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Original Article

Evaluation of the Metabolic Profile of Ringer Lactate versus


Ringer Acetate in Nondiabetic Patients Undergoing Major
Surgeries
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Sindhu Balakrishnan, Manjulatha Kannan, Sunil Rajan, Shyam Sundar Purushothaman, Rajesh Kesavan, Lakshmi Kumar
Department of Anaesthesiology and Critical Care, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
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Abstract
Background: Stress‑induced neuroendocrine and metabolic changes lead to intraoperative hyperglycemia which is related to surgery and
the type of intravenous fluids used. Aims: The primary objective was to assess the incidence of hyperglycemia with use of lactate versus
acetate‑based intravenous fluids in nondiabetics undergoing major surgeries. Incidence of lactatemia and metabolic acidosis were also assessed.
Settings and Design: Prospective parallel group observational study conducted in a tertiary care institute. Subjects and Methods: A total
of 208 nondiabetic patients undergoing major head and neck free flap or abdominal surgeries were included in the study. Group A received
Ringer lactate, and Group B received Ringer acetate as intraoperative maintenance fluid. Intraoperative blood sugar, pH, and lactate levels
were monitored. Statistical Tests Used: Chi‑square test and independent “t” test were used for analysis. Results: Intraoperative hyperglycemia
was more frequent in Group A than B (17.3 vs. 18.4%). Group B patients undergoing gastrointestinal (GI) surgeries showed higher blood
glucose at 2, 4, 6, and 8 h when compared to flap surgeries. In Group A, significantly higher blood sugar values were noted at 2 and 8 h in
those undergoing GI surgeries. Group B patients undergoing GI surgeries had significantly higher lactate levels at 6 and 8 h. Group B patients
had significant acidosis when surgeries lasted >6 h. Conclusion: Nondiabetic patients undergoing major abdominal surgeries who received
acetate‑based fluids had relatively higher intraoperative blood sugar levels as compared to those receiving lactated solutions, but the incidence
of hyperglycemia was comparable. When the duration of surgery exceeded 6 h, acetate‑based solutions resulted in significantly higher lactate
levels with progressive metabolic acidosis.

Keywords: Acetate, hyperglycemia, lactate, metabolic acidosis

Introduction Hyperglycemia in the perioperative period has been recognized


as one of the risk factors for increased mortality and morbidity.
Surgery provokes major changes in the neuroendocrine,
We balance our anesthetic techniques to reduce the stress
metabolic, and immune systems which result in the stress
response and its deleterious effects. There are numerous studies
response.[1] Patients are exposed to multiple other factors such as, which have looked into the blood glucose levels in diabetic
perioperative fasting, temperature fluctuations, use of multiple patients undergoing cardiac surgery and in critically ill patients.
drugs besides tissue damage, and bleeding all of which adds to Perioperative blood glucose is not routinely monitored in
this stress response. The stress response results in the systemic nondiabetic patients and has not been well studied. The choice
release of adrenocorticotrophic hormone (ACTH), cortisol, of fluid is dependent on the underlying illness that a patient
catecholamine, aldosterone, arginine vasopressin (AVP), has. Lactate containing fluids are avoided in diabetic patients,
glucagon, acute‑phase reactants, and cytokines to provide the
host with energy along with retention of sodium and water Address for correspondence: Dr. Manjulatha Kannan,
to maintain cardiovascular homeostasis. This stress state can Department of Anaesthesiology, Amrita Institute of Medical Sciences,
result in harmful effects on the patient such as hyperglycemia, Kochi - 682 041, Kerala, India.
E‑mail: manjudoc.kannan22@gmail.com
cardiovascular instability (hypertension and tachycardia), and
immunosuppression.[2]
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How to cite this article: Balakrishnan S, Kannan M, Rajan S,


DOI: Purushothaman SS, Kesavan R, Kumar L. Evaluation of the metabolic profile
10.4103/aer.AER_109_18 of ringer lactate versus ringer acetate in nondiabetic patients undergoing
major surgeries. Anesth Essays Res 2018;12:719-23.

