Volume replacement with a new

balanced crystalloid solution

Fluids in the ICU, 21 Nov 2019, 16.30-16.50

Chairs: I. Tsangaris

ATHENA 2019 International Conference

19-21 November 2019, Divani Caravel Hotel, Athens, Greece

Pavlos M. Myrianthefs

Professor, Pulmonary & Critical Care

General Hospital of Kifissia, Greece

Disclosure - Conflict of Interest

• In the last five years I received honoraria

for educational lectures/activities from

Baxter, Norma Hellas, Chiesi Hellas,

Astellas Pharma, Pfizer & MSD

Principles of Fluid Therapy

• Most (all) ICU patients receive fluids

– replace free water, electrolytes, glucose, and plasma

constituents (e.g., albumin) loses

– increase intravascular volume

• absolute hypovolemia (resulting from blood loss, diarrhea,

decreased oral intake) or

• effective hypovolemia (increased venous capacitance

resulting from sepsis, medications, adrenal insufficiency)

• In order to increase ventricular preload, cardiac

output, restoring hemodynamic stability, tissue

perfusion and DO2

Semler MW et al • Principles of Fluid Therapy • Ch 59 In: Crit Care Nephr • 3rd Edition • 2019, pp 350-355

Fluid administration: a paradigm shift

• Changing from the administration of large volume (>2 L) and rates to a more targeted and personalised approach.

– Messina A et al. Fluids in shock. ICU Management and Practice 2018; 18(3):154-157

• Recognition of the potential harm according to the type, the volume of fluid and the duration of administration

– Rewa O et al. Principles of Fluid Management. Crit Care Clin 2015; 4:785-801 – Morgan TJ. The ideal crystalloid – what is ‘balanced’? Curr Opin Crit Care 2013;

19:(4):299-307

• Serious side effects include: hyperchloraemic acidosis, electrolyte disturbances, renal dysfunction - AKI, RRT need, glycocalyx layer disruption - edema, death

– Malbrain MLNG et al. Principles of fluid management and stewardship in septic shock. Ann. Intensive Care 2018; 8:66

Recent concepts/knowledge

• Fluids should be considered as a drug, and administered after testing preload dependencyand with continuous evaluation of preload dependency/CO response

– Messina A et al. Fluids in shock: fluid management during shock from physiology to bedside. ICU Management and Practice. 2018; 18(3): 154-157

• Recognition that until recently fluid administration was based on physiological principles (e.g. MAP) rather than on evidence from clinical trials

– Myburgh J. Patient-Centered Outcomes and Resuscitation Fluids. NEJM 2018;378(9): 862-863

Fluid management: the paradigm of

antibiotics: fluid stewardship initiative!

• The 4 D’s concept of

fluid therapy

• A conceptual

framework looking at

fluids as drugs (like

antibiotics):

– Drug selection (type)

– Dosing

– Duration and

– De-escalation

• ROSE concept: 4

different phases/

stages in the time-

course of shock

management

– Resuscitation

– Optimization

– Stabilization and

– Evacuation

Malbrain et al. Ann. Intensive Care (2018) 8:66

Fluids in the ICU: indications and volume

status during different phases of shock

• Maintenance: daily requirements

• Replacement of daily ongoing loses

• Resuscitation to restore intravascular volume (shock states)

Hoste E.A et al, Brit J Anaesth 2014; 113 (5): 740–7

different stages of resuscitation and fluid

management

Hoste E.A et al, Brit J Anaesth 2014; 113 (5): 740–7

20-30 mL/kg of IV

crystalloid in the

form of fluid

boluses.

clinical data, including hemodynamics, urine

output, and static or dynamic predictors of

“fluid responsiveness” : Fluid Challenge, PLR,

PPV, EEOT

net even fluid balance

fluid mobilization,

fluid removal during

recovery, diuretics

Fluid administration: continuous evaluation of

preload dependency/CO response

• Fluid challenge test may lead to futile fluid administration (needless fluid overload)

– Cecconi M, et al. Fluid challenges in ICU: the FENICE study. ICM 2015; 41(9): 1529-37.

