Learning Outcome

Upon completion the clinician will be able to:

• Recognize the signs and symptoms of low blood glucose and its associated risk factors
• Understand the importance of accurate nursing diagnosis
• Prioritize appropriate nursing management 
• Determine the appropriate time to seek assistance
• Identify patient outcomes
• Educate the patient regarding signs, symptoms, treatment and how to avoid hypoglycemia

Introduction

Hypoglycemia is often defined by a plasma glucose concentration below 70 mg/dL; however, signs and symptoms may not occur until plasma glucose concentrations drop below 55 mg/dL. The symptoms of Whipple's triad have been used to describe hypoglycemia since 1938.  For Whipple's triad, the practitioner must first recognize symptoms of hypoglycemia, then obtain low blood glucose, and finally, demonstrate immediate relief of symptoms by the correction of the low blood glucose.  Glucose is the primary metabolic fuel for the brain under physiologic conditions. Unlike other tissues of the body, the brain is very limited in supplying its glucose. Expectedly, the brain requires a steady supply of arterial glucose for adequate metabolic function. Potential complications can arise from an interruption in the glucose supply. As such, protective mechanisms to guard against low serum blood glucose (hypoglycemia) have evolved in the body. 

During fasting states, serum glucose levels are maintained via gluconeogenesis and glycogenolysis in the liver. Gluconeogenesis is the pathway in which glucose is generated from non-carbohydrate sources.  These non-carbohydrate sources could be protein, lipids, pyruvate or lactate. In contrast, glycogenolysis is the breakdown of glycogen into glucose product. Much of glycogenolysis occurs in hepatocytes (liver) and myocytes (muscle).

Hypoglycemia is most often seen in patients suffering from diabetes who are undergoing pharmacologic intervention. Amongst this group, patients with type 1 diabetes are three times as likely to experience hypoglycemia as compared to patients with type 2 diabetes when receiving treatment.

Nursing Diagnosis

According to the North American Nursing Diagnosis Association International 9 (NANDA-I), the nursing diagnosis of risk for unstable blood glucose level poses many additional risks and additional nursing diagnoses for the patient. [1] The nurse's responsibility is to diagnose human responses within the nurse's scope and level of competency. [2] It is vital that critical thinking is used to identify and understand the risk factors of unstable blood glucose levels, particularly low levels for the sake of this topic, and the accompanying signs and symptoms upon presentation of the patient. Nursing diagnoses are important as they help to guide the nursing care plan, as well as determine the patient's outcome. Clear nursing diagnoses are key for each patient and should be individualized based on the patient's specific presentation. It is also vital that nurses make nursing diagnoses and not medical diagnoses, which are made by advanced providers and clinicians. 

Making correct nursing diagnoses is strongly dependent upon knowledge of the patient's past medical and social history, physical assessment and pertinent laboratory data. The accuracy of the information gathered is also a determining factor. In the case of unstable blood glucose, it is important to know whether the patient has a medical diagnosis of type I or type II diabetes, any current pharmacologic therapy, history of unstable blood glucose or hypoglycemia, adherence to a special diet or medications, current or recent illnesses that could affect the glucose, and social history. Physical activity and other social history include alcohol intake (which could affect gluconeogenesis and glycogenolysis) and drug use (which could inhibit the patient's desire to eat in addition to causing negative physiologic effects). A correct nursing diagnosis is vital to achieving the outcome of a stable blood glucose level, in addition to avoiding negative outcomes, such as organ damage, coma, and death. Frequent monitoring of the patient's glucose level is vital during an episode of unstable or low blood glucose.

Causes

In patients who do not have diabetes, hypoglycemia is uncommon, but when it occurs, there are a few major causes of hypoglycemia: pharmacologic, alcohol, critical illness, counter-regulatory hormone deficiencies, and non-islet cell tumors.

