ROX Index: Predicting Who Is or Isn’t Going to Fly on HFNC

We have all had this patient. Someone who is in acute hypoxemic respiratory failure, let’s just call it pneumonia of some sort or ARDS, and the regular nasal cannula or a venti-mask can’t cut it. They’re not at the severity where you can eyeball the patient and just know that they need to be intubated. Those folks just get tubed. You put them on high-flow nasal cannula to try to bring up their sats and decrease their work of breathing. Is there something that you can use to predict, though, if the patient isn’t going to fly and may need to be intubated? This is where the ROX index comes in to play. Before getting into all this, I’d like to tip my hat to Dr. Oriol Roca and his team who published the concept and subsequent data on the ROX index. They’ve changed the way we use high-flow nasal cannula forever.

Why reach for HFNC first

In 2015, Frat, et al. published the FLORALI trial where they randomized over 300 patients who had acute hypoxemic respiratory failure to receive with non-invasive ventilation (BiPAP or CPAP in layman’s terms), conventional oxygen therapy (non-rebreather, venti-mask, etc.), or high-flow nasal cannula. In this study they found that patients with a P/F ratio ≤ 200 did better with the high-flow as opposed to the other two. In addition, they had a higher survival rate at 90 days. For the sake of filling in the knowledge gaps for the uninitiated, P/F ratio is a way to categorize the severity of ARDS. The equation is PaO2/FiO2. You get the PaO2 from an ABG. You get the FiO2 from the oxygenation device you’re using to provide oxygen to your patient.

Per the ARDS Definition Task Force (known as the Berlin Criteria), there are 3 categories of ARDS based on the P/F ratio. Mild: 200 mm Hg < PaO2/FiO2 ≤ 300 mm Hg. Moderate: 100mmHg < PaO2/FiO2 ≤ 200 mmHg. Severe: PaO2/FiO2 ≤ 100 mmHg. People often stumble on entering these numbers on their calculator. Remember to use the decimal point for the FiO2. Lets sat the PaO2 is 100 on 40% FiO2, that means the P/F ratio is 250. That fits the patient in the mild category.

Getting back to the FLORALI trial mentioned above and cited in the bibliography below, patients who had a P/F of < 200 were associated with having a lower mortality, more ventilator-free days, and lower risk for intubation. Most of these patients had pneumonia. There’s a downside to waiting too long to pull the trigger and intubate your patients which is why the ROX index was designed to help us determine whether the patient is safe or should be intubated.

Since these data were published, HFNC has gained a significant amount of traction. So much so that the most recent clinical practice guideline published in December of 2020 in the Intensive Care Medicine journal gave a strong recommendation for the use of high-flow nasal cannula in hypoxemic respiratory failure. Adding further praise to the system came just a few days ago in the 2021 update of the Surviving Sepsis Campaign Guidelines where recommendation 47 states “For adults with sepsis‐induced hypoxemic respiratory failure, we suggest the use of high flow nasal oxygen over non‐invasive ventilation”.

The problem remains that we are flying blind, though. When someone is placed on mechanical ventilation, or even placed on NIV, there’s a pretty interface that provides us data of how the patient is breathing. We can see their respiratory rate, tidal volumes, and tinker with other details to help us see exactly what the patient is doing and in what direction they’re heading. It is significantly more challenging to do this with a patient on high-flow. In fact, it’s impossible. But help has arrived.

How Much Flow Should We Start Our Patients On?

In a study by Li et al. published in November of 2021, they found that the optimal flow for most patients was between 30-40L/min. They made a pragmatic recommendation of starting patients on 40L/min and I could personally say I agree with this. It makes sense. Typically, I start my patients on 50L of flow if their work of breathing is concerning but they took additional steps beyond my “gut feeling” to reach this conclusion.

What is the ROX index?

The ROX index is defined as the ratio of oxygen saturation as measured by pulse oximetry (SpO2)/FiO2 to respiratory rate (RR). Please don’t use the 18 or 20 that is copy-pasted into everyones chart. To accurately obtain this you may have to get up and observe the patient breathing for a minute and count their respirations. Don’t call me weird, although I am, but I sometimes watch the patients breathe without being noticed in the window or inside the room to count their respiratory rate. Like all equations, the validity depends on the numbers you put into it. What’s the saying? You can put in chicken poop and expect to get out chicken soup?

