Abstract
IntroductionSevere sepsis is associated with approximately 50% mortality and accounts for tremendous healthcare costs. Most patients require ventilatory support and propofol is commonly used to sedate mechanically ventilated patients. Volatile anesthetics have been shown to attenuate inflammation in a variety of different settings. We therefore hypothesized that volatile anesthetic agents may offer beneficial immunomodulatory effects during the course of long-term intra-abdominal sepsis in rats under continuous sedation and ventilation for up to 24 hours.MethodsSham operation or cecal ligation and puncture (CLP) was performed in adult male Wistar rats followed by mechanical ventilation. Animals were sedated for 24 hours with propofol (7 to 20 mg/kg/h), sevoflurane, desflurane or isoflurane (0.7 minimal alveolar concentration each).ResultsSeptic animals sedated with propofol showed a mean survival time of 12 hours, whereas >56% of all animals in the volatile groups survived 24 hours (P <0.001). After 18 hours, base excess in propofol + CLP animals (−20.6 ± 2.0) was lower than in the volatile groups (isoflurane + CLP: -11.7 ± 4.2, sevoflurane + CLP: -11.8 ± 3.5, desflurane + CLP -14.2 ± 3.7; all P <0.03). Plasma endotoxin levels reached 2-fold higher levels in propofol + CLP compared to isoflurane + CLP animals at 12 hours (P <0.001). Also blood levels of inflammatory mediators (tumor necrosis factor-α, interleukin-1β, interleukin-10, CXCL-2, interferon-γ and high mobility group protein-1) were accentuated in propofol + CLP rats compared to the isoflurane + CLP group at the same time point (P <0.04).ConclusionsThis is the first study to assess prolonged effects of sepsis and long-term application of volatile sedatives compared to propofol on survival, cardiovascular, inflammatory and end organ parameters. Results indicate that volatile anesthetics dramatically improved survival and attenuate systemic inflammation as compared to propofol. The main mechanism responsible for adverse propofol effects could be an enhanced plasma endotoxin concentration, leading to profound hypotension, which was unresponsive to fluid resuscitation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0751-x) contains supplementary material, which is available to authorized users.
Highlights
Severe sepsis is associated with approximately 50% mortality and accounts for tremendous healthcare costs
Blood levels of inflammatory mediators were accentuated in propofol + cecal ligation and puncture (CLP) rats compared to the isoflurane + CLP group at the same time point (P
The main mechanism responsible for adverse propofol effects could be an enhanced plasma endotoxin concentration, leading to profound hypotension, which was unresponsive to fluid resuscitation
Summary
Severe sepsis is associated with approximately 50% mortality and accounts for tremendous healthcare costs. Most patients require ventilatory support and propofol is commonly used to sedate mechanically ventilated patients. We hypothesized that volatile anesthetic agents may offer beneficial immunomodulatory effects during the course of long-term intra-abdominal sepsis in rats under continuous sedation and ventilation for up to 24 hours. Intubation and mechanical ventilation are needed in about 55% to 70% of septic patients admitted to an intensive care unit (ICU) [11], which makes sedation inevitable [12]. Based on this fact, it is crucial to determine the effect and impact of sedatives on the course of sepsis. Wake-up time can be considerably delayed after a prolonged application of benzodiazepines and Schläpfer et al Critical Care (2015) 19:45 propofol has become a widely-used alternative worldwide [13]
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