Author: Brandon O

Podcast: Play in new window | Download

Subscribe: Apple Podcasts | Spotify | Android | Pandora | iHeartRadio | TuneIn | RSS

Find us on Patreon here!

Buy your merch here!

We discuss the phenomenon of CPR-induced consciousness (i.e. patients demonstrating awakeness during resuscitation) with Jack Howard, Intensive Care Paramedic at Ambulance Victoria in the northern suburbs of Melbourne, Australia, and first author on a recent literature review and Delphi-derived expert guideline on CPRIC management.

Takeaway lessons

1. Data is light, but perhaps 1% of cardiac arrests have some form of consciousness witnessed.
2. It is primarily a problem because of the potential to delay or interfere with care (either due to the emotional confrontation and surprise, or from actual physical interference with medical care). However, there are also ethical questions about patient suffering.
3. The first response in many people seeing CPRIC will be to stop CPR and assume they’ve made a mistake about loss of pulses.
4. CPRIC is associated with better outcomes, probably as a marker of better neurologic perfusion before and/or during arrest.
5. There was general agreement by the panel that ketamine should be used as first-line for CPRIC. If unavailable or if it fails, the group was unable to agree on a best second line; fentanyl, midazolam, or a paralytic are all options. In CPRIC that physically interferes with care, larger doses are appropriate.
6. Paralytics as a first line (without sedation) are never recommended.
7. There is minimal data on the effect on outcomes when CPRIC is treated. One small Ambulance Victoria study had a trend towards lower rates of ROSC when sedation was used.
8. Speak to patients as though they can hear and understand you.
9. It is not clear but very possible that a larger number of patients than those who demonstrate external awareness may have a degree of subclinical consciousness; interviews of survivors and EEG analysis has supported this.
10. Many CPRIC patients will have ROSC, but if they don’t, they are probably excellent candidates for ECPR/ECMO or other rescue interventions. A minimum of 45 minutes of resuscitation should be offered.

References

• The guideline: Howard J, Grusd E, Rice D, et al. Development of an international prehospital CPR-induced consciousness guideline: A Delphi study. Paramedicine. 2023;0(0). doi:10.1177/27536386231215608
• The preliminary scoping review: Howard J, Lipscombe C, Beovich B, Shepherd M, Grusd E, Nudell NG, Rice D, Olaussen A. Pre-hospital guidelines for CPR-Induced Consciousness (CPRIC): A scoping review. Resusc Plus. 2022 Nov 28;12:100335. doi: 10.1016/j.resplu.2022.100335. PMID: 36465817; PMCID: PMC9713363.
• The study mentioned about awareness during CPR: Parnia S, Keshavarz Shirazi T, Patel J, Tran L, Sinha N, O’Neill C, Roellke E, Mengotto A, Findlay S, McBrine M, Spiegel R, Tarpey T, Huppert E, Jaffe I, Gonzales AM, Xu J, Koopman E, Perkins GD, Vuylsteke A, Bloom BM, Jarman H, Nam Tong H, Chan L, Lyaker M, Thomas M, Velchev V, Cairns CB, Sharma R, Kulstad E, Scherer E, O’Keeffe T, Foroozesh M, Abe O, Ogedegbe C, Girgis A, Pradhan D, Deakin CD. AWAreness during REsuscitation – II: A multi-center study of consciousness and awareness in cardiac arrest. Resuscitation. 2023 Oct;191:109903. doi: 10.1016/j.resuscitation.2023.109903. Epub 2023 Jul 7. PMID: 37423492.

Podcast: Play in new window | Download

Subscribe: Apple Podcasts | Spotify | Android | Pandora | iHeartRadio | TuneIn | RSS

We discuss the medications typically used after organ transplant, their impact on critical illness, and how to manage them when these patients show up sick—with Olivia Philippart, transplant clinical pharmacist specializing in liver and kidney transplant at University of Kentucky HealthCare.

Find us on Patreon here!

Buy your merch here!

