Fluids and Lactate. A/Prof Peter Morley

Fluids and Lactate A/Prof Peter Morley

RCTs Other evidence

Plan Background information Crystalloids Which crystalloid? Colloids Crystalloids v colloids Once that s settled, how much fluid

Fluids and fluids balance

Most of the body is water infants (75% of total body weight) young males (60%) young females (54%) elderly males (50%) elderly females (45%)

Where is the water? 2/3 in intracellular fluid (40% of body weight) 1/3 in extracellular fluid (20% of body weight) 1/4 of ECF is intravascular in plasma (5% of bw) Blood volume (including RBCs) approx 7-8% bw

Fluid requirements obligatory fluid requirement metabolism obligatory losses urine evaporation

Fluid requirements (2) amount required correlates with metabolic rate 80-110 ml/100kcal (approx. 1ml/kcal) Children 0-10 kg 0 + 100ml/kg/day 10-20kg 1000 + 50ml/kg[in excess of 10]/day >20kg 1500 + 20ml/kg[in excess of 20]/day Adults 30-40 ml/kg/day

Water balance per day input (2500 ml) oral fluids (1400 ml) food (700 ml) metabolic oxidation (400 ml) output (2500 ml) urine (1500 ml) lung (500 ml) skin (400 ml) faeces (100 ml)

Fluid requirements (3) additional fluid requirement inceased losses gastrointestinal urinary tissues/third space specific deficiencies carrier fluid for medications resuscitation

Indications for IV therapy and types of solutions used

Which route for fluid (and medication) administration gastrointestinal tract best route cheaper more physiological avoids risks of intravenous access

Risks of intravenous access infection site time in situ trauma site unwanted material air non-iv sustances restrictions mobility nursing time

When is the gastrointestinal tract inappropriate not allowed to/don t want to (nil orally) no point functional ileus mechanical obstruction anatomical resected diseased nutrients broken down red blood cells insulin etc. too slow resuscitation

N Engl J Med 2015;372:1349-58.

Types of fluid crystalloid Colloid (including blood products)

Plan Background information Crystalloids Which crystalloid? Colloids Crystalloids v colloids Once that s settled, how much fluid

Crystalloid normal saline (0.9%) Hartmanns (5% glucose)

What is in crystalloids? Normal Hartmanns 5% saline glucose Na + 150 130 0 K + 0 5 0 Ca ++ 0 2 0 Cl - 150 110 0 HCO - 3 0 30* 0 Glucose 0 0 278 mosm 300 277 278 ph 4-7 5-7 3.5-6.5 (components as mmol/l) *as lactate (d- & l-)

Crystalloid pharmacokinetics provides water and electrolytes intravascular half life 8 minutes Water/5% glucose distributes to TBW equilibrium 80mL/L NS/Hartmanns distributes to extracellular fluid volume at equilibrium 200-250mL/L intravascular

200 ml/hr N Saline means over 30 min: 100 mls given and 20-25 mls added to intravascular volume (<1%)

200 ml/hr N Saline means over 5 hours: 1000 mls given and 200-250 mls added to intravascular volume (10%)

Traditional indications for crystalloids simple replacement of losses losses crystalloid-like volume replacement not urgent

Problems with crystalloids? fluid overload inadequate resuscitation dilution oedema specific to fluid hyperglycaemia hyperchloraemia hyponatraemia

Plan Background information Crystalloids Which crystalloid? Colloids Crystalloids v colloids Once that s settled, how much fluid

Nsaline vs Hartmanns

During the control period, patients received standard intravenous fluids. After a 6-month phase-out period (August 18, 2008, to February 17, 2009), any use of chloride-rich intravenous fluids (0.9% saline, 4% succinylated gelatin solution, or 4% albumin solution) was restricted to attending specialist approval only during the intervention period; patients instead received a lactated solution (Hartmann solution), a balanced solution (Plasma-Lyte 148), and chloride-poor 20% albumin. The implementation of a chloride-restrictive strategy in a tertiary ICU was associated with a significant decrease in the incidence of AKI and use of RRT.

