Spine J. 2006 May-Jun;6(3):335-43.

Methylprednisolone treatment in acute spinal cord injury: the myth challenged through a structured analysis of published
literature.
Sayer FT, Kronvall E, Nilsson OG.

Department of Neurosurgery, Lund University Hospital, Lund 221 85, Sweden. Faisal.Sayer@neurokir.lu.se

Abstract
BACKGROUND CONTEXT: Methylprednisolone has evolved during the 1990s, through the results obtained from the National Acute Spinal Cord Injury Studies NASCIS II and
III, as a standard treatment in acute spinal injury.
PURPOSE: To evaluate the scientific basic for the use of methylprednisolone in acute spinal cord injury.
STUDY DESIGN: Systematic review of the accumulated literature.
METHODS: Critical evaluation of the data obtained in the NASCIS II and III studies plus other accumulated literature.
RESULTS: Analyses have been made on subgroups of the study populations, and the results were based on statistical artefacts. Furthermore, improved functional recovery
shown by these studies was not clinically significant.
CONCLUSION: There is insufficient evidence to support the use of methylprednisolone as a standard treatment in acute spinal cord injury.

PMID: 16651231 [PubMed - indexed for MEDLINE]

Neurosurg Anesthesiol. 2008 Apr;20(2):140-2.

Methylprednisolone in acute spinal cord injury: a tarnished standard.

Miller SM.

NYU School of Medicine and Bellevue Hospital Center, NY, USA. Sanford.miller@med.nyu.edu

PMID: 18362778 [PubMed - indexed for MEDLINE]

Surg Neurol. 2007;68 Suppl 1:S37-41; discussion S41-2.

Pitfalls in treatment of acute cervical spinal cord injury using high-dose methylprednisolone: a retrospect audit of 111
patients.
Lee HC, Cho DY, Lee WY, Chuang HC.

Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan 404, ROC.

Abstract
BACKGROUND: Earlier studies suggested that the use of high-dose IV MP was the gold standard of care for the treatment of ASCI, but this has been debated. This study aims
to identify the effects of high-dose MP in treatment of cervical SCI and how the treatment might be improved.
METHODS: The medical records of 138 patients with cervical spinal injury secondary to blunt injuries were retrospectively reviewed to determine the steroid administration
protocol, effects, and complications. The findings on admission were compared with those at discharge and at the most recent outpatient follow-up visit. Significant neurologic
improvement was defined as increase in at least 1 clinical grade according to the Frankel classification system.
RESULTS: Significantly more motor and sensory recovery was noted (complete ASCI, 69% vs 0; incomplete ASCI, 70% vs 50%) in patients treated with surgery and MP than in
patients without such treatment. Moreover, 87% (14/16) of patients with complete ASCI (unlike patients with incomplete [8/28, 28.6%] and mild [2/14, 14.3%] ASCI) treated with
MP had steroid-related complications, and 1 patient died from sepsis related to a perforated peptic ulcer. Mean hospitalization was significantly shorter for the patients who
underwent tracheostomy (49 days, ranged from 22 to 110 days) vs nontracheostomy(94 days, ranged from 28-268 days).
CONCLUSION: Early intervention with surgery and MP is critical. Although treatment with MP for 24 or 48 hours significantly improves motor and sensory function of patients
with ASCI, harmful side effects limit its functional efficacy in patients with complete ASCI. Early tracheostomy can shorten hospital stay in patients with complete ASCI.
 CONTROVERSIES IN TRAUMA

CENTRAL NERVOUS SYSTEM TRAUMA: SHOULD WE ALWAYS USE STEROIDS ?—Michael T. Fitch, MD, PhD, Assistant
Professor, Department of Emergency Medicine, Wake Forest University, School of Medicine, Winston- Salem, NC

