Patients with coronavirus disease (COVID-19) are described as exhibiting oxygen levels incompatible with life without dyspnea. The pairing-dubbed happy hypoxia but more precisely termed silent hypoxemia-is especially bewildering to physicians and is considered as defying basic biology. This combination has attracted extensive coverage in media but has not been discussed in medical journals. It is possible that coronavirus has an idiosyncratic action on receptors involved in chemosensitivity to oxygen, but well-established pathophysiological mechanisms can account for most, if not all, cases of silent hypoxemia. These mechanisms include the way dyspnea and the respiratory centers respond to low levels of oxygen, the way the prevailing carbon dioxide tension (Pa CO 2) blunts the brain's response to hypoxia, effects of disease and age on control of breathing, inaccuracy of pulse oximetry at low oxygen saturations, and temperature-induced shifts in the oxygen dissociation curve. Without knowledge of these mechanisms, physicians caring for patients with hypoxemia free of dyspnea are operating in the dark, placing vulnerable patients with COVID-19 at considerable risk. In conclusion, features of COVID-19 that physicians find baffling become less strange when viewed in light of long-established principles of respiratory physiology; an understanding of these mechanisms will enhance patient care if the much-anticipated second wave emerges.
This report summarizes current physiological and technical knowledge on esophageal pressure (Pes) measurements in patients receiving mechanical ventilation. The respiratory changes in Pes are representative of changes in pleural pressure. The difference between airway pressure (Paw) and Pes is a valid estimate of transpulmonary pressure. Pes helps determine what fraction of Paw is applied to overcome lung and chest wall elastance. Pes is usually measured via a catheter with an air-filled thin-walled latex balloon inserted nasally or orally. To validate Pes measurement, a dynamic occlusion test measures the ratio of change in Pes to change in Paw during inspiratory efforts against a closed airway. A ratio close to unity indicates that the system provides a valid measurement. Provided transpulmonary pressure is the lung-distending pressure, and that chest wall elastance may vary among individuals, a physiologically based ventilator strategy should take the transpulmonary pressure into account. For monitoring purposes, clinicians rely mostly on Paw and flow waveforms. However, these measurements may mask profound patient-ventilator asynchrony and do not allow respiratory muscle effort assessment. Pes also permits the measurement of transmural vascular pressures during both passive and active breathing. Pes measurements have enhanced our understanding of the pathophysiology of acute lung injury, patient-ventilator interaction, and weaning failure. The use of Pes for positive end-expiratory pressure titration may help improve oxygenation and compliance. Pes measurements make it feasible to individualize the level of muscle effort during mechanical ventilation and weaning. The time is now right to apply the knowledge obtained with Pes to improve the management of critically ill and ventilator-dependent patients.
Pes monitoring provides unique bedside measures for a better understanding of the pathophysiology of acute respiratory failure patients. Including Pes monitoring in the intensivist's clinical armamentarium may enhance treatment to improve clinical outcomes.
Pulse oximetry is universally used for monitoring patients in the critical care setting. This article updates the review on pulse oximetry that was published in 1999 in Critical Care. A summary of the recently developed multiwavelength pulse oximeters and their ability in detecting dyshemoglobins is provided. The impact of the latest signal processing techniques and reflectance technology on improving the performance of pulse oximeters during motion artifact and low perfusion conditions is critically examined. Finally, data regarding the effect of pulse oximetry on patient outcome are discussed.
To determine the mechanisms of acute respiratory distress and failure in patients with chronic obstructive pulmonary disease (COPD), we studied 17 ventilator-supported patients who failed a trial of spontaneous breathing and 14 patients who tolerated such a trial and were successfully extubated. Immediately before the weaning trials, maximal inspiratory pressure was not statistically different between the two groups (p = 0.48). On discontinuation of the ventilator, the failure group immediately developed rapid shallow breathing, and higher values of dynamic lung elastance (EdynL) (p < 0.01) and intrinsic positive end-expiratory pressure (PEEPi, p < 0.03) than did the success group. Between the onset and end of the trial, the failure group developed further increases in EdynL (p < 0.0001) and PEEPi (p < 0.0001), and increases in inspiratory resistance (p < 0.009) and inspiratory pressure-time product (PTP) (p < 0.0001). Partitioning of PTP at the end of the trial revealed a 111% increase in the PEEPi component, a 33% increase in the non-PEEPi elastic component, and a 42% increase in the resistive component (all p < 0.0001). Despite the increase in PTP, 13 of the failure patients developed an increase in PaCO2. The product of PTP and PaCO2, an index of inefficient CO2 clearance, was more than twice as high in the failure group than in the success group at the end of the trial (p < 0.0005). Thus, development of acute respiratory distress during a failed weaning attempt was due to worsening of pulmonary mechanics, which in conjunction with rapid shallow breathing led to inefficient clearance of CO2.
