One of the central things we do for neuro patients in control their ICP. But, does tight control of ICP improve outcomes? Is ICP the best thing for us to be optimizing, especially if brain ischemia is what we're trying to avoid? What about brain tissue oxygenation? I'll quickly review the evidence, and you decide. Lundberg demonstrating ICP measured from an EVD in TBI patients. Lundberg, N., Troupp, H., Lorin, H. (1965). Continuous Recording of the Ventricular-Fluid Pressure in Patients with Severe Acute Traumatic Brain Injury Journal of Neurosurgery 22(6), 581-590. https://dx.doi.org/10.3171/jns.1965.22.6.0581 Model showing independent effects of ICP and blood pressure on TBI outcomes. Marmarou, A., Anderson, R., Ward, J., Choi, S., Young, H., Eisenberg, H., Foulkes, M., Marshall, L., Jane, J. (1991). Impact of ICP instability and hypotension on outcome in patients with severe head trauma Journal of Neurosurgery 75(Supplement), S59-S66. https://dx.doi.org/10.3171/sup.1991.75.1s.0s59 Mortality in TBI over the past 150 years (note the large decrease through the 70s and 80s). Stein, S., Georgoff, P., Meghan, S., Mizra, K., Sonnad, S. (2010). 150 Years of Treating Severe Traumatic Brain Injury: A Systematic Review of Progress in Mortality Journal of Neurotrauma 27(7), 1343-1353. https://dx.doi.org/10.1089/neu.2009.1206 BEST-TRIP trial comparing invasive ICP monitoring to clinical exam and CT. No difference in outcomes in severe TBI patients. Chesnut, R., Temkin, N., Carney, N., Dikmen, S., Rondina, C., Videtta, W., Petroni, G., Lujan, S., Pridgeon, J., Barber, J., Machamer, J., Chaddock, K., Celix, J., Cherner, M., Hendrix, T. (2012). A Trial of Intracranial-Pressure Monitoring in Traumatic Brain Injury The New England Journal of Medicine 367(26), 2471-2481. https://dx.doi.org/10.1056/NEJMoa1207363 Meta-analysis of invasive ICP studies. Observational studies consistently show a benefit to ICP monitoring. Shen, L., Wang, Z., Su, Z., Qiu, S., Xu, J., Zhou, Y., Yan, A., Yin, R., Lu, B., Nie, X., Zhao, S., Yan, R. (2016). Effects of Intracranial Pressure Monitoring on Mortality in Patients with Severe Traumatic Brain Injury: A Meta-Analysis PLOS ONE 11(12), e0168901. https://dx.doi.org/10.1371/journal.pone.0168901 Original Lancet article discussing secondary injury from ischemia in TBI. Graham, D., Adams, J. (1971). ISCHÆMIC BRAIN DAMAGE IN FATAL HEAD INJURIES The Lancet 297(7693), 265-266. https://dx.doi.org/10.1016/s0140-6736(71)91003-8 First studies to look at outcome in TBI patients using Licox Santbrink, H., Maas, A., Avezaat, C. (1996). Continuous Monitoring of Partial Pressure of Brain Tissue Oxygen in Patients with Severe Head Injury Neurosurgery 38(1), 21-31. https://dx.doi.org/10.1097/00006123-199601000-00007 Valadka, A., Gopinath, S., Contant, C., Uzura, M., Robertson, C. (1998). Relationship of brain tissue PO2 to outcome after severe head injury Critical Care Medicine 26(9), 1576-1581. https://dx.doi.org/10.1097/00003246-199809000-00029 BOOST-II trial. Respiratory interventions were able to improve PbO2 in TBI patients, and that group showed an improved outcome, including disability and mortality. Okonkwo, D., Shutter, L., Moore, C., Temkin, N., Puccio, A., Madden, C., Andaluz, N., Chesnut, R., Bullock, M., Grant, G., McGregor, J., Weaver, M., Jallo, J., LeRoux, P., Moberg, D., Barber, J., Lazaridis, C., Diaz-Arrastia, R. (2017). Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase-II Critical Care Medicine 45(11), 1907. https://dx.doi.org/10.1097/CCM.0000000000002619

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Managing ICP in TBI Patients

Does Lasix work to control your ICP? Is it synergistic with mannitol? No. Oh, you want evidence? Fine... ech... Todd, M., Cutkomp, J., Brian, J. (2006). Influence of Mannitol and Furosemide, Alone and in Combination, on Brain Water Content after Fluid Percussion Injury Anesthesiology 105(6), 1176-1181. https://dx.doi.org/10.1097/00000542-200612000-00017

