In its original notion, yes. In its widespread popular distortion, no. Harriet Hall explains.
A recent article in the American Journal of Respiratory and Critical Care Medicine about hypoxemia and covid-19 concludes with this:
In conclusion, COVID-19 has engendered many surprises, but features that baffle physicians are less strange when contemplated through the lens of long-established principles of respiratory physiology.
Read this paper when you're well rested and well fed and you will find it a great exercise in the physiology of hypoxemia. It's much more about that, and the misconceptions derived from our current obsession with pulse oximetry, than it is about covid.
First let's list what I think are some
of the main ideas in the paper.
There was widespread over-reliance and misunderstanding of pulse oximetry.
There is not a simple correlation between dyspnea and hypoxemia.
The threat of hypoxemia is poorly
understood by clinicians.
The seeming paradox of asymptomatic hypoxemia is not unique to covid-19 but is explained by well established principles of respiratory physiology.
Dyspnea is mediated by hypercapnia, afferent signals produced by inflammatory stimuli, mechanical properties of the lungs and, least of all, hypoxemia. As will be brought out in the physiology below, multiple conditions seem to have a permissive effect on the dyspnea produced by hypoxemia.
Hypercapnia is a very important cause of dyspnea. It has a permissive effect on hypoxemia as a cause of dyspnea. Hypercapnia causes a drop in pH in the blood perfusing the CNS respiratory control center. An acute increase in pCO2 of 10 mm Hg quickly causes profound dyspnea. The situation is different for hypoxemia. As pO2 falls there appears to be a threshold of 60 mm Hg below which stimulation of ventilation and dyspnea occur. (The so called hypoxic drive). In terms of mechanism, hypoxemia stimulates the carotid bodies which send messages to the respiratory control center. From there impulses are relayed to the cortex cruising the sensation of dyspnea. The correlation between dyspnea and the ventilatory response to hypoxemia is poor. This response to hypoxemia is blunted if the pCO2 is 39 or below. These responses are blunted in individuals with diabetes and individuals over 65 which constitute a high portion patients presenting clinically with covid.
Could covid have effects on the brain that blunt the dyspnea response? A similar question has been asked regarding the symptom of anosmia. ACE2, the receptor for covid-19, is expressed both in the carotid bodies and the nasal mucosa so mucosal effects rather than brain involvement could account for these manifestations. This is a question yet to be answered.
The authors imply that our usual concerns about low pulse oximeter readings are misdirected. Another quote from the article:
Physicians are fearful of hypoxemia, and many view saturations between 80% and 85% as life threatening. We served as volunteers in an experiment probing the effect of hypoxemia on breathing patterns; our pulse oximeter displayed an SpO2 of 80% for over an hour, and we were not able to sense differences between an SpO2 of 80% and an SpO2 of 90% (24). In investigations on control of breathing and oximeter accuracy, subjects experience an SpO2 of 75% (12), or briefly 45% (25), without serious harm. Tourists on drives to the top of Mount Evans near Denver experience oxygen saturations of 65% for prolonged periods; many are comfortable, whereas some sense dyspnea (25).
The finding of a low pulse oximetry reading does not enable a complete physiological assessment. Instead it should lead the clinician to ask: what's going on? Pitfalls in the interpretation of pulse oximetry were cited in the article. Correlation with blood gas readings deteriorates at lower levels of saturation. Accuracy of pulse oximetry is less in critically ill patients than in normal volunteers. The oxyhemoglobin dissociation curve should factor into any interpretation of pulse oximetry readings but this is seldom the topic of bedside discussions. Fever and low pH, common in critically ill patients, cause a shift of the curve to the right. This leads to lower saturation readings at a given pO2. It is an adaptive mechanism by which hemoglobin unloads oxygen more readily. Herein lies another reason why oxygen saturation correlates poorly with dyspnea: the carotid bodies respond to changes in pO2 but not to oxygen saturation.
Further complicating the discussion is
the definition of terms. Though not addressed in the article,
there is the common confusion between hypoxemia and hypoxia. Low pO2
or saturation readings indicate hypoxemia. However, to diagnose
hypoxia, which is a reduction in oxygen delivery to the tissues,
one must apply the oxygen delivery equation. This equation takes into
account hemoglobin bound oxygen, oxygen dissolved in plasma,
hemoglobin concentration and cardiac output. As to the
definition of hypoxemia the authors point out that it has been an
evolving concept. The definition of hypoxemia is not essential, but
rather a matter of usage and convention. For example, in the 1990s it
was often defined as the raw number without regard to the FiO2.
Recently hypoxemia is more often referred to in terms of the oxygen
requirement. Both are important: the former for estimating oxygen
delivery and the latter for making an assessment of ventilation and
After reading this article I have the following concluding thoughts:
We over rely on pulse oximetry. Blood gases are underutilized.
Misunderstanding of pulse oximetry readings is widespread.
The hypoxemia of covid-19 is not as unique as popularly believed.
From a recently published study:
The aim of this study was to investigate whether oral anticoagulants can provide efficacy and safety profiles better than no anticoagulant in patients with stages 4 or 5 chronic kidney disease and atrial fibrillation.
