REGIONAL PATHOLOGY in Clinical Anaesthesia

Regional pathology

1. REGIONAL PATHOLOGY BY DR ONYEOJI CHINEDU (DA, UNIBEN, FMCA) CONSULTANT ANAESTHETIST FMC ASABA, DELTA STATE.

2. INTRODUCTION Looks at some medical pathology related to the various systems of the body and how it affects anaesthesia . Asthma Stroke Renal failure Muscular disease

3. ASTHMA

4. INTRODUCTION Reversible airways obstruction, resulting from bronchoconstriction , bronchial mucosal oedema and mucus plugging. Causes high airways resistance, hypoxaemia , air trapping and increased work of breathing. Two main forms exist: Extrinsic Intrinsic

5. INTRODUCTIONS CONT’D Extrinsic allergic: begins in childhood; may have an associated family history of atopy (e.g. hayfever , eczema), is episodic and tends to respond to therapy. I ntrinsic : adult onset; no allergic family history. Nasal polyps are common and exacerbations occur with infection and aspirin. Less responsive to treatment .

6. INTRODUCTION CONT’D B ronchi show increased sensitivity to triggering agents, constricting when normal bronchi may not. During anaesthesia , surgical stimulation or stimulation of the pharynx or larynx may cause bronchospasm .

7. ACUTE SEVERE ASTHMA Signs of a severe attack: - inability to talk. - tachycardia >110 beats/min. - tachypnoea >25 breaths/min. - pulsus paradoxus >10 mmHg. - peak expiratory flow rate (PEFR) <50% of predicted normal .

8. ACUTE SEVERE ASTHMA CONT’D Signs of life-threatening attack: Silent chest on auscultation. Cyanosis . Bradycardia . Exhausted Confused or unconscious patient.

9. ACUTE SEVERE ASTHMA CONT’D Arterial blood gas measurement: Hypoxaemia from V̇/Q̇ mismatch. Reduced arterial PCO2 from hyperventilation. There is poor correlation between FEV1 and arterial PCO2 . Other problems: pneumothorax , infection, dehydration. Hypokalaemia is common due to corticosteroids, catecholamine administration and respiratory alkalosis.

10. MANAGEMENT G eneral medical and ICU management: First-line therapies: Humidified O2 with high FIO2. Nebulised salbutamol 2.5–5 mg or terbutaline 5–10 mg 4-hourly (may be given continuously

11. MANAGEMENT CONT’D In severe asthma; Iv salbutamol 250 μg may be given, followed by 5–20 μg /min. Nebulised ipratropium bromide 0.1–0.5 mg may be alternated with β2-agonists. Corticosteroids ; e.g. hydrocortisone 100–200 mg 4hourly iv, or by infusion.

12. MANAGEMENT CONT’D S econd-line therapies: Magnesium sulfate 1.2–2.0 g iv over 20 min as a single dose. Aminophylline 3–6 mg/kg iv, followed by 0.5 mg/ kg/h . Inhalational anaesthetic agents, ketamine and adrenaline have been used in resistant cases

13. ANAESTHETIC MANAGEMENT OF PATIENTS WITH ASTHMA: PREOPERATIVELY: Preoperative assessment is directed towards respiratory function Frequency of attacks Severity of attacks (hospital admissions) Drug therapy (including corticosteroids). Last episode

14. ANAESTHETIC MANAGEMENT OF PATIENTS WITH ASTHMA CONT’D I nvestigations: CXR PEFR/ spirometry (especially pre- and post-bronchodilator) A rterial blood gas interpretation. P remedication: N ebulised bronchodilators . Preoperative physiotherapy may also be useful. Steroid cover may be required

15. ANAESTHETIC MANAGEMENT OF PATIENTS WITH ASTHMA CONT’D Perioperatively : Regional anaesthesia if suitable. Thiopental has been implicated as causing bronchospasm , although this is controversial. Propofol , etomidate and ketamine are suitable alternatives. Volatile agents cause bronchodilatation .