Rewa O et al. Principles of Fluid Management. Crit Care Clin 2015; (4):785-801

End-Expiratory

Occlusion Test

PPV

PLR

EEOT

Updated questions regarding fluids

administration: when to B start & stopB

• “When to start intravenous fluids?”

• “When to stop intravenous fluids?”

• “When to start de-resuscitation or activefluid removal?” and

• “When to stop de-resuscitation?”

Malbrain MLNG et al. Principles of fluid management and stewardship in septic shock. Ann. Intensive Care

(2018) 8:66

4 D’s: focus on “drug selection”

• Data from RCTs showed that the type of solution for a given patient at a given time, may adversely affect patient – centered outcomes (morbidity & mortality):– Osmolality, tonicity, pH, electrolyte composition (Cl-, Na+, P+,

Ca++, Mg++ etc.)

– Levels of other metabolically active compounds (lactate, acetate, malate, etc.)

– Clinical factors (co-morbidity - underlying conditions, kidney or liver failure, presence of capillary leak, acid–base equilibrium, albumin levels, fluid balance, etc.)

– Indications (resuscitation, maintenance, replacement) & Contraindications

– Toxicity: metabolic acidosis and acute kidney injury

Myburgh J et al, Resuscitation Fluids. N Engl J Med 2016;369;13

Malbrain MLNG et al. Principles of fluid management and stewardship in septic shock. Ann.

Intensive Care 2018; 8:66

IV solutions

• What are IV solutions?

– Chemically-prepared solutions used to

replace lost fluid volume, molecules &

deliver medication through the IV route

• Different IV solutions have different

actions within the body

– These properties depend on how the solution

is manufactured and the specific materials it

contains

Benner RW, Drake JW (eds). Chapter 3, Intravenous Fluid Selection. In: IV therapy for EMS.

Pearson Prentice Hall; 2005.

Treatment Choices for Fluid

Management: types of solutions

• Crystalloid– Unbalanced

• Sodium Chloride 0,9%

• Glucose 5%

– Balanced• Plasmalyte

• Ringer’s-Lactate

• Ringer’s-Acetate

• Hartmann’s

• Colloids

– Natural

• Albumin 5, 20, 25%

• Blood products /plasma

– Semi-Synthetic

• HES

• Dextrans

• Gelatins 3, 3.5, 4%

different fluids, different indications, different action,

different side effects

Van Zundert AAJ, et al., Volume Therapy. Is there a colloideal solution? Anaesthesia 2007; 9(1):43-57

Myburgh JA, et al, N Engl J Med 2013;369:1243-51

Significant differences in composition among different fluid

supposed advantage of colloids over

crystalloids

• Colloids are composed of large molecules designed to remain in the intravascular space for several hours, increasing plasma osmotic pressure and reducing the need for further fluids.

– Messina A et al. ICU Management and Practice. 2018; 18(3): 154-157

– The volume-sparing effect of colloids, as compared with crystalloids, is considered to be an advantage (?), which is described in a 1:3 ratio of colloids to crystalloids to maintain intravascular volume

– Myburgh J et al. N Engl J Med 2016;369;13

• Subsequent studies challenged this concept in sepsis, where alterations in glycocalyx & endothelial permeability may lead to extravasation of colloid’s large molecules, abolishing their advantage.

– Brunkhorst FM, et al. N Engl J Med 2008; 358(2): 125-39.

– Malbrain et al. Ann. Intensive Care (2018) 8:66

revised Starling equation for the endothelial glycocalyx

layer model of transvascular fluid exchange

• Intact glycocalyx layer – When capillary pressure (transendothelial pressure gradient) is low,

as in hypovolemia or sepsis and septic shock, or during hypotension (anaesthesia induction), albumin or plasma substitutes have noadvantage over crystalloid, since they all remain intravascular

• Disrupted glycocalyx layer – The glycocalyx layer is a fragile structure and is disrupted by

surgical trauma - systemic inflammation or sepsis, but also by rapid infusion of fluids (e.g. saline). Thus, there is an increasedtranscapillary flow, albumin leakage and risk of tissue oedema

– Woodcock TE, et al. Revised Starling equation and the glycocalyx model of transvascular fluid exchange. Br J Anaesth 2012; 108:384–394.

