Sabina Beata Paradi
April 19, 1983 – June 30, 2007
Autonomic Storms
Autonomic Storms:  Treatment and Information in Brief (Table of contents follows)                

Author:  Bodo Parady, PhD, Children's Hospital Oakland Research Institute  Oakland, CA

Autonomic Storms can be the product of traumatic brain injury(TBI), spinal cord injury(SCI), or sepsis.  There is an association of storming with diffuse axonal injury (DAI). 

In treating TBI or autonomic storming, consider the following treatment objectives ( references found in body text below ):

  1. Minimize sedation (eg. opioids and propofol) and taper sedation to avoid autonomic instability. (Acute, post Acute, Chronic)  Extended use of opioids (and likely all sedation) is associated with the development of DAI, excessive ICU seizures, and sepsis.  On autopsy, DAI was associated with excessive opioid use in victims with no history of TBI (Neiss, et al. 2002).  Over one third of all seizures in ICU are directly attributable to rapid withdrawal of opioids [ PubMed 8492924 ], and should be considered as a cause of autonomic storms. Consider avoiding sedation and avoiding treatment modalities that require extended sedation, such as placement on a ventilator, and extended waiting for MRI or CAT which require a sedated patient.  Sedation can be associated with sepsis and leaky gut in TBI & SCI patients.  Withdrawal of sedatives from either addiction or extended treatment can induce autonomic storming from sepsis or leaky gut without prior brain injury.  Most opioids are linked to immunosuppression (see #3 below) attacking the hypothalamus–pituitary–adrenal axis and natural killer cell activity, so consider the use of buprenorphine instead of standard of care opioids (Franchi, et al, 2006).
  2. Manage the intestinal sequelae.  (Acute) Because of the profound immunosuppression associated with moderate to severe TBI and SCI, anticipate intestinal sepsis or leakage in the gut and manage it with Miralax or other orally (or nasogastric) administered high molecular weight PEG (polyelthylene glycol).  PEG is commonly used in laxatives and skin care products and is safe and nonimmunogenic. Recent research in rats and mice with experimental sepsis found that both high and low molecular weight PEG administered orally improved survival [ Pubmed 20009757 ].   There appears to be some risk in low molecular weight PEG [ Biondi et al, 2002 ], while high molecular weight PEG appears to have little risk.
  3. Assume the patient is septic and apply hemodiafiltration.  Given that the patient has a fever of unknown origin (storming usually presents with fever) and that TBI is profoundly immunosuppressive, the assumption that the patient is septic, while prospective, is reasonable.  Acting on the prospect of sepsis will do no harm and may spare the patient the complications of systemic nosocomial infection. Continuous venovenous hemodiafiltration has been used to treat the critically ill septic patients.  One study applyed hemoperfusion with a polymyxin B-immobilized fiber as a treatment, followed by continuous venovenous hemodiafiltration with a polymethylmethacrylate membrane (Sakamoto, etl al, 2010 DOI: 10.4103/0972-5229.76080 ).   Hemofiltration is indicated when high levels of lactate are observed, a marker for sepsis, and it is precisely high levels of lactic acid that are observed within hours following severe to moderate TBI (George Brooks, 2010, UC Berkeley, private communication).  For the brain injured patient, it is critical to maintain continuous veno-venous hemofiltration and not employ intermittent hemodialysis which is associated with cerebral edema In PMID: 10440514 .
  4. Consider maintaining the patient's core temperature at 35º C (Acute) using feedback cooling (e.g. the ArcticSun).  TBI or storming patients have poorer outcomes with either higher or lower core temperatures.  Excursions to higher temperatures can cause storming, brain damage, organ damage, and treatment emergencies.  A rapid rise in temperature usually precedes a storm.  Returning elevated temperature to normal immediately may halt a storm from running its course, will improve patient comfort, and may reduce tissue damage.
  5. Manage immunosuppression.  (Acute)  Immunosuppression for medium to severe TBI is profound, and aggravated by surgery, trauma, and opioids. Severe TBI and extensive surgery such as a hemicraniectomy are associated with profound immunosuppression.  Expect the patient to manifest bizarre infections such as intestinal fungal infections, eg. zygomycosis, in addition to more common MRSA, and other hospital borne resistant infections.  Expect fungal/yeast infections of the gut if bacterial antibiotics have been administered.  Because of the ICU setting for TBI patients, expect carbapenem resistance, and both bacterial and fungal biofilms, both of which are nearly impossible to treat with antibiotics (they may require surgery or debridement).  Any severe TBI patient that presents with a fever needs a full bacteriological and mycological workup using QPCR.  In female patients, expect flareups of Candida spp. infections.  In New York City hospitals, there is a published history of antibiotic resistant acinetobacter infections afflicting ICU patients.  Acinetobacter is symbiotic with Candida biofilms, which are associated with central lines and IVs, that are at the root of systemic infection. Resistant systemic infections could leave your patient in a coma irrespective of primary brain injury.  To understand the interrelationship between storming's autonomic sympathetic instability and an unstable immune system,  I recommend reading the paper by Nance & Sanders, 2007 at Pubmed.
  6. Consider TPN (Total parenteral nutrition)  (Acute)  TPN may be the simplest and safest measure to bring about a superior outcome.  Care must be exercised to prevent systemic infection.
  7. Consider a ketogenic diet.  (Acute) A recent 2011 publication by Nam, et al in Epilepsia discussed administering a ketogenic diet to control the seizures of status epilepticus for four patients.
  8. Control sepsis or leaky gut.  (Acute)  TBI or SCI can cause bacteria to leak from the gut releasing endotoxins which in turn can induce additional brain or spinal damage.  This loop between the brain and gut could set up a vicious cycle.  High levels of lactate can indicate the onset of complications. This is an oft overlooked cause of autonomic storms, and can be related to opioid or sedation withdrawal. Any sign of abdominal distress may warrant intestinal sterilization and conversion to TPN.  Sepsis can lead to MODS ( multiple organ disfunction syndrome) which can be a complication of TBI or SCI.
  9. Consider cerebrospinal fluid drainage, ventricular shunts, or laparotomy to reduce intra cerebral pressure (ICP).  (Emergency)  These methods are clinically successful and If the patient is responsive to ICP reduction, focus treatment on reducing ICP.  If the patient is not responsive to any reduction in ICP, focus treatment on increasing cerebral perfusion pressure, avoiding osmolar therapies that can open the blood brain barrier (e.g. mannitol), as those treatments will tend to open the intestinal barrier.  Consider that a cause of diffuse axonal injury (DAI), or widespread white matter destruction, is the invasion of endotoxins from the gut [ Pubmed id 12438674 ] through a disturbed blood brain barrier.
  10. Apomorhine Pump:  (Long term TBI recovery)  Apomorphine (apomorphine is not an opioid) is a parasympathetic stimulant and dopamine agonist.  It is being used in Parkinson's disease and for stimulation of deeply comatose patients [Int Brain Injury Assoc.].  Apomorphine more importantly targets the dopamine receptors in the hypothalamus, the control center for autonomic storming.  It counteracts the sympathetic nervous system.  Given the recent success with long term comatose TBI patients, it must be administered continuously which is why the patch form should be considered for long periods, such as months to a year.  Giving apomorphine intermittently has been a failure, and only a pump, patch or IV drip should be considered.
  11. And lastly (drugs are low on my list, but uncontrolled seizures are an emergency) look to the following reviews for the standard of care medications and doses used to control seizures in the ICU:

          Varelas & Spanaki (2006) Managment of Seizure in the Critically Ill

          Mirski & Varelas (2008) Seizures and Status Epilepticus in the Critically Ill

          Shorvan & Ferlisi (2011) The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol

"In two recent survey studies from England that analyzed outcome data for patients after a severe traumatic head injury, there was no improvement in outcome from the mid-1990s onward—for the next 10 years—despite an improved general intensive care. During the same period, outcome markedly improved for other types of trauma patients."  Journal of Trauma, 2009:  Grande & Reinstrup, "Do Conventional Treatments of Severe Traumatic Head Injury Worsen Outcome?

(For general issues associated with health care and brain injury, visit Sabina's Healthcare Page )

Table of Contents (click on term to jump to section)


What is an Autonomic Storm?

Causes (Etiology) of Autonomic Storms

Family Education for Autonomic Storms

Current Treatment of Autonomic Storms

Basic Treatment of Autonomic Storms

Drug Therapies for Autonomic Storms

Temperature Management and Control with Cooling Blankets and Jackets

Nursing Inconstancy


Caregiver Support


Cases with Minimal Outcomes

The Future

Future Drug Therapies

Future Nutritional Support

Future Mechanical Support

Protocol Recommendations

References and Links


I attended Sabina as her father during her hospitalization for traumatic brain injury.  The experience of dealing with the medical system, doctors, hospital staffs, attorneys, family, friends, and press was overwhelming.  Given my experience in the management of Sabina's care at the end of her life, there are many things that must be taught to others..  As a result, I offer my collected experience, research, and understanding of autonomic storms for others.  See Sabina's Healthcare page  for background on her hospital care and what has been learned.  Much of the information relating to treatment for TBI may be relevant to patients suffering stroke, brain surgery complication, or brain aneurysm.

 What is an Autonomic Storm?

An autonomic storm is the massive increase in sympathetic nervous activity that might simply be called a hyper-stress response due to an insult to the brain or brainstem (non-professionals, click here to view the brain structure).  Storms often onset days or weeks after traumatic brain injury and decrease over time.  Typically long delay in onset is due to an increase in intracranial pressure, and in her case may have been associated with hydrocephalus [1].  One of the most common complications of severe TBI is autonomic storms often referred to as dysautonomia

The dangers of autonomic storms are the high fevers that can cause additional brain damage, and high blood pressure and heart rate that can cause fatal heart attacks, and cardiac and organ damage.  It is this recurring damage that can make autonomic storms degenerative, leading often to poor outcomes.  Critical to treatment is breaking this cycle of storm trigger, storm onset, fever pushing storms deeper and longer.   What appear as tiny changes in vital signs presage the onset of storms that should spur instant and strong nursing intervention.  Any laxity by any member of the nursing team can produce irreversible neurological damage.

Autonomic storms may be "Serotonin Syndrome" [ Boyer & Shannon, New England Journal of Medicine 2005] in that manifestations can overlap. Serotonin Syndrome results "from therapeutic drug use, intentional self-poisoning, or inadvertent interactions between drugs".  Serotonin syndrome is often missed because diverse symptoms such as tremor, diarrhea, and hypertension are not associated with drug  administration or withdrawal.  Serotonin Syndrome is iatrogenic in almost all cases.

One oddity is that the term "autonomic storm" arose in the 50s to describe the conditions of REM sleep [click here].  The quote is:  "When REM kicks in the [...] blood flow to the brain increases, breathing and heartbeats become irregular, the hands and face start to twitch and voluntary muscle controls are lost."   For a more comprehensive review on sleep storms  click here .  Given that autonomic storms can be circadian in injured patients, one is tempted to think that storms could be linked to the body's attempt to resume normal brain and sleep activity.  Another oddity, is that astronauts in weightless conditions suffer “autonomic storms” where perhaps because the brain is receiving confusing signals is reacting with strong fight or flight response [click here].  There is a more bizarre possibility and that is presence of intense cosmic penetrating radiation; this would be linked to the evidence of the bright flashes seen by early astronauts – go to NASA report .  This does in fact make sense since storms can be linked to what is called diffuse axonal injury where there is a little damage all over the brain, and since the brain is considered to be the organ most sensitive to radiation.

Sabina suffered severe traumatic brain injury when being struck by the truck when crossing the street in Manhattan.  She was unconscious when struck.  She suffered no other injury.  To relieve pressure on the brain, she underwent a decompressive craniectomy, an operation to remove part of her skull.  Autonomic storms may appear soon after injury, or may be delayed.  In Sabina's case, the incidence and severity of storms was delayed about one month from injury. 

Storms are not to be confused with dystonia which the autonomic stretching of extremities, often called posturing, and is a long term effect of TBI.  The symptoms are often the similar to those for tetanus, with fever, posturing, etc. suggesting that the site of disturbance is similar.  Autonomic storms are also called:

  • paroxysmal sympathetic hyperactivity
  • episodic hypersympathetic state
  • paroxysmal sympathetic storms (PSS)
  • diencephalic seizures
  • midbrain dysregulatory syndrome
  • brainstem attacks
  • autonomic dysfunction syndrome
  • fever of central origin
  • central fever
  • neurostorming
  • acute midbrain syndrome
  • hypothalamic-midbrain dysregulation syndrome
  • hyperpyrexia associated with sustained muscle contractions
  • sympathetic storms
  • acute hypothalamic instability
  • paroxysmal autonomic instability with dystonia (PAID)

I con 






No structural causes have been identified with autonomic storms.  What is known, is that storms are due to suppression of the sympathetic nervous system.  The symptoms of storms are well known and include [2]: 

  • fever (pyrexia)
  • sweating (diaphoresis or hyperhidrosis, leave it to the profession to have two obscure words  mean the same thing)
  • rapid heartbeat (tachycardia)
  • high blood pressure (hypertension)
  • rapid breathing (tachypnea)
  • dystonia and posturing

Key to storming is the rapid onset, rapid rise in many of the vital signs, and cascading of symptoms to extreme levels.  They further point out that these events are often confused with epileptic seizures, which can be caused by hydrocephaly, infection, or pulmonary embolism.

The only treatment that they suggest for storms is pain relief, and temperature management.  It is important to recognize triggering events of storms and dehydration.

According to the Primer on the Autonomic Nervous System [David Robertson, I. Biaggioni,  G. Burnstock, P.A. Low, Academic Press], autonomic storms can be caused by encephalitic infection.  This is certainly possible in Sabina's case due her infection due to drug resistant acinetobacter in the first weeks of her hospital stay.  This may have been due to poor operating room sanitation, among other causes.  A research report  [3] reflecting common medical knowledge states that the origin of autonomic storms is basically not understood.

Probably the most ironic aspect is that autonomic storms increase the need for higher levels of nutrition due to the energy loss during the storms and fevers.  Management of nutrition for those suffering TBI was one of Sabina's dietary management activities at Morgan-Stanley Children's Hospital, her last assignment as Nutrition fellow..

 Causes (Etiology) of Autonomic Storms

The conventional causes of autonomic storms are listed by Rabinstein in 2008 [ PubMed 18334137 ]:

  • Neuroleptic malignant syndrome
  • Malignant hyperthermia
  • Lethal catatonia
  • Cushing response
  • Spinal cord injury
  • Encephalitis
  • Seizures
  • Hydrocephalus ( Related directly to Cerebral Hypertension, or increased Intracerebral pressure )

Rabinstein et al [4] list the causes of autonomic storms resulting from severe head injury:

  • Diffuse axonal injury, basically diffuse concussion,  may be seen in children as "shaken baby syndrome"
  • Post resuscitation encephalopathy due to an anoxic-ischemic insult, this corresponds to drowning or asphyxiation
  • Intracerebral hemorrhage
  • brain or brainstem tumors
  • hydrocephalus  

Severe brain injury can result in huge releases of catecholamines (neurotransmitters that include adrenaline, basically a stress response).  These catecholamines can produce seizures, fluid in the lungs, and cardiac stress injury.  The storms usually diminish shortly after injury, though some, like Sabina can develop storms in the later phases of recovery.

Hypothesis for the Origin of Autonomic Storms

Contrary to conventional medical rubric, this author offers the following iatrogenic causes for autonomic storming:

  • Precipitate Sedation withdrawal
    1. Propofol
    2. Benzodiazipine
    3. Opiate
    4. Barbiturate
  • Normal addictive drug withdrawal such as when weaning off a ventilator
    1. Benzodiazipine
    2. Opiate
  • Severe immunosuppression resulting from primary traumatic injury, and additional immunosuppression resulting from neurosurgery used to manage ICP or CPP which can result in:
  1. Opportunistic fungal infection
  2. Resistant hospital borne bacterial infections
  3. Sepsis
  4. Multi-compartment syndrome
  • Secondary intestinal infection related to injury and sedation withdrawal
    1. Endotoxin release
    2. D-Lactate acidosis
    3. Leaky gut
  • Secondary pneumonia related to precipitate sedation withdrawal

Why is this list contrary to conventional rubric?  One can only guess, but first on the list I will put:  “No one was looking for it”; And second:  Application and use of sedation is so ingrained in standard surgical and medical practice that its side effects are viewed as a component of the ailment being treated.  The latin phrase post hoc ergo, propter hoc comes to mind, which means essentially, “because it is, therefore it is”.  It is the improper association of two time related events to mistakenly infer causality.

