Anaesthesia, 1992, Volume 47, pages 399-401
Transdermal hyoscine with patient-controlled analgesia
P. SEMPLE, T. H. MADEJ, R. G. WHEATLEY, I. J. B. JACKSON
AND
J. STEVENS
Summary Transdermal hyoscine (Scopoderm TTS CIBA) was compared with placebo in 67 patients receiving postoperative analgesia via a patient-controlled analgesia system. AN patienrs underwent an abdominal hysterectomy and had a standard anaesthetic. They werefiillowed up in recovery and daily,for 3 days postoperatively. Fewer patients in the hyoscine group suffered emetic sequelae in recovery and on the third postoperative day ( p < 0.05). The hyoscine group received h a y the number of supplementary antiemetic doses compared to placebo. However, despite transdermal hyoscine there was still a high (78%) incidence of nausea and vomiting. The only SignjJcant ( p < 0.05) increase in side effects attributable to hyoscine was a higher reported incidence of visual disturbance on the second day.
Key words Complications; nausea, vomiting. Antiemetic; transdermal hyoscine. Analgesia; patient controlled analgesia.
Patient-controlled analgesia (PCA) is used frequently in our hospital but we have observed a high incidence of nausea and vomiting with this technique [I]. This may in part be due to a reluctance to administer intramuscular antiemetics. Antiemetics are not administered routinely with PCA, unlike when intramuscular opioids are used. Clearly an alternative to the intramuscular route of administration of antiemetics would be desirable. Transdermal hyoscine has been shown to be an effective antiemetic for motion sickness [2-41; however, its use for preventing postoperative nausea has not been so well demonstrated [5-71. These studies used intramuscular postoperative analgesic regimens which result in peaks and troughs of opioid blood concentration. Patients receiving PCA are prescribed small doses of analgesia which they are able to self-administer at frequent intervals and may be expected to have a more constant blood concentration. Transdermal drug delivery also offers a mechanism to achieve and maintain a relatively constant drug concentration [8]. This was the rationale for studying the effectiveness of transdermal hyoscine in patients receiving PCA. Method Patients aged between 18 and 65 years and of ASA status 1 or 2 requiring general anaesthesia for abdominal hysterec-
tomy were recruited into the trial. The study was approved by the Hospital Medical Ethics Committee and written informed consent was obtained. The patients were randomly allocated to receive either a hyoscine transdermal patch or a matching placebo patch. On the evening before surgery the use of PCA was explained and patients were informed that an intramuscular antiemetic would be available on request postoperatively. Oral temazepam 20 mg was given 2 h pre-operatively and the patch, or placebo, applied behind the ear. The placebo was a standard waterproof dressing (Johnson and Johnson) and each hyoscine patch was covered by a similar dressing, so that its identity could not be distinguished from placebo by patient or assessor. The patches were applied by a nurse who was not involved with subsequent assessment. A standard anaesthetic was given consisting of induction with thiopentone 3-5 mg.kg-', followed by fentanyl 3-5 pg.kg-' and a bolus of vecuronium 0.1 mg.kg-' with increments as necessary. Anaesthesia was maintained using enflurane in 70% nitrous oxide and 30% oxygen. Residual muscular relaxation was antagonised at the end of surgery with atropine 1.2 mg and neostigmine 2.5 mg. No patient was given pre- or intra-operative antiemetics. Postoperative analgesia was provided by PCA started in the recovery room. The PCA was set to deliver a 1 mg bolus of morphine with a lockout time of 5 min. No
P. Semple, FFARCS, Registrar, T.H. Madej, FFARCS, Consultant, R.G. Wheatley, FFARCS, Consultant, I.J.B. Jackson, FFARCS, Consultant, J. Stevens, FFARCS, Registrar, Department of Anaesthesia, York District Hospital, Wigginton Road, York YO3 7HE. Correspondence should be addressed to Dr. T.H. Madej please. Accepted 18 October 1991. 0003-2409/92/040399
+ 03 $03.00/0
@ 1992 The Association of Anaesthetists of G t Britain and Ireland
399
400
P. Semple et al. Table 1. Patient characteristics with pre-, per- and postoperation details. Data expressed as mean (SEM)[range]. Hyoscine group (n = 37) Age; years Weight; kg Duration of pre-operative starvation; min Duration of anaesthetic; min Total dose of morphine; mg
Placebo group (n = 30)
46 (13) [28-641 68.5 (1.5) [49-861 530 (18) [300-810] 72 (5) [40-1201 77.5 (6.5) [26-2101
