Rheumatology in the ICU Eduardo Santiago M.D 05/16/2012 Airways Problems in Rheumatologic Disorders Synovial joints: CA and CT Laryngeal Involvement in RA • Cricoarytenoid joint arthritis. • Long standing RA but also in newly diagnosed patients. • Prevalence: 40%-88%. • Acute or chronic process with slow progression of airflow obstruction. • Fiberoptic endoscopy is most sensitive: flexible rhino laryngoscopy. Laryngeal Involvement in RA • Intubation can lead to mucosal edema, compromise of airway caliber and stridor and airway obstruction post extubation. • Risk Factors: Laxity of joint capsule and large synovial folds. Treatment • Severe airway obstruction: Secure airways in OR, Surgeon support, awake fiber optic intubation. • Helium/oxygen mixture improve airflow. • Acute: systemic glucocorticoids, local periarticular steroids can improve CA function. • Chronic: surgery: lateralizing one of the vocal folds, arytenoidectomy vs. tracheostomy. Atlantoaxial instability • C1-C2 instability causing brain stem or spinal cord compression. • Prevalence: 25%. • Independent of disease duration or patient’s age but is most common in patients with severe peripheral joint involvement. • Ligamentous laxity induced by inflammation. Atlantoaxial instability • High risk of neurologic injury for cervical manipulation in RA patients. • Avoiding hyperextension and maintaining cervical spine in midline w/o extension. • Awake fiberoptic intubation is recommended. Wegener Granulomatosis • • • • Major upper airway life threatening complication. Subglottic stenosis prevalence: 20%. Acute inflammation or scar formation. Corticosteroids, immunosuppression, intralesional steroids. • Tracheostomy. • Intratracheal dilation injection ( intralesional long acting corticosteroid injection and mechanical dialtion). Relapsing Polycondritis • Recurrent episodes of inflammation of cartilaginous and connective tissue structures. • Type II collagenous antibodies. • Respiratory involvement associated with high mortality. • Compromise of glottic, supra or subglottic, trachea and first and second order bronchi. Relapsing Polycondritis • Encroachment of airway by inflammatory swelling. • Formation of mass of fibrous tissue. • Dissolution of tracheobronchial with subsequent collapse during respiration. • Corticosteroids ( MTP ) and immunosuppression, plasmapheresis. • Surgery: tracheostomy in cases of subglottic involvement. • Endotracheal prostheses and stents. Pulmonary Renal Syndromes in ICU Anti GBM Disease • Acute Pulmonary hemorrhage, oliguric acute renal failure and anti GBM antibodies. • 1 case per 2 million white people. Anti GBM Disease • Type IV collagen. • Alpha chains: alpha1 to 6. • Alpha 3: lung, kidney, seminiferous duct, choroids plexus, optic lens and inner ear. • Autoimmune response to Alpha-3 NC-domain: Anti GBM Syndrome. • Genetic susceptibility: HL DR15, HLA DR 4 Pathogenesis Anti GBM Disease • Anti GBM antibodies ( anti alpha-3, Type IV antibodies). • Double positive: Anti GBM and ANCA p or ANCA c. • 20%-30% of Anti GBM are double positive, >75% ANCA p positive. • 8-10% ANCA vasculitis are double positive. Anti GBM Disease • Hemoptysis: severity is variable. • Alveolar hemorrhage: infectious and non infectious, cigarrete smoking. • HLM in alveolar and small airways, interstitial infiltrates, lymphocytic infiltration in alveolar septae and peri broncovascular interstitium. • DAD: proteinaceous infiltrates and hyaline membranes. Anti GBM Disease • Crescent formation and GBM destruction. • Epithelial crescents in more than 50% of the glomeruli is a poor prognostic factor. Therapy • Pulse methylprednisolone, cyclophosphamide and plasmapheresis. • MP: 30mg/kg, on alternate days for 3 doses. Follow by oral prednisone for 12 months. • CP: 2mg/kg, daily dose, should be reduced by 0.5mg/kg every 3 months. • Plasma exchange: 4 liter plasma exchanges daily or on alternate days. Small Vessel Vasculitis • Wegener's: c-ANCA or PR3 ANCA (65%) or pANCA or MPO ANCA (20%). • Microscopic Polyangiitis and CCS: p-ANCA or MPO ANCA. Treatment • Accurate determination of disease severety. • Remission induction phase. • Maintenance phase. Treatment • Induction therapy: MP IV 7mg/kg on 3 consecutive days, then prednisone 1mg/kg per day for 1 month, alternate date schedule and the dose is reduced by 10mg/week