Surgical trauma produces a stress response that determines a variety of neuroendocrine responses, including sympathetic activation, as reflected by changes in catecholamine plasma concentrations [1,2]. Several studies have shown that anaesthetic management can attenuate perioperative stress [3-5]. The increases in the plasma concentrations of noradrenaline (NA) and adrenaline (A) in patients undergoing elective abdominal surgery reflect an adrenergic response to afferent pain stimuli that is not blocked by general anaesthesia [1,6]. Much evidence drawn from adult patients has accumulated, which indicates that neuroaxial blockade prevents a predominant part of the endocrine changes following lower abdominal and lower extremity surgery [3,4,7], but the influence of caudal anaesthesia on catecholamine concentrations in children has still not been investigated thoroughly. Caudal anaesthesia combined with general anaesthesia is now used increasingly in children because it relieves pain successfully, has few side-effects and is easy to perform .
The purpose of this study was to assess the influence of caudal anaesthesia combined with general an-aesthesia on the plasma concentrations of A and NA in children undergoing ilioinguinal herniorrhaphy.
After the approval of the local ethics committee and written parental consent, 40 male paediatric patients ASA class I, aged between 1 and 8 years, undergoing elective ilioinguinal herniorrhaphy, were randomly assigned to two groups (control group and caudal group). Exclusion criteria included: children who had a haemoglobin of less than 11 g dL−1, any contraindication to regional anaesthesia, failed block and intraoperative episodes of hypoxia, hypercarbia, hypothermia with or without post-operative shivering.
The control group (n=20) received general anaesthesia (GA). Induction was with increasing concentrations of halothane 0.5% every three to five breaths in a mixture of N2O/O2 (50:50) up to 4%. After the disappearance of the eyelash reflex, a laryngeal mask of an appropriate size was inserted, and the end-tidal halothane concentration was maintained throughout the procedure in all the children in both groups at 1.5 MAC. After the insertion of the laryngeal mask and before surgical incision, fentanyl was administered intravenously up to 2 μg kg−1 in boluses of 5 μg over 5 min.
In this group, children who reacted to the surgical stimulus with increased heart rate and/or respiratory rate were given additional intravenous fentanyl titrated using doses of 5 μg, up to 4 μg kg−1. Patients breathed spontaneously through a Bain circuit, with a fresh gas flow of three times the minute volume.
The caudal group (n=20) received general anaesthesia as in the control group, but without intravenous fentanyl and combined with caudal block with bupivacaine 0.25%, 1 mL kg−1 to a maximum volume of 25 mL. The caudal block was performed after the child was anaesthetized and placed in the lateral position. The sacral hiatus was located by palpating the bony cornua on either side, the skin was prepared with povidone swabs, and a single caudal injection was performed with either a 21 or 23 G needle, using the fully aseptic technique. The block was considered successful when the operation was performed without the use of additional intravenous fentanyl or without increasing the concentration of the inhalation agents. Surgery was performed with standard intraoperative monitors (non-invasive blood pressure, pulse oximeter, electrocardiogram, capnography, precordial stethoscope and body temperature).
Ringer's lactate was infused intravenously at a rate of 4-6 mL kg−1 h−1 using an infusion pump.
All the children received 30 mg kg−1 paracetamol rectally after the induction of anaesthesia.
The patients in both groups did not receive any premedication drugs. However, the parents were allowed to be present during the induction of anaesthesia performed in a paediatric induction room.
An intravenous catheter was inserted into an antecubital vein after the application of Emla cream (Astra, Sodertalge, Sweden) containing lignocaine 25 mg g−1 and prilocaine 25 mg g−1 1 h before the induction of anaesthesia. Three mL of peripheral venous blood was aspirated three times: during the induction period (T0); at the end of surgery (T1); and when the children achieved an Aldrete score  of 10 points in the PACU (T2). Blood pressure and heart rate were noted during the time of blood withdrawal.
Plasma was separated and stored at −70°C. Plasma catecholamines were adsorbed onto albumina and then eluted and measured using a high-performance liquid chromatograph (HPLC) with an electrochemical detector .
