Effect of transdermal hyoscine on nausea and vomiting during and after middle ear surgery under local anaesthesia

Transcription

1 British Journal of Anaesthesia 1996; 76: Effect of transdermal hyoscine on nausea and vomiting during and after middle ear surgery under local anaesthesia P. HONKAVAARA Summary The efficacy of transdermal hyoscine in the reduction of nausea, retching and vomiting was compared with placebo during and after stapedoand tympanoplasty under local anaesthesia in a double-blind, prospective and randomized study. In the placebo group (n 29), 69 % of the patients were free from emetic symptoms during and 41 % after the operation. The corresponding figures were 93 % (P 0.05) and 74 % (P 0.05) in the hyoscine group (n 27). The patients in the placebo group needed more droperidol during and after operation (P 0.05). The frequency of side effects was similar in both groups. In posturography the patients with emetic sequelae in the placebo group had a markedly deteriorated upkeep of posture (P 0.05) measured as body sway velocities. A strong correlation was found between motion sickness and emetic sequelae after surgery, and patients with a history of motion sickness benefited most from hyoscine. (Br. J. Anaesth. 1996; 76: 49 53). Key words Vomiting, nausea. Vomiting, antiemetics. Surgery, otolaryngological. Premedication, hyoscine. Drug delivery, transdermal. Introduction was found to reduce postoperative nausea and vomiting (PONV) in two recent studies after middle ear surgery under general anaesthesia [1, 2]. The percentages of patients suffering from PONV in the placebo groups were 80 % and 62 %. Although vertigo and dizziness are well known complications after stapedoplasty [3] no study has been published on emetic symptoms and middle surgery under local anaesthesia. Assessment of earlier studies performed in our clinic indicated that stapedoplasty caused considerable PONV while tympanoplasty produced a little less. Transdermal hyoscine has been shown to be antiemetic both in motion sickness [4] and postoperatively after different types of surgery [1, 2, 5 9]. One of the many causes of PONV [10] may be increased stimulation of the vestibular apparatus by surgery, and this could be enhanced further by increased vestibular sensitivity caused by opioids [11, 12]. Any possible vestibular component to PONV and its modification by transdermal hyoscine might be revealed by computerized posturography [13, 14]. Thus, the present work was designed to study the occurrence of PONV and need for rescue antiemetics during and after stapedo- and tympanoplasties performed under local anaesthesia and the effect of transdermal hyoscine. Patients and methods Informed consent was obtained from 56 ASA class I-II patients, aged yr, scheduled for stapedoor tympanoplasty under local anaesthesia. Exclusion criteria included: regular or temporary use of antiemetic drugs, and vomiting or retching within 24 h before the operation. The Ethics Committee of the Otolaryngological Hospital approved the study. Patients were allocated randomly to a placebo (n 29) or a hyoscine (n 27) group in a double-blind study. On the afternoon of the day before surgery, a history of motion sickness and PONV and the menstrual data [10, 15] were noted. Thereafter, on the basis of the randomization, either an inactive patch or an identical hyoscine patch (Scopoderm 0.5 mg 72 h 1 ) was applied to the skin of the postauricular area opposite the operative side after cleansing the skin with diethyl ether. In order to secure the patch, it was covered by an adhesive tape. Evaluation of postural stability by computerized posturography [16] was performed as follows: (1) before applying the test patch during the afternoon before operation, (2) before premedication on the morning of the operation, (3) 24 h after surgery and (4) 1 week after the operation. In posturography, the patient stands on a force platform connected to a computer. The system records the movement of the centre-point of forces (the sway path). The calculated length of the sway path during analysis gives the mean sway velocity [17]. The posturographies were made under a 3-min sequence, during which the recordings were made with both the eyes open and closed for 30 s after a period of initial stabilization for both eyes open and closed. Patients with uncompensated vestibular function before surgery (mean sway velocity over 3 cm s 1 during the control recording (1) with their eyes closed), were excluded from statistical processing of the results of posturography: two from the placebo group and four from the hyoscine group. The Romberg quotient is P. HONKAVAARA, MD, Department of Anaesthesia, Otolaryngological Hospital, University of Helsinki, Haartmaninkatu 4E, SF Helsinki, Finland. Accepted for publication: August 1, 1995.

