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T R A U M A N O T E B O O K

Scenario 1

A 15-year-old high school football player presents to theemergency department with paraesthesia and paralysis ofall extremities following a violent collision on the playingfield. After assessing the patient, the emergency physicianorders a 30 mg/kg IV bolus of methylprednisolone (MP)to be given over 15 minutes. This bolus is followed 45minutes later by a 5.4 mg/kg/h continuous IV infusion ofMP administered during the next 23 hours. The initial lat-eral cervical spine radiograph and subsequent C-spineseries are all negative for fractures. The patient is admittedto the pediatric intensive care unit with a diagnosis ofspinal cord injury (SCI) without radiographic abnormali-ty. During the next few days, he has a gradual return of allmotor and sensory function and is eventually dischargedhome.

Scenario 2

A 43-year-old construction worker is involved in a sin-gle-vehicle rollover crash. Paramedics responding to thescene institute full spinal immobilization, with a back-board and neck brace. The patient is transported to thenearest trauma center, where he presents with quadriple-gia. His lateral C-spine film reveals a compression frac-ture at C5 with bony fragments impinging on the spinalcanal. The same high-dose MP protocol outlined in sce-nario 1 is initiated, but in this instance, the patient doesnot experience any appreciable return of neurologicfunction. Instead, a severe case of pneumonia develops,requiring a tracheostomy and prolonged ventilatory sup-port in the trauma-neurosurgical ICU. Almost 3 weeks

Methylprednisolone

in Acute Spinal Cord Injury:

Fact or Fantasy?

Jeffrey Walker, Oregon ENA, is Critical Response Nurse and LauraCriddle, Oregon ENA, is Clinical Nurse Specialist, Oregon HealthSciences University, Portland, Ore.For reprints, write: Laura M. Criddle, MS, RN, CEN, CCRN, 28384Hafferman Road, Scappoose, OR 97056; E-mail: criddlel@ohsu.edu.J Emerg Nurs 2001;27:401-3.Copyright © 2001 by the Emergency Nurses Association.0099-1767/2001 $35.00 + 0 18/9/115705doi:10.1067/men.2001.115705

Authors: Jeffrey Walker, RN, BA, CCRN, CEN, and Laura M.Criddle, MS, RN, CEN, CCRN, Portland and Scappoose, Ore

Section Editor: Maureen Harrahill, RN, MS, ACNP-CS

402 JOURNAL OF EMERGENCY NURSING 27:4 August 2001

TRAUMA NOTEBOOK/Walker and Criddle

after his injury, he is finally weaned from the ventilatorand is transferred to a rehabilitation facility.

The case for high-dose MP in acute SCI

The tragic and devastating nature of SCIs is apparent toanyone who has been involved with this patient popula-tion. During the past decade, the use of high-dose MPinfusion for the treatment of acute SCI has come to beviewed as a “standard of practice” by authorities in thenursing literature.1,2 What is the scientific basis for thisassertion?

In 1990, the results of the National Acute Spinal CordInjury Study 2 (NASCIS 2) were released. This prospec-tive, randomized, multicenter trial compared the effects ofthe now-standard 24-hour MP dosing protocol withnaloxone and with placebo. An arbitrary 12-hour limitfrom injury to initiation of treatment was used. Motor andsensory functions were assessed using a numeric scoringsystem at the time of entry into the study, and then theywere reassessed at 6 weeks, 6 months, and 1 year.

In the NASCIS 2 study, 487 patients were randomizedacross 10 different treatment centers. Taken as a whole, nosignificant difference in recovery was noted between the 3treatment groups. However, a subset of patients who weretreated with MP within 8 hours of injury demonstrated a“statistically significant” improvement in motor and senso-ry function at 6 weeks and at 6 months. On the basis ofthis evidence, the 24-hour dosing regimen quickly becamestandard treatment for acute SCI.3

NASCIS 2 was followed by NASCIS 3, the results ofwhich were published in 1997. This study was also aprospective, randomized, multicenter trial with 3 treatmentarms. However, instead of comparing 2 different medica-tions and an untreated control, NASCIS 3 compared agroup of patients with acute SCI treated with tirilazad mesy-late, a group treated with the 24-hour NASCIS 2 MP pro-tocol, and a third group receiving the MP infusion for 48hours. Only patients who could be randomized and havetherapy initiated within 8 hours were included. Similar tothe NASCIS 2 trial, a numeric motor and sensory functionscoring system was used. Assessments were performed at thetime of randomization and repeated at 6 weeks and at 6months, but patients were not reassessed at 1 year.

Altogether, 499 patients were enrolled in NASCIS 3from 16 different treatment centers. When compareddirectly, the administration of tirilazad mesylate showed noadvantage, and there was only a small difference in out-come between the 24- and 48-hour MP groups. Closeranalysis determined that there was a statistically significantadvantage to the longer regimen for patients in whom MPinitiation had been delayed between 3 and 8 hours. As aresult, the NASCIS 3 authors recommended that the 48-hour protocol be implemented for this subgroup ofpatients with acute SCI.4

The case against high-dose MP

Despite extensive protocol implementation, the conclu-sions of NASCIS 2 and 3 regarding the efficacy of high-dose MP in the treatment of acute SCI are far from uni-versally accepted. Critics have mounted attacks from anumber of different directions. Many critics question themethods by which the conclusions were derived. Forexample, of the 487 patients studied in NASCIS 2, themajority received treatment between 8 and 12 hours afterinjury, well outside the period in which statistically signif-icant differences in assessment scores were noted. In fact,of the nearly 500 patients enrolled, only 66 were treatedwith MP and 69 were randomized to placebo during this8-hour window. The small number of subjects actuallyincluded in the final data analysis yield results that aremuch less convincing.5

Perhaps the strongest criticism of the NASCIS 2 con-clusions is that a similarly designed French study, pub-lished in 2000, could not reproduce its results.6 Becausereproducibility is the backbone of scientific credibility, thefailure to meet this standard relegates NASCIS 2 to thecategory of “interesting but not persuasive” studies.

