Ringers Acetate Solution

In Clinical Practice

Dr Iyan Darmawan Medical Department, PT Otsuka Indonesia

Background
IV therapy is one of most crucial aspects of patient care NS -----------> hypovolemia w/ concomitant hyponatremia, hypochloremia or metabolic alkalosis N2/D5---------> maintenance to replace IWL RA -------------> best approximates ECF

.
RESUSITASI RUMATAN

Kristaloid
Asering RL/NS

Koloid
Dextran Gelatin

Elektrolit
KAEN

NUTRISI

Repair
Mengganti kehilangan akut (hemorrhage, GI loss, rongga ke3) 1. Kebutuhan normal (IWL + urin+ feses) 2. Dukungan nutrisi

Survey Pemakaian infus di Ruang Perawatan Interna Maret 2003 *

3% % 17 9% 5% 6%

RL Asr KAEN

9%

% 10

D-NS Dextr NS AA Other

% 41

*) Widi Astuti, dkk.Data Survey NCE 2003

Total 35 RS, 56 ruangan (int) * Data : Survey NCE Total 28 RS,29 ruangan (ped)

.
.

Ringer Asetat
USA EROPA,UK JEPANG THAILAND

ASERING

COMPOSITION(in mmol/L)
Ringers Aeetate Plasma

Na + K+ ClCa++ Asetat-

130 4 109 2,7 28

135-145 3.5- 5 95-105 1.1-1.15 22-26

LACTATE VS. ACETATE

Na Lactate Bicarbonate
100 mEq/hr

Na Acetate

Bicarbonate
250-400 mEq/hr

LACTATE VS. ACETATE

C2H3O2- + 2O2 ( Acetate ) C3H5O3- + 3O2
( Lactate )

CO2 + H2O + HCO32CO2 + 2H2O + HCO3-

METABOLISME
1. SODIUM LAKTAT ( HATI )
CH3CH(OH)COONa + CO2 +H2O CH3CH(OH)COOH + 3 O2 NaHCO3 + CH3CH(OH)COOH ( Laktat ) 3 CO2 + 3 H2O : TCA Cycle

2. SODIUM ASETAT ( OTOT )

CH3COONa + CO2 +H2O CH3COOH + 2 O2
GLUkOSA
LDH

NaHCO3 + CH3COOH ( Asetat ) 2 CO2 + 2 H2O : TCA Cycle

L- LAKTAT

G-6-P

GLIKOGEN

Asetil KoA PIRUVAT sintetase

ASETAT
2 CO2

Asetil - KoA

TCA Cycle

H2O

SHOCK SYNDROMES
In shock states such as septic shock, tissue hypoxia and impaired hepatic gluconeogenesis and oxidation elevate plasma lactate by approx. 600% AR may be better alternative to LR

Wolfe RR, Miller HI: cardiovascular and metabolic responses during burn shock in the guinea pig. Am J Physiol 1976;231:892-897

HEPATIC INSUFFICIENCY
AR vs LR during induced hepatic insufficiency in rabbits. Hepatic artery, portal vein and bile duct were ligated and vessels were clamp for 20 minutes. AR or LR administered within that 20 minutes. In LR group: 75% reduction in ATP and a 7-fold increase in AMP Conclusion: in hepatic insufficiency, gluconeogenesis is inhibited and the liver fails to metabolize lactate
Nakatani T, et al. Effects of Ringers acetate solutions during transient hepatic inflow occlusion in rabbits. transplantation 1995;59(7):952-57

SURGICAL PROCEDURES
Current clinical practice adopts the use of LR or isotonic solution during major operations. Kashimoto compared the effects of LR and AR on core body and peripheral temperature during isoflurane or sevoflurane anesthesia the use of AR during early period of Isoflurane anesthesia was associated with maintained central temp.
Kashimoto S. Comparative effects of Ringers acetate and lactate solutions on intraoperative central and peripheral temperatures. J Clin Anesth1998;10(1):23-27

Ringers Acetate
Pendekatan rasional dalam resusitasi cairan

Na+ K+ Cl-

Ca++
Acetate-

130 4 109 3 28

mEq mEq mEq mEq mEq

1. 2. 3. 4.

