Hypertonic sodium lactate versus lactated ringer's solution for intravenous fluid therapy in operations on the abdominal aorta. Hypertonic saline and dextran after coronary artery surgery mobilises fluid excess and improves cardiorespiratory functions. Serum osmolar and electrolyte changes associated with large infusions of hypertonic sodium lactate for intravascular volume expansion of patients undergoing aortic reconstruction. Hypertonic saline for intraoperative fluid therapy in transurethral resection of the prostate. [Comparison of postoperative volume therapy in heart surgery patients]. Effects of hypertonic saline (7.5%) on extracellular fluid volumes compared with normal saline (0.9%) and 6% hydroxyethyl starch after aortocoronary bypass graft surgery. Cardiac compliance and effects of hypertonic saline. Hypertonic saline fluid therapy following surgery: a prospective study. Hypertonic saline (7.5%) decreases perioperative weight gain following cardiac surgery. [The effect of hypertonic saline infusion on lumbar epidural anesthesia]. Comparison of the acute hemodynamic effects of hypertonic or colloid infusions immediately after mitral valve repair. Intraoperative colloid administration reduces postoperative nausea and vomiting and improves postoperative outcomes compared with crystalloid administration. Response of extravascular lung water to intraoperative fluids. Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery. Normal saline versus lactated Ringer's solution for intraoperative fluid management in patients undergoing abdominal aortic aneurysm repair: an outcome study.
Fifty-eight patients who were to undergo aortic reconstruction were prospectively randomized into two groups to compare the effects of perioperative fluid replacement with isotonic and hypertonic crystalloid solutions. Blood loss was replaced with packed red blood cells, and additional fluid was given as either Ringer's lactate solution (RL, 130 mEq sodium/L, 274 mOsm/L) or a hypertonic balanced salt solution (HSL, 250 mEq sodium/L, 514 mOsm/L). Fluid was administered to maintain the cardiac filling pressure within 3 torr of the preoperative level and the cardiac output (CO) at or above the preoperative level. The groups were similar with respect to age, preexisting disease, duration of operation, and operative blood loss. During the operation, the RL group required 9.5 +/- 0.8 L of fluid, whereas the HSL group required 4.5 +/- 0.3 L (P less than 0.001). Pulmonary, cardiac, and renal functions were adequately maintained in both groups. There were no significant differences between the groups with regard to CO, urine output, or creatinine clearance during the operation and early postoperative period. Postoperatively, the intrapulmonary shunt was 20 +/- 1% in the RL group and it was 16 +/- 1% in the HSL group (P less than 0.05). The amount of sodium infused and the cumulative sodium balance at the completion of the study period were similar in both groups. Serum sodium and osmolarity were significantly greater in the HSL group (P less than 0.001), reaching a maximum of 151 +/- 1 mEq/L and 305 +/- 2 mOsm/L, respectively. Two patients in the HSL group had a persistent elevation in serum osmolarity (greater than 320 mOsm/L) during operation, for which they received RL for the balance of the resuscitation. There were no complications that could be attributed to the hypertonicity of the solution. HSL is effective for resuscitation of patients with extracellular fluid deficit and is safe provided that the serum sodium and osmolarity are monitored during periods of large volume administration. Extracorporeal circulation induces increased capillary permeability with fluid leakage into the interstitial space, resulting in positive fluid balance and intravascular hypovolaemia. Hypertonic saline 75 mg.ml-1 in dextran 70, 60 mg.ml-1 (HSD) seems to be of benefit in patients with impaired perfusion. The purpose of the study was to investigate the effects of HSD infusion on fluid balance and cardiorespiratory functions just after the end of cardiac surgery.
                Twenty patients with 3-vessel coronary artery disease undergoing elective coronary artery bypass surgery were studied. A standard regimen for anaesthesia, extracorporeal circulation and monitoring was used. The patients were allocated to receive just after the end of surgery either HSD or isotonic saline (4 ml.kg-1 during 30 min) at random in a double-blind single infusion. Ringer's acetate solution was added as needed to stabilise haemodynamics postoperatively.
                HSD caused mobilisation of the retained intraoperative fluid excess, and increased diuresis. Despite reduced need for extra fluid and a decreased cumulative fluid balance, after HSD infusion patients had increased filling pressures of the heart and improved cardiac output. HSD infusion also induced reduced intrapulmonary venous admixture and improved PaO2 in the early postoperative period.
                The present study documents that infused hypertonic saline with dextran just after the end of cardiac surgery resulted in mobilisation of the intraoperative fluid excess with increased urine output in the early postoperative period and improved gas exchange. Despite reduced need for extra i.v. fluid and decreased cumulative fluid balance, after HSD infusion the patients had increased filling pressures of the heart with improved cardiac output. To better define the serum osmolar and compositional changes associated with the infusion of a large volume of hypertonic saline solution (sodium of 250 milliequivalents per liter), we compared resuscitation using a hypertonic crystalloid (HSL) to Ringer's lactate (RL) in 52 patients undergoing aortic reconstruction. There were no differences between the groups in any of the preoperative measurements, the duration of operation, operative blood loss or transfusion requirement. The RL group required 9.5 liters of fluid intraoperatively as compared with 6.3 liters required by the HSL group (p less than 0.01). There was no significant difference between the groups in the amount of sodium infused to achieve resuscitation or in the sodium balance at the end of the study period. Hypernatremia (average maximum serum sodium: 157 milliequivalents per liter) and hyperosmolarity (average maximum serum osmolarity: 320 milliosmoles per liter) resolved in the HSL group within 48 hours. Correction of the hyperosmolar state was thought to be due to the judicious administration of free water and a decrease in renal free water clearance. The HSL group required significantly greater potassium administration during the early postoperative period due to increased kaluresis. HSL is safe and effective for use in the resuscitation of moderate blood volume deficit. Changes in serum sodium values and in osmolarity resolve rapidly. The serum potassium level should be monitored closely and replaced aggressively. We tested hypertonic saline solution (HS) to determine its effectiveness in surgical procedures for prostatic hypertrophy. We randomly selected 40 patients undergoing elective transurethral resection of the prostate for either infusion of HS (3% NaCl) at 4ml·kg(-1)·min(-1) (HS group) or lactated Ringer's solution (LR) at 8 ml·kg(-1)·min(-1) (LR group). Anesthesiologists regulated the intraoperative infusion rate as needed to maintain blood pressure. There were no differences in systolic blood pressure, heart rate, central venous pressure, or arterial blood oxygenation between the two groups. In the HS group, plasma sodium, chloride, and osmolality, measured in the recovery room, were significantly increased; however, they returned to preanesthetic levels the day after surgery. In the LR group, in contrast, plasma sodium decreased significantly and this lower value persisted for 1 day. An osmolar gap exceeding 10mOsm·kg(-1) was observed in 2 patients in the HS group, but plasma sodium remained at normal values. However, in the 1 patient in the LR group whose osmolar gap exceeded 10mOsm·kg(-1), plasma sodium was 115 mEq·I(-1). HS, at a low dose, is useful in the intraoperative management of transurethral resection of the prostate. Patients who have undergone cardiac surgery with use of extracorporeal circulation frequently reveal marked hypovolaemia in spite of a highly positive fluid balance. This is thought to be due to transient microvascular damage and extravascular fluid shift. Further volume replacement to achieve haemodynamic stability in the postoperative period may cause fluid overload and congestive heart failure. The present study was designed to investigate whether this fluid overload could be avoided by using a hypertonic-hyperoncotic solution (group I: HHL, 10% hydroxyethylstarch 200/0.5 in 7.2% saline) instead of two different standard colloid solutions (group II: HA, 5% albumin; group III: HES, 6% hydroxyethylstarch in 0.9% saline).
                Twenty-one patients meeting our criteria for hypovolaemia immediately after cardiac surgery were randomly assigned to three groups. Patients in group I received HHL in increments of 150 ml, while patients in group II and group III were given HA and HES respectively in increments of 500 ml until hypovolemia was corrected. Haemodynamic assessment was done using a pulmonary artery thermodilution catheter. Intra- and extravascular volumes, including extravascular lung water (EVLW), intrathoracic blood volume (ITBV), and total blood volume (TBV) were measured by the double indicator technique using lung water software (COLD-System, Pulsion, Munich, Germany).
