Effect of intravenous metoclopramide on intraocular pressure: A prospective, randomized, double-blind, placebo-controlled studyKS Sudheera, N Bhardwaj, S Yaddanapudi
Department of Anaesthesia and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0022-3859.41800
Source of Support: None, Conflict of Interest: None
Background: Prevention of rise in intraocular pressure (IOP) is essential in patients undergoing surgery for perforated eye injuries. Metoclopramide, a prokinetic agent, is commonly used to hasten gastric emptying in emergency surgeries. Aim: To study the change in IOP after intravenous metoclopramide and to study the influence of metoclopramide on change in IOP after succinylcholine and tracheal intubation. Settings and Design: A randomized, double-blind, placebo-controlled study of 60 patients undergoing non-ophthalmic elective surgery. Materials and Methods: Sixty American Society of Anesthesiologists (ASA) I adult patients were randomly assigned to receive normal saline (Group C) or metoclopramide 10 mg (Group M) 30 min before the induction of anesthesia. Thiopentone was used for induction and succinylcholine for tracheal intubation. Intraocular pressure was measured in both the eyes pre and post drug treatment and succinylcholine and tracheal intubation using Perkins applanation tonometer. Statistical Analysis: Student's t-test and repeated measures ANOVA were used. A P value <0.05 was considered as significant. Results: Intraocular pressure was consistently lower in Group M than in Group C after the test drug, though the difference was not statistically significant. Intraocular pressure decreased significantly after administration of thiopentone and increased significantly in Groups C and M after tracheal intubation ( P < 0.01). Intraocular pressure was comparable between the groups at all the times. Conclusions: Metoclopramide does not cause a clinically significant change in IOP nor does it influence the changes in IOP during anesthesia and tracheal intubation. Metoclopramide shows a trend towards decrease in IOP, though clinically insignificant. Therefore metoclopramide can be used to promote gastric emptying in patients with perforated eye injury.
Keywords: Emergency surgery, intraocular pressure, metoclopramide, perforated eye injury
The control of intraocular pressure (IOP) is essential in patients undergoing surgery for perforated eye injury as any increase in IOP can result in damage to the eye and loss of vision. , Patients with perforated eye injuries usually present for emergency surgery and are considered to be 'full stomach'. They are thus at high risk for pulmonary aspiration of gastric contents. Metoclopramide, a gastric prokinetic agent is commonly administered to hasten gastric emptying and hence reduce the risk of pulmonary aspiration in patients undergoing emergency surgery.  However, the effect of metoclopramide on IOP is not well documented in humans. Parris and colleagues demonstrated a small increase in IOP (1.5 mmHg) after administration of intravenous metoclopramide.  But, this study lacked statistical validity due to the small number of patients studied. Topical metoclopramide has been observed to cause a decrease in IOP.  Injection of metoclopramide into the vortex veins has also been found to result in decrease of IOP in experimental animals. 
The present study was thus conducted to determine the effect of intravenous metoclopramide on IOP in adult patients undergoing elective non-ophthalmic surgery under general anesthesia. We additionally studied the effect of metoclopramide on the increase in IOP that occurs after administration of succinylcholine and tracheal intubation.
A randomized, placebo-controlled, double-blind study was conducted in 60 American Society of Anesthesiologists physical Status I patients of either sex, aged 20-50 years, undergoing elective non-ophthalmic surgical procedures under general anesthesia. The Ethics Committee of the Institute approved the study. Written, informed consent was obtained from all patients prior to surgery. Patients who had received any antiemetics prior to surgery and those with any eye pathology or previous surgery on the eye were excluded from the study. They were premedicated with 5-10 mg of diazepam orally the night before and on the morning of surgery. The patients were assigned by simple randomization using a random number table, into 2 groups to receive 2 ml of either normal saline (Group C) or metoclopramide 10 mg (Group M) intravenously, approximately 30 min prior to the induction of anesthesia, which was induced with a sleep dose of intravenous thiopentone. Tracheal intubation was performed 45 sec after the administration of 1.5 mg.kg−1 of succinylcholine. Anesthesia was maintained during the study period with 33% oxygen and 67% nitrous oxide. After the completion of the study, anesthesia was conducted as per the requirement of the surgery.