Clinical assessment of the activity of tumor necrosis factor (TNF) against human cancer has been limited by a dose-dependent cardiovascular toxicity, most frequently hypotension. TNF is also thought to mediate the vascular collapse resulting from bacterial endotoxin. The present studies address the mechanism by which TNF causes hypotension and provide evidence for elevated production of nitric oxide, a potent vasodilator initially characterized as endotheliumderived relaxing factor. Nitric oxide is synthesized by several cell types, including endothelial cells and macrophages, from the guanidino nitrogen of L-arginine; the enzymatic pathway is competitively inhibited by -me yl-L-arginine. We found that hypotension induced in pentobarbital-anesthetized dogs by TNF (10 ,ug/kg, i.v., resulting in a fall in mean systemic arterial pressure from 124.7 ± 7 to 62.0 ± 22.9 mmHg; 1 mmHg = 133 Pa) was completely reversed within 2 min following administration ofNG-methyl-L-arginine (4.4 mg/kg, i.v.). In contrast, NG-methyl-L-arginine failed to reverse the hypotensive response to an equivalent depressor dose of nitroglycerin, a compound that acts by forming nitric oxide by a nonenzymatic, arginine-independent mechanism. The effect of NG-methyl-L-arginine on TNF-induced hypotension was antagonized, and the hypotension restored, by administration of excess L-arginine (100 mg/kg, i.v.). Our rmdings suggest that excessive nitric oxide production mediates the hypotensive effect of TNF.Tumor necrosis factor (TNF) is a cytotoxic protein produced by macrophages upon activation by bacterial endotoxin (1, 2). In addition to a spectrum of cytotoxic and immunologic actions, TNF causes marked hypotension in mammals (1, 3). The observations that bacterial endotoxin elicits TNF production (4, 5) and that pretreatment of animals with anti-TNF antibodies abolishes the hypotensive action of endotoxin (6) suggest that TNF is the key mediator of endotoxic shock in vivo. Although TNF is known to promote hemorrhagic necrosis of some animal tumors (7), its clinical promise as an antineoplastic agent is limited by severe dose-dependent side effects, predominantly hypotension (8, 9). Despite the clinical importance of TNF-induced hypotension, its mechanism is unknown.The present study addresses the possibility that increased nitric oxide production accounts for TNF-induced hypotension. Earlier studies established that endothelium-derived nitric oxide is a labile modulator of vascular tone (10, 11). Originally termed endothelium-derived relaxing factor (EDRF, ref. 12), nitric oxide is responsible for the vascular smooth muscle relaxation elicited by acetylcholine, bradykinin, and many other endogenous vasorelaxants. L-Arginine is the biosynthetic precursor of endothelium-derived nitric oxide (13)(14)(15)(16), and NG-methyl-L-arginine (L-MeArg) is a competitive inhibitor of this pathway (14, 15). The finding that administration of L-MeArg causes a moderate increase in blood pressure by an arginine-reversible mechanism in the anesthetized guine...
In 11 ventilator-dependent patients, we undertook a head-to-head comparison of patient-ventilator interaction during four ventilator modes: assist-control ventilation (ACV), intermittent mandatory ventilation (IMV), pressure support (PS), and a combination of IMV and PS. Progressive increases in IMV rate and PS level each decreased inspiratory pressure-time product (PTP) (p < 0.0001). These reductions in PTP were greater with PS than with IMV at lower but proportional levels of maximal assistance (p < 0.005). When PS 10 cm H2O was added to a given level of IMV, greater reductions in PTP were achieved not only during intervening (PS) breaths (p < 0.001), but also during mandatory (volume-assisted) breaths (p < 0.0005); this additional unloading during mandatory breaths was proportional to the decrease in respiratory drive (dP/dt) during intervening breaths (r = 0.67, p < 0.0001). Maximal unloading occurred with ACV, achieving more than a fivefold decrease in PTP compared with unassisted breathing. Decreases in PTP were confined to the post-trigger phase, and PTP of the post-trigger phase correlated with dP/dt (r = 0.78, p < 0.0001). Effort during the trigger phase remained constant despite marked changes in drive and intrinsic positive end-expiratory pressure (PEEPi). Ineffective triggering occurred with all modes, and wasted PTP increased with increasing levels of assistance as a result of the accompanying decrease in drive and increase in volume. Breaths preceding nontriggering efforts had shorter respiratory cycle times (p < 0.0005) and expiratory times (p < 0.0001) and higher PEEPi (p < 0.0001), indicating that neural-mechanical asynchrony resulted from inspiratory activity commencing prematurely before elastic recoil pressure had fallen to a level that could be overcome by a patient's muscular effort. Thus, increases in the level of ventilator assistance produced progressive decreases in inspiratory muscle effort and dyspnea,which were accompanied by increases in the rate of ineffective triggering.
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