CLINICAL ARTICLE

J Neurosurg Pediatr 20:567–574, 2017

Lessons learned from administration of high-dose

methylprednisolone sodium succinate for acute pediatric
spinal cord injuries
Michelle C. Caruso, PharmD, BCPS,1 Margot C. Daugherty, MSN, MEd, RN, CEN,2
Suzanne M. Moody, MPA,2 Richard A. Falcone Jr., MD, MPH,2 Karin S. Bierbrauer, MD,3 and
Gary L. Geis, MD4
Divisions of 1Pharmacy, 2Trauma Services, 3Neurosurgery, and 4Emergency Medicine and Center for Simulation and Research,
Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio

OBJECTIVE  Methylprednisolone sodium succinate (MPSS) has been studied as a pharmacological adjunct that may
be given to patients with acute spinal cord injury (ASCI) to improve neurological recovery. MPSS treatment became the
standard of care in adults despite a lack of evidence supporting clinical benefit. More recently, new guidelines from neu-
rological surgeon groups recommended no longer using MPSS for ASCI, due to questionable clinical benefit and known
complications. However, little information exists in the pediatric population regarding MPSS use in the setting of ASCI.
The aim of this paper was to describe steroid use and side effects in patients with ASCI at the authors’ Level 1 pediatric
trauma center in order to inform other hospitals that may still use this therapy.
METHODS  A retrospective chart review was conducted to determine adherence in ordering and delivery according to
the guideline of the authors’ institution and to determine types and frequency of complications. Inclusion criteria included
age < 17 years, blunt trauma, physician concern for ASCI, and admission for ≥ 24 hours or treatment with high-dose
intravenous MPSS. Exclusion criteria included penetrating trauma, no documentation of ASCI, and incomplete medical
records. Charts were reviewed for a predetermined list of complications.
RESULTS  A total of 602 patient charts were reviewed; 354 patients were included in the study. MPSS was administered
in 59 cases. In 34 (57.5%) the order was placed correctly. In 13 (38.2%) of these 34 cases, MPSS was administered ac-
cording to the recommended timeline protocol. Overall, only 13 (22%) of 59 patients received the therapy according to
protocol with regard to accurate ordering and administration.
Among the patients with ASCI, 20 (55.6%) of the 36 who received steroids had complications, which was a significantly
higher rate than in those who did not receive steroids (8 [24.2%] of 33, p = 0.008). Among the patients without ASCI,
10 (43.5%) of the 23 who received steroids also experienced significantly more complications than patients who did not
receive steroids (50 [19.1%] of 262, p = 0.006).
CONCLUSIONS  High-dose MPSS for ASCI was not delivered to pediatric patients according to protocol with a high de-
gree of reliability. Patients receiving steroids for pediatric ASCI were significantly more likely to experience complications
than patients not receiving steroids. The findings presented, including complications of steroid use, support removal of
high-dose MPSS as a treatment option for pediatric ASCI.
https://thejns.org/doi/abs/10.3171/2017.7.PEDS1756
KEY WORDS  spinal cord injury; pediatric; methylprednisolone; trauma; neck injury; spine

T
reatment options for acute spinal cord injury (ASCI) effects, including inhibition of lipid peroxidation, calcium
are limited. Methylprednisolone sodium succinate influx, and ischemia and antiinflammatory activity.6 The
(MPSS) has been studied as a pharmacological ad- National Acute Spinal Cord Injury Study (NASCIS) tri-
junct that may be given postinjury to improve neurologi- als, beginning in the mid-1980s, reported improved motor
cal recovery. MPSS possesses a variety of neuroprotective and sensory scores at follow-up after treatment with high-

ABBREVIATIONS  AANS = American Association of Neurological Surgeons; ASCI = acute spinal cord injury; CNS = Congress of Neurological Surgeons; EMR = electronic
medical record; GI = gastrointestinal; ICU = intensive care unit; ISS = Injury Severity Score; MPSS = methylprednisolone sodium succinate; NASCIS = National Acute Spi-
nal Cord Injury Study; SCI = spinal cord injury.
SUBMITTED  January 30, 2017.  ACCEPTED  July 6, 2017.
INCLUDE WHEN CITING  Published online October 6, 2017; DOI: 10.3171/2017.7.PEDS1756.

