1) The document discusses the principles and evidence for early management of spinal cord injuries, including early surgery within 24 hours, maintaining mean arterial blood pressure between 85-90 mmHg, and the use of methylprednisolone.
2) Ongoing clinical trials are exploring optimal perfusion pressure targets as well as neuroprotective agents like riluzole.
3) Specialized spinal cord injury units allow for up-to-date management and access to clinical trials exploring new treatments.
My talk in April 2015 Malaysia on Best Practices and Resuscitation Workflow. The new 2015 resuscitation guidelines is expected to be released in Oct 2015.
My talk in April 2015 Malaysia on Best Practices and Resuscitation Workflow. The new 2015 resuscitation guidelines is expected to be released in Oct 2015.
The use of adrenaline in cardiac arrest resuscitation has been advocated since the 1960s. Laboratory studies and anecdotal experience showed improved rates of return of spontaneous circulation (ROSC) with the use of adrenaline at a dosage of approximately 0.01 mg/kg. This led to the widespread adoption of adrenaline administration during cardiac arrest into every resuscitation guideline for decades to come. Extensive laboratory studies characterized the beneficial physiological effects of adrenaline during cardiac arrest and closed-chest cardiopulmonary resuscitation (CC-CPR). Adrenaline administered during CC-CPR results in peripheral arterial vasoconstriction that raises the aortic pressure, particularly during the relaxation phase of CC-CPR. This increase in aortic pressure results in an increased aortic to right atrial pressure gradient that drives blood flow to the myocardium during CC-CPR. This pressure gradient is known as the coronary perfusion pressure (CPP) and has been shown to correlate with ROSC in both laboratory investigations and clinical studies. During the 1990s, the use of “high-dose” adrenaline showed increased rates of ROSC compared to “standard-dose” adrenaline. However, it was subsequently recognized that larger doses of adrenaline did not result in improved survival. Furthermore, questions have been raised as to whether or not “standard-dose” adrenaline improves survival from cardiac arrest. Recent meta-analyses have raised serious questions about the value of adrenaline, showing a benefit for achieving ROSC but no clear evidence of improved long-term survival. Controlled clinical trials to address this question are now underway. However, there is another important issue that needs to be addressed: the “route” of administration. With the growing interest in endovascular resuscitation, the use of intra-aortic adrenaline titration offers a means of rapidly and effectively delivering adrenaline to peripheral arterial effector sites while providing arterial pressure and CPP monitoring to guide titration of adrenaline doses to achieve an optimal hemodynamic effects while avoiding excessive adrenaline doses.
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ACLS 2015 Updates - The Malaysian PerspectiveChew Keng Sheng
This set of slide was presented during the Kelantan Resuscitation Update 22 Nov 2015 in accordance to the latest ACLS/ILCOR 2015 Guidelines. However, I have emphasized on certain important aspects relevant within the Malaysian context. Nonetheless, in general, there are no major changes for this year 2015
Haemorrhagic stroke is an important cause of morbidity and mortality worldwide. Of the complications of this type of stroke, haematoma expansion is one of the most important, common and dangerous. The spot sign helps to predict haematoma expansion in patients of haemorrhagic stroke.
Delaney shares insights into the mysterious world of statistics and trials. This 12 minute podcast is particularly useful for Registrars preparing for their exams and was recorded at BCC4. For similar podcasts and audio; head to www.intensivecarenetwork.com and to rego for BCC5 in Cairns, check out www.bedsidecriticalcare.com
BCC4: Michael Parr on ICU - Surviving Trauma GuidelinesSMACC Conference
Michael Parr, director of Liverpool ICU in Australia, speaks about "Surviving Trauma Guidelines". He does so through the use of an interesting case of a patient admitted to ICU following a MVA. This educational podcast was recorded at BCC4.
