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Tuberculosis in the Intensive Care Unit

Tuberculosis in the Intensive Care Unit. Dr Arthur Chun-Wing LAU Associate Consultant, Dept of Intensive Care and Honorary Assoc Cons, Division of Respiratory & Critical Care Medicine, Dept of Medicine Pamela Youde Nethersole Eastern Hospital Hong Kong.

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Tuberculosis in the Intensive Care Unit

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  1. Tuberculosis in the Intensive Care Unit Dr Arthur Chun-Wing LAU Associate Consultant, Dept of Intensive Care and Honorary Assoc Cons, Division of Respiratory & Critical Care Medicine, Dept of Medicine Pamela Youde Nethersole Eastern Hospital Hong Kong

  2. Aims: to present some specific issues of pulmonary TB patients admitted to the Intensive Unit (ICU) about • Presentation • Diagnosis • Treatment • Outcomes

  3. Robert Koch, Germany, 1843 - 1910 Ref: TB & Chest Service, Dept of Health, The Govt of HKSAR

  4. Top among the “Asian Dragons” “We’re being held here like prisoners, but we didn’t commit a crime,” Siyasanga Lukas, 20, who has been here since 2006, said before escaping last week. “I’ve seen people die and die and die. The only discharge you get from this place is to the mortuary.” South Africa Mar 2008 TB can become untreatable. 4.6 per 100,000 population in the United States: Centers for Disease Control and Prevention. Trends in Tuberculosis Incidence --- United States, 2006. MMWR, Mar 23, 2007, 56(11); 245 – 250)

  5. PYNEH Data CHARACTERISTICS AND OUTCOMES OF PULMONARY TUBERCULOSIS PATIENTS REQUIRING INTENSIVE CARE IN HONG KONG Henry Chun-Yu CHEUNG Arthur Chun-Wing Lau Alfred Yan-Fat CHAN Hoi-Ping SHUM Grace Sin-Man LAM Natalie Yuk-Wah LEUNG Angus Ho-Yin LO Loletta Kit-Ying SO Wing-Wa YAN Loretta Yin-Chun YAM Abstract presented at APSR 2007

  6. Inclusion • Time: June 1996 to May 2007 • Place: Medical High Dependency Unit (MHDU) or Intensive Care Unit (ICU) • Person: • hospital discharge diagnosis of “Tuberculosis”, (ICD-9CM coding 010.1 to 010.8 and 011-018) • microbiologically or histologically confirmed active tuberculosis infection of the lungs with or without extrapulmonary involvement diagnosed during the admission episode or subsequently after death

  7. Results and Discussion

  8. Results • 50 patients in final analysis • 44 new TB cases, and • 6 old cases • one under active anti-TB drug treatment • one with treated tuberculosis • one with history of untreated tuberculosis • one extensively drug-resistant tuberculosis (XDR-TB) deemed untreatable already before admission

  9. Demographics

  10. Comorbidities * includes asthma, chronic obstructive pulmonary disease, bronchiectasis, interstitial lung disease ** on prednisolone-equivalent ≥ 7.5 mg per day for ≥ 1 month

  11. Presentation - can be acute or not distinguishable from simple pneumonia.

  12. Difference from overseas study • No documented case of HIV/AIDS in our patients • Total 277 cases were reported from 1996 to 2005 in Hong Kong • Percentage of TB cases with HIV infection • 0.68% in 2005 in Hong Kong • c/w > 12% in the US • Hong Kong TB-HIV Registry. TB & Chest Service and Special Preventive Programme (SPP), Public Health Services Branch, Department of Health (DH) • Centers for Disease Control and Prevention. Trends in Tuberculosis Incidence --- United States, 2006. MMWR, Mar 23, 2007, 56(11); 245 – 250

  13. Review of TB & ICU studies Including ex-alcoholics Less alcoholism and HIV in oriental series

  14. Possible emergencies involving pulmonary TB • Respiratory failure • Shock • Massive hemoptysis • Concomitant involvement of other systems

  15. Predominant reasons for ICU admission Deceased vs survived p-value 0.516 PYNEH 2007

  16. Diagnosis • Issues: • Often depends on CXR and smear positivity • Clotting derangement: invasive dx often not possible • Desaturation: bronchoscopy may not possible • AFB Culture: too “late” for acute illness

