Bleeding in Knee Arthroplasty After Preconditioning With Sevoflurane
Condition: Blood Loss, Surgical; Blood Transfusion
MeSH terms: Hemorrhage; Blood Loss, Surgical
Study type: Interventional

Summary: 
      Knee arthroplasty is performed with restriction of blood flow by use of the pressure
      tourniquet. Ischemia of skeletal musculature is accompanied by the formation of reactive
      oxygen species and release of vasoactive factors. Inhaled anesthetics were described as
      possible protective factors, termed "ischemic preconditioning". The objective of this
      investigation is to observe the effects of preconditioning with inhaled anesthetic on
      bleeding in the postoperative period of knee arthroplasty surgery. The study will be
      prospective and randomized. Patients will be allocated by means of a randomized table in two
      groups: Group Preconditioning (GP) - subarachnoid and general anesthesia with preconditioning
      with 1 minimal alveolar concentration (MAC) for 15 minutes before the installation of the
      ischemia by tourniquet; Group control (GC) - subarachnoid and general anesthesia with
      sevoflurane without preconditioning. Will be evaluated: hemoglobin and hematocrit, platelet
      count and coagulogram, electrolytes and creatinine, lactate and glycemia. Volume of drainage
      will be evaluated until drainage is withdrawn and need for transfusion measuring the number
      of bags of blood concentrate and volume transfused. Pain assessment will be done by means of
      visual analog scale. Morbidity will be recorded up to the 30th postoperative day by chart
      analysis. Patients will be allocated to the study groups by random number table. Data will be
      presented descriptively, frequently, mean and standard deviation, or medians and distribution
      in 25-75% percentiles. The comparison between continuous measurements will be made by means
      of repeated measures intra-group analysis of variance (ANOVA) and Student's t-test for
      evaluation between groups. The need for transfusion will be compared by Fisher's exact test.
      Pain intensity will be compared by Wilcoxon test for non-parametric data. A commercially
      available statistical package - SPSS version 15.0 (SPSS Inc.) will be used. A value of P
      <0.05 will be considered statistically significant.
    

Detailed description: 
      The use of pneumatic tourniquet allows a clear surgical field by restricting blood flow to
      the area to be operated, which implies at least intraoperative bleeding, but with a high risk
      of postoperative bleeding.

      The late bleeding associated with tourniquet use appears to be due to the imbalance between
      coagulation and fibrinolysis. The use of antifibrinolytics, such as tranexamic acid and
      epsilon aminocaproic acid, has been shown to reduce postoperative bleeding, reducing the need
      for transfusion of blood components postoperatively, without increasing the risk of
      thromboembolism. The effects of tourniquet, which can be maintained at intervals of 75 to 100
      minutes, include elevation in blood pressure while it is insuflated, cardiac index elevation
      during ischemia and its subsequent elevation at the moment of release to the circulation, at
      which time there is also an increase in oxygen consumption as well as the release of CO2.
      This increase in oxygen consumption is directly related to the time of ischemia.

      Skeletal muscles's ischemia is accompanied by anaerobic glycolysis, formation of reactive
      oxygen species, and release of vasoactive factors. Inhaled anesthetics, such as isoflurane
      and sevoflurane, have been described as possible protective factors for both cardiac and
      skeletal muscles, although the literature still suggests the need for additional studies. Its
      use in the period before the onset of ischemia is called "ischemic preconditioning".

      The objective of this investigation will be to observe the effects of an inhalational
      anesthetic, commonly used in anesthesia on bleeding, in the results of coagulation tests and
      in the consumption of blood components in the postoperative period of knee arthroplasty
      surgery.

      Goals

      To compare the effects of preconditioning with sevoflurane in total knee arthroplasty surgery
      by:

        1. Coagulogram for coagulation times;

        2. Volume of blood drainage in the postoperative period;

        3. Need and volume of blood transfusion;

        4. Dosage of arterial pH, lactate and CPK enzyme;

        5. Immediate postoperative morbidity and up to 30 days postoperatively.

      Statistic

      Data will be presented by descriptive tables and frequency, mean and standard deviation, or
      medians and distribution in 25-75% percentiles for data that do not find a normal
      distribution. The Kolmogorov-Smirnov test will determine if there is a normal distribution.

      Values for hemoglobin, hematocrit, platelet count, arterial blood gas values, electrolytes,
      creatinine, CPK, lactate, blood glucose and coagulogram will be compared by analysis of
      variance (ANOVA).

      The intragroup analyzes will use repeated measures ANOVA and the Dunnett test if there is a
      significant difference between the moments of the same group, since the test may be better
      considered for comparison with a control (preoperative) time. Between the groups, the values
      will be compared moment by moment with Student's t-test.

      The need for transfusion, considering the number of CC bags, will be compared by Fisher's
      exact test and its volume by Student's t-test. Pain intensity in the postoperative period
      will be evaluated by visual analogue scale and compared by Wilcoxon's test for non-parametric
      data between the time of entry and discharge of RPA. A commercially available statistical
      package - SPSS version 15.0 (SPSS Inc.) will be used. A value of P <0.05 will be considered
      statistically significant.

      Patients will be allocated to the study groups by random number table. Briefly, generating a
      list of two-digit numbers determines the order of entry of patients into the study groups. A
      minimum expected difference between the means of the treatments (groups) established at 500
      ml for the required volume of postoperative transfusion, standard deviation at 400 ml, with
      test power at 80% and significance level in 5% suggesting a distribution of 15 patients in
      each group, considering losses in 50%.
    

Intervention name(s): Sevoflurane; Propofol
Intervention type(s): Drug; Drug
Intervention description(s): Patients will receive 1 MAC sevoflurane for 15 minutes before the installation of member ischemia by tourniquete; Patients will receive propofol for 15 minutes before the installation of member ischemia by tourniquete
Intervention MeSH terms: Propofol; Sevoflurane
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Patients will be allocated by means of a randomized table in 2 groups:
GP - patients will be anesthetized with sevoflurane associated with subarachnoid anesthesia and will be preconditioned with 1 MAC sevoflurane for 15 minutes before the installation of ischemia by tourniquete
GC - patients will be anesthetized with sevoflurane associated with subarachnoid anesthesia
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Blood Loss, Surgical; Blood Transfusion; Arthroplasty, Replacement, Knee; anesthetic preconditioning