Elevated Lactate & Lactate in Sepsis

Elevated Lactate & Lactate in Sepsis

The most worrisome cause of lactate elevation is an elevated lactate from tissue hypo-perfusion & shock, resulting in decreased oxygen delivery to the cells. However, the differential for lactate elevation is broader than simply “shock states.” 

Patients with liver disease such cirrhotics & alcoholics will have poor lactate clearance and can have an elevated lactate level due to hepatic dysfunction. Medications can also lead to a high lactate level, such as albuterol (and other sympathomimetics), metformin, alcohol, & carbon monoxide poisoning (inability to deliver oxygen to tissues). Lastly, muscle activity in heavy exercise and seizures will also result in an elevated lactate level.  

In patients with suspected sepsis, why do we get an initial lactate and repeat it in 6 hours? 

There is an established link between mortality and elevated lactate. This is also a core quality measure decided by the Center of Medicare and Medicaid Services that should be met in patients presenting in sepsis. This is based off of SEP-1, which is controversial and has more or less protocoled sepsis care. The bottom line is CMS wants this measure completed and they hold the purse strings. 

What does the 2021 Surviving Sepsis Campaign say about lactate?

“For adults suspected of having sepsis, we suggest measuring blood lactate. Weak recommendation, low-quality evidence ”

“For adults with sepsis or septic shock, we suggest guiding resuscitation to decrease serum lactate in patients with elevated lactate level, over not using serum lactate. 

During acute resuscitation, serum lactate level should be interpreted considering the clinical context and other causes of elevated lactate

Weak recommendation, low-quality evidence”

The latest surviving sepsis guidelines do recommend measuring lactate levels and guiding resuscitation to decrease serum lactate over not using serum lactate. The panel does recognize that normal serum lactate levels are not achievable in all patients with septic shock, but many studies support resuscitative strategies that decrease lactate toward normal. Serum lactate level should be interpreted within the clinical context and other causes of elevated lactate should be considered. Also, lactate alone is neither sensitive nor specific enough to rule-in or rule-out sepsis. 

In summary, remember we are concerned an elevated lactate may be due to a shock state, such as sepsis. The differential though is broader than shock/hypotension. Lactate can be useful in both diagnosing and guiding resuscitation in sepsis/septic shock, but its use is nuanced and should be interpreted in the wider clinical setting. Remember to get an initial and repeat lactate in suspected sepsis to fulfill the core quality measures set by CMS.

Sources:

Evans, L., Rhodes, A., Alhazzani, W. et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med 47, 1181–1247 (2021). https://doi.org/10.1007/s00134-021-06506-y
https://emcrit.org/pulmcrit/acep-septic-shock/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975915/
Moving Beyond the Centers for Medicare and Medicaid Services' "Severe Sepsis and Septic Shock Early Management Bundle" Core Quality Measure, Jeremy Faust, annals of emergency medicine

Pediatric Fever

Infant < 28 days: Do everything & give empiric Abx (Ceftazidime, Acyclovir (HSV) & Ampicillin) ^

CBC, BMP, Blood Cx (1 set), UA, Urine Cx, LP, RVP*

^There are new guidelines regarding patients who are between 3-4 weeks of age where LP may be deferred. There is a lot of controversy still regarding its adoption.

28 days to 2 months / 1st set of vaccines: Do everything however LP & Abx dependent on PECARN Rule for Low Risk Fever

CBC, BMP, Blood Cx (1 set), UA, Urine Cx, RVP*, Pro-Calcitonin

PECARN Rule for Low Risk Fever: LP if any of the following is positive: Pro-Cal > 0.5, ANC > 4090/micoL, Positive UA (due to seeding of CNS). PECARN Rule for Low Risk Fever was done in full term infants without chronic medical problems, no prolonged NICU stay - use discretion in patients with multiple risk factors.

If performing LP, the patient will need abx (Ceftriaxone 100mg/kg) coverage pending CSF studies.

2 months - 4 months / 2nd set of vaccines: Partial Sepsis. No LP unless clinical signs of meningitis due to blood brain barrier

CBC, BMP, Blood Cx (1 set), UA, Urine Cx, RVP*.

