Clonidine and Dexmedetomidine Increase the Pressor Response to Norepinephrine in Experimental Sepsis

Géloën, Alain; Chapelier, K; Cividjian, Andrei; Dantony, Emmanuelle; Rabilloud, Muriel; May, Carl; Quintin, Luc

doi:10.1097/ccm.0b013e3182986248

Cited by 65 publications

(85 citation statements)

References 28 publications

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“…DEX is a highly selective α-2 adrenoceptor agonist and inhibits sympathetic activity effectively (8,9). In recent years, increasing basic and clinical studies have proved that DEX protected against different types of organs.…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine protects against acute kidney injury through downregulating inflammatory reactions in endotoxemia rats

et al. 2015

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Abstract. Approximately 42% of patients with sepsis undergo acute kidney injury (AKI), which evidently influences patient survival. However, effective therapy strategies are lacking, thus, the present study investigated the protective effects of dexmedetomidine (DEX), a highly selective α-2 adrenoceptor agonist, in rat sepsis models. Rat sepsis models were generated through lipopolysaccharide injection (LPS; 5 mg/kg) in the tail vein. Rats were pretreated with DEX (10 µg/kg) 10 min before LPS injection to observe its protective effects. Of note, a unique α-2-adrenergic receptor antagonist, yohimbine (YOH; 1 mg/kg, intraperitoneally), was also used to antagonize the protective effects of DEX 30 min before DEX exposure. Thirty-two male Sprague Dawley rats were randomly divided into the Sham, LPS, DEX + LPS and YOH + DEX + LPS groups (n=8/group). All the rats were sacrificed 4 h later to observe the pathological changes of renal tissue, including plasma creatinine (Cr), blood urea nitrogen (BUN), kidney injury molecule-1 (KIM-1) and high mobility group protein 1 (HMGB-1) expression. Interleukin 6 (IL-6), IL-18 and tumor necrosis factor α (TNF-α) were all determined to examine the mechanisms of LPS-induced AKI relative to inflammatory reaction. The results indicated that AKI induced by LPS was serious. Renal pathological injury, plasma Cr, BUN, IL-6, IL-18 and TNF-α were all evidently increased in varying degrees. KIM-1 and HMGB-1 expression was upregulated in the LPS group (P<0.05 vs. Sham group). However, when rats were pretreated with DEX, AKI induced by LPS was decreased significantly. Renal pathological injury, plasma Cr, BUN, IL-6, IL-18, TNF-α, and KIM-1 and HMGB-1 expression were all reduced (P<0.05 vs. LPS group). In addition, exposure of the α-2-adrenergic receptor antagonist, YOH, eliminated this reduction. In conclusion, DEX protected against sepsis-induced AKI through depressing the inflammatory reaction, mechanisms of which may be associated with α-2 receptors inhibition. IntroductionSepsis, also called septicemia, is a serious complication of patients undergoing pathogen infection, trauma, burn, hypoxia, reperfusion injury and surgery, which could affect myocardial contractility, decreased organ oxygen uptake capacity, and can lead to septic shock and multiple organ dysfunction syndrome. This state is called systemic inflammatory response syndrome (1,2). The incidence of sepsis is extremely high in the intensive care unit (ICU), with a mortality of ≤40-80%. As reported, the kidney is one of the most susceptible target organs of sepsis (3). Approximately 50% of patients suffer from acute kidney injury (AKI) caused by sepsis. Notably, mortality of these patients is as high as 70% (4,5). However, the mechanisms of sepsis-induced AKI remain unclear and effective therapy strategies are also lacking.Inflammatory factors, such as interleukin 6 (IL-6), IL-18 and tumor necrosis factor α (TNF-α), play an important role in the pathological and physiological process, particularly IL-18. As recently reported, IL-1...

