Continuing Education Activity

Scopolamine is a medication used in the management and treatment of motion sickness and postoperative nausea/vomiting. It is in the antimuscarinic class of drugs. This activity describes the indications, actions, and contraindications of scopolamine as a valuable agent in managing motion sickness, postoperative nausea/vomiting, and other disorders when applicable. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent for members of the interprofessional team) in the management of patients with motion sickness, postoperative nausea/vomiting, and related conditions.

Objectives:

• Outline the mechanism of action of antimuscarinic antiemetics.
• Describe the administration of antimuscarinic antiemetics.
• Identify the adverse effects and contraindications of antimuscarinic antiemetics.
• Explain the importance of collaboration and communication within the interprofessional team to improve outcomes for patients affected by postoperative nausea and vomiting and patients receiving antimuscarinic antiemetics.

Indications

Several medications indicated for antiemetic use produce antimuscarinic effects, most often as part of their adverse effect profiles. This article will focus on scopolamine, a drug that acts as an antiemetic primarily through its antimuscarinic mechanism of action.[1]

Two common indications for the use of scopolamine are motion sickness and postoperative nausea and vomiting (PONV). Less common indications are also listed below.

Motion Sickness

• A scopolamine patch is indicated for the prophylaxis of motion sickness in patients with a prior history of the condition.
• It can also be used to treat existing motion sickness if avoidance of stressors is not possible.
• Although a transdermal patch is more common, a faster onset has been reported with the combination of transdermal scopolamine with oral scopolamine, discussed further in the Administration section of this article.[2][3][4]

Postoperative Nausea and Vomiting (PONV)

• A scopolamine patch is indicated as part of a complete anesthetic plan, in conjunction with additional antiemetics, for patients with an increased risk of PONV.
• The following factors have been found to correlate with increased risk of PONV:
  1. Female gender 
  2. Non-smoker status 
  3. History of PONV
  4. History of motion sickness
  5. Young age
  6. History of migraine
  7. Obesity
  8. Use of postoperative opioids
  9. Use of inhalational agents including N2O
  10. A long duration of anesthesia 
• The following factors may contribute to increased risk of PONV, but their significance is currently unclear[5]: 
  1. Type of surgery (e.g., open versus laparoscopic)
  2. Presence of postoperative pain
  3. Postoperative pain with a pelvic or visceral origin
• One objective measure developed and commonly used is the simplified Apfel score, which comprises the following factors:
  1. Female gender 
  2. Non-smoker
  3. History of PONV
  4. Use of postoperative opioids
• If three or four of the Apfel score conditions are present, scopolamine is an additional antiemetic medication that the clinician can add to the patient’s care plan. However, an Apfel score of 3 or 4 does not necessitate the use of scopolamine; likewise, a patient with an Apfel score of 2 or lower may still receive scopolamine.[6][5][7]

Enhanced Recovery After Surgery (ERAS) Protocols

• Many centers implement ERAS protocols for various types of surgeries. A crucial component of these protocols is the control of PONV. ERAS protocols vary from center to center and on the type of surgery. Although some studies don’t explicitly report the sequence/types of antiemetics used, several studies reported the use of scopolamine as a standard part of their ERAS protocol.[8][9][10]

Refractory nausea and vomiting

Dizziness

Vertigo

Drooling[2]

Depression (off-label)[11][12][13]

Mechanism of Action

Acetylcholine Receptors

The nervous system utilizes many neurotransmitters for communication and function. The primary neurotransmitter of the parasympathetic nervous system is acetylcholine (ACh). ACh is synthesized in the cytoplasm of presynaptic neurons by the enzyme choline acetyltransferase (ChAT). It is subsequently relocated to synaptic vesicles by vesicular acetylcholine transporter (VAChT), where it is stored. When the presynaptic neuron becomes stimulated via depolarization, ACh gets released through exocytosis into the synaptic cleft, where it acts on presynaptic and postsynaptic receptors by binding to them. These receptors include muscarinic (M) and nicotinic (N) types, each with their respective subtypes. There are five subtypes of muscarinic receptors, M1 thru M5, all of which are G protein-coupled receptors.[14]

Scopolamine

Scopolamine (also known as hyoscine) is an alkaloid compound. It competitively antagonizes the action of ACh at muscarinic receptors both centrally and peripherally. It is selective to muscarinic receptors but is non-selective between the muscarinic receptor subtypes (M1 thru M5). Because ACh is the principal neurotransmitter of the parasympathetic nervous system, scopolamine acts as a parasympatholytic agent.[1][13][15]

Nausea and Vomiting

Multiple proposed mechanisms of nausea and vomiting involve various systems (e.g., vestibular, gastrointestinal, etc.). Furthermore, the specific pathways that these systems utilize to stimulate nausea and vomiting are not clearly understood. The precise locations and functions of nervous system structures involved in nausea and vomiting require further research.

