evidence, epistemology,equipoise and pediatric trauma craig downs, ms, do; facem, faap, facop, fccm...

Evidence, Epistemology,Equipoise and Pediatric Trauma

Craig Downs, MS, DO; FACEM, FAAP, FACOP, FCCM

Assistant Professor, Child Health

Pediatric Critical Care

University of Missouri-Columbia

Columbia, Missouri

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Evidence, Epistemology, Equipoise and Pediatric Trauma

And How Pediatric Critical Care Happens to be intertwined in all the Above

Why we should Talk About These Things

And What we Should Expect when we “look” at the “Evidence”

And How we consider each patient in a complete, autonomous way

And How we can pass all we “know” along to those who really need to “know”

And If we can really maintain “Balance” in our Decisions

And How we can use what we know to always improve all our patient outcomes

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Definitions:

Evidence: First an example:

In 1988 there were 350,000 cases of Polio worldwide. In 2012, there were 223. (This is Evidence: Grade 1; Class 1: FACT)

Getting to Zero cases is likely to require spending billions of Dollars (US) and going to remote regions of the World, confronting Taliban Militants to get to the last unprotected Children on Earth. (This is conjecture, dream or what have you: sometimes called opinion; and is not subject to a test of any type; not an RCT or otherwise)

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“To see the world in a grain of sand,

And a heaven in a wild flower

hold infinity in the palm of your hand

and eternity in an hour” W. Blake

Since Time before Time, Children have been left on the streets, in closets, chained to work places and otherwise debased. They have been Abused, Tortured, Killed and Abandoned.

In the late 1800’s and early 1900’s, Children were considered Property and were bought and sold.

Trauma remains the Largest Killer of Children ages: 1-17, thus, it behooves us to witness and stop this Epidemic 4


Estimate of the cost of Childhood Trauma:

$357 Billion per year

$257 Billion per year in lost quality of life

15% of all Medical Spending due to Trauma

95% of serious head injuries due to AHT

AHT requires intense investigation without prejudice

AHT mortality: 15-38% and morbidity high

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Children change—this is not something new—throughout their days. However, the maxim: “Children are just little Adults” vastly debases Children and All those who Do and Would Provide Medical Care to and for Children.

“Could there be any better way to get my nose rubbed in the truth of impermanence than to love a child in a jagged, careless world? and even if everything goes absolutely perfectly, I know that this particular Skye—the one who warbles and passionately sucks on the bill of his rubber duck as he splashes with me in the tub—is going to dissolve like bubble bath. Yesterday he was kicking bulge in my belly as I swam laps in the July sun; tomorrow he’ll be a middle-aged man, weeping and scattering my ashes in a mountain lake” Anne Cushman, Buddhist writer and mother. 6


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Definition: EVIDENCE:

As used in the phrase: “Evidence-Based Medicine”

First used by Gordan Guyatt, 1991

Evidence-Based Medicine, ACP Journal Club, 1991, Volume: 114; (Supplement. 2); A16; Guyatt, G.

In 2001: The New York Times judged EBM as the idea of the year with respect to the procurement of knowledge in Medicine.

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History of EBM:

1972: Archie Cochrane, director of the Medical Research Council Epidemiology Research Unit in Cardiff, Wales publishes: Effectiveness and Efficiency: Random Reflections on Health Services

Late 1980s/early 1990s: Guyatt and David Sackett from Toronto; and David Eddy from Duke begin publishing additional works.

Basic Premise (at the start/since severely modified): we should treat where there is evidence of benefit and not treat where there is evidence of no benefit (or harm).

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There are other kinds of Evidence

Every Clinician Must be Aware

Fact: and these Facts may change, and the “Truth” may be altered.

