Pitfalls in treatment of acute cervical spinal cord injury using high-dose methylprednisolone: a retrospect audit of 111 patients

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Surgical Neurology 68 (2007) S1:37 – S1:42 www.surgicalneurology-online.com

Trauma

Pitfalls in treatment of acute cervical spinal cord injury using high-dose methylprednisolone: a retrospect audit of 111 patients Han-Chung Lee, MD, Der-Yang Cho, MD⁎, Wen-Yuan Lee, MD, Hao-Che Chuang, MD Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan 404, ROC Received 17 November 2006; accepted 20 June 2007

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. © 2007 Elsevier Inc. All rights reserved.

Keywords:

Acute spinal cord injury; Methylprednisolone; NASCIS; EMT; Tracheostomy

1. Introduction Accidents are the fourth leading cause of death in Taiwan and an even more common cause of death in the second and third decades. Paralysis by trauma to the spinal cord is one of

Abbreviations: ASCI, acute spinal cord injury; EMT, emergency medical team; IV, intravascular; MP, methylprednisolone; NASCIS, National Acute Spinal Cord Injury Studies; SCI, spinal cord injury. ⁎ Corresponding author. Tel.: +886 4 22052121x4434; fax: +886 4 22062121x4435. E-mail address: [email protected] (D.-Y. Cho). 0090-3019/$ – see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.surneu.2007.06.085

the most physically disabling and psychologically devastating conditions. Its socioeconomic impact is significant depending on the level of independence. The high-dose intravenous MP protocol has become the standard of care for ASCI since publication of the NASCIS II and III in 1990 and 1997 [3,4]. The authors reported that MP, when administered within 8 hours of injury, resulted in statistically significant motor and sensory recovery in both complete and incomplete SCI. However, whether the NASCIS actually showed the benefits of high-dose MP [18] is debatable because of its harmful side effects. This study aimed to evaluate the effects of high-dose MP in treatment of cervical SCI and to

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Table 1 Frankel classification system

Table 3 Demographic and clinical characteristics of patients with SCI

A No sensory or motor function distal to neurologic lesion (complete injury) B Sensory sparing only C Motor sparing that is not functional (ie, motor strength is not sufficient to permit or significantly ease performance of activities of daily living) D Motor sparing that is functional E Complete recovery

Feature

determine how these effects might be improved and the side effects reduced. 2. Patients and methods Between January 2002 and December 2003, 138 patients with cervical spinal injury secondary to blunt injuries were admitted to China Medical University Hospital, Taichung, Taiwan, ROC. This 1300-bed hospital and the attached multispecialty clinic serve as a referral trauma center for middle Taiwan. Patients are often treated at smaller community hospitals before transfer to this hospital. Inpatient and outpatient records were retrospectively reviewed. The database included sex, age, date and time of injury, mechanism, date of referral and admission, associated injuries, length of hospital stay, and surgical interventions. Serial neurologic evaluations were performed by 1 of 5 neurosurgical attending staff. The findings on admission were compared with those at discharge and at the most current outpatient follow-up visit. Significant neurologic improvement was defined as increase of at least 1 clinical grade according to the Frankel classification system, which describes degrees of distal sensory and motor preservation after spinal injury (Table 1) [1,12,21]. Records were also reviewed to determine which steroid administration protocols were used and whether the high-dose protocol as outlined in NASCIS II and III was used. The time interval between injury and the onset

Table 2 Age distribution of incidence of injuries stemming from T/A and falls

T/A indicates traffic accident.

Age (y) Range Mean b40 40-60 N60 Total (patients) Sex Male Female Injury mechanisms Falls Road traffic accidents Diving mishaps Miscellaneous Injury level C1-C2 C3-C5 C6-C7 Injury severity score Range Mean

Total population and % of total Complete SCI

Incomplete SCI

Mild incomplete SCI

22-82 47.5 5 (20%) 9 (36%) 11 (44%) 25

10-86 49 16 (36%) 12 (27%) 17 (37%) 45

18-78 45 11 (26%) 15 (37%) 15 (37%) 41

16 (64%) 9 (36%)

29 (65%) 16 (35%)

26 (64%) 15 (36%)

13 (52) 10 (40%)

16 (36%) 27 (60%)

12 (27%) 29 (73%)

2 (8%) 2 (4%) 3 (10%) 15 (60%) 7 (30%)