The use of adrenaline in cardiac arrest resuscitation has been advocated since the 1960s. Laboratory studies and anecdotal experience showed improved rates of return of spontaneous circulation (ROSC) with the use of adrenaline at a dosage of approximately 0.01 mg/kg. This led to the widespread adoption of adrenaline administration during cardiac arrest into every resuscitation guideline for decades to come. Extensive laboratory studies characterized the beneficial physiological effects of adrenaline during cardiac arrest and closed-chest cardiopulmonary resuscitation (CC-CPR). Adrenaline administered during CC-CPR results in peripheral arterial vasoconstriction that raises the aortic pressure, particularly during the relaxation phase of CC-CPR. This increase in aortic pressure results in an increased aortic to right atrial pressure gradient that drives blood flow to the myocardium during CC-CPR. This pressure gradient is known as the coronary perfusion pressure (CPP) and has been shown to correlate with ROSC in both laboratory investigations and clinical studies. During the 1990s, the use of “high-dose” adrenaline showed increased rates of ROSC compared to “standard-dose” adrenaline. However, it was subsequently recognized that larger doses of adrenaline did not result in improved survival. Furthermore, questions have been raised as to whether or not “standard-dose” adrenaline improves survival from cardiac arrest. Recent meta-analyses have raised serious questions about the value of adrenaline, showing a benefit for achieving ROSC but no clear evidence of improved long-term survival. Controlled clinical trials to address this question are now underway. However, there is another important issue that needs to be addressed: the “route” of administration. With the growing interest in endovascular resuscitation, the use of intra-aortic adrenaline titration offers a means of rapidly and effectively delivering adrenaline to peripheral arterial effector sites while providing arterial pressure and CPP monitoring to guide titration of adrenaline doses to achieve an optimal hemodynamic effects while avoiding excessive adrenaline doses.
To enable screen reader support, press shortcut Ctrl+Alt+Z. To learn about keyboard shortcuts, press shortcut Ctrl+slash.
ACLS 2015 Updates - The Malaysian PerspectiveChew Keng Sheng
This set of slide was presented during the Kelantan Resuscitation Update 22 Nov 2015 in accordance to the latest ACLS/ILCOR 2015 Guidelines. However, I have emphasized on certain important aspects relevant within the Malaysian context. Nonetheless, in general, there are no major changes for this year 2015
Haemorrhagic stroke is an important cause of morbidity and mortality worldwide. Of the complications of this type of stroke, haematoma expansion is one of the most important, common and dangerous. The spot sign helps to predict haematoma expansion in patients of haemorrhagic stroke.
Delaney shares insights into the mysterious world of statistics and trials. This 12 minute podcast is particularly useful for Registrars preparing for their exams and was recorded at BCC4. For similar podcasts and audio; head to www.intensivecarenetwork.com and to rego for BCC5 in Cairns, check out www.bedsidecriticalcare.com
BCC4: Michael Parr on ICU - Surviving Trauma GuidelinesSMACC Conference
Michael Parr, director of Liverpool ICU in Australia, speaks about "Surviving Trauma Guidelines". He does so through the use of an interesting case of a patient admitted to ICU following a MVA. This educational podcast was recorded at BCC4.
A guide to beginners helping writing thesis protocol.
Comparison between USG guided Suprascapular Nerve block and Interscalene Nerve Block post operative analgesia after arthroscopic shoulder surgery- a prospective randomized double blind study.
Neurointerventional Therapy for Brain Aneurysms and Acute Stroke Allina Health
By Yasha Kadkhodayan, MD. Overview of interventional neuroradiology approaches to brain aneurysm and stroke care, discussion of processes in place at Abbott Northwestern to enhance the delivery of stroke care.
Remote Ischaemic Conditioning: A Paper Review & Uses in Paramedic Practicebgander23
A 2 part presentation. Part 1 reviews a paper on the long-term clinical outcomes of STEMI patients undergoing remote ischaemic perconditioning prior to primary percutaneous coronary intervention. The 2nd part looks at how this technique can be used in Paramedic practice.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Contemporary management of spinal injury by Dr Jonathon Ball
1. RNSH
CONTEMPORARY
EARLY MANAGEMENT OF
SPINAL CORD INJURY
CICM ASM 2019
Dr Jonathon R. Ball
FRACS AMA(M) BMed BMedSc(Hons) GradDipBiomedE
Neurosurgeon and Spinal Surgeon
Royal North Shore and North Shore Private Hospitals www.spinesurgeon.sydn
ey
@DrJonathonBall
#spinesurgsydney
2. RNSH
"One having a dislocation in a vertebra of
his neck, while he is unconscious of his
two legs and his two arms, and his urine
dribbles. An ailment not to be treated.”
