ANAESTHESIA FOR ELECTIVE NEUROSURGERY J. DINSMORE DEPARTMENT OF ANAESTHESIA,  ST. GEORGE’S HOSPITAL, LONDON, UK
<ul><li>Neuroanaesthesia continues to develop and expand </li></ul><ul><li>Knowledge and expertise of the anaesthetist may...
<ul><li>The emphasis remains on the provision of good operative conditions, assessment and preservation of neurological fu...
BASIC PRINCIPLES <ul><li>Provision of optimal operative conditions, maintenance of cerebral perfusion pressure (CPP), and ...
DRUGS <ul><li>Despite theoretical benefits of i.v agents, volatile agents remain popular. </li></ul><ul><li>Numerous studi...
<ul><li>In a study comparing desflurane, isoflurane, and sevoflurane in a porcine model of intracranial hypertension, at e...
<ul><li>In 2 different studies in healthy patient: </li></ul><ul><ul><li>Isoflurane was found to impair autoregulation, al...
<ul><li>Propofol has many theoretical advantages by: </li></ul><ul><ul><li>Reducing cerebral blood volume (CBV) and ICP an...
<ul><li>The effects of desflurane, isoflurane at 1 MAC and propofol on the CBF velocity investigated in children. </li></u...
<ul><li>In patients with normal ICP. </li></ul><ul><ul><li>CPP decreased under propofol but not sevoflurane at moderate hy...
<ul><li>Reduction in CBF with propofol has been associated with decrease in jugular venous o2 saturation, particularly at ...
<ul><li>Detrimental effects of nitrous oxide are well documented. </li></ul><ul><li>Inhalation of nitrous oxide 50% causes...
<ul><li>Addition of nitrous oxide to propofol or sevoflurane doesn’t alter regional CBF but does attenuate reduction in CB...
<ul><li>A study in 700 patients showed the drugs used for induction or maintenance  of anesthesia were not independent ris...
STEROIDS <ul><li>Dexamethasone is routinely prescribed to reduce cerebral oedema, but even a single 10mg dose can increase...
<ul><li>Adverse metabolic and cerebral ischaemic effects of high-blood glucose concentrations are well documented.  </li><...
POSITIONING <ul><li>Optimal patient positioning can reduce ICP and brain swelling. </li></ul><ul><li>In patient undergoing...
<ul><li>MRI study in healthy volunteers supports the clinical findings of an improvement in cerebrovascular and intracrani...
MONITORING <ul><li>Aims to detect changes in cerebral haemodynamics, oxygenation, and neuronal function.  </li></ul><ul><l...
<ul><li>Both i.v and volatile agents affect evoked potential characteristics </li></ul><ul><li>Propofol causes significant...
RECOVERY <ul><li>A speedy recovery allows prompt neurological assessment and early detection of complications. </li></ul><...
<ul><li>A study comparing (a) sevoflurane and fentanyl with (b) propofol and remifentanil </li></ul><ul><ul><li>No differe...
<ul><li>A study comparing (a) sevoflurane and remifentanil with (b) propofol and remifentanil more hypotension in (a) </li...
<ul><li>Propofol with remifentanil rather than sufentanil was associated with an earlier return of cognitive function. </l...
<ul><li>Systemic hypertension is common during emergence and may contribute to the development of post operative hematomas...
PAIN, NAUSEA AND VOMITING <ul><li>Codein-based analgesia is often inadequate. </li></ul><ul><li>Acetominophen and NSAIDS r...
<ul><li>Scalp infiltration using bupivacaine 0.375% with epinephrine 1:200 000 or ropivacaine 0.75% decrease postoperative...
<ul><li>There is no convincing evidence in favour of one anti-emetic agent over another.  </li></ul><ul><li>In high risk p...
<ul><li>Metoclopromide and scopolamine have also been used with some success </li></ul><ul><li>In non-neurosurgical patien...
FUTURE  PERSPECTIVES <ul><li>With further advances in imaging, computing, and optics the use of minimally invasive and fun...
<ul><li>The use of intraoperative MRI will increase. </li></ul><ul><li>Endoscopic surgery is now routine for intraventricu...
<ul><li>The advantages of minimally invasive surgery include: </li></ul><ul><ul><li>Reduced trauma to normal tissue </li><...
