|Year : 2013 | Volume
| Issue : 3 | Page : 128-134
Challenging aspects of and solutions to diagnosis, prevention, and management of hypoglycemia in critically ill geriatric patients
Vishal Sehgal1, Sukhminder Jit Singh Bajwa2, Upinder Khaira3, Rinku Sehgal3, Anurag Bajaj3
1 Department of Medicine, Commonwealth Medical College, Scranton, PA, USA
2 Department of Anaesthesiology and Intensive Care Medicine, Gian Sagar Medical College, Banur, Patiala, Punjab, India
3 The Wright Center for Graduate Medical education, Scranton, PA, USA
|Date of Web Publication||19-Oct-2013|
Sukhminder Jit Singh Bajwa
Department of Anaesthesiology and Intensive Care, Gian Sagar Medical College and Hospital, Ram Nagar, Banur, Patiala, Punjab
Source of Support: None, Conflict of Interest: None
There is a worldwide pandemic of diabetes. Also there is a gradual and steady increase in the elderly population. Often clinicians are faced with managing dysglycemia in the elderly with underlying sepsis and multiple comorbidities. This predisposes the elderly to potentially increased chances of hypoglycemia in inpatient settings. This article reviews the altered renal physiology and its effects in the management of dysglycemia in the elderly population. It also emphasizes the role of renal insufficiency and sepsis as the main etiological factors for hypoglycemia in both diabetics and nondiabetics in the inpatient settings.
Keywords: Chronic kidney disease, diabetes, elderly, hyperglycemia, hypoglycemia
|How to cite this article:|
Sehgal V, Bajwa SS, Khaira U, Sehgal R, Bajaj A. Challenging aspects of and solutions to diagnosis, prevention, and management of hypoglycemia in critically ill geriatric patients. J Sci Soc 2013;40:128-34
|How to cite this URL:|
Sehgal V, Bajwa SS, Khaira U, Sehgal R, Bajaj A. Challenging aspects of and solutions to diagnosis, prevention, and management of hypoglycemia in critically ill geriatric patients. J Sci Soc [serial online] 2013 [cited 2020 May 28];40:128-34. Available from: http://www.jscisociety.com/text.asp?2013/40/3/128/120052
| Introduction|| |
The worldwide pandemic of diabetes has increased the healthcare costs exponentially even in the developing world. The twin problems of potentially preventable hyper- and hypoglycemia are a huge cost burden to the society. ,,
According to the American Diabetes Association (ADA), the total costs of diagnosed diabetes have risen to $245 billion in 2012 from $174 billion in 2007, when the cost was last examined. Majority of the cost is incurred in the inpatient care of diabetes [Figure 1]. The problem gets compounded by the increasing elderly population which is diabetic. In United States, more than 25% of the elderly are diabetic and the number is rapidly increasing. 
The elderly usually have multiple comorbidities which further compound the problem.  Also this set of population is frequently on polypharmacy and invariably has underlying chronic kidney disease (CKD) which presents a clinical conundrum for the clinician. Uncontrolled diabetes is related to increased readmissions to the hospital.  The risk of hyperglycemia has to be weighed against hypoglycemia which is potentially more devastating for this set of population.  Hypoglycemia is considered to be the main limiting factor in the treatment of hyperglycemia.  It increases cardiovascular and all-cause mortality in hospitalized diabetic patients.  Hypoglycemia is associated with increased morbidity, mortality, increased length of hospital stay (LOS) and increased healthcare costs. , Also the longer the LOS, the more the chances of hypoglycemia in inpatient settings.  As such less stringent glycemic control in the elderly and critical care patients is warranted. 