Post-operative pain was assessed every 5 min in the PACU using a modified Children's Hospital of Eastern Ontario Pain Scale (m CHEOPS) . Patients with a pain score greater than five were given 1 μg kg−1 intravenous fentanyl in divided doses.
Statistical analysis was performed using multiple comparisons by ANOVA for repeated measurements, followed by the Bonferroni post hoc test and unpaired Student's t-test for the parametric data. Values are presented as means ± SD and range. Statistical significance was assumed when the P-value was ≤0.05.
There were no significant differences between the groups in terms of demographic data (Table 1). Three patients from the caudal group were withdrawn from the study because of a low Spo2 of 93% for 2 min (two patients) and failed caudal block (one patient), and three additional children were included in the study to bring n to 20. Four patients from the control group were excluded: one because of hypothermia of less than 35°C, three because of difficulty in blood sampling in the PACU, and four additional children were added to the study.
There was no significant difference in the baseline plasma levels of A and NA (P>0.05) between the two groups (Table 2). There was a significant difference in A levels between the two groups at T1 (P=0.004) and T2 (P<0.001) (Table 2). We also found significant differences in NA concentrations between the two groups at T1 (P=0.0004) and T2 (P<0.0001) (Table 2).
In the caudal group, there was a significant decrease in the A concentrations when comparing T0 (220.45 ± 174.0 pg ml−1) with T1 (124.8 ± 67.0 pg ml−1) and with T2 (82.0 ± 48.0 pg ml−1) (P=0.0008; Fig. 1). Similar differences were found in the NA concentrations at the three different times: T0 (606.9 ± 350.0 pg ml−1), T1 (269.9 ± 115.0 pg ml−1) and T2 (233.0 ± 135.0 pg ml−1) (P < 0.0001; Fig. 2).
In the control group, we found a significant increase in the A plasma values comparing the T0 values (198 ± 136.0 pg ml−1) with the T2 values (315.2 ± 205.0 pg ml−1) (P=0.019; Fig. 3). A similar increase was found in the NA plasma values of T0 (431.2 ± 164.0 pg ml−1) compared with T2 (642.55 ± 282.0 pg ml−1) (P=0.013; Fig. 4)
In the control group, there was no significant increase in the systolic blood pressure between T0 (97 mmHg±7), T1 (105 mmHg ± 9) and T2 (108 mmHg ± 7) (P>0.05). However, we found a significant increase in the heart rate values between T0 (123 min−1 ± 12) and T2 (133 min−1 ± 13) (P=0.04).
In the caudal group, there was no significant difference in the systolic blood pressure at the three stages of operation, T0 (97 mmHg ± 10), T1 (99 mmHg ± 10) and T2 (101 mmHg ± 10) (P > 0.05). There were also no significant differences in heart rate values between T0 (122 min−1 ± 15), T1 (125 min−1 ± 12) and T2 (129 min−1 ± 14) (P>0.05).
End-tidal CO2 (ETCO2) increased in both groups of patients during the procedure, so we assisted ventilation manually to keep the ETCO2 at a value of 5.3-6.4 kPa. The mean value of ETCO2 at 5 min in the GA group was 5.4 ± 0.8 kPa and in the caudal group was 5.6 ± 0.7 kPa. At 10 min, the ETCO2 was 5.8 ±0.7 kPa in the control group and 6.0 ± 0.5 kPa in the caudal group. At 15 min, the ETCO2 was 5.6 ± 0.7 kPa in the control group and 5.7 ± 0.7 kPa in the caudal group. There were no significant differences in ETCO2 between the groups at 5, 10 and 15 min (P>0.05)
Only one patient from the caudal group required intravenous fentanyl and so (by definition) had a failed caudal block, which excluded him from the study. The mean intravenous fentanyl administered intraoperatively in the control group was 2.5 μg kg−1.
There were no significant statistical differences in the pain scores between the two groups (Table 1).
