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Acetate- Versus Lactate-Buffered Crystalloids for Prevention of Post-ERCP Pancreatitis in Patients Without Access to Rectal NSAIDs: A Multicentre Double-Blind Randomized Trial.

BACKGROUND: Aggressive peri-procedural intravenous fluid (IVF) therapy with lactated Ringer's solution (LR) reduces the risk of post-ERCP pancreatitis (PEP), but the standard 8-h protocol is impractical in outpatient settings and the optimal fluid type remains uncertain. We compared LR with an acetate-buffered balanced crystalloid (AC) using a symptom-guided 4-h aggressive IVF protocol. METHODS: This multicentre, double-blind, randomized superiority trial was conducted at three academic hospitals in Korea where rectal NSAIDs are unavailable. Adults with native papillae and moderate-to-high PEP risk were randomized to receive LR or AC. The IVF protocol comprised 10 mL/kg boluses before and after ERCP, followed by 3 mL/kg/h for 4 hours and extended to 8 hours if abdominal pain developed or worsened. The primary outcome was PEP incidence; secondary outcomes included early post-ERCP pain and adverse events. RESULTS: Of 813 patients (404 LR, 409 AC), PEP occurred in 12.4% of the LR group and 11.5% of the AC group (relative risk [RR] 0.93; 95% CI, 0.64-1.35; P = 0.70). Rates of mild (7.9% vs. 7.1%) and moderate (4.5% vs. 4.4%) PEP were similar, and no severe PEP or fluid overload occurred. Among the 68.3% of patients who remained asymptomatic at 4 hours and required only 4-h IVF, PEP occurred in 7.4%, with no cases of severe PEP. CONCLUSION: In this superiority trial, acetate-buffered crystalloid did not reduce PEP compared with lactated Ringer's solution, and no significant safety differences were observed between the two agents. Lactated Ringer's remains the recommended first-line crystalloid for aggressive hydration when rectal NSAIDs are unavailable. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05832047).

Humans

Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock.

BACKGROUND: Whether treatment with balanced crystalloid fluid leads to better outcomes than 0.9% saline in children treated for septic shock is debated. METHODS: In this pragmatic clinical trial conducted at 47 emergency departments in five countries, patients (2 months to <18 years of age) with suspected septic shock and abnormal perfusion were randomly assigned to receive fluid resuscitation with either balanced fluid or 0.9% saline for up to 48 hours. The primary outcome was a major adverse kidney event (a composite of death, new renal-replacement therapy, or persistent kidney dysfunction) at 30 days after enrollment or hospital discharge, whichever occurred first. RESULTS: Of 9041 enrolled patients, 277 (6.1%) in the balanced-fluid group and 282 (6.2%) in the 0.9%-saline group withdrew from the trial, leaving 4235 and 4247 patients, respectively, for analysis. A primary-outcome event occurred in 137 patients (3.4%) in the balanced-fluid group and in 124 (3.0%) in the 0.9%-saline group (difference, 0.4 percentage points; 95% confidence interval [CI], -0.5 to 1.3; risk ratio, 1.10; 95% CI, 0.88 to 1.40; P&#x2009;=&#x2009;0.85). The median number of hospital-free days during 28 days after enrollment was 23 (interquartile range, 19 to 25) in both groups. Hyperchloremia occurred in 868 patients (31.4%) in the balanced-fluid group and in 1383 (49.0%) in the 0.9%-saline group; hypernatremia in 52 (1.8%) and 89 (3.1%), respectively; and hyperlactatemia in 260 (19.8%) and 228 (16.7%). No differences in other safety outcomes or adverse events were seen. CONCLUSIONS: Among children treated for septic shock, no significant difference was seen in the incidence of death, new renal-replacement therapy, or persistent kidney dysfunction when fluid resuscitation was administered with balanced fluid as compared with 0.9% saline. (Funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; PRoMPT BOLUS ClinicalTrials.gov number, NCT04102371.).

