1 Resuscitation 66 (2005) Review Spinal cord injury (SCI) Prehospital management, Michael Bernhard a,, André Gries a, Paul Kremer b, Bernd W. Böttiger a, a Department of Anesthesiology, University of Heidelberg, Im Neuenheimer Feld 110, D Heidelberg, Germany b Department of Neurosurgery, University of Heidelberg, Im Neuenheimer Feld 400, D Heidelberg, Germany Received 8 April 2004; received in revised form 1 March 2005; accepted 1 March 2005 Abstract Up to 20,000 patients annually suffer from spinal cord injury (SCI) and 20% of these die before being admitted to the hospital in the United States as well as in the European Union. Prehospital management of SCI is of critical importance since 25% of SCI damage may occur or be aggravated after the initial event. Prehospital management includes examination of the patient, spinal immobilisation, careful airway management (intubation, if indicated, using manual in-line stabilisation), and cardiovascular support (maintenance of mean arterial blood pressure above 90 mmhg) and blood glucose levels within the normal range. It is still not known whether additional specific therapy is useful. Studies have not demonstrated convincingly that methylprednisolone (MPS) or other pharmacological agents really have clinically significant and important benefits for patients suffering from SCI. Recently published statements from the United States also do not support the therapeutic use of MPS in patients suffering from SCI in the prehospital setting any more. Moreover, at this stage, it is not known whether therapeutic hypothermia or any further pharmacological intervention has beneficial effects or not. Therefore, networks for clinical studies in SCI patients should be established, as a basic requirement for further improvement in outcome in such patients Elsevier Ireland Ltd. All rights reserved. Keywords: Spinal cord injury; Emergency treatment; Fluid therapy; Blood pressure; Drug therapy Contents 1. Introduction Epidemiology Incidence and prevalence of SCI Causes of SCI Location of SCI Prehospital findings of SCI SCI-associated injuries Prehospital management of SCI Primary evaluation and resuscitation of vital functions Patient immobilisation Oxygenation and airway management Prehospital problems Prehospital solutions Cardiovascular support Presented in part at the Third International Interdisciplinary Congress EuroNeuro 2002, from September 2002, in Munich, Germany by B.W. Böttiger. A Spanish translated version of the Abstract and Keywords of this article appears as Appendix at /j.resuscitation Corresponding authors. Tel.: ; fax: address: (M. Bernhard) /$ see front matter 2005 Elsevier Ireland Ltd. All rights reserved. doi: /j.resuscitation
2 128 M. Bernhard et al. / Resuscitation 66 (2005) Effects of systemic hypotension Fluid resuscitation Pharmacological treatment NASCIS NASCIS 1 clinical relevance NASCIS NASCIS 2 clinical relevance NASCIS NASCIS 3 clinical relevance Statement on the treatment with steroids in prehospital management of SCI Steroids are harmful in traumatic brain injury Transportation and type of trauma centre Conclusions References Introduction This paper presents an overview of current practice in the prehospital management of acute spinal cord injury (SCI). Epidemiology, examination, patient immobilisation, airway management, cardiovascular support, and pharmacological treatment are discussed Epidemiology Incidence and prevalence of SCI The annual incidence of SCI including prehospital fatalities has been estimated at per million inhabitants in the United States which equates to about 20,000 patients every year. About 20% of these patients die before they are admitted to the hospital [1 3]. This incidence of SCI is associated with a prevalence of about 200,000 patients in the United States . Of these SCI patients 50 70% are between 15 and 35 years of age, while 4 14% are 15 years old or younger. The maleto-female ratio is 4:1. In 1990, the estimated costs for therapy of SCI in the United States were around US$ 4 billion per year . Therefore, SCI is a major cause of mortality and morbidity in young individuals and as a result has a major impact on society as a whole Causes of SCI The most frequent causes of SCI in adults are motor vehicle accidents (40%), falls (21%), acts of violence (15%), and sports-related injuries (13%). In children SCIs are mostly due to sports (24%) and water recreational activities (13%) [1,4] Location of SCI In a retrospective chart view of 331 patients, Domeier et al. described the distribution of SCI as 29% cervical, 24% thoracic, 37% lumbar, and 10% sacral, due to the varying stability of the spine (Figs. 1 and 2) . Fig. 1. Spine injury with fracture and dislocation of C 5. Rupture of front and rear longitudinal ligament. Such injury is associated with a risk of spinal cord injury Prehospital findings of SCI The following clinical symptoms associated with SCI are useful in identifying patients who require specific prehospital treatment: lumbar pain, head injury and altered mental status, cervical pain, neurological deficit, thoracic pain, and spinal tenderness (Table 1) . It is very important to know that pain from SCI is not necessarily localized in the area of injury. In 18% of cervical, in 63% of thoracic, and in 9% of lumbar injuries, the pain is located elsewhere . If there is pain in a site that can be