©AANS, 2017 J Neurosurg Pediatr  Volume 20 • December 2017 567

M. C. Caruso et al.

dose MPSS. After NASCIS II and NASCIS III, high-dose facility located in southwestern Ohio. The trauma center
MPSS therapy became widely considered as a standard of is an American College of Surgeons–designated Level 1
care for ASCI. pediatric center and admits, on average, 2100 trauma pa-
Criticisms of the NASCIS trials included study designs, tients annually.
data quality, statistical analysis, interpretation, and con-
clusions.1,4,8,10,11 The primary outcome analyses of all 3 Patient Population
NASCIS trials have shown no clinical benefit, and the only
The institutional Trauma Registry was queried for pa-
positive effects seen with high-dose MPSS therapy were
tients who met the standard inclusion criteria for ICD-9
determined through post hoc subgroup analysis. Subse- injury codes 800–959. We further limited the ICD-9 codes
quent studies have raised concerns regarding the safety of to 806, 847, and 952–953, which were indicative of pos-
this therapy in light of the results from the NASCIS trials sible ASCI. Patients were included if they were less than 17
and the known complications of high-dose steroids.2,5,7,9,12 years of age, presented with blunt trauma, had a document-
In 2002, due to insufficient evidence, the American ed physician concern for ASCI, and were either admitted
Association of Neurological Surgeons (AANS)/Congress for ≥ 24 hours or received MPSS for ASCI (initiated at
of Neurological Surgeons (CNS) Joint Section of Disor- our institution or a referring hospital). Exclusion criteria
ders of the Spine and Peripheral Nerves recommended the included penetrating trauma, no documentation of ASCI,
use of MPSS as an option, not as a guideline or standard.1 and incomplete medical records.
Given the lack of data regarding the use and complications
of MPSS among pediatric patients, a multidisciplinary
consensus guideline for use at our institution was imple- Patient Data
mented for the administration of this therapy in ASCI Patient information was retrospectively collected from
when the following criteria were met: 1) blunt mechanism the Trauma Registry and included demographics (age, sex,
of injury, 2) patient presentation within 8 hours of injury, and race), length of stay, mechanism of injury, date/time
and 3) presence of neurological and/or sensory deficit(s) of injury, referring hospital information, Injury Severity
(symptoms of paresthesia alone did not qualify). If the pa- Score (ISS), discharge diagnosis, outcome (alive vs de-
tient was transferred from an outside facility and MPSS ceased), and discharge disposition.
administration had already been initiated, this would be Electronic medical record (EMR) reports, including
completed per guidelines, even in the presence of a nega- EmSTAT (Version 1.30), WORx (Version 3.4), and EPIC
tive MRI study. (Version Spring 2008), were run to determine if any of the
Therapy at our institution followed the NASCIS II patients from the Trauma Registry query had orders for
and NASCIS III protocols for dosing and administration, MPSS during their visit. Paper charts were requested for
which consisted of methylprednisolone administration patients treated prior to implementation of the EMR sys-
with a bolus dose followed by a 45-minute pause and then tem. Charts were manually reviewed by the trauma nurse
a 23-hour continuous infusion. The dose and administra- educator and emergency medicine clinical pharmacist for
tion instructions remained the same during the time of the the following data elements: steroid treatment, including
study. The unusual administration requirements for this guideline adherence; gastrointestinal (GI) ulcer prophy-
therapy were found to present challenges with prescribing, laxis; and a predetermined list of side effects attributed to
given the various order entry systems in place at our in- steroid use. Data were entered into a database, and interra-
stitution, dispensing by the pharmacy, and administration ter reliability was assessed on 20% of the charts to ensure
and monitoring by nursing personnel. accuracy.
To the best of our knowledge, no studies currently ex-
ist describing problems associated with prescribing or ad- Statistical Analysis
ministering high-dose MPSS therapy. To address this gap Descriptive frequencies were generated for patient
in the literature, we studied the medication use process for demographics, guideline adherence, and complications.
this treatment at our institution. Our specific aims were to Categorical and binary variables were summarized by fre-
determine 1) adherence in ordering and delivery of medi- quency (%), and continuous variables were summarized
cations according to the guideline and 2) the types and by median and range. Statistical comparisons between co-
frequency of complications. horts (i.e., those who received steroids and those who did
not) were analyzed using the chi-square test with p < 0.05
Methods considered significant.
Study Design
This was a retrospective, cross-sectional cohort chart Results
review of pediatric trauma cases involving patients who During the 10-year study period, 20,223 injured pa-
presented to our institution from January 1, 2000, through tients were treated at our institution. Applying our inclu-
September 30, 2010. The Cincinnati Children’s Hospital sion criteria and the aforementioned ICD-9 codes yielded
Medical Center institutional review board approved the 602 patient records. A total of 248 charts were excluded
protocol for the study prior to commencement. for the following reasons: age (17 cases), incomplete medi-
cal records (32 cases), length of stay < 24 hours without
Setting administration of MPSS (187 cases), no ASCI suspected
Our institution is a 643-bed academic tertiary-care (7 cases), or penetrating trauma (5 cases). Of the 354 in-