What does ROX stand for?

Respiratory rate-OXygenation

Where did the ROX index come from?

This concept has actually been around in the literature since 2016 where Roca, et al. published a 4-year prospective observational 2-center cohort study of 157 patients. For the sake of maintaining your attention, they found that at 12 hours at ROX index of ≥ 4.88 meant that the patient was safe from needing to be intubated. It’s not 100%, but it’s quite good. The fine details of this paper can be accessed in the actual paper. Patients were started on a minimum of 30L of flow and 100% FiO2. They were trying to hit a goal O2 saturation > 92%.

Some other goodies that can be teased out of this paper include that the median duration of those who did well on the high-flow was 3 days and those who didn’t lasted about one day. This did find that patients intubated after 48 hours of being on high-flow did not have a worse prognosis.

The diagnostic accuracy of ROX was superior to SpO2/FiO2 or RR with an AUROC of 0.74, 0.83, and 0.87 at 12, 18, and 24h respectively. For those of you rusty at AUROC, that means acceptable, outstanding, and outstanding.

A nifty vector was published by Tatkov which plots the FiO2 in the x-axis and RR in the y-axis and shows us what certain values mean.

Further improving the ROX index

So you might ask yourself, is one study enough to prove the functionality of the ROX index? Roca, et al went at it again in 2019, published a validation study, and further delineated other parameters for the ROX index. Again, a prospective observational cohort study was performed over 2 years rather than over 4 years like their previous study. The authors found that ROX was better than looking at SpO2/FiO2, RR, PaCO2, flow, SpO2, FiO2, and lactate to predict the need for mechanical ventilation.

Predicting HFNC Success

  • ROX ≥ 4.88 at 2, 6, and 12 hours means you’re in the safe zone. The authors called it a “high chance of success”.

Predicting HFNC failure

  • ROX < 2.85 at 2 hours
  • ROX < 3.47 at 6 hours
  • ROX < 3.85 at 12 hours
  • Intubation is most likely the correct way to go for these patients

The Gray Zone

The authors admit that these findings are not absolute and that there is actually a gray zone between 4.88 and, say, 3.85 at the 12 hour mark. Clinical judgement reigns supreme here. This is where we tinker with the flow and consider proning our patient to improve their oxygenation and work of breathing. Mauri, et al. tinkered with the flow rates to illicit a change in the ROX index of the patients in their analysis of data collected during physiologic studies.

Is there a nice flow chart with the ROX index to help us manage these patients better?

Yes, there is. But for copyright purposes, I will not share the image here. I will, instead, have you CLICK HERE to download the paper. As a bonus, that paper provides an algorithm on using HFNC or NIV on preoxygenation for intubation.

Is the ROX index reliable in COVID?

To be honest, the data is a bit all over the place. Thankfully, Prakash et al. published a systematic review and meta-analysis last month (currently 10/6/21 at the time of this update) that analyzed this. When I attempted to compile the data myself, it was challenging to ascertain the validity of many of the papers as some were pre-published papers. A significant challenge posed by COVID to the ROX index is that many of us have cared for COVID patients who have been on high-flow for days and even weeks. The prospective observational studies by Roca did not follow patients for that long. In fact, many of us had never cared for patients on high-flow for this extensive of a time period before the pandemic. They found that the ROX index was excellent at predicting the need for intubation with “the AUC of ROX-index for probability in predicting HNFC failure was 0.81 (95% CI, 0.77–0.84)”.

Wrapping it up.

To finish things off, hope you have another tool to help you take care of your critically ill patient who has acute hypoxemic respiratory failure. Intubation is by no means benign and neither is the whole process of mechanical ventilation. We should safely try to avoid intubating the people who do not need to be intubated by using technologies such as NIV and HFNC. Check out more posts regarding NIV or HFNC HERE.

Disclosure: I am a consultant for a company who makes HFNC devices but I am in no way being compensated by them for this post. This is why I have linked all the articles and encourage you to read them for yourself and not trust me.

