Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02079064 |
| Other study ID # |
Anesthesia 98T |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
February 27, 2014 |
| Last updated |
October 10, 2017 |
| Start date |
January 2014 |
| Est. completion date |
July 2017 |
Study information
| Verified date |
October 2016 |
| Source |
Theodor Bilharz Research Institute |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The aim of this prospective randomized study is to evaluate the perioperative effects of
inhalational anesthesia (desflurane) and intravenous anesthesia (propofol) on hemostasis in
patients undergoing splenectomy with liver cirrhosis guided by the new technology (ROTEM) and
the traditional laboratory hemostatic markers.
Description:
After obtaining approval from the Institutional Research Ethics Committee and informed
written consent, thirty adult patients aged 25- 55 years of either sex, American Society of
Anesthesiologists (ASA) class II- III (Child A) suffering from cytopenia scheduled for
elective splenectomy will be recruited. Pancytopenia is defined as anemia (hemoglobin < 13.5
g/dL-male; <12 g/dL-female); leucopenia (total leukocyte count < 4,000/mm3) and
thrombocytopenia (platelet count < 150,000/mm3). Child B and C, Hb < 10 g/dL platelet count <
50,000/mm3, White Blood Cells (WBCs) < 2,000/mm3, prothrombin time [PT] ＞ 16 s and INR > 1.7,
extremes of age, obese patients (body mass index >35 kg m-2), and those using oral
anticoagulants, other antithrombotic drugs, or oral contraceptives, will be excluded from the
study.
All patients will be premedicated with 0.05 mg kg-1 i.v midazolam half an hour before
operation. In the operating room, continuous pulse oximetry, electrocardiogram, non-invasive
arterial blood pressure, PECO2, end-tidal anesthetic agent, neuromuscular monitoring, core
temperature (Infinity Kappa, Dräger, Lübeck, Germany) and hourly urine output will be
monitored throughout the operation. Depth of anesthesia will be monitored by using Bispectral
index (BIS). All IV fluids will be warmed, and a warm air blanket (Bair Hugger) will be
applied to every patient.
Thirty eligible patients will be allocated randomly to one of two equal groups (15 patients
each) according to a computer generated randomization list: group D; maintenance of
anesthesia with inhaled desflurane at 1 minimum alveolar concentration (MAC); group P,
maintenance of anesthesia with target-controlled infusion (TCI) propofol with a target plasma
concentration of propofol between 2 and 5 µg ml-1. The concentration of volatile anesthetics
or the rate of infusion of injected anesthetics will be titrated to maintain the BIS
numerical value between 40-50.
Anesthesia will be induced in both groups using i.v. fentanyl 1.5- 2 µg kg-1 and propofol 2-
2.5 mg kg-1. Atracurium 0.5 mg kg-1 will be administered for neuromuscular block and
continued according to the response to train-of-four peripheral nerve stimulation. After
intubation, patients will be mechanically ventilated with 30% oxygen in air throughout
surgery using a low flow system (1L min-1) to adjust an end-tidal carbon dioxide (PECO2)
between 30- 35 mmHg. Acetated Ringer's solution will be given as a preload and maintenance at
a rate of 5-7 ml kg-1 h-1. Patients' systolic arterial pressures will be maintained at 100
mmHg or 70% of the preoperative value, whichever is higher. Hypotension will be treated with
i.v. crystalloid fluid loading or intravenous boluses of ephedrine as appropriate. No colloid
transfusion will be allowed. Transfusions of red blood cells will be used to maintain
hemoglobin levels equal to or above 8 g dl-1. Platelets or fresh frozen plasma will be
infused only when indicated by ROTEM. At the end of surgery, neuromuscular blockade will be
antagonized with 0.05 mg kg-1 neostigmine and 0.02 mg kg-1 atropine. Postoperative analgesia
was provided by intravenous infusion of 1 gm acetaminophen and IV meperidine 1 mg kg-1 every
12 hours. Patients are given an anti-emetic ondansetron 4 mg postoperatively.
Blood Sampling:
Five blood samples will be collected; before operation, after ligation of splenic artery,
immediate post-operative, 24 hours and three days after the operation. Each time, five ml of
venous blood will be collected and assessment of the following parameters will be performed:
Complete blood picture:
1. Hemoglobin Concentration (by electronic cell counter).
2. Hematocrit (by electronic cell counter).
3. Platelet count (by electronic cell counter).
4. Red blood cells (by electronic cell counter).
5. White blood cells (by electronic cell counter).
Screening hemostatic tests:
1. Prothrombin Time (PT) (by conventional method).
2. International Normalized Ratio (INR) (by conventional method).
3. Partial Thromboplastin Time (PTT) (by conventional method).
Specific hemostatic tests:
1. Soluble platelet selectin (sP-selectin) [enzyme-linked immunosorbent assay (ELISA)].
2. Fibrinogen level (coagulation method).
3. D-dimer level (ELIZA).
At each sample time (0.3 ml blood) will be taken for measuring the following ROTEM variables:
- The time until initial fibrin formation (clotting time CT).
- The kinetics of fibrin formation and clot development (clot formation time (CFT) and α-
angle).
- The ultimate strength and stability of the fibrin clot (maximum clot firmness MCF).
- Clot lysis (fibrinolysis). The previous parameters provide information about platelet
activation, fibrin formation and clot retraction (all stages of the developing and
resolving clot). Blood samples are activated extrinsically (by tissue factor) and
intrinsically (by contact activator) via commercially available tests. Furthermore,
fibrinogen levels will be assessed by measuring clot strength (MCF) in the presence of
platelet inhibition (e.g., fib-TEM). This modified MCF represents the fibrin clot that
developed in the absence of any platelets, i.e., the functional fibrinogen [6].
Routine laboratory tests:
1. Serum creatinine.
2. Alanine aminotransferase (ALT),aspartate aminotransferase (AST), albumin, bilirubin.
Routine investigations will be performed pre-, post-operative and on the third day.
Follow up of each patient will be done at out-patients clinic after one month to have
thorough clinical examination, liver and kidney function tests, Child's Turcotte Pugh (CTP)
score assessment, laboratory hematological tests and ROTEM assessment. This is important to
assess post-operative complications, efficacy of splenectomy in improving cytopenia, and the
influence of splenectomy on the natural course of disease.
Statistical Analysis:
No previous study was conducted to assess the effects of anesthetic agents on hemostasis
during splenectomy with liver cirrhosis guided by ROTEM. Thus the calculation of the sample
size is difficult and also the reagents required for ROTEM are expensive so we designed this
thesis to be a pilot study. A sample size was chosen to be 15 patients in each group.
Comparison between the two groups will be performed using Mann-Whitney test, while comparison
within each group will be performed using Wilcoxon sign rank test. Comparison between
repeated measures in both groups was performed using ANOVA. The data are considered
significant if p values are ≤ 0.05. Statistical analysis will be performed with the aid of
the Statistical Package for the Social Sciences (SPSS) computer program, version 12 windows
(IBM, USA).
