부적절 항이뇨 증후군의 치료의 기본은 저나트륨 교정입니다.
어떻게 교정할 것인가?
학생 때 보던 해리슨을 버려서 예전 책에는 어떻게 기술되었는지 보고자 2007년 워싱턴 매뉴얼을 살펴보았습니다.
요약하면 이렇습니다.
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1. 저나트륨혈증을 너무 빨리 교정하면 체액 증가가 있으면서 central pontine myelinolysis (CPM)이 발생할 수 있다. 24시간 동안 12 mEq/L 이상을 교정하면 위험이 증가하며 24시간 동안 천천히 교정해서 > 12 mEq/L로 올리는 것이 처음에 아주 빨리 교정해서 이후 몇 시간 동안에는 천천히 교정하는 것보다 더 위험하다. 즉, 초기에 아주 빨리 교정했다가 이후 몇 시간에 걸쳐 속도 조절을 하여 그 결과가 < 12 mEq/L라면 천천히 교정해서 하루 >12 mEq/L 교정한 것보다 덜 위험하다. 하루 교정 강도가 더 중요하다. |
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2. 이와 같은 문제에도 불구하고 obtundation, seizure와 같은 신경학적 징후가 있는 저나트륨혈증의 경우에는 저나트륨혈증의 빠른 교정이 중요하다. 즉, CPM 가능성 때문에 치료를 주저하는 것은 환자들 더 위험한 상황에 두게 되는 것이다. |
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3. 급성 저나트륨혈증의 경우에 24시간 동안에는 10 mEq/L를 넘지 않도록 하고, 48시간 동안에는 < 18 mEq/L가 되게 하라. 만성 저나트륨혈증 환자에서는 증상 유무와 관계 없이 12 mEq/L를 넘지 않도록 하며 5-8 mEq/L/d가 합리적이다. |
최근 책인 Goldman-Cecil, Williams Textbook, UpToDate 내용을 살펴보면,
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증상이 있는 심한 저나트륨혈증이 있는 경우에는 저나트륨혈증을 교정해야 합니다. 수분제한으로 보수적으로 치료하는 것은 적극적으로 치료한 것보다 더 좋지 않은 결과를 초래하였습니다. Correction of hyponatremia is associated with markedly improved neurologic outcomes in patients with severely symptomatic hyponatremia. In a retrospective review of patients who presented with severe neurologic symptoms and serum [Na + ] below 125 mmol/L, prompt therapy with isotonic or hypertonic saline resulted in a correction in the range of 20 mEq/L over several days and neurologic recovery in almost all cases; in contrast, in patients who were treated with fluid restriction alone, there was very little correction over the study period (<5 mmol/L over 72 hours), and the neurologic outcomes were much worse, with most of these patients either dying or entering a persistently vegetative state. Based on this and similar retrospective analyses, prompt therapy to rapidly increase the serum [Na + ] represents the standard of care for treatment of patients presenting with severe symptoms of hyponatremia. 만성 저나트륨혈증은 brain volume regulation 조절 결과로 훨씬 증상이 덜 합니다. 그렇기 때문에 증상이 없는 저나트륨혈증처럼 보이지만 많은 환자들에서 신경학적 증상이 있습니다. 경하거나 좀 더 미묘해서 그렇습니다. 결과적으로 저나트륨혈증과 관련된 어떠한 신경학적 증상이 있는 모든 저나트륨혈증 환자들은 저나트륨혈증의 만성과 관련 없이 치료 대상입니다. 또한 치료를 하지 않으면 저나트륨혈증이 더 악화되어 더 위험해 질 수 있습니다. As discussed earlier, chronic hyponatremia is much less symptomatic as a result of the process of brain volume regulation. Because of this adaptation process, chronic hyponatremia is arguably a condition that clinicians feel less concerned about, which has been reinforced by the common usage of the descriptor asymptomatic hyponatremia for many such patients. However, as discussed, it is clear that many such patients very often have neurologic symptoms, even if milder and more subtle in nature. Consequently, all patients with hyponatremia who manifest any neurologic symptoms that could possibly be related to the hyponatremia should be considered candidates for treatment of the hyponatremia, regardless of the chronicity of the hyponatremia or the level of serum [Na + ]. An additional reason to treat even asymptomatic hyponatremia effectively is to prevent a lowering of the serum [Na + ] to more symptomatic and dangerous levels during treatment of underlying conditions (e.g., increased fluid administration via parenteral nutrition, treatment of heart failure with diuretics). 증상의 소실, 혈청 나트륨 농도가 125 mEq/L, 하루에 10-12 mE/L 이상 교정, 48시간 동안 18 mq/L 이상 교정, ODS 고위험 환자에서 하루 8 mEq/L 이상 교정 시에는 치료를 중단합니다. Active treatment with any therapy should be stopped when the patient’s symptoms are no longer present, a safe serum [Na + ] (usually >125 mmol/L) has been achieved, or the rate of correction has reached maximum limits of 10 to 12 mmol/L within 24 hours, 18 mmol/L within 48 hours, or 8 mmol/L over any 24-hour period in patients at high risk of ODS Williams Textbook of Endocrinology, 14th edition |
