Avoiding, Not Managing, Drug Withdrawal Syndrome in the Setting of COVID-19 Acute Respiratory Distress Syndrome. Comment on Ego et al. How to Manage Withdrawal of Sedation and Analgesia in Mechanically Ventilated COVID-19 Patients? 2021, , 4917.

The management of sedation in the setting of COVID-19 ("COVID") by Ego et al. [..

How should dexmedetomidine and clonidine be prescribed in the critical care setting?

Cardiac, ventilatory and kidney management in the critical care setting has been optimized over the past decades. Cognition and sedation represent one of the last remaning challenges. As conventional sedation is suboptimal and as the sedation evoked by alpha-2 adrenergic agonists ("cooperative" sedation with dexmedetomidine, clonidine or guanfacine) represents a valuable alternative, this manuscript covers three practical topics for which evidence-based medicine is lacking: a) Switching from conventional to cooperative sedation ("switching"): the short answer is the abrupt withdrawal of conventional sedation, immediate implementation of alpha-2 agonist infusion and the use of "rescue sedation" (midazolam bolus[es]) or "breakthrough sedation" (haloperidol bolus[es]) to stabilize cooperative sedation.

Is the Sympathetic System Detrimental in the Setting of Septic Shock, with Antihypertensive Agents as a Counterintuitive Approach? A Clinical Proposition.

Mortality in the setting of septic shock varies between 20% and 100%. Refractory septic shock leads to early circulatory failure and carries the worst prognosis. The pathophysiology is poorly understood despite studies of the microcirculatory defects and the immuno-paralysis.

Clinical Practice: Should we Radically Alter our Sedation of Critical Care Patients, Especially Given the COVID-19 Pandemics?

The high number of patients infected with the SARS-CoV-2 virus requiring care for ARDS puts sedation in the critical care unit (CCU) to the edge. Depth of sedation has evolved over the last 40 years (no-sedation, deep sedation, daily emergence, minimal sedation, etc.).

Hypothesis: Fever control, a niche for alpha-2 agonists in the setting of septic shock and severe acute respiratory distress syndrome?

During severe septic shock and/or severe acute respiratory distress syndrome (ARDS) patients present with a limited cardio-ventilatory reserve (low cardiac output and blood pressure, low mixed venous saturation, increased lactate, low PaO2/FiO2 ratio, etc.), especially when elderly patients or co-morbidities are considered. Rescue therapies (low dose steroids, adding vasopressin to noradrenaline, proning, almitrine, NO, extracorporeal membrane oxygenation, etc.

Building on the Shoulders of Giants: Is the use of Early Spontaneous Ventilation in the Setting of Severe Diffuse Acute Respiratory Distress Syndrome Actually Heretical?

Acute respiratory distress syndrome (ARDS) is not a failure of the neurological command of the ventilatory muscles or of the ventilatory muscles; it is an oxygenation defect. As positive pressure ventilation impedes the cardiac function, paralysis under general anaesthesia and controlled mandatory ventilation should be restricted to the interval needed to control the acute cardio-ventilatory distress observed upon admission into the critical care unit (CCU; "salvage therapy" during "shock state"). Current management of early severe diffuse ARDS rests on a prolonged interval of controlled mechanical ventilation with low driving pressure, paralysis (48 h, too often overextended), early proning and positive end-expiratory pressure (PEEP).

Do we feel pain during anesthesia? A critical review on surgery-evoked circulatory changes and pain perception.

The difficulty of defining the three so-called components of « an-esthesia » is emphasized: hypnosis, absence of movement, and adequacy of anti-nociception (intraoperative « analgesia »). Data obtained from anesthetized animals or humans delineate the activation of cardiac and vasomotor sympathetic reflex (somato-sympathetic reflex) and the cardiac parasympathetic deactivation observed following somatic stimuli. Sympathetic activation and parasympathetic deactivation are used as monitors to address the adequacy of intraoperative anti-nociception.