• Thus, interstitial expansion – tissue and organ oedema – is neither eliminated nor even reduced by colloids

– Malbrain MLNG et al. Ann. Intensive Care 2018; 8:66

– James MF, et al. the FIRST trial. Br J Anaesth 2011; 107:693–702.

What is the best fluid for my critically ill

patient?

How Intensivists select fluid in acute

resuscitation ?

• No guidelines available

• the choice of fluid used waslargely dictated by regional orlocal institutional practiceand individual providerpreferences rather than guided by high qualityevidence from RCTs

– Raghunathan K, et al. Choice of fluid in acute illness: what should be given? Br J Anaesth2014;113(5):772–83.

colloid solutions 48%

crystalloid solutions 33%

blood products 28%

What do we need to know: semi-synthetic

colloids

• Starch-based colloids are linked to renal injury - AKI,RRT needs and excess blood product requirementsplus an increased mortality rate in severe sepsis

– Myburgh JA, et al. N Engl J Med 2012; 367:1901–1911.

– Brunkhorst FM, et al. N Engl J Med 2008; 358:125–139.

– Perner A, et al. N Engl J Med 2012; 367:124–134.

• Dextrans, Gelatine-based fluids are related to renal toxicity

– Bayer O, et al. Crit Care Med 2012; 40:2543–2551.

– Mahmood A, et al. Br J Surg 2007; 94:427–433.

• Hydroxyethyl starches (HES) are contraindicated and thus abandoned in case of septic shock, burns, patients with acute or chronic kidney injury or in case of oliguria not responsive to fluids (within 6 h)

– Rhodes A, et al. Surviving sepsis campaign, 2016. Intensive Care Med2017;43(3):304–77.

What do we need to know: natural

colloids

• Colloids vs. Crystalloids

• In an heterogeneous ICU patients population, the use of either 4% albumin or N/S 0,9% for fluid resuscitation results in similar outcomes at 28 days

• Safety and costs should be further evaluated

The SAFE Study N Engl J Med 2004; 350:2247-2256

A Comparison of Albumin and Saline for

Fluid Resuscitation in the Intensive Care

Unit

Fluid resuscitation in TBI: natural

colloids

• In this post hoc study of critically ill patients with TBI, fluid resuscitation with albumin was associated with higher mortality rates than was resuscitation with saline and thus should be avoidedin this group

The SAFE Study Investigators. N Engl J Med 2007; 357:874-884

probability

of survival

at 28 days

probability

of survival

at 24

months

What do we need to know: indications for

natural colloids – albumin

• It is justified – reasonable to use albumin as a

resuscitation fluid in patients with hypoalbuminemia

– Rhodes A, et al. Surviving sepsis campaign. 2016.

Intensive Care Med. 2017;43(3):304–77.

– Caironi P, et al. Albumin replacement in patients with

severe sepsis or septic shock. N Engl J Med.

2014;370(15):1412–21.

• The safer indication for albumin use in shock is in

patients with liver failure

– Salerno F, et al. Albumin infusion improves outcomes of

patients with spontaneous bacterial peritonitis. Clin

Gastroenterol Hepatol 2013; 11(2): 123-30.e1.

Colloids vs. Crystalloids

• In hypovolemia or sepsis and especially septic shockor during hypotension (anaesthesia induction), albuminor plasma substitutes have no advantage over crystalloid infusions, since they all remain intravascular.

– Malbrain MLNG et al. Principles of fluid management and stewardship in septic shock. Ann. Intensive Care 2018; 8:66

• In general, balanced crystalloids are the most promising fluids in patients in shock over saline while semi-synthetic colloids should be definitively abandoned in septic shock, burns, acute or chronic kidney injury, or oliguria not responsive to fluids

– Rhodes A, et al. Surviving Sepsis Campaign. 2016. Intensive Care Med 2017; 43(3):304-77.