Among critically ill adults with sepsis, resuscitation with balanced fluids was associated with a lower risk of in-hospital mortality. If confirmed in randomized trials, this finding could have significant public health implications, as crystalloid resuscitation is nearly universal in sepsis. (Crit Care Med 2014; 42:1585 1591)

Other crystalloids? hypertonic saline hypotonic saline combinations (e.g. 4% and 1/5, plasmalyte)

Plan Background information Crystalloids Which crystalloid? Colloids Crystalloids v colloids Once that s settled, how much fluid

Colloid Gelofusin Dextrans Hydroxyethyl starches Albumin

What is in colloids? Geofusin 4% solution of succinylated gelatin Mol. Weight 30,000 Na 154 Cl 120, ph 7.1 7.7 Dextran polysaccharides fractionated into different molecular sizes 70 (M.W. 70,000), 40 (M.W. 40,000) Hydroxyethyl starches (HES) are produced by hydroxyethyl substitution of amylopectin, a D-glucose polymer, obtained from sorghum or maize

Albumin? Human albumin is a naturally occurring monodisperse colloid. Solutions (4% and 20%) are prepared from human plasma and heat treated to ensure that neither hepatitis nor HIV can be transmitted 4%: treatment of hypovolaemia 20% human albumin is used for the treatment of hypoalbuminaemia in the presence of salt and water overload (e.g. hepatic failure with ascites).

Colloid pharmacokinetics provides water and electrolytes plus additional components intravascular half life hours distributes mainly to intravascular space hypertonic solutions attract more fluid

OH S INTENSIVE CARE MANUAL

Traditional teaching about indications for colloids? volume replacement is urgent (?) specific blood products are not necessary anti-thrombotic properties desired (?) Keen to induce acute kidney injury

Problems with colloids? fluid overload inadequate resuscitation dilution allergy (oedema) renal impairment specific to fluid Hydroxyethyl starches and renal impairmet Dextrans and bleeding blood products (disease transmission, incompatible)

Blood products red blood cells plasma normal serum albumin specific components clotting factors immunoglobulins

In this multicenter, parallel-group trial, we randomly assigned patients in the intensive care unit (ICU) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less (lower threshold) or when the level was 9 g per deciliter or less (higher threshold) during the ICU stay.

N Engl J Med 2014;371:1381-91.

A large trial of transfusion strategies in older mechanically ventilated patients is feasible. This pilot trial found a nonsignificant trend toward lower mortality with restrictive transfusion practice. (Crit Care Med 2013; 41:2354 2363)

multicenter, parallel-group trial, patients older than 16 years, undergoing nonemergency cardiac surgery, 17 centers in the United Kingdom. Patients with a postoperative hemoglobin level of less than 9 g per deciliter were randomly assigned to a restrictive transfusion threshold (hemoglobin level <7.5 g per deciliter) or a liberal transfusion threshold (hemoglobin level <9 g per deciliter).

NNH = 60

Unintended consequences of fixed treatment protocols

N Engl J Med 2015;372:1410-8. Transfusion of fresh red cells, as compared with standard-issue red cells, did not decrease the 90-day mortality among critically ill adults.

Plan Background information Crystalloids Which crystalloid? Colloids Crystalloids v colloids Once that s settled, how much fluid

Summary Our systematic review of randomised controlled trials showed that, for each of these patient categories, the risk of death in the albumin treated group was higher than in the comparison group The pooled relative risk of death with albumin was 1.68 (95% confidence interval 1.26 to 2.23) and the pooled difference in the risk of death was 6% (3% to 9%) or six additional deaths for every 100 patients treated We consider that use of human albumin solution in critically ill patients should be urgently reviewed

N Engl J Med 2004;350:2247-56. In (>7000) patients in the ICU, use of either 4 percent albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days. The ratios of the volume of albumin to the volume of saline administered during the first four days were as follows: 1:1.3 on day 1, 1:1.6 on day 2, 1:1.3 on day 3, and 1:1.2 on day 4.

