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 Table of Contents  
Year : 2020  |  Volume : 7  |  Issue : 1  |  Page : 68-70

Hydrocortisone and ulinastatin for miliary tuberculosis-induced septic shock and adult respiratory distress syndrome in the intensive care unit

Department of Critical Care Medicine, B & C Medical College Teaching Hospital and Research Center, Birtamod, Jhapa, Nepal

Date of Submission22-Apr-2019
Date of Decision20-Oct-2019
Date of Acceptance19-Nov-2019
Date of Web Publication19-Jun-2020

Correspondence Address:
Niraj Kumar Keyal
Department of Critical Care Medicine, B and C Medical College Teaching Hospital and Research Centre, Birtamode, Jhapa
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/cjhr.cjhr_45_19

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Hydrocortisone and ulinastatin are anti-inflammatory agent. We hereby report the case of a patient of sputum-positive miliary pulmonary tuberculosis that developed adult respiratory distress syndrome with septic shock. The patient was treated with anti-tubercular drugs, antibiotics, inotropes, vasopressors, hydrocortisone, and ulinastatin. From this, we want to emphasize that hydrocortisone and ulinastatin can be one of the treatment options in refractory shock patient not responding to conventional treatment but requires randomized controlled trial to confirm the effectiveness of this combination.

Keywords: Hydrocortisone, miliary tuberculosis, septic shock, ulinastatin

How to cite this article:
Keyal NK, Nakarmi M. Hydrocortisone and ulinastatin for miliary tuberculosis-induced septic shock and adult respiratory distress syndrome in the intensive care unit. CHRISMED J Health Res 2020;7:68-70

How to cite this URL:
Keyal NK, Nakarmi M. Hydrocortisone and ulinastatin for miliary tuberculosis-induced septic shock and adult respiratory distress syndrome in the intensive care unit. CHRISMED J Health Res [serial online] 2020 [cited 2021 Feb 26];7:68-70. Available from: https://www.cjhr.org/text.asp?2020/7/1/68/286887

  Introduction Top

Miliary tuberculosis (TB) that requires mechanical ventilation has mortality of 69%.[1] It is due to coexistence of different comorbid conditions and the intensive care unit (ICU)-related complications. The incidence of immune reconstitution inflammatory syndrome in human immunodeficiency virus (HIV)-negative patients is probably 2%–23% and in HIV-positive patients is 32%–36%.[2] This is the first case report that has used hydrocortisone and ulinastatin in combination for the treatment of miliary TB-induced septic shock and respiratory failure.

  Case Report Top

A 20-year-old female of weight 40 kg, without any significant past medical and surgical history presented to emergency department with a history of fever, significant weight loss for 1 month, and shortness of breath for 7 days. At presentation in emergency department, her Glasgow Coma Scale was 15/15. Her pulse rate was 130 beats/min, blood pressure was 80/40 mmHg, respiratory rate was 42 breaths/min, oxygen saturation was 80% on room air, and temperature of 100°F. On auscultation, chest bilateral crepitations were present. Cardiovascular and per abdominal examinations were normal. Arterial blood gas analysis showed Type 1 respiratory failure with metabolic and lactic acidosis. She was immediately resuscitated and intubated.

Her blood investigation profiles were total leukocyte count (TLC) - 14,000/mm3, platelets - 100,000/mm3, hemoglobin (Hb) - 9 gm/dl, urea - 48 mg/dl, creatinine - 1.1 mg/dl, sodium and potassium were normal. Liver function test was normal. Chest X-ray showed bilateral miliary pattern [Figure 1]. She was diagnosed with miliary TB with secondary bacterial infection with septic shock. The tracheal aspirate was sent for gram staining, acid-fast bacilli (AFB) staining, and culture.
Figure 1: Chest X-ray showing miliary patten

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The patient was started on meropenem, doxycycline, vasopressors, hydrocortisone, isoniazid, rifampicin, ethambutol, pyrazinamide, fluids, and ventilator support. She was adequately resuscitated with fluid and noradrenaline was started at 0.1 mg/kg/min. Her blood pressure was still around 80/40 mm Hg. Noradrenaline dose was increased; however, no increase in blood pressure was noted. Vasopressin and adrenaline were also started. Hydrocortisone was also started at dose of 50 mg six hourly. Blood pressure was still around 85/40 mm Hg. After 6 hour of resuscitation with fluid and vasopressors there was no increase in blood pressure. Ulinastatin was started at dose of 2 million units in 100 ml of normal saline two times a day. Blood pressure was 100/60 after 6 h of starting ulinastatin. Dose of the vasopressors was decreased from the second hospital day and was subsequently stopped on day 4 of admission. Tracheal aspirate for AFB was positive and Gram-staining and culture showed Klebsiella pneumoniae sensitive to meropenem, piperacillin-tazobactam, and doxycycline. She developed new infiltrate on chest X-ray [Figure 2] that developed suspicion of ventilator-associated pneumonia, but there was no increase in TLC, secretion, and requirement of vasopressors. Therefore, the diagnosis of immune reconstitution inflammatory syndrome was made, and no change in medication was done. Tracheostomy was done on the seventh hospital day after multiple failure of spontaneous breathing trials. Improvement in chest X-ray was seen from the 9th day of hospital admission.
Figure 2: Chest X-ray showing new infiltrate

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The patient was shifted out of the ICU after 14 days in the medicine ward. Her stay at the ward was uneventful and was discharged on 28 days of hospital stay.

