Effect of adding dexamethasone to intrathecal bupivacaine on blood sugar of controlled diabetic patients undergoing diabetic foot surgeries

Eman A Ismail; Fatma Askar; Asmaa Toni; Mohamed Elyounsi; Omnia Askar

doi:10.4103/roaic.roaic_23_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 9 | Issue : 4 | Page : 302-309

Effect of adding dexamethasone to intrathecal bupivacaine on blood sugar of controlled diabetic patients undergoing diabetic foot surgeries

Eman A Ismail¹, Fatma Askar¹, Asmaa Toni¹, Mohamed Elyounsi², Omnia Askar¹
¹ Department of Anesthesia, Faculty of Medicine, Assiut University, Assiut, Egypt
² Department of Plastic Surgery, Faculty of Medicine, Assiut University, Assiut, Egypt

Date of Submission	14-Apr-2022
Date of Decision	04-May-2022
Date of Acceptance	22-Jun-2022
Date of Web Publication	29-Dec-2022

Correspondence Address:
MD Eman A Ismail
Associate Professor, Department of Anesthesia, Faculty of Medicine, Assiut University, Assiut 71515
Egypt

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/roaic.roaic_23_22

Abstract

Background Spinal anesthesia is acceptable in patients undergoing diabetic foot surgery. The duration of the spinal anesthesia has been improved by the addition of other drugs such as opioids, dexmedetomidine, clonidine, and dexamethasone. Dexamethasone may affect blood glucose levels. The primary outcome of the study was the effect of a single dose of intrathecal dexamethasone on blood glucose levels during the first 24 h postoperatively.
Patients and methods After approval, 60 diabetic patients, American Society of Anesthesiologists grades 2 and 3 with ages ranging from 20 to 70 years were enrolled in this randomized, double-blinded, placebo-controlled trial. All patients who underwent diabetic foot surgery under spinal anesthesia have controlled type II diabetes. Patients were randomly allocated into two equal groups: the control group was given intrathecal 2.5 ml of hyperbaric bupivacaine 0.5% plus 1 ml of 0.9% sodium chloride. The dexamethasone group was given intrathecal 2.5 ml of hyperbaric bupivacaine 0.5% plus 4 mg of dexamethasone.
Results The control group had significantly lower levels of blood sugar at different times compared with the dexamethasone group. However, at the end of 24 h, nonsignificant changes were present between the two groups. Also, using 200 mg/dl as a cutoff for high blood sugar, there were nonsignificant changes all through the 24 h in both groups. Moreover, dexamethasone prolongs the duration of analgesia and decreases paracetamol requirements during the first 24 h postoperatively.
Conclusions Addition of intrathecal dexamethasone did not change postoperative glycemic evolution in controlled diabetic patients undergoing diabetic foot surgery. However, it significantly prolongs the duration of analgesia and decreases analgesic consumption during the first 24 h postoperatively.

Keywords: blood sugar, dexamethasone, diabetic foot, intrathecal bupivacaine, pain

How to cite this article:
Ismail EA, Askar F, Toni A, Elyounsi M, Askar O. Effect of adding dexamethasone to intrathecal bupivacaine on blood sugar of controlled diabetic patients undergoing diabetic foot surgeries. Res Opin Anesth Intensive Care 2022;9:302-9

How to cite this URL:
Ismail EA, Askar F, Toni A, Elyounsi M, Askar O. Effect of adding dexamethasone to intrathecal bupivacaine on blood sugar of controlled diabetic patients undergoing diabetic foot surgeries. Res Opin Anesth Intensive Care [serial online] 2022 [cited 2023 Mar 26];9:302-9. Available from: http://www.roaic.eg.net/text.asp?2022/9/4/302/365790

Introduction

Diabetic foot is one of the most serious complications of diabetes and is defined as a foot affected by ulceration that is associated with neuropathy as nerve damage affects the motor, sensory, and autonomic fibers, or peripheral arterial disease of the lower limb, which commonly affects the segments between the knee and the ankle. When minor injuries are complicated by infection, it increases the demand for blood in the foot. An inadequate blood supply may result in foot ulceration, potentially leading to limb amputation. The prevalence of diabetic foot ulceration in the diabetic population is 4–10%; the condition is more frequent in older patients. It is estimated that about 5% of all patients with diabetes present with a history of foot ulceration, while the lifetime risk of diabetic patients developing this complication is 15% [1].