16. ANAESTHETIC MANAGEMENT OF PATIENTS WITH ASTHMA CONT’D Atracurium may cause histamine release V ecuronium , Pancuronium , Rocuronium do not. O pioid analgesic drugs may release histamine but are commonly given. Fentanyl may be a good alternative to morphine.

17. ANAESTHETIC MANAGEMENT OF PATIENTS WITH ASTHMA CONT’D Risk of bronchospasm during intubation may be reduced by spraying the larynx and trachea with lidocaine . Iv lidocaine 1–2 mg/kg may also be used to reduce the incidence of bronchospasm on intubation and extubation β-adrenergic receptor antagonists should be avoided. Dehydration should be avoided

18. STROKE “Rapidly developing clinical sign of focal or global disturbance of cerebral function with symptoms lasting 24hrs or longer or leading to death with no other cause rather than of vascular origin.” (WHO ) Stroke or cerebrovascular accident (CVA) is when blood flow to a part of the brain is compromised as a result of blockage or rupture of blood vessel leading to death of brain cells.

19. CLASSIFICATION Clinical classification Completed stroke: focal deficit is persistent and not worsening Evolving stroke: focal deficit continues to worsen after about 6 hrs from onset Transient Ischaemic attack: focal deficit last from a few seconds to 24hrs with complete recovery

20. CLASSIFICATION CONT’D Classification of complete stroke Ischaemic stroke (85%): could be thrombotic or embolic Haemorrhagic stroke (15%) :could be intracerebral bleed or subarachnnoid haemorrhage bleed.

21. CLASSIFICATION CONT’D Stages of stroke Acute: < 7days Subacute : Early as 2 to 4 wks or late 1 to 4 months Chronic : > 6 months

22. ISCHAEMIC STROKE Infarction (85%–90%), e.g. caused by atheroma , embolism, arteritis /arterial spasm or hypotension. If symptoms resolve within 24 h defined as a transient ischaemic attack. CT scanning may reveal evidence of permanent damage. Recurrent multiple small emboli may cause vascular dementia.

23. ISCHAEMIC STROKE RISK FACTORS Hypertension Artherosclerosis Diabetes mellitus Polycythemia Hyperlipidemia DIC Obesity Valvular heart disease Cigerrete smoking Oral Contaceptives Alcohol Coccaine Folic acid defficiency Atrial fibrillation Homocysteinaemia Cerebral autosomal dorminant arteropathy with subcortical infarcts

24. HAEMORRHAGIC STROKE Haemorrhage (10%–15%) Primary (spontaneous) intracerebral haemorrhage (ICH) accounts for 85% Results from is due to rupture of small arteries/arterioles due to hypertension or amyloid angiopathy . More common in patients taking anticoagulant drugs.

25. HAEMORRHAGIC STROKE CONT’D Secondary ICH causes include Trauma. Rupture of aneurysms (resulting in subarachnoid haemorrhage ) or arteriovenous malformations. Cocaine poisoning Haemorrhagic transformation of ischaemic infarcts.

26. HAEMORRHAGIC STROKE RISK FACTORS Severe hypertenstion Coagulopathies Cigertte smoking Aneurysms Vascular malformations Trauma Tumours Drug abuse Mycotic aneurysms

27. DIFFERENCE BETWEEN ISCHAEMIC AND HAEMORRHAGIC STROKE ISHAEMIC Occurs at rest No loss of consciousness Absent headache No convulsion No vomiting Normal/moderate Bp Raised ICP symptoms not maked Hx of Past TIAs No neck stiffnes / kerng signs HAEMORRHAGIC Occurs peak of activity Loss of conscious Throbbing headache Convulsion Vomiting Severe hypertension Marked symptoms of raised ICP TIAs not commonly present Neck stiffness/ kernig sign may be present.

