Effects of ketanserin on microcirculatory alterations in septic shock: An open-label pilot study

J Crit Care. 2015 Dec;30(6):1156-62. doi: 10.1016/j.jcrc.2015.07.004. Epub 2015 Jul 17.

Abstract

Introduction: Microcirculatory alterations in sepsis are associated with increased morbidity and mortality. These alterations occur despite macrohemodynamic resuscitation. Alternative pro-microcirculatory strategies, including vasodilatory drugs, have been suggested to improve capillary blood flow. Ketanserin, a serotonin receptor antagonist, is an attractive candidate because of its vasodilatory, antithrombotic, and anti-inflammatory effects.

Methods: This is an open-label pilot study on the effect of ketanserin administration on microcirculatory alterations in septic shock, defined as microvascular flow index (MFI)≤2.5 after a strict macrohemodynamic resuscitation protocol. Sidestream dark-field imaging was applied to assess the microcirculation. A stepwise incremental dose regiment was applied until an MFI>2.9, the primary end point, was reached.

Results: Ten patients (Acute Physiology and Chronic Health Evaluation IV scores of 115 [100-136]) were included. Baseline MFI was 1.71 (1.31-2.32) and was significantly increasing to 2.96 (2.54-3.00; P=.021) during the ketanserin infusion. The total ketanserin dose was 0.09 (0.08-0.13) mg/kg per patient in 60 (30-60) minutes. In 3 patients (30%), the ketanserin infusion was discontinued due to refractory hypotension.

Conclusion: An improvement in microcirculatory perfusion was observed during ketanserin administration in patients with septic shock after macrohemodynamic resuscitation. This finding needs further exploration in a placebo-controlled setting.

Keywords: Ketanserin; Microcirculatory alterations; Septic shock; Sidestream dark-field images.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Capillaries
  • Female
  • Hemodynamics / drug effects
  • Humans
  • Hypotension
  • Inflammation
  • Ketanserin / administration & dosage*
  • Male
  • Microcirculation / physiology*
  • Middle Aged
  • Mouth Floor / blood supply
  • Pilot Projects
  • Resuscitation / methods
  • Sepsis / mortality
  • Serotonin Antagonists / therapeutic use
  • Shock, Septic / blood*
  • Shock, Septic / drug therapy*
  • Shock, Septic / mortality
  • Vasodilator Agents / administration & dosage

Substances

  • Serotonin Antagonists
  • Vasodilator Agents
  • Ketanserin