Can consider one dose of IV ceftriaxone (75mg/kg) if WBC > 15k, WBC < 5k, or Band to Neutrophil Ratio greater than 0.2. The evidence is not very robust and practice varies.

4 months - 6 months / 3rd set of vaccines: Urine

UA, Urine Cx, RVP*

6 months - 12 months: Urine collection requirement varies

• Females: UA, Ucx, RVP*

• Circumcised males- No urine, RVP*

• Uncircumcised males- Urine if fever > 48 hrs , RVP*

1- 2 years of age: Urine collection in females

• Female: UA, UCx, RVP*

• Males: No urine, RVP*

*RVP can be useful for finding a source of fever (calming parent anxiety, limiting atypical Kawasaki workup etc...). However, remember patients can have more than one concomitant source of illness and a positive RVP should not prevent one from finishing the appropriate workup in each age group.

Mountain Sickness

Mountain sickness

Background: At higher altitudes, there is less oxygen. For example, at 10,000 feet, the air is 14% oxygen while at sea level in NYC, we are breathing in 21% oxygen. Mountain sickness is the manifestation of the body’s response to hypoxia. 

Clinical features: 

Usually only occurs in altitudes greater than 8000 ft unless patients are particularly susceptible to hypoxia (COPD, anemia). This is also why when flying, airplane cabins are usually pressurized to 7-8000 ft. Patients who have experienced altitude sickness are more likely to have repeat episodes when returned to the same altitude. A quicker rate of ascent is also more likely to lead to mountain sickness. Most often presents the 1st night or 2nd night at higher elevations. The average duration of symptoms in cases that self resolve is one day (the body successfully acclimates). 

Clinical criteria (most are CNS symptoms since the brain is most sensitive to hypoxia): An individual above 8000 feet presents with headache and one of the following

- GI symptoms

- Sleep disturbance

- Dizziness/lightheadedness 

The feared complications of mountain sickness are High Altitude Cerebral Edema (HACE) & High Altitude Pulmonary Edema (HAPE). 

Treatment & Prevention:

In mild mountain sickness, the patient can descend to a lower altitude (1000-3000 ft lower) or stop the ascent and acclimate for 12-36 hours. Acetazolamide (125-250 mg BID) can be used to speed up acclimation by increasing respiratory rate from the resultant metabolic acidosis. For patients who have moderate to severe mountain sickness, immediate descent 1000-3000 feet is indicated. Low flow oxygen, especially at night, can be helpful. Hyperbaric oxygen therapy can be considered. Lastly, besides acetazolamide, dexamethasone 4 mg q6 can be considered.

The best preventative measure is gradual ascent. Acetazolamide prophylaxis indicated in those who have previously experienced acute mountain sickness or anticipate a rapid ascent to altitude. Start 24 hours before ascent and continue until 48 hours after reaching final altitude. Dexamethasone can be started the day of ascent and likewise continued until the first two days at altitude. Ibuprofen also helps. 

HACE

Severe and uncommon form of acute mountain sickness. Basically, it is a progression of acute mountain sickness resulting in AMS & ataxia from cerebral edema due to hypoxia. Treatment is immediate descent, supplemental O2, dexamethasone, & acetazolamide. Other treatments for increased ICP (mannitol etc…) are of undetermined benefit.

HAPE

Hypoxic pulmonary vasoconstriction led to pulmonary hypertension and eventual pulmonary edema due to elevated pulmonary artery pressures. Patients can have bilateral opacities on CxR and a better clinical appearance than their O2 saturations suggest. Immediate descent, minimizing exertion, supplemental O2, expiratory positive airway pressure mask (forces some PEEP in a non-intubated patient), nifedipine, & sildenafil (promotes pulmonary artery vasodilation) are possible treatment options.  

https://www.ncbi.nlm.nih.gov/books/NBK430716/

https://wikem.org/wiki/High_altitude_pulmonary_edema

https://wikem.org/wiki/Acute_mountain_sickness

Imray C, Wright A, Subudhi A, Roach R. Acute mountain sickness: pathophysiology, prevention, and treatment. Prog Cardiovasc Dis. 2010 May-Jun;52(6):467-84. doi: 10.1016/j.pcad.2010.02.003. PMID: 20417340