Effects of Dexmedetomidine vs Propofol in Patients With Intra-abdominal Sepsis

NCT04718714 | Completed Phase 4

• 1 other identifier: 00008718
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Sepsis is defined as systemic response to infection ,and it is a main problem in ICU and despite advance in supportive care, the mortality rate in patients with severe sepsis continues to exceed 30% \[Bone RC 1993\].The effects of bacterial invasion of body tissues result from combined actions of enzymes and toxins produced by micro-organisms themselves and by a network of proinflammatory mediators and cytokines as tumour necrosis factor α and interleukin 6 which are overexpressed after various noxious insults\[P.Delong et al. 2006\],\[ Yealy et al. 2014\]. the patients who are subjected to abdominal surgery in order to treat the cause surgically,and many of these surgical procedures are lengthy and are at risk for either pre-operatively or post-operatively with steady increase in intra-abdominal pressure(IAP) \[Malbrain ML et al. 2007\] Intra-abdominal hypertension (IAH) is defined as IAP equal to or greater than 12 mmHg whereas abdominal compartment syndrome (ACS) is defined as IAP greater than 20 mmHg, abdominal perfusing pressure (APP) is used to predict prognosis of both IAH and ACS \[Malbrain ML et al. 2006\]. The choice for using a sedative agent in ICU for mechanically ventilated patients post-operatively is therefore a crucial one as these patients are under hyperstress state and often require drugs for sedation and analgesia\[ Chanques G et al. 2006\]. Analgesics and sedation agents have clearly been shown to alter cellular function and other mediators of immune system with wide range of immune modulation ,ranging from immunosuppressive effects to significant anti-inflammatory effects during endotoxaemia\[ Taniguchi et al. 2004\] Also sedation and /or analgesia have the potential to reduce IAP through improvement of abdominal wall compliance. Although propofol and dexmedetomidine are used for sedation in ICU there are limited data on their effects on inflammatory responses and IAP in septic patients. In clinical practice, septic patients treated with dexmedetomidine have shorter time on the ventilator as compared with those treated with lorazepam, a benzodiazepine and this beneficial effect of dexmedetomidine is more pronounced in septic patients than in nonseptic patients. This outcome may be partly the result of dexmedetomidine induced reduction in pulmonary inflammatory mediators and lung tissue damage.\[ M. Ueki et al. 2014\] Midazolam is known to inhibit certain aspects of the immune function. It was suggested that benzodiazepines bind to specific receptors on macrophages and inhibit their capacity to produce IL-1, IL-6, and TNFα. Propofol, nowadays, has become a preferred sedative in ICU because it offers advantages over benzodiazepines in terms of lack of accumulation, quick onset, easy adjustment, and fast recovery after discontinuation. \[ Jacobi J et al. 2002\]

Conditions

Septic Peritonitis

Outcome Measures

Primary Outcomes (3)

• interleukin 1 plasma concentration

  interleukin 1 plasma concentration will be measured three times, at admission ,24 hours after admission and 48 hours after admission

  48 hours

• interleukin 6 plasma concentration

  interleukin 6 plasma concentration will be measured three times ,at admission ,24 hours after admission and 48 hours after admission

  48 hours

• intraabdominal pressure per mmHg

  intraabdominal pressure will be measured three times ,at admission ,24 hours after admission and 48 hours after admission

  48 hours

Secondary Outcomes (1)

• difference of mean time of ventilator free days

  28 days

Study Arms (3)

midazolam

ACTIVE COMPARATOR

postoperative ventilation and sedation with continuous intravenous infusion of midazolam only for 24 hours

Drug: Midazolam

propofol

ACTIVE COMPARATOR

postoperative ventilation and sedation with continuous intravenous infusion of propofol only for 24 hours

Drug: Propofol

dexmedetomidine

EXPERIMENTAL

postoperative ventilation and sedation with continuous intravenous infusion of dexmedetomidine only for 24 hours

Drug: Dexmedetomidine

Interventions

Midazolam DRUG

loading dose intravenous infusion of 0.2 mg/kg over 10 minutes followed by a maintenance dose of 0.02 -0.2 mg /kg/hr. over 24 hours.

midazolam

Propofol DRUG

loading dose intravenous infusion of one mg/kg over 15 minutes followed by a maintenance dose of 20-80 microgram/kg/min. over 24 hours.

propofol

Dexmedetomidine DRUG

loading dose of dexmedetomidine of one µg/kg over 10 minutes followed by maintenance dose of 0.2 -1.5 µg/kg/hr. over 24 hours.

dexmedetomidine

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• patients aged18 years old or more and had the criteria of intraabdominal sepsis as evident by quick sofa score of 2 or more and have done intraabdominal surgical procedures

You may not qualify if:

• children pregnant women Patients who receive neuromascular blockers during the first 48 hours of ICU admission known allergy or contraindication to propofol ,dexemedetomidine or midazolam known or suspected brain death

Sponsors & Collaborators

• Assiut University: lead

Study Sites (1)

Faculty of Medicine, Assiut University

Asyut, 71515, Egypt

Location

MeSH Terms

Interventions

Midazolam; Propofol; Dexmedetomidine

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: assistant lecturer at anaesthesia and ICU department faculty of medicine assiut university

Study Record Dates

• First Submitted: January 15, 2021
• First Posted: January 22, 2021
• Study Start: January 23, 2021
• Primary Completion: April 10, 2021
• Study Completion: April 10, 2021
• Last Updated: April 27, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)