Spravato and Surgery: Perioperative Management
Spravato (esketamine nasal spray) is not absolutely contraindicated for patients undergoing surgery, but it must be held on the day of the surgical procedure due to significant risks of sedation, dissociation, blood pressure elevation, and cognitive impairment that could complicate anesthetic management and postoperative recovery.
Key Perioperative Concerns
The FDA label for Spravato identifies several critical issues that make same-day administration problematic for surgical patients 1:
Sedation and Loss of Consciousness
- 48-61% of patients develop sedation after Spravato administration
- 0.3-0.4% experience complete loss of consciousness
- Patients require mandatory 2-hour monitoring after each dose until clinically stable
- Additive effects occur with other CNS depressants used in anesthesia 1
Cardiovascular Effects
- Blood pressure peaks at approximately 40 minutes post-dose and remains elevated for up to 4 hours
- 3-19% of patients experience increases ≥40 mmHg systolic or ≥25 mmHg diastolic
- Absolute contraindication in patients with aneurysmal vascular disease, arteriovenous malformations, or history of intracerebral hemorrhage 1
- This creates significant risk when combined with surgical stress and anesthetic agents
Dissociative and Cognitive Effects
- 61-84% of patients experience dissociative symptoms (distortion of time/space, derealization, depersonalization)
- Cognitive impairment persists for at least 40 minutes, with performance returning to baseline by 2 hours
- Driving ability remains impaired up to 8 hours post-dose in some patients 1
Practical Management Algorithm
On the Day of Surgery:
- Hold Spravato - do not administer on the morning of or day of the procedure
- The combination of sedation, dissociation, blood pressure instability, and cognitive impairment creates unacceptable risk when layered with general anesthesia
Timing Considerations:
- Given the 2-hour mandatory monitoring period and up to 4-hour duration of blood pressure effects, patients should not receive Spravato within at least 24 hours of their scheduled surgery
- For patients on twice-weekly dosing: schedule the last dose at least 2-3 days before surgery when possible
- For emergency surgery: inform the anesthesiologist of recent Spravato use (timing, dose) as this impacts anesthetic management
Postoperative Resumption:
- Resume Spravato only after the patient is:
- Hemodynamically stable
- No longer requiring parenteral opioids or significant CNS depressants
- Able to comply with the 2-hour post-dose monitoring requirement
- Typically 48-72 hours postoperatively for most procedures
Important Caveats
Cardiovascular Screening: Before any elective surgery, ensure patients do not have undiagnosed conditions that would make Spravato absolutely contraindicated (aneurysms, arteriovenous malformations, history of intracerebral hemorrhage) 1. These same conditions may also influence surgical risk stratification.
Drug Interactions: The perioperative guidelines emphasize that serotonergic agents (which esketamine is) increase risk of serotonin syndrome when combined with other serotonergic medications commonly used perioperatively (ondansetron, metoclopramide, certain opioids like tramadol, fentanyl, methadone) 2. This risk persists even after holding Spravato due to the pharmacologic effects of other perioperative medications.
Anesthesia Communication: Always inform the anesthesia team about Spravato use, as esketamine's NMDA receptor antagonism may alter anesthetic requirements and the patient's response to ketamine-based anesthetics if used intraoperatively 3, 4.
Depression Management: Continue the concomitant oral antidepressant throughout the perioperative period unless specifically contraindicated. The oral antidepressant provides baseline mood stabilization while Spravato is held 1.