What are the reasons for emphasizing sedative withdrawal?  Sedative withdrawal is linked directly to profound immunosuppression.  This immunosuppression has two primary targets:  The gut with its normal bacterial ecology, and the lung which is sensitized in ventilated patients.  One manifest irony is that sedatives are often given to manage ventilated patients.  Ventilator patients when they are weaned off ventilation need to have carefully managed dosage reduction of sedation.

Procedures administered to TBI patients should be considered as to avoid the need for sedation.  As an example, if cerebral perfusion pressure can be managed with the less invasive protocols such as the Lund protocol or laparotomy or lumbar drainage, they should be tried before hemicraniectomy which will require massive and extended sedation.  Remember also that sedation will be required to replace the bone flap at a later time which in a compromised patient is excessive risk.

The conventional causes of autonomic storms are listed by Rabinstein in 2008 [ PubMed 18334137 ]:

  • Neuroleptic malignant syndrome
  • Malignant hyperthermia
  • Lethal catatonia
  • Cushing response
  • Spinal cord injury
  • Encephalitis
  • Seizures
  • Hydrocephalus ( Related directly to Cerebral Hypertension, or increased Intracerebral pressure )

According to the Primer on the Autonomic Nervous System [David Robertson, I. Biaggioni,  G. Burnstock, P.A. Low, Academic Press], autonomic storms can be caused by encephalitic infection. 

Rabinstein et al [4] list the causes of autonomic storms resulting from severe head injury:

  • Diffuse axonal injury, basically diffuse concussion,  may be seen in children as "shaken baby syndrome".  I differ from the view DAI is directly associated with trauma.  Autopsy evidence shows that DAI is directly associated with excessive use of opioids.  This leads to the conclusion that sedation for the ventilator and sedation for surgery can be causes.
  • Post resuscitation encephalopathy due to an anoxic-ischemic insult, this corresponds to drowning or asphyxiation
  • Intracerebral hemorrhage
  • Brain or brainstem tumors
  • Hydrocephalus  

Severe brain injury can result in huge releases of catecholamines (neurotransmitters that include adrenaline, basically a stress response).  They are chemical relatives of poison oak/poison ivy.  These catecholamines can produce seizures, fluid in the lungs, and cardiac stress injury.  The storms usually diminish shortly after injury, though some, like Sabina can develop storms in the later phases of recovery which in her case points strongly at a role for sedation.

Detailed Patient History for the Origin of Autonomic Storms

When I observed Sabina in the formation of her storms, one of the indicators of storm onset was hyperperistalsis which would then evolve into all the other symptoms including the rise in temperature.  That observation led me to conclude that the doctors and nurses were missing something essential in the development of storms and the recovery from brain injury.

This is certainly possible in Sabina's case due her infection due to drug resistant acinetobacter in the first weeks of her hospital stay.  This may have been due to poor operating room sanitation, among other causes.  A research report  [3] reflecting common medical knowledge states that the origin of autonomic storms is basically not understood.

Let’s review Sabina’s timelines for storming and timeline of her stay in intensive care.

·       Days -7 to 0:  Sabina had contracted a hospital borne infection due to her role as clinical dietician, and was taking a Z-Pak that included powerful antibiotics.  She was ill with infection the day of her injury.

·       Day 1:  Injury and surgery for hemicraniectomy to remove a bone flap to reduce Intracerebral pressure.  Begin sedation with propofol.

·       Day 2:  Sabina was observed under heavy sedation with a very large bottle of propofol hanging by her bed.

·       Day 3:  Sedation with propofol stopped.

·       Day 4:  Observation of fever

·       Day 5:  Sabina set up for MRI, sedated with propofol in preparation.  MRI unavailable, search for source of fever begun,

·       Day 6 and 7, propofol continued, MRI still broken

·       Day 9:  Source of fever believed to be acinetobacter pneumonia, resistant strain

·       Day 10:  Ventilator unit replaced because it was thought that it was the source of pneumonia

·       Interim:  Constant search for infective agents since Sabina seemed to have fevers and infection of unknown origin

·       Interim:  Sabina was in coma and likely under sedation of one form or another

·      Day 20:  Sabina manifest limb stiffness and posturing.  This could be attributed to Serotonin Syndrome [ see above ]

·       Day 33:  Sabina regains consciousness (perhaps sedation was being lifted?) to be able to control her hands and legs under command

·       Evening day 33:  Sabina suffers raging storm, fever reaches 108 degrees

·       Day 36:  Sabina given fentanyl patches to control storming


Let’s compare this timeline to this fatality due to uncontrolled autonomic storming related to a fatality associated withdrawal from opiates, and that is Henry Granju, where uncontrollable storming began approximately one month after cessation of a heroin drug habit (  What is noteworthy is the onset of storming about one month after cessation of opiates in Henry’s case and propofol in Sabina’s case.  What makes it the more noteworthy in Sabina’s case is the late onset, suggesting less association of the storms with TBI, and the constant struggle with her immunosuppressed condition that started before her head injury. 

The likely role of leaky gut related to the development of storms and secondary brain injury stands out because of the role of immunosuppression, and the known neurotoxic effects of bacterial endotoxins and D-Lactate.  There are two models evolving in the research community that autonomic storms may be associated with breakdown of the upper intestinal barrier admitting both bacterial endotoxins or bacterial D-Lactate into the circulatory system. 

Sepsis, Gram Negative Bacteria:  Endotoxins/Lipopolysaccharides and D-Lactate Acidosis

Sepsis is associated with breakdown of the gut a common effect of moderate to severe TBI, causing toxins to be transported into the patient's circulatory system.  I recommend the prophylactic feeding of PEG 15/20. 

Endotoxins are generally lipopolysaccharides produced by gram-negative bacteria found in the normal gut.  Lipopolysaccharides are a chemical combination of lipids (fats) and carbohydrates, and elicit a strong immune response.  Endotoxins are at the core this author’s model for the cause of autonomic storms.  Endotoxins are released into the body because severe injury can cause the intestinal barrier (and blood brain barrier) to open, and sedatives/opiods given for severe pain can open the intestinal barrier when withdrawn.  The resulting intestinal barrier opening, “leaky gut”, then under increased intestinal pressure makes glucose rich serum available to gut bacteria.  This additional two way traffic between the blood and bacteria increases bacterial growth, endotoxin release, and D-Lactate production.  The D-Lactate production can produce D-Lactate acidosis which can induce widespread organ damage.

The recent paper PMID 20071615 indicates that endotoxins sensitize patients to hypoxia and brain damage.  Their work with newborns lambs indicated  endotoxins impaired cerebral perfusion by inducing severe vasoconstriction and endothelial dysfunction.  They found that of the lambs that survived endotoxin exposure, they needed to maintain adequate cerebral oxygen perfusion.  A lesson that should translate to the clinic.

D-Lactate is a neurotoxic [ DOI: 10.1152/ajpendo.00063.2007 ] produced by bacteria in the colon and small intestine.  Anaerobic, gram-negative rod shaped bacteria, including Lactobacilli consume unabsorbed carbohydrates, especially glucose, to produce D-Lactate.  If D-Lactate is produced to excess as the result of various intestinal disorders that impair absorption of carbohydrates, this excess results in D-Lactic acidosis.  D-lactic acidosis is associated with coma, ataxia, encephalopathy, and CNS impairment.

There is direct evidence [ PMID 2920883 ]of mucosal lesions in the upper GI tract after severe TBI that has the same appearance as sepsis, surgery, or other stress.  They found that mucosal injury occurred often without any evidence of bleeding.  Typically this stress gastritis occurs about 12 hours after severe TBI.  This stress gastritis can induce the uptake of endotoxins (the blood-brain barrier is physically similar to the mucosal lining of the upper GI).


Watching Sabina’s episodes also saw rapidly rising heartbeat with skipped beats and the like.  From this, one might infer that the cause of storming in brain injured patients may not be due to issues associated with the mid or lower brain, but may be due to a lack of orderly communication from the cortex.  Extending this, storming might be an extreme form of epilepsy that includes temperature disregulation.

Sabina may have suffered from diffuse axonal injury or its effects such as hydrocephalus which resulted from increased intracranial pressures.  Such injury does not show up in CT or normal MRI, but might be detectable by small bleeds using advanced MRI.  Newer imaging studies such as Diffusion Tensor Imaging can illuminate the extent of damage that other methods cannot.  The problem with diffuse axonal injury is that it is due to secondary floods of catecholamines and has a delayed onset, meaning that the patient's condition can deteriorate later in recovery.  In some ways this is a grab bag, but may have origins in the secondary effects of uncontrolled storming.  Key treatment is controlling intracranial pressure and containing hydrocephalus.

Rabenstein et al. have a discussion of direct physical mechanisms causing storms that is worth reading, but since this is still an academic research topic with no definitive conclusions, there is little to be gained from discussing these mechanisms here.  


Benzodiazepines:  One very confounding aspect is that the treatment of those in ICUs for TBI includes long term sedation with benzodiazepines.  Withdrawal symptoms from benzodiazepines are exactly that which storms exhibit:  tremors, hyperthermia, diaphoresis, hypertension, tachycardia, and seizure” [ click here and click here ]. The first reference makes note of the same set of symptoms as autonomic storming, “Also, unlike previous reports, our patient experienced other classic symptoms, such as abrupt agitation, tremors, tachycardia, tachypnea, and hyperpyrexia.”, which was seen in a case of propofol withdrawal.  At the time, I questioned whether Sabina was suffering from withdrawal symptoms; no one would answer me. 


Morphine/Opioids:  A significant cause of hyperthermia/fevers and storming?  The PubMed article 17584116  states “The drugs of abuse results in profound hyperthermia and widespread alterations in neurochemical metabolism in the central nervous system (CNS). […] Work done in our laboratory suggest that hyperthermia caused by these drugs is responsible for BBB disruption and neurodegeneration. This hypothesis is further supported by our observation that pretreatment with a potent antioxidant compound H-290/51 attenuates the BBB disruption and induces marked neuroprotection following morphine induced withdrawal and methamphetamine induced neurotoxicity.“   There are a number of anecdotes pointing to the fevers and storming resulting from opiate/opioid withdrawal, not the least of which is the death of a 17 year old boy who succumbed to uncontrolled storming and death following the withdrawal from addiction [ Henry Granju's Long Night ].

Anyone making any treatment decisions needs to bear in mind the causation, and not just the patient's manifestation.  Recovery paths and expectations might be far different from what grouped statistics might point to.

 Family Education for Autonomic Storms

The Journal of Neuroscience Nursing [click here] offers the following statement on the topic of family education on storming which is worth repeating here:

"The family is dealing with many unknowns at this time, leading to an array of emotions. The injury, hospitalization, equipment, ICU setting, and separation all play a part in their anxiety, frustration, and fears. These variables, and many more, make this time stressful. The onset of storming with its characteristic presentation of distress can signal problems to the family. Family education is an important aspect of the management of the TBI individual, especially in the individual enduring storming. This education should be geared toward reviewing the etiology of the storming, the treatment plan, and goals; clarifying that the storming may not necessarily require ICU care; clarifying potential duration of sympathetic dysfunction; and most importantly, identifying how they can help. The family can be useful in identifying triggers or treating an episode."

Without appropriate family care and education, all will be lost as family support can collapse.  The patient can be lost due to lack of will and hysteria by family members.  Storms are frightening, appear quite painful, and severe ones can diminish permanent capability.  Family members can literally freak out and become quite disturbed.  Signs of this need to be dealt with.  Appropriate time with an expert physician  is needed to lay out prognoses, and what can be expected.  Family spiritual and psychological care needs to be systematized, and scheduled.

The following observation is offered without attribution.  "Every individual and family circumstance is different. I wouldn't begin to try to second guess any patient's or family's choices or decisions. It is and should be very personal and private. What seems right and appropriate for one, is not for another.  Individuals with storming have obviously sustained very severe brain injury. Yes, they can survive with aggressive medical treatment, but will likely have significant disability (both cognitive and physical).  Some parents would view this as an intolerably low quality of life; others would accept any level of function, so long as the individual was alive.

Unfortunately, decisions about whether to provide life-sustaining acute care cannot be put off and have to be made when stress is at its maximum. Decisions are made according to what parents, in consultation with professionals, believe is in the best interest of their child. It will never be easy no matter what guidelines anyone comes up with."

 Current Treatment of Autonomic Storms

 Basic Treatment of Autonomic Storms

Again the Journal of Neuroscience Nursing [click here] provides guidance on the role of nursing in the management of storms.  Here is their quote:

"Frequent assessment, monitoring of vital signs, and providing basic care provides the nurse with the key elements needed to define the problem.  Astute nursing care can identify the triggers, reduce the occurrence, severity and duration of episodes, and alert the nurse to seek pharmacological intervention to treat the outward expression of the phenomena. The nurse not only is instrumental in the diagnosis of the storming but also is the moderator of the storm."

Translating this into plain English:  Lousy nursing means lousy outcomes because of the damage wrought by uncontrolled storms due to fevers.  Sabina had at a major uncontrolled and neglected storm at St Vincent's shortly after being classified as conscious, i.e.  following commands.  The neglected storm and Sabina's return to deeper coma was apparently due to inattention.  The storms could be stopped if caught early with changes in heart rate, blood pressure and temperature.  The longer the vital signs were neglected, the easier it was for a storm to become uncontrolled.

Without excellent nursing, and attentive nursing, a patient with severe storming has no chance of any meaningful recovery.  Their situation will worsen due to the recurring fevers and the damage that fevers will bring.  Any gap in nursing, even one shift or part of one shift can be a catastrophe.  At St Vincent's, the nursing varied from superb and very caring, to contemptuous.  In a neuro-ICU setting this is a formula for less than average outcomes.  At Columbia Presbyterian, the nursing was generally top notch and attentive.  Where Sabina had a final setback there was when we had multiple stresses due to nursing misdiagnoses, and stressful testing and withdrawal of food, and then we had a nurse on shift that had not dealt with Sabina before, missing the signs of an impending storm.  Once the signs of storm were missed, Sabina slipped again back in to coma after following my commands. 

According to Rabenstein, et all, autonomic storms start 5 to 7 days after injury, but can start even earlier. The storms usually follow a daily pattern, going from 1 to 3 times per day, lasting from 2 to 10 hours.  Later in recovery, they become much less frequent, but become more severe after a stimulus.  This was the course in Sabina's case.  We were not instructed by any staff member at Columbia Presbyterian of this general course.  What we did observe is that the staff was not alerted to this, and they were not prepared to deal with this crescendo or climax.  They were not vigilant in aborting the more severe, less frequent storms.  Complacency took over just at the time they needed to be more alert and proactive.  This could be referred to as the "Storms before the calm".

At that point the realization sunk in that Sabina had no chance because of the realities of nursing.  Future patient management should adopt methods like artificial intelligence to signal the start of storms from the computer logged vital signs.  Such an AI  system would either signal the nursing staff or provide computerized injections of key drugs to stop storms similar to the baclofen pump.  Without such AI and automated therapeutic control,  patients like Sabina will have virtually no hope of any recovery if they slip into a damaging storm and unmanaged hydrocephalus.  When physicians said it would be a miracle if Sabina had a meaningful recovery, the miracle would be drawing superb nursing staff at every turn.

The management of storms simply needs automation.  Human staff is simply not up to the task.   There is always a weak link.  This points to dispensing drugs like the baclofen pump, perhaps including titrated propanolol, benzodiazepines, among others into the bloodstream, as suggested by the paper “Alternative treatment in the management of combined hyperadrenergia and spasticity in the adult with a severe traumatic brain injury: A case report where a  baclofen  pump was installed for 26 year old woman who was in a hyperadrenergic state.  Basically her case offered almost identical presentation to Sabina’s:  “evacuation and craniotomy with resultant severe TBI. During acute hospitalization, she was nonresponsive, unable to follow commands, and her hospital course was complicated by tachycardia, fevers, and hypertension”. 

One thing for physicians, nurses, and families to be aware is the need for weaning away from the myriad of drugs given the patient to control storming, all of which contribute to a lower response state than the patient would have without drugs.  Care needs to be taken in weaning to minimize wild fluctuations in storming that can be released with weaning.  Bromocriptine can be useful in controlling storms during weaning, avoiding the need to whack the patient with more serious, sedating drugs. 

