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Injury to the brain continues to be a unique thing in medicine. These injuries are scary and unfamiliar to many health care providers. There is a finality to them. Their consequences are hidden a little bit; the asystole is easy to figure in the emergency room but the suppression and brain death isn’t something so easily recognized.
They’re what you might imagine, along with polytrauma, as poster child conditions for tertiarization and transfer to a higher level of care.
In truly catastrophic injury to the brain however, I’m not sure that’s a good thing.
My institution has had a small discussion lately on just what ethics and the law requires of us as a place with full neuro specialty coverage.
I’ll make up an example:
A 61 year old man comes into a small community hospital’s emergency room. He was found down at home by his wife and last seen normal four hours previously. He wouldn’t wake up and he was breathing slowly and shallowly. The ambulance crew intubated him. In the emergency room his pupils are large and don’t react to light and he doesn’t do anything when the doctor hurts him. He’s in a very deep coma. If the physician working the emergency room felt comfortable doing a brain death exam, which he doesn’t, the patient might have some very primitive reflexes left but his condition is very serious.
A CT scan of the head is performed and shows a large bleed within the brain.
The bleed was probably caused by high blood pressure. In reality however, the patient’s condition is essentially terminal and the cause of the bleed isn’t important at this point.
The small hospital has an intensive care unit and an open bed. It however has no neurosurgeons, nor indeed even neurologists who round at the hospital. And so the physician in the emergency room starts trying to transfer the patient to a hospital where a neurosurgeon can see the patient.
There are really two issues here. The first is a legal issue concerning a law called EMTALA. EMTALA is a law that dictates transfers for higher care amongst hospitals that accept Medicare (virtually all hospitals). In very broad terms it puts responsibilities and requirements on both the hospital trying to transfer the patient and the hospital that might accept the patient. The former has a responsibility to stabilize a patient. They cannot refuse care in an emergency as a matter of lack of payment or inquire about payment prior to treatment to stabilize. Nor can they transfer a patient after stabilization merely as a matter of lack of ability to pay. The latter has a non-discrimination requirement, that specifically reads,
A participating hospital that has specialized capabilities or facilities (such as burn units, shock-trauma units, neonatal intensive care units, or (with respect to rural areas) regional referral centers as identified by the secretary in regulation) shall
not refuse to accept an appropriate transfer of an individual who requires such specialized capabilities or facilities if the hospital has the capacity to treat the individual.
Case law on the non-discrimination provision is scarce but in catastrophic injury, where no specialized intervention will alter the course of the patient’s condition, I would argue that the patient doesn’t require specialized care. And not merely cases where the patient is brain dead at the time of the transfer request but also in situations where brain death is inevitable or the condition is otherwise not survivable. The patient and family can proceed to comfort measures at any hospital, there is no specialization about such care.
The second issue is an ethical one. Do hospitals with specialized capabilities owe something to patients and families to transfer as a matter of finality and closure. In that we’re saying, “Watch, we did everything we could…”?
While I’m somewhat empathetic to such an argument I have trouble with it. I think it reflects a problem in both the expectations we have of health care as patients and how physicians are trained to deal with end of life. Really it is a shame for physicians to come out of training without basic palliative and communication skills. Even the physician in the small rural emergency room should have such a skill set. The capability to have an end of life discussion with families, even if the medical issue falls somewhat outside their scope of specialty.
I’m also somewhat disappointed in how some referring physicians appear to place priority in getting the patient off their hands over the patient’s well being. I’ve had cases where even after discussion with the consulting physician at an outside hospital and having seen the films and described in no uncertain terms to the other doc that the injury is not survivable that they continue to press for transfer.
I may be wearing blinders here but, and I think much of this is subconscious, I can only draw a single conclusion from such arguing. The continued pressure to accept the patient in transfer, after I’ve explained there is nothing to do for them, is a condemnation of my analysis of the situation. They’re basically calling into question my competency; my faculty’s compentency.
And I’m okay with that in the sense that I’m not going to take offense. What I have trouble with is they’re now trying to transfer their patient to a consultant who they don’t think is competent.
I don’t know how they can have the patient’s best interests in mind and work to transfer them to another physician they’ve basically said they don’t trust.
The issue gets more complex of course and I could continue writing. What if the patient was 6 months old instead of 61 years but the situation, in terms of the finality of the condition, remained the same? How many physicians on the line at the accepting hospital are literally too lazy to accept the transfer and work for any reason not to?
In general however, in an honest physician-to-physician phone call, with terminal conditions, where nothing will be done at the accepting hospital, no matter the patient’s age, I’m not sure transfer is a good thing. It significantly contributes to costs, provides false hope and contributes to our societal expectations at the end of life.
