Introduction

Hemorrhagic syndrome is a common problem after cardiac surgery. In the performed studies, the rate of bleeding after cardiac surgery (coronary artery bypass surgery) has been reported as 5% to 25%. When there is blood circulation in the cardiopulmonary bypass machine (CBP), due to the interaction between blood and the inner surface of the device, platelet activity is impaired and the fibrinolytic reaction is intensified, which leads to coagulation disorders. It also increases bleeding in patients, which leads to the increasing need for packed-cell transfusion and other blood products. The transfusion of  blood products has various side effects such as infectious complications including transmission, viral hepatitis, hemolytic and non-hemolytic reactions, and suppression of the immune system.

Various measures can be taken to reduce the incidence of hemorrhagic syndromes including autotransfusion method and diluting blood during surgery to reduce the use of allogeneic blood products. However, after surgery and patient's admission to the intensive care unit (ICU), hemorrhage continues as mediastinal blood drainage, and leads to the increasing use of blood products, various associated complications, prolonged ICU stay, and increased mortality rate.

Since the stimulation of fibrinolysis and reduced coagulation factors such as fibrinogen may lead to mediastinal hemorrhage, in this study, we evaluated and compared the use of tranexamic acid and fibrinogen in reducing mediastinal bleeding and decreasing the administration of blood products after open heart surgery.

Materials and Methods

This study (No. 910289) was performed on 13 October 2012 after the approval of the ethics committee of Mashhad University of Medical Sciences and obtaining written informed consents from the patients in the teaching hospitals of this university.

This study was a prospective interventional clinical trial. The study population included all children referring to Dr. Sheikh Hospital in Mashhad-Iran, who were candidates for elective hypospadias surgery. The two-stage sampling method was applied; in the first stage, the eligible subjects were selected by easy non-random method and in the second stage, they were randomly assigned to two groups. Field data collection method was applied and data were gathered using checklists and observation.

The inclusion criteria were as follows: 1) American Society of Anesthesiologists class Ι and ΙΙ (ASA); 2) 2-6 years of age; 3) candidate for hypospadias surgery; 4) absence of early coagulopathy [disorders associated with platelet count (PLT), international normalized ratio (INR), prothrombin time (PT), and partial thromboplastin time (PTT)]; 5) lack of diabetes; 6) non-consumption of Non-steroidal anti-inflammatory drugs (NSAIDS), 48 hours before surgery; 7) no excessive consumption of glucocorticoid; and 8) no need for supplemental doses of corticosteroid before anesthetic induction.

The exclusion criteria were as follows: 1) Out-of-range temperature of the operation room; 2) amino acid sensitivity; 3) operation time of more than 2.5 hours or less than 2 hours; 4) initial body temperature of <36°C or >38°C; 5) use of sympathomimetics (ephedrine-atropine) before or during the surgery; 6) intraoperative use of heating devices; and 7) more than 20% changes in blood pressure and heart rate.

The study variables included the study group, body temperature, age, sex, bleeding, and awakening time.

The sample size was calculated according to the formula, derived from the article of

 Selden and colleagues (1), with regard to the body temperature of patients in the two  groups (undergoing surgery) after waking up (36.56±0.1 and 35.76±0.1, respectively). However, the mentioned study was conducted on adults and unfortunately, no other sources were available. Body temperature was similar in both groups at the start of the study.

The sample size calculation showed that the current study could be conducted with any sample volume to reach the desired results. However, to be certain about the outcome of the study, the sample size was considered as 20 patients in each group.

Among children, aged 2 to 6 years, who were candidates for hypospadias surgery and had referred to Dr. Sheikh Hospital, 40 cases were randomly selected.  Afterwards, the patients were randomly divided into case and control groups, using the random assignment table. The basal body temperature of children in both groups was measured and recorded with a tympanic probe before serum injection.

In the study group, administration of 10% amino acid (2cc/kg/h) was started two hours before the surgery, which continued during the operation with normal saline solution (as a preservative solution). According to the formula and based on the patient's weight, the calculated amount of amino acid was deducted from the preservative solution and was continued until the end of the operation (maximum rate of amino acid was 4 cc/kg/h, and the maximum amount was 1 gr/kg). In the control group, normal saline solution was solely injected.

Fentany l 2 μg/kg, thiopental sodium 5 mg/kg, and atracurium 0.5 mg/kg were used for the patients' anesthesia and propofol 100 μg/kg/min was used for the intraoperative maintenance. After general anesthesia (GA), body temperature was measured at moment zero using the same probe.

