Clinical trial NCT02944292: Effect of Sedation on Intra-abdominal Pressure
Official title: Prospective, Interventional Multicentre Study on the Effect of Deepening of Sedation on Intra-abdominal Pressure
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Intra-abdominal Hypertension
Keywords: Intra-abdominal pressure
Intra-abdominal hypertension
Lead sponsor: Tartu University Hospital
Sponsor class: OTHER
First posted: 2016-10-25
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Intra-abdominal pressure
timeFrame: At 30 minutes after the start of deepening of sedation (propofol bolus)
Secondary outcomes:
measure: Intra-abdominal pressure
timeFrame: After sedative bolus; at 1) 15, 2) 30, 3) 60 minutes after starting the continuous infusion of propofol
measure: Richmond Agitation-Sedation Scale
timeFrame: After sedative bolus; at 1) 15, 2) 30, 3) 60 minutes after starting the continuous infusion of propofol
measure: Spontaneous and total respiratory rate
timeFrame: After sedative bolus; at 1) 15, 2) 30, 3) 60 minutes after starting the continuous infusion of propofol
measure: Tidal volume
timeFrame: After sedative bolus; at 1) 15, 2) 30, 3) 60 minutes after starting the continuous infusion of propofol
measure: PEEP, Ppeak, Pplat
timeFrame: After sedative bolus; at 1) 15, 2) 30, 3) 60 minutes after starting the continuous infusion of propofol
measure: Total number of vasopressor and inotrope boluses
timeFrame: During the intervention
measure: Maximal increase in dose of noradrenaline
timeFrame: During the intervention
measure: Mean arterial pressure
timeFrame: After sedative bolus; at 1) 15, 2) 30, 3) 60 minutes after starting the continuous infusion of propofol
measure: Abdominal perfusion pressure
timeFrame: After sedative bolus; at 1) 15, 2) 30, 3) 60 minutes after starting the continuous infusion of propofol
Other outcomes:
Locations:
city: Tartu
country: Estonia
facility: Tartu University Hospital
state: Tartumaa
Study officials:
affiliation: Tartu University Hospital; University of Tartu
name: Joel Starkopf, MD PhD
role: STUDY_DIRECTOR
affiliation: University of Tartu
name: Annika Reintam Blaser, MD PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
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citation: 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.
citation: 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.
citation: 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.