15L:5L 3:1 OH S INTENSIVE CARE MANUAL

N Engl J Med 2013;369:1243-51.

The structure and function of the endothelial glycocalyx layer, a web of membrane-bound glycoproteins and proteoglycans on endothelial cells, are key determinants of membrane permeability in various vascular organ systems. The integrity, or leakiness, of this layer, and thereby the potential for the development of interstitial edema, varies substantially among organ systems, particularly under inflammatory conditions, such as sepsis, and after surgery or trauma, when resuscitation fluids are commonly used. N Engl J Med 2013;369:1243-51.

In this post hoc study of critically ill patients with traumatic brain injury, fluid resuscitation with albumin was associated with higher mortality rates than was resuscitation with saline.

N Engl J Med 2014;370:1412-21. In patients with severe sepsis, albumin replacement in addition to crystalloids, as compared with crystalloids alone, did not improve the rate of survival at 28 and 90 days.

Administration of albumin compared to saline did not impair renal or other organ function and may have decreased the risk of death.

There is no evidence from randomised controlled trials that resuscitation with colloids reduces the risk of death, compared to resuscitation with crystalloids, in patients with trauma, burns or following surgery. Furthermore, the use of hydroxyethyl starch might increase mortality. As colloids are not associated with an improvement in survival and are considerably more expensive than crystalloids, it is hard to see how their continued use in clinical practice can be justified.

In (7000) patients in the ICU, there was no significant difference in 90-day mortality between patients resuscitated with 6% HES (130/0.4) or saline. However, more patients who received resuscitation with HES were treated with renal-replacement therapy.

Plan Background information Crystalloids Which crystalloid? Colloids Crystalloids v colloids Once that s settled, how much fluid

200 ml/hr N Saline means over 30 min: 100 mls given and 20-25 mls added to intravascular volume (<1%)

200 ml/hr N Saline means over 5 hours: 1000 mls given and 200-250 mls added to intravascular volume (10%)

Fluid administration Bolus 0 to 30 ml/kg Maintenance 0-200 ml/hr Time till review response minutes to hours

Inadequate response to fluids? tap not on full? plug not in consider pharmacology inotrope infusion dopamine dobutamine adrenaline titrated boluses of vasoconstrictors adrenaline metaraminol

What endpoints? blood (perfusion) pressure heart rate (and rhythm) urine output but beware vasoconstrictors decreasing oxygen delivery diuretics (including renal dose dopamine)

Peri-operative fluids?

Perioperative intravenous fluid should replace the minor physiological losses (0.5 1 ml/kg/h) and the blood loss. Fluid loss to a third space is negligible. Avoid postoperative weight gain which is a reliable marker of fluid overload. Fluid overload results in alterations in the endothelial glycocalyx resulting in fluid shift toward the interstitium, causing increased postoperative morbidity. Decreased urinary output is physiological during major surgery and not a surrogate parameter for hypovolemia alone or renal dysfunction.

Perioperative fluid management of the colorectal surgical patient has evolved significantly over the last five decades. Older notions espousing aggressive hydration have been shown to be associated with increased complications. In the preoperative phase, data suggests that avoidance of preoperative bowel preparation and avoidance of undue preoperative dehydration can improve outcomes. Although the type of intraoperative fluid given does not have a significant effect on outcome, data do suggest that a restrictive fluid regimen results in improved outcomes. Finally, in the postoperative phase of fluid management, a fluid-restrictive regimen, coupled with early enteral feeding also seems to result in improved outcomes.

We recommend that both perioperative fluid choice and therapy be individualized. Patients should receive fluid therapy guided by predefined physiologic targets. Specifically, fluids should be administered when patients require augmentation of their perfusion and are also volume responsive.