3 (7%) 31 (69%) 11 (24%)

28 (70%) 13 (30%)

18-36 20

13-34 16

8-22 11

of steroid administration was determined. All complications were listed. 3. Results Of the 138 patients with cervical spinal injury (44 female and 94 male; mean age, 48.5 years [range 10-86 years]) treated between January 2002 and December 2003,

Table 4 Results of treating complete and incomplete SCI Features

Rate of surgery No. using MP Rate of complication related to MP use Survival rate Length of hospitalization (d) Mean hospital stay (d) Significant improvement in Frankel scale score OP MP + OP EMT transferred directly Complete recovery rate Transferred from clinics Complete recovery rate OP indicates surgery.

Total population Complete SCI

Incomplete SCI

Mild SCI

18/25 16 14/16

31/45 28 8/28

26/41 14 2/14

23/25 28-268

45/45 4-116

41/41

71.8

21.6

0/7 11/16 9/12 0 2/4 0

4/8 21/31 14/19 4/19 7/12 1/12

H.-C. Lee et al. / Surgical Neurology 68 (2007) S1:37–S1:42 Table 5 Frankel scores at the time of admission compared with those at the time of discharge for 12 patients with complete SCI transported by the EMT directly Admission

A B C D E

Discharge A

B

C

3

7

2

D

E

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Table 7 Frankel scores at the time of admission compared with those at the time of discharge for 19 patients with incomplete SCI transported by the EMT directly Admission

Discharge A

B

A B C D E

C

D

E

3 1

1 6 4

1 3

25 had complete SCI, 45 had incomplete SCI, and 41 had simple paresthesia due to mild cord contusion. The other 27 had fractures of the axis and/or atlas and were excluded. Injury was due to road traffic accidents in 60% (83/138, most in the young age group [10-50 years old]) and falls in 36% (55/138, most in the old age group) (Table 2). Diving accidents, assault, and a forceful blow to the face were responsible for the injuries in 2, 1, and 1 patient, respectively. No spinal cord injuries were due to penetrating trauma. Thirty-nine (28.3%) patients were transferred from smaller community hospitals, 20 of these were surgically treated, and the mean interval between injury and transfer was 6.9 hours (range, 2-23 hours). Ninetynine patients were transported directly from the accident site by the EMT, 65 of these were surgically treated, and the mean interval between injury and transport was 23 minutes (range, 7-45 minutes). Tables 3 and 4 list the demographic data for the 25 patients with complete SCI and the 45 patients with incomplete SCI. Surgical procedures to achieve spinal cord decompression or vertebral column ability were performed in 75 patients including 18 (of 25) with complete SCI, 31 (of 45) with incomplete SCI, and 26 (of 41) with minor cord contusion. Surgical procedures ranged from anterior cervical diskectomy and fusion to open reduction and internal fixation of the spine with corpectomy and bone graft or with internal fixation devices. The philosophy of the neurosurgery staff is to provide early decompression and stabilization of spinal cord injuries whenever possible. Surgery-related complications were noted in 7 (of 75, 9%) patients, including 2 with wound infection, 2 with displacement of the screw and plate, 1 with esophageal perforation, 1 with postoperative progression to quadriplegia and accumulation of epidural

hematomas, and 1 with complete SCI, who had epidural abscess 1 month after surgery and later died from sepsis. Of the 42% (58/138) of patients given MP correctly according to the NASCIS II and III, 16 had complete SCI, 28 had incomplete SCI, and 14 had mild spinal cord contusion. Intravenous H2 blocking agent was given simultaneously to prevent adverse gastrointestinal effects and stress ulcers. Steroid-related complications were noted in 14 (of 16, 87.5%) patients with complete SCI, 8 (of 28, 28.6%) patients with incomplete SCI, and 2 (of 14, 14.3%) patients with mild spinal cord contusion. These included peptic ulcer, upper gastrointestinal bleeding, perforated peptic ulcer, and urinary tract infection. One patient with complete SCI died from sepsis related to a perforated peptic ulcer. In total, 23 patients with complete SCI survived, but all failed to develop sufficient motor strength to permit the performance of activities of daily living. The length of hospitalization was 28 to 268 days (mean, 71.8 days). Significant changes in Frankel score were observed in 11 (69%) of the 16 patients treated with surgery and MP administration (Tables 5 and 6). Moreover, 9 (75%) of the 12 patients transported by the EMT directly showed significant functional improvement by the time of discharge, with Frankel scores improved from A to C in 2 patients. However, only 2 (50%) of the 4 patients transferred from other hospitals improved. The condition of the other 7 patients with complete SCI did not improve, even the 2 who accepted surgery. In total, 45 patients with incomplete SCI survived. The length of hospitalization was 4 to 116 days (mean, 21.6 days). Significant change in Frankel score was observed in 21 of the 31 patients treated with surgery and MP administration (Tables 7 and 8). In addition, 14 (73.7%) of 19 patients

