Glucose Management and Nutrition

Jennifer A. Frontera

Hyperglycemia in critically ill patients, often referred to as stress hyperglycemia, is characterized by increased gluconeogenesis, elevated insulin levels, insulin resistance, and increased IGF-binding protein 1. Elevated catecholamines, cortisol, growth hormone, and glucagon also occur in the context of critical illness, contributing to hyperglycemia. Hyperglycemia has been shown to lead to worse outcomes among various critically ill populations and has the highest adjusted odds ratios for mortality among cardiac and neurologic patients.

Acute hyperglycemia is common after neurologic injury. It occurs in 30 to 70% of patients and may be mediated by an acute stress response, hypothalamic injury, or catecholamine surge at the time of neurologic injury. Animal models of brain ischemia suggest that hyperglycemia worsens acidosis, excitotoxicity, and breakdown of the blood-brain barrier with consequent edema or hemorrhagic transformation. Elevated admission glucose and prolonged hyperglycemia have been linked to worse outcomes in patients with ischemic stroke, intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI).3,4,6,7,8,9 Prolonged hypoglycemia, which can occur as a complication of glucose management, can also lead to neurologic deterioration. Finding the appropriate glucose range and the best way to maintain normoglycemia in the neurologically critically ill is an active area of research.

Case Example

You are called by the neuro-intensive care unit (NICU) nurse because a patient you recently admitted with subarachnoid hemorrhage has a point of care glucose level of 253 mg/dL.

Questions

What was the patient’s admission glucose?
What was the last glucose value?
Has the patient received any dextrose solutions or insulin?
Is the patient receiving steroids or intravenous (IV) pressors?
Is the patient being fed currently?

Urgent Orders

Remove dextrose from any IV infusions, if possible.
Initiate insulin infusion protocol or administer subcutaneous insulin.

History and Examination

History

Does the patient have a history of diabetes? Does the patient have a history of diabetic ketoacidosis (DKA) or hyperosmotic nonketotic hyperglycemia? Does the patient take oral hypoglycemics or insulin at home?

Physical Examination

Vitals: Blood pressure, heart rate, respiratory rate, urine output
General: Assess volume status (mucous membranes, skin tenting, ins and outs).
Cardiovascular: Assess for tachycardia (evidence of possible volume depletion).
Extremities: Assess for diabetic ulcers.

Neurologic Examination

A full neurologic examination, including assessment of mental status, cranial nerves, motor skills, and reflexes, as well as a sensory and cerebellar exam, should be performed on all patients.

Mental status: Assess for level of arousal, attention, orientation.

Cranial nerve: Assess for funduscopic evidence of diabetes (macular degeneration).
Motor skills: Standard assessment
Sensory skills: Assess for evidence of diabetic neuropathy (stocking-glove sensory loss, including large fiber proprioception, vibration and light touch, and small fiber pain or temperature loss).
Reflexes: May be decreased if evidence of diabetic neuropathy

Differential Diagnosis

Stress hyperglycemia related to acute neurologic injury and critical illness
Underlying diabetes (check history and HgbA1c)
Hyperglycemia related to dextrose administration

Life-Threatening Diagnoses Not to Miss

Prolonged untreated hyperglycemia can worsen outcomes in neurologic patients.
Diabetic ketoacidosis occurs more commonly in type I diabetics, but it also occurs in type II. If glucose is >400 mg/dL, this must be considered.
Hyperosmotic nonketotic hyperglycemia (HONK): Similar laboratories for DKA, ketosis not seen.

Diagnostic Evaluation

Serial point of care glucose, HgbA1c

Microdialysis (if available):

Hyperglycemic: Elevated brain glucose
Hypoglycemic: Low brain glucose levels (<2 mmol/L)
When low brain glucose leads to metabolic distress: elevated glutamate (>5 µM) and elevated lactate/pyruvate (>25 to 40 mmol/L) are seen.