For these reasons, the exact mechanisms by which scopolamine prevents nausea and vomiting are unclear. The proposed pathways generally involve scopolamine inhibiting cholinergic communications between higher CNS centers, the reticular formation in the brainstem, the vestibular nuclei, the cerebellum, the glossopharyngeal nerve, and the vagus nerve. Additional structures may be involved, and scopolamine’s exact role is unclear. Furthermore, all five muscarinic receptor subtypes M1 thru M5 show expression in the brain, and the roles of each subtype relative to nausea and vomiting remain unclear.[15][16][17][18]

A discussion of the mechanisms involved in scopolamine’s adverse effects is in the Adverse Effects section of this article.

Administration

Transdermal vs. Oral

The preferred method for administering scopolamine is via a transdermal therapeutic system (TTS-patch) due to increased bioavailability and decreased adverse effects. There is a 1.5 mg patch commercially available, and it is generally the specific patch used. As previously mentioned, oral scopolamine has demonstrated effectiveness when combined with the transdermal patch; however, this mode of administration is uncommon.

Placement Location and Timing

The 1.5 mg patch should be placed behind the patient’s ear on an area of skin without hair. Placement should occur several hours before the patient’s surgery. Reports range from 4 hours before the anticipated end of the procedure to the night before surgery. If used for the prophylaxis of motion sickness, placement should occur 6 to 8 hours before the nausea-inducing event. Due to the timing requirement, patients presenting for surgery should be evaluated for PONV risk as early as possible to properly formulate an anesthetic plan with enough time to permit the ideal usage of scopolamine if indicated.

The patch is designed to release an initial priming dose to achieve steady-state concentrations in an acceptable amount of time. It then continues to release medication slowly, a topic discussed in greater detail in the Mechanism of Action section of this article. Due to its mechanism of release, if the continual antiemetic effect is required, the patch can be replaced every 72 hours. If scopolamine is used preoperatively for the prophylaxis of PONV, the patch can be removed the day following surgery.

Importance of Hand Hygiene

A crucial element of the administration of scopolamine is the counseling of the patient and/or their family. In addition to remaining vigilant about adverse effects, anyone removing the patch needs to understand the importance of hand hygiene. After removal of the scopolamine patch, the skin location where the patch was, and the operator’s hands, require thorough washing with soap and water. After touching a scopolamine patch, patients should also be instructed to avoid touching their faces, especially their eyes. A significant number of adverse effects related to the scopolamine patch are due to contamination by the patient or by an individual changing or touching the patch.[2][3][5][15][16]

Note: Although the following administration methods appear in the published literature, every patient should receive a specific plan based on their medical team’s assessment and clinical expertise. Prior to administering scopolamine, a thorough history and physical exam are necessary to rule out contraindications and to anticipate adverse effects accurately. 

Adverse Effects

Scopolamine’s adverse effect profile is due to its antagonism of muscarinic receptors. The more commonly reported adverse effects are listed below, with xerostomia and CNS symptoms being significantly more common than ophthalmic symptoms. However, scopolamine non-selectively affects all five muscarinic receptor subtypes (M1 thru M5), and anticholinergic symptoms, or anticholinergic syndrome, are theoretically possible.[10] Additionally, there are over 600 medicinal products with anticholinergic activity. The antimuscarinic effects of these products have the potential to exacerbate the adverse effects of scopolamine.[1][19][20]

Most Common

• Xerostomia (dry mouth)
• Central Nervous System Symptoms:
  • Dizziness
  • Confusion
  • Agitation
  • Delirium
• Ophthalmic Symptoms:
  • Visual impairment, including blurred vision
  • Mydriasis

Rare Adverse Effects [10][21][22][23][24][25]

• Acute angle-closure glaucoma
• Urinary retention
• Withdrawal symptoms upon cessation of scopolamine

Discussion on Ophthalmic Symptoms and Glaucoma

Mydriasis is a potential complication of scopolamine. Although reports exist of bilateral cases, the literature suggests that the majority of cases of mydriasis are unilateral and ipsilateral to the side of their scopolamine patch, caused by the patient self-contaminating by touching their patch and then touching their eyes.[2]