                Correction of hypovolaemia-related haemodynamic parameters and restoration of normal TBV were achieved by 236 +/- 80 ml of HHL (group I), 857 +/- 244 ml of HA (group II) and 1000 +/- 0 ml of HES (group III) respectively. TBV increased significantly in each group, compared to baseline values. EVLW did not change significantly in any group. We found that the volume-augmenting effect of HHL per millilitre infused solution was more than four times that of HA and HES, primarily as a result of increasing plasma osmolality due to an increase of plasma sodium levels. This pronounced effect on intravascular volume of HHL lasted for only 2 h following infusion, however, and did not lead to any unwanted side effects. In the period between 2 and 20 h after primary volume replacement, further fluid therapy with colloids and crystalloids, guided by clinical signs of hypovolaemia, was necessary in each group of patients. The overall fluid requirements for the first 20 h after operation did not differ among the three resuscitation regimens.
                We found that HHL is a safe and effective solution for acute correction of hypovolaemia after cardiac surgery. The advantages of a smaller initial volume load by HHL cannot be maintained for longer than 2 h. To compare the effects of hypertonic (7.5%) saline (HS), normal (0.9%) saline (NS), and 6% hydroxyethyl starch (HES) on extracellular fluid volumes in the early postoperative period after cardiopulmonary bypass.
                A prospective, randomized, double-blind study.
                University teaching hospital.
                Forty-eight patients scheduled for elective coronary artery bypass graft surgery.
                Patients were randomly allocated to receive 4 mL/kg of HS, NS, or HES during 30 minutes when volume loading was needed during the postoperative rewarming period in the intensive care unit. Plasma volume was measured using a dilution of iodine-125-labeled human serum albumin. Extracellular water and cardiac output were measured by whole-body impedance cardiography.
                Plasma volume had increased by 19 +/- 7% in the HS group and by 10 +/- 3% in the NS group (p = 0.001) at the end of the study fluid infusion. After 1-hour follow-up time, the plasma volume increase was greatest (23 +/- 8%) in the group receiving HES (p < 0.001). The increase of extracellular water was greater than the infused volume in the HS and HES groups at the end of the infusion. One-hour diuresis after the study infusion was greater in the HS group (536 +/- 280 mL) than in the NS (267 +/- 154 mL, p = 0.006) and HES groups (311 +/- 238 mL, p = 0.025).
                The effect of HS on plasma volume was short-lasting, but it stimulated excretion of excess body fluid accumulated during cardiopulmonary bypass and cardiac surgery. HS may be used in situations in which excess free water administration is to be avoided but the intravascular volume needs correction.
                Copyright 2001 by W.B. Saunders Company To demonstrate the advantages of a 1.8% hypertonic saline solution (HS) over a Ringer's lactate solution (RL) during and after major intra-abdominal surgery, 28 patients were randomly allocated to one of two groups as follows: 13 patients received RL and 15 patients received HS. All patients were studied preoperatively, peroperatively and postoperatively for 72 hours. Peroperatively RL or HS were infused at a rate sufficient to maintain a pulmonary capillary wedge pressure (PCWP) and central venous pressure (CVP) within 3 mm Hg of the initial value. The left ventricular end-diastolic volume index (LVEDVI) was calculated from determination of stroke index and ejection fraction with a mobile gamma camera. Biopsy specimens were taken from the rectus abdominis muscle for evaluation of edema. The two groups of patients were comparable for age, length of surgery and length of aortic cross-clamping. Preoperatively natremia, serum osmolarity, PCWP and LVEDVI were similar in both groups. A significant (p = 0.01) difference was noted, during and after surgery, between the sodium levels in the two groups, but the levels remained within normal limits. Serum osmolarity remained similar for the two groups (p = 0.49). During and after surgery, PCWP (p = 0.1) and CVP (p = 0.7) remained within 3 mm Hg of the initial values with no significant difference between the two groups. The HS group received significantly (p = 0.002) less liquid than the RL group. At the end of surgery, the LVEDVI dropped in both groups. This drop was significantly (p = 0.04) more important in the RL group than in the HS group.