Intrathecal Morphine for Analgesia in Minimally Invasive Cardiac Surgery

A Randomized, Placebo-controlled, Double-blinded Clinical Trial

Richa Dhawan, M.D., M.P.H.; Danisa Daubenspeck, D.O.; Kristen E. Wroblewski, M.S.; John-Henry Harrison, M.D.; Mackenzie McCrorey, M.S.P.A.C.; Husam H. Balkhy, M.D., Mark A. Chaney, M.D.


Anesthesiology. 2021;135(5):864-876. 

In This Article

Abstract and Introduction


Background: Intrathecal morphine decreases postoperative pain in standard cardiac surgery. Its safety and effectiveness have not been adequately evaluated in minimally invasive cardiac surgery. The authors hypothesized that intrathecal morphine would decrease postoperative morphine consumption after minimally invasive cardiac surgery.

Methods: In this randomized, placebo-controlled, double-blinded clinical trial, patients undergoing robotic totally endoscopic coronary artery bypass received either intrathecal morphine (5 mcg/kg) or intrathecal saline before surgery. The primary outcome was postoperative morphine equivalent consumption in the first 24 h after surgery; secondary outcomes included pain scores, side effects, and patient satisfaction. Pain was assessed via visual analog scale at 1, 2, 6, 12, 24, and 48 h after intensive care unit arrival. Opioid-related side effects (nausea/vomiting, pruritus, urinary retention, respiratory depression) were assessed daily. Patient satisfaction was evaluated with the Revised American Pain Society Outcome Questionnaire.

Results: Seventy-nine patients were randomized to receive intrathecal morphine (n = 37) or intrathecal placebo (n = 42), with 70 analyzed (morphine 33, placebo 37). Intrathecal morphine patients required significantly less median (25th to 75th percentile) morphine equivalents compared to placebo during first postoperative 24 h (28 [16 to 46] mg vs. 59 [41 to 79] mg; difference, −28 [95% CI, −40 to –18]; P < 0.001) and second postoperative 24 h (0 [0 to 2] mg vs. 5 [0 to 6] mg; difference, −3.3 [95% CI, −5 to 0]; P < 0.001), exhibited significantly lower visual analog scale pain scores at rest and cough at all postoperative timepoints (overall treatment effect, −4.1 [95% CI, −4.9 to –3.3] and –4.7 [95% CI, −5.5 to –3.9], respectively; P < 0.001), and percent time in severe pain (10 [0 to 40] vs. 40 [20 to 70]; P = 0.003) during the postoperative period. Mild nausea was more common in the intrathecal morphine group (36% vs. 8%; P = 0.004).

Conclusions: When given before induction of anesthesia for totally endoscopic coronary artery bypass, intrathecal morphine decreases use of postoperative opioids and produces significant postoperative analgesia for 48 h.


Coronary artery bypass grafting (CABG) is traditionally performed via median sternotomy. In an attempt to avoid sternotomy, minimally invasive cardiac surgery was popularized in the 1990s (anterior minithoracotomy). Rapid clinical development of robotic telemanipulation in the late 1990s led to the creation of robotic cardiac surgery, a subset of which is totally endoscopic CABG, performed robotically via multiple thoracic ports.[1]

Inadequate postoperative analgesia has the potential to initiate pathophysiologic changes in all major organ systems, which may lead to substantial morbidity, including chronic pain syndromes.[2–4] While median sternotomy pain may be severe, pain after minimally invasive cardiac surgery (anterior minithoracotomy and/or robotic thoracic ports) seems consistently more intense and challenging to control.[5,6] In the current era of enhanced recovery after surgery, adequate postoperative analgesia allowing immediate tracheal extubation is oftentimes difficult to achieve in patients undergoing minimally invasive cardiac surgery.[7,8]

As minimally invasive cardiac surgery has become increasingly utilized, numerous regional analgesic techniques have been applied without reliable success.[5,6,9,10] Reasons for inconsistency include the wide variety of thoracic incisions used and technical difficulty/unreliability of the regional techniques. Intrathecal morphine has numerous potential advantages during minimally invasive cardiac surgery, yet has not been adequately evaluated in the current enhanced recovery after surgery era. In this randomized, placebo-controlled, double-blinded clinical investigation, we hypothesize that 5 mcg/kg intrathecal morphine in patients undergoing robotic totally endoscopic CABG with immediate tracheal extubation (operating room/immediate postoperative period) will decrease postoperative morphine consumption.