ORIGINAL ARTICLE
The Effects of Different Doses of Remifentanil on Intraocular Pressure after Tracheal Intubation: A Randomized, Double-blind and Prospective Study KENAN KAYGUSUZ, MD, M. ILKER TOKER, MD, ICLAL OZDEMIR KOL, MD, HAYDAR ERDOGAN, MD, SINAN GURSOY, MD, CANER MIMAROGLU, MD
ABSTRACT We investigated the effects of alfentanil and different doses of remifentanil on intraocular pressure (IOP) and hemodynamic responses during laryngoscopy and endotracheal intubation in 60 patients. IOP values decreased significantly from 30 seconds before the intubation to 5 minutes after intubation measurements compared to baseline values in all the groups. However, a significant increase in IOP was recorded in the 0.5-lg remifentanil group after tracheal intubation.
I N T R O DU C T I O N
REPRINTS Kenan Kaygusuz, MD, Department of AnesthesiologyCumhuriyet University School of Medicine, Sivas, 58140, Turkey. E-mail:
[email protected]. Drs. Kaygusuz, Kol, Gursoy and Mimaroglu are from the Department of Anesthesiology and Drs. Toker and Erdogan are from the Department of Ophthalmology, Cumhuriyet University School of Medicine, Sivas 58140, Turkey. The authors have stated that they do not have a significant financial interest or other relationship with any product manufacturer or provider of services discussed in this article. The authors also do not discuss the use of off-label products, which includes unlabeled, unapproved, or investigative products or devices. The authors investigated the effects of alfentanil, and different doses of remifentanil on intraocular pressure (IOP) and hemodynamic responses during laryngoscopy and endotracheal intubation. Submitted for publication: 3/1/07. Accepted: 3/27/07. Annals of Ophthalmology, vol. 39, no. 3, Fall 2007 Ó Copyright 2007 by ASCO All rights of any nature whatsoever reserved. 1530-4086/07/39:198–204/$30.00. ISSN 1558-9951 (Online)
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Normal intraocular pressure (IOP) values are between 10–20 mmHg and variations of 2–3 mmHg are accepted as normal (1). IOP is affected by the changes in aqueous humor volume, central venous pressure, and extra-ocular muscle functions (2,3). Hemodynamic values and IOP should be kept stabile during surgery for cataract, glaucoma, and certain ocular diseases. For this reason, the proper use of anesthetic agents and anesthesia techniques are important. The IOP, blood pressure and HR increases associated with laryngoscopy and endotracheal intubation have been reported in many studies (4–7). After induction of anesthesia, when the sympathetic responses are not adequately suppressed, IOP increase, together with other important hemodynamic changes, can cause potential risks associated with laryngoscopy and endotracheal intubations (4,8–10). Most of the analgesic agents reduce IOP by decreasing muscle tension, depressing central nervous system, and facilitating aqueous humor flow (11). Remifentanil, which is a commonly administered agent for anesthesia induction, is the ultra-short acting, selective, mu-receptor agonist, which is 20–30 times more
potent than alfentanil. It has a rapid onset of analgesia with a peak effect 1 minute after administration (12). In this study, the effects of alfentanil and different doses of remifentanil on the hemodynamic responses and IOP during endotracheal intubations were investigated.
