Night shift is about to start. You are getting a bedside handover. This 40 yr old with Traumatic Brain Injury (TBI), was admitted after a MVA, is intubated, sedated & has an EVD in place.ICP & CPP are being monitored and to be treated if the need arises.

As he is walking out, the Fellow smiles & says -'Since you already know about Tranexamic Acid (TA), why don't you tell us about - Hormones, Cooling & Surgery (not the usual Primary Surgery to remove blood) in TBI, during morning rounds'.

Hormones, Cooling & Surgery in TBI ?- your tiered brain (despite the 80 hrs work rule) is stimulated. Luckily it's a Q night (you are not even allowed to say it - fear of Jinx..).

TBI it seems is a complex disease (you still are searching for a simple one). There appears to be some Primary Insults and later on Secondary Insults.Seems like 'Mitochondrial damage; Inflammatory Mediator's; Apoptosis, Neurotransmitter Excitotoxicity' - can lead to more cell death & vasogenic edema - propagating the injury & worsening outcome (you suspect these same people are blamed in almost every disease we cannot treat well - Round up the usual Suspects).

Hormones in TBI - on Dr Google - 'Steroids & Progesterone' pop up.Everyone knows steroids don't work - so you pursue Progesterone.





Progesterone was touted for its Neuroprotective benefits in animal models & small studies. It appears to work at all the factors causing Secondary Injury & luckily had some Fancy Named Studies done.





SYNAPSE Trial in NEJM Dec 25th 2014. A multi center trial from 7/2010 - 9/2013 across 21 countries, randomized 1195 Pt's with GCS of 8 or lower to Progesterone (591) vs Placebo (588). Glasgow Outcome Score (GOS) at 6 months (moderate disability & Good outcome) was similar in both 50.4% vs 50.5% .





PROTECT 111 in NEJM Dec 25th 2014. A multi center trial across Trauma centers in USA from 4/10 - 10/13.The trial was stopped early after 882 Pt's were recruited due to futility. Good outcome was seen in 51% of Progesterone grp vs 55.5% in Placebo group.





Sorry Progesterone...

Raised ICP is another mechanism that leads to worse outcomes.A monitor is needed to monitor it, with EVD being preferred, as along with measuring ICP it can treat it by draining CSF.Theory Being - Avoid raised ICP --> Improve Outcome.





Cooling or Hypothermia as means to treat raised ICP or prevent it from reaching harmful levels & improve outcome, was looked at by the - POLAR (

JAMA 2018; 320(21); pp 2211-2220)

& EUROTHERM 3235

(

NEJM Dec 17th,2015 pp 2403-2412)

trials. No Survival benefit was seen. Side Effects were more in Hypothermia Arm.





Fancy Surgery for TBI? - Decompressive Craniectomy for raised ICP jumps out & there are 2 fancy named studies also:





DECRA trial in NEJM April 21, 2011. A multi center randomized trial involved 155 Pt's in which Bi-frontal Decompressive Craniectomy(73) was compared vs medical treatment(82).Unfavorable outcome was more in DC (Craniectomy) group 70% vs 51%. Mortality was similar in both groups 19% vs 18%.





RESCUEicp Trial in NEJM Sept 22 pp 1119-1130.across multiple centers randomized 408 Pt's with severe refractory ICP despite 2 tier therapies to Decompressive Craniotomy (201) vs Medical treatment (188). Mortality was significantly lower in Craniotomy arm (26.9% vs 48.9%). this however came a the cost of more Pt's surviving in Vegetative state or severe disability.



S

o what Now : No hypothermia for Raised ICP. Treat it Medically (Hypertonic Saline > Mannitol), if still raised Pentobarbital can be used.If Decompressive Surgery is to be offered, the Family needs to understand improved survival comes at a cost of worse Neurologic Outcome. No way of saying who is going to survive with a better Neurologic outcome.







