Septic Shock and Toxic Alcohols

Today's case involved a middle-aged man presenting with an acute onset of fever and symptoms compatible with pneumonia.  He was hypotensive, tachycardic, febrile, and hypoxemic requiring supplemental oxygen.  His X-ray was consistent with community-acquired pneumonia, and he was treated with antibiotics and

admitted to internal medicine.

There were several valuable learning points:

-Prior to the case discussion, we talked about some toxic alcohol ingestions.  The main four alcohols you’ll deal with are ethanol (drinking alcohol), ethylene glycol (antifreeze, bright yellow), methanol (windshield washer fluid), and isopropanol (rubbing alcohol).  Ethanol causes an osmolar gap but should not in and of itself cause an anion gap (it can produce alcoholic ketoacidosis and occasionally a lactic acidosis).  Isopropanol is a secondary alcohol meaning that when it’s oxidized, it forms a ketone, not a ketoacid as in DKA.  Thus, it produces an osmolar gap, profound intoxication, but no anion gap.  Ethylene glycol and methanol both produce an osmolar gap initially, and then as they are converted to their acid counterparts by the liver, they produce increasing anion gaps.  Ethylene glycol produces oxalate nephropathy and is quite toxic.  Methanol produces formic acid which is extremely neurotoxic.  The ultimate therapy to remove either one is fast, high throughput dialysis.

-The actual alcohols themselves are relatively innocuous, so the main goal is preventing conversion into acids.  To do that, you need to inhibit alcohol dehydrogenase.  The easiest and cheapest way if there are no other options is with ethanol.  This can be given orally (e.g. whiskey) or IV.  The less intoxicating option is fomepizole which inhibits alcohol dehydrogenase, but is quite expensive and only available in hospitals.  In addition to preventing conversion from the initial alcohol, steps can be taken to prevent conversion into the final toxic byproduct.  Pyridoxamine and thiamine help shunt metabolites of ethylene glycol away from the oxalic acid pathway.  Folate helps shunt methanol byproducts away from formic acid.  Thus, in suspected cases of toxic alcohol ingestion (e.g. high anion gap, high osmolar gap, altered mentation) it is reasonable to start all of those shunting cofactor therapies while preparing for dialysis.

-We spoke about the SIRS (systemic inflammatory response syndrome) criteria which are: temperature above 38C or less than 36C, respiratory rate above 20 or PaCO2 less than 32mmHg, heart rate above 90/min, and WBC count <4 or="">12,000 or >10% band neutrophils.  This syndrome does not have to accompany an infection, and can classically be seen in patients with burns, or patients with pancreatitis.  If it is accompanied by infection, we call it sepsis. If sepsis is accompanied by end-organ dysfunction (renal failure, altered mentation, heart failure, etc.) we call it severe sepsis.  If after a fluid challenge of around 20-30cc/kg crystalloid, the blood pressure is still less than 90mmHg systolic, we call it septic shock.

-More than 10 years ago, a landmark trial (Rivers trial) demonstrated that Early Goal Directed Therapy in the emergency department had a mortality benefit for patients with septic shock.  Most of the principles of sepsis management from that trial have been incorporated into our daily practice, but more recent trials have demonstrated equivalency between “usual care” and “protocolized care” in sepsis.  That said, the initial principles from the Rivers trial were: early antibiotics and crystalloid fluids given until a central venous pressure of 8-12mmHg was reached.  If the mean arterial pressure (MAP) was less than 65mmHg despite those fluids, vasopressors like norepinephrine were started to achieve a MAP of 65mmHg.  Once those goals were reached, the patient’s central venous oxygen saturation (a measure of how much oxygen the body is extracting from the blood) was measured.  If it was under 70%, there was deemed to be some degree of septic myocardial dysfunction.  The intervention was dobutamine (an inotrope) if the hematocrit was normal, or transfusion if the hematocrit was < 30%.  Urine output less than 0.5cc/kg/hr was also an indication for either inotropes or transfusions.

-There were many criticisms of this trial.  The ED had a “code sepsis” area where ER physicians managed the majority of the patients’ early care.  All patients received central venous catheterization (no longer a real practice here).  There were issues involving the cost and financial incentives from the trialists around the central venous catheter’s oxygen saturation probe which could measure it in real time.

-We talked about the organisms that typically cause community-acquired pneumonia (CAP).  They include S. pneumoniae, M. catarrhalis, and H. influenza.  Additionally, atypical organisms like legionella, chlamydophila, and mycoplasma can cause this syndrome.  Legionella is acquired from contaminated water sources and not airborne transmission.  It is typically tested with a urinary antigen test, and should be considered in those with septic shock, elderly patients, or immunocompromised patients.  Patients ill enough to require hospital admission should be treated with a beta lactam (ceftriaxone) and macrolide (azithromycin) combination or a respiratory quinolone (moxifloxacin or levofloxacin).  Just because the patient is “sick” does not mean that he or she requires piperacillin/tazobactam in the absence of Pseudomonas risk factors or previous antibiotic exposure.  Piperacillin is inferior therapy to ceftriaxone for most causes of community-acquired pneumonia.

Further reading:

Rivers, E., Nguyen, B., Havstad, S., Ressler, J., Muzzin, A., Knoblich, B., ... & Tomlanovich, M. (2001). Early goal-directed therapy in the treatment of severe sepsis and septic shock. New England Journal of Medicine, 345(19), 1368-1377.

Kraut, J. A., & Kurtz, I. (2008). Toxic alcohol ingestions: clinical features, diagnosis, and management. Clinical Journal of the American Society of Nephrology, 3(1), 208-225.