Spontaneous and Oxytocin-induced Contractility After Exposure to Intravenous Anesthetic Agents: an In-vitro Study in Human Myometrium
Condition: Postpartum Hemorrhage
MeSH terms: Postpartum Hemorrhage; Hemorrhage
Study type: Interventional

Summary: 
      Poor uterine tone after the birth of a baby may cause serious bleeding (called postpartum
      hemorrhage or PPH). This is a major cause of maternal death worldwide. In the developed world
      the cesarean section rate is increasing. There are two modalities for anesthesia for cesarean
      section; general and regional (eg. spinal anesthetic). General anesthesia has been associated
      with increased blood loss compared to regional and the reasons for this may be
      multifactorial. Some of the anesthesia gases have been studied and there is laboratory
      evidence to suggest that these gases may reduce the tone of the uterus and therefore cause
      increased blood loss due to poor uterine tone. To date there has been little study on the
      intravenous anesthesia agents. These agents are usually administered to anaesthetise the
      patient at the start of surgery (induction of anesthesia), however they can also be used
      instead of the gases to keep the patient asleep using a 'total intravenous anesthesia'
      technique. Laboratory work in rats has suggested that high doses of these intravenous drugs
      might reduce uterine tone, thus increasing the risk of blood loss. Interestingly, at low
      doses one of these drugs (ketamine) may actually increase uterine tone. Only one of these
      drugs has been studied in human uterine tissue. The investigators plan to compare three
      anaesthesia induction agents on human uterine tissue under physiological conditions in the
      laboratory.

      This study will be the first to compare these three drugs on human tissue. The investigators
      plan to determine the impact of these drugs on spontaneous uterine contractility and also
      contractilty induced by oxytocin, which is the drug most commonly administered to help
      contract the uterus after birth. This is important as it will help inform anesthesiologists
      as to the best drug to use depending on the clinical circumstance.

      The investigators hypothesize that the intravenous induction agents will cause a dose
      dependent decrease in spontaneous uterine contractility, similar to what has been described
      in the rat model. The investigators also expect that exposure to high concentrations of
      intravenous anesthesia induction agents will cause a blunted contractile response to
      oxytocin.
    

Detailed description: 
      There is an increasing need to fully understand the mechanisms that contribute to the higher
      blood loss after general anesthesia during cesarean section therefore it is important the
      investigators identify all pharmacological contributors to poor uterine tone. Furthermore,
      anesthesiologists are increasingly called upon to care for women undergoing a range of
      in-utero fetal surgeries which require a careful balanced anesthetic and strict control of
      uterine tone.

      This will be the first study that compares the three commonly used intravenous anesthesia
      agents on human myometrium: ketamine, etomidate and propofol. This study is required to allow
      doctors make informed decisions about which anesthesia agent is most suitable to manage their
      patient depending on clinical circumstances.

      The specific objective of this project is to investigate the pharmacological dose-response
      profiles of different anesthesia induction agents by in-vitro isometric tension measurements
      of contractions in gravid human myometrium. The investigators will study both spontaneous and
      oxytocin induced contractility.
    

Intervention name(s): Oxytocin; Ketamine; Propofol; Etomidate
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Oxytocin solution, 20nM concentration; Ketamine in solution, 10-4M to 10-7M; Propofol in solution, 10-4M to 10-7M; Etomidate in solution, 10-4M to 10-7M
Other intervention name(s): pitocin; ketamine HCl
Intervention MeSH terms: Ketamine; Propofol; Etomidate; Oxytocin
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: uterine contraction; oxytocin; ketamine; propofol; etomidate