In this episode I’ll:
1. Discuss an article about extended vs. intermittent infusion of piperacillin/tazobactam in critically ill patients.
2. Answer the drug information question “How should a naloxone infusion be weaned?”
3. Share a resource for researching toxicology concerns with medications.
One of the best parts of hosting a critical care pharmacy podcast is connecting with hundreds of great pharmacists. Many of them have told me they want practical, critical care pharmacy education, intended for practicing pharmacists. They want complex topics broken down into simple to remember and easy to apply concepts. They want skills they can apply at the bedside, not academic theory.
That’s one of the reasons I’ve opened Pharmacy Joe’s Critical Care Pharmacy Academy.
Every month in the Academy, I publish a skill-based Masterclass where I take about an hour to dive deep into a practical, critical care skill. The Masterclasses are self-paced and broken up into 5-15 minute video segments. Patient assessment and airway pharmacology are two examples of current Masterclasses.
To hear what current members have to say about the Academy, click here.
Article
Lead author: Sheung-Yin Fan
Published online in Pharmacotherapy November 2016
Background
Extended infusions of piperacillin-tazobactam are widely used but are based largely on common-sense (better time-above MIC should mean better outcomes) and retrospective data analysis. The authors of this study sought to determine whether critically ill patients receiving extended-infusion (EI) piperacillin/tazobactam would have improved clinical outcomes compared with patients receiving intermittent infusions.
Methods
The trial was an open-label, prospective study that took place in a 22-bed intensive care unit in a regional hospital in Hong Kong.
A total of 367 adults who had a diagnosis of either bacterial infection or neutropenic fever were assigned to receive piperacillin/tazobactam as either a 4-hour extended infusion or a 30-minute intermittent infusion.
The primary outcome was the 14-day mortality rate after initiation of piperacillin/tazobactam. Secondary outcomes included in-hospital mortality rate, time to defervescence, duration of mechanical ventilatory support, length of ICU stay, and duration of hospital stay.
Results
There was no difference in 14-day mortality between groups. The extended infusion group did have a faster time to defervescence (4 days vs. 6 days) compared to the intermittent infusion group. Otherwise, there was no difference in any of the other secondary outcome measures between groups.
A posthoc analysis was done that suggested a 14-day mortality benefit favoring extended infusion in patients with infectious organisms identified and also in those whom respiratory tract infection was diagnosed.
Conclusion
The authors concluded:
Both the extended infusion and non-extended infusion groups demonstrated similar 14-day mortality. Posthoc subgroup analysis revealed a mortality benefit in patients in the EI group who had infectious organisms identified or were diagnosed with respiratory tract infections.
Discussion
It is very important to have prospective trial data that supports the idea of using extended infusions of piperacillin-tazobactam. In that regard, this study can be used to affirm the decision of those that are already using extended infusion piperacillin-tazobactam. If a hospital has not yet switched to extended infusion piperacillin-tazobactam due to concerns with the quality of retrospective data, this study should prompt re-analysis of the risks and benefits to using extended infusion for piperacillin-tazobactam.
As always, it is inherently risky to rely on posthoc analysis to conclude risks of benefit or harm. Subgroup analysis that is not pre-specified can only be used to guide further study, not claim a benefit. For this reason, I would only draw a conclusion of “no difference between groups” rather than “superiority of extended infusion” from this data. I do think that extended infusion becomes the most rational choice even if it is no different than intermittent infusion, because it is associated with cost savings from using a lower amount of antibiotic.
Drug information question
Q: How should a naloxone infusion be weaned?
A: Slow enough so that re-sedation or respiratory failure does not occur in case opioids are still on board.
I cannot locate any official guidelines, studies or recommendations on how naloxone drips should be weaned. Given a duration of action for naloxone of 30 to 120 minutes; I prefer to wean in increments of 0.1 to 0.2 mg/hr every 1 to 2 hours. While this may be on the slow side, it should prevent re-sedation or respiratory failure from occurring. If the patient’s airway is protected and there is no risk of respiratory failure, I would be comfortable turning the naloxone off without any weaning. For more about naloxone listen to episode 25.
Resource
The resource I’d like to share is: TOXNET®: Toxicology Data Network
TOXNET is a group of databases covering chemicals and drugs, diseases and the environment, environmental health, occupational safety and health, poisoning, risk assessment and regulations, and toxicology. It is managed by the Toxicology and Environmental Health Information Program (TEHIP) in the Division of Specialized Information Services (SIS) of the National Library of Medicine (NLM). A mobile version of TOXNET is available.
Use TOXNET to find:
Specific chemicals, mixtures, and products
Chemical nomenclature
Chemicals that may be associated with a disease, condition or symptom
Chemicals associated with consumer products, occupations, hobbies, and more
Special toxic effects of chemicals in humans and/or animals
Citations from the scientific literature
TOXNET provides links to PubMed, NLM’s free web interface to the world’s biomedical literature, and to additional sources of toxicological information.
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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