Lactate and acetate

Today, Ringer’s solution is used with the addition of buffer in the form of lactate or acetate, of which the former is more common. Both ions are metabolized to bicarbonate in the body, albeit with certain differences. Lactate is metabolized in the liver and the kidneys with the aid of oxygen and under production of bicarbonate and carbon dioxide. Acetate is metabolized faster and in most tissues, and it consumes only half as much oxygen per mole of produced bicarbonate compared with lactate. Hence, lactate slightly increases the oxygen consumption [8] and might also raise plasma glucose, particularly in diabetic patients.[8,9] Large amounts of lactated Ringer’s confuse assays used to monitor lactic acidosis.

Both lactate and acetate are vasodilatators. Rapid administration aggravates the reduction of the systemic vascular resistance that normally occurs in response to volume loading. Both lactate and acetate are also fuels, although the calorific content in 1 liter of any Ringer’s solution is quite low (approximately 5 kcal).

Although the differences between lactate and acetate are usually negligible, several factors suggest that acetate is the better buffer in the presence of a compromised circulation and in shock. Lactate is metabolized in the liver and, therefore, Ringer’s acetate is to be preferred in patients with impaired liver function. A more detailed comparison between lactate and acetate as buffers is given in Chapter 25, “Transplantations.”

Pharmacokinetics

During intravenous infusion the Ringer’s solutions distribute from the plasma to the interstitial fluid space in a process that requires 25–30 min for completion. The distribution half-life is approximately 8 min.[5,10]

Distribution. There is a difference in the pattern of distribution for small and large volumes of the Ringer’s solutions. Infusing 300–400 ml at a rate of 10–20 ml/min will distribute fluid almost exclusively over the plasma volume.[11,12] This is rather due to the high compliance for volume expansion of the interstitial matrix than to a limiting effect of the capillary membrane. A three times higher rate of infusion overcomes the low compliance of the interstitial gel, but the fine filaments in the meshwork still retard the rate of the distribution, which explains why this process still requires 25–30 min to be completed. When the rate of infusion is further raised (50 ml/min and higher) the return of fluid from the interstitium to the plasma becomes progressively retarded, which is due to loss of stiffness in the matrix. Free fluid can even accumulate in the interstitium if an infusion is provided fast enough to overcome the normally negative interstitial fluid pressure.[1] This causes pitting edema, by which we can expect that the ratio of 1:2 for the fluid distribution between the plasma and interstitial fluid space has been abruptly reduced.

For the infusion rates normally used during surgery, the ratio of the plasma to the expandable parts of the interstitial fluid space is 1:2, which means that 33% of the infused fluid is retained in the plasma (if we disregard elimination).[13] However, slow distribution results in a stronger plasma volume expansion than offered by this relationship as long as the infusion continues (Figure 2.1).

Elimination. The elimination (by voiding) in volunteers is so rapid that the fluid may exhibit one-compartment kinetics, which has been interpreted to imply that the fluid is distributed only to the plasma and to areas of the interstitial fluid space with the highest compliance for volume expansion (half-life 20 min). In contrast, elimination is greatly retarded during surgery, where Ringer’s always exhibits two-compartment kinetics.[10] Infusion of 2 liters of Ringer’s in volunteers is followed by elimination of 50–80% of the fluid within 2 hours, whereas the corresponding figure in anesthetized patients is only 10–20%. This corresponds to a half-life of 200–400 min. Lowered blood pressure, vasodilatation and activation of the renin–aldosterone axis are factors thought to be responsible for the slow turnover of Ringer’s during anesthesia and surgery.[14] The retarded elimination facilitates the development of edema as the retained fluid distributes both in the plasma and the interstitial fluid space.

Clinical use

The pharmacodynamics of the Ringer’s solutions is strongly related to their capacity to expand the ECF volume.

These fluids may be used to replace preoperative losses of fluid due to diarrhea or bowel preparation. In contrast, vomiting should be replaced by normal saline.

The Ringer’s solutions are commonly used (in a volume of approximately 500 ml) to compensate the blood volume for the expansion of the vascular tree that occurs from induction of both regional and general anesthesia.

The Ringer’s solutions reverse the compensatory changes in blood pressure and sympathetic tone resulting from hypovolemia. There are numerous reports confirming that rapid infusion of Ringer’s is a life-saving treatment in excessive hemorrhage, owing to the resulting expansion of the plasma volume.