Gastroenteritis w/ dehydration Hemorrhage DSS BURNS

TERAPI CAIRAN

RESUSITASI

RUMATAN

KRISTALOID
(Na+ > 100 mEq) - RA (Asering) - RL - NaCl 0,9%

KOLOID
Dextran- 40

ELEKTROLIT
Na+ 50-60mEq; K+ 10-20 mEq (KAEN group)

NUTRISI
AA 10% (AMIPAREN) AA 5% (MINOVEL- 600) AA 3%( PAN- AMIN G D 10 % (KA-EN MG 3) Maltosa 10% (MARTOS )

Mengganti kehilangan akut

Memelihara keseimbangan

Terima Kasih

Ringer Asetat
Penggunaan di Bagian Ilmu Kesehatan Anak
Iyan Darmawan

Pendahuluan
RA bisa digunakan pada anak dan bayi Diindikasikan untuk resusitasi cairan
Ref: 1. Neonatal Hypernatremic Dehydration Secondary to Lactation Failure J Am Board Fam Pract 14(2):159-161, 2001. 2001 American Board of Family Practice 2. Darrow DC, ped Clin North Am 1959 & Talbot FB, Am J Dis Child 1938. 3. Guidelines for treatment of DKA, Swedish Pdiatric Association 1996 4. Dengue haemorrhagic fever: diagnosis, treatment, prevention and control. 2nd edition. Geneva : World Health Organization. 1997 5. Communicable Disease Epidemiology Office of Epidemiology Washington State Department of Health.

Ringer Asetat
1. Metabolisme asetat terutama di otot, tidak terganggu pada kelainan hati(1)
2. Komposisi mirip dengan plasma, tepat untuk menggantikan kehilangan akut cairan ekstraseluler. ( 2 ) 3. Kecepatan metabolisme asetat 250-400 mEq/jam , sedangkan laktat 100mEq/jam, dengan demikian asetat lebih cepat mengkoreksi asidosis.( 3) 4. Metabolisme asetat memerlukan sedikit O2 , dan melepaskan sedikit CO2.( 4 )

1. Loren A et al. Oxidation of lactate and acetate in rat skeletal muscle. Journal of Applied Physiology 1997 ; 83 ( 1 ) : p. 32 - 39. 2. Heimberger DC,M.Roland RW. Handbook of Clinical Nutrition.Mosby 1997 3. Anderud T, Lund T. Intensive Care of Patients with Burns. Tidskr Nor Laegenforen 1989; p.3197 - 3199. 4. Ringer acetate solution in clinical practice. Medimedia.1999

KOMPOSISI
Setiap 1 L mengandung

:
Elektrolit ( mEq )
Tek.Osmotik ( mOsm /L )

Na ASERING ( RA ) RINGER LAKTAT ( RL )

K 4 4

Cl

Ca2+ 3 3

Asetat Laktat 28 28

130 130

109 109

274 274

Cholera Guidelines
Patients in shock should be given rapid IV rehydration with a balanced multielectrolyte solution containing approximately 130 mEq/L of Na+, 25-48 mEq/L of bicarbonate, acetate or lactate ions, and 10-15 mEq/L of K+. Useful solutions include Ringer's lactate or WHO diarrhea treatment solution (4 g NaCl, 1 g KCl, 6.5 g sodium acetate and 8 g glucose/L)

Ref: Communicable Disease Epidemiology Office of Epidemiology Washington State Department of Health.2002

RA pada Ketoasidosis Diabetik

Resusitasi cepat NaCl 0,9% 12.5 ml/kg/jam selama 0-2 jam sampai sirkulasi tepi pulih

Fase rehidrasi lambat selama 48 jam dengan Ringer Asetat (Rumatan + 5% BB/24 jam)

Rumatan
Ref. Ragnar Hanas. Guidelines for treatment of DKA, Swedish Pdiatric Association 1996