The patients were monitored for body temperature, heart rate, blood pressure, and pulse oximetry. The patients' position was supine and routine NPO was performed.

During surgery, body temperature was recorded every 10 minutes in both groups, and the heating device was not used during the operation. The temperature of the prescribed sera was similar to the temperature of the operation room (kept at about 24°C). The measures to prevent hypothermia (including the operation room temperature, the temperature of the prescribed sera, and avoidance of wetting the body surface) were similarly taken in each group.

The rate of bleeding was recorded based on the suction volume and blood gas at the end of surgery. The patient's hematocrit was maintained at 30%; in case hematocrit was less than 30%, packed cell infusion was used. Variables were recorded until the end of the surgery and then the patients' awakening time (from the end of surgery to the first response to verbal stimulation) was recorded in both groups.

The collected data were entered into SPSS version 11.5.

Results

In the current study, the mean age of the patients was (4.17±1.64) years, which was (4.04±1.71) years in the case group and (4.29±1.60) years in the control group (P=0.630). The mean weight of the patients was (17.62±5.48) kg, which was (17.25±5.72) and (18.00±5.35) kg in the case and control groups (P= 0.630).

Duration of awakening time (from the end of surgery until the patient's waking-up) was (13.60± 4.91) min, with (11.90±5.27) and (15.30±3.96) min in the case and control groups (P= 0.027) (Table 1).

Table 1: Distribution of awakening time after surgery (in total and regarding the two groups)

The amount of intraoperative bleeding in all patients was (34.00±16.04) mL in total, with (32.75±16.32) CC and (35.26±16.08) CC in the case and control groups,         (P= 0.628) (Table 2).

Table 2: The amount of intraoperative bleeding in total and regarding the two groups

The patients’ body temperature at base time, after the induction of anesthesia, every ten minutes until the end of operation, and immediately after waking up in both groups is indicated in the following table. As it can be seen, although the patients’ body temperature was higher, before anesthesia and within the first few minutes, in the case group, the difference was not statistically significant. After 40 minutes of operation, the temperature was significantly different between the two groups; the temperature difference became even more significant as the surgery continued. T-test was used to measure body temperature at different times (Table 3) (Fig. 1).

Table 3: The patients' temperature in total and regarding the two groups at different times

             Fig. 1: The patients' body temperature

Discussion

In the current study, the length of awakening time was 13.60±4.91 min, which was 11.90±5.27 and 15.30±3.96 min in the case and control groups, respectively; there was a significant difference between the two groups. Intraoperative bleeding was 34.00±16.04 cc, which was not different between the groups.

Although the patients' body temperature was higher in the case group, the difference was not significant between the groups before, after, and 10 and 20 minutes after the start of surgery. However, this difference was significant in the next measurements and after waking up; this difference increased by time.

The effects of amino acid administration on patients' body temperature have been investigated by various researchers. In this study, the incidence of other complications such as shivering has been investigated, and the effect of amino acid administration along with different hypnotics has been compared to the effect of amino acid alone. These effects have been evaluated both in GA and epidural anesthesia (2,3) and in various surgical procedures such as open heart surgery (4). However, the analysis has not included children, which was the focus of our study.

Several studies on adults have fully examined the effects of amino acid administration on reducing shivering after surgery (5,6), decreasing intraoperative bleeding (7), improving immunologic function and accelerating wound healing (8), reducing the length of hospital stay (9), the patients' prognosis (4), and other associated complications (arrhythmias, hypertension, and myocardial ischemia) (10). In our study, we only examined the effect of amino acid administration on reducing bleeding and awakening time.

In most studies, it was shown that amino acid administration increases body temperature (11) or leads to a decrease in body temperature drop, compared to the control group (12,13); this was in consistence with the findings of our study. This effect has been rejected in only two studies (3,6), one of which included surgeries lasting more than 180 minutes (3).

The temperature drop, following amino acid administration, has been explained by  patients' increased thermal threshold (10), accumulation of body temperature (7), and reduced splanchnic oxygen uptake (1). It has been shown that fat movement is inhibited by amino acid administration (2), and nitrogen production is also reduced (12) without activating stress hormones or sympathoadrenal pathway (14).

This effect has been studied in various hypnotics such as propofol along with isoflurane (11) and sevoflurane along with propofol (3), which had various effects. Therefore, in our study, we used only one anesthetic method with one single hypnotic medication. This section describes various studies conducted  in  this  field,  and  we