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      A pandemic of cognitive bias

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      Intensive Care Medicine
      Springer Berlin Heidelberg

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          Abstract

          The Sars-CoV-2 pandemic is an unprecedented challenge to today’s clinicians: the urgent need to act, the lack of time to collect robust evidence and the collective fear of failure have created ideal conditions for cognitive biases to flourish. A cognitive bias is a systematic pattern of deviation from an established norm or rationality in judgment [1]. Individuals create their own “subjective reality” from their perception of the input. As a result, individuals’ construction of reality may guide their behavior in the world. Although some cognitive biases can be adaptive since they may lead to more effective actions in a given context, especially when timeliness is more valuable than accuracy, they may also lead to perceptual distortion, inaccurate judgment and illogical decisions as they result from our limited capacity for information processing. The current pandemic has given us many examples of cognitive biases. Hoarding food and toilet paper despite official assurances of sufficient and stable supply are examples of impaired decision-making: stressed people often believe that taking action, any action, no matter the kind, tends to resolve problems, a phenomenon known as action bias. Such a bias will naturally be amplified in a social context because of the human tendency to follow blindly the actions of the others (the “bandwagon effect”) out of fear of missing out on something [2]. Unfortunately, queuing in front of a supermarket can only create dangerous vicious circles by spreading infection and panic. The same happened with the use of hydroxychloroquine leading to misleading and harmful consequences [3]. Cognitive biases have been responsible for flawed narratives around key parts of our health system. For example, the notion that coronavirus disease 2019 (COVID-19) mortality rates are strictly dependent on the availability of ventilators has enabled a focus on one objective element of the system. However, this has come at the expense of forgetting that the patients on mechanical ventilation need a comprehensive healthcare support system, with a range of other equipment as well as suitably trained manpower and ventilators are a minimal part in the system. This is an example of what is called substitution bias, where, faced with a complex and difficult question (how to make sure the healthcare system is capable of delivering that support), an easier one (how to increase the supply of ventilators) is substituted. While intensivists may find it ridiculous to focus only on available ventilators, they have not been immune from cognitive bias. Notably, we lacked suitable definitions of what we were facing and have merely used the labels we had, an example of representativeness bias. As result, we named diffuse COVID-19 pneumonia as acute respiratory distress syndrome (ARDS) and accordingly we used ARDS ventilation protocols [4]. Similarly, once we labelled the problem as a “viral infection” we started using antiviral drugs developed for Ebola and HIV despite the absence of evidence to support their use in this context [5, 6]. Scientific research, whose role should be to guide our decisions, has not helped. The need to share information as quickly as possible has legitimized poor quality literature: EBM has stopped being Evidence-Based Medicine and has given way to Emergency-Based Medicine, with clinicians making decisions on the basis of hypotheses, anecdotes, case reports and ambiguous data. Without evidence to guide us, and therefore the ability to offer the right quality of care to patients, we have reacted to the pandemic by offering a “fruit salad” of different drugs whose efficacy is far to be recognized. Psychosocial norms teach us that inconsistency is not a desirable trait and consequently people try hard to maintain their intellectual commitments and beliefs even against evidence (known as commitment bias) [7]. It can, therefore, be difficult to admit one’s own irrational and faltering reactions to an emergency. However, it is only by accepting our limitations and understanding our cognitive biases that we can turn the current chaos into an opportunity.

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          Most cited references6

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          COVID-19 pneumonia: different respiratory treatments for different phenotypes?