<ul><li>Anaesthetists may be faced with providing care for a newly developed procedure. </li></ul><ul><li>A comprehensive ...
AWAKE CRANIOTOMY
AWAKE CRANIOTOMY <ul><li>Is gaining popularity worldwide </li></ul><ul><li>Routine for epilepsy surgery for many years, it...
<ul><li>Cortical mapping allows the planning of safe resection margins.  </li></ul><ul><li>With continuous neurological as...
<ul><li>It has been suggested that it could become routine for supratentorial tumors irrespective of functional cortex. </...
TECHNIQUES <ul><li>The anaesthetists must provide adequate analgesia and sedation, hemodynamic stability, and a safe airwa...
<ul><li>Numerous techniques have been described </li></ul><ul><ul><li>local anaesthesia  </li></ul></ul><ul><ul><li>consci...
<ul><li>Whatever technique is used, adequate local anaesthesia is essential. </li></ul><ul><li>Scalp infiltration with lar...
<ul><li>Several studies have demonstrated that absorption of local anaesthesic is rapid and that potentially toxic plasma ...
<ul><li>Propofol is the most frequently drug used for both sedation and general anaesthesia by providing: </li></ul><ul><u...
<ul><li>Propofol is often used as a target-controlled infusions and maybe combined with remifentanil when changes in infus...
<ul><li>In a study comparing propofol and remifentanil with propofol and fentanyl for conscious sedation, there was no dif...
<ul><li>Dexmedetomidine provides sedation and analgesia without respiratory depression  and has been used as a sole agent,...
<ul><li>Significant sedative synergism has been reported between midazolam and dexmedetomidine. </li></ul><ul><li>Dexmedet...
<ul><li>Any sedation inevitably runs the risk of hypoventilation or airway obstruction. </li></ul><ul><li>Patient position...
<ul><li>LMA is a popular adjunct. </li></ul><ul><ul><li>Well tolerated in lighter planes of anaesthesia particularly in co...
<ul><li>A cuffed oropharyngeal airway was used in 20 patients for AAA technique with spontaneous ventilation: </li></ul><u...
<ul><li>The use of NIPPV has obvious limitations . </li></ul><ul><li>Nasal mask </li></ul><ul><ul><li>Difficult to positio...
INTRAOPERATIVE CORTICAL TESTING <ul><li>There is considerable inter-patient variability in the anatomical location and cor...
<ul><li>A computer program relaying images to the surgeon </li></ul><ul><ul><li>Touch screen technology to allow dysphasic...
COMPLICATIONS <ul><li>It is difficult to tell which technique is associated with least complications. </li></ul><ul><li>Wh...
<ul><li>When comparing sedation with (a) propofol and remifentanil and (b) propofol and fentanyl there was no significant ...
<ul><li>A study comparing patients (a) sedated with propofol and fentanyl, (b) AAA technique with propofol and fentanyl an...
<ul><li>Comparing to standard GA, in AAA technique using propofol, spontaneous ventilation and no instrumentation: </li></...
 
<ul><li>In summary, awake craniotomy is safe and well tolerated </li></ul><ul><li>Careful patient selection, attention to ...