– Messina A et al. Fluids in shock. ICU Management and Practice. 2018; 18(3): 154-157

Colloids vs. Crystalloids

• Cost is another big issue for natural colloids

• Hospital prices in Greece – price bulletin

• Colloids

– 100 ml HA 200 g/L 50 ml = 27,29 €

– 100 ml HA 200 g/L 100 ml = 45,89 €

• Crystalloids

– N/S 0.9% 1000 ml = 0,97 €

• Ringers lactated 1000 ml = 1,02 €

• Plasmalyte 1000 ml = 1,64 €

The Crystalloid battle!

• Unbalanced

solutions

– Sodium Chloride 0,9%

– Glucose 5%

• Balanced solutions

– Plasmalyte

– Ringer’s - Lactate

– Ringer’s - Acetate

– Hartmann’s

Myburgh JA, et al. N Engl J Med 2013;369:1243-51

Significant differences

in electrolyte

composition

Significant differences in metabolically

active compounds and SID

• Plasma, SID = 40 mmol/L

Osmolality, tonicity, pH,

Morgan JT, The ideal crystalloid – what is ‘balanced’? Curr Opin Crit Care 2013;19(4):299-307

Question: Is Normal saline normal??

• Sodium = 154 mmol/L (9 g/L)

• Chloride = 154 mmol/L

• pH = 5.5

• Osmolarity = 308 mOsm/L

• SID = 0 mmol/L

• serum ≈ 135 - 145

• serum ≈ 94 - 111

• serum ≈ 7.40

• serum ≈ 385

• serum ≈ 40

Blumberg N et al. 0.9% NaCl – Perhaps not so normal after all? Transfusion and Apheresis Science 2018; 57:127–131

Crystalloids: N/S 0.9%adverse events

• Hyperkalemia due to concomitant metabolic acidosis secondary to a reduced SID despite it does not contain potassium

– Khajavi MR, et al. Renal failure, 2008; 30(5):535-9.

– Langer T, et al. Anaesthesiol Intensive Ther, 2015; 47 Spec No:78-88.

• Fluid-induced chloride loading/ hyperchloremia and worse outcomes, probably due to an impact on renal function

– Chowdhury AH, et al. Ann Surg 2012;256(1):18–24.

– Yunos NM, et al. JAMA 2012;308(15):1566–72.

– Young JB, et al. Ann Surg 2014;259(2):255–62.

• In large amounts it carries the risk of iatrogenic hypernatremic hyperchloremic normal anion gapmetabolic acidosis, AKI and death.

– Semler MW, et al. N Engl J Med, 2018; 378(9):829-39.

Plasma base-excess, and chloride, before and after

infusion of 30 ml/kg of 0.9% saline or Plasmalyte in

healthy adult volunteers

Base-excess 2.5 mM more negative

in saline. Greater metabolic

acidosis

Mean difference 5.4 mM more

chloride. Greater

hyperchloremia

Story DA et al., Cognitive Changes after Saline or Plasmalyte Infusion in Healthy Volunteers,

Anesthesiology 2013; 119 (3): 560-575

In healthy volunteers, 0.9% sodium chloride

increased adverse renal effects vs. Plasma-Lyte1

In a randomized, controlled, double-blind crossover

study in healthy volunteers, 0.9% sodium chloride

administration was associated with:

• Hyperchloremia

• Adverse effects on the kidney

o Decreased renal blood flow velocity, cortical tissue

perfusion, and urine volume

o Delay in time to first micturition

o Increase in weight and fluid retained in interstitial

compartment

Chowdhury AH et al. Ann Surgery 2012 ;256(1):18–24.

Time to first micturition

(p=0.006)

Total urine volume

(p=0.002)

Plasma-Lyte 90 min 833 mL

0.9% sodium chloride 142 min 533 mL

Charts adapted from Chowdhury et al.

