INTRAOCULAR PRESSURE CHANGES DURING RAPID SEQUENCE INDUCTION OF ANAESTHESIA: COMPARISON OF PROPOFOL AND THIOPENTONE IN COMBINATION WITH VECURONIUM

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1 Br. J. Anaesth. (1988), 60, INTRAOCULAR PRESSURE CHANGES DURING RAPID SEQUENCE INDUCTION OF ANAESTHESIA: COMPARISON OF PROPOFOL AND THIOPENTONE IN COMBINATION WITH VECURONIUM R. K. MIRAKHUR, W. F. I. SHEPHERD AND P. ELLIOTT Induction of anaesthesia with propofol (2,6,- diisopropylphenol) has been reported to be smooth, without major adverse effects and associated with rapid, smooth recovery [1 3]. Previous studies have shown that its use is also associated with significant reduction in intraocular pressure (IOP) and some benefit in attenuating the increase in IOP associated with tracheal intubation. In addition, many of these patients may present with a full stomach, but the use of perforated eye injuries. This is particularly so during induction of anaesthesia and tracheal intubation. In addition, many of these patients may present with a full stomach, but the use of suxamethonium (which is the neuromuscular blocking agent of choice for a rapid sequence induction in patients with a full stomach) may be considered contraindicated in patients with perforated eye injuries because of its well documented effect in increasing IOP. In the present study, intraocular pressure changes have been studied during a rapid sequence induction using propofol or thiopentone in combination with vecuronium. PATIENTS AND METHODS Forty adult patients conforming to ASA grades I or II were included in the study after their informed consent and approval from the Regional Ethics Committee had been obtained. All were to undergo elective ophthalmic surgery and any patient with an increased IOP (more than 20 mm Hg) before operation was excluded from the R. K. MIRAKHUR, M.D., PH.D., F.F.A.R.C.S., F.F.A.R.C.S.I.; P. ELLIOTT, M.D., F.F.A.R.C.S., Department of Clinical Anaesthesia, Royal Victoria Hospital, Belfast. W. F. I. SHEPHERD, F.R.C.S., Department of Ophthalmology, Queen's University of Belfast, Belfast. Accepted for Publication: October 9, SUMMARY Intraocular pressure (IOP) was measured during rapid sequence induction of anaesthesia using thiopentone or propofol as the induction agent and vecuronium for neuromuscular blockade. Vecuronium was administered in a dose of 0.15 mg kg~ 1 approximately 35 s before the induction agent. IOP was measured with a handheld app/anation tonometer before anaesthesia, following administration of the induction agent immediately after trachea/ intubation and cuff inflation and 1, 2 and 3 min later. IOP in the propofol group was significantly lower than in the thiopentone group, except immediately after induction, when reduction in IOP was similar and significant with both agents. IOP following intubation in patients in whom anaesthesia was induced with thiopentone was not significantly different from baseline values, but showed a significant increase from the pressure before intubation. In contrast, IOP after intubation in the propofol group remained not only significantly less than the baseline value, but also showed only a minimal and insignificant change in comparison with values before intubation. The frequency of side effects was low in both groups except for a significantly greater reduction in arterial pressure in those receiving propofol. study. Premedication consisted of diazepam mg by mouth. On arrival in the anaesthetic room the patient was given fentanyl 2 (ig kg" 1 i.v. Preoxygenation was carried out for 5 min with the face mask being held lightly by the patient. Vecuronium was administered in a dose of 0.15 mg kg" 1. This was followed, as soon as the earliest subjective feelings of muscle weakness such as the