45.5 (14) 68 (2)
[31-631 [54-971
550 (24) [360-9001 62 ( 3.5) [30-1051 82.5 (7.5) [31-1491
Table 2. Incidence of nausea and vomiting (number (percentage)). ~~~
~
Day one
Recovery
No nausea/vomiting; score 0 Nausea; score 1 Vomiting/retching; score 2
Day two
Day three
Hyoscine
Placebo
Hyoscine
Placebo
Hyoscine
Placebo
Hyoscine
Placebo
30 (81) 6 (16) I (3)
16 (53) 12 (40) 2 (7)
13 (35) 1 1 (30)
5 (16.6) I I (36.6) 14 (46.6)
26 (62) I I (30) 3 (8)
17 (57) 7 (23) 6 (20)
34 (92) I (3) 2 (5)
20 (66.6) 5 (16.6) 5 (16.6)
13 (35)
background infusion was given. Nausea and vomiting were treated with an intramuscular injection of cyclizine 50 mg on request. All patients were assessed in the recovery room and on the first, second and third days postoperatively. The patches were removed after 72 h. Assessments were made in recovery by the nursing staff and on the wards by members of the acute pain team. Nausea was assessed on a three-point scale: no nausea 0, nausea 1 and vomiting or retching 2. Patients were directly questioned about potential side effects of hyoscine including: dry mouth, visual disturbance or any ‘strange or unusual sensations’. The number of doses of antiemetic and total dose of morphine used were also recorded. Statistical analysis of the results was carried out using the unpaired t-test for demographic data, Fisher’s exact test for side effects, Welcher’s test for the number of antiemetic doses given and Chi-squared test for emetic scores. Statistical significance was taken as p < 0.05.
groups; the hyoscine group received on average 1.03 supplementary doses, the placebo group received over twice as many with a mean of 2.23 doses. Table 2 shows the incidence of nausea or vomiting for the four time periods in the two groups. For statistical analysis, patients with an emetic score of 1 or 2 were combined and Chi-squared calculated. There was a significant (p < 0.05) reduction in emetic sequelae in recovery and on the third postoperative day in the hyoscine groups. The percentage of patients experiencing nausea or vomiting at any time in the first 3 days postoperatively is shown in Table 3. Some degree of nausea or vomiting was present in 88% of the placebo group and 78% of the hyoscine group. The incidence of dry mouth, visual disturbance and any ‘unusual sensations’ on the first, second and third postoperative days is shown in Table 4. Significantly (p < 0.05) more patients reported visual disturbance on the second day in the hyoscine group.
Discussion Results Seventy-two patients were recruited into the trial but five were later withdrawn: two patients had problems with the PCA (one severe itching, one was unable to operate it) and both were converted to intramuscular analgesia, one patient was inadequately followed up, one patch was accidentally removed and one patient developed an allergy to the dressing. Of the remaining 67 subjects, 37 were in the active group and 30 in the placebo group. Age, weight, duration of pre-operative starvation, duration of operation and total dose of morphine were similar in both groups (Table 1). There was a significant (p < 0.01) difference in the number of antiemetic doses given between the two Table 3. Overall incidence of emetic sequelae. N o Nausea/ vomiting Nausea Hyoscine n = 31 Placebo n = 30
22% 13%
35% 33%
Vomiting/ retching 43% 53%
We have demonstrated that transdermal hyoscine reduced the incidence of postoperative nausea and vomiting in the recovery room and o n the third postoperative day. Uppington et al. [6], in a similar patient group receiving intramuscular opioids, found an improvement in emetic scores in the first 24 h only. Jackson et al. [5], with a more diverse group of patients, found improvement in the maximal degree of recorded emesis within the first 24 h. Reduction of emesis early in the recovery period is important as this will lessen the chance of aspiration of gastric contents. Koski et al. [7] failed to demonstrate any improvement on emetic scores with hyoscine; however, these patients had varying operations, anaesthetics and analgesic regimens, such that a therapeutic effect may have been missed despite large patient numbers. The pattern of improvement in emetic scores in our patients does not suggest that hyoscine had an antiemetic effect with PCA, as patients would be using relatively little PCA morphine in recovery and at 72 h. Recently Bailey et af. [9] demonstrated the effectiveness of transdermal hyoscine after laparoscopy in outpatients. An antimotion
Transdermal hyoscine with PCA
40 1
Table 4. Patients experiencing side effects (number (percentage)).