Case 31
Edwin Smith Papyrus
c1600 BCE
9. RNSH
Early Surgery
‘Conservative treatment is infinitely superior to
any immediate surgical procedure …
Incidents of tragic events … are high enough to
make any surgeon very circumspect before
indulging in any surgical procedure’
Sir Ludwig Guttman. 1973.
10. RNSH
2017 –
“ early surgery be offered …. regardless of level”
Early (<24 hr) Surgery
Fehlings et al. Global Spine J. 2017. 7(3 Suppl):195S-202S.
11. RNSHSTASCIS (2012)
• Non-randomised, multicentre, prospective cohort study
• 313 patients with cervical SCI
• ‘19.8% of patients undergoing early surgery showed a
>2 grade improvement in AIS’
• ‘compared to 8.8% in the late decompression group’
• ‘complications occurred in 24.2% of early surgery
patients and 30.5% of late surgery patients (p = 0.21)’
12. RNSH
• 20 studies (11 RCTS, 9 observational)
– 1162 pts (ASIA A <72 hrs)
– 28.1% improved ≥1 AIS grade
– early surgery : 46.1% improved
– late surgery : 25% improved
13. RNSH
• 13 studies
– 422 pts (ASIA A)
– outcome : ≥2 AIS grade
– early surgery : 22.6% improved
– late surgery : 10.4% improved
14. RNSHSCI-POEM
• 309 patients with SCI
• recruitment completed 2019
• 19 clinics in Europe
• early surgery (< 12 hrs) vs late surgery (12 hrs – 14 days)
• 1o endpoint – ISNCSCI motor score
• results in 2020
16. RNSH
2013 –
“ maintenance of MAP between 85 and 90 mm Hg for the first 7 days”
Ryken et al. Neurosurgery. 2013. 72(3S): 84-92.
Spinal Cord Perfusion
21. RNSHOngoing Trial
Mean Arterial Pressure in Spinal Cord Injury (MAPS)
(ClinicalTrials.gov Identifier: NCT02232165)
• University of Calgary/University of Texas
• n = 100
• C0-T12/ASIA A, B, C
• Group 1 – target MAP >65 mmHg
• Group II – target MAP > 85 mmHg
• Non-inferiority
• Outcome – ISNCSCI motor score
• Estimated Completion Date : June 2019
32. RNSH
2013 –
“ administration of
methylprednisolone ….
is not recommended”
Hurlbert et al. Neurosurgery. 2013. 72(3S): 93-105.
Methylprednisolone
33. RNSH
2017 –
“ a 24-hour infusion of high-
dose MPSS be offered ....
within 8 hours … as a
treatment option”
Fehlings et al. Global Spine J. 2017. 7(3 Suppl):201S-137S.
Methylprednisolone
34. RNSHAOSpine Guideline (2017)
Fehlings et al. Global Spine J. 2017. 7(3 Suppl):116S-137S.
NASCIS II – Issues
1. Subgroup analysis - ? a priori
2. Right sided motor scores – small effect
36. RNSHRISCIS
• international multi-centre
• placebo controlled
• double blind
• randomised trial
• target enrolment : 351 subjects
• Adults – 18 to 75 years
• Present to spinal unit within 12 hours injury
• Cervical spine level – C4 to C8
• AIS A, B and C
37. RNSHRISCIS
• international multi-centre
• placebo controlled
• double blind
• randomised trial
• target enrolment : 351 subjects
• 24 centres open – 170 subjects to date
• Australian sites & recruitment
– Prince of Wales Hospital (19 subjects)
– Royal North Shore Hospital (17 subjects)
– Royal Adelaide Hospital (8 subjects)
– John Hunter Hospital (0 subjects)
– AUSTRALIAN TOTAL (43 subjects : 26% worldwide)
47. RNSH
• 36 patients treated
– 28 cervical injuries ASIA A, B, C
• Riluzole
– First dose 50mg by mouth within 12 hours injury
– Continued twice a day for 14 days
• 6 months follow-up
• Historical controls from registry data
Phase I Human Trial
49. RNSHSummary
• Emerging evidence and new treatments in acute SCI
– perfusion
• early surgery
• MAP targets
• perfusion pressure & pressure reactivity
– neuro-protection
• methylprednisolone
• neuroprotective trials
• Specialised units offer access to up to date knowledge
and clinical trials
50. RNSHComprehensive Care
‘Surgeons of whatever specialty
who are engaged in the immediate treatment
of spinal paraplegics and tetraplegics
should take account of
all aspects of the treatment
and not merely the spine itself’
Sir Ludwig Guttman. 1973.
