“Silent hypoxaemia” and COVID-19 intubation

COVID-19: Keeping the baby in the bath (Part 2)

Life is short, and art long, opportunity fleeting, experimentations perilous, and judgment difficult

Hippocrates

Please Sir, can I have some ketamine and a blue cigar

…what the combative, agitated, hypoxic patient really means (according to Dr Cliff Reid (@cliffreid) ;“blue cigar” is a colloquial term for endotracheal tube)

One of the “paradigm shifts” in circulation is to not intubate COVID-19 patients solely for hypoxaemia and to not intubate them early. We wonder, were clinicians really intubating patients solely for hypoxaemia before COVID-19? Hypoxaemia alone should rarely be an indication for intubation. Indeed, Martin Tobin has written an excellent article on the physiological principles to consider in the respiratory management of COVID-19, including the decision to intubate (Tobin, 2020). What has been perplexing about the COVID-19 pandemic is the apparently frequent presentation of patients with “silent hypoxaemia” characterised by low arterial oxygen content with few or no other respiratory symptoms (Levitan, 2020; Tobin, 2020; Xie et al, 2020). This is typically accompanied by an increased alveolar-arterial gradient in oxygen tension, and thus represents some combination of ventilation-perfusion mismatch or intra-pulmonary shunting (diffusion limitation being very unlikely except at sub-atmospheric fractions of inspired oxygen (FiO2)) (Tobin, 2020). The phenomenon of “silent hypoxaemia”, though, is not unique to COVID-19 despite being poorly documented in the literature. It occurs when ambient FiO2 is decreased under experimental conditions (Tobin, 2020) and we sometimes observe it in patients with cardiac shunt from congenital heart disease, and with intra-pulmonary shunt from primary lung diseases like atelectasis or even severe liver disease (hepato-pulmonary syndrome). Dyspnoea, the perception of breathlessness, primarily results from airflow obstruction, increased ventilatory demand, respiratory muscle dysfunction, or anxiety – not hypoxaemia (Baldwin & Cox, 2016).

Our understanding is that the call to intubate COVID-19 patients early arose from the early experience of COVID-19 management in China (Zuo et al, 2019; Meng et al, 2020). The Chinese Society of Anesthesiology Task Force on Airway Management’s initial recommendation was to proceed with endotracheal intubation “for patients showing no improvement in respiratory distress, tachypnea (respiratory rate greater than 30 per minute), and poor oxygenation (Pao2 to Fio2 ratio less than 150 mmHg) after 2-h high-flow oxygen therapy or noninvasive ventilation” (Zuo et al, 2019; Meng et al, 2020). Meng et al (2020) note that this was liberalised (allowing even earlier intubation) after concerns that the high mortality rate of intubated patients in Wuhan was related to delayed intubation, especially as patients with “silent hypoxaemia” may not look unwell. Meng et al (2020) also note that “in Wuhan, most of the patients were on either high-flow oxygen therapy or bilevel positive airway pressure ventilation when the intubation was called”. Concerns about the potential for infectious spread from high flow oxygen delivery and non-invasive ventilation (NIV), which have been considered “Aerosol-Generating Procedures” (AGPs), further reinforced calls to “intubate early” (Brewster et al, 2020).

The “early intubation” strategy makes sense for two reasons: (1) patients with COVID-19 can deteriorate rapidly (e.g. from minimal oxygen requirements to life-threatening hypoxaemia and respiratory distress in hours) and (2) it takes time to deal with the logistical complexity of preparing for, and performing, intubation of patients with COVID-19. This logistical complexity arises from needing to transfer the patient to an appropriate location for intubation while maintaining infection control measures and the need for for the intubation team to assemble, don appropriate personal protective equipment (PPE), and prepare for this potentially life-or-death intervention. Most importantly, disease progression may limit the patient’s ability to be effectively pre-oxygenated and various measures to combat this (such as the use of NIV or continuous positive airway pressure (CPAP)) have pros and cons. NIV/CPAP may increase the risk of virus transmission as they are classed as AGPs or may be poorly tolerated by deteriorating patients with an altered mental state. However, waiting to intubate a hypoxic patient until they require close to an FiO2 of 1.0 makes induction and intubation high risk and even potentially lethal. Both pre-intubation hypoxaemia and absence of pre-oxygenation are associated with a much higher risk of cardiac arrest (De Jong et al, 2018), as is hypoxaemia during emergency airway management (Mort, 2004).

