SpMet

The other day a DO called and advised me that SpMet functionality has been added to the LP15 monitors on the cars.  His question was - what is the clinical significance of SpMet?  And away we go . . .

What is methemoglobin (Met-Hb)?  (I am going to abbreviate hemoglobin as Hb here forward)

Met-Hb: an altered state of Hb in which the FERROUS (Fe 2+) irons of heme are oxidized to the FERRIC (Fe 3+ state).  (The heme portion of the Hb molecule is were oxygen binds).

FERRIC Hb CANNOT bind oxygen.

When there is a lot of FERRIC Hb around, the remaining 'good' FERROUS Hb has a HIGHER affinity for oxygen - that is - the remaining 'good' Hb will not let go of the oxygen it is carrying and oxygen delivery to the tissues is further impaired (if you have studied human physiology, this results in the oxygen dissociation curve shifting to the LEFT).


What is the net effect of Met-Hb formation (increasing Met-Hb levels compared to normal Hb) in the bloodstream?

The patient becomes functionally anemic.  Oxygen delivery to the tissues and organs becomes even more impaired in that the remaining 'normal' Hb won't let go of the oxygen it is carrying.

Do normal healthy individuals produce Met-Hb?

Yes.  We auto-oxidize some of our Hb (from ferrous to ferric form) every day and maintain a steady-state level of about 1% Met-Hb.

What is the disease state know as methemoglobinemia?

There are actually 2 types of methemoglobinemia: CONGENITAL and ACQUIRED.

What is congenital methemoglobinemia?

As the name implies, it is a genetic disease - the patient is born with the condition.  In congenital methemoglobinemia the patient can have Met-Hb levels as high as 40% (of total Hb).  Most of these patients, despite having a high SpMet reading will be asymptomatic.  They may have a headache or complain of easy fatigability.  These patients will be chronically cyanotic (bluish discoloration of the skin and mucous membranes).

What is acquired methemoglobinemia?

This is what we are on the look-out for.  It is a rapid increase in Met-Hb levels.  Oxygen binding and oxygen delivery to the tissues is acutely impaired and the patient becomes rapidly cyanotic and symptomatic.  Early symptoms include headache, fatigue, dyspnea, and lethargy.  As Met-Hb levels rise, respiratory depression, decreased LOC, shock, seizures, and death can occur.

What medications or exposures can cause (acute) acquired methemoglobinemia?

• Benzene derivatives: common industrial chemical, also a principal product of combustion of PVC (polyvinyl chloride)
• Chloroquine: a drug used for malaria treatment and prophylaxis
• Dapsone: a drug used to treat PCP pneumonia (which primarily affects patients with HIV/AIDS),
• Local anesthetics (benzocaine, lidocaine): 
• Metoclopramide (Reglan)
• Napthoquinone: found in diesel exhaust particles
• Napthalene: was once the primary ingredient in moth balls
• Nitrites
• Amyl nitrite: component of the Lily Cyanide antidote kit, abused as "poppers"
• Nitroglycerin: an old friend
• Nitric oxide: this is NOT nitrOUS oxide = laughing gas; nitric oxide is used mostly in the ICU setting for patients with severe pulmonary hypertension and ARDS in the setting of right ventricular failure
• Phenacetin: used to be a component of Vicks, used to be sold in pill form as an anti-pyretic, US FDA ordered the drug to be removed from all substances in 1983 due to carcinogenic and kidney damaging properties
• Phenazopyridine: aka Pyridium - a urinary tract analgesic
• Primaquine: a drug used to treat PCP pneumonia and malaria
• Sulfonamides: most medications with contain 'sulfa'

OK.  So that is a long list.  What are some examples of typical clinical scenarios where I might encounter a patient with acute/acquired methemoglobinemia?

