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Mortality rates associated septic shock remains unacceptably high, around 20-50%, with refractory hypotension in half of these patients. Widespread vasodilatation involves the activation of the soluble intracellular enzyme guanylate cyclase (GC) by nitric oxide (NO), resulting in the production of cyclic guanosine monophosphate (cGMP). Initially discovered as an endothelium-derived relaxing factor in blood vessels, NO is made by the enzyme nitric oxide synthase (NOS). It has been suggested that the inhibition of NO generation might be a treatment option for sepsis and septic shock. Methylene blue (MB) is a dye that easily crosses cell membranes, inhibits iNOS, and is capable of inhibiting the GC enzyme in vascular smooth muscle cells.Early use of MB can block the progressive decrease in systemic vascular resistance of patients unresponsive to noradrenaline and mitigate the need for prolonged vasoconstrictor use. The investigators propose to study the effect of methylene blue on cirrhotic adults with sepsis, with refractory vasoplegia unresponsive to maximum doses of noradrenaline and vasopressin.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Methylene Blue | Experimental | Methylene Blue intravenous route, 2 mg/kg Loading Dose over 30 minutes, followed by 0.5 mg/kg/hr for 6 hours |
|
| Standard Treatment | No Intervention |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Methylene Blue | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Survival in both groups | 2 days |
| Measure | Description | Time Frame |
|---|---|---|
| Systemic Vascular Resistance | Change in SVR | 6 hours |
| Mean Arterial Pressure | Improvement in MAP | 6 hours |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Karthik Ponnappan, MD | Institute of Liver and Biliary Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Liver Coma ICU, Institute of Liver and Biliary Sciences | New Delhi | National Capital Territory of Delhi | 110070 | India |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24151551 | Result | Bassi E, Park M, Azevedo LC. Therapeutic strategies for high-dose vasopressor-dependent shock. Crit Care Res Pract. 2013;2013:654708. doi: 10.1155/2013/654708. Epub 2013 Sep 15. | |
| 16134766 | Result | Park BK, Shim TS, Lim CM, Lee SD, Kim WS, Kim DS, Kim WD, Koh Y. The effects of methylene blue on hemodynamic parameters and cytokine levels in refractory septic shock. Korean J Intern Med. 2005 Jun;20(2):123-8. doi: 10.3904/kjim.2005.20.2.123. |
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| ID | Term |
|---|---|
| D012772 | Shock, Septic |
| D056987 | Vasoplegia |
| D008103 | Liver Cirrhosis |
| D012769 | Shock |
| D005355 | Fibrosis |
| ID | Term |
|---|---|
| D018805 | Sepsis |
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
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| ID | Term |
|---|---|
| D008751 | Methylene Blue |
| ID | Term |
|---|---|
| D010640 | Phenothiazines |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D006575 | Heterocyclic Compounds, 3-Ring |
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| Decrease of vasopressor dose of 20 percent from time of start of test drug. | Effect on decreasing vasopressor doses | 6 hours |
| 11588440 | Result | Kirov MY, Evgenov OV, Evgenov NV, Egorina EM, Sovershaev MA, Sveinbjornsson B, Nedashkovsky EV, Bjertnaes LJ. Infusion of methylene blue in human septic shock: a pilot, randomized, controlled study. Crit Care Med. 2001 Oct;29(10):1860-7. doi: 10.1097/00003246-200110000-00002. |
| 12500513 | Result | Memis D, Karamanlioglu B, Yuksel M, Gemlik I, Pamukcu Z. The influence of methylene blue infusion on cytokine levels during severe sepsis. Anaesth Intensive Care. 2002 Dec;30(6):755-62. doi: 10.1177/0310057X0203000606. |
| 20109575 | Result | Juffermans NP, Vervloet MG, Daemen-Gubbels CR, Binnekade JM, de Jong M, Groeneveld AB. A dose-finding study of methylene blue to inhibit nitric oxide actions in the hemodynamics of human septic shock. Nitric Oxide. 2010 May 15;22(4):275-80. doi: 10.1016/j.niox.2010.01.006. Epub 2010 Jan 28. |
| D010335 |
| Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D011183 | Postoperative Complications |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |