Multimodal Analgesic Therapy With Gabapentin and Its Association With Postoperative Respiratory Depression

Alexandre N. Cavalcante, MD; Juraj Sprung, MD, PhD; Darrell R. Schroeder, MS; Toby N. Weingarten, MD


Anesth Analg. 2017;125(1):141-146. 

In This Article

Abstract and Introduction


Background: Gabapentinoids are widely used in perioperative multimodal analgesic regimens. The primary aim of this study was to determine whether gabapentin was associated with respiratory depression during phase-I postanesthesia recovery after major laparoscopic procedures.

Methods: We retrospectively reviewed the electronic health records of 8567 patients who underwent major laparoscopic procedures (lasting ≥90 minutes) from January 1, 2010, to July 31, 2014. We assessed potential associations among patient and perioperative variables and episodes of respiratory depression during phase-I recovery. Multivariable and propensity score–matched analyses were performed to assess potential associations between preoperative gabapentin use and postoperative respiratory depression.

Results: The incidence of respiratory depression was 153 (95% confidence interval [CI], 146–161) episodes per 1000 cases. Multivariable analysis showed that gabapentin was associated with respiratory depression (odds ratio [OR], 1.47 [95% CI, 1.22–1.76]; P < .001). These results were confirmed by propensity score–matched analysis among a subset of patients who did not have analgesia supplemented by intrathecal opioids (OR, 1.26 [95% CI, 1.02–1.58]; P = .04). Older patients and those who received more intraoperative opioids had increased risk of respiratory depression. Those who had an episode of respiratory depression had a longer phase-I recovery (P < .001) and an increased rate of admission to a higher level of care (P = .03).

Conclusions: The use of gabapentin is associated with increased rates of respiratory depression among patients undergoing laparoscopic surgery. When gabapentinoids are included in multimodal analgesic regimens, intraoperative opioids must be reduced, and increased vigilance for respiratory depression may be warranted, especially in elderly patients.


Multimodal analgesic therapies for acute postoperative pain have become popular under the premise that combining analgesics with different mechanisms of action improves pain control when mitigating the adverse effects of individual medications.[1–3] Such analgesic therapies have been used to improve patient satisfaction and hasten convalescence. However, to avoid complications, this approach must consider the analgesic and opioid-sparing effects of the individual components, a task made complex by patient-specific drug sensitivities, age, and comorbid conditions. Therefore, precisely accounting for all these interactions is difficult in the clinical practice.

Gabapentinoids (gabapentin and pregabalin) are frequently included in multimodal analgesic regimens. Although recent meta-analyses have demonstrated that their use reduces the need for opioids and improves postoperative pain, they induce sedation.[4,5] When taken in isolation, gabapentinoids do not have respiratory depressive properties,[6,7] but when administered in combination with the ultrashort-acting opioid remifentanil, pregabalin potentiated respiratory depression.[8] Similarly, gabapentin was associated with respiratory depression during postanesthesia recovery in patients undergoing total joint arthroplasty.[9] Given this new evidence, neglect of the interaction between gabapentinoids and opioids may increase the risk of postoperative respiratory depression.

Our institution follows the commonly used postanesthesia care unit (PACU) discharge criteria[10] and additionally assesses patients during phase-I recovery for signs of respiratory depression (termed as respiratory-specific events): (1) hypoventilation; (2) apnea; (3) hypoxemia; and (4) episodes of severe pain, despite moderate to profound sedation (termed as pain-sedation mismatch).[11,12] Surgical patients who experience these events have increased rates of postoperative respiratory complications and require more resources for their care.[9,12,13] Also, at our institution, the decision to include gabapentin in the multimodal analgesic regimen for major laparoscopic procedures varies by surgical specialty.[1,14] These factors provide an opportunity to review a large cohort of patients and allow us to assess the potential associations between preoperative use of gabapentin and respiratory depression.

The primary aim of this study was to test the hypothesis that gabapentin is associated with respiratory depression during phase-I recovery after major laparoscopic procedures. Secondary aims included assessing other patient and perioperative factors to identify potential associations with respiratory depression and to determine whether episodes of respiratory depression were associated with outcomes.