Abstract
BackgroundSeptic patients often require sedation in intensive care unit, and midazolam is one of the most frequently used sedatives among them. But the interaction between midazolam and septic shock is not known. The aim of this study is to investigate the effects of midazolam on preload dependency in an endotoxic shock model by evaluating systemic vascular tone and cardiac function.MethodsEighteen rabbits were randomly divided into three groups: Control group, MID1 group and MID2 group. Rabbits underwent ketamine anaesthesia and mechanical ventilation, and haemodynamic assessments were recorded in three groups (T0). Endotoxic shock was induced by lipopolysaccharide intravenously, and fluid resuscitation and norepinephrine were administered to obtain the baseline mean arterial pressure (MAP) (T1). Rabbits received equivalent normal saline (Control) and two consecutive dosages of midazolam: 0.3 mg kg−1 h−1 (MID1) and 3 mg kg−1 h−1 (MID2) (T2). Rabbits received another round of fluid challenge and norepinephrine infusion to return the MAP to normal (T3).ResultsNo significant differences in haemodynamic parameters were observed in three groups at T0, T1 or T3. Midazolam infusion significantly increased pulse pressure variation (PPV) and stroke volume variation (SVV) compared to the values in Control group, and MAP, central venous pressure (CVP), mean systemic filling pressure (Pmsf) and cardiac output (CO) decreased at T2. Same effects were observed with increasing doses of midazolam, and resistance for venous return (Rvr) decreased (MID1 vs. MID2) at T2. PPV and SVV increased significantly at T2 compared to the values at T1. MAP, CVP, Pmsf and CO decreased in MID1 and MID2 groups. Rvr also decreased in MID2 group (T2 vs. T1). Midazolam did not affect cardiac function index, systemic vascular resistance or artery resistance (T2 vs. T1).ConclusionsMidazolam administration promoted preload dependency in septic shock models via decreased venous vascular tone without affecting cardiac function.
Highlights
Septic patients often require sedation in intensive care unit, and midazolam is one of the most frequently used sedatives among them
In the present experimental, randomized study, we investigated the effects of midazolam on preload dependency in rabbits subjected to endotoxic shock with norepinephrine infusion by evaluating the systemic vascular system and cardiac function
No differences were detected between the Control, MID1 and MID2 groups with respect to the time to achieve endotoxic shock (29.1 ± 6.8, 28.4 ± 7.2 and 29.0 ± 7.0 min, respectively; p > 0.05) or the volume of administered fluid during T0–T1 and T1– T2
Summary
Septic patients often require sedation in intensive care unit, and midazolam is one of the most frequently used sedatives among them. Septic shock is a deleterious systemic host response to infection characterized by hypotension that is not reversed with fluids alone. Septic shock is a common reason for admission to the intensive care unit (ICU) [1]. The response to fluid challenge is complicated by Patients with septic shock generally require mechanical ventilation, which makes the use of sedative drugs almost imperative to reduce anxiety and agitation and facilitate care. Chen et al Ann. Intensive Care (2018) 8:59 used to sedate patients in the ICU, and a recent survey demonstrated that midazolam remains widely used [4]. Midazolam attenuates the release of catecholamines in vivo and induces vasoplegia, which contributes to the resulting haemodynamic changes [7, 8]
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