DBD III & IV

O2 2-4 L/menit RA 20 ml/kg bolus dalam 30 menit

Syok teratasi

Syok tidak teratasi

RA 10 ml/kg/jam

Teratasi

Dextran 40 10-20 ml/kg Tidak Teratasi

Stabil dalam 24 jam

RA 5 ml/kg/jam Stop < 48 jam 3 ml/kg/jam

Ht turun Ht tetap/naik FFP 10 ml/kg Dextran 20 ml/kg

Sri Rezeki, Hindra Irawan Satari. Demam Berdarah Dengue. FKUI.1999

ASERING
Ringers acetate

PERDARAHAN

TRAUMA

RESUSITASI

ASERING

GASTROENTERITIS AKUT DISERTAI DEHIDRASI

Terima Kasih

Acetated Ringers Solution

(Additional usage)
Scientific Meeting

Grand Melia Hotel, 5 April 2003

Iyan Darmawan
Medical Director, PT Otsuka Indonesia

TERAPI CAIRAN

RESUSITASI

RUMATAN

KRISTALOID
(Na+ > 100 mEq) - RA (Asering) - RL - NaCl 0,9%

KOLOID
Dextran- 40

ELEKTROLIT
Na+ 50-60mEq; K+ 10-20 mEq (KAEN group)

NUTRISI
AA 10% (AMIPAREN) AA 5% (MINOVEL- 600) AA 3%( PAN- AMIN G D 10 % (KA-EN MG 3) Maltosa 10% (MARTOS )

Mengganti kehilangan akut

Memelihara keseimbangan

Fluid Therapy
RD5,RLD5, RAD5,DGAA KAEN3B KAENMG3
NaCl3% NaHCO3 Glu 20%,40% Mannitol

NS, RL, RA, Colloids

Acute replacement (rehydrate, restore perfusion)

Maintenance

Repair correct extreme/ symptomatic elect derangement

Acetated Ringers (or modified)

Plasmalyte/Baxter Normosol-R/Abbott Veen-D/Hoechst Acetar/Thai Otsuka

Asering/PTOI

Indications of AR
Replacement fluid for resuscitation
gastroenteritis, burn,hemorrhagic shock, DSS

Intraoperative Preloading anestesi regional Priming solution for cardiopulmonary bypass (CPB) Replacement during acute stroke

AR & LR
LACTATE:
Primarily in the liver, and to lesser degree the kidney, lactate is metabolized to pyruvate, which is then converted to CO2 and H2O (80%) or glucose (20%), and regeneration of bicarbonate1 ACETATE: metabolized mainly in muscles and to a lesser extent in tissues such as kidney, heart and liver2 Coenzyme A Acetate + H+-------- Acetyl-CoA
hydrogen source

Krebs cycle

Carbonic acid -------- bicarbonate

Ref. 1.Rose BD. Clinical Physiology of Acid-Base and Electrolyte Disorders. McGraw-Hill 4th ed 1994 p 554 2. Maxwell MH, Kleeman CR, Narins RG. Clinical Disorders of Fluid and Electrolyte Metabolism. MacGraw-Hill 1987 4th edition p 1063

METABOLISME

1. SODIUM

LAKTAT ( HATI )
NaHCO3 + CH3CH(OH)COOH ( Laktat ) 3 CO2 + 3 H2O : TCA Cycle

CH3CH(OH)COONa + CO2 +H2O CH3CH(OH)COOH + 3 O2

2. SODIUM ASETAT ( OTOT )

CH3COONa + CO2 +H2O CH3COOH + 2 O2 GLUkOSA L- LAKTAT LDH G-6-P GLIKOGEN NaHCO3 + CH3COOH ( Asetat ) 2 CO2 + 2 H2O : TCA Cycle

PIRUVAT Asetil KoA sintetase ASETAT Asetil - KoA

2 CO2

TCA Cycle

H2O

Average pH
Ringers lactate 6.75

Ringers acetate Normal saline

7 6.25

Ringers Acetate : Intraoperative Use

AR is suitable as vehicle of maintenance propofol

Nonaka A, Tamaki F, Sugawara T, Oguchi T, Kashimoto S, Kumazawa T: [Premixing of 5% dextrose in Ringer's acetate solution with propofol reduces incidence and severity of pain on propofol injection]. Masui 1999 Aug;48(8):862-7

Intraoperative Use
Masui 1999 Aug;48(8):862-7

Nonaka A, Tamaki F, Sugawara T, Oguchi T, Kashimoto S, Kumazawa T: [Premixing of 5% dextrose in Ringer's acetate solution with propofol reduces incidence and severity of pain on propofol injection].
prospective, randomized, double-blinded trial. 96 patients: 1% propofol 20 ml; Group C, normal saline 2 ml, Group L, 2% lidocaine 2 ml Group A, 5% dextrose in Ringer's acetate solution 2 ml.