The present review is written with an aim to highlight the basic and essential clinical measures to prevent hypoglycemia in the critically ill geriatric population. The search strategies included extensive scrutiny of literary evidence from internet resources, journals and textbooks of endocrinology and anesthesiology, and intensive care among endocrinologists, anesthesiologists and intensivists of high academic caliber. The literature was explored for full text articles and abstracts from various search engines such as PubMed, Medscape, Scopus, Science Direct, Medline, Yahoo, Google Scholar, and many others, using key words like diabetes mellitus, geriatric, hyperglycaemia, hypoglycaemia, and insulin.
Hypoglycemia has traditionally been defined as low blood sugars with symptoms of hypoglycemia.  The cut-off value for hypoglycemia remains debatable with most favoring a value of <63 mg/dl. , But the exact definition needs to be individualized. In our opinion, any self-monitored blood glucose value <70 mg/dl should alert the patient or clinician regarding harmful effects of hypoglycemia.
The ADA working group on hypoglycemia  has classified hypoglycemia into the following categories:
Incidence of hypoglycemia
- Severe hypoglycemia: hypoglycemia requiring assistance and use of carbohydrates or glucagon.
- Documented symptomatic hypoglycemia: symptoms of hypoglycemia with BGM < 70 mg/dl.
- Asymptomatic hypoglycemia: no symptoms but BGM < 70 mg/dl.
- Probably symptomatic hypoglycemia: symptoms but no documented BGM.
- Relative hypoglycemia: symptomatic but BGM > 70 mg/dl.
Type 1 diabetes has much more incidents of hypoglycemia as compared to type 2 diabetes. This is because recurrent hypoglycemia impairs the counter regulatory mechanisms to subsequent hypoglycemia. There are countless episodes of asymptomatic hypoglycemia, two episodes of symptomatic hypoglycemia and one episode of severe hypoglycemia per year.
Type 2 diabetes is much more frequent and clinically we see many more cases of hypoglycemia in type 2 diabetics. In 50% of the cases, insulin is responsible, and in 20% cases, it is long-acting sulphonylureas  which are considered to cause hypoglycemia.
Consequences in the elderly
It is a known fact that the incidence of neuroglycopenic manifestations in the elderly is higher as compared to autonomic manifestations. This includes dizziness, delirium, subsequent falls, and increased risk of dementia. In a diabetes control and complications trial, the patients on more intensive control had a higher level of hypoglycemia.  In addition, the ACCORD trial recommended an HBA1C target of less than 8% in people with life expectancy of less than 10 years.
Risk factors for hypoglycemia in the elderly
Numerous mechanisms are responsible for a higher incidence of hypoglycemia the elderly population as compared to the younger population. These include, but are not limited to, the following:
Causes of hypoglycemia in inpatient settings
- Impaired counter regulatory mechanisms: These may be due to many reasons. The most common cause is a prior history of severe hypoglycemia which may be the result of intensive glycemic control.
- Insulin excess is also an important cause. This may be due increased exogenous insulin per se or secondary to long-acting secretagogues especially sulphonylureas. In general, in non-critically ill patients, using insulin less than 0.6 U/kg has been associated with lesser episodes of hypoglycemia.  Another important cause in hospital settings may be the decreased metabolism of insulin in AKI. This would be discussed in detail here.
The cause of hypoglycemia in the elderly diabetic population is a complex interplay between multiple factors and is seldom attributable to one single cause [Figure 2]. In the inpatient settings, failure to adjust the diabetic medications with the diminished oral intake is the most common correctable cause of hypoglycemia in the hospitalized elderly diabetics. ,
Also, the elderly are at risk of severe hypoglycemia which can be secondary to higher possibility of hypoglycemic unawareness due to autonomic neuropathy. , Elderly have multiple co-morbidities and are on polypharmacy which compounds the problem. Insulin and long-acting insulin secretagogue may cause profound hypoglycemia in the elderly leading to increased cardiovascular adverse events in inpatient settings. , Besides some medications such as quinolones, which are frequently used in the hospital settings, could potentiate hypoglycemia in hospitalized patients.  In the critical care settings when patients have multiorgan dysfunction, this gets magnified due to the changed metabolism of hypoglycemic agents. This is especially true for elderly patients with congestive heart failure (CHF) or sepsis in whom low flow states cause an altered metabolism of drugs in the kidney and liver.  Adrenal insufficiency in such settings could also potentially cause hypoglycemia.
