Sedation for ER Ophthalmic Evaluation

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Article initiated by:
Cason Robbins MD, Chase Miller, Emily H Jung, MD, Samiksha Fouzdar Jain, MD, Sri Meghana Konda
All contributors:
Carrie Hemmer, MD, Cason Robbins MD, Chase Miller, Connor J. Eggleston, Emily H Jung, MD, Grayson W Armstrong MD MPH, Kunal Sualy, MD, Samiksha Fouzdar Jain, MD, Steven Young, Grant A. Justin, MD, Samiksha Fouzdar Jain, MD, Sri Meghana Konda, Grayson W Armstrong MD MPH
Assigned editor:
Grayson W Armstrong MD MPH
Review:
Assigned status Update Pending
 by Grayson W Armstrong MD MPH on January 6, 2024.


Introduction

Common ophthalmic complaints to emergency departments are conjunctivitis, corneal injuries without a foreign body, corneal injury with a foreign body, eye pain, and hordeolum with sedation at times needed for adequate evaluation.[1]  A thorough ophthalmic examination is a unique medical procedure due to the level of cooperation required from the patient to obtain complete diagnostic evaluation. Ocular examination and techniques in the emergency department can present additional challenges as patients are often in pain, have significant anxiety, or are in the pediatric population. Partial or complete sedation can be advantageous for a successful examination in an emergent environment. However, some special considerations related to performing a comprehensive ophthalmic exam need to be considered when selecting an agent for procedural sedation in the emergency department. More specifically, the level of sedation depends on the clinical scenario, patient age, comorbidities, and the level of analgesia desired in conjunction with the exam. The effects of the sedative would ideally help facilitate correct eye positioning on examination and not impede the ability of the patient to respond to questions, obey commands like where to direct their eyes or result in significant changes in ophthalmic findings such as intraocular pressure (IOP). Most data for sedation and anxiolysis has been done in the setting of dental or minor ED procedural exams and has to be extrapolated for specific use in the ophthalmic examination.

Ketamine (intravenous or intramuscular), midazolam (intravenous, intranasal, or oral), dexmedetomidine (intravenous or intranasal), and propofol (IV) are four commonly used options for sedation in the emergency room. Fentanyl is an additional option for sedation. Fewer adverse events have been associated with minimal sedation with midazolam and dexmedetomidine, compared to dissociative sedation with ketamine.

Chloral hydrate is an agent that was historically used as a sedative; however, it is no longer recommended for use in the pediatric population and is no longer available in the United States, due to its high frequency of adverse effects and its various risks (i.e., no reversal agent, narrow therapeutic index, and prolonged effect).

In situations where consent for sedation is not provided, use of ocular point-of-care ultrasound (POCUS) has been shown to be helpful in the preliminary assessment of ophthalmic emergencies.

Monitoring

The use of procedural sedation, while useful, is associated with various side effects including respiratory depression, bradycardia, laryngospasm, hypotension, and hypersalivation. Procedural sedation should therefore be administered by a physician with adequate knowledge of the medications, side effects, and who can appropriately manage any issues that arise.

It is recommended to monitor vital signs with any of the sedation agents, with the use of EKG, O2 sat, blood pressure q5-15min, and end tidal CO2.

Indications for ER Ophthalmic Exam

Pediatric patients have the highest chance of needing sedation for successful ophthalmic exam completion. While infants and toddlers may be unable to remain still or sufficiently follow commands, high procedure-related anxiety and pain may also limit the efficacy of non-sedated exams in older children. Furthermore, reducing stress related to ophthalmic exams for children can help to facilitate beneficial future health care experiences.

Significant pain, high anxiety levels, or intellectual disability may also be reasons sedation is necessary for adults. Corneal abrasions and foreign bodies account for approximately 20% of ophthalmic-related ED visits and are often associated with high levels of pain.[2] Anxiolysis may be necessary to administer topical anesthetic drops and dilating drops to perform a thorough anterior segment exam, posterior segment examination, scleral depressed fundus examination, and intraocular pressure measurement in some patients. Especially in cases of blunt ocular trauma, forced duction tests can induce the oculocardiac (trigeminovagal) reflex causing bradycardia when assessing possible muscle entrapment. Keep in mind agents that may decrease heart rate.

