Clinical conundrums in the management of common geriatric endocrine issues in the perioperative settings: A narrative review

INTRODUCTION

Modern medicine has prolonged life and has allowed for more elderly patients presenting for operative procedures. Advanced age is associated with a myriad of metabolic issues discovered not uncommonly in the perioperative period. Often, it is the comorbidities that define and predict the prognosis of the elderly population during hospital visits.^[1] Older people tend to have multiple endocrine comorbidities, translating into polypharmacy-related complications. All this accentuates the cost of healthcare.^[2] Here, we illustrate several common and sometimes not-so-common perioperative endocrine issues that many anaesthesiologists will encounter, especially when dealing with elderly patients. We conducted a literature search related to this topic (last 25 years) using databases and search engines (PubMed Central, Embase, Scopus, and Google Scholar) using words such as ‘perioperative’, ‘adrenal adenoma’, ‘diabetes mellitus’, ‘thyroid storm’, ‘geriatric’, and ‘hypothyroidism’. We included studies specific to the geriatric population in the perioperative period. We found original articles including randomised trials, observational studies, systematic reviews, meta-analyses, clinical recommendations, retrospective studies, and case reports related to perioperative endocrine disorders in older people. We did not include articles not in the English language and those whose full text could not be accessed. We favoured experimental research studies and meta-analyses. The interesting literature that was obtained thereby, along with our interpretation of the research, is presented in this review.

PERIOPERATIVE MANAGEMENT OF DIABETES

Diabetes mellitus type 2 (DM2) is a major metabolic disorder with insidious onset. It remains asymptomatic with respect to pain until the advanced stages, although it may still produce other symptoms, including but not limited to frequency of micturition and polydipsia. The elderly population often dismisses symptoms of diabetes as mere ageing. If the blood glucose is uncontrolled prior to surgery, it could exponentially increase with the stress of the surgery. Any surgical intervention leads to a stress response by increasing catecholamines, cortisol, and cytokines.^[3] Additionally, glucagon and growth hormone oppose the action of insulin, leading to decreased insulin sensitivity and higher blood sugar; this process is accentuated in older people, who have higher insulin resistance at baseline. The conglomeration of these factors leads to metabolic processes such as upregulation of gluconeogenesis, glycogenolysis, and ketogenesis, resulting in a state of diabetic ketoacidosis(DKA) if not properly addressed.^[4,5] The process is even more challenging in older people, as they have multiple underlying comorbidities. The increase in short and long-term mortality in older people (3.5% and 22% respectively)^[6] can be attributed to comorbidities such as cardiac disease and diabetes. Complications such as respiratory infections, urinary tract infections) and kidney injury often leads to admissions in critical care units.^[7]

The United States Preventive Services Task Force recommends screening all adults aged 40 to 70 years who have risk factors for DM2.^[8] The American Diabetes Association (ADA) recommends screening all overweight adults with risk factors for DM2. These recommendations are not specific to pre-operative settings or older people. The word ‘overweight’ seems to be overemphasised in all the screenings for DM2. This may not be true in elderly patients who tend to have sarcopenic obesity, so routine screening for DM2 should be done before all elective and emergent surgeries.^[9]

The perioperative screening for DM2 with glycosylated haemoglobin (HbA1c) remains controversial. HbA1c is sometimes falsely high or low. In anaemic states, it is falsely high, and in the case of rapid red blood cell turnover, it tends to be falsely low. Also, there is no clear-cut HbA1c number associated with a better post-operative outcome. In a study on veterans for joint replacement surgery, it was found that a decreased HbA1c was associated with better clinical outcomes. Postponing elective joint surgeries with HbA1c values greater than 8% resulted in intensification of glycaemic control and possibly better awareness on the part of the patient.^[10] Also, it would be reasonable to postpone surgeries with acutely hyperglycaemic states such as DKA and non-ketotic hyperosmolar state.^[5]

