Prospective, Randomized Comparison of Epidural Versus Parenteral Opioid Analgesia in Thoracic Trauma

Thoracic trauma is a significant cause of morbidity and mortality in our society. It ranks second only to head injury as a cause of traumatic death in the United States. One of every four deaths resulting from trauma is attributable to a thoracic etiology. 1 Pain associated with flail chest or multiple rib fractures can result in voluntary splinting and muscle spasms, which subsequently leads to decreased ventilation and atelectasis. Compromise of pulmonary function can also cause hypoxemia, an increase in shunt fraction, or pneumonia, which may require mechanical ventilation. 2 Adequate relief of rib and chest-wall pain allows the patient to breathe deeply, avoid intubation, 3 and clear secretions effectively, minimizing pulmonary complications. 4 We havepreviously shown that the epidural route of analgesia is superior to intrapleural administration for analgesia and improves pulmonary function in patients with thoracic trauma. 5 Any acute injury produces a spectrum of physiologic responses. The neuroendocrine system responds by increased activity, which includes autonomic control of cardiac contractility and peripheral vascular tone, hormonal response to stress and volume depletion, and local microcirculatory mechanisms that are organ-specific and regulate regional blood flow. Multiple stimuli associated with traumatic injury can initiate these responses, including pain, hypoxemia, hypercarbia, and emotional arousal, to name a few. 6,7 Somatic pain is generated by the response of nociceptors through the A-delta fibers, which are activated by high-intensity stimuli. These afferent signals then undergo central integration that modulates the efferent output, leading to sympathetically mediated vasoconstriction and secretion of corticotropin-releasing factor, the primary autonomic and endocrine responses to somatic pain, respectively. Repeated insults or hemorrhage potentiate this effect. Blocking afferent signals resulting from pain in patients undergoing elective thoracotomy has been shown to reduce systemic catecholamine levels significantly. 8 An additional host response to injury involves a coordinated expression of cytokines that act both systemically and locally with profound effects on organ function. Cytokines differ from the classic hormones in the following manner: 1. They are bioactive at very low concentrations locally that may not be detectable systemically. 2. They are produced by many cell types at many sites in the body. 3. They are induced based on the nature of the insult. 4. They have important autocrine, paracrine, and endocrine functions (Table 1). Table 1. Proposed Roles of Cytokines in Response to Injury 5. Serum levels of cytokines probably represent largely overflow rather than an endocrine function. 9 A traumatic wound, with or without hypotension, produces similar systemic immunomodulation. Levels of tumor necrosis factor-alpha (TNF-α) may increase after injury. 10 Serum levels of interleukin (IL)-1β are elevated, 11 IL-2 levels are decreased, 12,13 and IL-6 levels are elevated shortly after injury and remain elevated for several days. 14 Finally, within 8 hours of injury, circulating levels of IL-8 are increased. 15 Although many studies have characterized the inflammatory mediators associated with traumatic injury, 11–13 little is know about the effects of the route of analgesia administration on pain relief, pulmonary function, and systemic inflammatory mediators in patients with significant thoracic injury. Randomized controlled studies of patients undergoing elective thoracotomy have proven that epidural anesthesia and postoperative continuous epidural analgesia decrease the stress response associated with surgical trauma compared with parenteral analgesia. 8 However, in that study, epidural anesthesia was given before surgery, before the stress was initiated. The purpose of this study was to investigate the effect of route of analgesia delivery after severe chest injury on analgesia, pulmonary function, urinary catecholamine levels, and plasma cytokine levels by comparing parenteral versus epidural opioid analgesia. Effective pain control should improve pulmonary mechanics and reduce the neuroendocrine and immune response. Any of these outcomes may also reduce complications.