(ABSTRACT TRUNCATED AT 250 WORDS) Successful resuscitation of the injured may be achieved more rapidly and with less fluid using hypertonic crystalloid solutions than with isotonic solutions. This randomized, double-blind study compared 0.9% normal saline (NS) to 1.8% hypertonic saline (HS) in 20 postoperative coronary artery bypass patients suffering uniform injury. Study solutions were administered to maintain physiologic endpoints: heart rate, blood pressure, and pulmonary capillary wedge pressure. The groups were similar with respect to age, body surface area, operative procedure, intraoperative fluid status, and intraoperative and postoperative red cell transfusion requirements. HS patients required 30% less fluid than NS patients and were in negative fluid balance during the study (-1,715 +/- 732 ml/24 hr, HS, vs. +266 +/- 825 ml/24 hr, NS; p less than 0.01). In contrast, NS patients were in positive fluid balance after 8 hours. Moreover, HS patients experienced less chest tube drainage than NS patients (981 +/- 88 ml, HS, vs. 1,700 +/- 285 ml, NS; p less than 0.01). Systemic and pulmonary hemodynamic measurements, oxygen delivery, oxygen consumption, and shunt fraction did not differ between the two groups. Serum sodium and osmolality increased in the HS group and peaked at 12 hours (145.4 +/- 1.4 mEq/L and 308.7 +/- 2.0 mOsm/kg, respectively) and correlated with the volume of HS infused (correlation coefficient = 0.81). No deaths occurred and no complication was attributed the hypertonicity of the solution. We conclude that 1.8% hypertonic saline is a safe alternative to isotonic crystalloid therapy in the fluid management of postoperative patients. Decreased third-space losses may occur with HS as suggested by the lower thoracic losses in the HS group; 1.8% NaCl may be the preferred solution in situations where excess free water administration is not desired, and where interstitial edema is detrimental to function and/or survival. To compare the effects of 7.5% hypertonic saline (HS) and 0.9% normal saline (NS) on perioperative weight gain in cardiac surgical patients.
                Prospective, randomized study.
                University teaching hospital.
                Patients (n = 72) scheduled for elective coronary artery bypass graft surgery.
                Patients were randomly assigned to receive either 7.5% HS (36 patients) or 0.9% NS (36 patients) as a single dose of 4 mL/kg over 30 minutes during the postoperative rewarming phase in the intensive care unit.
                Weight gain until the first postoperative morning was significantly greater in the NS group than in the HS group (1.9 plus minus 1.4 kg, median, 2.1 kg; 0.8 plus minus 1.5 kg, median, 0.8 kg; p = 0.005). One-hour diuresis after the fluid infusion was significantly greater in the HS group compared with the NS group (501 plus minus 282 mL and 237 plus minus 173 mL; p < 0.001). In the linear regression model, the 2 most important factors affecting the perioperative weight gain were the volume of fluid infused postoperatively in the intensive care unit (4,098 plus minus 916 mL in the HS group and 4,589 plus minus 1,344 mL in the NS group) and the total diuresis after surgery (3,351 plus minus 1,035 mL in the HS group and 2,942 plus minus 846 mL in the NS group).
                HS had an intense diuretic effect, which reduced intraoperative fluid retention. This effect was confirmed by the lesser increase in body weight measured on the first postoperative morning.
                Copyright 2002, Elsevier Science (USA). All rights reserved. The author compared hemodynamic effects of fluid loading during epidural anesthesia with 7.2% hypertonic saline (HS), lactate Ringer's (LR) or isotonic saline solutions in 24 ASA 1 patients undergoing elective lower abdominal or pelvic surgery, allocated randomly into three groups. The first two groups, patients received equal amounts of sodium (2.2 mmol.kg-1), and the latter group, isotonic saline solutions for 1-2 ml.kg-1.h-1 as control. After epidural injection (2%mepivacaine 0.1 ml.cm(Height)-1), fluid loading was performed for 20 minutes. The volume of fluid loading was significantly larger in group LR (979.3 +/- 154.7 ml) than the other two groups (HS: 104.5 +/- 20.0 ml, NS: 48.8 +/- 8.3 ml) (P < 0.05). The number of blocked segments was similar in three groups. Magnitude of hypotension was no significantly different among the groups 20 minutes after fluid loading, but recovered to the control level in group HS. In all groups heart rate decreased but the decrease was significant only in group HS. But, in group HS, stroke index increased after fluid loading and remained elevated. Increase of extracellular volume in group HS was observed by bioelectrical impedance analysis as in group LR. The author concludes that HS may be useful especially in the case not requiring a large volume of fluid loading. Finding ideal concentration, volume, and speed of infusion of intravenous fluids would be clinically useful. To determine the acute hemodynamic effect of hypertonic saline and/or colloid solutions as volume resuscitation in postoperative mitral valve repair patients.
