Scientific Letter
Hyponatremia in COPD: A Little Known Complication
La hiponatremia en la EPOC, una complicación poco conocida
Javier Miguel Martín Guerra
, Miguel Martín Asenjo, Luis Ángel Sánchez Muñoz, Carlos Jesús Dueñas Gutiérrez
Corresponding author
Servicio de Medicina Interna, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
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Diseases that may present with SIADH include lung infections (pneumonia, pulmonary abscess, tuberculosis, aspergillosis), asthma, COPD, lung tumors, cystic fibrosis, and acute respiratory failure.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> Hypoxia is associated with ADH secretion,<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a> but hypercapnia is more commonly associated with this phenomenon.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Both in stable COPD and during exacerbations, hyponatremia, due to its prevalence, its impact on prognosis, and varying etiologies (which can coexist), is a challenge for the clinician and requires appropriate follow-up and treatment. Although the relationship between COPD and SIADH is often mentioned in the literature, we did not find any references to hyponatremia caused by SIADH in COPD (Medline and Pubmed searches, keywords: SIADH and COPD).</p><p id="par0025" class="elsevierStylePara elsevierViewall">For this reason, we believe that our report of a patient with SIADH due to COPD is of interest and provides a good illustration of certain aspects of the differential diagnosis and treatment.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Our patient was an 84-year-old man, active smoker, with a history of benign prostate hypertrophy and exacerbator phenotype COPD with emphysema, and very severe obstruction (FEV1 27%), receiving treatment with siladosin, omeprazole, and glycopyrronium/indacaterol. He presented with intense dyspnea and cough with greenish expectoration. The only finding of note on physical examination was the presence of disperse rhonchi in both hemithoraxes and the absence of edema or signs of fluid overload. O<span class="elsevierStyleInf">2</span> saturation was 89% with home oxygen therapy at 2<span class="elsevierStyleHsp" style=""></span>l per minute (lpm). Clinical laboratory tests showed microcytic anemia (hemoglobin 10<span class="elsevierStyleHsp" style=""></span>g/dl), plasma sodium 111<span class="elsevierStyleHsp" style=""></span>mEq/l (normal value [NV]: 135–155<span class="elsevierStyleHsp" style=""></span>mEq/l), plasma osmolarity 229<span class="elsevierStyleHsp" style=""></span>mOsm/l (NV: 280–300), PCR 64<span class="elsevierStyleHsp" style=""></span>mg/l (NV: 0–5), normal creatinine levels, urinary sodium 76<span class="elsevierStyleHsp" style=""></span>mEq/l (NV: 54–150), and urine osmolality 273<span class="elsevierStyleHsp" style=""></span>mOsml/l (NV: 30–1400); arterial blood gases with O<span class="elsevierStyleInf">2</span> at 2<span class="elsevierStyleHsp" style=""></span>lpm: pH 7.35, pCO<span class="elsevierStyleInf">2</span> 54.8<span class="elsevierStyleHsp" style=""></span>mmHg, pO<span class="elsevierStyleInf">2</span> 57<span class="elsevierStyleHsp" style=""></span>mmHg, and HCO<span class="elsevierStyleInf">3</span> 29.7. Chest X-ray showed clamping of both costophrenic angles, signs of air trapping, and a slight increase in density reflecting scarring in the right lower lobe, present in previous X-rays. Given the suspected respiratory infection and the patient's history of COPD with very severe obstruction, treatment began with oxygen therapy, aerosol therapy, and beta-lactam and macrolide antibiotics. For the hyponatremia, water restriction at less than 500<span class="elsevierStyleHsp" style=""></span>cc/day was prescribed (according the Furst formula<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a>), plus diet with salt, furosemide, and hypertonic saline. The patient's sodium levels in blood did not normalize after completion of COPD treatment (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), and no changes were observed on physical examination. Repeat clinical laboratory tests showed plasma sodium 124<span class="elsevierStyleHsp" style=""></span>mEq/l, plasma osmolarity 247<span class="elsevierStyleHsp" style=""></span>mOsm/l, urine sodium 62<span class="elsevierStyleHsp" style=""></span>mEq/l, and urinary osmolarity 372<span class="elsevierStyleHsp" style=""></span>mOsm/l, with normal thyroid and adrenal function. After ruling out other possible causes, a diagnosis of SIADH due to an exacerbation of emphysema phenotype COPD was given, and treatment began with tolvaptan 15<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h, leading to normalization of blood sodium in 4 days. The dose was reduced to 7.5<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h, and sodium levels in blood were normal in subsequent visits.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">SIADH is characterized by the sustained release of arginine-vasopressin (ADH) in the absence of the usual stimuli, particularly hyperosmolarity and hypovolemia. Diagnosis is based on hyponatremia, plasma hypoosmolarity, urinary sodium >40<span class="elsevierStyleHsp" style=""></span>mmol/l, and urinary osmolarity >100<span class="elsevierStyleHsp" style=""></span>mOsm/kg, after ruling out processes that involve loss of effective blood volume (heart failure, cirrhosis with ascites, etc.), and normal renal, adrenal, and thyroid function has been confirmed.