28. COMPARISON BETWEEN THROMBOTIC AND EMBOLIC STROKE EMBOLIC Maximal symptoms at onset May recover rapidly Multiple sings and symptom not corresponding to any vascular distribution THROMBOTIC Stepwise deterioration overtime Improvement is gradual Signs and symptoms correspond to single vascular distribution

29. INVESTIGATIONS CT Scan/ MRI. CT detects> 90% of bleeds. Differentiate the stroke. Lipid profile S/E/Ur/Cr RBS Urinalysis FBC LP for CSF analysis if SAH is suspected ECG Chest Xray

30. OBJECTIVES OF TREATMENT Restore Cerebral Circulation Treat identified risk/ Predisposing Factors Reduce raised ICP Treat complications Limit disability Prevent future occurrence

31. TREATMENT Nurse in 30 head up to encourage venous drainage Rehydration. With N/S to improve penumbra perfusion Iv Mannitol 500mls over 20-30mins for cerebral oedma if present Anticoagulant e.g Aspirin 150-375mg/ dly for 2wks then 75mg daily if haemorrhagic stroke is excluded

32. TREATMENT CONT’D Elevated BP. Ischaemic stroke don’t treat except systolic is > 220mmHg or Diastolic > 120 mmHg or MAP > 145mmHg Targeted BP in Ischaemic stroke is 180/110mmHg and 160/110mmHg in Haemorrhagic stroke Monotherapy is advocated. E.g Nifedipine , Atenolol or ACE inhibitor can be used.

33. TREATMENT CONT’D Antioxidants e.g Vit . C and E Analgesic and Sedation in SAH Insulin may be required for stress induced Hyperglycemia. Avoid oral intake until swallowing test is done Ensure early physiotherapy and mobilization Life style modification if indicated

34. ANAESTHETIC CONSIDERATIONS FOR PATIENTS WITH ESTABLISHED STROKES: Assessment for predisposing conditions, e.g. hypertension, coagulation disorders, embolic conditions, trauma, arteritis due to connective tissue diseases, infections. Immobility predispose to risk of DVT Contractures: may affect drip sites. Risk of DVT. Bulbar lesions and laryngeal incompetence, and autonomic disturbances.

35. ANAESTHETIC CONSIDERATIONS FOR PATIENTS WITH ESTABLISHED STROKES Communication difficulties. Severe hyperkalaemia after suxamethonium has been reported up to 6 months after stroke. Hyperventilation and reduction of cerebral blood flow, and hypotension, should be avoided during anaesthesia . Cerebral steal may occur. Confusion is common postoperatively.

36. RISK OF STROKE DURING ANAESTHESIA Increased in cardiac surgery, carotid endarterectomy and neurosurgery. Perioperative ischaemic stroke occurs with an incidence of 0.1%–0.6% in non-cardiac surgery. Incidence is increased in patients with previous stroke. An interval of at least 6 months between stroke and elective surgery is suggested.

37. RENAL FAILURE

38. INTRODUCTION Loss of renal function causing abnormalities in electrolyte fluid and acid–base balance with increases in plasma urea and creatinine . Divided into Acute renal failure Chronic renal failure

39. CHRONIC RENAL FAILURE Irreversible Often follows acute kidney injury . Glomerulonephritis (commonest cause) Others causes include Pyelonephritis Diabetes Polycystic disease Vascular disease Hypertension Drugs Familial causes.

40. CLASSIFIED ACCORDING TO GFR INTO DIFFERENT STAGES: - normal: healthy with GFR ≥90 ml/min. - stage 1: damage with GFR ≥90 ml/min. - stage 2 (mild): GFR 60–89 ml/min. - stage 3 (moderate): GFR 30–59 ml/min. - stage 4 (severe): GFR 15–29 ml/min. - stage 5 (established failure): GFR <15 ml/min or on dialysis.

