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P Perioperative administration of single-dose dexamethasone helps reduce postoperative nausea and vomiting, inflammation, and pain. However, it is unclear which dose achieves these effects while minimizing the hyperglycemic impact in patients with diabetes. The purpose of this review was to elucidate the most appropriate perioperative dose of dexamethasone for diabetic patients, and whether it is necessary to withhold it in patients with poor glycemic control.
A systematic review.
A literature search using PubMed and Cochrane Database of Systematic Reviews revealed 17 potential evidence sources. Eight sources met the inclusion criteria. Sources included one systematic review with meta-analysis, one randomized control trial, and six observational studies.
Evidence suggests diabetic patients who receive dexamethasone perioperatively are more likely to develop postoperative hyperglycemia, with a maximum blood glucose increase of 30 to 45 mg/dL in the first 24 hours following a single dose. One study described increased blood glucose levels with escalating doses, but no other sources have supported that finding. The available studies were markedly heterogeneous in both design and proportion of diabetic subjects included, and most were of low quality.
There is not enough evidence to quantify the hyperglycemic effect of commonly used dexamethasone doses, and rigorous studies are needed to inform practice.
It remains unclear what the most effective dose of dexamethasone is to achieve these positive effects while minimizing its hyperglycemic effect. A review of the latest evidence is necessary to determine the appropriate perioperative dose of dexamethasone for diabetic patients and to examine if there is justification for withholding it in patients with poor glycemic control.
A rise in blood glucose is a particular concern in diabetic patients because it may contribute to delayed wound healing or increase the risk of postoperative infection.
The relationships between perioperative hyperglycemia, elevated HbA1c, and poor surgical outcomes are well-documented. Patients with both a HbA1c ≥ 6% and postoperative blood glucose ≥ 200 mg/dL are 4 times at higher risk of experiencing severe complications after emergency abdominal surgery.
It is difficult to isolate the hyperglycemic effect of single-dose dexamethasone because surgery stimulates an endogenous corticosteroid response. The stress response to surgery increases blood glucose, while the peripheral utilization of glucose decreases.
The question guiding this review was: “In diabetic patients undergoing surgical procedures, does dexamethasone 8-12 mg significantly increase postoperative blood glucose levels compared to 4-6 mg?” The target population included adult patients with diabetes mellitus type 1 or type 2 undergoing a variety of surgical procedures. Patients on chronic steroids, the critically ill, pregnant patients, and the pediatric population were excluded. The intervention was dexamethasone 8 to 12 mg administered intravenously around the time of induction, versus a lower dose of 4 to 6 mg, commonly used for PONV prophylaxis. The outcome was postoperative blood glucose level obtained within 24 hours after surgery to match the expected duration of the hyperglycemic effect of dexamethasone.
A systematic search for the best current evidence was conducted using PubMed and Cochrane Database of Systematic Reviews. Guidelines from professional organizations were also reviewed. The following keyword combinations were used in the search: dexamethasone AND diabetes OR diabetic OR hyperglycemia OR blood glucose OR blood sugar AND postoperative OR surgery. In addition, the “Similar Articles” feature in PubMed was employed to expand the search. The search was limited to English-language full-text articles published between January 1, 2005 and March 1, 2021, applied to include most present-day anesthetic agents.
The authors screened potential sources by title, then abstract, and finally by full text to determine eligibility for inclusion. Inclusion criteria were adult patients undergoing a surgical procedure under general or spinal anesthesia, diagnosis of diabetes mellitus type 1 or type 2, and intravenous dexamethasone administration. Due to differences in onset time, studies that examined dexamethasone administered predominantly by the oral or intramuscular route were rejected. Sources examining patients with chronic steroid use, critical illness, or pregnancy were excluded.
The following levels of evidence were considered for inclusion: systematic reviews of randomized controlled trials with or without meta-analysis, randomized controlled trials (RCTs), and observational studies. Individual studies included in a systematic review were not separately appraised. Reference lists of appraised sources were also considered. The evidence was appraised using the method described by Melnyk and Fineout-Overholt.
All sources examined the association between the perioperative administration of single-dose dexamethasone and postoperative blood glucose, where glycemic response to dexamethasone was either the primary or secondary outcome. Dexamethasone dose ranged from 4 to 12 mg. Only 2 studies reported using a placebo.
Another study included elective procedures performed below the level of the umbilicus, most commonly general surgery, but gynecology, orthopedics, plastic surgery, and other specialties also represented a small number of cases.
