Ringer's lactate solution
Ringer's lactate solution, also known as lactated Ringer's solution or Hartmann's solution, is a sterile, isotonic crystalloid fluid administered intravenously to replace fluids and electrolytes in patients experiencing dehydration, hypovolemia, or electrolyte imbalances.[1] It is designed to closely mimic the electrolyte composition of human extracellular fluid, containing sodium chloride, sodium lactate (which metabolizes to bicarbonate), potassium chloride, and calcium chloride, with an osmolarity of approximately 273 mOsm/L and a pH around 6.5.[1][2] The solution's typical composition per liter includes 130 mEq of sodium, 109 mEq of chloride, 4 mEq of potassium, 1.5–3 mEq of calcium, and 28 mEq of lactate, making it a balanced, buffered alternative to normal saline for volume resuscitation.[1][2] Developed in the 1880s by British physiologist Sydney Ringer as a physiological salt solution to maintain frog heart function, it was later modified in 1932 by American pediatrician Alexis Hartmann, who added sodium lactate to counteract metabolic acidosis in dehydrated infants.[3] This addition transformed it into a versatile agent for clinical use, particularly in pediatrics and emergency settings.[3] Medically, Ringer's lactate is widely employed for aggressive fluid resuscitation in cases of trauma, surgery, sepsis, burns, and severe dehydration, as it helps restore circulating volume while minimizing risks like hyperchloremic metabolic acidosis associated with unbalanced saline solutions.[1][4] It is preferred over 0.9% normal saline in scenarios involving biliary or pancreatic losses and is listed on the World Health Organization's List of Essential Medicines for its role in treating hypovolemic shock and maintaining acid-base balance.[1][4] Caution is advised in patients with alkalosis, hyperkalemia, or impaired lactate metabolism, such as those with liver dysfunction, due to potential risks of fluid overload or electrolyte disturbances.[4]Composition and Properties
Chemical Composition
Ringer's lactate solution, also known as lactated Ringer's solution, is an isotonic crystalloid fluid composed primarily of sodium chloride, sodium lactate, potassium chloride, and calcium chloride dissolved in water for injection.[2] The lactate component is included as an organic buffer, serving as a precursor to bicarbonate through hepatic metabolism, which helps mitigate acidosis during fluid administration.[5] In the standard United States Pharmacopeia (USP) formulation, one liter of the solution provides the following ionic concentrations: 130 mEq of sodium, 4 mEq of potassium, 2.7 mEq of calcium, 109 mEq of chloride, and 28 mEq of lactate (equivalent to approximately 3.1 g of anhydrous sodium lactate).[5] The lactate ion has the molecular formula C₃H₅O₃⁻ and is present as the sodium salt to maintain electroneutrality and physiological compatibility.| Ion | Concentration (mEq/L) |
|---|---|
| Sodium (Na⁺) | 130 |
| Potassium (K⁺) | 4 |
| Calcium (Ca²⁺) | 2.7 |
| Chloride (Cl⁻) | 109 |
| Lactate (C₃H₅O₃⁻) | 28 |
Physical and Physiological Properties
Ringer's lactate solution is a clear, colorless liquid designed for intravenous administration.[7] Its density is approximately 1.005 g/mL at 25°C, which closely approximates that of human plasma and facilitates seamless integration during infusion.[8] The solution remains stable when stored at controlled room temperature (20–25°C), with brief exposures up to 40°C not adversely affecting its integrity; protection from excessive light is recommended to maintain sterility and prevent degradation.[9] Physiologically, Ringer's lactate is isotonic with an osmolarity of 273 mOsm/L, closely matching the typical range of human plasma osmolarity (280–300 mOsm/L), which minimizes osmotic shifts and cellular disruption upon administration.[1][10] This osmolarity renders it slightly hypotonic compared to fluids like 0.9% normal saline (approximately 308 mOsm/L), potentially offering advantages in scenarios requiring milder osmotic effects. The solution's pH ranges from 6.0 to 7.5, with a typical value around 6.5, supporting physiological compatibility without causing significant acid-base disturbances.[1] The inclusion of lactate provides a buffering capacity, as it is metabolized in the liver to bicarbonate, which helps maintain pH stability during infusion and corrects metabolic acidosis by generating an alkalinizing effect equivalent to about 28 mEq/L of bicarbonate.[1] This metabolic conversion enhances the solution's role in sustaining acid-base balance, distinguishing it from unbuffered crystalloids.[11] Ringer's lactate exhibits good compatibility with most intravenous drugs and additives, remaining non-reactive in standard mixtures and allowing co-administration without precipitation or instability in many cases.[12] However, it should not be infused simultaneously with citrate-anticoagulated blood products through the same line due to the risk of clotting from calcium-lactate interactions, though compatibility has been demonstrated with certain additive-solution preserved red blood cells during rapid infusion.[13][14]Clinical Applications