41. CLINICAL FEATURES Affects all systems GIT: Nausea, Diarrhoea,Anoreixia , GI bleeding CNS: Restless leg, Insomnia , Parasthesia CVS: Aneamia GUT: Nocturia , Polyuria , Amenorrhea, Impotence MSS: Oedema , bone pains MUCOCUTANEOUS: Pruritus , Easy Brusing , GI bleeding

42. MANAGEMENT Reduce blood pressure Dietary restriction of K intake Protein Salt Correct acidosis by bicarbonate supplementation Avoid fluid overload. Treat anaemia Hypocalcemia and Hyperphosphatemia should be treated.

43. MANAGEMENT CONT’D Dialysis Renal transplant

44. ANAESTHESIA IN RENAL FAILURE Preoperatively: Features of the underlying disease must be assessed, e.g. diabetes, hypertension. Assessment of features of renal failure, in particular Cardiovascular complications, Fluid and electrolyte and Acid–base derangements.

45. ANAESTHESIA IN RENAL FAILURE Dialysis may be required before surgery. Treat Hypovolaemic and watch out for to perioperative hypotension. Anaemia may be chronic with compensatory mechanisms. Patients may be at risk of aspiration of gastric contents due to autonomic neuropathy if present.

46. ANAESTHESIA IN RENAL FAILURE CONT’D pre-existing arteriovenous fistulae or shunts should be noted. premedication as required. perioperatively : Iv cannulae should not be sited near arteriovenous fistulae, which should be loosely padded for protection Potassium-containing iv fluids should be avoided

47. ANAESTHESIA IN RENAL FAILURE CONT’D . Drugs whose actions are not terminated by renal excretion are preferred. Thus a common technique consists of propofol atracurium isoflurane sevoflurane . Drugs that accumulate in renal failure (e.g. mor­phine ) should be used with caution.

48. ANAESTHESIA IN RENAL FAILURE CONT’D Suxamethonium (not contraindicated) unless there is pre-existing peripheral neuropathy or hyperkalaemia . Nephrotoxic drugs (e.g. NSAIDs) should be avoided Regional techniques if suitable, e.g. brachial plexus block for fistula formation. postoperatively: close attention to fluid balance is important

49. GUILLAIN-BARRÉ SYNDROME

50. INTRODUCTION Also known as Acute inflammatory polyneuropathy described in 1916, although previously reported by Landry in 1859. Commonest cause of acute paralysis in the Western world. A number of variants are described.

51. INTRODUCTION CONT’D 95% of cases have a demyelinating polyneuropathy ; in the remainder the axon itself is affected. Incidence is 1–2 per 100 000. 60% of cases follow an infective process (URTI or diarrhea illness) within the previous 6 weeks.

52. INTRODUCTION CONT’D Infectious agents implicated include Campylobacter, Mycoplasma , Cytomegalovirus and HIV. May occasionally follow vaccination .

53. INTRODUCTION CONT’D Thought to be an autoimmune condition . Antiganglioside antibodies are associated with the axonal variant, although no specific antibodies have been identified in the commoner demyelinating form.

54. MOST COMMON GBS SUBTYPE Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) is the most common form and accounts for around 85–90% of cases. The clinical features are of symmetrical ascending motor weakness with hypo- or areflexia .

55. MOST COMMON GBS SUBTYPE The underlying pathological process involves inflammation and destruction of the myelin sheaths surrounding peripheral nerve axons by activated macrophages. This leads to slowing and blockage of conduction within peripheral nerves causing muscle weakness. Severe cases may develop secondary axonal damage.

56. CLINICAL FEATURES Progressive weakness, usually bilateral and symmetrical. Typically ascending from the legs but may affect any region first. Cranial nerve involvement is common. Weakness typically develops over 1–7 days and reaches a nadir in 4 weeks. Areflexia is invariable.

57. CLINICAL FEATURES cont’d 30% require mechanical ventilation. Recovery takes from several weeks to months, and up to years if axonal damage has occurred. 10%–15% are left with residual disability. 5% relapse.