© 2018 Anesthesia: Essays and Researches | Published by Wolters Kluwer - Medknow 719
Balakrishnan, et al.: Lactated fluids doesn’t cause hyperglycemia

and potassium‑containing fluids are avoided in patients with Half of the total deficit was corrected in the 1st hour of surgery
renal failure. The aim of perioperative fluid therapy is to and the remaining half of the deficit was corrected in the next 2
maintain tissue perfusion, cellular oxygenation and to maintain h. The maintenance fluids were administered to maintain mean
homeostasis of fluids and electrolytes. arterial pressure (MAP) >65–70 mmHg and urine output >0.5
ml/kg/h. Blood loss exceeding the maximum allowable loss
Aim of study was assessed and replaced with three times the volume of loss
The primary objective of this study was to compare the by maintenance fluid used as per the study group the patient
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incidence of hyperglycemia with the use of lactate versus belonged to. After replacement with crystalloids if the patients’
acetate based intravenous fluids in nondiabetic patients MAP was still found low blood and blood products or 0.45%
undergoing major surgeries of duration >3 h. Secondary saline with 20% albumin or inotropes and vasopressors were
objectives were to study the incidence of lactatemia and used to maintain the normal hemodynamic status.
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metabolic acidosis in these patients.


ABG was repeated every 2 h as per the protocol, and the
blood glucose, lactates, and acid‑base status of the patients
Subjects and Methods were documented. Blood glucose value of >180 mg/dl were
The present study was conducted at a tertiary care hospital considered as hyperglycemia and treated with an insulin bolus.
in South India in the Department of Anesthesiology during The insulin dose was calculated by blood sugar value/100 and
the period from December 2014 to August 2016. This was was administered as bolus. Blood sugars were rechecked after
a prospective parallel group observational study. After 1 h if insulin was used. Insulin infusion was instituted for
the Hospital Ethical Committee approval was obtained, sugar value >200 mg/dl and the total amount of insulin used
nondiabetic patients with preoperative glucose random blood in each patient was calculated at the end of surgery. Blood
sugar <140 mg/dl or fasting blood sugar <110 mg/dl and lactate and acidosis were also assessed from the ABG and it
postprandial blood sugar <140 mg/dl were selected to be was documented.
included in the study. Patients were allocated to one of the two
study groups. Group A patients received Ringer Lactate as the Numerical variables were expressed as a mean and standard
maintenance fluid while Group B patients received only Ringer deviation, whereas categorical variables were expressed as
acetate (Kabilyte, Fresenius KabiR) as the maintenance fluid. frequency and percentages. To obtain association of categorical
variables such as acidosis between the Ringer Lactate and
The patients were allotted into either Group A or Group B Ringer acetate groups, Chi‑square test was applied. To compare
based on the choice of fluid of the covering consultant the statistical significance of numerical variables such as
anesthesiologist. A search of the literature did not reveal glucose and lactate with groups and subsets, independent “t”
any studies comparing Ringer lactate with Ringer acetate in test was applied. The statistical analysis was performed using
nondiabetic patients. As there was no similar study published, SPSS software Version 20.0 for Windows (IBM Corporation
an initial pilot study was done with 10 patients in each group. ARMONK, NY, USA).
Based on the results of the pilot study for obtaining 80% power
and 95% confidence interval a minimum sample size of 211 Results
was required in each group.
The data of 217 patients were analysed [Figure 1]. The two
All patients who were nondiabetic and were to undergo elective groups had comparable demographic characters such as age,
prolonged surgeries of >3 h were included in the study. The weight, sex, ASA physical status, and type of surgery or type
other inclusion criteria were age between 18 and 80 years, the of anesthesia. We analyzed the blood glucose levels between
American Society of Anesthesiologists (ASA) physical status the two groups. It was found that only 17.3% (n = 18) in
1–3 patients undergoing nephrectomy, gastrectomy, colectomy, Group A had a blood glucose level of >180 mg/dl, whereas
open prostatectomy, nephroureterectomy, ureteric reimplantation, in Group B 18.4% (n = 19) had a glucose level >180 mg/dl.
and free flap surgeries were included. Diabetic patients, patients This difference was not statistically significant (P = 0.831)
undergoing emergency surgery, pregnant women and patients [Figure 2]. The blood glucose levels of the patients in the two
with renal failure and liver disease were excluded from the study. groups were studied two hourly. There was no statistically
All patients were administered general anesthesia, and the significant difference between the two groups [Table 1].
need for epidural anesthesia was decided based on the type of On comparing blood glucose, based on the type of surgery
surgeries the patients were to undergo. Patients undergoing patient underwent (i.e., GI vs. free flap), Group B patients
gastrointestinal (GI) surgical procedures had received who underwent GI surgeries showed significantly higher
general anesthesia with epidural whereas patients undergoing blood glucose levels at 2 h (136.59 ± 27.62, P = 0.002), 4 h
laparoscopic surgeries or flap surgeries did not receive an (144 ± 30.30, P = 0.027), 6 h (151.32 ± 30.89, P = 0.017) and
epidural. An arterial line was secured, and an arterial blood 8 h (161.83 ± 22.17, P = 0.009) [Table 2] whereas Group A
sample was obtained to have baseline blood glucose, lactate, patients who underwent GI surgeries, showed significantly
and acid‑base status. Arterial blood gas (ABG) was then higher blood sugar values only at 2 h (133.63 ± 31.04, P = 0.03)
collected every 2 h until the end of surgery. and at 8 h (182.15 ± 40.09, P = 0.007) as shown in Table 3.