Unfortunately sometimes in neurosurgery when you do a surgery you have to leave the part of the skull you remove to access the brain off. The most common situation is in neurotrauma.
A patient has had an extensive injury and perhaps there scalp has been opened and the underlying skull is exposed to the outside and poses a real infection risk.
Or their skull has been fractured so badly that it can’t cosmetically be put back together very well.
Or they have their skull put back on after surgery but it gets infected and then the infected piece of bone has to be removed and can’t be used again.
In these cases we sometimes use custom made implants which are built by biomedical firms off of a special CT scan. They are pretty amazing and can give great results. They’re also expensive and to be honest I’m not one hundred percent sure how they’re made.
But it comes as no surprise to me that the rise of commercial 3D printing might disrupt the, admittedly small, market for such cranioplasty implants and substantially lower costs.
Now replacing large portions of people’s skulls is not necessarily new. Back in 1997, Science Daily reported on advances in implants that involved using CT and MRI scans to create a model of the skull and then have a special implant manufactured from medical-grade plastic. What’s different about the 3D printed approach is that implants are lower cost and can be customized to specifically fit the patient. Additionally, if the implant doesn’t quite work out, replacements are readily available.
Other implants are coming, I would imagine. It is likely to be pretty impressive technology.
In case you missed it our Secretary of State, Hilary Clinton, has a cerebral venous sinus thrombosis. Such may be a consequence of her mild traumatic brain injury earlier in December. But considering these can be relatively asymptomatic things, especially in older individuals, and that the madame Secretary has a likely procoaguable disposition, considering her history of deep venous thrombosis, it may just be this clot in her right transverse sinus was found incidentally on a follow up brain MRI.
The Heart has a good video on Mrs. Clinton’s condition. An NEJM review article from 2005 can be found here (PDF).
In general these are clots in the large draining veins from the brain. They’re associated with procoaguable states including a strong association with pregnancy; as well as with cancer and trauma and infections of the inner ear amongst other things but in at least 15% and perhaps as many as 30 or 40% of cases no underlying risk factor or etiology is identified. They can lead to raised intracranial pressure by cerebral edema in the areas where blood backs up and by affecting the reabsorption of cerebral spinal fluid. Raised intracranial pressure can have relatively non-specific findings including headache, nausea, the consequences of papilledema. At times they can lead to frank venous inarcts; venous strokes in the brain. These strokes can even be hemorrhagic. his can lead to more devastating consequences. Or they can be asymptomatic.
As with venous clots elsewhere the treatment is generally anticoagulants. And it appears Mrs. Clinton is back on coumadin, although there are other, newer oral anticoagulants that could serve the same treatment. Typically it would be expected for her to continue treatment for at least six months, depending on what repeat imaging and exam shows.
The brain is encased in a closed box – the skull. Anything added to the box can raise the pressure inside of it and, the thought is, damage brain potentially secondary to that raised pressure. In situations where things have been added to the box secondary to trauma – blood or edema – it has long been thought that knowing just how high the pressure was inside the skull, and doing things to lower that pressure, would improve the outcomes in patients who have suffered traumatic brain injuries. It has become essentially standard of care. The Guidelines for the Management of Severe Traumatic Brain Injury give level II credence to,
Intracranial pressure (ICP) should be monitored in all salvageable patients with a severe traumatic brain injury (TBI; Glasgow Coma Scale [GCS] score of 3–8 after re- suscitation) and an abnormal computed tomography (CT) scan. An abnormal CT scan of the head is one that re- veals hematomas, contusions, swelling, herniation, or compressed basal cisterns.
And level III credence to,
ICP monitoring is indicated in patients with severe TBI with a normal CT scan if two or more of the following features are noted at admission: age over 40 years, uni- lateral or bilateral motor posturing, or systolic blood pres- sure (BP) 90 mm Hg.
I would say on their training and anecdotal experience plenty of neurosurgeons, those still involved in trauma and critical care, might give intracranial pressure monitoring even more weight.
Despite this, there is considerable equivocality to the role of intracranial pressure monitoring. While a majority of published retrospective studies have claimed that intracranial pressures above a certain level are associated with a worse outcome and have tried to assign causality to such by claims that controlling pressures below such levels leads to better outcomes, the data, even from these retrospective looks, is hardly homogenous.
There were no group differences in age, gender, or GCS. After adjusting for multiple potential confounding factors including, admission GCS, age, blood pressure, head AIS, and injury severity score (ISS), ICP monitoring was associated with a 45% reduction in survival (OR = 0.55; 95% CI, 0.39-0.76; p < 0.001).