3 M. Bernhard et al. / Resuscitation 66 (2005) Abdominal bleeding or traumatic brain injury in patients suffering from multiple trauma cause higher mortality rates than SCI. Therefore, it is necessary that in severely injured patients, treatment priorities should be established based on their injuries, vital signs, and the injury mechanisms, according to established advanced trauma life support (ATLS) principles. Therefore, prehospital treatment in patients with multiple trauma should be always conducted in accordance with the management of the principal life threatening injury, but the subsequent management of SCI must be born in mind all the time . 2. Prehospital management of SCI Fig. 2. Spinal cord injury: haematoma (H) with shift and compression of the spinal cord (M; this figure is kindly provided by Dr. Bodo Kress, Department of Neuroradiology, University of Heidelberg, Germany). related to SCI, it is necessary to take special care because the location of injury can be in another segment of the spine. Moreover, if a spinal injury is identified, there can be further injuries at other spine segments in up to 15%  SCI-associated injuries It is well known that SCI occurs in 5 10% of patients suffering from severe traumatic brain injury (TBI); conversely, 25 50% of patients with SCI have an associated head injury [7,8]. Moreover, SCI occurs in 10 30% of patients with multiple trauma. The majority of trauma in Europe is blunt. Abdominal and thoracic trauma are often associated with severe haemorrhage; SCI occurs in up to 30% of these patients. Therefore, SCI should always be considered in patients with multiple trauma, as well as in those with minor trauma who report spinal pain and/or have sensory or motor symptoms, and in those with an altered mental status [9,10]. Table 1 Prehospital clinical findings by cervical to lumbar spinal cord injury  Lumbar pain 37% Head injury 36% Altered mental status 31% Cervical pain 15% Neurological deficit 15% Back pain 13% Thoracic pain 11% Spinal tenderness 8% The goal of prehospital management of SCI is to reduce neurological deficit and to prevent any additional loss of neurological function. Therefore, prehospital management at the scene should include a rapid primary evaluation of the patient, resuscitation of vital functions (airway, breathing, circulation; the ABCs ), a more detailed secondary assessment, and finally definitive care (including transport and admission to a trauma centre). Moreover, after arrival at the scene, it is important to read the scene and to appreciate the mechanism of injury in order to identify the potential for SCI. Prehospital management in general and the management of the airway and ventilation in particular should include immobilisation of the spine in suspicious cases to reduce the risk of a secondary SCI. Cardiovascular support and pharmacological treatment complete the initial prehospital management of SCI. Ultimately, the level of the trauma centre and the time to appropriate surgical treatment may determine neurological outcome [12 15]. The improved prognosis of patients suffering from SCI today is reflected by the general changes in prehospital care, in particular rapid triage to facilities with SCI expertise, and advances in medical, surgical and rehabilitative care. From a scientific point of view however, the specific factors determining the improved outcome today have not been clearly identified  Primary evaluation and resuscitation of vital functions In the initial examination  of the patient, the airway, breathing, and circulation (the ABCs ) should be evaluated, controlled and restored according to recommended guidelines . Secondary examination: a more thorough evaluation should be performed ( head to toe/whole-body check ). In particular, this examination should focus on patients with a potential SCI and complaints of pain in the neck or back, tenderness to palpation, signs of muscle weakness, paralysis or altered sensation, signs of incontinence, priapism, increased skin warmth or flushing, and other superficial signs of injury . Prehospital findings should be documented precisely.
4 130 M. Bernhard et al. / Resuscitation 66 (2005) Patient immobilisation Historically, it is estimated that up to 25% of SCI may be aggravated after the initial insult, either during transport or early in the course of treatment [18,19]. It should be mentioned that these data are more than 20-years old, and no data are available from actual studies. Careful movement and the use of appropriate extrication techniques are crucial in all trauma patients with SCI or in mechanisms of injury with the potential to cause spinal injury and SCI. Immobilisation of the entire spine is a management priority and should be undertaken in a systematic fashion. The patient should be immobilised in a neutral spine position at the scene and during transport by using a rigid cervical collar, sandbags on either side of the head, and on a rigid backboard with straps [8,18,19]. In Europe, the vacuum splint device in combination with a rigid cervical collar is a common option for immobilisation . However, although immobilisation devices are generally effective in limiting motion of the cervical spine, they may be associated with important morbidity (i.e., discomfort, pressure sore, decubitus ulcer, and restriction of respiration) [8,19]. Therefore, immobilisation devices should be removed when any lesion of the spinal cord or spine is excluded with certainty after in-hospital diagnostic tests have been performed . Systems of immobilisation such as the Kendrick extrication device (KED) in combination with a rigid cervical collar are useful to provide almost complete immobilisation of the head and torso. These systems are often used to immobilise patients with suspected SCI during extrication after a motor vehicle crash. The time to apply these devices may be long and therefore, they should only be applied if there are no life-threating injuries and the patient s vital functions are stable. Moreover, these devices are inappropriate in situations where rapid extrication is necessary (e.g., fire in car with an entrapped patient) . Here, the patient should be evacuated using manual in-line stabilisation with all available rescue manpower Oxygenation and airway management Prehospital problems Possible problems associated with SCI are acute respiratory failure and hypoxia caused by hypoventilation, aspiration, or impaired diaphragmatic function as a consequence of injuries to the upper cervical region (C 3 5 ) . When the SCI spares the diaphragm but paralyses the intercostal and abdominal muscles, there may be inadequate coughing, paradoxical rib movement on spontaneous ventilation, decrease in vital capacity (50%) and functional residual capacity (85% of predicted values), and loss of active expiration . Complete injury above the C 3 level leads to apnoic respiratory arrest and death unless immediate ventilatory assistance is provided . This may indicate the need to intubate the trachea urgently . Other problems of airway management in patients suffering from SCI