Legal

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About the Legal:

Anything presented in support of an assertion

May be strong or weak

Strong: Provides direct Proof of the Truth of an assertion

Weak: Consistent, but does not rule out other, even contradictory assertions (circumstantial evidence)

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About the Scientific: (Medical—sometimes)

Observations and Experiments

May support, refute or modify

Develop Theory

Develop Hypothesis

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In Philosophy:

Evidence is tied to Epistemology

Epistemology is the study of the nature of knowledge: suppositions, conclusions and all that happens in between—how we know things; the structure of knowledge itself

From the Greek: Episteme: Knowledge

Thus: “what” we “know”; “how” we “know” and “why” we “know” all become important in understanding Evidence

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Definition: Equipoise:

Equipoise, and Clinical Equipoise provide the ethical basis for medical research involving patients assigned to different treatment arms of a clinical trial. Clinical Equipoise was first used by:

Benjamin Freedman: NEJM; 1987 in: Special Article: Equipoise and the Ethics of Clinical Research; New England Journal of Medicine; vol. 317; No. 3; pages: 141-145

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One Part of New Paradigm of EBM was to eliminate the “Expert”. This was part of the very early days of EBM, and has since been the source of intense and voluminous discussion. Subsequently, EBM has recognized “Expert” in the grading system, although at the lowest level of “evidence”

Why this is a Problem: at the interface of Medicine and Law: the Daubert Standard: This “Standard” provides a rule of evidence regarding the admissibility of an “Expert” witness testimony in a US Federal Legal Proceeding. 15


The Daubert Trilogy:

3 US Supreme Court cases:

Daubert v Merrell Dow: 1993; via Rule 702 of the Federal rules of Evidence, didn't incorporate general acceptance test.

General Electric Co v Joiner: a district court judge could exclude “expert” testimony when gaps existed between the evidence relied upon by an expert and his/her conclusion

Kumho Tire Co v Carmichael: 1999; the judges gatekeeping function identified in Daubert applies to all expert testimony, including that which is non-scientific. 16


What then is “Evidence”?

How can we “Experiment” Scientifically using Children so that we have epistemic awareness and proceed with Equipoise?

Axioms in philosophy are not axioms until they have proved upon our pulses; we read fine things but never feel them to the full until we have gone the same steps as the author. John Keats 17


Evidence and Equipoise have detractors

Miller, F.G. & Brody, H.; A Critique of Clinical Equipoise: Therapeutic Misconception in the Ethics of Clinical Trials; The Hastings Center Report; 2003; 33 (3); 19-28

Veatch, R; The Irrelevance of Equipoise; Journal of Medical Philosophy, 2007, 32(2); 167-83

Tonelli, M.R.; Integrating Clinical Research in Clinical Decision Making; New Challenges in Translational Medicine, 2011, 47(1); 26-30

Zoccali, C.; Evidence-based medicine: The Clinician’s Perspective; Nephrology, Dialysis and Transplantation; 1999; 14(suppl. 3); 42-45 18


Vaclev Havel

“It is I who Must Begin”

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What I would like to Indicate:

“When I use a word,” Humpty Dumpty said in rather a scornful tone, “it means just what I choose it to mean—neither more nor less.”

“The question is,” said Alice, “whether you can make words mean so many different things”“The question is,” said Humpty Dumpty, “which is to be master— That’s all”

(Through the Looking Glass: Chapter 6)

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In general, we believe:

EBM has Value and Non-value

Using EBM requires Equipoise

“To show that the optimal practice of clinical medicine, though requiring the knowledge of the results of clinical and bench research, demands that doctors thoughtfully consider both evidentiary and non-evidentiary warrants for action in each attempt to deliver the best care to a particular individual” Tonelli, MA; Integrating Evidence into Clinical Practice: an Alternative to Evidence-based Approaches: J. Eval. Clinical Practice; 2006, v.12 No. 3;

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As One Example of How Things Change/are Impermanent:

“Renal Dose Dopamine: From Hypothesis to Paradigm to Dogma to Myth and, Finally, Superstition?” Jones, D and Bellomo, R; J. Intensive Care Medicine; 2004; accessed at: http://jic.sagepub.com/content/20/4/19

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A Second Example:

“Revising a Dogma: Ketamine for Patients with Neurological Injury?’ Himmelseher, & Durieux; Anesth. Analg. 2005; vol. 101; pages: 524-534

• With These Two examples we begin to have an appreciation for:

• Understanding what we “know” as Evidence

• The Ethics of what we do because we “know”

• The Loss of Equipoise that prevents us from doing further studies.