          The Surviving Sepsis Campaign panel recently recommended that “mechanically ventilated patients with COVID-19 should be managed similarly to other patients with acute respiratory failure in the ICU [1].” Yet, COVID-19 pneumonia [2], despite falling in most of the circumstances under the Berlin definition of ARDS [3], is a specific disease, whose distinctive features are severe hypoxemia often associated with near normal respiratory system compliance (more than 50% of the 150 patients measured by the authors and further confirmed by several colleagues in Northern Italy). This remarkable combination is almost never seen in severe ARDS. These severely hypoxemic patients despite sharing a single etiology (SARS-CoV-2) may present quite differently from one another: normally breathing (“silent” hypoxemia) or remarkably dyspneic; quite responsive to nitric oxide or not; deeply hypocapnic or normo/hypercapnic; and either responsive to prone position or not. Therefore, the same disease actually presents itself with impressive non-uniformity. Based on detailed observation of several cases and discussions with colleagues treating these patients, we hypothesize that the different COVID-19 patterns found at presentation in the emergency department depend on the interaction between three factors: (1) the severity of the infection, the host response, physiological reserve and comorbidities; (2) the ventilatory responsiveness of the patient to hypoxemia; (3) the time elapsed between the onset of the disease and the observation in the hospital. The interaction between these factors leads to the development of a time-related disease spectrum within two primary “phenotypes”: Type L, characterized by Low elastance (i.e., high compliance), Low ventilation-to-perfusion ratio, Low lung weight and Low recruitability and Type H, characterized by High elastance, High right-to-left shunt, High lung weight and High recruitability. COVID-19 pneumonia, Type L At the beginning, COVID-19 pneumonia presents with the following characteristics: Low elastance. The nearly normal compliance indicates that the amount of gas in the lung is nearly normal [4]. Low ventilation-to-perfusion (VA/Q) ratio. Since the gas volume is nearly normal, hypoxemia may be best explained by the loss of regulation of perfusion and by loss of hypoxic vasoconstriction. Accordingly, at this stage, the pulmonary artery pressure should be near normal. Low lung weight. Only ground-glass densities are present on CT scan, primarily located subpleurally and along the lung fissures. Consequently, lung weight is only moderately increased. Low lung recruitability. The amount of non-aerated tissue is very low; consequently, the recruitability is low [5]. To conceptualize these phenomena, we hypothesize the following sequence of events: the viral infection leads to a modest local subpleural interstitial edema (ground-glass lesions) particularly located at the interfaces between lung structures with different elastic properties, where stress and strain are concentrated [6]. Vasoplegia accounts for severe hypoxemia. The normal response to hypoxemia is to increase minute ventilation, primarily by increasing the tidal volume [7] (up to 15–20 ml/kg), which is associated with a more negative intrathoracic inspiratory pressure. Undetermined factors other than hypoxemia markedly stimulate, in these patients, the respiratory drive. The near normal compliance, however, explains why some of the patients present without dyspnea as the patient inhales the volume he expects. This increase in minute ventilation leads to a decrease in PaCO2. The evolution of the disease: transitioning between phenotypes The Type L patients may remain unchanging for a period and then improve or worsen. The possible key feature which determines the evolution of the disease, other than the severity of the disease itself, is the depth of the negative intrathoracic pressure associated with the increased tidal volume in spontaneous breathing. Indeed, the combination of a negative inspiratory intrathoracic pressure and increased lung permeability due to inflammation results in interstitial lung edema. This phenomenon, initially described by Barach in [8] and Mascheroni in [9] both in an experimental setting, has been recently recognized as the leading cause of patient self-inflicted lung injury (P-SILI) [10]. Over time, the increased edema increases lung weight, superimposed pressure and dependent atelectasis. When lung edema reaches a certain magnitude, the gas volume in the lung decreases, and the tidal volumes generated for a given inspiratory pressure decrease [11]. At this stage, dyspnea develops, which in turn leads to worsening P-SILI. The transition from Type L to Type H may be due to the evolution of the COVID-19 pneumonia on one hand and the injury attributable to high-stress ventilation on the other. COVID-19 pneumonia, Type H The Type H patient: High elastance. The decrease in gas volume due to increased edema accounts for the increased