Adolescent

The therapeutic use of albumin.

In this review, we condense and summarize the results of studies on the therapeutic use of human albumin to promote the more efficient use of this costly resource. Reports of major controlled and uncontrolled therapeutic trials, reviews, and summary articles published in English between 1972 and 1991 were identified through library and MEDLINE searches. Case series, prospective studies, and blinded therapeutic trials were identified from the bibliographies of these sources. All sources were critically evaluated for information about the comparative physiologic results and patient outcomes of the therapeutic use of albumin solutions, crystalloid solutions, and volume expanders other than albumin. The therapeutic use of albumin is of marginal benefit for many conditions for which it has been administered, apparently because of the body's capacity to quickly compensate for rapid colloid osmotic shifts. Human studies show little or no demonstrable value for albumin when it is administered for nutritional supplementation, wound healing, perioperative fluid replacement, treatment of early thermal injury, or therapy during extensive retroperitoneal surgery (including aortic aneurysm resection). Therapeutic albumin has well-defined value in several special circumstances: large-volume paracentesis in cirrhotic patients, acute nephrotic syndromes with diuretic resistance, organ transplantation, and plasmapheresis. Additional studies are needed to compare the efficacy of albumin with other volume expanders. For most purposes, balanced crystalloid solutions are satisfactory substitutes for colloid volume expanders and can be obtained at a fraction of the cost of colloid volume expanders.

Albumins

Net absorption of water, electrolytes, glucose, and folate from the in vivo, neurally isolated canine jejunum.

This study was designed to determine the effects of neural isolation of the jejunoileum (a model of intestinal transplantation) on jejunal absorptive function and associated changes that might occur over time. Net absorption of a simple, balanced crystalloid solution perfused in an 80 cm enterically isolated jejunal loop was assessed in two groups of conscious dogs with neurally intact jejunal loops or neurally isolated jejunal loops. Experiments were conducted 2, 4, and 8 weeks after surgery during fasting and after feeding to determine temporal changes. Net absorption of water and electrolytes (sodium, potassium, and chloride), glucose, and folate and loop transit times were not different (p greater than 0.05) between groups at any time point despite the presence of ongoing watery diarrhea and weight loss (15% +/- 8% body weight) in the dogs with neurally isolated jejunoileum. The effects of neural isolation (extrinsic denervation and disruption of enteric neural continuity and lymphatic drainage) do not appear to decrease net absorptive capacity for water, electrolytes, simple sugars, or folate when evaluated between 2 and 8 weeks after neural isolation. The watery diarrhea and weight loss do not appear to be related to a jejunal secretory diarrhea. These findings may have important implications in the transplanted small intestine.

Animals

Plasma volume substitution.

Blood loss up to 10-15% of the total blood volume can be substituted by mere crystalloids. A quicker and more stable volume replacement can be accomplished with colloid solutions. Combination of artificial colloids (e.g., dextran 60, dextran 70 or hydroxyethyl starches with high degree of hydroxyethylation) with crystalloids (isotonic balanced solutions) produces a long lasting volume effect. Due to dose limitation recommendations for the artificial colloids, volume substitution may be continued, at a later stage, by albumin.

Blood Volume

Dilutional re-expansion with crystalloid after massive hemorrahage: saline versus balanced electrolyte solution for maintenance of normal blood volume and arterial pH.