Anaesthesiologists need to be well-versed about the pros and cons of common diabetes drugs and need to be astute in the appropriate use of insulin in the perioperative settings. We would start with metformin, which is a common diabetic drug used for glycaemic control. Traditionally, it was held on the day of the surgery until the patient was tolerating the diet due to the risk of metabolic acidosis. However, recent meta-analysis studies have shown that there was no increased risk of lactic acidosis in over 70,000 patients.^[11] Based on this study, it would be prudent not to hold metformin on the day of the surgery, especially when no exposure to nephrotoxic drugs is expected. It may be prudent to hold the drug if the patient is at risk of lactic acidosis.^[12-14] This may be especially true in elderly patients with congestive heart failure.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been widely adopted for glycaemic control because of their beneficial effects on renal and cardiovascular health.^[15] But the pitfall for this is the rare chance of the development of euglycaemic DKA with this drug class. To avoid this, it has been recommended to hold these drugs for 3 days prior to surgery [Figure 1]. If SGLT-2 inhibitors are taken and the patient requires emergent surgery, then the patient needs to be monitored for euglycaemic DKA until the stress of surgery is over, which is typically 72 hours^[16] [Figure 1]. If sulphonylureas are taken, then one must watch for hypoglycaemia. The scrutiny period would depend on the half-life of the individual drug, which varies widely.

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Figure 1:

Recommended hold duration of oral hypoglycaemics and glucagon-like peptide-1 (GLP-1) agonists in the pre-operative period (hours); metformin and DPP-4 inhibitors need not be held routinely; sulphonylureas to be held on the day of the surgery; SGLT-2 inhibitors to be held 3 days prior to the surgery; long-acting GLP-1 agonists to be held a week before the surgery; short acting GLP-1 agonists to be held 12-24 hours before the surgery. DPP: Dipeptidyl peptidase, SGLT: Sodium-glucose cotransporter

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Dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used for the management of DM2.^[3] These drugs should be continued and administered on the day of surgery as soon as the patient is ready to swallow. Because of their glucose-dependent mechanism, they do not cause hypoglycaemia.^[17]

There has been widespread adoption of glucagon-like peptide-1 (GLP-1) agonists in clinical practice. These drugs are known to delay gastric emptying and increase the chance of aspiration during the induction of anaesthesia. It has been recommended by the American Association of Clinical Anesthesiologists to hold this drug for 1 week in the pre-operative period to reduce the risk of aspiration. Shorter-acting GLP-1 agonists such as liraglutide may be held up to 24 hours before the surgery [Figure 1]. If emergency surgery is needed and the patient is on a GLP-1 agonist, a rapid sequence induction should be performed, and appropriate precautions should be taken to prevent the risk of aspiration.^[18-20]

One needs to be circumspect in dosing insulin in elderly patients perioperatively, as there exists a chance of hyperglycaemia or hypoglycaemia if not dosed correctly. Elderly patients frequently have underlying chronic kidney disease (CKD), which puts them at high risk for hypoglycaemia.^[21] When the glomerular filtration rate drops below 60ml/min, insulin metabolism is compromised, putting older people at risk for hypoglycaemia. Severe hypoglycaemia could also potentially precipitate acute coronary syndrome, as they frequently have coronary artery disease. This reinforces the importance of diligent perioperative risk stratification in perioperative settings.^[22] Often, CKD is overlooked in the perioperative risk stratification as it is asymptomatic in its early stages.^[22] Another pertinent point is whether the patient has diabetes mellitus type 1 (DM-1) OR DM2. For DM-1, there is a need to consider a 50% dose reduction for long-acting insulin like insulin glargine, detemir, or degludec. For intermediate-acting insulin like neutral protamine hagedorn (NPH), a dose reduction to 70-90% can be considered. Also, on the morning of surgery, a dose reduction to 50% can be considered.^[23] [Figure 2]. If the patient is on an insulin pump, no adjustments are normally needed. The current hybrid closed-loop systems have an automated insulin delivery system and should be continued.^[24] The clinician will need to be more conservative in dosing insulin in elderly patients with CKD, especially those on dialysis. These patients are at a very high risk of perioperative hyperglycaemia.