In contrast, crystalloid fluid cannot reverse drug-induced hypotension.[14] If a crystalloid bolus has no effect in reversing hypotension during surgery, the anesthetist should change strategy and lighten the anesthesia, or else institute treatment with an adrenergic drug, rather than providing several liters of crystalloid fluid.

As crystalloids are inexpensive and carry no risk of allergic reactions, a Ringer’s solution is often used to replace smaller blood losses while colloids are withheld until 10–15% of the blood volume has been lost. The commonly recommended dosage is to infuse three times as much Ringer’s as the amount of blood lost (3:1 principle). If the patient’s legs are placed in stirrups, a 2:1 replacement scheme can be used, with the last third given as a bolus infusion when the legs are lowered from the stirrups.[15]

There are concerns about the use of Ringer’s in brain injury, because the fluid is slightly hypotonic (270 mosmol/kg) and increases brain cell mass when the central nervous system is traumatized. Normal saline is likely to be a better choice during neurosurgery and also in acute trauma. In volunteers, however, acetated Ringer’s did not increase the ICF volume, as shown by the fact that the urinary sodium concentration was only half as high as that of the plasma.[16]

All Ringer’s should be infused cautiously in patients with renal insufficiency, since these patients may not be able to excrete an excess amount of crystalloid fluid.

The buffered Ringer’s solutions contain 2 mmol/l of calcium and therefore cause coagulation in the infusion line if given together with erythrocytes preserved with citrate. This agent operates as an anticoagulant by binding calcium, which is a co-factor in the coagulation process.

Dosing

The rate and volume of infused Ringer’s solutions vary considerably during surgery. Overall, the volumes used in clinical practice today are lower than they were in the 1980s and 1990s. The most widely used basic rate of infusion to provide is 3–4 ml/kg per hour, i.e. about 300 ml per hour in an adult male. In major surgery, a widely advocated concept is to provide a basic rate of 2 ml/kg per hour of one of the buffered Ringer’s solutions and then to increase the fluid administration whenever stroke volume decreases by >10% (goal-directed fluid therapy). To provide a Ringer’s solution only at a rate of 2 ml/kg per hour or less with no additional infusions increases the risk of postoperative nausea.[17]

In healthy adult females, very rapid infusions of Ringer’s (2 liters over 15 min) caused swelling sensations, dyspnea, and headache.[18] This rate (133 ml/min) should not be exceeded in the absence of severe hypovolemia. No symptoms were observed after infusing the same volume more slowly.

In elderly and debilitated patients, the rate of infusion of crystalloid fluid should be further reduced and adjusted according to the patient’s cardiovascular status.

Too rapid volume loading might be complicated by instant pulmonary edema. Both the dilution of the plasma proteins and the increased cardiac pressures promote such edema, which should be treated with acute vasodilatation, administration of loop diuretics, and application of continuous positive airway pressure (or positive end-expiratory pressure if the patient is mechanically ventilated).

There is also a risk of pulmonary edema developing in the postoperative period if the total volume infused during the day of surgery amounts to 7 liters or more. Arieff [19] reported development of pulmonary edema in 7.6% of 8,195 patients who underwent major surgery. The mortality in this group was 11.9%.

Volume loading with 3 liters of lactated Ringer’s in volunteers (mean age 63 years) reduced the forced expiratory capacity and the peak flow rate.[20]

Outcome studies using prospective registration of postoperative adverse events have demonstrated that crystalloid fluid administration during colonic surgery should be closer to 4 ml/kg per hour than 12 ml/kg per hour.[21] One of the earliest problems is that >2 liters prolongs the gastrointestinal recovery time after surgery, which has not been described after administration of hydroxyethyl starch.[22] Larger volumes of crystalloid electrolyte fluid promote a large number of postoperative complications, such as impaired wound healing and pneumonia.[23] Many similar outcome studies will be discussed later in this book that advise the anesthetist about the optimal infusion rates during various surgeries.

The restrictive protocol is best studied, and of undisputable value, in open abdominal surgery. Patients undergoing laparoscopic cholecystectomy and bariatric surgery seem to fare better with a more liberal program (7 ml/kg per hour or higher). There is little evidence that a restrictive fluid program is of value in the postoperative care unit, where the fluid turnover is normal, or rather slightly accelerated, owing to the surgical inflammatory response.