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Citations:
Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, Prat G, Boulain T, Morawiec E, Cottereau A, Devaquet J, Nseir S, Razazi K, Mira JP, Argaud L, Chakarian JC, Ricard JD, Wittebole X, Chevalier S, Herbland A, Fartoukh M, Constantin JM, Tonnelier JM, Pierrot M, Mathonnet A, Béduneau G, Delétage-Métreau C, Richard JC, Brochard L, Robert R; FLORALI Study Group; REVA Network. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015 Jun 4;372(23):2185-96. doi: 10.1056/NEJMoa1503326. Epub 2015 May 17. PMID: 25981908.
Link to Article
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ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669. PMID: 22797452.
Link to Article

Rochwerg B, Einav S, Chaudhuri D, Mancebo J, Mauri T, Helviz Y, Goligher EC, Jaber S, Ricard JD, Rittayamai N, Roca O, Antonelli M, Maggiore SM, Demoule A, Hodgson CL, Mercat A, Wilcox ME, Granton D, Wang D, Azoulay E, Ouanes-Besbes L, Cinnella G, Rauseo M, Carvalho C, Dessap-Mekontso A, Fraser J, Frat JP, Gomersall C, Grasselli G, Hernandez G, Jog S, Pesenti A, Riviello ED, Slutsky AS, Stapleton RD, Talmor D, Thille AW, Brochard L, Burns KEA. The role for high flow nasal cannula as a respiratory support strategy in adults: a clinical practice guideline. Intensive Care Med. 2020 Dec;46(12):2226-2237. doi: 10.1007/s00134-020-06312-y. Epub 2020 Nov 17. PMID: 33201321; PMCID: PMC7670292.
Link to Article
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Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Møller MH, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021 Oct 2:1–67. doi: 10.1007/s00134-021-06506-y. Epub ahead of print. PMID: 34599691; PMCID: PMC8486643.
Link to Article
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Li J, Scott JB, Fink JB, Reed B, Roca O, Dhand R. Optimizing high-flow nasal cannula flow settings in adult hypoxemic patients based on peak inspiratory flow during tidal breathing. Ann Intensive Care. 2021 Nov 27;11(1):164. doi: 10.1186/s13613-021-00949-8. PMID: 34837553.
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Roca O, Messika J, Caralt B, García-de-Acilu M, Sztrymf B, Ricard JD, Masclans JR. Predicting success of high-flow nasal cannula in pneumonia patients with hypoxemic respiratory failure: The utility of the ROX index. J Crit Care. 2016 Oct;35:200-5. doi: 10.1016/j.jcrc.2016.05.022. Epub 2016 May 31. PMID: 27481760.
Link to Article

Roca O, Caralt B, Messika J, Samper M, Sztrymf B, Hernández G, García-de-Acilu M, Frat JP, Masclans JR, Ricard JD. An Index Combining Respiratory Rate and Oxygenation to Predict Outcome of Nasal High-Flow Therapy. Am J Respir Crit Care Med. 2019 Jun 1;199(11):1368-1376. doi: 10.1164/rccm.201803-0589OC. PMID: 30576221.
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Mauri T, Carlesso E, Spinelli E, Turrini C, Corte FD, Russo R, Ricard JD, Pesenti A, Roca O, Grasselli G. Increasing support by nasal high flow acutely modifies the ROX index in hypoxemic patients: A physiologic study. J Crit Care. 2019 Oct;53:183-185. doi: 10.1016/j.jcrc.2019.06.020. Epub 2019 Jun 21. PMID: 31254849.
Link to Article

