Gb syndrome : ICU management

The advent of plasma exchange and intravenous immunoglobulins has dramatically improved the prognosis of patients with GBS. Despite this fact, mortality and morbidity rates remain unacceptably high. Until better therapies are developed, the appropriate utilization of immune-modulating therapy and careful attention to supportive care issues will help to minimize these unfavorable outcomes

1. GB SYNDROME ICU MANAGEMENT Presenter: Dr. Ravi Kumar Moderator: Dr. Aruna Bharti

2. Introduction Guillain-Barre syndrome (GBS) is a demyelinating disorder of the peripheral nervous system, which is monophasic (single peak) with spontaneous remission. Acute Fulminant Demyelinating Inflammatory Polyradiculoneuropathy

3. Guillain-Barre and Strohl 1916 acute areflexic paralysis followed by recovery

4. Epidemiology Population based studies suggest a crude average annual incidence of rates from 0.4 to 1.7/100,000 population. Incidence is higher in males than females as well as in older (age > 60 years) compared with younger people (age < 18 years). The occurrence rate is higher for whites than for blacks.

5. Etiology Post infectious One to three weeks After an acute GI infection Compylobactor jejuni Other Agents HHV(EBV, CMV) Mycoplasma Pneumoniae Recent immunization - Swine influenza vaccine, Older rabies vaccine Lymphoma, HIV + ve , SLE

6. Pathogenesis An autoimmune basis. All GBS results from immune responses to non self antigens(infectious agents, vaccines) that misdirect to host nerve tissue through a resemblance of epitope(molecular mimicry). Neural targets are gangliosides. Anti gangliosides ab- GM1(20-50% cases of C. jejuni ) Anti GQ1ab - >90% MFS

7. GBS has been subdivided into the clinical variants – Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP) Acute Motor Axonal Neuropathy (AMAN) Acute Motor Sensory Axonal Neuropathy (AMSAN).

8. AIDP (Acute Inflammatory Demyelinating Polyradiculoneuropathy ) Adults>children Rapid recovery Anti GM1 ab ( 50%) Demyelinating First attack on schwan cell surface Wide spread myelin damage Variable sec axonal damage

9. AMAN (Acute Motor Axonal Neuropathy) Children, young adults Axonal First attack on node of ranvier Macrophage infiltration Axonal damage is variable

10. Miller fischer variant Adult, children Anti GQ1 b ab > 90% Pupillary paralysis Only 5 % GBS

11. Clinical features MOTOR SYSTEM Rapidly evolving areflexic motor paralysis with or without sensory disturbance Ascending type of paralysis Typically starts in proximal legs 10% will 1 st develop weakness in face or arms severe resp muscle weakness in 10-30% pts oropharyngeal weakness in ~ 50%

12. DEEP TENDON REFLEXES Attenuate or disappear in a few days after onset CRANIAL NERVES Facial diparesis – 50% affected individuals Ophthalmoplegia – Miller Fischer variant Pupillary paralysis Optic atrophy

13. SENSORY SYSTEM Myelinated fibres severely affected Proprioception is more affected than pain & temperature BLADDER Only in severe cases, transiently If bladder dysfunction is a prominent features and comes early in the course, think other than GBS – Spinal Cord Disease.

14. PAIN Deep aching pain may be present Dysesthetic pain in extremities Self limiting usually Respond to analgesics

15. AUTONOMIC INVOLVEMENT Common Seen even in mild cases Wide fluctuation in blood pressure Postural hypotension Cardiac dysrrythmias Can be fatal All require monitoring 30% require ventilatory support

16. Diagnosis The diagnosis is based on - Clinical presentation (progressive symmetric limb weakness following an acute infectious illness) Results of nerve conduction studies (slowing of nerve conduction due to demyelination) Cerebrospinal fluid analysis (elevated protein content in 80%)

17. CSF ANALYSIS Raised CSF protein (100-1000mg/dl) Without accompanied by pleocytosis Albuminocytological dissociation present Slow nerve conduction velocity prolonged or absent F waves Prolonged or absent F waves are pathognomonic and reflect demyelination at level of nerve roots ELECTROMYOGRAPHY

18. Treatment The treatment of Guillain-Barré syndrome mostly involves supportive care. Initiate as soon as possible 2 weeks after the first motor symptoms- immunotherapy is no longer effective plasmapheresis or intravenous immunoglobulin G are equally effective in producing short-term improvement.

