Dose-dependent influence of barbiturates but not of propofol on human leukocyte phagocytosis of viable Staphylococcus aureus

Ploppa, Annette; Kiefer, Ralph-Thomas; Nohé, Boris; Haeberle, Helene A.; Dieterich, Hans-Jürgen; Unertl, K.; Krueger, Wolfgang A.

doi:10.1097/01.ccm.0000199067.71968.6e

Cited by 24 publications

(9 citation statements)

References 28 publications

(39 reference statements)

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“…The effect of propofol on phagocytosis has not been clear. Some investigators have reported that propofol inhibits phagocytosis in neutrophils and macrophages in vitro (11,30), and others described no effect of propofol on human leukocyte phagocytosis (42).…”

Section: Discussionmentioning

confidence: 99%

Propofol inhibits pressure-stimulated macrophage phagocytosis via the GABA_A receptor and dysregulation of p130cas phosphorylation

Shiratsuchi

Kouatli

et al. 2009

American Journal of Physiology-Cell Physiology

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Surgical stress and anesthesia result in systemic immunosuppression. Propofol, a commonly used anesthetic agent, alters immune cell functions. Previously, we demonstrated that extracellular pressure increases macrophage phagocytosis. We hypothesized that propofol might influence pressure-induced macrophage phagocytosis in monocytes from patients undergoing surgery. Pressure (20 mmHg above ambient pressure) augmented phagocytosis in monocytes from non-propofol-anesthetized patients but reduced phagocytosis in monocytes from propofol-anesthetized patients. In vitro, propofol stimulated phagocytosis but reversed pressure-induced phagocytosis in THP-1 macrophages and monocytes from healthy volunteers. The GABAA receptor antagonists picrotoxin and SR-95531 did not affect basal THP-1 phagocytosis or prevent pressure-stimulated phagocytosis. However, picrotoxin and SR-95531 negated the inhibitory effect of pressure in propofol-treated cells without altering propofol-induced phagocytosis. Phosphorylation of the adaptor protein p130cas was inversely related to phagocytosis: it was inhibited by pressure or propofol but increased by pressure + propofol compared with propofol alone. Reduction of p130cas by small interfering RNA in THP-1 macrophages increased basal phagocytosis and prevented pressure and propofol effects. In conclusion, propofol may alter macrophage responses to pressure via the GABAA receptor and p130cas, whereas pressure also acts via p130cas but independently of GABAA receptors. p130cas may be an important target for modulation of macrophage function in anesthetized patients.

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Section: Discussionmentioning

confidence: 99%

Propofol inhibits pressure-stimulated macrophage phagocytosis via the GABA_A receptor and dysregulation of p130cas phosphorylation

Shiratsuchi

Kouatli

et al. 2009

American Journal of Physiology-Cell Physiology

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“…In addition, pentobarbital directly enhanced the viabilities of cells, and protected cells from apoptosis induced by deferoxamine mesylate-induced hypoxia. Further, in an in vitro model substantially different effects of barbiturates and propofol were found on phagocytosis of Staphylococcus aureus [126]. The inhibitory effects of barbiturates demonstrated a strong dose-dependency.…”

Section: Resultsmentioning

confidence: 99%

Intensive care unit-acquired infection as a side effect of sedation

et al. 2010

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IntroductionSedative and analgesic medications are routinely used in mechanically ventilated patients. The aim of this review is to discus epidemiologic data that suggest a relationship between infection and sedation, to review available data for the potential causes and pathophysiology of this relationship, and to identify potential preventive measures.MethodsData for this review were identified through searches of PubMed, and from bibliographies of relevant articles.ResultsSeveral epidemiologic studies suggested a link between sedation and ICU-acquired infection. Prolongation of exposure to risk factors for infection, microaspiration, gastrointestinal motility disturbances, microcirculatory effects are main mechanisms by which sedation may favour infection in critically ill patients. Furthermore, experimental evidence coming from studies both in humans and animals suggest that sedatives and analgesics present immunomodulatory properties that might alter the immunologic response to exogenous stimuli. Clinical studies comparing different sedative agents do not provide evidence to recommend the use of a particular agent to reduce ICU-acquired infection rate. However, sedation strategies aiming to reduce the duration of mechanical ventilation, such as daily interruption of sedatives or nursing-implementing sedation protocol, should be promoted. In addition, the use of short acting opioids, propofol, and dexmedetomidine is associated with shorter duration of mechanical ventilation and ICU stay, and might be helpful in reducing ICU-acquired infection rates.ConclusionsProlongation of exposure to risk factors for infection, microaspiration, gastrointestinal motility disturbances, microcirculatory effects, and immunomodulatory effects are main mechanisms by which sedation may favour infection in critically ill patients. Future studies should compare the effect of different sedative agents, and the impact of progressive opioid discontinuation compared with abrupt discontinuation on ICU-acquired infection rates.

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“…Unfortunately, high-dose barbiturates have numerous, potentially life-threatening, adverse effects [6,7]. Complications may include prolonged iatrogenic coma, even after cessation of the infusion; hypotension as a consequence of venous pooling, peripheral vasodilatation, and impaired myocardial contractility [8,9]; respiratory depression [10]; severe electrolyte and endocrine disturbances [11,12]; and immunosuppression with frequent nosocomial infections [13][14][15]. We present here a case demonstrating that an exacerbating factor may, in some cases, be the accumulation of propylene glycol, the vehicle used to administer intravenous pentobarbital and phenobarbital.…”

Section: Introductionmentioning

confidence: 99%

Propylene Glycol Toxicity Complicating Use of Barbiturate Coma

Bledsoe

Kramer

2008

Neurocrit Care

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Dose-dependent influence of barbiturates but not of propofol on human leukocyte phagocytosis of viable Staphylococcus aureus

Cited by 24 publications

References 28 publications

Propofol inhibits pressure-stimulated macrophage phagocytosis via the GABA_A receptor and dysregulation of p130cas phosphorylation

Propofol inhibits pressure-stimulated macrophage phagocytosis via the GABA_A receptor and dysregulation of p130cas phosphorylation

Intensive care unit-acquired infection as a side effect of sedation

Propylene Glycol Toxicity Complicating Use of Barbiturate Coma

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Dose-dependent influence of barbiturates but not of propofol on human leukocyte phagocytosis of viable Staphylococcus aureus

Cited by 24 publications

References 28 publications

Propofol inhibits pressure-stimulated macrophage phagocytosis via the GABAA receptor and dysregulation of p130cas phosphorylation

Propofol inhibits pressure-stimulated macrophage phagocytosis via the GABAA receptor and dysregulation of p130cas phosphorylation

Intensive care unit-acquired infection as a side effect of sedation

Propylene Glycol Toxicity Complicating Use of Barbiturate Coma

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Product

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Propofol inhibits pressure-stimulated macrophage phagocytosis via the GABA_A receptor and dysregulation of p130cas phosphorylation

Propofol inhibits pressure-stimulated macrophage phagocytosis via the GABA_A receptor and dysregulation of p130cas phosphorylation