Takeaway

Scopolamine may be most suited for post-discharge PONV in same day patients, and is associated with an increased risk for in-hospital adverse events.

Key Points

• Used a retrospective cohort study
• Primary outcomes assessed were delirium, pneumonia, in-hospital death, new antipsychotic use, readmission, and new onset urinary retention within 7 days post-surgery
• Total of 403,816 (201,908 pairs) perioperative scopolamine users and nonusers
• Study utilized a large nationwide inpatient database for comprehensive analysis
• Increased risk of in-hospital adverse events associated with scopolamine use
• Significant risk observed in patients aged 70+
• Elevated risk also noted in age groups 20-29, 30-39, 40-49, 50-59, and 60-69

Excerpts

concerns have emerged regarding the potential for increased side effects, particularly in elderly patients. This population faces an elevated risk of delirium and potential side effects due to scopolamine’s anticholinergic properties [9]. The adverse effects of scopolamine are well documented, with patients receiving transdermal scopolamine commonly experiencing effects such as urinary retention, dry mouth, mydriasis, visual disturbances, and amblyopia

found a significant association between perioperative scopolamine administration and an increased risk of delirium and mortality. Notably, scopolamine administration was linked to a heightened mortality risk across all age groups, with the magnitude of this risk escalating with each advancing decade—tripling in individuals aged 60–69 and quadrupling in those aged 70 and older

Scopolamine may elevate the risk of mortality by directly inducing neuroinflammation and disrupting the regulatory mechanisms that control it.

Recent studies in animal models demonstrate that scopolamine provokes inflammation in the brain and is used experimentally to induce learning and memory deficits, thereby mimicking Alzheimer’s disease in mice [20,21,22]. Acetylcholine, a neurotransmitter, is crucial in modulating the brain’s inflammatory response by inhibiting cytokine release from microglia [23].

Scopolamine’s anticholinergic properties may compromise this inhibitory effect, leading to unchecked neuroinflammation. This unchecked release of proinflammatory cytokines can further activate microglia, creating a feedback loop that perpetuates neuroinflammation, potentially causing sustained brain damage even months after exposure [24].

This persistent and uncontrolled neuroinflammation results in neurotoxicity, severe and prolonged delirium, persistent dementia, and, ultimately, death.

Postoperative pneumonia, a marker of sedation (a key feature of delirium), increased in patients over 50

patients who received scopolamine were over 70% more likely to require antipsychotic medication in the days following surgery, suggesting their use was driven by other factors, such as agitation.

Scopolamine use was also associated with an increased risk of urinary retention across all age groups.

scopolamine use carries inherent risks and should be judiciously considered, with a clear evaluation of the benefit-to-risk ratio

perioperative scopolamine usage was associated with a significantly increased risk of in-hospital mortality, delirium, pneumonia, new antipsychotic utilization, readmission, and urinary retention both within all age cohorts after major surgery, but especially in the > 60 age cohort

Scopolamine is most suited for post-discharge nausea and vomiting in ambulatory patients given its 4-hour onset time, and its 72-hour duration.

Abstract

Background

Scopolamine is a widely used antiemetic in anesthetic practice, particularly for postoperative and post-discharge nausea and vomiting. Despite its frequent usage and recognized efficacy, concerns have emerged regarding the potential for increased side effects, particularly in elderly patients. Further research is needed to assess safety and determine age thresholds for adverse events. This study hypothesizes associations between perioperative scopolamine use, worse clinical outcomes, increased pneumonia, delirium, urinary retention, and readmissions.

Methods

A large, retrospective cohort study was performed using the TriNetX Analytics Network database on patients undergoing major surgical procedures between Jan 1, 2009, and March 21, 2018, to examine the impact of perioperative scopolamine use on in-hospital adverse events. Patients were divided into age groups and compared to a control group. The primary outcomes assessed were delirium, pneumonia, in-hospital death, new antipsychotic use, readmission, and new onset urinary retention within 7 days post-surgery. 1:1 propensity score matching was performed to reduce bias. Relative risk and risk differences with 95% confidence intervals were estimated.

Results

After 1:1 propensity score matching, we identified a total of 403,816 (201,908 pairs) perioperative scopolamine users and nonusers. The cohorts of 20-29, 30-39, 40-49, 50-59, 60-69, and 70 + contained 22,910 (11,455 pairs), 44,170 (22,085 pairs), 58,590 (29,295 pairs), 71,660 (35,830 pairs), 88,386 (44,193 pairs), and 118,100 (59,050 pairs) patients respectively. Across older age cohorts, after propensity score matching, perioperative scopolamine recipients had significantly increased relative risk and risk difference of delirium, pneumonia, in-hospital mortality, new antipsychotic use, readmission, and new-onset urinary retention.

Conclusions

In this cohort study, perioperative scopolamine usage was associated with a significantly increased risk of in-hospital adverse events, both within the 70 + age cohort and among the 20-29, 30-39, 40-49, 50-59, and 60-69 age cohorts after major surgery. These findings highlight the need for careful assessment of scopolamine's risks and benefits, especially for patients aged 40 and older. Scopolamine may be most suited for post-discharge nausea and vomiting in ambulatory patients and clinicians should reassess its standard use for postoperative nausea and vomiting, favoring shorter-acting agents with fewer side effects.

Citation

Sun G, Torjman MC, Min KJ. A comprehensive analysis of in-hospital adverse events after scopolamine administration: insights from a retrospective cohort study using a large nationwide inpatient database. BMC Anesthesiol. 2024 Nov 28;24(1):438. doi: 10.1186/s12871-024-02824-y. PMID: 39604832; PMCID: PMC11604008.

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