For those seeking learn about the current standard on treatment of traumatic brain injury, there is a reference [click here].  Another thorough review of the treatment of autonomic storms by Lemke at Froedtert Memorial Lutheran Hospital is found in this reference [click here].  One key point made is the role of patient family in identifying the onset of storms [ click here ].  In Sabina's case, we often saw the beginnings of storms ( stomach churning, or stirring, dilated pupils, temperature increases or pulse rate increases) and obtained nursing assistance to abate the storm at onset.  I recommend looking at the list on Table 1, page 17 in “Medical Aspects of the Low Response State after TBI” by Blackman [ click here ] to understand the many issues associated with the storming patient.  There is a recent review by Abend of Philadelphia Children’s Hospital in various treatment aspects of uncontrolled seizures, including induction of coma [ click here ].

Lund Protocol

The Lund protocol was developed at Lund University to deal with adrenergic stimulation after TBI.  I consider it to be the most effective drug treatment regimen for TBI because it target adrenergic stimulation.  Their results are quite good considering the condition of the patients treated, but there is some resistance to offering the protocol with the usual caveat that good care and not the treatment itself is what matters.  I disagree in part, in that good care is essential but that the Lund protocol does offer a real difference.  It has been proven in a number of randomized studies [ click here ] and steers away from craniectomy as the last resort and toward a chain of drugs to deal the many aspects of TBI and its sequelae.  Here is a summary [Trauma: Critical Care By William C. Wilson, Christopher M. Grande, David B. Hoyt] :

Lund  Protocol for Raised ICP

General physiologic homeostasis

·       Reduce capillary hydrostatic pressure to maintain cerebral perfusion pressure at 60-70 torr

o      Metoporol,    Clonidine Ergotamines

·       Reduce ICP below 25 torr

o      ErgotaminesPentothal

·       Reduce stress, sedate, anti-anxiety

o      Benzodiazepine derivativesOpiods, Fentanyl,  Pentothal maintenance

·       Fluid maintenance

o      Albumin, Whole blood, Frusemide,  Parenteral nutrition

·       Other methods

o      CSF drainage to reduce ICP

o      Head of bed elevation

o      Neuromuscular blockade

o      Diuretics

o      Hyperventilation

Second tier treatments

·       Barbiturate coma

·       Optimised hyperventilation

·       Hypothermia

·       Decompressive craniectomy

Emergency Treatments for TBI

Confronted with a serious TBI after the patient’s vital signs are stabilized, if the patient has intracranial hypertension, it must be relieved.  My review suggests that the following three steps be followed in order if the intracranial pressure (ICP) is not relieved ( color code:  Green, suitable for all cases; yellow, review suitability controllable complications; and orange, complications not controllable):

1.     Avoid any stimulation

2.     Intubation and ventilation to maintain appropriate CO2 and O2 partial pressures.

3.     Administer a bolus of mannitol with or without hypertonic saline

4.     Hypothermia with ArcticSun ( no cooling blankets for this please to avoid shivering )

5.     Administer a bolus of thiopental, followed by barbiturate maintenance.

6.     Perform a decompressive laparotomy (need indication of high IAP) or lumbar drain (basal cisterns must be intact)

7.     If absolutely all else fails, then perform a decompressive craniectomy

Sadly, none of these measures other than proper ventilation has any substantial documented probability of success.  That is why am I discouraging craniectomy or hemicraniectomy,  because there have been no comprehensive randomized trials comparing it with other modalities, and the two recent modalities (laparotomy or lumbar drain) that appear to offer an alternative to the overly drastic craniectomy that has not demonstrated clear benefit in a randomized study.  There is also the issue of coma duration, where some consider that a patient in a coma for more than six hours will have lasting brain damage that can severely limit recovery.

Basically the Cochrane Database reports on Mannitol, hypothermia, barbiturate therapy, and craniectomy, do not indicate any improvement in outcome over random chance in a statistically significant randomized study.  Here are the references:

Hyperventilation therapy:  Showed a not statistically significant beneficial effect on mortality at one year, which was not supported by an improvement in neurological recovery.  Click here .

Hypothermia:  No significant effect on outcomes.  Low quality trials overemphasized effect.  Possible pneumonia.  Click here.

Barbiturates do not alter mortality.  Not significantly better than mannitol.  RR for uncontrolled ICP was 0.81.  Click here .

Craniectomy:  Statistical evidence is thin.  The Cochrane review quotes:  There is no evidence from randomized controlled trials that supports the routine use of secondary decompressive craniectomy to reduce unfavorable outcomes in adults with severe TBI and refractory high ICP”.  The trial conducted with pediatric patients is too small to be fully statistically significant.  Click here . 

Mannitol:  Basically no clear benefit. Click here.

Intracranial Pressure (ICP) and Cerebral Perfusion Pressure (CPP)

In general, emergency surgeons place the most weight in ICP as an indicator of the severity of TBI.  An alternate view in the British Journal medicine as referenced in the heading, views CPP as the more important.  They encourage monitoring ICP, and mean arterial pressure (MAP) to derive CPP=MAP-ICP.  CPP is key to assuring adequate oxygenation and perfusion of the brain to prevent secondary ischemia.  They recommend monitoring “jugular bulb oxygen saturation (SjvO2); brain tissue pO2 monitoring (PtiO2); transcranial doppler measurement of blood flow velocity- pulsatality index (PI)”.


In a UVa trauma center study, their data from a preliminary study indicate “that intense, aggressive management of CPP can lead to good neurological outcomes despite extremely high ICP. Aggressive CPP therapy should be performed and maintained even though apparently lethal ICP levels may be present. Further study is needed…”


TBI, Increased Intra-Abdominal Pressure and Abdominal Compartment Syndrome

This seems like an unlikely collection, but the association of increased intra-abdominal pressure and increased Intracerebral pressure has been quantified [ reference ].  The reason is fairly simple, pressure in the cerebrospinal fluid is transmitted from the abdomen, partially by pressing into the spinal column and mostly by pressing into the thorax and thus increasing blood pressure, thereby transmitting pressure up to the brain.  Since blood is essentially incompressible, the brain sees increased Intracerebral pressure.  Not a good thing.  This leads to hydrocephaly and ultimately to storming.  Abdominal compartment syndrome (ACS) is extensively elevated intra-abdominal pressure that may be caused by organ failure like pancreatitis, or can cause multiple organ failure.

What are the risk factors to elevated intra-cerebral pressure due to elevated intra-abdominal pressure that may be surprising?  Here is a referenceable list that should be noted by any attending trauma physician (Sabina fit all four of these risk factors) :

1.               There is new evidence for the association of ACS with endotoxins being released by the gut causing “leaky gut”.  The endotoxin release may indirectly be induced by various signals from the brain injury such as cytokines and leukotrienes that can open the blood brain barrier, and also the tight junctions in the gut[ PMID 2996417 ].  It must be emphasized that this is indirect injury to the gut induced by severe trauma elsewhere.

2.               Physically fit young, athletic women have chronically elevated intra-abdominal pressure [ reference ].

3.               Extended or heavy administration of propofol can lead to pancreatitis and then abdominal compartment syndrome [ reference ]

4.               Administration of propofol to pediatric patients is specifically forbidden because of the high incidence of abdominal compartment syndrome.  My view is that this caution should apply to any adult who is slight of build since propofol is unsuitable due to low body weight.

5.               Bulemia has been associated with high intra-cerebral pressure [ reference ].  It is my view that any TBI patient that has suffered an eating disorder, whether bulimia or anorexia should be carefully checked for high intra-abdominal pressure.

If there is elevated intra-abdominal pressure, administration of decompressive laparotomy is discussed below.

Propofol, TBI and Its Complications

Before we get into the emergency treatments, the issue of propofol in its role in altering recovery after TBI needs to be considered.  Interesting since propofol has now suggested in playing a key role in Michael Jackson’s death.  Propofol reduces ICP and is a reversible sedative but also drops blood pressure, worsening cerebral perfusion; not a good thing for TBI.

First of all, in [ Vasile ] the use of propofol is not recommended for TBI patients because they have double the risk of propofol infusion syndrome.    Just to emphasize the point that in addition to pediatric TBI cases, propofol should not be administered to slight of build adults because: “Adults have larger carbohydrate stores and require lower doses of propofol for sedation than do children, which might account for the rarity of this syndrome in adults,from [ Sabsovich et al 2007 ].  Sabina had an eating disorder and a dress size zero.  Shame on any physician that uses propofol in TBI for any person under 100 pounds.

One thing to be concerned about is multiple compartment syndrome, or abdominal compartment syndrome which is a result of multiple organ failure, a possible manifestation of PRIS.  PRIS has been regarded to be all or nothing manifested in death, but recent work has begun to identify various levels leading to death.  In Sabina’s case, she suffered a common side effect of propofol which is pancreatitis.  Pancreatitis in turn will lead to abdominal compartment syndrome [ reference ] which in turn leads to increases in intracranial pressure, and thus hydrocephalus, a cause of autonomic storms. This gets to be absurdly circular with propofol being used as a backstop for uncontrolled storming.  The cardiac damage associated with propofol is also a red flag that propofol may be associated with induction of  multiple compartment syndrome ( the heart being in the thorax, the pancreas in the abdomen ) thus driving up intra-cerebral pressure, endangering the TBI patient. 

Propofol dosages and usage are coming under question [Fodale 2008].  Triggering drugs for PRIS include catecholamines and steroids.  Well, guess what?  TBI patients may have a flood of catecholamines triggered by glutamate release, and the cycle of excitotoxicity.  PRIS can be a perfect storm for TBI patients, even without administration of the triggering administration of catecholamines often used to raise the blood pressure of TBI patients.

Given that Multiple Compartment Syndrome could be induced by propofol, it may be wise to consider decompressive laparotomy, or lumbar drainage for these patients. 

Avoid Stimulation (Quiet please!)

Funny that I should have to mention this with all the chaos surrounding emergency rooms, surgeries, and ICUs, but this is important.  Loud noise, suctioning, and excess stimulation such as patient movement, raise intracranial pressure [ click here ].  TBI patients should have a very quiet isolation room.  In Sabina’s case bringing her out of coma often resulted in raised ICP, setting her back with the autonomic storms.  Her care should have been managed with completely different sedation such as the barbiturates.  The Taylor Study points out that high peak ICP levels are to be avoided.  Note that stimulation produces high peak pressures.   EMT personnel please take note.

Intubation and Ventilation


Osmotic Therapy


Mannitol and hypertonic saline are widely used to control cerebral edema and intracranial hypertension.  Mannitol  has been used for nearly half a century, with little understanding of its mechanisms.  No protocols have been established.  It is not clear that mannitol has any benefit beyond the first administration.  Research widely varies on the efficacy of mannitol and saline administration. A good review of the role of hypertonic saline and mannitol for the treatment of cerebral edema is by Rabenstein (2006).  A recent review conducted by Himmelseher (2007) states that there is no benefit to outcome in hypertonic saline for TBI.  He cautions against high osmolar loads which can cause saline to invade the brain tissue.  Another study says that hypertonic saline is more effective than mannitol in reducing ICP [ Infanti ].  Knapp (2005) conducted a review of pediatric guidelines employing both mannitol and hypertonic saline.

Hypertonic saline has been suggested as a component of combination therapy [ Margulies, et al, 2008 ].

There are a number of studies looking at the effect of administering hypertonic saline with or without other components.  One study is looking at administering saline and dextran before hospital admission [ click here ].  There is an review of the early treatment of TBI with hypertonic saline [ 8 ] along with a discussion of how to manage blood pressure and respiration in the critical care minutes after injury.  Slow withdrawal is recommended to reduce rebound in ICP, no matter what the osmotic agent.

Pyruvate ( Sodium Pyruvate, Ethyl Pyruvate )

Sodium pyruvate is an alternative to supplying Ringer’s lactate and sodium hyperperfusion after TBI to restore osmolarity, and the pyruvate is to restore essential energy resources after neural injury. 

My view is that supplying pyruvate to patients suffering traumatic brain injury is essential to restoring lost ATP from the TCA cycle.  TBI has been shown to induce expression and phosphorylation of pyruvate dehydrogenase by pyruvate dehydrogenase kinase (PDHK), thus inhibit the production of ATP, in disturbed glucose metabolism [ Xing et al, 2009 ].  They hypothesized that TBI induced excess phosphorylation of pyruvate dehydrogenase causing ATP underproduction and threatening the mitochondrial energy supply.  Supplying pyruvate substrate could increase the rate of ATP production without the need to consume ATP in the production of glucose 6-phosphate in glycolysis.

PDHK is upregulated in the presence of ATP.  In the course of TBI, one the first cellular releases due to cell swelling and stretching is the release of ATP from endothelial stores.  A possible mechanism for the induction of glycolysis disregulation is this intercellular release of ATP.

To me the most disturbing aspect of the report by Xing et al, is that a sham hemicraniectomy caused marked increases in the phosphorylation of pyruvate dehydrogenase.  This could seriously compound the energy depletion due to TBI.  High lactate to pyruvate ratios have been associated with poor prognosis, and a measure of disturbance of glycolysis.

Argatroban (approved for human use, experimental for TBI)

Argatroban in an anticoagulant, and direct thrombin inhibitor.  It has been administered in an animal model of subarachnoid hemorrhage [Sugawara, et al, 2009 ]to reduce the effects of the disruption of the blood brain barrier.  Thrombin is seen as disrupting the BBB causing swelling and edema after ischemia, the disruption of blood supply to the brain, and hemorrhage. The animal model tests successfully reduced brain cell death, and reduced swelling and inflammation.  Since argatroban is approved for human use, it is a possible salvage treatment.  A suggested application of argatroban after any surgery might be to mitigate the effects of blood in the cerebrospinal fluid inducing brain cell death, one of the dangers of decompressive craniectomy.


Urea has long been used as an osmotic agent for reducing ICP.  Urea has been shown to be neurprotective of myelinolysis in the treatment of hyponatremia with saline [Soupart], suggesting that it might be an important adjunct to hypertonic saline for TBI. Urea has been shown to be protective of oxygen deprivation and is needed where high levels of salt are present.  Urea has not been as popular since it crosses the BBB more easily than salt and is thought to not to have as strong a hypermolar pressure reducer as salt [Bhardwaj 2004] .  Randomized trials comparing mannitol, NaCl, urea, and glycerol have not been performed.

Hypothermia (induced)

There is a study in Australia in New Zealand to determine if children with severe TBI can be treated with hypothermia to 32 degrees Celsius improve over non chilled children [ click here ].  There was a clinical study at various in the US to test the same cooling methods [ click hereclick here ]. ].  The follow-up is ongoing [

Decompressive Laparotomy

A decompressive laparotomy is a relatively new surgical treatment to relieve refractory intracranial hypertension introduced by neurosurgeons at the University of Maryland [ click here ].  It is a procedure where a small hole is put into the abdominal cavity and drains fluids to relieve intracranial hypertension.  Here is a quoted explanation:

“It is plausible that the decompressive laparotomy reduces the positive pressure applied to the diaphragm and shifts the compliance curve of the lungs. This restores pulmonary compliance, allowing for improved buffering of volume and pressure changes arising from both the lung and the abdomen.”

Decompressive laparotomy has had at least one miracle recovery where a 16 year old with severe concussion and refractory hypertension went back to school restored getting As in her courses [click here ].  This patient was also given life support as part of the therapy.  Given my daughter’s horrible experience, this is truly amazing.

Consider also that laparotomy is indicated for high abdominal pressures.  These pressures can be caused by abdominal compartment syndrome which in turn can be caused by organ failure such as pancreatitis or kidney failure.  Or chronically high abdominal pressures can be the result of patients in a high condition of abdominal tone, such as female athletes or heavy exercisers [Daly and also Bø K. Urinary incontinence, pelvic floor dysfunction, exercise and sport. Sports Med. 2004;34:451-464].

Lumbar Drainage

Lumbar drainage is the process of tapping off CSF in the lumbar region to reduce ICP.  It has been shown to be a safe and effective means of reducing refractory increases in ICP [ Murad, et al. 2008 ] provided that the basal cisterns are visible.  A ventriculostomy should be in place before a drain can be effected, and the authors recommend it to be standard practice for treatment of intracranial hypertension.

Better than expected outcomes were been observed after 6 months post intracranial hypertensive event by [Abadal-Centellas et al 2007 ].  They found few if any complications compared to other treatments including hypothermia or decompressive craniectomy.  The point out that CSF drainage was contraindicated because of transstentorial herniation, but they pointed to other studies that indicated such a risk did not exist.   The only deaths in their study occurred when the basal cisterns were crushed, and specifically recommend not using lumbar drainage in those cases.

In contrast, this study did not predicate the installation of a ventriculostomy prior to lumbar drainage.  They recommend lumbar drainage where midline shift in the third ventricle is less than 10mm, and there mustbe no surgical mass.  The patient must be followed closely to manage the rate of drain carefully to avoid downward brain herniation.  They found that ventriculostomies performed poorly or not at all in providing drainage and recommended lumbar drainage to provide reduction in ICP.

