The article is issued in the form of presentation presented at symposium

Georgian Critical Care Medicine Institute Page1 The article is issued in the form of presentation presented at symposium

Vasoactive drugs for vasodilatatory shock. A.Muhamed Mukhar (Cairo, Egypt)

Here is presented studies of vasoactive drug usage during vasodilatory shock. Are discussed issues of minimal perfusion pressure during severe sepsis and characteristics of regional blood flow. Treatment results by dopamine, norepinephrine, epinephrine and phenylephrine are studied. Effectiveness of dopamine and norepinephrine, also phenylephrine and norepinephrine are compared. Brought in here is conclusion, that Norepinephrine, vasopressin, and epinephrine may be used safely with similar survival outcomes.

Key words: vasoactive drugs, vasodilatatory shock.

Vasoactive drug therapy in the treatment of shock states aims to achieve a minimal perfusion pressure and maintain adequate global and regional flow.

What is minimum perfusion pressure?

Is there any benefit to increase MAP above 65 mmHg on global or regional blood flow ? 28 patients with septic shock treated with fluid and vassopressors randomized into 2 groups  Control group MAP maintained at 65 mmHg

 Second group MAP was increased to 85 mmHg

Georgian Critical Care Medicine Institute Page2 What about regional blood flow?

Orthogonal Polarization Spectral (OPS) imaging of sub lingual microcirculation The tissue embedding the microcirculation is illuminated by polarized green light.

The hemoglobin is used as contrast agent, so that red blood cells are imaged as dark moving globules against a white/grayish background.

Georgian Critical Care Medicine Institute Page3 Side stream dark field image of the sublingual microcirculation

Assessment of Regional Blood Flow using OPS of sublingual microcirculation

 16 patients with septic shock treated with escalating dose of norepinephrine to target MAP 60, 70, 80, and 90 mmHg.

 Systemic hemodynamics and sublingual microcirculation were measured. Sublingual microcirculation in

healthy volunteer

Sublingual microcirculation in patients with septic shock

Georgian Critical Care Medicine Institute Page4 Which Agent?

Is there a difference between Norepinephrine and Epinephrine in management of septic shock?

 Prospective multicenter double-blinded randomized controlled trial

 330 patients were randomized to receive either epinephrine or norepinephrine plus Dobutamine  The primary outcome was 28-day all-cause mortality.

Georgian Critical Care Medicine Institute Page5 • Prospective double-blinded randomized controlled trial

• 280 patients were randomized to receive either epinephrine or norepinephrine • Primary outcome MAP > 70 in the first 24 hours

Georgian Critical Care Medicine Institute Page6 Dopamine or Norepinephrine

• 252 adult patients with septic shock randomized to receive either Dopamine (DA) or Norepinephrine (NE) as initial vasopressor therapy

• Primary end point was 28 days mortality • Secondary end point was organ dysfunction

• Multi-center randomized study

• 1679 patients with any type of shock randomized to receive either Dopamine or Norepinephrine • Primary end point was 28 days mortality

Georgian Critical Care Medicine Institute Page8 • Randomized animal study

• Mice are subjected to polymicrobial sepsis by CLP and received either saline or Dopa • Dopamine infusion did inhibit splenocyte proliferation and release of cytokines

Phenylephrine or Norepinephrine

• 32 patients with septic shock randomized to receive either phenylephrine or norepinephrine to achieve MAP between 65 and 75 mm Hg

Georgian Critical Care Medicine Institute Page9 Vasopressin or Norepinephrine

Georgian Critical Care Medicine Institute Page10 Terlipressin or Vasopressin?

Terlipressin in Septic Shock

 Terlipressin is synthetic lycine vasopressin

 Terlipressin is a pro-drug exerting only moderate intrinsic vasopressin activity

 Terlipressin is characterized by a more specific V1 agonistic effect (V1:V2 ratio = 2.2:1)

 During recent years, terlipressin has also been identified as a useful non-adrenergic vasopressor in the treatment of catecholamine-refractory septic shock

Georgian Critical Care Medicine Institute Page13 Conclusion

 The hemodynamic management of vasodilatory shock often requires use of vasoactive agents.  Current evidence does not support recommendation of one vasopressor over another.

 The finding of significantly more cardiac arrhythmias associated with dopamine administration is concerning.

 The limited information available with phenylephrine suggests that this drug should be used as a second line agent in septic shock.

 Norepinephrine, vasopressin, and epinephrine may be used safely with similar survival outcomes.

Georgian Critical Care Medicine Institute Page14 vazoaqtiuri medikamentebis gamoyeneba vazodilataciuri Sokis dros.

a.muhamed muxar (kairo, egvipte)

Seswavlilia vazodilataciuri Sokis dros vazoaqtiuri preparatebis gamoyeneba. ganxilulia minimaluri perfuziuli wnevis sakiTxebi mZime

sefsisis dros. regionaluri sisxlis mimoqcevis Taviseburebani.

Seswavlilia dopaminiT, norepinefriniT, epinefriniT da fenilepriniT mkurnalobis Sedegebi. Sedarebulia dopaminisa da norepinefrinis, aseve fenileprinis da norepinefrinis efeqturoba. motanilia daskvna, rom norepinefrini, vazopresini da epinefrini SeiZleba iqnas erTnairi SedegebiT gamoyenebuli.