THANK YOU
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Anaesthesia for elective neurosurgery journal (zuhura)

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Anaesthesia for elective neurosurgery journal (zuhura)

  1. 1. ANAESTHESIA FOR ELECTIVE NEUROSURGERY J. DINSMORE DEPARTMENT OF ANAESTHESIA, ST. GEORGE’S HOSPITAL, LONDON, UK
  2. 2. <ul><li>Neuroanaesthesia continues to develop and expand </li></ul><ul><li>Knowledge and expertise of the anaesthetist may directly influence patient’s outcome </li></ul><ul><li>Evolution of neurosurgical practice is accompanied by new challenges with greater focus on functional and minimally invasive procedures </li></ul>
  3. 3. <ul><li>The emphasis remains on the provision of good operative conditions, assessment and preservation of neurological function, and a rapid, high quality recovery </li></ul>
  4. 4. BASIC PRINCIPLES <ul><li>Provision of optimal operative conditions, maintenance of cerebral perfusion pressure (CPP), and cerebral oxygenation. </li></ul>
  5. 5. DRUGS <ul><li>Despite theoretical benefits of i.v agents, volatile agents remain popular. </li></ul><ul><li>Numerous studies have described their differential effects on cerebral hemodynamics and intracranial pressure. </li></ul>
  6. 6. <ul><li>In a study comparing desflurane, isoflurane, and sevoflurane in a porcine model of intracranial hypertension, at equipotent doses and normocapnia, cerebral blood flow (CBF) and ICP were greatest with desflurane and least with sevoflurane. </li></ul><ul><li>Sevoflurane cause the least vasodilatation. </li></ul>
  7. 7. <ul><li>In 2 different studies in healthy patient: </li></ul><ul><ul><li>Isoflurane was found to impair autoregulation, although this was reversible with hyperventilation. </li></ul></ul><ul><ul><li>Autoregulation was virtually intact with sevoflurane 1-1.2% at normocapnia </li></ul></ul><ul><li>Sevoflurane appears to be most suitable volatile agent for neuroanaesthesia (although large-scale studies are needed) </li></ul>
  8. 8. <ul><li>Propofol has many theoretical advantages by: </li></ul><ul><ul><li>Reducing cerebral blood volume (CBV) and ICP and; </li></ul></ul><ul><ul><li>Preserving both autoregulation and vascular reactivity. </li></ul></ul><ul><li>In healthy subject, propofol reduced CBF more than sevoflurane at equipotent concentrations. </li></ul>
  9. 9. <ul><li>The effects of desflurane, isoflurane at 1 MAC and propofol on the CBF velocity investigated in children. </li></ul><ul><li>When propofol was changed to desflurane the middle cerebral artery flow velocity increased. </li></ul><ul><li>When desflurane was changed to isoflurane, there was no further change. </li></ul><ul><li>Neurosurgical patient anesthetised with propofol were found to have lower ICP and higher CPP than those with isoflurane and sevoflurane. </li></ul>
  10. 10. <ul><li>In patients with normal ICP. </li></ul><ul><ul><li>CPP decreased under propofol but not sevoflurane at moderate hypotension. </li></ul></ul><ul><ul><li>CPP decreased under sevoflurane but not propofol at hypocapnia. </li></ul></ul>
  11. 11. <ul><li>Reduction in CBF with propofol has been associated with decrease in jugular venous o2 saturation, particularly at hypocapnia. </li></ul><ul><li>However, increases in propofol concentrations don’t affect jugular venous bulb o2 saturations. </li></ul>
  12. 12. <ul><li>Detrimental effects of nitrous oxide are well documented. </li></ul><ul><li>Inhalation of nitrous oxide 50% causes significant increase in estimated CPP and a decrease in zero flow pressure. </li></ul><ul><li>In patients with decreased intracranial compliance any increase in CBV and ICP would be detrimental. </li></ul>
  13. 13. <ul><li>Addition of nitrous oxide to propofol or sevoflurane doesn’t alter regional CBF but does attenuate reduction in CBF and cerebral metabolic rate for oxygen produced by the agents alone. </li></ul><ul><li>Sevoflurane also reduces the o2 extraction fraction at moderate depth of anesthesia. </li></ul>
  14. 14. <ul><li>A study in 700 patients showed the drugs used for induction or maintenance of anesthesia were not independent risk factors for intraoperative brain swelling. </li></ul><ul><li>Risk factors included: </li></ul><ul><ul><li>ICP at the start of surgery </li></ul></ul><ul><ul><li>The degree of midline shift in CT scan </li></ul></ul><ul><ul><li>Histological diagnosis of glioblastoma/ metastasis </li></ul></ul>