Dry mouth Visual disturbance Any unusual sensations
Day one Hyoscine/Placebo
Day two Hyoscine/Placebo
Day three Hyoscine/Placebo
35 (96) 14(38) 5 (14)
21 (57) 15 (4l)* 3 (8)
I 1 (30)
27 (90) 9(30) 5 (17)
17 (57) 6 (20) I (3)
8 (22) 3 (8)
6 (20) 5 (17) 2 (7)
~~
* p c: 0.05 compared to placebo. sickness effect may be important in both outpatients and our own study. The hyoscine group received a significantly lower number of supplementary doses of antiemetic; less than half of the placebo group. This suggests that the patch may have been having greater beneficial effect than suggested by the well established emetic scoring system used [lo]. Other authors have tried to score the severity and frequency of nausea and/or vomiting [6,7]. Overall the number of supplementary antiemetic doses given in both groups appears low compared with the incidence of nausea and vomiting. Patients with PCA may be offered less antiemetic or may be less likely to request an intramuscular injection. There was an increased incidence of visual disturbance in the hyoscine group on day two but no other differences in the side effects at any other time. Studies on inpatients undergoing major operations have been similar with regard to side effects. Uppington et al. [6] also showed increased incidence of visual disturbance at 48 h, whilst Koski et a / . [7] and Jackson et al. [ 5 ] showed no significant difference. In contrast, studies on outpatients have a high incidence of side effects [9,1 I]. In our patients, the overall incidence of nausea and vomiting was high: 78% in the hyoscine group, 88% in the placebo group. This may have been due to a number of factors: no pre- or intra-operative antiemetic, direct questioning, female patients [ 121, abdominal operations [ 131 and a long assessment period including recovery. Our figures are comparable with other studies [I41 and demonstrate the high incidence of postoperative emesis that has received editorial comment [I 51. We conclude that despite an improvement in emetic scores the incidence of nausea and vomiting was so high as not to recommend transcutaneous hyoscine as a sole agent in the management of postoperative nausea and vomiting in patients receiving PCA.
Acknowledgments We thank the gynaecologists and nursing staff for their cooperation and the anaesthetic secretary for her help in preparing the manuscript.
References [I] WHEATLEY RG. MADUTH. JACKSON IJB, HUNTERD. The first year’s experience of an acute pain service. British Journal uf Anaesthesia 1991; 67: 353-9. [2] PRICE NM, SCHMlTT LG, MCGUIRE J. S H A W JE, TROBOUGH G. Transdermal Scopolamine in the prevention of motion sickness at sea. Clinical Pharmacology and Therapeutics 198 I; 2 9 414-9. [3] V A N MARIONWF. BONGAERTSMCM, CHRlSTlAANSE JC, HG. VANOUWERKERK W. Influence of transdermal HOFKAMP scopolamine on motion sickness during 7 days’ exposure to heavy seas. Clinical Pharmacolugy and Therapeutics 1985; 38: 301-5. [4] GREYBIEL A, CRANMER DB, WOODCD. Antimotion