Rationale behind high-dose steroids: therapy not helpful for initial injury to glial cells and neurons; secondary
therapies based on secondary reaction to injury; brain and spinal cord do not tolerate inflammation well; inflammatory
process involves free radicals, lipid peroxidation, and production of inhibitory molecules, creating environment not
supportive of tissue repair and potential chemical barrier to tissue regrowth, regeneration, and repair; cellular substrate
gone in some cases; cavities develop weeks after injury (inhibitory to healing process); intense inflammatory reaction
after traumatic injury extends to areas not directly injured (target this process with therapy); steroids’ ability to modify
inflammation leads to theory that steroid use in trauma potentially helpful to central nervous system (CNS); animal
data— methylprednisolone potentially efficacious; therapy started at time of injury
Studies: National Acute Spinal Cord Injury Study I (NASCIS I; 1984)—no true placebo group; 2 different doses of
steroids used to look at whether higher dose better than lower dose; no clinical difference found
NASCIS II (1990): multicenter prospective randomized double-bind trial comparing high-dose methylprednisolone
to naloxone (Narcan) or placebo; 95% of patients had 1-yr follow-up; majority of patients enrolled within 12 hr of
injury; primary end point defined as change in neurologic examination; neurologic examinations consisted of motor
strength and pinprick and touch sensations performed at baseline, 6 wk, 6 mo, and 1 yr; results—at 6 wk, no
significant difference in any parameter; at 6 mo, no significant difference in motor function but slight significant
increases in pinprick and touch sensations; subgroup analysis—patients who received steroids within 8 hr (<40% of
patients in study); at 6 wk, slight statistically significant increases in motor function and touch, but not in pinprick;
at 6 mo, statistically significant increase in motor function (5-point increase), pinprick, and touch in steroid group;
no significant differences found in patients receiving steroids at >8 hr; conclusion that beneficial effect limited to
those treated within 8 hr; reaction to results—news releases about unpublished data exaggerated implications of
results; National Institutes of Health (NIH) distributed protocol for steroid use to all emergency departments (EDs)
in United States so they could implement immediately; when data released 6 mo later, scientific community
concluded that initial enthusiasm of popular press not matched by strength of data
NASCIS II updated (1991): 1-yr data from study; no significant differences in patient populations; slight increases
in pinprick and touch seen at 6 mo gone by 1 yr; subgroup analysis (steroid at ≤8 hr) showed only 5-point increase
in motor strength (on scale of 70 points); complications in 1-yr group include twice risk for urinary tract infection
(UTI) in steroid group and increased risk for gastrointestinal (GI) bleeding (not statistically significant)
NASCIS III (1997): multicenter trial; no placebo group; high-dose methylprednisolone for 24 hr vs high-dose
methylprednisolone for 48 hr vs tirilazad for 48 hr; 92% follow-up rate; patients received therapy within 8 hr;
examination of motor strength, pinprick and touch sensations, and functional score; found no significant difference
in overall patient group by 1 yr; subgroup analysis of patients receiving steroids in 3 to 8 hr showed statistically
significant difference in motor strength at 6 mo (this difference not present at 1 yr); interpretation that patients who
got steroid within 3 hr of injury should get steroids for 24 hr, those who got steroid 3 to 8 hr after injury should get
steroids for 48 hr, and no increased benefit from tirilazad; statistically significant increase in UTI in 48-hr steroid
group
Other studies: Japanese study (1994)—placebo vs steroid; no significant difference in primary outcomes; subgroup
analysis showed sensory but no motor improvements with steroids; retrospective studies—showed no difference in
neurologic status or functional independence scores in patients receiving or not receiving steroids
Controversy: overall, NASCIS studies negative by primary end point; only positive results came from subgroup
analysis; unclear etiology of 8-hr cutoff (authors say 8 hr represented median time at which patient had received or not
received steroids); only 40% of trial patients in subgroup analysis; paper (2000) pointed out that group that got placebo
>8 hr after injury did worse than those who got placebo <8 hr after injury; question of why motor score only parameter
with statistical significance at 1 yr and functional relevance of this; no placebo group in NASCIS III trial (point of
criticism); functional independence scores do not correlate with 5-point increase in motor score, leading to question of
clinical significance; meaning of increase in motor score—recovery of 5 motor points potentially equivalent to recovery
of one spinal level; could be clinically relevant or not, depending on level; scoring system potentially fundamentally
flawed (5 points could mean up one spinal level or 1-point increase in different distal muscles adding up to 5 points,
statistically but not clinically significant for overall function); NASCIS III (only study that looked at function) did not
have placebo group and did not find differences in function
Harmful side effects: high-dose steroids not benign treatment; small study showed evidence of steroid-induced
myopathy; small prospective study showed higher incidence of pulmonary and GI complications; NASCIS I found
higher incidence of wound infection in those on high-dose methylprednisolone; NASCIS III found higher incidence of
UTI and pneumonia in those given 48 hr of methylprednisolone
Places using steroids: European Cervical Spine Research Society—survey; majority said they used steroids or should
