Dihydroergotamine and mobilization after major orthopedic surgery. 342. The effects of dihydroergotamine (DHE) on the degree of mobilization and response to ...
Dihydroergotamine and mobilization after major orthopedic surgery The effects of dihydroergotamine (DHE) on the degree of mobilization and response to orthostatic stress after total hip arthroplasty were studied. In the mobilization study, 78 patients received DHE, 0.5 mg im, twice a day from the day of surgery until full mobilization was achieved. Eighty-four patients who received placebo served as controls. There was no significant difference in the time until the first day of mobilization or the degree of mobilization. In the orthostatic test condition, subgroups of 61 patients receiving placebo and 55 patients receiving DHE were subjected to orthostatic testing. There were no differences in cardiovascular response to bed rest or in orthostatic stress. We conclude that DHE does not stabilize the cardiovascular reaction to orthostatic stress, nor does it enhance mobilization in patients after total hip arthroplasty. (CLIN PHARMACOL THER 1986;39:342-4.)
Benn R. Duus, M.D., Per Holmich, M.D., Carsten T. Larsen, M.D., Peer Wille-Jorgensen, M.D., Arne Bjerg-Nielsen, M.D., and Steen Christensen, M.D. Hvidovre, Denmark The importance of early mobilization after surgery is known to every surgeon. However, a serious obstacle to early mobilization is the tendency of patients to collapse as a result of deficient postural adaptation. Martin
et al.' found that 31% of patients undergoing abdominal surgery showed signs of poor postural adaptation. Dihydroergotamine (DHE) is known to normalize circulatory regulation in subjects with orthostatic hypotension, probably because of a central stabilizing effect.' Our aim was to study whether DHE was able to stabilize the cardiovascular reaction to orthostatic stress and to improve mobilization after total hip arthroplasty.
METHODS After informed consent, 162 consecutive patients scheduled for total hip arthroplasty were allocated to either placebo or DHE dosing (0.5 mg b.i.d. subcutaneously). Dosing was started 1 hour before operation and continued for at least 1 week thereafter or until full mobilization was attained. Trained physiotherapists evaluated the degree of mobilization. Patients were assessed with regard to the functional level that could be expected of each patient. Scores were divided into three From the Department of Orthopaedic Surgery, Hvidovre Hospital, University of Copenhagen. Received for publication Oct. 28, 1985; accepted Nov. 8, 1985. Reprint requests to: Henn Duus, M.D., Willemoesgade 39, 3.tv, DK-2100 Copenhagen 0, Denmark.
342
classes: better than expected, expected, and worse than expected. One hundred sixteen of the patients were randomly chosen and subjected to an orthostatic blood pressure test the day before surgery and immediately after mobilization. Blood pressure was measured with a mercury manometer by the auscultatory method. The radial artery pulse was counted over 30 seconds. Recordings were made after subjects rested 10 minutes in the supine position and after subjects stood 1, 3, 5, and 7 minutes in the erect position. Orthostatic symptoms were also measured. Orthostatic hypotension was defined according to the definition of Thulesius.5 The use of potential hypotensive drugs, the presence of varicose veins and anemia, and the height and weight of the patients were recorded. Interactions and correlations between variables were analyzed with multidimensional contingency table methods based on chi-square tests and partial correlation coefficients (Goodman-Kruskals gamma') and methods for analysis of covariance (analysis of blood pressure and heart rate).
RESULTS Table I lists patient characteristics. There were no differences between the two groups with regard to average age, sex, weight, height, use of potential hypotensive drugs, varicose veins, and anemia. Figs. 1 and 2 show the variation in systolic blood pressure and heart rate. There was no significant dif-
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Dihydroergotamine and postoperative mobilization
mmHG
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BEATS/MIN
160 -
100 -
155 -
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BEFORE OPERATION
'"---
ss,
150 -
AFTER OPERATION
95 -
90 145
-
\
140 -
135
BEFORE OPERATION
85
AFTER OPERATION
--
-
80
130 -
125
-
120
-
75
70 /z ' 10
1
3
L-,,-A SUPINE POSITION
5
10
7min
SUPINE POSITION
ERECT POSITION
Fig. 1. Mean systolic blood pressure before and after arthro) and in those plasty in the patients who received DHE ( who received placebo (- - - -). The standard deviation was calculated to be between 17.8 and 27.0 mm Hg.
Table
7min
5
3
1
1
ERECT POSITION
Fig. 2. Mean heart rate before and after arthroplasty in the ) and in those who received patients who received DHE ( placebo (- - - -). The standard deviation was calculated to be between 12.0 and 15.4 bpm.