2 380 BRITISH JOURNAL OF ANAESTHESIA Grade TABLE I. Grading of iniubating conditions Criteria TABLE II. Intraocular pressure (mm Hg±SD). Differences from baseline significant: *P < 0.01; **P < Differences significant between propofol and thiopentone groups at all times except baseline and after induction; P < 0.05-P < Excellent Satisfactory Fair Poor Good jaw relaxation, vocal cords open, no response to intubation Good jaw relaxation, vocal cords open, minimal reaction to intubation Jaw relaxed, cords moving, intubation requiring firm pressure and accompanied by moderate bucking or coughing Intubation impossible because of poor jaw or cord relaxation 1 min after intubation 2 min after intubation 3 min after intubation Propofol Thiopentone ±2.75 k ** ** 9.9 ±2.79*' * 13.0± *' * 5.9±2.48* ±3.63** * ** heaviness of the eyelids appeared, by the rapid administration of propofol or thiopentone, in a dose sufficient to abolish verbal communication with the patient. Cricoid pressure was applied immediately after administration of the induction agent and intubation and cuff inflation carried out 30 s later. Ventilation was started at this stage with nitrous oxide and isoflurane in oxygen. IOP was measured using a hand-held applanation tonometer before induction of anaesthesia (using amethocaine), after administration of the induction agent, immediately after intubation and cuff inflation and 1, 2 and 3 min later. Heart rate and systolic arterial pressure were measured at the same time as IOP using an electrocardiograph and oscillotonometer (Dinamap). The time to onset of complete blockade and duration of clinical neuromuscular blockade by vecuronium were determined using a peripheral nerve stimulator (Myotest) delivering a train-offour stimulation at 2 Hz every 10 s via cutaneous electrodes. Onset of complete block was denned as the time from administration of the blocking drug to the disappearance of all four responses, and the duration of clinical blockade as the time from administration of the myoneural blocker to the reappearance of all the four responses. Further smaller increments of vecuronium were administered as required at this stage. Intubating conditions were graded on a four-point scale as excellent, satisfactory, fair or poor, according to criteria listed in table I. Residual neuromuscular blockade was antagonized at the end of surgery with a mixture of neostigmine and glycopyrrolate. Side effects such as pain on injection, hiccup or spontaneous movements were also recorded. Patients were questioned the next day about the acceptability of anaesthesia. The results were tested for statistical significance by analysis of variance and t tests. Intubating conditions were compared using the Fisher's Exact Test. RESULTS The mean age and weight were 40 (16.4) yr (SD) and 66 (12.9) kg for the propofol group, and 43 (18.3) yr and 71 (12.7) kg for the thiopentone group, respectively, and these were not significantly different. The baseline IOP values were 14.4 (2.4) and 14.1 (2.75) mm Hg in the propofol and thiopentone groups, respectively; again the difference was not significant. IOP decreased significantly (P < 0.001) following administration of both propofol and thiopentone (table II). The reduction was greater with propofol (5.3 mm Hg or 37%) than with thiopentone (4.3 mm Hg or 30%), but this difference between the groups was not statistically significant. The IOP after intubation and cuff inflation increased from 9.8 mm Hg to 13.0 mm Hg in the group in whom anaesthesia was induced with thiopentone. Although it was still less than the baseline value, the increase from the value just before intubation was significant (P < 0.01). The IOP in the group given propofol increased from 9.1 to only 9.9 mm Hg following intubation and this change was not statistically significant. IOP was significantly less than (P < 0.01) the baseline values in both groups for the remainder of the study period. IOP values in the propofol group were significantly lower (P < 0.05) than in the thiopentone group throughout the study period, with the exception of the value recorded immediately after induction. Mean systolic arterial pressures (table III) before induction of anaesthesia were not sig-

