Skip to main content
Annals of Intensive Care
Download PDF

Basing intubation of acutely hypoxemic patients on physiologic principles

Annals of Intensive Care volume 14, Article number: 86 (2024) Cite this article

Abstract

The decision to intubate a patient with acute hypoxemic respiratory failure who is not in apparent respiratory distress is one of the most difficult clinical decisions faced by intensivists. A conservative approach exposes patients to the dangers of hypoxemia, while a liberal approach exposes them to the dangers of inserting an endotracheal tube and invasive mechanical ventilation. To assist intensivists in this decision, investigators have used various thresholds of peripheral or arterial oxygen saturation, partial pressure of oxygen, partial pressure of oxygen-to-fraction of inspired oxygen ratio, and arterial oxygen content. In this review we will discuss how each of these oxygenation indices provides inaccurate information about the volume of oxygen transported in the arterial blood (convective oxygen delivery) or the pressure gradient driving oxygen from the capillaries to the cells (diffusive oxygen delivery). The decision to intubate hypoxemic patients is further complicated by our nescience of the critical point below which global and cerebral oxygen supply become delivery-dependent in the individual patient. Accordingly, intubation requires a nuanced understanding of oxygenation indexes. In this review, we will also discuss our approach to intubation based on clinical observations and physiologic principles. Specifically, we consider intubation when hypoxemic patients, who are neither in apparent respiratory distress nor in shock, become cognitively impaired suggesting emergent cerebral hypoxia. When deciding to intubate, we also consider additional factors including estimates of cardiac function, peripheral perfusion, arterial oxygen content and its determinants. It is not possible, however, to pick an oxygenation breakpoint below which the benefits of mechanical ventilation decidedly outweigh its hazards. It is futile to imagine that decision making about instituting mechanical ventilation in an individual patient can be condensed into an algorithm with absolute numbers at each nodal point. In sum, an algorithm cannot replace the presence of a physician well skilled in the art of clinical evaluation who has a deep understanding of pathophysiologic principles.

Case report-vignette

A 73-years old man with history of hypertension is admitted to the hospital with cough, chills, and dyspnea on exertion. On arrival his peripheral oxygen saturation (SpO2) on room air ranges from 80 to 83%. Following administration of 4 L·min− 1oxygen by nasal cannula, SpO2increases to 94%. He is afebrile (37.5 °C), normotensive. Heart rate is 93 bpm and respiratory rate is 20 bpm. The patient is in no apparent respiratory distress. He tests positive for SARS-CoV2. Chest radiograph demonstrates bilateral mid and lower lung opacities (Fig. 1). Two days later he is transitioned to high-flow oxygen through nasal cannula. At times, SpO2is in the low 80s% and occasionally in the 70s%. Computed tomography of the chest demonstrates multiple bilateral ground glass opacities and consolidations(Fig. 2).Although tachypneic, he continues to report no respiratory distress. His mentation is normal. Should he be intubated?

Fig. 1
figure 1

Portable chest radiograph of index case obtained on hospital admission. Bilateral mid and lower lung interstitial and airspace opacities. Right hemidiaphragm elevation with lateral lobulated contour stable when compared to previous chest imaging (not shown)

Full size image
Fig. 2
figure 2

Computed tomography of the chest of index case obtained on day-2 of hospital admission: Multiple bilateral ground glass opacities and consolidations. The exam was negative for pulmonary embolus (not shown)

Full size image

Background

Notwithstanding that intensivists strive to support the function of all vital organs, at a fundamental level their primary goal is to ensure that a patient’s oxygenation is sufficient to avoid cerebral hypoxia. To this end, investigators initiate invasive ventilation in patients who remain hypoxemic despite implementation of noninvasive oxygenation strategies based on different oxygenation thresholds [1]. Unfortunately, these thresholds have serious limitations that can result in either overly liberal intubation (unnecessarily exposing patients to the risks of inserting an endotracheal tube [2] and of invasive ventilation [3, 4] ) or overly conservative intubation (exposing patients to the dangers of hypoxia [5,6,7]). The situation becomes even more perplexing when the decision to intubate is based not on presumed tissue hypoxia (as indirectly suggested by oxygenation indexes), but rather on the unclear association between poor oxygenation indexes and worse clinical outcomes [1, 8].

In this review we will first discuss intubation criteria based on oxygenation thresholds and their limitations. Then, we will discuss our approach to intubation based on clinical observations and physiologic principles. Our focus is on acutely hypoxemic patients, with or without COVID-19, who are variably tachypneic but who are neither in apparent respiratory distress nor in shock.

Intubation criteria based on SpO2 thresholds

Some investigators recommend intubation when SpO2 readings are less than 92% [9,10,11], 90% [12,13,14,15], 88% [16], or 85% [17, 18]. Technical limitations of the devices used to record SpO2 confound its interpretation. Moreover, the inherent inaccuracy of SpO2 in estimating both the volume of oxygen transported in the arterial blood (convective oxygen delivery), and the pressure gradient driving oxygen from the capillaries to the cells (diffusive oxygen delivery)(Fig. 3) [19, 20] cast serious doubts on the clinical utility of these thresholds.

Fig. 3
figure 3

Schematic representation of the movement of oxygen from inhaled gas to tissue mitochondria. This movement requires both diffusion and convection of oxygen. Diffusion of oxygen, or diffusive oxygen delivery, is a passive phenomenon whereby the gradient in oxygen pressure (∆PO2) drives oxygen from the alveolus to the plasma (left blue arrow) and from the plasma to the interstitial fluid and tissue mitochondria (right blue arrow). Convective (perfusive) oxygen delivery (DO2) is an energy-requiring process that relies on the work performed by the respiratory and cardiac pumps to move the oxygen carried in the blood from the lungs to the peripheral tissues. Convective oxygen delivery is a function of cardiac output (Qc) and arterial oxygen content. Arterial oxygen content is mainly determined by hemoglobin (Hb) concentration and percentage saturation of hemoglobin with oxygen (SaO2), with only a small contribution determined by the partial pressure of oxygen (PaO2) (see text for details)

Full size image

Drawbacks of SpO2 monitoring devices

Pulse oximetry estimates arterial oxygen saturation (SaO2) by illuminating the skin and measuring changes in light absorption of oxyhemoglobin (HbO2) and reduced hemoglobin (Hb) [21]. SpO2 can differ from true SaO2 (measured with a CO-oximeter) as much as ± 4% or more [22,23,24,25,26] (Fig. 4). The inaccuracy of SpO2 in identifying SaO2 combined with the sigmoid shape of the oxygen oxyhemoglobin dissociation curve (Fig. 5), has major implications for the recognition of early deterioration of gas exchange in patients with normal baseline arterial oxygen pressure (PaO2) [27]. This is because on the upper near-horizontal portion of the dissociation curve, large changes in PaO2 cause little changes in SaO2. For instance, with a 95% confidence limit of about ± 4%, an SpO2 reading of 95% could represent any PaO2 that starts from 130 mmHg (i.e., SaO2 of 99%) and deteriorates to 61 mm Hg (i.e., SaO2, of 91%) (Fig. 5) [28].

