ABSTRACT
Objective To investigate the clinical efficacy of methylene blue in the treatment of refractory hypotension caused by vascular paralysis during the course of vasodilatory shock. Methods The related articles were searched by retrieving the terms using methylene blue, vascular paralysis, hemodynamics, hypotension, vasodilatory shock in CNKI, China Biomedical Literature database, Wanfang database, PubMed, Springer Link, and BIOSIS Previews database. The retrieval time was from January 1994 to June 2017. The randomized clinical trials (RCTs) which using methylene blue as the experimental group, normal saline or catecholamine as the control in the treatment of refractory hypotension caused by vascular paralysis during the course of vasodilatory shock were collected. The primary end points were mean arterial pressure (MAP) immediately or 1 hour after the methylene blue administration, and the mortality at the longest follow-up available; the secondary end point was serum lactic acid (Lac) 1 hour after the methylene blue administration. Literature screening, data extraction and quality evaluation were carried out by two researchers. Meta analysis was performed using RevMan 5.3 software. The sensitivity analysis was performed in two trials with low risk of bias. The funnel plot for MAP was performed in five relative trials to analyze the research and publication bias. Results Totally 269 relative articles were collected, according to the inclusion and exclusion criteria, finally 6 RCTs with 214 patients were enrolled, 108 in methylene blue group, and 106 in control group. Four of the studies were considered to have mild to moderate risk of bias, two studies of high risk of bias. The Meta-analysis demonstrated that compared with the control group, methylene blue could significantly improve MAP [mean difference (MD) = 4.87, 95% confidence interval (95%CI) = 2.61 to 7.13, P < 0.000 1], reduce the serum Lac levels (MD = -1.06, 95%CI = -1.98 to -0.14, P = 0.02), and the mortality was decreased without statistical difference [odds ratio (OR) = 0.58, 95%CI = 0.25 to 1.31, P = 0.19]. Sensitivity analysis was performed in two trials with low risk of bias, which demonstrated methylene blue could exactly increase MAP (MD = 8.93, 95%CI = 1.55 to 16.32, P = 0.02). Funnel plot for MAP was performed in five relative trials which found no obvious publication bias. Conclusions Methylene blue could significantly increase MAP in the patients with refractory hypotension caused by vascular paralysis during the course of vasodilatory shock, decrease the Lac levels, and does not increase the risk of death. Therefore, methylene blue should be a potential and safe vasoconstrictor.
ABSTRACT
Arginine vasopressin (AVP), also known as antidiuretic hormone, is a peptide endogenously secreted by the posterior pituitary in response to hyperosmolar plasma or systemic hypoperfusion states. When administered intravenously, it causes an intense peripheral vasoconstriction through stimulation of V₁ receptors on the vascular smooth muscle. Patients in refractory shock associated with severe sepsis, cardiogenic or vasodilatory shock, or cardiopulmonary bypass have inappropriately low plasma levels of AVP (‘relative vasopressin deficiency’) and supersensitivity to exogenously-administered AVP. Low doses of AVP and its synthetic analog terlipressin can restore vasomotor tone in conditions that are resistant to catecholamines, with preservation of renal blood flow and urine output. They are also useful in the treatment of refractory arterial hypotension in patients chronically treated with renin-angiotensin system inhibitors, cardiac arrest, or bleeding esophageal varices. In the perioperative setting, they represent attractive adjunct vasopressors in advanced shock states that are unresponsive to conventional therapeutic strategies.