Ketamine

Ketamine is a phencyclidine derivative that binds the N-methyl-D-aspartate (NMDA) receptor and thereby acts as a dissociative sedative. [3] Onset of sedation for intramuscular administration is about 5 minutes. Ketamine may cause tachycardia and hypertension. However, it has the potential to induce hypotension in catecholamine-depleted patients. Respiratory depression is rare but also possible, and bronchodilation is a potential benefit. Hypersalivation may occur, which predisposes patients to laryngospasm; oftentimes, this is mitigated with an anticholinergic. Common side effects include vomiting and recovery agitation. Hallucinations are most common in patients older than 15 years of age. Associated with less vomiting and significantly shorter recovery times compared to intramuscular administration, intravenous administration may be more preferable in children with readily available vascular access.[4] Premedicating pediatric patients with ondansetron can help reduce the frequency of vomiting. Ketamine is contraindicated in patients younger than three months of age and those with psychosis, and is relatively contraindicated in pediatric patients with increased intraocular pressure (glaucoma, eye injury), thyroid disease, and airway instability, among other conditions.[5] [6][7]

Effect on IOP:

Despite conflicting evidence regarding the use of ketamine in children with possible increased intraocular pressure, it is best to use other sedative options for patients with a strong likelihood of increased intraocular pressure whenever possible.[8]

Ketamine Dosing

IV

  • Pediatric
    • 0.5-2mg/kg with 0.5-1mg/kg if clinically indicated. Caution should be taken with patients less than 3 months of age due to possible airway complications.[9]
  • Adult
    • 1-4.5 mg/kg by slow injection over 60 seconds with additional doses of 0.5-4.5 mg/kg as needed to maintain sedation.[10]

Intramuscular

  • Pediatric
    • 3-4mg/kg but caution should be taken with patients less than 3 months of age due to possible airway complications.[9]
  • Adult
    • 6.5-13 mg/kg with additional doses of 3.25-13 mg/kg as required by the patient’s anesthetic needs.[10]
Oral, intranasal, rectal, epidural, and other routes of pharmaceutical administration for ketamine are not approved by the Food and Drug Administration of the United States of America.[10]

Midazolam

Midazolam is a short-acting benzodiazepine that acts as a mild to moderate sedative.[11] Onset of sedation is less than 10 minutes for intranasal administration and about 30 minutes for oral administration. Paradoxical reactions (i.e. inconsolable crying, hyperactivity, and aggressive behavior) may occur in up to 3% of patients, particularly in younger children.[12] Respiratory depression may also occur with midazolam use, which may be transiently reversed with flumazenil, 0.01mg/kg. However, flumazenil is seldom used given its short half-life and tendency to unmask seizures. [13] Midazolam should be used with caution in patients with underlying myocardial depression, due to its mild negative inotropic effects.[14]

Effect on IOP:

Midazolam may induce a transient, minor decrease in IOP, however the only study conducted exclusively in the pediatric population did not demonstrate any significant IOP lowering effect.[15][16][17]

Midazolam Dosing

IV

  • Pediatric
    • 6 months to 5 years old: 0.05–0.1 mg/kg; up to 0.6 mg/kg may be required to reach the desired level of sedation.[18]
    • 6-12 years old: 0.025–0.05 mg/kg; up to 0.4 mg/kg may be required to reach the desired level of sedation, but total dose usually does not exceed 10 mg.[18]
    • 12–16 years of age: Dose as adults; although some patients in this age range may require higher than recommended adult doses, total dose usually does not exceed 10 mg.[18]
      • Effects should be seen within 2-3 minutes until further administering a dose in small increments or beginning the procedure.
  • Adult
    • Healthy adults <60 years old: Titrate dose slowly to desired sedative effect. No more than 2.5 mg should be administered at first; some patients may respond to as little as 1.0 mg.[18] Wait at least 2-3 minutes to fully evaluate the sedative effect, and if additional sedation is necessary, continue to titrate using small increments to reach the appropriate level of sedation. Total dose of ≤5 mg is generally adequate.[18]
    • Patients ≥60 years old with significant comorbities: Reduce dose and monitor carefully for adverse effects. 1.0-1.5 mg over 2 minutes while evaluating for side effects for 2 minutes. Dose can be increased up to 3.5 mg maximum to reach desired sedative level. [18]
    • Care must be taken with administering midazolam alongside an opiate agonist or other CNS depressant and the dose is recommended to be lowered by approximately 30% in healthy adults less than 60 years of age and by 50% in adults over 60 years of age with significant comorbitities.[18]

Oral

  • 0.25-0.75 mg/kg up to a maximum of 20 mg.[19]
  • Younger patients or less cooperative patients may require a higher dose up to 1.0 mg/kg for a maximum of 20 mg.[19]