3 RAPID SEQUENCE INDUCTION AND IOP 381 TABLE III. Systolic arterial pressure (mm Hg±SD). Differences significant compared with baseline: *P<0.05; **P < Differences significant between propofol and thiopentone groups throughout except baseline (P < 0.005) TABLE V. Intubating conditions and neuromuscular blockade Propofol (n = 20) Thiopentone (n = 20) 1 min after intubation 2 min after intubation 3 min after intubation Propofol ** 129± ** 108±21.6** ** Thiopentone ± ±30.3* 158± ±28.8* Intubating conditions Excellent Satisfactory Time (± SD) to onset of complete blockade (s) Duration (± SD) of clinical blockade (min) ± ± ± ±6.7 TABLE IV. Heart rate (beat min' 1 ±SD). Differences from blockade are shown in table V. All the intubations were graded as satisfactory, but more baseline significant: *P<0.05; **P < Differences significant between propofol and thiopentone throughout (P were < graded as excellent in those receiving 0.01) except baseline propofol (17 compared with 13). The onset and Propofol Thiopentone duration of clinical blockade of the initial mg kg" 1 dose of vecuronium were 187 and 210 s and 42 and 44 min, respectively, in propofol and thiopentone groups (ns) ±19.1** ** The average induction doses of propofol and 1 min after intubation ±16.4** thiopentone were 2.5 and 5.4 mg kg" 1, respectively, and the majority of injections were made 2 min after intubation ±15.7** 3 min after intubation ±14.6* to a vein on the dorsum of the hand. End-tidal carbon dioxide concentration during surgery was maintained between 3.5 and 4.0 %. One patient in each group complained of mild discomfort on administration of the induction agent. There were no other side effects. Four patients in the propofol group and six in the thiopentone group suffered from nausea, vomiting or both in the immediate postoperative period. There was no venous sequelae 24 h after anaesthesia. The induction sequence was deemed acceptable by all patients when they were questioned the day after anaesthesia. nificantly different in the two groups. Arterial pressure decreased significantly (P < 0.005) in the propofol group and remained so throughout the study period except after intubation. In the thiopentone group the only significant changes in arterial pressure were an increase after intubation (P < 0.01) and a decrease 3 min later (P < 0.05). The average peak decrease in systolic arterial pressure was 25.4% in the propofol group and 7.1% in the thiopentone group. Eleven patients receiving propofol demonstrated a decrease in arterial pressure of greater than 25%, three of these exhibiting a reduction of more than 40%. However, hypotension was transient and responded to ml of crystalloid solutions. Heart rate responses in the two groups were also different (table IV). There was no significant change in mean heart rate in those given propofol, but heart rate increased significantly in those given thiopentone (P < 0.01) with a peak increase of approximately 37 % after intubation. The average time between administration of vecuronium and induction agent was approximately 35 s. The intubating conditions and the onset and duration of clinical neuromuscular DISCUSSION Induction of anaesthesia for repair of a perforated eye injury in a patient with a full stomach is a challenging situation for the anaesthetist. The important considerations are the protection of the airway from the hazard of regurgitation and aspiration of the gastric contents, and preventing increases in IOP, consequent upon tracheal intubation, with the harmful possibility of further damage to the eye and even loss of the intraocular contents. The role of neuromuscular blocking agents has been the subject of many previous investigations, but in the present study the choice

4 382 BRITISH JOURNAL OF ANAESTHESIA of the induction agent and the induction sequence itself have been examined. Suxamethonium is considered the myoneural blocker of choice for facilitating tracheal intubation during a rapid sequence induction in patients with a full stomach. However, its use is associated with an increase in IOP [6-8]. Vecuronium was used in the present study both for its beneficial effect in terms of a significant reduction in IOP [9, 10] and for its relatively short duration of action and lack of side effects, even when used in a moderately large dose of 0.15 mg kg~ l [11]. It is well known that tracheal intubation itself may produce an increase in IOP irrespective of the neuromuscular blocking agent used [6, 8, 12, 13]. On this basis and because they could find no evidence of extrusion of ocular contents from