Mydriatics are routinely administered in the eyes of dogs to facilitate examination of the lens and posterior segment of an eye. They are also used to dilate the pupils in various situations, such as in preparation for electroretinography, cataract surgery, or any surgical procedure that requires mydriasis. Tropicamide is a synthetic antimuscarinic agent that inhibits the action of acetylcholine on the iris sphincter1 and is commercially available in 0.5% and 1% ophthalmic solutions. In dogs, tropicamide is the most frequently used topical drug for induction of mydriasis for diagnostic purposes (diagnostic mydriasis) because of its rapid onset of action (10 to 20 minutes), completeness of pupil dilation, and relatively short duration of action (6 to 8 hours).2,3 Drugs for diagnostic mydriasis should be administered in accordance with the principle of safe mydriasis outlined by Mapstone4 in 1970. However, tropicamide-induced mydriasis has been associated with an abnormally increased IOP in dogs,5 cats,6 and humans.7,8 Results of an ultrasound biomicroscopy study9 indicate that, in dogs, a slight narrowing of the ciliary cleft entry is associated with pupil dilation induced by topical instillation of tropicamide in the eyes. Therefore, an important concern for dogs receiving mydriatic agents is the potential risk for induction or exacerbation of an acute increase in IOP.
In most dogs, ophthalmic examinations can be performed without medication; however, use of sedatives and related agents may be necessary to perform examinations in uncooperative or reluctant patients. In fact, administration of a sedative is sometimes essential to achieve adequate immobilization for a thorough ophthalmic examination.8 Sedatives and related agents have the potential to decrease pain and stress for the patient and to enhance safety for both the patient and examiner. A number of chemical agents and a combination of techniques are available for sedation, and the agent or technique selected is generally dependent on the physiologic state of the patient and type of procedure that is being performed.10 Factors that affect eye position, pupil size, and IOP are important considerations during selection of sedation protocols for patients undergoing ophthalmic examinations.11
Butorphanol tartrate is a synthetic κ-opiod receptor agonist and μ-opiod receptor antagonist. In veterinary practice, butorphanol is generally considered to have low analgesic properties12 and is commonly used as a premedication in combination with other drugs.13 In dogs and cats, butorphanol is also recommended for achieving moderate short-term sedation with minimal adverse effects.14,15 Results of 1 study16 suggest that, in dogs, butorphanol can induce adequate sedation for ophthalmic examination but may interfere with some ophthalmic variables. Most notably, substantial pupillary constriction and an increase in IOP were observed in dogs for up to 45 minutes after IM administration of 0.2 mg of butorphanol/kg.16
The purpose of the study reported here was to evaluate changes in pupil size and IOP after topical application of a 0.5% tropicamide ophthalmic solution in the eyes of dogs sedated with butorphanol. We hypothesized that systemic administration of butorphanol might affect tropicamide-induced mydriasis and that butorphanol and tropicamide may act synergistically to increase the IOP of dogs.
Materials and Methods
Animals
All study procedures conformed to the statement of the Association for Research in Vision and Ophthalmology and European Community Council directive (86/609/EEC) regarding use of animals in vision research. Twelve adult laboratory Beagles (6 spayed females and 6 castrated males) with a mean age of 4.5 years (range, 2 to 7 years) were used for the study. All dogs were university-owned research animals and had been housed in a laboratory animal facility for at least 3 months prior to study initiation. All dogs were considered healthy on the basis of results of a physical examination and ophthalmologically normal on the basis of results of an ophthalmic examination that included slit-lamp biomicroscopy,a rebound tonometry,b Schirmer tear test Ic assessment, and indirect ophthalmoscopy.d
Study design
All dogs received each of 2 treatments (butorphanol or saline [0.9% NaCl] solution) in a randomized crossover study. There was at least a 1-week washout period between treatments. For each dog prior to study initiation, the order in which the 2 treatments were administered was determined by block randomization, and the eye designated to receive tropicamide was randomly determined with a table of random numbers. Tropicamide was instilled in the same eye following both treatments.