use steroids; majority also did not entirely believe evidence supports use; Colorado—when medical directors of trauma
centers and emergency medical services (EMS) surveyed, 98% reported using steroids for spinal cord injury, but 50%
uncertain or did not believe data supported use; data from 1996 showed only 65% of patients got steroids per guidelines
in Colorado (practice not following recommendations); North American Spine Society—survey showed majority used
steroids mainly in fear of litigation if steroids not used; 24% believe it improves recovery; rest of those surveyed used
because of hospital protocol; Canadian Spine Surgeons—66% survey response; 25% do not use steroids; remainder of
surgeons surveyed use steroids because of peer pressure (35%) or fear of litigation (35%)
Steroid use in practice: prospective audit—100 patients in spinal cord unit in England; 25% received steroids by
protocol; 10% of patients given steroids incorrectly; remainder did not get steroids at all; review—spinal cord injury
patients in South Carolina (1993-2000); 50% of patients received steroids; study from Ireland—28 of 196 patients given
steroids; only 6 received steroids according to NASCIS III protocol; practice suggests majority of patients with spinal
cord injuries not getting steroids
Head injury: steroids used in patients with brain injury for >30 yr; posttraumatic inflammatory changes thought
harmful; review (1997)—included all randomized trials done up to that date; data inconclusive as to risk or
benefit; Cortico- steroid Randomization After Significant Head Injury (CRASH) trial (1990-2004)—prospective
multicenter randomized double-blind placebo-controlled trial of adults with clinically significant head injury, Glasgow
Coma Scale (GCS) ≤14; 10,000 patients enrolled; 48 hr of methylprednisolone vs placebo; primary outcome death
within 2 wk or disability at 6 mo; 99% follow-up; mortality at 2 wk 21% in steroid group vs 18% in placebo
group, ie, relative risk for mortality 1.18; mortality increased with steroids; based on this study, recommendation that
steroids not be used in head injury; mechanism of worsened outcome unclear (no obvious increase in infections or GI
bleeding); trial investigators felt use of steroids in spinal cord injury should remain area of debate (spinal cord trials
small, compared to this study, and emphasis from those focused on subgroup effects)
Standard of care: steroids not standard of care in head injury; literature still says steroid use for spinal cord injury
“standard of care”; many people do not support use of methylprednisolone and think studies do not support making it
standard of care; no Food and Drug Administration (FDA) indication or guidelines from American Association of
Neurological Surgeons (AANS);legal definition of standard of care (Black’s Law Dictionary)—“degree of care which a
reasonably prudent physician should exercise under same or similar circumstances”; to prove professional negligence—
must have duty to provide care, breach of care standard, and damage or injury from action or inaction; historically, have
allowed for geographic variation (communities decide standard of care), but with standardization of medical education,
many cases no longer based on local standard of care, but national or specialty standards; standard of care not
equivalent to “majority”; according to concept of “respectable minority,” when given treatment deemed acceptable by
reputable or respected minority of colleagues, it may be accepted as standard of care if controversy exists as to
treatment; establishing standard of care in court—expert witness testimony; literature; published medical guidelines
(often used as evidence)
Published guidelines for methylprednisolone and spinal cord injury: National Association of EMS Physicians—
evidence for use of high-dose steroids for spinal cord injury remains inconclusive and not standard of care for out-of-
hospital emergency medical care; Canadian Spine Society and Canadian Neurosurgical Society—“there is insufficient
evidence to support the use of high-dose methylprednisolone within eight hours following an acute closed spinal cord
injury as a treatment standard or as a guideline for treatment”; “treatment option for which there is weak clinical
evidence”; AANS and Congress of Neurological Surgeons (Guidelines for the Management of Acute Cervical Spine and
Spinal Cord Injuries)—insufficient evidence to support as treatment standard or treatment guideline; treatment with
methylprednisolone for 24 or 48 hr recommended as option in treatment of patients with acute spinal cord injuries (but
should be undertaken only with knowledge that evidence suggesting harmful side effects more consistent than any
suggestion of clinical benefit); speaker suggests possibility that specific patient might benefit from this protocol, but
data do not help identify those patients and data not strong enough to support giving to everyone
Cases: head injury—paraplegic with T8 fracture and head injury; data supportive of not using steroids because of head
injury;L3 burst fracture—paraplegic; cauda equina or nerve root injury excluded from NASCIS trials because below
spinal cord; no data to support this type of injury benefits form steroids; C6 fracture and facet dislocation—complete
paralysis; speaker does not know whether this patient could benefit from steroids; multiple injuries—T5 fracture;
question whether patient at increased risk for steroid complications
Conclusion: controversy remains about steroids for spinal cord injuries; published guidelines from professional
organizations provide support for not using this treatment; contraindications for steroid use include head injury;
question of standard of care remains; critical discussion in community important in deciding course of action for
physicians in area