When administered in sufficient amounts, normal saline and Lactated Ringer's Solution are equally effective in maintaining adequate circulatory volumes despite severe blood loss and resultant hypoproteinemia. Arterial pH is maintained within normal limits when either solution is used for resuscitation provided the circulatory volume has been re-expanded to adequate levels for good tissue perfusion and support of aerobic metabolism. The pH of the infused solutions has no effect on blood pH under these circumstances. Fourteen splenectomized dogs were subjected to continuous hemorrhage and simultaneous replacement with either normal saline or Lactated Ringer's Solution. The cumulative replacement volume ratio necessary for equilibration after 61% RBC depletion was 7:1 crystalloid to the whole "undiluted" blood shed, in both groups. Indicators of pulmonary-circulatory physiology remained stable within normal limits. Arterial pH did not exhibit significant changes from normal values after resuscitation with NS or LRS. The group infused with LRS exhibited no change in arterial pH, 7.40 plus or minus .07 initial and 7.40 plus or minus .09 final; in the group with NS replacement a slight decrease from control was noted, 7.40 plus or minus .07 initial and 7.36 plus or minus .06 final. These differences, however, are not statistically significant. Of the 14 subjects, 13 were long-term survivors. The one death was associated with a technical mishap shortly after completion of the experiment. Because banked blood imposes a "net" alkaline metabolic load (sodium citrate), patients expected to be transfused with large volumes of stored blood might be better resuscited with normal salin than with Ringer's Lactate Soultions, to minimize or avert the otherwise resultant metabolic alkalosis.

Animals

Ovarian hyperstimulation syndrome in novel reproductive technologies: prevention and treatment.

OBJECTIVE: To overview the world literature on ovarian hyperstimulation syndrome (OHSS) and modes of prevention and treatment of OHSS. STUDY SELECTION: All the pertinent literature on OHSS, its prevention, and strategies for treatment were reviewed. PREVENTION: Key to prevention is proper identification of the population at risk, which includes women with either the hormonal or the morphological signs of polycystic ovarian disease, high serum estradiol (E2) before human chorionic gonadotropin (hCG) administration (E2 greater than 4,000 pg/mL), multiple follicular response (greater than 35), younger age, and lean habitus. When a high risk situation is recognized, ovulatory dose of hCG may be reduced, avoided (with cycle cancellation), or substituted by gonadotropin-releasing hormone or its agonist. Luteal support with hCG is to be bypassed. To minimize risk of OHSS, endogenous pregnancy-drived hCG may be eluded by judicious cryopreservation of all embryos. Last, follicular aspiration will allow higher levels of E2 and larger number of follicles to be matured with lesser risk of OHSS than conventional ovulation induction without follicular aspiration. TREATMENT: In-house for the severe and intensive care for the critical form. Meticulous fluid and electrolyte balance using both crystalloids and colloids (albumin) until hemoconcentration abates. Paracentesis is indicated for tight ascites, deteriorating kidney functions, and symptomatic relief. Diuretics may be prudently used once hemodilution is achieved. Dopamine drip may be used as a renal rescue, whereas heparin is indicated for thromboembolic phenomena and surgery reserved for abdominal catastrophies. Therapeutic interruption of an early gestation may be lifesaving when all other measures have failed. CONCLUSIONS: Although severe and critical OHSS may not be completely avoided, early recognition of high-risk factors, judicious prevention schemes, and treatment strategies should reduce the complication and long-term sequelae of this iatrogenic syndrome.

Chorionic Gonadotropin

Acute plasmapheresis during cardiac surgery: volume replacement by crystalloids versus colloids.

Acute plasmapheresis (APP) is an additional tool for blood conservation during cardiac surgery. In a randomized study of 60 aortocoronary bypass patients undergoing APP, the influence of replacement of the withdrawn autologous plasma (10 mL/kg) by either colloids (low molecular weight hydroxyethyl starch solution [6% HES 200/0.5]) or crystalloids (Ringer's solution) was investigated. APP was performed by means of a centrifugation technique producing platelet-poor plasma. During and after cardiopulmonary bypass (CPB), either a cell saver (CS) or a hemofiltration (HF) device was also used for blood concentration. Almost three times as much crystalloid as HES solution was necessary for replacement of autologous plasma. Fluid balance during CPB was significantly more positive in the crystalloid patients, particularly when a CS was used. Blood loss was highest in the crystalloid patients in whom a CS was used in addition to APP, and these were the only patients who needed packed red cells. The platelet count, AT-III and fibrinogen plasma concentrations, colloid osmotic pressure, albumin, and total protein were significantly less compromised in the patients with colloid volume replacement. These parameters were closest to control values in patients receiving colloid replacement and HF. It is concluded that colloid is preferred for replacement of autologous plasma withdrawn by APP, and HF is superior to the CS when the combined technique for blood conservation is used.