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Medicine, Philosophy, and How we Think as Physicians are intimately related to the Actions we undertake for the Individual and Society. We must care for the Whole Person, as well as the Whole Society. Thus, any study, any source of Evidence, must add to our Epistemic Base, and each Therapy, when No Therapy is clearly superior to another, requires an Ethical Stance with Clinical, Systemic, and Research Equipoise. The Truth of Pediatric Critical Care and the Truth of the Care of the Pediatric Trauma Patient comes from Knowledge of Physiology, Pathophysiology, Anatomy, Biochemistry, the Sciences of Engineering, Physics, Cell Biology, Complex Systems and assorted others. 25


“Medicine and Philosophy oscillate about each other like strands of a complex double helix of the intellect. They are intermittently drawn together by their immersion in man’s preoccupations with that existence.”

“A central Problem in Technological Societies is the Judicious containment of the Expert.”

“A Philosophical Basis of Medical Practice; Towards a Philosophy and Ethic of the Healing Professions” E. Pelegrino and D. Thomasma; Oxford Press; 1981

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Vaclev Havel: “Education is the Ability to Perceive the Hidden Connections between Phenomena”

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“Review Article: The Genetic predisposition to adverse outcome after Trauma” Giannoudis, PV; van Griensven, M; Tsiridis, E; Pape. HC; 2007; British: J. Bone Joint Surgery; 89B No. 10; October; pages: 1273-1279

(From the Abstract): Technological advances and shorter rescue times have allowed early and effective resuscitation after trauma and brought attention to the host response to injury. This review examines the current evidence the genetic predisposition to adverse outcome after trauma. 29


Current Evidence indicates that the early SIRS response in Children and Adults following Trauma and/or major surgery is characterized by pro inflammatory cytokine release, microcirculatory disturbance, cell-mediated immune disfunction followed by a (sometimes over) compensatory response from the anti-inflammatory system which can predispose children (and adults) to opportunistic infection, multiple organ dysfunction syndrome and death.

Since about 2006; the vascular Endothelial Glycocalyx has been a subject of significant research. This lines the endothelium, changes the Starling Law, is altered significantly by trauma and resuscitation fluids and may be the “Next Big Thing” to target in critical care of children who have been subjected to trauma.

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Trauma is the leading cause of Death in Infants and Children ages 1-14 in the USA

Head Injury: 38% of the overall injury burden

Motor Vehicle Trauma is the cause of most injuries

over 5000 traumatic Deaths per year in the US

Trauma causes 50% of Deaths ages 5-34 years

Over $16 Billion (>16,000,000,000) spent each year caring for children who are less than 16 years of age who sustain Traumatic Injuries

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30 million ED visits per year for children

Think about Alcohol in anyone over age: 12 years (various studies have found this to be a discriminator) (although it may change)

Don’t need to do a Rectal Exam in children unless there is a very specific reason, and then they should be sedated/or during another anesthesia event. (several studies; class 1/2 i.e. : good to very good evidence)

Think about Child Abuse and when you do; there must be (at the right time) a dilated Ophthalmologic Exam

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Highest childhood in-hospital mortality after Trauma: Adult Hospitals with Pediatric Units: 2.4%

Lowest childhood in-hospital mortality after Trauma: Pediatric Hospitals: 0.9%

Think about suicide/attempted suicide when adolescent alone in MVC.

