lactate: how sick is your patient

Litteton/Porter/Parker EMS Wayne Guerra, MD, MBA

Lactate: How Sick Is Your Patient?

Littleton/Porter/Parker EMS

Wayne Guerra, MD, MBA


Objectives

• What is lactate?

• Pathophysiology

• Why should I care?

• Sepsis

• Sepsis EMS Pilot Study

Case

73 yo female, family calls because of weakness.

She has no complaints except for nausea and vomiting x2

Meds: Remicaide, Lisinipril, Motirin, Vicodin

PMH: RA, Htn,


Case contd.

105/60, 95, 22, 100.6

Lungs: CTA

Ht: RRR

Abd: soft NT

Neuro: nonfocal


Case contd./ED Course

WBC: 12 with 75 Neut, 5 Bands

7: wnl

UA: 20-30 WBC, 1+ bact

CXR: wnl



Treatment:

Tylenol

NS 250 cc/hr

Levoquin 500mg IV

Admit to Medicine



Bed becomes available after 4 hours in ED

Vitals before going upstairs:

82/40, 90, 20, 99.2


Case contd./ED Hosp Course

Second IV placed

1 liter NS bolus

SBP remains in 80s

Lactate: 5.5

Patient admitted to ICU

Dies after 4 days with ARDS and ARF



History

• 1789: Carl Whilhelm Sheele identified lactic acid in sour milk

• 1833: chemical structure identified


History

• 1922: Otto Meyerhoff and Archibald V. Hill win Nobel prize for energy capabilities of carbohydrate metabolism

• Accepted that lactate production caused acidosis


History

• Late 1950s: Huckabee established:

Hypoperfusion → Lactic Acidosis

• 1976: Cohen and Woods:

↓ Tissue Oxygenation → Lactic acidosis


Is Lactate Bad?

• Correlation versus causation

• Heart rate and septic shock


Energy (ATP) Production

• Aerobic

• Anaerobic

• Creatine Phosphate (CP-ATP)

CP + ADP → C + ATP


Aerobic ATP Production

• Most complicated

• Can utilize many types of fuel

• Most efficient

• Slowest process

• Occurs within the mitochondria– Pyruvate + NAD → CO2 + H2O + NADH

CoA acetyl-CoA

Krebs Cycle then produces ATP


Anaerobic ATP Production

• Very fast

• Uses locally available glycogen (glucose)

• Also called “Glycolysis”

• Forced pathway with hpoperfusion


Lactate Production: Glycolysis

2 H+

Glycolysis

2 H+

Glycolysis


Lactate Production: Glycolysis

• Body’s response is the Cori cycle


Lactate Clearance: Cori Cycle

2 H+

2 H+

End Result:*Net loss 4 ATP*If unable to compensate ↑ lactate and acidosis (↑ H+)


Anaerobic Metabolism(Tissue Hypoxia)

• Increased production of lactate and H+

• Decreased utilization of lactate and H+

• End Result– Increased Lactate– Acidosis


Lactate Truths and Myths

• Does not cause muscle burning or fatigue

• Does not cause acidosis

• Important source of fuel for glucose production in the liver

• Good indirect measure of tissue hypoperfusion


Definitions

• Normal lactate: – Unstressed: 1-0.5 mmol/L– Stressed: < 2 mmol/L

• Hyperlactatemia: 2-5 mmol/L

• Lactic acidosis: usually > 5 mmol/L with associated metabolic acidosis


Hyperlactatemia

• Normal perfusion

• Normal tissue oxygenation

• Transient hypoperfusion


Lactic Acidosis

• Type A

– Tissue hypoxia• Tissue hypoperfusion• Reduced arterial oxygen content


Lactic Acidosis

• Type B

– Not due to tissue hypoxia• Type B1: (common disorders) hepatic

failure, DM, cancer, renal failure• Type B2: (drugs and toxins) biguanides,

alcohols, iron, isoniazid, salicylates• Type B3: is due to inborn errors of

metabolismhttp://emedicine.medscape.com/article/768159-overview


Most Common Diseases

• Shock– Hemorrhagic– Septic– Cardiogenic

• Respiratory failure

• AKA

• Anemia


Most Common Diseases

• Toxins

• Glucose-6-Phospahte deficiency

• Inborn errors of metabolism


Treatment of Lactic Acidosis

• Correct Tissue Hypoxia– Increase perfusion– Increase oxygenation



• Increase Perfusion– Aggressive fluid replacement– Isotonic saline preferred– Avoid lactate containing solutions– Avoid vasoconstrictors– Treat underlying cause



• Increase Oxygenation– High flow O2– CPAP– Intubation



• NaHCO3– Can cause increase lactate and H+– Reserved for severe metabolic acidosis

