Symptomatic Hyponatremia with Hypoxia Is a Medical Emergency
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View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector http://www.kidney-international.org commentary © 2006 International Society of Nephrology see original article on page 1319 rection of serum sodium concentration Symptomatic hyponatremia with and one who died in the absence of any therapeutic interventions to correct her hypoxia is a medical emergency hyponatremia.4 We now understand that much heterogeneity exists among 1 JP Kokko patients with hyponatremia. Some patients will tolerate a relatively con- Patients presenting with the combined finding of severe symptomatic servative approach, whereas others are at hyponatremia and hypoxia have such high mortality rates that they high mortality risk if their symptomatic should be admitted to an intensive care unit and intubated sooner rather hyponatremia is not corrected rapidly. than later. Without delay, these patients need rapid correction of their Many clinicians have made important serum sodium by 8–10 mequiv. per liter and an increase in their partial contributions to this area; perhaps the studies of Ayus, Arieff , and their col- pressure of arterial oxygen to values above 70 mm Hg. leagues are most direct in pointing out Kidney International (2006) 69, 1291–1293. doi:10.1038/sj.ki.5000252 that the patients at highest risk are the ones with the combined fi nding of symp- tomatic hyponatremia and hypoxia.5–7 It Hyponatremia is a frequent electro- sodium concentration was rapidly cor- should be noted that neither the early lyte abnormality among hospitalized rected from 106.3 to 151.8 mequiv. per clinical observations (before 1992) nor patients. In general, it is classified as liter with the use of hypertonic saline. animal studies addressed the possible acute (less than 48 hours in duration) Similar fi ndings of CPM could not be adverse eff ect of hypoxia on outcomes in versus chronic (more than 48 hours in duplicated by Ayus and colleagues2 symptomatic hyponatremia. To under- duration). It is further characterized as when hyponatremia in their rats was stand why hypoxia is a severe comorbid asymptomatic versus symptomatic (agi- increased by 14–25 mequiv. per liter in factor requires a paragraph on brain cell tation, depressed sensorium, grand mal the fi rst 24 hours, that is, not overcor- volume regulation. seizures). Th is simple, albeit superfi cial, rected rapidly to values above normal. Essentially all cells have the capacity classifi cation is important, as it suggests However, physicians are taught not to to regulate their volume. Th e regulation an appropriate therapeutic approach to a harm their patients, and therefore the of cell volume by the brain cells is criti- given patient. Before the 1980s, many of fear of CPM caused such concern that cally important because acute swelling us who were in clinical practice felt that many physicians became afraid to of the brain cells is limited by the fi xed if we saw a laboratory abnormality, it treat symptomatic hyponatremia, even skull, which will cause pressure necrosis should be corrected rapidly. However, it when they recognized that failure to and/or transtentorial herniation. On the was becoming evident that patients with treat was associated with high mortal- other hand, rapid shrinkage in response symptomatic hyponatremia had an unac- ity rates. Th is conservative view against to an external hypertonic gradient can ceptably high mortality rate whether rapid correction of plasma sodium con- cause adverse cellular events including they were left untreated or whether centration was supported by a careful putative disruption of controlled mye- their sodium concentration was rapidly paper by Sterns,3 in which he observed lin synthesis and degradation. Cell vol- corrected. In a classic paper published among his 62 patients that the previ- ume regulation has been studied more in 1981,1 Kleinschmidt-DeMasters and ously noted high mortality rates with extensively when cells are challenged to Norenberg reported an experimental symptomatic hyponatremia were not protect their volume by exposure to a study in rats that was based on their pre- nearly as high as some of the literature hypo-osmotic external milieu than when vious clinical experience showing that then suggested if the low sodium con- they are exposed to a hypertonic envi- central pontine myelinolysis (CPM) is an centration was corrected at low versus ronment such as a rapid rise in plasma ‘iatrogenic disorder’ caused by rapid cor- high rates. Nevertheless, many patients sodium concentration. When cells are rection of hyponatremia. Although their were still dying when symptomatic exposed to a hypo-osmotic environment conclusion that CPM is an iatrogenic hyponatremia was left untreated and (hyponatremia), they swell unless there disorder was correct, it should be noted allowed to correct with spontaneous is an appropriate