MATERIAL AND METHODS This study was conducted after obtaining local ethical committee approval and written patient consent. Sixty patients between 18 and 50 years of age were included in this double-blind, randomized study. All patients were ASA I–II and underwent elective nonophthalmic surgery with general anesthesia. The patients who had ocular, cardiac, respiratory, neuromuscular diseases, increased intracranial pressure, esophageal reflux, hiatus hernia, drug allergy and sedative and narcotic drug usage history in last 24 hours were excluded from the study. The patients were randomly divided into three groups: 20 lg/kg IV alfentanil was given to the patients in alfentanil group (n = 20); 1 lg/kg IV remifentanil was given to the patients in 1-lg remifentanil group (n = 20); and 0.5 lg/kg IV remifentanil was given to the patients in 0.5-lg remifentanil group (n = 20). All patients had premedication with intramuscular midazolam (0.07 mg/kg) 30 minutes before induction. The patients were taken in to the operation room and their electrocardiography, non-invasive blood pressures and peripheral oxygen saturations were monitored (Critic Care 1100, Critic Care System Inc., USA). The preoxygenation was applied for 3 minutes before induction. The inductions of patients in three groups were performed with 2 mg/kg propofol and the muscle relaxations were obtained with 0.1 mg/kg vecuronium. The study drugs were injected by diluting with 5 mL normal saline immediately following induction agents. Tracheal intubation was performed 90 seconds after the study drugs. All tracheal intubations were made after induction by the same physician (K.K.). Anesthesia was maintained with 2% sevoflurane (Sevorane liquid 250 mL, Abbott, UK) in 50% N2O/ O2. ETCO2 values were held between 35 and 45 mmHg during the anesthesia induction and maintenance. IOP measurements (mmHg) were made by the same physician (M.I.T.) by using Perkins Applanation tonometer (Clement Clarke, International LTD., UK) from left eyes at supine position, after dropping
topical anesthetic proparacain (Alcain, Alcon, Belgium). IOP was measured 5 minutes before induction and accepted as baseline value. Following the administration of the study drugs, subsequent measurements were performed 30 seconds before intubation (60 seconds after the study drugs) and 1, 2, and 5 minutes after the intubation. Mean arterial pressure (MAP), heart rate (HR), and oxygen saturation (SpO2) values were also recorded simultaneously with the IOP measurements. Hypotension was defined as systolic blood pressure 0.05), a significant increase was determined in the 0.5-lg remifentanil group (p < 0.05). Figure 2 displays MAP of the study groups measured at baseline, 30 seconds ANN OPHTHALMOL. 2007;39 (3) ..............................................199
TABLE 1 Age, Sex, and Weight of the Alfentanil and 1 and 0.5-lg Remifentanil Groups. Data 294 were Expressed as Mean ± SD Alfentanil Age (year) Sex (M/F) Weight (kg)
35.00 ± 2.31 10/10 68.25 ± 2.20
1-lg remifentanil
0.5-lg remifentanil
30.50 ± 2.32 11/9 68.70 ± 2.11
30.55 ± 2.29 12/8 64.70 ± 1.61
Figure 1—Intraocular pressure values of the alfentanil and 1-lg and 298 0.5-lg remifentanil groups. Data were expressed as mean ± SE. BL—baseline; Label a—p < 0.05 vs. baseline value of alfentanil and 1 and 0.5-lg remifentanil groups, b—p < 0.05 vs. 30-sec before intubation value of 0.5-lg remifentanil group respectively.
before and 1, 2, and 5 minutes after the intubation. MAP value decreased significantly in 30 seconds before and 1, 2, and 5 minutes after the intubation measurements below the baseline value in the all groups (p < 0.05). There was no significant increase in MAP after the intubation compared to the value before intubation (30 seconds before intubation measurement) in the alfentanil group (p > 0.05); however, a significant increase was determined in the 0.5-lg and 1-lg remifentanil groups (p < 0.05). Figure 3 presents HR values of the study groups measured at baseline, 30 seconds before the intubation, and 1, 2, and 5 minutes later after the intubation. There were significant decreases of HR value in 30 seconds before and 5 minutes after intubation measurements compared to baseline values in the alfentanil and 1-lg remifentanil groups (p < 0.05). ANN OPHTHALMOL. 2007;39 (3) ..............................................200
Meanwhile HR was decreased significantly below the baseline value in 30 seconds before intubation measurement (p < 0.05), but increased significantly in 1 minute after intubation measurement in the 0.5-lg remifentanil group (p < 0.05). While there was no significant increase of HR value after intubation according to the value before intubation (30 seconds before intubation measurement) in the alfentanil group (p > 0.05), the significant increases were determined in the 0.5-lg and 1-lg remifentanil groups (p < 0.05). When the baseline values were compared for IOP, MAP and HR, the difference between the three groups was not significant (p > 0.05). When the IOPs were compared between the groups; 30 seconds before intubation value of 0.5-lg remifentanil group was found lower than 30 seconds before intubation
Figure 2—Arterial pressure value of the alfentanil and 1 and 0.5-lg remifentanil groups. Data were expressed as mean ± SE. BL—baseline; Label a—p < 0.05 vs. baseline value of alfentanil and 1-lg and 0.5-lg remifentanil groups, respectively; Labels b,c—p < 0.05 vs. 30-s before intubation value of 1 and 0.5-lg remifentanil groups; Label d—p < 0.05 vs. 30-s before intubation value of alfentanil group; Label e—p < 0.05 vs. 2-min after intubation value of alfentanil group.
