Brit: Welcome back to the emDocs.net podcast. I’m Brit Long, and I’m joined by Manny Singh. You can access the podcast from our homepage on emDocs.net and subscribe in iTunes. We have included a summary of all of these points with respective links for further reading. Manny, what are we looking at today?
Manny: We have two COVID related posts. The first is on chloroquine and hydroxychloroquine toxicity, and the second is on oxygen escalation therapy in COVID.
Let’s get to our first post on toxicity of HC and chloroquine. We aren’t going to delve in the literature behind the efficacy, or lack thereof, for these treatments. Let’s just say that the current literature has many limitations including lack of comparator groups, small sample sizes, and significant biases. Please see the post on April 6 for further information on these medications for COVID-19. These medications can cause in vitro viral inhibition through several mechanisms, but ultimately lead to a change in endosomal pH.
When it comes to the pharmacokinetics, both have a high volume of distribution with some mild protein binding. The bioavailablity is pretty high, with hepatic metabolism and renal excretion for both. The half life of chloroquine is 3-5 days, but the half life for HC is 40 days!
Brit: The interesting thing about these medications is their toxicity. Even at therapeutic dosing, there are a fair number of adverse effects:
But the big issue is that these medications, particularly chloroquine, can cause TCA-like effects. Chloroquine is a definite 1 pill can kill toxin in kids. Both medications can cause sodium and potassium channel blockade, leading to widened QRS and QT intervals. However, they can also cause bradycardia and hypokalemia.
Ingestions of 5 g for adults and 1 g in kids is severe, with hypotension, long QRS, and ventricular fibrillation. Signs and symptoms typically begin 1-3 hours after ingestion. Respiratory depression is common EKG will show wide QRS and/or QT, as well as AV blocks, ST/T wave changes, and several other changes. CNS symptoms can vary from headache to severe altered mental status.
Manny: Treatment, like most ingestions, involves primary supportive care, but gastrointestinal decontamination can be considered with charcoal 1g/kg if the patient is intubated,
For those with severe toxicity including apnea, hypotension, cardiovascular collapse, dysrhythmias, intubate and provide epinephrine and high-dose diazepam Combining early mechanical ventilation with administration of high-dose diazepam and high-dose epinephrine showed potential benefit with less cardiovascular toxicity. Diazepam may have a central antagonistic effect, anticonvulsant effect, antidysrhythmic effect and interaction inverse to chloroquine/hydroxychloroquine, and decrease the chloroquine & hydroxychloroquine induced-vasodilation.
Start IV epinephrine at 0.25 mcg/kg/min, increasing by 0.25 mcg/kg/min until SBP > 90 mm Hg or MAP > 65 mm Hg. The dose of diazepam is 1-2 mg/kg over 30 minutes then 1-2mg/kg/day for 2-4 days. This is a large amount of diazepam, which may exhaust your hospital’s supply.
For a widened-QRS, treat with sodium bicarbonate treatment, but this may worsen hypokalemia. You can consider giving 1-2 mEq/kg IVP NaHCO3 in combination with evaluating the patient’s degree of cardiotoxicity and hypokalemia. Potassium repletion is tough, but if < 1.9, replete. Intralipids do not have any data supporting their use, and VV ECMO may help those who have not responded to other therapies.
Brit: Our next post deals with something difficult. Treating the patient with COVID-19 and hypoxemia. There are several types of patients with COVID-19: those who have mild disease who hopefully we don’t see in the ED, those with mild hypoxemia and symptoms but do well with therapy, those who are moderately to severely hypoxemic but otherwise appear well and may later develop severe symptoms, and those with hyperacute progression who decompensate quickly. This is becoming more and more common, especially with that happy hypoxemic patient. Recent literature suggests our strategy of early intubation may not be beneficial and may result in patient harm, so what do we have that can help these patients?
This post provides you with a strategy for escalating oxygen, but Manny, what do we need to do first?
Manny: PPE is absolutely essential in taking care of these patients. If possible, place these patients in a negative pressure room, but many of us are in centers where these may not be immediately available due to the surge of COVID-19. A room with a closed door will also work, and providers should wear full airborne, contact, and droplet precautions. Haircover and eyewear are also vital, especially if placing the patient on non-invasive ventilation, or if anticipating intubation. We have a great post on PPE that delves into this so please check that out on the site. Brit, what do we have when it comes for escalation?