In another study by [ Tuettenberg et al 2009 ] of lumbar drainage, they found mixed results, although it is not clear from their prospective study what differences there were in protocol at the various institutions.  What has been most criticized in the employment of lumbar drainage is the 6% brain herniation rate that results directly in death.  There is further comment by [ Abadal et al 2009 ].


Indications for surgery are of major shifting of the brain mass or herniation which is often caused by very high intracranial pressures.  When herniation is visible, the prognosis is poor for a meaningful recovery.  In Sabina's case, she was administered a hemicraniectomy to relieve pressure from the swelling resulting from a concussion.  Remember that concussions are much like bruises, and like bruises they can swell up.  With the brain, this swelling is confined inside the skull which can result in more damage and higher ICP.

It is my hope that neurosurgeons not perform a hemicraniectomy if they can bring down ICP with any other means.  Craniectomies are viewed as a last resort rescue.  Even the Cochrane database [ Sahuquillo ] admits that “There is no evidence from randomized controlled trials that supports the routine use of secondary decompressive craniectomy to reduce unfavorable outcomes in adults with severe TBI and refractory high ICP.”  They still go on to recommend it because of the lack of alternatives.  Another review [Albanese, 2003] measured 25% socialization after one year, complications in 84% of the cases, a GCS < 8, for 40 patients under craniectomy.  Under a literature review by Danish [2009], after 6 months they found a mortality rate of 28.2%, and a typical quality of life with a GCS of only 4 among survivors (notice that removing the dead makes things look a bit better).

There is a reason to avoid craniectomies:  the development of paradoxical herniations after craniectomy [ Vilela ].  This is due to a pressure gradient that causes the brain to compress on itself, which can be managed through unusual positioning.  In all likelihood, Sabina suffered a paradoxical herniation given her history and posturing at that time, as the case presented by Vilela speaks of such a herniation 6 weeks post surgery.   Hemicraniectomies have come under severe criticism because of many possible complications.  There is currently a clinical trial study by Dr Stiver at UCSF [click here].

When is the skull restored with a cranioplasty?  Current practice seems to dictate cranial restoration at 6 months [ Holland and Nakaji, 2004 ].   They viewed craniectomy as the best means to restore a dire situation when intracranial hypertension is intractable, ie. refractory.   A number of others have questioned even the need to control ICP, if CPP is adequate.  And as you can read here there are a number of other lesser therapies that can intercept CPP and IH/ICP, in particular the Lund protocol, removal of pressure on the abdomen, or CSF withdrawal.

Six months seems quite long, and does seem to make the patient vulnerable to a number of complications if the skull is not restored.  Frankly seeing a patient without a bone flap in place, is a continued horror that makes the case appear very dire and not worth rescue.  Any neurosurgeon worth his salt needs if he deems the procedure necessary, needs to spend a lot of time with the family justifying them of the need for hemicraniectomy, and the positive outcomes.

What is the main reason that I am against craniectomies?  I will give you a reason that may surprise patient families and physicians:  It is hideous and massively disfiguring.  Why does that matter?  Because those who have love and care for the patient view them as grotesque, creating an emotional reaction against the patient that cannot be mitigated or erased.  This affects the family because they will be unlikely to support continuing intensive care, opting to “pull the plug”.  The tendency will be to draw away from the patient denying them love and affection.  The same thing plays on the nursing and care staff.  Care may often be lacksidasical at best, and at worst withdrawn.  The relatively poor prognosis of craniectomy patients wears on the staff making them likely to find other things to do than care for the patient.

This patient revulsion extends beyond the period when the patient has had the skull flap removed and then replaced.  In Sabina’s case, her restoration was imperfect and gave her an unbalanced appearance which put her mother off, seeing her child as being deformed by all the medical work.  I am afraid that ICU neurosurgeons do not understand this and have been too quick to apply craniectomy which they consider relatively simple, very direct solution to elevated intracranial pressure, rather than more complex treatment modalities.

·       Expansion of contusions

·       Opposite new subdural and epidural hematomas

·       External cerebral herniation

·       Cerebrospinal fluids circulation may be disturbed and produce subdural hygromas, a pus like sac or lump that may need treatment.

·       There may be a paradoxical herniation following a lumbar puncture

Later in recovery, the TBI patient that underwent hemicraniectomy may develop:

·       Syndrome of the trephined composed of cognitive, neurological, or psychological deficits

·       Persistent vegetative state

Are hemicraniectomies wasteful:  A Medscape Review [S. F. Danish, et al]

“Those who are skeptical of the procedure raise several questions.  Does the craniectomy quantitatively control raised ICP?  Does brain herniating through the defect escalate the problems?  What prognostic information can we give the families of those for whom the procedure is being proposed?  Do the results justify the treatment?”

That question of medical benefit for such a radical procedure is treated in the review.  The Medscape review points out there are no randomized, prospective trials.  There is a widespread perception that the procedure is futile because the outcomes for those with severe head injuries are often limited with many patients falling into a vegetative state or manifesting severe motor disabilities.  The authors point out that such severe disabilities are not always a foregone result.

Currently there are a number of clinical trials to determine the relative effectiveness of early hemicraniectomy [ click here ].

Is it possible that hemicranectomies are a significant cause of autonomic storms?  One significant concern is that by not keeping the skull reasonably contained, that hemicraniectomies are the cause of autonomic storms.  I cannot prove this, but since autonomic storms seem to point to lesions in the upper spine or lower brain, that opening the skull will tend to separate the brain from spine if there is excessive brain swelling.  There you have it.  In Sabina’s case, my view is that her storms were iatrogenic;  The storms began to appear two months after surgery;  I see the storms as caused by contemporaneous (to the start of storming) brain swelling and spinal distortion from the brain because the skull could not contain the brain.

Systemic injury after trauma (yet another reason to avoid hemicraniectomy for TBI)  Inflammatory changes after any trauma depend on the severity and the distribution of the injury and can be modified by the medical treatment. They precede the development of organ dysfunction and may be used for monitoring purposes. Among these, pro-inflammatory cytokines appear to be the most reliable parameters.  For reference [ click here ].

Drug Therapies for Autonomic Storms

Drug therapies for autonomic storms are discussed in the following section.  I would refer physicians and nurses to  "Treatment of Paroxysmal Sympathetic Hyperactivity"[1] and eMedicine [6] for dosages and treatment protocols.  This section abstracts information from the public literature on treatment options.


Baclofen Pumps

Baclofen is a GABA agonist which stimulates the opening of the K+ channel which prevents the Na+ channel from opening.  That in turn, prevents the voltage dependent Ca2+ channels from opening, which in turn suppresses neurotransmitter release, thus halting storming.

Another treatment modality used with some success in pediatric patients is the early use of an intrathecal baclofen pump [5].  I attempted to have the staff at Columbia Presbyterian look into installing a baclofen pump for Sabina.  I was not able to get anyone to consider employing a baclofen pump. They apparently have not reached wide use as therapy for autonomic storms.  It is quite effective in controlling spasticity, and for storming patients this can cut short a developing storm, and provide a path to rehabilitation.

The study [3] recommended the use of baclofen pumps in early therapy for autonomic storms for TBI patients, despite the fact that the FDA approved them only for those in therapy after one year.  In the cases presented, baclofen therapy eliminated all storms and fever, weaning patients away from all forms of IV and drug therapy. 

Currently there is a clinical trial to evaluate the use of continuous infusion for TBI patients with the baclofen pump.  The baclofen pump is available from Medronic with the included list of patient qualifiers.

Beta Blockers (e.g. propanolol)

Beta blockers are used to control excitability of the adrenal glands, a basic stress response.  It can be used to control the triggers of a storm when properly timed.

Benzodiazepines (Valium and relatives)

Benzodiazepines are commonly used sedatives for TBI, and are cheaper than propofol.  Long term use produces a longer tail as metabolites accumulate in the system.  As with propofol, they depress cerebral metabolism.  One very confounding aspect is that the treatment of those in ICUs for TBI includes long term sedation with benzodiazepines.  Withdrawal symptoms from benzodiazepines are exactly that which storms exhibit:  “tremors, hyperthermia, diaphoresis, hypertension, tachycardia, and seizure” [ click here and click here ].


Bromocriptine is an ergotamine which is related to LSD, used to treat pituitary tumors and Parkinson's.  Bromocriptine has been used successfully to treat patients in a Persistent Vegetative State [4] having autonomic storms from TBI.  It has been used successfully with morphine sulphate, and beta blockers to bring them under control [click here].  Treatment often continues for months with tapering as the patient stabilizes.  Recurrence of symptoms is always problematic.  Use of bromocriptine has been associated with better outcomes.

Bromocriptine is a neural Nitric Oxide Synthase (nNOS) inhibitor and works by inhibiting the action of NO in cell death and excitotoxicity [ click here ].


Botox was applied in Sabina's case to limit the damaging effects of unmitigated posturing.  Her muscles were freezing in place and botox was applied to make rehabilitation possible.  There is a clinical trial in its late phases to evaluate the effect of botox in relieving spasticity in the limbs due to storming and TBI [ click here ]. The study publication found little difference between low or high dilution on the final effects of botox on relieving spasticity [ click here ].


Dantrolene is a muscle relaxant, useful only in controlling posturing [22].




Dexmedetomindine is a relatively new therapy tried on one individual unresponsive to morphine, fentanyl, labetalol, lorazepam, metoprolol, and clonidine. After 72 hours IV therapy with Dexmedetomindine no further storming was observed [7].



Gabapentin is an anticonvulsant which can offer considerable relief to autonomic storms [3].  It has been used with success in the early post acute phase of TBI.  Gabapentin was able to control symptoms while withdrawing other drugs. 

A study at Walter Reed showed gabapentin to have significant anticonvulsive effects after ischemic events (stroke and TBI) [ click here ]  They cited its calcium T channel blocking effect as key, and that gabapentin was effective in stopping seizures when Phenobarbital or benzodiazepines. 

I am not sure if the staff at Columbia Presbyterian had available or used gabapentin in Sabina's therapy.  I asked that it be used and was not given a straight answer.


Glycopyrrolate is an anticholinergic, used to limit drooling in patients with low response.  It is among a long list of many drugs given to patients with low response [ click here ]. 


Opioids are currently the first line of defense against the raging fevers that can occur in storms, and they are also used to relieve the great pains associated with TBI.  They are simple to administer, injection, IV, or patch, and are fairly fast acting.  Opioids do come with complications, which leads me to discourage their use.  Potent opioids administered in high doses for some period of time create withdrawal symptoms that can both mimic many of the symptoms of storms, and trigger them.  They can be effective in managing symptoms, but leave an array of complications.  One possible complication is damage to the cerebellum (cerebellar syndrome a form of tremor) that has been observed in heroin abuse [  The cerebellum and its disorders

 By Mario-Ubaldo Manto, Massimo Pandolfo ]. 


There is an excellent recent review titled [ Ionic storm in hypoxic/ischemic stress: Can opioid receptors subside it? ] that points out the seeming contradictory evidence that opiods both quiet and excite the Ca++ channels.  Since it is the neurons that appear to be excited by opiods, and because neurons are more sensitive to energy loss, it may be best to avoid opiods in treating storms as they may induce long term neuronal damage.  There is some evidence that opioids are neuroprotective during hypoxic/anoxic stress.


Sabina's storms were treated with Fentanyl patches after other opioid use seemed ineffective.  Fentanyl is perhaps the most powerful, known opioid.  It was used at St  Vincent to control her storms after the disastrous storm that stanched her consciousness on March 31.  There is caution applied to the use of fentanyl which can increase intracranial pressure.  At St Vincent's, excessive pressure resulted in hydrocephaly which needed separate treatment.  This may have been due to fentanyl.  Clearly the staff at St Vincent's was trying lots of things, but frankly seemed out of their league.


One issue brought up by Blackman [ Paroxysmal Autonomic Instability With Dystonia after Brain Injury, 2004 ] is the problem of opioid complications.  First there is constipation.  I had a heated argument with the nurse practitioner in the last week of June at Columbia Presbyterian.  She wanted extensive, painful MRI studies on why Sabina was constipated.  Basically I told her to get her head out of her backside and think for one second.  The studies were negative, and the stress did her no good since she was kept from nutrition for days.  I was fit to be tied. 


The other more dangerous complication is vomiting.  Sabina suffered vomiting in her last week, and many other times.  Vomiting in a comatose patient is a dangerous complication that can cause choking, in addition to nutritional deficits.


It was at that point, the other complication of opioids started to come to my focus, and this is described by this quote from Blackman:  "Withdrawal from opiate therapy may provoke signs that falsely suggest [Autonomic Storms]."  Sabina was on the most extreme opioid known to man:  Fentanyl.  It was during this time that she was to be prepared and weaned for rehab.


It may be possible to generalize a theory based on Sabina's case:  That autonomic storms as a sequelae to TBI can be severely aggravated by overuse of sedation whether it be propofol for surgery, or later use of fentanyl to quell storms.  Brain injury, opioids and sedatives all act to aggravate the brain, gut interaction.   This theory puts in question a large portion of the treatment of autonomic storms.  New treatment models are needed.


References point to morphine sulphate as a better means to control storms.  It may have been that morphine doses could not be increased further at St Vincent's which meant a turn to stronger opioids such as fentanyl.  This tolerance to opioids may have been the result of excessive propofol use in the first week that increased Sabina's tolerance to sedatives.  This is only a conjecture that suggests further study.


Naltrexone (ReVia) has been shown to be effective in controlling storms [6].




Pentobarbital, like phenobarbital is a barbiturate of medium duration with a 48 hour half life.  It is far more depressive and more strongly blocks the voltage dependent Ca++ channels.  It is suitable for ICU usage only, but may need to be used in refractory epileptic events, or storming [ click here ].   Pentothal (below) is in far more common usage in intensive care.


Pentobarbital is significantly more effective than propofol or midolazam in blocking refractory seizures [ click here ].  Its use should be considered in autonomic storming cases.  Pentobarbital may be the ultimate weapon against the seizures of storming.  Pentobarbital and pentothal have been used in TBI to bring down neural activity to limit damage from excitotoxicity.


The barbiturates have been often superseded in modern intensive care practice by propofol, but in cases where coma needs to be induced for more than one day, I question the use of propofol.  Pentobarbital’s half life is about as long as the maximum limit on usage for propofol.  The list of propofol complication is legion, especially in extended use where it is entirely inappropriate, and is completely inappropriate with pediatric patients.  In my view this makes propofol inappropriate in patients of slight build, such as Sabina who suffered propofol’s complications.  I had asked the staff at St Vincent’s to administer a barbiturate coma instead of propofol which was administered to Sabina for over a week, but they demurred; they kept her on propofol saying: “just another day, just another day” until she finally had pancreatitis as a result.  Because of the Ca++ T channel blocking characteristics, I support the use of barbiturates over propofol for TBI.


Rabenstein in his 2006 review, questions the efficacy of barbiturates in improving outcomes.


Pentothal (Thiopentone, Thiopental)


Sodium Pentothal, an ultra short acting, three minute redistribution, long duration barbiturate, is metabolized to pentobarbital, so all the actions of pentobarbital (above) apply.  They have been used in combination [ click here ].  It is the most appropriate drug in ICU to control uncontrolled increases in intracranial pressure.  It is a powerful anticonvulsant for those that do not respond to other drugs [ click here ].  A study showed “Thiopental appeared to be more effective than pentobarbital in controlling intracranial hypertension refractory to first-tier measures”.




Phenobarbital is long established barbiturate sedative with long half life (up t 120 hours), well known for its anti-seizure properties. Phenobarbital is a Ca++ T channel blocker, which makes it strongly neuroprotective, and thus a top choice in TBI and stroke therapy [ click here ].  It has been used in tapering an injured patient away from dangerous extended propofol administration [ click here ].


Interestingly, Phenobarbital is a preferred treatment for febrile seizures [ click here ], which often occur in children of a few months age.  There presentation is virtually identical to Sabina’s autonomic storming. 

Propofol  (Diprivan)

Propofol is a preferred sedative because it is strong, and can be turned on and off in a short period of time.  Propofol depresses cerebral metabolism.  It is fat based and can only be used for short periods of time.  It does require caloric adjustment, fact that I learned from Sabina's nutrition colleagues.  Overuse has the well known complication of pancreatitis [click here or here ].  There are many case of pancreatitis for propofol infusions over an extended time.  Fat deposits are an additional complication.  Sabina contracted pancreatitis at St Vincent's which I ascribe to multi-day administration of propofol.  Propofol is only to be used as an anesthetic for a limited time, no more than 3 days. 