Annals of Surgery July 2012, 256(1): 18-24

Chloride-Liberal vs. Chloride-Restrictive

Intravenous Fluid Administration

• Single center, 6 months before-and-after study

• Chloride-rich fluids (0.9% saline, 4% gelatin, or 4% HA) were made available only after prescription by the attending specialist for specific conditions vs. Hartmann & Plasma-Lyte148 solutions

• Restricting IV chloride intake was associated with a significant decrease in the incidence of AKI and the use of RRT

• Saline prescription decreased from 2411 L to 52 L (3.2 vs. 0.06 L/patient; P.001)

Development of Stage 2 or 3 AKI

Renal Replacement Therapy

Yunos NM, et al. JAMA. 2012;308(15):1566–72.

Chloride Liberal Fluid are associated with

greater risk of AKI & RRT

Yunos et al Intensive Care Med 2015;41:257-264

• Prospective, open-label, Single center sequential period pilot study

• Chloride-liberal vs. chloride-restrictive IV fluid administration

RRTAKI

0.9% NaCl vs.

Plasma-Lyte

• RCT, 46 adult trauma patients

• Examining change in base excess, pH, serum electrolytes, fluid balance, resource utilization, and in-hospitalmortality.

Young JB et al. Saline vs. Plasma-Lyte A in initial resuscitation of trauma patients. Ann Surg 2014;259(2):255–62

0.9% NaCl, vs. Plasma-Lyte APlasma-Lyte had

Young JB et al. Saline vs. Plasma-Lyte A in initial resuscitation of trauma patients. Ann Surg2014;259(2):255–62.

More patients required

Mg++ supplementation in

the N/S 0.9% group.

faster correction of

base excess status less hyperchloremia

faster stabilization

pH status

Balanced crystalloids vs. saline critically

ill adults

• RCT, 5 ICUs at an academic center, 15,802 adults assigned to receive N/S 0.9% or balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A)

• the use of balanced crystalloidsfor I.V. fluid administration resulted in a lower rate of– the composite outcome of death from

any cause,

– new renal-replacement therapy,

– persistent renal dysfunction than the use of saline.

Semler MW, et al. Balanced crystalloids versus saline in critically ill adults. the SMART study. N Engl J Med 2018;378(9):829–39.

Subgroup Analysis of Rates for the Composite

Outcome of Death, New Receipt of RRT, or Persistent

Renal Dysfunction

Semler MW, et al. Balanced crystalloids versus saline in critically ill adults. the SMART study. N Engl J Med2018;378(9):829–39.

Balanced fluids were associated with lower in-

hospital mortality in patients with sepsis1

A retrospective database cohort study of 53,448 sepsis patients in ICU by hospital Day 2

Raghunathan K, et al. Crit Care Med 2014;42:1585-91.

Sepsis patients receiving greater balanced fluid proportions were observed to have

progressively lower in-hospital mortality.

95% Cl Adjusted Mortality (Marginal Fixed Effects)

0% 20% 40% 60% 80% 100%

Absolu

te In-H

ospital M

ort

alit

y

Total fluid that is balanced by day 2

24%

20%

16%

12%

8%

4%

0%

Based on the propensity matched cohort of 6,730 (3,365 balanced fluids group, 3,365 no balanced fluids group)

Hyperchloremia was associated with increased

morbidity and mortality after non-cardiac surgery1

A retrospective observational study

comparing 30-day mortality patients

with post-operative hyperchloremia

vs. those with normal chloride

22,851 surgical patients

• The hyperchloremia group had longer

length of stay (LOS): 7.0 days vs. 6.3 days

(p<0.01)

• More likely to have risk of post-operative

renal dysfunction: 12.9% vs. 9.2%

(p<0.01)

McCluskey SA et al. Anesth Analg 2013;117(2):412–21.

0,0%

0,5%

1,0%

1,5%

2,0%

2,5%

3,0%

3,5%

4,0%

Acute Post-OpHyperchloremia

Normal chloride

*p<0.01

**

Note: The cause of post-op hyperchloremia was not

determined in this study; infusion fluids were not analyzed.

