In this episode I’ll:
1. Discuss an article that evaluates continuous vs intermittent dosing of cefazolin during CABG surgery.
2. Answer the drug information question “Can I give heparin subcutaneously for VTE prophylaxis to a patient with an epidural catheter in place?”
3. Share an update on a resource I use to evaluate drug interactions.
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Article
Lead author: Bethany Shoulders
Published in Pharmacotherapy February 2016
Background
Cefazolin is routinely used to prevent surgical site infection following coronary artery bypass grafting (CABG). Such infections have been associated with hospital readmissions and increased mortality rates.
Cardiopulmonary bypass decreases the serum concentrations of cefazolin but small pilot studies of continuous infusion of cefazolin vs standard intermittent infusion have shown higher serum and tissue levels at the site of incision.
Methods
The study was a retrospective pre and post intervention cohort study in a large academic medical center. The goal was to determine whether intraoperative continuous-infusion (CI) cefazolin reduced the incidence of surgical site infections (SSIs) compared with intermittent (INT) cefazolin dosing in patients undergoing coronary artery bypass grafting (CABG) on cardiopulmonary bypass (CPB).
The study included 516 adults who underwent CABG on CPB and received cefazolin intraoperatively between June 1, 2013, and December 31, 2014. Patients in the first 9 months of the study period received INT dosing and patients in the last 9 months received CI dosing.
The CI cohort included 232 patients and the INT cohort included 284 patients.
Results
The primary end point was incidence of SSIs. The overall incidence of SSIs was decreased in patients receiving CI cefazolin, although this did not reach statistical significance (4.6% in the INT cohort vs 1.7% in the CI cohort, p=0.116).
Superficial SSIs were significantly reduced in the CI cohort (2.8% in the INT cohort vs 0.4% in the CI cohort, p=0.039). In the regression analysis, CI cefazolin decreased the odds of SSI by 66%, although it did not reach statistical significance (p=0.077). Safety end points were not significantly different between groups.
Conclusion
The authors concluded that CI cefazolin significantly decreased the incidence of superficial SSIs compared with INT cefazolin in patients undergoing CABG on CPB, without increasing the risk for adverse effects.
The authors also stated this study was underpowered to detect a significant difference in overall SSIs and that larger, randomized studies are required to validate the superiority of CI cefazolin.
Discussion
Continuous infusion of cefazolin makes sense given the time above MIC dependent killing of beta-lactam antibioitics.
Cefazolin has no incompatibilities with other medications used routinely in CABG, so tying up an extra IV port with a continuous infusion is not likely to be a concern.
Although protocol adherence was not statistically different between groups, the primary reason for protocol non-adherence in the intermittent group was failure to re-dose, while the primary reason in the continuous infusion group was failure to adjust for renal insufficiency. This would tend to favor the continuous infusion group since they received more cefazolin than the protocol called for.
Because the study was retrospective in nature I agree with the author’s conclusions that randomized studies should be done to evaluate the superiority of the continuous infusion dosing strategy to prevent surgical skin infections in patients undergoing CABG.
Drug information question
Q: Can I give heparin subcutaneously for VTE prophylaxis to a patient with an epidural catheter in place?
A: Yes, as long as you give it twice daily rather than 3 times daily.
The 2010 American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines state:
The widespread use of subcutaneous heparin and paucity of complications suggests that there is little risk of spinal hematoma associated with this therapy.
Resource
Back in episode 12 when I talked about evaluating QTc interactions I mentioned the great drug interaction reference book by Hansten & Horn: Top 100 Drug interactions. The authors recently released the 2016 edition of this book.
I’ve used this great handbook for over 7 years, and I highly recommend it. The authors do a fantastic job of sorting through the ocean of “gee whiz” drug interaction and coming up with those interactions which are actually clinically significant.
They have an entire section on QTc interactions and the handbook is worth the $19.95 you’ll invest in it on amazon. The book is also available on the mobile platform skyscape, but I advise against using the digital format at this time as it is much more difficult to navigate and use quickly compared to the paperback version.
I’ve ordered my 2016 copy of this handbook and you can get yours using my link to amazon.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
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