568 J Neurosurg Pediatr  Volume 20 • December 2017

 Lessons learned from methylprednisolone for pediatric ASCI

FIG. 1. Inclusion and exclusion summary. Values in parentheses indicate numbers of patients/charts. LOS = length of stay. *Pa-
tients with LOS < 24 hours were excluded only if they did not receive MPSS.

cluded charts for patients 0–17 years of age, 69 (19.5%) stay was 5.3 days (range 1–51 days). More of the patients
showed an eventual diagnosis of ASCI (ICD-9 codes of were male than female, and the majority were white. No
806, 952, or 953), while the remaining 285 (80.5%) did not significant differences in demographics were noted be-
(Fig. 1). Of the patients with ASCI, 36 (52.2%) received tween patients receiving steroids and those not receiving
steroids. Of those without ASCI, 23 (8.1%) received ste- steroids. No significant differences were noted in demo-
roids. This resulted in a total of 59 patients (16.7%) treated graphics between patients with and without ASCI. Patients
with high-dose MPSS (Fig. 2). who received steroids, both those with and without ASCI,
The average age of all patients included in this study had lower average Injury Severity Scores (ISSs) and length
was 11.9 years (range 0–17 years). The average length of of hospital stay than those not receiving steroids (Table 1).

FIG. 2. ASCI status and steroid exposure with resulting steroid orders.

J Neurosurg Pediatr  Volume 20 • December 2017 569

M. C. Caruso et al.

Medication Ordering and Administration were nausea/vomiting, fever, hypertension, an increase in