During each treatment phase, each dog received an IM injection of butorphanol tartratee (0.2 mg/kg, IM) or an equivalent volume of sterile saline solution in the right gluteal muscles. The same investigator (SJ) administered all injections. One drop of 0.5% tropicamide ophthalmic solutionf was topically instilled in the designated eye and 1 drop of artificial tear solution was topically instilled in the other (control) eye 10 minutes after the IM injection and again 5 minutes later as described.17
Clinical assessment and data collection
For each dog, the extent of sedation was subjectively assessed and the pupil size and IOP of each eye were measured at 20 (T−20), 10 (T−10), and 0 (immediately before; T0) minutes before and at 10 (T10), 20 (T20), 30 (T30), 45 (T45), 60 (T60), 70 (T70), and 80 (T80) minutes after the IM injection. The T20, T30, T45, T60, T70, and T80 assessments corresponded to 5, 15, 30, 45, 55, and 65 minutes, respectively, after topical instillation of the second drop of the assigned ophthalmic solution to each eye.
For each dog at each assessment, the extent of sedation was scored on a scale of 0 to 3, which was adapted from previous studies18–20 (Appendix). For each eye, the pupil size was measured at its greatest diameter in the horizontal meridian with a Jameson caliper placed adjacent to, but not in contact with, the cornea as described.21 The investigator measuring the pupil size wore a binocular head loupe with 2.5X magnification so that the pupil diameter could be accurately assessed. The lighting conditions within the examination room remained constant throughout the study and corresponded to artificial illumination with a range of 48 to 51 cd/m2. Intraocular pressure was measured by rebound tonometry.b For each pupil size and IOP measurement, the dog was minimally restrained in either a sitting position or sternal recumbency to avoid a possible effect of body position on the IOP measurement.22 Care was also taken to avoid exertion of excessive pressure on the globes, which could likewise affect IOP.23 The same investigator (SJ) obtained all measurements to minimize variation in measurements over time.
At each assessment, clinical signs associated with ocular irritation, including blepharospasm, conjunctival hyperemia, conjunctival edema, and aqueous flare, were individually evaluated on a subjective scale of 0 to 3, where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Other potential adverse effects associated with the assigned treatment or tropicamide were recorded when present. At the end of the observation period (T80), 1 drop of Bengal rose staing was topically applied to the cornea of each eye to detect signs of epithelial damage resulting from tropicamide administration or repetitive IOP measurements.
Statistical analysis
Descriptive data were generated for each of 4 treatment groups (sedated + control [eyes treated with artificial tears following butorphanol administration], sedated + trop [eyes treated with tropicamide following butorphanol administration], unsedated + control [eyes treated with artificial tears following administration of saline solution], and unsedated + trop [eyes treated with tropicamide following administration of saline solution]), and results were reported as the mean ± SD. Outcomes of interest were pupil size and IOP. Each outcome was compared over time and among the 4 treatment groups by use of a repeated-measures ANOVA. The model included fixed effects for treatment period (1 or 2), sedation (butorphanol or saline solution), dilation (tropicamide or artificial tears), the interaction between sedation and dilation (which defined the 4 groups), and assessment time (T−20 to T80) and a random effect for dog to account for repeated measures within each subject. Additionally, for the sedated + trop and unsedated + trop groups, pupil size was regressed against assessment times from T30 to T80 (ie, 15 to 65 minutes after instillation of the second drop of tropicamide) to determine the rate of onset of mydriasis. The linear regression equation and corresponding coefficient of determination (r2) were determined for each group, and the rate of mydriasis onset was compared between the 2 groups. All analyses were performed with commercially available statistical software,h and values of P < 0.05 were considered significant.
Results
Dogs
All 12 dogs became clinically sedate following butorphanol administration. Sedation was classified as mild for 9 dogs and moderate for 3 dogs. Subjectively, each dog became more cooperative for pupil size and IOP measurements as clinical signs of sedation became more evident. No changes in the position of the globe or the nictitating membrane were observed for any of the dogs. Excessive ptyalism was noted for the 3 dogs that became moderately sedate. None of the dogs developed signs of ocular discomfort (eg, blepharospasm or epiphora) following tropicamide instillation or evidence of epithelial defects in either eye at the end of either treatment period.
