When There Are Acute Changes In Mental Status In Patients With Diabetes

   As podiatric physicians in 2010, we are better trained than ever to manage patients’ problems. Even more importantly, we are well versed in making appropriate, well-timed referrals when needed. In the following case study, that particular acumen was critically important.

   A 78-year-old male with type 2 diabetes underwent resection of the first metatarsophalangeal base and debridement of an underlying ulcer, which has at times been infected. The plan was to inspect the bone for osteomyelitis, place the patient on oral antibiotics and not primarily close the plantar lesion, but pack it open instead. Resection of the phalangeal base would ease the deforming hallux interphalangeus.

   Examination revealed a hallux limitus and the physician determined that at the patient’s age and activity level, a Keller arthroplasty would serve him well, preventing further breakdown and possible osteomyelitis. The plantar lesion did not undergo primary closure but physicians packed it instead.

   The hospital discharged the patient within a week after bone cultures and histology showed no evidence of osteomyelitis. He received a prescription for oral antibiotics and received instruction to keep a clinic appointment in 48 hours. However, he was a no-show for his appointment. Phone calls to his home, all of which were documented, went unanswered over a period of two weeks.

   About a month after his discharge from the hospital, the patient went to the emergency department of the hospital accompanied by his wife. His extremity was in the same dressing he received upon preparation for discharge although now it was soiled and loose. His wife reported that they had never filled the prescription for antibiotics because they “did not understand the instructions about the medicine or coming back.” She also noted that they “didn’t have anything to change the dressings with.”

   When the patient went to the emergency department, he was running a fever and “not making any sense,” according to his wife. When pressed for an explanation, she told the residents and attendings that when her husband woke up, he was not able to complete a sentence and he barely recognized her. She asked if he wanted a cup of coffee and he looked at her as if she had asked him if he wanted a cup of dirt instead. This frightened her. She got him his usual cup of coffee and put it up to his lips to prompt him in his usual activity. He acted like he did not know how to open his lips.

   This patient’s past medical history is positive for type 2 diabetes, which was diagnosed at the age of 34. The man is hypertensive, moderately obese and has early signs of renal disease. The patient neither smokes nor drinks. He has a history of diabetic foot ulcerations having had two on the right hallux interphalangeal joint.

What To Consider In The Differential Diagnosis

   Patients who have an acute change in mental status commonly present to the emergency department and this presents a difficult diagnostic task. It is important to conduct a focused history and physical exam. As a surgeon, it is your responsibility to take charge in the management of your patient. The more you can figure out upon the initial evaluation, the more time you will save (instead of just automatically handing your patient off to another service such as infectious disease, neurology or internal medicine).

A common mnemonic to consider is AEIOU-TIPSM, which is as follows:1

   A: alcohol, toxins
   E: endocrine, electrolytes
   I: insulin, diabetes-related, hypoglycemia
   O: oxygen, opiates
   U: uremia
   T: trauma, temperature
   I: infection
   P: psychiatric, poisoning, porphyria
   S: stroke, seizure, shock, subarachnoid hemorrhage
   M: metabolic; hyperammonia

   A recently published retrospective study of 595 patients admitted to the emergency department found trauma, hypoglycemia and stroke to be the three most common causes of acute mental status (AMS).1 The average age of patients in the study was 51.5 years. The common etiologies of AMS changes in the elderly patients of this study (one-third were over the age of 70) were diabetes, hypertension, renal dysfunction and infection.

   One should immediately note the type of AMS the patient has and whether it involves mental clouding, confusion, delirium, obtundation, stupor or coma. The presence of focal or lateralized neurological defects, as well as the timing and duration of symptoms.2

   This type 2 diabetic male presented one month after undergoing a Keller arthroplasty for offloading an ulcer. The patient had never taken prescribed antibiotics. He did have extreme signs of mental decline. This points to a few differentials.

What You Should Know About Diabetic Ketoacidosis

   Usually developing in less than 24 hours, diabetic ketoacidosis (DKA) is commonly accompanied by hyperglycemia, ketosis and acidosis. Polyuria, polydipsia, polyphagia and weakness can be present for days before the patient typically presents with vomiting and ketoacidosis. Mental status can range anywhere from being fully alert to lethargic to being in a coma. Reduced skin turgor, tachycardia, hypotension, dry mucous membranes and overall dehydration are evident. Kussmaul’s respiration and acetone smelling breath are common. The patient’s body temperature can be normal or low, or a fever may be present with an underlying infectious etiology.3,4

   It is of vital importance to determine the underlying etiology of the DKA in order to treat. Commonly known etiologies include: infection (pneumonia, urinary tract infection and sepsis), inadequate insulin, new-onset diabetes, myocardial infarction, pancreatitis and stroke. Diabetic ketoacidosis can also be caused by certain drugs.3,4

   Diabetic ketoacidosis usually presents in patients with type 1 diabetes but is now more common in patients with type 2 diabetes. Newton and colleagues studied 138 patients admitted for DKA and found only small differences in the initial presentation of type 1 versus type 2 DKA.5