on the second month. • IV Cyclophosphamide: 0.5mg/kg at monthly intervals ( less side effects than oral) • Oral Cyclophosphamide: 2mg/kg per day. Treatment • Rituximab (anti CD 20 chimeric monoclonal antibody). • Infliximab. • Plasma exchange or plasmapheresis, twice daily for 7 days in patients with significant pulmonary hemorrhage and renal failure. • IVIG in severe pulmonary hemorrhage. Catastrophic Antiphospholipid Syndrome • APLS: Thrombosis, thrombocytopenia, recurrent fetal loss and increased APL antibodies. • CAPS: subset characterize with fulminant clinical course with widespread vascular occlusion involving at least three organs in association with ACL or LA. • Thrombocytopenia and MAHA. Pathology and Pathophysiology • Non inflammatory, thrombotic microangiopathy of small vessels resulting in MOF. • APL: immunoglobulins that bind plasma proteins or phospholipid micro particles. • Activation of platelets, monocytes, tumor cells or endothelial cells leading to pro coagulant state. Role of APL antibodies • Tissue ischemia and necrosis leading to SIRS. • SIRS= altered hemostasis, increased coagulation and microvascular fibrin deposition. Catastrophic Antiphospholipid Syndrome • Prior history of APS in 50% to 70%. • Precipitating factors are found in 22%. • Infections, trauma, surgical procedures, tissue biopsies, pregnancy and post fetal demise, malignancy, withdrawal from anticoagulation. Catastrophic Antiphospholipid Syndrome • Diffuse injury to the capillary endothelial and epithelial cells resulting in ALI and ARDS. • Microvascular thrombi causing endothelial damage, neutrophil influx and cytokines release. • Alveolar hemorrhage . Catastrophic Antiphospholipid Syndrome • Valvular vegetations. • Coronary artery occlusion with cardiac failure and circulatory collapse. • Thrombus formation within the cardiac chambers. Catastrophic Antiphospholipid Syndrome • Renal thrombotic microangiopathy of the glomerular capillaries and small renal arteries. Treatment • Anticoagulation and r/o infection. • Steroids, plasmapheresis, IVIG. • Plasmaphresis: removal of B2GPI, cytokines and mediators that promote coagulation. SLE SLE • Infections is the most common form of pulmonary involvement. • Lupus Pneumonitis. • Alveolar Hemorrhage. • Acute Reversible Hypoxemia. • Shrinking Lung Syndrome. • Drug Reaction. Acute Lupus Pneumonitis • • • • • Exclusion diagnosis. Clinical diagnosis. Dyspnea, cough, fever and hemoptysis. R/O infection. Incidence: 0.9-12%. Initial presentation or in patients who have been already diagnosed with SLE. • Mortality: 50% Acute Lupus Pneumonitis • Inflammation and tissue injury, no vasculitis: alveolitis, alveolar necrosis, alveolar hemorrhage, edema, interstitial pneumonitis, hyaline membranes, capillary thrombosis, deposition of complement and immunoglobulins. Acute Lupus Pneumonitis • High dose corticosteroids: 1-2 mg/day. • Cyclophosphamide, Plasmapheresis. DAH • Mortality 40%-90%. • 2% of SLE patients. • Young woman with new or establish diagnosis of SLE. • Cough, dyspnea, fever, hemoptysis, fall in hematocrit (70%-100%) and pulmonary infiltrates. • Elevated ANA and low complement levels. • Active Nephritis. DAH • BAL: Increasingly or persistently bloody returns. • Mononuclear and polymorphonuclear cell infiltrates, hyaline membranes, alveolar necrosis, edema, microvascular thrombosis, hemosiderin laden macrophages and capillaritis. DAH • High dose corticosteroids ( prednisone 1-3 mg/kg/day or MTP 1g/day for 3 days followed by prednisone 60mg/day). • Adjunctive immunosuppressive ( Cyclophosphamide 500-1000mg/m2/day every 4 weeks) and plasmapheresis ( three to four sessions) in critically ill or non responders. • Broad spectrum antibiotics. • In patients on MV, antibiotics were continued until extubation. Drug Reaction • Cellular interstitial pneumonia: azathioprine, mycophenolate mofetil. • Chronic eosinophilic pneumonia: NSAIDS. • Early onset pneumonitis or upper lobe predominance fibrosis and bilateral pleural thickening: Cyclophosphamide. • MTX induced lung injury. Shrinking Lung Syndrome • Dyspnea, respiratory muscle dysfunction, small lung volume, elevated hemi diaphragms, basilar atelectasis. • Respiratory muscle weakness, including diaphragmatic dysfunction. • Steroids. Acute Reversible Hypoxemia • Active SLE and acute onset of hypoxemia with normal radiologic imaging studies. • Endothelial cell and complement-activated neutrophil aggregation within pulmonary capillaries (Pulmonary leuko-aggregation). • Elevated A-a gradient, reduced VC and DLCO. • Elevated complement degradation products. • Steroids. Neuropsychiatric Manifestations • • • • CVA Transverse Myelitis Seizures Aseptic Meningitis CVA • RR for stroke: 8. • 5%-20%. • Association with APL antibodies, anti neuronal antibodies, and emboli from cardiac valvular lesions. Transverse Myelitis • Infrequent manifestation. 