Lactate Ringer’s versus Normal Saline
NS generates hyperchloremic acidosis
The table above clearly demonstrates the acidity of normal saline compared to LR. In fact, it under-represents this because the pH of LR is actually 7.4 in vivo if the body fully metabolizes lactate. Many practitioners ignore the acid/base effects of normal saline believing that it is negligible unless exorbitant volumes are given. This is simply untrue as demonstrated by the study below where 300 patients with abdominal sepsis were randomized to 20cc/kg LR vs NS (average of 1L). ABGs were obtained before and after fluid bolus. There was an average pH decrease of 0.11 down to 7.21 with a 1L bolus of NS compared to no change with LR!
NS administration trends towards increased blood loss and blood transfusions
The recent review by Cochrane concludes no difference in blood loss or transfusion requirements between buffered fluids and nonbuffered fluids. Unfortunately, that the meta-analysis fell victim to the heterogeneity of its included studies; half of which compared buffered vs non-buffered heterostarches. When looking specifically at the RCTs of LR vs NS, one sees a clear trend toward increased blood loss and RBC transfusions in the normal saline group in patients undergoing large surgeries with propensity for bleeding. In fact, LR seems to induce a procoagulable state whereas NS introduces a hypocoagulable state in patients undergoing major surgery detected through TEG.
66 patients undergoing aortic reconstructive surgery randomized to LR vs NS.
30 patients undergoing major spine surgery randomized to LR vs NS.
NS administration trends towards acute kidney injury
The macula densa uses NaK2Cl channels to sense the concentration of salt in the distal convoluted tubule. The delivery of Cl is increased with chloride rich fluids and stimulates the macula densa to trigger tubuloglomerular feedback, reducing GFR and blood flow to the nephron. In healthy kidneys, this is of little clinical consequence. But in patients with severe illness, CKD, NSAID use, or exposure to nephrotoxins, this can precipitate acute tubular injury and acute renal failure.
The ICU of Austin Hospital (Melbourne) found a significant reduction in acute kidney injury and renal replacement therapies after implementation of chloride restrictive fluid strategy.
Hyperkalemia – LR is safer than NS in hyperkalemia
Two studies look at this question indirectly. Both involved randomizing patients undergoing renal transplantation to LR or NS. Both independently found that NS was more likely to produce hyperkalemia while LR tends to cause hypokalemia. 52 ESRD patients undergoing surgery was randomized to LR vs NS. Baseline K for the LR group was 4.6 and demonstrated a 0.6mEq drop. Baseline K for the NS group was 4.3 and demonstrated 0.5mEq increase.
In the O’Malley study, 5/26 patients in the NS group developed hyperkalemia (K > 6) versus none in the LR group. They also showed that 8/26 patients in the NS group developed significant acidosis (pH < 7.20) requiring bicarb drip versus none in the LR group.
Blood Transfusions – LR is safe with modern blood transfusions
The evolution of thought process on this topic is very interesting to follow historically.
Ryden SE, Oberman HA. Compatibility of common intravenous solutions with CPD blood. Transfusion. 1975;15(3):250-5. This study demonstrated grossly visible clot formation in vitro in samples of LR and CPD preserved (citrate, phosophate, dextrose) whole blood when incubated for 5 minutes. It also demonstrated that blood hemolyzed in 1/4NS or 1/2NS with no hemolysis when mixed with NS. This data convinced the American Association of Blood Banks to prohibit the use of LR with blood products despite the fact that we no longer use whole blood or CPD preservation.
King WH, Patten ED, Bee DE. An in vitro evaluation of ionized calcium levels and clotting in red blood cells diluted with lactated Ringer’s solution. Anesthesiology. 1988;68(1):115-21. This study looked at LR with CPD preserved pRBCs instead of whole blood. It concluded that that the probability of micro-clot formation in vitro is less than 1% if 100mL of LR is added to a unit of pRBCs and that a mixture of LR:pRBC of 3:1 is safe.
