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Sufentanil or clonidine for blunting the increase in intraocular pressure during rapid-sequence induction

Georgiou, M.; Parlapani, A.; Argiriadou, H.; Papagiannopoulou, P.; Katsikis, G.; Kaprini, E.

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European Journal of Anaesthesiology (EJA): November 2002 - Volume 19 - Issue 11 - p 819-822
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Rapid-sequence induction is an established technique in emergency anaesthesia to minimize the risk of pulmonary aspiration. Even though succinyl-choline remains unsurpassed in providing ideal intubating conditions [1], it is known to cause an increase in intraocular pressure (IOP) principally through prolonged fasciculation of the extraocular muscles. This may have detrimental effects in emergency surgical procedures of the open eye. When the globe of the eye is open, i.e. during certain surgical procedures or after traumatic perforation, the IOP approaches atmospheric pressure. Any factor that normally increases IOP will tend to cause drainage of aqueous humour or extrusion of the vitreous humour through the wound. The latter is a serious complication that can permanently damage vision.

Laryngoscopy and tracheal intubation induce changes in haemodynamic variables (hypertension), which may worsen this increase in IOP caused by succinylcholine. Many studies have examined the effects of anaesthetic and related drugs on IOP, and various pharmacological strategies have been suggested to prevent the hypertensive response to laryngoscopy and intubation and the increase in IOP. Opioids or clonidine are widely used to control haemodynamic responses induced by tracheal intubation. The aim of the study was to compare in patients without eye or cardiovascular pathology the effects of clonidine or sufentanil on the IOP during rapid sequence induction.


After approval by the local Ethics Committee and informed written consent, 32 ASA I-III patients, scheduled for elective non-ophthalmic surgery, were included in this prospective, double-blind and randomized study. Exclusion criteria were age >60 yr, a history of eye illness, arterial hypertension, ischaemic heart disease, congestive heart failure, the use of anti-hypertensive or cardiovascular drugs, or upper airway abnormalities, which might prolong the time required for intubation (Mallampati classification >2). Patients were randomly allocated to two groups when they arrived in the operating theatre: Group A received sufentanil 0.05 μg kg−1 intravenously (i.v.) 5 min prior to induction, and Group B received clonidine 2 μg kg−1 i.v. 5 min prior to induction.

An 18-G i.v. catheter was inserted and hydration with at least 500 mL lactated Ringer's solution i.v. was established. Standard monitoring was used throughout the study, including non-invasive arterial pressure, electrocardiography, heart rate (HR; lead II), capnometry and pulse oximetry. Basic haemodynamic variables were recorded. Syringes containing aqueous solutions of either sufentanil or clonidine were prepared in a double-blind fashion by one of the authors who was not involved in data recording. Patients and investigator anaesthetists were blinded about the patient group allocation. After 10 min of preoxygenation (O2 4 L min−1), the study drug was infused in both groups of patients and general anaesthesia was induced with fentanyl 5 μg kg−1 i.v. followed by a sleep dose of thiopental 5 mg kg−1 i.v. The Schioetz tonometer was used just before the succinylcholine administration (t0) to record IOP by one of the authors who was unaware of the already given test drug. Succinylcholine was then administrated at a dose of 1 mg kg−1 in both study groups. When the fasciculations had ceased, the IOP was measured for the second time (t1). The trachea was intubated under direct vision laryngoscopy and the correct position of the tracheal tube was verified by auscultation of the chest and by capnometry. If the trachea could not be intubated at the first attempt with direct laryngoscopy, the patient was excluded from the study. Immediately after tracheal intubation, IOP was measured for a third and last time (t2). Vecuronium 0.1 mg kg−1 provided the neuromuscular blockade. HR and mean arterial pressure (MAP) were also recorded at the same time intervals. A Julian anaesthesia machine (Dräger, Lübeck, Germany) was used, and lung ventilation was adjusted to maintain the end-tidal carbon dioxide partial pressure between 4.3 and 4.6 kPa. Anaesthesia was maintained in both groups with sevoflurane (1-3%) in a mixture of oxygen (33%) and air (67%).

Data are the mean ± SD. Parametric data were compared between groups by a paired t-test. Statistical significance was assumed if P < 0.05. Non-parametric data were analysed using χ2-tests between groups. Analysis was performed with the Statistical Package for the Social Sciences® (SPSS, Inc, Chicago, IL, USA).


Patient characteristics data did not differ between the two groups (Table 1). Changes in IOP in both groups during induction, laryngoscopy and intubation are presented in Figure 1. Of the 37 enrolled patients, two patients from Group A and three patients from Group B had to be withdrawn because of failure to intubate the trachea at the first attempt at direct laryngoscopy. Intubating conditions were equally good in both groups. Thirteen of 15 patients in the sufentanil group (Group A) and 14 of 17 patients in the clonidine group (Group B) achieved excellent intubating conditions, while two of 15 and three of 17 patients in Groups A and B respectively achieved good intubating conditions.

Table 1
Table 1:
Patient characteristics data.
Figure 1
Figure 1:
Intraocular pressure att 0: baseline; t 1: after succinylcholine administration; t 2: immediately after tracheal intubation. •: Group A; ○: Group B. *versus Group A, P < 0.05; **versus Group B, P < 0.05.

Within group changes in IOP

The clonidine group (Group B) experienced a gradual increase of IOP. The rise in IOP means in Group B reached statistical significance immediately after tracheal intubation (t2) compared with that measured just before the administration of succinylcholine (t0) (22.7 versus 16.3 mmHg; P < 0.05). After the end of fasciculations and before tracheal intubation (t1), IOP were higher (ns) compared with those measured at t0 (17.4 versus 16.3 mmHg).