outward movement that in their experiments the rats’ serum water diureses. Th is led Kidney Interna- of intracellular solutes. Th is is largely tional to devote a “Nephrology Forum” accomplished by activation of leak path- 1Department of Medicine, Emory University School to “Treating hyponatremia: damned if way channels that initially allow outward of Medicine, Atlanta, Georgia, USA we do and damned if we don’t,” in which diff usion of potassium and chloride and Correspondence: JP Kokko, Emory University School of Medicine, 69 Jesse Hill, Jr. Drive, Suite 205, Berl described being presented with two later allow outward diff usion of organic Atlanta, Georgia 30303, USA. patients with hyponatremia, one who solutes. It is beyond the scope of this E-mail: [email protected] developed CPM following rapid cor- Commentary to review these processes; Kidney International (2006) 69 1291 commentary the interested reader is directed to an in those patients who had their serum remaining diff erence in sodium concen- excellent review of this topic by Pas- sodium concentration corrected at rates tration. I advise not to raise the sodium antes-Morales and colleagues.8 Many below 0.55 mequiv. per liter per hour.10 concentration much over 120 mequiv. biologic regulatory processes are not So what is the clinician to conclude per liter in the fi rst 24 hours and then symmetric. This certainly is the case from all these studies when faced with to correct the remaining defi cit at a rate when cellular processes are activated to a severely hyponatremic patient? Th ere that improves serum concentration protect the volume of cells exposed to is no question that many asymptomatic each 24 hours by 50% of the desired a hypertonic milieu that would tend to patients with normal arterial oxygen fi nal sodium concentration. One of the shrink them. Under these circumstances saturation and severe hyponatremia do practical issues I have faced in the emer- the cell must gain net solute against elec- well without rapid correction of their gency room is the unavailability of 3% trochemical gradients and requires much serum sodium concentration; how- NaCl or an enormous delay in getting it more oxygen-dependent energy than is ever, it is now clear that symptomatic there. Given the lack of any evidence to provided by activation of outward leak hyponatremic patients, especially if the contrary, I have recommended push- pathway channels. Th us it is evident that they are female and hypoxic with arte- ing an ampoule of NaHCO3 in these conditions in which oxygen availability rial partial pressure of oxygen below circumstances (an ampoule usually con- is limited are just those conditions in 70 mm Hg, should receive rapid cor- tains either 44 or 50 mequiv. NaHCO3); which cells are unable to have suffi cient rection of their sodium concentration this will allow time to get the 3% NaCl inward transport rates of solutes to pro- to safe levels. Th us, to use Berl’s color- delivered. I feel that the weight of the tect against cell shrinkage. ful choice of words,4 one must conclude literature supports initiation of the cor- As they report in this issue,9 Ayus, that we are damned if we don’t, or at rection of the osmolality as soon as it is Armstrong, and Arieff have carried least the patient is. feasible. I make these same therapeutic out an important series of studies that Now comes the important question of recommendations also for patients who extends many of their previous obser- how to administer the sodium, and at have symptomatic hyponatremia but vations. Th ey show in three groups of what rate it will decrease the very high normal oxygenation. Although these rodents that hypoxia interferes with mortality associated with the combi- patients do not have the same high risk normal brain cell volume adaptation in nation of hypoxia and hyponatremia. of mortality as hypoxic patients, they response to hyponatremic challenges. In The literature supports the view that nevertheless are at increased risk of hyponatremic animals, hypoxia aggra- the rate of correction should be at least dying. If, on the other hand, the patient vated cerebral edema, decreased cerebral 0.55 mequiv. per liter per hour. It is is hypoxic for any reason (central res- perfusion, and led to histologic abnor- impractical in an acute hospital setting piratory depression secondary to brain malities in the cerebellum, thalamus, to try to calculate accurately how much edema, pneumonia, or any other cause), reticular formation, and basal ganglia.9 sodium to give. First, it is diffi cult to or if the patient’s arterial oxygen begins Many of these histologic fi ndings are obtain accurate patient weights, good to drop during the course of treatment, similar to those that have been noted estimates of total body water, and esti- then he or she should be hospitalized previously to occur when hyponatremia mates of bone weight (approximately in an intensive care unit and intubated has been rapidly corrected.