Early severe acute respiratory distress syndrome: What's going on? Part II: controlled vs. spontaneous ventilation?

The second part of this overview on early severe ARDS delineates the pros and cons of the following: a) controlled mechanical ventilation (CMV: lowered oxygen consumption and perfect patient-to-ventilator synchrony), to be used during acute cardio-ventilatory distress in order to "buy time" and correct circulatory insufficiency and metabolic defects (acidosis, etc.); b) spontaneous ventilation (SV: improved venous return, lowered intrathoracic pressure, absence of muscle atrophy). Given a stabilized early severe ARDS, as soon as the overall clinical situation improves, spontaneous ventilation will be used with the following stringent conditionalities: upfront circulatory optimization, upright positioning, lowered VO2, lowered acidotic and hypercapnic drives, sedation without ventilatory depression and without lowered muscular tone, as well as high PEEP (titrated on transpulmonary pressure, or as a second best: "trial"-PEEP) with spontaneous ventilation + pressure support (or newer modes of ventilation).

Early severe acute respiratory distress syndrome: What's going on? Part I: pathophysiology.

Severe acute respiratory distress syndrome (ARDS, PaO₂/FiO₂ < 100 on PEEP ≥ 5 cm H₂O) is treated using controlled mechanical ventilation (CMV), recently combined with muscle relaxation for 48 h and prone positioning. While the amplitude of tidal volume appears set < 6 mL kg⁻¹, the level of positive end-expiratory pressure (PEEP) remains controversial. This overview summarizes several salient points, namely: a) ARDS is an oxygenation defect: consolidation/ difuse alveolar damage is reversed by PEEP and/or prone positioning, at least during the early phase of ARDS b) ARDS is a dynamic disease and partially iatrogenic.

Pressor Response to Noradrenaline in the Setting of Septic Shock: Anything New under the Sun-Dexmedetomidine, Clonidine? A Minireview.

Progress over the last 50 years has led to a decline in mortality from ≈70% to ≈20% in the best series of patients with septic shock. Nevertheless, refractory septic shock still carries a mortality close to 100%. In the best series, the mortality appears related to multiple organ failure linked to comorbidities and/or an intense inflammatory response: shortening the period that the subject is exposed to circulatory instability may further lower mortality.

A centrally acting antihypertensive, clonidine, combined to a venous dilator, nitroglycerin, to handle severe pulmonary edema.

A patient, with known left ventricular failure presented with severe pulmonary edema, an ejection fraction of 10% to 15%, knee mottling, and lactates of 7 mM L⁻¹. He was treated with unusually high-dose nitroglycerin (NTG) intravenously (IV; NTG ≈ 70 mg for 1 hour). To suppress dyspnea, systolic blood pressure had to be lowered from ≈ 150-160 to ≈ 100-120 mm Hg.

Acute iterative bronchospasm and "do not re-intubate" orders: sedation by an alpha-2 agonist combined with noninvasive ventilation.

A male patient presented with bronchospasm and acute respiratory distress. The patient had presented 2 previous episodes of severe bronchospasm following abdominal surgery, leading twice to intubation, mechanical ventilation, and conventional sedation. As the patient positively rejected a third episode of intubation + mechanical ventilation, noninvasive ventilation (pressure support = 8 cm H₂O, positive end-expiratory pressure = 10 cm H₂O), inhaled therapy, and clonidine orally (≈ 4 μg/kg) were combined.

Swift recovery of severe hypoxemic pneumonia upon morbid obesity.

A morbidly obese (body mass index = 55.5) female patient presented with severe hypoxemic community acquired pneumonia [PaO2/FiO2 (P/F) = 57] with primarily right basal atelectasis, but without bilateral opacities in the upper lobes on the chest X-ray. Major O2 desaturations led the nurses to object to moving the patient to the prone position: muscle relaxation combined to prone position was impossible.

