FreshBrains: Recent Episodes

Bill Gross

neuroscience... served fresh!

View Details

Does tightly managing #ICP help our patients? Is there a better way? (spoiler: Licox @integra_life)

View Details

Does that work? Is it a good idea?

View Details

Is there any evidence behind our OR attire

Maybe? Sort-of? ... take a listen.

View Details

Our inaugural TIA! (mini-episodes reviewing a specific article)

This one is is discussing an article that measured awareness under anesthesia – more common than you might expect...

Sanders, R., Gaskell, A., Raz, A., Winders, J., Stevanovic, A., Rossaint, R., Boncyk, C., Defresne, A., Tran, G., Tasbihgou, S., Meier, S., Vlisides, P., Fardous, H., Hess, A., Bauer, R., Absalom, A., Mashour, G., Bonhomme, V., Coburn, M., Sleigh, J. (2017). Incidence of Connected Consciousness after Tracheal Intubation Anesthesiology 126(2), 214-222. https://dx.doi.org/10.1097/ALN.0000000000001479

Gaskell, A., Hight, D., Winders, J., Tran, G., Defresne, A., Bonhomme, V., Raz, A., Sleigh, J., Sanders, R. (2017). Frontal alpha-delta EEG does not preclude volitional response during anaesthesia: prospective cohort study of the isolated forearm technique. British journal of anaesthesia 119(4), 664-673. https://dx.doi.org/10.1093/bja/aex170

View Details

This episode we cover a brief overview of the history of neurosurgery, from ancient trephination through the contributions of Harvey Cushing in establishing the modern field.

How far back were people doing surgery on the head? What was holding us back from doing real brain surgeries, and why did it not flourish until this century? Why was Harvey Cushing the perfect person to be the "father" of modern neurosurgery?

References Used:

Really good book (and not too long) going over the development of neurosurgery through time.

Fascinating book with lots of detail covering the history of all aspects of neurosurgery. Goes into a lot of depth for each topic and technique. Also includes very nice pictures.

This entire issue is full of interesting articles on the history of perioperative care, including hemostasis, hyperosmolar agents. I also loved the article on the development of the frontotemporal craniotomy.

Neurosurgical Focus: Volume 36 (2014): Issue 4 (Apr 2014): History of Craniotomy, Cranioplasty, and Perioperative Care

Another great issue of Neurosurgical Focus on history. This one also includes a couple articles on the history of infection.

Neurosurgical Focus: Volume 18: Issue 4 (Apr 2005): History of Brain Tumor Surgery

Very nice overview of the history of neurosurgery, from ancient times through the modern era.

Liu, C., Apuzzo, M. (2003). The Genesis of Neurosurgery and the Evolution of the Neurosurgical Operative Environment: Part I—Prehistory to 2003 Neurosurgery 52(1), 3. https://dx.doi.org/10.1097/00006123-200301000-00001

History of William Bovie, and the development of his electrosurgical device.

O'Connor, J., Bloom, D. (1996). William T. Bovie and electrosurgery Surgery 119(4), 390-396. https://dx.doi.org/10.1016/s0039-6060(96)80137-1

Description of the first brain tumor operation, performed in 1884.

Kirkpatrick, D. (1984). The first primary brain-tumor operation Journal of Neurosurgery 61(5), 809-813. https://dx.doi.org/10.3171/jns.1984.61.5.0809

View Details

How good are we at predicting outcome in severe TBI? Do all patients do bad, or are there some that recover?

On this episode Karl dives into the data to give us an update on what the data supports.

Literature Referenced:

What early predictions do we make?

Barlow, P., Teasdale, G. (1986). Prediction of Outcome and the Management of Severe Head Injuries: The Attitudes of Neurosurgeons Neurosurgery 19(6), 989-991. https://dx.doi.org/10.1227/00006123-198612000-00014

How good are we at predicting outcomes in ICU patients?

Kaufmann, M., Buchmann, B., Scheidegger, D., Gratzl, O., Radü, E. (1992). Severe head injury: should expected outcome influence resuscitation and first-day decisions? Resuscitation 23(3), 199-206. https://dx.doi.org/10.1016/0300-9572(92)90003-u

Brain Trauma Foundation guidelines on prognosis in severe TBI

https://www.braintrauma.org/guidelines/prognosis

IMPACT calculator to model TBI outcome

http://www.tbi-impact.org/

Updated practice guidelines on the management of patients with disorders of consciousness

Giacino, J., Katz, D., Schiff, N., Whyte, J., Ashman, E., Ashwal, S., Barbano, R., Hammond, F., Laureys, S., Ling, G., Nakase-Richardson, R., Seel, R., Yablon, S., Getchius, T., Gronseth, G., Armstrong, M. (2018). Practice guideline update recommendations summary: Disorders of consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research Neurology 91(10), 10.1212/WNL.0000000000005926. https://dx.doi.org/10.1212/wnl.0000000000005926

View Details

Is ketamine safe to use in TBI patients (or anyone with increased ICP)?