  17. Diagnosis • Sputum (41 patients) • S+: 29 (58%) – c/w sputum positive for AFB smear in ~37% on presentation (HK chest service, 2004) • S- C+: 12 (24%) • Bronchoalveolar lavage (14 patients) • S+: 7 (50%) • S- C+: 6 (12%) • For the 18 sputum S- cases, only 2 cases were BAL S+ • Transbronchial lung bx • Done in 8 patients, 7 +ve (2 diagnosed solely by TBLB) • Others: • TB bone marrow: 5 • TB meningitis: 1 • TB urinary tract: 4 • TB GI tract: 3 • Sputum +ve for bacteria at hospital admission: 1 • Blood culture +ve at hospital admission: 3 (6%) Sharma SK, et al. 2006

  18. Noninvasive and rapid dx of TB Quick and definite dx can be difficult

  19. Management

  20. TB with sputum smear + and R pleural effusion

  21. Blood test results

  22. Medications

  23. Options of anti-tuberculosis medications limited

  24. Worst drug regimen in the 1st 7 days of ICU admission

  25. Percentage within the subgroups of survivors or deceased receiving different anti-TB medication regimens PYNEH

  26. Renal replacement therapy and anti-TB drugs Different duration? Different blood flow? Different combination: Hemodiafiltration?

  27. A lot of limitations in Rx. Yew WW. Clinica Chimica Acta 2001

  28. Events • * include all forms of acute hemodialysis or hemofiltration

  29. Paradoxical reactions during tuberculosis treatment in patients with and without HIV co-infection Paradoxical rxn more common in disseminated TB. Breen RAM. Thorax 2004

  30. Supplemental steroid- ? Benefits the “sickest” patients • TB + adrenal failure : 8 – 55% (Barnes DJ et al 1986, Ellis ME 1986) • Rifampicin: Precipitated adrenal crisis in pre-existing adrenal failure (Elansary 1983, Kawai 1985, Sandr 1988); inducer of hepatic microsomal enzymes (increases steroid metabolism and clearance) • Suppression of possible paradoxical reaction during immune reconstitution • as treatment for TB-related ARDS (Tominaga 2000) or ARDS in general (Meduri 1998) • general benefit for septic shock in relative adrenal insufficiency (Annane 2002) Documented benefits of steroid only in known adrenal failure + rifampicin.

  31. Steroid for septic shock in general(High dose studies, e.g. methylprednisolone 30mg/kg) • The effects of high-dose corticosteroids in patients with septic shock. A prospective, controlled study • N Engl J Med 1984 Nov 1;311(18):1137-43. • A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. • N Engl J Med 1987 Sep 10;317(11):653-8. • Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. The Veterans Administration Systemic Sepsis Cooperative Study Group. • N Engl J Med 1987 Sep 10;317(11):659-65 • None of the trials found a mortality benefit • Only 1 trial noted decreased duration to shock resolution associated with the administration of glucocorticoid

  32. N = 300, RCT randomized within 8 hrs of the onset of septic shock To receive placebo or Hydrocortisone (50mg Q6H) + fludrocortisone (50mcg QD) Classify the patients to have adequate adrenal reserve/ inadequate reserve by ACTH stimulation test (i.e. Short synacthen test - SST) Low dose studies JAMA 2002 Aug 21;288(7):862-71.

  33. Results • Results • In the inadequate adrenal reserve group, hydrocortisone administration was associated with decreased • 28 days mortality (63% vs 53%, p = 0.02) • ICU mortality • Hospital mortality • More vasopressor withdrawal within 28 days • No difference in mortality in adequate adrenal reserve group

  34. N= 499, RCT • All with septic shock and remained hypotensive or required treatment with vasopressors for at least 1 hour after adequate fluid resuscitation • Study group • Hydrocortisone 50mg Q6H for 5 days, then tapered during a 6 days period

  35. NEJM 2004 Mortality benefits of steroid for septic shock not established. Issues in dx of absolute and relative adrenal insufficiency?? Loriaux L. NEJM 2004

  36. TB & ARDS Mortality of ARDS in general: 30 – 60% Sharma SK. Int J Tuberc Lung Ds 2006.

  37. Regimen: Methylprednisolone iv 2mg/PBW in kg stat then 0.5mg/kg q6h for 14D then 0.5 mg/kg q12h for 7D then taper • Design: N=180, RCT, ARDS of at least 7 days’ duration • Conclusion: These results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology. In addition, starting methylprednisolone therapy more than two weeks after the onset of ARDS may increase the risk of death. No benefit of steroid for ARDS.