Human Medical Uses
Ringer's lactate solution is primarily indicated for the treatment of hypovolemia resulting from conditions such as trauma, surgery, burns, and dehydration, where it serves as an isotonic crystalloid for rapid volume expansion and restoration of electrolyte balance.[1] In trauma and surgical settings, it is commonly used to replace extracellular fluid losses and maintain hemodynamic stability during perioperative care, including as a vehicle for intravenous medications. For burn patients, it is the preferred fluid in formulas like the Parkland protocol, which calculates resuscitation volume as 4 mL/kg/% total body surface area burned, administered over the first 24 hours with half given in the initial 8 hours post-injury to address hypovolemic shock and metabolic acidosis.[15] Additionally, it is employed in the management of metabolic acidosis, particularly when associated with dehydration or tissue hypoperfusion, as the lactate component is metabolized to bicarbonate, aiding acid-base correction without exacerbating hyperchloremia.[5] Specific protocols for its administration emphasize weight-based dosing to ensure safe and effective resuscitation. In hemorrhagic shock, Advanced Trauma Life Support (ATLS) guidelines recommend an initial bolus of 20 mL/kg of warmed Ringer's lactate for both adults and pediatric patients, repeated as needed based on clinical response, such as improvement in blood pressure, heart rate, and urine output, while monitoring to avoid fluid overload.[16] For adults, this typically equates to 1-2 liters initially, titrated to maintain a mean arterial pressure of at least 65 mmHg, whereas in pediatrics, dosing is strictly weight-adjusted (e.g., 20 mL/kg bolus for severe dehydration), with ongoing maintenance at 4-6 mL/kg/hour adjusted for age, condition, and renal function to prevent hyponatremia or hyperkalemia.[17] In perioperative maintenance, infusion rates of 2-4 mL/kg/hour are standard for adults undergoing major procedures, scaled down proportionally for children to support fluid homeostasis without altering serum electrolytes significantly.[7] Clinical evidence supports its efficacy in critical conditions like sepsis and diabetic ketoacidosis (DKA). A multicenter retrospective study of septic patients with hypotension demonstrated that initial resuscitation with Ringer's lactate, compared to normal saline, was associated with reduced all-cause mortality (adjusted odds ratio 0.53; 95% CI 0.41–0.7).[18] Similarly, in a randomized trial of adults with sepsis-induced hypotension, Ringer's lactate resuscitation was associated with improved 28-day survival compared to saline, along with lower incidence of acute kidney injury.[19] For DKA, a prospective study in adults showed that Ringer's lactate achieved faster resolution of high anion gap metabolic acidosis (adjusted hazard ratio 1.325; 95% CI 1.121–1.566) compared to saline.[20] In DKA more broadly, balanced fluids like Ringer's lactate accelerate ketoacidosis resolution and reduce hyperchloremia compared to saline, supporting its use in weight-based boluses of 10-20 mL/kg followed by maintenance infusion.[21]Veterinary Uses
Ringer's lactate solution serves as a cornerstone of fluid therapy in veterinary medicine, particularly for correcting dehydration, restoring electrolyte balance, and supporting hemodynamic stability across various species. In small animals such as dogs and cats, it is routinely administered during surgical procedures to maintain intravascular volume and prevent hypotension, as well as in hypovolemic shock where initial intravenous boluses of 10-20 mL/kg are given over 15-30 minutes to rapidly expand plasma volume and improve perfusion.[22][23] For renal failure in these species, it aids in diuresis and acid-base correction by providing balanced electrolytes that mimic plasma composition, helping to mitigate azotemia without exacerbating hyperkalemia in early stages.[24][25] In large animals, including horses and cattle, Ringer's lactate is essential for managing colic in equines, where it addresses fluid shifts from gastrointestinal obstruction or inflammation, often administered at rates of 4-11 mL/kg initially and repeated based on clinical response to alleviate endotoxemia and support renal perfusion.[26][27] For dehydration in cattle, it replenishes losses from diarrhea or heat stress, with typical dosages of 2-5 mL per pound of body weight (approximately 4.4-11 mL/kg) given 1-3 times daily, adjusted to account for ongoing enteric fluid sequestration.