There are case reports of acute angle-closure glaucoma after the administration of scopolamine. This complication is rare. Patients affected by this complication likely have underlying pathology or abnormal anatomy that predisposes them to acute angle closure in the event of mydriasis through at least two mechanisms. Aqueous humor becomes blocked from flowing from the posterior to the anterior chamber of the eye, building up intraocular pressure. Patients can present with the following signs and symptoms:

• Nausea and vomiting
• Severe headache
• Severe ocular pain
• Blurred vision
• Red-eye
• Dilation of pupil

Glaucoma is an ophthalmic emergency that can result in blindness if untreated promptly, and an ophthalmology consultation is important.[26][27][28][29]A distinction should be made with patients with open-angle glaucoma as these patients can safely use transdermal scopolamine patches.[30]

Elderly Patients

Elderly patients are at an increased risk of and are more vulnerable to adverse anticholinergic effects due to differences in metabolism, excretion of medications, and changes in the CNS. In the elderly, antimuscarinic medications may correlate with increased morbidity for several reasons, including increased risk of falls. Scopolamine and antimuscarinic medications should be used very cautiously in elderly patients.[31][32][33][34][35]

Contraindications

The following are contraindications to scopolamine:

• Hypersensitivity to the medication or a component of the drug delivery system
• Glaucoma
• Urinary retention
• Pregnancy

Although one study mentions pregnancy as a contraindication for scopolamine in one study, another study indicates that although the scopolamine crosses the placenta, it’s considered nonteratogenic.[4][15]

Toxicity

The reversal of scopolamine toxicity is not a widely reported topic. However, based on the mechanism of toxicity, physostigmine can be used to reverse anticholinergic symptoms. There are reports of the use of physostigmine in cases of scopolamine toxicity. The patient then requires monitoring for a cholinergic crisis with atropine available at the bedside. Additionally, as with most poisonings, vital signs and ECG should be obtained and monitored.[10][36][37]

Enhancing Healthcare Team Outcomes

Postoperative nausea and vomiting (PONV) is a ubiquitous presentation when caring for postoperative patients. The incidence is estimated to be about 30% in the average patient and can rise as high as 70% in the high-risk patient. PONV is a significant concern because it prolongs recovery room time, can lead to increased hospital admissions and unanticipated complications. Additionally, the prevention of PONV is vital to the patient's mental wellbeing.

A patient's risk of experiencing PONV can be reliably anticipated and predicted using several measures, including the Apfel score. In patients with increased risk, a multimodal approach, including the use of multiple antiemetic medications, is the proper approach in the prevention of PONV.[5] [Level 1] One potential antiemetic medication that has shown effectiveness in reducing the incidence of PONV is the transdermal scopolamine patch.[38] [Level 1]

Due to the pharmacokinetics and pharmacodynamics of the scopolamine patch, it requires application several hours before the start of the patient's surgery. It can also be applied the previous night. The patient's healthcare team must remain vigilant about identifying patients at high risk for PONV. If scopolamine is indicated, there is sufficient time before the procedure to administer the drug effectively.

Scopolamine commonly causes dry mouth, blurred vision, and sedation. As an antimuscarinic medication, scopolamine has the potential to cause anticholinergic symptoms, including tachycardia, urinary retention, and acute angle-closure glaucoma. There are also reports of withdrawal symptoms from the medication. The patient's health care team must be aware of these potential complications to recognize them and begin management as soon as possible; this is especially true for elderly patients who are at increased risk of complications, including falls.[10][21][29][38] [Level 2]

A collaborative healthcare team approach is the best method for addressing PONV. Clinicians need to accurately identify which patients will be candidates for antiemetic prophylaxis or therapy and coordinate with nurses and pharmacists for its delivery. Nurses will be administering the medication and need to fully understand the points discussed in this activity regarding proper administration and handling of the drug, particularly in patch form. The pharmacist should complete a full drug-drug interaction check and verify dosing while also watching for mitigating factors like age that may require therapy modification. Both the pharmacist and nurse will report any issues or concerns to the treating clinician. These points highlight some of how an interprofessional team approach will be most successful in providing PONV care. [Level 5]

Finally, a common mechanism of ophthalmic symptoms from scopolamine is self-contamination by the patient. The interprofessional health care team, including the pharmacist, will counsel the patient on hand washing and proper hand hygiene after touching the scopolamine patch. In addition to the morbidity associated with the actual adverse effect, the clinical signs associated with unilateral mydriasis may often be misinterpreted, leading to misdiagnosis, increased costs, and delay of proper treatment.[2] [Level 5]