When to hold neostigmine (acetylcholinesterase inhibitor) drip for symptomatic or severe bradycardia?

When to Hold Neostigmine Drip for Bradycardia

Neostigmine drip should be held when the patient develops symptomatic bradycardia or when heart rate falls below 50 beats per minute, and atropine should be administered to reverse the bradycardic effects. 1

Understanding Neostigmine's Effect on Heart Rate

• Neostigmine is an acetylcholinesterase inhibitor that has been associated with bradycardia as a known adverse effect 1
• The FDA label specifically warns about bradycardia risk with neostigmine administration 1
• The bradycardic effect is due to neostigmine's cholinergic properties, which increase acetylcholine levels at the sinoatrial node 1

Management Algorithm for Neostigmine-Induced Bradycardia

When to Hold Neostigmine:

1. Symptomatic bradycardia - Hold neostigmine immediately if the patient develops:

   • Acutely altered mental status
   • Ischemic chest discomfort
   • Acute heart failure
   • Hypotension
   • Other signs of shock 2

2. Severe bradycardia - Hold neostigmine when heart rate falls below 50 beats per minute, even without symptoms 3

3. High-risk patients - Use extra caution and consider holding neostigmine at higher heart rates in patients with:

   • Coronary artery disease
   • Cardiac arrhythmias
   • Recent acute coronary syndrome
   • Myasthenia gravis 1

Immediate Management of Neostigmine-Induced Bradycardia:

1. First-line treatment: Administer atropine 0.5 mg IV every 3-5 minutes to a maximum total dose of 3 mg 2

   • Atropine directly counteracts the cholinergic effects of neostigmine 1
   • Doses of atropine <0.5 mg may paradoxically worsen bradycardia 2

2. If bradycardia persists despite atropine:

   • Consider β-adrenergic agonists with rate-accelerating effects:
     • Dopamine (2-10 μg/kg/min) 2
     • Epinephrine (2-10 μg/min) 2
   • Consider transcutaneous pacing (TCP) if medications fail 2

3. For refractory cases:

   • Prepare for transvenous pacing if the patient does not respond to medications or TCP 2
   • In specific scenarios (spinal cord injury, cardiac transplant patients), aminophylline may be considered 4

Special Considerations

• Cardiac transplant patients: These patients may be particularly sensitive to neostigmine-induced bradycardia, and the heart rate response to atropine may be blunted due to denervation 2, 5

• Neurocritically ill patients: When using neostigmine for acute colonic pseudo-obstruction, bradycardia occurred in 3.2% of patients in one study and was successfully managed with atropine 6

• Prevention: When administering neostigmine for neuromuscular blockade reversal, an anticholinergic agent (atropine or glycopyrrolate) should be given prior to or concomitantly with neostigmine to prevent bradycardia 1, 3

  • Glycopyrrolate 10 μg/kg mixed with neostigmine provides the most stable heart rates 3

Pitfalls and Caveats

• Avoid relying solely on atropine in patients with type II second-degree or third-degree AV block, as these bradyarrhythmias may not respond to cholinergic reversal 2

• Be aware that neostigmine can cause a cholinergic crisis which may present with extreme muscle weakness similar to myasthenic crisis but requires different treatment 1

• Do not delay implementation of external pacing for patients with poor perfusion while waiting for atropine to take effect 2