Pupil size
For each of the 4 treatment groups, the distribution of the pupil size data over the duration of the observation period was summarized (Figure 1). The mean pupil size prior to injection of butorphanol or saline solution did not differ significantly (P = 0.12) among the 4 treatment groups (Figure 2). The mean ± SD pupil size for the sedated + control (3.73 ± 0.34 mm) and unsedated + control (3.97 ± 0.15 mm) groups remained fairly consistent throughout the observation period. For the sedated + trop and unsedated + trop groups, onset of pupil dilation occurred within 10 minutes after tropicamide instillation, and pupil size reached its maximum value (approx 12 mm) for the observation period at T80 for both groups. Overall, pupil size was not significantly (P = 0.11) affected by butorphanol administration, regardless of tropicamide use, but was significantly (P < 0.001) affected by tropicamide instillation. The rate of mydriasis onset was slower (albeit not significantly so) for the sedated + trop group than for the unsedated + trop group. The linear regression equation was y = 0.007x + 7.2 (r2 = 0.9968) for the unsedated + trop group and y = 0.05x + 5.58 (r2 = 0.9568) for the sedated + trop group. Following tropicamide instillation, it took 15 and 28 minutes for the eyes of the unsedated + trop and sedated + trop groups, respectively, to achieve sufficient mydriasis24,25 (pupil size > 8 mm) for comprehensive examination of the lens and fundus.
Box-and-whisker plots that summarize the distributions of the aggregate data for pupil size (A) and IOP (B) for each of 4 treatment groups (sedated + control [eyes treated with artificial tears following butorphanol administration], sedated + trop [eyes treated with tropicamide following butorphanol administration], unsedated + control [eyes treated with artificial tears following administration of saline {0.9% NaCl} solution], and unsedated + trop [eyes treated with tropicamide following administration of saline solution]) in a study of 12 healthy adult Beagles that received an IM injection of butorphanol (0.2 mg/kg) or an equal volume of sterile saline solution followed 10 minutes later by topical instillation of a 0.5% tropicamide or artificial tear (control) ophthalmic solution (1 drop/eye, twice, 5 minutes apart) in each eye. The study had a randomized crossover design with a 1-week washout period between treatment periods. Each dog received butorphanol during one treatment period and saline solution during the other treatment period, the order of which was randomly determined. For each dog, the eye designated for topical instillation of tropicamide was randomly selected prior to study initiation, and the same eye was used for tropicamide instillation during both treatment periods. For each plot, the lower and upper limits of the box represent the 25th and 75th percentiles, respectively; the plus sign within the box represents the mean; the solid line within the box represents the median; and the whiskers delimit the 5th and 95th percentiles. *Means differ significantly (P < 0.001) between treatment groups linked by brackets.
Citation: American Journal of Veterinary Research 80, 1; 10.2460/ajvr.80.1.95
Box-and-whisker plots that summarize the distributions of the aggregate data for pupil size (A) and IOP (B) for each of 4 treatment groups (sedated + control [eyes treated with artificial tears following butorphanol administration], sedated + trop [eyes treated with tropicamide following butorphanol administration], unsedated + control [eyes treated with artificial tears following administration of saline {0.9% NaCl} solution], and unsedated + trop [eyes treated with tropicamide following administration of saline solution]) in a study of 12 healthy adult Beagles that received an IM injection of butorphanol (0.2 mg/kg) or an equal volume of sterile saline solution followed 10 minutes later by topical instillation of a 0.5% tropicamide or artificial tear (control) ophthalmic solution (1 drop/eye, twice, 5 minutes apart) in each eye. The study had a randomized crossover design with a 1-week washout period between treatment periods. Each dog received butorphanol during one treatment period and saline solution during the other treatment period, the order of which was randomly determined. For each dog, the eye designated for topical instillation of tropicamide was randomly selected prior to study initiation, and the same eye was used for tropicamide instillation during both treatment periods. For each plot, the lower and upper limits of the box represent the 25th and 75th percentiles, respectively; the plus sign within the box represents the mean; the solid line within the box represents the median; and the whiskers delimit the 5th and 95th percentiles. *Means differ significantly (P < 0.001) between treatment groups linked by brackets.
