Fiftieth Anniversary of Uncovering the Tuskegee Syphilis Study: The Story and Timeless Lessons.

This year marks the 50th anniversary of the uncovering of the Tuskegee syphilis study, when the public learned that the Public Health Service (precursor of the CDC) for 40 years intentionally withheld effective therapy against a life-threatening illness in 400 African American men. In 2010, we learned that the same research group had deliberately infected hundreds of Guatemalans with syphilis and gonorrhea in the 1940s, with the goal of developing better methods for preventing these infections. Despite 15 journal articles detailing the results, no physician published a letter criticizing the Tuskegee study. Informed consent was never sought; instead, Public Health Service researchers deceived the men into believing they were receiving expert medical care. The study is an especially powerful parable because readers can identify the key players in the narrative and recognize them as exemplars of people they encounter in daily life-these flesh-and-blood characters convey the principles of research ethics more vividly than a dry account in a textbook of bioethics. The study spurred reforms leading to fundamental changes in the infrastructure of research ethics. The reason people fail to take steps to halt behavior that in retrospect everyone judges reprehensible is complex. Lack of imagination, rationalization, and institutional constraints are formidable obstacles. The central lessons from the study are the need to pause and think, reflect, and examine one's conscience; the courage to speak; and above all the willpower to act. History, although about the past, is our best defense against future errors and transgressions.

ARDS: hidden perils of an overburdened diagnosis.

A diagnosis of ARDS serves as a pretext for several perilous clinical practices. Clinical trials demonstrated that tidal volume 12 ml/kg increases patient mortality, but 6 ml/kg has not proven superior to 11 ml/kg or anything in between. Present guidelines recommend 4 ml/kg, which foments severe air hunger, leading to prescription of hazardous (yet ineffective) sedatives, narcotics and paralytic agents. Inappropriate lowering of tidal volume also fosters double triggering, which promotes alveolar overdistention and lung injury. Successive panels have devoted considerable energy to developing a more precise definition of ARDS to homogenize the recruitment of patients into clinical trials. Each of three pillars of the prevailing Berlin definition is extremely flimsy and the source of confusion and unscientific practices. For doctors at the bedside, none of the revisions have enhanced patient care over that using the original 1967 description of Ashbaugh and colleagues. Bedside doctors are better advised to diagnose ARDS on the basis of pattern recognition and instead concentrate their vigilance on resolving the numerous hidden dangers that follow inevitably once a diagnosis has been made.

Why COVID-19 Silent Hypoxemia Is Baffling to Physicians.

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 (PaCO2) 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.

Misconceptions of pathophysiology of happy hypoxemia and implications for management of COVID-19.

In the article "The pathophysiology of 'happy' hypoxemia in COVID-19," Dhont et al. (Respir Res 21:198, 2020) discuss pathophysiological mechanisms that may be responsible for the absence of dyspnea in patients with COVID-19 who exhibit severe hypoxemia. The authors review well-known mechanisms that contribute to development of hypoxemia in patients with pneumonia, but are less clear as to why patients should be free of respiratory discomfort despite arterial oxygen levels commonly regarded as life threatening. The authors propose a number of therapeutic measures for patients with COVID-19 and happy hypoxemia; we believe readers should be alerted to problems with the authors' interpretations and recommendations.

Long-Term Outcome after Prolonged Mechanical Ventilation. A Long-Term Acute-Care Hospital Study.