  38. Outcomes and disease severity at ICU admission • References: • Knaus W, Draper E, Wagner D, et al: APACHE II: A severity of disease classification system. Crit Care Med 1985; 13:818-829 • Vincent J, Moreno R, Takala J, et al: The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. Intensive Care Med 1996; 22:707-710 • Murray JF, Matthay MA, Lucy JM, Flick MR. An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis. 1988; 138: 720-723.

  39. Ryu YJ. Respirology 2006.

  40. Outcomes Standardized Mortality Ratio (SMR) = Actual number of deaths / ∑ROD SMR > 1 represents a higher than expected mortality rate Ref: Knaus W, Draper E, Wagner D, et al: APACHE II: A severity of disease classification system. Crit Care Med 1985; 13:818-829

  41. Overall SMR in HK ICU’s (4Q06 and 1Q07) Error bars represents 95% CI Reference: COC (ICU), Hospital Authority. APACHE Project. The 1st Report. Oct 2007.

  42. Outcomes poorer than predicted by APACHE II score. Review of SMR in TB with acute resp failure APACHE II score underestimated the actual number of deaths in tuberculosis patients requiring intensive care (Lee 2003, Ryu 2007)

  43. Factors associated with mortality • Overall • APACHE II score • degree of lung injury (reflected by LIS) • Multiorgan failure: organ dysfunction (reflected by SOFA score • Blood tests • low hemoglobin level • low albumin • low PaO2/FiO2 ratio • Clinical events • requirement for mechanical ventilation • acute renal failure with or without requirement for acute dialysis • shock (reflected by requirement for inotrope infusion) • nosocomial pneumonia • Hyponatremia • Treatment delay for ≥ 30 days • Chronic pancreatitits • Sepsis • Nosocomial pneumonia • Acute renal failure Ref: Mehta 1996, Zahar 2001, Lee 2003, Erbes 2006, Ryu 2007, PYNEH 2007

  44. Infection Control: for airborne droplet nuclei (<5um) • Patient • Early diagnosis • Prompt isolation • Early initiation of chemotherapy • Personal • N95 N-95 personal respirators • N: for use against non-oil-based aerosols such as aqueous aerosols including secretions or fluids bearing tubercle bacilli • 95% efficiency at excluding particles of 0.3 microns • Environment • room with monitored negative air pressure • CDC recommendation: 6 or more air changes per hour in isolation facilities, remove 90% of airborne contaminants in 23 minutes • UV germicidal irradiation: UV-C wavelengths 100 – 290 nm (254 – 260 nm is germicidal), UVGI active ventilation devices • High-Efficiency Filtration: high-efficiency particulate aerosol (HEPA) filtration units - remove 99.97% of particles down to 0.3 microns in diameter, require more powerful ventilation units to pull/push air through them

  45. Conclusion: TB in ICU • TB can present acutely or not distinguishable from bacterial pneumonia • Less alcoholism & HIV in oriental series • Quick and definite dx sometimes can be difficult • A lot of limitations during treatment • Paradoxical reaction more common • Benefits of steroid in know adrenal failure only • Survival benefit of steroid for septic shock in general not established • Survival benefit of steroid for ARDS in general not established • Outcomes poorer than predicted by APACHE II scores

  46. Implications for future • More collaboration between TB experts and critical care physicians in research, esp. • Rapid and noninvasive diagnosis required • Drugs and other adjuctive treatment

  47. Thank you! Acknowledgment Dr Henry Chun-Yu CHEUNG Dr Natalie Y. W. LEUNG Dr Hoi-Ping SHUM Dr Grace Sin-Man LAM Dr Alfred Yan-Fat CHAN Dr Angus H. Y. LO Dr Loletta K. Y. SO Dr Wing-Wa YAN Dr Loretta Yin-Chun YAM & All PYNEH Resp team and ICU team members

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