Citation: American Journal of Veterinary Research 80, 1; 10.2460/ajvr.80.1.95
Box-and-whisker plots that summarize the distributions of the aggregate data for pupil size (A) and IOP (B) for each of 4 treatment groups (sedated + control [eyes treated with artificial tears following butorphanol administration], sedated + trop [eyes treated with tropicamide following butorphanol administration], unsedated + control [eyes treated with artificial tears following administration of saline {0.9% NaCl} solution], and unsedated + trop [eyes treated with tropicamide following administration of saline solution]) in a study of 12 healthy adult Beagles that received an IM injection of butorphanol (0.2 mg/kg) or an equal volume of sterile saline solution followed 10 minutes later by topical instillation of a 0.5% tropicamide or artificial tear (control) ophthalmic solution (1 drop/eye, twice, 5 minutes apart) in each eye. The study had a randomized crossover design with a 1-week washout period between treatment periods. Each dog received butorphanol during one treatment period and saline solution during the other treatment period, the order of which was randomly determined. For each dog, the eye designated for topical instillation of tropicamide was randomly selected prior to study initiation, and the same eye was used for tropicamide instillation during both treatment periods. For each plot, the lower and upper limits of the box represent the 25th and 75th percentiles, respectively; the plus sign within the box represents the mean; the solid line within the box represents the median; and the whiskers delimit the 5th and 95th percentiles. *Means differ significantly (P < 0.001) between treatment groups linked by brackets.
Citation: American Journal of Veterinary Research 80, 1; 10.2460/ajvr.80.1.95
Mean ± SD pupil size (A) and IOP (B) over time for the sedated + control (black squares), sedated + trop (white squares), unsedated + control (black circles), and unsedated + trop (white squares) groups described in Figure 1. Each data point represents the mean for 12 eyes. The vertical dotted line represents IM injection of butorphanol or saline solution. The arrows indicate topical instillation of the assigned ophthalmic solution in each eye. See Figure 1 for remainder of key.
Citation: American Journal of Veterinary Research 80, 1; 10.2460/ajvr.80.1.95
Mean ± SD pupil size (A) and IOP (B) over time for the sedated + control (black squares), sedated + trop (white squares), unsedated + control (black circles), and unsedated + trop (white squares) groups described in Figure 1. Each data point represents the mean for 12 eyes. The vertical dotted line represents IM injection of butorphanol or saline solution. The arrows indicate topical instillation of the assigned ophthalmic solution in each eye. See Figure 1 for remainder of key.
Citation: American Journal of Veterinary Research 80, 1; 10.2460/ajvr.80.1.95
Mean ± SD pupil size (A) and IOP (B) over time for the sedated + control (black squares), sedated + trop (white squares), unsedated + control (black circles), and unsedated + trop (white squares) groups described in Figure 1. Each data point represents the mean for 12 eyes. The vertical dotted line represents IM injection of butorphanol or saline solution. The arrows indicate topical instillation of the assigned ophthalmic solution in each eye. See Figure 1 for remainder of key.
Citation: American Journal of Veterinary Research 80, 1; 10.2460/ajvr.80.1.95
IOP
For each of the 4 treatment groups, the distribution of the IOP data over the duration of the observation period was summarized (Figure 1). Similar to pupil size, the mean IOP did not differ significantly among the 4 treatment groups prior to injection of butorphanol or the saline solution (Figure 2). The mean IOP did not differ significantly from that at baseline (T−20) at any time during the observation period for the unsedated + control (P = 0.40) and unsedated + trop (P = 0.86) groups. Intraocular pressure was significantly (P < 0.001) affected by butorphanol administration regardless of tropicamide instillation. Between baseline and T80, the mean ± SD IOP increased from 14.33 ± 0.3 mm Hg to 17.0 ± 0.71 mm Hg for the sedated + control group and from 14.0 ± 0.4 mm Hg to 16.7 ± 0.3 mm Hg for the sedated + trop group. Moreover, the mean IOP did not differ significantly (P = 0.84) between the sedated + control and sedated + trop groups at any time during the observation period. Although the IOP for both the sedated + control and sedated + trop groups increased by approximately 20% following butorphanol administration, all IOP measurements were within the reference range (15 to 25 mm Hg) for dogs, except those for a moderately sedate dog; for that dog, the IOP was 26 mm Hg at T10, T20, and T30.
