Effect of Sedation on Intra-abdominal Pressure

• ClinicalTrials.gov Identifier: NCT02944292
• Recruitment Status: Unknown
• First Posted: October 25, 2016
• Last Update Posted: December 8, 2017
• Sponsor: Tartu University Hospital
• Information provided by (Responsible Party): Joel Starkopf, Tartu University Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Intra-abdominal Hypertension	Procedure: Deepening of sedation; Drug: Propofol	Phase 4

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prospective, Interventional Multicentre Study on the Effect of Deepening of Sedation on Intra-abdominal Pressure
• Actual Study Start Date: November 2016
• Estimated Primary Completion Date: December 2018
• Estimated Study Completion Date: December 2018

Arms and Interventions

Arm

Intervention/treatment

Experimental: All enrolled patients; 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; Deepening of sedation will be achieved with a bolus and subsequent continuous infusion of propofol.; Drug: Propofol; 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).

Outcome Measures

Primary Outcome Measures :

1. Intra-abdominal pressure [ Time Frame: At 30 minutes after the start of deepening of sedation (propofol bolus) ]

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Martin Padar, MD; +372 5037911; martin.padar@kliinikum.ee

Contact: Joel Starkopf, MD PhD; +372 731 8400; joel.starkopf@kliinikum.ee

Locations

Estonia

Tartu University Hospital; Recruiting

Tartu, Tartumaa, Estonia, 51014

Contact: Martin Padar, MD +3725037911 martin.padar@kliinikum.ee

Contact: Joel Starkopf, Professor, MD, PhD joel.starkopf@kliinikum.ee

Sponsors and Collaborators

Tartu University Hospital

Investigators

• Study Director: Joel Starkopf, MD PhD; Tartu University Hospital; University of Tartu
• Study Director: Annika Reintam Blaser, MD PhD; University of Tartu

More Information

Study Data/Documents: Study Protocol 

Publications:

Malbrain ML, Chiumello D, Pelosi P, Wilmer A, Brienza N, Malcangi V, Bihari D, Innes R, Cohen J, Singer P, Japiassu A, Kurtop E, De Keulenaer BL, Daelemans R, Del Turco M, Cosimini P, Ranieri M, Jacquet L, Laterre PF, Gattinoni L. Prevalence of intra-abdominal hypertension in critically ill patients: a multicentre epidemiological study. Intensive Care Med. 2004 May;30(5):822-9. Epub 2004 Feb 3.

Malbrain ML, Chiumello D, Pelosi P, Bihari D, Innes R, Ranieri VM, Del Turco M, Wilmer A, Brienza N, Malcangi V, Cohen J, Japiassu A, De Keulenaer BL, Daelemans R, Jacquet L, Laterre PF, Frank G, de Souza P, Cesana B, Gattinoni L. Incidence and prognosis of intraabdominal hypertension in a mixed population of critically ill patients: a multiple-center epidemiological study. Crit Care Med. 2005 Feb;33(2):315-22.

Reintam A, Parm P, Kitus R, Kern H, Starkopf J. Primary and secondary intra-abdominal hypertension--different impact on ICU outcome. Intensive Care Med. 2008 Sep;34(9):1624-31. doi: 10.1007/s00134-008-1134-4. Epub 2008 May 1.

Cheatham ML, Malbrain ML, Kirkpatrick A, Sugrue M, Parr M, De Waele J, Balogh Z, Leppäniemi A, Olvera C, Ivatury R, D'Amours S, Wendon J, Hillman K, Wilmer A. Results from the International Conference of Experts on Intra-abdominal Hypertension and Abdominal Compartment Syndrome. II. Recommendations. Intensive Care Med. 2007 Jun;33(6):951-62. Epub 2007 Mar 22.

Treggiari MM, Romand JA, Yanez ND, Deem SA, Goldberg J, Hudson L, Heidegger CP, Weiss NS. Randomized trial of light versus deep sedation on mental health after critical illness. Crit Care Med. 2009 Sep;37(9):2527-34. doi: 10.1097/CCM.0b013e3181a5689f.

Rello J, Diaz E, Roque M, Vallés J. Risk factors for developing pneumonia within 48 hours of intubation. Am J Respir Crit Care Med. 1999 Jun;159(6):1742-6.

Malbrain ML, Cheatham ML, Kirkpatrick A, Sugrue M, Parr M, De Waele J, Balogh Z, Leppäniemi A, Olvera C, Ivatury R, D'Amours S, Wendon J, Hillman K, Johansson K, Kolkman K, Wilmer A. Results from the International Conference of Experts on Intra-abdominal Hypertension and Abdominal Compartment Syndrome. I. Definitions. Intensive Care Med. 2006 Nov;32(11):1722-32. Epub 2006 Sep 12.

• Responsible Party: Joel Starkopf, Professor of Anaesthesiology and Intensive Care, Tartu University Hospital
• ClinicalTrials.gov Identifier: NCT02944292
• Other Study ID Numbers: 16062
• First Posted: October 25, 2016
• Last Update Posted: December 8, 2017
• Last Verified: December 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Joel Starkopf, Tartu University Hospital:

Intra-abdominal pressure; Intra-abdominal hypertension

Additional relevant MeSH terms:

Intra-Abdominal Hypertension; Hypertension; Vascular Diseases; Cardiovascular Diseases; Compartment Syndromes; Muscular Diseases; Musculoskeletal Diseases; Propofol; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Anesthetics, Intravenous; Anesthetics, General; Anesthetics