How should dexmedetomidine and clonidine be prescribed in the critical care setting? / Como a dexmedetomidina e a clonidina devem ser prescritas no ambiente de terapia intensiva?

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. b) Switching from conventional to cooperative sedation in unstable patients (e.g., refractory delirium tremens, septic shock, acute respiratory distress syndrome, etc.): to avoid hypotension and bradycardia evoked by sympathetic deactivation, the short answer is to maintain the stroke volume through volume loading, vasopressors and inotropes. c) To avoid these switches and associated difficulties, alpha-2 agonists may be considered first-line sedatives. The short answer is to administer alpha-2 agonists slowly from admission or endotracheal intubation up to stabilized cooperative sedation. The "take home" message is as follows: a) alpha-2 agonists are jointly sympathetic deactivators and sedative agents; b) sympathetic deactivation implies maintaining the stroke volume and iterative assessment of volemia. Evidence-based medicine should document our propositions.

O manejo cardíaco, ventilatório e renal no ambiente de terapia intensiva tem melhorado nas últimas décadas. Cognição e sedação representam dois dos últimos desafios a vencer. Como a sedação convencional não é ideal, e a sedação evocada por agonistas adrenérgicos alfa-2 (sedação "cooperativa" com dexmedetomidina, clonidina ou guanfacina) representa uma alternativa valiosa, este artigo abrange três tópicos práticos para os quais há lacunas na medicina baseada em evidência. O primeiro deles é a mudança de sedação convencional para sedação cooperativa ("mudança"): a resposta curta consiste em retirada abrupta de sedação convencional, implantação imediata de infusão de um agonista alfa-2 e uso de "sedação de resgate" (bolos de midazolam) ou "sedação agressiva" (haloperidol em bolos) para estabilizar a sedação cooperativa. O segundo tópico é a mudança de sedação convencional para sedação cooperativa em pacientes instáveis (por exemplo: delirium tremens refratário, choque séptico, síndrome do desconforto respiratório agudo etc.), pois, para evitar a hipotensão e a bradicardia provocadas por desativadores simpáticos, a resposta curta é manter o volume sistólico por administração de volume, vasopressores e inotrópicos. Por fim, para evitar essas mudanças e dificuldades associadas, os agonistas alfa-2 podem ser sedativos de primeira linha. A resposta curta é administrar agonistas alfa-2 lentamente desde a admissão ou intubação endotraqueal, até estabilização da sedação cooperativa. Dessa forma, conclui-se que os agonistas alfa-2 são, ao mesmo tempo, agentes desativadores simpáticos e sedativos, bem como a desativação simpática implica na manutenção do volume sistólico e na avaliação persistente da volemia. A medicina baseada em evidência deve documentar esta proposta.

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. The acute circulatory distress is treated with volume expansion, administration of vasopressors (usually noradrenaline: NA), and inotropes. Ventilation and anti-infectious strategy shall not be discussed here. When circulation is considered, the literature is segregated between interventions directed to the systemic circulation vs. interventions directed to the micro-circulation. Our thesis is that, after stabilization of the acute cardioventilatory distress, the prolonged sympathetic hyperactivity is detrimental in the setting of septic shock. Our hypothesis is that the sympathetic hyperactivity observed in septic shock being normalized towards baseline activity will improve the microcirculation by recoupling the capillaries and the systemic circulation. Therefore, counterintuitively, antihypertensive agents such as beta-blockers or alpha-2 adrenergic agonists (clonidine, dexmedetomidine) are useful. They would reduce the noradrenaline requirements. Adjuncts (vitamins, steroids, NO donors/inhibitors, etc.) proposed to normalize the sepsis-evoked vasodilation are not reviewed. This itemized approach (systemic vs. microcirculation) requires physiological and epidemiological studies to look for reduced mortality.

Como a dexmedetomidina e a clonidina devem ser prescritas no ambiente de terapia intensiva? / How should dexmedetomidine and clonidine be prescribed in the critical care setting?

RESUMO O manejo cardíaco, ventilatório e renal no ambiente de terapia intensiva tem melhorado nas últimas décadas. Cognição e sedação representam dois dos últimos desafios a vencer. Como a sedação convencional não é ideal, e a sedação evocada por agonistas adrenérgicos alfa-2 (sedação "cooperativa" com dexmedetomidina, clonidina ou guanfacina) representa uma alternativa valiosa, este artigo abrange três tópicos práticos para os quais há lacunas na medicina baseada em evidência. O primeiro deles é a mudança de sedação convencional para sedação cooperativa ("mudança"): a resposta curta consiste em retirada abrupta de sedação convencional, implantação imediata de infusão de um agonista alfa-2 e uso de "sedação de resgate" (bolos de midazolam) ou "sedação agressiva" (haloperidol em bolos) para estabilizar a sedação cooperativa. O segundo tópico é a mudança de sedação convencional para sedação cooperativa em pacientes instáveis (por exemplo: delirium tremens refratário, choque séptico, síndrome do desconforto respiratório agudo etc.), pois, para evitar a hipotensão e a bradicardia provocadas por desativadores simpáticos, a resposta curta é manter o volume sistólico por administração de volume, vasopressores e inotrópicos. Por fim, para evitar essas mudanças e dificuldades associadas, os agonistas alfa-2 podem ser sedativos de primeira linha. A resposta curta é administrar agonistas alfa-2 lentamente desde a admissão ou intubação endotraqueal, até estabilização da sedação cooperativa. Dessa forma, conclui-se que os agonistas alfa-2 são, ao mesmo tempo, agentes desativadores simpáticos e sedativos, bem como a desativação simpática implica na manutenção do volume sistólico e na avaliação persistente da volemia. A medicina baseada em evidência deve documentar esta proposta.