Providing anesthesia for diabetic patients is a challenge because of associated serious comorbidities in these patients. Spinal anesthesia is reasonable and acceptable in patients undergoing diabetic foot surgery [2]. The quality and duration of spinal anesthesia has been improved by the addition of other drugs such as opioids, dexmedetomidine, clonidine, magnesium sulfate, neostigmine, ketamine, midazolam, and dexamethasone [3].

Dexamethasone is a potent synthetic glucocorticoid with anti-inflammatory, immunomodulating, analgesic, anti-shivering, and antiemetic effects. In the perioperative setting, low dose is administered primarily for nausea and vomiting prophylaxis. The neuroendocrine and inflammatory stress response caused by surgery may be modulated by steroids. Intraoperative use of dexamethasone reduced pain and analgesic consumption, improved mood and fatigue scores, and improved recovery after surgery [4].

The primary outcome of this study was the effect of a single dose of intrathecal dexamethasone (4 mg) on blood glucose levels during the first 24 h postoperatively.

Secondary outcomes included postoperative first analgesic request, total dose of analgesia in 24 h, intraoperative and postoperative nausea and vomiting (PONV), and postoperative wound infection.

Patients and methods

This randomized, double-blinded, and placebo-controlled study was carried out on 60 diabetic patients, American Society of Anesthesiologists grades 2 and 3 in the age range of 20–70 years. All patients have controlled type II diabetic patients [random blood sugar (RBS <180 mg/dl] from both sexes who underwent diabetic foot surgery at our hospitals. This study was registered at ClinicalTrials.gov (NCT03871049) and approved by the Local Research Ethics Committee of our institution (Ref 2019/IRB017100728). The study was conducted from January 2020 to September 2021 in the Plastic Surgery Department.

The exclusion criteria included patient refusal, patients with major cardiac, respiratory, renal, hepatic disorders or uncontrolled diabetes mellitus, history of chronic use of analgesic medication or hypersensitivity to drugs used in the study, preoperative use of steroids, and any contraindication to regional anesthesia. Written informed consent from all participants was obtained. The study was conducted in adherence with the CONSORT guidelines and the regulations and amendments of the Helsinki Declaration.

Preoperative management

All patients were assessed clinically before surgery including full history, thorough clinical examination, and laboratory investigations (fasting and RBS, blood picture, liver, and kidney functions). Patients were premedicated with oral diazepam 5 mg the night before surgery. Also, patients were kept on an insulin sliding scale. In the operating room, patients have basic monitoring including ECG, noninvasive blood pressure, and pulse oximetry. Baseline values of heart rate, mean arterial blood pressure, and arterial oxygen saturation were recorded.

Intravenous access was established, and each patient was preloaded with 500 ml of normal saline (0.9%). Patients were randomly allocated into two equal groups according to computer-generated randomization code (n=30 for each): The control group (group I) was given intrathecal 2.5 ml of hyperbaric bupivacaine 0.5% plus 1 ml of 0.9% sodium chloride. The dexamethasone group (group II) was given intrathecal 2.5 ml of hyperbaric bupivacaine 0.5%, plus 4 mg (1 ml) dexamethasone. To maintain the blinding of the study, an assistant anesthetist, who was not involved in the study, prepared the study drugs.

Under complete aseptic technique, the subarachnoid block was performed in the sitting position using a 25 G spinal needle at the L3–L4 interspace. The study medication was slowly injected. Then, the patient turned supine. The attending anesthesiologist was not aware of the content of the injected solution and was not involved in the patient assessment. The time at which the injection was completed was considered the zero time of the study, and all the times were recorded from this time. Monitoring and assessment were carried out by another investigator blinded to the studied solution. Estimated fluid requirement and maintenance fluid were replaced with Ringer’s lactate. Intraoperative monitoring of heart rate, mean arterial blood pressure, and oxygen saturation were recorded every 5 min from the zero time intraoperatively. Bradycardia (below 60 beats/min) was treated with intravenous atropine 0.5 mg. Hypotension (mean blood pressure below 20% of the basal reading) was treated by fluid bolus and/or ephedrine. Any episode of bradycardia, hypotension, or desaturation was recorded and treated. Postoperative analgesia was assessed using a visual analog scale (VAS), which ranges from 0 to 10 (0=no pain at all, 10 maximum unimaginable pain).