30-Day mortality

Entire cohort

n=22,851

Matched cohort

n=8532

Acute postoperative hyperchloremia

(serum chloride >110 mmol/L) is

common, with an incidence of 22%. (RR 1.6 or risk increase of 1.1%)

Hyperchloremia was associated with

increased risk of mortality1

Retrospective observational study in non-cardiac surgery

McCluskey SA et al. Anesth Analg 2013;117(2):412–21.

There is a linear increase in the probability of mortality between 100 and 125 mmol/L

in both before and after propensity-matched cohort.

Spline function graph of the probability of dying within 30 days of surgery and the postoperative maximum

serum chloride concentration on postoperative day 1 or day 2. A, Unadjusted figure. B, Adjusted by

propensity match.

EUMP/MG37/16-0005

February 2017

Plasma-Lyte may reduce morbidities vs. 0.9%

sodium chloride1

Retrospective cohort study; 3:1 propensity match

• Patients undergoing major abdominal surgery receiving only 0.9% sodium

chloride (N=2778) or Plasma-Lyte (N=926) on day of surgery (N=3704)

*Major morbidity: respiratory failure, cardiac complications, major gastrointestinal dysfunction, infectious complications, and acute renal failure. †Minor complications: minor gastrointestinal dysfunction and electrolyte disturbances.

Primary endpoint: Major morbidity, defined as one or more major complications (P<0.001).*

Secondary endpoints: Minor complications† (P<0.05), acidosis-related tests (P<0.001), 30-day

re-hospitalization (P=0.39).

Mortality

Gastrointestinal

Renal

Cardiac

Respiratory

Major hemorrhage

Major infection

Composite

Favors balanced crystalloid Odds ratio Favors 0.9% sodium chloride

0.1

Matched propensity

cohort

1 10

Shaw AD et al. Major complications, mortality, and resource utilization after open

abdominal surgery: 0.9% saline compared to Plasma-Lyte. Ann Surg 2012; 255(5):821–9.

Reduced resource utilization associated

with Plasma-Lyte vs. 0.9% sodium chloride1

Patients receiving Plasma-Lyte needed• Less acidosis management (arterial blood gases & lactic acid)

• Less blood transfusion

• Less dialysis (4.8 times less)

In addition:• Less volume infused

Shaw AD et al. Major complications, mortality, and resource utilization after open

abdominal surgery: 0.9% saline compared to Plasma-Lyte. Ann Surg 2012; 255(5):821–9.

Propensity matched cohort Balanced fluid N=926

Normal 0.9% sodium chloride

N=2,778

*p<0.05

+p<0.001

Incid

en

ce (

%)

Buffers Blood transfusion ABG Lactic acid Dialysis

*

+

+

+

+

Effects of high- vs. low-chloride fluids for

perioperative and critical care resuscitation

• Meta-analysis assessing endpoints in patients receiving

isotonic or near isotonic crystalloids for replacement or

resuscitation

– High-chloride crystalloids (unbalanced - saline) were

associated with a significantly increased

• Risk of AKI/renal failure (RR 1.64, 1.27–2.13; p<0.001)

• Risk of hyperchloremia/metabolic acidosis (RR 2.87, 1.95–4.21; p<0.001)

• Blood transfusion volume (Standardized Mean Difference [SMD]

0.35, 0.07–0.63; p=0.014)

• Mechanical ventilation time (SMD 0.15, 0.08-0.23; p<0.001)

• High-chloride fluids did not affect mortality

Krajewski ML et al. Meta-analysis of high- versus low-chloride content in perioperative and

critical care fluid resuscitation. Br J Surg 2015;102(1):24–36.

balanced solutions vs. saline

• The use of balanced solutions may avoid complications

associated with saline.

• Balanced solutions have theoretical advantages that

should be compared with the risk of hyperchloraemic

acidosis after large volume resuscitation with normal

saline.

• Consequently, balanced solutions are probably the

best choice as a first-line fluid therapy in patients with

shock

– Messina A et al. Fluids in shock. ICU Management and Practice.

