Adjuvant acetazolamide in patients with acute severe exacerbation of COPD and noninvasive ventilation

The aim of the study was to investigate an efficacy of short-term treatment with acetazolamide (ACET) in patients with acute exacerbation of COPD (AECOPD) and noninvasive ventilation (NIV). Methods. This was a prospective case-control study. The study involved 20 patients. Inclusion criteria were as follows: AECOPD; pH > 7.33; PaCO2 > 48 mmHg; HCO₃– > 26 mmol/L; and treatment with NIV. Clinical characteristics, Charlson comorbidity index, APACHE II score, arterial blood gases, and serum electrolytes were recorded before inclusion. Patients were defined as cases when they had received ACET (500 mg per day) for 3 days; they were compared to a matched control group who did not receive ACET. Clinical parameters, arterial blood gases, serum electrolytes, potential adverse effects, and length of hospital stay were monitored daily. Results. No significant differences in baseline characteristics, comorbidities, or concomitant drugs used were found between the groups. Mean duration of hospital stay was significantly shorter in the ACET group (16.2 ± 8.4 days vs 19.1 ± 2.8 days; p = 0.023). An iIntra-group analysis showed a significant improvement in clinical and arterial blood gas parameters in both groups already in the first day of the treatment. In the ACET group, systolic blood pressure (SBP), respiratory rate (RR), and SpO2 significantly improved at day 4 (112.5 ± 4.9 mmHg vs 125 ± 7.1 mmHg (p = 0.001); 15.2 ± 1.1 min^–1 vs 17.1 ± 0.9 min^–1 (p = 0.001) and 94.7 ± 1.1% vs 92.3 ± 0.8% (p = 0.0001), respectively). There was a significant decrease in PaCO2, pH and HCO₃– at day 3 (48 ± 3.8 mmHg vs 52.4 ± 5.3 mmHg (p = 0.0288); 7.374 ± 0.4 vs 7.502 ± 0.17 (p = 0.0015) and 26.4 ± 2.8 mmol/L vs 36.9 ± 4.1 mmol/L (p = 0.00001), respectively) and day 4 (44 ± 2.4 mmHg vs 48.4 ± 4.6 mmHg (p = 0.0115); 7.387 ± 0.02 vs 7.480 ± 0.02 (p = 0.00001) and 24.2 ± 2.1 mmol/L vs 35.6 ± 3.0 mmol/L (p = 0.00001), respectively) in the ACET group. No adverse events were recorded in both groups. Conclusions. ACET adjuvant to NIV appears to be effective and could prevent post-NIV alkalosis occurrence and could reduce the length of hospital stay in patients with AECOPD and mixed metabolic disorders (respiratory acidosis and metabolic alkalosis).

1. Lopez A.D., Shibuya K., Rao C. et al. Chronic obstructive pulmonary disease: current burden and future projections. Eur. Respir. J. 2006; 27 (2): 397–412. DOI: 10.1183/09031936.06.00025805.

2. Gunen H., Hacievliyagil S.S., Kosar F. et al. Factors affecting survival of hospitalised patients with COPD. Eur. Respir. J. 2005; 26 (2): 234–241. DOI: 10.1183/09031936.05.00024804.

3. Sene M.G., Wagner D.P., Wagner R.P. et al. Hospital and 1-year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease. JAMA. 1995; 274 (23): 1852–1857. DOI: 10.1001/jama.1995.03530230038027.

4. Rivera-Fernandez R., Navarrete-Navarro P., Fernandez-Mondejar E. et al. Six-year mortality and quality of life in critically ill patients with chronic obstructive pulmonary disease. Crit. Care Med. 2006; 34 (9): 2317–2324. DOI: 10.1097/01.CCM.0000233859.01815.38.

5. Melissa J.B., Erin M.T. Respiratory stimulant use in chronic obstructive pulmonary disease. Ann. Pharmacother. 2004; 38 (10): 1722–1725. DOI: 10.1345/aph.1E039.

6. Avdeev S.N. Noninvasive ventilation in patients with chronic obstructive pulmonary disease in a hospital and at home. Pul’monologiya. 2017; 27 (2): 232–249. DOI: 10.18093/0869-0189-2017-27-2-232-249 (in Russian).

7. Heming N., Urien S., Fulda V. et al. Population pharmacodynamic modeling and simulation of the respiratory effect of acetazolamide in decompensated COPD patients. PLoS ONE. 2014; 9 (1): e86313. DOI: 10.1371/journal.pone.0086313.

8. Krintel J.J., Haxholdt O.S., Berthelsen P. et al. Carbon dioxide elimination after acetazolamide in patients with chronic obstructive pulmonary disease and metabolic alkalosis. Acta Anaesthesiol. Scand. 1983; 27 (3): 252–254.