Hypoglycemia may also be seen in elderly nondiabetic patients in inpatient settings. A retrospective study by Mendoza et al. concluded that CKD was the most common cause of hypoglycemia in the elderly nondiabetics [Figure 3]. This was followed by alcohol intoxication, liver failure, sepsis, cancer, and endocrine disorders. 
Insulin metabolism and renal insufficiency
Renal function should be assessed diligently for preventing hyper- and hypoglycemia. Insulin has a molecular weight of about 6000. About 60% of insulin is excreted through the kidneys by glomerular filtration and about 40% is excreted by extraction from peritubular vessels. In the proximal tubular cells, it is transported to lysosomes which break it down to amino acids. About 1% of insulin is excreted unchanged in the urine. With the decreasing glomerular filtration rate (GFR) in CKD, insulin metabolism remains constant. This is because even though GFR decreases, there is a concomitant increase in the extraction of insulin from peritubular vessels. But when GFR falls below 15, there is a decrease in the metabolism of insulin and a patient gets predisposed to hypoglycemia.
In general, when GFR drops below 60, there is an increased incidence of hypoglycemia in both diabetics and nondiabetics.  This is due to decreased renal gluconeogenesis and decreased antiinsulin hormones due to autonomic neuropathy.
Uremia impairs the tissue sensitivity to insulin which gets better when the patient is dialyzed. Anemia also contributes to insulin resistance which tends to improve when erythropoietin is started. The clinician needs to be aware of these conundrums while caring for the elderly with CKD. Most elderly patients have underlying CKD and the drugs need to be dosed based on their changing renal profile.  This is especially true for oral hypoglycemic and long-acting insulin. Insulin dosing as per the decreased creatinine clearance has been shown to decrease the incidence of inpatient hypoglycemia. , Even after using short-acting insulin in patients with hyperkalemia with underlying renal insufficiency, they remain at risk of hypoglycemia secondary to decreased insulin metabolism. 
Clinical manifestations of hypoglycemia could be myriad. Though easily recognized in the young and middle-aged people, it may be obscure in elderly patients who could have masking of hypoglycemia awareness secondary to dementia, polypharmacy, comorbidities, and adverse drug reactions.
Elderly especially those with a compromised renal function are at a heightened risk of hypoglycemia when treated with long-acting sulphonylureas in the hospital settings.  The elderly often have dementia and cognitive impairment which are independently associated with an increased risk for hypoglycemia.  Postsurgical patients are at a heightened risk for hypoglycemic complications. This is more so when they have poor preoperative glycemic control. 
Classically, symptoms may be subclassified as autonomic or neuroglycopenic [Figure 4]. An autonomic response may manifest as sweating, weakness, tachycardia, palpitations, tremor, or paresthesia which may result in falls in the elderly and subsequent hospitalization.  Neuroglycopenia may manifest as confusion, seizure, focal deficits, and loss of consciousness.
Severe hypoglycemia (BG < 40) impairs the hormonal and autonomic response to subsequent hypoglycemia.  This may contribute directly to increased morbidity and mortality associated with diabetes. This negates the survival benefits associated with a tight control of hyperglycemia. , Hypoglycemia is a prognostic marker for mortality in the hospitalized elderly nondiabetics. 
It is mandatory during the management of hypoglycaemia to hold off all the hypoglycemic medications. If the patient is able to swallow safely, rapidly absorbed carbohydrate should be given. If the patient has an altered mental status and is unable to swallow, he should be managed by giving an intravenous (IV) bolus of 50 ml of 50% dextrose.