There has never been a randomized trial of intracranial pressure monitoring for traumatic brain injury. At least there hadn’t. An ambitious project led by Dr. Randall Chestnut, based on U.S. money but out of centers in latin America with the ALAS and LABIC, just presented at the Congress of Neurological Surgeons. Patients with severe traumatic head injuries (Glasgow Coma Scale =<8) were randomized into those received intracranial pressure monitors and those note. Those not underwent standard therapies for suspected elevated intracranial pressures based on imaging characteristics and neurological exam; the same therapies directed at those patients who had monitors placed and had documented elevated intracranial pressures. There doesn’t appear to be a short term survival difference between the groups.
It isn’t a knock against the role of elevated intracranial pressure in outcomes following traumatic brain injury. It is, at least a slight knock it would appear, against invasive monitoring. Treating for presumed elevated intracranial pressure based solely off imaging findings and clinical exam appears to be just as efficacious, at least on some metrics, as treating a known intracranial pressure.
Monitoring intracranial pressure, while a common and relatively simple procedure, still requires an invasiveness that is not without risk and morbidities. It entails an incision on the scalp and creating a hole in the skull and then opening the cover around the brain to insert a foreign device into the brain itself. If it is true that the information provided by that device does nothing to improve the management and outcomes of brain injured patients then it is hard to justify such insertion on a routine basis as has become the standard of care. I’m interested to read when the results are finally published.
The New York Times features a piece about the adaptations of the skulls of animals prone to head banging, such as woodpeckers, that help prevent traumatic brain injury.
The brains of most animals that are prone to head banging — these include deer and other antlered mammals, as well as various birds — are relatively small and (unlike a human’s) smooth-surfaced; and they’re bathed in only small amounts of cerebrospinal fluid, leaving little room for the brain to move and be shocked by the sudden decelerations and accelerations of their weaponized heads.
Moreover, both rams and woodpeckers are scrupulous in the precise, single-direction fashion in which they smash their heads into things, whether trees or one another: The aim is such that there’s very little side-to-side torsion exerted on the brain, none of the movement that induces whiplash injury and other kinds of damage.
No where in medicine are the dreams for stem cells bigger than in treatment of diseases of the central nervous system. From neurodegenerative diseases to strokes to traumatic brain and spine injuries considerable work has been done. Specific attention being paid to autologous adult bone marrow stem cells which do not carry the risk of cancer, rejection and are readily available. Previous work has documented their ability to cross the blood brain barrier and to differentiate from BMSCs into microglia and neuralcells. In a recent edition of Neurosurgery a group from the Hokkaido University Graduate School of Medicine presented BMSC use in a rat model of TBI.
Osanai, Toshiya, Satoshi Kuroda, Taku Sugiyama, Masahito Kawabori, Masaki Ito, Hideo Shichinohe, Yuji Kuge, Kiyohiro Houkin, Nagara Tamaki, and Yoshinobu Iwasaki. “Therapeutic Effects of Intra-Arterial Delivery of Bone Marrow Stromal Cells in Traumatic Brain Injury of Rats – In Vivo Cell Tracking Study by Near-Infrared Fluorescence Imaging.” Neurosurgery 70:435-444, 2012.
The group induced “traumatic” lesions in 12 Sprague-Dawley rats by exposing a unilateral sensorimotor area with craniotomy and applying a freezing 7mm cylinder (cooled in liquid nitrogen) to the dura over the area causing an underlying lesion and significant post injury motor dysfunction.
Of the 12 rats 6 were then injected with an extimated 2 x 10^6 bone marrow stem cells in 200 microliters of saline through the ipsilateral internal carotid and 6 were injected similiarly with 200 microliters of saline. The injections occured 7 days post injury. The group derived the BMSC non-autologous bone marrow from the femurs of other Sprague-Dawley rats after death. These were labeled with PKH26 prior to implantation and with fluroscent cell markers for optical imaging.
The outcomes were functional recovery, in vivo optical imaging and histological examination after euthanasia.
Optical imaging showed that in the ipsilateral side to the injury the injected BMSC left the vasculature and began engrafting into the damaged cortex as quickly as 1-3 hours after injection.
After death of the animals histological examination of the brain showed that the PKH26 labeled cells were primarily to be found in the damaged hemisphere and 22% showed NeuN and 18% showed GFAP implying that the BMSC were differentiating into neural elements.
The implanted animals showed statistically better motor improvement at 2 and 3 weeks post implantation.