Figure 3—Heart rate value of the alfentanil and 1 and 0.5-lg remifentanil groups. Data were expressed as mean ± SE. BL—baseline; Labels a,b,c—p < 0.05 vs. baseline value of alfentanil and 1 and 0.5-lg remifentanil groups, respectively; Labels d,e—p < 0.05 vs. 30-s before intubation value of 1 and 0.5-lg remifentanil groups.
value of alfentanil group (p < 0.05). The difference between the other measurements was not significant (p > 0.05). When the MAP value were compared, 30 seconds before intubation value of alfentanil group was found higher than 30 seconds before intubation value of the
1-lg remifentanil group (p < 0.05). At 2 minutes after intubation, the value of alfentanil group was lower than that of 0.5-lg and 1-lg remifentanil groups (p < 0.05) (Fig. 2). When the HR values were compared, we found an increase in HR of 0.5-lg remifentanil group compared to the alfentanil and 1-lg ANN OPHTHALMOL. 2007;39 (3) ..............................................201
remifentanil groups for 5 minutes after intubation measurement, but not reaching statistical significance (p > 0.05).
DISCUSSION Hemodynamic parameters and IOP must be kept stabile during the surgery of cataract, glaucoma, and certain ocular diseases. Therefore, the type and dosage of selected anesthetic agent and its administration technique are important. Increase in the IOP, blood pressure, and HR associated with laryngoscopy and endotracheal intubation has been reported in many studies (4–7). IOP increase associated with tracheal intubation was higher than the IOP increase after the use of succinylcholine (13–15). Although the mechanism of the IOP elevation is not completely clear, the sympathetic response originating from the tracheal intubation was thought to be involved (8,9). One method to reduce IOP and hemodynamic response is to use analgesics (15–19). The IOP lowering mechanism of alfentanil and remifentanil can be same with that of other central nervous system depressants. This mechanism can be explained by intra- or extra-ocular muscle relaxation, the facilitation of the aqueous humor drainage, or the decreased aqueous humor production (7,8). It is known that propofol decreases IOP and attenuates hemodynamic response by reducing sympathic response (14,20). Additionally, it is known that non-depolarizing muscle relaxants have no affect or slightly decrease IOP (3,21). In this study, in all the groups, propofol was used for the anesthesia inductions and vecuronium bromide was used as muscle relaxant. For this reason, we assumed that the hemodynamic findings and IOP would be comparable for all the groups. We observed a decrease in the IOP before the intubation with the administration of the study drugs in all the groups. However, while the IOP after the intubation were not increased compared to that before intubation in alfentanil and 1-lg remifentanil groups, it was increased in 0.5-lg remifentanil group. This might be explained by the failure of remifentanil dose in 0.5-lg remifentanil group in suppressing the responses associated with laryngoscopy and intubation. In our study, the low dose remifentanil reduced the IOP compared to baseline value in 0.5-lg remifentanil, but it could not sufficiently suppress the responses associated with the tracheal intubations. As our study, Ng et al. (22) reported that 1 lg/kg remifentanil application before the anesthetic inductions blocked the IOP increase related to succinylcholine and the tracheal intubation. ANN OPHTHALMOL. 2007;39 (3) ..............................................202