Dextrose infusion should ensure the delivery of 6-9 mg/kg per minute of glucose to maintain BGM above 80. Amounts needed vary depending upon the cause and severity of hypoglycemia.
Blood glucose is measured 10-15 min after the initial IV bolus and monitored every 30-60 min thereafter until stability is reached.
If glucose cannot be given by parenteral or oral routes, glucagon, 1 mg intramuscular (IM) or subcutaneous (SC),
Critical care setting
Severe hypoglycemia may be seen in sepsis especially in the elderly.  Hypoglycemia in patients with sepsis is associated with an increased risk of mortality.  Other comorbidities which increase the potential for hypoglycemia in critical care settings include renal insufficiency, hepatic insufficiency, septic shock, mechanical ventilation, and intensive insulin control. , In critical care settings, hypoglycemia could be a biomarker of adverse outcomes rather than cause as patients with acute hypoglycemic episodes are sick and frail with multiple comorbidities.  Evidence supports the use of less stringent criteria for glycemic control in critical care settings with the target glucose level of 140-180 mg/dl. ,,,,,,, In selected patients, a target level of of 110-140 mg/dl may be appropriate. The aim should be to avoid extremes of glucose rather than euglycemia.  A large absolute decrease in blood glucose levels, especially if <100, should alert the clinician about impending hypoglycemia and should trigger a preventive step. , ADA strongly recommends using IV insulin in critical care settings and switching to SC insulin with basal bolus insulin (BBI) when stable.  IV insulin should be restricted to critical care settings only as the incidence of hyper- and hypoglycemia significantly increases if the patient is allowed to eat.  BBI is superior to sliding scale insulin (SSI) in the inpatient management of hyperglycemia although risk of mild hypoglycemia is more with BBI. ,,,,, Poorly controlled glucose in critical care settings is highly detrimental as glycemic control in an ICU is a measure of quality of care, safety, and cost. 
Assessment, prevention, and patient self-recognition is the key to successfully prevent postoperative hypoglycemia.  Poor preoperative glycemic control is associated with poor postoperative outcomes.  Perioperative glycemic control should be based on outpatient treatment regimens and underlying comorbidities to minimize hypo- and hyperglycemia.  In the inpatient settings, there is a tendency for intensive glycemic control to minimize the risk of infection, but that should be weighed against the risk of hypoglycemia. , The Society for Ambulatory Anesthesia does not issue any guidelines for glycemic control in perioperative settings during ambulatory surgery due to lack of any good quality evidence. 
Metformin may be used as an adjunct to insulin in the postoperative period if there is no renal insufficiency or any other contraindication. 
Use of sulfonylureas (especially glyburide) in the elderly may be associated with an increased risk of hypoglycemia both in outpatient and inpatient settings.  These should preferably be withheld during hospitalization to minimize the risk of hypoglycemia.  Glipizide is acceptable if sulfonylureas have to be used due to their short life and minimal renal clearance. Insulin analogs, both, short and long acting, are proven to be more effective if renal insufficiency is taken into account while prescribing the same. 
| Conclusion|| |
In the elderly population, sepsis and CKD are the main pathologies that should alert the clinician about the possibility of hypoglycemia in both diabetics and nondiabetics. The hallmark of the glycemic control in hospitalized patients is to avoid hypoglycemia while optimizing glycemic control. , Continuous glucose monitoring is an upcoming tool which could be used in the coming years to minimize hypoglycemia in hospitalized settings. , An institution-wide glucose management program with a multidisciplinary approach is the best way to decrease inpatient hypoglycemic episodes while ensuring optimum glycemic control. ,,,,,,,,, Meticulous attention should be paid in transition from IV to SC and also from outpatient to inpatient to minimize hypoglycemia.  Universal education of all medical personnel in the management of dysglycemia could potentially minimize hypo- and hyperglycemia. ,,,, This would improve patient outcomes and decrease morbidity, mortality, and cost associated with dysglycemia management.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]