Swift recovery of severe acute hypoxemic respiratory failure under non-invasive ventilation.

Background: In the setting of severe acute respiratory distress syndrome (ARDS; PaO2/FiO2 < 100), the cut-off point for switching from non-invasive ventilation to intubation combined to mechanical ventilation is poorly defined.

Results: The swift resolution over 10 h of a severe acute hypoxemic respiratory failure (P/F = 57) caused by aspiration following heroin overdose, using non-invasive ventilation (NIV)-high PEEP (15-20 cm H2O)-low pressure support (8 cm H20) is reported. The success in treating non-invasively severe hypoxia was presumably linked to a highly restricted subset: healthy young patient, minimal alteration of consciousness, non-combativeness, absence of severe metabolic acidosis, quick resolution of supraventricular arrhythmia, one-to-one supervision by the intensivist in the critical care unit.

Is there a place for pressure-support ventilation and high positive end-expiratory pressure combined to alpha-2 agonists early in severe diffuse acute respiratory distress syndrome?

Acute respiratory distress syndrome (ARDS) is associated with a high mortality linked primarily to co-morbidities (sepsis, cardiac failure, multiple organ failure, etc.). When the lung is the single failing organ, quick resolution of ARDS should skip some complications arising from a prolonged stay in the critical care unit.

Combination of clonidine sedation and spontaneous breathing-pressure support upon acute respiratory distress syndrome: a feasibility study in four patients.

Introduction: As alpha-2 agonists preserve ventilator drive, patients presenting with acute respiratory distress syndrome (ARDS, Pa02/FiO2 < 200) were managed using sedation with an alpha-2 agonist, clonidine, combined to spontaneous ventilation (SV) + pressure support ventilation (PS).

Methods: Sedation was provided by an alpha-2 agonist, clonidine 1-2 microg x kg(-1( x h(-1), without bolus administration, and supplemented with a neuroleptic, loxapine, if needed. Four patients presenting with ARDS were managed with pressure support ventilation (PS = 8 cm H20,rarely 10-12 cm H20) and high PEEP (10-20 cm H20).

[Dexmedetomidine and clonidine: a review of their pharmacodynamy to define their role for sedation in intensive care patients].

Alpha-2 adrenergic agonists ("alpha-2 agonists") present multiple pharmacodynamic effects: rousable sedation, decreased incidence of delirium in the setting of critical care, preservation of respiratory drive, decreased whole body oxygen consumption, decreased systemic and pulmonary arterial impedance, improved left ventricular systolic and diastolic function, preserved vascular reactivity to exogenous catecholamines, preserved vasomotor baroreflex with lowered set point, preserved kidney function, decreased protein catabolism. These pharmacodynamic effects explain the interest for these drugs in the critical care setting. However, their exact role for sedation in critically ill-patients remains open for further studies.

Dexmedetomidine and clonidine: from second- to first-line sedative agents in the critical care setting?

In the critical care setting, α-2 agonists present a multifaceted profile: sedation combined with arousability, suppression of delirium, preservation of respiratory drive, reduced O(2) consumption, preserved renal function, and reduced protein metabolism. In addition, this review details the reduced arterial impedance, improved left ventricular performance, preserved vascular reactivity to exogenous amines, preserved cardiac baroreflex reactivity, preserved vasomotor baroreflex activity combined with a lowered pressure set point: these features may explain the good tolerance observed when α-2 agonists are used as continuous infusion without any loading dose. Reviewing the literature allows one to suggest that a new management appears possible with arousable sedation.

Alpha-2 agonists to reduce vasopressor requirements in septic shock?

One of the unsolved problems of septic shock is the poor responsiveness, or reduced vascular reactivity, to vasopressors used to increase blood pressure (BP). Attempts to restore vascular reactivity with NO inhibitors or low dose steroids have met with little success. Low vascular reactivity, which may lead to refractory shock and death, is linked to desensitization or down-regulation of alpha-1 adrenergic receptors.