Table 6 Frankel scores at the time of admission compared with those at the time of discharge for 4 patients with complete SCI who were transferred from the local hospitals

Table 8 Frankel scores at the time of admission compared with those at the time of discharge for 12 patients with incomplete SCI who were transferred from the local hospitals

Admission

Admission

A B C D E

Discharge A

B

2

2

C

D

E

Discharge A

A B C D E

B

C

D

E

2 3

1 3 2

1

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Table 9 Frankel scores at the time of admission compared with those at the time of discharge for 8 patients with incomplete SCI not treated with MP Admission

Discharge A

A B C D E

B

C

1

2 1

D

E

2 2

transported directly by the EMT showed significant functional improvement by the time of discharge, and 4 (21%) of these 19 patients recovered completely by the time of last follow-up visit. However, 7 (58.3%) of 12 patients who were transferred from a local hospital showed significant functional improvement by the time of discharge, and only 1 (9.3%) of these recovered completely by the time of last follow-up visit. Eight patients with incomplete SCI were surgically treated, but without MP. Significant functional improvement (increase in Frankel score) was seen by the time of discharge in 4 (50%) of these 8 patients, and none recovered completely (Table 9). Thirteen (of 23, 56.5%) of the patients with complete SCI underwent a tracheostomy during their hospitalization, which was 22 to 110 days (mean, 49 days), and 10 (43.5%) did not (length of hospitalization, 28-268 days [mean, 94 days]). 4. Discussion Acute SCI occurs as a result of failure (due to flexion, extension, axial, rotation, and distraction overload) of the osteoligamentous spinal column. Spinal cord injury in its mildest form is a cord concussion with brief transient neurologic deficits [9,28] and in its most severe form leads to complete and permanent paralysis. The severity of the initial tissue disruption and subsequent secondary injury (including local vascular changes and ischemia within the spinal cord [6,23], lipid peroxidation by free radicals [8,13], excitotoxicity [glutamate] and electrolyte imbalances [22,26], necrotic and apoptotic cell death [15,19], and inflammatory/immunologic response [7,14]) depends on the amount of energy delivered to the spinal cord. The early medical and surgical interventions for patients with ASCI performed in our hospital attempted to minimize this secondary injury and protect the neural elements that initially withstood mechanical injury. In our study, better functional improvement at the time of discharge was achieved in patients with ASCI transported directly to our facility by the EMT than in those who were transferred to our facility from another hospital. This occurred because the necessary medical and surgical intervention was provided much earlier (23 minutes vs 6.9 hours) to the former group. As we know, all patients with suspected ASCI should be treated at the scene and transported to the nearest hospital,

