Mixed Acid-Base Disorders, Hydroelectrolyte Imbalance and Lactate Production in Hypercapnic Respiratory Failure: The Role of Noninvasive Ventilation Claudio Terzano 1 , Fabio Di Stefano 1 , Vittoria Conti 1 *, Marta Di Nicola 2 , Gregorino Paone 1 , Angelo Petroianni 1 , Alberto Ricci 1 1 Fondazione Eleonora Lorillard Spencer Cenci, Sapienza University of Rome, Rome, Italy, 2 Laboratory of Biostatistics, Department of Biomedical Science, University ‘‘G. d’Annunzio’’ of Chieti-Pescara, Chieti, Italy Abstract Background: Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with comorbidities and multidrug therapy is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV) when treating hypercapnic respiratory failure. Methods: Sixty-seven consecutive patients who were hospitalized for hypercapnic COPD exacerbation had their clinical condition, respiratory function, blood chemistry, arterial blood gases, blood lactate and volemic state assessed. Heart and respiratory rates, pH, PaO 2 and PaCO 2 and blood lactate were checked at the 1st, 2nd, 6th and 24th hours after starting NIV. Results: Nine patients were transferred to the intensive care unit. NIV was performed in 11/17 (64.7%) mixed respiratory acidosis–metabolic alkalosis, 10/36 (27.8%) respiratory acidosis and 3/5 (60%) mixed respiratory-metabolic acidosis patients (p = 0.026), with durations of 45.169.8, 36.268.9 and 53.364.1 hours, respectively (p = 0.016). The duration of ventilation was associated with higher blood lactate (p,0.001), lower pH (p = 0.016), lower serum sodium (p = 0.014) and lower chloride (p = 0.038). Hyponatremia without hypervolemic hypochloremia occurred in 11 respiratory acidosis patients. Hypovolemic hyponatremia with hypochloremia and hypokalemia occurred in 10 mixed respiratory acidosis–metabolic alkalosis patients, and euvolemic hypochloremia occurred in the other 7 patients with this mixed acid-base disorder. Conclusions: Mixed acid-base and lactate disorders during hypercapnic COPD exacerbations predict the need for and longer duration of NIV. The combination of mixed acid-base disorders and hydro-electrolyte disturbances should be further investigated. Citation: Terzano C, Di Stefano F, Conti V, Di Nicola M, Paone G, et al. (2012) Mixed Acid-Base Disorders, Hydroelectrolyte Imbalance and Lactate Production in Hypercapnic Respiratory Failure: The Role of Noninvasive Ventilation. PLoS ONE 7(4): e35245. doi:10.1371/journal.pone.0035245 Editor: Mauricio Rojas, University of Pittsburgh, United States of America Received October 9, 2011; Accepted March 12, 2012; Published April 23, 2012 Copyright: ß 2012 Terzano et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The authors have no support or funding to report. Competing Interests: The authors have declared that no competing interests exist. * E-mail: vittoria_conti@hotmail.com Introduction Hypercapnic respiratory failure is a complex condition associated with the malfunction of various organs and systems crucial for many physiological processes, leading to an acid-base imbalance. Carbon dioxide (CO 2 ) is not the only independent variable that may cause alterations in acid-base status. Total serum protein, albumin in particular, plays an important role, as does the strong ion difference (SID), that is the difference between the strong positive ions in the plasma (sodium (Na + ), potassium (K + ), calcium (Ca 2+ ), and magnesium (Mg 2+ )) and the strong negative ions (chloride (Cl 2 ) and lactate (Lac 2 )): SID~ Na z zK z zCa 2z zMg 2z  à { Cl { zLac { ½ : ð1Þ At pH 7.4, 37uC and a partial carbon dioxide tension of 40 mmHg, the ideal value of SID is 42 mmol/L . An increased SID causes alkalosis; a reduced SID causes acidosis. Altering SID means altering the water dissociation equilibrium. This provides more/less H + for electroneutrality, with a change in [H + ], and so a change in pH. Acid-base and electrolyte balance are part of the same picture because, for a given increase in CO 2 , the only way to minimize the resulting acidemia is to produce compensatory metabolic alkalosis, which is obtained through complex urinary ion excretion mechanisms [2]. Thus, fluid homeostasis depends on the correct relationship between lung and kidney activities because they regulate most of the CO 2 and hydrogen (H + ) concentrations in the extracellular volume, whose total solutes consist almost entirely of Na + , Cl 2 and bicarbonate ions (HCO 32 ). In hypoxic and hypercapnic COPD patients, fluid homeostasis is disturbed, with avid retention of sodium and water [3]. The increase in sodium retention by the kidneys during COPD, and PLoS ONE | www.plosone.org 1 April 2012 | Volume 7 | Issue 4 | e35245