   Type 2 patients had less severe acidosis and near normal serum potassium levels, but needed a longer course of treatment. Insulin non-adherence was a major factor as this contributed to 85 percent of all admissions. Infections were a factor in 38 percent of all admissions. Twenty-two percent of patients with type 1 diabetes had infections and 48 percent of patients with type 2 diabetes had infections. These infections included: urinary tract infection (UTI), upper respiratory tract (URT) infections, pneumonia, cellulitis and cutaneous abscesses. There was a small subset of patients (10 percent) who had pancreatitis.5

   Recent studies reveal that beta-hydroxybutyrate (BHB) is considered far superior to nitroprusside method (urine ketones, serum ketones) for monitoring ketone concentrations in DKA. Beta-hydroxybutyrate accounts for the majority of the serum ketones found in DKA.4,6,7 This is now considered a vital test for diagnosis and management, and can now even be done via finger stick.4,7

   Serum hyperkalemia often results due to the extracellular shift of potassium due to acidemia, serum hyperosmolarity, osmotic diuresis and hyperglycemia from the severe insulin deficiency of DKA.3,4 Hypokalemia is also not uncommon, due to osmotic diuresis, which can cause total body depletion of the extracellular potassium.8 In a 2007 study of 56 patients with DKA, researchers found potassium levels to be normal in 52.5 percent of patients, hyperkalemia in 36.5 percent and hypokalemia in 14 percent with the differences not being statistically significant.9 Another study reported the average potassium value to be around 5.6 mEq/kg.10

   In addition to monitoring electrolytes, one can check dehydration by ordering the following labs: total serum protein, amylase, creatinine phosphokinase and albumin.4 All will most likely be elevated with DKA. Creatinine will most likely be falsely elevated due to blood acetoacetate levels as Assadi and colleagues demonstrated.11 Leukocytosis is generally present in DKA proportional to the serum ketone concentration with values >25,000 usually indicating infection.7

What About Lactic Acidosis Or Hyperglycemic Hypersmolar Syndrome?

   Lactic acidosis. This is another cause of a high anion gap acidosis and will mimic DKA symptomology.7 A recent nested case-control analysis concentrated on 50,048 patients with type 2 diabetes. Authors revealed that metformin and sulfonylurea use have been linked to lactic acidosis in rare instances. Sulfonylureas are more likely to produce a profound hypoglycemia.12 Accordingly, one may want to inquire about diabetes medication use as it may be a factor in the differential. Other common causes of lactic acidosis include drug toxicity of salicylate, methanol, ethylene glycol and paraldehyde, as well as chronic renal failure.7

   Hyperglycemic hyperosmolar syndrome (HHS). One should always concurrently consider HHS as a differential diagnosis with DKA in the diabetic patient with an AMS.3,4,7 Hyperglycemic hypersmolar syndrome is very similar to DKA but usually develops over days to weeks rather than acutely over 24 hours.4

   Polyuria, polydipsia and fever from underlying infections do occur. There is also a significant alteration (or decline) in mental status, which is often the most outstanding presentation. Abdominal pains, vomiting, nausea and Kussmaul’s respirations generally do not occur.4 Stroke-like symptoms often occur as well. These include focal epileptic seizures and focal neurological defects (hemiparesis, hemiplegia, increased muscle tone, stroke or meningitis-like symptoms).13,14

   Infections such as UTIs and pneumonia are usually the underlying causes of HHS.4 Myocardial infarction, stroke, thyrotoxicosis and even hyperthyroid Grave’s disease can promote the release of counterregulatory hormones leading to hyperglycemia and hyperosmolarity.4,15

Significant laboratory findings for HHS include:

   • Plasma glucose >600
   • Arterial pH >7.30
   • Serum bicarbonate (mEq/L) >15
   • Effective serum osmolality > 320 mOsm/kg
   • Anion gap <12 (absence of significant ketoacidosis but 50 percent of patients may still have this)

Could Sepsis Be A Possible Diagnosis?

   Sepsis. The patient in this case was lethargic. He was running a fever, did not take antibiotics for post-op infection control and had previously received treatment for a plantar foot ulcer. Therefore, you should consider the mnemonic SEPTIC, which is as follows:16

   S: shock
   E: elevated temperature
   P: decreased platelets
   T: tachycardia/tachypnea
   I: increased white blood cell count
   C: confusion

   Sepsis is the presence of bacteria in the systemic circulation. Sepsis releases endotoxins and cause systemic illness. The dysfunctional neutrophils in a diabetic immune system prevent chemotaxis and phagocytosis of bacteria. Foot infections can quickly become systemic in part due to the anatomical connection of the pelvic veins draining into the spinal venous plexus, which has no anatomical valves. Research has also established that the epidural space, intervertebral disc, paraspinal soft tissues, lung, heart, kidney and bone all contribute to contiguous bacterial spread.