51. RNSH
Thank you
‘The Injured Lioness’ from Lion Hunt of Ashurbanipal.
Nineveh, Assyria c640 BCE. The British Museum
57. RNSH
Thank you
‘The Injured Lioness’ from Lion Hunt of Ashurbanipal.
Nineveh, Assyria c640 BCE. The British Museum
Editor's Notes
Good afternoon.
Before my substantive presentation, I would like to thank the organisers of this meeting for the honour and privilege of been asked to present on a topic that id both an area of passion and personal interest.
Today I will be discussing key issues in the early management of acute spinal cord injury.
The earliest evidence based recommendation regrading spinal cord injuries is found in the Edwin Smith Papyrus from c1600 BCE Egypt that concludes that spinal cord injury is an ailment “Not to be treated”. Spinal cord Injuries since, have long been considered a somewhat ‘hopeless’ case.
And today SCI remains a devastating neurologic injury with significant consequences for the injured and their community. In pure financial terms the estimated cost of SCI in 2009 was $2 billion dollars annually. The lifetime care costs for an individual with SCI was almost $10 million. As opposed to brain injury, where ill advised treatment may produce a “devastated survivor”, a spinal cord injured patient is very likely to survive and anything we can do that may save neurologic function needs to be fairly considered. There are massive functional implications from small neurologic improvements – one level can make the difference between mechanical ventilation or spontaneous breathing, between a breath controlled or hand controlled wheelchair, between independent transfer or being hoist dependent.
The general principles of management include the suspicion of injury, appropriate measures to protect the spine, adequate resuscitation of the patient, investigations to define the injury.
It is this area of specific management, which I will concentrate on today.
At a basic science level, we know that a spectrum of biochemical and cellular events progresses over the seconds, hours, days and weeks following the injury. The goal of early management is to interrupt, slow or ameliorate the events, preventing secondary injury and improving neurologic and functional outcome.
The last 10 years have seen a number of evidence based guidelines published on various aspects of spinal cord injury, some of which provide conflicting recommendations regarding treatment. I will refer to these guidelines today especially the 2013 guidelines published in the journal Neurosurgery and the 2017 guidelines published in the Global Spine Journal by the AOSpine group.
Today, I would like to discuss specific areas of recent controversy and progress and I have divided these into perfusion and protection strategies.
In erm of perfusion, I will focus on early surgery, MAP targets and concepts of perfusion pressure and pressure reaciivty. In terms of neuroprotection, I will cover the ongoing controversy around methylprednisolone and trials of neuroprotective agents.
The early stages of secondary spinal cord injury are characterized by ischaemia of neural tissue. It is thought that early surgery, by decompressing the cord, may prevent this secondary injury.
Historically, prominent figures in spinal injury care have warned against surgery. Sir Ludwig Guttman was the founder of modern rehabilitation care and the Paralympic movement and, in his historic text on cord injury warned against the tragic events that ensue from surgical meddling.
However, the latest 2017 guidelines provide the recommendation that early surgery be offered for adult patients with acute cord injury. The quality of evidence is low and the strength of the recommendation weak.
The most convincing single study regarding decompression was the STASCIS study. This was a non-randomized multi-centre prospective cohort study of 313 patients with cervical SCI. Almost 20% of patients undergoing early (<24 hours) surgery had a >2 grade improvement in AIS, compared to 9% in the late decompression group. The argument that early surgery was attendant with a higher rate of complications was not demonstrated to be true.
In the last 12 months, there have been 2 meta-analyses that have reported the results of surgery in SCI. The first compiled data on over one thousand patients with complete injuries from 20 studies and reported that early surgery was associated with a greater chance of neurologic improvement, as measured as a one or more grade improvement in AIS grade.
A one grade improvement in AIS may not confer functional improvement, .........