sickness efficancy of Scopolamine 12 and 72 hours after transdermal administration. Aviation Space and Environmental Medicine 1982; 53: 770-2. (51 JACKSON SH, SCHMITT L, MCGUIRE J, HALLM. Transdermal Scopolamine as a preanesthetic drug and postoperative antinauseant and anti-emetic. Anesthesiology 1982; 57: A330. [6] UPPINGTON J, DUNNET J, BLOGGCE. Transdermal hyoscine and postoperative nausea and vomiting. Anaesthesia 1986; 41: 16-20. T. [7] KOSKI EMJ, MATTILA, MAK, KNAPIKD. TOIVANEN RUUSUKALLIO H. ANDERSON P. FREUDENTHAL Y. Double blind comparison of Transdermal Hyoscine and placebo for the prevention of postoperative nausea. British Journal of Anaesthesia 1990; 64: 16-20. [8] NIMMO WS. The promise of transdermal drug delivery. British Journal of Anaesthesia 1990; 64: 7- 10. [9] BAILEYPL. STREISAND JB, PACENL, BUBBERSSJM, EASTKA, S, STANLEY TH.Transdermal scopolamine reduces MULDER nausea and vomiting after outpatient laparoscopy. Anesthesiology 1990; 72: 977-80. [lo] DUNDEE JW, NicHoLL RM, MOOREJ. Studies of drugs given before anaesthesia 111. A method for the studying of their effects on postoperative vomiting and nausea. British Journal of Anaesthesia 1962; 34: 527-35. [Ill GIBBONS PA. NICOLSON SC, BETTS EK, ROSENBERRY KR, JOBESD.R. Scopolamine does not prevent postoperative emesis after pediatric eye surgery. Anesthesiology 1984; 61: A435. [I21 BELLVILLE JW, BROSSIDJ, HOWLAND WS. Postoperative nausea and vomiting IV. Factors related to postoperative nausea and vomiting. Anesthesiology 1960; 21: 186-93. [ I31 JANHUNENL, TAMMISTO T. Postoperative vomiting after different modes of general anaesthesia. Annales Chirurgiae et Gvnaecologiae Fenniae 1972; 61: 152-9. [I41 PALAZZOMGA, STRUNIN L. Anaesthesia and Emesis 1. etiology. Canadian Anaestherists Society Journal 1984; 31: 178-87. [I51 ARONSONJK, SEARJW. Editorial. Transdermal hyoscine (Scopolamine) and postoperative vomiting. Anaesthesia 1986; 41: 1-3.
Transdermal hyoscine with patient-controlled analgesia
P. SEMPLE, T. H. MADEJ, R. G. WHEATLEY, I. J. B. JACKSON
AND
J. STEVENS
Summary Transdermal hyoscine (Scopoderm TTS CIBA) was compared with placebo in 67 patients receiving postoperative analgesia via a patient-controlled analgesia system. AN patienrs underwent an abdominal hysterectomy and had a standard anaesthetic. They werefiillowed up in recovery and daily,for 3 days postoperatively. Fewer patients in the hyoscine group suffered emetic sequelae in recovery and on the third postoperative day ( p < 0.05). The hyoscine group received h a y the number of supplementary antiemetic doses compared to placebo. However, despite transdermal hyoscine there was still a high (78%) incidence of nausea and vomiting. The only SignjJcant ( p < 0.05) increase in side effects attributable to hyoscine was a higher reported incidence of visual disturbance on the second day.
Key words Complications; nausea, vomiting. Antiemetic; transdermal hyoscine. Analgesia; patient controlled analgesia.