Think about Drugs of Abuse, as well as Drugs that are legal, and don’t show up on typical Toxicology screen

Think about Quality, Safety and Whole Family Care 33


Evidence: having the family present during resuscitation, trauma activation, or other significant events in the life of the child does not interfere with care; does provide appropriate family interactions, and does enable care givers and families to more completely understand each other.(published evidence from multiple family question/surveys and from interviews with physicians immediately after CPR events and such: NO RCT—how would you do it? does this mean that we can’t use this data?; and my own evidence from Pre-hospital to ED, Pediatric Units, and PICUs over the past 30 years; the first paper I read about this topic was published in 1979)

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Quality Improvement Aspects:

Trauma System Organization

IMPACT study: a Prospective RCT

In-Hospital Care

Long-Term Care

Quality of Life

Family Burden

PTSD

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Radiology Care: ALARA

Use CAT scan carefully

Use Radiographs Appropriately

Pediatric blunt trauma patients receive a major radiation burden in their initial evaluation, while children who are transferred from a first hospital endure an even higher dose of radiation. from: Evaluation of Radiation Exposure to Pediatric Trauma Patients: Tepper, B; Brice, JH; Hobgood, CD; The Journal of Emergency Medicine, vol. 44; No. 3; pages: 646-652 2013

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More than 62 Million CAT scans/year in the US

More than 7 Million Pediatric CAT scans/year in the US

Pediatric Trauma patients receive an average dose of 12.8 mSv/trauma incident. 2009 statistics from Pediatric Academic Society.

11.42 people will get radiation induced cancer for every 10,000 exposed to 10 mSv (NAS)

Pediatric population more sensitive by a factor of 3-10

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In a 1 year old who has a CAT scan using typical adult CAT scan parameters:

Risk of Dying from Cancer: 1 in 550 after ONE abdominal CAT scan

Risk of Dying from Cancer: 1 in 1500 after ONE brain CAT scan

Estimated risks of radiation induced fatal cancer from Pediatric CT. ; AJR (Am J Roentgenol) 2001, Vol. 176; pages: 289-96; Brenner, D; Elliston, C; Hall, E.; Berdon, W 38


Radiation exposure from CT scans in Childhood and subsequent risk of Leukemia and Brain Tumors: A retrospective Cohort Study, Lancet, 2012

178,604 children age <22 yrs; 1998-2005

No Cancer prior to first CT

283,919 CT scans

Leukemia: 74

Brain Tumor: 135

If >30 mGy; RR leukemia: 3.18

if >50 mGy: RR Brain Tumor: 2.82 39


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BRAIN TRAUMA

Recent Data: 1.7 million people with TBI/year: USA

Of Children aged: 0-14 Years of age

474,000 ED visits per year

35,000 Hospitalizations per year

2,174 Deaths per year

cdc.gov/ncipc/tbi/coaches_tool_kit.htm

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BRAIN TRAUMA

According to CDC estimates: 5.3 million Americans have long-term or life time need for help

From Concussion to Severe Brain Trauma may have many functional problems:

Thinking

Sensation

Language

Emotion 47


BRAIN TRAUMA: SUMMARY OF RECOMMENDED PRACTICE IN PICU

Allow Family Contact

Avoid Hyperglycemia

Avoid Hypercarbia

Avoid Hyperthermia

Avoid Hypothermia

Hyperosmolar Therapy

Prevent Seizures 48


BRAIN TRAUMA: SUMMARY OF RECOMMENDED PRACTICE IN PICU

Treat Pain and Agitation

Mid-line neck, 30 degree head elevation

Pentobarbital for severe/refractory ICP

Decompressive Craniectomy

EVIDENCE: None of the above has an RCT as evidence/proof but we do them, and it is likely that there would be no Equipoise to even do an RCT.

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Mechanism of action: Hyperosmolar Agents:

Q = (πΔPr⁴)/(8νl)

Thus, both Mannitol and Hyperosmolar Saline reduce the ICP due to rheologic effects, and not osmotic diuresis. They both reduce blood viscosity, which allows for reduced vessel caliber while maintaining blood flow, represented by Poiseulle’s Law—as noted above.