lung elastance. High right-to-left shunt. This is due to the fraction of cardiac output perfusing the non-aerated tissue which develops in the dependent lung regions due to the increased edema and superimposed pressure. High lung weight. Quantitative analysis of the CT scan shows a remarkable increase in lung weight (> 1.5 kg), on the order of magnitude of severe ARDS [12]. High lung recruitability. The increased amount of non-aerated tissue is associated, as in severe ARDS, with increased recruitability [5]. The Type H pattern, 20–30% of patients in our series, fully fits the severe ARDS criteria: hypoxemia, bilateral infiltrates, decreased the respiratory system compliance, increased lung weight and potential for recruitment. Figure 1 summarizes the time course we described. In panel a, we show the CT in spontaneous breathing of a Type L patient at admission, and in panel b, its transition in Type H after 7 days of noninvasive support. As shown, a similar degree of hypoxemia was associated with different patterns in lung imaging. Fig. 1 a CT scan acquired during spontaneous breathing. The cumulative distribution of the CT number is shifted to the left (well-aerated compartments), being the 0 to − 100 HU compartment, the non-aerated tissue virtually 0. Indeed, the total lung tissue weight was 1108 g, 7.8% of which was not aerated and the gas volume was 4228 ml. Patient receiving oxygen with venturi mask inspired oxygen fraction of 0.8. b CT acquired during mechanical ventilation at end-expiratory pressure at 5 cmH2O of PEEP. The cumulative distribution of the CT scan is shifted to the right (non-aerated compartments), while the left compartments are greatly reduced. Indeed, the total lung tissue weight was 2744 g, 54% of which was not aerated and the gas volume was 1360 ml. The patient was ventilated in volume controlled mode, 7.8 ml/kg of tidal volume, respiratory rate of 20 breaths per minute, inspired oxygen fraction of 0.7 Respiratory treatment Given this conceptual model, it follows that the respiratory treatment offered to Type L and Type H patients must be different. The proposed treatment is consistent with what observed in COVID-19, even though the overwhelming number of patients seen in this pandemic may limit its wide applicability. The first step to reverse hypoxemia is through an increase in FiO2 to which the Type L patient responds well, particularly if not yet breathless. In Type L patients with dyspnea, several noninvasive options are available: high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV). At this stage, the measurement (or the estimation) of the inspiratory esophageal pressure swings is crucial [13]. In the absence of the esophageal manometry, surrogate measures of work of breathing, such as the swings of central venous pressure [14] or clinical detection of excessive inspiratory effort, should be assessed. In intubated patients, the P0.1 and P occlusion should also be determined. High PEEP, in some patients, may decrease the pleural pressure swings and stop the vicious cycle that exacerbates lung injury. However, high PEEP in patients with normal compliance may have detrimental effects on hemodynamics. In any case, noninvasive options are questionable, as they may be associated with high failure rates and delayed intubation, in a disease which typically lasts several weeks. The magnitude of inspiratory pleural pressures swings may determine the transition from the Type L to the Type H phenotype. As esophageal pressure swings increase from 5 to 10 cmH2O—which are generally well tolerated—to above 15 cmH2O, the risk of lung injury increases and therefore intubation should be performed as soon as possible. Once intubated and deeply sedated, the Type L patients, if hypercapnic, can be ventilated with volumes greater than 6 ml/kg (up to 8–9 ml/kg), as the high compliance results in tolerable strain without the risk of VILI. Prone positioning should be used only as a rescue maneuver, as the lung conditions are “too good” for the prone position effectiveness, which is based on improved stress and strain redistribution. The PEEP should be reduced to 8–10 cmH2O, given that the recruitability is low and the risk of hemodynamic failure increases at higher levels. An early intubation may avert the transition to Type H phenotype. Type H patients should be treated as severe ARDS, including higher PEEP, if compatible with hemodynamics, prone positioning and extracorporeal support. In conclusion, Type L and Type H patients are best identified by CT scan and are affected by different pathophysiological mechanisms. If not available, signs which are implicit in Type L and Type H definition could be used as surrogates: respiratory system elastance and recruitability. Understanding the correct pathophysiology is crucial to establishing the basis for appropriate treatment.
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            Knee-deep in the big muddy: a study of escalating commitment to a chosen course of action