may occur if there are associated facial and thoracic injuries , i.e., pneumothorax or aspiration from pharyngeal hamorrhage. Tracheal intubation attempts in patients with an unstable spine according to some case reports may lead to severe SCI and death [22,23]. To preserve the spine and spinal cord integrity, to reduce any resulting neurological deficit and to prevent any additional loss of neurological function, the patient must be intubated with great care and benefits must be balanced against risk. The role of rapid sequence induction for intubation of the trachea in the prehospital trauma setting by trained EMS staff is crucial and may be used as an advanced airway management technique to improve the success of intubating the trachea . Intubation of the trachea in patients suffering from SCI should be accompanied by rapid sequence induction in order to reduce coughing and spontaneous movements. The use of succinylcholine in patients with SCI may cause bradycardia leading to arrest secondary to hyperkalaemia, but it is probably safe to use it during the first 48 h after SCI . In a retrospective study of 140 patients suffering from traumatic cervical spine fracture, the distribution of the fracture site was as follows: 19% C 1 2, 21% C 3 4, and 60% C 5 7 . In human subjects without any cervical abnormality , and in fresh human cadavers , the vast majority of cervical movement from orotracheal intubation using direct laryngoscopy occurs at the atlantooccipital and atlantoaxial joints. The subaxial cervical segments (C 2 5(7) ) are displaced less frequently. From studies on cadavers, it is known that the use of manual in-line stabilisation (please see below) results in significantly less anteriorposterior displacement during orotracheal intubation than the use of a rigid cervical collar . Furthermore, it is more difficult to open the mouth with a rigid cervical collar in place and cervical mobility is restricted, which makes intubation more difficult with the risk of airway compromise, difficult intubation, and aspiration Prehospital solutions Continuous pulse oximetry is used in patients with SCI to detect hypoxia. Immediately after arrival at the scene and always before intubation, the patient should receive oxygen via a face mask (preoxygenation) and the neck should be immobilised. Intubation of the trachea (or another method of securing the airway) and controlled ventilation are indicated if saturation (S p O 2 ) is persistently less than 90%, if the respiratory rate is low, or if the Glasgow Coma Scale (GCS) is less than 9. Intubation of the trachea should be performed in accordance with the concept of rapid sequence induction . When intubation is urgent, the rigid cervical collar should be opened and manual in-line stabilisation (MILS) applied to ensure mechanical stability of the spine . MILS means that a second person immobilises the cervical spine in a neutral position using both hands on each side of patient s head in order to prevent any movement of the neck . After successful intubation the rigid cervical collar should be reapplied. MILS reduces cervical spine
5 movement during intubation of the trachea, but it does not totally prevent movement [31,32]. Alternative airway devices such as the laryngeal mask, the intubating laryngeal mask and the Combitube may exert greater pressure on the cervical vertebrae than conventional intubation techniques, these devices should only be used when routine intubation is not possible . An accepted in-hospital standard in patients suffering from SCI is fibreoptic tracheal intubation , but this technique is not often used in the prehospital setting Cardiovascular support M. Bernhard et al. / Resuscitation 66 (2005) Possible cardiovascular problems associated with SCI are neurogenic and hypovolaemic shock. Neurogenic shock may occur in SCI above T 5 when the injury has caused a sympathectomy below the level of injury. Neurogenic shock is associated with hypotension secondary to arteriolar and venous vasodilatation, hypotension secondary to loss of the sympathetic outflow from the splanchnic vascular beds, and bradycardia secondary to interruption of the sympathetic innervation of the heart [8,25]. These pathophysiological changes cause pooling of blood in the extremities and reduction of central venous return. Thus, neurogenic shock may be associated with a systolic blood pressure (SBP) less than 70 mmhg and with severe bradycardia below 60 beats per minute. Both multiple trauma and severe haemorrhage can be associated with SCI in up to 30% of cases. Hypovolaemic shock may be associated with SBP of less than 90 mmhg and tachycardia. Other causes of hypotension associated with tachycardia should be excluded (e.g., blood loss associated with other injuries) . It may be possible to distinguish neurogenic from hypovolaemic shock but they are often combined in the prehospital situation . The major goal in SCI is to reestablish circulation to the neural tissue. Therefore, during the management of neurogenic shock, the patient should be in the Trendelenburg position, with atropine and a catecholamine administered intravenously, if indicated. To re-establish the circulation in neural tissue during hypovolaemic shock the patient should also be in the Trendelenburg position and receive intravenous fluids. However, fluid resuscitation should be used with special care in this situation because it can lead to pulmonary oedema . At least two 14G IV cannulae should be used. The desired mean arterial blood pressure (MAP) is at least 90 mmhg; each episode of hypotension (SBP less than 90 mmhg) should be avoided or corrected as quickly as possible [9,34]. To achieve the desired MAP, fluid resuscitation plays an essential role in prehospital management of SCI associated with hypovolaemia  Effects of systemic hypotension Prospective controlled studies reflecting the effects of hypotension in SCI on neurological outcome are lacking. Nevertheless, it is well known that hypotension is a frequent Fig. 3. Hypotension is a common phenomenon and may lead to secondary brain damage in patients suffering from severe traumatic brain injury (TBI). In a prospective study in patients suffering from severe TBI, early hypotension (systolic blood pressure (SBP) <90 mmhg; n = 248/717) during prehospital care was associated with a doubling of mortality (55% vs. 27%; p < 0.05). Moreover, late hypotension (SBP <90 mmhg; n = 117/493) during intensive care unit (ICU) stay was also associated with a 3.8-fold higher mortality (66% vs. 17%; p < 0.05) and significantly worse neurological outcome . cause of cerebral ischemia secondary to severe traumatic brain injury (TBI) . In these patients, hypotension in the early stages (SBP less than 90 mmhg) was associated with a doubling of mortality (55% versus 27%; p < 0.05). Moreover, hypotension occuring later during the intensive care unit (ICU) stay was associated with a 3.8-fold higher mortality (66% versus 17%; p < 0.05) and significantly worse neurological outcome (Fig. 3) . These data demonstrate that when hypotension occurs, it may be associated with secondary brain damage in patients suffering from severe TBI. Based on the extrapolation of these findings, hypotension should be avoided by adequate prehospital management Fluid resuscitation Crystalloids and colloids. For fluid resuscitation in the prehospital setting crystalloids or colloids can be given although which is to be preferred is still a matter of debate. Crystalloid solutions are isooncotic and offer varying osmolarities (Table 2). Compared with crystalloids, colloids have the same osmolarity but a different oncotic pressure (Table 2). To varying degrees, colloids can cause anaphylaxis Table 2 Characteristics of crystalloid and colloid solutions  Osmolarity (mosmol/l) Oncotic pressure (mmhg) Ringer s lactate NaCl (0.9%) NaCl (7.5%) Plasma Dextran 70 (6%) Dextran 40 (10%) HES (6%)
6 132 M. Bernhard et al. / Resuscitation 66 (2005) Table 3 Side effects of colloid solutions  Blood coagulation Dextran Gelatin + ++ HES (450/0.7) ++ + HES (200/0.5; 130/0.4) : high; ++: moderate; +: low. Anaphylaxia and disturbances in blood coagulation. In particular, dextran and HES (450) have clinically important effects on blood coagulation (Table 3). Therefore, they may not be used in a situation with SCI. Some clinicians prefer gelatin or HES (200/0.5 or 300/0.4) in treating SCI patients (Table 3) [37,38] Hypertonic hyperosmotic solutions. The concept of small-volume resuscitation (SVR) uses hypertonic hyperosmotic solutions and to provide the initial therapy for severe hypovolaemia and shock associated with trauma . No clinical studies on SVR have been carried out in patients with SCI. However, some data are available from patients with multiple trauma, and severe TBI. In an earlier prospective, randomized, double-blinded clinical trial, 166 trauma patients with SBP less than or equal to 100 mmhg were divided into two groups . One group received 250 ml lactated Ringer s solution as the initial volume loading, while the second group was treated with 250 ml HHS (7.5% sodium chloride/dextran 70). In the group with multiple trauma (among them some with severe TBI), patients treated with HHS showed a better survival at hospital discharge. In the subgroup with severe TBI alone, the differences in survival did not reach statistical significance. However, HHS also was associated with a tendency toward improving survival in this subgroup (Fig. 4) . Another recently study by Cooper et al.  could not show a significant benefit. In this prospective, doppleblinded, and controlled study, 229 patients suffering from severe head injury (GCS < 9) and suffering from a SBP less than or equal to 100 mmhg were randomly divided into two groups: one group (n = 114) received an initial infusion with 250 ml of hypertonic 7.5% saline solution (without oncotic combination), while the other group (n = 115) was treated with 250 ml of lactated Ringer s solution. Additionally, both groups received conventional fluid management. Survival to hospital discharge was similar in both groups (55% versus 50%; p = 0.32). After 6 months, the survival rate was not significantly different between both groups (55% versus 47%; p = 0.23) (Fig. 5) . It should be mentioned however, that the difference of 8% between the groups was perhaps remarkable. With more patients in such a trial, the difference could approach significance. Additionally, the data from subgroup analysis presented by Cooper et al.  showed a non-significant lower median ICP (10 mmhg versus 15 mmhg; p = 0.08) and a non-significant shorter duration of CPP under 70 mmhg (9.5 h versus 17 h, p = 0.06) for patients treated with hypertonic saline solution in the Fig. 4. Hypertonic hyperosmotic solutions (HHS) may be administrated in prehospital management of patients suffering from multiple trauma or severe traumatic brain injury (TBI) with systolic blood pressure (SBP) <100 mmhg: In a prospective, randomized, double-blind clinical trial, 166 trauma patients with SBP < 100 mmhg were divided into two groups. One group (n = 83) received 250 ml lactated Ringer s solution as the initial volume loading, while the second group (n = 83) was treated with 250 ml HHS (7.5% sodium chloride/dextran 70), initially. In the entire cohort, patients with HHS treatment showed a better survival to hospital discharge. In the subgroup with patients suffering from TBI, differences in survival did not reach statistical significance. However, HHS was associated with a tendency toward improving survival in this subgroup . Fig. 5. In a prospective, dopple-blinded, and controlled study, 229 patients suffering from severe head injury (GCS < 9) and a systolic blood pressure less than or equal to 100 mmhg were randomly divided into two groups: one group (n = 114) received an initial infusion with 250 ml of hypertonic 7.5% saline solution (without oncotic combination), while the other group (n = 115) was treated with 250 ml of lactated Ringer s solution. Additionally, both groups received conventional fluid management. Survival to hospital discharge was similar in both groups (55% vs. 50%; p = 0.32). After 6 months, the survival rate was not significant different between both groups (55% vs. 47%; p = 0.23) . Also in this recently published study, hypertonic saline solution was associated with a tendency toward improving hospital discharge and survival after 6 months in patients suffering from neurotrauma.