As if to be somewhat circular, the symptoms of pancreatitis can include fever, vomiting, and dehydration.  The fever of course can aggravate the storms, and may trigger them, and dehydration can create its own problems with the brain.  There have also been recent cases of infections caused by propofol due to impurities in its components.


On the positive side, propofol is proposed to have free radical scavenging properties, which is being tested in a French clinical trial [ click here ].


Most serious is Propofol Infusion Syndrome (PRIS).  PRIS is associated with higher levels of morbidity.  It is associated with high doses or administration over extended periods (>48 hours) [ click here ].  Certainly Sabina had propofol for well over 100 hours in her first two weeks of hospitalization.  What is most curious is the vicious cycle that propofol can create, which is precisely the catecholamine release cascade cycle associated with a negative inotropic effect, which means weakening of the muscle contractions, in particular the heart. 


This negative inotropic effect in turn causes the release of catecholamines to meet the needs of the body to maintain a steady blood pressure.  As this catecholamine surge increases, we create autonomic storms, which in turn increases the need to administer more propofol.  The catecholamine release breaks down skeletal and heart muscle tissue.  All of this is just too closely associated with Sabina's progressive collapse into autonomic storming to make me comfortable.


Interestingly, the FDA issued a warning against Propofol, that it not be used in immune compromised patients [click here].  Sabina had a head injury and was under Z-tabs for a hospital borne infection contracted as her work as a dietetics fellow before injury.  Specific directives and recommendations are against administration to anyone under 16 (which I take to mean those small in frame, which Sabina definitely was, being a size zero), or for more than 48 hours, or it can trigger PRIS [ ].  The incidence of PRIS is more common with brain injury.  At Bronx Montefiore Hospital (where Sabina received a job offer as dietitian shortly before being struck) staff administered phenobarbitol to taper away from extended propofol usage [ click here ].  Oddly enough, I had asked the physicians at St Vincent’s to turn to phenobarbitol in the first week of Sabina’s stay in ICU; they refused.


There is a case report of  a patient that suffered the same set of symptoms of storming after propofol withdrawal:  “Also, unlike previous reports, our patient experienced other classic symptoms, such as abrupt agitation, tremors, tachycardia, tachypnea, and hyperpyrexia.” [ click here ].  No differential diagnosis can be made in the case of TBI. 


The Center for Disease Control has noted the excessive association with infection and septic shock with propofol.  This association appears due to lack of aseptic handling of propofol by hospital personnel, as propofol has been shown to be a growth medium for bacteria [ click here ].  St Vincent’s at the time of Sabina’s surgery had shortcomings with sanitation.  Sabina was infected with acinetobacter, for which propofol supports rapid growth [“Microbial growth and endotoxin production in the intravenous anesthetic propofol.”, Infect Control Hosp Epidemiol. 1991 Sep;12(9):535-9.]


Currently there is a clinical trial to determine if Precedex should replace Propofol for TBI patients.



Tylenol (Acetaminophen ) was used extensively to control the fever during storming.  It seems that this was done at St Vincent's partly because getting morphine involved too much trouble, and no one could leave the floor to do all the paperwork.  Tylenol was not very effective in managing fevers.

Sodium Valproate,  Valproate semisodium

Both Sodium Valproate, Valproate semisodium are derivatives of valproic acid, and are among the most powerful anticonvulants, being employed against status epilepticus  [ Bolano, et al, 1998 ].  They found it to be neuroprotective, and prevented many of the complications seen in kainate induced epilepsy.   Valproates are Ca++ T-channel inhibitors [ White, 1999 ].  Valproates could have a significant role in controlling autonomic storming.


 Temperature Management and Control with Cooling Blankets and Jackets

Management of patient core temperature is critical to preventing further ischemic damage to the brain. [6]  The chart there indicates that excessive temperature is also a general effect of intracranial hypertension.

Certainly drug therapies can manage patient temperature, which when elevated can trigger many complications.  Temperature management can be least invasively managed with cooling vests, blankets and the like.  They are not desirable for continuous use, and can be effective when patient monitoring by staff may be under stress.

At St Vincent's, the Arctic Sun cooling system was applied to Sabina to keep fevers down.  When Sabina had her first storm in ICU, afterward I sought to keep her fevers down and asked for the cooling blankets to be applied when she would have temperature excursions.  Temperature excursions were the first clue that she would have another storm.

The ArticSun system was available to TBI and NICU patients at St Vincent's and I asked that it be used on Sabina.  Because she was placed in ICU, there were no people trained in its employment.  Essentially I had to set the equipment up myself.  The only person trained in its use, an NICU male nurse, was protective about the information that he had on setting ArcticSun.  He seemed not to want to let anyone else know how to use it in a scheme to protect what he considered his superior expertise.  I found his attitude distasteful and job protective.  He was not one to share readily and train others in its use.

After rigging it up, I found that the nurse spoken of above had not noted that parts were missing from the system.  I had contacted the manufacturer, Medivance, to supply the missing part, and to get the training manual.  The original training manual attached to the ArcticSun had the key setup page torn out of it, necessitating contacting manufacturing support.  I found this negligent.

As for research  on the use of ArcticSun, one nurse was familiar with the use of cooling blankets, having working in a NICU in Colorado and pointed that facility had emphasized management of patient temperature.  The cooling of patients with temperature controlled circulation was studied by staff at Columbia Presbyterian [7].  Even so, when Sabina was at NYP under the care of these same physicians, they chose not to control temperature using this device.  They stayed with various drug protocols.  I can only theorize why they would not use a cooling system and that would be for long term ICU care, such cooling would be limited in the time it can be used, and drug methods are more understood and easier to administer.  There was a great deal of nursing staff resistance using the ArcticSun and found the system often disconnected when the night crew came in.

At St Vincent's drug therapies were not rigorous, and the major advantage that ArcticSun had at St Vincent's was because of staff lassitude and inattention, the ArcticSun device would automatically maintain patient temperature without requiring nursing intervention.  This was a great relief to the parents in going to bed at night, knowing that Sabina would not be damaged by fever overnight due to staff inattention.  A recent study at Mass General Hospital used the ArcticSun in critical care and found that aggressively treating fever improved outcomes[8].

Notice that the amount of time a patient may use the ArcticSun continuously is limited.  For that reason, my recommendation would be to use ArcticSun nightly only, when staffing can be short or under stress.  Setup and removal can take considerable time, and the vests need constant replacement, as they are somewhat disposable.  Such careful use can extend the useful life this non-invasive, non-drug method of saving the brain. 

The key virtue of the ArcticSun is that feedback to central fevers and storms is almost instantaneous due to the temperature sensors.   Quick response to storms is essential to keeping them quelled with minimal force and effort.  No nurse needs to step up from their station.  Sabina generally responded well and her storms were not getting out of control with the liquid cooling.

The threshold of brain damage is regarded to be at around 109 degrees.  Other references set the temperature of 106 for hyperpyrexia, a medical emergency [ click here ].  Even if measured patient temperatures are measured below that, the rapidly rising temperatures of storms can create local hot spots that take time to level out.  The physics of thermal conduction cry out for extreme caution with rapidly rising temperatures, even if measured temperatures are well below the well established threshold of damage.  It is important for  nursing staff to be responsive to the earliest sign of storming and quickly contain temperature excursions.

One cannot emphasize the danger of continued elevated patient temperatures enough.  The reference Storm et al  [ click here ]point to "symmetric cerebellar pyramidal cell destruction" as being due to "excessive hyperthermia".  This can lead to decompensation where the thermoregulatory systems keep attacking the brain, making recovery very limited.

Rule number one:  Get the temperature under control.  Fast.


 Nursing Inconstancy

Perhaps the most deadly aspect of Sabina's care was nursing.  An irritating aspect of Sabina's care was the wide range in nursing care.  It varied from skilled, loving and dedicated to unskilled, disdainful, and lazy.  Oddly enough, mostly it was between these two poles.  Daytime crews tended to be the former, and nighttime crews tended to be the latter, though this was by no means uniform.  Occasionally one will detect the sense of "oh let them die, they are too much trouble" by the nurses.  If this sort of attitude is ever detected, those nurses have no place in NICU.

TBI or autonomic storm patients need consistent, high levels of care to assure positive outcomes.  Anything less, and you have persistent vegetative state.  Storms need immediate response to minimize damage and the excursions that they can take.  I say that Sabina's outcome was due to poor care simply because she did achieve consciousness and could follow a series of commands on March 30, 2007.  Poor attention by the night staff allowed a storm to develop to a massive fever of about 108F.  After which Sabina fell back into coma and had more difficulty with storms.  Someone on the nursing staff should be saying "mea culpa".  This was completely preventable.  It was complicated by the fact that Sabina was not in the care of a neuroICU nurse, but an ICU nurse, and the ICU nurse had a reputation for being inattentive, some would say lazy.

Just to be clear, brain death begins at 106 degrees [ reference ].  I blame St Vincent's hospital Sabina's inability to recover and ultimately for Sabina's death.

There is another aspect of nursing that lead to inconsistent results.  It is the nurse that has inconsistent training with the rest of the staff.  A nurse that does things their own way, or a different way.  This can mess things up and create results not in the interests of the patients.

One final thing about nursing that needs consideration is those nurses that may not be the most skilled.  They have one way they learned things, and they are not about to step out of the bounds that their training gave them.  They will argue with the patient's family and not respect any disagreement.  This came up both at St Vincent's and NYP.

At the bottom line is that nursing care needs strong, consistent management.  Any gaps in nursing  and management, and the patient will find a way to fall into the gaps in care.  My father did literally, busting his head open on floor in his hospital room..  Sabina fell into it six feet.

I would recommend hiring a full time neurologist to review all aspects of care.  While at NYP, a very rich spouse of a stroke patient did this to good effect, and I commend her for it.  Her outside neurologist often corrected and adjusted medical care for the patient.  But realistically, who has the money since providers will not pay?  Most people just do not know what value this can bring to care and their own comfort.  People just don’t think to do it since they think that they are getting the best possible care.  Don’t be fooled by reputations of the staff.  You need to have your own professional review of all the activity.  You simply are in no position to argue with hospital staff.  They often treat the questions and opinions of patients and families with complete disregard.  My message is:  Spend the money on an bringing in your own neurologist, even if you think that you can barely afford it.

Bringing in your own neurologist may not be simple.  I tried to get a respected physician to take my daughter's case and he would not take it, so I gave up on the idea.  You may need to get an out of state physician to review of your case.  Persist until you find one.   Do not rely on hospital staff.





Control of muscular injury






Time and again, prognosis for functional recovery is slim, especially with the recurrence of storms.  Contrary to widely held opinion, Verity in “Do seizures damage the brain? The epidemiological evidence” , 1998, suggests a good prognosis for febrile convulsions and status epilipticus in children.  They separate febrile convulsion lasting longer than half  an hour from status epilepticus, calling them lengthy febrile convulsions.  Verity states that various studies show prolonged seizure activity can damage neurons.  However, Verity concludes that brain damage was much less common that generally thought, although controlling prolonged seizures must be regarded as a medical emergency.  He comforts parents with “epidemiological evidence that if seizures cause ‘brain damage’ it happens rarely.”  Remember, Verity does not deal with convulsions in what might be called storming in  a state of diminished consciousness.

However, the prognosis for storming patients in an extended coma lasting more than six hours, and a persistent vegetative state (PVS), is generally negative:  Meaningful recovery is rated at 3% [ Dana Foundation Website ].  For those seeking a detailed review of  autonomic storms and their prognosis, refer to the refence below[8].  There are somewhere around 30,000 in the US suffering PVS where what appears to be consciousness, is activity arising from lower brain centers.

As discussed above in the causes section, more research is needed to understand the association of causes and conditions going into the prognoses.  For example lumping all TBI cases together and coming up with a prognosis, would be unjustifiable, because those that suffered visible brain damage would differ in prognosis from those with little brain damage, but were suffering hydrocephalus which can be remediated.  There are myriad complexities in prognosis.

I wish to offer everyone caution in easily accepting a negative long term prognosis:   Basically data are drawn in large part from lower income regions where head injuries are more prevalent and medical care may be limited.  For more information click here .

A better discussion would be:  "What are the limits to recovery, based on visible, physical damage?"  Not:  "What do we expect looking at all patients with this sort of condition?"   

Prognoses need to be delivered in a very personal context, and not in front of a team.  Likewise, it needs to be delivered individually to husband and wife so that each can ask questions, and also together, so that mental linkages can be established.  These sessions should not be separated in time.  Of the doctors that we dealt with had the best way of delivering prognoses, but failed to take questions answered to one of us, back to the other one.  There can be sense of triangulation with the doctor's responses played back in a separate prism.

As for TBI, the primary method for making prognoses is the Glasgow scale of consciousness.   Recently, there is a prospect  for more accurate prognoses through measurement of the glutamine to glutamate ratio shortly after injury [ click here ].  There is a review on the imaging of glutamate toxicity associated with increased neuron excitation [ click here ].  Suffice it to day, increased glutamate levels are associated with poor outcomes, and by implication, storming.  Depressed glucose levels have also been shown to correlate with poor outcomes [ click here ].


Recovery from brain injury is difficult.  There are a number of resources available, a good resource for therapies is .  With the presence of autonomic storms, the process of recovery is made much more complex, and requires additional nursing support to manage control of any residual storming.  Few organizations exist that can handle the intense therapy needed along with the high level of nursing needed to manage recovery.  Many simply give up trying for any meaningful recovery given the long odds on getting everything just right.  Standards for therapy allow only so many hours per day, and from what has been observed, that is often not enough to bring about meaningful recovery.

Recovery for patients suffering from storming, becomes a black hole from which few climb out of.  The rationing of therapy to those who benefit most from it, can result in storming patients who need more therapy for tinier gains, never getting enough to rebuild anything.

Long Term Recovery and Alzheimer’s

There is a risk factor of Alzheimer’s and dementia associated with TBI.  For a review of the topic, click on Head injury and dementia by Jellinger.   There is research association shown between the beta amyloid plaques produced even in young patients, with the amyloid plaques of Alzheimer’s.  The mechanism is thought to be through effects of apolipoprotein E.  More study is suggested.

 Caregiver Support




An excellent web resource for caregivers is .  There are huge attitude and psychological  problems that affect the care of those recovering from brain injury.  It is a hard slog that few can handle.

There is much evidence, including the case discussed below of Terry Wallis, that intense, continuous, and loving caregiver support is essential in the recovery of TBI patients.  There is ongoing clinical trial being conducted to learn more about this process [ click here ].

The key problem in dealing with storms is the need to provide intense therapy in an environment of storming that blocks therapy, and many of the drugs used to prevent epilepsy and storming dull the faculties, making recovery difficult.

Coma and the Persistent Vegetative State




Coma is well known to most people as a state where a patient is alive and not responsive.  Coma can last for varying periods of time.  When coma lasts more than a couple of months, a patient is often declared to be in a “persistent vegetative state”.

One of the better reviews of what the prognosis can be for coma and persistent vegetative state is in this section [click here ] in the book Neurologic Rehabilitation:  a guide to diagnosis, prognosis, and treatment planning:  by Mills et al.  I recommend reviewing it or similar sections with patient’s families.  Often physicians and nurses express opinions more than fact in their patient care and discussion with families.  Having something in writing and not spoken is essential.  A published or independent viewpoint is essential because the viewpoint of staff can become suspect and not believable by overstressed family members.

Coma Stimulation

Patients with severe brain injuries like Sabina who exhibit autonomic storming, tend to be in comas, or drifting in and out of coma.  Being in a coma presents a major obstacle to recovery, and autonomic storms tend to interfere with even the modest goals of coma stimulation.  The tendency to abandon hope is overwhelming.  Recovery is put as a miracle, and setbacks such as storms throw everything into reverse.

Bringing patients out of coma has been the topic of many studies in the past, and the experience has been collected into an overview at International Working Party Report On The Vegetative State – 1996 By Dr. Keith Andrews [ click here ].




Patients with severe brain injuries like Sabina who exhibit autonomic storming, tend to be in comas, or drifting in and out of coma.  Being in a coma presents a major obstacle to recovery, and autonomic storms tend to interfere with even the modest goals of coma stimulation.  The tendency to abandon hope is overwhelming.  Recovery is put as a miracle, and setbacks such as storms throw everything into reverse.

Bringing patients out of coma has been the topic of many studies in the past, and the experience has been collected into an overview at International Working Party Report On The Vegetative State – 1996 By Dr. Keith Andrews [ click here ].

Cognitive Rehabilitation

There is an excellent, though dated, review of cognitive rehabilitation by Stuss et al.:  Cognitive Neurorehabilitation, the title being a bit redundant.

