The combination of normal saline and lactated ringer's solution for large intravascular volume infusion

Corresponding author: Zeynep Eti MD, Marmara University Hospital, Department of Anesthesiology Tophanelioğlu cad. No: 13-15, Altunizade, 34662 IstanbulTelephone: 0 216 339 99 89 Fax: 0 216 339 99 89 E-mail: emineeti@superposta.com

Marmara Medical Journal 2004;17(1);22-27

THE COMBINATION OF NORMAL SALINE AND LACTATED RINGER'S

SOLUTION FOR LARGE INTRAVASCULAR VOLUME INFUSION

Zeynep Eti, Arzu Takıl, Tümay Umuroğlu, Pınar Irmak, F.Yılmaz Göğüş

Objective: The aim of this study was to evaluate the perioperative effects of large intravascular volume infusion of both normal

saline (NS) and lactated Ringer's (LR) solution on electrolytes and acid base balance.

Materials and Methods: In 20 patients, aged between 20-70 years, undergoing major spine surgery, ASA I-II NS and LR

solutions were infused at the rate of 20 mL.kg -1_.h -1 _{peroperatively and 2.5 mL.kg} -1_.h -1 _{postoperatively by switching between the two}

solutions every other liter. Mean arterial pressure, heart rate, oxygen saturation, end-tidal carbondioxide pressure, central venous pressure, esophageal temperature were recorded every 15 minutes and crystalloid infusion volumes, urinary output, blood loss, and blood transfusion volumes were recorded hourly peroperatively. Electrolytes (Na+_,K+_,Cl-_{) and arterial blood gases were measured}

preoperatively, every hour peroperatively and at the 1st_{, 2}nd_{, 4}th_{, 6}th_{, 8}th_{, 12}th_{, 16}th_{, 20}th _{and 24}th _{hours postoperatively.}

Results: Arterial pH, HCO3 and base excess values decreased and serum Cl- values increased significantly peroperatively. Arterial CO2 pressure increased significantly at peroperative 6th _{h (p 0.05).}

Conclusion: The combination of NS and LR solutions causes not only hyperchloremic acidosis peroperatively but also a mixed

acidosis postoperatively.

Keywords: Normal saline, Lactated Ringer's solution, Hyperchloremic acidosis

YÜKSEK VOLÜMDE % 0.9 SERUM FİZYOLOJİK VE LAKTATLI

RINGER SOLÜSYONLARININ BİRLİKTE KULLANIMI

ÖZET

Amaç: Yüksek volümde % 0.9 serum fizyolojik (SF) ile hiperkloremik metabolik asidoz ve hipernatremi, ringer laktat (RL)

infüzyonu ile de postoperatif asidoz ve hafif hiponatremi geliştiği gösterilmiştir. Bu çalışmada, major vertebra cerrahisinde, yüksek volümde SF ve RL solüsyonlarının birlikte kullanımının elektrolit ve asit baz dengesi üzerine etkilerinin belirlenmesi amaçlanmıştır.

Gereç ve Yöntem: Elektif vertebra cerrahisi geçirecek, ASA I-II, 20-70 yaş arasında 20 hasta çalışmaya alındı. 5 mg/kg tiyopental

ve 0.1 mg/kg vekuronyum bromid ile indüksiyon sonrası anestezi idamesi % 70 N2O içinde oksijen ve 2 MAC sevofluran ile sağlandı.

Tüm hastalara SF ve RL her 1 litrede değiştirilerek peroperatif dönemde 20 ml/kg/s, postoperative dönemde 2.5 ml/kg/s hızla verildi. Tüm hastalarda ortalama arter basıncı, kalp atım hızı, SpO2, ETCO2, CVP, vücut sıcaklığı, idrar miktarı, kristalloid miktarı, kan kaybı ve

kan transfüzyon miktarları 30 dakika ara ile kayıt edildi. Preop, perop 1 saat ara ile ve postop 0, 1, 2, 4, 6, 6, 12, 16, 20 ve 24.saatlerde arteryel kan gaz ve elektrolit değerleri (Na+_{, K}+_{, Cl}-_{) ölçüldü. Elde edilen veriler tek yönlü ANOVA ve Tukey- Kramer testleri ile}

istatistiksel olarak karşılaştırıldı (p<0.05).