2018; 18(3): 154-157

Are all the balanced solutions are the

same?• Bicarbonate

• Electrolyte composition

• Metabolically active compounds

• Advantages of acetate (Plasmalyte) over lactate (R/L)

• Prospective randomized study in 104 living donors undergoing right hepatectomy

• The use of LR solution results in poorer immediate post-operative lactate and liver profiles (pH, BE, Lactate, Bilirubin, Albumin, PT).

• Plasmalyte may be more desirable than LR solution in donors requiring administration of large volumes of fluid or those with small anticipated remnant livers.

Shin WJ et al . Acta Anaesthesiol Scand 2011; 55: 558–564

Plasma-Lyte maintained lactate levels vs.

Hartmann’s/Lactated Ringer’s (LR)

0.9% sodium chloride

LR

Plasma-Lyte2.0

1.5

1.0

0.5

0.0

0 30 60 90 End

Time

Lacta

te (

mM

/L)

Chart adapted from Hadiomioglu N et al. Anesth Analg 2008, 107:264–9.2

Baseline Post-operative

PL HS p-value PL HS p-value

Lactate (mmol/L) 0.97 (0.41) 1.1 (0.45) 0.20 1.9 (1.13) 2.9 (1.76) 0.02

Charts adapted from Chowdhury et al.

Annals of Surgery July 2012, 256(1): 18-24

Chart adapted from Shin WJ et al. Acta Anaes Scand 2011, 55:558–64.3

Ind End 3-hr POD 1 POD 2

Lacta

te (

mm

ol/l)

*

LR group

Plasma-Lyte group

Lactate change

8

6

4

2

0

LR significant, progressive increase in lactate levels

during kidney transplantation2

Associated with poorer immediate post-operative lactate

and liver profiles in living donor right hepatectomy3

Chart adapted from Weinberg L et al. Minerva Anestesiol.2015;81:1288–97.4

Initial post-operative lactate levels have been reported to predict morbidity, mortality & outcomes.

Lactated Ringer’s has been associated with elevated serum lactate levels compared with Plasma-

Lyte.2,3

1. Fuller BM, Dellinger RP Curr Opin Crit Care. 2012;18(3):267–72. 2. Hadiomioglu N et al. Anesth Analg 2008;107:264-9. 3. Shin WJ

et al. Acta Anaesthesiol Scand 2011;55:558-64. 4. Weinberg L et al. Minerva Anestesiol.2015;81:1288–97.

Elevated lactate levels in several patient types may indicate: 1) higher mortality1 2) patients at higher risk of worse outcome1

Plasma-Lyte maintained lactate levels vs. Hartmann’s1

Multicentre, prospective, double blind, randomized controlled

trial in 60 major liver resection patients.

Weinberg L et al. Minerva Anestesiol. 2015;81:1288–1297.

Charts adapted from Chowdhury et al. Annals of Surgery. 2012;256(1):18–24.2

Plasma-Lyte Hartmann’s p value

MAJOR COMPLICATIONS

Sepsis 1 (3%) 2 (7%) n/a

Myocardial infarction 0 4 (13%)

MINOR COMPLICATIONS

Superficial wound infection 1 (3%) 1 (3%)

Post-operative ileus delaying discharge 0 (0) 3 (10%)

Pneumonia 0 2 (7%)

Pulmonary congestion 1 (3%) 4 (13%)

Pneumothorax 1 (3%) 0

Cardiac arrhythmias 2 (7%) 3 (10%)

PATIENT OUTCOMES

No. of patients with a minor or major complication 6 (20%) 17 (56%) 0.007

Length of hospital stay days (median) 5.9 7.8 0.04

Hospital death within 30 days of surgery 0 2 (7%) 0.49

Potential to reduce complications in liver resection patients receiving

Plasma-Lyte vs. Hartmann’s solution.

Hartmann’s sol. vs. Plasmalyte 148

• Patients receiving Plasmalyte had similar acid base status to Hartmann’s solution but developed less hyperlactatemia and hyperchloremia, and had higher plasma magnesium and lower ionized calcium levels.