Physical Therapy

Occupational Therapy

Speech Therapy






The miracle of Katelyn Atwell [click here and click here ] who overcame an "irreversible coma" due to an infection and graduated from high school.  She suffered a year of storming.

The most miraculous recovery from coma, though it is not published that the victim suffered from autonomic storms, is the nineteen year recovery of Terry Wallis.  Recovery was far from complete, but he was able to speak again.  See details about Terry Wallis.  Look for it on the Discovery Health Channel.  The most interesting and miraculous part of Terry’s recovery is the role of rewiring of the brain as seen in PET scans, and the role of constant interaction with the family to stimulate recovery.  There is also a current clinical trial to test the effect of familial support.

There are the story of Brian Cressler who was in a coma for 18 months, and came out and could speak.  Key for him was intense and continuous therapy so that he could return some function, and can swim.

There is the story of Brent who at 19 was able to restore a great deal of movement after having been in coma for two months through the use of a baclofen pump in rehab.

 Cases with Minimal Outcomes

One issue that is the primary concern of patients with autonomic storming, is that outcomes are generally minimal.  Outcomes do vary with age, in that pediatric patients can experience meaningful recoveries.  Any adult over 30 is unlikely to make a meaningful recovery, and over 40, death is often not far away even with heroic measures.

Often what happens is that the extended hospitalization goes into extended rehabilitation with some positive recovery, but if motor control of the body is lost, communication can consist of eye blinks, or similar minimal motion.  There are two choices for such a patient, one is to place them in a long term care facility such as Northeast Center, or take them home and care for them.  The burden on the family, in either case, is monumental.  The cost will be a fortune, the emotions will be beyond imaginable, and the outcome is often death in a few months or years.  It will tear at the very souls of the family members.

Lemke has the detailed case of a 24 year old male with a severe concussion and brain bleeding [ click here ].  After seven months and aggressive treatment, he is confined to a wheelchair with minimal coordination and attention.  He was treated with high doses of fentanyl early in the course of treatment.

One case is that of Aubrey Robbins in Oklahoma, who went into a coma sometime in 2002 at the age of 16.  The continuing ordeal of her parents is described on Aubrey's website [Website].

Debbie Rich age approximately 45, sustained traumatic brain injury in a traffic accident in North Carolina, April 4, 2003 and died July 8, 2007 with very limited recovery, and an extended deterioration [Website],  The family offers a advice to those caring for severely impaired TBI victims on their website.  They point to the statistic that every 23 seconds someone suffers traumatic brain injury.

Barbara Lillian Romanish 17 years old and pregnant sustained injuries in a car accident, never recovered fully and died after giving birth to a baby [ website ].  She suffered "diffuse axonal injury", basically like shaken baby syndrome where the head is sheared from the spinal column, severing contact with the body.  Diffuse may imply that they could not see anything inn the scans or x-rays.

There is some indication that more intensive rehabilitation can improve outcomes.  Currently, intensive rehabilitation is being tested in Denmark in a clinical trial [ click here ].

 The Future

My goal for the future is twofold.  First is to get proper treatment and diagnoses through the appropriate trauma center for future victims of brain injury.  The second, and what this section deals with, is to encourage the development of effective treatments for brain injury to assure better outcomes and meaningful recoveries.

Some ideas that might be pursued in the future are to look at autism, and hyperactivity and how they are treated since they can exhibit storm-like behavior [reference and reference].  A possible idea would be to look at administering drugs such as Ritalin since it blocks the re-uptake of dopamine.  Similarly, amphetamines block the re-uptake of adrenaline.  There are myriad risks associated with ADHD stimulants, but the mechanism needed is one that blocks the cascade of neurotransmitters by fooling the cells that are dumping them into thinking that the levels are already too high -- a suppression mechanism.  Another might be to look at biofeedback to restore appropriate circadian control over storming events.  These ideas are mine in that no one else is suggesting them, so please regard that in your thoughts.

Autonomic storming has also been triggered by scorpion stings [ reference ].  An excellent description of the autonomic storming associated with scorpions can be found in Davidson’s Clinical Cases. Such effects may be a reason to look at scorpion venom/antivenom and its components for a possible mechanism to block the effects of TBI induced storms.  Perhaps a model as simple as desensitization might work, if the patient were desensitized to scorpion venom, they might suppress the massive release of catecholamines.  The future is being divided into drugs, nutritional support, and mechanical support.

Perhaps key in improving outcomes for TBI and storming patients is prevention and possible repair of cell membrane damage.  A review of glutamate damage from excitotoxicity, and the ensuing destructive feedback loops has been presented [ click here ]

 Future Drug Therapies

Application of the following therapies may require extensive justification and study.  Unless otherwise specified, none of these therapies are recommended by any sanctioning body.

Ammonia (Smelling Salts)

Ammonia is the final breakdown product of protein metabolism, produced in large quantities by the liver and excreted by the kidneys.  Ammonia is also the component of smelling salts, used to induce quick awakening from a fainting spell or revive boxers after a concussion.  The following quote piqued my curiosity by indicating at least short term benefit from ammonia after head injury [ British Journal of Sports Medicine ]:

“With regard to sporting concussions, the real danger is that reaching for smelling salts in this situation is not a substitute for a careful and complete neurological assessment. More serious head injuries may often masquerade in the early stages as a minor head injury and inexperienced careers may falsely assume that an initial improvement, thought to be due to the beneficial effects of smelling salts, may well mask the development of more sinister complications.”

The rapid effect of resuscitation may be due to the ease with which ammonia crosses the blood brain barrier.   Where ammonia may fit in is in its chemical role in the synthesis of glutamine by amidation of glutamate in the astrocytes [ click here ].  Ammonia is seen an indicator for the severity of TBI and the likelihood of developing intracranial hypertension [ click here ].  I would suggest that application of ammonia to the patient would push the reaction creating ammonia towards the left.  Most post traumatic ammonia is created in the following reaction:

            Glutamine ßà Glutamate + Ammonia 

An excess in the ratio of glutamate to ammonia could be made stoichiometric through administration of ammonia, thus allowing conversion of glutamate to glutamine, instead of having glutamate pile up because of lack of ammonia. 

It is the excess of glutamate that induces cell death through opening the Ca++ channel, and glutamates role in promoting the action of peptidases which in turn release more glutamate.  Conversion induced by ammonia reduces the destructive effects of glutamate.  If ammonia has a role in reducing neural cell death, it will likely be in the first minutes and hours after TBI, or in onset of storming.  Currently there is no trial planned to test the effect of ammonia on TBI. 

It is my view that ammonia could play a key role in a timed sequence of treatments for TBI.  For example, ammonia given directly at the site of head injury, may need to be followed by administration of oxygen, and osmotic therapy, and then followed by drug therapy, and then …  Any role of ammonia in the treatment of TBI is purely hypothetical, and there is no recommendation for its use.


Amphetamines are not a standard, accepted TBI therapy.  Perhaps the most optimistic of the Cochrane Database reports pointed to Monoaminergic agonists (eg. Amphetamines) as “The authors state that there is an urgent need to explore the effectiveness of interventions, such as MAAs, for the enhancement of brain repair after a severe injury.”, even though available data was sketchy. Click here .


Apomorphine, a morphine degradation product,  is dopamine receptor agonist, historically used to treat Parkinson’s .  There is a current clinical trial for apomorphine.  It has been shown to be effective in reduce amyloid beta deposition in a model of Alzheimer’s disease [ click here ].



Interestingly, atomoxetine, another drug used to treat ADHD has proven to be of value in treating TBI [click here]. Key to the study in rates was that low doses were critical in getting improved cognition.  If this drug works in human TBI cases, it will need to be titrated to very low levels.  The  same theory could hold for other ADHD drugs.  There may be a significant response for autonomic storms.

Beta-2 Receptor Antagonists

Beta-2 receptor antagonists are a new class of drug being tried out for efficacy in reducing intra-cranial pressure for TBI [ click here ].   Two of these drugs were tried out and lowered the peak ICP to 9.45 (±2.01) torr in the intervention patients compared to 21.89 (±4.69) torr, P = 0.0018 in the control group.  Expect to hear more about XY2405 (Anatibant) and Bradycor CP-0127.  They operate by reducing edema and by reducing the deleterious effects of the catecholamine release triggered by glutamate influx.

Bumetanide and Furosemide (Lasix)

Bumetanide and furosemide are familiar friends to hypertensive and cardiac patients, being the diuretics that are almost universally given to reduce edema.  Bumetanide is 40x more powerful than furosemide.  They are  cation–chloride cotransporter inhibitors.  In animal model tests, they promoted biochemical (ATP) and histological recovery in injured brain tissue [click here].  Basically, they avert the edema of injured, swollen brain tissue.

As discussed above, Na+ channel blocking is key to heading off the cascade of disaster averting the Ca++ channels opening.  The effects of the cation–chloride transport inhibitors is to reduce Na+ influx via the NKCC-1 cotransporter (cotransporters Na–K–Cl cotransporter isoform I, NKCC-1), thereby offering neuroprotection [ click here ].


Caffeinol is a combination of coffee and alcohol administered immediately after stroke or TBI.  Low doses of coffee (2-3 cups) and alcohol (one drink) have been shown to be consistently highly protective of neural cells [ Stroke 2003 ].  Apparently caffeinol does not interfere with other therapy.  It has the virtue that it could be applied anywhere by anyone, even in remote areas to offer protection to those who must suffer long transport times.  It is less effective with those who drink regularly.  Caffeinol has been tested in a rat model for TBI and proven effective [ click here ].  Possible mechanisms for its effect include buffering instabilities in the stimulation of GABA receptors.  Caffeine is a stimulator of GABA, while alcohol is an inhibitor of GABA receptors, and together they could stabilize the GABA receptors from the effects of excessive sympathetic or parasympathetic stimulation.  

Neuroprotection may also be conferred by its ability to reduce NO, nitric oxide, in the same way that uric acid and dehydroascorbic acid do.  Perhaps the alcohol potentiates this effect through more rapid uptake, or increasing the rate of the GLUT1 transporters across the cell membrane, or as a reducing agent.  Studies have shown that either large doses of alcohol or long duration dosage of alcohol increases the NO production [ click here ].  Another possible explanation for the effect of alcohol is its effect of vasoconstriction, pressing more caffeine across the blood-brain barrier.

Another explanation of the ameliorative effects of caffeine could be the stimulation of internal release of Ca++.  The inrush of Ca++ into the cytoplasm appears to stimulate teardown of the microtubules at the site membrane disruption [ click here ].  The effect of releasing cellular Ca++ might have the effect of halting the intrusion of Ca++ and may help to limit teardown of the microtubules.

Speaking anecdotally, I had a 95 year old great aunt who had a horrible diet heavy in cholesterol and never saw a doctor.  She had two continuous habits:  She drank two strong cups of coffee every day and one shot of the good stuff every day.  She only died because of a fall.  Who knows?


Cethrin is a polypeptide Ca++ channel blocker used to good effect on spinal reconstruction to restore axons  It is rho kinase (ROCK) inhibitor.  ROCK It may have application to TBI and storming [ click here ].  Its effect is mostly with the tight junctions with the capillaries and the astrocytes.

Currently for spinal decompression, Cethrin is applied as a past to the damaged area [ click here ].  For TBI, this modality might be applied during hemicraniectomy, or could be applied through a smaller opening in brain.

McKerracher and Higuchi[102] have developed a therapy that exploits the fact that all known myelin and extracellular matrix inhibitors identified thus far signal via activation of the guanosine triphosphatase Rho. When activated, Rho binds to Rho kinase (ROCK), noted to be a key regulator of axonal growth cone dynamics and cellular apoptosis. Their work involves a toxin produced by Clostridium botulinum, C3 transferase, which is a specific inhibitor of Rho. Interruption of this final common pathway thus has the potential to be more potent than efforts to antagonize any single myelin inhibitor. This agent facilitated axonal growth and promoted functional recovery in a mouse model of SCI.[32] The early neurological improvement observed in the C3-treated animals suggested an additional neuroprotective effect. Supporting this, Dubreuil et al.[38] subsequently demonstrated a reduction in p75-dependent apoptosis in association with their therapy.

To improve cellular permeability, McKerracher's group created a recombinant version incorporating a transport sequence. The resulting protein, referred to as BA-210, was commercialized by BioAxone Therapeutic and brought to clinical trial. In the human application, BA-210 is mixed with Tisseal (the combination being called Cethrin), which is applied to the dura at the time of spinal decompression. A Phase I/IIa multicenter, doseescalation trial in humans was initiated under the leadership of the senior author (M.G.F.) at the University of Toronto. Thirty-seven patients with complete SCIs were recruited from 10 North American sites. Cethrin was given within 7 days of injury during spinal stabilization/ decompression surgery. Injuries from T-2 to T-12 and C-4 to T-1 were subject to separate analysis, and 6-month follow-up is planned. Some results from this trial have been released and appear very promising. No significant adverse events have been associated with the Cethrin administration. Of greater interest, a 27% conversion rate from ASIA Grade A to B, C, or D was observed. This must be interpreted with caution given the early phase of this trial and its unrandomized nature; however, this rate of improved neurological function was deemed promising, and a subsequent Phase II study is being conducted under the sponsorship of Alseres Pharmaceuticals.

Channel Blockers (Sodium channel blockers, Calcium channel blockers) and Glutamate/Aspartate Receptor Antangonists

Channel blockers block the flows of various ions across the cell membranes.  A significant Japanese study [ click here ] demonstrated that both excessive activity in the sodium and calcium channels and overstimulation of the glutamate receptors led to neural cell death when deprived of oxygen and glycogen.  They tested both N-methyl-D-aspartate and non- N-methyl-D-aspartate receptor antagonists and found them to reduce neural cell injury.  They tested L-type, N-type and P-type calcium channel blockers, and found them to significantly reduce neural cell damage, especially in combination.  The combination of the three also significantly reduced the glutamate release.  Another study [ click here ] found that blocking the N-channel was the only one to reduce neural activity, while the other channels tended to increase neuroexcitation.  This seems to be borne out by clinical trials that found L-channel calcium blockers to be ineffective [ click here ]

There are also T-type calcium channel blockers which are generally used as anti-epileptics.  They have been studied and found to reduce neuronal death [ click here ] .

As for sodium blockers, most are of the procaine/lidocaine variety, and modulate the sodium channels externally.  Curiously saxotoxin and tetrodotoxin modulate the sodium channels internally.  Tetrodotoxin was shown also to block the glutamate release when oxygen and glucose are depleted.   Currently these agents are not used because of their powerful toxicity.  There are novel drug delivery methods in development that could make these agents therapeutic.

Most curiously is that caffeine is a sodium channel blocker by unknown mechanism.  This is perhaps the reason for the neuroprotective effects of Caffeinol (see above).

It is known that magnesium ions block calcium channels [ click here ], and thus could provide neuroprotection. There is a relevant discussion in the book Excitotoxins: The Taste that Kills by Russell Blaylock.


Citicoline nutritionally  has been shown in rats to improve memory and it indicated as a remedy for memory loss in aging.  It is seen to increase brain cell supplies of phosphatide choline [
click here ].  It is believed to have neuroprotective effects in clinical trial [ click here ].  It has been suggested as a component of combination therapy [ Margulies, et al, 2008 ].


Clonidine may be useful for treating spasticity in autonomic storms, the posturing component [click here ].  It is used in treating Tourette's, and is similar to guanfacin.

CPPene (Midafotel, SDZ EAA 494)

CPPene is a powerful, competitive NMDA receptor antagonist. It was tried for use against epilepsy, but offered no neuronal protection [ click here ] and had significant side effects.  CPPene may have a role for storming patients since the side effects are not germane to a comatose or debilitated patient, but not as a preventative.  In animal models, it mitigated excitotoxicity which is the neural cell death due to glutamate release, a possible model for autonomic storms.  It may have a role shortly after initial injury or ischemia (lack of oxygen) [ click here ].  Another similar drug, Selfotel had similar difficulties for patients and was discontinued.  Newer drugs that are similar may offer better results. 

Darbepoetin alfa (Aranesp®)

Darbeopetin alpha is used to treat anemia and has been implicated in doping scandals.  Currently there is a clinical trial to prove that severe TBI can be treated safely with darbepoetin alpha and that it reduces glutamate through EPO receptor activation.

Dehydroascorbic acid

Dehydroascorbic acid is the oxidized form of Vitamin C.  This is the form most able to cross the blood-brain barrier by using the GLUT1 glucose transporter.  It, like uric acid, has the potential for reducing damage from NO (nitric oxide) during anoxic (lack of oxygen to the brain or parts of the brain) events.  A research paper by Huang et al [ click here ] points to “potent cerebroprotection” in tests on ischemic stroke, where oxygen is deprived.  IV administration could have application in both TBI and storming.

