The role of different anesthetic techniques in altering the stress response during cardiac surgery in children: a prospective, double-blinded, and randomized study

Abstract

Objectives: Our goal was to evaluate the role of three anesthetic techniques in altering the stress response in children undergoing surgery for repair of congenital heart diseases utilizing cardiopulmonary bypass in the setting of fast tracking or early tracheal extubation. Furthermore, we wanted to evaluate the correlation between blunting the stress response and the perioperative clinical outcomes.

Design: Prospective, randomized, double-blinded study.

Setting: Single center from December 2008 to May of 2011.

Patients: Forty-eight subjects (low-dose fentanyl plus placebo, n = 16; high-dose fentanyl plus placebo, n = 17; low-dose fentanyl plus dexmedetomidine, n = 15) were studied between ages 30 days to 3 years old who were scheduled to undergo repair for a ventricular septal defect, atrioventricular septal defect, or Tetralogy of Fallot.

Methods: Children undergoing surgical repair of congenital heart disease were randomized to receive low-dose fentanyl (10 mcg/kg; low-dose fentanyl), high-dose fentanyl (25mcg/kg; high-dose fentanyl), or low-dose fentanyl plus dexmedetomidine (as a 1 mcg/kg loading dose followed by infusion at 0.5mcg/kg/hr until separation from cardiopulmonary bypass. In addition, patients received a volatile anesthetic agent as needed to maintain hemodynamic stability. Blood samples were tested for metabolic, hormonal and cytokine markers at baseline, after sternotomy, after the start of cardiopulmonary bypass, at the end of the procedure and at 24 hours postoperatively.

Measurements and main results: Forty-eight subjects (low-dose fentanyl plus placebo, n = 16; high-dose fentanyl plus placebo, n = 17; low-dose fentanyl plus dexmedetomidine, n = 15) were studied. Subjects in the low-dose fentanyl plus placebo group had significantly higher levels of adrenocorticotropic hormone, cortisol, glucose, lactate, and epinephrine during the study period. The lowest levels of stress markers were seen in the high-dose fentanyl plus placebo group both over time (adrenocorticotropic hormone, p= 0.01; glucose, p = 0.007) and at individual time points (cortisol and lactate at the end of surgery, epinephrine poststernotomy; p < 0.05). Subjects in the low-dose fentanyl plus dexmedetomidine group had lower lactate levels at the end of surgery compared with the low-dose fentanyl plus placebo group (p < 0.05). Although there were no statistically significant differences in plasma cytokine levels between the three groups, the low-dose fentanyl plus placebo group had significantly higher interleukin-6:interleukin-10 ratio at 24 hours postoperatively (p < 0.0001). In addition, when compared with the low-dose fentanyl plus placebo group, the low-dose fentanyl plus dexmedetomidine group showed a lower norepinephrine level from baseline at poststernotomy, after the start of cardiopulmonary bypass, and at the end of surgery (p ≤ 0.05). Subjects in the low-dose fentanyl plus placebo group had more postoperative narcotic requirement (p = 0.004), higher prothrombin time (p ≤ 0.03), and more postoperative chest tube output (p < 0.05). Success of fast tracking was not significantly different between groups (low-dose fentanyl plus placebo 75%, high-dose fentanyl plus placebo 82%, low-dose fentanyl plus dexmedetomidine 93%; p = 0.39).

Conclusions: The use of low-dose fentanyl was associated with the greatest stress response, most coagulopathy, and highest transfusion requirement among our cohorts. Higher dose fentanyl demonstrated more favorable blunting of the stress response. When compared with low-dose fentanyl alone, the addition of dexmedetomidine improved the blunting of the stress response, while achieving better postoperative pain control.

Figure 1

Flow chart of the study design. TOF = Tetralogy of Fallot; VSD = ventricular septal defect; AVSD = atrioventricular septal defect; HDF = high-dose fentanyl plus placebo; LDF + DEX = low-dose fentanyl plus dexmedetomidine; LDF = low-dose fentanyl plus placebo; TNF-α = tumor necrosis factor-α; IL = interleukin; CPB = cardiopulmonary bypass; ANH = acute normovolemic hemodilution; CTICU = cardiothoracic intensive care unit; POD1 = postoperative day 1.

Figure 2

Fentanyl use and chest tube output in the first 24 hr after surgery. Subjects receiving low-dose fentanyl plus placebo (LDF) demonstrated higher use of fentanyl in the first 24 hr after surgery (A) compared with subjects receiving high-dose fentanyl plus placebo (HDF) or low-dose fentanyl plus dexmedetomidine (LDF + DEX) (p = 0.004, two-way analyses of variance). Subjects receiving LDF demonstrated higher chest tube output (B) compared with the HDF group over the same period. *p < 0.05 HDF versus LDF; **p < 0.01 LDF-DEX versus LDF. Boxes represent median and interquartile range, and whiskers represent minimum-maximum.

Figure 3

Plasma hormonal and metabolic stress markers. Subjects receiving high-dose fentanyl plus placebo (HDF) (shaded triangle) exhibited lower plasma levels of ACTH (A) and glucose (C) over the study period compared with subjects receiving low-dose fentanyl plus placebo (LDF, open circle) or low-dose fentanyl plus dexmedetomidine (LDF + DEX, closed square) (p ≤ 0.01, repeated-measures analyses of variance [RM-ANOVA] for both markers). Subjects receiving HDF had lower cortisol levels (B) at the end of surgery and lower epinephrine levels (E) after sternotomy compared with the LDF group. Subjects in both the HDF and LFD + DEX groups had lower lactate levels (D) at the end of surgery compared with subjects in the LDF group. For norepinephrine at the end of surgery (F)(double closed circle), LDF + DEX gave significantly lower level than HDF and LDF groups (p < 0.05). *p < 0.05 HDF versus LDF, #p < 0.05 HDF versus LDF + DEX, ^&p < 0.05 LDF + DEX versus LDF, Ωp < 0.05 LDF + DEX versus LDF and HDF. Data represent mean (SEM).