If DKA or HONK suspected: Serial arterial blood gas (ABG; metabolic acidosis), serum osmolarity, chemistry panel (particularly K+, Na, HCO₃, creatinine), anion gap (>12 mEq/L is abnormal), urine and serum ketones (Β–hydroxybutyrate if available).

Blood glucose should be monitored hourly until stable and other laboratories checked every 2 to 4 hours depending on the severity and clinical response.

Treatment

Insulin

Changes in feeding, IV infusions, steroid and pressor use, sepsis, and liver or renal failure affect glucose control.
Protocolized insulin infusions can allow for tight control.
Blood glucose levels are checked every hour after admission. When two consecutive glucose levels an hour apart exceed a certain threshold (e.g., 110 mg/dL), an insulin infusion is initiated. A standard infusion contains 100 U of regular insulin in 100 mL of normal saline (NS).
Some protocols will combine dextrose infusions with insulin to temper potential hypoglycemia. Glucose-insulin-potassium infusions are used in some centers, though potassium infusion can cause hypotension. Potassium levels should be checked regularly (at least daily) in patients on insulin infusion because insulin drives potassium intracellularly and can lead to hypokalemia.
Subcutaneous insulin may have less reliable absorption in patients who are edematous.
When patients are ready to leave the ICU and are receiving a regular feeding regimen, IV insulin can be converted to long-acting insulin.
- To convert to neutral protamine Hagedorn (NPH insulin): Calculate the total regular insulin received over the last 24 hours. Two-thirds of the total dose received can be given as NPH (subcutaneously) divided every 6 hours. Sliding scale insulin should be instituted for additional coverage. NPH doses can be adjusted on a daily basis.

Feeding

Glucose control can only be achieved when a feeding regimen is accounted for.
Feeds should be initiated at 20 mL/h and increased by 15 mL every 8 hours until the goal rate is reached. Feeds should be held for elevated residuals (2 x hourly rate of feeds).
Replete electrolytes to normal levels prior to initiation and advancement of feeds. PO₄ should be maintained >2.5 mg/dL to avoid acute refeeding syndrome.
Enteral nutrition (either orally [PO], via nasogastric tube [NGT], or via percutaneous endoscopic gastrostomy [PEG] tube) is generally preferred to parenteral nutrition because it limits gut translocation of bacteria, and the rates of infection (particularly fungemia) are higher with parenteral nutrition. However, in circumstances where enteral nutrition is not possible for prolonged periods of time (>7 days), parenteral nutrition may be necessary (Table 19.1).¹

Treatment of DKA and HONK (Table 19.2)

Complications of DKA/HONK treatment: Cerebral edema occurs in 0.5 to 1% of DKA episodes (less common in HONK) 12 to 24 hours after initiation of treatment and is more frequent in children. Mortality is 20 to 25%, and 15 to 35% of survivors have permanent neurologic sequelae. Treat with mannitol or hypertonic saline as with other intracranial pressure (ICP) crises. The 2006 American Diabetes Association (ADA) guidelines suggest a maximum reduction in plasma osmolality of 3 mOsm/kg/hour.²

Prognosis

Admission and prolonged hyperglycemia affect outcome after neurologic injury:
- Subarachnoid hemorrhage (SAH): Admission glucose and prolonged hyperglycemia are independently associated with death or severe disability, fewer independent activities of daily living, prolonged length of stay, and hospital complications including symptomatic vasospasm.^3,4
- Intracerebral hemorrhage (ICH): Hyperglycemia is associated with increased mortality and ICH expansion.^5,6
Traumatic brain injury (TBI): Prolonged elevated glucose is associated with a worse neurologic examination, increased mortality, and prolonged length of stay.⁷
Ischemic stroke: Hyperglycemia predicts hemorrhagic transformation after IV or intra-arterial thrombolysis, is associated with infarct expansion on magnetic resonance diffusion-weighted imaging, and is related to worse outcome, prolonged length of stay, and higher medical costs.^8,9