In addition to questioning the reliability of the conclu-sions supporting the use of high-dose MP, critics have alsostressed that the data presented in both NASCIS 2 and 3indicate that patients treated with methylprednisolone facedan increased risk of complications such as sepsis, pneumonia,and delayed wound healing. Given the significance of thesecomplications in a quadriplegic patient, it seems essential toconsider whether the supposed benefits of this therapy out-weigh its potential risks.

TRAUMA NOTEBOOK/Walker and Criddle

The NASCIS definition of “improved outcome” isalso a subject of debate. The motor assessment scale usedin NASCIS 2 and 3 assigns 1 point for a flicker of move-ment in a tested muscle and 0 points for no movement atall. In NASCIS 2, there was only an overall difference of5.2 points between the MP protocol group and the place-bo group in motor assessment scores (17.2 vs 12.0, respec-tively) out of a maximum possible score of 70. If, for exam-ple, these 5.2 points indicated that a patient regained aflicker of movement in 5 different muscles where there hadpreviously been none, then the functional difference in thepatient’s outcome is still essentially zero.7 A C5 quadri-plegic who can twitch his thumb and big toe remains asdependent in his care needs as one who cannot. Critics ofMP use argue that this outcome fails to warrant the risk ofsevere, life-threatening complications and longer, costlierICU stays.

Importantly, in the NASCIS 2 study, the differencesin assessment scores between patients receiving MP andplacebo disappeared by the 1-year follow-up examination.This finding seems to indicate that any advantage associat-ed with MP therapy was temporary at best.5 Based on thesedata, it is interesting that the NASCIS 3 study designspecifically did not include reassessment at 1 year. Addedto these criticisms is the fact that the primary NASCISauthors themselves conducted the only evidence-basedmedicine reviews of the MP studies.

Altogether, the case for high-dose MP in patients withacute SCI is less than compelling.

Conclusion

In light of the debate, which of the initial scenarios repre-sents a patient responding to the effects of MP? Is it the15-year-old football player with a full recovery or the 43-year-old construction worker who experienced multiplecomplications and remained quadriplegic? Is it neither oneor both?

Given the controversial nature of the evidence sup-porting the use of high-dose MP to treat acute SCI, it isreasonable to ask how this protocol ever became a “stan-dard of care.” Perhaps the answer lies in the fact that thepurported results of NASCIS 2 were widely publicized at

the time of their release and there now exists a strong pub-lic opinion that “steroids work” in the treatment of acuteSCI. Faced with this perception, physicians are under-standably reluctant to accept the potential legal conse-quences of not giving the public what it expects. After all,who wants to stand before a jury considering a multimil-lion dollar settlement to a new quadriplegic and meet anattorney’s assertion that “You didn’t even try”?

Regardless of the arguments for or against the use ofMP, the decision about whether to institute a high-doseMP protocol rests with the physician, not the nurse. Asnurses, however, we can avoid instilling a false sense ofhope in patients and their families who desperately want tobelieve that the cure for SCI can be found in an IV bag.We can also learn to remain suspicious of the emotionalappeal of new “standards of care” and, instead, follow theprecepts of evidence-based practice and wait for the judg-ment of science before rushing to embrace new “cures.”

REFERENCES1. Hickey JV. Vertebral and spinal cord trauma. In: Hickey JV, edi-

tor. The clinical practice of neurological and neurosurgical nurs-ing. 4th ed. Philadelphia: Lippincott; 1997. p. 440.

2. Prendergast V. Acute spinal cord injury. Crit Care Nurs ClinNorth Am 2000;12:499-508.

3. Bracken M, Shepard M, Collins W, Holford T, Young W, BaskinD, et al. A randomized controlled trial of methylprednisolone ornaloxone in the treatment of acute spinal cord injury. N Engl JMed 1990;322:1405-11.

4. Bracken M, Shepard M, Holford T, Leo-Summers L, Aldrich E,Fazl M, et al. Administration of methylprednisolone for 24 or 48hours or tirilazad mesylate for 48 hours in the treatment of acutespinal cord injury. JAMA 1997;277:1597-604.

5. Hurlbert J. Methylprednisolone for acute spinal cord injury: aninappropriate standard of care. J Neurosurg 2000;93(1 Suppl):1-7.

6. Pointillart V, Petitjean M, Wiart L, Vital J, Lassie P, Thicoipe M,et al. Pharmacological therapy of spinal cord injury during theacute phase. Spinal cord 2000;38:71-6.

7. Nesathurai S. Steroids and spinal cord injury: revisiting theNASCIS 2 and NASCIS 3 trials. J Trauma 1998;45:1088-93.

Contributions for this column are welcomed and encouraged.Submissions should be sent to:

Maureen Harrahill, RN, MS, ACNP-CS1404 SE Malden, Portland, OR 97202

503 494-6007 • harrahim@ohsu.edu

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