Macro and Microcirculatory Effects of the Combination of Norepinephrine and Octreotide for the Treatment of Cirrhotic Patients With Hemorrhagic Shock

Study Overview
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Brief Summary
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Octreotide is used to decrease portal pressure of cirrhotic patients admitted for variceal bleeding. When patients are in haemorrhagic shock, the recommended drug to increase arterial pressure is norepinephrine. Microcirculatory effects of octreotide when it is added to noradrenaline has not been investigated yet. The aim of the study is to evaluate the effect of octreotide plus norepinephrine for patient with haemorrhagic shock after variceal bleeding.

Official Title
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Macro and Microcirculatory Effects of the Combination of Norepinephrine and Octreotide for the Treatment of Cirrhotic Patients With Hemorrhagic Shock

Conditions
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Haemorrhagic Shock, Variceal Hemorrhage

Intervention / Treatment
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* Drug: Octreotide Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients more than 18 years old patient with liver cirrhosis patient with haemorrhagic shock due to variceal bleeding patient with an arterial blood pressure less than 65 mmHg despite patient able to express consent signed written informed consent form patient covered by national health insurance Exclusion Criteria: patient less than 18 years old patient non covered by national health insurance pregnant or breast feeding patent known octreotide allergy cardiac arrest because of shock refused consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: octreotide (25 µg/hour) perfusion<br>octreotide (25 µg/hour) plus norepinephrine will be administered for patient with haemorrhagic shock after variceal bleeding during 2 to 5 days according recommendations and regular protocol in the medical unit | Drug: Octreotide Injection<br>* Patients admitted in intensive care unit after variceal hemorrhage treated with norepinephrine perfusion will received an additional octreotide perfusion during one hour.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of microcirculatory flow index | microcirculatory flow index will be measured with sidestream dark field handheld microscope. Baseline is before octreotide perfusion. Flow characteristics of the microvasculature will be quantified using the microcirculatory flow index (MFI) according to the recommendations from the consensus on microcirculatory imaging by De Backer et al. This index will be calculated after the image will be divided into four quadrants, and the predominant type of flow (absent = 0, intermittent = 1, sluggish = 2, abnormal = 3, and hyperdynamic = 4) would be estimated in the vessels smaller than 25 μm by the operator. The final MFI score is a value obtained from the average score of the four areas. | one hour after octreotide perfusion | 
| Change from baseline of microcirculatory flow index | microcirculatory flow index will be measured with sidestream dark field handheld microscope. Baseline is before octreotide perfusion. Flow characteristics of the microvasculature will be quantified using the microcirculatory flow index (MFI) according to the recommendations from the consensus on microcirculatory imaging by De Backer et al. This index will be calculated after the image will be divided into four quadrants, and the predominant type of flow (absent = 0, intermittent = 1, sluggish = 2, abnormal = 3, and hyperdynamic = 4) would be estimated in the vessels smaller than 25 μm by the operator. The final MFI score is a value obtained from the average score of the four areas. | 2 hours after octreotide perfusion | 
| Change from baseline of microcirculatory flow index | microcirculatory flow index will be measured with sidestream dark field handheld microscope. Baseline is before octreotide perfusion. Flow characteristics of the microvasculature will be quantified using the microcirculatory flow index (MFI) according to the recommendations from the consensus on microcirculatory imaging by De Backer et al. This index will be calculated after the image will be divided into four quadrants, and the predominant type of flow (absent = 0, intermittent = 1, sluggish = 2, abnormal = 3, and hyperdynamic = 4) would be estimated in the vessels smaller than 25 μm by the operator. The final MFI score is a value obtained from the average score of the four areas. | 6 hours after octreotide perfusion | 
| Change from baseline of microcirculatory flow index | microcirculatory flow index will be measured with sidestream dark field handheld microscope. Baseline is before octreotide perfusion. Flow characteristics of the microvasculature will be quantified using the microcirculatory flow index (MFI) according to the recommendations from the consensus on microcirculatory imaging by De Backer et al. This index will be calculated after the image will be divided into four quadrants, and the predominant type of flow (absent = 0, intermittent = 1, sluggish = 2, abnormal = 3, and hyperdynamic = 4) would be estimated in the vessels smaller than 25 μm by the operator. The final MFI score is a value obtained from the average score of the four areas. | 12 hours after octreotide perfusion | 
| Change from baseline of microcirculatory flow index | microcirculatory flow index will be measured with sidestream dark field handheld microscope. Baseline is before octreotide perfusion. Flow characteristics of the microvasculature will be quantified using the microcirculatory flow index (MFI) according to the recommendations from the consensus on microcirculatory imaging by De Backer et al. This index will be calculated after the image will be divided into four quadrants, and the predominant type of flow (absent = 0, intermittent = 1, sluggish = 2, abnormal = 3, and hyperdynamic = 4) would be estimated in the vessels smaller than 25 μm by the operator. The final MFI score is a value obtained from the average score of the four areas. | 24 hours after octreotide perfusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percentage of perfused vessels | percentage of perfused vessels will be measured with sidestream dark field handheld microscope | before and one hour after octreotide perfusion | 
| percentage of perfused vessels | percentage of perfused vessels will be measured with sidestream dark field handheld microscope | 2 hours after octreotide perfusion | 
| percentage of perfused vessels | percentage of perfused vessels will be measured with sidestream dark field handheld microscope | 6 hours after octreotide perfusion | 
| percentage of perfused vessels | percentage of perfused vessels will be measured with sidestream dark field handheld microscope | 12 hours after octreotide perfusion | 
| percentage of perfused vessels | percentage of perfused vessels will be measured with sidestream dark field handheld microscope | 24 hours after octreotide perfusion | 
| functional capillary density | functional capillary density will be measured with sidestream dark field handheld microscope | before and one hour after octreotide perfusion | 
| functional capillary density | functional capillary density will be measured with sidestream dark field handheld microscope | 2 hours after octreotide perfusion | 
| functional capillary density | functional capillary density will be measured with sidestream dark field handheld microscope | 6 hours after octreotide perfusion | 
| functional capillary density | functional capillary density will be measured with sidestream dark field handheld microscope | 12 hours after octreotide perfusion | 
| functional capillary density | functional capillary density will be measured with sidestream dark field handheld microscope | 24 hours after octreotide perfusion | 
| Mean arterial pressure | Mean arterial pressure | before and one hour after octreotide perfusion | 
| Mean arterial pressure | Mean arterial pressure | 2 hours after octreotide perfusion | 
| Mean arterial pressure | Mean arterial pressure | 6 hours after octreotide perfusion | 
| Mean arterial pressure | Mean arterial pressure | 12 hours after octreotide perfusion | 
| Mean arterial pressure | Mean arterial pressure | 24 hours after octreotide perfusion | 
| heart rate | heart rate | before and one hour after octreotide perfusion | 
| heart rate | heart rate | 2 hours after octreotide perfusion | 
| heart rate | heart rate | 6 hours after octreotide perfusion | 
| heart rate | heart rate | 12 hours after octreotide perfusion | 
| heart rate | heart rate | 24 hours after octreotide perfusion | 
| ejection fraction | ejection fraction | before and one hour after octreotide perfusion | 
| ejection fraction | ejection fraction | 2 hours after octreotide perfusion | 
| ejection fraction | ejection fraction | 6 hours after octreotide perfusion | 
| ejection fraction | ejection fraction | 12 hours after octreotide perfusion | 
| ejection fraction | ejection fraction | 24 hours after octreotide perfusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microcirculation, octreotide, norepinephrine, Variceal Hemorrhage, Haemorrhagic Shock