  15. 15. STEROIDS <ul><li>Dexamethasone is routinely prescribed to reduce cerebral oedema, but even a single 10mg dose can increase blood glucose concentrations in non-diabetic patient. </li></ul><ul><li>Whether tight glycaemic control improves outcome in elective neurosurgical patients is yet to be established. </li></ul>
  16. 16. <ul><li>Adverse metabolic and cerebral ischaemic effects of high-blood glucose concentrations are well documented. </li></ul>
  17. 17. POSITIONING <ul><li>Optimal patient positioning can reduce ICP and brain swelling. </li></ul><ul><li>In patient undergoing craniotomy for cerebral aneurysm, a 10 deg reverse Trendelenburg tilt decreased ICP although CPP was unchanged. </li></ul><ul><li>In children with space occupying lesion, brain swelling was more pronounced and the ICP higher in prone position compared with supine. </li></ul>
  18. 18. <ul><li>MRI study in healthy volunteers supports the clinical findings of an improvement in cerebrovascular and intracranial compliance from the supine to sitting position because of reduced intracranial blood and CSF volume. </li></ul>
  19. 19. MONITORING <ul><li>Aims to detect changes in cerebral haemodynamics, oxygenation, and neuronal function. </li></ul><ul><li>Intraoperative electrophysiological monitoring may help to prevent postoperative deficits. Detection of neurological injury: </li></ul><ul><ul><li>Sensitivity of 79% </li></ul></ul><ul><ul><li>Negative predictive value of 96% </li></ul></ul>
  20. 20. <ul><li>Both i.v and volatile agents affect evoked potential characteristics </li></ul><ul><li>Propofol causes significantly less suppression at a comparable depth of anesthesia. </li></ul><ul><li>Electrophysiological monitoring is also used to assess the depth of anaesthesia </li></ul>
  21. 21. RECOVERY <ul><li>A speedy recovery allows prompt neurological assessment and early detection of complications. </li></ul><ul><li>New shorter acting agents have made a rapid recovery easier to achieve. </li></ul><ul><li>Studies have failed to demonstrate consistent differences between volatile agents and TIVA. </li></ul>
  22. 22. <ul><li>A study comparing (a) sevoflurane and fentanyl with (b) propofol and remifentanil </li></ul><ul><ul><li>No differences in emergence time, early postoperative cognitive function, pain, nausea or vomiting </li></ul></ul><ul><ul><li>More episodes of intraoperative hypotension and hypertension in (b) </li></ul></ul>
  23. 23. <ul><li>A study comparing (a) sevoflurane and remifentanil with (b) propofol and remifentanil more hypotension in (a) </li></ul><ul><li>Comparison of alfentanil, fentanyl, and remifentanil </li></ul><ul><ul><li>No significant differences in hemodynamics and respiratory variables </li></ul></ul><ul><ul><li>Reduce time of eye opening in remifentanil group </li></ul></ul>
  24. 24. <ul><li>Propofol with remifentanil rather than sufentanil was associated with an earlier return of cognitive function. </li></ul>
  25. 25. <ul><li>Systemic hypertension is common during emergence and may contribute to the development of post operative hematomas. </li></ul><ul><li>Increased use of remifentanil maybe associated with more postoperative hypertension. </li></ul><ul><li>α- 2 agonist dexmedetomidine has been shown to provide good hemodynamic stability, attenuating the response to intubation and emergence. </li></ul>
  26. 26. PAIN, NAUSEA AND VOMITING <ul><li>Codein-based analgesia is often inadequate. </li></ul><ul><li>Acetominophen and NSAIDS remain controversial. </li></ul><ul><li>Morphine causing increased incidence of nausea, vomiting, and urinary retention. </li></ul><ul><li>Multimodal analgesia regimes seem to be more successful (reduce opiod side effects, provison of effective pain control) </li></ul>
  27. 27. <ul><li>Scalp infiltration using bupivacaine 0.375% with epinephrine 1:200 000 or ropivacaine 0.75% decrease postoperative pain scores and morphine consumption, but only for the first 2h after surgery. </li></ul>
  28. 28. <ul><li>There is no convincing evidence in favour of one anti-emetic agent over another. </li></ul><ul><li>In high risk patients, it maybe necessary to use a combination of antiemetics </li></ul><ul><li>Ondansetron, droperidol, and dexamethasone can each reduce the risk of nausea and vomiting by 25%. </li></ul>
  29. 29. <ul><li>Metoclopromide and scopolamine have also been used with some success </li></ul><ul><li>In non-neurosurgical patients, TIVA with propofol and the use of air rather than nitrous oxide have been shown to be effective. </li></ul>