Fig. 4
figure 4

(Modified from [26])

Relationship between arterial blood oxygen saturation (SaO2) measured with a CO-oximeter and the difference (bias) between peripheral oxygen saturation (SpO2) measured with six different fingertip pulse oximeters and SaO2. Each oximeter is indicated by a different symbol. Measurements were obtained in 22 heathy volunteers of different ethnicities during controlled laboratory hypoxia conditions. In the absence of bias, all the datapoints would rest on the red broken horizontal line (zero bias). Instead, all pulse oximeters demonstrated either positive bias (signifying overestimation of SaO2) or negative bias (signifying underestimation of SaO2). Bias worsened as subjects became more hypoxemic. These results are similar to those recorded with larger benchtop pulse oximeters [91].

Full size image
Fig. 5
figure 5

Relationship between arterial oxygen pressure (PaO2) and percentage saturation of hemoglobin with oxygen (SaO2) applicable when the pH of the blood is 7.40 and temperature is 37° C. Since oximeters have 95% confidence limits for SaO2 of about ± 4%, an oximeter reading of 95% could represent a PaO2 of 61 mm Hg (saturation 91%) or a PaO2 of 130 mm Hg (saturation 99%). The right vertical axes represent values of arterial oxygen content (CaO2) based on the common hemoglobin concertation in a healthy adult of 15 g/dL or based on the hemoglobin concentration of 7 g/dL, a hemoglobin concentration below which providers usually transfuse packed red blood cells. (See text for details)

Full size image

Pulse oximeters are less accurate in patients with increased melanin. In one of the original studies on this phenomenon, Jubran and Tobin [29] reported that in critically ill, mechanically ventilated patients, pulse oximetry is 2.45 times less accurate in Black patients. Over the last three decades, the findings of Jubran and Tobin [29] have been corroborated by multiple investigators [25, 30,31,32]. For instance, Burnett al [31] compared SpO2 vs. SaO2 in more than forty-five thousand patients undergoing general anesthesia. In that study, the occurrence of occult hypoxemia, defined as SaO2 < 88%, when SpO2 reading remained > 92%, was 2.1% in Blacks, 1.8% in Hispanics, and 1.1% in Whites. More recently, in a study of nearly three thousand patients with COVID-19, Crooks et al. [30] reported occult hypoxemia in 6.9% patients of mixed ethnicities, in 5.4% Black, 5.1% Asian and 3.2% White patients [30]. The large 95% confidence limits (see Table 1 in Crooks et al. [30]) indicate that pulse oximetry provides both falsely high and falsely low saturations in all ethnicities. An additional confounder is that the difference between SpO2 and SaO2 is not reproducible (in magnitude or direction) [33]. These observations raise several considerations. The inaccuracy of pulse oximeters with skin pigmentation rests on the fact that reference calibration curves continue to rely on White volunteers [34]. Pulse oximetry either overestimates or underestimates SaO2 in all ethnicities. It is possible that the reduced accuracy of pulse oximeters in patients with increased melanin have contributed to the increased morbidity and mortality of these patients before and during the COVID-19 pandemic [32, 35, 36].

Drawbacks of using SpO2 to estimate oxygen delivery

Convective (perfusive) oxygen delivery (DO2) is an energy-requiring process that relies on the work performed by the respiratory and cardiac “pumps” [19]. Convective DO2 is the product of cardiac output (Qc) and arterial blood oxygen content (CaO2). The latter, in turn, is the product of SaO2 and Hb. (Under most circumstances the amount of oxygen dissolved in the blood is negligible.) SpO2 gives only an estimate of SaO2, that is, in turn, but one contributor to convective DO2. Accordingly, a given SpO2 estimation of SaO2, even if high, can be inadequate in securing sufficient convective DO2 to the brain if Hb or Qc are critically reduced. At the same time, a low estimation of SaO2 can still secure sufficient convective DO2 to the brain if the cardiovascular compensatory mechanisms are adequate, and Hb and SaO2 are not critically reduced.

The diffusion of oxygen from the alveoli to the pulmonary capillaries and from the systemic capillaries to the cells, or diffusive DO2, is a passive phenomenon that depends on the gradient in partial pressure of oxygen (PO2), tissue capillary density, and the ability of the cell to take up and use oxygen [19] (Fig. 3). The technical limitations in obtaining valid SpO2 recordings and the many factors that modulate the oxygen-dissociation curve (see below) make it unrealistic to use SpO2 to estimate diffusive DO2.

Intubation criteria based on SaO2 thresholds

Cognizant of the limitations of SpO2 readings, some investigators recommend intubation of hypoxemic patients when SaO2 is less than 92% [37], 90% [37], 85% [38, 39] or 80% [39].

Drawbacks of SaO2monitoring devices

SaO2 can be directly measured using core laboratory CO-oximeters, or it can be calculated using point-of-care devices [40]. CO-oximeters determine SaO2 spectrophotometrically. They are considered the reference standard technique to measure SaO2 [40]. These devices exhibit good intra-device reproducibility [41] yet, as expected, they exhibit inter-device discrepancy, both between two identical devices produced by the same manufacturer [42] or between two devices produced by different manufacturers [43]. Inter-device discrepancy increases as hypoxemia worsens [42, 43].

Point-of-care devices calculate SaO2 using algorithms that rely on measured parameters such as arterial pH, PO2 and PCO2 [40]. Point-of-care calculation of SaO2 increasingly deviates from SaO2 measured by CO-oximetry under hypoxemic conditions. For instance, in a study of more than three thousand samples, Gunsolus et al. [40] recorded an increase in the percent difference between measured and calculated SaO2 of about ± 2% when PaO2 was greater than 90 mm Hg to ± 20% or more when PaO2 was 50 to 60 mmHg or less (see Fig. 1 in Gunsolus et al. [40]).

Drawbacks of using SaO2 to estimate oxygen delivery

As with SpO2, high or low SaO2 values do not necessarily signify sufficient or insufficient convective DO2 to the brain. In regard to diffusive DO2, as already noted, large decreases in PaO2 to the right of the upper inflection point of the oxygen-dissociation curve cause only small changes in SaO2. This limits the usefulness of SaO2 readings in identifying decreases in diffusive DO2(Fig. 5). This is compounded by right or left shifts of the oxygen-dissociation curve. The curve shifts to the right (a lower SaO2 is required to achieve a given PaO2) with acidosis, increases in PCO2, 2,3-diphosphoglycerate, with certain hemoglobinopathies and fever [44, 45]. With the latter, a common occurrence in many critically ill patients, any given PaO2 will be associated with a lower SaO2 [45]. At a temperature of 37 °C, a PaO2 of 60 mm Hg (at normal pH and PaCO2) will be accompanied by an SaO2 of 91.1%. Temperature elevation to 40 °C will produce an SaO2 of 85.8% (5.3% decrease) [46].