1%-2%. • Early manifestation or within 5 years of diagnosis. • Vasculitis or arterial thrombosis associated with APL antibodies. • CSF: elevated proteins, pleocytosis, low glucose (<30mg/dl) • MRI: Cord edema. • Prednisone, Cyclophosphamide and Plasmapheresis. Seizures • Common manifestation. • Grand mal seizures are most common. • Multifactorial: anti neuronal antibodies, focal ischemia, infarcts caused by vasculitis or APL antibodies, embolic phenomenon and hemorrhage. Aseptic Meningitis • Headache, meningeal signs and CSF pleocytosis (<200-300 cells, lymphocytes). • Respond to corticosteroids. • Rule out infectious process, NSAIDS or Azathioprine induced aseptic meningitis. Renal Failure • • • • • Drugs: NSAIDs Hypovolemia Sepsis Previous renal disease. Lupus Nephritis: urinary sediment: proteinuria, casts, RBC. • Low complement levels and elevation of anti DNA antibody. SLE/Renal Failure • Before to start aggressive immunosuppression, considerer degree of disease reversibility. • Disease reversibility: Renal biopsy?. Scleroderma • Limited cutaneous sclerosis (CREST): Raynaud phenomenon and skin thickening in face and distal extremities. • PAH. • Diffuse systemic sclerosis: aggressive course, constitutional symptoms, widespread skin thickening, gastrointestinal involvement, pulmonary fibrosis or renal disease. • • • • PAH Acute Aspiration Alveolar Hemorrhage Renal Crisis PAH • Prevalence of PAH is 10-15%. • CREST: isolated phenomenon, absence of pulmonary fibrosis. • Diffuse Scleroderma: advanced pulmonary fibrosis. • PAH symptoms can predate SSc manifestations. • More prevalent in patients with limited cutaneous sclerosis. PAH • Autoimmune process causing damage of vascular endothelium. • Transforming Growth Factor Beta and fibroblast proliferation. • Infiltration of mononuclear cells, Th2 lymphocytes. • High prevalence of anti endothelial cell antibodies (AECA). • IgM AECA has been associated with increase production of endotelin 1. • Decreased NO and Prostacyclin. • Increased Thromboxane and endotelin 1. Right Ventricular Failure • • • • • R/O other causes of RVF: Infectious process PE Ischemic cardiomyopathy Pericardial tamponade Right Ventricular Failure • • • • Oxygen Diuretics Vasodilators Inotropes Right Ventricular Failure • Inhale NO: less risk for systemic hypotension with significant decrease in PVR, mPAP, RVEDP and increases CO. • PGE1: systemic hypotension, mainly in patients with poor vasoreactivity, low CO or high RAP. Right Ventricular Failure • Dobutamine,amrinone,milrinone, dopexamine: inotropic vasodilators. • NE rise SBP, does not significantly rise PVR and excellent inotrope. • Pulmonary vasodilators + systemic vasoconstricting inotropes • Atrial septostomy? Pulmonary Renal Syndrome • Rare complication associated with mortality. • Exclusion diagnosis: DAH + ARF. • More than 80% of patients has normal BP vs. hypertensive crises in SSc renal crisis. • Associated with MAHA and thrombocytopenia. • Segmental necrotizing crescentic glomerulonephritis. • Plasma renin activity. • Poor response to therapy. Hypertensive Renal Crisis • • • • • • Acute malignant hypertension. Diffuse cutaneous disease. High dose corticosteroids. High renin states. Large doses of ACEI. ARB, CCB, prostacyclin, ERA in refractory cases. Pathogenesis • Endothelial cell injury, intimal proliferation with luminal narrowing, decreased renal perfusion, increased renin production, malignant hypertension and RF. • ET-1 Treatment • ACEi • HD Bibliography Bibliography • Alveolar Hemorrhage in SLE: Presentation and Management. Chest 2000;118;1083-1090. • Pulmonary and Thrombotic Manifestations of SLE. Chest 2008;133;271-280. • Pulmonary Renal Syndromes in the ICU. Crit Care Clin.2002 (18):881-895. • CAPS. Crit Care Clin.2002(18):805-817.