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Symptoms are non-specific, and can range from nausea, dizziness, general malaise, agitation and confusion to seizure or coma in cases of sudden onset or very low blood sodium levels.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> SIADH is the most common cause of hyponatremia, and its heterogeneous etiology<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a> includes most importantly infections, drugs, tumors<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> (particularly small cell lung carcinoma), COPD, and asthma. Hyponatremia due to SIADH occurs quite frequently in small cell carcinoma, sometimes as a first manifestation,<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">9–11</span></a> and is associated with decreased survival.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Both COPD and small cell lung carcinoma are a cause of SIADH and strongly associated with smoking, so blood sodium must also be monitored in patients with COPD and a heavy accumulated consumption of tobacco.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Treatment of hyponatremia due to SIADH differs, depending on two different clinical scenarios. In acute situations with moderate/severe symptoms (sleepiness, confusion, stupor, respiratory distress), and plasma Na<span class="elsevierStyleSup">+</span> <120<span class="elsevierStyleHsp" style=""></span>mEq/l, treatment should begin with 3% hypertonic saline.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a> The initial infusion rate will be 0.5<span class="elsevierStyleHsp" style=""></span>mg/kg/h or 1–2<span class="elsevierStyleHsp" style=""></span>ml/kg/h, depending on neurological signs.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> Treatment with tolvaptan (a selective vasopressin V2-receptor antagonist) may be considered, depending on progress. When SIADH develops with mild hyponatremia, water restriction and furosemide should be considered, and in patients who are not candidates for these measures or whose clinical symptoms persists, the use of tolvaptan is recommended.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">COPD exacerbation is a cause of SIADH, as demonstrated by Chanela et al.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a> However, in our patient, hyponatremia persisted for almost 10 days after resolution of the infectious COPD exacerbation, and in the follow-up visit the patient continued to require tolvaptan to maintain normal sodium levels. A more typical course in SIADH due to COPD exacerbation would have been transient hyponatremia that normalized after resolution of the exacerbation.</p><p id="par0060" class="elsevierStylePara elsevierViewall">We believe that this case of SIADH associated with a COPD exacerbation illustrates the need to include blood sodium monitoring in the management of these patients, in order to detect and reduce the morbidity and mortality of this fluid-electrolyte imbalance.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a> It is also important to remember that this syndrome can, albeit rarely, be the first manifestation of lung cancer.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Martín Guerra JM, Martín Asenjo M, Sánchez Muñoz LÁ, Dueñas Gutiérrez CJ. La hiponatremia en la EPOC, una complicación poco conocida. Arch Bronconeumol. 2018;54:391–393.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1064 "Ancho" => 1567 "Tamanyo" => 82999 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Course of blood sodium levels during admission.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 55 | 4 | 59 |
| 2024 October | 533 | 61 | 594 |
| 2024 September | 612 | 59 | 671 |
| 2024 August | 560 | 68 | 628 |
| 2024 July | 546 | 50 | 596 |
| 2024 June | 338 | 47 | 385 |
| 2024 May | 462 | 56 | 518 |
| 2024 April | 255 | 42 | 297 |
| 2024 March | 363 | 30 | 393 |
| 2024 February | 394 | 25 | 419 |
| 2023 March | 97 | 2 | 99 |
| 2023 February | 551 | 43 | 594 |
| 2023 January | 498 | 44 | 542 |
| 2022 December | 419 | 47 | 466 |
| 2022 November | 630 | 41 | 671 |
| 2022 October | 665 | 64 | 729 |
| 2022 September | 489 | 61 | 550 |
| 2022 August | 415 | 50 | 465 |
| 2022 July | 403 | 61 | 464 |
| 2022 June | 432 | 71 | 503 |
| 2022 May | 416 | 61 | 477 |
| 2022 April | 571 | 64 | 635 |
| 2022 March | 506 | 73 | 579 |
| 2022 February | 604 | 67 | 671 |
| 2022 January | 530 | 62 | 592 |
| 2021 December | 468 | 70 | 538 |
| 2021 November | 526 | 68 | 594 |
| 2021 October | 618 | 89 | 707 |
| 2021 September | 465 | 78 | 543 |
| 2021 August | 415 | 82 | 497 |
| 2021 July | 455 | 77 | 532 |
| 2021 June | 471 | 157 | 628 |
| 2021 May | 386 | 100 | 486 |
| 2021 April | 1165 | 247 | 1412 |
| 2021 March | 641 | 51 | 692 |
| 2021 February | 467 | 53 | 520 |
| 2021 January | 415 | 36 | 451 |
| 2020 December | 413 | 49 | 462 |
| 2020 November | 450 | 37 | 487 |
| 2020 October | 358 | 39 | 397 |
| 2020 September | 466 | 18 | 484 |
| 2020 August | 387 | 27 | 414 |
| 2020 July | 443 | 29 | 472 |
| 2020 June | 20 | 4 | 24 |
| 2020 March | 297 | 22 | 319 |
| 2020 February | 658 | 34 | 692 |
| 2020 January | 494 | 28 | 522 |
| 2019 December | 489 | 37 | 526 |
| 2019 November | 476 | 34 | 510 |
| 2019 October | 492 | 27 | 519 |
| 2019 September | 553 | 37 | 590 |
| 2019 August | 411 | 46 | 457 |
| 2019 July | 451 | 33 | 484 |
| 2019 June | 500 | 49 | 549 |
| 2019 May | 474 | 41 | 515 |
| 2019 April | 457 | 55 | 512 |
| 2019 March | 373 | 34 | 407 |
| 2019 February | 209 | 30 | 239 |
| 2019 January | 67 | 13 | 80 |
| 2018 December | 2 | 1 | 3 |
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