The oxygen-dissociation curve shifts to the left (a higher SaO2 is required to achieve a given PaO2) with the inverse of the physiological factors listed above, and also with fetal hemoglobin and carbon monoxide intoxication. A leftward shift in the curve, which is inevitable with a decrease in arterial carbon dioxide pressure (PaCO2), a common occurrence in hypoxic patients [45] means that small decreases in SaO2 (and SpO2) are associated with large decreases in PaO2 [47].

Intubation criteria based on PaO2 thresholds

Investigators have proposed instituting invasive ventilation when PaO2 is less than 65 mm Hg [48], 60 mm Hg [13, 49], 50 mmHg [37, 50], and 45 mm Hg [17].

Drawbacks of using PaO2 to estimate oxygen delivery

PaO2 is only an indirect indicator of CaO2. Accordingly, it gives limited insight into convective DO2. Capillary PO2 is the driving pressure for O2 to diffuse into the cells (Fig. 3), and results from an interplay of PaO2, convective DO2, oxygen consumption and shifts in the oxygen dissociation curve [44, 51,52,53]. In other words, even a normal (or near normal) PaO2 does not automatically guarantee sufficient diffusive DO2 when tissue perfusion is reduced (stagnant hypoxia), or with anemia (anemic hypoxia) and when the mitochondria are unable to make use of oxygen (histotoxic hypoxia) [52,53,54,55,56,57,58].

Intubation criteria based on PaO2/FiO2 thresholds

In hypoxemic patients investigators recommend intubation when the arterial-to-inspired oxygen (PaO2/FiO2) ratio is less than 200 [12, 59], 100 [18], or 85 [60].

Drawbacks of using the PaO2/FiO2 ratio

Accurate recordings of PaO2 are easily obtainable. In contrast, the variable entrainment of ambient air during oxygen supplementation in most non-intubated patients makes it impossible to know with certainty the FiO2 reaching the trachea [61, 62]. For instance, a high-flow oxygen system through nasal cannula set at a flow of 50 L·min− 1 and an FiO2 of 60% generates an FiO2 anywhere between 35% and 60% [62] – the result is an underestimation of the true PaO2/FiO2 ratio. Such underestimation may induce intensivists to intubate patients who are not hypoxemic. The confounding factor of ambient air entrainment is underscored by the observation that placement of a surgical mask in patients receiving high-flow oxygen through nasal cannula increased PaO2 an average of 20 mm Hg [63].

Another drawback of the PaO2/FiO2 ratio stems from the curvilinear relationship between PaO2 and FiO2 that varies with the degree of ventilation–perfusion inequality and shunt [64, 65]. For instance, in patients with ARDS and a fixed shunt, alterations in FiO2 caused PaO2/FiO2 to fluctuate unpredictably by greater than 100 mmHg [66]. In patients who fulfil all ARDS criteria, administration of 100% oxygen for 30 min caused PaO2/FiO2 to increase such that 58.5% were no longer categorized as ARDS [67].

Regarding convective and diffusive DO2, PaO2/FiO2 ratio plays no role in any biological process and is misleading in the assessment of oxygen physiology [64, 65]. For example, Yarnell and Brochard (who agree we quote their personal communication, August 12, 2023), reported that the unadjusted hospital mortality on day-28 of over two thousand seven hundred patients with acute hypoxemic respiratory failure of non-COVID-19 patients who were never intubated was not greater than the mortality of patients intubated within 3 hours or after 3 hours after meeting a PaO2/FiO2 ratio threshold of less than 80, 100 or 150. The investigators advise caution as results can vary across centers and patient groups. The same investigators also computed the saturation-to-inspired oxygen (SF) ratio in the same cohort of patients [68]. Then, they performed an adjusted analysis and concluded that different SF ratio thresholds for intubation “can either increase or decrease the expected mortality, with the direction of effect likely depending on baseline mortality risk and clinical context”.

Intubation criteria based on CaO2 thresholds

In 2021, Voshaar et al. [69] proposed a therapeutic strategy that calls for invasive ventilation when hypoxemic patients with severe COVID-19 pneumonia and presumed normal cardiac function had a CaO2 of less than 9 mL O2 ∙ 100-1 mL of blood despite implementation of noninvasive oxygenation strategies. In that non-randomized, retrospective, study conducted in 78 patients admitted in two German hospitals, the mean (± SD) nadir in SpO2 was 84.4 ± 6.5%. Overall mortality was 7.7%, which was three times lower than the mortality of patients hospitalized with severe COVID-19 pneumonia in Germany [70].

Drawbacks of using CaO2 as an intubation criteria

The proposed CaO2 threshold of 9 mL O2 ∙ 100− 1 mL of blood is based on calculations made from two isolated observations, one in healthy subjects [71] and the other in anesthetized, paralyzed healthy piglets [72]. Yet, for this threshold to be an appropriate justification to escalate therapy, several major assumptions must be made. First, CaO2 must be a valid estimate of diffusive and convective DO2. Next, one must assume that the value of global convective DO2 below which oxygen consumption becomes delivery-dependent (critical DO2) is known and that global critical DO2 and brain’s regional critical DO2 have identical values. Finally, the physiologic effects of a decrease in CaO2 are independent from the mechanism that caused that decrease. Unfortunately, these assumptions are either incorrect or have not been tested.

Drawbacks of using CaO2to estimate oxygen delivery

CaO2 gives incomplete information about diffusive and convective DO2. Accordingly, unless critically decreased, CaO2 cannot inform the physician about a patient’s cerebral oxygen supply.

A given CaO2 results from a combination of a myriad of Hb and SaO2 values. For example, a Hb concentration of less than 7 g/dL is a common threshold for transfusion of red blood cells [73, 74]. When Hb is 7 g/dL and the diffusion pressure – or PaO2 – is in the normal range of 80 to 95 mm Hg and the corresponding SaO2 is 95 to 97%, the CaO2 will range from 9.4 to 9.6 mL O2 ∙ 100-1 mL of blood (Fig. 5). This is a situation which most patients can safely tolerate [73, 74]. To achieve similar CaO2 values when Hb is 15 g/dL, PaO2 has to decrease to 25.2 to 25.5 mm Hg and SaO2 has to decrease to 45.8 to 46.5% (Fig. 5). With only few exceptions (see below), these values of PaO2 and SaO2, even in healthy subjects, cause loss of consciousness, myotonic twitches, and convulsions [6]. In other words, CaO2 gives no direct information about oxygen supply to the brain limiting its utility in informing a decision to intubate the individual patient.

