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

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

Interventions

DRUG

Midazolam

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.

DRUG

Propofol

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.

DRUG

Dexmedetomidine

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.

Sponsors & Collaborators

• Assiut University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

SINGLE

Model

PARALLEL

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-01-23

Primary Completion

2021-04-10

Completion

2021-04-10

Countries

• Egypt

Study Locations