[27][28] Species-specific adaptations are critical; in ruminants like cattle and sheep, standard Ringer's lactate formulations may require modification due to rumen physiology, which impairs lactate metabolism and reduces its alkalizing effect by about half compared to monogastrics, prompting preferences for acetated alternatives or supplemental bicarbonate in metabolic acidosis cases.[29][30] For horses, veterinary preparations often incorporate higher potassium levels (e.g., via added KCl at 20-40 mEq/L) to counteract hypokalemia from prolonged colic or diuretic use, ensuring compatibility with equine electrolyte demands during extended therapy.[31][28] Guidelines from the American Veterinary Medical Association highlight its role in exotic pets and wildlife rehabilitation, such as oral or intravenous rehydration in dehydrated birds, small mammals, or reptiles during capture myopathy or trauma recovery, with dosing scaled to body size (e.g., 5-10 mL/kg boluses in small exotics) to avoid overload while promoting rapid stabilization.[32][25]Pharmacology
Mechanism of Action
Ringer's lactate solution functions primarily as a balanced electrolyte solution that replenishes key ions lost during hypovolemia or dehydration, thereby restoring physiological homeostasis. Sodium, the principal cation, expands extracellular fluid volume by increasing intravascular oncotic pressure and facilitating water retention, which supports overall circulatory volume maintenance. Potassium aids in preserving cellular membrane potential, essential for nerve conduction and muscle contraction, while calcium promotes blood coagulation by activating clotting factors and stabilizing platelet aggregation. These electrolyte components mimic plasma composition, allowing for isotonic replacement without significant shifts in osmotic balance.[6][1] The lactate component plays a critical role in acid-base regulation through hepatic metabolism. Administered lactate is primarily converted to bicarbonate in the liver via the Cori cycle, where it undergoes transformation to pyruvate and subsequently integrates into gluconeogenesis or the tricarboxylic acid cycle, ultimately generating bicarbonate to buffer excess hydrogen ions. This process can be represented by the simplified metabolic pathway: \text{Lactate}^- + \text{H}^+ \rightarrow \text{Pyruvate} \rightarrow \text{CO}_2 + \text{H}_2\text{O} with the net effect of raising blood pH in states of metabolic acidosis. Unlike direct bicarbonate infusion, this gradual conversion minimizes risks of alkalosis or CO2 retention.[1] By providing a balanced anion profile with lactate instead of high chloride concentrations, Ringer's lactate avoids inducing hyperchloremic metabolic acidosis, a common complication of normal saline administration that results from chloride excess diluting bicarbonate levels. This preservation of acid-base equilibrium supports sustained organ function during resuscitation. In hypovolemic states, the solution enhances hemodynamics by expanding preload, which improves cardiac output and tissue perfusion, thereby alleviating hypoperfusion-related ischemia.[33][1]Pharmacokinetics and Metabolism
Upon intravenous administration, Ringer's lactate solution achieves 100% bioavailability and provides immediate expansion of the intravascular volume, with approximately 20-25% of the infused volume remaining in the bloodstream while the majority rapidly distributes to the extracellular fluid compartment, equilibrating within 25-30 minutes.[1][34][35] The lactate component undergoes primary metabolism in the liver, where it is converted to bicarbonate at a rate of approximately 0.8 mmol/kg/h in healthy adults, with a plasma half-life of 20-40 minutes under normal conditions; excess sodium, potassium, calcium, and chloride ions are primarily excreted via renal glomerular filtration and tubular handling.[1][36][37] In patients with hepatic or renal impairment, lactate clearance is prolonged due to reduced metabolic capacity, which can elevate serum lactate levels and increase the risk of lactic acidosis; during prolonged infusions, monitoring of serum lactate concentrations and anion gap is essential to assess metabolic status and guide therapy.[1][38][39]History and Development
Invention and Early Use
In 1882, British physiologist Sydney Ringer developed an isotonic saline solution while investigating the factors essential for maintaining the contraction of isolated frog heart tissue. Ringer discovered that the absence of calcium ions led to rapid cessation of cardiac activity, prompting him to formulate a balanced electrolyte solution containing sodium chloride, potassium chloride, and calcium chloride to mimic extracellular fluid and sustain organ viability ex vivo. This original Ringer's solution, without lactate, marked a foundational advancement in understanding electrolyte requirements for cellular function. During World War I, Ringer's solution gained early clinical adoption for battlefield resuscitation, where it was administered intravenously to wounded soldiers to restore fluid volume