Fig. 6
figure 6

Index patient after completing twelve weeks of pulmonary rehabilitation after hospital discharge

Full size image

Physiologic approach to intubation

Basing the decision to intubate hypoxemic patients on physiologic principles requires knowledge of the minimal oxygen supply to maintain a tissue PO2 capable to sustain the oxidative metabolism of the brain. Although uncertain, such critical tissue PO2 is probably about 20 mmHg or less [75, 76]. In a healthy subject at rest, the mean oxygen consumption of the brain is about 46 mL.min− 1 and its blood flow is about 620 mL.min− 1 [7]. This corresponds to an arterial-to-venous oxygen content difference of 7.4 mL O2 ∙ 100− 1 mL of blood when hemoglobin and pH are within normal values [7]. The lowest CaO2 to secure such difference in oxygen content while maintaining a venous PO2 (and by implication a cerebral PO2 [7]) greater than 20 mm Hg is 13.8 mL O2 ∙ 100− 1 mL of blood. This corresponds to a PaO2 of 36 mm Hg and SaO2 of 68% [7]. This is the oxygenation experienced by tourists on drives to the top of Mount Evans (4350 m) for prolonged periods; many are comfortable, whereas some sense dyspnea [77]. It is important to note that the above computations are oversimplifications as they ignore hypoxia-induced increases in Qc and hyperventilation-induced hypocapnia with its associated cerebral vasoconstriction [78]. They also ignore the complex mechanisms that regulate cerebrovascular reactivity, cerebral metabolism during hypoxia [56, 78] and the large inter-individual variation in tolerance to hypoxia [6]. Accordingly, there is no simple answer to the question: what is the safe lower limit of PaO2 or SaO2 or CaO2? For example, a PaO2 of 36 mm Hg (and accompanying SaO2 of 68%), will be insufficient to sustain the oxidative metabolism of the brain in a patient who is anemic [54]. It will also be insufficient when cerebral perfusion is sub-optimal such as in patients with pre-existent cerebrovascular disease [79], decreased cardiac output [79], insufficient mean arterial blood pressure [54, 80] or cerebral vasoconstriction induced, for instance, by acute hypocapnia [6, 54]. At the same time, a PaO2 as low as 25 mmHg, with a corresponding SaO2 of about 45%, can ensure consciousness and by implication the oxidative metabolism of the brain in acclimatized mountaineers [81], and in patients with acute-on-chronic respiratory failure [82]. These are situations associated with compensatory polycythemia [81], maximal cerebral vasodilatation [7] and cellular adaptations to hypoxia [83].

How can we inform our decision to intubate a hypoxemic patient who is not in apparent respiratory distress? Considering the uncertainties about the critical cerebral PO2 [7, 76, 84], the non-uniform cerebral distribution of PO2 and oxygen demands [80, 85], the complex mechanisms that regulate cerebrovascular reactivity and cerebral metabolism during hypoxia [56, 78], the technical difficulties in monitoring cerebral PO2 [84] and the dangers associated with a liberal approach to insert an endotracheal tube [2] and institute invasive ventilation [3, 4], we see the decision of when to insert an endotracheal tube as one of the most challenging faced by any intensivist. Cognizant of these uncertainties, we consider intubation when our hypoxemic patient in neither apparent respiratory distress (operationally defined as the clinically observable corollary of dyspnea based on a patient’s display of physical/clinical signs) nor in shock becomes cognitively impaired suggesting emergent cerebral hypoxia [6]. When deciding to intubate, we also consider additional factors including blood pressure, and estimations of cardiac function, peripheral perfusion, CaO2 and its determinants. These additional factors, with all their limitations, are the indices we use in hypoxemic patients with coexistent pathologies that themselves cause cognitive impairment. In such cases, it remains to be determined whether computing the Intensive Care Unit Respiratory Distress Observation Scale or IC-RDOS, developed to assess dyspnea in critically ill patients who cannot easily communicate [86], may be helpful. We also recognize that whether the decision to institute invasive ventilation should be more liberal in patients with greater predicted mortality and less liberal in patients with lower predicted mortality is unknown [68].

Intubation of hypoxemic patients: Nosology, tacit knowledge, and the future

The focus of this physiologic review is the intubation of the hypoxemic patient is neither in apparent respiratory distress nor shock. There is a paucity of research that evaluates this group of patients – and no randomized controlled trials. Unfortunately, the nosology of the disease entity under consideration and the crucial contribution of tacit knowledge in medical decision making, make the design and the applicability of such hypothetical randomized controlled trials dubious if not impossible.

Nosology and clinical trials

Nosology is the branch of medical science dealing with the classification of diseases. Some diseases can be classified in etiologic or causal terms (e.g., Legionnaires’ disease) [5]. Diseases classified in etiologic or causal terms allow for complete scientific rigor [5]. This contrasts with syndromes (e.g., ARDS) or clinical entities (e.g., a patient in respiratory distress who is ‘tiring out’), which are defined by way of a description of symptoms and signs [5]. Hypoxemia in a patient in no apparent respiratory distress reflects a disease entity with indistinct boundaries. This has crucial implications in the design of clinical trials of these patients. When designing such a hypothetical trial, investigators must come up with a list of inclusion and exclusion criteria that serve as nodal points, which must be diligently (rigidly) followed to ensure the internal consistency of the study [87]. As discussed in this review, however, the soundness of oxygenation thresholds is fundamentally imprecise. Even if such a hypothetical study were undertaken, how would the clinician implement its results in his or her clinical practice?

Tacit knowledge and clinical decision making

In the context of our hypothetical study, hypoxemic respiratory failure can be defined without making any subjective value judgement – i.e., investigators would be required to rigidly follow a priori inclusion and exclusion criteria. This strategy, however, does not reflect bedside clinical decision making [87]. When making decisions about the treatment of an individual patient it is not possible to avoid subjective value judgments (things being assessed on a scale of goodness or badness) [5, 88]. Physicians base the decision to intubate on their clinical gestalt. Physicians may not be able to articulate the precise reasons behind this decision in the form of words [89]. This is because a wise physician standing at a patient’s bedside senses a great deal of worthwhile information—much more than can be expressed in words [5]. In short, there is a very large tacit coefficient to clinical knowledge—physicians know much more than they can communicate verbally [89, 90]. There is an enormous difference between the assessment made by an experienced physician standing at a bedside and the assessment the same physician makes on hearing information (about the same patient) relayed over the telephone by a junior resident [5]. An experienced and wise physician employs intuition rather than explicit rules in deciding what is best for a particular patient in a particular setting [5]. The practice of clinical medicine at the bedside involves cognitive processes and skill performances that cannot be incorporated into randomized controlled trials or observational research studies. A physician who regards such intuition as unscientific and thus flawed demonstrates a fundamental misunderstanding of both the epistemology of science and of the nature of clinical practice [89].