retrospective analysis of case records, Libonati, Leahy and Ellison [14] advocated that it was safe to use suxamethonium in patients with perforated eye injuries, and this view has been supported in a more recent review [15]. However, Libonati, Leahy and Ellison [14] reviewed the records of fewer than 50% of the patients admitted with such eye injuries. In addition, they did not comment on the visual function of these patients and they could not have known if avoiding suxamethonium would have resulted in better functional results. It has been shown that, although the IOP increases following intubation with the use of both depolarizing and non-depolarizing neuromuscular blockers, the change is less with the use of the latter [8]. Non-depolarizing blocking agents such as pancuronium or alcuronium have been recommended for rapid sequence induction in patients with perforated eye injuries [16, 17], this suggestion being based on the fact that, in these studies, IOP after intubation was not significantly higher than the baseline values, even though the IOP increased following intubation. The technique of induction, in addition to the induction agent itself, has received little attention in rapid sequence inductions, regarding effects on IOP. Thiopentone is known to produce a significant reduction in IOP [13, 18]. Recent studies have not only confirmed this, but also shown that the newer agent, propofol, produces an even greater reduction in IOP and that its use may attenuate the subsequent increase in IOP produced by intubation [4, 5]. It appears that this advantage of propofol is also apparent when it is used as part of a rapid sequence induction. This benefical effect of propofol may be the result of significantly greater hypotension with its use [2, 4, 5, 19], lack of antanalgesic action [20] or a possible greater "depth of anaesthesia " [21]. The doses of propofol and thiopentone required to induce anaesthesia in the present study are similar to those reported by others during normal induction in adult patients [2, 22]. The technique of induction has been shown to have important effects on IOP. Where an induction agent such as thiopentone is administered in a conventional manner before large doses of atracurium or vecuronium, there is still an increase in IOP following intubation [23]. This also occurs when propofol is the induction agent [24]. In the present study the administration of the induction agents after vecuronium ensured that the intubation was carried out at the peak effect of the induction agent and also approximately 90 s after administration of vecuronium (approximately 35 s between administration of the neuromuscular blocker and the induction agents, s for administering the induction agent, and intubation 30 s after their administration). It has been shown previously that intubating conditions with vecuronium in doses of mg kg" 1 are satisfactory at approximately 90 s and that intubation using these doses can be carried out in the absence of complete paralysis [11, 25]. As a result of the use of propofol, vecuronium and this induction sequence, intubation was associated with only a small, insignificant increase in IOP. Careful assessment of the airway should be made before administration of the neuromuscular blocker, as would be the practice in any other situation. In the event of anticipated difficulty in intubation, it is prudent to avoid the use of myoneural blockade, to starve the patient and to use other means of securing the airway. Because of the significantly greater reduction in arterial pressure with the use of propofol, this agent should be used with caution or even avoided in situations in which severe hypotension is undesirable. However, the advantage of good control of IOP in otherwise healthy patients with perforated eye injuries may outweigh the risk of hypotension, which is usually transient and responds to simple measures such as i.v. fluid administration [5]. In conclusion, good control of IOP is achieved during a rapid sequence induction when vecuronium is followed by propofol. This may be a suitable technique for induction of anaesthesia in