70% 33% 25%

pain

AR is suitable as vehicle of maintenance propofol

Obstetric Use
Masui 1999 Sep;48(9):977-80 Onizuka S, Kawano T, Takasaki M, Sameshima H, Ikenoue T Comparison of the effect of rapid infusion of lactated and that of acetated Ringer's solutions on maternal and fetal metabolism and acid-base balance].

20 patients; combined spinal and epidural 25 ml/kg/hr

Acetated Ringer's solution is better than lactated Ringer's solution in rapid infusion before cesarean section because of the correction of neonatal lactic acidosis.

Intraoperative Fluid during Hepatectomy

Masui 1995 Dec;44(12):1654-60 Nakayama M, Kawana S, Yamauchi M, Tsuchida H,Iwasaki H, Namiki A[Utility of acetated Ringer solution as intraoperative fluids during hepatectomy].

Hemodynamics, metabolism, blood gas and renal & liver functions. Twenty patients 15 ml/kg/hr with the first 500 ml and thereafter reduced to 10 ml/kg/hr.

AR as intraoperative fluid in hepatectomy

Lactate Level (mg/dl) (Lactate level at the end of operation) 48.6 + 16.4

50 45 40 35 30 25 20 15 10 5 0

29.1 + 14.3

Ringer's lactate Ringer's acetate

n = 20

Nakayama M, Kawana S, Yamauchi M, Tsuchida H, Iwasaki H, Namiki A[Utility of acetated Ringer solution as intraoperative fluids during hepatectomy], Masui 1995 Dec;44(12):1654-60

Effect on Core Temperature

J Clin Anesth 1998 Feb;10(1):23-7

Kashimoto S, et al Comparative effects of Ringer's acetate and lactate solutions on intraoperative central and peripheral temperatures. PATIENTS: 60 ASA physical status I and II patients undergoing general surgery.
INTERVENTIONS: Following induction with 5 mg/kg of thiamylal and 0.1 mg/kg of vecuronium, patients were randomly assigned to one of four groups (15 patients per group). They received inhalation anesthetics (66% nitrous oxide [N2O] and 1.0% to 2.0% isoflurane or 1.3% to 2.6% sevoflurane) and LR or AR

Effect on Core Temperature Tympanic Membrane Temperature

(temperature of tympanic membrane)

p<0.05

AR more suitable as intraoperative fluid vs NS

Anaesthesia 1994 Sep;49(9):779-81
McFarlane C, Lee A

A comparison of AR and 0.9% saline for intra-operative fluid replacement.

The exclusive use of 0.9% saline intra-operatively can produce a temporary hyperchloraemic acidosis which could be given false pathological significance. In addition it may exacerbate an acidosis resulting from an actual pathological state. The use of a balanced salt solution such as AR may avoid these complications.

AR as priming solution in CPB

Anesthesiology 2000 Nov;93(5):1170-3
Liskaser FJ, Bellomo R, Hayhoe M, Story D, Poustie S, Smith B, Letis A, Bennett M

Role of pump prime in the etiology and pathogenesis of cardiopulmonary bypass-associated acidosis.
Plasmalyte 148 vs Polygeline+ Ringer in 22 patients

With the Haemaccel-Ringer's prime, the metabolic acidosis was hyperchloremic ( Cl-, +9.50 mEq/l; CI, 7.00-11.50). With Plasmalyte, the acidosis was induced by an increase in unmeasured anions, most probably acetate and gluconate. The resolution of these two processes was different because the excretion of chloride was slower than that of the unmeasured anions ( base excess from t1 to t3 = -1.60 for Haemaccel-Ringer's vs. +1.15 for Plasmalyte; P = 0.0062).

