Comparison between epidural and opioid analgesia for infants undergoing major abdominal surgery.

BACKGROUND: Epidural analgesia is considered optimal for postoperative pain management after major abdominal surgery. The potential to decrease anesthetic and opioid exposure is particularly desirable for infants, given their vulnerability to respiratory depression and concern for anesthetic neurotoxicity. We reviewed our experience with infants undergoing major abdominal surgery to determine if epidural catheter use decreased anesthetic and opioid exposure and improved postoperative analgesia. METHODS: This retrospective cohort study included infants (<12 months) who underwent exploratory laparotomy, ureteral reimplantation, or bladder exstrophy repair between November 2011 and November 2014. Primary outcomes of anesthetic exposure (mean endtidal sevoflurane) and intraoperative opioid administration were compared between infants who received epidural catheters and those who did not. Secondary outcomes included postoperative pain and sedation scores and morphine equivalents administered 0-24 and 24-48 hours after surgery. RESULTS: Of 158 eligible infants, 82 were included and 47 received epidurals. Patients with epidurals underwent bladder exstrophy repair (N = 9), ureteral reimplantation (N = 8), and exploratory laparotomy (N = 30). Infants with epidurals received less intraoperative fentanyl (2.6 mcg/kg (0,4.5) vs 3.3 mcg/kg (2.4,5.8), P = 0.019) and morphine (6% (3/47) vs 26% (9/35), P = 0.014) in univariate analysis. After controlling for age and emergency surgery, differences in long-acting opioid administration persisted, with significantly less morphine given in the epidural group (OR 0.181; 95% CI 0.035-0.925; P = 0.040). Mean endtidal sevoflurane concentrations were similar between groups. There was no significant difference in postoperative median morphine equivalents. CONCLUSION: Placement of epidural catheters in infants undergoing major abdominal surgery is associated with decreased long-acting opioid requirements intraoperatively. Epidural placement does not preclude opioid exposure however, as opioids may be administered for indications other than nociceptive pain in the difficult-to-assess postoperative infant. Further prospective studies are warranted to better quantify the effect of epidural analgesia on intraoperative anesthetic exposure in infants.

Eucapnic intermittent hypoxia augments endothelin-1 vasoconstriction in rats: role of PKCdelta.

We reported previously that simulating sleep apnea by exposing rats to eucapnic intermittent hypoxia (E-IH) causes endothelin-dependent hypertension and increases constrictor sensitivity to endothelin-1 (ET-1). In addition, augmented ET-1-induced constriction in small mesenteric arteries (sMA) is mediated by increased Ca(2+) sensitization independent of Rho-associated kinase. We hypothesized that exposing rats to E-IH augments ET-1-mediated vasoconstriction by increasing protein kinase C (PKC)-dependent Ca(2+) sensitization. In sMA, the nonselective PKC inhibitor GF-109203x (3 microM) significantly inhibited ET-1-stimulated constriction in E-IH arteries but did not affect ET-1-stimulated constriction in sham arteries. Phospholipase C inhibitor U-73122 (1 microM) also inhibited constriction by ET-1 in E-IH but not sham sMA. In contrast, the classical PKC (cPKC) inhibitor Gö-6976 (1 microM) had no effect on ET-1-mediated vasoconstriction in either group, but a PKCdelta-selective inhibitor (rottlerin, 3 microM) significantly decreased ET-1-mediated constriction in E-IH but not in sham sMA. ET-1 increased PKCdelta phosphorylation in E-IH but not sham sMA. In contrast, ET-1 constriction in thoracic aorta from both sham and E-IH rats was inhibited by Gö-6976 but not by rottlerin. These observations support our hypothesis that E-IH exposure significantly increases ET-1-mediated constriction of sMA through PKCdelta activation and modestly augments ET-1 contraction in thoracic aorta through activation of one or more cPKC isoforms. Therefore, upregulation of a PKC pathway may contribute to elevated ET-1-dependent vascular resistance in this model of hypertension.

Loss of alpha2B-adrenoceptors increases magnitude of hypertension following nitric oxide synthase inhibition.

Vascular alpha(2B)-adrenoceptors (alpha(2B)-AR) may mediate vasoconstriction and contribute to the development of hypertension. Therefore, we hypothesized that blood pressure would not increase as much in mice with mutated alpha(2B)-AR as in wild-type (WT) mice following nitric oxide (NO) synthase (NOS) inhibition with N(omega)-nitro-l-arginine (l-NNA, 250 mg/l in drinking water). Mean arterial pressure (MAP) was recorded in heterozygous (HET) alpha(2B)-AR knockout mice and WT littermates using telemetry devices for 7 control and 14 l-NNA treatment days. MAP in HET mice was increased significantly on treatment days 1 and 4 to 14, whereas MAP did not change in WT mice (days 0 and 14 = 113 +/- 3 and 114 +/- 4 mmHg in WT, 108 +/- 0.3 and 135 +/- 13 mmHg in HET, P < 0.05). MAP was significantly higher in HET than in WT mice days 10 through 14 (P < 0.05). Thus blood pressure increased more rather than less in mice with decreased alpha(2B)-AR expression. We therefore examined constrictor responses to phenylephrine (PE, 10(-9) to 10(-4) M) with and without NOS inhibition to determine basal NO contributions to arterial tone. In small pressurized mesenteric arteries (inner diameter = 177 +/- 5 microm), PE constriction was decreased in untreated HET arteries compared with WT (P < 0.05). l-NNA (100 microM) augmented PE constriction more in HET arteries than in WT arteries, and responses were not different between groups in the presence of l-NNA. Acetylcholine dilated preconstricted arteries from HET mice more than arteries from WT mice. Endothelial NOS expression was increased in HET compared with WT mesenteric arteries by Western analysis. Griess assay showed increased NO(x) concentrations in HET plasma compared with those in WT plasma. These data demonstrate that diminished alpha(2B)-AR expression increases the dependence of arterial pressure and vascular tone on NO production and that vascular alpha(2B)-AR either directly or indirectly regulates vascular endothelial NOS function.