Hemodynamic parameters including heart rate, mean blood pressure, and peripheral oxygen saturation were recorded in the postanesthesia care unit every 15 min until complete recovery from anesthesia. The severity of pain was measured with VAS every 6 h. Analgesia was done with the use of intravenous paracetamol 1 g when VAS more than or equal to 4. Duration of effective analgesia was taken from the time of intrathecal drug administration to the first supplementation with analgesia. Total number of paracetamol dosage was recorded. During follow-up, any nausea and/or vomiting were recorded and treated with 4 mg of ondansetron intravenously. Wound infection was recorded after 1 week during the follow-up.

Blood glucose was measured by the Stat Strip glucose meter (Gluco Dr. Auto A) (made in Korea). Blood used to determine glucose concentrations was collected from finger prick capillary blood samples drawn from a warmed upper extremity. Samples were collected preanesthesia (baseline) and then 1-, 6-, 12-, and 24-h postinjection. We have recorded the incidence of hyperglycemic episodes defined as a blood glucose level more than or equal to 200 mg/dl [5]. The area under the curve where the blood glucose level was more than 200 mg/dl throughout 24 h was calculated and determined as a primary outcome. Oral hyperglycemic agents were held, and patients were managed with sliding scale insulin according to blood glucose levels.

The sample size was calculated on RBS at 24 h as a primary outcome. Based on a previous study [6], to be able to detect a 20 mg increase in RBS with an alpha level of 0.05 and a power of 80%, 26 patients in each group were required. Four patients were added to each group to compensate for possible dropouts.

Statistical analysis

Data were verified, coded by the researcher, and analyzed using SPSS, version 24 (IBM_SPSS, Statistical Package for the Social Sciences, version 24. Standard version. Copyright, 2012-2016, 2016; SPSS Inc., Armonk, New York, USA). Descriptive statistics: means, SDs, and percentages were calculated. χ² test was used to compare the difference in the distribution of frequencies among different groups. Shapiro–Wilk test was used to test the data normality. For continuous variables, independent sample t test analysis was carried out to compare the means of normally distributed data. Repeated measures analysis of variance test was calculated to test the mean differences of the data that followed normal distribution and had repeated measures (between groups, within groups, and overall difference). A P value less than 0.05 was considered significant.

Results

[Figure 1] shows the CONSORT flowchart. The two studied groups were matched for age (57.3 vs. 53.1 years, P=0.160), sex (male/female ratio was 17/13, 20/10, P=0.596), and weight (73.6 vs. 74.9, P=0.686) ([Table 1]). There were no statistical differences between the two groups regarding the type of surgical procedures (debridement, toe, transmetatarsal, or ray amputations).

Figure 1 CONSORT flow diagram.

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Table 1 Baseline characteristics of the studied groups

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There was a significant difference in the mean RBS between the two treatment modalities over time (P<0.001) ([Figure 2]). The mean RBS was significantly lower in group I than group II at 5-min before intrathecal injection, 1, 6, and 12 h postinjection (P=0.004, P<0.001, P=0.002, and P<0.001, respectively). However, at the end of 24 h, a nonsignificant lower level was recorded (P=0.428). For group I, RBS levels showed significant reduction till 24 h (P<0.001), while RBS levels for group II exhibited stepwise elevation over the study period (P<0.001) ([Table 2]). However, after 1 h there was no blood glucose concentration equal to or more than 200 mg/dl in the two groups. After 6 h, there were six patients who had blood sugar more than 200 mg/dl in group I compared with five patients in group II. After 12 and 24 h, four patients had blood sugar of more than 200 mg/dl in both groups ([Table 2]). In addition, the mean sum of RBS for the 24 h after treatment was lower in group I than group II (144.3±19.1 vs. 173±10.9, P<0.001). Conversely, using 200 mg/dl as a cutoff for high blood sugar revealed that the two groups were matched regarding the effect of treatment, that is, at 12 and 24 h; 13.3% of both groups had an RBS more than 200 mg/dl ([Table 2]).

Figure 2 Levels of RBS (mg/dl) among study groups over time. RBS, random blood sugar. G I=control group. G II=dexamethasone group.