                Prospective, randomized trial.
                Postoperative cardiac intensive care unit of Broussais Hospital.
                Twenty-six patients who underwent mitral valve repair were prospectively studied. Two patients were excluded during the study.
                During the immediate postoperative period, when wedge pressure decreases to <8 mm Hg, patients were randomly assigned to receive 250 mL of either hypertonic saline 7.2%-hydroxyethyl starch 6% (molecular weight, 200,000; hydroxyethylation ratio, 0.5) solution (HS-HES group), hypertonic saline 7.2% solution (HS group), or hydroxyethyl starch 6% solution (HES group). The infusion was completed within 15 mins. No additional volume was infused throughout the study.
                Standard hemodynamic measurements and echocardiographic data demonstrated that HS-HES and HS induced a higher increase in left ventricular end-diastolic area than HES. In the HS-HES and HS groups, systemic vascular resistances decreased significantly and end-systolic area tended to decrease. In the HES group, systemic vascular resistances did not change and end-systolic area tended to increase. Accordingly, ejection fraction increased significantly by 21% and 18% with HS-HES (from 50.5 +/- 5.5 to 61.2 +/- 4.8) and HS (from 49.7 +/- 3.6 to 58.8 +/- 3.3), respectively, and did not change with HES. A major increase in cardiac index was observed after hypertonic solutions infusion, from 2.9 +/- 0.3 to 4.1 +/- 0.4 L/min/m2 in the HS-HES group and from 2.7 +/- 0.3 to 3.8 +/- 0.4 L/min/m2 in the HS group. Then, cardiac index progressively returned to baseline values within the 3 hrs after the infusion. No significant difference was observed between HS-HES and HS. In these groups, plasma sodium increased significantly after the infusion and remained higher than baseline values throughout the study. Adverse events were observed only with hypertonic solution administration: hypotensive episodes, sudden increases in pulmonary capillary wedge pressure, and ventricular arrhythmias. These side effects are likely attributable to a too-high dose and/or rate of infusion. All patients included in the study were discharged from the hospital before the 10th postoperative day.
                We conclude that in patients who have undergone mitral valve repair, postoperative infusion of hypertonic saline solutions increases left ventricular preload and left ventricular ejection fraction. The use of these hypertonic solutions may be of interest in patients with valvular cardiomyopathy. A titrated dose and a low rate of infusion may substantially improve the safety. The debate over colloid versus crystalloid as the best solution for intraoperative fluid resuscitation is not resolved. Published studies have shown that mortality is not related to the specific fluid used for resuscitation. In addition, the quality of postoperative recovery between colloid and crystalloid has not been well investigated. In a prospective, blinded fashion, we investigated the effects of colloid and crystalloid resuscitation on nausea and vomiting and on the postoperative patient recovery profile. Patients undergoing major elective noncardiac surgery were randomized to receive 6% hetastarch in saline (HS-NS), 6% hetastarch in balanced salt (HS-BS), or lactated Ringer's solution (LR) on the basis of a fluid administration algorithm. The anesthetic was standardized. Hemodynamic targets included maintenance of arterial blood pressure, heart rate, and urine output within a predefined range. A postoperative morbidity survey was performed at baseline and daily after surgery. Ninety patients participated in the study, with 30 patients in each group. The amounts of study fluid (mean +/- SD) administered were 1301 +/- 1079 mL, 1448 +/- 759 mL, and 5946 +/- 1909 mL for the HS-NS, HS-BS, and LR groups, respectively (P < 0.05, HS-NS and HS-BS versus LR). Both the HS-NS and HS-BS (colloid) groups had a significantly less frequent incidence of nausea and vomiting, use of rescue antiemetics, severe pain, periorbital edema, and double vision. We concluded that intraoperative fluid resuscitation with colloid, when compared with crystalloid administration, is associated with an improvement in the quality of postoperative recovery. The effect of Ringer's Lactate (RL) and a colloid containing salt solution Plasmanate (PL) on extravascular lung water (EVLW) during aortic surgery was evaluated in a prospective study of 18 patients. Measured blood loss was replaced with packed red blood cells. In addition to red blood cell replacement, either RL or PL was infused (1) to maintain the cardiac output (CO) equal to or greater than the preoperative value, (2) to maintain the pulmonary capillary wedge pressure (PCWP) plus or minus 2 mmHg of preoperative values, and (3) to keep the urinary