From 2001 to 2017, a cohort of patients with stages 4 or 5 chronic kidney disease and atrial fibrillation based on electronic medical records were selected from Chang Gung Memorial Hospital system in Taiwan. Patients were divided into nonvitamin K antagonist oral anticoagulants (NOACs), warfarin, and nonanticoagulated groups. They were followed from the index date to the occurrence of the study outcomes or for 5 years, whichever occurred first. The outcomes were admissions due to ischemic stroke or systemic embolism or major bleedings. Survival analyses were conducted to estimate the incidence rates of outcomes.
A total of 3771 patients with atrial fibrillation and estimated glomerular filtration rate less than 30 mL/min/1.73m 2 were enrolled, of whom 2971 were in the nonanticoagulated group, 280 in the NOAC group, and 520 in the warfarin group. About 25% of all subjects (940 patients) were on dialysis. The mean follow-up was 3.2 years. After adjusting for sex, age, comorbidities, and comedication, the warfarin group had a significantly higher risk of ischemic stroke or systemic embolism (adjusted hazard ratio [aHR] 3.1, 95% confidence interval [CI] 2.1-4.6) than the nonanticoagulated group. The NOAC group had a similar risk of ischemic stroke or systemic embolism (aHR 1.1; 95% CI 0.3-3.4) to that of the nonanticoagulated group. Both the warfarin and the NOAC groups had a significantly higher major bleeding risk than the noncoagulated group (aHR 2.8 [95% CI 2.0-3.8] for warfarin; aHR 3.1 [95% CI 1.9-5.2] for NOAC).
The use of NOACs or warfarin is not more effective than using no anticoagulants at all in reducing the risk of ischemic stroke or systemic embolism. Both NOACs and warfarin are associated with increased risk of major bleeding. Our results do not support the use of anticoagulants in patients with atrial fibrillation and stages 4-5 chronic kidney disease.
From an accompanying editorial:
The present study makes a significant contribution to the controversial field of oral anticoagulation in chronic kidney disease patients and advises against an unselected anticoagulant treatment of elderly chronic kidney disease stages 4-5 patients with atrial fibrillation to prevent thromboembolic events. Physicians are again left with an individualized approach to these patients weighing carefully in the inherent benefits and risks of oral anticoagulation.
From a recently published review:
Elevated blood pressure is common in patients who are hospitalized. There are no guidelines and few recommendations to help inpatient providers manage patients with elevated blood pressure. There are no normal reported values for blood pressure in the inpatient and recording circumstances often widely vary. Many factors may influence blood pressure such as pain, anxiety, malaise, nicotine withdrawal, or withholding home medications. This review of available literature suggests potential harm and little to no potential benefit in treating asymptomatic patients with elevated blood pressure. This review also found no evidence that asymptomatic elevated blood pressure progresses to lead to end-organ damage. However, there are clear instances of hypertensive emergency where treatment is indicated. Conscientious adjustment of an anti-hypertensive regimen should be undertaken during episode of elevated blood pressure associated with end-organ damage.
Look at the epicardial fat. From a recent paper in the green journal:
Psoriasis is a systemic inflammatory disorder that can target adipose tissue; the resulting adipocyte dysfunction is manifest clinically as the metabolic syndrome, which is present in ≈20%-40% of patients. Epicardial adipose tissue inflammation is likely responsible for a distinctive pattern of cardiovascular disorders consisting of 1) accelerated coronary atherosclerosis leading to myocardial infarction, 2) atrial myopathy leading to atrial fibrillation and thromboembolic stroke, and 3) ventricular myopathy leading to heart failure with a preserved ejection fraction. If cardiovascular inflammation drives these risks, then treatments that focus on blood pressure, lipids, and glucose will not ameliorate the burden of cardiovascular disease in patients with psoriasis, especially in those who are young and have severe inflammation. Instead, interventions that alleviate systemic and adipose tissue inflammation may not only minimize the risks of atrial fibrillation and heart failure but may also have favorable effects on the severity of psoriasis. Viewed from this perspective, the known link between psoriasis and cardiovascular disease is not related to the influence of the individual diagnostic components of the metabolic syndrome.
McAdam and the Damiani/Levine diagnostic criteria. 12 RPC is diagnosed if 3 of 6 clinical findings are present: 1) auricular chondritis; 2) nonerosive inflammatory arthritis; 3) nasal chondritis; 4) ocular inflammation, including conjunctivitis, keratitis, scleritis, episcleritis, or uveitis; 5) laryngotracheal chondritis; and 6) cochlear or vestibular damage presenting as sensorineural hearing loss, tinnitus, or vertigo. A diagnosis of RPC also can be made if a patient meets one of 6 criteria AND has compatible cartilage biopsy histology or meets 2 of 6 criteria AND improves clinically after receiving corticosteroids or dapsone. 2
RPC is a rare inflammatory disease with a peak age of onset between ages 40 and 50 years and an estimated incidence of 3.5 cases per million people per year. 3 Cases have been diagnosed across all racial groups. Men and women are equally affected. 3 RPC is defined by abrupt-onset inflammation of the cartilaginous ear, nose, joints, laryngotracheobronchial tree, or heart valves. The disease usually follows an indolent, relapsing-remitting course but may also present fulminantly and threaten vision and organ function. 4 …
Up to one-third of cases of RPC present prior to, during, or after another disease. 6 The most commonly associated syndrome is systemic vasculitis, followed by rheumatoid arthritis and systemic lupus erythematosus.