Takeaway lessons

1. Most kidney transplants will end up on a calcineurin inhibitor like tacrolimus (or the older cyclosporine), an anti-proliferative like mycophenolate mofetil (Cellcept) or the older azathioprine, and possibly corticosteroids (e.g. prednisone). Formulations for some of these may need to be adjusted based on your formulary, so consult your pharmacist to get the equipotent dose.
2. How these patients present, their degree of immunosuppression, and risk of rejection, are all heavily dependent on the time since transplant. A patient <6 weeks from transplant is high risk for nosocomial infections (e.g. post-op complications). A patient years out is mainly at risk of the same infections as anybody else, in addition to opportunistic infections related to their immunosuppression.
3. Latent viral infections unmasked by immunosuppression or acquired from the transplant are usually not a surprise, as these are tested for as part of the initial workup.
4. The highest risk of organ rejection and hence the highest degree of immunosuppression is in organs with substantial amounts of lymphoid tissue transplanted. The highest is small bowel, then lung, then heart/kidney/pancreas, then the least in liver (liver transplant can actually overall support immune function). Some livers can be maintained on monotherapy, while lungs usually need triple therapy, and often dual therapy is used in the middle category.
5. Durations of therapy for identified infections may be longer in the immunosuppressed than for routine ICU care.
6. Mycophenolate is the first agent to consider dose reducing or holding in the setting of active bacterial infection. How to handle this depends on the severity of infection and degree of concern for rejection.
7. Both our calcineurin inhibitors (tacrolimus and cyclosporine) are primarily cleared in the liver and gut, so when there is liver impairment or bowel problems, dose decreases are often needed. Dietary intake also reduces drug absorption whereas NPO status may increase it. These drugs are heavily protein bound so albumin fluctuations (e.g. from malnutrition) may impact free levels.
8. Drug interactions are common as well; CYP3A4 or PGP inhibitors like diltiazem or verapamil, azole antifungals, amiodarone, macrolides (although not azithromycin), and paxlovid will tend to increase levels, while inducers like phenytoin or phenobarbital will tend to decrease them.
9. Overall, the therapeutic index of the calcineurin inhibitors is small, so have a low threshold for checking trough levels early and often.
10. After holding a dose, the serum levels will normalize within 3-5 half-lifes, but full return of immune function may take several weeks. However, the baseline level of immunosuppression is usually not so profound that the difference between “off” and “on” is huge and binary.
11. Organ rejection is possible but rare when drugs are acutely held (for days, maybe a week or two) in setting of severe infection, as this is already a relatively immunosuppressed state. However, this depends heavily on the time from transplant, and the organ transplanted.
12. Mycophenolate levels (or mercaptopurine levels for the older azathioprine) tend not to fluctuate as much; the metabolism (via glucuronidation) is not as sensitive to hepatic function, so monitoring levels is rarely needed.
13. Most of our immunosuppressants are not significantly renally cleared, so renal injury (even dialysis) usually require no dose adjustment. However, they can be nephrotoxic, so high levels may CAUSE renal injury, not vice versa.
14. Tacrolimus is available in either immediate release capsule (taken twice daily) or a long-acting form (taken once daily). The latter helps to decrease peaks and some of the neurotoxicity (seizure, tremors), but cannot be opened. There is an 80% conversion between formulations (multiply the long-acting dose by 1.2, then divide by half to get the short-acting BID equivalent). Levels checked should always be troughs.
15. Short-acting tacrolimus capsules should not be opened and put down tubes, but can be opened and given sublingually (50% dose reduction)—just dribbled under the tongue—although nurses need to take special precautions like gowning and double gloving. There is also a liquid tacrolimus formulation available.
16. IV tacro exists, but has substantially higher nephrotoxicity, and the dose conversion is tricky; other routes are preferred.
17. Cyclosporine is available in suspension which can go down a feeding tube, or via IV form (dose reduction needed).
18. IV mycophenolate is available (1:1 conversion), as well as a liquid suspension.
19. Steroids can be used in the ICU as usual (e.g. stress dosing), and indeed temporarily converting transplant patients to a pure steroid regimen is a reasonable approach during critical illness (remember: 20 mg hydrocortisone is equivalent to 5 mg prednisone).
20. It’s generally sound to touch base with someone who knows a patient’s transplant history, even years out (often just their normal nephrologist, pulmonologist, etc in that case, not necessarily the original transplant team), when these patients are admitted for critical illness.
21. Calcineurin inhibitors can cause headaches, seizures, even PRES, hyperkalemia and hypomagnesemia, and hypertension, hypercholesterolemia, hyperglycemia/diabetes. Attributing these effects to the drug is usually a diagnosis of exclusion.

References

From: Fishman JA. Infection in Organ Transplantation. Am J Transplant. 2017 Apr;17(4):856-879. doi: 10.1111/ajt.14208. Epub 2017 Mar 10. PMID: 28117944.