A Perkins applanation tonometer was calibrated against a Goldman tonometer and was used for all the measurements of IOP. Intraocular pressure was measured by a blinded observer in both the eyes after instilling 4% lignocaine topically, with the patient in supine position. The tear film was stained with sodium fluorescein to visualize the semicircular rings. Topical antibiotic drops were instilled after the last measurement of IOP.
Intraocular pressure, heart rate (HR) and noninvasive blood pressure (NIBP) were measured before and 2, 5 and 15 min after the administration of the test drug. Once the patient was inside the operation theatre, continuous monitoring of ECG, oxygen saturation (SpO 2 ) and end tidal carbon dioxide (ETCO 2 ) was initiated. Intraocular pressure, HR, NIBP were recorded before and after the injection of thiopentone, and 2 and 5 min after tracheal intubation.
A sample size of 30 patients per group was required to detect a difference in IOP of 4 mmHg (and an SD of 4 mmHg) with 90% power and an α error of 0.05. The parametric data were expressed as mean ± SD and compared between the two groups using Student's t-test. Data within each group was compared with the baseline values and analyzed using repeated measures of ANOVA and Tukey's test. A P value <0.05 was considered as significant.
There were 30 patients each in Groups C and M with similar baseline characteristics. Group M had significantly more female patients compared to Group C [Table 1]. The patients underwent non-ophthalmic elective surgeries including ENT surgery, ambulatory gynecological procedures, laparoscopic cholecystectomy, breast surgery and laparotomy [Table 2]. Both the groups were comparable with regard to the amount of diazepam, thiopentone and succinylcholine used [Table 1]. The time interval from the administration of test drug to the time of induction of anesthesia was similar in both the groups.
Intraocular pressure measurements
Intraocular pressure was measured in both the eyes in all the patients and mean of the two readings was considered for statistical analysis. There was an insignificant decrease in IOP from the baseline, 2, 5 and 15 min after the test drug in Group C and Group M [Table 3]. At all the measurement times, the IOP was comparable in the two groups [Table 3], [Figure 1].
Intraocular pressure decreased after the injection of thiopentone by 4.8 mmHg in Group C and by 5.3 mmHg in Group M. This decrease was statistically significant ( P < 0.01). Intraocular pressure increased by 4.5 mmHg in Group C and by 3.7 mmHg in Group M, 2 min after tracheal intubation. The increase in IOP was also present 5 min after tracheal intubation and was statistically significant ( P < 0.01). On intergroup comparison, the IOP values were similar in the two groups before and after injection of thiopentone as well as after tracheal intubation [Table 3], [Figure 1].
As there was a difference in gender distribution in the two groups, the mean IOP in male and female patients was compared. The IOP was found to be similar in male and female patients except at 2 min after administration of the test drug and 2 min after tracheal intubation when it was significantly lower in female patients than male patients [Table 4].
There was no significant change in the baseline HR after administration of the test drug in either of the groups. There was a significant increase in HR in both the groups after injection of thiopentone. The increase persisted till 5 min after intubation [Figure 2]. The HR was comparable between the two groups at baseline, as well as after administration of test drug and thiopentone, and after tracheal intubation.
There was no significant change in the baseline systolic blood pressure (SBP) or diastolic blood pressure (DBP) for 15 min after administration of the test drug in either of the groups, except a small decrease in DBP 5 min after the test drug in Group C. There was no significant change in SBP or DBP after the injection of thiopentone, but both SBP and DBP increased significantly 2 and 5 min after tracheal intubation in Group C ( P < 0.01). In Group M, there was a significant decrease of SBP and DBP after the injection of thiopentone ( P < 0.01) and a significant increase in both the pressures 2 min after tracheal intubation [Figure 2]. The SBP and DBP were comparable between the two groups at all the observation times.
Management of emergency anesthesia for a patient with an open eye injury and 'full stomach' usually involves intravenous administration of a prokinetic agent such as metoclopramide, 20 to 30 min before the induction of anesthesia followed by rapid sequence induction and tracheal intubation.  We studied the effect of this technique of anesthesia on IOP in patients receiving metoclopramide or placebo. As the effect of intravenous metoclopramide on IOP is not well known, we selected patients without any eye pathology for the study.
We observed that the IOP decreased after injection of placebo as well as metoclopramide. However, the change in IOP was small (0.9 and 1.2 mmHg after placebo and metoclopramide respectively) and not clinically relevant. Also the IOP values after placebo and metoclopramide were comparable at all points of observation. Though insignificant, metoclopramide showed a trend towards decrease in IOP which was consistent at all measurement points. As anticipated, administration of succinylcholine and intubation resulted in a significant increase in IOP in both the groups. However, the post-intubation IOP was comparable in the two groups indicating that metoclopramide did not affect the increase in IOP occurring after succinylcholine and intubation.
