Common misconceptions and mistakes

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  Extreme hyperglycemia always implies profound dehydration and is pathognomonic for a hyperosmolar-type presentation

  
  
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  Diabetic ketoacidosis (DKA) always requires aggressive fluid resuscitation

  
  
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  Attributing ketoacidosis to starvation

  
  
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  Attributing obtundation to hyperosmolarity when the calculated serum osmolality (without the blood urea nitrogen [BUN]) is < 360 mOsm/kg

  
  
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  Failing to administer potassium to a DKA patient on presentation because his or her potassium was normal (ie, 3.5 mmol/L)

Acute diabetic presentations

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  Diabetics in crisis present on a spectrum from DKA to the hyperglycemic hyperosmolar nonketotic syndrome (HHNKS)

  
  
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  Management decisions should be made based on the specific derangements occurring at the time of presentation and not on the type of diabetes (ie, type 1 or 2) or a single feature of the presentation (eg, extreme hyperglycemia) ( Fig. 23.1 )

  
  

  
  

  
  

  

  
  

  
  

  Comparison of the presenting chemistries and calculated values regarding tonicity and water deficit for a patient with hyperglycemic hyperosmolar nonketotic syndrome (HHNK) and a patient with diabetic ketoacidosis (DKA), highlighting that the important difference between the presentations is not the magnitude of the hyperglycemia but rather the sodium and the bicarbonate. The bicarbonate signifies the presence (or absence) of a severe metabolic acidosis and the sodium reflects the duration of the illness, as water depletion takes time (days to weeks). Both patients have an extremely elevated glucose because both are in renal failure. The HHNKS patient’s renal failure is likely a result of volume depletion. His corrected sodium is 166 mmol/L, proving he has suffered weeks of glycosuria and is profoundly volume depleted. The DKA patient, however, sick for only 24–48 hours deserves more thought. In this case the DKA patient had significant baseline disease (chronic kidney disease [CKD] III) and was on an angiotensin-converting-enzyme (ACE) inhibitor. The HHNKS patient was lethargic. His tonicity, or calculated serum osms without the blood urea nigrogen (BUN), were 364 mOsm/kg—a satisfying explanation for lethargy. Interestingly, the DKA patient’s calculated osms, including the BUN, were 360 mOsm/kg. If he had been lethargic, he would have been vulnerable to the common mistake of misattributing obtundation to hyperosmolarity based on an ineffective osm, namely BUN. His tonicity, or relevant calculated osmolality, is only 346 mOsm/kg, meaning that lethargy should be worked up.

  
  
  
  
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  Do not attempt to treat via algorithm

  
  
  
  
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    Manage each derangement independently; for example:

    
    
    
    
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      Ketoacidosis is treated with insulin and prompts a search for a possible sympathetic stressor (ie, infection or myocardial infarction ), even if indiscretion (medication/insulin noncompliance) is likely

      
      
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      Extreme hyperglycemia occurs as a consequence of renal failure (most often prerenal azotemia); therefore it is treated with insulin, resuscitation (ie, IVF), and possibly a workup of acute kidney injury (AKI)

      
      
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      Hypernatremia occurs as a consequence of profound water depletion (often > 10 L) caused by weeks of severe hyperglycemia and glycosuria; therefore it is treated with enteral free water replacement and improved glucose control

    
    

  
  

Ketoacidosis

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  Respect ketosis:

  
  
  
  
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    Measurable serum ketones causing a significant metabolic acidosis is never normal physiology

    
    
    
    
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      Do not attribute to starvation

    
    
    
    
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    Ketoacidosis occurs in (only) three clinical situations:

    
    
    
    
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      DKA, the hyperglycemic hyperosmolar state with ketoacidosis, or alcoholic ketoacidosis (AKA)

      
      
      
      
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        The common feature of all three is absolute or relative lack of insulin (ie, insulinopenia )

      
      

    
    
    
    
