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Bleeding in Knee Arthroplasty After Preconditioning With Sevoflurane

Primary Purpose

Blood Loss, Surgical, Blood Transfusion

Status
Completed
Phase
Not Applicable
Locations
Brazil
Study Type
Interventional
Intervention
Sevoflurane
Propofol
Sponsored by
University of Sao Paulo General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Blood Loss, Surgical focused on measuring Blood Loss, Surgical, Blood Transfusion, Arthroplasty, Replacement, Knee, anesthetic preconditioning

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • indication for knee arthroplasty

Exclusion Criteria:

  1. Physical state according to classification from American Association of Anesthesiologists (ASA) III or higher,
  2. Obesity (body mass index, BMI, greater than 30),
  3. Renal insufficiency - patients on a dialysis program or with a serum creatinine level above 1.4 mg / dL,
  4. Hematocrit less than 30% or hemoglobin less than 10g / dL,
  5. Records of myocardial infarction during the last 6 months, unstable angina pectoris,
  6. History of coagulation disorders,
  7. Use of oral anticoagulants, heparin or acetylsalicylic acid in the last 5 days.

Sites / Locations

  • Hospital das Clínicas - Faculdade de Medicina da Universidade de Sao Paulo

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

GP - sevoflurane

GC - control

Arm Description

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 and will be preconditioned with intravenous propofol for 15 minutes before the installation of ischemia by tourniquete.

Outcomes

Primary Outcome Measures

Blood loss
Volume of blood drainage in the postoperative period;

Secondary Outcome Measures

Blood transfusion
Need and volume of blood transfusion;
Morbidity
Immediate postoperative morbidity and up to 30 days postoperatively.

Full Information

First Posted
December 14, 2017
Last Updated
February 24, 2021
Sponsor
University of Sao Paulo General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03379103
Brief Title
Bleeding in Knee Arthroplasty After Preconditioning With Sevoflurane
Official Title
Effects on Bleeding in Knee Arthroplasty After Ischemic Preconditioning With Sevoflurane
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
February 2, 2018 (Actual)
Primary Completion Date
December 19, 2018 (Actual)
Study Completion Date
December 19, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Sao Paulo General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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: Coagulogram for coagulation times; Volume of blood drainage in the postoperative period; Need and volume of blood transfusion; Dosage of arterial pH, lactate and CPK enzyme; 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%.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Blood Loss, Surgical, Blood Transfusion
Keywords
Blood Loss, Surgical, Blood Transfusion, Arthroplasty, Replacement, Knee, anesthetic preconditioning

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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
Outcomes Assessor
Masking Description
Statistical analysis will not open label for group allocation
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GP - sevoflurane
Arm Type
Active Comparator
Arm Description
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
Arm Title
GC - control
Arm Type
Placebo Comparator
Arm Description
GC - patients will be anesthetized with sevoflurane associated with subarachnoid anesthesia and will be preconditioned with intravenous propofol for 15 minutes before the installation of ischemia by tourniquete.
Intervention Type
Drug
Intervention Name(s)
Sevoflurane
Intervention Description
Patients will receive 1 MAC sevoflurane for 15 minutes before the installation of member ischemia by tourniquete
Intervention Type
Drug
Intervention Name(s)
Propofol
Intervention Description
Patients will receive propofol for 15 minutes before the installation of member ischemia by tourniquete
Primary Outcome Measure Information:
Title
Blood loss
Description
Volume of blood drainage in the postoperative period;
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
Blood transfusion
Description
Need and volume of blood transfusion;
Time Frame
24 hours
Title
Morbidity
Description
Immediate postoperative morbidity and up to 30 days postoperatively.
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: indication for knee arthroplasty Exclusion Criteria: Physical state according to classification from American Association of Anesthesiologists (ASA) III or higher, Obesity (body mass index, BMI, greater than 30), Renal insufficiency - patients on a dialysis program or with a serum creatinine level above 1.4 mg / dL, Hematocrit less than 30% or hemoglobin less than 10g / dL, Records of myocardial infarction during the last 6 months, unstable angina pectoris, History of coagulation disorders, Use of oral anticoagulants, heparin or acetylsalicylic acid in the last 5 days.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joaquim E Vieira, MD, PhD
Organizational Affiliation
University of Sao Paulo School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital das Clínicas - Faculdade de Medicina da Universidade de Sao Paulo
City
São Paulo
ZIP/Postal Code
01246-903
Country
Brazil

12. IPD Sharing Statement

Citations:
PubMed Identifier
8119009
Citation
Burkart BC, Bourne RB, Rorabeck CH, Kirk PG, Nott L. The efficacy of tourniquet release in blood conservation after total knee arthroplasty. Clin Orthop Relat Res. 1994 Feb;(299):147-52.
Results Reference
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16078916
Citation
Cid J, Lozano M. Tranexamic acid reduces allogeneic red cell transfusions in patients undergoing total knee arthroplasty: results of a meta-analysis of randomized controlled trials. Transfusion. 2005 Aug;45(8):1302-7. doi: 10.1111/j.1537-2995.2005.00204.x.
Results Reference
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PubMed Identifier
19007970
Citation
Kagoma YK, Crowther MA, Douketis J, Bhandari M, Eikelboom J, Lim W. Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery: a systematic review of randomized trials. Thromb Res. 2009 Mar;123(5):687-96. doi: 10.1016/j.thromres.2008.09.015. Epub 2008 Nov 12.
Results Reference
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PubMed Identifier
22623147
Citation
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Citation
Girardis M, Milesi S, Donato S, Raffaelli M, Spasiano A, Antonutto G, Pasqualucci A, Pasetto A. The hemodynamic and metabolic effects of tourniquet application during knee surgery. Anesth Analg. 2000 Sep;91(3):727-31. doi: 10.1097/00000539-200009000-00043.
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Citation
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Citation
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Citation
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Citation
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Citation
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Bleeding in Knee Arthroplasty After Preconditioning With Sevoflurane

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