720 Anesthesia: Essays and Researches ¦ Volume 12 ¦ Issue 3 ¦ July-September 2018


Balakrishnan, et al.: Lactated fluids doesn’t cause hyperglycemia

Lactate levels were compared between the two groups. It flap surgeries. In the patients receiving lactate‑based solution
was again noted that patients in group B undergoing GI higher blood sugars were noted in the patients undergoing
surgeries had a significantly higher lactate levels at 6 h GI surgeries, but the occurrence was less frequent. When the
(2.86 ± 1.58, P = 0.005) and at 8 h (3.69 ± 1.93, P = 0.002) incidence of hyperglycemia (blood glucose level >180 mg/dl)
as shown in Figure 3. In Group A, patients a similar rise in was compared between the two groups, there was no significant
lactate levels were not observed in patients undergoing GI difference between the two groups.
surgery [Figure 4].
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Hyperglycemia in the perioperative period results in increased


When Group A and Group B were compared to assess the morbidity and mortality outcome after surgery.[2,3] We balance
influence of fluids on acid‑base profile, Group B showed our anesthetic techniques to reduce the stress response and
significant acidosis in patients whose surgeries lasted >6 h its deleterious side effects. Intraoperative blood glucose in
(18.6%, P = 0.027) as in Table 4. nondiabetic patients undergoing elective major surgery under
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general anesthesia have been studied, and it has been found


Discussion that dextrose containing fluids as opposed to ringer lactate
increases the incidence of hyperglycemia in this subset of
Stress response to surgery and anesthesia may be aggravated
patients.[4] The choice of fluid is dependent on the underlying
by multiple factors such as preoperative fasting, temperature
illness the patient has. Ringer Lactate is the most common
fluctuations, use of drugs, tissue damage, and bleeding. The
maintenance fluid used in the perioperative period but always
stress response results in the systemic release of ACTH,
with the fear of lactates being converted to glucose especially
cortisol, catecholamine, aldosterone, AVP glucagon, acute
in diabetic patients. However, in our study, it was found
phase reactants, and cytokines in an effort to provide the
that there was no significant difference in the incidence of
host with energy along with retention of sodium and water
hyperglycemia based on the duration of surgery in the two
to maintain cardiovascular homeostasis. This high‑stress
groups.
state can result in harmful outcomes for the patient.
Gastrointestinal surgeries are associated with increased stress
We observed a significantly higher blood glucose levels in
response as well as higher fluid shifts, blood losses, and hence
the patients receiving acetate based solution undergoing GI
greater hemodynamic fluctuations when compared to flap
surgery when compared to patients undergoing reconstructive
surgeries which are more superficial surgeries. Higher blood
glucose levels were seen in patients undergoing GI surgeries
Table 1: Two hourly comparison of blood glucose in both the groups, though a significantly higher level of
between the two groups glucose was observed in patients receiving ringer acetate.
This was also noticed by Kumar et al.[5] in their study where
Glucose Group n Mean±SD P
G2H A 104 130.19±28.57 0.689
B 103 131.71±25.67 Table 3: Glucose levels in different surgeries based on
G4H A 103 138.79±28.66 0.572 duration in Group A
B 100 141.02±27.57
G6H A 60 146.15±24.09 0.660
Glucose Type of surgery n Mean±SD P
B 59 144.02±28.59 Baseline GI 78 108.28±17.16 0.639
G8H A 29 163.72±32.82 0.105 Flap 26 106.46±16.79
B 34 152.26±22.14 G2H GI 73 133.63±31.04 0.033
SD=Standard deviation Flap 30 119.83±15.76
G4H GI 71 140.19±29.96 0.393
Flap 29 134.62±24.46
Table 2: Glucose levels in different surgeries based on G6H GI 37 148.24±23.92 0.398
duration in Group B Flap 22 142.78±24.49
G8H GI 18 182.15±40.09 0.007
Glucose Type of surgery n Mean±SD P
Flap 16 148.75±13.83
Baseline GI 73 109.96±15.95 0.615 SD=Standard deviation, GI=Gastro intestinal
Flap 30 108.30±13.03
G2H GI 73 136.59±27.62 0.002
Flap 30 119.83±15.33 Table 4: Comparison of acidosis between the two groups
G4H GI 71 144.90±30.30 0.027 Groups Duration Acidosis P
Flap 29 131.52±16.14 (h)
No acidosis, n (%) Acidosis, n (%)
G6H GI 37 151.32±30.89 0.017
Flap 22 131.73±19.22 A <6 52 (88.1) 7 (11.9) 0.093
G8H GI 18 161.83±22.17 0.009 >6 34 (75.6) 11 (24.4)
Flap 16 141.50±16.98 B >6 57 (95) 3 (5) 0.027
SD=Standard deviation, GI=Gastro intestinal <6 35 (81.4) 8 (18.6)