58. CLINICAL FEATURES cont’d Sensory disturbance: Paraesthesia occurs in 50%, usually with glove and stocking distribution Reduced touch, sensation and joint position sense may also occur. Pain (e.g. in the calves and back) is common and may be a presenting feature. Numbness and paraesthesia starts distally and ascends in a similar fashion to the motor weakness in 80% of patients.

59. CLINICAL FEATURES cont’d Features autonomic disturbance include Hypotension or Hypertension Tachy - and Bradyarrhythmias , Paralytic Ileus and Urinary retention.

60. DIAGNOSIS By history/clinical features. CSF protein is raised (without an increase in white cell count) in >90% of patients after a few days. Nerve conduction studies help to differentiate demyelination from axonal damage. It’s a diagnosis of exclusion . Investigation is aim at excluding other differentials on the list.

61. INVESTIGATIONS cont’d Infection screen Send serology for Campylobacter jejuni , Cytomegalovirus, Epstein-Barr virus, Herpes simplex virus, Mycoplasma pneumoniae . HIV antibodies should be considered. Stool cultures looking for evidence of gastrointestinal infections particularly Campylobacter jejuni .

62. INVESTIGATIONS cont’d Radiological A CT brain is indicated to exclude other causes of symptoms and evidence of raised intracranial pressure prior to performing a lumbar puncture. An MRI of the spine may show selective anterior spinal nerve root enhancement with gadolinium and will exclude cervical nerve impingement.

63. INVESTIGATIONS cont’d Lumbar puncture Cell count and glucose are usually normal with a raised protein, although the latter may also be normal in first two weeks. Nerve conduction studies Findings depend on subtype of GBS. The majority show demyelinating pattern while some patients may show evidence of axonal loss with little or no demyelination .

64. INVESTIGATIONS cont’d Respiratory function tests These may show reduced vital capacity, maximal inspiratory and expiratory pressures. Arterial blood gases may indicate progressive respiratory failure.

65. DIFFERENTIAL DIAGNOSIS Neurological Myasthenia gravis Eaton-Lambert ( myasthenic ) syndrome Multiple sclerosis Transverse myelitis Metabolic Hypokalaemic periodic paralysis Hypermagnesaemia Hypophosphataemia Acute intermittent porphyria

66. DIFFERENTIAL DIAGNOSIS cont’d Infective Post diphtheria neuropathy Polio Botulism Tick paralysis Drugs / toxins Heavy metal poisoning (e.g. lead) Biological toxins (including snake and scorpion toxins) Drugs (including stavudine , nitrofurantoin and aminoglycosides ) Other Acute polymyositis Critical illness myopathy

67. MANAGEMENT Multi-disciplinary input is important in all aspects of the care of patients with GBS both in the acute phase and rehabilitation of patients. Therapies may be classified as being supportive or immunomodulatory .

68. MANAGEMENT cont’d Supportive: - Turning/nursing care/physiotherapy. - Prophylaxis against DVT . - Adequate nutrition. - Prompt treatment of infection, e.g. urinary, respiratory.

69. MANAGEMENT cont’d Appropriate treatment of haemodynamic abnormalities. Respiratory: close monitoring of vital capacity; 15 ml/kg is usually taken as the minimum before IPPV is instituted, together with other features of respiratory failure. Early tracheal intubation may be indicated if bulbar failure coexists. Tracheostomy is often necessary because prolonged respiratory support may be required.

70. MANAGEMENT cont’d Intravenous Immunoglobulin therapy ( IVIg ) is now the specific treatment of choice: 0.4 g/kg/day iv over 3–5 days . Plasma exchange is equally effective as IVIg speeding recovery and is most beneficial if performed within the first 2wks daily for 4 to 5 days.