Conclusion

It is not possible to articulate the indications for mechanical ventilation in the individual patient in the form of a list of items. In clinical practice, the decision to insert an endotracheal tube is based, rather, on clinical judgement, gestalt, and tacit knowledge [5]. Our failure to formulate a list of indications does not mean that we advocate a laissez-faire approach to instituting mechanical ventilation. For instance, earlier we mentioned the limitations of PaO2 in informing us on the patients’ cerebral oxygen supply. This does not mean that we consider PaO2 unimportant. When we learn that a patient is acutely and persistently hypoxemic despite implementation of noninvasive oxygenation strategies, we immediately consider steps to institute invasive ventilation. But it is not possible to pick a PaO2 breakpoint at which the benefits of invasive ventilation will decidedly outweigh its hazards across all patients. It is futile to imagine that decision making about instituting invasive ventilation can be condensed into an algorithm with numbers at each nodal point. In sum, an algorithm cannot replace the presence of a physician well skilled in the art of clinical evaluation who has a deep understanding of pathophysiologic principles [5].

Coda

Our index patient spent 38 days in the hospital, 16 of which in the intensive care unit. Despite SpO2in the 80s% (and occasionally in the 70s%) while on high-flow oxygen through nasal cannula, he never developed respiratory distress. His mentation remained normal; he attentively watched television and appropriately conversed with family using his cell phone. He was not intubated. The patient was discharged home on 2 L·min− 1oxygen. Supplemental oxygen was discontinued one month after discharge. He successfully completed outpatient pulmonary rehabilitation(Fig. 6).

Data availability

This is a Review paper. The sources for the review are listed in the reference list and are available on PubMed.

Abbreviations

∆PO2 :

Gradient in oxygen pressure

CaO2 :

Arterial blood oxygen content

DO2 :

Oxygen delivery

Hb:

hemoglobin

HbO2 :

Oxyhemoglobin

PaCO2 :

Arterial carbon dioxide pressure

PaO2/FiO2 :

Arterial-to-inspired oxygen ratio

PaO2 :

Arterial oxygen pressure

PO2 :

Partial pressure of oxygen

Qc:

Cardiac output

SaO2 :

Arterial oxygen saturation

SD:

Standard deviation

SF:

Saturation-to-inspired oxygen ratio

SpO2 :

Peripheral oxygen saturation

References

  1. Yarnell CJ, Johnson A, Dam T, Jonkman A, Liu K, Wunsch H, et al. Do thresholds for invasive ventilation in hypoxemic respiratory failure Exist? A cohort study. Am J Respir Crit Care Med. 2023;207(3):271–82.

    Article  PubMed  Google Scholar 

  2. Stauffer J. Complications of translaryngeal intubation. In: Tobin MJ, editor. Principles and practice of mechanical ventilation. New York: McGraw-Hill, Inc; 2013. pp. 895–939.

    Google Scholar 

  3. Doidge JC, Gould DW, Ferrando-Vivas P, Mouncey PR, Thomas K, Shankar-Hari M, et al. Trends in Intensive Care for patients with COVID-19 in England, Wales, and Northern Ireland. Am J Respir Crit Care Med. 2021;203(5):565–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Wjst M, Wendtner C. High variability of COVID-19 case fatality rate in Germany. BMC Public Health. 2023;23(1):416.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Laghi F, Tobin MJ. Indications for mechanical ventilation. In: Tobin MJ, editor. Principles and practice of mechanical ventilation. 3rd ed. New York: McGraw-Hill, Inc; 2013. pp. 129–62.

    Google Scholar 

  6. Shaw DM, Cabre G, Gant N. Hypoxic hypoxia and brain function in Military Aviation: Basic Physiology and Applied perspectives. Front Physiol. 2021;12:665821.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Lumb AB, Thomas CR. Nunn and Lumb’s Applied Respiratory Physiology. 9 ed. Amsterdam, Netherlands: Elsevier; 2021.

    Google Scholar 

  8. Ajmani GS, Patel BK. To intubate or not intubate, that is the question. Am J Respir Crit Care Med. 2023;207(3):233–5.

    Article  PubMed  Google Scholar 

  9. Ahmad I, Jeyarajah J, Nair G, Ragbourne SC, Vowles B, Wong DJN, El-Boghdadly K. A prospective, observational, cohort study of airway management of patients with COVID-19 by specialist tracheal intubation teams. Can J Anaesth. 2021;68(2):196–203.

    Article  CAS  PubMed  Google Scholar 

  10. De Vita N, Scotti L, Cammarota G, Racca F, Pissaia C, Maestrone C, et al. Predictors of intubation in COVID-19 patients treated with out-of-ICU continuous positive airway pressure. Pulmonology. 2022;28(3):173–80.

    Article  PubMed  Google Scholar 

  11. Vaschetto R, Barone-Adesi F, Racca F, Pissaia C, Maestrone C, Colombo D et al. Outcomes of COVID-19 patients treated with continuous positive airway pressure outside the intensive care unit. ERJ Open Res. 2021;7(1).

  12. Osman A, Via G, Sallehuddin RM, Ahmad AH, Fei SK, Azil A, et al. Helmet continuous positive airway pressure vs. high flow nasal cannula oxygen in acute cardiogenic pulmonary oedema: a randomized controlled trial. Eur Heart J Acute Cardiovasc Care. 2021;10(10):1103–11.

    Article  PubMed  Google Scholar 

  13. Hernandez G, Vaquero C, Colinas L, Cuena R, Gonzalez P, Canabal A, et al. Effect of Postextubation High-Flow nasal cannula vs noninvasive ventilation on Reintubation and Postextubation Respiratory failure in high-risk patients: a Randomized Clinical Trial. JAMA. 2016;316(15):1565–74.

    Article  CAS  PubMed  Google Scholar 

  14. Sagiroglu G, Baysal A, Copuroglu E, Gul Y, Karamustafaoglu Y, Dogukan M. Does early use of bilevel positive airway pressure (bipap) in cardiothoracic intensive care unit prevent reintubation? Int J Clin Exp Med. 2014;7(10):3439–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. WHO. Clinical care for severe acute respiratory infection: toolkit: COVID-19 adaptation. Toolkit update 2022. Geneva, Switzerland: World Health Organization 2022. Available from https://www.who.int/europe/publications/i/item/WHO-2019-nCoV-SARI-toolkit-2022-1

  16. Patel BK, Wolfe KS, Pohlman AS, Hall JB, Kress JP. Effect of Noninvasive Ventilation delivered by Helmet vs Face Mask on the rate of endotracheal intubation in patients with Acute Respiratory Distress Syndrome: a Randomized Clinical Trial. JAMA. 2016;315(22):2435–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Maggiore SM, Jaber S, Grieco DL, Mancebo J, Zakynthinos S, Demoule A, et al. High-Flow Versus VenturiMask Oxygen Therapy to Prevent Reintubation in Hypoxemic patients after Extubation: a Multicenter Randomized Clinical Trial. Am J Respir Crit Care Med. 2022;206(12):1452–62.