output greater than or equal to 30 cc/hr. Cardiac output, EVLW, PCWP, serum colloid osmotic pressure (COP), and intrapulmonary shunt fraction (Qs/Qt) were measured serially. All baseline values were similar between groups. The groups were well matched for age, associated disease, operating time, blood loss, and blood transfusions. During operation, the RL group required two times the rate of infusion of the PL group. Urine flow rates were similar on the day of surgery, but by postoperative days one and two, the PL group had approximately one-half of the urine flow rate compared to the RL group. Cardiac output and Qs/Qt increased in both groups. EVLW did not change after operation in either group, despite marked decrease in COP in the RL group. These data indicate that crystalloid resuscitation to physiologic endpoints does not increase extravascular lung water. Thus, manipulation of COP by PL was unnecessary in these patients. Intraoperative hypovolemia is common and is a potential cause of organ dysfunction, increased postoperative morbidity, length of hospital stay, and death. The objective of this prospective, randomized study was to assess the effect of goal-directed intraoperative fluid administration on length of postoperative hospital stay.
                One hundred patients who were to undergo major elective surgery with an anticipated blood loss greater than 500 ml were randomly assigned to a control group (n = 50) that received standard intraoperative care or to a protocol group (n = 50) that, in addition, received intraoperative plasma volume expansion guided by the esophageal Doppler monitor to maintain maximal stroke volume. Length of postoperative hospital stay and postoperative surgical morbidity were assessed.
                Groups were similar with respect to demographics, surgical procedures, and baseline hemodynamic variables. The protocol group had a significantly higher stroke volume and cardiac output at the end of surgery compared with the control group. Patients in the protocol group had a shorter duration of hospital stay compared with the control group: 5 +/- 3 versus 7 +/- 3 days (mean +/- SD), with a median of 6 versus 7 days, respectively ( = 0.03). These patients also tolerated oral intake of solid food earlier than the control group: 3 +/- 0.5 versus 4.7 +/- 0.5 days (mean +/- SD), with a median of 3 versus 5 days, respectively ( = 0.01).
                Goal-directed intraoperative fluid administration results in earlier return to bowel function, lower incidence of postoperative nausea and vomiting, and decrease in length of postoperative hospital stay. Metabolic acidosis and changes in serum osmolarity are consequences of 0.9% normal saline (NS) solution administration. We sought to determine if these physiologic changes influence patient outcome. Patients undergoing aortic reconstructive surgery were enrolled and were randomly assigned to receive lactated Ringer's (LR) solution (n = 33) or NS (n = 33) in a double-blinded fashion. Anesthetic and fluid management were standardized. Multiple measures of outcome were monitored. The NS patients developed a hyperchloremic acidosis and received more bicarbonate therapy (30 +/- 62 mL in the NS group versus 4 +/- 16 mL in the LR group; mean +/- SD), which was given if the base deficit was greater than -5 mEq/L. The NS patients also received a larger volume of platelet transfusion (478 +/- 302 mL in the NS group versus 223 +/- 24 mL in the LR group; mean +/- SD). When all blood products were summed, the NS group received significantly more blood products (P = 0.02). There were no differences in duration of mechanical ventilation, intensive care unit stay, hospital stay, and incidence of complications. When NS was used as the primary intraoperative solution, significantly more acidosis was seen on completion of surgery. This acidosis resulted in no apparent change in outcome but required larger amounts of bicarbonate to achieve predetermined measurements of base deficit and was associated with the use of larger amounts of blood products. These changes should be considered when choosing fluids for surgical procedures involving extensive blood loss and requiring extensive fluid administration.
                Predominant use of 0.9% saline solution in major surgery has little impact on outcome as assessed by duration of mechanical ventilation, intensive care unit stay, hospital stay, and postoperative complications, but it does appear to be associated with increased perioperative blood loss.
HS reduces the volume of intravenous fluid required to maintain patients undergoing surgery but transiently increases serum sodium. It is not known if HS effects patient survival and morbidity but it should be tested in randomized clinical trials that are designed and powered to test these outcomes.