Bulgular: Arteryel pH, HCO3- ve baz fazlalığı değerlerinde peroperatif belirgin azalma ve serum klor değerlerinde belirgin artış saptandı. Serum sodyum ve potasyum değerlerinde değişiklik saptanmadı. Arteryel pCO2 değerleri intraoperatif 6.saatte belirgin artış

gösterdi. Hemodinamik parametreler, PaO2, SpO2, SaO2, ETCO2, CVP, kan kaybı, kan transfüzyonu ve hemoglobin konsantrasyonları

açısından istatistiksel fark saptanmadı.

Sonuç: Yüksek volümde SF ve RL solüsyonlarının birlikte kullanımı hiperkloremik metabolik asidoz gelişimini

engelleyememesinin yanı sıra karbondioksit değerlerinde artış ile asidozun artmasına neden olmaktadır. Major cerrahi girişimlerde, yüksek volümde SF ve RL solüsyonlarının birlikte kullanımının sadece SF veya RL kullanımına göre bir üstünlük sağlamadığı sonucuna varılmıştır.

INTRODUCTION

Beyond all technological developments in

anesthesiology, perioperative fluid

management during surgery is a major

problem. Crystalloids are the main and the

first step fluids to supply hemodynamic

stability for normovolemia when large fluid

and blood loss occur during major surgery

.

Normal saline (NS) and lactated Ringer's

(LR) solutions are the most commonly used

crystalloids because of their similarity with

human plasma. However, published data

showed that hyperchloremic metabolic

acidosis occurs in the course of large NS

infusion

. In our previous study comparing

the effects of large volume infusion of NS and

LR, we concluded that although LR infusion

did not cause hyperchloremic metabolic

acidosis as did NS, it did lead to postoperative

respiratory acidosis and mild hyponatremia.

As none of these solutions seemed to be the

“ideal” choice to supply hemodynamic

stability during major surgery, we

hypothesized that a combination of the two

(switching between the two solutions every

other liter) may be a better alternative.

The aim of this study was to evaluate the

effects of the combination of NS and LR

solutions on acid base balance and

electrolytes during major spine surgery by

switching between the two solutions every

other liter.

METHODS

After Institutional Ethics Committee approval

and the patients' written consent, were

obtained 20 patients, ASA physical status I

and II, aged between 20-70 yrs, undergoing

elective major spine surgery (Cotrel–

Dubousset posterior spinal instrumentation)

were enrolled in the study.

The patients were premedicated with atropine

0.5 mg and midazolam 0.07 mg/kg IM

preoperatively. General anesthesia was

induced with thiopental sodium at the rate of

5mg/kg and vecuronium bromide 0.1 mg/kg

IV. After endotracheal intubation, anesthesia

was maintained with oxygen in 70% nitrous

oxide and 1.5%-2% sevoflurane. The patients

were ventilated mechanically to maintain

PaCO2 as close as possible to 40 mmHg.

The combination of NS and LR solutions

were infused 20 mL.kg

.h

intraoperatively

and 2.5 mL.kg

.h

for postoperative 24 hours

by switching between the two solutions every

other liter. Patients with over 20% blood loss

were given blood transfusions. 500 mL of

colloid solution (Gelofusine) was

administered for the first 500 mL blood loss.

Intraoperative monitoring included

continuous monitoring of mean arterial

pressure, heart rate, oxygen saturation,

end-tidal carbondioxide pressure, central venous

pressure and esophageal temperature in all

patients. The values were recorded every 15

minutes. Crystalloid infusion volumes,

urinary output, blood loss, and blood

transfusion volumes were recorded hourly.