Most cases of hypoglycemia occur in diabetic patients who are undergoing therapeutic intervention with meglitinides, sulfonylureas, or insulin. Drugs are the most common cause of hypoglycemia.[3] Metformin, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose co-transporter 2 inhibitors (SGLT-2), and dipeptidyl peptidase-4 (DPP-4) inhibitor use does not lead to hypoglycemia.Non-diabetic patients with intact hepatic function will rarely experience fasting hypoglycemia because of preventative counter-regulatory measures. Episode of true hypoglycemia in a non-diabetic patient is likely due to iatrogenic causes such as the surreptitious use of insulin. Other potential causes of hypoglycemia are critical illness, alcohol, cortisol deficiency, or malnourishment.

Alcohol inhibits gluconeogenesis in the body, but does not affect glycogenolysis. Thus, hypoglycemia occurs after several days of alcohol consumption and after glycogen stores are depleted.

In critical illness states, for example, end-stage liver disease, sepsis, starvation, or renal failure, glucose utilization exceeds glucose intake, glycogenolysis and/or gluconeogenesis. The result of this imbalance is hypoglycemia. Counter-regulatory hormone deficiencies can occur as in states of adrenal insufficiency. Hypoglycemia associated with such deficiencies are rare. Non-islet cell tumors may also be a cause of hypoglycemia through increased secretion of insulin-like growth factor 2 (IGF-2).[4] IGF-2 increases glucose utilization, which can lead to hypoglycemia.

Insulinomas are hyperfunctioning islet cell tumors associated with increased insulin secretion. They can be life-threatening and primarily manifest with postprandial hypoglycemia. Although these tumors are rare, MEN1 should be a consideration in the workup of suspected cases.

Risk Factors

Hypoglycemia is common with type 1 diabetes, particularly in those patients receiving intensive insulin therapy. Severe hypoglycemic events have been reported to be anywhere between 62 to 320 episodes per 100 patient-years in type 1 diabetes.[5] As opposed to patients who have type I diabetes and require insulin therapy exclusively, patients with type II diabetes experience hypoglycemia relatively less frequently compared to patients with type I diabetes. This can be due, in part, to pharmacotherapies that do not induce hypoglycemia like metformin. The incidence of hypoglycemia in patients with type II diabetes has been reported to be approximately 35 episodes for 100 patient-years.[6] There are no reported disparities in incidents based on gender.

Those with a previous history of hypoglycemia are at risk of subsequent episodes, especially if the initial cause was not determined. Excessive physical activity, insufficient dietary intake, history of gastric bypass, excessive alcohol consumption, and weight loss also put individuals at risk for hypoglycemia. Additional risk factors include acute illnesses consistent with hypovolemia, cognitive deficits and/or dementia, advanced age and low fasting glycemia. [1]

Assessment

The clinical manifestations of hypoglycemia can be classified as either neuroglycopenic or neurogenic. Neuroglycopenic signs and symptoms are signs and symptoms that result from direct central nervous system (CNS) deprivation of glucose. These include behavioral changes, confusion, dizziness, headache, fatigue, seizure, coma, and potential death if not immediately corrected. Severe hypoglycemia can cause hemophilia and aphasia, masquerading as a stroke. [7] However, correcting the hypoglycemia usually resolves stroke-like symptoms. Neurogenic signs and symptoms can either be adrenergic (tremor, palpitations, tachycardia, anxiety) or cholinergic (hunger, diaphoresis, paresthesias). Neurogenic symptoms and signs arise from sympathoadrenal involvement (either norepinephrine or acetylcholine release) in response to perceived hypoglycemia. 

A detailed history is essential in evaluating hypoglycemia. Pertinent issues that should be addressed while taking a patient's history include 

• A detailed medication history
• History of alcohol and/or drug use
• History of psychiatric disorders
• Personal or family history of diabetes mellitus or multiple endocrine neoplasia syndromes (MEN)
• Unintentional weight changes
• Changes in medication
• Consideration of acute kidney injury or renal failure
• Symptoms of other hormone deficiencies
• It is also important to note the context of the hypoglycemic episode relative to meals or exercise.