   If a foot ulcer becomes infested with bacteria and does not receive proper treatment, cellulitis can develop and quickly spread to deeper muscles, tendons and bone. This can lead to osteomyelitis. The hematogenous spread of bacterial pus from a localized foot infection to the systemic circulation is possible and can seed numerous toxins in any part of the body.17

   Sage, Pinzur and colleagues reported on three patients. The study demonstrated the effects of recalcitrant foot infections becoming global sepsis. Possible etiologies included psoas muscle abscess, cervical spine osteomyelitis, epidural abscess and septic shock.17

   Septic shock can result from the sudden release and uptake of endotoxins. This can cause confusion, coma, fever, hypotension, tachycardia, tachypnea and renal failure, among other things. Gram-negative and gram-positive aerobic and anaerobic bacteria are known culprits.17

   Diagnostic tests for septic foot include complete blood count (CBC) with differential count, erythrocyte sedimentation rate (ESR), SMA-12 (complete metabolic panel), HgA1c, blood culture, X-rays, magnetic resonance imaging, non-invasive vascular testing, gram stain and culture.18

Why One Would Consider Stroke In The Differential Diagnosis

   Stroke. Although this patient did not demonstrate any focal neurological deficits, one could still consider stroke due to his acute change in mental status. It is known in various studies that patients with diabetes have a higher relative risk for developing stroke than non-diabetics.19,20 Cardiovascular autonomic neuropathy (CAN) is common in diabetes and often develops secondary to prolonged hyperglycemia, microangiopathy, macroangiopathy, distal symmetrical polyneuropathy, elevated HgA1c levels, retinopathy and other known complications of diabetes.21

   Cardiovascular autonomic neuropathy alone is an increased risk factor for stroke in patients with diabetes and can be a major player in “silent ischemia” due to accelerated cerebral vascular damage and changes in cerebral blood flow.20-22 Proteinuria (≥20 and <200 µg/min) is an independent risk factor for stroke in patients with type 2 diabetes.23 Serum uric acid levels >295 µmol/L are known to be a strong predictor for cerebral vascular events in type 2 diabetes.24 A neurosurgery or cardiovascular consult might be warranted as well for this patient.

What You Should Know About Diagnostic Testing And Lab Values

   The most common etiologies of mental status changes are related to changes in the patient’s blood work. Blood panels will show abnormalities in electrolytes, white blood cell (WBC) counts, sodium, ammonia and glucose levels among others. Fluctuations in all of these can cause acute mental status changes.

   In this particular patient, the treating physician should consider the more obvious potential cause of infection. One can determine this through blood cultures, ESR and WBC counts. The physician may also rule out stroke by obtaining a computed tomography (CT) scan, if warranted, after a thorough neurologic exam. This patient had no neurologic deficits so the CT was unnecessary.

   Less likely for this patient are etiologies such as trauma leading to subdural hematoma, alcohol, opiates, uremia, trauma, heat stroke, psychiatric issues, porphyria, poisons, seizure and shock.

   In addition to discovering an abnormally high glucose level upon admission, the treating physician also ordered an arterial blood draw and a Chem 12. The patient’s blood culture was negative after 24 hours. Urinalysis was positive for ketones and negative for bacteria. Arterial pH was less than 7 while serum bicarbonate was less than 10. Serum ketones were positive. The anion gap was (Na+) – (Cl+HCO3) >12.

Final Notes

   The well-trained podiatrist has made the diagnosis before he or she orders the MRI. One orders the advanced study to confirm the diagnosis and not to make the diagnosis. It is much the same way with a well-made referral.

   By the time attendings questioned the residents and medical students about the potential etiology, they had determined the two most likely diagnoses: diabetic ketoacidosis or an infection-related etiology. A bedside check of the patient’s blood sugar, although extremely high at 650, was not definitive for ketoacidosis because it would often be elevated in the presence of an infection.

   The residents performed a physical examination, which did not reveal a neurologic deficit, and the lower extremity exam did not indicate an extensive foot infection. The wound did not probe deeply. There was no cellulitis and only slight exudates.

   The patient received a referral for an internal medicine consultation. Physicians ordered labs for the internist to review.

   When the internist reviewed the chart and examined the patient, he joined the podiatry team on rounds. He complimented the residents on their complete workup. He noted that he did not have to order any additional testing and that the residents had diagnosed the problem correctly on their own. The internist confirmed the diagnosis of diabetic ketoacidosis, which was brought on by the patient’s non-adherence with his insulin regimen and further exacerbated by his infection.

    “At this rate, podiatry is going to put me out of business,” the internist added.

Mr. Lang is a third-year student in the Class of 2011 at the College of Podiatric Medicine and Surgery at Des Moines University.

Dr. Satterfield is a Clinical Adjunct Professor at the Western University College of Podiatric Medicine. She is a Fellow and President-Elect of the American College of Foot and Ankle Orthopedics and Medicine.

Dr. Steinberg is an Assistant Professor in the Department of Plastic Surgery at the Georgetown University School of Medicine in Washington, D.C. Dr. Steinberg is a Fellow of the American College of Foot and Ankle Surgeons.

References:

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