Electrolytes (Na

,K

,Cl

) and arterial blood

gases were measured preoperatively, every

hour peroperatively and at the

1

,2

,4

,6

,8

,12

,16

,20

and 24

hours

postoperatively. Serum albumin and total

protein concentrations were measured and

anion gaps (Na-[Cl+HCO3]) were calculated

preoperatively and at the end of the surgery.

IV patient-controlled analgesia with morphine

was administered to all patients. All measured

data were compared with two-way repeated

measures of analyses of variance and post-hoc

testing was performed by the Tukey-Kramer

test statistically. Student's t test was

performed for unpaired data and a p<0.05 was

considered significant.

RESULTS

In Table I demographic data of the patient

characteristics and duration of the surgery and

in Table II the NS and LR infusion volumes,

urinary output, total blood loss and blood

transfusion volumes were presented. There

was no significant difference between the

infusion volumes of NS and LR (p>0.05).

Table I: Demographic characteristics and duration of surgery

Age (year) 47 ± 20 (20-70)

Body weight (kg) 61 ± 13 (41-80)

Duration of surgery (min) 326 ± 70 (255-465)

ASA classification 1.4 ± 0.5 (I and II)

Values are mean ± SD (ranges)

Table II: Intraoperative crystalloid volume, blood loss and blood transfusion volume, urinary output

Normal saline solution (mL) 2843 ± 913 (2000-4300)

Lactated Ringer’s solution (mL) 2575 ± 914 (1700-4000)

Blood loss (mL) 2286 ± 1091 (650-4200)

Blood transfusion volume (mL) 1854 ± 697 (1000-3200)

Urinary output (mL) 494 ± 381 (120-1300)

Values are mean ± SD (ranges) Serum sodium concentrations did not change significantly intraoperatively and postoperatively (Table III). Serum chloride concentrations increased significantly at the 4th _hour

intraoperatively and persisted until the 6th hour postoperatively (Table III). Serum potassium concentrations decreased significantly during the first two hours intraoperatively (Table III).

Table III: Serum sodium, chloride and potassium concentration

SODIUM CHLORIDE POTASSIUM (mEq/L) (mEq/L) (mEq/L)

Preoperative 140±2 108±5 4.4±0.4 Intraoperative 1 141±2 113±4 3.7±0.4∗∗ 2 140±2 115±4 3.8±0.4* 3 141±3 116±4 4.0±0.5 4 140±3 120±8∗∗ 4.0±0.7 5 144±3 121±9∗∗ 3.8±0.3 6 142±2 120±6∗∗ 4.7±1.2 Postoperative 1 141±3 119±8∗∗ 4.0±0.4 2 141±3 117±8* 4.0±0.4 4 140±3 117±8* 4.0±0.6 6 141±3 116±6 4.0±0.4 8 141±4 115±7 4.0±0.4 12 140±3 113±6 4.0±0.3 16 139±3 113±7 3.8±0.5 20 139±4 110±4 3.8±0.5 24 138±6 110±5 3.8±0.3

Values are mean ± SD

Arterial pH values decreased significantly at the 3rd hour intraoperatively and persisted until the 16th hour postoperatively (Table IV). Bicarbonate concentrations decreased significantly at the 1st

hour intraoperatively and returned to preoperative

values at the 8th _{hour postoperatively (Table IV).}

Base excess values decreased significantly at the 2nd hour intraoperatively and persisted until the 12th hour postoperatively (Table IV).