The effect of intravenous metoclopramide on IOP is not well established. We found only one study in literature in which this effect was investigated.  In this study the IOP increased within 5 min of metoclopramide administration. Also there was an additional increase in IOP within 3 min of succinylcholine administration in the metoclopramide group, significantly greater than the increase observed in the control group. However, only 10 patients were included in this study and the study was not randomized or blinded. Moreover, the IOP was measured using Schiotz tonometer, which is not a very accurate instrument.  It is subject to errors related to ocular rigidity and corneal curvature. We used Perkins applanation tonometer to measure IOP in the present study.  This tonometer is more accurate, its accuracy being comparable to that of Goldman tonometer, the gold standard for IOP measurement.  The variable expulsion of intraocular blood during tonometry may influence the pressure measurement. Repeated measurements reduce the IOP,  similar to the phenomenon observed during tonography. This could explain the decrease in IOP observed on repeated measurements in both the groups, which was clinically irrelevant.
Topical administration of metoclopramide and droperidol has been found to lower IOP in healthy volunteers. However, this decrease in IOP is similar to the effect in the placebo-treated eyes.  Metoclopramide when injected into rabbit eyeballs through vortex veins has been observed to lower the IOP.  Lavin and colleagues had shown that metoclopramide, a dopamine receptor blocker, has no ocular hypotensive action in man, though metoclopramide antagonizes the ocular hypotensive action of bromocriptine.  Timolol which is widely used in the treatment of glaucoma acts by inhibiting the formation of aqueous humor. There is evidence showing that this reduction in aqueous humor formation might be caused by elimination of dopaminergic function in the eyes, resulting in decreased blood flow to the ciliary body, rather than by β-adrenergic blockade.  Metoclopramide is thought to lower the IOP by this mechanism. The factors affecting IOP are movement of aqueous humor, changes in choroidal blood volume (CBV), central venous pressure (CVP), and extraocular muscle tone.  Although arterial blood pressure exerts some control over IOP, its effect over a physiologic range of blood pressures is small.  In our study we observed no change in HR, SBP and DBP after metoclopramide.
In our study we chose a sample size of 30 patients per group to detect a difference in 4 mmHg with 90% power and an alpha error of 0.05. But it is practically difficult to say what rise in IOP would result in expulsion of ophthalmic contents in patients with perforated eye injury. It may depend upon the size and site of the laceration. A perforated eye with large laceration may have expulsion of its contents even with slightest increase in IOP, whereas a small injury in the eye may require higher pressure for expulsion of ophthalmic contents.
In our study all the patients were healthy subjects with normal preoperative fluid status, scheduled for elective surgical procedures and no change in central venous pressure (CVP) was expected during the period of study. Potent inhaled anesthetics reduce IOP in a dose-dependent manner.  Thus we did not use any inhalation agent during the period of the study.
There were more female patients in Group M than in Group C in the present study. At most points of observation, the IOP was similar in male and female patients, except 2 min after test drug and 2 min after tracheal intubation, when it was lower in female patients. We could not find any report in the literature of difference in IOP in male and female subjects.
Among the muscle relaxants used in anesthesia, succinylcholine causes a transient but significant increase in IOP of 10 to 20 mm Hg.  Laryngoscopy and endotracheal intubation are the anesthesia-related practices most likely to increase IOP significantly.  Several pretreatment regimens have been advocated to control the sympathetic response to tracheal intubation and to attenuate the increase in IOP after succinylcholine administration.
Such pretreatments include the intravenous administration of lidocaine, sufentanil, remifentanil, beta adrenergic receptor blocking agents.  These drugs attenuate the increase in IOP, but do not consistently abolish this response to succinylcholine. On the other hand, there are no clinical case reports of further eye damage, loss of vitreous, or other complications in open eye surgery associated with succinylcholine administration. 
In conclusion, metoclopramide does not cause a clinically significant change in IOP nor does it influence the changes in IOP during anesthesia and tracheal intubation. Metoclopramide shows a trend towards decrease in IOP, through it is clinically insignificant. Therefore metoclopramide can be used to promote gastric emptying in patients with perforated eye injury.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]