    Article  PubMed  Google Scholar 

  18. Wermke M, Schiemanck S, Hoffken G, Ehninger G, Bornhauser M, Illmer T. Respiratory failure in patients undergoing allogeneic hematopoietic SCT–a randomized trial on early non-invasive ventilation based on standard care hematology wards. Bone Marrow Transpl. 2012;47(4):574–80.

    Article  CAS  Google Scholar 

  19. Leach RM, Treacher DF. The pulmonary physician in critical care * 2: oxygen delivery and consumption in the critically ill. Thorax. 2002;57(2):170–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Poole DC, Musch TI, Colburn TD. Oxygen flux from capillary to mitochondria: integration of contemporary discoveries. Eur J Appl Physiol. 2022;122(1):7–28.

    Article  CAS  PubMed  Google Scholar 

  21. Jubran A. Pulse oximetry. In: Tobin MJ, editor. Principles and practice of intensive care monitoring. New York: McGraw-Hill, Inc; 1998. pp. 261–87.

    Google Scholar 

  22. Severinghaus JW, Naifeh KH. Accuracy of response of six pulse oximeters to profound hypoxia. Anesthesiology. 1987;67(4):551–8.

    Article  CAS  PubMed  Google Scholar 

  23. Cecil WT, Thorpe KJ, Fibuch EE, Tuohy GF. A clinical evaluation of the accuracy of the Nellcor N-100 and Ohmeda 3700 pulse oximeters. J Clin Monit. 1988;4(1):31–6.

    Article  CAS  PubMed  Google Scholar 

  24. Louie A, Feiner JR, Bickler PE, Rhodes L, Bernstein M, Lucero J. Four types of pulse oximeters accurately detect hypoxia during low perfusion and motion. Anesthesiology. 2018;128(3):520–30.

    Article  PubMed  Google Scholar 

  25. Sjoding MW, Dickson RP, Iwashyna TJ, Gay SE, Valley TS. Racial Bias in Pulse Oximetry Measurement. N Engl J Med. 2020;383(25):2477–8.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Lipnick MS, Feiner JR, Au P, Bernstein M, Bickler PE. The Accuracy of 6 Inexpensive pulse oximeters not cleared by the Food and Drug Administration: the possible global Public Health implications. Anesth Analg. 2016;123(2):338–45.

    Article  CAS  PubMed  Google Scholar 

  27. Sorbini CA, Grassi V, Solinas E, Muiesan G. Arterial oxygen tension in relation to age in healthy subjects. Respiration. 1968;25(1):3–13.

    Article  CAS  PubMed  Google Scholar 

  28. Tobin MJ. Respiratory monitoring in the intensive care unit. Am Rev Respir Dis. 1988;138(6):1625–42.

    Article  CAS  PubMed  Google Scholar 

  29. Jubran A, Tobin MJ. Reliability of pulse oximetry in titrating supplemental oxygen therapy in ventilator-dependent patients. Chest. 1990;97(6):1420–5.

    Article  CAS  PubMed  Google Scholar 

  30. Crooks CJ, West J, Morling JR, Simmonds M, Juurlink I, Briggs S et al. Pulse oximeter measurements vary across ethnic groups: an observational study in patients with COVID-19. Eur Respir J. 2022;59(4).

  31. Burnett GW, Stannard B, Wax DB, Lin HM, Pyram-Vincent C, DeMaria S, Levin MA. Self-reported Race/Ethnicity and intraoperative Occult Hypoxemia: a retrospective cohort study. Anesthesiology. 2022;136(5):688–96.

    Article  CAS  PubMed  Google Scholar 

  32. Wong AI, Charpignon M, Kim H, Josef C, de Hond AAH, Fojas JJ, et al. Analysis of discrepancies between pulse oximetry and arterial oxygen saturation measurements by race and Ethnicity and Association with Organ Dysfunction and Mortality. JAMA Netw Open. 2021;4(11):e2131674.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Van de Louw A, Cracco C, Cerf C, Harf A, Duvaldestin P, Lemaire F, Brochard L. Accuracy of pulse oximetry in the intensive care unit. Intensive Care Med. 2001;27(10):1606–13.

    Article  PubMed  Google Scholar 

  34. Tobin MJ, Jubran A. Pulse oximetry, racial bias and statistical bias. Ann Intensive Care. 2022;12(1):2.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Price-Haywood EG, Burton J, Fort D, Seoane L. Hospitalization and mortality among black patients and White patients with Covid-19. N Engl J Med. 2020;382(26):2534–43.

    Article  CAS  PubMed  Google Scholar 

  36. Fawzy A, Wu TD, Wang K, Robinson ML, Farha J, Bradke A, et al. Racial and ethnic discrepancy in pulse oximetry and delayed identification of treatment eligibility among patients with COVID-19. JAMA Intern Med. 2022;182(7):730–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Pisano A, Yavorovskiy A, Verniero L, Landoni G. Indications for Tracheal Intubation in patients with Coronavirus Disease 2019 (COVID-19). J Cardiothorac Vasc Anesth. 2021;35(5):1276–80.

    Article  CAS  PubMed  Google Scholar 

  38. Delclaux C, L’Her E, Alberti C, Mancebo J, Abroug F, Conti G, et al. Treatment of acute hypoxemic nonhypercapnic respiratory insufficiency with continuous positive airway pressure delivered by a face mask: a randomized controlled trial. JAMA. 2000;284(18):2352–60.

    Article  CAS  PubMed  Google Scholar 

  39. Nava S, Carbone G, DiBattista N, Bellone A, Baiardi P, Cosentini R, et al. Noninvasive ventilation in cardiogenic pulmonary edema: a multicenter randomized trial. Am J Respir Crit Care Med. 2003;168(12):1432–7.

    Article  PubMed  Google Scholar 

  40. Gunsolus IL, Love SA, Kohl LP, Schmidt M, Apple FS. Low pO2 contributes to potential error in Oxygen Saturation calculations using a point-of-care assay. Am J Clin Pathol. 2017;149(1):82–6.

    Article  PubMed  Google Scholar 

  41. Johnson PA, Bihari DJ, Raper RF, Haughton MA, Fisher MM, Herkes RG. A comparison between direct and calculated oxygen saturation in intensive care. Anaesth Intensive Care. 1993;21(1):72–5.

    Article  CAS  PubMed  Google Scholar 

  42. Gehring H, Duembgen L, Peterlein M, Hagelberg S, Dibbelt L. Hemoximetry as the gold standard? Error assessment based on differences among identical blood gas analyzer devices of five manufacturers. Anesth Analg. 2007;105(6 Suppl):S24–30.

    Article  PubMed  Google Scholar 

  43. Porath M, Sinha P, Dudenhausen JW, Luttkus AK. Systematic instrumental errors between oxygen saturation analysers in fetal blood during deep hypoxemia. Clin Chim Acta. 2001;307(1–2):151–7.

