There were no differences in consumption of propofol and remifentanil between group D and group E but both consumed significantly less compared with group C (P = 0.002, P = 0.018; P = 0.001, P < 0.0001) (Table 4).
The recovery profile was assessed by the time taken from cessation of propofol to eye opening and tracheal extubation. There was no statistically significant difference among groups (Table 4). The incidence of agitation was less in group D (6.7 %) than in group C (26.7%) (P = 0.038) (Table 4). No patients experienced nausea, vomiting, or shivering in the PACU. No other severe adverse effects were observed in any group.
The results of the present study indicate that dexmedetomidine can be used as an adjunct to general anesthesia to suppress stress responses in open gastrectomy surgery. The effects of a combined a dexmedetomidine/TIVA technique on the surgical stress response were comparable to that of a combined epidural/TIVA technique.
The stress response to surgery initiates a predictable cascade of physiologic and metabolic events through direct activation of the sympathetic and somatic nervous systems.20 The effects of combined epidural/general anesthesia on the plasma concentrations of catecholamines and Cor have been investigated in several studies. Some studies have demonstrated that the levels of catecholamines do not increase significantly among patients receiving general anesthesia combined with epidural anesthesia.21,22 Li et al.22 reported that intraoperative epidural analgesia attenuated the plasma concentration of Cor during nephrectomy. The authors hypothesized that epidural blockade attenuates or inhibits surgical stress by preventing afferent neural stimuli from reaching the central nervous system and efferent activation of the sympathetic nervous system.
Over the past few years, cytokines and the more accepted stress hormones such as Cor and catecholamines have received attention as mediators of perioperative responses to surgery.1,23 Many clinical studies have shown that proinflammatory and antiinflammatory cytokines are pivotal for the acute-phase inflammatory and immunologic response after surgical trauma, and the most important cytokines in this regard are TNF-α, IL-6, and IL-10.24–26 The release of TNF-α is 1 of the main cytokines that mediate the early response to tissue injury. IL-6 is the primary stimulus for acute responses, and plasma levels of IL-6 are reportedly related to the severity of surgical trauma.27 IL-10 is involved in immunomodulation and has an inhibitory action. IL-10 also has been shown to inhibit the synthesis of IL-6 by monocytes and act as a natural antagonist to inflammatory cytokines in a host-protective manner.28 Moselli et al.29 reported that intraoperative epidural analgesia attenuated the surgery-induced proinflammatory response (TNF-α and IL-6) and increased anti-inflammatory IL-10. In recent years, the antiinflammatory effects of dexmedetomidine have also been evaluated. Studies in animals and in intensive care patients have shown that dexmedetomidine can reduce cytokine secretion, which subsequently alleviates inflammation and reduces mortality.30,31 Plasma TNF-α and IL-6 in our groups had a significantly rapidly increased and circulating IL-10 concentrations also increased during and after surgery, and the level of TNF-α, IL-6, and IL-6/IL-10 ratio was significantly different among groups. Epidural anesthesia and dexmedetomidine seemed to have a significant effect on TNF-α and IL-6 release. The IL-6/IL-10 ratio was related to the prognosis of patients with the systemic inflammatory reaction syndrome with a high ratio indicating poor prognosis.32 Our study certainly suggests that the IL-6/IL-10 ratio was greater in group C than in groups D and E at celiac exploration and tracheal extubation. Thus, with respect to the limitation of surgery-associated stress, epidural anesthesia and dexmedetomidine partially attenuated surgical stress responses among patients undergoing elective open gastrectomy.
The anesthetic- and analgesic-sparing effects of dexmedetomidine have been well documented in animal and human studies.39,40 Dutta et al.41 reported that a dexmedetomidine plasma concentration of 0.66 ng/mL reduced the propofol dose required for sedation and induction of anesthesia by 40% to 70%. Previous studies42–44 have shown that epidural anesthesia may reduce anesthetic requirements. In the present study, anesthetic doses required to maintain the same BIS values were significantly reduced by dexmedetomidine and combined epidural/general anesthesia.
Rapid emergence from anesthesia and postoperative recovery are important demands on modern anesthetics. In general, both propofol and remifentanil meet these criteria.45 Some studies suggest that the sedative property of dexmedetomidine delays postoperative recovery and prolongs discharge time.46,47 In our study, the depth of anesthesia was maintained by the same BIS value, and dexmedetomidine was discontinued at peritoneal closure. There was no difference in the groups regarding the time of eye opening and tracheal extubation.
Emergence agitation has been reported in up to 20% of adult patients after general anesthesia.48,49 In several studies, intraoperative administration of dexmedetomidine reduced emergence agitation in children by 57% to 70% compared with control groups.50,51 Kim et al.52 reported that intraoperative dexmedetomidine infusion significantly reduced emergence agitation after nasal surgery in adult patients. Consistent with previous results,52 dexmedetomidine was also effective in reducing emergence agitation in our study.
There are several limitations to this study. First, we used single blinding because the patients in the epidural group had an obvious epidural infusion pump attached to them. The lack of blinding, however, should not have affected the primary outcome of the stress response but may have possibly influenced clinical assessment in the PACU. Second, we only enrolled patients undergoing elective open gastrectomy and excluded patients with ASA physical status ≥III and body mass index ≥30 kg/m2, which limited the external generalizability of our results. Third, it was necessary to give morphine to the dexmedetomidine and control groups for pain relief, and this may potentially have confounded the results. Most significantly, our study focused only on the intraoperative effects of dexmedetomidine or epidural combined with TIVA. This was a short study and it did not assess for functional outcomes such as recovery of bowel function because this may have required a larger study population and a longer study period. Given that the degree of stress response throughout the perioperative period may have affected different outcomes, the results from this study would justify the conduct of a more comprehensive trial involving sicker patients, a longer period of dexmedetomidine administration, the assessment of various functional outcomes, and the measurement of more specific markers such as various ILs and TNF.
In summary, intraoperative infusion of dexmedetomidine reduces surgical stress responses to an extent comparable to epidural anesthesia when combined with TIVA for abdominal surgery, without compromising hemodynamic stability. Further studies are required to see whether the reduction in stress response translates to improved clinical outcomes.
The authors thank Dr. Jun Li from the Department of Orthopedics, The Second Affiliated Hospital of Anhui Medical University for revised the manuscript.
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