SCREENING FOR BLUNT CARDIAC TRAUMA: SHOULD WE OR SHOULDN’T WE ?—Kenji Inaba, MD, Assistant Professor
of Surgery, Division of Trauma and Surgical Critical Care, Keck School of Medicine at the University of Southern
California, Los Angeles

Controversy: name—cardiac concussion; blunt cardiac trauma; myocardial contusion; in 1992, nomenclature unified as
blunt cardiac injury (BCI); inconsistent definition—>300 publications in last decade but no consistency in description
of injury; reported incidence varies from 7% to 71%; wide spectrum of injury from mild contusion to wall to rupture;
clinically benign to catastrophic; no gold standard imaging, laboratory or electrocardiography (ECG)
findings; pathologic diagnosis—each of injuries along spectrum has pathologic diagnosis; useful in patients who have
expired, but not so helpful clinically
Clinical goals: identify clinically significant BCI; define population at risk; find sensitive screening test for clinically
significant injuries
Clinically significant BCI: structural—wall motion abnormalities with depressed cardiac function; septal perforation,
valve damage, and wall rupture (all rare in survivors); conduction abnormality—arrhythmias (atrial fibrillation most
common)
People at risk: symptomatic; associated chest trauma; high-risk mechanism; well validated screening criteria do not
exist; rely on associated chest trauma and mechanism to guide screening (sensitive, but not specific for BCI)
Screening: Eastern Association for the Surgery of Trauma (EAST) guidelines—discharge patient if admission ECG
normal; monitor for 24 to 48 hr if admission ECG abnormal (several case reports show that patients with mechanical
chest trauma have normal admission ECG and die from conduction abnormality); “no single test or combination of tests
has proven consistently reliable in detecting cardiac injury”; troponin I—acute myocardial infarction (MI) literature
describes serum cardiac troponin as sensitive and specific marker of cardiac injury; serum troponin potentially elevated
even in patients without mechanical chest trauma; prospective 30-mo study—asked whether troponin and ECG can act
together synergistically to help diagnose patient at risk for BCI; looked at seriously injured patients with mechanical
chest trauma; did serial ECG and troponin I, looking at 0- and 8-hr times; patients with clinically significant
BCI, ie, hemodynamic abnormalities resulting from cardiac wall motion abnormalities, arrhythmias requiring treatment,
and structural defects detected on trans-thoracic echocardiography; (13% positive for clinically significant BCI) found
cardiac troponin I alone had sensitivity of 73%, and ECG alone had sensitivity of 89%, but together, sensitivity 100%;
conclusion that normal ECG and normal troponin I at 0 and 8 hr indicated no clinically significant BCI
Summary: clinically significant BCI includes myocardial damage affecting output, arrhythmias, and (rarely) valve and
wall disruption; no clear guidelines for at-risk patients; troponin I and ECG if applied to right patient population
sensitive screen for diagnosis of BCI
Algorithm: patient with blunt chest trauma should have ECG and troponin I; if either positive, get echocardiography
and look for structural abnormalities and arrhythmias; if ECG and troponin I negative, repeat both in 8 hr; if either
positive at 8 hr, continue work-up; if negative, and other work-up completed, can discharge; sinus tachycardia, heart
rate variability or speed—majority of studies have omitted sinus tachycardia, so when studies look at electrical
dysfunction or conduction abnormalities, atrial fibrillation that requires treatment number-one arrhythmia