Given the complicated nature of ordering and admin- white blood cell count, and bradycardia.
istration of this therapy, the accuracy of the ordering pro-
cess was investigated. The 3 components of the medica- Discussion
tion order investigated included drug, dose, and route. As a
composite outcome, the therapy was ordered correctly for ASCI is a critical injury in the pediatric and adult
the purposes of this study in 57.6% of cases (n = 34). The populations, with the potential for long-term disability for
medication was ordered correctly as MPSS for 53 (89.8%) the patient and significant costs for the family and health
patients. Four (6.8%) patients had additional steroids or- care community. It is only natural that health care provid-
dered after the completion of MPSS therapy, and in 2 cases ers would explore and implement therapies at the bedside
(3.4%) the drug was unable to be determined. The correct early in the management of suspected ASCI with the goal
dose was ordered per guideline for 41 (69.5%) patients; of reducing long-term morbidity. In 2002, the AANS/CNS
there were 12 orders (20.3%) with incorrect dosing, and Joint Section on Disorders of the Spine and Peripheral
for 6 orders (10.2%) the dosing could not be determined. Nerves recommended the use of MPSS as an option, not
The route of administration was correctly ordered as intra- as a guideline or standard.1 Our institution recognized this
venous for 58 (98.3%) orders and could not be determined recommendation, realizing it was not targeted toward pe-
due to lack of documentation in the medical record for one diatric patients. After thorough evaluation, the multidisci-
order (1.7%) (Table 1). plinary consensus was to incorporate clinical concern and
Of the 59 cases in which patients received MPSS, the patient status as factors in decision making for administra-
order was placed correctly in 34 (57.6%). In 13 (38.2%) of tion of MPSS for ASCI for pediatric patients presenting to
these 34 cases, the medication was administered following our institution, following the institutional guideline. How-
the recommended timeline protocol, while in 15 (44.1%) ever, the complex nature of the high-dose MPSS protocol,
it was not administered per the guideline. Due to lack of with multiple inclusion criteria and a complicated dosing
medication administration record (MAR) data, 6 (17.6%) regimen, contributes to the unlikeliness that the health
of the orders could not be assessed for administration de- care team will implement the protocol exactly as it was
tails. intended, especially when it is applied infrequently.
Overall, only 13 (22%) of 59 patients received the ther- Thus, it comes as no surprise that in our study of those
apy according to protocol with regard to accurate medica- patients at a Level 1 trauma center with a clinical suspicion
tion ordering and administration (Table 1). of ASCI and MPSS ordered, only 13 (22%) of 59 had cor-
Of the patients ordered MPSS, 38 (64.4%) were also rect order and administration of steroids per the guideline.
ordered GI ulcer prophylaxis with an H2 blocker or proton Of the 69 patients ultimately diagnosed with ASCI, only
pump inhibitor per guideline; 21 (35.6%) of the patients 8 (11.6%) received the correct order and administration of
did not receive an order for this therapy (Table 1). steroids per the guideline. While we were not surprised to
find that the adherence to the guideline was under 100%,
Patient Complications we were surprised at how few times the therapy was ad-
Among the patients with ASCI, 20 (55.6%) of the 36 ministered as intended, especially given the intense insti-
who received steroids had complications, which was a sig- tutional focus on patient and medication safety with pedi-
nificantly higher rate than in the patients with ASCI who atric-specific resources in place, such as the EMR system.
did not receive steroids (8 [24.2%] of 33, p = 0.008). In the Similar problems with inaccurate administration of this
group without ASCI, 10 (43.5%) of the 23 who received protocol in adults have been shown. In a study by Lee et
steroids experienced complications, which again was a al., only 42% of patients (58 of 138) were given MPSS cor-
significantly higher rate than the corresponding rate in rectly according to the NASCIS II and III protocols.6 Oth-
the patients without ASCI who did not receive steroids (50 er studies, which describe complications associated with
[19.1%] of 262, p = 0.006) (Table 1). high-dose MPSS for ASCI, do not discuss ordering or ad-
The frequency of complications in the pediatric pa- ministration errors.7,12 In our study, the results for accurate
tients who received steroids is shown in Table 2. Table 3 ordering and administration were lower than reported by
shows the frequency of complications among patients with Lee et al., which could be due to the population (pediat-
and without ASCI and with and without steroid exposure. ric) served and the low frequency with which this protocol
Patients receiving steroids experienced the highest num- was used in our population. Based on the findings of poor
bers of complications per individual, as many as 6 com- compliance with the protocol, a worksheet was created to
plications in a patient with ASCI and 9 complications in a assist staff with timing of administration of the bolus and
patient without ASCI. continuous infusion of MPSS. GI prophylaxis was also in-
Table 4 shows the types and frequency of specific com- corporated into the worksheet as a reminder to order in
plications in patients with and without ASCI and with the EMR. An electronic health record order-set was also
and without steroid exposure. On average, pediatric pa- created (once the EMR system was implemented), which
tients receiving steroids had 2.3 complications per patient automated the dose and timing in the EMR.
compared with 1.8 complications per patient in those not Given the infrequent or uncommon nature of ASCI in
receiving steroids. In patients receiving steroids, the most our pediatric population, it makes sense for providers to
common complications were nausea/vomiting, hypergly- look for algorithms, guidelines, or protocols to simplify
cemia, bradycardia, fever, and hypertension. In patients and prescribe care. However, there is innate danger when
not receiving steroids, the most common complications applying these protocols if a patient does not meet inclu-