Patient-controlled analgesia (PCA) is used frequently in our hospital but we have observed a high incidence of nausea and vomiting with this technique [I]. This may in part be due to a reluctance to administer intramuscular antiemetics. Antiemetics are not administered routinely with PCA, unlike when intramuscular opioids are used. Clearly an alternative to the intramuscular route of administration of antiemetics would be desirable. Transdermal hyoscine has been shown to be an effective antiemetic for motion sickness [2-41; however, its use for preventing postoperative nausea has not been so well demonstrated [5-71. These studies used intramuscular postoperative analgesic regimens which result in peaks and troughs of opioid blood concentration. Patients receiving PCA are prescribed small doses of analgesia which they are able to self-administer at frequent intervals and may be expected to have a more constant blood concentration. Transdermal drug delivery also offers a mechanism to achieve and maintain a relatively constant drug concentration [8]. This was the rationale for studying the effectiveness of transdermal hyoscine in patients receiving PCA. Method Patients aged between 18 and 65 years and of ASA status 1 or 2 requiring general anaesthesia for abdominal hysterec-
tomy were recruited into the trial. The study was approved by the Hospital Medical Ethics Committee and written informed consent was obtained. The patients were randomly allocated to receive either a hyoscine transdermal patch or a matching placebo patch. On the evening before surgery the use of PCA was explained and patients were informed that an intramuscular antiemetic would be available on request postoperatively. Oral temazepam 20 mg was given 2 h pre-operatively and the patch, or placebo, applied behind the ear. The placebo was a standard waterproof dressing (Johnson and Johnson) and each hyoscine patch was covered by a similar dressing, so that its identity could not be distinguished from placebo by patient or assessor. The patches were applied by a nurse who was not involved with subsequent assessment. A standard anaesthetic was given consisting of induction with thiopentone 3-5 mg.kg-', followed by fentanyl 3-5 pg.kg-' and a bolus of vecuronium 0.1 mg.kg-' with increments as necessary. Anaesthesia was maintained using enflurane in 70% nitrous oxide and 30% oxygen. Residual muscular relaxation was antagonised at the end of surgery with atropine 1.2 mg and neostigmine 2.5 mg. No patient was given pre- or intra-operative antiemetics. Postoperative analgesia was provided by PCA started in the recovery room. The PCA was set to deliver a 1 mg bolus of morphine with a lockout time of 5 min. No
P. Semple, FFARCS, Registrar, T.H. Madej, FFARCS, Consultant, R.G. Wheatley, FFARCS, Consultant, I.J.B. Jackson, FFARCS, Consultant, J. Stevens, FFARCS, Registrar, Department of Anaesthesia, York District Hospital, Wigginton Road, York YO3 7HE. Correspondence should be addressed to Dr. T.H. Madej please. Accepted 18 October 1991. 0003-2409/92/040399
+ 03 $03.00/0
@ 1992 The Association of Anaesthetists of G t Britain and Ireland
399
400
P. Semple et al. Table 1. Patient characteristics with pre-, per- and postoperation details. Data expressed as mean (SEM)[range]. Hyoscine group (n = 37) Age; years Weight; kg Duration of pre-operative starvation; min Duration of anaesthetic; min Total dose of morphine; mg
Placebo group (n = 30)
46 (13) [28-641 68.5 (1.5) [49-861 530 (18) [300-810] 72 (5) [40-1201 77.5 (6.5) [26-2101
45.5 (14) 68 (2)
[31-631 [54-971
550 (24) [360-9001 62 ( 3.5) [30-1051 82.5 (7.5) [31-1491
Table 2. Incidence of nausea and vomiting (number (percentage)). ~~~
~
Day one
Recovery
No nausea/vomiting; score 0 Nausea; score 1 Vomiting/retching; score 2
Day two
Day three
Hyoscine
Placebo
Hyoscine
Placebo
Hyoscine
Placebo
Hyoscine
Placebo
30 (81) 6 (16) I (3)
16 (53) 12 (40) 2 (7)
13 (35) 1 1 (30)
5 (16.6) I I (36.6) 14 (46.6)
26 (62) I I (30) 3 (8)
17 (57) 7 (23) 6 (20)
34 (92) I (3) 2 (5)
20 (66.6) 5 (16.6) 5 (16.6)
13 (35)
background infusion was given. Nausea and vomiting were treated with an intramuscular injection of cyclizine 50 mg on request. All patients were assessed in the recovery room and on the first, second and third days postoperatively. The patches were removed after 72 h. Assessments were made in recovery by the nursing staff and on the wards by members of the acute pain team. Nausea was assessed on a three-point scale: no nausea 0, nausea 1 and vomiting or retching 2. Patients were directly questioned about potential side effects of hyoscine including: dry mouth, visual disturbance or any ‘strange or unusual sensations’. The number of doses of antiemetic and total dose of morphine used were also recorded. Statistical analysis of the results was carried out using the unpaired t-test for demographic data, Fisher’s exact test for side effects, Welcher’s test for the number of antiemetic doses given and Chi-squared test for emetic scores. Statistical significance was taken as p < 0.05.