Suggested Reading

Czekajlo MS, Milbrant EB: Corticosteroids increased short and long-term mortality in adults with traumatic head
injury. Crit Care 9:E21, 2005; Eck JC et al: Questionnaire survey of spine surgeons on the use of methylprednisolone
for acute spinal cord injury. Spine 31:E250, 2006; Elie MC: Blunt cardiac injury. Mt Sinai J Med 73:542,
2006; Frampton AE, Eynon CA: High dose methylprednisolone in the immediate management of acute, blunt spinal
cord injury: what is the current practice in emergency departments, spinal units, and neurosurgical units in the
UK? Emerg Med J 23:550, 2006; Holanda MS et al: Cardiac contusion following blunt chest trauma. Eur J Emg
Med 13:373, 2006; Hurlbert RJ: Strategies of medical intervention in the management of acute spinal cord
injury. Spine 31:S16, 2006; Lai CH et al: A case of blunt chest trauma induced acute myocardial infarction involving
two vessels. In Heart J 47:639, 2006; Pai M: Diagnosis of myocardial contusion after blunt chest trauma using 18F-FDG
positron emission tomography. Br J Radiol 79:264, 2006; Rajan GP, Zellweger R: Cardiac troponin I as a predictor of
arrhythmia and ventricular dysfunction in trauma patients with myocardial contusion. J Trauma 57:801, 2004;Sauerland
S, Maegele M: A CRASH landing in severe head injury. Lancet 364:1291, 2004; Sayer FT et al:Methylprednisolone
treatment in acute spinal cord injury: the myth challenged through a structured analysis of published
literature.Spine 6:335, 2006; Tsutsumi S et al: Effects of the Second National Acute Spinal Cord Injury Study of high-
dose methylprednisolone therapy on acute cervical spinal cord injury-results in spinal injuries center. Spine 31:2992,
2006; Vaquero J et al: Early administration of methylprednisolone decreases apoptotic cell death after spinal cord
injury. Histol Histopathol21:1091, 2006; Wadia RS: Corticosteroid use in head injuries. Natl Med J India 18:25, 2005.

Educational Objectives
 The goal of this program is to increase awareness of the role of steroids in the treatment of spinal cord and head
injuries and improve screening for blunt cardiac injury. After hearing and assimilating this program, the clinician will
be better able to:
1. Explain the purported rationale for use of high-dose steroids in the treatment of spinal cord injury.
2. Explain why controversy exists about use of high-dose steroids in the treatment of spinal cord injury.
3. Discuss the standard of care and published guidelines for the use of methylprednisolone for spinal cord injury
and head injury.
4. Describe the spectrum of injury associated with cardiac injury and appraise the clinical significance of this
diagnosis.
5. Assess the screening modalities available for the diagnosis of cardiac injury and how they fit into the work-up of
patients with blunt chest trauma.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members to disclose
relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any
identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a
proprietary business or commercial interest. For this program, the faculty reports nothing to disclose.

Acknowledgements

Dr. Fitch was recorded at The 17th Annual June Jam, held June 9-11, 2006, in Myrtle Beach, SC, and sponsored by the
North Carolina College of Emergency Physicians. Dr. Inaba was recorded at the 13th Annual USC Trauma/Critical Care
Symposium, held May 22-23, 2006, in Pasadena, CA, and sponsored by the Division of Trauma/Critical Care and the
Office of Continuing Medical Education at the Keck School of Medicine of the University of Southern California, and
the Institute of Continuing Education for Nurses, Department of Nursing, Los Angeles, and USC Medical Center. The
Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.