Analysis of preincisional and postincisional treatment with alpha2-adrenoreceptor agonist clonidine regarding analgesic consumption and hemodynamic stability in surgical patients.

Anesthesiology, Resuscitation and Intensive Care Medicine Clinic, University Hospital "Dubrava", Zagreb, Croatia.
Collegium antropologicum (Impact Factor: 0.61). 01/2008; 31(4):1065-70.
Source: PubMed

ABSTRACT Preemptive analgesia aims to prevent the sensitization of central nervous system, hence the development of pathologic pain after tissular injury. The aim of the study was to assess the effect of preincisional clonidine treatment on analgesic consumption and hemodynamic stability compared to clonidine administered at the end of the operation and control group. Ninety-one patients undergoing elective colorectal surgery were randomly assigned to four groups: peroral clonidine before operation, epidural clonidine before operation, epidural clonidine at the end of operation, and epidural saline before operation as a control group. After the operation, patient-controlled analgesia with epidural morphine was instituted. Analgesic consumption, blood pressure and heart rate were obtained at 1, 2, 6 and 24 h postoperatively, and the cumulative consumption of analgesics was assessed at the end of the study period. Significant differences (p < 0.05) in postoperative systolic blood pressure, with highest hemodynamic stability was observed at 1 h and 6 h in the group of patients administered epidural clonidine before operation. In this group of patients we found significant reduction in analgesic consumption during the study period (p < 0.05), compared to other groups. The cumulative consumption of analgesics assessed at the end of the study period was significantly reduced (p < 0.05) in the group of patients administered epidural clonidine before operation (8.40 +/- 3.74, respectively) as compared with the peroral clonidine before operation (16.79 +/- 5.75, respectively), epidural clonidine at the end of the operation (11.11 +/- 4.24, respectively) and control group of patients (18.00 +/- 6.45, respectively). Preincisional administration of epidural clonidine was associated with a significantly lower analgesic use, lower cumulative analgesic consumption and greater hemodynamic stability, in comparison with other groups.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Multimodal analgesia is designed to optimize pain relief by coadministering drugs with distinct mechanisms of action or by combining multiple pharmacologies within a single molecule. In clinical settings, combinations of monoamine reuptake inhibitors and opioid receptor agonists have been explored and one currently available analgesic, tapentadol, functions as both a µ-opioid receptor agonist and a norepinephrine transporter inhibitor. However, it is unclear whether the combination of selective norepinephrine reuptake inhibition and µ-receptor agonism achieves an optimal antinociceptive synergy. In this study, we assessed the pharmacodynamic interactions between morphine and monoamine reuptake inhibitors that possess different affinities and selectivities for norepinephrine and serotonin transporters. Using the rat formalin model, in conjunction with measurements of ex vivo transporter occupancy, we show that neither the norepinephrine-selective inhibitor, esreboxetine, nor the serotonin-selective reuptake inhibitor, fluoxetine, produce antinociceptive synergy with morphine. Atomoxetine, a monoamine reuptake inhibitor that achieves higher levels of norepinephrine than serotonin transporter occupancy, exhibited robust antinociceptive synergy with morphine. Similarly, a fixed-dose combination of esreboxetine and fluoxetine which achieves comparable levels of transporter occupancy potentiated the antinociceptive response to morphine. By contrast, duloxetine, a monoamine reuptake inhibitor that achieves higher serotonin than norepinephrine transporter occupancy, failed to potentiate the antinociceptive response to morphine. However, when duloxetine was coadministered with the 5-HT3 receptor antagonist, ondansetron, potentiation of the antinociceptive response to morphine was revealed. These results support the notion that inhibition of both serotonin and norepinephrine transporters is required for monoamine reuptake inhibitor and opioid-mediated antinociceptive synergy; yet, excess serotonin, acting via 5-HT3 receptors, may reduce the potential for synergistic interactions. Thus, in the rat formalin model, the balance between norepinephrine and serotonin transporter inhibition influences the degree of antinociceptive synergy observed between monoamine reuptake inhibitors and morphine.
    PLoS ONE 09/2013; 8(9):e74891. DOI:10.1371/journal.pone.0074891 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Dyslipidemia is an important risk factor in cardiovascular diseases. Different studies have shown that Apolipoprotein B (Apo B) is one of the best predictors in determining cardiovascular diseases and patients follow up after cardiovascular events. We hypothesized that there is a relation between Apo B levels and cardiovascular events in patients who have myocardial infarction (MI). In addition, Apo B may be an appropriate marker for following these patients after MI. In this study, 220 patients with acute myocardial infarction were allocated at their admission to the hospital. They were followed for three months after MI and their morbidity and mortality rates were evaluated. Apo B levels were measured immunoturbidimetrically. Apo B levels were significantly higher in patients with the events including coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) and malignant arrhythmias (P = 0.001). Apo B levels can be an appropriate indicator of cardiovascular events in patients after MI.
    01/2012; 4(3):61-4. DOI:10.5681/jcvtr.2012.015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Postoperative pain as an important medical concern is usually treated by opioids which also are of various inevitable side effects. The aim of this study was to assess the efficacy of multimodal preincisional premedication on preventing post-cholecystectomy acute pain. In a randomized clinical trial, sixty patients undergoing open cholecystectomy were randomized into two groups. Before anesthesia induction, Diclofenac suppository (100 mg) and oral Clonidine (0.2 mg) were administered in the first group. Immediately before operation, patients received Ketamine (1 mg/kg IV) while the control group received placebo. The site of incision was infiltrated by the surgeon with 20 mL Bupivacaine 0.25% in both groups. Anesthesia induction and maintenance were similar in both groups. The severity of pain was recorded 2, 4, 6, 12, 24 and 48 hours after operation according to Visual Analogue Scale. The severity of pain at two defined stages (6 and 12 hours later) was significantly less in the intervention group than the control group (P<0.005). The average pain severity score was less than the control group (P<0.005). In our study, the administration of Clonidine, Diclofenac and Ketamine and bupivacaine infiltration to the site of incision, altogether was associated with a significant decrease in pain score and opioid requirement after cholecystectomy in comparison to bupivacaine infiltration to the site of incision.
    01/2012; 4(3):65-8. DOI:10.5681/jcvtr.2012.016


Available from