Propofol increases morbidity and mortality in a rat model of sepsis

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.

Remote Ischemic Preconditioning

“…propofol, fluranes, opioids) seem to interfere with the effects of preconditioning, either by counteracting or mimicking protective mechanisms. [31][32][33] Two major trials on RIPC for cardiac surgery surprisingly concluded with the absence of benefits for patients. 34,35 Although many reasons may come into play, a plausible explanation for failed protection through RIPC is that the pharmacological agents used in these 2 trials have neutralized any RIPC benefits or have pre-engaged protective routes otherwise activated through RIPC.…”

Anaesthetic management and unplanned admission to intensive care after thoracic surgery

“…The inhalational anaesthetic technique offers a simple and reliable way to control the depth of anaesthesia; to protect the organs against ischaemia‐reperfusion injury; to potentiate the effects of neuromuscular blocking agents and to decrease airway resistance . In experimental models of sepsis, exposure to halogen‐containing hydrocarbons has been shown to improve survival, whereas propofol anaesthesia is associated with increased mortality along with larger systemic release of endotoxins . Likewise, in thoracic surgery with one‐lung ventilation, the early pulmonary protective effect of inhalational anaesthesia is accompanied by lower levels of alveolar inflammatory mediators, when compared with i.v.…”

ET-26 hydrochloride (ET-26 HCl) has similar hemodynamic stability to that of etomidate in normal and uncontrolled hemorrhagic shock (UHS) rats

“…Exposure to trauma leads to hemorrhagic shock, which requires surgical intervention to control the bleeding. Induction of anesthesia using the commonly used anesthetic propofol carries an increased risk of hypotension, resulting in cardiovascular adverse effects [ 4 ]. Etomidate can be used as an alternative to propofol in order to prevent, or reduce the risk of hemodynamic instability during the induction of anesthesia.…”