Coronary Artery Bypass

Hydroxyethyl starch 120, dextran 70 and acetated Ringer's solution: hemodilution, albumin, colloid osmotic pressure and fluid balance following replacement of blood loss in pigs.

Twenty healthy pigs weighing 12-17 kg were anesthetized and the small intestines were exteriorized into saline-moistened gauze. During a 2-h period 4% of the animals' body weight was bled through an arterial cannula in six increments and replaced immediately by the fluid tested: hydroxyethyl starch 120 (HES, Plasmafusin, Orion Corp., Mw 120,000), dextran 70 (DEX) and Ringer's acetate (RA). The amount of fluid infused for replacement of blood loss was equal to the amount of blood withdrawn in the colloid groups but fourfold in the RA group. Five non-bled pigs served as controls. After the hemodilution the laparotomy was closed and the animals received only 5% dextrose (2 ml/kg/min) during a 5-h follow-up period. The synthetic colloids caused a more effective dilution of hemoglobin and albumin than did RA. The colloid osmotic pressure (COP) was well maintained by the plasma substitutes but decreased in the RA group to 64% of the initial values. A stable urinary output and no edema formation was found in the HES and DEX groups. The RA animals were unable to excrete the excess crystalloid, which resulted in a strikingly positive fluid balance persisting throughout the study. Thus, the synthetic colloids were superior to RA in expansion of the plasma volume, maintenance of the COP and prevention of fluid accumulation. The effect of the two colloids was similar except that COP was slightly better maintained during the follow-up period in animals which received HES 120.

Animals

Crystalloid vs. colloid resuscitation: is one better? A randomized clinical study.

The effects of hemodynamic resuscitation with protein-containing or balanced salt solution were studied prospectively in 29 patients undergoing abdominal aortic surgery. Blood loss was replaced with packed red cells and extracellular volume with either Ringer's Lactate (RL) or 5% albumin in Ringer's lactate (ALB). Fluids were given to maintain the pulmonary capillary wedge pressure (PCWP) equal to or within 5 torr above preoperative (PO) levels, the cardiac output (CO) equal to or greater than preoperative values, and the urine output at least 50 ml/hr. Serum colloid osmotic pressure (COP), CO, PCWP, the gradient between COP and PCWP (COP-PCWP), and intrapulmonary shunt (Qs/Qt) were measured PO, intraoperatively (IO), and daily for 3 days. The measured variables were similar PO in both groups. Operation time, estimated blood loss, and transfusions were similar. Total fluids received for resuscitation (day of operation) was 11.3 +/- 0.8 liters (RL) and 6.2 +/- 0.4 liters (ALB). Fluid balance at the end of resuscitation was 8.4 +/- 0.8 liters (RL) and 3.4 +/- 0.5 liters (ALB). Maximum decrease in COP was 40% (P less than 0.001) in the RL group and was insignificant in the ALB group. The COP-PCWP decreased from 11 +/- 1 to 2 +/- 1 in RL (P less than 0.001) and insignificantly in ALB. Qs/Qt increased slightly in both groups following operation but was not different between groups. Fluid balance, total fluid infused, sodium balance, total sodium infused, COP, or COP-PCWP did not significantly correlate with Qs/Qt. Two patients in the ALB group experienced pulmonary edema associated with normal COPs and elevated PCWPs. There were no cases of pulmonary edema associated with low COPs and normal PCWPs in the crystalloid group. These data seriously question the necessity to maintain COP by using protein-containing solutions during acute hemodynamic resuscitation. When titrated to physiological end points, even large volumes of balanced salt solutions are tolerated well.