7 M. Bernhard et al. / Resuscitation 66 (2005) intensive care unit, in comparison with patients treated with Ringer s solution. Lewis  discussed in his accompanying editorial the expected effects of hypertonic solution. Because there was a non-significant trend toward improving survival to hospital discharge and survival at 6 month, Lewis suggested that further studies with a larger sample size are needed to determine the potential therapeutic effects of HHS . From the actually available data it is not absolutely clear whether hypertonic or hypertonic hyperosmotic solutions do lead to a clinical benefit in the management of patients with TBI. There are no further clinical data concerning HHS in SCI available. We only have further data from experimental studies. The positive effects of HHS in experimental SCI include the attenuation of leukocyte adhesion, an increase in spinal cord blood flow, and an improvement in neurological function and survival [43 45]. From a scientific point of view, it is still unknown whether HHS has a clinical benefit in the management of patients with TBI or SCI. Therefore, in cases where hypotension or multiple trauma are combined with SCI, the use of HHS as SVR may be justified and not harmful, and possibly indicated according to these data, but controlled clinical trials in SCI patients are still lacking Glucose. Fluid resuscitation in the prehospital setting should not include glucose as an infusion, because there are at least two problems associated with glucose. Firstly, glucose metabolises rapidly, resulting in free water, which supports oedema formation. Secondly, there is the risk of hyperglycaemia with an increase in the anaerobic glycolysis rate, which increases lactate and reduces ph. We know that in different settings, including stroke, cardiac arrest, and others, that elevated blood glucose levels are associated with a negative effect on outcome [46,47]. Although clinical studies about the effects of elevated blood glucose levels in SCI do not exist, it can be speculated that they are probably the same in SCI. Clinical data do exist for the association of blood glucose levels and outcome in patients with severe TBI and with a GCS of 8 or below. In a prospective study in 267 patients undergoing surgery to drain an intracranial hematoma and/or to place a device for intracranial pressure monitoring, there was a significant relationship between high blood glucose levels and high intracranial pressure. To investigate neurological outcome, the authors used the Glasgow Outcome Scale (GOS, 1 = dead, 2 = vegetative state, 3 = severe disablility, 4 = moderate disability, 5 = good recovery). Post-operative blood glucose levels higher than 200 mg/dl were associated in 20% of cases with a GOS of 4 or 5 and in 80% with a GOS of 1 3, while post-operative blood glucose levels lower than 200 mg/dl were associated in 83% of cases with a GOS of 4 or 5 and only in 17% with a GOS of 1 3 (Fig. 6) . No clinical data are available on treatment with insulin in SCI patients, only for the use of insulin in critically ill Fig. 6. Blood glucose levels higher than 200 mg/dl may lead to a worse neurological outcome. In a prospective study in 267 patients undergoing surgery to drain an intracranial haematoma and/or to place a device for intracranial pressure monitoring, there was a significant relationship between high blood glucose levels and high intracranial pressure. To investigate neurological outcome, the authors used the Glasgow Outcome Scale (GOS, 1 = dead, 2 = vegetative state, 3 = severe disablility, 4 = moderate disability, 5 = good recovery). Post-OP blood glucose levels higher than 200 mg/dl were associated in 20% of cases with a GOS of 4 or 5 and in 80% with a GOS of 1 3, while post-op blood glucose levels lower than 200 mg/dl were associated in 83% of cases with a GOS of 4 or 5 and only in 17% with a GOS of 1 3 (p < 0.001) . patients in the intensive care unit (ICU). A prospective, randomised controlled study included 1548 patients admitted to a surgical ICU who were being mechanically ventilated. These patients were randomly assigned to receive either intensive insulin therapy (blood glucose levels between 80 and 110 mg/dl) or conventional treatment if the blood glucose levels exceeded 215 mg/dl with a maintenance of blood glucose at a level between 180 and 200 mg/dl. Intensive insulin therapy reduced mortality during the ICU stay from 8.0% (conventional therapy; n = 783) to 4.6% (intensive insulin therapy; n = 765) with p < 0.05 (Fig. 7) . In a subgroup analysis including 63 patients with neurological disease, cerebral trauma or brain surgery, intensive insulin therapy was associated with a mortality rate of 18.2%, compared to 23.3% in the conventional therapy group. Therefore, the goal of treatment is probably but this is indirect evidence only and based on an extrapolation from data obtained in other patient cohorts to reach a blood glucose level within normal range, which means i.v. glucose administration is only necessary in cases of acute hypoglycaemia. In the early management of patients with SCI, blood glucose levels should be measured and if necessary, insulin administered to produce blood glucose levels within the normal range as soon as possible. It should be mentioned that it is uncommon to use insulin in the prehospital environment. Therefore, in reality the glucose level should be measured and treated as soon as possible in the course of in-hospital management.