  30. 30. FUTURE PERSPECTIVES <ul><li>With further advances in imaging, computing, and optics the use of minimally invasive and functional procedures will continue to increase. </li></ul><ul><li>Neuronavigation systems have improved the ability to treat seemingly inaccessible intracranial lesions. </li></ul>
  31. 31. <ul><li>The use of intraoperative MRI will increase. </li></ul><ul><li>Endoscopic surgery is now routine for intraventricular pathology and likely to extend into all types of intracranial surgery. </li></ul>
  32. 32. <ul><li>The advantages of minimally invasive surgery include: </li></ul><ul><ul><li>Reduced trauma to normal tissue </li></ul></ul><ul><ul><li>Preservation of function </li></ul></ul><ul><ul><li>More rapid recovery </li></ul></ul><ul><ul><li>Reduced morbidity </li></ul></ul><ul><ul><li>Shorter hospital stay </li></ul></ul><ul><li>Some procedures can be performed under minimal or local anaesthesia </li></ul>
  33. 33. <ul><li>Anaesthetists may be faced with providing care for a newly developed procedure. </li></ul><ul><li>A comprehensive preoperative assessment and management is essential. </li></ul><ul><li>Awareness of potential complications and vigilance enables early identification of airway compromise, seizures, and changes in neurological status. </li></ul>
  34. 34. AWAKE CRANIOTOMY
  35. 35. AWAKE CRANIOTOMY <ul><li>Is gaining popularity worldwide </li></ul><ul><li>Routine for epilepsy surgery for many years, it is now increasingly used for the removal of intracranial lesions in or adjacent to eloquent brain. </li></ul><ul><li>Maximal tumour resection seems to be an important determinant in prognosis, increasing in median survival time and time to recurrence. </li></ul>
  36. 36. <ul><li>Cortical mapping allows the planning of safe resection margins. </li></ul><ul><li>With continuous neurological assessment maximal resection with minimal postoperative neurological dysfunction can be achieved. </li></ul><ul><li>Functional stereotactic neurosurgery is increasingly being used in the surgical treatment of movement disorders. </li></ul>
  37. 37. <ul><li>It has been suggested that it could become routine for supratentorial tumors irrespective of functional cortex. </li></ul><ul><li>In prospective trials of 200 patients, the procedure was well tolerated with reduced intensive care time and hospital stay. </li></ul>
  38. 38. TECHNIQUES <ul><li>The anaesthetists must provide adequate analgesia and sedation, hemodynamic stability, and a safe airway but also an alert, cooperative patient for neurological assessment. </li></ul>
  39. 39. <ul><li>Numerous techniques have been described </li></ul><ul><ul><li>local anaesthesia </li></ul></ul><ul><ul><li>conscious sedation </li></ul></ul><ul><ul><li>general anaesthesia using asleep-awake-asleep (AAA) with or without airway instrumentation </li></ul></ul><ul><li>With no consensus as the optimal regimen, most institutions have developed their own techniques. </li></ul>
  40. 40. <ul><li>Whatever technique is used, adequate local anaesthesia is essential. </li></ul><ul><li>Scalp infiltration with large volumes of local anaesthetics or scalp block carries potential risk of local anaesthesia toxicity in patients who are already prone to seizures. </li></ul>
  41. 41. <ul><li>Several studies have demonstrated that absorption of local anaesthesic is rapid and that potentially toxic plasma concentrations were achieved in some patients. </li></ul><ul><li>However the clinical signs and symptoms suggestive of toxicity were not evident. </li></ul>
  42. 42. <ul><li>Propofol is the most frequently drug used for both sedation and general anaesthesia by providing: </li></ul><ul><ul><li>Titratable sedation </li></ul></ul><ul><ul><li>Rapid smooth recovery </li></ul></ul><ul><ul><li>Decrease the incidence of seizures </li></ul></ul><ul><ul><li>When stopped for awakening, minimizes interference with electrocorticographic recordings. </li></ul></ul>
  43. 43. <ul><li>Propofol is often used as a target-controlled infusions and maybe combined with remifentanil when changes in infusion rates of both drugs correlate well with effect site concentrations. </li></ul>
  44. 44. <ul><li>In a study comparing propofol and remifentanil with propofol and fentanyl for conscious sedation, there was no difference. </li></ul><ul><li>AAA technique using propofol and remifentanil showed that adequate conditions were obtained in 98% of patient with a median wake up time of 9 mins </li></ul>