Ricard JD, Roca O, Lemiale V, Corley A, Braunlich J, Jones P, Kang BJ, Lellouche F, Nava S, Rittayamai N, Spoletini G, Jaber S, Hernandez G. Use of nasal high flow oxygen during acute respiratory failure. Intensive Care Med. 2020 Dec;46(12):2238-2247. doi: 10.1007/s00134-020-06228-7. Epub 2020 Sep 8. PMID: 32901374; PMCID: PMC7478440.
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Goh KJ, Chai HZ, Ong TH, Sewa DW, Phua GC, Tan QL. Early prediction of high flow nasal cannula therapy outcomes using a modified ROX index incorporating heart rate. J Intensive Care. 2020 Jun 22;8:41. doi: 10.1186/s40560-020-00458-z. PMID: 32587703; PMCID: PMC7310118.
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Karim HMR, Esquinas AM. Success or Failure of High-Flow Nasal Oxygen Therapy: The ROX Index Is Good, but a Modified ROX Index May Be Better. Am J Respir Crit Care Med. 2019 Jul 1;200(1):116-117. doi: 10.1164/rccm.201902-0419LE. PMID: 30896964; PMCID: PMC6603054.
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Tatkov S. ROX vector to complement ROX index during nasal high flow therapy of hypoxemic patients. J Crit Care. 2020 Aug;58:129. doi: 10.1016/j.jcrc.2019.08.012. Epub 2019 Oct 18. PMID: 31635954.
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Hill NS, Ruthazer R. Predicting Outcomes of High-Flow Nasal Cannula for Acute Respiratory Distress Syndrome. An Index that ROX. Am J Respir Crit Care Med. 2019 Jun 1;199(11):1300-1302. doi: 10.1164/rccm.201901-0079ED. PMID: 30694696; PMCID: PMC6543722.
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Spinelli E, Roca O, Mauri T. Dynamic assessment of the ROX index during nasal high flow for early identification of non-responders. J Crit Care. 2020 Aug;58:130-131. doi: 10.1016/j.jcrc.2019.08.013. Epub 2019 Oct 18. PMID: 31635957.
Link to Article

Tatkov S. Nasal High-Flow Therapy: Role of FiO2 in the ROX Index. Am J Respir Crit Care Med. 2019 Jul 1;200(1):115-116. doi: 10.1164/rccm.201902-0376LE. PMID: 30896967; PMCID: PMC6603067.
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Spinelli E, Mauri T. From monitoring to individualized settings during nasal high flow: ROX index to optimize flow rate? J Crit Care. 2020 Aug;58:133. doi: 10.1016/j.jcrc.2019.08.014. Epub 2019 Oct 18. PMID: 31635956.
Link to Article

ROX in COVID-19
Fink DL, Goldman NR, Cai J, El-Shakankery KH, Sismey GE, Gupta-Wright A, Tai CX. ROX Index to Guide Management of COVID-19 Pneumonia. Ann Am Thorac Soc. 2021 Feb 26. doi: 10.1513/AnnalsATS.202008-934RL. Epub ahead of print. PMID: 33636094.
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Gianstefani A, Farina G, Salvatore V, Alvau F, Artesiani ML, Bonfatti S, Campinoti F, Caramella I, Ciordinik M, Lorusso A, Nanni S, Nizza D, Nava S, Giostra F. Role of ROX index in the first assessment of COVID-19 patients in the emergency department. Intern Emerg Med. 2021 Mar 1:1–7. doi: 10.1007/s11739-021-02675-2. Epub ahead of print. PMID: 33646507; PMCID: PMC7917022.
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Chandel A, Patolia S, Brown AW, Collins AC, Sahjwani D, Khangoora V, Cameron PC, Desai M, Kasarabada A, Kilcullen JK, Nathan SD, King CS. High-Flow Nasal Cannula Therapy in COVID-19: Using the ROX Index to Predict Success. Respir Care. 2021 Jun;66(6):909-919. doi: 10.4187/respcare.08631. Epub 2020 Dec 16. PMID: 33328179.
Link to Article
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Fink DL, Goldman NR, Cai J, El-Shakankery KH, Sismey GE, Gupta-Wright A, Tai CX. ROX Index to Guide Management of COVID-19 Pneumonia. Ann Am Thorac Soc. 2021 Feb 26. doi: 10.1513/AnnalsATS.202008-934RL. Epub ahead of print. PMID: 33636094.
Link to Article
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Suliman LA, Abdelgawad TT, Farrag NS, Abdelwahab HW. Validity of ROX index in prediction of risk of intubation in patients with COVID-19 pneumonia. Adv Respir Med. 2021;89(1):1-7. doi: 10.5603/ARM.a2020.0176. Epub 2021 Jan 20. PMID: 33471350.
Link to Article