Three of the 20 patients in the caudal group, who had a pain score greater than five, received a mean of 14.5 μg intravenous fentanyl (range 5-30) in PACU. Eight patients from the control group, who had a pain score of greater than five, received a mean of 18.5 μg of intravenous fentanyl (range 5-25 μg) in the PACU. There was no statistical difference between the two groups in the fentanyl doses administered in the PACU.
This study compares the effect of two different anaesthetic techniques on the stress responses reflected by plasma catecholamine concentrations in male paediatric patients undergoing ilioinguinal herniorrhaphy. We found significant increases in the catecholamine concentrations in the general anaesthesia group, comparing induction with immediate post-operative values. Adding caudal anaesthesia to general anaesthesia prevented increasing catecholamine values during the intraoperative and immediate post-operative period.
It has been demonstrated that the anaesthetic technique can modulate the endocrine responses to surgery [3,4,12]. However, it seems that inhalation anaesthesia alone is unable to suppress the stress response to surgery . In a recent study, Taylor et al. demonstrated that the addition of intravenous fentanyl in doses of 3 and 15 μg kg−1 to inhalation anaesthesia does not modify the stress response as reflected by interleukin-6 levels. On the other hand, studies using high doses of fentanyl (75 μg kg−1) have demonstrated a significant suppression of the stress response to surgery .
Among the several anaesthetic methods known to modify the stress response to surgery in adults, epidural anaesthesia is probably the most promising technique [3,6]. However, the correlation between suppression of the stress response by epidural anaesthesia, post-operative complications and clinical outcome is still controversial [1,6,16].
Epidural anaesthesia suppresses an increase in the stress hormones in patients undergoing lower abdominal surgery , and it has proved to be effective in reducing the response to surgical stress in children, as reflected by changes in cortisol levels .
However, epidural anaesthesia does not attenuate the stress response to upper abdominal surgery completely, probably because of the inability of epidural anaesthetics to block the afferent neural input arising from the upper abdomen .
The use of caudal block in paediatric surgery combined with general anaesthesia has become increasingly widespread, especially for surgery below the umbilicus. The major goal is to provide pain relief, while decreasing the concentration of the inhalation agents and avoiding narcotic use, thus decreasing the risks of perioperative cardiorespiratory complications.
Dupont et al. and Nakamura and Takasaki  investigated the effect of caudal anaesthesia on perioperative stress. As in the present study, caudal anaesthesia blocked the rise in plasma A and NA in children undergoing minor abdominal surgery. In contrast to Nakamura and Takasaki's  results, we found a significant increase in the A and NA values in the general anaesthesia group, while Dupont et al. reported only an increased level of A in general anaesthesia.
Children in both groups were maintained with endtidal halothane concentrations of 1.5 MAC in a mixture of N2O/O2 in our attempt to obtain similar depths of anaesthesia. Thus, the decrease in the catecholamine concentrations in the caudal group seems to be unrelated to depth of anaesthesia, but related to the blockade of the afferent nociceptive impulses to the hypothalamus, which in turn inhibits the pituitary adrenocortical axis stimulation.
Despite the significant difference between the catecholamine concentrations, we did not find any significant differences in the pain scores between the two groups. These findings could be related to the difficulty of pain assessment in children, especially those unwilling or unable to verbalize .
The activation of the sympathetic nervous system can have a detrimental effect on the cardiovascular system, protein metabolism and metabolic rates [1,6]. These responses, it may be hypothesized, could seriously affect high-risk children with cardiac disease and those with poor nutritional status.
The use of regional anaesthesia and analgesia may be associated with a diminished response of the sympathetic nervous system . However the lack of a definable continuum of outcomes of anaesthesia makes it difficult to determine whether one anaesthetic technique is associated with a better outcome than another.
The conclusion of this study is that a significant increase in catecholamine concentrations occurs in children undergoing ilioinguinal herniorrhaphy under general anaesthesia alone, while caudal block combined with general anaesthesia is effective in reducing the catecholamine response to this type of surgery. This study was performed in healthy children, and further investigation is needed in high-risk children to evaluate the effect on clinical outcomes of the decreased plasma levels of A and NA resulting from the caudal block.
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