Effect of Sedation on Intra-abdominal Pressure

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

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.

Study Overview

• Status: Unknown
• Conditions: Intra-abdominal Hypertension
• Intervention / Treatment: Procedure: Deepening of sedation; Drug: Propofol

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 Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Martin Padar, MD; Phone Number: +372 5037911; Email: martin.padar@kliinikum.ee
• Study Contact Backup: Name: Joel Starkopf, MD PhD; Phone Number: +372 731 8400; Email: joel.starkopf@kliinikum.ee

Study Locations

• Estonia
  • Tartumaa
    • Tartu, Tartumaa, Estonia, 51014
      • Recruiting
      • Tartu University Hospital
      • Contact: Martin Padar, MD; Phone Number: +3725037911; Email: martin.padar@kliinikum.ee
      • Contact: Joel Starkopf, Professor, MD, PhD; Email: joel.starkopf@kliinikum.ee

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: 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

Publications and helpful links

General 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. doi: 10.1007/s00134-004-2169-9. 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. doi: 10.1097/01.ccm.0000153408.09806.1b.
• 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, Leppaniemi 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. doi: 10.1007/s00134-007-0592-4. 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, Valles J. Risk factors for developing pneumonia within 48 hours of intubation. Am J Respir Crit Care Med. 1999 Jun;159(6):1742-6. doi: 10.1164/ajrccm.159.6.9808030.
• Malbrain ML, Cheatham ML, Kirkpatrick A, Sugrue M, Parr M, De Waele J, Balogh Z, Leppaniemi 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. doi: 10.1007/s00134-006-0349-5. Epub 2006 Sep 12.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2016
• Primary Completion (ANTICIPATED): December 1, 2018
• Study Completion (ANTICIPATED): December 1, 2018

Study Registration Dates

• First Submitted: October 14, 2016
• First Submitted That Met QC Criteria: October 23, 2016
• First Posted (ESTIMATE): October 25, 2016

Study Record Updates

• Last Update Posted (ACTUAL): December 8, 2017
• Last Update Submitted That Met QC Criteria: December 6, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Intra-abdominal pressure; Intra-abdominal hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Musculoskeletal Diseases; Muscular Diseases; Compartment Syndromes; Hypertension; Intra-Abdominal Hypertension; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; Propofol
• Other Study ID Numbers: 16062

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Study Data/Documents

1. Study Protocol