Intranasal

  • 0.4-0.5mg/kg with doses closer to 0.5mg/kg associated with reduced anxiety from pateints as well as mildly longer recovery times.[20]

Intramuscular

  • 0.1-0.15 mg/kg up to 0.5 mg/kg for notably anxious patients although total dose does not typically exceed 10 mg.[18]

Dexmedetomidine

Dexmedetomidine is a selective alpha-2 adrenergic receptor agonist that acts as a potent sedative and also provides analgesia. Onset of sedation for intranasal administration is about 30 minutes. In contrast to many other sedatives, dexmedetomidine causes minimal respiratory depression in children and minimal recovery agitation.[21] Side effects of dexmedetomidine include transient oxygen desaturation and unexpected changes in heart rate and blood pressure, and thus it should be avoided in patients who are receiving medications with rate-slowing action, those with cardiac conduction disorders, and those who may not tolerate increased pulmonary artery pressure or decreased cardiac output.[22] Additional rare side effect includes respiratory depression. If used with drugs like remifentanil, can have severe bradycardia; this is less likely if drug is infused over long period of time. There is a risk of prolonged sedation and duration of recovery in the ED, especially at higher doses. In a randomized control trial comparing intranasal dexmedetomidine to oral chloral hydrate during pediatric ophthalmic examinations, dexmedetomidine showed superior sedation rates while also delivering better eye positioning on anterior segment exam.[23] Adults can also receive intranasal formulations of the drug at 2-3mcg/kg.

Effect on IOP:

Of note, IV and IM dexmedetomidine have been shown to transiently decreased IOP.[24]

Dexmedetomidine Dosing

IV

  • Adult
    • 0.5-1.0 mcg/kg over 10 minutes as a loading infusion.[25]
    • Maintenance of sedation can be achieved by an infusion rate of 0.6 mcg/kg per hour.[25]

Intranasal

  • Pediatric
    • (3 months to 3 years old) 1-2 mcg/kg[26]

Intramuscular

  • 1-4 mcg/kg using sequential injections of low amounts of dexmedetomidine to achieve desired level of sedation.[27]

Propofol

Propofol appears to act via GABAergic inhibition of the central nervous system and is available in the intravenous formulation.[28] Its duration of onset is rapid, within 40-60 second, so care should be taken during administration. It is highly lipid-soluble, limiting its duration of action (approximately 5-15 minutes). It has no analgesic properties but does serve as an antiemetic along with its sedative properties. Hypotension may occur with use. Propofol can quickly cause deep sedation and respiratory depression/apnea and should only be used by qualified practitioners who are comfortable managing airways when necessary. Adverse reactions include myoclonus, pain with administration, anaphylaxis, bacterial contamination, and myocardial depression.

Effect on IOP:

Propofol does not appear to induce a significant decrease in IOP.[29]

Propofol Dosing

Recommended use of larger veins (e.g. antecubital fossa) and lidocaine locally to avoid acute pain associated with administering propofol.[30]

IV

  • Pediatric
    • 3-18 years old: 1.0 mg/kg (bolus) over 30-60 seconds with consideration being taken for level of sedation required for procedure as well as potential comorbities.[31]
  • Adult
    • 0.5-1.5mg/kg (bolus), over 30-60 seconds with consideration being taken for level of sedation required for procedure as well as potential comorbities.[31]

Fentanyl

Fentanyl is a synthetic opioid agonist that interacts primarily with the mu-receptor that is safe for procedural sedation and analgesia. Onset of action in 3-5min, and duration of action 30-60min. Fentanyl is a very potent lipophilic drug that is 75-125x more potent than morphine. Overall this medication allows the patient to remain hemodynamically stable. Compared to morphine, this medication causes no histamine release. Has reversal agent with naloxone. Nausea/vomiting can occur, which can be treated with ondansetron. Respiratory depression is a risk, especially at higher doses, narcotic-naïve patients, and when used in conjunction with other respiratory depressing medications. Chest wall rigidity is a rare complication, preventing effective ventilation. Thought to be at higher doses but reported at lower doses in pediatric population.