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Acute Hyponatremia If hyponatremia is known to be acute (<24 to 48 hours) and is accompanied by severe neurologic symptoms (e.g., seizures or decreased level of consciousness), correction should be rapid—a sodium infusion of 4 to 6 mmol/L in 4 to 6 hours should be sufficient to reverse the most severe neurologic symptoms. The total increase in sodium concentration should not exceed 6 to 12 mmol/L in the first 24 hours or 18 mmol/L within 48 hours. Treatment relies on water restriction, with concentrated saline reserved for symptomatic patients in whom the response to vasopressin antagonists is too slow. Chronic Hyponatremia Symptomatic hyponatremia or sodium concentrations below 125 to 130 mmol/L require specific treatment, but mild degrees of asymptomatic hyponatremia can be tolerated for long periods. In patients who are known to have developed hyponatremia gradually or in whom there is no previous record, the targeted rate of increase in sodium concentration should not exceed 0.5 mmol/L/hour, and the total rise in sodium concentration should not exceed 8 mmol/L in any 24-hour period, even (and especially) if the initial sodium concentration is extremely low (<110 mmol/L), provided the hyponatremia is not accompanied by severe neurologic symptoms. Patients with severe degrees of chronic hyponatremia in the setting of malnutrition, alcoholism, or chronic illness are particularly susceptible to osmotic demyelination. Frequent monitoring of the plasma sodium concentration and osmolality is crucial. If the safe target rate of correction is exceeded, osmotic demyelination can be prevented by slowing the correction rate, returning to a lower plasma sodium concentration by the judicious readministration of hypotonic solutions, or administering vasopressin analogues (see later). Goldman-Cecil Medicine, 26th edition |
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Mild-to-moderate symptoms Initial hypertonic saline therapy using either a continuous infusion or a 50 to 100 mL bolus followed by a continuous infusion to raise the serum sodium by 3 to 4 mEq/L may be justified in the first three to four hours in patients with distressing symptoms (eg, confusion and lethargy). In the calculations described above, 500 mL of hypertonic saline initially raised the serum sodium by 6.5 mEq/L in a 60 kg woman and 4.6 mEq/L in a 70 kg man. Thus, raising the serum sodium by 4 mEq/L in four hours would require approximately 300 mL of hypertonic saline in the woman and 400 mL in the man. These calculations are only estimates and the serum sodium should be measured at two to three hours. The total elevation in serum sodium in the first 24 hours should be no more than 8 mEq/L UpToDate 2020.08.05 |
만성 저나트륨혈증의 하루 교정 한계를 이전 문헌에는 12 mEq/L를 넘지 않도록 하였다면, 최근 문헌들에는 8mEq/L를 넘지 않도록 보수적으로 권고합니다.
치료를 하지 않아서 brain swelling, herniation을 일으키는 것보다 치료를 하는 것이 환자들에게 덜 위험한 것이며, 치료를 너무 적극적으로 하면 ODS가 발생하므로 하루 교정 한도를 ~ 8 mEq/L로 합니다.
* 저나트륨혈증 환자 치료에서 하루 교정해야 할 나트륨을 계산하고 이것에 못 미치게 나트륨을 교정하면 질책을 받던 때가 있었습니다. Maximal limit를 정해 놓고 그 정도에 맞게 교정을 하면 치료를 잘 한 것이고 그렇지 못하면 계산을 잘못해서 치료를 못한 것으로 여겨졌던 때가 있어 적어 봅니다. 같은 체중이어도 사람마다 body fluid가 다른데 어떻게 계산된 결과 대로 되겠습니까?
Ref. UpToDate 2020.08.05
Williams Textbook of Endocrinology, 14th edition
Goldman-Cecil Medicine, 26th edition