There is no agreed-upon lab value that defines hypoglycemia. Hypoglycemia is said to be present when the patient has symptoms consistent with hypoglycemia in addition to a low serum glucose measurement (less than  70 mg/dL). This perspective reflects the idea that hypoglycemia is a clinical presentation coupled with a lab finding of low serum glucose rather than a pure chemistry finding. Typically neurogenic and neuroglycopenic symptoms of hypoglycemia occur at a glucose level of or below 50 to 55 mg/dL, but this threshold can vary from individual to individual.

Patients who have diabetes can present with symptoms of hypoglycemia at relatively higher serum glucose levels. The chronic hyperglycemia alters the "set point" in which neuroglycopenic/neurogenic symptoms become apparent. This phenomenon is referred to as "pseudohypoglycemia" because the serum glucose may be within normal range despite symptom presentation.

It is the nurse's responsibility to assess for signs and symptoms of hypoglycemia, as indicated above, and to report any abnormal findings. It is also the nurse's responsibility to assess that medications are taken as prescribed and report any possible side effects of hypoglycemia. Some medications are known to have a side effect of hypoglycemia, in addition to insulin and other antidiabetic medications. Additional medications that may cause hypoglycemia are pentamidine, disopyramide, diuretics, regular use of salicylates, and the combination of diuretics, ACE inhibitors, and beta-blockers. 

Evaluation

As previously mentioned, documentation of Whipple’s triad is a potential indicator of hypoglycemia, and any initial laboratory evaluation should confirm hypoglycemia. Other pertinent labs to consider include insulin, proinsulin, and C-peptide levels during any episode of suspected hypoglycemia. If C-peptide levels are low in the presence of high insulin levels, the patient has received exogenous insulin. The pro-form of insulin created within the body is attached to C peptide. The body then cleaves C peptide from the pro-form of the molecule to create active insulin. Elevated C-peptide levels and insulin levels can be seen with secretagogue agents such as sulfonylureas or insulin secretagogues since both classes of agents stimulate endogenous insulin secretion.

Once the use of exogenous insulin administration is ruled out, sources of endogenous hyperinsulinemia need to be considered. Localization is usually performed via abdominal computed tomography (CT) with MRI.

Further nursing responsibilities while working with the interdisciplinary team in the evaluation of hypoglycemia, include monitoring blood glucose levels at fasting and postprandial. It is important to monitor these levels and to be aware of the hypoglycemic episodes are reactive, occurring after meals. These parameters are also important to monitor, as they may guide the provider in determining if there is a possible presence of insulinoma or extra-pancreatic tumor and if biochemical testing should be performed. [8]

Medical Management

Identification of a hypoglycemic patient is critical due to potential adverse effects including coma and/or death. Severe hypoglycemia can be treated with intravenous (IV) dextrose followed by infusion of glucose. For conscious patients able to take oral (PO) medications, readily absorbable carbohydrate sources (such as fruit juice) should be given. For patients unable to take oral agents, a 1-mg intramuscular (IM) injection of glucagon can be administered. Once the patient is more awake, a complex carbohydrate food source should be given to the patient to achieve sustained euglycemia. More frequent blood glucose monitoring should occur to rule out further drops in blood sugar.

Nonpharmacological management of recurrent hypoglycemia involves patient education and lifestyle changes. Some patients are unaware of the serious ramifications of persistent hypoglycemia. As such, patients should be educated on the importance of routine blood glucose monitoring as well as on the identification of the individual's symptoms of hypoglycemia.  If lifestyle changes are not effective in preventing further episodes, then pharmacologic intervention should be modified. Patients should be advised to wear a medical alert bracelet and to carry a glucose source like gel, candy or tablets on their person in case symptoms arise. In the outpatient setting, reviewing blood sugar logs as well as food logs may be helpful in identifying problem areas for the patient.

