ADVERSE EFFECTS OF RESUSCITATION WITH LACTATED RINGER COMPARED WITH RINGER SOLUTION AFTER SEVERE HEMORRHAGIC SHOCK IN RATS Ricarda Rohrig,* Thomas Ro ¨ nn,* Sven Lendemans, † Thorsten Feldkamp, ‡ Herbert de Groot,* and Frank Petrat* *Institut fu ¨ r Physiologische Chemie, † Klinik fu ¨ r Unfallchirurgie, and ‡ Klinik fu ¨ r Nephrologie, Universita ¨ tsklinikum, Universita ¨ t Duisburg-Essen, Essen, Germany Received 9 Feb 2012; first review completed 1 Mar 2012; accepted in final form 19 Apr 2012 ABSTRACT—Lactated Ringer (LR) is a widely used resuscitation fluid that is known to mediate beneficial effects on acid- base balance when compared with normal saline. We here compared LR with the more physiological Ringer solution (RS) regarding acid-base status, hemodynamics, survival, and organ injury following fluid resuscitation subsequent to severe hemorrhagic shock. Anesthetized rats were hemorrhaged to a mean arterial blood pressure of 25 to 30 mmHg within 30 min. After 60 min, they were resuscitated with either RS or LR (three times the shed blood volume) or with RS or LR plus blood (shed blood plus twice its volume) within 30 min. Subsequently, the animals were observed for further 150 min. When the rats were resuscitated with pure LR or RS, all animals of the shock/LR group, but only three of eight shock/RS group rats were dead 100 min later (median survival, 50 T 13.1 vs. 120 T 14.1 min; P G 0.05). Coadministration of the shed blood with RS or LR increased the survival rates to 100%. In these blood-resuscitated groups, organ injury, especially of the kidney, was diminished by the use of RS compared with LR. Time-matched acid-base parameters were not different in all shock groups until death of the animals or euthanasia at the end of experimental time. We conclude that, in severe hemorrhagic shock, resuscitation with RS leads to an improved outcome compared with resuscitation with LR, regardless whether blood is coadministered or not. KEYWORDS—Ischemia, reperfusion, kidney, crystalloids, normal saline, acid-base balance, blood ABBREVIATIONS—HEPES V 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; BE V base excess; BW V body weight; CK V creatine kinase; LDH V lactate dehydrogenase; LR V lactated Ringer; MAP V mean arterial blood pressure; MPO V myeloperoxidase; NS V normal saline; PCO 2 V carbon dioxide partial pressure; PO 2 V oxygen partial pressure; RS V Ringer solution; bpm V beats per min INTRODUCTION Hemorrhagic shock is one of the major causes of death among trauma patients (1). It causes an imbalance of oxygen supply and consumption leading to tissue hypoxia (2). Fatal consequences may either result directly from excessive blood loss or secondarily from multiple organ failure (3). Among the various resuscitation strategies that have been developed, using numerous fluids and regimens, the princi- ple to stop blood loss and restore tissue perfusion by volume replacement has first priority (4). Subsequent to a prolonged shock state, however, impaired tissue perfusion can still persist following resuscitation (5). In the 1880s, Sydney Ringer analyzed for the first time beneficial effects of inorganic ions on heart contractility (67). These investigations led to the formulation of Ringer solution (RS), an isotonic fluid containing sodium, potassium, and calcium chlorides (Table 1). In the 1930s, Hartmann and Senn (7) tried to overcome metabolic acidosis in children by using RS supplemented with bicarbonate. Soon they realized that very high intravenous quantities were required to be effective. Moreover, the administration of RS-bicarbonate resulted in a rebound reaction finally leading to alkalosis. Thus, Hartmann and Senn supplemented RS with lactate, an anion that is metabolized by the liver, with the intention to antagonize acidosis but avoiding rebound alkalosis. Up to now, lactated Ringer (LR) is widely used in resusci- tation of hypovolemic shock including hemorrhagic shock (8Y10). In experiments with hemorrhaged swine, resuscitation with LR improved hemodynamic parameters, blood coagu- lation, and survival compared with resuscitation with normal saline (NS) (11Y13). In a dog model of hemorrhagic shock, LR was equally effective as NS in reconstituting blood volume and arterial pH (14), and in rats LR and NS were equally ef- fective in the treatment of moderate hemorrhagic shock, whereas for massive hemorrhagic shock resuscitation with LR was advantageous (14, 15). Unlike the several comparisons of LR with NS, only one study compares LR with unsubstituted RSVthe actually more correct comparisonVin a hemorrhagic shock model (16). In dogs, which were resuscitated either with RS, LR, or otherwise modified RS following moderate hemorrhage, LR improved acid-base balance compared with the unsubstituted RS control. Here, we tested LR against RS in a rat model of severe hem- orrhagic shock with particular focus on survival and organ injury Address reprint requests to Herbert de Groot, MD, PhD, Institut fu ¨r Physiologische Chemie, Universita ¨tsklinikum Essen, Hufelandstr. 55, D-45122 Essen, Germany. E-mail: herbert.de-groot@uni-duisburg-essen.de. DOI: 10.1097/SHK.0b013e31825b4ed9 Copyright Ó 2012 by the Shock Society 137 SHOCK, Vol. 38, No. 2, pp. 137Y145, 2012 Copyright © 2012 by the Shock Society. Unauthorized reproduction of this article is prohibited.