But how early is “too early” intubation? Meng et al (2020) emphasise that “timely, but not premature, intubation” is vital, but also acknowledge that we lack an evidence base for how to determine this. The right timing for intubation depends on the patient: their anticipated trajectory (including their rate of deterioration and severity of illness) and other patient factors such as coexistent conditions. Some factors are often more important as indications for intubation than hypoxaemia, such as excessive work of breathing or worsening fatigue (in general, if a patient asks to be intubated for these reasons, we should listen!). Altered mental state and agitation, especially when they prevent compliance with existing oxygen therapy, are also important reasons why early intubation is sometimes required. Coexistent conditions may carry an increased risk of complications if intubation is delayed, such as an anatomically difficult airway requiring awake intubation with spontaneous breathing. Sometimes intubation is required to facilitate investigations or therapies that the patient won’t otherwise tolerate because the patient cannot be positioned or transferred safely. In practice, patients who are intubated for hypoxaemia in the context of a pneumonia or acute respiratory distress syndrome (ARDS) usually have some combination of increased work of breathing, fatigue, altered mental state, or a worrying trajectory.  

Some hypoxaemic patients exhibit intra-pulmonary shunting, which is signified by a failure to respond to increasing FiO2 (Tobin, 2020). This may occur in patients with COVID-19, as suggested by case reports of dual-phase computed tomography findings (Lang et al, 2020). In this circumstance, the clinician needs to decide if the patient is adequately oxygenated or not. Sometimes, tolerating lower arterial oxygen saturations is appropriate such as when the patient is not distressed and has normal mentation. This is a common approach in patients with chronic lung disease who never achieve “normal” arterial oxygen saturations even when in their best possible state of health. Indeed, Tobin argues that organ dysfunction is unlikely unless oxygen delivery falls to as low as 25% of normal (Tobin, 2020), which may not occur until SpO2 falls below 80% depending on the patient’s cardiac output and oxygen extraction. However, the implications of profound hypoxaemia on the development of pulmonary hypertension and right heart dysfunction over a period of days to weeks are hard to judge, but are cause for concern in ARDS (Zochios et al, 2017). As bedside clinicians, if we decide that there is a need to improve oxygenation in a patient with intra-pulmonary shunt then intubation and mechanical ventilation may be helpful. Intubation and positive pressure ventilation can help re-recruit lung, can allow bronchoscopy to performed safely if sputum plugging is suspected as a cause of atelectasis, and can facilitate other (often not well proven) therapies for refractory hypoxaemia such as inhaled nitric oxide or veno-venous ECMO. 

COVID-19 is tricky for clinicians because few of us have much experience with the trajectory of these patients. Unfortunately, the published literature so far only gives an incomplete picture and is coloured by circumstances such as variation in local practice and how overwhelmed the health system is. Nevertheless, one part of the picture that is clearly emerging is that a subset of patients with COVID-19 develop prolonged, severe lung disease. It is also clear that some patients receive treatment with high flow nasal cannulae (HFNC) or NIV/CPAP and recover without the need for intubation.

Importantly, claims that either strategy – early intubation or avoidance of intubation – are more effective than the other are premature. We need more data. Basing claims that intubation is harmful solely on the high mortality of mechanically ventilated patients is unwise, because these patients are usually the sickest cohort and (no surprise here) sick patients tend to do worse than those that are not so sick. On the other hand, an aggressive early intubation strategy may result in less sick patients receiving mechanical ventilation and better outcomes may occur simply because of patient selection. One could argue that early intubation is necessary given that if a patient with COVID-19 is sick enough then prolonged intubation and mechanical ventilation are inevitable anyway. On the other hand, one could argue that patients with COVID-19 are at risk of ventilator-induced lung injury (VILI) and that intubation should be avoided if at all possible as mechanical ventilation itself may contribute to their prolonged need for mechanical ventilation. These opposite interpretations can really only be resolved by a randomised control trial as confirmation bias leads us to believe our own interpretation is correct. The answer may lie somewhere in the middle. Ultimately, we are reminded of the landmark FEAST trial (Maitland et al, 2011), when considering such dilemmas. In the FEAST trial, clinicians were convinced that the septic children randomised to aggressive fluid resuscitation improved within hours of treatment, in comparison with the fluid restricted control group. Unfortunately, the data told a different tale, these patients may have looked better to clinicians but they still died at greater rates.