(<7.15)

NaHCo3 req =

(Bicarb desired – Bicarb observed) x .4 x BW(kg)



• Experimental Therapies– Carbicarb

• ½ NaHCO3 (sodium bicarbonate) • ½ Na2CO3 (sodium carbonate)• Animal studies only• Caused decreased lactate and improved pH


Why

• Pre-hospital vital signs ≠ hypoperfusion

• Pain and Anxiety → Epinephrine release

• Occult hypoperfusion, compensated shock, cryptic sepsis


Why

• Identify occult hypoperfusion earlier

• Initiate fluid resuscitation earlier

• Increased urgency


Golden Hour

• Dr Adams Crowley– Maryland Shock Trauma– First statewide EMS– First civilian use of medical helicopters

• Critics: Dr. Bryan Bledsoe

• Trauma, Stroke, MI, Sepsis


Why

• Hypotension → Increased M & M

• Identify early

• Initiate treatment and urgency

• Prevent hypotension

The significance of non-sustained hypotension in emergency department patients with sepsis

http://icmjournal.esicm.org/journals/abstract.html?v=0&j=134&i=0&a=1448_10.1007_s00134-009-1448-x&doi=


Can Lactate Level Measurement in the Pre-Hospital Setting

Identify Occult Hypoperfusion?


Pre-Hospital Lactate and Mortality

Critical Care 2008, 12:R160


The prognostic value of blood lactate levels relative to that of vital signs in the pre-hospital

setting: a pilot study

Critical Care 2008, 12:R160: http://ccforum.com/content/12/6/R160


Netherlands StudyConclusions

• Lactate level > 3.5 mmol/L identifies a high risk group with mortality of 41% (26% for <3.5)

• Lactate level < 3.5 mmol/L had a NPV of 88% for mortality



• Improvement in lactate levels in the EMS setting correlates with ↓ mortality– Hazard of death decreased 80% for every

63% decrease in lactate level in the pre-hospital setting



• Lactate > 5 mmol/L & pH < 7.35– 75% Mortality

• Lactic acidosis and shock– Median survival 28 hours– Only 17 % discharged from hospital


Why

• Vital signs cannot always predict hypoperfusion– In the hospital

– In the EMS setting


Future

• Can the Netherlands results be duplicated?– Gunnerson, Richmond Virginia

• What EMS Treatments → ↓ Lactate

• Sepsis EMS Pilot Study

Sepsis


Suit against Memorial Hermann claims negligence caused man's sepsis, death

Mariana Bridi da Costa


Sepsis can strike, kill shockingly fast


Sepsis EMS Pilot Study

• Sepsis– Estimated 215,000 deaths per year– Up to 40-50% mortality– 750,000 illnesses

• AMI (2005 CDC Death Rates)– 151,004 deaths


What Can We Do?

• Early assessment/recognition

• Early Goal Directed Therapy – Reduces mortality up to 50%

• Begins in the field with 911 response


Pathophysiology

Bacterial Infection

• Chemotaxis - – Secretes chemical signals – causes reactions

• Capillary vasodilatation • Increased vascular permeability• Leukocytes (White Blood Cells) combat infection

• Edema– Pain, redness and swelling


Pathophysiology

• Systemic infection– Can not maintain perfusion

• Release of pro-inflammatory cytokines– Powerful vasodilators

• Release of anti-inflammatory mediators– Inhibit production of

inflammatory components.


PathophysiologyRespiratory System

• Acute Respiratory Distress Syndrome (ARDS)– 40% Mortality Rate

• Surfactant – Maintains alveolar

tension– Decreases in sepsis

ARDS



SIRS

• Systemic Inflammatory Response Syndrome

• Causes:– Trauma

– Severe Burns

– Pancreatitis

– Ischemia

– Infection

Infection MODS


SIRS – Signs and SymptomsTwo or More• Temperature:

– >38 C (100.4 F) or <36 C (96.8 F)

• Heart Rate:– >90 beats/min (Outside Factors?)

• Respiratory Rate– >20 breaths/min (Mechanically Ventilated)

• White Blood Cell (Leukocyte) Count– >12,000 or <4,000 or >10% immature

Infection MODS


Sepsis

• SIRS with documented or suspected infection.– Bacterial– Viral– Fungal– Protozoa

Infection MODS


Sepsis – High Risk FactorsHigher Risk• Extremes of Age• Multiple co

morbidities• Recent

hospitalization– 2 million hospital

acquired infections per year.