Brit: If the patient is altered, in respiratory failure, or has failed other therapies, then intubate the patient. If the patient does not require emergent intubation, we can use a strategy incorporating escalation of oxygen therapy. At each step, look at the patient, rather than just the oxygen saturation number. Ask the patient how he/she is feeling, and incorporate the respiratory rate into your assessment. If the patient is not improving and feeling worse, then move to the next step.
Start with a NC at 5-6 liters per minute. This provides a fraction of inspired oxygen up to 45%, but this varies based on inspiratory peak flow. In a patient with NC at 5 LPM with no surgical mask, the dispersion of exhaled air can reach 40 cm. Thus, have the patient wear a surgical mask or face mask, which drastically reduces droplet spread and aerosolization
Manny: Next try a Venturi mask, which provides more precise oxygen delivery between 24-60% via an entrainment device that mixes air with oxygen. Up-titrate based on patient symptoms up to 60% using specified oxygen flow rates (typically 2-15 LPM). Dispersal can reach 40 cm, like the NC. Similar to the NC, place a face mask over the Venturi mask to reduce dispersal. If this is not available, use a non-breather mask up to 15 LPM. The reservoir bag should be inflated to prevent hypercapnia, which typically needs flow rates over 8 LPM. Again, cover with face mask if you are using a NRB.
Brit: Your third step is to combine a NC at 6 LPM plus a non-rebreather at 15 LPM, covered by a facemask. If the patient does not improve, go with HFNC. This reduces anatomic dead space, work of breathing, and respiratory rate, while increasing positive pressure, compliance, and oxygen flow. Flow rates can reach 60 LPM. Studies evaluating HFNC for hypoxemia in COVID-19 and other disease states have found reduction in mortality and the need for intubation and ICU admission. The World Health Organization (WHO) and Society of Critical Care Medicine (SCCM) recommend HFNC over NIPPV in patients with COVID-19 and respiratory failure. There was initial concern of aerosolization with HFNC, but this has not been demonstrated in the literature. Studies suggest HFNC was not a risk factor for transmission during SARS-CoV-1, and based on a simulation study, dispersal at 60 LPM is 4.8-17 cm . However, there may be a risk of viral dispersal with tube disconnection.
Manny: Start at 100% FiO2, with the flow rate at 20-30 LPM and titrate up to a maximum of 60 LPM if needed. This will be based on patient comfort level – the higher the rate, the more uncomfortable. Keep in mind this is the opposite of what we normally do, as typically we titrate FiO2 second. The post has a link to a great video discussing HFNC. The post also discusses the ROx index, which is the SpO2 over the FiO2 over the respiratory rate. This score measured successively at 2, 6 and 12 hours can help predict who will succedd/fail HFC, but do not dismiss your clinical assessment at the bedside.
Brit: The fifth step is noninvasive ventilation. If you have access to a helmet device, this may reduce viral dispersal and aerosolization, but many places don’t have access to this. Aerosolization is a risk when using NIPPV, though a tight-fitting mask and viral filter decrease this risk. There is a lot of debate about whether you should use CPAP versus Bipab, but We recommend CPAP over BPAP to improve oxygenation and mean airway pressures, but BPAP can be used for those with obstructive or cardiac pathologies. Make sure to use viral filters to create a closed ventilation system.
Manny: Great points. Lastly, the bottom of the post has some great tips on using a ventilator for CPAP and BiPAP mode, as well as some videos, using the IMPACT system. Now is a good time to familirazie yourself with the machines you have in your department. Reach out to your RT colleague and have them show you the ropes.
If other measures have not helped, the final step in escalation is intubation. Intubation in itself has a lot of nuances. EMcrit has already put out a lot of great resources on it, so check it out in the link of the post.
Brit: This rounds out our summary of the key emDOCs posts. Thanks for joining us, and stay tuned for our next episode. Feel free to comment on our site and let us know if you have any feedback. Stay safe and healthy everyone!