19. Immunoglobulin G infusion (0.4 g/kg/day for 5 days) Neutralize autoantibodies or cytokines, saturate macrophage Fc receptors, or inhibit complement activation. Plasmapheresis 40-50 ml/kg four times a week up to 2 weeks Nonselectively removes immunoglobulins, complement, and cytokines, all of which may play a role in the pathogenesis of GBS. Immunoglobulin G is often preferred because it is easiest to administer

20. Glucocorticoids are not effective in GBS Meta-analysis of relevant studies shown no advantage of IV methylprednisolone & suggested less improvement in patients treated with oral corticosteroids. [Hughes RAC, Swan AV, Raphae¨l JC, Annane D, van Koningsveld R, van Doorn PA. Immunotherapy for GuillainBarre ´ syndrome: a systematic review. Brain. 2007;130(9): 2245-2257.]

21. Severe cases INTENSIVE CARE UNIT -labile dysautonomia -forced vital capacity of less than 20 mL/kg -severe bulbar palsy -Any patients exhibiting clinical signs of respiratory compromise [ Walgaard C, Lingsma HF, Ruts L, Drenthen J, van Koningsveld R, Garssen MJ, et al. Prediction of respiratory insufficiency in Guillain-Barré syndrome. Ann Neurol. 2010 Jun. 67(6):781-7.] [Hughes RA, Rees JH. Clinical and epidemiologic features of Guillain-Barré syndrome. J Infect Dis. 1997 Dec. 176 Suppl 2:S92-8.]

22. Monitor Resp status closely (follow VC ), up to 30% may req ventilatory support The most sensitive measure of respiratory muscle strength is the maximum inspiratory pressure ( Pimax ) A Pimax <30 cm H2O is evidence of severe respiratory muscle weakness If VC has fallen below 15 mL/Kg or Pimax – 25cm H 2 O – intubation [ Wijdicks EFM, Borel CO. Respiratory management in acute neurologic illness. Neurology. 1998;50(1):11-20.]

23. Respiratory Consequences of Neuromuscular Weakness

24. Drug-induced neuromuscular blockade is sometimes needed to manage ventilator-dependent patients who are agitated and difficult to ventilate. Hypostatic pneumonia : Anti-microbial therapy, nebulization, ventilation Venous thromboembolism : LMWH & thromboguards used to prevent DVT and consequent pulmonary thromboembolism

25. Dysautonomia Autonomic dysfunction occurs to some degree in 65% of patients with GBS. Manifestations includes brady- or tachy-arrhythmias, episodic hypertension, orthostatic hypotension, abnormal hemodynamic responses to vasoactive medications, gastrointestinal dysfunction, and sweating abnormalities.

26. Patients with autonomic complications are managed in ICU with continuous cardiac and blood pressor monitoring. If fluctuations are severe enough to cause end-organ damage, quickly titratable, short-acting medications are recommended to avoid hypotension. Cessation of enteral feeding, gastric decompression, promotility agents, reduced opiate medications, and parental nutrition may be needed to overcome gastrointestinal autonomic dysfunctions.

27. To minimize infection risks, intermittent catheterization is preferred over indwelling urinary catheters Malnutrition Patients with GBS are at high risk for inadequate nutrition throughout the course of their illness. Progressive bulbar dysfunction or adynamic ileus can limit or eliminate oral intake. nutritional support should begin as quickly as possible by appropriate means ( eg , modified diet, nasogastric tube, or parenteral nutrition).

28. IMMUNOMODULATION Immunomodulatory treatment in GBS has been used to hasten recovery. Intravenous immunoglobulin (IVIG) and plasma exchange have proved equally effective

29. Other Immobility Complications Careful body positioning, appropriate bracing, pressure point padding, and frequent position changes are all warranted. Patients with incomplete eye closure from facial weakness are also at risk for exposure keratitis. Good corneal hygiene with artificial tears, lubricants & careful lid-taping is essential

30. Psychiatric Complications This dramatic loss of independence & prolonged hospitalization may produces several psychiatric complications. Anxiety occurs in 82% of patients, with moderate or severe depression occurring in two thirds of patients. Selective serotonin reuptake inhibitors (SSRIs) and anxiolytics are often helpful [Weiss H, Rastan V, Mu¨llges W, Wagner RF, Toyka KV. Psychotic symptoms and emotional distress in patients with Guillain-Barre´ syndrome. Eur Neurol. 2002;47(2):74-78.]

31. Thank you..