By Andrew Cheng, MD
How do you measure neurological outcome after acute brain injury? What is the optimal dose and duration of targeted temperature management after cardiac arrest? How does this differ in traumatic brain injury? And how can this be best measured and monitored in the neuro-ICU? These were among some of the questions posed, discussed and debated at the recent seventh International Hypothermia and Temperature Management Symposium, held in Sydney, Australia, from Aug. 28-30, 2018.
The Sofitel Darling Harbour, next to the new Sydney International Convention Centre and Sydney Aquarium, provided the setting for the seventh International Hypothermia and Temperature Management Symposium.
A biennial conference organized by scientific experts in the field of targeted temperature management (TTM) in emergency and critical care medicine, the symposium has its foundations in Japan when the inaugural meeting was held in Tokyo in 2004, organized by professor Nariyuki Hayashi. Subsequent meetings have been held in Miami (chair Dalton Dietrich), Lund, Sweden (co-chairs Hans Friberg and Taduesz Wieloch), Tokyo (chair Ken Nagao), Edinburgh, Scotland (chair Peter Andrews) and Philadelphia (co-chairs Fred Rincon and David Gaeski).
Chaired by Manoj Saxena and Naomi Hammond, with major academic sponsorship by The George Institute for Global Health and the University of New South Wales, this symposium focused on recent advances in the field of temperature management related to basic science, clinical research and innovative technology with the objective of translating contemporary scientific knowledge into a practical message that can be applied to everyday clinical practice. Highlights included the plenary sessions given by professors Alistair Gunn (Auckland, New Zealand), Peter Andrews and Dalton Dietrich.
Panel discussion, chaired by Manoj Saxena and patient advocate Nyrie Simpson, on measuring outcomes — what really matters?
Following an outstanding exposition of the preclinical foundations of therapeutic hypothermia, professor Gunn proceeded in his next lecture to demonstrate how hypothermia has shown significant impact on improving outcomes after neonatal birth asphyxia. A paediatrician scientist who has conducted groundbreaking basic research on the mechanisms and treatment of asphyxial brain injury, professor Gunn helped to develop a range of novel, clinically relevant fetal sheep paradigms with research that helped to establish the technique of “therapeutic cooling” to reduce brain injury due to low oxygen levels at birth.
Professor Andrews presented his plenary on the future of hypothermia for traumatic intracranial hypertension after Eurotherm. This was a particularly important discussion in light of the all the recent clinical trials of therapeutic hypothermia in traumatic brain injury (TBI) that have failed to demonstrate a positive impact of temperature management — despite decades of basic science research that have demonstrated the effects of even small variations in temperature on neuronal vulnerability and the negative impact of fever on neurological outcome after acute brain injury.
The Australian Zoo, located in Darling Harbour, was the setting of the welcome ceremony that greeted delegates to the Symposium.
Professor Dietrich, who is editor-in-chief of the Therapeutic Hypothermia and Temperature Management journal and one of the founding chairs of the IHTMS, shared in his plenary some of the research work he and his team have conducted on the effects of brain temperature on inflammation and the cerebral vasculature in mild TBI (or concussion) work, which had recently been acknowledged in the form of a $1.6M grant by the National Insititute of Health (NIH) and National Institute of Neurological Disorders and Stroke (NINDS).
New themes introduced at this symposium included the emerging role of extracorporeal membrane oxygenation (ECMO) and advanced multimodality monitoring, not only to monitor neurological recovery of the patient but to refine the delivery of TTM and improve our understanding of the neurobiological processes that take place during temperature management.
Sessions on ECMO included presentation of the Australian ECMO-CPR study by Andrew Udy (Melbourne, Australia), while Tetsuya Sakamoto and Noritoshi Ito (Japan) presented the findings of the SAVE-J study, a prospective registry of patients who underwent extracorporeal E-CPR vs standard care. Marc Conterato (Minneapolis) presented the case for induced hypothermia/ECMO in pre-hospital care for patients with refractory cardiac arrest with the experience of the Minnesota Resuscitation Consortium initiative.