Glycemic control has been an important aspect of medical management due to the association between glycated hemoglobin levels and cardiovascular events in diabetes mellitus type 2 patients. In the 2008 ACCORD trial, it was determined that intensive therapy (defined as a goal hemoglobin A1C less than 6.0%) did not significantly reduce major cardiovascular events and was associated with increased mortality and risk for hypoglycemia.[9] It should be noted, however, that the intensive therapy group had proportionally more participants using rosiglitazone compared to the standard therapy group (91.2% versus 57.5%), thus possibly contributing to an increased incidence of cardiovascular events in the intensive therapy group.

The 2009 VADT study additionally studied the effect of intensive blood glucose control in a sample of 1791 veterans with poorly controlled diabetes mellitus type 2. More rigid glycemic control did not appear to have a significant effect on cardiovascular outcomes, although it did improve microalbuminuria compared to the standard therapy arm.[10]  The results, however, cannot be extrapolated to females since 97% of the study participants were male. Besides, there was a significant dropout (approximately 15%), limiting statistical power.

Regarding endogenous sources of insulin, insulinomas are often managed surgically. Evidence of an insulinoma should prompt workup or investigative effort into potential multiple endocrine neoplasia (MEN) disorders.

Nursing Management

Nursing management of hypoglycemic episodes may consist of pharmacologic and non-pharmacologic actions. Immediate and frequent glucose monitoring is vital for any patient presenting with symptoms of unstable blood glucose, particularly with hypoglycemia. Nursing management includes administering glucose tablets (approximately three), glucose gel, or carbohydrates for the conscious patient. Carbohydrates may consist of 4 to 6 ounces of fruit juice or soda (not sugar-free), saltine crackers, or hard candy (only if the patient is alert). For the unconscious patient, nursing management of hypoglycemia includes obtaining adequate intravenous access, and possible administration of 50% dextrose or glucagon, per the facility's protocol or provider's order.

Outcome Identification

Expected immediate nursing outcomes for patients experiencing hypoglycemia should include monitoring and maintaining blood glucose levels within normal limits and resolution of hypoglycemic signs and symptoms. For patients who experienced neurological changes or loss of consciousness, the nurse should expect the patient to regain consciousness with no deficits, such as paresthesia or aphasia. This includes the resolution of behavioral changes, confusion, and seizures that sometimes mimic stroke. [7] The nurse should be certain that the hypoglycemic episode has resolved prior to leaving the patient unattended. 

Expected long term outcomes for the patient should consist of: regular monitoring of glucose levels, maintaining normal glucose levels, maintaining normal hemoglobin A1c levels, adherence to medications, diet, and medical appointments, evidence of the patient's ability to recognize the signs and symptoms of hypoglycemia, self-management of hypoglycemia, and understanding of when and what information to report to the provider.

Coordination of Care

An interprofessional approach to hypoglycemia is recommended.

Adequate measures to minimize hypoglycemic events involve participation and effective communication between the primary care physician, endocrinologists, diabetes educators, pharmacist, diabetic nurse, the patient's family, and the patient. The cornerstone of this management is the patient.

Patient education should address the importance of relatively detailed documentation regarding blood glucose levels, timing, units of insulin administered, and any pertinent notes such as increased/decreased food intake or exercise relative to blood glucose measurements. Such documentation allows a primary care physician or endocrinologist to make appropriate adjustments to diabetic medication therapy to best optimize blood glucose levels. Stability of blood glucose levels can be obtained with consistent dietary and exercise habits in addition to the appropriate timing of insulin therapy to avoid drastic spikes and dips in blood glucose levels. Hospitalized patients with newly diagnosed diabetes can be taught insulin administration and self-injections while in the hospital. Discussions with the patient will help decide the best medications to achieve safe glycemic control. Group education classes and local event planning can help diabetic patients learn and grow their knowledge between themselves as well as others in the household.

Non-adherence to medication or diet are the most common cause of treatment failure. Patients should monitor for signs or symptoms of hypoglycemia and have sources of glucose (for example, hard candy, fruit juice) immediately available. Developing programs to educate healthcare staff has also shown to provide better outcomes. Teaming up with local pharmacies or grocery stores can help some of the barriers often encountered by diabetic patients.

