Terlipressin for Refractory Septic Shock
Palavras-chave
Resumo
Descrição
Norepinephrine was recommended as the first vasopressor for septic shock resuscitation.
For the patient who did not response to high dose norepinephrine, epinephrine was recommended.
Both norepinephrine and epinephrine action via the alpha adrenergic stimuli to increase vascular smooth muscle contraction, induced vasoconstriction and increase arterial blood pressure. It also action via beta adrenergic stimuli, to increase heart rate and myocardial contractility, then increase stroke volume and cardiac output.
Too much alpha and beta adrenergic stimulation, especially during received high dose norepinephrine and or epinephrine associated with vasoconstriction induce organs ischemia.
The most common organ ischemia included myocardial ischemia, bowel ischemia and limbs ischemia.
Cardiac arrhythmia was also the most common complication associated with high dose norepinephrine and or epinephrine.
Atrial fibrillation was the most common reported arrhythmia, however, fatal arrhythmia included ventricular fibrillation and tachycardia were also reported.
Vasopressin was recommended as an alternative vasopressor, in case patient did not response to norepinephrine and or epinephrine.
Terlipressin, a selective V1 receptor binding with long half life, was reported that it main action is to increase blood pressure via the different mechanism from norepinephrine and epinephrine.
To use terlipressin, combine with norepinephrine and or epinephrine among refractory septic shock, could decrease the usage dose of norepinephrine and epinephrine as well as lower the side effects of too high adrenergic stimuli.
The benefit effect of terlipressin could be demonstrated when prescribe among the septic shock patients who required high dose of adrenergic vasoactive agents.
Terlipressin plus norepinephrine and or epinephrine could maintain or even improve blood pressure and tissue perfusion with lower fatal side effects than norepinephrine and or epinephrine without terlipressin.
datas
| Última verificação: | 03/31/2020 |
| Enviado pela primeira vez: | 04/06/2020 |
| Inscrição estimada enviada: | 04/06/2020 |
| Postado pela primeira vez: | 04/08/2020 |
| Última atualização enviada: | 04/06/2020 |
| Última atualização postada: | 04/08/2020 |
| Data real de início do estudo: | 04/02/2020 |
| Data Estimada de Conclusão Primária: | 03/30/2025 |
| Data Estimada de Conclusão do Estudo: | 07/30/2025 |
Condição ou doença
Intervenção / tratamento
Drug: Terlipressin group
Drug: Placebo group
Fase
Grupos de Armas
| Braço | Intervenção / tratamento |
|---|---|
| Active Comparator: Terlipressin group Terlipressin acetate 1 mg in 0.9% normal saline (NaCl) 50 mL (0.02 mg/mL) Initial dose 20 mcg/hr (1 mL/hr) titrate increase 1 mL/hr every 30 min to 100 mcg/hr (5 mg/hr) to keep mean arterial blood pressure (MAP) > 65 mmHg If MAP > 75 mmHg for > 30 min, decrease epinephrine and norepinephrine until < 0.15 mcg/kg/min, then decrease terlipressin until stop | Drug: Terlipressin group Terlipressin (20-100 mcg/hr) plus norepinephrine and/or epinephrine |
| Placebo Comparator: Placebo group Placebo 0.9% NaCl 50 mL Initial dose 1 mL/hr titrate increase 1 mL/hr every 30 min to 5 mg/hr to keep mean arterial blood pressure (MAP) > 65 mmHg If MAP > 75 mmHg for > 30 min, decrease epinephrine and norepinephrine until < 0.15 mcg/kg/min, then decrease placebo until stop | Drug: Placebo group 0.9% NaCl plus norepinephrine and/or epinephrine |
Critério de eleição
| Idades qualificadas para estudar | 18 Years Para 18 Years |
| Sexos elegíveis para estudo | All |
| Aceita Voluntários Saudáveis | sim |
| Critério | Inclusion Criteria: - Septic shock according to Sepsis-3 definition - Evidence of adequate fluid - Received norepinephrine 0.2 mcg/kg/min or more - Received norepinephrine plus epinephrine (any dose) - Mean arterial lower than 65 mmHg or lactate > 2 mmol/liter Exclusion Criteria: 1. Septic shock diagnosis > 48 hours before 2. Receive intravenous fluid < 30 mL/kg before enrollment 3. Do-not-resuscitation and terminally ill 4. Refractory to treatment malignancy 5. Pregnancy 7. Chronic renal failure stage 5 with no plan for long term renal replacement therapy 8. Cirrhosis child C 9. Cardiogenic shock 10. Acute decompensated heart failure 11. Evidence of left ventricular ejection fraction (LVEF) < 35% 12. Acute coronary syndrome within 72 hours 13. Severe valvular heart disease 14. Documented life-threatening tachyarrhythmia before enrollment 15. Diagnosis of acute mesenteric ischemia before enrollment 16. Previous diagnosis of Raynaud's phenomenon 17. Known peripheral arterial disease 18. Refuse to sign the informed consent by patient or representative |
Resultado
Medidas de Resultado Primário
1. Achieve target blood pressure with low dose adrenergic agents [6 hours after initiate study drug]
Medidas de Resultado Secundário
1. 28 day mortality [28 days]
2. Mean arterial blood pressure [72 hours]
3. Hospital mortality [90 days]
4. ICU mortality [90 days]