TIA – Using furosemide to control ICP

What is the evidence behind the things we are forced to wear in the OR? Do they help? Are they voodoo? On this episode, Karl takes us through the evidence behind the different pieces of OR attire. Some things seem to work... some things do nothing... some things might actually be harmful. ? Literature Referenced: Overview of adoption of OR attire through history, by examining historical photographs. Adams, L., Aschenbrenner, C., Houle, T., Roy, R. (2016). Uncovering the History of Operating Room Attire through Photographs. Anesthesiology 124(1), 19-24. https://dx.doi.org/10.1097/aln.0000000000000932 Case report of surgeon performing appendectomy on himself. Rogozov, V., Bermel, N. (2009). Auto-appendectomy in the Antarctic: case report BMJ 339(dec15 1), b4965-b4965. https://dx.doi.org/10.1136/bmj.b4965 An experimental study of how clothing effects the dispersal of staph. Hill, J., Howell, A., Blowers, R. (1974). EFFECT OF CLOTHING ON DISPERSAL OF STAPHYLOCOCCUS AUREUS BY MALES AND FEMALES The Lancet 304(7889), 1131-1133. https://dx.doi.org/10.1016/s0140-6736(74)90885-x First experimental study on surgical draping. Beck, W., Collette, T. (1952). False faith in the surgeon's gown and surgical drape The American Journal of Surgery 83(2), 125-126. https://dx.doi.org/10.1016/0002-9610(52)90196-7 RCT including cloth vs. paper drapes for CABGs. Bellchambers, J., Harris, J., Cullinan, P., Gaya, H., Pepper, J. (1999). A prospective study of wound infection in coronary artery surgery European Journal of Cardio-Thoracic Surgery 15(1), 45-50. https://dx.doi.org/10.1016/s1010-7940(98)00255-3 Cochrane review on using plastic adhesive drapes. Webster, J., Alghamdi, A. (2015). Use of plastic adhesive drapes during surgery for preventing surgical site infection Cochrane Database of Systematic Reviews 4(4), CD006353. https://dx.doi.org/10.1002/14651858.cd006353.pub4 Disposable gowns have less infectious risk than multi-use gowns. Moylan, J., Kennedy, B. (1980). The importance of gown and drape barriers in the prevention of wound infection. Surgery, gynecology & obstetrics 151(4), 465-70. https://www.ncbi.nlm.nih.gov/pubmed/7414454 Large study of the effect of using jackets on surgical site infections (spoiler: none). Stapleton, E., Frane, N., Lentz, J., Armellino, D., Kohn, N., Linton, R., Bitterman, A. (2019). Association of Disposable Perioperative Jackets With Surgical Site Infections in a Large Multicenter Health Care Organization JAMA Surgery 155(1), 15-20. https://dx.doi.org/10.1001/jamasurg.2019.4085 Association of mouth flora with surgical site infections HAMILTON, A. (1905). DISSEMINATION OF STREPTOCOCCI THROUGH INVISIBLE SPUTUM.IN RELATION TO SCARLET FEVER AND SEPSIS. JAMA: The Journal of the American Medical Association XLIV(14), 1108. https://dx.doi.org/10.1001/jama.1905.92500410032001g First study testing the association of using masks and surgical site infections. Orr, N. (1981). Is a mask necessary in the operating theatre? 63(6), 390-2. Study of 41 patients testing the association of masks with surgical site infections. Chamberlain, G., Houang, E. (1984). Trial of the use of masks in the gynaecological operating theatre. Annals of the Royal College of Surgeons of England 66(6), 432-3. https://www.ncbi.nlm.nih.gov/pubmed/6391343 Larger study (>3000 patients) testing efficacy of masks. No difference in infections. Tunevall, T. (1991). Postoperative wound infections and surgical face masks: A controlled study World Journal of Surgery 15(3), 383-387. https://dx.doi.org/10.1007/bf01658736 Full RCT of using masks by non-scrubbed staff. No difference in infections. Webster, J., Croger, S., Lister, C., Doidge, M., Terry, M., Jones, I. (2010). Use of face masks by non-scrubbed operating room staff: a randomized controlled trial ANZ Journal of Surgery 80(3),

OR Attire

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

TIA – Awareness under anesthesia

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

History of Neurosurgery

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

Recovery in Severe TBI

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

Ketamine in TBIs

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

Does dexamethasone worsen mortality in GBM?

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

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