1. 2017;20;173-184Perioperative Ketamine Administration for Thoracotomy Pain
   Systematic Review
   David Lindsay, MD, Muhammad Y. Qadri, MD, PhD, Alan D. Kaye, MD, PhD, James H. Diaz, MD, Daniel W. Moyse, MD, and Srinivas Pyati, MD.

BACKGROUND: Of all the postsurgical pain conditions, thoracotomy pain poses a particular therapeutic challenge in terms of its prevalence, severity, and ensuing postoperative morbidity. Multiple pain generators contribute to the severity of post-thoracotomy pain, and therefore a multimodal analgesic therapy is considered to be a necessary strategy. Along with opioids, thoracic epidural analgesia, and paravertebral blocks, N-Methyl-D-Aspartate (NMDA) receptor antagonists such as ketamine have been used as adjuvants to improve analgesia.

OBJECTIVE: We reviewed the evidence for the efficacy of intravenous and epidural administration of ketamine in acute post-thoracotomy pain management, and its effectiveness in reducing chronic post-thoracotomy pain.

STUDY DESIGN: Systematic literature review and an analytic study of a data subset were performed.

METHODS: We searched PubMed, Embase, and Cochrane reviews using the key terms “ketamine,” “neuropathic pain,” “postoperative,” and “post-thoracotomy pain syndrome.” The search was limited to human trials and included all studies published before January 2015. Data from animal studies, abstracts, and letters were excluded. All studies not available in the English language were excluded. The manuscript bibliographies were reviewed for additional related articles. We included randomized controlled trials and retrospective studies, while excluding individual case reports.

RESULTS: This systematic literature search yielded 15 randomized control trials evaluating the efficacy of ketamine in the treatment of acute post-thoracotomy pain; fewer studies assessed its effect on attenuating chronic post-thoracotomy pain. The majority of reviewed studies demonstrated that ketamine has efficacy in reduction of acute pain, but the evidence is limited on the long-term benefits of ketamine to prevent post-thoracotomy pain syndrome, regardless of the route of administration. A nested analytical study found there is a statistically significant reduction in acute post-thoracotomy pain with IV or epidural ketamine. However currently, the evidence for a role of ketamine as a preventative agent for chronic post-thoracotomy pain is insufficient due to the heterogeneity of the studies reviewed with regard to the route of administration, dosage, and outcome measures.

LIMITATIONS: The evidence for a role of ketamine as a preventative agent for chronic post-thoracotomy pain is insufficient due to the heterogeneity of the studies reviewed.

CONCLUSION: The majority of randomized controlled trials reviewed show no role for ketamine in attenuating or preventing post-thoracotomy pain syndrome at variable follow-up lengths. Therefore, additional research is warranted with consideration of risk factors and long-term follow-up for chronic post-thoracotomy pain though the evidence for benefit appears clear for acute post-thoracotomy pain.

Key words: Ketamine, postoperative, thoracotomy pain, post thoracotomy pain syndrome, neuropathic pain