Effect of Using Ringer's Lactate, with and without Addition of Dextrose, on Intra-Operative Blood Sugar Levels in Infants Undergoing Facial Cleft Surgeries.

BACKGROUND: Addition of glucose in the intraoperative fluid is a routine practice in infants. Under general anesthesia, due to neuroendocrine stress response, this could result in overt hyperglycemia. AIMS: The aim of this study was to find whether the addition of 2% dextrose to Ringer's lactate (RL) caused hyperglycemia compared to no addition of dextrose to RL. SETTINGS AND DESIGNS: This prospective randomized study was conducted in 100 infants undergoing facial cleft surgery at a tertiary care institution. SUBJECTS AND METHODS: Group D received RL with 2% dextrose and Group R received RL without the addition of dextrose. Blood sugars were measured at induction, 1 h and 2 h later. Hyperglycemia was defined as blood sugar >150 mg/dL and hypoglycemia as <70 mg/dL. STATISTICAL ANALYSIS USED: Pearson's Chi-square test, Paired t-test, Mann-Whitney test, and Independent sample t-test were used as applicable.
RESULTS: Baseline blood sugar was comparable in both groups. A significant increase in blood sugar values from baseline was seen in both groups, but the increase was significantly more in Group D at 60 min (136.5 ± 41.9 vs. 109.2 ± 20.5) and at 120 min (150.1 ± 45.5 vs. 123.1 ± 31.7). The incidence of hyperglycemia was 50% in Group D and 12% in Group R. No patient developed hypoglycemia intraoperatively. No significant correlation between blood sugar and hours of fasting was established.
CONCLUSION: Routine addition of dextrose to RL is not essential during short surgeries under general anesthesia in infants, provided preinduction blood sugar level is >70 mg/dL and intraoperative sugars are periodically monitored.

INTRODUCTION

The 2nd Congress of the European Society for Paediatric Anaesthesiology in 2010 has recommended that pediatric intraoperative fluid should have an osmolarity close to the physiologic range and addition of 1%–2.5% instead of 5% glucose to avoid hypoglycemia, lipolysis, or hyperglycemia.[1] Addition of glucose in the intra-operative fluid has been a routine practice in this age group, although limited studies have successfully concluded the correct and most appropriate intraoperative maintenance fluid.

General anesthesia without supplemental regional anesthesia might result in elevated blood sugar levels secondary to stress response of anesthesia and surgery. Increased levels of cortisol and catecholamines augment glucose production because of increased hepatic glycogenolysis and gluconeogenesis along with reduced peripheral utilization of glucose.[23] Hence, there exists a high possibility that supplementing dextrose intraoperatively without regular blood sugar estimation might result in hyperglycemic episodes which can lead to osmotic diuresis, impairment of neurological outcome, and risk of hypoxic episodes under anesthesia.[4]

Aim of the study

The primary objective of this study was to find whether the use of Ringer's lactate (RL) with the addition of 2% dextrose as the intra-operative maintenance fluid resulted in hyperglycemia.

The secondary objectives included the impact of the use of RL on intra-operative blood sugar levels and assessment of the hemodynamic responses, as a manifestation of hypoglycemia, seen with the use of both the fluids.

SUBJECTS AND METHODS

This prospective randomized study was performed after obtaining the Institutional Ethical Committee clearance and consent from parents of the patients. One hundred and eleven patients aged 1 month to 1 year, of the American Society of Anesthesiologists (ASA) physical status Class 1, undergoing facial cleft repair surgery, without a supplemental regional block, lasting >2 h, were assessed for eligibility and 100 were recruited into the study. Infants of diabetic mothers and infants with diabetes were excluded.

Patients were kept fasting 6 h for solids and formula feeds, 4 h for breast milk and 2 h for clear fluids. On the day of surgery, they were randomly allotted to either Group D or Group R based on computer-generated random sequence of numbers and concealment of allocation was assured using sequentially numbered opaque sealed envelopes. All patients received general anesthesia as per a standardized protocol. Following induction with 8% sevoflurane in oxygen, pulse-oximeter electrocardiograph and noninvasive blood pressure monitors were attached, and a peripheral intravenous (IV) line was secured. The first random blood sugar reading was taken soon after induction, before initiating IV fluid administration.

All patients in Group D received RL with 2% dextrose irrespective of blood sugar reading, whereas Group R patients received plain RL if blood sugar was 70 mg/dL or above. This was done to reduce chances of the infant going into hypoglycemia, in the absence of glucose supplementation, as blood sugar was borderline. Blood sugar was checked half-hourly if the blood sugar reading was below 80 mg/dL, and hourly if the blood sugar was equal to or above 80 mg/dL in both the groups for 2 h. If at any time blood sugar value was between 70 and 80 mg/dL it was subsequently measured every 30 min. Blood sugar values were checked using a standard glucose meter (FreeStyle Optium H System, Copyright© 2015 Abbott Laboratories. Abbott Park, Illinois, USA) with test strips.