Albumins

Correlation of changes in body weight and pulmonary vascular pressures with lung water accumulation during fluid overload.

The accumulation of excess lung water is a major concern after the infusion of large amounts of crystalloid solution. The parameters used to monitor total body and lung water balance include changes in body weight, and the measurement of pulmonary vascular and plasma colloid osmotic pressures. We studied the reliability of these parameters in predicting lung water during severe fluid overload in nephrectomized sheep. We found that the normal lung appeared resistant to excess fluid accumulation, particularly when compared to the splanchnic circulation. Body weight change was an unreliable index of lung water with a correlation coefficient of 0.43. Pulmonary vascular pressures were the best index (r = 0.83) with lung water accumulating rapidly after capillary pressure exceeded 30 cm H2O. The difference between pulmonary capillary pressure and plasma colloid osmotic pressure was not as reliable (r = 0.72) as was capillary pressure alone.

Animals

Fluid therapy and the resuscitation of traumatic shock.

Fluid management of the traumatized patient begins with assessment of volume status via palpation of pulses; evaluation of mental status; and measurement of urine output, arterial blood pressure, and central pressures. Intravascular line placement and choice of initial resuscitation fluids should be individualized to the clinical situation, although in most situations a crystalloid solution continues to be the initial fluid of choice. Following initial stabilization, the intravenous fluid administered can be tailored to a given situation, chosen only after the deranged fluid balance is sequentially classified according to alterations of volume, concentration, and composition. Parenteral fluids may be divided into two groups: crystalloids and colloids. The indications, complications, and controversies surrounding various resuscitation modalities have been reviewed.

Colloids

Does the addition of albumin to the prime solution in cardiopulmonary bypass affect clinical outcome? A prospective randomized study.

Colloid solution is commonly used to increase the oncotic pressures of priming solutions used in the cardiopulmonary bypass circuit. To study the effectiveness of this practice, we prospectively randomized 100 adult patients undergoing cardiac operations to receive Ringer's lactate solution plus 50 gm of albumin (group A) or Ringer's lactate solution alone (group B) as the prime solution for the bypass circuit. Personnel involved in the management of these patients were blinded concerning the group to which the patients had been randomized. Forty clinical parameters related to perioperative fluid balance, cardiopulmonary function, and renal function were studied. Although group B received a larger volume of crystalloid solution intraoperatively (p less than 0.05), had a lower mean cardiac filling pressure (p less than 0.05), and had a higher hematocrit value (p less than 0.05) in the immediate postoperative period, all mean values for both groups were within the normal range. There were no differences between the two groups with regard to postoperative clinical parameters of cardiopulmonary and renal function, nor was outcome affected by the addition of albumin to the prime solution. We conclude that there is no clinically detectable advantage for the practice of adding 50 gm of albumin to the priming solution of bypass circuits in adults undergoing cardiac operations. Routinely supplementing the bypass prime solution with albumin adds significant cost, estimated to be approximately $10,000 per 100 cases, without demonstrable clinical benefits. Whether this practice can be of value in selected cases needs to be further studied.

Albumins

[Hemodynamic, coagulation and glycoregulation changes induced by brain death].

Brain death results in various changes in circulation haemostasis, acid-base balance and glycoregulation. This study was carried out between February 1988 and December 1988 in 91 patients with brain death. Age range was between 6 and 58 years. The cause of brain death was brain trauma (71%) and vascular malformations (26%). In all patients a cardio-vascular collapse occurred at the moment of brain death, requiring an intravascular loading (466.3 +/- 240.3 ml.h-1) with crystalloids and albumin. Dopamine was used in 70% of cases at the dose of 3 micrograms.kg.min-1 to improve kidney and splanchnic perfusion. No alterations of acid-base balance were observed in these patients who admitted for organ donation in a short delay (17.1 +/- 6 h). Haemostasis was modified in all patients but the alterations occurred before the brain death and were related to brain injury. Further investigations are required for a better understanding of glycoregulation changes as they could influence pancreatic transplant survival. Hormonal changes have also to be more extensively studied for possible physiopathologic causes of the variations. A better understanding of these alterations will be of benefit for management of patients in brain death and potential organ donors.