Dexmedetomidine (Precedex®)

Dexmedetomidine is a sedative employed by intensive care units and anesthesiologists.  It can provide sedation without respiratory depression.  It is currently undergoing clinical trial to replace propofol to reduce brain injury expansion.


Erythropoetin is a hormone that regulates red blood cell production.  Certainly one positive effect in TBI is having additional O2 carrying capacity induced by additional RBCs.  Erythropoetin is suggested for treatment of TBI because it is neuroprotective and enhances recovery, has few side effects.  It has time window of 6 hours post insult (Brines et al., 2000; Cherian et al., 2007). Erythropoetin may inhibit apoptosis,  offer anti-inflammatory activity, and can reduce vasospasm.

It has been suggested as a component of combination therapy [ Margulies, et al, 2008 ].


Escitalopram increases neurotransmitter levels of serotonin by blocking its reuptake. Escitalopram of all SSRIs (Selective Serotonin Reuptake Inhibitor)  has the highest affinity for the human serotonin transporter.  Escitalopram at low doses has been demonstrated to restore cognition to non-depressed stroke patients, in addition to being used to reduce typical post-stroke depression since it is an antidepressant.  Escitalopram appears to be most effective in restoration when taken the first few months after stroke [ Medscape ].


So far the major effect observed is that women have a larger window of therapy before markers of neural cell death are observed [click here   Typically women go 14 days before serious secondary injury is observed to the brain, whereas men go 3 days before the markers peak. ].


Glutamine is a form of glutamic acid that more easily pass into the brain.  There is considerable evidence that glutamate neurotoxicity is due to its participation peptide kinases [ click here ].  Glutamine can suppress the effect of glutamine.  Glutamate is detoxified by the attachment of ammonia to form glutamine.


Homeopathy has long been regarded on the edge of quackery.  Homeopathy is mode of treatment that treats disease with minute doses of chemicals that induce symptoms similar to the disease.  A recent study published by Harvard physicians demonstrated that homeopathy made measurable improvements in patients with mild TBI [ click here ].  Certainly more research needs to be done in this area.  For families of patients, I see nothing wrong with bringing in a homeopathic physician to attempt treatment, especially during rehab.  Areas to explore for storming are tetanus toxin and scorpion venom which have manifestations similar to storming.

Dana Ullman referring back to the Harvard study, lists homeopathic remedies for various aspects of autonomic storming and TBI on his website [ click here ] for those interested in pursuing a methodology that does no harm.

Human Growth Hormone (HGH)

Human Growth Hormone is thought to confer restorative properties to TBI patients and because there is a deficiency in HGH in many TBI patients, it there is some thought to bring HGH levels to normal in a current clinical trial [ click here ].


Recent research at NYP using insulin to control ischemic damage after TBI  has not demonstrated positive outcomes [ Oddo et al, 2008 ].  Hyperglycemia needs to be controlled early after brain injury to contain damage.   There is a current clinical trial to determine the effect of strict glycemic control on the outcome of subarachnoid hemorrhage, common in TBI.  The essence of the problem is that the brain needs a lot more energy to overcome injury, and that energy comes from glucose normally.  Alternate sources such as sodium pyruvate or ketone bodies may be more important than insulin.

The theoretical basis for insulin administration for TBI is that it reduce the mitochondrial energy requirements when nutrients are available [ Liu, et. al., 2009 ].  Insulin suppress autophagy, which is the process of the cell consuming bits of itself, organelles, that have become degraded, such as the mitochondria, to avert starvation.   Where things get weird is that acute, short term treatment with insulin promotes production of ATP, extended use of insulin produces the inverse.  The interpretation is that the chronic suppression of atophagy causes problems with the cells, degrading their function.  Cells require sufficient renewal to prevent them wearing out, and the mitochondria need to be renewed.

Ketamine (Ketalar)

Ketamine is a widely used anesthetic with unusual properties, in that it does not lower blood pressure.  It has been used recreationally as it is a dissociative anesthetic.  Ketamine is being tested clinically in Israel for TBI because it is thought to lower intracranial pressure, not to increase as some have theorized [ click here ].  Ketamine is an NMDA receptor antagonist.  There are warnings on ketamine producing Olney's lesions, a form of brain damage caused by neurotoxicity of NMDA receptor antagonists [ click here ].  The effect of NMDA receptor antagonists on Olney's lesions appears stronger in females [ click here ].


Lithium has been found to stimulate neurogenesis and to be neuroprotective.  Mice were repeatedly treated with injections of lithium over 12 days, found a 25% increase in new cells in the dentate gyrus . evidence suggesting that mood stabilizers and antidepressants exert neurotrophic effects and may therefore be of use in the long-term treatment of other neuropsychiatric disorders [ click here ].  Depression is a major problem for TBI patient recovery, so lithium may play a long term role in the treatment of TBI, stroke, and perhaps AD, especially if it can induce neurogenesis in long term.

Magnesium Sulphate (Epsom Salts)

There was clinical trial to test its effectiveness in TBI to reduce swelling in the early hours after injury; the study determined that magnesium sulphate had NO positive effect [ click here ].  It is now being testing for neuroprotective treatment for stroke [ click here ]. 

Manganese and Manganese Superoxide Dismutase

Manganese is a dietary trace element involved in reduction enzymes, in particular Manganese Superoxide Dismutase (Mn-SOD) which is concentrated in the mitochondria..  This makes it a possible therapeutic agent for reducing the destructive effects of superoxides, and in particular in brain injury.  These superoxides in turn are implicated in the peroxidation of lipoproteins in the brain.  Adding manganese or Mn-SOD has been shown to be effective in protecting brain neurons from oxidative damage [ click here ]which can result in cell death..

Methylphenidate (Ritalin)

Methylphenidate has been tested in TBI cases and has improved memory, attention, concentration, and mental processing [ reference ].  It may have use in autonomic storming.

Nicotinamide (Amide of Niacin, Vitamin B3)

Nicotinamide is a derivative of niacin, a vitamin commonly used in high doses for cardiovascular illness.  Nicotinamide does not cause the flushing common with niacin, and is more easily transported across cell membranes.  Nicotinamide is a component of nicotinamide adenine dinucleotide usually abbreviated NAD+ . NAD+ is an oxidizer and when it contributes an electron to reactions, it turns into NADH a reducing agent.  This action considered essential to mitochondrial and cell energy usage.  Most relevant to TBI and storming is NAD+’s role in cell death in neurons due to toxic excitations [ click here ].  Their research indicates providing sufficient NAD+ may have role in relieving bioenergetic stress in toxic excitations associated with Alzheimer’s disease and stroke.  This indicates a possible role in the treatment of TBI and autonomic storms.  An additional role for NAD+ is its ability to add or remove chemical groups from peptides which may be associated with the actions of peptidases and their inhibitors, key to the release of catecholamines.

Significant animal studies have shown that administration of nicotinamide to be effective if administered in doses of 50 mg/kg in any window up to 24 hours, extending to many days, with longer treatments needed if nicotinamide is applied outside of a 4 hour post-insult window [ Hoane, et al, 2008 ].

Currently available trials in Parkinson patients, shows no clinical effect [ click here ].


NNZ-2566 from Neuron Pharma is a neuroprotective agent in a rat model, and is tri-peptide analog of Glypromate [
click here ].  NNZ-2566 is currently in clinical trial at Walter Reed [ click here ].   Cytokines play a role in inflammation of the brain, especially in TBI, and cause additional tissue damage, and NNZ-2566 is thought to mitigate cytokine response.   From Neuron: “Glypromate® (or Glycine-Proline-Glutamate) is a naturally occurring small molecule neuroprotectant, derived from IGF-1 (Insulin-like Growth Factor), that is produced in the brain but does not bind to IGF-1 receptors."   Tests on animals have shown that glypromate, which occurs naturally in the brain, produces impressive brain repair in rats if injected within hours after heart attacks.


Oxytocin has some tantalizing aspects, perhaps in a role of controlling storms.  Oxytocin has been widely studied as a means of controlling the symptoms of withdrawal from opioid addiction [ click here ].  Well, as discussed here, the symptoms of opioid withdrawal are very hard to separate from storming.  Furthermore, weaning a TBI patient from opioids is a horribly complicating factor in recovery and rehab; opioid withdrawal can trigger and mimic storming.

Mechanisms on how this could help are unclear, but two aspects may be at work.  One is that oxytocin is a vasopressor antagonist, and the other is that oxytocin is associated with pituitary and forebrain activity with various mechanisms at play.


P188 is a surfactant that can be applied for human use that has been associated with reducing cell membrane repair through reduced membrane pressure [ click here ].  It may be a therapy that could be applied after injury intrathecally to reduce brain cell damage and cell death.  It could have a major role in stopping the onset of autonomic storming by reducing the Ca++ influx induced by membrane tension.  Quoting from the referred paper:

"We have previously reported that promotion of membrane repair acutely with the non-ionic surfactant poloxamer 188 (P188) restored cell viability to control values at 24 h postinjury. Here, we showed that P188 significantly inhibits apoptosis and prevents necrosis. "

Perfluorocarbon emulsion

Perfluorocarbon emulsions consist of perfluorocarbons which carry 50x more oxygen than blood emulsified with egg yolk solids into water.  The goal is to deliver oxygen to compromised neural cells resulting from stroke or TBI.  Currently the company Oxygen Biotherapeutics, here ]. is in European clinical trials to apply perfluorocarbons to TBI [

Pituitary adenylate cyclase activating polypeptide

PACAP has been shown effective reducing damage to TBI, Parkinson’s, and ischemia.  Recent testing for diffuse axonal injury showed PACAP to be effective in reducing secondary injury.

Proadifen, SKF-525A, Hydrochloride

2-diethylamino-ethyl-2,2-diphenylpropylacetate (SKF-525A) Hydrochloride is a neural Nitric Oxide Synthase (nNOS) inhibitor and works by inhibiting the action of NO in cell death and excitotoxicity [ click here ].  Proadifen also blocks glibenclamide-sensitive K+-channels.  It also inhibits platelet thromboxane synthesis. It has not been put into clinical trial for treatment of storming or TBI.

Progestin , progesterone or progestin metabolites

There is a patent on the treatment of concussion with progestin or its metabolites.   It seems to stop development of the neurological degeneration which leads to storms.  Progestin is the synthetic form of progesterone, a steroid used in birth control pills.  Perhaps progesterone might be as effective, which is beginning phase III clinical trial [ click here ]. 

Progesterone is neuroprotective regulating the genes that control cell death, and may affect TBI through its reduction of extracellular fluid volume.  It tends to pull sodium from cells, which may combat the calcium channel opening drawing in Ca++ effected by glutamate.

It has been suggested as a component of combination therapy [ Margulies, et al, 2008 ].

Pyruvate, Sodium Pyruvate

Pyruvate is an essential component of the citric acid cycle in cellular metabolism, and adding it offers an energy substrate that easily crosses the BBB [ Fukushima et al. 2009 ] and is seen as having a significant role in the management of TBI. New studies indicate that mannitol, should be replaced with either sodium lactate [18807008] or sodium pyruvate.   Also important are its roles and an antioxidant, avoiding uptake of zinc, DNA repair, and recycling lactate as an energy, most important since high lactate levels are associate with negative reactions in TBI.


Retigabine is a novel anti-epileptic drug, a potassium channel agonist, opening specific voltage dependent potassium channels.  It is also increases the effect of GABA in calming neuroexcitability.  By opening the K+ channels, it has relatively little negative effect on the heart.  It may prove of some use in calming the storming patient.

Ritalin (Methylphenidate)

Ritalin is being tested at
Dartmouth for relieving symptoms of TBI later in recovery and rehab [ click here ].  The goal is to relieve memory and attention deficit.


Rolipram is a phosphodiesterase inhibitor, and an anti-inflammatory.  It has been used to ameliorate spinal cord injury through regeneration of severed axonal bodies.

Research on Rolipram applied to TBI by Atkins et al 2007, focused on the period from 15 minutes to two days after insult.  They were able to restore cyclic AMP levels to sham levels, reduced cortical contusion, and neuronal cell survival.  They demonstrated lower levels of inflammatory markers, and fewer observable amyloid beta deposits, the classical markers of Alzheimer’s disease.  Hanila and Filbin, 2008, reviewed various studies and suggest that Rolipram could restore severed spinal cord axons by elevating intracellular cyclic AMP.  If implemented, this could be part of a strategy to restore spinal cord injury.


Rosglitazone is an anti diabetic, with anti-inflammatory properties, and possibly has beneficial properties in Alzheimer’s disease for those with the apoE-4 allele.  Various experiments demonstrated that rosiglitazone increased expression of the GLT1/EAAT2 glutamate transporter that prevented the extracellular glutamate levels from rising to neurotoxic values [ Romera, et al, 2007 ] .


Statins are anti-cholesterol drugs that possess strong anti-inflammatory properties.  Statins have been suggested as a component of combination therapy [ Margulies, et al, 2008 ].

SKF-525A, Hydrochloride

SKF-525A, Hydrochloride is a neural Nitric Oxide Synthase (nNOS) inhibitor and works by inhibiting the action of NO in cell death and excitotoxicity [ click here ].  It also blocks glibenclamide-sensitive K+-channels.  It also inhibits platelet thromboxane synthesis. It has not been put into clinical trial.


SLV334 is a peptidase/protease inhibitor.  Protease inhibitors may be important in the treatment of storms because they inhibit the action of peptidases which split the peptides to release enzymes that produce large quantities of catecholamines and neurotransmitters, the cascades of which cause storming.  Think of peptidases like the wardens in a jail, holding the keys but releasing all the prisoners in case fire.  Think of the protease inhibitors as the local sheriff stopping the warden from doing this erroneously.

SLV334 is produced by Solvay [
presentation ].  It is currently in phase 2a clinical trial in the US [ click here ].  It has been demonstrated in animal models to be neurprotective and cell protective.


Strychnine is a well known poison derived from the nux vomica tree.  It was regarded as a glycine antagonist and chloride/cation channel blocker.  It was widely used in the before 1940 (see below) as a stimulant.  Subsequent research has shown strychnine to block the NMDA- activated channels, with and effect similar to Mg++ [click here].  The research showed strychnine to be an open channel blocker, and is not a glycine antagonist.  Perhaps the reason strychnine is not used widely is there is no money in selling it so research into TBI is not done, and because it does cause death at near therapeutic doses.

There are novel drug delivery methods in development that could make strychnine therapeutic again by significantly lowering toxicity while maintaining effectiveness.

Topiramate + Phenytoin (Dilantin)

There are currently clinical trials to determine if a combination of Topiramate and  Phenytoin can relieve seizures in TBI patients [
click here ] .  Topiramate is currently an anti-epileptic. Phenytoin is of course the famous anti-epileptic of One Flew over the Cuckoo's Nest.  It was a famous orphan drug that essentially replaced phenobarbitol as a less sedative anti-seizure drug. The goal is to eliminate epileptic seizures as a result of TBI by early application, and observe neuroprotective properties leading to better outcomes.

Phenytoin is a Ca++ T channel blocker, which makes it strongly neuroprotective, and thus could be a good choice in TBI and stroke therapy [ click here ].


Triheptanoin is a seven carbon fatty acid unsaponified triglyceride that metabolizes to ketone bodies that easily cross the blood brain barrier.  The fatty acids are a substrate for components of the TCA or citric acid cycle or Krebs cycle.  Any role for triheptanoin is purely hypothetical, and is based on its ability to provide energy in cases where the metabolism of glucose is disrupted.  Its role in TBI and storming is because of research with horses that demonstrate:  “Fatigue was not associated with depletion of citric acid cycle intermediates” and avoided fatigue during sub maximal exercise [1964558].  Brain injury deprives the brain of energy with the accumulation of lactate.  Triheptanoin could avoid the onset fatigue in the brain and the resulting destruction to lactate.

A key life saving application may be to alleviate the complications associated with the application of propofol.  Propofol infusion syndrome is associated with cardiomyopathy and rhabdomyolysis.  Triheptanoin has been tested and shown to relieve the same injuries as the propofol iatrogenic injuries [12122118] because of a:  “defect in energy production results from a depletion of the catalytic intermediates of the citric acid cycle via leakage through cell membranes (cataplerosis)”.