.............. so the second meta-analysis compiled data on over four hundred patients from 13 studies and again reported that early surgery was associated with a greater chance of neurologic improvement, as measured as a two or more grade improvement in AIS grade – which is more likely to confer functional improvement.
Just completed enrolment is a European study that aims to look at ultra-early surgery within 12 hours using a more sensitive indicator of outcome, the ISNCSCI motor score. The results, expected next year, are eagerly awaited.
When thinking about spinal cord perfusion, it is useful to consider the spinal cord perfusion pressure. Analogous to the cerebral perfusion pressure in brain injury, the spinal cord perfusion pressure is calculated as the MAP minus the intraspinal pressure. While decompressive surgery may reduce intraspinal pressure, elevating MAP may also improve spinal cord perfusion.
The 2013 guidelines suggest maintaining a MAP between 85 and 90 mm Hg for the first 7 days following injury. However, the underlying evidence is of poor quality.
This 2017 systematic review of relevant evidence shows the studies are all largely retrospective case series, often involve no comparison group and some didn’t define the MAP goals.
One of the better studies (from Michigan in the US), published in 2015,
Was a retrospective analysis of prospectively collected minutely ABP data on 100 patients. For 74, there was an outcome ISNCSCI recorded and three subgroups were defined according to the amount of improvement – no improvement, one grade, two grades.
The group who had a 2 or more improvement in AIS grade had a higher average MAP and a lower proportion of MAP values below 85mmHg. These are just associations and an ongoing trial ....
An ongoing trial in North America aims to examine the question whether elevated MAP will be associated with improved neurologic outcome.
A parallel stream of research has looked at measuring the actual spinal cord perfusion pressure. Much of the research in this area has come out of St Georges Hospital in London, led by Professor Marios Papadopoulos.
He has placed a subdural Codman microsensor catheter at the level of injury and measured the subdural pressure.
It has been shown that the subdural pressure is maximal at the site of injury because the swollen cord is compressed against the dura.
In one patient who consented to an intraparenchymal, as well as a subdural catheter, there was a very good correlation between the 2 measurements, showing the subdural measurement is an appropriate surrogate for intraspinal pressure.
They have shown in various studies that increasing SCPP improves blood flow, improves the amplitude of motor evoked potentials, improves biochemical parameters as assessed by microdialysis and, in incomplete patients, improves neurologic examination findings.
In terms of neurologic outcome, in these graphs, the black and white bars represent improvement in AIS grade by 1 or 2 grades respectively.
It can be seen that with decreasing ISP or increasing SCPP, there is a increasing proportion of subjects improving.
If we focus on the SCPP, it can be seen that the greatest improvement occurred with SCPP > 90 mmHg. If you think the average ISP in an injured cord is 20-30 mmHg, you can imagine what a significant task it is to achieve this perfusion pressure.
So the investigators set about calculating the optimal SCPP.
They did this using the pressure reactivity index. This has been used in brain injuries and is an indicator of autoregulaton. Pressure reactivity measures the smooth muscle response to to changing perfusion pressures and is calculated as a running correlation coefficient of the SCPP and the ISP. Where values around zero reflect intact autoregulation and numbers more than zero reflect deranged regulation – that is the ISP increases directly with increased perfusion.
Plotting sPRx against SCPP yields a U-shaped relationship and the optimal SCPP is the SCPP associated with the lowest PRx. In this pooled analysis the SCPPopt was about 80 to 90 mmHg.
As with the SCPP, there is a very good correlation of biochemical and clinical assessments of outcome with deviation away from the SCPPopt.
So we are left with this very significant target that even the current BP recommendations will not achieve.
So our strategies can be increase the MAP, but this can be difficult in a patient with neurogenic shock requiring high doses of inotropes and the consequent complications.
Alternatively, we can try and decrease the ISP or calculate individualized SCPPopt targets.
By that I mean calculated a SCPPopt for each patient. Previously, the PRx could only be calculated after treatment but software now allows real time calculation of these parameters.
Here we can see the U curves for 2 patients and how they have differing SCPPopt. This is the main focus of research in this area at this time.
In terms of decreasing ISP, it is not influenced by changes in pCO2, mannitol, anaesthetic agents. Interestingly, it can be increased with supine positioning after laminectomy (esp in thoracic injuries).