2 50 British Journal of Anaesthesia a derived ratio between mean sway velocity values recorded in non-visual and visual conditions and it is used commonly to describe the effect of visual control on posture. The repeatability of the posturography as a test of postural stability has been shown to be good [18]. Before local anaesthesia the patients were questioned on the presence of sedation, dry mouth, anxiety, dizziness, blurred vision, urinary difficulties or other symptoms. Thereafter, the placebo group received glycopyrronium 0.2 mg i.v. and the hyoscine group received saline from identical syringes containing the same volume, each with its own code number in a double-blind manner. Premedication comprised oxycodone 0.1 mg kg 1 i.m min before operation. Local anaesthesia was performed with lignocaine containing adrenaline. Fentanyl 1 g kg 1 was given before local anaesthesia and thereafter during operation as 25- g doses for analgesia. Diazepam in 2.5-mg doses was used for sedation, if needed. Monitoring before, during and after operation included arterial pressure with automatic oscillotonometer, electrocardiogram and haemoglobin oxygen saturation ( S p O ). During operation patients 2 received oxygen 2 4 litre min 1 via nasal cannulae. Postoperative pain was treated with diclofenac 1 mg kg 1 i.v. or with paracetamol 10 mg kg 1 suppositories in patients who could not tolerate diclofenac. In addition, oxycodone 0.05 mg kg 1 i.v. or 0.1 mg kg 1 i.m. was used if needed. (Note that diclofenac is registered in Finland for i.v. use, but this is not the case in all countries.) A trained nurse, who was unaware of the nature of the study drug, enquired for vertigo and assessed the occurrence of nausea, retching and vomiting during operation and at the following times; 0 2, 2 6, 6 12, and h after the end of the surgery. If the patient experienced more than one symptom, for example both nausea and vomiting, she was listed as having vomited. During the first 0 2 h after surgery the patients were in the recovery room and thereafter in the ward. Droperidol 10 g kg 1 i.v. or i.m. was given for vomiting, retching or prolonged nausea, at a minimum interval of 30 min. Vertigo was scored as follows: 0 no vertigo, 1 slight sensation of vertigo, 2 strong sensation of vertigo, 3 has to avoid head movement and 4 has to keep eyes closed. STATISTICS ANOVA, followed by the Bonferroni/Dunn procedure, if appropriate, was used for parametric data, and the chi-square test with Yates correction or Fisher s exact test for non-parametric data. Logistic regression analysis was used to find predictors for PONV. The Spearman rank correlation coefficient was applied to the posturography data. A P value less than 0.05 was regarded as significant. Results There were no significant differences in patient characteristics or details of the local anaesthesia between the groups (table 1). The number of female Table 1 Characteristics of patients undergoing stapedo- and tympanoplasty, mean values (SD or range). No statistical differences between groups Stapedo-/tympanoplasty 23/6 20/7 Sex (M/F) 11/18 12/15 Age (yr) 41 (21 55) 38 (22 53) Weight (kg) 70 (18) 71 (12) Duration of operation (min) 73 (20) 78 (21) Peroperative drugs Fentanyl (µg kg 1 ) 1 (0.3) 1 (0.2) Diazepam (mg kg 1 ) (0.041) (0.038) Lignocaine (mg kg 1 ) 1, 24 (0.38) 1, 18 (0.29) Postoperative oxycodone No. of patients Median dose (mg kg 1 ) 0.11 ( ) 0.10 ( ) Table 2 Percentage of patients suffering from emetic symptoms during and after stapedo- and tympanoplasty under local anaesthesia receiving preoperatively either a placebo or hyoscine patch, * P < 0.05 compared with placebo group Peroperatively No symptoms 69 93* Nausea 21 7 Retching 0 0 Vomiting 10 0 Mean number of nausea and vomiting (SD) 0.41 (0.73) 0.07 (0.27)* Postoperatively No symptoms 41 74* Nausea 17 7 Retching 14 0 Vomiting patients having normal menstrual cycles was 15 in the placebo group and 14 in the hyoscine group. The distribution of the patients between the different phases of the menstrual cycle was similar in both groups. In logistic regression analysis the following variables were found to be predictors for PONV: sex (P 0.001), vertigo score (P 0.001), history of motion sickness (P 0.05), treatment with hyoscine patch (P 0.05) and the other variables studied were not predictors for PONV. During operation 69 % of patients in the placebo group were devoid of nausea and vomiting and the corresponding value for the hyoscine group was 93 % (P 0.05). No retching occurred during operation. Patients in the placebo group had more emetic episodes peroperatively than the patients in the hyoscine group (P 0.05) (table 2). During the first 24 h after surgery the number of patients having any emetic symptoms was less (7/27 vs 17/29, P 0.05) in the hyoscine group than in the placebo group (table 2). Both the number of patients needing and the number of doses needed of the rescue antiemetic (droperidol) was significantly higher in the placebo group during operation, in the ward (2 24 h) and for the whole study. There was no significant difference in the time from local anaesthesia to the need for droperidol (table 3).