Effect on IOP:

IOP is usually decreased with fentanyl.[32]

Discussion

The most common systemic sedatives and their mechanisms, effects, and significant side effects have been detailed above; however, other pharmaceutical agents can achieve similar outcomes. In addition, combination therapy using multiple drugs above simultaneously has also been studied (e.g. ketamine and propofol[33], ketamine and dexmedetomidine[34]). Choosing which sedative to use in an ED ophthalmic exam will largely depend on the availability of each treatment option as well as the individual patient factors and comorbidities. Caution and careful adjustments of dose must be made for patients using opiates or other CNS depressive agents. For example, a patient presenting with respiratory pathologies could favor the use of dexmedetomidine or ketamine to achieve sedation because these agents are not known to interact with that system negatively. The physician must evaluate these individual variables among others before selecting a sedative to perform an optimal exam in regards to both diagnostic accuracy and patient experience in the ED setting.   

References

  1. ↑ Vaziri K, Schwartz SG, Flynn HW Jr, Kishor KS, Moshfeghi AA. Eye-related Emergency Department Visits in the United States, 2010. Ophthalmology. 2016;123(4):917-919. doi:10.1016/j.ophtha.2015.10.032
  2. ↑ Channa R, Zafar SN, Canner JK, Haring RS, Schneider EB, Friedman DS. Epidemiology of Eye-Related Emergency Department Visits. JAMA Ophthalmol. 2016;134(3):312–319. doi:10.1001/jamaophthalmol.2015.5778
  3. ↑ Green, Steven M., and Charles J. Coté. "Ketamine and neurotoxicity: clinical perspectives and implications for emergency medicine." Annals of emergency medicine 54.2 (2009): 181-190.
  4. ↑ Roback MG, Wathen JE, MacKenzie T, Bajaj L. A randomized, controlled trial of i.v. versus i.m. ketamine for sedation of pediatric patients receiving emergency department orthopedic procedures. Ann Emerg Med. Nov 2006;48(5):605-12. doi:10.1016/j.annemergmed.2006.06.001
  5. ↑ Green SM, Roback MG, Kennedy RM, Krauss B. Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. Ann Emerg Med. May 2011;57(5):449-61. doi:10.1016/j.annemergmed.2010.11.030
  6. ↑ Drayna PC, Estrada C, Wang W, Saville BR, Arnold DH. Ketamine sedation is not associated with clinically meaningful elevation of intraocular pressure. Am J Emerg Med. Sep 2012;30(7):1215-8. doi:10.1016/j.ajem.2011.06.001
  7. ↑ Wadia S, Bhola R, Lorenz D, Padmanabhan P, Gross J, Stevenson M. Ketamine and intraocular pressure in children. Ann Emerg Med. Oct 2014;64(4):385-388.e1. doi:10.1016/j.annemergmed.2014.01.029
  8. ↑ Halstead SM, Deakyne SJ, Bajaj L, Enzenauer R, Roosevelt GE. The effect of ketamine on intraocular pressure in pediatric patients during procedural sedation. Acad Emerg Med. Oct 2012;19(10):1145-50. doi:10.1111/j.1553-2712.2012.01450.x
  9. ↑ 9.0 9.1 Coté CJ, Lerman J, Anderson BJ, eds. A Practice of anesthesia for infants and children. 6th ed. Philadelphia, PA: Elsevier, Inc; 2019: 140-2.
  10. ↑ 10.0 10.1 10.2 Par Pharmaceutical, Inc. Ketalar® (ketamine hydrochloride) injection prescribing information. Chestnut Ridge, NY; 2018 Jul.
  11. ↑ Davis, P., Cladis, F., Motoyama, E. (2011). Smith’s Anesthesia for Infants and Children. Eighth Edition.
  12. ↑ Golparvar M, Saghaei M, Sajedi P, Razavi SS. Paradoxical reaction following intravenous midazolam premedication in pediatric patients - a randomized placebo controlled trial of ketamine for rapid tranquilization. Paediatr Anaesth. Nov 2004;14(11):924-30. doi:10.1111/j.1460-9592.2004.01349.x
  13. ↑ Coté CJ, Lerman J, Anderson BJ, eds. A Practice of anesthesia for infants and children. 6th ed. Philadelphia, PA: Elsevier, Inc; 2019: 140-2.
