ว ทยาการความก าวหน าในการร กษาผ ป วยบาดเจ บ กระด กส นหล งและไขส นหล ง. Piyawat Bintachitt, MD.

Transcription

1 ว ทยาการความก าวหน าในการร กษาผ ป วยบาดเจ บ กระด กส นหล งและไขส นหล ง Piyawat Bintachitt, MD.

2 Thank you

3 Outline Pathophysiology Neurological classification Imaging Airway management Cardiovascular management Decompressive surgery Intravenous methylprednisolone Neuroprotection Neurogeneration

4 Spinal cord injury (SCI) affects 1.3 million North Americans. More than half occurring after trauma. In Thailand, Spinal cord injury?

5 Male 40 years, car accident, Bilateral facet dislocation C5/6 with complete cord injury C6

6 Male 45 years, Fall from height, AS with fracture C3/4 and C6/7 with complete cord injury C5

7 Female 40 years, fall from tree, Unilateral facet dislocation C4/5 with complete cord injury C5

8 Pathophysiology SCI is two phases overlap primary and secondary injury

9 ROS = reactive oxygen species

10 The spinal cord damage results from primary and secondary mechanisms that start at the moment of the injury and go on for days and even weeks.

11 Neurological classification After initial general stabilization, it is important to perform a through neurological examination. The American Spinal Injury Association (ASIA) standard for neurological and functional classification is the recommended preferred tool.

12 Sensory exam 28 dermatomes (C2 to S4-5) on right and left sides, light touch and pinprick, three-point scale, 0 = absent to 2 = normal or intact Motor exam 10 paired myotomes (C5-T1 and L2 S1), Test voluntary external anal sphincter contractions, grading from 0 to 5

13 ASIA A = no sensory or motor functions in sacral segments S4-S5 B = Sensory is preserved below injury, no motor function is preserved C = Motor function is preserved below the neurological levels, and more than half below have muscle grade less than 3 D = Motor function is preserved below the neurological levels, and at least half the muscle below have muscle grade > 3 E = Sensation and motor functions are normal

14 Prognosis 85% of ASIA A patients will not regain function. Of the 15% who will improve, only 3% will have useful motor function. More half (54%) ASIA B patients, and the vast majority (86%) of ASIA C-D patients will regain function.

15 Imaging SCI guideline in trauma patients: Neck pain Spinal tenderness Neurological related spine Who cannot assessed (unconscious, uncooperative, incoherent or intoxicated) ***Need a radiographic study of the spinal cord***

16 The National emergency x-radiography utilization study (nexus) protocol Identify low risk for cervical fracture/subluxation/ dislocation Sensitivity 99%, negative predictive value 99.9% Five criteria: 1. No posterior midline cervical tenderness. 2. No intoxication. 3. No Normal mental status. 4. No other painful injuries. 5. No neurological deficit.

17 Canadian C-spine rule Three question: 1. The presence of a high-risk factor that mandates radiography (age > 65 years, dangerous mechanism of trauma, or paresthesias in extremities). 2. The presence of low risk factors allowing safe assessment of the range of motion. 3. The ability to actively rotate the neck 45 degree to left and right. 100% sensitivity an 42.5% specificity

18 The imaging modality of choice is computed tomography (CT).

19 If CT scan is not available, a three-view x-ray is recommended (AP, odontoid and lateral views), being supplemented.

20 Magnetic resonance imaging (MRI) Obtained, when feasible, in the first 48 hours after trauma. Detect lesion 6% of the cases CT is normal. A normal initial MRI is usually associated with complete recovery.

21 Magnetic resonance imaging (MRI) Tool to classify: severity and predict outcome based on the pressure of hemorrhage, extent of edema, and severity of the initial compression.

22 Intraspinal hemorrhages (>1 cm long) as well as longitudinal T2 signal changes > 3 cm, are associated with poor prognosis.

23 Airway management Respiratory complications are the main course of morbidity and mortality in acute SCI (incidence 36% to 83%). Reduced vital capacity, retention of secretions, and autonomic dysfunction all play a role.

24 2/3 patients require mechanical ventilator form atelectasis, pneumonia or respiratory failure. Virtually 100% of lesions above C5 require intubation (the phrenic nerve originates from C3-C5), performed by electively.

25 ***Avoid hyperextension, rotation, and other movements of neck during intubation.*** When possible, awake, fiberoptic intubation is performed. In-line stabilization without traction is an alternative when a fiber optic laryngoscope or bronchoscope is unavailable.

26 Only 40% of patients with lesions above C4 are successfully extubated. ***Predictors of the need for tracheostomy**** ASIA A lesions extent of the lesion smoking previous lung disease Some studies advocate that early tracheostomy (within 10 days) to a shorter ICU and reduction in the length of time of mechanical ventilator.

27 Cardiovascular management Hypotension after SCI is frequent. hypovolemia in poly-trauma Direct cervical or thoracic spinal trauma neurogenic shock

28 Neurogenic shock Results from the interruption of sympathetic tone due to disruption in supraspinal control, and an intact parasympathetic influence via the vagus nerve, leading to an imbalance in the autonomic control.

29 Cardiovascular management ***The current recommendation is strictly avoid hypotension.*** Maintain mean arterial pressure (MAP) at mmhg for seven days after injury (level III evidence).

30 The mainstay of treatment is intravenous fluid therapy (mainly with crystalloid) to maintain a euvolemic or slightly hypervoluemic status, in association with vasopressors. ***It is important to have invasive blood pressure monitoring with an arterial line.***

31 The main predictors of poor cardiovascular function requiring resuscitation and support are high cervical and complete lesions. Cardiovascular instability may be transient and episodic, but can also be recurrent in the first 7-10 days after injury.