    Article  CAS  PubMed  Google Scholar 

  44. Bunn HF. Oxygen delivery in the treatment of Anemia. N Engl J Med. 2022;387(25):2362–5.

    Article  CAS  PubMed  Google Scholar 

  45. Tobin MJ, Laghi F, Jubran A, Why. COVID-19 Silent Hypoxemia is Baffling to Physicians. Am J Respir Crit Care Med. 2020;202(3):356–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kelman GR. Digital computer subroutine for the conversion of oxygen tension into saturation. J Appl Physiol. 1966;21(4):1375–6.

    Article  CAS  PubMed  Google Scholar 

  47. Rahn H, Fenn WO. A graphical analysis of the respiratory gas exchange. Washington, DC:: Am. Physiol. Soc.; 1955.

    Google Scholar 

  48. Antonelli M, Conti G, Rocco M, Bufi M, De Blasi RA, Vivino G, et al. A comparison of noninvasive positive-pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure. N Engl J Med. 1998;339(7):429–35.

    Article  CAS  PubMed  Google Scholar 

  49. Kalita J, Kumar M, Misra UK. Serial single breath count is a reliable tool for monitoring respiratory functions in Guillain-Barre Syndrome. J Clin Neurosci. 2020;72:50–6.

    Article  PubMed  Google Scholar 

  50. Tan D, Walline JH, Ling B, Xu Y, Sun J, Wang B, et al. High-flow nasal cannula oxygen therapy versus non-invasive ventilation for chronic obstructive pulmonary disease patients after extubation: a multicenter, randomized controlled trial. Crit Care. 2020;24(1):489.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Roy TK, Popel AS. Theoretical predictions of end-capillary PO2 in muscles of athletic and nonathletic animals at VO2max. Am J Physiol. 1996;271(2 Pt 2):H721–37.

    CAS  PubMed  Google Scholar 

  52. Taylor JH, Mulier KE, Myers DE, Beilman GJ. Use of near-infrared spectroscopy in early determination of irreversible hemorrhagic shock. J Trauma. 2005;58(6):1119–25.

    Article  PubMed  Google Scholar 

  53. Mancini DM, Bolinger L, Li H, Kendrick K, Chance B, Wilson JR. Validation of near-infrared spectroscopy in humans. J Appl Physiol (1985). 1994;77(6):2740–7.

    Article  CAS  PubMed  Google Scholar 

  54. Yeager CE, Bleck TP. Cerebral hemodynamics. In: Magder S, Malhotra A, Hibbert KA, Hardin CC, editors. Cardiopulmonary monitoring basic physiology, tools and bedside management for the critically ill. Cham, Switzerland: Springer; 2021. pp. 153–63.

    Chapter  Google Scholar 

  55. Jacobsen A, Nielsen TH, Nilsson O, Schalen W, Nordstrom CH. Bedside diagnosis of mitochondrial dysfunction in aneurysmal subarachnoid hemorrhage. Acta Neurol Scand. 2014;130(3):156–63.

    Article  CAS  PubMed  Google Scholar 

  56. Svedung Wettervik T, Engquist H, Hanell A, Howells T, Rostami E, Ronne-Engstrom E, et al. Cerebral blood Flow and Oxygen Delivery in Aneurysmal Subarachnoid Hemorrhage: relation to Neurointensive Care targets. Neurocrit Care. 2022;37(1):281–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Cilley RE, Scharenberg AM, Bongiorno PF, Guire KE, Bartlett RH. Low oxygen delivery produced by anemia, hypoxia, and low cardiac output. J Surg Res. 1991;51(5):425–33.

    Article  CAS  PubMed  Google Scholar 

  58. van der Hoeven MA, Maertzdorf WJ, Blanco CE. Relationship between mixed venous oxygen saturation and markers of tissue oxygenation in progressive hypoxic hypoxia and in isovolemic anemic hypoxia in 8- to 12-day-old piglets. Crit Care Med. 1999;27(9):1885–92.

    Article  PubMed  Google Scholar 

  59. Kluge S, Janssens U, Welte T, Weber-Carstens S, Marx G, Karagiannidis C. German recommendations for critically ill patients with COVID–19. Med Klin Intensivmed Notfmed. 2020;115(Suppl 3):111–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Squadrone V, Massaia M, Bruno B, Marmont F, Falda M, Bagna C, et al. Early CPAP prevents evolution of acute lung injury in patients with hematologic malignancy. Intensive Care Med. 2010;36(10):1666–74.

    Article  PubMed  Google Scholar 

  61. Bazuaye EA, Stone TN, Corris PA, Gibson GJ. Variability of inspired oxygen concentration with nasal cannulas. Thorax. 1992;47(8):609–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Ritchie JE, Williams AB, Gerard C, Hockey H. Evaluation of a humidified nasal high-flow oxygen system, using oxygraphy, capnography and measurement of upper airway pressures. Anaesth Intensive Care. 2011;39(6):1103–10.

    Article  CAS  PubMed  Google Scholar 

  63. Montiel V, Robert A, Robert A, Nabaoui A, Marie T, Mestre NM, et al. Surgical mask on top of high-flow nasal cannula improves oxygenation in critically ill COVID-19 patients with hypoxemic respiratory failure. Ann Intensive Care. 2020;10(1):125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Dantzker DR. Gas exchange in the adult respiratory distress syndrome. Clin Chest Med. 1982;3(1):57–67.

    Article  CAS  PubMed  Google Scholar 

  65. West JB. State of the art: ventilation-perfusion relationships. Am Rev Respir Dis. 1977;116(5):919–43.

    CAS  PubMed  Google Scholar 

  66. Gowda MS, Klocke RA. Variability of indices of hypoxemia in adult respiratory distress syndrome. Crit Care Med. 1997;25(1):41–5.

    Article  CAS  PubMed  Google Scholar 

  67. Ferguson ND, Kacmarek RM, Chiche JD, Singh JM, Hallett DC, Mehta S, Stewart TE. Screening of ARDS patients using standardized ventilator settings: influence on enrollment in a clinical trial. Intensive Care Med. 2004;30(6):1111–6.

    Article  PubMed  Google Scholar 

  68. Yarnell CJ, Angriman F, Ferreyro BL, Liu K, De Grooth HJ, Burry L, et al. Oxygenation thresholds for invasive ventilation in hypoxemic respiratory failure: a target trial emulation in two cohorts. Crit Care. 2023;27(1):67.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Voshaar T, Stais P, Kohler D, Dellweg D. Conservative management of COVID-19 associated hypoxaemia. ERJ Open Res. 2021;7(1).

