July 1997
Intrathecal morphine for coronary artery bypass grafting and early extubation.
Chaney MA, Furry PA, Fluder EM, Slogoff S. Anesthesia and Analgesia 1997; 84:241-8.

[ see abstract below ]

There has been considerable interest recently in the use of regional analgesic techniques in cardiac surgery, including intrathecal and epidural opioids. These have been promoted both in an effort to facilitate early tracheal extubation and "fast tracking" as well as improve postoperative pain control.

In the February 1997 issue of Anesthesia and Analgesia, Chaney et al present a study on the use of intrathecal morphine in patients undergoing coronary artery bypass grafting. Their results are rather surprising, and illustrate some of the pitfalls associated with these kinds of studies.

In a prospective, double-blind fashion they randomized 40 patients scheduled to undergo coronary artery bypass grafting to receive either 10 mcg/kg intrathecal morphine or placebo. The anesthetic technique consisted of fentanyl (up to 20 mcg/kg) and midazolam (up to 10 mg total), supplemented by isoflurane as indicated. Postoperatively, ventilatory weaning and tracheal extubation proceeded according to standard criteria; thereafter, pain requirement via morphine patient controlled analgesia (PCA) was measured.

Their results suggested that patients who had received intrathecal morphine, ventilatory weaning and tracheal extubation were considerably delayed, without a statistically significant decrease in postoperative PCA requirement. Specifically, the mean time to tracheal extubation was increased from 7.6 h to 10.9 h, and three patients had tracheal extubation substantially delayed because of ventilatory depression. Although patients receiving intrathecal morphine required less PCA morphine in 48 h (42.8 vs. 55 mg), this did not reach statistical significance.

No complications were reported related to epidural bleeding or hematoma formation. Patients with preexisting coagulopathy or who were on intravenous or subcutaneous heparin were excluded. The surgeons agreed a priori that if a bloody tap were encountered (none were), surgery would be delayed 24 h. The intrathecal morphine was administered prior to anesthetic induction, about two hours prior to systemic heparinization.

The group of patients appeared to have been at moderately high risk. In four patients (20%) in the intrathecal morphine group and five patients (25%) in the control group, tracheal extubation was delayed because of hemodynamic, pulmonary or bleeding complications. By the authors' criteria (CPK-MB and ECG changes), 12 out of the 40 patients studied (30%) developed perioperative myocardial infarction.

The authors conclude that " ...the optimal dose of intrathecal morphine (and) ... optimal intraoperative baseline anesthetic that will provide significant analgesia, yet not delay extubation in the immediate postoperative period, remains to be elucidated."

Four possibilities may have contributed to this outcome:

1. Was the dose of intrathecal morphine too large? 10 mcg/kg is equivalent to 0.8 mg in an 80 kg patient, much larger than the doses commonly used for other procedures. It is possible that had a larger number of patients been studied, the difference in postoperative PCA morphine requirement may have reached statistical significance. However, lowering the dose of intrathecal morphine makes it even less likely that such a difference could be found.
   
   
2. Was the dose of intraoperative fentanyl too large? It is well known that ventilatory depression with intrathecal or epidural morphine is exacerbated by the concomitant use of systemic opioids. Even in the placebo group the mean time to tracheal extubation (7.6 h) is considerably longer than that demonstrated in series on "fast track" approaches to coronary artery bypass surgery. On the other hand, one patient in each group experienced intraoperative awareness. The authors acknowledge this by stating that they have subsequently changed their clinical practice to use less fentanyl and more midazolam, although they do not present any data with the modified regimen.
   
   
3. Were the patients selected too sick? 20-25% had complications that postponed tracheal extubation; this might reflect the authors' institutional approach to "fast track" all patients until they "fall off the tracks."
   
   
4. Is there a real additional benefit to the use of intrathecal morphine for pain control after median sternotomy (compared with thoracotomy)? Considerable success appears to have been achieved using systemic techniques (low-dose fentanyl, propofol or midazolam, inhalational anesthesia, PCA) for "fast tracking" and early tracheal extubation.
   
   

• A more select low risk patient population, to increase the proportion of patients that might be expected to benefit from "fast tracking."
  
  
• An anesthetic technique that minimizes the risk of additive opioid effects yet maintains good intraoperative control and amnesia.
  
  
• A dose of intratheal morphine (e.g. 5 mcg/kg) that provides postoperative analgesia without respiratory depression.
  
  
• A large enough number of subjects to be able to statistically distinguish between the two groups.

Until that time we should reserve, but not throw out, judgement on the use of intrathecal morphine in coronary artery bypass surgery.



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