Rationale: Patients managed at a long-term acute-care hospital (LTACH) for weaning from prolonged mechanical ventilation are at risk for profound muscle weakness and disability. Objectives: To investigate effects of prolonged ventilation on survival, muscle function, and its impact on quality of life at 6 and 12 months after LTACH discharge. Methods: This was a prospective, longitudinal study conducted in 315 patients being weaned from prolonged ventilation at an LTACH. Measurements and Main Results: At discharge, 53.7% of patients were detached from the ventilator and 1-year survival was 66.9%. On enrollment, maximum inspiratory pressure (Pimax) was 41.3 (95% confidence interval, 39.4-43.2) cm H2O (53.1% predicted), whereas handgrip strength was 16.4 (95% confidence interval, 14.4-18.7) kPa (21.5% predicted). At discharge, Pimax did not change, whereas handgrip strength increased by 34.8% (P < 0.001). Between discharge and 6 months, handgrip strength increased 6.2 times more than did Pimax. Between discharge and 6 months, Katz activities-of-daily-living summary score improved by 64.4%; improvement in Katz summary score was related to improvement in handgrip strength (r = -0.51; P < 0.001). By 12 months, physical summary score and mental summary score of 36-item Short-Form Survey returned to preillness values. When asked, 84.7% of survivors indicated willingness to undergo mechanical ventilation again. Conclusions: Among patients receiving prolonged mechanical ventilation at an LTACH, 53.7% were detached from the ventilator at discharge and 1-year survival was 66.9%. Respiratory strength was well maintained, whereas peripheral strength was severely impaired throughout hospitalization. Six months after discharge, improvement in muscle function enabled patients to perform daily activities, and 84.7% indicated willingness to undergo mechanical ventilation again.

New device for nonvolitional evaluation of quadriceps force in ventilated patients.

INTRODUCTION: In mechanically ventilated patients, nonvolitional assessment of quadriceps weakness using femoral-nerve stimulation (twitch force) while the leg rests on a right-angle trapezoid or dangles from the bed edge is impractical. Accordingly, we developed a knee-support apparatus for use in ventilated patients. METHODS: Ninety subjects (12 ventilated patients, 28 ambulatory patients, and 50 healthy subjects) were enrolled. Twitches with leg-dangling, trapezoid, and knee-support setups were compared. RESULTS: Knee-support twitches were similar to trapezoid twitches but smaller than leg-dangling twitches (P < 0.0001). Inter- and intraoperator agreement was high for knee-support twitches at 1 week and 1 month. In ventilated patients, knee-support twitches were smaller than in healthy subjects and ambulatory patients (P < 0.004). DISCUSSION: The new knee-support apparatus allows accurate recording of quadriceps twitches. The ease of use in ventilated patients and excellent inter- and intraoperator agreement suggest that this technique is suitable for cross-sectional and longitudinal studies in critically ill patients. Muscle Nerve 57: 784-791, 2018.

Effect of Atypical Sleep EEG Patterns on Weaning From Prolonged Mechanical Ventilation.

BACKGROUND: Approximately one-third of acute ICU patients display atypical sleep patterns that cannot be interpreted by using standard EEG criteria for sleep. Atypical sleep patterns have been associated with poor weaning outcomes in acute ICUs. RESEARCH QUESTION: Do patients being weaned from prolonged mechanical ventilation experience atypical sleep EEG patterns, and are these patterns linked with weaning outcomes? STUDY DESIGN AND METHODS: EEG power spectral analysis during wakefulness and overnight polysomnogram were performed on alert, nondelirious patients at a long-term acute care facility. RESULTS: Forty-four patients had been ventilated for a median duration of 38 days at the time of the polysomnogram study. Eleven patients (25%) exhibited atypical sleep EEG. During wakefulness, relative EEG power spectral analysis revealed higher relative delta power in patients with atypical sleep than in patients with usual sleep (53% vs 41%; P < .001) and a higher slow-to-fast power ratio during wakefulness: 4.39 vs 2.17 (P < .001). Patients with atypical sleep displayed more subsyndromal delirium (36% vs 6%; P = .027) and less rapid eye movement sleep (4% vs 11% total sleep time; P < .02). Weaning failure was more common in the atypical sleep group than in the usual sleep group: 91% vs 45% (P = .013). INTERPRETATION: This study provides the first evidence that patients in a long-term acute care facility being weaned from prolonged ventilation exhibit atypical sleep EEG patterns that are associated with weaning failure. Patients with atypical sleep EEG patterns had higher rates of subsyndromal delirium and slowing of the wakeful EEG, suggesting that these two findings represent a biological signal for brain dysfunction.