In this episode I’ll:
1. Discuss an article about using ketamine infusion for sedation in mechanically ventilated patients.
2. Answer the drug information question “Can patients undergoing therapeutic hypothermia receive continuous heparin infusion?”
3. Share a resource for HIV guidelines.
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Article
Ketamine Infusion for Adjunct Sedation in Mechanically Ventilated Adults
Lead author: Lara M. Groetzinger
Published ahead of print in Pharmacotherapy December 2017
Background
Although ketamine was first patented for use in humans over 50 years ago, it continues to grow in popularity. There are twice as many articles in pubmed mentioning ketamine in 2017 as there were 10 years ago, and each of the last 3 years has seen over 1000 articles mentioning ketamine. Much of the information on ketamine is centered around it’s use as a procedural sedative or as a non-opioid analgesic.
More data is being made available on the use of ketamine for continuous sedation in critically ill patients. As recently as episode 238 I talked about a retrospective review of ketamine infusion in critically ill patients. If you are not familiar with the effects of ketamine and potential uses in critically ill patients jump back to episode 16 for a review.
Methods
The authors of this study conducted a retrospective review of mechanically ventilated patients receiving continuous ketamine infusion over a 4 year period at a single academic hospital. The authors examined data on dosing, the effect of ketamine on other sedatives, total sedative use, Riker Sedation-Agitation Scale (SAS) scores, adverse drug reactions (ADRs), and hemodynamic variables.
Results
In the 4 year period 91 patients were found to have received ketamine infusion. The median dose used was 0.41 mg/kg/hr and the highest dose used was 2.5 mg/kg/hour. The median duration of ketamine use was 2.8 days and the longest duration of use was 14.7 days. Concomitant sedatives were reduced or discontinued in 63% of patients within 24 hours of initiating ketamine. Propofol and benzodiazepines were the most commonly discontinued sedatives.
There was a statistically significant increase from 55% to 61% in the number of sedation scores documented in the goal range for the 24-hour period after ketamine initiation compared with the immediate 24 hours prior. There was also a statistically significant decrease from 33% to 27% in the number of sedation scores rated as agitated after ketamine was initiated. Hemodynamic variables were not changed significantly after ketamine was started. Seven patients (7.7%) required discontinuation of ketamine infusion due to an adverse reaction.
Conclusion
The authors concluded:
Continuous ketamine infusion for adjunct light sedation was well tolerated in a cohort of critically ill adults, with an acceptable safety profile. Prospective studies of ketamine infusion are warranted to further establish its efficacy as a sedative in this population.
Discussion
The previous study discussed in episode 238 found that decreased sedative doses came at the cost of an increase in the number of patients that required dexmedetomidine or antipsychotics. The study discussed in this episode contained almost triple the number of patients and showed no such increase in sedative use with the addition of ketamine.
When other sedatives have failed or are contraindicated, ketamine appears to have value as an adjunctive sedative agent in critically ill patients. Data on meaningful outcomes such as delirium, length of stay, and mortality are needed before ketamine can be considered on equal footing as propofol, fentanyl, midazolam, or dexmedetomidine for routine use as a continuous infusion.
I would like future studies of ketamine to analyze separately the patients who received a sub-anesthetic dose of ketamine compared with those that received an anesthetic dose.
Finally, with all the attention on the unique benefits of ketamine, the adverse reactions are sometimes overlooked. In this study, there were seven adverse drug reactions to ketamine. Two were judged probable – dysphoria and nystagmus. Five were judged possible – two tachycardia, two increased agitation, and one ventricular tachycardia. When considering ketamine use in your patients, remember to weigh the known risks and benefits before making a decision!
Drug information question
Q: Can patients undergoing therapeutic hypothermia receive continuous heparin infusion?
A: Yes, if there is a compelling indication for full-dose anticoagulation such as a known thrombus.
An elevated bleeding risk with therapeutic hypothermia means that the decision to anticoagulate a patient should not be taken lightly. You can see some protocols that highlight their recommendation to use anticoagulants when indicated like this one from Mass General.
On page 2 they say:
Note that hypothermia is recommended in patients who have received systemic thrombolysis with IV tPA or who are concurrently being treated with antiplatelet agents or anticoagulants (such as IV heparin).
Another option if you are not doing this already is to target 36°C for these patients. This review article explains:
Although mild to moderate hypothermia has some effect on the coagulation system the clinical risk of bleeding associated with cooling appears to be very low. This will, however, increase significantly if the patient has moderate-to-severe acidosis. No effects of hypothermia on coagulation occur in any patient as long as temperature is ≥35°C, and patients at very high bleeding risk can safely be cooled to this temperature.
Resource
The resource for this episode is the US Department of Health and Human Services Clinical Guidelines for HIV/AIDS Information. These guidelines can be found at https://aidsinfo.nih.gov/guidelines. There is information on adult antiretroviral regimens, opportunistic infections, occupational post-exposure prophylaxis, and more.
I like to use these antiretroviral guidelines as a reference to make sure my patients are on an appropriate regimen. During the medication reconciliation process, if I cannot match the patient’s current regimen to one in the guidelines, I call the outpatient provider and check to see if I am missing information or if there is a reason for an alternate regimen.
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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