carefully and expeditiously. Moreover, the hospital should be equipped to handle such injuries. However, in Taiwan, the number of injuries exceeds the capacity of the EMT, and patients are frequently transported to the nearest local duty hospital, where spinal cord injuries go untreated. The medical centers are distributed in Taiwan so that anyone can be transported to one of them within 2 hours. Because these patients need to be treated as quickly as possible, it is very important to identify the hospitals capable of delivering trauma care. The patient should be transported to a trauma center directly, unless they have unstable vital signs. The use of corticosteroid, particularly MP, in the setting of ASCI, began more than 30 years ago and was rationalized on the basis of its well-recognized antiinflammatory properties that were thought to reduce spinal cord edema [10,11]. Although their precise mechanisms of action are not completely known, corticosteroids have the potential to stabilize membrane structures, maintain the blood–spinal cord barrier (potentially reducing vasogenic edema), enhance spinal cord blood flow, alter electrolyte concentrations at the site of injury, inhibit endorphin release, scavenge damaging free radicals, and limit the inflammatory response to injury [2,24,27]. The NASCIS I, II, and III were largescale prospective, randomized, double-blinded, multicenter clinical trials for the use of MP in SCI. National Acute Spinal Cord Injury Study I showed no difference in motor or sensory recovery in 2 groups of 10 daily doses of either 100 or 1000 mg of MP begun 48 hours after ASCI in 330 patients [29]. National Acute Spinal Cord Injury Study II reported that MP administered within 8 hours of injury resulted in statistically significant motor and sensory recovery in both complete and incomplete ASCI [3]. National Acute Spinal Cord Injury Study III, published in 1997 [4,5], concluded that MP administered within 3 hours of injury should be maintained for 24 hours, and when administered 3 to 8 hours after injury, it should be maintained for 48 hours. However, there is some disagreement over whether the NASCIS actually showed the benefits of high-dose MP, and evidence suggests it has harmful side effects and causes steroid myopathy [16,25]. Significant motor and sensory recovery in our patients with complete and incomplete ASCI (complete ASCI, 69% vs 0; incomplete ASCI, 70% vs 50%) were noted after surgery and MP administration compared with patients without such treatment. Unfortunately, all patients with complete ASCI, whether treated surgically and/or given MP administration, failed to recover sufficient motor strength to permit performance of activities of daily living. Moreover, 87% of patients with complete ASCI who accepted MP administration have steroid-related complications, and 1 patient died because of sepsis that related to the perforated peptic ulcer. In addition, the same situation was not shown in incomplete (8/28, 28.6%) and mild (2/14, 14.3%) ASCI. The same result was reported in 2001 by Matsumoto et al [17]. The authors focused on potential medical complications after ASCI. Patients treated with MP had a higher incidence of complications compared with

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placebo-treated patients (56.5% vs 34.8%). Pulmonary complications and gastrointestinal complications were the most significant in these 2 groups and were the same as our results. This result reminded us that in the use of MP after ASCI, we have to be more careful and to stop the MP administration for complete ASCI. Respiratory failure always occurs in patients with complete ASCI (especially those with cervical lesions at or just below the C5 level) for 2 reasons. First, the stomach contents are frequently aspirated (the incidence of gross gastric aspiration in trauma victims with neurologic injury being as high as 38%) [20]. Second, the lesions below the C5 level affect intercostals and abdominal muscles, resulting in respiratory impairment predominantly from inspiratory and expiratory muscle weakness. Ventilator dependence and iatrogenic pneumonia prolonged hospitalization and limited further rehabilitation. The performance of early tracheostomy in 13 patients significantly shortened their mean stay in our hospital (49 days; range, 22-110 days for treated patients vs 94 days; range, 28-268 days for untreated patients). 5. Conclusion Early surgical intervention and MP administration is critical for ASCI. All patients with suspected ASCI should be treated at the scene and transported to the nearest hospital that is best able to provide trauma care. If patients have unstable vital signs, they should be transported quickly to the nearest hospital. Although treatment with MP for either 24 or 48 hours significantly improves motor and sensory function in patients with both complete and incomplete ASCI, we suggest that its use should be limited in patients with complete ASCI because functional improvement is limited, and the risk of harmful side effects is high in this group. Early tracheostomy is advocated for patients with complete ASCI. It can shorten the length of hospitalization significantly. References [1] Amar PA, Levy ML. Pathogenesis and pharmacological strategies for mitigating secondary damage in acute spinal cord injury. Neurosurgery 1999;44:1027-40. [2] Bracken MB, Collins WF, Freeman DF, et al. Efficacy of methylprednisolone in acute spinal cord injury. JAMA 1984;251(1):45-52. [3] Bracken MB, Shepard MJ, Collins WF, et al. A randomized, controlled trial of methylprednisolone and naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med 1990;322(20):1405-11. [4] Bracken MB, Shepard MJ, Holford TR, et al. Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study. JAMA 1997;277 (20):1597-604. [5] Bracken MB, Shepard MJ, Holford TR, et al. Methylprednisolone or tirilazad mesylate administration after acute spinal cord injury: 1-year follow up. Results of the third National Acute Spinal Cord Injury Randomized Controlled Trial. J Neurosurg 1998;89(5):699-706.

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Commentary Doctor Lee et al report on the outcome of 138 patients who have experienced SCI from blunt trauma. Most of the patients were treated with MP and surgical decompression/