8 134 M. Bernhard et al. / Resuscitation 66 (2005) Table 4 National Acute Spinal Cord Injury Study 2  Changes in function a Placebo Methylprednisolone p 6 weeks (n = n.r.) Motor n.r. n.r. Pinprick n.s. Touch n.s. 6 months (n = n.r.) Motor n.r. n.r. Pinprick Touch Results in all patients (n = 487). n.r. = not reported; n.s. = not significant. a Change in function, scores for motor function ranged from 0 to 70, and scores sensation of prinprick/touch ranged from 29 to 87. Fig. 7. Intensive insulin therapy may improve outcome in critically ill patients. A prospective, randomised, controlled study included 1548 patients admitted to a surgical ICU who were being mechanically ventilated. These patients were randomly assigned to receive either intensive insulin therapy (blood glucose levels between 80 and 110 mg/dl) or conventional treatment, if the blood glucose level exceeded 215 mg/dl with a maintenance of blood glucose at a level between 180 and 200 mg/dl. Intensive insulin therapy reduced mortality during the ICU stay from 8.0% (conventional therapy; n = 783) to 4.6% (intensive insulin therapy; n = 765) with p < 0.05 . 3. Pharmacological treatment Some experimental studies have suggested that treatment with methylprednisolone (MPS) may be beneficial in SCI [50,51]. Possible positive effects of MPS are cell membrane stabilisation, inhibition of lipid peroxidation and a reduction of oxygen free radicals, increased blood flow, and a reduction of oedema and inflammation . The most important clinical studies considered methylprednisolone (MPS) naloxone, tirilazad mesylate, and GM-1 gangliosides. Indeed, the clinical use of MPS was investigated in the United States in three National Acute SCI Studies (NASCIS) NASCIS 1 The first NASCIS trial was a multicentre study and included 330 patients in a double-blind setting [52,53]. These patients were randomised to receive either MPS 100 mg i.v. bolus/day for 10 days or MPS 1000 mg i.v. bolus/day for 10 days. The results showed no difference in neurological recovery at 6 weeks, 6 months, and 1 year after MPS administration. However, a significantly increased incidence of wound infections was found in the group receiving the higher dose of 1000 mg MPS as compared to the group receiving 100 mg MPS (9.3% versus 2.6%, relative risk 3.6; p = 0.01)  NASCIS 1 clinical relevance The major problem of NASCIS 1 was related to the fact that no results from placebo-treated groups were obtained. Therefore, the results were inconclusive and it was still not known whether MPS is useful in SCI  NASCIS 2 Consequently, NASCIS 2 was performed in the 1980s [55,56]. A multicentre, randomised, double-blind, placebocontrolled trial of 487 patients evaluated the efficacy and safety of MPS (30 mg i.v. bolus/kg mg/kg/h for 23 h continuously, n = 162) and naloxone (5.4 mg i.v. bolus/kg mg/kg/h for 23 h continuously, n = 154) within 12 h after SCI and placebo. Neurological function was assessed on admission and based on an expanded motor score that ranged from 0 to 70 and an expanded pinprick/touch sensitivity score that ranged from 29 to 87. The study evaluated the changes with regard to these scores. Interestingly, no data on motor function were reported for any patient (Table 4) . Regarding reaction to pinprick and touch, the patients in the MPS-treated group did not show a significant increase as compared to the placebo group after 6 weeks. Nevertheless, the data did suggest a small but significant increase in pinprick and touch function (p = 0.012) after 6 months (Table 4) . However, the question remains as to whether an improvement of 10.0 versus 6.6 on a scale from 29 to 87 really represents a clinically relevant improvement [54,57]. The results from the 1-year follow-up did not show any positive effect in either the MPS or the naloxone group. Compared to placebo, the results in all patients were not as positive as expected. Yet, a subgroup analysis in patients who were treated within 8 h after SCI showed a small but significant increase in motor function and prinprick and touch sensitivity both after 6 weeks and after 6 months (Table 5) . The 1-year follow-up showed a small but significant increase in motor function in MPS-treated patients (12.0 versus 17.2, p = 0.030; based on an expanded motor score that ranged from 0 to 70) . Naloxone used within 8 h after SCI had no effect NASCIS 2 clinical relevance After the NASCIS 2 trial, MPS treatment within 8 h of SCI became a standard therapy in acute SCI in the United States and in many other parts of the world, despite the fact
9 M. Bernhard et al. / Resuscitation 66 (2005) Table 5 National Acute Spinal Cord Injury Study 2  Changes in function a Placebo Methylprednisolone p 6 weeks (n = 196) Motor Pinprick n.s. Touch months (n = 185) Motor Pinprick Touch Subgroup analysis. Patients treated within 8 h. n.s. = not significant. a Change in function, scores for motor function ranged from 0 to 70, and scores sensation of prinprick/touch ranged from 29 to 87. that problems and major criticism were published about the study [54,57,58]. Only minor benefits demonstrated in subgroup analyses were documented and a major criticism of the subgroup analysis was that demographic data were lacking. It was not shown whether the minor positive effect was really balanced from baseline. In addition it was not stated whether the subgroup was defined in advance, which is a major prerequisite for scientific quality of clinical studies in any subgroup. Another problem was that no functional test was performed, nor were group size calculations made in advance. Apparently, there are major limitations and missing data in the publication of this study. Moreover, MPS-treated patients presented with clinically important side effects (e.g., wound infection: MPS 7.1% versus naloxone 3.3% versus placebo 3.6%; p = 0.21). Clearly, therefore, this study could not be considered a basis for the general recommendation for using MPS in SCI patients  NASCIS 3 Following these unconvincing data, the NASCIS 3 study was performed in the 1990s [59,60]. This study evaluated the efficacy and safety of MPS (30 mg i.v. bolus/kg initially mg/kg/h for 24 h continuously, n = 166) versus MPS (30 mg i.v. bolus/kg initially mg/kg/h for 48 h continuously, n = 167) versus tirilazad combined with MPS (initial 30 mg MPS i.v. bolus mg tirilazad i.v. bolus/kg mg tirilazad i.v. bolus/kg every 6 h for 48 h, n = 166) in a multicentre, randomized, double-blind trial in 499 patients with SCI [59,60]. The analysis of all patients treated with MPS complying with the protocol for 48 h showed a small but significant difference in motor function after 6 weeks compared to patients treated with MPS for 24 h (8.8 versus 12.4, p = 0.04; based on an expanded motor score that ranged from 0 to 70) (Table 6). Interestingly, the results in the intent-to-treat analysis were not significant (Table 6). Tirilazad showed the same effects as MPS for 24 h (10.4 versus 12.4, p = 0.37). A subgroup analysis of patients treated within 3 8 h after SCI showed small but significant changes in motor function for intent-to-treat and complied with protocol analyses (Table 7). Patients treated within 3 8 h after SCI also showed Table 6 National Acute Spinal Cord Injury Study 3  Changes in function a Methylprednisolone p 24 h 48 h Intent-to-treat 6 weeks (motor) 9.0 (n = 151) 11.8 (n = 154) months (motor) 13.4 (n = 142) 16.8 (n = 149) 0.07 Complied with protocol 6 weeks (motor) 8.8 (n = 144) 12.4 (n = 145) months (motor) 13.2 (n = 136) 16.9 (n = 141) 0.06 Results in all patients, treated with MPS. a Change in function, scores for motor function ranged from 0 to 70. an increase of 1 in motor function on the admission score. Data for patients treated under 3 h after SCI did not show any effect NASCIS 3 clinical relevance As for NASCIS 1 and 2, again, major problems and major criticisms of NASCIS 3 have been published [54,57,58]. The first problem was that the treatment arms appeared to be unbalanced. The numbers of patients with normal baseline for motor function in the treatment arms of MPS administered for 24 h and MPS administered for 48 h were significantly different (25% versus 14%; p = 0.007). Therefore, the major results of the study should be interpreted with caution. Moreover, again, most of the benefit is shown in subgroup analysis only. In NASCIS 3, there are 36 potential subgroups. With 20 subgroups only and by chance alone, one subgroup reached statistical significance at p < In addition, following the administration of MPS for 48 h, an increase in side effects was shown (e.g., severe pneumonia: 24 h MPS 2.6% versus 48 h tirilazad 0.6% versus 48 h MPS 5.8%; p = 0.02) [54,57]. Therefore, even after NASCIS 3, it is still questionable from a scientific point of view whether treatment with MPS is beneficial in patients suffering from SCI or not Statement on the treatment with steroids in prehospital management of SCI Based on the data presented above, some reviews refrained from use of MPS in the treatment of patients with SCI [61,62]. Table 7 National Acute Spinal Cord Injury Study 3  Changes in function a Methylprednisolone p 24 h 48 h Intent-to-treat 6 weeks (motor) 7.6 (n = 76) 12.5 (n = 84) months (motor) 11.2 (n = 71) 17.6 (n = 80) 0.01 Complied with protocol 6 weeks (motor) 7.0 (n = 72) 13.4 (n = 80) months (motor) 10.8 (n = 68) 18.0 (n = 77) Subgroup analysis. Patients treated within 3 8 h. a Change in function, scores for motor function ranged from 0 to 70.
10 136 M. Bernhard et al. / Resuscitation 66 (2005) Additionally, in a consensus conference, the American Association of Neurologic Surgeons and the Congress of Neurologic Surgeons  stated with a review of the literature from 1966 to 2001 that treatment with methylprednisolone for either 24 or 48 h is recommended as an option in the treatment of patients with acute spinal cord injuries that should be undertaken only with the knowledge that the evidence suggesting harmful side effects is more consistent than any clinical benefit. Moreover, in the recently published position paper of the National Association of Emergency Medical Services Physicians (NAEMSP)  in 2004, the NAEMSP stated that the evidence on the use of high-dose steroids for SCI remains inconclusive, the treatment with steroids should not be considered the standard of care, and routine use of steroids in EMS is not supported Steroids are harmful in traumatic brain injury MPS has been used to treat neurotrauma for more than three decades now. The corticosteroid randomization after significant head injury (CRASH) trial was performed from 1999 to 2004 following the lack of sufficiently large trials and was recently published in The Lancet . This study evaluated the efficacy and safety of MPS (initially 2000 mg for 1 h i.v mg/h for 48 h i.v., n = 4985) versus placebo (n = 4979) in a large-scale multicentre, randomized trial in patients suffering from head injury (GCS < 14) within 8 h of injury. The intent-to-treat analysis showed a highly significant increase in mortality within 2 weeks in the group treated with MPS as compared to the group treated with placebo (21.1%, n = 1052 versus 17.9%, n = 893; relative risk 1.18 with 95% confidence interval: ; p = ). The relative risk of death at 2 weeks due to MPS in prespecific subgroup analyses was not different based on injury severity (p = 0.22) . The incidence of complications with MPS as compared to placebo was as follows: seizure (8.7% versus 7.6%), haematemesis or melaena requiring transfusion (1.6% versus 1.3%), wound infection (3.2% versus 2.9%), and pneumonia (13.4% versus 12.4%), respectively . The authors of the CRASH trial stated that their results could also have implications for use of corticosteroids in SCI and that, because of the emphasis on the subgroup effects in the NASCIS studies, the use of corticosteroids in SCI should remain an area of debate . When the results of the CRASH trial are extrapolated to the annual incidence rate of severe head trauma worldwide, is frightening to calculate how many patients might have been harmed by treatment with corticosteroids. Therefore, Sauerland and Maegele  stated in their accompanying editorial to the CRASH trial that the key message of the CRASH, however, is that applying treatments with unproven effectiveness is like flying blindly. In future, we should avoid trusting in underpowered clinical trails with surrogate rather than clinical endpoints, and transferring evidence from one disease to another. 