AR superior to HES as CPB Prime

Acta Anaesthesiol Scand 1993 Oct;37(7):652-8
Kuitunen A, et al. Hydroxyethyl starch as a prime for cardiopulmonary bypass: effects of two different solutions on haemostasis.
Forty-five patients undergoing coronary bypass grafting were prospectively randomised to three groups and received in a double-blind manner as their CPB prime either 20 ml.kg-1 LMW-HES (Mw 120,000), 20 ml.kg-1 HMW-HES (Mw 400,000) or Ringer's acetate 2000 ml. The final volume of the prime was completed to 2000 ml with Ringer's acetate in the HES groups. Anaesthesia and CPB management were standardised. Plasma levels of von Willebrand factor antigen and factor VIII procoagulant activity were significantly more depressed after CPB in both HES-groups as compared with the crystalloid prime group. In addition, APTT was more prolonged and the maximal amplitude of thromboelastographic tracing was more decreased in the HES-groups.

It is concluded that it may be advisable to avoid HES solutions in the CPB prime, especially in patients with an increased risk for bleeding after cardiac operations.`

AR more cost-effective than colloids

Acta Anaesthesiol Scand 1995 Jul;39(5):671-7

Tollofsrud S, et al. Fluid balance and pulmonary functions during and after coronary artery bypass surgery: Ringer's acetate compared with dextran, polygeline, or albumin.
The most expensive colloid fluid regimen (albumin) cost about 230 US$ more per patient than the RAc fluid regimen. We conclude that Ringer's acetate for volume replacement to stabilize haemodynamics during and after CAB surgery is associated with increased fluid retention only during the intraoperative period, compared with dextran 70 or polygeline, and with a lower serum colloid osmotic pressure and net lung capillary filtration pressure postoperatively, compared with all three colloid groups. This does not affect pulmonary functions adversely.

AR for acute stroke patients

Fluid Therapy for Acute Stroke

Avoid hypotonic infusion No Lactate --- Ringer solution/NS No glucose Had specific effect to combat acidosis Ideally neuroprotective

NS & RS can cause hyperchloremic acidosis

Osm Intracell distributio n Risk of Lactate Hyperchloremic acidosis

NS RL RA D5 RS

308 273 273 278 310

+ -

+
(Cl- 154 mEq/L)

+ -

+
(Cl- 155.5 mEq/L)

Ringers acetate is slightly hypotonic

(measured osmolarity 273.4 mOsm/L)

Plasma osmolarity 285 + 5 mOsm/L

Vol of MgSO4 added into 1L Asering

Current Osmolarity of Desired ml of 20% MgSO4 Asering (Ringers acetate) osmolarity to be added to 1L

Mg
12 mEq 17 mEq

273.4 273.4

285 290

7.25 10.375

273.4
273.4

295
300

13.5
16.625

22.41 mEq
27.5 mEq

1 ml MgSO4 20% ~ 1.66 mEq

Conclusion
AR is an alternative to LR/NS as resuscitation fluid Other indications include: intraoperative fluid therapy in various surgical settings , initiating parenteral fluid in acute phase of stroke Priming solution in CPB

ASERING
Ringers acetate

PERDARAHAN

TRAUMA

RESUSITASI

ASERING

GASTROENTERITIS AKUT DISERTAI DEHIDRASI

Terima Kasih

Maintenance Fluid Therapy

Iyan Darmawan, Medical Department Otsuka, Indonesia iyan@ho.otsuka.co.id

. Rational Fluid regimen

correct timing correct indications, dosage correct product (composition, concentration) tailored to patients fluid and electrolyte status, not diagnosis good monitoring cost-effective

DN Lobo et al. (UK)* .

The most recent UK National Confidence Enquiry into Perioperative Deaths report has documented that a number of surgical patients die because of inappropriate fluid management by inadequately trained staff. Questionnaires to 200 doctors (100 Group A; 50 Group B; and 50 Group C) Group A: preregistration house officers questioned within 10 days of starting their job; Group B 6-8 weeks; Group C surgical senior house officers.