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Figure 1: Flow diagram

The secondary objective of our study was to look at lactate


levels and the metabolic acidosis. We observed a higher lactate
level in patients undergoing GI surgery with duration >6 h
receiving ringer acetate solution. There was also a higher
incidence of acidosis in the Ringer acetate group undergoing
prolonged surgeries.
Higher lactate levels in Ringer acetate group are different from
the previous studies conducted by Kumar et al.[8] in donor
hepatectomy and Hadimioglu et al.[7] in kidney transplantation.
Kumar et al.[8] concluded that the acetated fluids had higher
bicarbonate, lesser base deficit, glucose, and chloride as well
as lower lactate than Ringer’s lactate with normal saline.
Hadimioglu[9] et al. compared three fluids normal saline,
Ringer’s lactate, and plasmalyte and found that the best
Figure 2: Comparison of incidence of hyperglycemia between the groups metabolic profile is with plasmalyte. The contradicting result
in our study cannot be explained.
progressively higher blood glucose was noticed in the Kabilyte
The finding of a higher incidence of acidosis in the ringer
group. Acetate has a role in carbohydrate and fat metabolism
acetate group in our study is contradictory to the previous
and can rarely cause a slight increase in glucose level.[6] These
study conducted by Hofmann‑Kiefer et al.[10] who found that
results were similar to the previous study done by Maitra acetated and lactated solutions did not show any superior
et al.[7] which showed that maintenance fluid therapy with acid‑base profile over each other. One of the reasons could
dextrose‑containing solution resulted in a higher incidence of be the lower pH range of the Ringer acetate solution which is
hyperglycemia when compared to Ringer’s Lactate. The choice 4.0–8.0 when compared to Ringer lactate which is 6–7.5. The
of fluids along with the type of surgery the patient undergoes more physiological pH of Ringer lactate may have resulted in
influences the blood glucose level in this subset of patients. less acidosis in this group.

722 Anesthesia: Essays and Researches ¦ Volume 12 ¦ Issue 3 ¦ July-September 2018


Balakrishnan, et al.: Lactated fluids doesn’t cause hyperglycemia
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Figure 3: Lactate levels in Group B undergoing different surgeries Figure 4: Lactate levels in Group A undergoing different surgeries

Limitations of our study are that the use of steroids and use of Financial support and sponsorship
vasopressors or inotropes have not been assessed and analyzed. Nil.
These drugs could also increase the blood glucose level by
stimulating glycolysis and gluconeogenesis. Preoperative Conflicts of interest
volume status of the patient was not assessed as the central line There are no conflicts of interest.
was inserted only after induction of GA, and it was not inserted
in all patients. This might have an influence on the blood glucose References
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based solutions, but the incidence of hyperglycemia was not of different crystalloid solutions on acid‑base balance and early kidney
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surgery exceeded 6 h, use of acetate‑based solutions resulted Conzen P, et al. Influence of an acetate‑and a lactate‑based balanced
in significantly higher lactate levels with progressive metabolic infusion solution on acid base physiology and hemodynamics: An
acidosis. observational pilot study. Eur J Med Res 2012;17:21.

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