4. Transportation and type of trauma centre The choice of vehicle depends on the patient and the local setting. Both ground and helicopter transportation are possible. In order to make a decision about the type of trauma centre, it is necessary to consider the status of the patient (haemodynamically stable versus unstable). Stable patients should be transported to the nearest level 1 centre, if it can be reached within a given period. Sometimes a longer transportation time to a level 1 trauma centre is preferable. Unstable patients should be transported to the nearest trauma centre in order to achieve haemodynamic stabilisation, even if this is not a level 1 trauma centre for SCI. Second-line transportation to a level 1 injury centre for SCI should then be undertaken after the patient has been stabilised haemodynamically . Carvell and Grundy  compared the results of spinal surgery in 420 consecutive patients with SCI in a spinal treatment centre with other patients who underwent primary surgery in another hospital and who were transported to the spinal treatment centre secondarily. These authors stated that complications were more frequent in patients undergoing spinal surgery before transfer to the centre. Furthermore, the longer the delay in transfer, the higher the incidence of pressure sores . Devivo et al.  compared patients admitted within 1 day of injury who received all subsequent care within the system with patients who received their acute care services elsewhere and who were admitted to the system solely for rehabilitation. Both patient groups were comparable with respect to age, neurological status and extent of spinal cord lesion, pre-existing major medical conditions, associated injuries, ventilator dependency and acute surgical procedure experience. Findings revealed a statistically significant reduction in acute care and total length of stay and a highly significant reduction in the incidence of pressure ulcers for patients admitted within 1 day of injury. Moreover, for patients admitted within 1 day of injury, mortality rates were lower than reported previously for patients not admitted to an organised SCI care system. However, Jones and Bagnall  stated in their recently published analyses for the Cochrane Database that the current evidence does not enable conclusions to be drawn about the benefits or disadvantages of immediate referral versus late referral to SICs. Well-designed, prospective experimental studies with appropriately matched controls are needed. Therefore, there is an ongoing discussion in this area. 5. Conclusions There is no doubt that prehospital management of SCI is very important, since 25% of SCI damage may occur or be aggravated after the initial event. The prehospital management of acute SCI includes examination of the patient, spinal immobilisation, oxygenation, and careful airway management as well as cardiovascular support (Table 8). Emergency
11 M. Bernhard et al. / Resuscitation 66 (2005) Table 8 Prehospital management of spinal cord injury (SCI) Examination of the patient Primary survey: airways, breathing, and circulation (the ABCs ). Secondary survey: more thorough evaluation ( whole-body-check ) Patient immobilisation Neutral supine position with rigid cervical collar, sandbags on either side of the head, and rigid backboard. Alternative: vacuum splint device in combination with rigid cervical collar Airway management Pulse oximetry, O 2 administration via face mask, rigid cervical collar; intubation of the trachea, if saturation persistently <90%, hypoventilation, Glasgow Coma Scale < 9; intubation of the trachea in patient under manual in-line stabilisation Cardiovascular support Neurogenic shock (SCI above Th 5 ): systolic blood pressure <70 mmhg; bradycardia: Trendelenburg position; i.v. administration of atropine, dopamine, arterenol. Hypovolemic shock (multiple trauma): systolic blood pressure <100 mmhg; tachycardia: Trendelenburg position; fluid resuscitation. Maintenance of mean arterial blood pressure >90 mmhg; avoid episodes of hypotension (systolic blood pressure below 90 mmhg) Fluid resuscitation Physiological NaCl or Ringer s solution, colloids (prefer Gelatine or HES (200/0.5 or 300/0.4)) hypertonic hyperosmotic solutions Blood glucose levels Within normal range as soon as possible Transportation and trauma centre Stable patient: nearest level 1 centre. Hemodynamically unstable patient: nearest trauma centre; second-line transportation after hemodynamic stabilisation to a level 1 injury centre for SCI treatment to reduce the risk of a secondary SCI includes intubation of the trachea, if indicated (under manual in-line stabilisation), and maintaining MAP above 90 mmhg and blood glucose levels within the normal range (Table 8). It is still not clear from a scientific point of view whether additional specific therapy is useful or not. It has not been demonstrated convincingly that early MPS treatment really has clinically important benefits for a patient suffering from SCI. Despite wider-spread use of MPS, important questions concerning specific drug therapy have not been answered nor have the available date shown convincingly whether treatment with MPS really works. Therefore, a reevaluation of NASCIS 2 and 3 primary data is indicated before definite conclusions can be drawn . In a consensus conference, the American Association of Neurologic Surgeons and the Congress of Neurologic Surgeons stated that the evidence of the treatment with MPS of patients suffering from SCI suggesting harmful side effects is more consistent than any suggestion of clinical beneftit . 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