Discussion
For the healthy and ophthalmologically normal dogs of the present study, mydriasis induced by topical instillation of a 0.5% tropicamide ophthalmic solution did not exacerbate the increase in IOP caused by butorphanol (0.2 mg/kg, IM), nor did sedation with butorphanol prevent tropicamide-induced mydriasis. Results of other studies indicate that, in dogs, administration of butorphanol at a dose of 0.1 does not provide clinically relevant sedation,19 whereas administration of butorphanol at a dose of 0.4 mg/kg results in ventral rotation of the globe, which can preclude ophthalmic examination.26 Therefore, we chose to administer to the dogs of the present study an intermediate dose (0.2 mg/kg) of butorphanol with the knowledge that it would provide sufficient sedation to allow examination of the eyes without affecting the position of the globe or nictitating membrane.16 We chose to administer butorphanol by the IM route because that route is more readily achievable than IV injection in uncooperative or agitated subjects, and the onset of the drug's sedative effects is quicker following IM versus SC injection.14
All 12 dogs of the present study became mildly (n = 9) or moderately (3) sedate within 10 to 20 minutes after butorphanol administration and remained so for the remaining duration of the observation period (approx 60 minutes). Butorphanol-induced sedation was characterized by behavior moderation (quieting) and subjects that were more amenable to measurement of pupil size and IOP. However, as previously mentioned, sedation did not impede ophthalmic examination. Excessive salivation was observed for the 3 dogs that were classified as becoming moderately sedate following butorphanol administration. In dogs, ptyalism is also associated with administration of methadone, another opioid,27 but we were unable to find any information or hypotheses regarding the mechanism, assuming one exists, of opioid-induced ptyalism. Ptyalism is considered a clinical manifestation of nausea, which is often defined as excessive salivation, lip licking, frequent and exaggerated swallowing, lethargy, restlessness, and panting.28 However, butorphanol, unlike morphine (another opioid), is recommended as an antiemetic for the prevention of chemotherapy-induced emesis.29
Exogenous opioids have a species-dependent pupillary effect, which is presumed to be mediated through a central mechanism or by a potential direct effect on opioid receptors within the iris.30 Morphine induces miosis in dogs,31,32 rabbits,33 and humans34 and mydriasis in cats,32 mice, and monkeys.35 In dogs, the miotic potency of butorphanol is 8 times that of morphine.36 In a recent study,16 administration of butorphanol (0.2 mg/kg; the same dose administered to the dogs of the present study) to dogs resulted in a 35% decrease in mean pupil size. In the present study, the mean pupil size for the sedated + control group (ie, dogs administered butorphanol without tropicamide) decreased slightly, albeit not significantly, from baseline beginning 20 minutes after butorphanol administration and lasted for the remainder of the observation period. The study population (n = 12 dogs) for the present study was approximately half that of the other study16 (22), which might have limited the power to detect significant alterations in pupil size during the present study. Nevertheless, most anesthetics and sedatives, except for dissociative agents such as ketamine,37 cause some degree of miosis in dogs.11 It has been suggested that mydriasis achieved prior to sedation is usually unaffected by the miotic properties of sedatives that are subsequently administered38 and that mydriasis is more difficult to achieve after onset of sedation.39 Contrary to morphine,39 in the present study, administration of butorphanol to dogs prior to tropicamide instillation in an eye did not prevent mydriasis but did delay its onset slightly. In general, a pupil diameter of 8 to 10 mm is considered necessary for comprehensive examination of the lens and fundus of dogs.24,25 Following tropicamide instillation in the eyes of the dogs of the present study, mydriasis sufficient for examination of the lens and fundus was achieved within 15 minutes for unsedated dogs versus 28 minutes (ie, a 13-minute delay) for sedated dogs. Although that delay does not represent a major concern, it should be considered in the context of intensive daily clinical practice.
For the dogs of the present study, butorphanol increased IOP independent of pupil size (ie, tropicamide use). For the sedated + control group, the magnitude of the mean IOP increase from baseline ranged from 1.25 mm Hg (8.9%) at T10 to 4.3 mm Hg (33.7%) at T45, which was comparable to that (1.1 mm Hg [7%] at T10 to 2.7 mm Hg [20%] at T45) reported for the control eyes of butorphanol-sedated dogs of another study.16 Collectively, the results of the present study and that other study16 confirmed that butorphanol increases the IOP of dogs, which is in contrast to other opioids that are generally assumed to decrease IOP regardless of the route of administration or species.12,40,41 Despite the lack of scientific data, we hypothesized that the mechanism by which butorphanol increases IOP is dependent on extraocular muscle tone (as is suspected for ketamine37), aqueous humor dynamics, or choroidal blood flow.42 Those are the 3 main factors known to influence IOP43; therefore, alterations in those factors need to be investigated in butorphanol-sedated dogs. Results of the present study did not support the idea that the changes in IOP were associated with tropicamide-induced mydriasis. For example, the significant increase in IOP from baseline observed for the sedated + control group was not accompanied by a concurrent or significant change in pupil size. Similarly, the significant mydriasis observed in the unsedated + trop group was not accompanied by a concurrent increase in IOP. In fact, a significant increase in IOP was observed only following butorphanol administration.