More importantly than showing functional recovery this paper’s biggest showing is a clinically, real world applicable method of stem cell administration, within a time frame that would be reasonable for clinicians and patient’s suffering traumatic brain injury.
Don’t get me wrong, cerebrally I know that the data supports its use whole heartedly. These are, typically, patients whom Plavix has helped save from further heart or brain attacks. The risk they face from such far outweighs the risk of an intracranial bleed. That said, it is hard to put aside what I see everyday; that is trauma patients with large bleeds associated with antiplatelet or anticoagulant use.
The drug is set to lose its patent protection on Thursday. Faced with an expected influx of cheaper generic alternatives, Bristol-Myers Squibb, which sells Plavix in the United States under a partnership with Sanofi-Aventis, has said it no longer plans to actively promote the drug.
“This is one of the behemoth drugs that really defined the drug industry in the ’90s,” said Catherine J. Arnold, an analyst for Credit Suisse.
Senator Mark Kirk is the junior Senator from Illinois. He currently holds President Obama’s old seat which he won in a special election in 2010 to replace Roland Burris.
He has apparently suffered a large right sided, non-dominant hemisphere middle cerebral artery stroke, potentially after a carotid artery dissection on that side. And he’s now undergone a decompressive craniectomy on the right from the late edema suffered with such a large stroke.
Dr. Fessler said the stroke “will affect his ability to move his left arm, possibly his left leg and possibly will involve some facial paralysis. Fortunately, the stroke was not on the left side of his brain, in which case it would affect his ability to speak, understand and think.”
Chances for a full mental recovery were “good” but chances for a full physical recovery were “not great,” Fessler said.
The doctor said he was hopeful that, after rehabilitation at an acute care facility, Kirk would regain the use of his left leg, but said prospects for regaining the full use of his left arm were “very difficult.”
He said recovery is a matter of weeks or months — “it’s not going to be days.” Kirk’s relative youth and good physical shape are positives, Fessler said, and he expects Kirk could return to “a very vibrant life.”
I’m sure they’ve been aggressive considering his age and functional status, not to mention his stature. But to feel the need to go ahead with a craniectomy following a stroke implies a large area of ischemia. Decompressive craniectomy for large middle cerebral artery strokes is not terribly uncommon and the popularity for it has probably grown over the decades. As one, admittedly international paper, describes it.
Decompressive craniotomy in the setting of acute brain swelling from massive MCA infarct is a life saving procedure. It should be considered in patients with initial good GCS, who are deteriorating in neurological status. With the team effort of neurologist and neurosurgeons these cases have good outcome contrary to the natural history of disease…Thus an ideal candidate for decompressive craniotomy is the victim who is young, with no risk factors, who presents early and has nondominant, middle cerebral artery territory infarct, with a reasonable Glasgow Coma Scale with no (or) early signs of herniation. The key for success of these cases of large MCA infarcts is early detection. Clinicians should concentrate on formulating newer clinical, radiological and technical protocols to detect the suitable patients at an early stage.
Certainly from what we know Senator Kirk appears to be an ideal candidate. From the description of his possible long term deficits he appears to have had a large non-dominant hemisphere middle cerebral artery stroke. He is relatively young and fit. And, as The Chicago Tribune describes it, he presented with a relatively good exam and deteriorated quickly.
My thoughts and prayers are with him and his family. He has a long road ahead of him.
The Corticosteroid Randomization After Significant Head injury (CRASH) trail was a huge international double blinded randomized trial which collected a huge cohort of patients suffering traumatic brain injuries with GCS less than 14 on presentation and presenting within 8 hours of injury and randomizing them to receiving a 48 hour course of methylprednisolone versus a placebo. The final results were published in The Lancet in 2005.
As if that was not enough the database collected for the study was the largest, most complete database of patients following head injury in the world. It included more than 10,000 patients from across the world and had a very high rate of follow up through 6 months. This database was used to create a prognostic model for outcome following head injury. Published in the British Medical Journal in 2008 the CRASH model has become one of more widely cited outcome prediction models in clinical practice when dealing with patients with head injury.
MRC CRASH Trial Contributors. “Predicting Outcome after Traumatic Brain Injury: Practical Prognostic Models Based on Large Cohort of International Patients.” Bmj 336.7641 (2008): 425-29
The original paper is available for free as full text on the BMJ website.
This was a retrospective review of outcome of a large cohort of patients.
The database included 10,008 patients originally collected for the CRASH Trial. The database contained information on a large number of variables but the prognostic model focused on 9 initial variables: age, sex, etiology of the trauma, time on presentation, GCS on presentation, pupil reactivity on presentation, results of CT scan, whether the patient had a major extracranial injury, level of per capita income in the country where the injury occured.