and support hemodynamic stability amid limited blood transfusion capabilities. Military physicians recognized its utility over plain saline for temporary volume expansion, though it was often combined with colloids like gum acacia to prolong effects, highlighting its role in early trauma care protocols. In the 1930s, American pediatrician Alexis F. Hartmann modified Ringer's solution by incorporating sodium lactate to address metabolic acidosis, particularly in children suffering from dehydration due to diarrheal diseases. Hartmann's experiments demonstrated that intravenous sodium lactate was rapidly metabolized to bicarbonate, effectively correcting acid-base imbalances without causing alkalosis in normal subjects, leading to the solution's standardization in the United States for pediatric and general acidosis management. This lactated variant, initially tested in human trials for its buffering capacity, established Ringer's lactate as a versatile intravenous fluid for clinical use.[40]Naming and Standardization
Ringer's lactate solution is known under various names reflecting regional preferences and historical developments. In the United States, it is primarily referred to as Lactated Ringer's solution, emphasizing the addition of sodium lactate to the original Ringer's formulation. In the United Kingdom, Australia, and other Commonwealth countries, it is commonly called Hartmann's solution, honoring Alexis Hartmann, the pediatrician who introduced lactate to improve the solution's buffering capacity in the 1930s. Historically, an earlier variant known as Ringer-Locke's solution incorporated glucose alongside the electrolytes and was used in physiological research during the late 19th and early 20th centuries.[1][41][42] Standardization of Ringer's lactate advanced through inclusion in major pharmacopeias and international health lists, ensuring consistent quality and availability. It was first listed in the World Health Organization's Model List of Essential Medicines in 1977 under the name "compound solution of sodium lactate," recognizing its critical role in fluid resuscitation and electrolyte replacement in resource-limited settings. In the United States, the formulation is standardized as Lactated Ringer's Injection in the United States Pharmacopeia (USP), with monographs specifying its composition, sterility, and stability to meet pharmaceutical standards for intravenous use. These milestones facilitated widespread adoption in clinical practice by establishing uniform manufacturing and dosing guidelines. International formulations exhibit minor differences in electrolyte concentrations to align with regional pharmacopeial requirements or clinical preferences. For instance, Hartmann's solution prevalent in Europe and Australia typically contains slightly higher levels of sodium (131 mmol/L versus 130 mmol/L in the US version), potassium (5 mmol/L versus 4 mmol/L), calcium (2 mmol/L versus 1.5 mmol/L), and chloride, while maintaining equivalent lactate (28 mmol/L). Some European variants, such as those described in the European Pharmacopoeia, may substitute acetate for lactate or adjust ion balances for specific applications like perioperative care, reflecting adaptations to local regulatory standards without altering the solution's overall isotonic profile.[43][1] In the 2020s, amid the COVID-19 pandemic, global health authorities updated guidelines to reinforce Ringer's lactate's role in critical care. The World Health Organization's 2020 clinical management protocol for severe acute respiratory infection due to COVID-19 recommended crystalloids, including normal saline and Ringer's lactate, for initial fluid resuscitation in hypotensive patients.[44] Similarly, the US Centers for Disease Control and Prevention referenced balanced solutions including Ringer's lactate in broader sepsis and shock management frameworks applicable to COVID-19 cases, emphasizing conservative fluid strategies to avoid overload in respiratory-compromised individuals.[45] These endorsements highlighted the solution's ongoing relevance in emergency response and pandemic preparedness.Formulations and Variations
Standard Formulations
The standard formulation of Ringer's lactate solution, also known as Lactated Ringer's Injection, USP, is defined by the United States Pharmacopeia (USP) and National Formulary (NF) as a sterile, nonpyrogenic solution containing specific concentrations of electrolytes in water for injection.[46] This formulation is designed to approximate the electrolyte composition of human plasma, providing isotonic balance for intravenous administration. The precise composition ensures physiological compatibility and stability, with the following components per liter:| Component | Amount (g/L) |
|---|---|
| Sodium chloride (NaCl) | 6.0 |
| Potassium chloride (KCl) | 0.30 |
| Calcium chloride dihydrate (CaCl₂·2H₂O) | 0.20 |
| Sodium lactate (anhydrous) | 3.1 |