groups; the hyoscine group received on average 1.03 supplementary doses, the placebo group received over twice as many with a mean of 2.23 doses. Table 2 shows the incidence of nausea or vomiting for the four time periods in the two groups. For statistical analysis, patients with an emetic score of 1 or 2 were combined and Chi-squared calculated. There was a significant (p < 0.05) reduction in emetic sequelae in recovery and on the third postoperative day in the hyoscine groups. The percentage of patients experiencing nausea or vomiting at any time in the first 3 days postoperatively is shown in Table 3. Some degree of nausea or vomiting was present in 88% of the placebo group and 78% of the hyoscine group. The incidence of dry mouth, visual disturbance and any ‘unusual sensations’ on the first, second and third postoperative days is shown in Table 4. Significantly (p < 0.05) more patients reported visual disturbance on the second day in the hyoscine group.
Discussion Results Seventy-two patients were recruited into the trial but five were later withdrawn: two patients had problems with the PCA (one severe itching, one was unable to operate it) and both were converted to intramuscular analgesia, one patient was inadequately followed up, one patch was accidentally removed and one patient developed an allergy to the dressing. Of the remaining 67 subjects, 37 were in the active group and 30 in the placebo group. Age, weight, duration of pre-operative starvation, duration of operation and total dose of morphine were similar in both groups (Table 1). There was a significant (p < 0.01) difference in the number of antiemetic doses given between the two Table 3. Overall incidence of emetic sequelae. N o Nausea/ vomiting Nausea Hyoscine n = 31 Placebo n = 30
22% 13%
35% 33%
Vomiting/ retching 43% 53%
We have demonstrated that transdermal hyoscine reduced the incidence of postoperative nausea and vomiting in the recovery room and o n the third postoperative day. Uppington et al. [6], in a similar patient group receiving intramuscular opioids, found an improvement in emetic scores in the first 24 h only. Jackson et al. [5], with a more diverse group of patients, found improvement in the maximal degree of recorded emesis within the first 24 h. Reduction of emesis early in the recovery period is important as this will lessen the chance of aspiration of gastric contents. Koski et al. [7] failed to demonstrate any improvement on emetic scores with hyoscine; however, these patients had varying operations, anaesthetics and analgesic regimens, such that a therapeutic effect may have been missed despite large patient numbers. The pattern of improvement in emetic scores in our patients does not suggest that hyoscine had an antiemetic effect with PCA, as patients would be using relatively little PCA morphine in recovery and at 72 h. Recently Bailey et af. [9] demonstrated the effectiveness of transdermal hyoscine after laparoscopy in outpatients. An antimotion
Transdermal hyoscine with PCA
40 1
Table 4. Patients experiencing side effects (number (percentage)).
Dry mouth Visual disturbance Any unusual sensations
Day one Hyoscine/Placebo
Day two Hyoscine/Placebo
Day three Hyoscine/Placebo
35 (96) 14(38) 5 (14)
21 (57) 15 (4l)* 3 (8)
I 1 (30)
27 (90) 9(30) 5 (17)
17 (57) 6 (20) I (3)
8 (22) 3 (8)
6 (20) 5 (17) 2 (7)
~~
* p c: 0.05 compared to placebo. sickness effect may be important in both outpatients and our own study. The hyoscine group received a significantly lower number of supplementary doses of antiemetic; less than half of the placebo group. This suggests that the patch may have been having greater beneficial effect than suggested by the well established emetic scoring system used [lo]. Other authors have tried to score the severity and frequency of nausea and/or vomiting [6,7]. Overall the number of supplementary antiemetic doses given in both groups appears low compared with the incidence of nausea and vomiting. Patients with PCA may be offered less antiemetic or may be less likely to request an intramuscular injection. There was an increased incidence of visual disturbance in the hyoscine group on day two but no other differences in the side effects at any other time. Studies on inpatients undergoing major operations have been similar with regard to side effects. Uppington et al. [6] also showed increased incidence of visual disturbance at 48 h, whilst Koski et a / . [7] and Jackson et al. [ 5 ] showed no significant difference. In contrast, studies on outpatients have a high incidence of side effects [9,1 I]. In our patients, the overall incidence of nausea and vomiting was high: 78% in the hyoscine group, 88% in the placebo group. This may have been due to a number of factors: no pre- or intra-operative antiemetic, direct questioning, female patients [ 121, abdominal operations [ 131 and a long assessment period including recovery. Our figures are comparable with other studies [I41 and demonstrate the high incidence of postoperative emesis that has received editorial comment [I 51. We conclude that despite an improvement in emetic scores the incidence of nausea and vomiting was so high as not to recommend transcutaneous hyoscine as a sole agent in the management of postoperative nausea and vomiting in patients receiving PCA.