570 J Neurosurg Pediatr  Volume 20 • December 2017

 Lessons learned from methylprednisolone for pediatric ASCI

TABLE 1. Demographics, steroid usage, and guideline compliance

All Patients ASCI ICD-9 Codes No ASCI ICD-9 Codes

Characteristic (n = 345) w/ Steroids (n = 36) No Steroids (n = 33) w/ Steroids (n = 23) No Steroids (n = 262)
Sex
 Male 230 (65.0) 26 (72.2) 24 (72.7) 15 (65.2) 165 (63.0)
 Female 124 (35.0) 10 (27.8) 9 (27.3) 8 (34.8) 97 (37.0)
Race
 White 267 (75.4) 27 (75.0) 20 (60.6) 20 (87.0) 200 (76.3)
 Black 59 (16.7) 7 (19.4) 9 (27.3) 2 (8.7) 41 (15.6)
 Multiracial 5 (1.4) 0 (0.0) 1 (3.0) 0 (0.0) 4 (1.5)
 Other 21 (5.9) 2 (5.6) 3 (9.1) 1 (4.3) 15 (5.7)
 Hispanic 2 (0.6) 0 (0.0) 0 (0.0) 0 (0.0) 2 (0.8)
Age in yrs
 Mean 11.9 13.2 10 14.5 11.8
 Range 0–17 5–17 0–16 9–17 0–17
LOS in days
 Mean 5.3 4.7 9.2 3.4 5
 Range 1–51 1–27 1–32 1–16 1–51
ISS
 Mean 12 11 16 5.3 12
 Range 1–50 1–34 1–43 1–50 1–45
Steroids for SCI 59 (16.7) 36 (100.0) 0 (0.0) 23 (100.0) 0
  Ordered per guideline
  Yes 34 (57.6) 22 (61.1) NA 12 (52.2) NA
  No 18 (30.5) 11 (30.6) NA 7 (30.4) NA
  Not sure 7 (11.9) 3 (8.3) NA 4 (17.4) NA
  Med per guideline
  Yes 53 (89.8) 33 (91.7) NA 20 (87.0) NA
  No 4 (6.8) 2 (5.6) NA 2 (8.7) NA
  Not sure 2 (3.4) 1 (2.8) NA 1 (4.3) NA
  Dose per guideline
  Yes 41 (69.5) 26 (72.2) NA 15 (65.2) NA
  No 12 (20.3) 6 (16.7) NA 6 (26.1) NA
  Not sure 6 (10.2) 4 (11.1) NA 2 (8.7) NA
  Route per guideline
  Yes 58 (98.3) 35 (97.2) NA 23 (100.0) NA
  No 0 (0.0) 0 (0.0) NA 0 (0.0) NA
  Not sure 1 (1.7) 1 (2.8) NA 0 (0.0) NA
  Administered per guideline
  Yes 13 (38.2) 8 (36.4) NA 5 (41.7) NA
  No 15 (44.1) 10 (45.5) NA 5 (41.7) NA
  Not sure 6 (17.6) 4 (18.2) NA 2 (16.7) NA
  Ulcer med given
  Yes 38 (64.4) 25 (69.4) NA 13 (56.5) NA
  No 21 (35.6) 11 (30.6) NA 10 (43.5) NA
Complications
 Yes 88 (24.9) 20 (55.6) 8 (24.2) 10 (43.5) 50 (19.1)
 No 266 (75.1) 16 (44.4) 25 (75.8) 13 (56.5) 212 (80.9)
LOS = length of stay; med = medication; NA = not applicable.
Numbers in parentheses represent percentages.