  70. Karagiannidis C, Mostert C, Hentschker C, Voshaar T, Malzahn J, Schillinger G, et al. Case characteristics, resource use, and outcomes of 10 021 patients with COVID-19 admitted to 920 German hospitals: an observational study. Lancet Respir Med. 2020;8(9):853–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Lieberman JA, Weiskopf RB, Kelley SD, Feiner J, Noorani M, Leung J, et al. Critical oxygen delivery in conscious humans is less than 7.3 ml O2 x kg(-1) x min(-1). Anesthesiology. 2000;92(2):407–13.

    Article  CAS  PubMed  Google Scholar 

  72. van der Hoeven MA, Maertzdorf WJ, Blanco CE. Mixed venous oxygen saturation and biochemical parameters of hypoxia during progressive hypoxemia in 10- to 14-day-old piglets. Pediatr Res. 1997;42(6):878–84.

    Article  PubMed  Google Scholar 

  73. Holst LB, Haase N, Wetterslev J, Wernerman J, Guttormsen AB, Karlsson S, et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014;371(15):1381–91.

    Article  PubMed  Google Scholar 

  74. Hebert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion requirements in critical care investigators, Canadian critical care trials Group. N Engl J Med. 1999;340(6):409–17.

    Article  CAS  PubMed  Google Scholar 

  75. Pennings FA, Schuurman PR, van den Munckhof P, Bouma GJ. Brain tissue oxygen pressure monitoring in awake patients during functional neurosurgery: the assessment of normal values. J Neurotrauma. 2008;25(10):1173–7.

    Article  PubMed  Google Scholar 

  76. Doppenberg EM, Zauner A, Watson JC, Bullock R. Determination of the ischemic threshold for brain oxygen tension. Acta Neurochir Suppl. 1998;71:166–9.

    CAS  PubMed  Google Scholar 

  77. Bickler PE, Feiner JR, Lipnick MS, Batchelder P, MacLeod DB, Severinghaus JW. Effects of Acute, Profound Hypoxia on healthy humans: implications for safety of tests evaluating pulse oximetry or tissue oximetry performance. Anesth Analg. 2017;124(1):146–53.

    Article  PubMed  Google Scholar 

  78. Claassen J, Thijssen DHJ, Panerai RB, Faraci FM. Regulation of cerebral blood flow in humans: physiology and clinical implications of autoregulation. Physiol Rev. 2021;101(4):1487–559.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Da Silva I, Bleck TP. Cerebral hemodynamic monitoring techniques. In: Magder S, Malhotra A, Hibbert KA, Hardin CC, editors. Cardiopulmonary monitoring basic physiology, tools, and bedside management for the critically ill. Cham, Switzerland: Springer; 2021. pp. 337–57.

    Chapter  Google Scholar 

  80. Madhok DY, Vitt JR, Nguyen AT. Overview of neurovascular physiology. Curr Neurol Neurosci Rep. 2018;18(12):99.

    Article  PubMed  Google Scholar 

  81. Grocott MP, Martin DS, Levett DZ, McMorrow R, Windsor J, Montgomery HE. Caudwell Xtreme Everest Research G. arterial blood gases and oxygen content in climbers on Mount Everest. N Engl J Med. 2009;360(2):140–9.

    Article  CAS  PubMed  Google Scholar 

  82. Campbell EJ. The J. Burns Amberson lecture. The management of acute respiratory failure in chronic bronchitis and emphysema. Am Rev Respir Dis. 1967;96(4):626–39.

    CAS  PubMed  Google Scholar 

  83. West JB. Physiological effects of Chronic Hypoxia. N Engl J Med. 2017;376(20):1965–71.

    Article  CAS  PubMed  Google Scholar 

  84. Le Roux P, Menon DK, Citerio G, Vespa P, Bader MK, Brophy GM et al. Consensus summary statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care: a statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine. Neurocrit Care. 2014;21 Suppl 2:S1-26.

  85. Erecinska M, Silver IA. Tissue oxygen tension and brain sensitivity to hypoxia. Respir Physiol. 2001;128(3):263–76.

    Article  CAS  PubMed  Google Scholar 

  86. Persichini R, Gay F, Schmidt M, Mayaux J, Demoule A, Morelot-Panzini C, Similowski T. Diagnostic Accuracy of Respiratory Distress Observation scales as surrogates of Dyspnea Self-report in Intensive Care Unit patients. Anesthesiology. 2015;123(4):830–7.

    Article  PubMed  Google Scholar 

  87. Tobin MJ, Jubran A, Laghi F. Noninvasive strategies in COVID-19: epistemology, randomised trials, guidelines, physiology. Eur Respir J. 2021;57(2).

  88. Cimino JJ. Development of expertise in medical practice. In: Sternberg RJ, Horvath JR, editors. Tacit Knowledge in Professional Practice: researcher and practitioner perspective. Mawhvah, NJ: Lawrence Erlbaum Associates, Inc.; 1999. pp. 101–20.

    Google Scholar 

  89. Polanyi M. Personal knowledge: towards a post-critical philosophy. Chicago: University Press of Chicago; 1974.

    Google Scholar 

  90. Patel VL, Arocha JF, Kaufman DR. Expertise and tacit knowledge in medicine. In: Sternberg RJ, Horvath JR, editors. Tacit Knowledge in Professional Practice: researcher and practitioner perspective. Mawhvah, NJ: Lawrence Erlbaum Associates, Inc.; 1999. pp. 75–99.

    Google Scholar 

  91. Singh AK, Sahi MS, Mahawar B, Rajpurohit S. Comparative evaluation of accuracy of pulse oximeters and factors affecting their performance in a Tertiary Intensive Care Unit. J Clin Diagn Res. 2017;11(6):OC05–8.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

Franco Laghi and Hameeda Shaikh report a grant from Veterans Administration Research (1 I01 RX002803-01A1).

Author information

Authors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine, Hines Veterans Affairs Hospital (111N) and Loyola University of Chicago Stritch School of Medicine, 60141, Hines, IL, USA

    Franco Laghi & Hameeda Shaikh

  2. Department of Physiology and Pharmacology, Center for Molecular Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

    Nicola Caccani

Authors
  1. Franco Laghi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hameeda Shaikh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nicola Caccani
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

FL, HS and NC contributed to the conception, and design of the work. FL, HS and NC contributed to the critical analysis of available literature and drafted the manuscript for intellectual content. FL, HS and NC had full access to the available literature and take responsibility for its critical analysis. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Franco Laghi.

Ethics declarations

Ethics approval and consent to participate

Non applicable.

Consent for publication

The patient depicted in Fig. 6 gave written inform consent for publication (using the official institutional consent form). The signed inform consent for publication is available to the Editorial office of Annals of Intensive Care upon request at any stage (including after publication).

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Laghi, F., Shaikh, H. & Caccani, N. Basing intubation of acutely hypoxemic patients on physiologic principles. Ann. Intensive Care 14, 86 (2024). https://doi.org/10.1186/s13613-024-01327-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13613-024-01327-w

Keywords