nonproprietary name for ( +)-2'-hydroxy-5,9-dimethyl-2-phenethyl-6,7-benzomorphan. Prepared originally at the National Institutes of Health (May & Eddy, 9), it was supplied for the present study through the courtesy of Smith, Kline & French Laboratories. It is marketed by them under the trade name of Prinadol.

05

5Levophenacylmorphan is the generic and proposed international non-proprietary name for (-)-3-hydroxy-N-phenacylmorphinan. It was supplied through the courtesy of Hoffman-La Roche, Inc. It has not been marketed.

06

6 Because of the low solubility of phenazocine and levophenacylmorphan, these agents were dissolved first in propylene glycol and normal saline added. The final concentration of propylene glycol was 25%. The propylene glycol-saline mixture was used for uniformity of conditions as the solvent for morphine and pethidine and for the placebo. We are indebted to the Parmacy Department of the National Institutes of Health for preparing all of the medications used in this study.

07

7 Personal communication, 1960.

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002

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003

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004

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005

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006

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007

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008

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009

MAY, E. L. & EDDY, N. B.: J. Org. Chem ., 24:294, 1959.

010

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011

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012

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