            Barry Staw (1976)
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              Hydroxychloroquine for the Prevention of Covid-19 — Searching for Evidence

              Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has generated a worldwide pandemic. The interruption of its spread depends on a combination of pharmacologic and nonpharmacologic interventions. Initial SARS-CoV-2 prevention includes social distancing, the use of face masks, environmental hygiene, and hand washing. 1 Although the most important pharmacologic interventions to prevent SARS-CoV-2 infection are likely to be vaccines, the repurposing of established drugs for short-term prophylaxis is another, more immediate option. Some researchers have promoted chloroquine and hydroxychloroquine for the treatment and prevention of illness from a variety of microorganisms, including SARS-CoV. 2 Hydroxychloroquine can inhibit replication of SARS-CoV-2 in vitro. 3 Some observational studies have suggested benefits of hydroxychloroquine for the treatment of Covid-19, whereas other treatment reports have described mixed results. 4 Boulware et al. now report in the Journal the results of a randomized trial testing hydroxychloroquine as postexposure prophylaxis for Covid-19. 5 This is described by the investigators as a “pragmatic” trial in which participants were recruited through social media and almost all data were reported by the participants. Adults who described a high-risk or moderate-risk exposure to someone with Covid-19 in their household or an occupational setting were provided hydroxychloroquine or placebo (by mail) within 4 days after the reported exposure, and before symptoms would be expected to develop. The authors enrolled 821 participants; an illness that was considered to be consistent with Covid-19 developed in 107 participants (13.0%) but was confirmed by polymerase-chain-reaction assay in less than 3% of the participants. The incidence of a new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]). Although participant-reported side effects were significantly more common in those receiving hydroxychloroquine (40.1%) than in those receiving placebo (16.8%), no serious adverse reactions were reported. This trial has many limitations, acknowledged by the investigators. The trial methods did not allow consistent proof of exposure to SARS-CoV-2 or consistent laboratory confirmation that the symptom complex that was reported represented a SARS-CoV-2 infection. Indeed, the specificity of participant-reported Covid-19 symptoms is low, 6 so it is hard to be certain how many participants in the trial actually had Covid-19. Adherence to the interventions could not be monitored, and participants reported less-than-perfect adherence, more notably in the group receiving hydroxychloroquine. In addition, those enrolled in the trial were younger (median age, 40 years) and had fewer coexisting conditions than persons in whom severe Covid-19 is most likely to develop, 7 so enrollment of higher-risk participants might have yielded a different result. The trial design raises questions about the expected prevention benefits of hydroxychloroquine. Studies of postexposure prophylaxis are intended to provide an intervention in the shortest possible time to prevent infection. In a small-animal model of SARS-CoV-2 infection, 8 prevention of infection or more severe disease was observed only when the experimental antiviral agent was given before or shortly after exposure. In the current trial, the long delay between perceived exposure to SARS-CoV-2 and the initiation of hydroxychloroquine (≥3 days in most participants) suggests that what was being assessed was prevention of symptoms or progression of Covid-19, rather than prevention of SARS-CoV-2 infection. Drugs for the prevention of infections must have an excellent safety profile. When hydroxychloroquine was initially promoted as a possible solution to SARS-CoV-2 infection, the safety of the drug was emphasized. 2 Under closer scrutiny, however, the potential for cardiac toxic effects and overall adverse outcomes have been emphasized, especially in persons with underlying coexisting conditions that increase the risk of severe Covid-19. 9 Boulware et al. report frequent mild side effects of hydroxychloroquine, but cardiac toxic effects could not be assessed. So, what are we to do with the results of this trial? The advocacy and widespread use of hydroxychloroquine seem to reflect a reasonable fear of SARS-CoV-2 infection. However, it would appear that to some extent the media and social forces — rather than medical evidence — are driving clinical decisions and the global Covid-19 research agenda. 10 On June 1, 2020, ClinicalTrials.gov listed a remarkable 203 Covid-19 trials with hydroxychloroquine, 60 of which were focused on prophylaxis. An important question is to what extent the article by Boulware et al. should affect planned or ongoing hydroxychloroquine trials. If postexposure prophylaxis with hydroxychloroquine does not prevent symptomatic SARS-CoV-2 infection (with recognition of the limitations of the trial under discussion), should other trials of postexposure prophylaxis with hydroxychloroquine continue unchanged? Do the participants in these trials need to be informed of these results? Do these trial results with respect to postexposure prophylaxis affect trials of preexposure prophylaxis with hydroxychloroquine, some of which are very large (e.g., the Healthcare Worker Exposure Response and Outcomes of Hydroxychloroquine [HERO-HCQ] trial, involving 15,000 health care workers; ClinicalTrials.gov number, NCT04334148)? The results reported by Boulware et al. are more provocative than definitive, suggesting that the potential prevention benefits of hydroxychloroquine remain to be determined.
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                Author and article information

                Contributors
                francescolanducci@gmail.com
                Journal
                Intensive Care Med
                Intensive Care Med
                Intensive Care Medicine
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0342-4642
                1432-1238
                27 October 2020
                : 1-2
                Affiliations
                [1 ]Anaesthesia and Intensive Care Department, San Giovanni Di Dio Hospital, Via di Torregalli 3, 50143 Florence, Italy
                [2 ]Anesthesiology Institute, Cleveland Clinic Abu Dhabi, Al Maryah Island, PO box 112412, Abu Dhabi, United Arab Emirates
                Author information
                http://orcid.org/0000-0001-9574-8713
                http://orcid.org/0000-0001-8270-2724
                Article
                6293
                10.1007/s00134-020-06293-y
                7590556
                33108517
                98673ea8-3879-465f-8228-d1935c1498a7
                © Springer-Verlag GmbH Germany, part of Springer Nature 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 29 September 2020
                : 12 October 2020
                Categories
                From the Inside

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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