Adolescent

Plasma osmotic changes during major abdominal surgery.

Fluid balance across the capillary membrane is maintained normally by a balance of hydrostatic and colloid osmotic pressures (COP). In 12 patients having major intra-abdominal procedures, the COP was followed during the operative and immediate postoperative periods. The patients' intraoperative fluid management consisted of replacing shed blood with blood and following Shires' concept of crystalloid replacement. Significant decreases in COP to approximately two thirds of the initial value occurred in patients having intra-abdominal procedures versus only a 10 percent decrease in those having peripheral procedures (greater than .001). As a result of this decrease in COP, the balance between hydrostatic and colloid osmotic pressures is lost and risk of pulmonary intersitial edema is increased.

Abdomen

Peroperative fluid management of the brain-dead multiorgan donor.

Brain-dead organ donors are often dehydrated and have serum electrolyte disorders. This study was designed to analyse the haemodynamic condition and serum electrolyte balance of liver donors. Two different fluid management plans for the harvesting operation were studied. Sixteen consecutive organ donors were included. They were randomly infused either with a combination of colloid (hydroxy ethyl starch) and electrolyte solution (group COL) or with crystalloid fluid alone (group CR). Arterial pressures, heart rate, central venous pressure and oesophageal temperature were monitored and serum electrolytes were analysed before the beginning of the operation and during harvesting. The amount of fluid needed in the COL group was significantly less (P less than 0.01) than in the CR group. There were no statistical differences between the groups in the haemodynamic parameters during the study period. The oesophageal temperature was maintained in both groups. All donors were initially hypernatraemic, but the serum sodium values returned towards normal during surgery in both groups. Immediate function was seen in all livers. In conclusion, the haemodynamic stability is maintained with a smaller infused volume if hydroxyethyl starch is combined with crystalloid fluids. The formation of interstitial oedema will be less when colloids are used, but its significance in organ donation needs further evaluation.

Adult

Fluid therapy in the PACU.

The goal of fluid therapy in the PACU setting is the restoration of blood volume and tissue perfusion. Choosing the type of fluid infusion depends on the preoperative, intraoperative, and postoperative condition of the patient. An understanding of the functional fluid compartments, the composition of body fluids and commercially available fluids, and the steps to evaluate fluid depletion allow one to determine the fluid needs of the patient. The orderly and expedient evaluation of fluid status of the postoperative patient involves the assessment of volume status, concentration status, composition status, and signs and symptoms of inadequate tissue perfusion. Recovery after surgery is a dynamic process, and fluid reassessment should be conducted periodically. Fluid challenges may be necessary in the hypovolemic patient or in patients with clear signs and symptoms of end-organ hypoperfusion. Weil and Rackow and Shoemaker provide useful approaches to fluid challenge guided by CVP and PAP monitoring. The decision of whether to use crystalloids or colloids for fluid resuscitation is complex, controversial, often determined by personal preference and concern over expense, and may be inconsequential as long as fluids are infused appropriate to the needs of the patient. There are disadvantages and advantages to both crystalloid and colloid fluid administration. As with any therapeutic intervention, there are complications with fluid administration, congestive heart failure and pulmonary edema being of more immediate concern. Finally, blood components are colloid-type solutions that should be reserved for specific patient problems. Red blood cells are indicated to increase oxygen-carrying capacity in patients with anemia. Platelets are used to treat bleeding associated with deficiencies in platelet number or function. Fresh frozen plasma is transfused to increase clotting factor levels in patients with demonstrated deficiency. A good understanding of fluid types available, of a systematic approach to evaluating fluid depletion, and of the indications for blood component therapy will allow one to make appropriate decisions when implementing fluid therapy in the PACU.

Blood Transfusion