Similarly, Alexander et al. (10) had shown that 1 lg/ kg remifentanil administration after the anesthesia induction blocked the IOP increases related to succinylcholine and the tracheal intubations. Sweeney et al. (15) tested 10 lg/kg alfentanil before anesthesia induction and found lower IOP values than basal IOP values after the alfentanil application. They reported that the IOP increased after the intubation following the induction, but this increase did not rise over the basal values. In our study, there was also a decrease in IOP 30 seconds before the intubation in the alfentanil group. However, unlike the findings by Sweeney et al., the IOP values did not increase after the intubation. This condition can either be explained by the fact that the dose of alfentanil used in our study was two times more than that used in the study by Sweeney et al. or by the use of vecuronium (3), which has been known to have little or no effect on IOP, as a muscle relaxant compared to succinylcholine. Eti et al. (23) reported that propofol 2.5 mg/kg and alfentanil 10 lg/kg decreased the IOP that was not changed after succinylcholine and the intubation in contrast to our findings. Zimmerman et al. (24) used propofol 2 mg/kg and alfentanil 40 lg/kg for the induction. They found that the IOP decreased after the induction and intubation below the basal values. We obtained similar results with Zimmerman et al., although their alfentanil dose was two times more than our dose. This can be due to the use of succinylcholine, a known IOP elevator by Zimmerman et al. Klemola et al. (25) combined propofol 2.5 mg/kg separately with remifentanil 3 lg/kg, remifentanil 4 lg/kg or alfentanil 30 lg/kg for the intubations without muscle relaxant. They reported that high dose remifentanil suppressed the hemodynamic responses in a better way. On the other hand, Lavazais et al. (26) reported that in contrast to high dose narcotics like alfentanil 30–40 lg/kg and remifentanil 4 lg/kg, low dose narcotics plus muscle relaxants cause more controlled hemodynamic and IOP changes. Similar results were obtained in our study, which showed that alfentanil 20 lg/kg or remifentanil 1 lg/ kg combined with a muscle relaxant was highly effective to control IOP and hemodynamic changes. Siniran et al. (27) reported that alfentanil 20 lg/kg given before the induction was effective to suppress hemodynamic response related to tracheal intubation. Mostafa et al. (28) studied the effect of alfentanil and fentanyl on the IOP, and they reported that alfentanil caused a decrease in MAP and HR below the basal values. We also determined a decrease in the MAP
and HR compared to the basal values in alfentanil group. It was also reported that alfentanil 30 lg/kg successfully diminished the cardiovascular effects of the tracheal intubation (29). Studies with remifentanil showed that remifentanil 1 lg/kg application during the induction was sufficient to suppress hemodynamic response related to the tracheal intubation (10,22,30). Thompson et al. (31) reported that remifentanil 0.5 lg/kg infused for a few minutes following a bolus dose of remifentanil 1 lg/kg during the induction was suitable for the suppression of the hemodynamic responses due to tracheal intubation. However approximately 50% of the patients experienced bradycardia in their study. Hare et al. (32) used three different doses of remifentanil (0.5, 1, and 1.25 lg/kg) during the anesthetic induction for controlling the hemodynamic responses associated with the laryngoscopy and tracheal intubation. In respect of this, remifentanil 0.5 lg/kg was insufficient to control the hemodynamic response after the intubation, higher remifentanil doses (1 and 1.25 lg/kg) were sufficient to suppress the hemodynamic response but bradycardia and hypotension developed in 7 of 20 patients administered remifentanil 1.25 lg/kg. In our study, the drugs were applied as bolus in the remifentanil groups, when the hemodynamic responses related to the intubation were controlled in the 1 lg/kg remifentanil administered group, the HR values after the intubation were increased compared to the values before the intubation and the baseline value in the 0.5 lg/kg remifentanil administered group. In summary, the IOP rise associated with the laryngoscopy and endotracheal intubation can be prevented by alfentanil 20 lg/kg or remifentanil 1 lg/kg without any hemodynamic instability, but remifentanil 0.5 lg/kg used with the same purpose may not be sufficient.
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