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    Insulinopenia (absolute vs relative)

    
    
    
    
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      Absolute lack of insulin occurs in type 1 diabetics who abstain from taking their insulin or in end-stage pancreatitis where > 90% of the pancreas has been destroyed

      
      
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      Relative lack of insulin occurs in type 1 or type 2 diabetics when faced with a significant sympathetic stimulus:

      
      
      
      
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        Increased sympathetic activity overwhelms the ability of insulin to signal fat storage, resulting in unchecked fatty lipolysis

        
        
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        This leads to increased free fatty acid (FFA) release and massive unregulated hepatic ketone generation

        
        
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        Sympathetic stimulation also directly suppresses beta cell insulin secretion (further promoting ketosis)

      
      

    
    
    
    
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    Ketoacidosis should prompt a search for hypersympathetic disease states

    
    
    
    
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      Myocardial infarction and infection are classic and common triggers and should always be screened for no matter how likely a lack of insulin administration is to blame

      
      
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      Methamphetamine (and other sympathomimetics) are capable of direct pancreatic insulin suppression, triggering hyperglycemia and ketoacidosis in type 2 diabetics (and vulnerable prediabetics)

    
    

  
  

Diabetic ketoacidosis classic presentation and pathophysiology

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  Insulin is held either to avoid hypoglycemia during an illness with poor per os (PO) intake (ie, vomiting) or when s ignificant illness leads to catecholamine excess relative to administered insulin:

  
  
  
  
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    For example, an individual takes 10 U of insulin but needs 30 U because of an unanticipated myocardial infarction and the increased sympathetic activity that ensues

  
  

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  Absolute (or relative) lack of insulin destabilizes adipose tissue, leading to massive fatty lipolysis, which releases free fatty acid (FFA) into the circulation

  
  
  
  
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    Unregulated hepatic FFA metabolism generates an excess of acetyl CoA, which is converted to acetoacetate and beta-hydroxybutyrate and then released into the blood; this lowers pH to a critical level, thereby threatening:

    
    
    
    
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      Hypercarbic respiratory failure secondary to diaphragmatic fatigue in the face of overwhelming metabolic acidosis

      
      
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      Hemodynamic collapse, arrhythmia, or pulseless electrical activity (PEA) arrest secondary to severe metabolic acidosis

    
    

  
  

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  Ketoacidosis is a poorly tolerated condition, and thus it always represents a short-duration illness with patients presenting 24–48 hrs after the onset (eg, last insulin dose or onset of extreme stressor)

  
  
  
  
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    Often the history reveals an obvious illness that led to cessation of insulin or inadequate administration

  
  

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  Patients present with a normal mental status, extreme dyspnea , and an obvious maximum ventilatory effort (ie, Kussmaul’s respirations), attempting to compensate for the severe acidosis

  
  
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  Abdominal pain, nausea, and vomiting are common symptoms that are caused by ketoacidosis itself and are often misattributed to a superimposed viral gastroenteritis

  
  
  
  
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    May be complicated by preexisting diabetic gastroparesis

  
  

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  A large, anion gap metabolic acidosis, as a result of ketones, is the central feature of the syndrome

  
  
  
  
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    Serum ketones positive (at some dilution, magnitude not helpful) is the gold standard for the diagnosis

    
    
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    Usually a small amount of lactic acid also detected (2–4 mmol/L)

    
    
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    If serum ketones cannot be measured in a timely fashion (laboratory limitation), ketoacidosis can be reasonably inferred in the appropriate clinical setting by demonstrating:

    
    
    
    
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      A large anion gap acidosis (> 25 mEq/L) with a lactate < 5 mmol/L

      
      
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      Positive urine ketones

      
      
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      No significant osmolar gap (to suggest ethylene or isopropyl alcohol ingestion)

    
    

  
  

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  Blood glucose is typically elevated in the 200–500 mg/dL range, not extremely high (ie, > 600 mg/dL)