J Neurosurg Pediatr  Volume 20 • December 2017 571

M. C. Caruso et al.

TABLE 2. Frequency of complications in the 59 patients who TABLE 3. Frequency of complications by ASCI and exposure to
received steroids steroids
No. of Complications Frequency* ASCI & No ASCI & ASCI & No ASCI &
No. of Steroids Steroids No Steroids No Steroids
1 13
Complications (n = 20) (n = 10) (n = 8) (n = 50)
2 8
3 4 1 10 3 3 30
4 2 2 3 5 3 8
5 1 3 3 1 1 6
6 1 4 2 0 0 5
7 0 5 1 0 1 1
8 0 6 1 0 0 0
9 1 7 0 0 0 0
8 0 0 0 0
*  Frequency (number of patients) for the specified number of complications.
9 0 1 0 0
The n value given under each column head is the total number of patients in
sion criteria. In this study, there were 23 patients who ul- that group (column) who experienced a complication.
timately were determined to not have ASCI who received
high-dose MPSS therapy, and 10 (43.5%) of these patients
had complications. Additionally, while protocols are use-
ful to standardize care for patients with similar conditions, hemorrhage, and pancreatitis; a worsening of head injury
Chang et al. summarize reasons why protocols are less outcome; the possibility of a missed hollow viscus injury
likely to be followed by clinicians when they are complex due to “masking” of abdominal signs; and myopathy.6,7,12
or difficult to follow: 1) clinicians resist them, 2) protocols Our pediatric data, with much larger numbers, mirrors
are inadvertently simplified so they do not apply to a wide these adult data, as we had an overall complication rate of
range of patient populations, and 3) they no longer account 24.9% in the 354 studied patients, with the steroid cohort
for complex physiology.3 In this study, where over the 10- (with and without ASCI) having a 50.8% complication
year study period high-dose MPSS was usually considered rate compared with a complication rate of 19.7% in the
standard therapy, 33 (47.8%) of 69 patients with ICD-9 nonsteroid cohort (with and without ASCI) (Table 1) (p
codes for ASCI did not receive steroids, which supports < 0.05). Complications in our study included respiratory,
the initial point of Chang et al. To their second point, in wound, or urinary tract infections in 10 (17%) of the 59 pe-
the current study, patients receiving MPSS had lower ISSs, diatric patients who received steroids and hyperglycemia
on average, than those who did not receive MPSS. We in 11 (18.6%) (Table 4). Additional complications associ-
believe that this is because those with higher ISSs likely ated with the use of MPSS in ASCI include longer hospital
had multisystem trauma or may have been unresponsive. stays and higher acute care charges.7 These complications
In patients with lower ISSs, the primary injury most often frequently require an intervention or additional reassess-
was isolated to the cervical spine, with associated neuro- ments and monitoring; therefore, we believe all compli-
logical symptoms, making the team more likely to focus cations were worth reporting. However, in our pediatric
on the primary injury and administer steroids. This is an patients who received steroids, we saw a shorter length of
important point to take into consideration when future hospital stay (Table 1). As discussed above regarding in-
treatments for ASCI are developed. jury severity and ISS scores, this may be reflective of the
High-dose MPSS therapy is not without complications. multisystem injuries sustained causing both lower recog-
The majority of studies describing complications associ- nition of ASCI initially and additional injury patterns that
ated with this therapy were conducted in adult patients. extended inpatient care.
A study by Suberviola and colleagues in 2008 examined More recently, a study by Cage et al. described compli-
the early complications of MPSS in ASCI patients.12 This cations associated with high-dose steroid administration in
was a retrospective evaluation of ASCI patients admit- pediatric patients with SCI.2 The authors found an overall
ted to an intensive care unit (ICU) between January 1994 infection rate of 26% in the 23 patients treated with high-
and December 2005. Patients were grouped according to dose steroids and 64% of the 11 SCI patients not treated
presence (n = 59) or absence (n = 23) of MPSS treatment. with steroids. Respiratory tract infections occurred in 45%
There were no significant differences at baseline with of patients not treated with steroids and in 9% of patients
respect to sex ratio, age (range 20.7–64 years), or degree treated with steroids. Hyperglycemia was present in all
of neurological deficit at ICU admission between the 2 patients in both groups. One patient treated with steroids
groups. The MPSS group had an increase in respiratory experienced GI bleeding, and wound infection rates were
tract infections (OR 8.19, 95% CI 1.10–358.6) and total in- not significantly different. Our pediatric data differed in
fections (p = 0.004). Hyperglycemia occurred in 52 (88%) that 6.8% (n = 4) of the 59 patients treated with steroids
of the 59-MPSS treated patients compared with 7 (30%) and 1.4% (n = 4) of the 295 patients not treated with ste-
of the 23 patients who were not treated with MPSS (OR roids experienced a respiratory tract infection. The reason
17.0, 95% CI 4.52–66.3). Additional potential adverse ef- for the difference is unclear, but it may be reflective of a
fects of high-dose MPSS treatment in trauma patients in- short length of stay in our pediatric patient population. The
clude an increased incidence of pulmonary embolism, GI rate of hyperglycemia in our study was 18.6% (n = 11) for
572 J Neurosurg Pediatr  Volume 20 • December 2017
 Lessons learned from methylprednisolone for pediatric ASCI