5 RAPID SEQUENCE INDUCTION AND IOP 383 patients with a full stomach who are to undergo repair of perforated eye injuries, provided there are no contraindications to either the use of any of the agents used or the technique itself. ACKNOWLEDGEMENTS The authors thank I.C.I, pic for supply of propofol used in the present study and for financial assistance, and Miss Sharon Connery for secretarial help. REFERENCES 1. Cummings GC, Dixon J, Kay NH, Windsor JPW, Major E, Morgan M, Sear JW, Spence AA, Stephenson DK. Dose requirements of ICI (Propofol, 'Diprivan') in a new formulation for induction of anaesthesia. Anaesthesia 1984; 39: Mackenzie N, Grant IS. Comparison of the new emulsion formulation of propofol with methohexitone and thiopentone for induction of anaesthesia in day cases. British Journal of Anaesthesia 1985; 57: Edelist G. A comparison of propofol and thiopentone as induction agents in outpatient surgery. Canadian Journal of Anaesthesia 1987; 34: Mirakhur RK, Shepherd WFI. Intraocular pressure changes with propofol ("Diprivan"): Comparison with thiopentone. Postgraduate Medical Journal 1985; 61 (Suppl. 3): 41^4. 5. Mirakhur RK, Shepherd WFI, Darrah WC. Propofol or thiopentone: effects on intraocular pressure associated with induction of anaesthesia and tracheal intubation (facilitated with suxamethonium). British Journal of Anaesthesia; 59: Pandey K, Badola P, Kumar S. Time course of intraocular hypertension produced by suxamethonium. British Journal of Anaesthesia 1972; 44: Cook JH. The effect of suxamethonium on intraocular pressure. Anaesthesia 1981; 36: Lavery GG, McGalliard JN, Mirakhur RK, Shepherd WFI. The effects of atracurium on intraocular pressure during steady state anaesthesia and rapid sequence induction: a comparison with succinylcholine. Canadian Anaesthetists Society Journal 1986; 33: 437^ Jantzen J-P, Hackett GH, Erdmann K, Earnshaw G. Effect of vecuronium on intraocular pressure. British Journal of Anaesthesia 1986; 58: Mirakhur RK, Shepherd WFI, Lavery GG, Elliott P. The effects of vecuronium on intra-ocular pressure. Anaesthesia 1987; 42: Mirakhur RK, Ferres CJ, Clarke RSJ, Bali IM, Dundee JW. Clinical evaluation of Org NC45. British Journal of Anaesthesia 1983; 55: Goldsmith E. an evaluation of succinylcholine and gallamine as muscle relaxants in relation in intraocular tension. Anesthesia and Analgesia 1967; 46: Joshi C, Bruce DL. Thiopental and succinylcholine action on intraocular pressure. Anesthesia and Analgesia 1975; 54: Libonati MM, Leahy JL, Ellison N. The use of succinylcholine in open eye surgery. Aneslhesiology 1985; 62: Cunningham AJ, Barry P. Intraocular pressure physiology and implications for anaesthetic management. Canadian Anaesthetists Society Journal 1986; 33: Litwiller RW, Difazio CA, Rushia EL. Pancuronium and intraocular pressure. Anesthesiology 1975; 42: Balamoutsos NG, Tsakona H, Kanakoudes PH, Iliadelis E, Georgiades CG. Alcuronium and intraocular pressure. Anesthesia and Analgesia 1983; 62: Verma RS. "Self-taming" of succinylcholine-induced fasciculations and intraocular pressure. Anesthesiology; 50: Fahy LT, VanMourik GA, Utting JE. A comparison of the induction characteristics of thiopentone and propofol. Anaesthesia 1985; 40: Briggs LP, Dundee JW, Bahar M, Clarke RSJ. Comparison of the effect of diisopropyl phenol (ICI 35868) and thiopentone on response to somatic pain. British Journal of Anaesthesia 1982; 54: Doze VA, Westphal LM, White PF. Comparison of propofol with methohexital for outpatient anesthesia. Anesthesia and Analgesia 1986; 65: McCollum JSC, Dundee JW. Comparison of the induction characteristics of four intravenous anaesthetic agents. Anaesthesia 1986; 41: Schneider MJ, Stirt JA, Finholt DA. Atracurium, vecuronium and intraocular pressure in humans. Anesthesia and Analgesia 1986; 65: Elliott P, Mirakhur RK, Shepherd WFI. Intraocular pressure during induction of anesthesia with propofol or thiopental followed by vecuronium: influence of an addition dose of the induction agent. Anesthesiology 1987; 67: A Agoston S, Salt P, Newton D, Bencini A, Boomsma P, Erdmann W. The neuromuscular blocking action of Org NC45, a new pancuronium derivative, in anaesthetized patients. A pilot study. British Journal of Anaesthesia 1980;52:53S-59S.