Table IV: pHa values, bicarbonate concentration and base deficit values

pHa Bicarbonate (mEq/L) Base deficit

Preoperative 7.40±0.03 23.2±1.5 -0.9±1.3 Intraoperative 1 7.41±0.03 20.5±1.5** -3.1±1.2 2 7.39±0.043 20.3±1.0** -3.6±1.3* 3 7.34±0.04∗ 19.8±1.6# -5.1±1.8** 4 7.33±0.03** 19.7±1.4# -5.8±1.5** 5 7.32±0.04** 19.4±2.1# -6.3±2.4# 6 7.29±0.05** 20.5±0.8** -6.2±0.5# Postoperative 1 7.27±0.06# 20.1±1.9# -6.4±2.6# 2 7.28±0.06# 20.7±2.0* -5.8±2.9# 4 7.30±0.06# 21.3±2.0* -4.9±2.6** 6 7.32±0.05# 21.6±1.6* -4.3±2.0** 8 7.32±0.04# 22.1±1.8 -3.9±2.0* 12 7.33±0.05** 22.2±1.4 -3.4±1.9 16 7.35±0.06 23.0±2.0 -2.3±1.9 20 7.37±0.04 23.0±2.0 -1.7±1.8 24 7.37±0.03 23.7±2.0 -1.1±1.6

Values are mean±SD

∗ p<0.05, ∗∗ p<0.01 and # p<0.001 compared with preoperative values Arterial PCO2 values increased significantly at the

6th _{hour intraoperatively and returned to}

preoperative values at the 12th _hour

postoperatively. Arterial PO2 and SO2 values

increased significantly at the 1st _hour

intraoperatively and persisted until the 16th _hour

Table V: PaCO2 ,PaO2 and SaO2 values (mmHg) (mean±SD)

PaCO2 PaO2 SaO2

Preoperative 37.5±3.7 99.3±27.9 96.7±1.9 Intraoperative 1 32.9±3.7 162.2±30.1# 99.3±0.4# 2 34.2±4.0 157.3±34.0∗∗ 99.1±0.7# 3 36.6±3.5 152.7±34.1∗∗ 98.8±0.9∗∗ 4 37.4±3.4 150.1±27.3∗∗ 98.8±0.5∗∗ 5 39.3±3.9 152.5±37.9∗∗ 98.8±0.6∗∗ 6 44.7±6.4* 152.7±42.1∗∗ 98.8±0.7∗∗ Postoperative 1 43.8±4.2* 145.3±43.9∗ 98.8±0.9∗∗ 2 44.0±4.0* 146.6±19.0∗ 98.6±0.5∗∗ 4 43.2±4.2* 153.9±31.8∗∗ 98.7±0.4∗∗ 6 42.2±3.9* 160.7±33.8∗∗ 98.8±0.7∗∗ 8 43.4±4.3 149.8±31.9∗∗ 98.7±1.1∗∗ 12 42.2±5.1 136.4±23.4∗ 98.4±1.2∗ 16 42.0±6.0 129.7±33.9 98.2±1.2 20 41.0±4.3 106.4±29.4 97.0±2.2 24 41.7±6.1 112.9±29.2 97.5±1.4 Values are mean±SD

∗ p<0.05, ∗∗ p<0.01 and # p<0.001 compared with preoperative values

Albumin concentration (from 4.06±0.57 to 2.42±0.57 g/dL) and anion gap (from 7.4±4.0 to (3.7±5.7 mEq/L) decreased significantly at the end of surgery (p<0.001).

No significant differences were observed in hemodynamic parameters (mean arterial pressure, heart rate), end-tidal carbon dioxide pressure, central venous pressure, body temperature and hemoglobin concentration.

DISCUSSION

The main result of this study was that the combination of large intravascular volume infusions of NS and LR changing the two

solutions every other liter caused hyperchloremic metabolic acidosis intraoperatively as well as mixed acidosis postoperatively.