• Cough Present• Indwelling Foley/IV• Wounds/Injuries• Para/Quadriplegic• Bedridden• Recent Antibiotic

Use

Infection MODS


Sepsis

• Common Causes?– Pneumonia– Urinary Tract Infections– Abdominal Surgery– Cellulitis– IV Drug Users

Infection MODS


Sepsis – High Risk Factors

• Immune Compromised– Diabetic– Cancer - chemotherapy– HIV– Systemic steroids– Anti-rejection medications

• Imuran, Cellcept, Neoral (cyclosporine), Myfortic

– Powerful anti-inflammatory medications• Humira, Enbrel, Remicade

Infection MODS


Septic Shock• Septic shock = sepsis + hypotension• Classic Distributive Shock Example

ALSO • Cardiac Function Compromised (Cardiogenic

Shock)• Massive Fluid Shift (Hypovolemic Shock)

Infection MODS


MODS • Multiple Organ Dysfunction

Syndrome– Damage or dysfunction to

more than one organ– Mortality 20 to 100%– Most frequent target = lungs

• Cell permeability• ARDS

– Renal failure– Heart failure


Sepsis AlertPilot Study

• Can septic patients be identified in the pre-hospital setting?– Does initiation of pre-hospital EGDT change

morbidity and mortality?– Does Sepsis Alert change ED treatment?– Does Sepsis Alert change ED/Hospital

morbidity and mortality?


Sepsis Alert (SIRS Criteria)

• > 18 years old• Not PregnantTwo or More:

• Temperature: >38 C(100.4° F) or <36 C (96.8° F)• Heart Rate: >90 beats/min • Respiratory Rate >20 breaths/minAnd:• Documented/Known/Suspected InfectionAnd• Hypoperfusion


Hypoperfusion

• Three ways to determine:• Systolic BP less than 90

• MAP < 65

• Lactate > 4 mmol/L


Mean Arterial Pressure (MAP)

• Average pressure during cardiac cycle

• MAP = (2*DBP) + SBP3

• 60 is minimum for tissue perfusion


EMS Lactate Levels

• Pre-hospital Lactate Meters

• Developed for Endurance Athletes

• Works like a glucometer


Sepsis Alert Procedure

• Assess Patient– Apply criteria to incident– If it fits:

• Notify Hospital—no destination requirement – Not all hospitals participating– Presented at Metro physicians in 11-2008

• Administer high flow O2• 2 large bore IVs• IV fluid boluses, according to protocol


Pre-Hospital Treatment

• All septic patients require:– Oxygen therapy– Fluids

• Boluses – 500 cc initially • 20ml/kg titrated to increase in BP (5 mmHg

indicates vascular response)• Carefully assess lung sounds

– Dopamine– Check glucose, maintain above 80


Sepsis Alert – ER ResponsePorter/Littleton/Parker

• Goal is to provide EGDT if needed• Patient goes to large resuscitation room.• Hospital Staff

– Nurse/ER Doc• Ultrasound• Central Line Kit

– Lab for blood cultures– X-Ray for CXR– Respiratory Therapist for rapid lactate measurement– House Supervisor


EGDT

• If treatment goals met within 6 hours:– Mortality decreased by 30-35%– Less overall IVFs administered– Less vasopressors administered– Decreased transfusions– Decreased hospital stay of 4 days


EGDT

• Goal is < 6 hours for all treatments

• Grade 1C Recommendations:– Central line placement– IV fluid boluses until CVP = 8-12– MAP between 65-90 mm Hg– Start vasopressors after CVP > 8


EGDT

• Grade 2C Recommendation: ScvO2 ≥ 70% – Maximize oxygenation with intubation if

necessary– CVP 8-12– MAP between 65 mm Hg and 90 mm Hg– Transfuse until hematocrit ≥ 30%– Use inotropic agents to improve cardiac

output


Sepsis Alert Criteria

• 18 years and older• Not Pregnant• Two or more of the following:

• Temperature (above 100.3° or below 96.8°)• Pulse > 90• RR > 20

• Suspected or documented infection• Hypoperfusion, as indicated by

• BP < 90 • MAP < 65 any one of these• Lactate > 4

Case Revisited

73 yo female, family calls because of weakness.

She has no complaints except for nausea and vomiting x2

Meds: Remicaide, Lisinipril, Motirin, Vicodin

PMH: RA, Htn,


Case Revisited

105/60, 95, 22, 100.6

Lungs: CTA

Ht: RRR

Abd: soft NT

Neuro: nonfocal


Case Revisited

When asked directly patient admits to dysuria

SIRS Criteria Met

Infection Suspected

Lactate drawn by EMS: 4.4

Sepsis Alert Called


Case Revisited

EGDT started immediately

First CVP: 4

Patient given 2 additional liters NS

Norepinephrine started

Admitted to ICU

Patient discharged home after 5 days


lactate: how sick is your patient

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