In this episode I’ll:
1. Discuss an article on push-dose norepinephrine.
2. Answer the drug information question “What is the dose of methylene blue for cardiac surgery related vasoplegia?”
3. Share a resource for hereditary angioedema.
The article for this episode recently appeared in a weekly literature digest for members of my Critical Care Pharmacy Academy. Every week I send Academy members a summary of the most important critical care pharmacy articles, including my analysis of where the article fits in practice. The literature summary is brief, relevant, and presented in audio and video format. You can find out more at pharmacyjoe.com/academy.
Article
Lead author: Desire Onwochei
Published in Anesthesia & Analgesia February 2017
Background
While push-dose vasopressor use is anecdotally reported in critical and emergency medicine scenarios, peer-reviewed data is limited to obstetric patients. Phenylephrine is most commonly used but is thought to cause reduced cardiac output. Norepinephrine adds beta-adrenergic activity compared to the pure alpha activity of phenylephrine. This results in greater heart rate and cardiac output. The ideal push-dose of norepinephrine is unknown.
The study authors sought to determine the effective norepinephrine dose, when given as intermittent intravenous (IV) boluses, to prevent postspinal hypotension in 90% of women undergoing elective cesarean delivery (ED90).
Methods
The study was a prospective, double-blind sequential allocation dose-finding study. Forty-term pregnant women undergoing elective cesarean delivery under spinal anesthesia received a set intermittent norepinephrine bolus of either 3, 4, 5, 6, 7, or 8 mcg every time their systolic blood pressure fell to below 100% of baseline. The primary outcome was the success of the norepinephrine regimen to maintain systolic blood pressure at or above 80% of baseline, from induction of spinal anesthesia to delivery.
Results
The estimated ED90 of norepinephrine was 5.49 mcg (95% CI 5.15-5.83).
Conclusion
The authors concluded:
The use of intermittent IV norepinephrine boluses to prevent spinal-induced hypotension in elective CD seems feasible and was not observed to be associated with adverse outcomes. Practically, we suggest an ED90 dose of 6 [micro]g. Further work is warranted to elucidate the comparative effects of intermittent IV bolus doses of phenylephrine and norepinephrine, in terms of efficacy and safety.
Discussion
I discussed push-dose vasopressors back in episode 4. If a push-dose vasopressor will prevent the patient from a complication of profound hypotension then it should be given. But my general opinion is that in the event of severe hypotension, a pharmacist at the bedside should make preparations for vasopressor infusions to avoid repeated dosing of push-dose vasopressors. Push-dose vasopressor use means the physician is playing the role of “smart pump” instead of the role of “resuscitationist” in an emergency.
All of the trial data for push-dose vasopressors that I can find is in obstetric patients. I have yet to see anything other than anecdotal information on the use of push-dose vasopressors in critically ill patients. The dose of phenylephrine IV push used in obstetric patients is 100-200 mcg, and this seems to be the dose that is anecdotally effective in critically ill patients. It is just as reasonable to extrapolate the results of this trial to critcally ill patients. Therefore if push-dose norepinephrine is used, the dose of 6mcg found in this study serves as a starting point.
Drug information question
Q: What is the dose of methylene blue for cardiac surgery related vasoplegia?
A: Most studies suggest a dose of methylene blue 1.5 – 2 mg/kg IV.
Vasoplegic syndrome occurs in a minority of patients during or after cardiopulmonary bypass. The syndrome is characterized by hypotension, high or normal COs, a low SVR, and increased requirements for fluids and vasopressors. Methylene blue is typically used for vasoplegia during the perioperative period only as a drug of last resort. Methylene blue is thought to restore vascular tone by inhibiting the response of blood vessels to cyclic GMP-dependent vasodilators.
Resource
The website All About Hereditary Angioedema has information for healthcare professionals about diagnosing, treating, and managing hereditary angioedema (HAE). Direct downloads of HAE treatment algorithms are available.
Hereditary angioedema is an extremely rare disease. Fortunately, it seems that for every rare disease there is an internet-based society that provides resources to healthcare professionals. Here are some examples of rare diseases with internet-based resources that I have previously discussed: Long QT syndrome in episode 151, Porphyria in episode 41, and NMS and MH in episode 40. Whenever I encounter a patient with a rare disease, I’ll search for a disease-specific organization that provides resources for healthcare professionals.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
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