In this episode I’ll:
1. Discuss an article on the discontinuation order of vasopressors in the management of septic shock.
2. Answer the drug information question “Why is daptomycin dosed once daily?”
3. Share a tip for responding to inpatient medical emergencies.
I have a 6-module program that teaches pharmacists how to respond to code blue and rapid response calls inside my Hospital Pharmacy Academy. For a limited time you can try out access to the Academy for 7 days for just $1. Just be sure to sign up before 10 pm EST on June 27, 2018. There are over 35 in-depth trainings on hospital pharmacy topics in the Academy, with more added each month. This is in addition to weekly literature digests to stay up to date with the medical literature, private community forums, full-text access to two major medical journals, and resources to make precepting easier. To sign up go to pharmacyjoe.com/trial.
Lead author: Kyeongman Jeon
Published in the journal Critical Care May 2018
The first two vasopressors generally used to treat septic shock are vasopressin and norepinephrine. The usual strategy is to add norepinephrine to vasopressin. There is no data to identify the appropriate strategy for weaning this combination of vasopressors in patients who are recovering from septic shock. The authors of this study sought to evaluate the incidence of hypotension with different tapering sequences in patients on norepinephrine and vasopressin recovering from septic shock.
Patients with septic shock receiving concomitant norepinephrine and vasopressin were randomly assigned to taper norepinephrine first (norepinephrine group) or vasopressin first (vasopressin group). The primary end point was the incidence of hypotension within one hour of tapering of the first vasopressor.
Before enrollment was complete, a significant difference in the incidence of hypotension was found and the study was stopped early. Over two-thirds of the patients in the norepinephrine group versus less than one-quarter in the vasopressin group developed hypotension after tapering the first vasopressor. This difference was statistically significant. These findings persisted at nearly the same percentages when the second vasopressor was tapered. The hazard ratio for hypotension from first tapering norepinephrine was 2.2.
The authors concluded:
Tapering norepinephrine rather than vasopressin may be associated with a higher incidence of hypotension in patients recovering from septic shock who are on concomitant norepinephrine and vasopressin. However, further studies with larger sample sizes are required to better determine the appropriate strategy for vasopressor tapering.
Every study seems to conclude that larger and additional studies are warranted. While there is certainly a lot more to be learned on this subject, tapering vasopressin first is a reasonable choice based on the results of this study. However, I would not treat the results of this study as “absolute” since trials that are stopped early have frequently overestimated treatment effects.
Drug information question
Q: Why is daptomycin dosed once daily?
A: Based on animal studies, the activity of daptomycin seems to correlate with the AUC/MIC (area under the concentration-time curve/minimum inhibitory concentration) for staph aureus. However, in the Phase 1 studies and Phase 2 pre-approval trials in adults patients, the incidence of CPK elevations appeared to be more frequent when daptomycin was dosed more frequently than once daily. Therefore, future trials proceeded with once-daily dosing regimens only.
Tip for responding to inpatient medical emergencies
You don’t need to know the cause of severe, symptomatic hyponatremia before treating it. Severe, symptomatic hyponatremia is characterized by a serum sodium < 125 mEq/L and symptoms such as seizure, mental status changes, respiratory depression, coma or obtundation.
Without immediate treatment, this can lead to cerebral edema, respiratory failure, permanent brain injury, or death. Such symptoms are generally seen when the hyponatremia develops acutely rather than chronically.
When a patient has severe, symptomatic hyponatremia, it should be promptly treated with hypertonic 3% saline. The simplest method is to give a 100 mL IV bolus of 3% saline, repeated up to 2 more times until symptoms resolve. Once symptoms resolve, it is important to determine what the cause of hyponatremia is before selecting the next course of treatment.
Remember to go to pharmacyjoe.com/trial before 10 pm EST on June 27, 2018, to get a 7-day trial to my Hospital Pharmacy Academy for just $1.
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.