Dining with faculty and friends on Sydney Harbour at the IHTMS.
Raimund Helbok (Innsbruck, Austria), who leads research in a major tertiary university hospital where multimodality monitoring is a standard of care, demonstrated the clinical utility of online monitoring of brain metabolism using microdialysis during TTM. The session received further contributions by Tobias Cronberg (Sweden) on the Lund experience of using continuous EEG for monitoring after cardiac arrest, Jonathan Rhodes (Edinburgh, Scotland) on the findings of brain tissue oxygen monitoring in TBI from the Eurotherm study, Anders Aneman (Sydney, Australia) on cerebrovascular autoregulation studies in post-cardiac arrest patients who received TTM, Kei Nishiyama (Japan) on TTM stratified by regional SO2 as measured by near infrared spectroscopy (NIRS), in addition to discussions on post-resuscitation brain monitoring by Markus Skrifvars (Helsinki, Finland) and Xiaofeng Jia (Baltimore).
Thematic sessions on the practical implementation of TTM was opened by a lecture entitled “Pharmacology and Induced Cooling: a Two-Way Street” by NCS immediate past president Gretchen Brophy (Virginia). Novel modalities of cooling featured in a session presented by Jon Rittenberger (Pittsburgh), Fred Rincon (Philadelphia), Kelly Harbour (Sydney) and Takahiro Miki (Japan).
Award of the Hayashi Prize to Akihito Inoue of Japan by Symposium Chair, Manoj Saxena.
Chair Manoj Saxena discussed fever prevention or induced normothermia for TBI as a concept for future study while some key current studies were then presented. Hans Friberg (Lund, Sweden) presented the international multicentre TTM-2 study after cardiac arrest, David Greer (Boston) presented the INTREPID study of fever prevention for acute vascular brain injury while Hitoshi Kobata (Osaka, Japan) discussed how hypothermia induced prior to emergent evacuation of acute subdural haemorrhage might influence outcome, as studied in the HOPES trial. This was followed by presentations of recent published clinical trials, including the HEAT study of permissive hyperthermia in severe sepsis by Paul Young (Wellington, New Zealand), the paediatric cardiac arrest trials by John Beca (Auckland, New Zealand), the J-Pulse HYPO registry by Hiroshi Nonogi (Shizuoka, Japan), the Hypothermia for Septic Shock study by Morten Bestle (Copenhagen), TTM studies for septic shock and meningitis by Frederique Schortgen (Paris) and the Time-differentiated Therapeutic Hypothermia (TTH48) trial by Hans Kirkegaard (Aarhus, Denmark).
One of the highlights of the symposium was a session devoted to improving how we assess long-term outcomes after brain injury. Following plenaries by Gisela Lilja (Lund, Sweden) and Carol Hodgson (Melbourne, Australia) on measuring outcomes in terms of neurocognitive and physical function, respectively, an interactive discussion followed in which a panel of multidisciplinary experts engaged with patients who had suffered traumatic brain injury and stroke. This well-received and widely acclaimed session offered the opportunity for both faculty and delegates to interact and learn about what really matters to our patients as an outcome after a life-changing brain injury.
Finally, one of the features of the IHTMS is the award of the Hayashi prize for the best oral abstract presentation of experimental or clinical research. This year, it was awarded to Akihiko Inoue (Japan) for his presentation, “Increased heart rate response during the rewarming phase of therapeutic hypothermia is associated with favorable neurological outcomes in out-of-hospital cardiac arrest patients.” Ome detō, mata au ma de (congratulations, and ’til we meet again)!
Andrew Cheng, MD, is senior staff intensivist at St. George Hospital, a major teaching hospital in Sydney for the University of New South Wales, with clinical focus in neurocritical care. His research interests include targeted temperature management in acute brain injury. Cheng was convener for the seventh International Hypothermia and Temperature Management Symposium.
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