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. 2021 Oct-Dec;33(4):600-615.
doi: 10.5935/0103-507X.20210087. Epub 2022 Jan 24.

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

[Article in English, Portuguese]
Dan Longrois  1 , Fabrice Petitjeans  2 , Olivier Simonet  3 , Marc de Kock  3 , Marc Belliveau  4 , Cyrille Pichot  5 , Thomas Lieutaud  6 , Marco Ghignone  7 , Luc Quintin  2
Affiliations

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

[Article in English, Portuguese]
Dan Longrois et al. Rev Bras Ter Intensiva. 2021 Oct-Dec.

Abstract
in English, Portuguese

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.

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Conflict of interest statement

Conflicts of interest: L Quintin holds US Patents 8 703 697, April 22, 2014: Method for treating early severe diffuse acute respiratory distress syndrome and 8 846 606 B2, September 30, 2014: Method and drug composition for treating septic shock hypotension.

Figures

Figure 1
Figure 1
Relationship between smooth muscle activity and the frequency of sympathetic nerve stimuli in capacitance and resistance vessels: frequency-response curve is deduced for resistance (dashed) and capacitance (continuous) in cat skin muscle.
Figure 2
Figure 2
Iterative passive leg raising (PLR) to address hypovolemia before administration of an alpha-2 agonist in patients presenting with circulatory instability.
Figure 3
Figure 3
“Start slow, go slow” administration of alpha-2 agonists in patients presenting with circulatory instability.
See this image and copyright information in PMC

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