If one is to discuss a therapy, one must know how it creates its action. 50


Not sufficient Evidence to recommend:

Anticonvulsants in children with Brain Trauma

Hypothermia in children with Brain Trauma

Corticosteroids: Not Recommended

Hyperthermia and Hypercarbia: a single episode of 1-2F elevation or a single episode of PaCO2 over 45 torr; has been associated with worse outcome—but no RCT has been done.

Serial imaging in the child with head trauma has not been validated. If needed/indicated: MRI better than CAT scan.

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As the care of the injured child moves into the future: look for further ways to care for the child with Brain Trauma:

Diffusion Tensor MR imaging

NIRS

Management of Oxidative Stress

Manipulation of Antioxidant reserves

Manipulation of the Endothelial Surface Layer —-the Glycocalx—

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Thoracic Trauma

Approximately 4-6% of the children hospitalized for Trauma

Second leading cause of death in childhood trauma: 25% of childhood trauma deaths

Most chest injuries can be managed non-operatively or with a chest tube.

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Concerning Resuscitative Thoracotomy:

No RCT has ever been done—only expert opinion and the outcome from expert surgeons

Resuscitative Thoracotomy:

Indication: Penetrating Trauma with measurable vital signs in the field

NO INDICATION: Blunt Trauma without measurable vital signs in the ED—they all die.

Consider: Blunt Trauma with vital signs in the ED and witnessed cardiac arrest. 54


Other Thoracic Injuries Children Sustain: THINK

Chest wall/rib

Pulmonary Parenchyma

Tracheobronchial Injury

Esophageal Injury

Traumatic Asphyxia

Diaphragm Injuries

Mediastinal/Great Vessel 55


A Few Words about Other Items:

Look for Prognostic Markers: Procalcitonin, IL-6; TNF-alpha; TREM-1; IL-10; CD14

Biological Markers that will predict Acute Kidney Injury: Urine/plasma Neutrophil gelatinase-associated lipocalin (NGAL)

Mortalin (Mitochondrial heat shock protein)

Presepsin (sCD14-subtype)56


If you are interested:

Biological Markers of Acute Kidney Injury; Siew, ED; Ware, LB; Ikizler, TA; J. Am. Soc. Nephrology; Vol. 22; 2011; pages: 810-820

Interleukin-6 as inflammatory marker referring to multiple organ dysfunction syndrome in severely injured children; Andruszkow, Fischer, Sasse, Brunnemer, Andruszkow, Gansslen, Hildebrand, Frink; Scandinavian J of Trauma, Resuscitation and Emergency Medicine; Vol 22, No 16; 2014

Mortalin and DJ-1 coordinately regulate hematopoietic stem cell function through the control of oxidative stress; Tai-Nagara; Matsouka; Ariga; Suda; Blood; Vol. 123, No. 1; Jan. 2014; 41-50

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Assessment of Antioxidant Reserves and Oxidative Stress in Cerebrospinal Fluid after Severe Traumatic Brain Injury in Infants and Children: Bayir, H; Kagan,V; Tyurina, Y; Tyurin, V; Ruppel, R; Adelson, PD; Graham, S; Janesko, K; Clark, RSB; Kochanek, P; Pediatric Research; Vol 51, No 5; 2002; pages: 571-578

Diffusion Tensor MR imaging Reveals Persistent White Matter Alteration after Traumatic Brain Injury Experienced during Early Childhood; Yuan, W; Holland, SK; Schmithorst, VJ; Walz, NC; Cecil, KM; Jones, BV; Karunanayaka, P; Michaud, L; Wade, SL; Am J Neuroradiology; Vol. 28, 1919-1925; 2007 58


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evidence, epistemology,equipoise and pediatric trauma craig downs, ms, do; facem, faap, facop, fccm...

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