  45. 45. <ul><li>Dexmedetomidine provides sedation and analgesia without respiratory depression and has been used as a sole agent, an adjunct, and a rescue drug for awake craniotomy. </li></ul><ul><li>When used for sedation during embolisation of cerebral arteriovenous malformation, dexmedetomidine 0.2-0.7µg/kg/h significantly impaired cognitive function. </li></ul>
  46. 46. <ul><li>Significant sedative synergism has been reported between midazolam and dexmedetomidine. </li></ul><ul><li>Dexmedetomidine 0.3-0.6µg/kg/h was used successfully as a sole agent during implantation of deep brain stimulators. </li></ul><ul><li>It provided satisfactory sedation, didn’t mask clinical sign of Parkinson’s disease and reduced the need of antihypertensive. </li></ul>
  47. 47. <ul><li>Any sedation inevitably runs the risk of hypoventilation or airway obstruction. </li></ul><ul><li>Patient positioning may limit access and further contribute to airway compromise. </li></ul>
  48. 48. <ul><li>LMA is a popular adjunct. </li></ul><ul><ul><li>Well tolerated in lighter planes of anaesthesia particularly in conjunction with propofol and remifentanil </li></ul></ul><ul><ul><li>Easy to insert and remove </li></ul></ul><ul><ul><li>Enables ventilation to be controlled </li></ul></ul>
  49. 49. <ul><li>A cuffed oropharyngeal airway was used in 20 patients for AAA technique with spontaneous ventilation: </li></ul><ul><ul><li>Airway manipulation required in 1/3 of patient in supine position, but none in lateral position </li></ul></ul><ul><ul><li>Airway manipulation is a safe alternative to the LMA </li></ul></ul>
  50. 50. <ul><li>The use of NIPPV has obvious limitations . </li></ul><ul><li>Nasal mask </li></ul><ul><ul><li>Difficult to position </li></ul></ul><ul><ul><li>Interfere with surgical field </li></ul></ul><ul><ul><li>Patient may find it unpleasent </li></ul></ul><ul><li>The successful use of pressure support ventilation has also been described in patient with OSA. </li></ul>
  51. 51. INTRAOPERATIVE CORTICAL TESTING <ul><li>There is considerable inter-patient variability in the anatomical location and cortical representation of speech areas. </li></ul><ul><li>Intraoperative mapping of speech involves the identification of Broca’s area by producing speech arrest. </li></ul><ul><li>Identification of other cortical speech areas by a series of naming and word/sentence comprehension tests using books/slides. </li></ul>
  52. 52. <ul><li>A computer program relaying images to the surgeon </li></ul><ul><ul><li>Touch screen technology to allow dysphasic patients to respond to images. </li></ul></ul><ul><li>In multilingual patients, localisation of speech maybe problematic as there maybe multiple cortical representation sites. </li></ul>
  53. 53. COMPLICATIONS <ul><li>It is difficult to tell which technique is associated with least complications. </li></ul><ul><li>When (a) neurolept analgesia was compared with (b) patient-controlled sedation using propofol for epilepsy surgery, the (b) group had fewer seizures but higher incidence of transient respiratory depression. </li></ul>
  54. 54. <ul><li>When comparing sedation with (a) propofol and remifentanil and (b) propofol and fentanyl there was no significant difference in complication rate but overall incidence of respiratory complications of 18%. </li></ul><ul><li>All adverse events were easily treated in patients receiving mannitol. </li></ul>
  55. 55. <ul><li>A study comparing patients (a) sedated with propofol and fentanyl, (b) AAA technique with propofol and fentanyl and spontaneous ventilation using LMA and (c) AAA technique with propofol, remifentanil and assisted ventilation using LMA </li></ul><ul><ul><li>Airway obstuction in 3 patients in (a) </li></ul></ul><ul><ul><li>All patients in (b) had E’CO2 > 6kPa </li></ul></ul><ul><ul><li>No complications in (c) </li></ul></ul>
  56. 56. <ul><li>Comparing to standard GA, in AAA technique using propofol, spontaneous ventilation and no instrumentation: </li></ul><ul><ul><li>No local anaesthetic toxicity, pulmonary aspiration, air embolism, death. </li></ul></ul><ul><ul><li>No difference in incidence of nausea, vomiting and seizures. </li></ul></ul><ul><ul><li>Arterial desaturation, higher levels of PaCo2, and hemodynamic complications (hypo/hypertension and tachycardia) more common </li></ul></ul>
  57. 58. <ul><li>In summary, awake craniotomy is safe and well tolerated </li></ul><ul><li>Careful patient selection, attention to details, and good communication are vital to keep the complications low. </li></ul>
  58. 59. THANK YOU

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