ABSTRACT 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. b) Switching from conventional to cooperative sedation in unstable patients (e.g., refractory delirium tremens, septic shock, acute respiratory distress syndrome, etc.): to avoid hypotension and bradycardia evoked by sympathetic deactivation, the short answer is to maintain the stroke volume through volume loading, vasopressors and inotropes. c) To avoid these switches and associated difficulties, alpha-2 agonists may be considered first-line sedatives. The short answer is to administer alpha-2 agonists slowly from admission or endotracheal intubation up to stabilized cooperative sedation. The "take home" message is as follows: a) alpha-2 agonists are jointly sympathetic deactivators and sedative agents; b) sympathetic deactivation implies maintaining the stroke volume and iterative assessment of volemia. Evidence-based medicine should document our propositions.

Mental health and stress among ICU healthcare professionals in France according to intensity of the COVID-19 epidemic.

BACKGROUND: We investigated the impact of the COVID-19 crisis on mental health of professionals working in the intensive care unit (ICU) according to the intensity of the epidemic in France. METHODS: This cross-sectional survey was conducted in 77 French hospitals from April 22 to May 13 2020. All ICU frontline healthcare workers were eligible. The primary endpoint was the mental health, assessed using the 12-item General Health Questionnaire. Sources of stress during the crisis were assessed using the Perceived Stressors in Intensive Care Units (PS-ICU) scale. Epidemic intensity was defined as high or low for each region based on publicly available data from Santé Publique France. Effects were assessed using linear mixed models, moderation and mediation analyses. RESULTS: In total, 2643 health professionals participated; 64.36% in high-intensity zones. Professionals in areas with greater epidemic intensity were at higher risk of mental health issues (p < 0.001), and higher levels of overall perceived stress (p < 0.001), compared to low-intensity zones. Factors associated with higher overall perceived stress were female sex (B = 0.13; 95% confidence interval [CI] = 0.08-0.17), having a relative at risk of COVID-19 (B = 0.14; 95%-CI = 0.09-0.18) and working in high-intensity zones (B = 0.11; 95%-CI = 0.02-0.20). Perceived stress mediated the impact of the crisis context on mental health (B = 0.23, 95%-CI = 0.05, 0.41) and the impact of stress on mental health was moderated by positive thinking, b = - 0.32, 95% CI = - 0.54, - 0.11. CONCLUSION: COVID-19 negatively impacted the mental health of ICU professionals. Professionals working in zones where the epidemic was of high intensity were significantly more affected, with higher levels of perceived stress. This study is supported by a grant from the French Ministry of Health (PHRC-COVID 2020).

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). Therefore, the time interval between arrival to the CCU and switching to spontaneous ventilation (SV) is not focused on normalizing the different factors involved in the pathophysiology of ARDS: fever, low cardiac output, systemic acidosis, peripheral shutdown (local acidosis), supine position, hypocapnia (generated by hyperpnea and tachypnea), sympathetic activation, inflammation and agitation. Then, the extended period of controlled mechanical ventilation with paralysis under general anaesthesia leads to CCU-acquired pathology, including low cardiac output, myoneuropathy, emergence delirium and nosocomial infection. The stabilization of the acute cardio-ventilatory distress should primarily itemize the pathophysiological conditions: fever control, improved micro-circulation and normalized local acidosis, 'upright' position, minimized hypercapnia, sympathetic de-activation (normalized sympathetic activity toward baseline levels resulting in improved micro-circulation with alpha-2 agonists administered immediately following optimized circulation and endotracheal intubation), lowered inflammation and 'cooperative' sedation without respiratory depression evoked by alpha-2 agonists. Normalised metabolic, circulatory and ventilatory demands will allow one to single out the oxygenation defect managed with high PEEP (diffuse recruitable ARDS) under early spontaneous ventilation (airway pressure release ventilation+SV or low-pressure support). Assuming an improved overall status, PaO2/FiO2≥150-200 allows for extubation and continuous non-invasive ventilation. Such fast-tracking may avoid most of the CCU-acquired pathologies. Evidence-based demonstration is required.

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. This implies that the management of the ventilator may be a life-saver by reducing the duration of mechanical ventilation, or detrimental by extending this duration, leading into critical care-acquired diseases. Indeed, a high PEEP (10-24 cm H2O) appears to be a life-saver in the context of early severe diffuse ARDS; c) tidal volume and plateau pressure cannot be identical for all patients; d) the only remaining rationale for CMV and muscle relaxation is to suppress patient-ventilator asynchrony and to lower VO2, during the acute cardio-ventilatory distress. Therefore, in early severe diffuse ARDS, this review argues for a combination of a high PEEP (preferably titrated on transpulmonary pressure) with spontaneous ventilation + pressure support (or newer modes of ventilation). However, conditionalities are stringent: upfront circulatory optimization, upright positioning, lowered VO2, lowered acidotic and hypercapnic drives, sedation without ventilatory depression and without lowered muscular tone. As these propositions require evidence-based demonstration, the accepted practice remains, in 2016, controlled mechanical ventilation, muscle relaxation, and prone position.

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). As these propositions require evidence-based demonstration, the reader is reminded that the accepted practice remains, in 2016, controlled mechanical ventilation, muscle relaxation and prone position.

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. CONCLUSION: Given the complications associated with tracheal intubation and mechanical ventilation on the one hand and with delayed intubation on the other hand, high PEEP-NIV may warrant study in a restricted set of patients closely monitored in a critical care environment.