臨床上如何選擇輸液/點滴(how to pick the optimal fluid for patient)

點滴如何補充？

當一個點滴打入體內後，這些液體會跑去哪？細胞內液還是細胞外液（組織或血管中）？

一、先釐清滲透壓（osmolarity）和張力（tonicity）的差別？

• 滲透壓 (osmolality)指的是溶液中溶質或顆粒濃度，指液體中有多少物質。
• 張力（tonicity）指能有效抓住水分在某個空間的能力，主要影響張力的是「不能跨越細胞膜的物質」，他們才具有張力。
• 例如：

氯(Cl)可提供張力，能把液體留在細胞外液(extracellular)。

Urea (BUN)提供無效的osmole，因為它可以自由地diffuse 到任何液體空間，無法有效的製造滲透壓差來影響水分的去處。

• 因此，公式如下：

Osmolarity = solute/(solute+solvent)  

Osmolality = solute/solvent (290~310mOsm/L)  

Tonicity = effective osmolality 

Plasma Osmolality = 2*(Na) + (Glucose/18) + (BUN/2.8) 

Plasma tonicity = 2*(Na) + (Glucose/18) 

二、身體的體液組成：

• 細胞內液(ICF)佔2/3
• 細胞外液(ECF)佔1/3
• 血漿5%
• 組織間液15%

因此，血管中液體佔總體液的1/12 (1/3*1/4=1/12)

例如：以70公斤的人，血管內的水分約3.5公升。

正常情況下，ICF和ECF滲透壓相等。

三、點滴分類：

• Crystalloids: solutions of small molecules in water (e.g. sodium chloride, Hartmann’s, Lactated Ringers, dextrose)

Isotonic fluids: e.g. Normal Saline, Lactated Ringers

Hypotonic Fluids: Water, Dextrose

• Colloids: solutions of larger organic molecules (e.g. albumin, Gelofusine)

四、打入的點滴會跑去體內的哪個部位：

• Isotonic fluids (e.g. 0.9% N/S, Lactated Ringers)

Tonicity 約280 mOsm/kg, 與血漿(plasma)差不多。鈉和氯都是有效的osmoles提供者（有張力），因此可維持打入的nacl維持在細胞外液。因此，若打入500ml (一瓶) N/S，會有約1/4在血漿(intravascular)中，約125ml。

• 葡萄糖水 (D5W, D10W)

零張力。因此打入的液體會分佈到細胞外液和細胞內液。因此打入的點滴，只有1/12會在血管中。例如：打入500ml D5W，只有41.6ml在血管中。

• Half saline (0.45% NaCl)

提供Tonicity 約154 mOsm/kg。液體走向約等於一半的isotonic，一半的D5W。因此，打入500ml 0.45% NaCl，約83.3ml在血管中 (250*1/4 + 250*1/12)。

⏩注意：若病人體在敗血性休克等發炎狀態，基本上血管通透性會增加，導致滯留於血漿中的體機會比預期的更少。

五、點滴的選擇：

Isotonic fluids: normal saline VS Lactated Ringers (LR)

• Normal saline：

提供154 mEq 鈉 ＆ 154 mEq 氯

所提供的氯比血漿中含的更多，血漿中約100mEq/L

治療水分流失與輕微鈉缺乏的代謝性鹼中毒

• LR：

含有 Na 130mEq/L, Cl 109mEq/L, K 4mEq/L, Ca 3mEq/L, lactate 28mEq/L, pH 6.5, 273mOsm/L

為等張溶液。

Lactate 於肝臟代謝成 bicarbonate，可治療輕度代謝性酸中毒。 

LR中的乳酸鈉(sodium lactate)有兩種用途，其一可以作為代謝性酸中毒的緩衝，可中和局部的酸；其二可被LDH (受傷的組織與紅血球皆會釋出) 轉化為丙酮酸 (Pyruvic acid)，當作能量來源，進入粒線體中氧化為CO2（TCA cycle）。 

燒傷、手術或外傷失血過多時，LR可做為血漿之代用品。 

🚫因含鈣，若與含磷製劑混合會產生沉澱，也不可與抗生素ceftriaxone並用（會導致沈澱阻塞血管）；與體外輸血液混合則會引起凝血，故應避免；乳酸性酸中毒者不可以使用。

• N/S VS LR： 

SALTED trial (link): Among noncritically ill adults treated with intravenous fluids in the emergency department, there was no difference in hospital-free days between treatment with balanced crystalloids and treatment with saline. (N Engl J Med 2018; 378:819-828)

SMART trial (link): Among critically ill adults, the use of balanced crystalloids for intravenous fluid administration resulted in a lower rate of the composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction than the use of saline. (N Engl J Med 2018; 378:829-839)