32 The vasopressor selection: In cervical or upper thoracic lesions with hypotension and bradycardia need chronotropic and inotropic effect = Norepinephrine (or alternatively, dopamine) Low thoracic hypotension from peripheral vasodilatation need pure vasopressor = phenylephrine

33 Decompressive surgery Progressive edema and hemorrhage contribute to the ongoing mechanical pressure on the microvascular circulation. Surgical decompression aims to relieve pressure, reducing secondary hypoxia and ischemia.

34 Indication for surgery Significant cord compression with progressive neurological impairment A fracture not responding to close reduction, such as unstable vertebral fracture

35 Decompression prior to 24 hours after SCI can be performed safely and is associated with improved neurologic outcome. At least a 2 grade AIS improvement at 6 months follow-up.

36 The results supports the principle of early intervention in the setting of spinal trauma and SCI.

37 Future for Early decompression The SCI-POEM is a European multicenter study Aim to compare decompression < 12 hours versus > 12 hours until 14 days. The final report is planned to be published in the end of 2017.

38 Intravenous methylprednisolone Methylprednisolone (MP) is a synthetic corticosteroid upregulated anti-inflammatory factors and decreases oxidative stress, enhancing endogenous cell survival in animal models of SCI. It reduces edema, prevents intracellular potassium depletion and inhibits lipid peroxidase.

39 Study for MP 1984, The National Spinal Cord Injury Study I 1990, The National Spinal Cord Injury Study II 1997, The National Spinal Cord Injury Study III Compared three treatment groups: MP for 48 hours, MP for 24 hours, tirilazad mesylate (a potent lipid peroxidation inhibitor ) for 24 hours In patients treated between three to eight hours from trauma, the 48-hour regimen was associated with a great motor, but not functional, recovery.

40 Recently, a meta-analysis and systematic review multiple randomized controlled trials and observational studies do not support methylprednisolone use in acute SCI since it has no long-term benefits. Besides, it increases gastrointestinal hemorrhage and has a trend to increase overall adverse events.

41 The last consensus does not recommend methylprednisolone for treatment of SCI.

42 Neuroprotection VS Nerogeneration

43 Neuroprotective agents prevent specific secondary injuries and neural damage. Neuroregenerative therapy promote axonal regrowth after the damage has occurred.

44 Neuroprotection NO BENEFIT Gangliosides Naloxone Nimodipine Tirilazard TRIAL Hypothermia Riluzole Minocycline Fibroblast growth factor Cytokine granulocyte colony stimulating factor

45 Hypothermia In animal studies, hypothermia decreased basal metabolic rate in the central nervous system, reduced inflammation, apoptosis, excitotoxicity, edema, gliosis, and increased angiogenesis. Traumatic SCI models showed improvement with the decreased temperature.

46 A small pilot study in humans with SCI exposed to hypothermia showed a trend towards neurological recovery (43% vs 21%) and no difference in complication rates.

47 Another study evaluated 35 ASIA A patients who were treated with hypothermia (33o C) for 48 hours, starting six hours post-injury. Four patients converted to ASIA B in the first 24 hour. 35.5% showed an improvement of at least one grade on the ASIA scale at the latest follow-up.

48 Future for Hypothermia Phase II/III trial named The Acute Rapid Cooling Therapy for Injuries of the Spinal Cord. This study (which is not yet recruiting) plans to evaluate different durations of hypothermia, starting within six hours post-trauma.

49 Riluzole A sodium-channel blocker, reduces secondary injury by blocking pathological activation of sodium channels and reducing the release of glutamate in preclinical models of SCI. A phase I/II trial demonstrated a benefit in motor and sensory

50 Future for Riluzole A phase II/III trail, the Riluzole in Spinal Cord Injury Study, is ongoing, to evalauate the aforementioned drug in cervical lesions will be completed in 2018.

51 Minocycline Minocycline is an antibiotic with anti-inflammatory properties including inhibition of tumor necrosis factor alpha, interlukin 1 beta, cyclooxygenase-2 and nitric oxide synthase. In a phase II study, the ASIA motor score improved in patients treated with minocycline (P = 0.05)

52 Future for Minocycline This led to a phase III trial, the Minocycline in Acute Spinal Cord Injury, which is currently recruiting until 2018.

53 Fibroblast growth factor Fibroblast growth factor has been shown to protect against excitotoxicity and to reduce free radical production in animal models of SCI.

54 Future for Fibroblast growth factor A fibroblast growth factor analogue called SUN was evaluated in a phase I/II trail completed in 2015, but results are pending.

55 Cytokine granulocyte colony stimulating factor Cytokine granulocyte colony stimulating factor is neuroprotective in SCI by promoting cell survival and inhibiting tumor necrosis factor alpha and interlukin 1 beta. There were two small, non-randomized studies that demonstrated improvements in ASIA motor scores with the drug use.

56 Neuroregeneration There are numerous targets and therapeutic opportunities using endogenous and exogenous repair mechanisms. The aim is to surpass barriers to recovery such as the loss of structural framework, cystic cavitation, scarring and inhibitory molecular signaling.

57 Ongoing studies: embryonic stem cells, induced pluripotent stem cells, olfactory ensheathing cells, Schwann cells, mesenchymal cells, and activated autologous macrophages. In preclinical studies, cellular transplantation alone, or in combination with other therapies, was associated with neurological recovery.

58 Small human studies also disclosed some degree of improvement. ***However, independent of treatment, most patients will undergo spontaneous recovery in the first six months after injury.***

59 Cellular transplantation The cellular transplantation remains an investigational and experimental therapy, will no formal recommendations.

60 Conclusion Spinal cord injury management has substantially changed over the last years. The pending trial results can have a significant impact on the standard of care. The small motor and sensory improvements can have profound effects on patient s lives.