What is the likely cause of coma and respiratory depression in a post-operative cardiac surgery patient with hypercapnia, prolonged QT interval, hypokalemia, hypomagnesemia, and hypocalcemia, who is taking beta blockers, quetiapine, and clonazepam?

From the Guidelines

This patient requires immediate intervention to address drug-induced CNS and respiratory depression with CO₂ narcosis, and management should prioritize securing the airway, correcting electrolyte abnormalities, and holding sedating medications, as evidenced by the latest guidelines 1. The patient's presentation of coma, respiratory depression, and QT prolongation is likely due to the interaction of clonazepam, quetiapine, and beta blocker, exacerbated by electrolyte derangements. Key actions include:

• Intubation and ventilatory support to address CO₂ narcosis
• Holding clonazepam and quetiapine, and temporarily discontinuing the beta blocker if the patient is bradycardic or hypotensive
• Correcting electrolyte abnormalities with 2g IV magnesium sulfate, 1-2g calcium gluconate IV, and increasing potassium to above 4.0 mmol/L
• Continuous cardiac monitoring and serial ECGs to track improvement of the prolonged QTc (483 ms)
• CT brain to rule out stroke or hemorrhage, and neurology consultation for coma evaluation and possible EEG if mental status doesn't improve
• Pharmacy consultation to address drug interactions and QT prolongation risks, as highlighted in a case study where normalization of QTc interval was achieved after withholding offending medications and correcting electrolytes 1. Given the high risk of further deterioration, including potential arrhythmias or respiratory arrest, ICU-level care is essential to manage this patient's condition effectively.

From the FDA Drug Label

In clinical trials, quetiapine was not associated with a persistent increase in QT intervals. However, the QT effect was not systematically evaluated in a thorough QT study. In post marketing experience, there were cases reported of QT prolongation in patients who overdosed on quetiapine [see OVERDOSAGE (10. 1)] , in patients with concomitant illness, and in patients taking medicines known to cause electrolyte imbalance or increase QT interval [see DRUG INTERACTIONS (7.1)]

The use of quetiapine should be avoided in combination with other drugs that are known to prolong QTc including Class 1A antiarrythmics (e.g., quinidine, procainamide) or Class III antiarrythmics (e.g., amiodarone, sotalol), antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QTc interval (e.g., pentamidine, levomethadyl acetate, methadone)

The patient's QT prolongation (483 ms) is a significant concern, and the use of quetiapine and other medications that may prolong the QT interval should be avoided. The patient's low Ca²⁺/Mg²⁺ levels may also increase the risk of QT prolongation.

• Medication Management: Hold quetiapine and clonazepam, and avoid other QT-prolonging or sedating medications.
• Electrolyte Correction: Correct Mg²⁺, Ca²⁺, and K⁺ levels to reduce the risk of QT prolongation and other cardiac complications.
• Monitoring: Continuously monitor the patient's ECG and vitals for signs of QT prolongation and other cardiac complications.

It is essential to exercise caution when managing this patient's medications and electrolyte levels to minimize the risk of QT prolongation and other cardiac complications 2, 2.

From the Research

Patient Summary

• Status: Post-cardiac surgery (for tamponade)
• Current Issue: Unresponsive ~4 hours after receiving clonazepam 1 mg
• Key Vitals/Labs:
  • PaCO₂: 66 mmHg (CO₂ retention)
  • QTc: 483 ms (prolonged)
  • Electrolytes:
    • K⁺: 3.5 mmol/L
    • Mg²⁺: 0.84 mmol/L
    • Ca²⁺ (corrected): ~1.83 mmol/L
  • On: Beta blocker, quetiapine, clonazepam

Likely Diagnosis

• Drug-induced CNS and respiratory depression with CO₂ narcosis, worsened by:
  • Quetiapine: sedative + QT prolongation
  • Clonazepam: potent respiratory depressant
  • Beta blocker: masks compensatory response
  • Electrolyte derangements: increase cardiac and CNS risks
• This diagnosis is supported by studies such as 3, which reports a case of coma after quetiapine overdose, and 4, which describes mental status change, myoclonus, electrocardiographic changes, and acute respiratory distress syndrome induced by quetiapine overdose.

Key Problems

• Coma / unresponsiveness
• Respiratory depression (CO₂ narcosis)
• QT prolongation (483 ms) with low Ca²⁺/Mg²⁺
• Polypharmacy interaction
• Post-op vulnerability
• These problems are consistent with the findings of 5, which discusses the management of the comatose patient, and 6, which provides a systematic approach to the unconscious patient.

Actions Taken / Plan

• Airway & Breathing:
  • Intubation likely needed (if not already)
  • ABG monitoring, repeat PaCO₂
  • Supportive ventilation
• Medication Management:
  • Hold clonazepam and quetiapine
  • Hold beta blocker temporarily if bradycardic or hypotensive
  • Avoid other QT-prolonging or sedating meds
• Electrolyte Correction:
  • Mg²⁺: 2 g IV Mg sulfate
  • Ca²⁺: 1–2 g calcium gluconate IV
  • K⁺: Raise to >4.0 mmol/L (IV/PO)
• Serial labs and ECGs
• Imaging & Monitoring:
  • CT Brain: Ordered to rule out stroke, bleed
  • Telemetry: Continuous monitoring for arrhythmias
  • Repeat ECGs: Monitor QTc trend
  • Consider EEG if status doesn’t improve
• Consults:
  • Neurology (coma workup, EEG?)
  • Pharmacy (drug clearance, QT risks)
  • ICU/critical care (if not already in unit)
• The plan is also informed by 7, which discusses the physiology of the respiratory drive in ICU patients and its implications for diagnosis and treatment.