They prognosed to two outcomes death within 14 days of injury or outcome at 6 months as measured by the Glasgow Outcome Score which they dicotomized into favorable outcomes (moderate disability or good recovery) and unfavorable outcomes (dead, vegetative state or severe disability).
They developed two models with the above variables: a basic model which excluded the findings on CT imaging and a CT model which included them.
Internally they validated the two models using bootstrap resampling. And then they externally validated the model using the 8000+ patients suffering head injury included in the independent International Mission for Prognosis And Clinical Trial (IMPACT) database. The original description of the IMPACT Trial is here on PubMed.
All nine of the variables included in the final two models independently had strong associations with both outcomes (death at 14 days and poor outcome at 6 months). The table showing the odds ratios for each variable can be found here.
Regression of outcome of model including CT scan findings
After this internal validation they compared their model to outcomes observed in the IMPACT Trial blinded.
CRASH model predictions of outcomes for patients enrolled in IMPACT versus variable outcome
It showed good discrimination in the external validation with a C-score of 0.77 (essentially the area under the reciever operator curve). And for the basic model and the CT model in high income countries there was very good calibration by the Hosmer-Lemeshow test.
The authors have published a calculator with predictive outcomes based on the regression. The calculator gives odds for death at 14 days and poor outcomes at 6 months based on both models.
The sample size of this study is legitimate and one of the stronger points of it. The database appears well maintained and exceptionaly complete considering the number of patients and the challenges of coordinating data collection across continents. Looking at the demographics it appears relatively representative. As well the follow up to 6 months is a legitimate end point for the goals of the study and the sample included a great number of patients to that end point.
The outcomes measured to seem clinically relevant and were set prior to the models being designed. The variables included in the regressions as well have previously been validated at predicting outcomes in other smaller studies and are clinically readily available.
The study found no difference in outcomes based on treatment, including the randomization to steroids or placebo in the trial itself, which is an important consideration.
It is true the CT model in particular showed comparatively poor calibration for patients injured in lower income countries. Even there however the Hosmer-Lemeshow measure isn’t particularly off. The smaller sample size of patients with readily available CT imaging findings may in part explain such.
The major critiques otherwise of the study seem to be those available to be leveled at all published prognostic models. Generalization is a difficult thing especially to individual anecdotal scenarios. However for a study with in vivo data from patients seemingly encountered early following representative head injury and undergoing real world salvage attempts the model shows remarkable, if not perfect, calibration and discrimination.
The models developed from the CRASH trial are very likely the “best” available prognostic models for predicting outcome early after traumatic head injury. The calculator published by the authors appears a valid and useful tool for any health care provider encountering significant neurotrauma. A “better” prognostic model for the prediction of outcome early after head injury seems unlikely.
A traumatic subdural with a pretty good shift deteriorates on his transfer from some rural area, gets to your hospital as a GCS of 7 and needs to go to the operating room emergently. His next of kin rode on the transport to your hospital. Other family members are en route by car but are some distance out.
You try to consent his next of kin using phrases like ‘emergency,’ ‘right now,’ ‘life and death’. The response is a lot of waffling, a request to wait until the rest of the family gets to the hospital, and calls to those same family members seeking advice.
I seem to have run into the above, or the equivalent, several times over my still young intern year. Not every night or every week, but a few times. Too many times.
I understand such situations are incredibly stressful for those presented with a decision for an emergent procedure (or not) for a loved one. I understand a lot of information is presented to them in a short period and they’re asked to digest it under stress and make one of the most important decisions of their lives.
I’m not sure it excuses trying to skirt the responsibility.
The most frustrating instances involve those legally responsible asking you as the provider to seek the opinion of other family members and to have them decide.
“Oh, I just don’t know! Can you call his sister and have her decide?”
“I’m happy to talk to her and anyone else in the family, but this is something I really need consent from you for.”
Admittedly it could be me. I don’t think so however. I think I present the situation generally with the proper sense of urgency and yet lay out the decision to be made and the options and the consequences of each option in a pretty down to earth and understandable way. The few times I’ve run into this, others – my residents, fellows, faculty – who have come along to talk to the family after me have had the same problem.
True, maybe as the first to attempt consent I’ve spoiled the whole pot for all who follow. More likely the commitment and responsibility owed to a loved one breaks down under the spotlight of the situation for some.
Decisions under time pressure, with limited information, with a loved one at stake are incredibly difficult and I try to check my frustration. However, a sense of responsibility is just sometimes lacking from those asked to choose to either put the pen to the consent form or to refuse to put the pen to the consent form.