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Section: Introductionmentioning

confidence: 99%

Dexmedetomidine protects against acute kidney injury through downregulating inflammatory reactions in endotoxemia rats

et al. 2015

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“…DEX affects contractility, HR, and CO and is characterized by a biphasic response of the MAP and Rsys [4]. A small but significant decrease in SV in critically ill shock patients receiving DEX was reported previously [8].…”

Section: Discussionmentioning

confidence: 68%

“…Dexmedetomidine (DEX) is characterized by an intrinsic vasoconstrictive effect [3], which increases norepinephrine efficacy [4] and affects systolic myocardial function [5]. Alternatively, propofol (PROP) induces dose-dependent vasodilatation [6], without affecting systolic myocardial function [7].…”

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confidence: 99%

Different effects of propofol and dexmedetomidine on preload dependency in endotoxemic shock with norepinephrine infusion

Liu

et al. 2015

Journal of Surgical Research

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“…Provided that volemia is optimized (little or no ventilator-evoked variations in vena cava, little or no increase in cardiac output or BP following passive leg rising), sympathetic de-activation through the use of alpha-2 agonists warrants interest: a) increased pressor response to noradrenaline in the setting of septic shock [128,129] or experimental sepsis [130,131] b) reduced pulmonary hypertension [132] c) increased diastolic compliance [133] d) reduced intraabdominal pressure [134] e) reduced microvascular permeability [135], of interest as high pulmonary water content is considered [136]. In this respect, the reader should note that alpha-adrenergic blockade decreases pulmonary extravascular leakage in the setting of experimental haemorrhage [137] f) diuresis [138] in the setting of ascites [139−141], cardiac failure [142] and critical care [143] g) lowered pro-inflammatory IL6 [144], increased anti-inflammatory IL10 [145] The use of SV in the setting of early severe diffuse ARDS remains seldom used [39,40].…”

Section: Sedationmentioning

confidence: 99%

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

Petitjeans

Pichot

Ghignone

et al. 2016

Anaesthesiol Intensive Ther

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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 VO 2 , 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. Anestezjologia Intensywna Terapia 2016, tom 48, nr 5, 354-366Key words: acute respiratory distress syndrome, ARDS, severe ARDS; acute hypoxic non-hypercapnic respiratory failure; driving pressure; tidal volume, Vt, low tidal volume, ultra-low tidal volume; positive end-expiratory pressure, PEEP; transpulmonary pressure; controlled mechanical ventilation; spontaneous ventilation; spontaneous breathing; pressure support, airway pressure release ventilation; sedation, cooperative sedation; alpha-2 adrenergic agonist, clonidine, dexmedetomidineThe previous chapter overviewed, for residents rotating through the critical care unit (CCU), basic pathophysiology required to analyze early severe acute respiratory distress syndrome (ARDS). An emphasis was placed on spontaneous ventilation both in the setting of the healthy volunteer and of severe ARDS. This chapter will address the pros and cons of controlled mechanical ventilation, with the help of muscle relaxation, as opposed to the putative advantages of spontaneous ventilation. So far, spontaneous ventilation has not achieved evidence-based demonstration: thus, as in part I, conjectures are within [….], following [1]. i. MUSCLE RELAXATiON VERSUS SPONTANEOUS VENTiLATiON?When muscle relaxation is considered, the overall picture appears to be simplified with 48 h of muscle relaxation [2]. A sober interpretation may be considered. a. Muscle relaxationIn severe ARDS (P/F < 120), muscle relaxation [2] lowered the mortality (45 to 31%; difference of −32%; P = 0.04), multiple organ failure (MOF), and barotrauma and led to more ventilator-free days and identical CCU-acquired paresis. Muscle relaxation was hypothesized to minimize excessive transpulmonary pressure, patient-to-ventilator asynchrony [2], ventilator-induced lung injury (VILI), atelectrauma, overdistension,...

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Clonidine and Dexmedetomidine Increase the Pressor Response to Norepinephrine in Experimental Sepsis

Abstract: The pressor response to norepinephrine was reduced following lipopolysaccharide and increased to baseline levels following α-2 agonists.

Cited by 65 publications

References 28 publications

Dexmedetomidine protects against acute kidney injury through downregulating inflammatory reactions in endotoxemia rats

Dexmedetomidine protects against acute kidney injury through downregulating inflammatory reactions in endotoxemia rats

Different effects of propofol and dexmedetomidine on preload dependency in endotoxemic shock with norepinephrine infusion

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

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