Acknowledgments We thank the gynaecologists and nursing staff for their cooperation and the anaesthetic secretary for her help in preparing the manuscript.
References [I] WHEATLEY RG. MADUTH. JACKSON IJB, HUNTERD. The first year’s experience of an acute pain service. British Journal uf Anaesthesia 1991; 67: 353-9. [2] PRICE NM, SCHMlTT LG, MCGUIRE J. S H A W JE, TROBOUGH G. Transdermal Scopolamine in the prevention of motion sickness at sea. Clinical Pharmacology and Therapeutics 198 I; 2 9 414-9. [3] V A N MARIONWF. BONGAERTSMCM, CHRlSTlAANSE JC, HG. VANOUWERKERK W. Influence of transdermal HOFKAMP scopolamine on motion sickness during 7 days’ exposure to heavy seas. Clinical Pharmacolugy and Therapeutics 1985; 38: 301-5. [4] GREYBIEL A, CRANMER DB, WOODCD. Antimotion sickness efficancy of Scopolamine 12 and 72 hours after transdermal administration. Aviation Space and Environmental Medicine 1982; 53: 770-2. (51 JACKSON SH, SCHMITT L, MCGUIRE J, HALLM. Transdermal Scopolamine as a preanesthetic drug and postoperative antinauseant and anti-emetic. Anesthesiology 1982; 57: A330. [6] UPPINGTON J, DUNNET J, BLOGGCE. Transdermal hyoscine and postoperative nausea and vomiting. Anaesthesia 1986; 41: 16-20. T. [7] KOSKI EMJ, MATTILA, MAK, KNAPIKD. TOIVANEN RUUSUKALLIO H. ANDERSON P. FREUDENTHAL Y. Double blind comparison of Transdermal Hyoscine and placebo for the prevention of postoperative nausea. British Journal of Anaesthesia 1990; 64: 16-20. [8] NIMMO WS. The promise of transdermal drug delivery. British Journal of Anaesthesia 1990; 64: 7- 10. [9] BAILEYPL. STREISAND JB, PACENL, BUBBERSSJM, EASTKA, S, STANLEY TH.Transdermal scopolamine reduces MULDER nausea and vomiting after outpatient laparoscopy. Anesthesiology 1990; 72: 977-80. [lo] DUNDEE JW, NicHoLL RM, MOOREJ. Studies of drugs given before anaesthesia 111. A method for the studying of their effects on postoperative vomiting and nausea. British Journal of Anaesthesia 1962; 34: 527-35. [Ill GIBBONS PA. NICOLSON SC, BETTS EK, ROSENBERRY KR, JOBESD.R. Scopolamine does not prevent postoperative emesis after pediatric eye surgery. Anesthesiology 1984; 61: A435. [I21 BELLVILLE JW, BROSSIDJ, HOWLAND WS. Postoperative nausea and vomiting IV. Factors related to postoperative nausea and vomiting. Anesthesiology 1960; 21: 186-93. [ I31 JANHUNENL, TAMMISTO T. Postoperative vomiting after different modes of general anaesthesia. Annales Chirurgiae et Gvnaecologiae Fenniae 1972; 61: 152-9. [I41 PALAZZOMGA, STRUNIN L. Anaesthesia and Emesis 1. etiology. Canadian Anaestherists Society Journal 1984; 31: 178-87. [I51 ARONSONJK, SEARJW. Editorial. Transdermal hyoscine (Scopolamine) and postoperative vomiting. Anaesthesia 1986; 41: 1-3.