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Table 2 Comparisons of random blood sugar (mg/dl) levels between the two groups over time

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[Table 3] shows the difference in the outcomes of the two treatment regimens. There were insignificantly higher rates of nausea and vomiting in group I compared with group II (P=0.115 and 0.381). Three patients in group I and two patients in group II developed intraoperative hypotension and were managed with ephedrine. On the other hand, group II had insignificant higher rates of wound infection (P=0.353). The mean required total paracetamol dose was significantly higher in group I than group II (P=0.015). The duration of analgesia was significantly (<0.001) longer in group II (2.9±0.5 h) compared with group I (1.9±0.5 h).

Table 3 Rate of outcomes among the studied groups

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Discussion

The present study showed that there were significant changes in the level of blood glucose between the two groups as the control group had significantly lower levels of blood sugar at different times compared with the dexamethasone group, but at the end of 24 h, nonsignificant changes were present between the two groups. Also, using 200 mg/dl as a cutoff for high blood sugar, there were nonsignificant changes all over 24 h in both groups. This means that the blood glucose levels were higher than usual on the first day following intrathecal dexamethasone injection; however, these levels were not critical. So, our study does not have an exaggerated hyperglycemic response to intrathecal dexamethasone in controlled diabetic patients.

Several studies have investigated the effect of dexamethasone, by different routes, on blood sugar. Many of them have documented an increase in blood glucose levels in the postoperative period following the use of dexamethasone as PONV prophylaxis [7],[8].

Hans et al. [9] found that after a bolus of 10 mg dexamethasone, blood glucose concentration profile in the first 6 h postoperatively was significantly higher in diabetic than in nondiabetic patients undergoing routine abdominal surgery and peaked 2 h after injection.

Also, Nazar et al. [10] observed that 8 mg intravenous dexamethasone administered after induction of laparoscopic bariatric surgery in patients with impaired glucose tolerance is associated with significantly increased postoperative blood glucose concentrations.

deGraft-Johnson et al. [11] found that patients in the dexamethasone group had higher blood glucose levels throughout the study period, especially at 8 and 24 h postoperatively. There was no difference in the incidence of clinically significant hyperglycemia between the control and study groups.

Lukins and Manninen showed that patients who were given dexamethasone intraoperatively and postoperatively had a higher peak glucose level compared with patients who received no dexamethasone or those who had been taking it before surgery and continued it during surgery. The peak blood glucose concentrations in this group occurred 9±2 h after the induction of anesthesia [12].

Purushothaman et al. [13] analyzed that PONV prophylaxis with intravenous dexamethasone 4 or 8 mg significantly increases blood glucose values compared with placebo. The rise of blood glucose started 3 h after the administration of dexamethasone, and patients had a sustained rise till 8 h following dexamethasone administration.

Also, Tien and colleagues showed an increase in postoperative blood glucose levels in both nondiabetics and diabetics after intravenous dexamethasone administration. The increase in blood glucose levels was greater in patients receiving intravenous dexamethasone compared with those receiving ondansetron for PONV prophylaxis. This increase was seen as early as 4 h after the induction of anesthesia [7].

However, Low et al. [14] found that hyperglycemic response is dose dependent as their study showed a greater postoperative blood glucose increase in diabetic patients following 8–10 mg of dexamethasone compared with 4 mg.

With injected epidural steroid, Lee et al. [15] found that an increased blood glucose level was the most frequent systemic reaction in diabetic patients. Also, Even et al. [16] found that a significant increase in blood glucose levels in diabetic patients occurred after epidural steroid injections.

Nazar and colleagues randomly allocated 40 nondiabetic and 30 diabetic patients undergoing laparoscopic surgery to receive intravenous dexamethasone or saline placebo. They concluded that all patients experienced comparable increases in blood glucose levels regardless of the diabetic status, with a more pronounced effect in patients receiving dexamethasone. Diabetic patients did not show a higher susceptibility than nondiabetics to develop postoperative hyperglycemia after the use of prophylactic dexamethasone for PONV [17].

Unlike the findings of our study, in patients undergoing gynecologic surgery, blood glucose concentrations during the first 24 h after administration of single low-dose dexamethasone did not differ from those observed after saline administration [6].