3 , PONV and ear surgery 51 Table 3 Need for rescue antiemetic (10 g kg 1 droperidol) during and after operation of stapedo- and tympanoplasty under local anaesthesia (mean (SD)), * P 0.05 between placebo and hyoscine groups. ** P Patients needing droperidol (%) peroperatively 31 7* 0 2 h h 41 11* total 59 22* Number of doses of droperidol mean (SD) peroperatively 0.31 (0.54) 0.07 (0.27)* 0 2 h 0.28 (0.65) 0.11 (0.32) 0 24 h 0.48 (0.69) 0.19 (0.62)** total 1.01 (1.49) 0.36 (1.00)* Time from local anaesthesia to need for droperidol (min) 335 (335) 215 (175) Figure 1 Differences in mean body sway in posturographies (Posturo.) 2 and 3 eyes open and closed, in the placebo and hyoscine groups when grouped in relation to retching and vomiting after surgery (mean, SD). group with no retching and vomiting, placebo group with retching and vomiting, hyoscine group with no retching and vomiting, hyoscine group with retching and vomiting. Posturographies 2 (in the morning before surgery) and 3 (24 h after surgery) revealed in the placebo group significantly more deterioration of postural stability in the patients suffering from retching and vomiting than in the patients without these symptoms. Both the differences in mean sway velocities (P 0.05) and Romberg quotient (P 0.05) had worsened, when rankings from differences in these recordings were assessed by Spearman rank correlation coefficient. In the hyoscine group there were no significant changes when postural stability was assessed in a similar fashion. There were no significant differences in the hyoscine group between the patients with or without emetic sequelae before and after administration of the hyoscine patch (posturographies 1 and 2). Figure 1 illustrates the mean differences in body sway velocities in different groups (posturographies 2 and 3), but it should be noted that statistically the rankings of the differences are assessed. There were 12 patients in the placebo group and nine patients in the hyoscine group with a positive history of motion sickness and the respective values for negative history of PONV were 16 and 13. The cross-tabulated results of the correlations between treatment, history of motion sickness and history of Table 4 Percentage of patients free from all emetic symptoms in relation to histories of PONV (hponv) and motion sickness (hmosi), * P 0.05 between placebo and hyoscine groups ** P During surgery free from all emetic symptoms (%) hmosi negative hmosi positive 33 89* hponv negative * hponv positive After surgery free from all emetic symptoms (%) hmosi negative hmosi positive 8 67* hponv negative 44 85** hponv positive PONV are shown in table 4. significantly increased the percentage of patients who were free of all emetic symptoms both during and after surgery (P 0.05). The respective increase was also significant in relation to negative history of PONV and being symptom-free during surgery (P 0.05). In the placebo group there was a positive correlation between a history of motion sickness and nausea and vomiting during (P 0.001) and after surgery (P 0.005). There was no significant effect of a history of motion sickness on nausea and vomiting in the hyoscine group, when assessed in a similar fashion. In all groups there was no correlation between positive histories of PONV and motion sickness. In the placebo group 14 % of the patients reported sedation before local anaesthesia and the corresponding value was 4 % in the hyoscine group. During the 24 h after surgery more patients in the placebo group reported vertigo (8/29) than in the hyoscine group (1/27, P 0.05). There were no significant differences in side effects immediately before local anaesthesia between placebo and hyoscine groups and they varied between 0 11 %. Discussion Transdermal hyoscine considerably increased the percentage of patients who were free from all emetic symptoms, and decreased the need for rescue antiemetic during and after stapedo- and tympanoplasties under local anaesthesia without increasing the frequency of side effects compared with the placebo group. The most clinically important finding was a reduced incidence of nausea and vomiting during operation, because emetic symptoms normally result in movement, which may lead to serious consequences during surgical manipulation in the middle ear. The use of glycopyrronium in the placebo group, in order to diminish salivation and thus to reduce the possibility of head movements during ear microsurgery caused by swallowing, may raise doubts about the design of the study. However, glycopyrronium is unable to cross the blood-brain barrier [19] and those muscarinic receptor antagonists that are effective in reducing nausea and vomiting act by blocking central muscarinic receptors in afferent