TABLE 4. Complications by ASCI and exposure to steroids

ASCI & Steroids No ASCI & Steroids Steroids ASCI & No Steroids No ASCI & No Steroids No Steroids Total
Complication (n = 20) (n = 10) (n = 30) (n = 8) (n = 50) (n = 58) (n = 88)
Nausea/vomiting 13 4 17 3 25 28 45
Hyperglycemia 6 5 11 1 5 6 17
Bradycardia 6 2 8 0 7 7 15
Fever 5 2 7 3 19 22 29
Hypertension 2 3 5 3 13 16 21
Increased WBC 2 2 4 0 7 7 11
Respiratory infection 2 2 4 2 2 4 8
UTI 2 1 3 0 3 3 6
Wound infection 2 1 3 1 0 1 4
Bacteremia 0 1 1 1 1 2 3
Myopathy 0 1 1 1 1 2 3
Decreased Hb, Hct 2 0 2 0 0 0 2
Adrenal suppression 0 0 0 1 1 2 2
Elevated LFTs 0 0 0 0 2 2 2
Tachycardia 0 0 0 1 0 1 1
Retroperitoneal bleed 0 0 0 1 0 1 1
Decubitus ulcer 1 0 1 0 0 0 1
Seizure 1 0 1 0 0 0 1
Ileus 0 1 1 0 0 0 1
Yeast infection 0 0 0 0 1 1 1
Numbness 0 0 0 0 1 1 1
Pancreatitis 0 0 0 0 1 1 1
Total 44 25 69 18 89 107 176
Average 2.2 2.5 2.3 2.3 1.8 1.8 2
Hb = hemoglobin; Hct = hematocrit; LFTs = results of liver function tests; UTI = urinary tract infection; WBC = white blood cell count.

patients treated with steroids and 2.0% (n = 6) for patients from our historical use of this therapy and relied on what
not treated with steroids. information was included in the charts. Second, while the
In 2013, the CNS published a Level 1 recommenda- data collectors were experienced, the authors were unable
tion against the administration of MPSS for the treatment to differentiate whether complications were attributable to
of ASCI.5 The report concludes that Class I, II, and III the high-dose MPSS or other traumatic injuries sustained.
evidence exists that high-dose steroids are associated with Third, we were unable to determine the effects of this ther-
harmful side effects, including death. As a consequence, apy from a retrospective study design, and thus we did not
most sites have now eliminated routine use of MPSS. For include patient outcomes in our results. Fourth, although
these reasons, and the data presented above, our institution we know that ordering, dosing, and administration was not
is now one of these sites and no longer considers high-dose ideal, we cannot assess whether unintended consequences
MPSS a therapy in suspected ASCI. may have resulted from or potential complications may
The current study can be generalizable to other com- have been avoided by stopping the intended therapy early
plex protocols for high-risk, low-frequency critical condi- or correcting the dosing. However, given the unclear ben-
tions. Leveraging such resources as computerized physi- efits from this therapy, it is possible that no impact would
cian order entry (CPOE) systems and medication infusion have been realized from either of these protocol deviations.
smart pumps to facilitate compliance with these protocols While our focus was on complications and difficul-
is important. Both the new CPOE system and new medica- ties with the medication use process, a limitation of our
tion infusion pumps were implemented after the study pe- data collection was the absence of patient outcomes. This
riod and were not available for use during the study period. could be an opportunity for future research in the pediatric
The current study has several limitations. This was a population. However, without obvious indication to begin
retrospective study that required the investigators to use steroid treatment in children with ASCI, it would likely
several sources of information, often for each patient. The require multicenter collaboration.
paper or scanned charts were at times incomplete. We in-
cluded as many patients (only 32 [5%] of the initial 602
charts were excluded for incomplete information) and Conclusions
chart data points as possible to learn as much as we could This study highlights an example of managing a com-
J Neurosurg Pediatr  Volume 20 • December 2017 573
M. C. Caruso et al.