Trauma?

NEJM 1994; 331: 1105-9

Aggressive volume resuscitation of patients with raaas before proximal aortic control predicted an increased perioperative risk of death, which was independent of systolic blood pressure. Therefore, volume resuscitation should be delayed until surgical control of bleeding is achieved. J Vasc Surg 2013;57:943-50.

What about sepsis? What is Early Goal Directed Therapy

N Engl J Med 2001;345:1368-77

N Engl J Med 2014;371:1496-506.

N Engl J Med 2015;372:1301-11.

We randomly assigned children with severe febrile illness and impaired perfusion to receive boluses of 20 to 40 ml of 5% albumin solution (albumin-bolus group) or 0.9% saline solution (saline-bolus group) per kilogram of body weight or no bolus (control group) at the time of admission to a hospital in Uganda, Kenya, or Tanzania (stratum A); children with severe hypotension were randomly assigned to one of the bolus groups only (stratum B). Fluid boluses significantly increased 48-hour mortality in critically ill children with impaired perfusion in these resource-limited settings in Africa.

Theoretically, colloids, containing suspensions of molecules with a molecular weight that makes them relatively impermeable to an intact capillary membrane, are retained within the intravascular compartment. Most of the evidence for the potential adverse effects of saline comes from observational studies comparing the effects of chloride-rich and chloride restricted solutions, such as buffered or balanced salt solutions, in cohorts of acutely ill patients. Saline is associated with a significant increase in mortality and use of renal replacement therapy in patients in ICU [45] and in those with sepsis [46], as well as a significant increase in major complications in patients undergoing surgery [47].

Plan Background information Crystalloids Which crystalloid? Colloids Crystalloids v colloids Once that s settled, how much fluid

Lactate It s all about the clearance

Lactic acidosis normal production is 20 mmols/kg/day, 70 kg:1400/day, 60/hr hepatic and renal metabolism Cohen & Woods classification type A = inadequate delivery of oxygen to meet requirements eg. seizures, cardiac arrest, hypoxia type B = no obvious defect in oxygen delivery eg. thiamine deficiency, biguanides, adrenergic

N Engl J Med 2014;371:1434-45.

N Engl J Med 2014;371:2309-19.

Normal N Engl J Med 2014;371:2309-19.

Tissue hypoxia N Engl J Med 2014;371:2309-19.

(Stimulated) Aerobic glycolysis

Aerobic glycolysis = stimulated glycolysis that depends on factors other than tissue hypoxia Activated in response to stress, an effective, albeit inefficient, mechanism for rapid generation of ATP. Epinephrine, β2 -adrenergic agonists, extensive trauma, cardiogenic or hemorrhagic shock, and pheochromocytoma, can cause hyperlactatemia through this mechanism Inflammatory states, can also drive aerobic glycolysis by cytokine-dependent stimulation of cellular glucose uptake Note: Aerobic glycolysis and tissue hypoxia are not mutually exclusive

In severe sepsis patients with hemodynamic stability, reflected by optimized baseline CVP and ScvO2, the bundle items of fluid bolus administration, achieving MAP >65 mmhg, and lactate clearance were independent predictors of outcome.

The addition of BD and lactate to triage vital signs increases the ability to distinguish major from minor injury.

Lower serum lactate levels at 12 h and 24 h, but not initially following cardiac arrest, are associated (on multivariate analysis) with survival to hospital discharge after resuscitation from CA and TH treatment.

Electrolytes: Lactate A guide to diagnostic Clinical Biochemistry Walmsley & White 1988

Electrolytes: Lactate 28 year old male admitted in status epilepticus second sample 3 hours after last convulsion A guide to diagnostic Clinical Biochemistry Walmsley & White 1988

Plan Background information Crystalloids Which crystalloid? Colloids Crystalloids v colloids Once that s settled, how much fluid

Lactate It s all about the clearance

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