4 52 British Journal of Anaesthesia pathways of the vomiting reflex [20]. Glycopyrronium has been shown not to affect gastric emptying and intestinal transit times [21]. The overall percentage of placebo-treated patients reporting emetic symptoms in this study was also the same as that in two recently published studies on PONV after middle ear surgery under general anaesthesia [1, 2]. Drugs effective in motion sickness include centrally acting muscarinic receptor antagonists [22] and there are no data suggesting that glycopyrronium affects the vestibular system [23]. Furthermore, it was given approximately 4 min before local anaesthesia with lignocaine containing adrenaline and the increase in pulse rate was masked by the tachycardia caused by the local anaesthesia. The results of this study are in agreement with earlier studies showing that transdermal hyoscine is an effective prophylactic against PONV [1, 2, 5 9]. In the present study, the patients in the placebo group with a history of motion sickness had a higher frequency of nausea and vomiting than the patients without motion sickness and this finding has also been reported elsewhere [1, 24, 25]. The reduction in nausea and vomiting in the hyoscine group, in relation to motion sickness may result from specific inhibition of the post-synaptic potential in the neurones of the vestibular nuclei [14]. This assumption is supported by the fact that in the placebo group there was a significant correlation between motion sickness and nausea and vomiting during and after surgery but this was not the case in the hyoscine group. Posturography revealed that the patients in the placebo group not suffering from retching and vomiting, had better vestibulo-spinal function after surgery than those suffering from these symptoms. In the hyoscine group there was no difference in deterioration in postural stability between those without emetic and those with emetic sequelae (retching and vomiting), which also supports a direct action of hyoscine on the vestibular system [14]. In a recently published study on the effect of transdermal hyoscine on PONV after outpatient ear surgery there was, in common with this study, both more PONV and vertigo in the placebo group [2]. In a recently published study on postoperative nystagmus and nausea [26] there was a marked correlation between PONV and nystagmus, which is also caused by vestibular dysfunction. The recordings were made earlier than in our study: the first after the patient was oriented to time and space in the recovery room and the second soon after arrival in the short-procedure unit. As described earlier [1], because the frequency of PONV after ear surgery declines throughout the first 24 h after operation it is possible that posturography performed 24 h after surgery was too late to reveal the real magnitude of correlation between PONV and postural instability. Vestibular symptoms in the form of imbalance and occasional dizziness have been reported to last weeks after surgery [3]. Acknowledgement I acknowledge the numerous discussions with the Professor in Otology, Ilmari Pyykkö, MD, during the preparation of the programme of posturography for this study, during assessment of the results of posturographies and during the revision of the manuscript. References 1. Honkavaara P, Saarnivaara L, Klemola U-M. Prevention of nausea and vomiting with transdermal hyoscine in adults after middle ear surgery during general anaesthesia. British Journal of Anaesthesia 1994; 73: Reinhart DJ, Klein KW, Schroff E. 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