The usual answer is “heck no!”, but where does this come from, and is it true?

This week, Karl and I talk about the origin of this believe and the evidence behind the safety of ketamine in TBIs (and how it might actually improve outcome...)

Literature Referenced:

Original Lancet letter that started everything. Four cases of increased ICP after ketamine administration.

Evans, J., Rosen, M., Weeks, R., Wise, C. (1971). Ketamine in neurosurgical procedures. Lancet (London, England) 1(7688), 40-1. https://www.ncbi.nlm.nih.gov/pubmed/4099342

Additional case reports at the time.

Gardner, A., Olson, B., Lichticer, M. (1971). Cerebrospinal-fluid Pressure during Dissociative Anesthesia with Ketamine. Anesthesiology 35(2), 226-8. https://dx.doi.org/10.1097/00000542-197108000-00029

List, W., Crumrine, R., Cascorbi, H., Weiss, M. (1972). Increased Cerebrospinal Fluid Pressure after Ketamine Anesthesiology 36(1), 98-99. https://dx.doi.org/10.1097/00000542-197201000-00023

GANER, A., DANNEMILLER, F., DEAN, D. (1972). Intracranial Cerebrospinal Fluid Pressure in Man During Ketamine Anesthesia. Anesthesia & Analgesia 51(5), 741. https://dx.doi.org/10.1213/00000539-197209000-00019

SHAPIRO, H., WYTE, S., HARRIS, A. (1972). KETAMINE ANAESTHESIA IN PATIENTS WITH INTRACRANIAL PATHOLOGY BJA: British Journal of Anaesthesia 44(11), 1200-4. https://dx.doi.org/10.1093/bja/44.11.1200

Wyte, S., Shapiro, H., Turner, P., Harris, A. (1972). Ketamine-induced intracranial hypertension. Anesthesiology 36(2), 174-6. https://www.ncbi.nlm.nih.gov/pubmed/5059108

Gibbs, J. (1972). The effect of intravenous ketamine on cerebrospinal fluid pressure. British journal of anaesthesia 44(12), 1298-302. https://www.ncbi.nlm.nih.gov/pubmed/4650346

Animal study in pigs showing that ketamine reduces CBF.

Björkman, S., Akeson, J., Nilsson, F., Messeter, K., Roth, B. (1992). Ketamine and midazolam decrease cerebral blood flow and consequently their own rate of transport to the brain: an application of mass balance pharmacokinetics with a changing regional blood flow. Journal of pharmacokinetics and biopharmaceutics 20(6), 637-52. https://www.ncbi.nlm.nih.gov/pubmed/1302766

First well designed human trial of ketamine administration in humans with intracranial pathology (tumors and SAH). Showed a decrease in ICP and CBF.

Mayberg, T., Lam, A., Matta, B., Domino, K., Winn, H. (1995). Ketamine does not increase cerebral blood flow velocity or intracranial pressure during isoflurane/nitrous oxide anesthesia in patients undergoing craniotomy. Anesthesia and analgesia 81(1), 84-9. https://www.ncbi.nlm.nih.gov/pubmed/7598288

First human trial of ketamine in TBI patients.

Albanèse, J., Arnaud, S., Rey, M., Thomachot, L., Alliez, B., Martin, C. (1997). Ketamine decreases intracranial pressure and electroencephalographic activity in traumatic brain injury patients during propofol sedation. Anesthesiology 87(6), 1328-34. https://www.ncbi.nlm.nih.gov/pubmed/9416717

Meta-analyses/reviews demonstrating the safety of ketamine in neuro patients.