I. Patient characteristics Orthostatic test
Mobilization score
Age (yr) Sex Female Male Weight (kg) Height (cm) Varicose veins (no. of patients) Hypotensive drugs (no. of patients) Anemia (no. of patients) Before operation After operation Data are K
-±
DHE group (n = 78)
Placebo group (n = 84)
DHE group (n = 55)
Placebo group (n = 61)
69.4 ± 9.4
69.0 ± 9.5
70.0 ± 8.3
67.0 ± 9.9
49 29
56 28
40 21
33 22
68.2 ± 14.6 163 ± 9.2
68.7 ± 12.9 163 ± 7.7
68.7 ± 13.7 162 ± 7.8
68.8 ± 16.5 163 ± 8.9
15
12
13
9
27
28
22
23
3
2 21
2
2
21
15
29
SD.
ference between the two groups or between the values before and after surgery in each group. Table II lists the postoperative mobilization scores. The mean ( ± SD) duration from operation to the first day of mobilization was 3.6 ± 1.1 days in the placebo group and 3.6 -1- 1.2 days in the DHE group. Again,
no statistically significant difference could be demonstrated. In the placebo group, nine patients had orthostatic reactions before surgery and 10 had orthostatic reactions postoperatively. Only three patients had orthostatic reactions both before and after surgery. In the DHE group
CLIN PHARMACOL THER MARCH 1986
344 Duus et al. Table II. Postoperative mobilization scores in the two groups Mobilization score
Better than expected As expected Worse than expected
DHE group (n = 78)
Placebo group (n = 84)
28
35
40
42
10
7
the numbers were five, 10, and one, respectively. In both groups 11 patients had orthostatic symptoms such as dizziness and nausea after surgery.
DISCUSSION Bed rest results in orthostatic intolerance with increased heart rate, lowered stroke volume, and lowered central blood volume.' DHE is known to lower the pulse rate and increase cardiac output, stroke volume, and central blood volume in the standing subject after orthostatic stress.' This is caused mainly by a constriction of the capacitance vessels in the muscles and skin.' In a normal subject, 300 to 500 ml blood is reported to be displaced into the legs as the subject stands.' The constrictor effect of DHE might cause decreased pooling of about 125 ml blood in the dependent regions, thus producing a stabilization of the central cardiovascular system in response to orthostatic testing in patients with orthostatic hypotension." Martin et al.' found these beneficial effects to be crucial to patients who had just undergone surgery. DHE dosing in the early postoperative period has been proposed to improve orthostatic tolerance and to enhance early mobilization.' We observed a decreased systolic blood pressure and increased pulse rate both in the supine and erect positions after surgery (Figs. 1 and 2). This might be explained by the postoperative period of bed rest and the consequently reduced plasma volume' as well as by the perioperative blood loss. We were not able to demonstrate any difference in the two groups with respect to cardiovascular response to bed rest or orthostatic stress. Neither could we demonstrate any difference with respect to degree of mobilization or duration before mobilization between the two groups. Some of the patients
who had orthostatic reactions before surgery did not do so afterwards, but there was no difference between the two groups. The risk of overlooking a marginal difference (type II error) between the two groups is extremely small, because the results are almost identical. The discrepancy between our results and those of Martin et al.' may be explained by the fact that we did not give the drug only to a selected group of patients with orthostatic symptoms, but to normal subjects as well. Thus DHE does not seem to have the same effects in normal individuals as in patients who have autonomic insufficiency. In conclusion, DHE does not stabilize the cardiovascular reaction to orthostatic stress, nor does it enhance mobilization in patients after major orthopedic surgery.
References Martin E, Immich H, Lutz H, Peter K. Die kreislaufbeeinflussung durch dihydroergotamin intramuskular in der friihen postoperativen phase. Med Klin 1976;71:9615. Jennings G, Esler M, Holmes R. Treatment of orthostatic hypotension with dihydroergotamine. Br Med J 1979;2:307. Liibke KO. A controlled study with dihydroergot on patients with orthostatic dysregulation. Cardiology 1976; 61(suppl 1):333-41. Nordenfeldt I, Mellander S. Central haemodynamic effects of dihydroergotamine in patients with orthostatic hypotension. Acta Med Scand 1972;191:115-20. Thulesius 0. Pathophysiological classification and diagnosis of orthostatic hypotension. Cardiology 1976; 61 (suppl ): 180-90 . Davis JA. A partial coefficient for Goodman and Kruskals' gamma. J Am Stat Assoc 1967;62:189-93. Chobanian AV, Lille RD, Tercyak A, Blevins P. The metabolic and haemodynamic effects of prolonged bed rest in normal subjects. Circulation 1974;49:551-9. Barbey K, Brecht K. Venentonus, venekapazitat und ihre messung. Med Welt 1965;15:727-32. Mellander S, Nordenfelt I. Comparative effects of dihydroergotamine and noradrenaline on resistance, exchange and capacitance functions in the peripheral circulation. Clin Sci 1970;39:183-201. Heller U, Heller G. Orthostase bei postoperativer friihmobilisation. Aerztl Prax 1977;29:424-6.