Patients should be advised to have fairly consistent exercise and dietary habits to avoid drastic spikes and dips in hour-to-hour blood glucose measurements.

Health Teaching and Health Promotion

Patient education remains a pivotal component in the prevention of hypoglycemic episodes. Focus on the prevention of hypoglycemia should include patient education on signs and symptoms that constitute hypoglycemia and early recognition of these signs and symptoms. Patient education should be individualized to each patient depending on the circumstances and should consist of self-monitoring and management of glucose. Proper diet, exercise, management of medications and limiting alcohol intake are also important in the prevention of hypoglycemia. It is vital that the patient is educated on when to contact the caregiver, health care provider and when to activate the emergency medical system.

Risk Management

Patient safety remains the priority in any event. The nurse should monitor the patient closely during and following a hypoglycemic episode. It is important to avoid leaving the patient unattended, due to the risks of worsening symptoms and the potential for falls.

In addition to patient safety, documentation is a key responsibility of the nurse with regard to reducing liability risks. Documentation should always be specific and clear to the reader. Following a hypoglycemic episode, the nurse should document glucose levels, signs and symptoms, actions performed, the patient's response to those actions, the name of the provider who was contacted, orders given and any events that preceded, followed or occurred during the time of the hypoglycemic episode. It is important to also document vital signs, any medications administered before, during or after. If the patient consumed a meal prior to the episode, this should also be documented. This will help cue the provider if the patient has possibly experienced postprandial hypoglycemia. Remember, if it hasn't been documented; the assumption is it hasn't been done.

Another key factor in reducing nursing liability risks is documentation of patient education. After appropriately educating the patient, the nurse should request the patient repeat the information back that was taught, also known as a "repeat back", or that the patient acknowledges understanding. The nurse should then document the education provided. For instance, document, "The patient verbalized understanding that a blood glucose level below 70 is considered low." An alternative is to document what the patient stated word for word. There may be instances when the patient may demonstrate an action, such as self-monitoring. This information should be documented.

Discharge Planning

Upon discharge be sure to provide the patient with written instructions regarding how to prevent and navigate a hypoglycemic episode. Written instructions should reinforce verbal education taught to the patient prior to discharge. Provide in writing, the names of providers, dates, times and locations of follow-up appointments when possible. Emphasize to the patient and family when to contact the medical provider and when to seek immediate medical attention.

Pearls and Other issues

Hypoglycemia in non-diabetic patients is uncommon. When it does occur, a critical illness, sustained alcohol use, malnutrition, and exogenous medications should be considered. Tumors may be a cause of hypoglycemia but are rare.

When addressing hypoglycemic episodes, keep in mind the possibility of postprandial hypoglycemia, as well as the Somogyi effect. The Somogyi effect results from insulin-induced hypoglycemia (particularly at night) and rebounds to hyperglycemia during the morning. Identifying this phenomenon is vital. When patients experience hypoglycemia particularly at night, this should be reported to the provider for the proper management of insulin in the diabetic patient.

Hypoglycemia is relatively common in neonates, particularly in mothers with uncontrolled diabetes. A 2017 study performed in Israel showed that 559 neonates out of 3595 neonates were observed to have a glucose level of less than 47 mg/dL.[11] Gestational glucose intolerance in the mother is usually attributed to the presence of human placental lactogen. Pregnant women with impaired glucose tolerance not responsive to diet or exercise can be started on insulin. Insulin does not cross the placenta although the fetus will be exposed to maternal hyperglycemia. Since the fetal pancreatic islet cells produce insulin starting at 10 weeks gestation, the fetal pancreas is capable of responding to hyperglycemia. Upon delivery, the newborn pancreas continues to secrete insulin although maternal hyperglycemia is withdrawn. Subsequently, the neonate’s glucose will decrease, resulting in an insulin-glucose imbalance and hypoglycemia.