In this episode I’ll:
1. Discuss an article about using IV acetaminophen in critically ill adults.
2. Answer the drug information question “Why is my post-op patient who is on rifampin at home still in pain after being given fentanyl?”
3. Share a resource for the treatment of intracranial hypertension after traumatic brain injury.
Article
Lead author: Hildy Schell-Chaple
Published in Critical Care Medicine July 2017
Background
To date, IV acetaminophen has only been proven to impact outcomes in a clinically meaningful way in patients undergoing a hysterectomy in Turkish hospitals.
The authors of this trial sought to determine the effects of IV acetaminophen on core body temperature, blood pressure, and heart rate in febrile critically ill patients (>38.2 °C). The study was a randomized, double-blind, placebo-controlled clinical trial enrolling 40 adult patients with fever in 3 ICUs within a single academic center.
Methods
Patients received an infusion of acetaminophen 1 g or normal saline placebo via IVMB over 15 minutes. Patient temperature and vital signs were measured every 5 to 15 minutes over a 4 hour period after the study drug was infused. The primary outcome looked at effects on temperature while the secondary outcomes looked at effects on blood pressure, heart rate, and respiratory rate.
Results
At the end of 4 hours, the only outcome that was statistically different than placebo was the difference in temperature. Not surprisingly, the group that received IV acetaminophen had a lower temperature by about half a degree Celsius.
There were statistically significant differences in heart rate and systolic blood pressure at time points prior to the end of the 4 hour study period. This was represented in the time-weight average mean values for each group. The acetaminophen group had a reduction in systolic blood pressure of 17 mmHg and a reduction in heart rate of 6 beats per minute compared to placebo.
Conclusion
The authors concluded:
Among febrile critically ill adults, treatment with acetaminophen decreased temperature, blood pressure, and heart rate. IV acetaminophen thus produces modest fever reduction in critical care patients, along with clinically important reductions in blood pressure.
Discussion
I see two limitations in the design of this study that prevent its generalizability.
First, while the study period lasted 4 hours, the normal dosing interval for IV acetaminophen is 6 hours. Because all of the effects on hemodynamics were over by 4 hours, the addition of 2 more hours to the study time would have likely significantly changed the time-weighted average mean values for effects on systolic blood pressure and heart rate.
Second, the comparison of IV acetaminophen to saline placebo is not a fair comparison when looking at effects on systolic blood pressure. Each gram of IV acetaminophen contains about 4 grams of mannitol. Mannitol has diuretic effects which can at least partially account for the reduction in systolic blood pressure between groups. To fairly evaluate effects of IV acetaminophen on blood pressure, patients in the placebo group must receive as much mannitol as patients in the acetaminophen group do.
Before considering using IV acetaminophen in critically ill patients, keep in mind that all patients at the beginning of the study had stable hemodynamic parameters.
I would like to see additional studies before using IV acetaminophen to affect hemodynamic parameters in critically ill patients with fever.
Drug information question
Q: Why is my post-op patient who is on rifampin at home still in pain after being given fentanyl?
A: Because rifampin is inducing the metabolism of fentanyl.
I recently encountered a patient with poor post-op pain control despite seemingly adequate doses of IV fentanyl. When I checked the patient’s home medication list to see if they were on opioids at home I noticed the patient was taking rifampin. Rifampin induces the metabolism of fentanyl, oxycodone, and morphine via induction of CYP450 enzymes including 3A4 and 2D6. I switched the patient to hydromorphone which is hepatically metabolized by glucuronidation and not the CYP 450 system. This seemed to work much better for the patient’s pain.
Resource
The resource for this episode is the staircase approach for the treatment of intracranial hypertension after traumatic brain injury. You can find a picture of this approach here.
Focus on brain injury – staircase approach for the treatment of intracranial hypertension after #TBI . https://t.co/hbzzZFzFWL pic.twitter.com/4klYQegaMx
— Intens Care Med (@yourICM) June 24, 2017
The approach involves a stepwise application of sedation, osmotic therapy, hyperventilation, hypothermia, and surgical decompression with or without barbiturates.
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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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