On the contrary, the mean IOP in the sufentanil group (Group A) did not exceed the baseline values at any time interval. The decrease in IOP did not reach statistical significance at any time interval (t1, t2) compared with the baseline. The maximum decrease in IOP was observed just before tracheal intubation (t1) (11.5 versus 15.0 mmHg), while immediately after intubation (t2), IOP means reached almost those measured at the baseline (14.0 versus 15.0 mmHg).

Between group changes in IOP

IOP did not differ significantly between Groups A and B before the administration of succinylcholine (t0).

The mean IOP were significantly lower in the sufentanil group compared with the clonidine group after the end of fasciculations and just before tracheal intubation (t1) (11.5 versus 17.4 mmHg; P < 0.05) and immediately after intubation (t2) (14.0 versus 22.7 mmHg; P < 0.05).

No adverse effect such as severe tachycardia or bradycardia, hypertension or hypotension, chest wall rigidity or postoperative respiratory depression, which could be attributed to the use of either clonidine or sufentanil, were recorded.


IOP is determined by the rate of production of aqueous humour, the vitreous volume, the choroidal blood volume, scleral rigidity, orbicularis oculi muscle tension and external pressure [2]. Many factors influence IOP such as genetic status, age, refractive error and race [3]. The intraoperative increase of IOP has to be avoided in patients suffering from glaucoma or penetrating eye injury. In the latter, the IOP equals atmospheric pressure and any further increase could result in further loss of ocular contents [3].

Rapid sequence induction utilizing succinylcholine as a neuromuscular-blocking agent is an established technique to minimize the risk of pulmonary aspiration. The main characteristic of succinylcholine is its speed of onset, allowing intubation in 30-60 s. However, it is associated with an increase in IOP (which it increases by 5-10 mmHg for 5-10 min after i.v. administration). This increase is enhanced during laryngoscopy and tracheal intubation [3]. We administrated succinylcholine in a dose of 1 mg kg−1 without any incidence of coughing or gagging. This thiopental was chosen as an induction agent because it is more widely used for rapid-sequence induction. Furthermore, thiopental is known to cause a decrease in IOP [4]. Edmondson and colleagues [5] showed that there was only a marginal increase of IOP after administration of thiopental 5 mg kg−1 and succinylcholine 1.5 mg kg−1. The lower mean rise in IOP in the study of Edmondson and colleagues could be attributed to differences in methods. Their paper investigated the 'dynamic' situation of rapid sequence induction, while the present paper studied IOP changes at specific time intervals in a more isolated manner. Variations in fentanyl dosage and in the speed of injection of thiopental could also influence IOP and explain the differences observed.

Most anaesthetic and hypnotic agents, including the volatile anaesthetics [6], barbiturates, opioids [7], neuroleptics and benzodiazepines [8], decrease IOP in proportion to the depth of anaesthesia [6], and several pretreatment regimens have been advocated to attenuate the IOP response to tracheal intubation [3,8-10]. The intention of the present study was to compare the ability of sulfentanil or clonidine i.v. to obtund the increase of IOP during rapid sequence induction with succinylcholine.

Clonidine is a central acting α-2-adrenoreceptor agonist that has been used as an antihypertensive agent [11]. Other pharmacological actions of clonidine include inhibition of central sympathetic hyperactivity [12], sedation [13], analgesia [14], and a decrease in IOP following i.v., oral or topical administration [15-17]. The effect of clonidine in IOP is caused by a direct vasoconstrictor effect on the afferent blood vessels of the ciliary process, even at very low concentrations, which results in reduction of aqueous humour production. Another mechanism for the decline of IOP could be the increase of the outflow facility caused by a reduction of the sympathetically mediated vasomotor tone of the ocular drainage system [18,19].

Sufentanil is a short-acting opioid known to attenuate the haemodynamic responses to endotracheal intubation and surgical manipulation (e.g. incision). Some clinicians believe that sufentanil compared with other opioids may provide the greatest autonomic suppression and control over blood pressure [3].

We observed that the clonidine group showed higher IOP at t1 (just before intubation) and at t2 (just after intubation) as compared with t0. These values were significantly higher when compared with the sufentanil group at the same time intervals. The mean IOP in the sufentanil group did not exceed the baseline values (t0) at any time interval.

Our results showed that clonidine given i.v. before induction of anaesthesia is inadequate for reducing IOP after succinylcholine administration. This could be explained by the fact that the peak effect of clonidine i.v. is achieved after 30-60 min, thus failing to reach adequate levels when intubation is attempted. As a result, it may be unsuitable for blunting the IOP increase in emergency operations requiring a rapid sequence induction. On the contrary, Polarz and colleagues [20] showed that oral premedication with clonidine could prevent the increase of IOP following succinylcholine administration, since the peak effect of oral clonidine is achieved after 2-4 h.

Badrinath and colleagues [12] found that the administration of sufentanil at subanaesthetic doses before induction of anaesthesia inhibits the increase of IOP associated with succinylcholine and tracheal intubation. Stirt and Chiu [21] showed that the combination of sufentanil or fentanyl with thiopental, and vecuronium or atracurium produced satisfactory conditions for tracheal intubation following rapid sequence induction without an increase in IOP.

In conclusion, the results show that the use of a small subanaesthetic dose of sufentanil may inhibit the increase in IOP associated with succinylcholine administration during rapid sequence induction. On the other hand, clonidine failed to show the same effect, probably due to its prolonged acting time.


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© 2002 European Academy of Anaesthesiology