Hyperchloremic metabolic acidosis developing after large intravascular volumes of NS has been described in many clinical studies 1-7_{. However the}

etiology and clinical relevance of this acidosis remain controversial. Some investigators called this “dilutional acidosis” suggesting that the mechanism was a dilutional reduction of plasma bicarbonate concentration whereas others explained it by the Steward model, emphasizing the importance of hyperchloremia resulting in a reduction of the strong ion difference (SID). In our previous study comparing the effects of large

volume infusion of NS and LR, we concluded that although large volume infusion of LR did not cause hyperchloremic metabolic acidosis as NS did, it led to postoperative respiratory acidosis and we suggested that the combination of NS and LR may be a better strategy as the removal of lactate as a bicarbonate precursor from the circulation would increase the SID and reduce acidosis 2. Also the metabolic acidosis caused by NS could stimulate ventilation and compensate the carbondioxide load. However, in this study we found that the combination of NS and LR caused an increase in serum chloride concentration and a decrease in bicarbonate concentration, resulting in intraoperative hyperchloremic metabolic acidosis. The addition of LR infusion did not prevent metabolic acidosis but it led to an increase in arterial carbondioxide pressure, resulting in a postoperative mixed acidosis. Although the mean postoperative arterial carbondioxide pressures were not higher than 45 mmHg in our patients, in four patients the values were found to be higher than 50 mmHg.

One of the main differences in our two studies is that at the end of surgery there was a significant decrease in albumin concentration and anion gap in this study. The decrease in anion gap resulting from increased chloride and decreased bicarbonate concentration supports hyperchloremia as the main mechanism of metabolic acidosis. According to the Steward model, the major determinant of hydrogen concentration in the body is the SID and a significant hyperchloremia decreasing SID is associated with a metabolic acidosis 6_{. Also Figge}

et al 8 _{demonstrated that a reduction in serum}

albumin of 1 g/dL reduced the anion gap by 2.5 mEq/L. It is obvious that acute dilutional hypoalbuminemia accompanied with rapid crystalloid infusion also reduced the anion gap 3_.

Besides, in vitro data showed a linear correlation between albumin and bicarbonate concentration 9_.

According to this information, the mechanism of metabolic acidosis associated with large intravascular infusion of NS can be explained by hyperchloremia but also the decrease in bicarbonate concentration.

As a result we conclude that using 20 mL.kg-1_.h-1

infusion of NS and LR in combination changing the solutions every other liter, causes hyperchloremic metabolic acidosis peroperatively and a mixed type acidosis (metabolic and respiratory) postoperatively after major spine surgery. We do not recommend using crystalloids instead of NS alone in a combination during major surgery.

REFERENCES

1. Boldt J. New light on intravascular volume

replacement regimens: What did we learn from the past three years? Anesth Analg 2003; 97:1595-1604.

2. Takıl A, Eti Z, Irmak P, et al. Early postoperative

respiratory acidosis after large intravascular volume infusion of lactated Ringer's solution during major spine surgery. Anesth Analg 2002; 95:294-298.

3. Scheingraber S, Rehm M, Schmisch C, et al. Rapid

saline infusion produces hyperchloremic acidosis in patients undergoing gynecologic surgery. Anesthesiology 1999; 90:1265-1270.

4. Blanloeil Y, Roze B, Rigal JC, et al.

Hyperchloremic acidosis during plasma replacement. Ann Fr Anesth Reanim 2002; 21:211-220.

5. Waters JH, Miller LR, Clack S, et al. Cause of

metabolic acidosis in prolonged surgery. Crit Care Med 1999; 27:2142-2146.

6. Rehm M, Conzen PF, Peter K, et al. The Stewart

model. “Modern” approach to the interpretation of the acid-base metabolism. Anaesthesist 2004; 53:347-357.

7. Miller LR, Waters JH, Provost C. Mechanism of

hyperchloremic metabolic acidosis. Anesthesiology 1996; 84:482.

8. Figge J, Jabor A, Kazda A, et al. Anion gap and

hypoalbuminemia. Crit Care Med 1998; 26:1807-1810.

9. Rossing TH, Maffeo N, Fencl V. Acid-base effects

of altering plasma protein concentration in human blood in vitro. J Appl Physiol 1986; 61:2260-2265.