• Thus, Plasmalyte, may improve the practice of physiologically optimal fluid selection for major liver resection

– Weinber L et al The effects of plasmalyte-148 vs. Hartmann’s solution during major liver resection: a multicentre, double-blind, randomized controlled trial. Minerva Anestesiol 2015;81:1288-97)

Are these data are translated into clinical

practice? YES!

• Global patterns of fluid resuscitation

• International, cross-sectional study, ≈ 400 ICUs

• 1/5 of patients in the ICU received I.V. resuscitation fluid

Hammond NE et al. Patterns of intravenous fluid resuscitation use in adult ICU patients between 2007 and 2014:

An international cross-sectional Study. PLoS One 2017;12(5):e0176292

changing pattern: Trends in fluid resuscitation

practices, 2007 vs. 2014

• Crystalloid use, predominantly buffered salt solutions, has significantly increased while colloid use has decreased, due to decreased use of HES

Hammond NE et al. Patterns of intravenous fluid resuscitation use in adult ICU patients between 2007 and 2014:

An international cross-sectional Study. PLoS One 2017;12(5):e0176292

buffered

salt

solutions

Characteristics of Plasmalyte solutiona physiologically balanced crystalloid (pH: 7.4)

• Osmolarity: 294 mOsm/L

• Na+: 140 mmol/L

• K+: 5 mmol/L

• Cl-: 98 mmo/L

• Mg++: 3 mmol/L

• Ca++: 0 mmo/L

• Acetate: 27 mmol/L

• Gluconate: 23 mmol/L

• Lactate: 0 mmol/L (hepatic dysfunction/deficiency)

• SID = 50 mmol/L

1.Shaw AD et al. Ann Surg 2012;255:821

2.Yunos et al. ICM 2015;41:257-269

3.McCluskey et al. Anesth Analg 2013;117:412–

21

4. Chowdhury AH et al, Ann Surg.

2012;256(1):18–24.

5.. Hadimioglu Anesth Analg 2008; 107(1): 264-

269.

Characteristics of Plasmalyte solution?a physiologically balanced crystalloid (pH: 7.4)

• It is similar to physiological plasma

• Better safety profile: – Does not lead to hyperchloremic

metabolic acidosis 1,5

– Reduces the likelihood of postoperative major or minor complications & mortality 1,3,4

– Reduces the risk of AKI, RRT needs

• No calcium, compatible with blood transfusion

• No interference with blood lactate diagnostics (bias)

• Clinically studied solution (trials)

1.Shaw AD et al. Ann Surg 2012;255:821

2.Yunos et al. ICM 2015;41:257-269

3.McCluskey et al. Anesth Analg 2013;

117:412–21

4. Chowdhury AH et al, Ann Surg. 2012;

256(1):18–24

5. Hadimioglu Anesth Analg 2008; 107(1): 264-

269

Plasmalyte indications/place in the ICU a physiologically balanced crystalloid (pH: 7.4)

• Finding a place for a crystalloid I.V. solution, Plasmalyte

• Resuscitation– Septic or Haemorrhagic shock and clinical conditions requiring

rapid blood transfusions

• Replacement of daily ongoing loses (drains or stomata, fistulas, hyperthermia, open wounds, polyuria)• To restore fluid balance e.g. after burns, head injury, fracture,

infection, peritoneal irritation

– Mild to moderate metabolic acidosis, even in case of lactate metabolism impairment

– Intraoperative fluid replacement

• Maintenance: daily basal requirements in water and electrolytes (GI, renal & insensible loss, 25–30 mL/kg of body weight, 1 mmol/kg K+, 1–1.5 mmol/kg Na+ per day)

Plasma-Lyte SPC, 2013.

Conclusions for Plasmalytea physiologically balanced crystalloid (pH: 7.4)

• There is a large amount of knowledge based on trials suggesting that Plasmalyte is a: – safe,

– effective I.V. solution

– minimal side effects and

– has comparative advantages due to its balanced composition (electrolytes, acetate, gluconate, osmolarity, SID)

– Similar costs (less volume required)

• having specific indications that can be easily used in everyday clinical practice as a part of personalized medicine to add on existing crystalloids

Thank you very

much!!