Tropicamide was not associated with a significant increase in IOP for the dogs of the present study, which was consistent with the findings of other studies.24,44,45 However, that finding was in contrast to results of 1 study5 in which topical instillation of 0.5% tropicamide ophthalmic solution in the eyes of dogs was associated with a significant increase in IOP. Unfortunately, the number of dogs treated with tropicamide in that study5 was small (n = 10) and the breed distribution was not described, and these facts impair interpretation of the results. In human medicine, topical instillation of mydriatics is associated with acute angle-closure glaucoma, particularly in patients with acute angles that are potentially occludable,7,46 and a similar association and risk have been described in glaucomatous dogs47 and cats.48 In regard to dogs specifically, topical instillation of a 1% tropicamide or 1% atropine ophthalmic solution in the eyes of dogs results in a significant increase in IOP in glaucomatous Basset Hounds but has no effect on the IOP of healthy control Beagles.47
The present study had a number of limitations. Only a small number of dogs were evaluated, and the study was likely underpowered, particularly for assessment of butorphanol-induced effects on pupil size. We believe that evaluation of a larger number of dogs would have permitted a more robust statistical analysis, which likely would have confirmed that butorphanol causes miosis in dogs, as is reported else-where.16 However, the number of dogs evaluated in the present study was sufficient for us to detect a significant increase in IOP associated with butorphanol administration. Another limitation was that dogs of only 1 breed (Beagle) were evaluated, and those dogs were specifically bred for research purposes. The pharmacological effects of opioids can vary among individual dogs of the same breed49 as well as among dogs of various breeds.50 The effect of topical instillation of tropicamide on IOP likewise appears to vary among breeds of dogs.51 Therefore, the results of the present study are unlikely to be generalizable to uncooperative or excitable dogs of various breeds that are commonly examined in clinical practice. Finally, the duration of the observation period (ie, 65 minutes after tropicamide instillation) was based on our clinical experience regarding the time required to perform a thorough ophthalmic examination in a dog. A longer observation period might have revealed further changes in pupil size or IOP that may or may not have been associated with the administered drugs, but it would not have reflected current clinical practice.
Results of the present study indicated that sedation of healthy, ophthalmologically normal Beagles with butorphanol (0.2 mg/kg, IM) did not prevent, but did slightly delay the onset of, mydriasis induced by topical application of a 0.5% tropicamide ophthalmic solution. Butorphanol administration was associated with a significant increase in IOP, which was not exacerbated by tropicamide-induced mydriasis. Although the butorphanol-induced increase in IOP was generally not sufficient to exceed the upper limit of the reference range for the healthy Beagles of this study, that may not be the case for dogs with or at risk for glaucoma, and care should be taken when butorphanol is administered to such dogs.
ABBREVIATIONS
| IOP | Intraocular pressure |
Footnotes
SL-14, Kowa Co, Tokyo, Japan.
Tonovet, Icare, Tiolat, Helsinki, Finland.
Test de Schirmer, Virbac, Carros, France.
Beta 200, Heine Optotechnik, Herrsching, Germany.
Dolorex, MSD Animal Health, Boxmeer, Netherlands.
Mydriaticum 0.5%, Laboratoire Théa, Clermont-Ferrand, France.
Rosix, Dioptrix, Toulouse, France.
SPSS SYSTAT, version 12.0, IBM Corp, Chicago, Ill.
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Appendix
Description of scoring system used to assess the extent of sedation for 12 healthy adult Beagles before and after IM administration of butorphanol (0.2 mg/kg) or an equal volume of sterile saline (0.9% NaCl) solution.
| Score | Criteria |
|---|---|
| 0 | No signs of sedation. |
| 1 | Mild sedation (subject remains standing or sitting but appears calm, is aware of its surroundings, and reacts to verbal stimulation). |
| 2 | Moderate sedation (subject appears sleepy and remains sitting or assumes sternal recumbency; subject does not react to verbal stimulation but can be aroused with physical stimulation). |
| 3 | Heavy sedation (subject is inactive and in lateral recumbency and is difficult to arouse with physical stimulation). |
Adapted from sedation scoring systems described previously.18–20