The BaSICS Randomized Clinical Trial (link): In this randomized clinical that included 10 520 patients in ICU, intravenous fluid bolus treatment with a balanced solution vs 0.9% N/S resulted in 90-day mortality of 26.4% vs 27.2%, respectively, a difference that was not statistically significant. Among critically ill patients requiring fluid challenges, treatment with a balanced solution compared with saline solution did not significantly reduce 90-day mortality. (JAMA. 2021;326(9):818-829)

Meta-analysis (link): The estimated effect of using balanced crystalloids versus saline in critically ill adults ranges from a 9% relative reduction to a 1% relative increase in the risk of death, with a high probability that the average effect of using balanced crystalloids is to reduce mortality.

• ⏩Normal saline與LR的差異，可能的差異點在於氯含量。

N/S中較多的氯離子可能會造成non-gap 的代謝性酸中毒（derangements in renal acid-base regulation）。

腎小管中的亨利氏環粗上行支中的緻密斑細胞 (macula densa)對遠曲小管中的氯化鈉濃度很敏感。

當氯化鈉濃度的降低時，緻密斑會啟動Na/K/2Cl cotransporter，導致：

1. 入球小動脈的血管擴張，提高腎小球血流量，以增加腎小球濾過率＆腎絲球濾過率
2. 增加renin釋放。

因此，當給予normal saline時，過多的氯離子流經緻密斑細胞時，腎臟可能會以為現在血流量過多過剩，引此會收縮入球小動脈，回饋到tubuloglomerular，使GFR下降。（理論假說，需更多investigation）

Hypotonic Fluids: D5W VS Half saline

• D5W：5% dextrose＋水 (50g of dextrose per liter)

添加葡萄糖的目的是使溶液呈現等滲壓以防止紅血球爆炸(lysis)。 一旦葡萄糖打入體內，會被迅速代謝，點滴就僅剩水(free water)，故張力為0。

用於補充熱量與水分。一瓶500ml D5W含有25g 糖（約五顆方糖、一罐330ml的可口可樂約含33g 糖）

 

⏩既然屬於free water，那打D5W會造成肺水腫(pulmonary edema)嗎？

• 肺間質具有一些防止肺水腫的機制(與有interstitial matrix有關)，以保護水分隨意流串。
• 在大多數情況下，肺水腫是由肺血管系統中的靜水壓力(hydrostatic pressure)增加所引起的，因此，導致肺水腫主要是血管中的體液增加和肺臟的微血管壁受損，使肺部血管內液體滲出血管外的速度，超過腎臟可排除的能力。(參考link)
• 一公升的D5W，只有83ml會進入血管中。

• Half saline (0.45% N/S)

用於水分流失多於氯化鈉流失的情形(eg. hypernatremia)，也可用來評估腎臟狀態及治療高滲透壓性糖尿病。

其他點滴：

• 台大 5 號（Taita No.5）：

含鈉離子 36 mEq/L、氯離子 17 mEq/L、鉀離子 18 mEq/L、 鎂離子 3 mEq/L、phosphate 12 mM/L，acetate 28 mEq/L 及 10% glucose

滲透壓為 669 mOsm/L。

適用於低磷血症病人之 phosphorus 補充(非糖尿病人)、持續性diarrhoea、肝炎、酒精中毒、營養不良患者之高熱能及電解質補充。 外科、婦產科手術前後營養及電解質之補充(尤其是骨折病人)。

含有磷，若與含鈣製劑混合會產生沉澱。

Colloid (albumin)

• 把水分抓到血管中的能力極高。
• 25g的 albumin可以增加血管中體積約450ml。
• 研究指出，在sepsis或icu病人中，比較使用albumin與isotonic fluids，albumin不能提供較好的結果。
• 腦部外傷病人使用albumin ，會增加兩年死亡率。
• 嚴重敗血症病人使用albumin，會降低28天死亡率。

SAFE Study (link): 6997 patients who underwent randomization. In patients in the ICU, use of either 4 % albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days. (N Engl J Med 2004; 350:2247-2256)

The CRISTAL Randomized Trial (link): Among ICU patients with hypovolemia, the use of colloids (gelatins, dextrans, hydroxyethyl starches, or 4% or 20% of albumin) vs crystalloids (isotonic or hypertonic saline or LR) did not result in a significant difference in 28-day mortality. Although 90-day mortality was lower among patients receiving colloids, this finding should be considered exploratory and requires further study before reaching conclusions about efficacy. (JAMA. 2013;310(17):1809-1817. doi:10.1001/jama.2013.280502)

• There were more days alive without mechanical ventilation in the colloids group vs the crystalloids group by 7 days (mean: 2.1 vs 1.8 days, respectively.
• Renal replacement therapy was used in 156 (11.0%) in colloids group vs 181 (12.5%) in crystalloids group (RR, 0.93 [95% CI, 0.83 to 1.03]; P = .19).