Zeiler, F., Teitelbaum, J., West, M., Gillman, L. (2014). The Ketamine Effect on ICP in Traumatic Brain Injury Neurocritical Care 21(1), 163-173. https://dx.doi.org/10.1007/s12028-013-9950-y

Wang, X., Ding, X., Tong, Y., Zong, J., Zhao, X., Ren, H., Li, Q. (2014). Ketamine does not increase intracranial pressure compared with opioids: meta-analysis of randomized controlled trials Journal of Anesthesia 28(6), 821-827. https://dx.doi.org/10.1007/s00540-014-1845-3

Cohen, L., Athaide, V., Wickham, M., Doyle-Waters, M., Rose, N., Hohl, C. (2015). The Effect of Ketamine on Intracranial and Cerebral Perfusion Pressure and Health Outcomes: A Systematic Review Annals of Emergency Medicine 65(1), 43-51.e2. https://dx.doi.org/10.1016/j.annemergmed.2014.06.018

View Details

Really? Decadron can worsen mortality in GBMs?

This week Karl and I go over the evidence showing that steroids might not be the best thing for GBM patients. Specifically, it looks like dexamethasone might interfere with the effectiveness of chemo and radiation, leading to worse outcomes.

Literature Referenced:

Opinion paper that summarizes the argument against using Decadron in GBM patients:

Wong, E., Swanson, K. (2019). Dexamethasone—Friend or Foe for Patients With Glioblastoma? JAMA Neurology 76(3) https://dx.doi.org/10.1001/jamaneurol.2018.4530

Retrospective post-hoc comparison of Decadron dose in NovoTTF vs. best physician’s choice (BPC) chemo.Patients were dichotomized to > or < 4mg/day. Improved survival seen in low Decadron dose group. NovoTTF patients: median OS 4.8mo vs. 11.0mo, BPC chemo patients: 6.0mo vs. 8.9mo (effect seemed to be more profound in TTF group).

Wong, E., Lok, E., Gautam, S., Swanson, K. (2015). Dexamethasone exerts profound immunologic interference on treatment efficacy for recurrent glioblastoma British Journal of Cancer 113(2), 232-41. https://dx.doi.org/10.1038/bjc.2015.238

A combination of 3 retrospective human patient cohorts and a mouse model of GBM looking at the correlation of Decadron with survival after RT. Also compared VEGF inhibitor in mouse model.Found worsening mortality associated with Decadron in all 3 cohorts using a multivariate model. In mouse model, Decadron made radiation therapy ineffective. VEGF inhibitors were able to control edema without worsening outcome.

Pitter, K., Tamagno, I., Alikhanyan, K., Hosni-Ahmed, A., Pattwell, S., Donnola, S., Dai, C., Ozawa, T., Chang, M., Chan, T., Beal, K., Bishop, A., Barker, C., Jones, T., Hentschel, B., Gorlia, T., Schlegel, U., Stupp, R., Weller, M., Holland, E., Hambardzumyan, D. (2016). Corticosteroids compromise survival in glioblastoma Brain 139(5), 1458-1471. https://dx.doi.org/10.1093/brain/aww046

First reference in the literature I could find to this effect.Tested the effects of adding dex to human glioma cell cultures, treated with vincristine, cytarabine, methotrexate (MTX), and adriamycin. Found that decadron attenuated the effect of all tested chemo agents.

Weller, M., Schmidt, C., Roth, W., Dichgans, J. (1997). Chemotherapy of human malignant glioma: Prevention of efficacy by dexamethasone? Neurology 48(6), 1704-1709. https://dx.doi.org/10.1212/wnl.48.6.1704

Developed findings from Weller (1997) to look at mechanisms. Demonstrated that dDcadron inhibits apoptosis in human astrocytoma cells in culture.

Gorman, A., Hirt, U., Orrenius, S., Ceccatelli, S. (2000). Dexamethasone pre-treatment interferes with apoptotic death in glioma cells Neuroscience 96(2), 417-425. https://dx.doi.org/10.1016/s0306-4522(99)00565-5

Phase II trial testing ipilimumab for brain melanoma mets. Included two cohorts: Cohort A - asymptomatic, Cohort B - symptomatic, taking Decadron. Cohort B survived longer.

Was this due to worse disease, or the Decadron treatment?

Margolin, K., Ernstoff, M., Hamid, O., Lawrence, D., McDermott, D., Puzanov, I., Wolchok, J., Clark, J., Sznol, M., Logan, T., Richards, J., Michener, T., Balogh, A., Heller, K., Hodi, F. (2012). Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial The Lancet Oncology 13(5), 459-465. https://dx.doi.org/10.1016/s1470-2045(12)70090-6

View Details

Want a taste of what's to come? The first full episode will be released shortly! Here's something to tide you over...