Selection bias may limit generalizability in observational designs due to a disproportionate number of subjects with severe disease between groups, with a potential for such disease to influence dexamethasone strategies.
Peak BG levels were observed as early as 2 to 3 hours following dexamethasone administration, but the hyperglycemic effect did not persist beyond 24 hours. In contrast, two studies found that perioperative dexamethasone was not associated with postoperative hyperglycemia.
reported that the change from baseline BG was statistically significant for diabetic and nondiabetic patients treated with dexamethasone; however, they found no significant difference in the diabetic and nondiabetic control groups. There were no clinically significant differences in the time to peak BG between those who received the 4 mg and 8 mg dose at 4 and 5 hours, respectively. The study also found a predictable rise in BG following treatment, peaking at 4 to 6 hours regardless of whether 4 mg or 8 mg had been administered.
They observed a parallel BG increase between groups peaking at 2 hours after dexamethasone administration; still, patients with diabetes had the most significant BG increase. There were no controls in this study as every subject received dexamethasone 10 mg.
the authors found that BG values peaked within 24 hours in all patient groups. For patients with diabetes, on postoperative day (POD) 1, the mean peak BG in patients who received dexamethasone was 201 mg/dL compared to 166 mg/dL for those that did not receive dexamethasone. In patients without diabetes, the mean peak BG was 135 mg/dL in dexamethasone-treated patients versus 121 mg/dL for the untreated group. The hyperglycemic effect of dexamethasone did not persist beyond POD 1.
A retrospective review of 238 diabetic patients who underwent primary joint arthroplasty
reported whether patients developed hyperglycemia, defined as any BG concentration ≥ 200 mg/dL. They observed postoperative hyperglycemia in 17.1% and 20.6% of the measurements during the first 24 and 72 hours, respectively. After controlling for confounding variables, patients who received dexamethasone had 4.07 (95% confidence interval [CI], 2.46-6.72) and 3.08 (95% CI, 2.34-4.04) higher odds of developing BG concentrations ≥ 200 mg/dL in the first 24 and 72 hours, respectively.
the authors also found that diabetic patients experienced significantly higher BG levels than nondiabetic patients, yet dexamethasone did not affect the increased BG concentration (P = .537). They did find an association between diabetes (P < .001), increasing HbA1c (P < .001), and increased BG levels, still dexamethasone had no influence (P = .595).
the maximum BG (median) for the dexamethasone group and the nondexamethasone group was 127 mg/dL and 130 mg/dL, respectively. The difference was not statistically significant (P = .594). Baseline BG levels for patients that did not receive dexamethasone were significantly higher than those that received dexamethasone, but according to the authors, the magnitude of the difference was small. Only 5.6% (95% CI, 3.8-7.5) of all patients had BG levels > 200 mg/dL.
The authors found no evidence of an association between dexamethasone administration and the odds of having postoperative BG levels > 200 mg/dL in diabetic or nondiabetic patients. The study sample consisted of a low proportion of diabetic patients.
Preoperative BG tended to be higher in patients with diabetes compared to patients without diabetes. However, the magnitude of BG increase from baseline was similar for both diabetic and nondiabetic patients.
found that the mean difference (MD) in the postoperative BG level of nondiabetic patients receiving dexamethasone was only slightly higher than that of patients not receiving it (MD 13 mg/dL, 95% CI, 6-21; 10 studies; 595 subjects; I² = 50%; low-quality evidence). They rated the evidence as low-quality due to the high risk of bias and wide CI. In patients with diabetes, the effect of dexamethasone was larger (MD 32 mg/dL, 95% CI, 15-49; 74 subjects; I² = 0%; very low-quality evidence).
evaluated the effects of 4 and 8 mg of dexamethasone in diabetic and nondiabetic patients receiving spinal anesthesia and learned that the increase in BG from baseline was similar in both groups despite higher preoperative BG values in those with diabetes. Blood glucose levels began to rise 3 hours after dexamethasone administration, with a sustained increase up to the last measured value. The investigators found that the hyperglycemic response in both diabetic and nondiabetic control groups was in the range of 10 to 15 mg/dL.
Conversely, both diabetic and nondiabetic treatment groups had a significant increase in the range of 40 to 43 mg/dL, with peak levels occurring between 4 and 6 hours after dexamethasone administration.