Hu M, Zhou Q, Zheng R, Li X, Ling J, Chen Y, Jia J, Xie C. Application of high-flow nasal cannula in hypoxemic patients with COVID-19: a retrospective cohort study. BMC Pulm Med. 2020 Dec 24;20(1):324. doi: 10.1186/s12890-020-01354-w. PMID: 33357219; PMCID: PMC7758183.
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Panadero C, Abad-Fernández A, Rio-Ramirez MT, Acosta Gutierrez CM, Calderon-Alcala M, Lopez-Riolobos C, Matesanz-Lopez C, Garcia-Prieto F, Diaz-Garcia JM, Raboso-Moreno B, Vasquez-Gambasica Z, Andres-Ruzafa P, Garcia-Satue JL, Calero-Pardo S, Sagastizabal B, Bautista D, Campos A, González M, Grande L, Jimenez Fernandez M, Santiago-Ruiz JL, Caravaca Perez P, Alcaraz AJ. High-flow nasal cannula for Acute Respiratory Distress Syndrome (ARDS) due to COVID-19. Multidiscip Respir Med. 2020 Sep 16;15(1):693. doi: 10.4081/mrm.2020.693. PMID: 32983456; PMCID: PMC7512942.
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Zaboli A, Ausserhofer D, Pfeifer N, Sibilio S, Tezza G, Ciccariello L, Turcato G. The ROX index can be a useful tool for the triage evaluation of COVID-19 patients with dyspnoea. J Adv Nurs. 2021 Aug;77(8):3361-3369. doi: 10.1111/jan.14848. Epub 2021 Apr 1. PMID: 33792953; PMCID: PMC8251286.
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Prower E, Grant D, Bisquera A, Breen CP, Camporota L, Gavrilovski M, Pontin M, Douiri A, Glover GW. The ROX index has greater predictive validity than NEWS2 for deterioration in Covid-19. EClinicalMedicine. 2021 May;35:100828. doi: 10.1016/j.eclinm.2021.100828. Epub 2021 Apr 25. PMID: 33937729; PMCID: PMC8068777.
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Prakash J, Bhattacharya PK, Yadav AK, Kumar A, Tudu LC, Prasad K. ROX index as a good predictor of high flow nasal cannula failure in COVID-19 patients with acute hypoxemic respiratory failure: A systematic review and meta-analysis. J Crit Care. 2021 Sep 7;66:102-108. doi: 10.1016/j.jcrc.2021.08.012. Epub ahead of print. PMID: 34507079; PMCID: PMC8424061.
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I initially covered this on IG back on 8/24/2019.

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We see this every day in the ICU. Patient with pneumonia sucking wind. Should we intubate them and place them on mechanical ventilation, or should we give them a shot and see if they fly on high flow nasal cannula? We all think we’re big shots and can call it just by seeing it. You know the type, I am the same way. I can tell a patient needs to be intubated as soon as I lay eyes on them. Big shot. Yep. This is true, or is it? We also know that delaying intubation is far worse for patient populations that just intubating them early on. What if there was a tool to help us with this decision? Wouldn’t that be great? How about a tool so simple that all you need is a pulse oximeter, a HFNC setup telling you the FiO2 being delivered to the patient, and a set of eyeballs to count a patients respiratory rate (because we all know that whatever device measures RR on the monitor is inaccurate and showing “apneic” more often than it should). Well, we’re all in luck! These authors came up with the ROX index which is (SpO2/FiO2)/RR. SpO2 is the number you get from the pulse oximeter and it’s on the monitor. It should be entered as a whole number. FiO2 is entered as a decimal. For example room air is 21% so 0.21. RR is, well, respiratory rate. Based on the data provided in this article, it should be a statistically significant prediction of whether your patient is going to be intubated or not. Hopefully the delay of mechanical ventilation we all are dreading should be avoided. This should also help you make the decision to just intubate the person before you leave your partner who is working the opposite shift with an airway dump, one of the worst kinds of dumps. A 🎩 tip to the authors! You can obtain the link to this article on my website: https://eddyjoemd.com or the click the link in the bio. Shout out to @sedka and @caseyhmorris for… You know.

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