  Discussion Top

Patient of miliary TB that require ICU admission has a high rate of comorbidities such as deranged liver function, chronic renal failure, chronic pancreatitis and HIV, multiorgan failure, and ICU-related complications such as nosocomial pneumonia, pneumothorax, and adult respiratory distress syndrome (ARDS).[3] Patient with miliary TB has mortality of 69%[4] than ARDS of any other causes requiring mechanical ventilation.

The role of corticosteroid in miliary TB with septic shock and ARDS is not well known. However, the probable mechanism by which corticosteroid act is by permitting anti-TB drug to penetrate into granulomas by disrupting granuloma formation and inhibiting release and activities of lymphokines and cytokines.

There is limited randomized control trial and case–control study that has shown that ulinastatin can reduce mortality, improves sequential organ failure assessment, and improves patient outcome in sepsis.[5],[6],[7],[8],[9] Japanese guidelines for sepsis provides very weak recommendation and insufficient evidence for use of ulinastatin in sepsis.[10] Studies have shown that ulinastatin has shown to improve mortality, oxygenation, and length of stay in acute respiratory distress and acute lung injury patients.[11]

Sepsis is a dysregulated inflammatory response of the body. Although the exact mechanism of ulinastatin is not clear, it attenuates the inflammatory response by acting at multiple sites[5] of septic response and decreases the production of inflammatory cytokines, enhances anti-inflammatory cytokines and prevents progression to multi-organ dysfunction syndrome.

Miliary TB with ARDS is severe sepsis and ulinastatin has shown to have a better outcome in sepsis. Therefore, it was used in our patient.

Ulinastatin and hydrocortisone in combination can play a role in the management of miliary TB-induced septic shock and ARDS immune reconstitution syndrome (IRS).

  Conclusion Top

Ulinastatin and hydrocortisone in combination can play a role in the management of military TB-induced septic shock, ARDS, and IRS. The understanding of its pathophysiology though is still unclear and needs further investigation.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Penner C, Roberts D, Kunimoto D, Manfreda J, Long R. Tuberculosis as a primary cause of respiratory failure requiring mechanical ventilation. Am J Respir Crit Care Med 1995;151:867-72.  Back to cited text no. 1
Cheng SL, Wang HC, Yang PC. Paradoxical response during anti-tuberculosis treatment in HIV-negative patients with pulmonary tuberculosis. Int J Tuberc Lung Dis 2007;11:1290-5.  Back to cited text no. 2
Erbes R, Oettel K, Raffenberg M, Mauch H, Schmidt-Ioanas M, Lode H, et al. Characteristics and outcome of patients with active pulmonary tuberculosis requiring intensive care. Eur Respir J 2006;27:1223-8.  Back to cited text no. 3
Hagan G, Nathani N. Clinical review: Tuberculosis on the intensive care unit. Crit Care 2013;17:240.  Back to cited text no. 4
Karnad DR, Bhadade R, Verma PK, Moulick ND, Daga MK, Chafekar ND, et al. Intravenous administration of ulinastatin (human urinary trypsin inhibitor) in severe sepsis: A multicenter randomized controlled study. Intensive Care Med 2014;40:830-8.  Back to cited text no. 5
Bashir F, Rather MA, Saleem B, Hamid A. A prospective randomized study using ulinastatin for the treatment of patient with severe sepsis. J Evol Med Dent Sci 2014;3:12241-6.  Back to cited text no. 6
Moon SW, Lee SW, Hong YS, Park DW, Jang IJ, Yoon YH, et al. The effect of urine trypsin inhibitor on the outcomes of severe sepsis and septic shock patients. J Korean Soc Emerg Med 2009;20:80-5.  Back to cited text no. 7
Linder A, Russell JA. An exciting candidate therapy for sepsis: Ulinastatin, a urinary protease inhibitor. Intensive Care Med 2014;40:1164-7.  Back to cited text no. 8
Xu Q, Yan Q, Chen S. Ulinastatin is effective in reducing mortality for critically ill patients with sepsis: A causal mediation analysis. Sci Rep 2018;8:14360.  Back to cited text no. 9
Oda S, Aibiki M, Ikeda T, Imaizumi H, Endo S, Ochiai R, et al. The Japanese guidelines for the management of sepsis. J Intensive Care 2014;2:55.  Back to cited text no. 10
Leng YX, Yang SG, Song YH, Zhu X, Yao GQ. Ulinastatin for acute lung injury and acute respiratory distress syndrome: A systematic review and meta-analysis. World J Crit Care Med 2014;3:34-41.  Back to cited text no. 11


  [Figure 1], [Figure 2]


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