71. MANAGEMENT cont’d Combining plasma exchange and IVIg has no additional benefit. Corticosteroids have no role. CSF filtration has been used occasionally in severe, resistant cases. Contraindications to IVIg include: previous anaphylactic reaction to IVIg and IgA deficiency

72. MANAGEMENT cont’d Contraindications to plasma exchange include: Coagulopathy , overwhelming sepsis, haemodynamic instability and shock. Side effects vary from mild to more severe and include nausea, vomiting, diarrhoea , fevers, coagulopathy , immunosuppression , hypocalcaemia which relates to the use of citrate and line related complications.

73. ANAESTHETIC CONSIDERATIONS Suxamethonium is absolutely contraindicated in patients with GBS. There have been a number of case reports of severe hyperkalaemia , life threatening arrhythmias, and cardiac arrest after its administration.

74. ANAESTHETIC CONSIDERATIONS Autonomic dysfunction occurs in around 70% of patients and may be life-threatening. Monitoring of the ECG, blood pressure and fluid balance is advisable. Common arrhythmia seen is sinus tachycardia Atrial and ventricular tachyarrhythmias , Prolonged QT interval Atrioventricular blocks Asystole

75. ANAESTHETIC CONSIDERATIONS Severe BP fluctuations. Treatment with Vasoactive drugs should be with care as effect may be exaggerated. Intubated patients with autonomic dysfunction may develop instability after tracheal suction

76. ANAESTHETIC CONSIDERATIONS Feeding is encouraged even in sedated and mechanically ventilated patient Enteral or parenteral feeding. Dietician input is useful to ensure adequate calorific, micronutrient, fluid and electrolyte intake . Prokinetic agents such as metoclopramide or erythromycin if paralytic ileus is present.

77. ANAESTHETIC CONSIDERATIONS Neuropathic pain is common and occurs in around 50% of patients. Non- opioid analgesics ( paracetamol , NSAIDs) in combination with opioid analgesia should be instituted initially, but may provide inadequate pain relief. Adjunctive treatments such as anticonvulsants (e.g. gabapentin or carbemazepine ), and tricyclic antidepressants may be effective.

78. ANAESTHETIC CONSIDERATIONS Venous thromboembolism prophylaxis Immobile patients are at very high risk of deep vein thrombosis and pulmonary emboli. Low molecular weight heparin in combination with either pneumatic compression devices or Anti-embolism stockings, are recommended until patients are able to walk unaided.

79. PROGNOSIS Most patients with GBS recover fully Therapy may take many months of intensive. 15 % of patients suffer persistent disability. 10 % are unable to walk unaided at one year . Recurrence in 2–5% of cases .

80. The mortality from GBS ranges from 2–12%. Common causes of death include Venous thromboembolism , Pneumonias, Arrhythmias and Complications related to dysautonomia .

81. CONCLUSION Asthma, Renal Failure, Stroke and GBS are pathologies that the anaesthetist may encounter from time to time in the practice of anaesthesia A good understanding of these pathologies and how it affects anaesthesia is necessary for effective perioperative and ICU management of these patients.

82. Thanks for listening

83. References Guillain - Barré Syndrome: Indications for Plasma Exchange. Transfusion Science 1999; 20 : 53–61. A McGrogan , GC Madle , HE Seaman, C S deVries . Epidemiology of Guillain-Barré Syndrome Worldwide. A systematic literature review. Neuroepidemiology 2009; 32 : 150-63 V Govoni , E Granieri . Epidemiology of the Guillain - Barré Syndrome. Current Opinion in Neurology 2001; 14 : 605-13. R Hughes, D Cornblath . Guillain - Barré Syndrome. The Lancet 2005; 366 : 1653-66

84. References Brian R. walker, Nichi R colledge et al (2014)- Davidson Principles and practice of medicine. 22 nd edition. Karen J. Marcdante , Robert N. kliegman (2015) – Nelson essentials of Paediatric . 7 th Edition.