Cull DL, Lally KP, Murphy KD. Compatibility of packed erythrocytes and Ringer’s lactate solution. Surg Gynecol Obstet. 1991;173(1):9-12. This study diluted CPD preserved whole blood in ratios of LR:pRBC of 5:1 to 1:20 and demonstrated that clotting occurred only at ratios of 1:1. Clinically relevant dilutions between 5:1 and 2:1 do not produce clots. And when these dilutions were passed through a 170 micron filter using NS diluted blood as a control group, there were no differences in flow rates. The authors concluded that LR can be safely used as a pRBC diluent in patients requiring rapid blood transfusions.
Lorenzo M, Davis JW, Negin S, et al. Can Ringer’s lactate be used safely with blood transfusions?. Am J Surg. 1998;175(4):308-10. This group compared infusion time, filter weight, and clot formation after admixing whole blood and PRBCs with NS, LR, and LR along with increasing concentrations of added calcium chloride from 1g to 5g. They found no differences except for the presence of visible clot in the LR + 5g calcium chloride mixture. They concluded that blood bank guidelines should be revised to allow the use of LR in the rapid transfusion of PRBC.
Hitherto, the most common pRBC preservatives are SAGM (dextrose, NaCl, adenine, mannitol) or AS-3 (dextrose, NaCl, adenine, citric acid, citrate, phosphate). Albert K, Van vlymen J, James P, Parlow J. Ringer’s lactate is compatible with the rapid infusion of AS-3 preserved packed red blood cells. Can J Anaesth. 2009;56(5):352-6. This study mixed LR with AS-3 pRBCs and used filters and ELISA to detect clot formation. There were no evidence of clot in the filters. ELISA found no difference between NS vs LR and that the levels of clot detected were subphysiologic, concluding that LR is compatible with AS-3 pRBC.
In terms of pRBC preserved with SAGM, the most common preservative, LR is also shown to be safe. Note that SAGM doesn’t even contain citrate. Levac B, Parlow JL, Van vlymen J, James P, Tuttle A, Shepherd L. Ringer’s lactate is compatible with saline-adenine-glucose-mannitol preserved packed red blood cells for rapid transfusion. Can J Anaesth. 2010;57(12):1071-7. They also used ELISA and 40micron filters and demonstrated that even at 1:1 dilution, LR:PRBC co-administration is safe and equivalent to NS:pRBC as long as dilution does not exceed 60min.
Lactate Clearance – LR spuriously elevates lactate in liver patients from decreased clearance
This question is answered in an elegant anesthesia paper. 30 patients with Child-Pugh grade A undergoing cholecystectomy were randomized to LR or Acetate Ringers. Lactate was elevated from 0.98 mmol/L to 1.86 mmol/L without increases to pyruvate or pH, suggesting that this lactate was due to accumulation from LR rather than increased production. In fact, serum ketones in this group dropped, suggesting that the body was forced to utilize ketones as an alternate source of fuel when it was unable to shuttle lactate through the Cori cycle.
Acetate Ringers did not elevate lactate and interestingly showed stable ketone levels. The absence of ketogenesis suggested that cirrhotic patients are able to effectively utilize acetate as a nutrient whereas they are unable to effectively utilize lactate. From this, the authors concluded that acetate ringers may be better for cirrhotic patients.
Cerebral Edema – Is the hypotonicity of LR safe in cerebral edema?
Physiology texts purports that L-lactate up to doses of 100 mmol/h will not accumulate unless there is severe liver dysfunction or major resection. This calculates out to 3.3 liters/hour of LR without accumulation of lactate in healthy patients. Up to 70% of the lactate goes through gluconeogenesis, raising glycogen and glucose levels.
Acetate can be given 300 mmol/h without accumulation and is metabolized extra-hepatically, especially in muscle. But it has been shown to cause hypotension during renal replacement therapy. Gluconate may be the best buffer as it has no reported toxicity with accumulation, and may be protective in post-ischemic dysfunction.