Effect of Sedation on Intra-abdominal Pressure

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of deepening of sedation on intra-abdominal pressure in mechanically ventilated adult patients with intra-abdominal hypertension.

Detailed Description
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The importance of intra-abdominal pressure (IAP) in critically ill patients has been addressed increasingly. Several studies have shown that elevated mean IAP is associated with adverse ICU outcomes. The prevalence of intra-abdominal hypertension (IAH) among critically ill patients is as high as 50% if defined according to maximal IAP and half of it if defined according to mean IAP. Development of IAH during ICU period is an independent risk factor for death. Considering such significant impact on patients' outcome, international conference of experts has agreed and published recommendations for treatment of IAH and abdominal compartment syndrome. Among others, deepening of sedation is suggested as treatment option. The recommendation is based on expert opinion; there are no controlled clinical studies available to support this approach. Importantly, recent studies have shown that deep sedation itself may be associated with worse outcome to patients. Treggiari et al suggest that a strategy of light sedation affords benefits with regard to reduction of intensive care unit stay and duration of ventilation without negatively affecting subsequent patient mental health or patient safety. Others have shown reduced ICU mortality as well as reduced incidence of ventilator-associated pneumonia in conjunction with light sedation. This is a prospective, interventional, multicentre study. There will be no control group. Study subjects: Adult, mechanically ventilated patients with IAP between 12 and 20 mmHg in at least two consecutive measurements, spontaneous breathing activity of at least 6 breaths/minute, RASS score between 0 and -4, if no contraindications to propofol administration are present and no other interventions to reduce IAP are planned. Study intervention: Sedation deepening will be achieved with a bolus of propofol 1 mg/kg followed by continuous infusion of propofol 3 mg/kg/h for one hour. Patients previously receiving propofol infusion will receive supplemental propofol per protocol up to a maximum infusion rate of 5 mg/kg/h. Series of measurements of IAP will be performed before (once) and after (repeatedly) intervention (deepening of sedation). Deepness of sedation will be assessed with RASS score.

Official Title
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Prospective, Interventional Multicentre Study on the Effect of Deepening of Sedation on Intra-abdominal Pressure

Conditions
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Intra-abdominal Hypertension

Intervention / Treatment
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* Procedure: Deepening of sedation
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older Mechanical ventilation IAP between 12 and 20 mmHg in at least two consecutive measurements within 1-12 h Spontaneous breathing activity of at least 6 breaths/minute RASS score between 0 and -4 Physician-led sedation (if sedated; as opposed to nurse-led protocol) Exclusion Criteria: Contraindication for propofol administration Contraindication for IAP measurement in supine position with head-of-bed at 0° Other intervention for reduction of IAP planned Previous propofol infusion rate >4 mg/kg/h

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: All enrolled patients<br>Study population: Adult, mechanically ventilated patients with IAP between 12 and 20 mmHg in at least two consecutive measurements, spontaneous breathing activity of at least 6 breaths/minute, RASS score between 0 and -4, if no contraindications to propofol administration are present and no other immediate interventions to reduce IAP are planned Intervention: Deepening of sedation Deepening of sedation will be achieved with a bolus of propofol followed by continuous infusion for one hour. | Procedure: Deepening of sedation<br>* Deepening of sedation will be achieved with a bolus and subsequent continuous infusion of propofol.<br>Drug: Propofol<br>* Propofol will be dosed according to lean body weight (LBW) for bolus administration and according to total body weight (TBW) for continuous infusion. All patients will receive a bolus of propofol 1 mg/kg LBW as a rapid infusion during one minute. Measurements will be made one minute after the ending of bolus infusion. Continuous infusion of propofol at a rate of 3 mg/kg/h will be started immediately following completion of measurements, not later than 5 minutes after bolus administration. The propofol infusion rate is decreased in case of hemodynamic instability by 1 mg/kg/h and until a minimum of 1 mg/kg/h, if needed. Maximum total dose of infusion of 5 mg/kg/h will not be exceeded (bolus not considered).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intra-abdominal pressure |  | At 30 minutes after the start of deepening of sedation (propofol bolus) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intra-abdominal pressure |  | After sedative bolus; at 1) 15, 2) 30, 3) 60 minutes after starting the continuous infusion of propofol | 
| Richmond Agitation-Sedation Scale |  | After sedative bolus; at 1) 15, 2) 30, 3) 60 minutes after starting the continuous infusion of propofol | 
| Spontaneous and total respiratory rate |  | After sedative bolus; at 1) 15, 2) 30, 3) 60 minutes after starting the continuous infusion of propofol | 
| Tidal volume |  | After sedative bolus; at 1) 15, 2) 30, 3) 60 minutes after starting the continuous infusion of propofol | 
| PEEP, Ppeak, Pplat |  | After sedative bolus; at 1) 15, 2) 30, 3) 60 minutes after starting the continuous infusion of propofol | 
| Total number of vasopressor and inotrope boluses | From the beginning of the bolus injection of propofol until the end of the continuous infusion of propofol | During the intervention | 
| Maximal increase in dose of noradrenaline | From the beginning of the bolus injection of propofol until the end of the continuous infusion of propofol | During the intervention | 
| Mean arterial pressure |  | After sedative bolus; at 1) 15, 2) 30, 3) 60 minutes after starting the continuous infusion of propofol | 
| Abdominal perfusion pressure |  | After sedative bolus; at 1) 15, 2) 30, 3) 60 minutes after starting the continuous infusion of propofol | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intra-abdominal pressure, Intra-abdominal hypertension