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


CONCLUSIONS
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.
Department of Intensive Care, Medical Center Leeuwarden, Leeuwarden, the Netherlands; Department of Translational Physiology, Academic Medical Center, Amsterdam, the Netherlands.
Namkje A R
NA
Vellinga
Department of Intensive Care, Medical Center Leeuwarden, Leeuwarden, the Netherlands.
Gerke
G
Veenstra
Department of Intensive Care, Medical Center Leeuwarden, Leeuwarden, the Netherlands.
Claudia
C
Scorcella
Department of Intensive Care, Medical Center Leeuwarden, Leeuwarden, the Netherlands. Electronic address: matty.koopmans@gmail.com.
Matty
M
Koopmans
Department of Clinical Pharmacy and Pharmacology, Medical Center Leeuwarden, Leeuwarden, the Netherlands.
Eric N
EN
van Roon
Department of Translational Physiology, Academic Medical Center, Amsterdam, the Netherlands.
Can
C
Ince
Department of Intensive Care, Medical Center Leeuwarden, Leeuwarden, the Netherlands; Department of Translational Physiology, Academic Medical Center, Amsterdam, the Netherlands.
E Christiaan
EC
Boerma
D000328:Adult; D000368:Aged; D002196:Capillaries; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007022:Hypotension; D007249:Inflammation; D007650:Ketanserin / Q000008:administration & dosage*; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D008875:Middle Aged; D009060:Mouth Floor / Q000098:blood supply; D010865:Pilot Projects; D012151:Resuscitation / Q000379:methods; D018805:Sepsis / Q000401:mortality; D012702:Serotonin Antagonists / Q000627:therapeutic use; D012772:Shock, Septic / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality; D014665:Vasodilator Agents / Q000008:administration & dosage
D012702:Serotonin Antagonists; D014665:Vasodilator Agents; D007650:Ketanserin
Ketanserin; Microcirculatory alterations; Septic shock; Sidestream dark-field images