Uric Acid

Uric acid is a byproduct of purine (things like adenine and guanine in DNA, ATP and AMP from cell biochemical processes, and caffeine in coffee) metabolism.  High levels of uric acid are associated with gout.  Uric acid is a scavenger of NO ( Nitric Oxide ) which in high concentrations is implicated in the death of neural cells.  Uric acid has been used to clear NO from cells in studies and reduces cell damage and death from excessive NO [ click here ].  The effects of NO are potentiated by lack of oxygen (hypoxia or anoxia).  Uric acid can cross the blood-brain barrier and is the body’s strongest antioxidant.  Vitamin C acts similarly, but does not easily pass over the blood-brain barrier.  No one has yet used uric acid therapeutically.

Vitamin K and Vitamin A   

It may be that hematomas/concussions may respond to vitamin K and A, which are often recommended for the treatment of bruising topically [ click here ] .  There may be a mechanism that would point to treating severe concussion with intravenous vitamin K and perhaps vitamin A immediately, and in the first couple of weeks.  Bruise treatment might also point to cooling treatment.  Arnica has also been mentioned in the treatment of bruising. 

Li et al at Harvard [ click here ] point to Vitamin K's role in preventing neuronal damage in neo-natal brain cells, and suggest no side effects.  Intravenous vitamin K has is used to treat anticoagulant excess, with the caveat that vitamin K can induce anaphylaxis [ click here ].  What is if interest is the mechanism by which vitamin K reduces bruising.  Clearly before vitamin K could be useful in TBI, the anaphylactic reaction must be understood and controlled.

The biochemical mechanisms of vitamin K center on the carboxylation of glutamate residues, turning them into gamma-carboxyglutamate.  In addition to restoring platelet clotting, there is evidence that vitamin K inhibits cell death due to oxidation in nerve cells [ click here ].  Vitamin K may be the most effective treatment to minimize damage to the patient, especially if used at the scene of accident and in the first minutes after injury. Vitamin K is currently used to relieve platelet abnormalities [ click here ] in the ICU.  K's role in the dealing with cell death and glutamate pathways, make it a candidate for a larger role.  Elsewhere on this page, is a discussion on high levels of glutamate being a predictor of poor outcomes.  It may be that the high levels of glutamate require higher levels of K to clear them. 

 Future Nutritional Support

One reason for separating nutritional support is that application of therapy may not require a medical or nursing protocol, in that support could be applied by a dietician.  The following are widely available vitamins and supplements with actions that could affect outcomes.   Studies would be welcomed.

N-acetyl-cysteine (NAC)

N-acetyl-cysteine (NAC) is an anti-oxidant used to   It is being applied in a clinical trial to mitigate deficiencie in balance, hearing, and cognition [ click here ].  Laboratory work has been done demonstrating mitigation of the effects of TBI if given in the first 8 to 24 hours.

Acetyl L-Carnitine & Lipoic Acid

L-Carnitine administration was administered to brain injured rats to boost mitochondrial function in the presence of hypoxia with numerous positive effects [ click here ].  L-Carnitine was used to mitigate the cardiac effects of scorpion stings that resulted in autonomic storms;  in the study,  L-Carnitine boosted the effective strength of the mitochondrial DNA in cell metabolism [ click here ].  A combination of acetyl -L-carnitine and alpha lipoic acid were used to increase mitochondrial activity [click here] and reduce the effects of enzyme damage and aging.  Given the benign nature of these agents, one might consider that they be added to a treatment regimen for TBI.   With some irony, the research on mitochondria was done at the Oakland Children's hospital in nutrition, where Sabina volunteered, by researchers at UC Berkeley where she studied nutrition and microbiology.

Most importantly there is a report that L-Carnitine affects the glutamate cycle protects against glutamate and kainic acid neurological toxicity.  Suppressing the glutamate cell toxicity is the key to recovery in TBI.

Dipeptide of Glutamine and Alanine  

This dipeptide was applied to TBI patients and in the study reduced NICU stay and lowered mortality [ click here ].  This is purely a nutritional therapy.  This dipeptide has been found to reduce infections in ICU stays [ click here ].  It has been used as nutritional therapy for pancreatitis [ click here ], a complication that afflicted Sabina.

Future Mechanical Support

Mechanical support is to refine the application the manner in which care is extended to the patient.

Automated drug administration

Automated drug administration is the administration of pharmaceuticals by mechanical means.  Currently only baclofen is administered through an intrathecal pump for TBI patients experiencing storms. Automated administration could be by sensing of storming triggers by a decision tree program, or by point and click administration from a nursing station.

It is possible that other drugs such as opioids, beta blockers, or anti-posturing drugs could be administered in this fashion.

Automated physical therapy

One area that Sabina suffered in was the lack of physical therapy.  I realize that there are limits on the time available from therapists.  One way to improve therapy is to create robotic therapy assistance.  Design would need to be injury proof and would require extensive engineering.

Dynamic Simulation

One area not fully explored it to model the brain cells mechanically, the brain, the meninges, skull and tissues for the full effects of head injury on the cell structure.  In particular, any tearing of the axons, brain interfaces to the lower brain, hearing, eyes and nasal cells could illuminate cellular treatment mechanisms that might ensure better outcomes.  It is the "diffuse axonal injury" that should receive some careful attention.  It is my view that if the cell tearing, and cell distension can be modeled, they might be treatable preventing cell death.  Programs DYNA3D, and LS DYNA should be applicable to TBI modeling.  These programs are capable of modeling shock waves in explosions and should be applicable shock waves in the brain.

Hypothermia (induced)

There is a study in Australia in New Zealand to determine if children with severe TBI can be treated with hypothermia to 32 degrees Celsius improve over non chilled children [ click here ].  There was a clinical study at various in the US to test the same cooling methods [ click hereclick here ]. ].  The follow-up is ongoing [

Imaging improvements

Imaging is constantly being improved.  For TBI patients, more refined resolution is needed to guide therapy and improve prediction accuracy.

Thermal Control improvements

Currently thermal cooling is severely limited because of the design of the cooling vests.  There has been recent research in New Zealand to test a head cooling device called CoolCap on newborns that protects them from brain damage due to oxygen deprivation [ CoolCap ].  It was part of a clinical trial reported in Lancet .  CoolCap is the subject of a current clinical trial in the US.  Cooling the head would seem to better than cooling vests for TBI patients since that is the region that generates the fever and needs rapid cooling to prevent brain injury.  I would encourage a version of CoolCap for adults, and one that is temperature feedback directed, preferably through temperature measurement at the ear.  A major advantage of cooling the head is that it does away with the complication of shivering with cooling vests, which could cause more heating and more storming.

As for cooling vests, to prevent infection and sores, these vests may only be applied for limited times.  Perhaps instead of pumping water in coolant jackets, cool air could be pumped onto the patient’s skin, in some sort of inflated garment or bed.  Water beds might be applicable to the lower part of the patient's body since most TBI patients must maintain some sort of elevated posture.  There is a patent on the colo-rectal heat exchanger [ click here ] that may be of great benefit in controlling temperature in the storming patient.  Getting good heat exchange, doing it quickly, and being able to repeat the process are essential for storming patients.

Hemodialysis is another option [ reference ] for cooling the patient.

Feedback response needs to be attuned to the needs of  a storming patient.  Small, rapid elevations in temperature needs to be attacked with fast, aggressive cooling to normal temperatures, often to stave off a storm.

Classical Medicine on Concussions


I came across Encyclopædia Medica by Chalmers Watson.  It describes in detail, the treatment of severe concussion in 1899.  Why is it interesting in this time of modern medicine?  Because it contains, like South American or tribal lore, remedies and cures that have been tested by time and experience without scientific theory.  Many of these experiences have been discarded because of general fashion, and because of the limitations of science to find any theoretic backing for some of the remedies, and because many of the practices were labor intensive – they lacked ease and efficiency.


I bring them to attention now because modern biochemistry and care may be catching up with some archaic practices.  Here is a series of quotes by Watson that may be worthy of attention, emphasis mine:

“Treatment of Concussion.—In the first stage the symptoms of shock must be met by keeping the head low, and applying warmth and friction to the surface of the body; a warm water [infusion] may be of some use, but alcoholic [See above on caffeinol] stimulants are only to be given with great caution in cases of profound and obstinate collapse, as their use may induce too severe reaction, and tend to produce haemorrhage or inflammatory action. A passing stimulant, such as aromatic spirit of ammonia, or inhalation of strong smelling salts [See above on ammonia] is less objectionable.”

“Such drugs as strychnia and strophanthus [Lo and behold, NMDA channel blockers, see above] used hypodermically must be reserved for desperate cases. […] Irrigation of the head with hot water [This is interesting because warmth is applied to reduce bruising, which has the same presentation as a concussion, followed by cold] is said by Horsley to be of great use in bringing about reaction in cases of severe concussion.”

    “The treatment of the second stage is to be directed towards preventing excessive reaction. The patient should be kept in bed in a dark and quiet room, his diet should be light, his bowels should be kept freely open, and on no account should he be allowed to read or transact any business until convalescence is well established. […]”

“In cases of cerebral irritation the use of an ice-bag to the shaved head,[interesting in light of the work done on the CoolCap, see above] small doses of bromide of ammonium, [here is our friend ammonia in a form transportable in the blood to the brain] and a digestible but nutritious diet, are the chief additional points of importance.”

Put Me in the Skeptical Camp

This section is devoted to cures that for one reason or another that I am skeptical of.  I would be happy to be proven wrong, and offer anyone the opportunity to prove me wrong.  Basically, there appear to be no unconventional therapies for autonomic storms. 

Glutathione, Intravenous

This is a therapy championed by Dr David Perlmutter of Florida.  There has been a video exclaiming its effectiveness against Parkinsonism with the theory that it prevents free radicals [ click here ].  The mechanism for relief is unclear, and there have been those who question the therapy [ click here ].

Hyperbaric Oxygen Therapy

This is another therapy championed by Dr David Perlmutter, among others.   There is the case of George Melendez who sustained a near drowning experience and benefited from hyperbaric oxygen therapy [Click here].  Hyperbaric oxygen currently has no place for autonomic storms caused by traumatic brain damage, other than to preserve organs for transplantation [reference].  There is a clinical trial in progress seeking new patients [ click here ]. 

Stem Cells

Some stem cell experimentation has been done on an infant with brain injury,  along with hyperbaric oxygen therapy, click here.  There is a clinical trial at U of Texas, not seeking participants [ click here ].  Personally, I am beginning to see stem cells as a solution in search of a problem [ Cell Medicine ].

 Protocol Recommendations

I am going to disclaim these recommendations since I am not a doctor or nurse, and administration of any protocols should be at a doctor's or nurse's judgment.

There are these focuses for treating storming and traumatic brain injury:

1.     General neuroprotection ( TBI first aid )

2.     Blood pressure and heart rate control

3.     Intracranial pressure

4.     Temperature control

5.     Glutamate cascade control

6.     Spasticity control

General neuroprotection is basically first aid, and measures that are most effective in the minutes and hours after injury.  TBI first aid for lay people:

1.     For the unconscious patient, smelling salts and artificial respiration if needed.

2.     For the conscious patient caffeinol is the most accessible measure and should be administered  if advanced first aid is not available. 

First aid by ambulance personnel should include osmotic therapy for moderate to severe injury.  The goal is to reduce cell membrane pressure differentials to minimize leakage of cell contents, and allow membrane repair sufficient time.

First line of attack on intracranial pressure in the past has been a mannitol bolus.  Next in line would be a bolus of thiopental initiating barbiturate therapy.  If that fails to bring down ICP, then presented with refractory intracranial hypertension, I would steer neurosurgeons to a decompressive laparotomy.  I consider a hemicraniectomy barbaric, and not likely to salvage the patient fully, although hemicriectomy is currently the treatment of choice for in hospital care to relieve the refractory intracranial hypertension.  Propofol should not be used at all because of its known hazards and the lack of patient history, and because anesthesia may be needed for extended periods and propofol may induce a cascade of catecholamines.  Hypothermia, or cooling the patient if means are available should be considered.  

Other low risk therapies to add are NAC, manganese, Mn-SOD, alpha lipoic acid, and L-acetylcarnitine (it protects against glutamate toxicity).  Vitamin K may be appropriate.  For the glutamate cascade control, the recommendation would be for glutamine administration as the simplest, with the addition of any of the peptidase inhibitors, if available.

Other agents associated with better outcomes are gabapentin, and bromocriptine to control epileptic events and storming.

For blood pressure and heart rate control (tachycardia), the beta blockers are preferred, with labetalol first choice.

Temperature control methods need to start early to be effective.  Vitals should be treated fairly quickly, and thermal control should be started in parallel. Control of temperature also stabilizes vitals.  For temperature control, feedback cooling would be a first choice.  Should that prove complicated, second would be the opioids, with morphine sulphate preferred.

Should the patient prove unresponsive to opioids and beta blockers, then dexmedetomindine should be tried.

For spasticity control, the first choice would be the baclofen pump.  Second would be dantrolene.  Gabapentin should be available for convulsive reactions.  Given the experiences published with the use of a baclofen pump on storming, I would advocate implanting a baclofen pump at the first diagnosis of a storming patient.  A baclofen pump could save an enormous amount of stress on the patient and staff, and get the patient to rehab much faster.

Current care practices for storming are not adequate to the job.  Above all of this is that for patients exhibiting storming, there needs to be an intensive care protocol that is a level above current care.  What happens in a storm is that onset comes within time frames of minutes.  Stopping a storm at onset reduces physical impact to the patient, and also lowers the need for nursing care.  Heading off a storm can mean minor drug or thermal treatments, whereas an uncontrolled, full blown storm can consume a team of three or four nurses for over eight hours, all with the strongest doses of the strongest drugs.  The problem is that nurses when they have other duties miss the little signals that a storm is incipient.  By the time it triggers their alarms, or they can free themselves to treat, things are out of control.

So, I am advocating either special protocols within ICUs to dedicate a single nurse to a storming patient, which can be a lesser qualified nurse, just a nurse sitting by the patient that can recognize a storm forming, and handle an array of initial treatments to head off a storm.  Or, I am advocating a post trauma, hyper-intensive care facility where storming patients are brought to that has a 1:1 patient/nurse ratio.  If proper nursing intensive care is not available, such as a facility without a neuro-ICU, I would strongly consider having a baclofen pump installed to minimize storming and its consequences.  Proper treatment of storming is difficult, stressful to both patient and nurse, and requires strong focus; no ordering of pad thai while on duty.

 References and Links

Whenever I now read, hear or see any instance of traumatic brain injury, my thoughts lead to questioning Sabina's care and circumstances of her death.  I have come to know others who had to deal with the recovery of traumatic brain injury.  Many of the medical care issues exposed apply generally to serious hospitalization, especially those with potentially fatal outcomes.

Our family's experience has led me to produce both a list of recommendations for patients and loved ones, and a proposal for a Patient's Bill of Rights [ go to Healthcare Page ].

[1]  Lemke, D. M., "Riding Out the Storm: Sympathetic Storming after Traumatic Brain Injury", Journal of Neuroscience Nursing, February 2004 • Volume 36, Number 1, .

] Rabinstein A. A,  E. E. Benarroch,  "Treatment of paroxysmal sympathetic hyperactivity"  Current Treatment Options in Neurology 2008;10(2):151-7,





Baguley, I.J. R. E Heriseanu, J A Gurka, A Nordenbo, I. D. Cameron, "




Gabapentin in the management of dysautonomia following severe traumatic brain injury: a case series "




, Journal of Neurology, Neurosurgery, and Psychiatry 2007;78:539-541 ,





Rabinstein A.A., & E. F.M. Wijdicks, "The Autonomic Storm", Primer on the Autonomic Nervous System, 2nd edition,  Academic Press.

[4] Turner, M.S,




"Early use of intrathecal baclofen in brain injury in pediatric patients", Acta Neurochir Suppl. 2003:87:81-3, .

[5] Kishner, S., "Post Head Injury Autonomic Complications: Treatment & Medication",





Goddeau Jr., R. P., S. B. Silverman & J. R. Sims, "Dexmedetomidine for the treatment of paroxysmal autonomic instability with dystonia", Neurocritical Care, .

[7] J. A. Blackman,  P. D. Patrick, M. L. Buck, R. S. Rust, Jr,  "Paroxysmal Autonomic Instability With Dystonia After Brain Injury", Arch.
Neurol. 61, Mar 2004, .

[8] Minardi, J., and Todd J. Crocco, MD, “Management of Traumatic Brain Injury:  First Link in Chain of Survival”,  MOUNT SINAI JOURNAL OF MEDICINE 76:138–144, 2009.

ICP -- Intracranial Pressure
NICU -- Neurological Intensive Care Unit
TBI -- Traumatic Brain Injury

Sabina had a spirit that shined on everyone that knew her.  May the Lord keep her close to Him.

Behold, I send an Angel before you to keep you in the way and to bring you into the place which I have prepared.


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