⏩推論可能原因是：albumin半衰期太短，只有12到16小時。體液擴張作用的半衰期僅2-3小時。因此，albumin多半用於因低白蛋白引起之肺水腫。通常搭配lasix使用。(先把過多的水分拉到血管中，在用lasix把過多的水脫掉)

六、點滴的給法：

原則上沒有缺乏體液或電解質等，一天人所需的輸液為：

水：Na：K：glucose= 3：2：1：1

水 30ml/kg

Na 2mEq/kg

K 1mEq/kg

Glucose 100g/day (最少) (腦部能量來源)

▲NICE Clinical Guideline [CG174] on Algorithms for IV fluid therapy (link)

七、人體攸關體液調節的激素：

• ADH (Antidiuretic Hormone)抗利尿激素。
• 體液高滲透壓時、循環血量減少時、神經刺激時會釋放ADH
• 參考：陳銳溢醫師的ADH抗利尿解說
• Atrial Natriuretic Peptide (ANP)

• Aldosteron ：促進使腎小管對鈉和水的再吸收和鉀的排除
• Estrogen:增加鈉的再吸收
• Progesteron：促進鈉和水之排出

延伸閱讀：

Intravenous fluid therapy in critically ill adults

 

Case study 1: 高血鈉

Case Scenario: 

Mr. XY, a 65-year-old male, was admitted to the emergency department with a history of a fall from the stairs. He had a left-sided subdural hematoma and was treated with surgical evacuation. His serum sodium levels were found to be elevated to 155 mEq/L.

Management Steps:

Step 1: Evaluate the severity of hypernatraemia

In this case, Mr. X has severe hypernatremia (serum sodium level > 150 mEq/L). Hypernatremia can cause cerebral dehydration and worsen neurological outcomes in SDH patients. Hence, it is important to manage hypernatremia aggressively.

Step 2: Identify the underlying cause

In this case, hypernatremia is likely due to the excessive loss of free water, which can occur as a result of fever, hyperventilation, or diabetes insipidus. It is essential to determine the underlying cause of hypernatremia as it can impact the treatment approach.

Step 3: Initiate fluid resuscitation

The initial goal of treatment is to correct fluid deficit and improve intravascular volume. Intravenous fluid should be started with isotonic or hypotonic solutions (e.g., 0.9% normal saline or 0.45% saline) at a rate that is calculated to replace the estimated fluid deficit. This can be calculated using the following formula:

Water deficit = [0.6 x body weight (kg) x (serum sodium/140-1)]

In this case, assuming a body weight of 70 kg, the estimated fluid deficit can be calculated as:

Water deficit = [0.6 x 70 x (155/140-1)] = 4.9 L

Therefore, Mr. XY needs to receive at least 4.9 L of hypotonic solution to replace his fluid deficit.

Step 4: Monitor serum sodium levels

Serum sodium levels should be monitored frequently (every 2-4 hours) to prevent overcorrection of hypernatremia, which can lead to cerebral edema and worsen neurological outcomes. The goal is to correct serum sodium levels at a rate of no more than 10-12 mEq/L per day.

Step 5: Adjust fluid therapy as needed

Fluid therapy should be adjusted based on serum sodium levels and urine output. If serum sodium levels continue to rise despite fluid therapy, or if urine output remains low, the possibility of underlying diabetes insipidus should be considered, and vasopressin or its analogs may be added to the management regimen.

Step 6: Manage underlying conditions

The underlying cause of hypernatremia should be managed appropriately. For example, if fever is the cause, antipyretics should be given to control fever. If diabetes insipidus is the underlying cause, desmopressin or other vasopressin analogs should be used.

Step 7: Avoid medications that can worsen hypernatremia

Special concerns:

The use of hypotonic solutions in patients with raised intracranial pressure (ICP) is controversial and depends on the individual patient's condition. Hypotonic solutions can cause cerebral edema and worsen intracranial hypertension in some patients, especially those with severe brain injury or SDH with raised ICP. Therefore, the choice of fluid therapy for these patients must be individualized and based on the patient's overall clinical picture, including their serum sodium levels, intravascular volume status, and ICP.

In general, isotonic solutions, are preferred over hypotonic solutions for fluid resuscitation in patients with SDH and raised ICP. Isotonic solutions can help maintain intravascular volume and avoid the risk of cerebral edema associated with hypotonic solutions. However, hypotonic solutions may be considered in patients with severe hypernatremia, as they can help rapidly correct hypernatremia and prevent further neurological damage.

released: Feb.2023