Moreover, Abdelmalak et al. [18] reported that the increase in blood glucose levels were greater in nondiabetic patients receiving dexamethasone, but that dexamethasone had no impact on the blood glucose change in diabetics. However, the number of patients who reached 200 mg/dl was insignificant between the two groups in our study. So, we can use intrathecal dexamethasone to increase the analgesic duration as several experiments demonstrated analgesic effects of dexamethasone in neuraxial and peripheral blocks [19].

Our study showed insignificantly lower rates of nausea and vomiting in the dexamethasone group compared with the control group. On the other hand, dexamethasone group had insignificantly higher rates of wound infection. Moreover, the total paracetamol dose and the mean total dose required were significantly higher in the control group than the dexamethasone group.

Movafegh and Ghafari [20] reported that addition of dexamethasone to lidocaine for spinal anesthesia provided significant prolongation of sensory and motor block compared with plain lidocaine.

Preoperative epidural administration of dexamethasone 5 mg, with or without bupivacaine, has been found to reduce postoperative pain and morphine consumption following laparoscopic cholecystectomy [21].

The mechanism of analgesia induced by intrathecal dexamethasone may be attributed to intraspinal prostaglandin production. Peripheral tissue stimulation by acute painful stimuli leads to sensitization of dorsal horn neurons of the spinal cord by the release of glutamate and aspartate. These amino acids activate N-methyl-D-aspartate receptors resulting in calcium ion influx, which leads to the activation of phospholipase A2. This in turn converts membrane phospholipase to arachidonic acid. Corticosteroids can reduce prostaglandin synthesis by the inhibition of phospholipase A2 through the production of calcium-dependent phospholipid-binding proteins called annexins and by the inhibition of cyclooxygenases during inflammation [22].

Šakić et al. [23] reported that the duration of spinal analgesia was prolonged with the addition of dexamethasone to intrathecal levobupivacaine compared with spinal levobupivacaine.Stryker et al. [24] showed that patients with a mean postoperative blood glucose of more than 200 mg/dl had an increased risk for wound complications. This may explain the insignificant finding in our study with the few patients that had RBS more than 200 mg/dl.

Dexamethasone is a synthetic glucocorticoid. Glucocorticoids are steroid hormones that regulate different actions of glucose homeostasis. It decreases glucose uptake and utilization in the skeletal muscle and adipose tissue by antagonizing insulin response. Glucocorticoids increase glycogen storage in the liver. In skeletal muscles, they regulate glycogenolysis and glycogen synthesis. Glucocorticoids regulate the secretion of glucagon and insulin. These hormones regulate the levels of blood glucose. The main function of glucocorticoid is to preserve glucose for the brain during stress [25].

The first limitation of our study is that we cannot eliminate the possibility of stress-induced hyperglycemia. Second, we were unable to record the exact meal timing or the calories the patients had consumed which affected the blood glucose levels. Also, we did not measure the preoperative glycosylated hemoglobin. Finally, we did not follow up our patients beyond the first week for the possibility of wound infection.

To the best of our knowledge, no previous studies have investigated the effect of intrathecal dexamethasone on blood glucose levels in diabetic patients. More studies are needed to explore the benefits as well as the complications of intrathecal dexamethasone in diabetic patients.

Conclusions

Addition of intrathecal dexamethasone did not change postoperative glycemia evolution in controlled diabetic patients undergoing diabetic foot surgery. However, it significantly prolongs the duration of analgesia and decreases analgesic consumption during the first 24 h postoperatively.

WHAT IS KNOWN

Intrathecal dexamethasone prolongs the duration of local anesthetics. It is unknown if it affects the blood glucose levels in diabetic patients.

WHAT IS NEW

Intrathecal dexamethasone may increase blood glucose levels in diabetic patients. However, that increase is not clinically significant. Moreover, it prolongs the duration of postoperative analgesia and decreases postoperative analgesic consumption.

Acknowledgements

The authors thank patients for their agreement to participate in the study.

Authors’ contributions: E.A.I. and F.A. have given substantial contributions to the conception and design of the manuscript. A.T., M.E., and O.A. have given acquisition, analysis, and interpretation of the data. E.A.I. and F.A. revised the manuscript critically.

Source (s) of support: Authors denote that the study has used local departmental resources with no external fund.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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