Original contribution
Results of a pilot study on the effects of propofol and dexmedetomidine on inflammatory responses and intraabdominal pressure in severe sepsis

https://doi.org/10.1016/j.jclinane.2008.10.010Get rights and content

Abstract

Study Objective

To compare the effects of an intravenous infusion of propofol and the alpha-2 adrenoceptor, dexmedetomidine, on inflammatory responses and intraabdominal pressure (IAP) in severe sepsis after abdominal surgery, specifically, serum cytokine levels (interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-α) and IAP.

Design

Prospective, single-center study.

Setting

University hospital.

Patients

40 adult ICU patients who had undergone ileus surgery and who were expected to require postoperative sedation and ventilation.

Interventions

Patients received either a loading dose infusion of propofol (Group P; n = 20) one mg/kg over 15 minutes followed by a maintenance dose of one to three mg/kg/hr (n = 20, Group P) or a loading dose of dexmedetomidine of one μg/kg over 10 minutes followed by a maintenance dose of 0.2-2.5 μg/kg/h (n = 20, Group D) at the 24th hour.

Measurements

Biochemical and hemodynamic parameters, cytokine levels, and IAP were recorded before the start of the study and at the 24th and 48th hours.

Main Results

TNF-α levels were significantly lower at the 24th hour (14.66 ± 4.40 pg/mL vs. 21.21 ± 11.37 pg/mL, respectively) and at the 48th hour (21.25 ± 15.85 pg/mL vs. 46.55 ± 35.99 pg/mL, respectively) in Group D. IL-1 levels were significantly lower at the 24th hour (5.03 ± 0.15 pg/mL vs. 6.23 ± 2.09 pg/mL, respectively) and the 48th hour (5.01 ± 0.37 pg/mL vs. 6.42 ± 2.76 pg/mL, respectively) in Group D. IL-6 levels were significantly lower at the 24th hour (253.1 ± 303.6 pg/mL and 511.3 ± 374.8 pg/mL, respectively) and at the 48th hour (343.5 ± 393.4 pg/mL and 503.7 ± 306.4 pg/mL, respectively) in Group D. Intraabdominal pressure also was significantly lower at the 24th hour (12.35 ± 5.84 mmHg vs. 18.1 ± 2.84 mmHg, respectively) and the 48th hour (13.9 ± 6.15 mmHg vs. 18.7 ± 3.46 mmHg, respectively) in Group D.

Conclusion

Dexmedetomidine infusion decreases TNF-a, IL-1, and IL-6 levels and IAP more than a propofol infusion.

Introduction

Sepsis is defined as the systemic response to infection. The deleterious effects of bacterial invasion of body tissues result from the combined actions of enzymes and toxins, produced by the micro-organisms themselves and by endogenous cells in response to the infectious process. Despite advances in supportive care, the mortality rate in patients with severe sepsis continues to exceed 30% [1], [2].

The highly selective and potent α2 agonist, dexmedetomidine, is an effective agent for sedation and analgesia in the intensive care unit (ICU) [3]. Taniguchi et al. [4] showed that, even in an in vivo experiment, dexmedetomidine has an inhibitory effect on cytokine responses that leads to endotoxemia. These findings suggest that one of the mechanisms of the anti-inflammatory effects of dexmedetomidine may be modulation of cytokine production by macrophages and monocytes [4]. In an in vitro study conducted by Rossano et al. [5], propofol induced a greater increase in interleukin (IL)-1α production than did midazolam, and both drugs increased tumor necrosis factor alpha (TNF-α) production from human monocytes. Furthermore, Larsen et al. [6] showed that propofol, even in low concentrations, augmented the lipopolysaccharide-stimulated TNF-α response. There has been little study of the effect of α2-adrenoceptor agonists and propofol on the inflammatory response in severely septic patients.

The clinical relevance of intraabdominal pressure (IAP) in the ICU setting is increasingly being recognized. Intraabdominal pressure is the steady-state pressure that is concealed within the abdominal cavity. A pathological increase in IAP has negative effects on splanchnic, respiratory, cardiovascular, renal, and neurological function. The cutoff measurement used to define intraabdominal hypertension (IAH) is defined as IAP equal to or greater than 12 mmHg, whereas abdominal compartment syndrome (ACS) is defined as IAP above 20 mmHg. Intraabdominal hypertension not only has harmful consequences on different organ systems, but is also associated with mortality [7], [8], [9], [10], [11]. Abdominal perfusion pressure (APP) is statistically better than either parameter alone in predicting patient survival from IAH and ACS. A target APP of at least 60mmHg correlates with improved survival from IAH and ACS [10].

Opioids increase skeletal muscle tone through a complex pathway involving the locus coeruleus and several transmitters, including glutamine agonism [12] and alpha-2 adrenergic inhibition [13]. After administration of opioids, the neural pathway associated with rhythmic activation of the abdominal muscles is the usual pathway associated with respiratory activation of these muscles. In dogs, during stable isocapnic anesthesia with pentobarbitone, abdominal muscle activity increased progressively; this activity led to increased ribcage motion despite constant inspiratory activity [14].

Although propofol and dexmedetomidine are used for sedation in the ICU, there are limited data on their effects on inflammatory responses and IAP in severely septic patients. The purpose of our study was to evaluate the effects of an intravenous (IV) infusion of propofol and the alpha-2 adrenoceptor agonist, dexmedetomidine, on serum cytokine levels (TNF-α, IL-1, IL-6) and IAP in severely septic patients after abdominal surgery.

Section snippets

Patient population and study design

The Regional Committee on Medical Research Ethics at Trakya University Hospital approved the study. Written, informed consent was obtained from patients when possible or from the next of kin. We studied 40 adult patients admitted to the ICU after ileus surgery and who were expected to require postoperative sedation and ventilation. Critically ill patients were included in the study as soon as they met at least two of the criteria of sepsis, as defined by the American College of Chest

Patient characteristics

The groups were similar for age, gender, body mass index, APACHE II score, SOFA score, types of surgery, operation time, dose of intraoperative fentanyl, source of infection, APP, fluid balance and CVP (Table 1). Twenty of 40 patients received a propofol infusion (Group P) and 20 received a dexmedetomidine infusion (Group D). In Group D and Group P, intraoperative fentanyl requirement was 525 (375-500) μg/kg and 500 (300-550) μg/kg, respectively. In the ICU, duration of sedative infusions was

Discussion

We aimed to select the best sedative drug for inflammatory responses and for IAP. We evaluated the effects of IV infusions of propofol and dexmedetomidine on serum cytokine levels (TNF-α, IL-1, IL-6) and IAP in severely septic patients after abdominal surgery. Our findings suggest that dexmedetomidine may prevent inflammatory effects and may decrease IAP more than propofol infusion in severely septic patients during sedation.

In the critically ill, IAP is frequently elevated above the patient's

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    Supported by University of Trakya Research Grant No. TUBAP 666, Edirne, Turkey.

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