Daily Sodium requirement for a healthy . 70 kg man (desired answer highlighted)

mmol/day Group A (%) Group B (%) Group C (%)

<60 60-100 101-150 151-180 >180 Dont know

18 26 18 1 37

2 10 60 4 4 20

2 36 38 4 2 18

Daily potassium requirement for a healthy . 70 kg man (desired answer highlighted)

mmol/day GroupA (%) Group B(%) Group C (%)

<60 60-80 >80 Dont know

38 47 1 14

22 70 8

20 70 2 8

Results .
Only 50% prescribed the desired amount of potassium About 26% prescribed > 2 L 0.9% saline/day. Less than 40% of respondents were given formal or informal guidelines on fluid and electrolyte prescribing on surgical firms

Knowledge relevant to fluid and electrolyte prescribing among surgical junior doctors is inadequate Teaching on the subject at both undergraduate and postgraduate levels does not prepare junior doctors for the task.

FLUID THERAPY
RESUSCITATION Repair MAINTENANCE

Crystalloid
RA/RL/NS

Colloid

ELECTROLYTES

NUTRITION

KAEN3B

1. Replace acute loss (hemorrhage, GI loss, 3rd space etc)

1. Replace normal loss (IWL + urine+ faecal) 2. Nutrition support

Electrolyte composition
mEq/L
Na+ K+ Ca2+ Mg2+ ClHCO3HPO42SO42Organic acid

ICF 15 150 150 2 27 1 10 100 20 63

ECF Plasma 142 142 4 5 3 103 27 2 1 5 16

Interstitial 144 144 4 2.5 1.5 114 30 2 1 5 6

Protein

Ion Distribution
ANION Suitable solution

COMPARTMENT CATION ICF ECF PLASMA ISF K+ Na+ Na+

Mg++ HPO4-, Prot

containing K+ Mg+ and HPO4Cl-, HCO3- Prot. High Na+ and ClCl- HCO3-

Perioperative IV Fluid Restrictions Helpful in Colorectal resection

Eliminate preoperative fluids and replacement for 3rd space loss Blood loss was replaced volume-forvolume with colloid 1000 ml Glucose 5% administered for the remainder of the day of operation On the surgical ward, any weight increase more than 1 kg was treated with furosemide All patients receive NGT 4 hours after surgery

vs

Standard regimen 500 ml colloid preloaded during epidural anes 3rd space loss NS Blood loss < 500 1-1,5 L NS > 500 colloid + 1-2 L crystalloid

Ann Surg.2003;238:641-648

Results (restricted vs standard)

Overall postop complications 33% vs 51% (p = 0.013) Cardiopulmonary comp 7% vs 24% (p=0.007) Tissue-healing complications 16% vs 31% (p =0.04) Deaths 0% vs 4.7% (p=0.12)
Ann Surg.2003;238:641-648

Fatal Postoperative Pulmonary Edema

A known postop complication, but the clinical manifestation and danger levels for fluid administration are not known Can occur within the initial 36 postoperative hours when net fluid retention exceeds 67 ml/kg/d

CHEST 1999;115:1371-1377

Hypoalbuminemia, ECF expansion and Picking the right infusion

Sequestration of fluid from ECW

% BODY WEIGHT

NORMAL ACUTE INJURY

ELECT & IV Col

35 30 25 20
IF ICW

PHASE OF RESOLUTION

3rd space

15 10 5
PL

Forming Sequestrated ECF

Sequestrated ECF

Resolving Sequestrated ECF

Kokko & Tannen Fluids & Electrolytes. WB Saunders 3 ed.p738

I.V. fluids

Diuresis

Why give excessive fluid?

Hypotension following induction of anesthesia Fluid sequestration during surgery Maintenance of BP after traumatic injury Excessive blood loss Postoperative fever

Type of Description dehydration

5,8

Common cause Serum osmolarity Vomiting, diarrhea Normal (275-295 mOsm/kg)

Isotonic

Balanced loss of water and sodium

Hypertonic

Water losses exceed sodium losses

Sodium losses exceed water losses

Fever

Increased (>300 mOsm/kg)

Decreased (<250 mOsm/kg)

Hypotonic

Overuse of diuretics