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Figure 2:

The recommended pre-operative insulin doses for diabetes mellitus type 1 (DM-1) measured as a per cent dose. Long acting insulins should be administered fully the evening before the surgery and not administered on the morning of the surgery; immediate-acting insulins such as NPH should be administered at roughly 75 per cent the evening before the surgery and at 50 per cent the morning before the surgery; rapid acting insulin such as aspart should be administered fully the evening before the surgery and not administered the morning of the surgery; any insulin pumps should be working at roughly half potential the evening before the surgery, with the same recommendation for the morning before the surgery. NPH: Neutral protamine hagedorn

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The pre-operative management would be slightly different in the case of DM2. The long-acting insulin the night before surgery should be dosed at 80% of the normal dose,^[25] but if there is a history of morning hypoglycaemia, a reduction of the dose to 50% of the regular dose can be considered. Also, if there is a history of morning hyperglycaemia, a full dose may be given. On the morning of the surgery, only 50% of the dose should be given.^[26] If NPH insulin is being used, which is not very common nowadays, we recommend giving 80% of the dose the night before surgery and 50% of the dose in the morning [Figure 3]. The morning dose may be skipped if the sugar is less than 120 milligrams per cent.^[23]

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Figure 3:

The recommended pre-operative insulin doses for diabetes mellitus type 2 (DM-2) measured as a per cent dose. Long acting insulins should be administered at roughly 77.5 per cent the evening before the surgery and 50 per cent the morning of the surgery; immediate-acting insulins such as NPH should be administered at roughly 77.5 per cent the evening before the surgery and at 50 per cent the morning before the surgery; rapid acting insulin such as aspart should be administered fully the evening before the surgery and not administered the morning of the surgery; any insulin pumps should be working at full potential the evening before the surgery, but at only 70 per cent the morning before the surgery. NPH: Neutral protamine hagedorn

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If the patient is using a non-hybrid insulin pump, it should be continued, and on the morning of the surgery, the basal rate should be reduced to 80%. The adjustments are not needed with modern hybrid closed-loop systems, as they are based on automated insulin delivery.^[27] If the insulin pump is interfering with the surgery, it may need to be removed. In that case, glucose may need to be monitored every 1-2 hours.^[28]

Perioperative glycaemic targets in the elderly

Before the topic is broached further, it is important to underline the problems associated with hyperglycaemia in the hospital. Hyperglycaemia in the critical care settings is associated with surgical site infections, increased acute coronary events, and increased length of stay in the hospital. Cardiac surgeries are common, and post-operative infections could be devastating for the patients. It costs the healthcare system a lot of money, aside from increased morbidity and mortality.^[5] For every 20 milligram/decilitre increase in blood glucose, the change in hyperglycaemia-related complications is an astounding 30%.^[29] In case of bariatric surgery, hyperglycaemia beyond the target range increases the risk of infection, death, and anastomotic failure, which leads to surgical intervention.^[30] A pertinent point here is that hyperglycaemia in non-diabetic patients carries an even worse prognosis when compared to patients having diabetes.^[31] This could be an outcome of an increased pro-inflammatory state in the body, which is reflective of the underlying comorbidities. As per the NICE-SUGAR trial, the target range for glycaemic control in hospital settings lies between 100 and 180 milligrams per cent.^[32] In critical care settings, the target is set at 100-140 milligram per cent^[32] [Figure 4]. This target minimises the risk of hyperglycaemic complications, and at the same time, prevents the morbidity and mortality related to hypoglycaemia. However, the glycaemic targets need to be slightly higher in elderly patients with underlying CKD as they are more prone to hypoglycaemia, especially in perioperative settings. Current guidelines do not specifically address this issue.^[33-34] In the NICE-SUGAR trial, the mean age of the patients was 60 years, and this did not specifically address glycaemic controls in the elderly population with underlying CKD.

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Figure 4:

Target ranges of glycaemic control should be roughly 100-180 mg% in hospital settings and 100-140 mg% in critical care settings

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PERIOPERATIVE MANAGEMENT OF THYROID DISORDERS

People who have thyroid disease should be assessed preoperatively to ensure an euthyroid state.^[35] This is especially important in older people, as they are often on polypharmacy, and this could interfere with the absorption of thyroid hormone replacement therapy, leading to an inappropriately treated hypothyroid state.^[36] Also, hypothyroidism is fairly common in older people, especially in women, and because of this, a pre-operative assessment of thyroid hormones is recommended in them.^[35]

If the patient has a goitre, an appropriate airway assessment should be done prior to the surgery.^[37] THRT should be continued in the perioperative settings.