Hypoglycemia was defined as blood sugar <70 mg/dL[5] and hyperglycemia as blood sugar >150 mg/dL.[6] At any point during the study, in both the groups, if the blood sugar reading was below 70 mg/dL, 25% dextrose at 1 mL/kg, double diluted with saline, was administered IV as a bolus to correct hypoglycemia. The fluid was administered according to body weight based on Holliday and Segar formula.[7] The study ended at 2 h of surgery, and for those receiving RL alone till that period, the fluid was changed to RL with 2% dextrose to reduce the risk of development of hypoglycemia as frequent monitoring of blood sugars were not done after the study period.

Hours of fasting, type of surgery and the total volume of IV fluid used were recorded. The heart rate (HR), the mean arterial pressure, as well as the body temperature, were documented every 30 min. Volume and the number of times 25% dextrose bolus was administered, if required, were also noted.

To calculate the sample size, a pilot study was conducted in 40 patients. With one group receiving RL and the other group receiving RL with dextrose, considering the blood sugar values at 60 min as primary objective (109.3 ± 14.549 vs. 136.473 ± 38.944), with 95% confidence interval and 90% power, the minimum sample size required to obtain statistically significant result was calculated as one hundred.

Independent sample t-test was used to analyze and compare the baseline blood sugar values and values at 60 min and 120 min between the two groups. Paired t-test was used to compare the blood sugar values at 60 min and 120 min in each group. Pearson's Chi-square test was used to calculate the incidence of hyper and hypoglycemia. Mann–Whitney test was used to compare the change in blood sugar from baseline at 60 min and 120 min in both the groups. Spearman's rank correlation test was used to analyze the correlation between baseline blood sugar and hours of fasting. The statistical analysis was done using IBM SPSS Statistics 20 for Windows 8 (SPSS Inc., Chicago, USA).

RESULTS

Mean age, weight, the volume of intraoperative fluids infused at the end of 2 h, distribution of gender and ASA physical status were comparable [Table 1]. Total of eleven patients had hypoglycemic baseline values in both Groups, 7 and 4, and were excluded, and an equal number of new cases were recruited [Figure 1]. Baseline blood sugar was comparable in both groups (91.7 ± 13.1 vs. 96.2 ± 15.9, P = 0.130). Significantly higher blood sugar values were seen in Group D as compared to Group R at 60 min (136.5 ± 41.9 vs. 109.2 ± 20.5) and at 120 min (150.1 ± 45.5 vs. 123.1 ± 31.7). There was a significant increase from baseline in blood sugar values in both groups (P < 0.001) and the rise was more in Group D [Table 2 and Figure 2]. Hyperglycemia occurred in 54% of patients in Group D and 12% in Group R [Figure 3]. No patient developed hypoglycemia intraoperatively. Analysis of the correlation between baseline blood sugar and hours of fasting yielded a result of no correlation with a correlation coefficient (r) of-0.003 and P = 0.98. Baseline as well as intraoperative HR and mean arterial pressure were also comparable [Table 3].

Table 1

Demographics and volume of intravenous fluids infused in 2 h

Figure 1

CONSORT flow diagram

Table 2

Comparison of blood sugar and changes from baseline in Group R and Group D

Figure 2

Changes in blood sugars

Figure 3

Comparison of hyper and euglycemia

Table 3

Comparison of heart rate and mean arterial pressure

DISCUSSION

This study showed that there was a significant increase in blood sugar levels intra-operatively when RL was used with as well as without supplemental dextrose. Addition of dextrose increased the incidence of intraoperative hyperglycemia to 50% as compared to only 12% when RL alone was used.

Studies have shown that use of RL alone during the peri-operative period did not result in hypoglycemia.[8] At the same time, it was also shown that addition of 2% dextrose to RL, although resulted in an increase in intraoperative blood glucose, did not increase it beyond the normoglycemic limits. As this practice might add an extra margin of safety against the development of hypoglycemia in infants, our institutional practice mandates the addition of 2% dextrose[1] to intraoperative maintenance fluid of infants weighing <10 kg and 1% dextrose[8] to that of children up to age of 2 years.