**Table 19.1** European Society for Clinical Nutrition and Metabolism Recommendations for Nutrition in Intensive Care Patients ^*
Recommemdation	Grade
All patients who are not expected to be on a full oral diet within 3 days should receive enteral nutrition.	C
Hemodynamically stable critically ill patients who have a functioning GI tract should be fed early (<24 h) using an appropriate amount of feed.	C
During the acute and initial phase of critical illness, in excess of 20–25 kcal/kg BW/d may be associated with a less favorable outcome.	C
During the anabolic recovery phase, the aim is to provide 25–30 kcal/kg BW/d.	C
Patients with severe undernutrition should receive enteral nutrition up to 25–30 total kcal/kg BW/d. If these target values are not reached supplementary, parenteral nutrition should be given.	C
Supplementary intravenous metoclopramide or erythromycin can be administered to patients with intolerance to enteral feeding (i.e., high gastric residuals).	C
Use enteral nutrition in patients who can be fed via the enteral route.	C
There is no significant difference in the efficacy of jejunal vs gastric feeding in critically ill patients.	C
Avoid additional parenteral nutrition in patients who tolerate enteral nutrition and can be fed approximately to the target values.	A
Use supplemental parenteral nutrition in patients who cannot be fed sufficiently via the enteral route. Consider careful parenteral nutrition in patients intolerant to enteral nutrition at a level equal to but not exceeding the nutritional needs of the patient.	C
Whole protein formulas are appropriate in most patients because no clinical advantage of peptide-based formulas has been shown.	C
Immune-modulating formulas (enriched with arginine, nucleotides, and omega 3 fatty acids) are superior to standard enteral formulas in patients with elective upper GI surgery, mild sepsis (APACHE II<10:48 AM 10/6/201010:48 AM 10/6/201015), trauma, and ARDS. Patients with severe sepsis who do not tolerate more than 700 mL of enteral formula per day should not receive immune-modulating formulas.	A-B
Glutamine should be added to standard enteral formula in burn and trauma patients.	A

Abbreviations: ARDS, acute respiratory disease syndrome; BW, body weight; GI, gastrointestinal.

^* See Chapter 22 for a summary of Grades of ESPEN evidence.

Data from: Kreymann KG, Berger MM, Deutz NE, et al. ESPEN Guidelines on Enteral
Nutrition: intensive care. Clin Nutr 2006;25(2):210–223.

**Table 19.2** Treatment of Diabetic Ketoacidosis (DKA) and Hyperosmotic Nonketotic Hyperglycemia (HONK)
Treatment	Comment
Fluid resuscitation	Volume deficit can be as high as 4–6 L because glucose acts as an osmotic diuretic. Replace with NS starting at 15–20 mL/kg BW/h.
Insulin	Begin intravenous infusion of regular insulin at 0.1 U/kg as IV bolus followed by 0.1 U/kg/h IV infusion. Check hourly blood glucose values and titrate as necessary. Replete potassium <3.3 mEq/dL prior to initiation of insulin infusion. If the serum glucose does not fall by 50–70 mg/dL from the initial value in the first hour, the bolus should be repeated, and the insulin infusion may be doubled every hour until glucose steadily declines. When glucose values are <200 mg/dL, IV fluids should be changed to D5NS and insulin continued until the anion gap is <12 mEq/L. Ketosis may persist for up to 24 hours. Do not discontinue the insulin infusion until the anion gap is closed. Correct the anion gap for the albumin level.
Potassium	May be normal or elevated at admission due to insulin deficiency. Potassium distribution is reversed (driven intracellularly) rapidly during insulin infusion. K + 20 mEq/L is generally added to IV fluids and potassium levels carefully monitored and maintained between 4.0–5.0 mEq/L.
Bicarbonate	HCO₃ can lead to rise in pCO₂ resulting in paradoxic decline in cerebral pH as CO₂ rapidly crosses the blood-brain barrier. Patients with pH <7.0 or life-threatening hyperkalemia may benefit from HCO₃administration.