  
  
  
  
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    Extreme hyperglycemia is only seen if concomitant renal failure is present

    
    
    
    
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      In straightforward DKA presentations, volume depletion is not usually significant enough to cause renal failure alone

      
      
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      Acute renal failure in this setting commonly represents acute or chronic renal disease often complicated by angiotensin-converting-enzyme (ACE) or angiotensin receptor blocker (ARB) therapy

    
    

  
  

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  Significant hyperkalemia (K ⁺ > 5.5 mmol/L) is expected and related to the magnitude of the acidosis (from acidotic shift of potassium out of cells)

  
  
  
  
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    If the potassium is normal or low on admission, it will drop to < 3 mmol/L (often < 2 mmol/L) when the acidosis resolves, possibly causing ventricular tachycardia and cardiac arrest

    
    
    
    
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      Hypokalemia, at a normal pH, implies total body potassium depletion as seen in the malnourished and in alcoholics (more common in AKA)

      
      
      
      
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        Hypokalemia should trigger the monitoring of phosphate (also vulnerable to total body depletion in alcoholism and malnutrition)

      
      

    
    

  
  

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  Serum sodium is normal

  
  
  
  
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    Blood glucose is usually not high enough to cause significant dilution

    
    
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    There is no protracted period of hyperglycemia and water diuresis to cause hypovolemic hypernatremia

  
  

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  Fluid-unresponsive hypotension is ominous and is likely related to the triggering event (eg, sepsis) or symptomatic acidosis (much less likely)

  
  
  
  
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    Patients with pure DKA are typically only mildly volume depleted (ie, 2–4 L down), given the short duration of their illness

  
  

Hyperglycemic hyperosmolar nonketotic syndrome (HHNK): classic presentation and pathophysiology

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  HHNK is most commonly seen in patients with poorly controlled type 2 diabetes who experience a subacute presentation, starting with poor glucose control and persistent hyperglycemia

  
  
  
  
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    This may occur as the de novo presentation of type 2 diabetes, or it may complicate known disease

    
    
    
    
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      In established type 2 diabetics, the poor glucose control is usually a result of medication and/or diet noncompliance, infection, or steroid administration for an unrelated problem

    
    

  
  

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  The syndrome starts within 2–3 weeks of polyuria and polydipsia from hyperglycemia and glycosuria, which lead to profound water depletion (5–10 L) and extreme hypovolemic hypernatremia, the central feature of the syndrome

  
  
  
  
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    The hypernatremia increases osmolality, drawing water out of cells, shrinking central neurons, and causing a decreased mental status (lethargy to obtundation) when serum osms rises above 360 mOsm/kg

    
    
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    The uncorrected presenting sodium is often only mildly elevated in the setting of extreme hyperglycemia (because of the dilutional effect this causes)

  
  

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  Symptomatic hypovolemia is caused by the sodium loss incurred by the osmotic diuresis (because salt follows water), manifesting as:

  
  
  
  
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    Orthostatic hypotension

    
    
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    Renal failure from decreased renal blood flow (RBF)

    
    
    
    
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      Often complicated by acute tubular necrosis (ATN) if the patient was taking an angiotensin blocker, ace inhibitor or nonsteroidal anti-inflammatory drug (NSAID)

    
    

  
  

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  Extreme hyperglycemia, glucose in the 600–1600 mg/dL range, occurs when glomerular filtration rate (GFR) approaches zero and glycosuria stops, allowing blood glucose values to soar

  
  
  
  
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    Extreme hyperglycemia (itself) causes few or no symptoms (ie, blurry vision) and is significant only in that it indicates oliguric renal failure

  
  

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  Patients present with decreased mental status (obtundation), profound volume depletion, and dehydration

  
  
  
  
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    Patients with pure HHNK are profoundly dehydrated (ie, >5 L free water deficit), and volume depleted (ie, >5L down), given the long duration of their illness