9. Berthelsen P. Cardiovascular performance and oxyhemoglobin dissociation after acetazolamide in metabolic alkalosis. Intensive Care Med. 1982; 8 (6): 269–274. DOI: 10.1007/BF01716736.

10. Bruno C.M., Valenti M. Acid-base disorders in patients with chronic obstructive pulmonary disease: a pathophysiological review. J. Biomed. Biotechnol. 2012; 2012: 915150. DOI: 10.1155/2012/915150.

11. Nigel R.W., Vivek K. Metabolic alkalosis in the critically ill. Crit. Rev. Clin. Lab. Sci. 2008; 36 (5): 497–510. DOI: 10.1080/10408369991239286.

12. Jones P., Greenstone M. Carbonic anhydrase inhibitors for hypercapnic ventilatory failure in chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. 2001; (1): CD002881. DOI: 10.1002/14651858.CD002881.

13. Fontana V., Santinelli S., Internullo M. et al. Effect of acetazolamide on post-NIV metabolic alkalosis in acute exacerbated COPD patients. Eur. Rev. Med. Pharmacol. Sci. 2016; 20 (1): 37–43. Available at: https://www.europeanreview.org/article/10126

14. Charlson M.E., Pompei P., Ales K.L. et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J. Chronic. Dis. 1987; 40 (5): 373–383.

15. Knaus W.A., Draper E.A., Wagner D.P., et al. APACHE II: a severity of disease classification system. Crit. Care Med. 1985; 13 (10): 818–829.

16. GOLD 2017. Global Strategy for the Diagnosis, Management and Prevention of COPD. Available at: http://goldcopd.org/gold-2017-global-strategy-diagnosis-management-prevention-copd/ [Accessed 20 March, 2018].

17. Saini V., Saini N., Kaur J. et al. Acid-base status in chronic obstructive pulmonary disease patients. Indian J. Clin. Biochem. 1993; 8 (1): 36–38. DOI: 10.1007/BF02867721.

18. Guerin C., Nesme P., Leray V. et al. Quantitative analysis of acid-base disorders in patients with chronic respiratory failure in stable or unstable respiratory condition. Respir. Care. 2010; 55 (11): 1453–1463.

19. DuBose Jr.T.D. Clinical approach to patients with acid-base disorders. Med. Clin. North Am. 1983; 67 (4): 799–813. DOI: 10.1016/S0025-7125(16)31178-6.

20. Fall P.J. A stepwise approach to acid-base disorders. Practical patient evaluation for metabolic acidosis and other conditions. Postgrad. Med. 2000; 107 (3): 249–263. DOI: 10.3810/pgm.2000.03.957.

21. Sood P., Paul G., Puri S. Interpretation of arterial blood gas. Indian J. Crit. Care Med. 2010; 14 (2): 57–64. DOI: 10.4103/0972-5229.68215.

22. Pastorekova S., Parkkila S., Pastorek J. et al. Carbonic anhydrases: current state of the art, therapeutic applications, and future prospects. J. Enzyme Inhib. Med. Chem. 2004; 19 (3): 199–229. DOI: 10.1080/14756360410001689540.

23. Swenson E.R. Carbonic anhydrase inhibitors and ventilation: a complex interplay of stimulation and suppression. Eur. Respir. J. 1998; 12 (6): 1242–1247.

24. Rialp Cervera G., Raurich Puigdevall J.M., Morán Chorro I. et al. Effects of early administration of acetazolamide on the duration of mechanical ventilation in patients with chronic obstructive pulmonary disease or obesity hypoventilation syndrome with metabolic alkalosis. A randomized trial. Pulm. Pharmacol. Ther. 2017; 44: 30–37. DOI: 10.1016/j.pupt.2017.03.002.

25. Faisy C., Meziani F., Planquette B. et al. Effect of acetazolamide vs placebo on duration of invasive mechanical ventilation among patients with chronic obstructive pulmonary disease: a randomized clinical trial. JAMA. 2016; 315 (5): 480-488. DOI: 10.1001/jama.2016.0019.

26. Bahloul M., Chaari A., Tounsi A. et al. Impact of acetazolamide use in severe exacerbation of chronic obstructive pulmonary disease requiring invasive mechanical ventilation. Int. J. Crit. Illn. Inj. Sci. 2015; 5 (1): 3–8. DOI: 10.4103/2229-5151.152296.

27. Faisy C., Mokline A., Sanchez O. et al. Effectiveness of acetazolamide for reversal of metabolic alkalosis in weaning COPD patients from mechanical ventilation. Intensive Care Med. 2010; 36 (5): 859–863. DOI: 10.1007/s00134-010-1795-7.

28. Bahloul M., Ammar R., Bouattour A. et al. Effects of early administration of acetazolamide on the duration of mechanical ventilation in patients with chronic obstructive pulmonary disease: still far from the truth? J. Thorac. Dis. 2017; 9 (6): 1393–1395. DOI: 10.21037/jtd.2017.05.41.