BG concentrations at baseline, 30 minutes, and 120 minutes after dexamethasone administration were significantly higher in the diabetic group (P < .001). Although the BG increase at 30 minutes did not reach statistical significance relative to baseline values (P = .287), at 120 minutes, it did (P < .001). Upon comparing BG concentrations at the 30- and 120-minute marks, the authors noted a statistically significant increase had occurred over time (P < .001). For the nondiabetic group, the BG increase at the 30- and 120-minute marks was statistically significant relative to baseline levels (P = .002 and P < .001, respectively). Upon comparing BG levels at the 30- and 120-minute marks, the authors also noted a statistically significant increase over time (P < .001). Reporting of baseline patient data and BG results were relatively insufficient in this study.
Relationship Between Dexamethasone Dose and Postoperative Blood Glucose
Few studies described the glycemic effects of specific doses of dexamethasone.
reported a significant BG increase in diabetic patients that received 4 and 8 mg compared to placebo. The investigators observed that the diabetic group that received 8 mg did not have higher BG values than the diabetic group that received 4 mg.
Unfortunately, they did not compare these two groups for statistical significance. On the other hand, they discovered that dexamethasone 8 mg caused a greater hyperglycemic response in nondiabetic patients compared to diabetic patients.
reported that patients who received 10 mg of dexamethasone had 3.52 (95% CI, 2.64-4.71; P ≤ .001) higher odds of exhibiting postoperative BG levels > 200 mg/dL within the first 72 hours compared to those who did not receive dexamethasone.
found no evidence of an association between dexamethasone administration and the odds of experiencing postoperative BG levels > 200 mg/dL (adjusted odds ratio [OR], 0.60; 95% CI, 0.19-1.87; P = .379).
Some anesthesia providers still face a dilemma regarding the dose of dexamethasone to administer to diabetic patients and whether the decision to withhold dexamethasone is defensible in patients with poor glycemic control. The quality of the included evidence in this review is low, given that six of eight studies are level IV evidence or less, and four of eight are retrospective. A significant limitation of the SR with meta-analysis
is that it only included two RCTs with small sample sizes in the subgroup analysis involving diabetic patients, and the quality of the studies was low.
Although diabetic patients tended to have higher BG levels, the evidence suggests the magnitude of the increase is similar in patients receiving dexamethasone regardless of diabetes status. Single-dose dexamethasone may induce a rise in BG of 30 to 45 mg/dL in patients with diabetes, with a peak effect in as early as 2 hours, and generally lasting less than 24 hours.
Still, the evidence remains inconclusive regarding the hyperglycemic effect of specific doses of dexamethasone. Rigorous studies are required to quantify the hyperglycemic impact of various doses of dexamethasone, especially the more common doses of 4 mg, 8 mg, and 10 mg.
The impact of inflammation precipitated by surgery on hyperglycemic response with dexamethasone is also unclear. The included studies were heterogeneous concerning the type of surgery, and no surrogate markers for perioperative inflammation were widely tested, such as C-reactive protein. This situation rendered any comparison by surgery type difficult.
Dexamethasone 4 mg IV for PONV prophylaxis has been recommended for diabetic patients undergoing same-day surgery.
Since a BG increase of 30 to 45 mg/dL following dexamethasone injection may occur, alternative PONV prophylaxis should be considered in patients with poorly controlled diabetes. Frequent BG monitoring is strongly recommended for all diabetic surgical patients for the first 24 hours after dexamethasone administration.
As part of the multidisciplinary team, perianesthesia nurses are essential to ensuring timely blood glucose testing and monitoring. This review enables perianesthesia nurses to identify patients at risk of hyperglycemia and empowers them to request a tailored monitoring and treatment strategy that matches an individual's risk for hyperglycemia. Such risk should be communicated during subsequent nurse-to-nurse handoff exchanges .
Diabetes 2030: Insights from yesterday, today, and future trends.
The views expressed in this article reflect the findings of a systematic review conducted by the authors and do not necessarily reflect the official policy or position of William Beaumont Army Medical Center, 528th Hospital Center, Uniformed Services University, Department of the Army, Defense Health Agency, Department of Defense, nor the United States Government.
Some of the authors are military service members. This work was prepared as part of their official duties. Title 17 USC 105 provides that “Copyright protection under this title is not available for any work of the United States Government.” Title 17 USC 101 defines United States Government work as a work prepared by a military service member or employee of the United States Government as part of that person's official duties.
Conflict of interest: No conflicts of interest to declare.