PERIOPERATIVE MANAGEMENT OF ADRENAL DISORDERS

In the elderly population, steroids are often used for the treatment of various autoimmune problems, as an adjunct to chemotherapy, and a myriad of other pro-inflammatory disorders. Often, these steroids are continued long-term, leading to adrenal insufficiency due to the suppression of the hypothalamic-pituitary-adrenal axis. These patients would benefit from stress-dose steroids in the perioperative settings.^[35] Often, there is overzealous supplementation of the steroids. Older people are at high risk for steroid-related psychosis, which could complicate the perioperative course.^[42], Under normal physiology, cortisol secretion rarely exceeds 200 mg/day, and often, much less than even that.^[43] There is no good data to define the exact dosage of the steroids in the perioperative settings, but superficial surgeries such as biopsies or dental cavity fillings do not require additional steroids.^[44] Minor surgeries like inguinal hernia repairs require 25 mg of hydrocortisone prior to the repair. Moderately complicated surgeries like total joint replacements would require hydrocortisone 50 mg prior to the surgery, and then 25 mg every 8 hours for 1-2 days.^[45] Major surgeries like cardiopulmonary bypass may need 100 mg of hydrocortisone prior to incision and then 50 mg every 8 hours for 2-3 days [Figure 5]. Thereafter, one could ease into physiological dosing of steroids.

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Figure 5:

The recommended corticosteroid dose measured in milligrams of IV hydrocortisone before incision. We recommend 100 milligrams for major surgeries, 50 milligrams for moderate surgeries, 25 milligrams for minor surgeries, and no dosage for superficial surgeries. IV: Intravenous

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It is pertinent to note here that there is a section of the population that may not require a stress dose of steroids. Patients who are taking less than 5 mg prednisone daily or have been on steroids for <3 weeks or are undergoing superficial procedures may not need these stress-dosed steroids.^[46]

Adrenal adenoma in the perioperative setting

Adrenal nodules are more common in older patients.^[47] Due to the widespread use of the abdominal scan in the modern practice of medicine, one can see adrenal incidentaloma in older people in the perioperative setting. This puts forward a clinical conundrum for the anaesthesiologist as to whether to proceed with the elective surgery or defer surgery and go for further testing. There are no guidelines or expert opinions on the subject.^[48]

In our opinion, if the patient had a computerised tomography of the abdomen, it is very important to define the density of the adrenal nodule with Hounsfield units (HU). This is critically important as most of the adrenal nodules with an HU of less than 10 are lipid-rich adenomas and in patients with such nodules, one may safely proceed with the surgery.^[49] The patient may need further follow-up with the endocrinologist in the post-operative period to screen for Cushing’s disease and primary hyperaldosteronism.^[50] If the density is between 10 and 20 HU, the patient would still need to be worked up to rule out any hormonal over-secretion and a potential for phaeochromocytoma. In patients with an adrenal nodule of density >20HU, elective surgery should be deferred until phaeochromocytoma is ruled out^[51] [Figure 6]. Of note, nodules are not common in the younger population and would need a hormonal work-up if symptomatic. Also, if the size of the nodule is greater than 4 cm, there is a high chance of malignancy statistically. Referral to a laparoscopic surgeon may be warranted after hormonal work-up is completed.

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Figure 6:

The risk stratification for adrenal adenomas in perioperative settings. Adrenal adenomas with a density of 20+ HU should defer elective surgery; densities of 10-20 HU should check for phaeochromocytoma before elective surgery; patients with <10 HU are safe to proceed to elective surgery. HU: Hounsfield units

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CLINICAL PEARLS

• The geriatric population frequently presents with uncontrolled endocrine issues in the perioperative setting.

• They frequently have underlying chronic kidney disease, which puts them at risk for malglycaemia.

• Appropriate management would include good pre-operative work-ups and insulin dosing based on comorbidities.

• Certain medications, including glucagon-like peptide-1 agonists, may need to be held before the surgery to prevent the risk of aspiration.

• Glycaemic targets may need to be individualised as the Nice-Sugar Trial was not specific to the elderly population in perioperative settings.

CONCLUSION

As the population continues to age, anaesthesiologists often confront elderly patients with multiple endocrine comorbidities who present for elective and emergent surgeries. The need of the hour is guidelines and expert panel recommendations on the management of the clinical conundrums in these patients. This would decrease the cost of healthcare, besides improving the morbidity and mortality.