  14. ↑ Sahyoun C, Krauss B. Clinical implications of pharmacokinetics and pharmacodynamics of procedural sedation agents in children. Curr Opin Pediatr. Apr 2012;24(2):225-32. doi:10.1097/MOP.0b013e3283504f88
  15. ↑ Carter K, Faberowski LK, Sherwood MB, Berman LS, McGorray S. A randomized trial of the effect of midazolam on intraocular pressure. J Glaucoma. Jun 1999;8(3):204-7.
  16. ↑ Mikhail M, Sabri K, Levin AV. Effect of anesthesia on intraocular pressure measurement in children. Surv Ophthalmol. 2017;62(5):648-658. doi:10.1016/j.survophthal.2017.04.003
  17. ↑ Oberacher-Velten I, Prasser C, Rochon J, Ittner KP, Helbig H, Lorenz B. The effects of midazolam on intraocular pressure in children during examination under sedation. Br J Ophthalmol. 2011;95(8):1102-1105. doi:10.1136/bjo.2009.173641
  18. ↑ 18.0 18.1 18.2 18.3 18.4 18.5 18.6 18.7 West-ward Pharmaceuticals. Midazolam hydrochloride injection prescribing information. Eatontown, NJ; 2017 Apr.
  19. ↑ 19.0 19.1 West-ward Pharmaceuticals. Midazolam hydrochloride syrup prescribing information. Eatontown, NJ; 2017 Apr.
  20. ↑ Peerbhay F, Elsheikhomer AM. Intranasal Midazolam Sedation in a Pediatric Emergency Dental Clinic. Anesth Prog. 2016;63(3):122-130. doi:10.2344/15-00016.1
  21. ↑ Sulton C, McCracken C, Simon HK, et al. Pediatric Procedural Sedation Using Dexmedetomidine: A Report From the Pediatric Sedation Research Consortium. Hosp Pediatr. Sep 2016;6(9):536-44. doi:10.1542/hpeds.2015-0280
  22. ↑ Hammer GB, Drover DR, Cao H, et al. The effects of dexmedetomidine on cardiac electrophysiology in children. Anesth Analg. Jan 2008;106(1):79-83, table of contents. doi:10.1213/01.ane.0000297421.92857.4e
  23. ↑ Cao Q, Lin Y, Xie Z, et al. Comparison of sedation by intranasal dexmedetomidine and oral chloral hydrate for pediatric ophthalmic examination. Paediatr Anaesth. 2017;27(6):629-636.
  24. ↑ Jones JH, Aldwinckle R. Perioperative Dexmedetomidine for outpatient cataract surgery: a systematic review. BMC Anesthesiol. 2020;20(1):75. Published 2020 Apr 4. doi:10.1186/s12871-020-00973-4
  25. ↑ 25.0 25.1 Hospira. Precedex® (dexmedetomidine) injection prescribing information. Lake Forest, IL; 2016 Apr.
  26. ↑ Cao Q, Lin Y, Xie Z, et al. Comparison of sedation by intranasal dexmedetomidine and oral chloral hydrate for pediatric ophthalmic examination. Paediatr Anaesth. 2017;27(6):629-636.
  27. ↑ Sun, Yang, et al. "Low-dose intramuscular dexmedetomidine as premedication: a randomized controlled trial." Medical Science Monitor: International Medical Journal of Experimental and Clinical Research 20 (2014): 2714.
  28. ↑ Davis, P., Cladis, F., Motoyama, E. (2011). Smith’s Anesthesia for Infants and Children. Eighth Edition.
  29. ↑ Mikhail M, Sabri K, Levin AV. Effect of anesthesia on intraocular pressure measurement in children. Surv Ophthalmol. 2017;62(5):648-658. doi:10.1016/j.survophthal.2017.04.003
  30. ↑ Hospira. Propofol injectable emulsion for IV administration prescribing information. Lake Forest, IL; 2020 Mar.
  31. ↑ 31.0 31.1 Wakai A, Blackburn C, McCabe A et al. The use of propofol for procedural sedation in emergency departments. Cochrane Database Syst Rev. 2015; CD007399.
  32. ↑ Sator-Katzenschlager SM, Oehmke MJ, Deusch E, Dolezal S, Heinze G, Wedrich A. Effects of remifentanil and fentanyl on intraocular pressure during the maintenance and recovery of anaesthesia in patients undergoing non-ophthalmic surgery. Eur J Anaesthesiol. 2004 Feb;21(2):95-100.
  33. ↑ Yan JW, McLeod SL, Iansavitchene A. Ketamine-Propofol Versus Propofol Alone for Procedural Sedation in the Emergency Department: A Systematic Review and Meta-analysis. Acad Emerg Med. 2015 Sep;22(9):1003-13.
  34. ↑ Tobias JD. Dexmedetomidine and ketamine: an effective alternative for procedural sedation? Pediatr Crit Care Med. 2012 Jul;13(4):423-7.
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