The pathogenesis of acropachy is unknown, except for the anatomic location, in that it is probably similar to that of pretibial myxedema. It appears that TRAb molecules bind to the TSH receptors of fibroblasts present in the periosteum region and trigger an inflammatory response, producing cell proliferation and glycosaminoglycan deposition (7,8). The musculoskeletal manifestation is almost never seen without the remaining components of the triad of orbitopathy, dermopathy, and acropachy (9,10). Some studies suggest smoking is a predisposing factor for acropachy in GD patients (9).
In most cases, acropachy is asymptomatic, but the main clinical manifestations are digital clubbing, skin tightness with or without digital clubbing and usually with small-joint pain (in severe cases), soft tissue edema, and reactional periosteum, and skin alterations in fingers and nails may also be present (7). The disorder mostly affects the metacarpus phalangeal and proximal interphalangeal regions in the upper and lower limbs, especially the ankles and metatarsal phalangeal joints (11).
A history of OSAS/CSAS, myocardial infarction and BMI greater than 30 are risk factors for ICU admission.
Non-survivors suffer more often from diabetes mellitus and (pre-existent) renal failure.
ICU patients develop renal failure and bacterial/fungal co-infections more often.
While most influenza patients have a self-limited respiratory illness, 5–10% of hospitalized patients develop severe disease requiring ICU admission. The aim of this study was to identify influenza-specific factors associated with ICU admission and mortality. Furthermore, influenza-specific pulmonary bacterial, fungal and viral co-infections were investigated.
199 influenza patients, admitted to two academic hospitals in the Netherlands between 01-10-2015 and 01-04-2016 were investigated of which 45/199 were admitted to the ICU.
A history of Obstructive/Central Sleep Apnea Syndrome, myocardial infarction, dyspnea, influenza type A, BMI greater than 30, the development of renal failure and bacterial and fungal co-infections, were observed more frequently in patients who were admitted to the ICU, compared with patients at the normal ward. Co-infections were evident in 55.6% of ICU-admitted patients, compared with 20.1% of patients at the normal ward, mainly caused by Staphylococcus aureus, Streptococcus pneumoniae, and Aspergillus fumigatus. Non-survivors suffered from diabetes mellitus and (pre-existent) renal failure more often.
The current study indicates that a history of OSAS/CSAS, myocardial infarction and BMI greater than 30 might be related to ICU admission in influenza patients. Second, ICU patients develop more pulmonary co-infections. Last, (pre-existent) renal failure and diabetes mellitus are more often observed in non-survivors.
The efficacy, safety, and clinical importance of extended-duration thromboprophylaxis (EDT) for prevention of venous thromboembolism (VTE) in medical patients remain unclear. We compared the efficacy and safety of EDT in patients hospitalized for medical illness.
METHODS AND FINDINGS:
Electronic databases of PubMed/MEDLINE, EMBASE, Cochrane Central, and ClinicalTrials.gov were searched from inception to March 21, 2019. We included randomized clinical trials (RCTs) reporting use of EDT for prevention of VTE. We performed trial sequential and cumulative meta-analyses to evaluate EDT effects on the primary efficacy endpoint of symptomatic VTE or VTE-related death, International Society on Thrombosis and Haemostasis (ISTH) major or fatal bleeding, and all-cause mortality. The pooled number needed to treat (NNT) to prevent one symptomatic or fatal VTE event and the number needed to harm (NNH) to cause one major or fatal bleeding event were calculated. Across 5 RCTs with 40,247 patients (mean age: 67-77 years, proportion of women: 48%-54%, most common reason for admission: heart failure), the duration of EDT ranged from 24-47 days. EDT reduced symptomatic VTE or VTE-related death compared with standard of care (0.8% versus 1.2%; risk ratio [RR]: 0.61, 95% confidence interval [CI]: 0.44-0.83; p = 0.002). EDT increased risk of ISTH major or fatal bleeding (0.6% versus 0.3%; RR: 2.04, 95% CI: 1.42-2.91; p less than 0.001) in both meta-analyses and trial sequential analyses. Pooled NNT to prevent one symptomatic VTE or VTE-related death was 250 (95% CI: 167-500), whereas NNH to cause one major or fatal bleeding event was 333 (95% CI: 200-1,000). Limitations of the study include variation in enrollment criteria, individual therapies, duration of EDT, and VTE detection protocols across included trials.
In this systematic review and meta-analysis of 5 randomized trials, we observed that use of a post-hospital discharge EDT strategy for a 4-to-6-week period reduced symptomatic or fatal VTE events at the expense of increased risk of major or fatal bleeding. Further investigations are still required to define the risks and benefits in discrete medically ill cohorts, evaluate cost-effectiveness, and develop pathways for targeted implementation of this postdischarge EDT strategy.