Effect of thoracic epidural analgesia on pro-inflammatory cytokines in patients subjected to protective lung ventilation during Ivor Lewis esophagectomy

Pain Physician. 2014 Jul-Aug;17(4):305-15.


Background: Thoracic epidural analgesia (TEA) has a well-known effect on neurohormonal response. Attenuation of stress response by post-operative epidural analgesia has shown beneficial effects such as lower pain scores and less immunological alterations.

Objectives: Investigation of the combined effects of TEA and protective lung ventilation on pro-inflammatory cytokines and patients' outcome after Ivor Lewis esophagectomy.

Study design: A randomized controlled study.

Setting: Academic medical center.

Methods: Thirty patients of the American Society of Anesthesiologists (ASA) I and II were randomly allocated into 2 groups: G1 (n = 15) patients received general anesthesia and were mechanically ventilated with 9 mL/kg during 2 lung ventilations, reduced to 5 mL/kg and 5cm H2O positive end expiratory pressure (PEEP) during one lung ventilation (OLV) or GII) (n = 15) patients received TEA and the same general anesthesia and mechanical ventilation used in G1. Assessment parameters included hemodynamics, pain severity, total analgesic consumption, and measurement of interleukins (IL) (IL-6 and IL-8) at baseline time after anesthetic induction (TBaseline,); at the end of the abdominal stage of the operation (TAbdo,); 15 minutes after initiation and at the end of OLV (TOLV 15) and (TOLV End) respectively; one and 20 hours after the end of the surgical procedure (TPostop1 and TPostop20), respectively, and patient's outcome also recorded.

Results: There was a significant reduction in mean arterial blood pressure (MAP) and pulse rate in GII during the intraoperative period, at Tabdo, TOLV15, and TOLV End (P < 0.05). The mean of systolic blood pressure (SBP) values were significantly lower in GII over all 3 post-operative days (P = 0.001), and the mean diastolic blood pressure (DBP) showed a significant reduction in GII for 16 hours post-operatively (P = 0.001). The mean of heart rate values showed a significant reduction in GII over all 3 post-operative days in comparison to GI (P = 0.001). The mean resting and dynamic VAS scores were significantly reduced in GII at all time periods studied in comparison to G1 (P = 0.001). The daily PCA morphine consumption was markedly decreased in GII compared to GI in the first 3 days post-operatively (P = 0.001). There were significant reductions in blood level of IL-6 and IL-8 in GII compared to G1 over the entire study period (P < 0.05). There were no significant differences in post-operative adverse effects between the 2 groups (P > 0.05). The duration of stay in PACU was significantly decreased in GII (10 ± 2 days) compared to GI (15 ± 3 days) (P = 0.001).

Limitations: This study is limited by its sample size.

Conclusion: Our study concluded that TEA reduced the systemic pro-inflammatory response and provided optimal post-operative pain relief. Although there were no significant differences in adverse events, there was a trend towards improved outcome. Further clinical studies with larger numbers of patients are required.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Analgesia, Epidural*
  • Analgesics, Opioid / administration & dosage
  • Anesthetics, Local / administration & dosage
  • Cytokines / blood*
  • Esophageal Neoplasms / surgery
  • Esophagectomy*
  • Female
  • Humans
  • Inflammation / blood
  • Interleukin-6 / blood
  • Interleukin-8 / blood
  • Male
  • Middle Aged
  • One-Lung Ventilation
  • Pain, Postoperative / blood
  • Pain, Postoperative / drug therapy*
  • Pain, Postoperative / immunology


  • Analgesics, Opioid
  • Anesthetics, Local
  • Cytokines
  • Interleukin-6
  • Interleukin-8