plex, infrequently used medication regimen in the pedi- nisolone in spinal cord trauma in children. Pediatr Surg Int
atric patient population. As demonstrated by the current 28:287–294, 2012
study, high-dose MPSS for ASCI may not be able to be 10. Sayer FT, Kronvall E, Nilsson OG: Methylprednisolone
treatment in acute spinal cord injury: the myth challenged
delivered to the patient according to the protocol with a through a structured analysis of published literature. Spine J
high degree of reliability. The findings presented, includ- 6:335–343, 2006
ing complications of steroid use, further support removal 11. Short DJ, El Masry WS, Jones PW: High dose methylpred-
of steroids from current practice in pediatric patients with nisolone in the management of acute spinal cord injury - a
ASCI. systematic review from a clinical perspective. Spinal Cord
38:273–286, 2000
12. Suberviola B, Gonzalex-Castro A, Llorca J, Ortiz-Melon F,
References Minambres E: Early complications of high-dose methylpred-
  1. American Association of Neurological Surgeons/Congress nisolone in acute spinal cord injury patients. Injury 39:748–
of Neurological Surgeons Joint Section on Disorders of the 752, 2008
Spine and Peripheral Nerves: Pharmacological therapy after
acute cervical spinal cord injury. Neurosurgery 50 (Suppl
3):S63–S72, 2002
  2. Cage JM, Knox JB, Wimberly RL, Shaha S, Jo C, Riccio Disclosures
AI: Complications associated with high-dose corticosteroid The authors report no conflict of interest concerning the materi-
administration in children with spinal cord injury. J Pediatr als or methods used in this study or the findings specified in this
Orthop 35:687–692, 2015 paper.
  3. Chang SY, Sevransky J, Martin GS: Protocols in the manage-
ment of critical illness. Crit Care 16:306, 2012 Author Contributions
  4. Hurlbert RJ: Methylprednisolone for acute spinal cord in-
Conception and design: all authors. Acquisition of data: Caruso,
jury: an inappropriate standard of care. J Neurosurg 93 (1
Daugherty. Analysis and interpretation of data: all authors. Draft-
Suppl):1–7, 2000
ing the article: Caruso, Daugherty, Moody. Critically revising the
  5. Hurlbert RJ, Hadley MN, Walters BC, Aarabi B, Dhall SS,
article: all authors. Reviewed submitted version of manuscript: all
Gelb DE, et al: Pharmacological therapy for acute spinal cord
authors. Approved the final version of the manuscript on behalf
injury. Neurosurgery 72 (Suppl 2):93–105, 2013
of all authors: Caruso. Statistical analysis: Caruso, Daugherty,
  6. Lee HC, Cho DY, Lee WY, Chuang HC: Pitfalls in the treat-
Moody. Administrative/technical/material support: Caruso,
ment of acute cervical spinal cord injury using high-dose
Daugherty, Moody. Study supervision: Caruso.
methylprednisolone: a retrospect audit of 111 patients. Surgi-
cal Neurosurg 68 Suppl 1:S37–S42, 2007 Supplemental Information
  7. Matsumoto T, Tamaki T, Kawakami M, Yoshida M, Ando
M, Yamada H: Early complications of high-dose methyl- Previous Presentations
prednisolone sodium succinate treatment in the follow-up Portions of this work were presented as a platform presentation at
of acute cervical spinal cord injury. Spine (Phila Pa 1976) the 2nd annual meeting of the Pediatric Trauma Society, Novem-
26:426–430, 2001 ber 6–7, 2015, in Scottsdale, Arizona.
  8. Nesathurai S: Steroids and spinal cord injury: revisiting the
NASCIS 2 and NASCIS 3 trials. J Trauma 45:1088–1093, Correspondence
1998 Michelle C. Caruso, Division of Pharmacy, Cincinnati Children’s
  9. Pettiford JN, Bikhchandani J, Ostlie DJ, St Peter SD, Sharp Hospital Medical Center, 3333 Burnet Ave., MLC 15010, Cincin-
RJ, Juang D: A review: the role of high dose methylpred- nati, OH 45229. email: [email protected].

574 J Neurosurg Pediatr  Volume 20 • December 2017