The London group performed duroplasty on a group of patients. Duroplasty involved opening the dura, sewing in a patch of tissue to increase the dural volume – similar to a decompressive crani - and have demonstrated that it reduces ISP and leads to a downwards shift in the U curve and SCPPopt and this in been further investigated as a new therapeutic strategy.
This brings me onto neuroprotective agents and starting with methylpredinisolone. The use of MPSS, as extensively studied in the NASCIS trials has long been a source of controversy.
The 2013 guidelines made a Level 1 recommendation that “administration of methylprednisolone is not recommended”.
The new 2017 guidelines have taken a polar opposite view stating “ a 24 hour infusion of high dose MPSS should be offered within 8 hours as a treatment option” – that is the NASCIS II protocol.
This Forrest plot from the new guideline indicates that the treatment effect favours MPSS.
However 49% of the effect is contributed by the NASCIS studies of which criticism abounds – issues regarding subgroup analysis and lack of stratification, post-hoc analysis amongst others – too great to go into now. Many reject the findings of these studies as a result.
The AOSpine group accepts the study was valid and as such, they are willing to accept that data.
I would caution that the magnitude of effect is small – only 3 ½ points on the motor scale – less than a motor level. The MCID on the ISNCSCI motor score is ~4.5.
Whether MPSS should be used may be an insoluable problem however the existence of these published guidelines (which we may well be judged by) behoves us to consider MPSS and be able to justify our decision regarding its use.
Finally I would like to talk about neuroprotective trials. I will focus on the RISCIS trial for which I am a principal investigator. I understand a trial of Minocycline has been halted and there is a trial of Cethrin about to start. VX-210 is applied epidurally at surgery and is an inhibitor of the enzyme Rho which itself prevents axonal regeneration.
There are a number of other agents in Phase I & II such as AntiNogoA, G-CSF, Glibenclamide and pooled GammaGlobulin.
RISCIS is an international, placebo controlled, double blind, randomised trial of Riluzole in acute traumatic spinal cord injury.
Recruitment started in 2015
RISCIS is an international, placebo controlled, double blind, randomised trial of Riluzole in acute traumatic spinal cord injury.
Recruitment started in 2015
Riluzole is a benzothiazole compound developed as an anti-convulsant. It has powerful Na channelblocking actions.
It is used in amyotrophic lateral sclerosis where its neuroprotecitve effects have been shown to increase ventilator & tracheotomy free survival and provide a modest increase in overall survival
The use of Riluzole in SCI is targeting the loss of Na gradient and excitotoxic neurotransmitter relase seen after SCI.
This model demonstrates a synaptic junction.
After spinal cord injury there is persistent activation of voltage dependent sodium channels.
The increase in intracellular sodium leads to cellular oedema through osmotic effects.
As a secondary effect, intracellular calcium and acidosis increases through the action of. Intracellular ATP is depleted through the activity of such homeostatic mechanisms.
The increase in sodium also leads to glutamate release ……
...... That actyivates post-synaptic Ca and Na channels and leading to glutamate mediated exicitotoxicty
Riluzole blocks the persistent activation of voltage dependent sodium channels and aims to prevent these downstream effects
There are 2 main published studies that examine riluzole in a rat model. In the riluzole animals, tissue preservation was greater at the epicenter of the injury and for a region around the injury.
The 2 images on the left are transverse section through the rat spinal cord at the level of injury. In the riluzole animals, the bottom picture, there is better preservation of tissue and this preservation was seen to extend around the region of injury. This preservation was greatest in the animals receiving Riluzole within 1 hour of injury …..
In both studies, the riluzole animals demonstrated better motor assessment. In this graph, demonstrating the BBB scores from injury until sacrifice at 6 weeks, it can be seen that those animals receiving riluzole within one hour had improved outcomes compared to those who had administration after 3 hours.
Of the 36 patients enrolled, there were 28 with cervical injuries.
The Riluzole was given within 12 hours of injury and continued twice daily for 14 days.
No significant toxicity was noted and outcomes were compared to historical controls from registry data ….
Riluzole was given to 36 patients with cervical SCI and compared to historical controls from registry data ….
No significant toxicity was noted and in all cervical patients combined there was improvement in mean motor score, in favour of Riluzole.
This is not evidence of effect but was enough to prompt this next Phase in trial …..