Some of us are lucky in that where we work our practice is to share the burden for difficult decisions such as when to intubate COVID-19 patients. Ideally, at least two intensivists are involved in making the decision to intubate and then in performing the procedure. Where we have the resources to do this, it is largely because of the good work of the public in following the public health strategies that prevents our health system being overloaded and gives us the capacity to perform at the highest level. Not everyone has this luxury.

As always, we should only intubate when necessary, but we must not leave it too late. This is why critical care needs highly trained, experienced clinicians involved in bedside care. It is also why we need more research.

Next, we will discuss Is COVID-19 ARDS? What about lung compliance?

Further reading

Please refer to the Safe Airway Society Consensus Statement on Airway Management and Tracheal Intubation for current Australia and New Zealand recommendations for the intubation of patients with COVID-19.

COVID-19: Keeping the baby in the bath series

  1. COVID-19: Keeping the baby in the bath (Introduction)
  2. “Silent hypoxaemia” and COVID-19 intubation
  3. Is COVID-19 ARDS? What about lung compliance?
  4. COVID-19: “To PEEP, or not to PEEP”?
  5. MacGyverism and “hacking COVID-19”
  6. Novel drug therapies and COVID-19 clinical trials
  7. Overcoming uncertainty in the Age of COVID-19

References

Chris is an Intensivist and ECMO specialist at The Alfred ICU, where he is Deputy Director (Education). He is a Clinical Adjunct Associate Professor at Monash University, the Lead for the  Clinician Educator Incubator programme, and a CICM First Part Examiner.

He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives. He was one of the founders of the FOAM movement (Free Open-Access Medical education) has been recognised for his contributions to education with awards from ANZICS, ANZAHPE, and ACEM.

His one great achievement is being the father of three amazing children.

On Bluesky, he is @precordialthump.bsky.social and on the site that Elon has screwed up, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

Jack Iwashyna LITFL

Critical care physician and health services researcher bringing the tools of social science and outcomes research to improve the care of patients with critical illnesses. I practice as an intensivist at the University of Michigan’s and the Ann Arbor VA's Critical Care Medicine units, where we work to bring the latest science and the best of clinical practice to patients  | iwashyna-lab  | @iwashyna |

Intensivist in Wellington, New Zealand. Started out in ED, but now feels physically ill whenever he steps foot on the front line. Clinical researcher, kite-surfer  | @DogICUma |

3 Comments

  1. Thoughtful review, guys. Thanks. We’ve managed hundreds of critically ill COVID patients at my institution and still have very little sense of when to intubate. We’re convinced that the initial paradigm, which was to intubate everyone who fails low-flow oxygen, was incorrect; that’s clear to us because many patients who would have been intubated using that paradigm have been carried through their illness with HFNC/NIV and discharged. But the very ill patients continue to be a tremendous challenge. We cared for a young healthy man with severe COVID for 12 (twelve) days on maximum HFNC support, most of which he spent proned, mostly saturating in the 80s. We waited and waited for him to turn the corner, constant chest physio, rotation, he of course got all of the likely useless medical therapies. He didn’t worsen, but didn’t improve. For 12 days. His saturations fell a bit, and we pulled the trigger and intubated, but I think this was more because at some point you have to call non-invasive oxygenation a failure and try something else. We are hopeful that science will provide answers, until then, all we can do is think carefully about how prior principles apply to this disease, which is what the three of you have done.

  2. Hello doctor
    I have just discovered this great and useful website .
    I have been reading the articles talking about covid management , cause I have a patient now in the ward whose saturation has fallen up to 75 without oxygen but with HNFC it rises to 90 , I am worried a bet cause I have came across some cases that suddenly deteriorated in a short time and intubated under a suboptimal conditions cause the time required to transfer and prepare PPE , as u said until now there is no Sharp line to determine a lot of descisions regarding covid patients management plan from the very start point which is intubation or not and the delimma continue to ventilator settings and then extubation . It seems all this steps currently is left to the judgment of the Doctor in charge for the care of the patient. Of course it puts a tremendous pressure upon us sailing through this uncharted area of medicine, and its getting worse when I found that what works perfectly for one patient isn’t guaranteed to work for another who may have apparently similar conditions .
    Again thank you for your great articles which was like a light in a dark tunnel .

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