It is believed that addition of glucose to the maintenance fluids is required as approximately 20% of the normal caloric needs are provided by IV glucose to avoid starvation ketoacidosis and protein degradation.[9] Moreover, it limits post-operative energy deficit and hyperglycemia, provides hourly energy requirements and avoids peri-operative hypoglycemia.[4]

Dextrose concentration and the rate of fluid administration intraoperatively varies according to the type of surgery, but 1%–2.5% dextrose containing isotonic fluids as maintenance fluid in infants has been proven to be most beneficial, by decreasing the incidence of hypoglycemia as well as hyperglycemia.[10]

Various concentrations of glucose as supplementation to IV fluids have been studied previously. 1% dextrose in RL had been shown to result in moderate postoperative hyperglycemia but avoided any perioperative hypoglycemic events.[4] Dextrose-containing solutions were found to be unnecessary to prevent hypoglycemia during elective surgery and even led to an increased incidence of hyperglycemia.[11]

In our study, analysis of the intra-operative blood sugar levels revealed a significant increase with and without addition of dextrose to RL. Similar observations were made by Dubois et al. in their study, wherein blood glucose levels had increased postoperatively in the groups of patients that received 1% and 2.5% dextrose, and also in the group that received RL without dextrose. But a concentration of 1% dextrose was considered as advantageous over higher concentrations as near normal blood sugar value was seen intra-operatively.[4]

Sümpelmann et al.[1] too, inferred on the same lines from their study on neonates that 1% dextrose as the intra-operative fluid maintained normoglycemia in this group of patients. And in older children and infants, it was demonstrated that the same concentration of 1% dextrose lead to hyperglycemia intra-operatively, but returned to normal levels in the post-operative period.

In our study, blood glucose levels increased with the use of 2% dextrose, with a few patients developing hyperglycemic values, but it increased without dextrose supplementation as well, probably secondary to the stress responses to anesthesia and surgery. Addition of dextrose in our study had significantly increased the incidence of intra-operative hyperglycemia to 50% as compared to only 12% when RL alone was used. This is in agreement with a previous study by Mierzewska-Schmidt[12] who compared the blood glucose values in three groups of children and found higher blood glucose values with glucose-containing solutions. The study differed from our study in that they used 5% glucose, 3.33% glucose, and Ringer's acetate as the intra-operative fluid. Use of Ringer's acetate without dextrose was concluded to be the safest IV fluid for intraoperative use in children aged 2–12 years during elective surgery.

Datta and Aravindan[6] in a review study on neonates, had advocated the use of 1%–2.5% dextrose, but patient population constituted of neonates, and thus, the data could not be extrapolated to the age group of 1 month to 1 year that we analyzed in the present study.

Observation that glucose containing fluids administered as maintenance fluid to treat presumed hypoglycemia actually caused worsening of hyperglycemia was made by Adenekan AT[13] but the age group studied by them was in the range of 3 months to 15 years and the two fluids compared were Ringer's acetate and 4.3% glucose. Some studies do advocate the use of dextrose in the intraoperative fluid to avoid hypoglycemia, but the concentrations of dextrose seem to vary. RL with 0.9% or 1% dextrose has been recommended for intraoperative fluid therapy in pediatric patients, as it reduces the risk of hyponatremia as well as hypoglycemia.[14]

Isotonic fluids are advised to be administered as maintenance fluid in all children over 1 month of age, as these infants are expected to maintain a normal blood sugar level during surgery, without dextrose. However, children with low body weight (<3rd centile), who are on parenteral nutrition or a dextrose containing solution preoperatively, surgery duration exceeding >3 h and children having extensive regional anesthesia are considered at risk of hypoglycemia if non-dextrose containing fluid is given. These patients should be given dextrose-containing solutions or have their blood glucose monitored during surgery.[6]

Eleven patients in our study who had baseline glucose levels of <70 mg/dL were found to have an average fasting period of 9 h due to various reasons like unexpected delays and refusal to feed. These patients received 25% dextrose as a bolus for correction of hypoglycemia. They were excluded from the study as the subsequent blood sugar values, if measured, would have been presumably high. Hence an equal number of new cases were recruited. We used 25% dextrose to correct hypoglycemia which was double diluted with normal saline and was given through a peripheral vein as facial cleft surgeries were usually performed with peripheral venous access only, unless there was a clear indication for a central venous line. As all our patients were of ASA physical status Class 1, no one had an existing central line to use. The study was restricted to 2 h as it was the usual surgical time duration of facial cleft surgeries such as chelioplasty and palatoplasty.

The major drawbacks of our study were that it was an unblinded one and the blood glucose estimation was done using capillary blood with glucose meter with test strips. Use of blood-glucose measurements with arterial blood gas analyzers would have yielded more accurate results. We have analyzed the hemodynamic parameters as part of the study as an indication of sympathetic responses to the development of intraoperative hypoglycemia, although these could occur due to inadequate depth of anesthesia or analgesia as well.

CONCLUSION

Routine addition of dextrose to RL was not found to be essential when used as intra-operative maintenance fluid during short surgeries under general anesthesia in infants, provided preinduction blood sugar level was >70 mg/dL and intraoperative sugars were periodically monitored.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.