Articaine Hydrochloride + Epinephrine Bitartrate + Nitroglycerin (IV Infusion)

2 documented mechanisms

This source documents more than one distinct mechanism for this pair. Each is shown with its own effect, advice and sources rather than merged into one.

1. Mechanism 1: Synergy

   Major

   via Articaine and Nitroglycerin

   What happens

   Coadministration of local anesthetics with other oxidizing agents that can also induce methemoglobinemia such as antimalarials (e.g., chloroquine, primaquine, quinine, tafenoquine), nitrates and nitrites, sulfonamides, aminosalicylic acid, dapsone, dimethyl sulfoxide, flutamide, metoclopramide, nitrofurantoin, phenazopyridine, phenobarbital, phenytoin, and rasburicase may increase the risk.

   What to do

   Close monitoring for signs and symptoms of methemoglobinemia is recommended if local anesthetics must be used with other methemoglobin-inducing agents. Signs and symptoms of methemoglobinemia may occur immediately or hours after drug exposure. Patients or their caregivers should be advised to seek medical attention if they notice signs and symptoms of methemoglobinemia (e.g., cyanotic skin discoloration, abnormal blood coloration, nausea, headache, dizziness, lightheadedness, lethargy, fatigue, dyspnea, tachypnea, tachycardia, palpitation, anxiety, and confusion). In severe cases, patients may progress to central nervous system depression, stupor, seizures, acidosis, cardiac arrhythmias, syncope, shock, coma, and death. Methemoglobinemia should be considered if central cyanosis is unresponsive to oxygen. Calculated oxygen saturation and pulse oximetry are generally not accurate in the setting of methemoglobinemia. The diagnosis can be confirmed by an elevated methemoglobin level of at least 10% using co-oximetry. Methemoglobin concentrations greater than 10% of total hemoglobin will typically cause cyanosis, and levels over 70% are frequently fatal. However, symptom severity is not always related to methemoglobin levels. Mild cases often respond to withdrawal of offending agents and symptomatic support. If a patient does not respond to administration of oxygen, clinically significant or symptomatic methemoglobinemia can be treated with methylene blue 1 to 2 mg/kg by slow intravenous injection over 5 to 10 minutes, which may be repeated within 30 to 60 minutes if necessary. Higher dosages of methylene blue (usually greater than 7 mg/kg) should be avoided, as it can paradoxically exacerbate methemoglobinemia. Additionally, methylene blue is ineffective and can cause hemolytic anemia in patients with G6PD deficiency. These patients may be treated with exchange transfusion, dialysis, and/or hyperbaric oxygenation in addition to symptomatic support.

   5 sources

   1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
   2. "Product Information. Marcaine HCl (bupivacaine)." Hospira Inc (2008):
   3. Guay J "Methemoglobinemia related to local anesthetics: a summary of 242 episodes." Anesth Analg 108 (2009): 837-45
   4. Skold A, Cosco DL, Klein R "Methemoglobinemia: pathogenesis, diagnosis, and management." South Med J 104 (2011): 757-61
   5. "Product Information. Zynrelef (bupivacaine-meloxicam)." Heron Therapeutics (2021):

2. Mechanism 2: Unknown

   Listed, not described

   via Epinephrine and Nitroglycerin

   The source lists this pair here and publishes no description, mechanism or citation for it.

   No sources recorded

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