Here are a few clinical examples: 

1. You are dispatched to a local urgent care center where a patient has developed acute onset respiratory distress.  The patient presented to the urgent care center 30 minutes ago with complaints of a sore throat and fever.  The patient did not have any respiratory distress.  The doctor discovered an abscess on the right tonsil.  He arranged for the patient to be transported by private ambulance to the University Medical Center for drainage of the abscess by an ENT physician.  Up to this point, the patient was not having any respiratory distress whatsoever.  In the meantime, in an effort to make the patient feel better, he sprayed the back of the oropharynx with Hurricaine Spray.  Within a few minutes the patient developed generalized cyanosis, respiratory distress, and decreased LOC.

2. The mother of a 27-year-old HIV positive patient calls 911 after she finds her son unconscious on the couch in his downstairs apartment.  He was recently started on all of his HIV medications 4 weeks ago after being discharged from a local hospital where he was treated for pneumonia.  He has been on Truvada, Kaletra, zidovudine, dapsone, and azithromycin for only the past 4 weeks.  His skin is cool, he appears pale with some bluish discoloration about his lips and fingers, and he is minimally responsive.  Room air Spo2 is 86%.  SpMet is 14%.  SpCO is 21%.  Upon starting an IV, the paramedic comments that the blood has a 'chocolate' appearance.  Even after the 100% NRB face mask was on the patient's face for 10 minutes, the Spo2 still read 86%.  An engine crew is called to evaluate the elevated SpCO reading and gets no CO readings on their meter.  The mother who lives in the home has no symptoms.

A few caveats about SpMet on the LP15 monitor:

SpMet levels > 20% are associated with clinical symptoms.  However, the SpMet measurement range on the LP15 Masimor Rainbow sensor is only 0-15%.  It is normal to have an SpMet reading of 1-2%.  Anything above 3% with the right clinical scenario, drug exposure, or toxic exposure is abnormal and should heighten your suspicion for methemoglobinemia.  Very sick patients can have as high as 40-70% Met-Hb in their blood - but again - the SpMet probe will only read up to 15%.

Elevated SpMet levels can give you a FALSE HIGH SpCO level.  The LP15 SpCO measurement range is 0-40%.  A CO meter can be used to verify absence of detectable atmospheric CO readings.  Again, you need to use common sense here and look at your environment and the clinical situation.  A patient at an urgent care center in a confined space small examination room surrounded by multiple asymptomatic care givers who is turning blue and did not have respiratory complaints a few minutes ago probably has methemoglobinemia and not CO toxicity.

Elevated SpMet levels can give you FALSE LOW SpO2 level.  It is very common for the SpO2 to sit in the mid 80% range and not change with O2 administration.  The bottom line - give all of these patient's high flow oxygen.

Is there anything we can do to treat suspected methemoglobinemia in the field?

ABCs.  High flow O2 +/- intubation.  IV.  ECG.  SpO2.  SpMet.  FS.  Good history.  Get med list. Consult.  Communicate your suspicion during consultation.  Rapid transport to the ED.
Think about at risk patients and the more common offending drugs: HIV, travel to areas with malaria, industrial chemicals, dapsone, sulfa drugs.
It is important to try to identifying and remove the patient from the offending agent (this is where your history and observation of the scene will be important).
Try to get an updated and accurate list of medications (including over the counter meds) as this will often contain the offending agent.
Rapid transport to the ED (for definitive treatment with administration of methylene blue 1-2 mg/kg IV).

Am I ever going to see this?

In an article from JAMA (April 2013) the overall prevalence of methemoglobinenmia during or after hospital procedures was only 0.035%.  The medical literature is dotted with case reports of methemoglobinemia in every age group with every type of exposure I listed above.  Masimo has the following bold statement on its website:

"Acquired Methemoglobinemia is fairly common and causes morbidity and mortality in both the inpatient and outpatient settings. Acquired methemoglobinemia is often unrecognized and thus untreated."

Dr. Rachel Ash-Bernal
and other researchers at Johns Hopkins Hospital

Acquired methemoglobinemia is probably not as common as Masimo would like you to think it is.  The statement is correct, however, in that you have to have your feelers up for this condition when you respond to a doctor's office, outpatient surgery center, or any health care facility as it is more likely to occur in these settings.