To help you differentiate between life-threatening tissue hypoxia and "pseudo-shocks" in the ED, use this clinical checklist. This helps separate true Type A (oxygen delivery) failure from Type B (metabolic) distractions.

The ED Hyperlactatemia Checklist

Step 1: Rule Out "Pseudo-Lactatemia"

[ ] The "Lactate Gap": Is there a discrepancy between the Point-of-Care (POC) and the lab?
- Suspicion: Ethylene glycol toxicity (glycolate is misread as lactate by some POC analyzers).
[ ] Sampling Error: Was the tourniquet on for $>2$ minutes or did the patient clench their fist repeatedly?
- Action: Repeat with a "straight stick" or arterial draw if the clinical picture doesn't match the number.

Step 2: Screen for Type A (Hypoxia/Ischemia)

[ ] Macro-Shock: Is the MAP $<65$ , or is there evidence of poor peripheral perfusion (mottling, CRT $>3$ sec)?
[ ] Occult Regional Ischemia: * [ ] Mesenteric: Is there "pain out of proportion" or a history of AFib/vascular disease?
- [ ] Compartment Syndrome: Any tense, painful limbs?
[ ] Oxygen Delivery Failure:
- [ ] Anaemia: Is the Hb $<7.0$ (or higher in CAD)?
- [ ] Hypoxemia: Is the $SaO_2$ significantly low?
- [ ] CO/Cyanide: Any history of house fires or industrial exposure?

Step 3: Screen for Type B (Metabolic/Drug-Induced)

[ ] The $\beta_2$ Surge: Has the patient received nebulized Salbutamol/Albuterol or is on an Epinephrine drip?
[ ] Liver Failure: Is the liver unable to clear the baseline lactate? (Check LFTs/INR).
[ ] Thiamine Deficiency: Is the patient at risk (alcohol use, malnutrition, hyperemesis
Action: Give 500mg IV Thiamine early.
[ ] Drug History: Has the patient taken Metformin (MALA), Linezolid, or NRTI antiretrovirals, or a paracetamol overdose?
Action: Supportive Care +/- NAC
[ ] Seizure: Did the patient have a generalized tonic-clonic seizure in the last 1–2 hours? (Expect rapid clearance).

Step 4: Assess Kinetics (The "Clearance" Test)

[ ] Serial Check: Repeat lactate in 2 hours.
- Failure to clear ( $<10\%$ drop): Signals ongoing "unpaid" oxygen debt or inadequate resuscitation.
- Rising lactate despite "normal" BP: Suggests worsening occult shock; consider early vasopressors or inotropes.

--------------------------------------------------------------------------------

Clinical and Diagnostic Management of Hyperlactatemia in the Emergency Department

Foundations of Lactate Physiology and the Evolution of Metabolic Interpretation

The clinical utilization of serum lactate in the emergency department has undergone a profound transformation, moving beyond its historical categorization as a simple byproduct of anaerobic metabolism to a critical marker of energetic flux, cellular signaling, and systemic stress.[1, 2, 3] In a physiological steady state, human metabolism maintains blood lactate concentrations between

0.5

and

1.5 mmol/L

.[4, 5] This concentration represents a dynamic equilibrium between continuous production—primarily by the skin, red blood cells, brain tissue, and skeletal muscles—and robust clearance mechanisms.[1, 4, 6] The average adult turnover rate of approximately

15

25 milliequivalents per kilogram per day

underscores the scale of this metabolic pathway.[5, 6]

The clearance of lactate is predominantly an aerobic process facilitated by the liver and kidneys. The liver is responsible for approximately

70%

75%

of circulating lactate removal, primarily through the periportal hepatocytes where it serves as a substrate for gluconeogenesis (the Cori cycle) or oxidation.[1, 2, 4] The kidneys contribute significantly as well, accounting for

20%

25%

of clearance through both direct excretion and metabolic utilization.[1, 2, 4] This sophisticated balance ensures that even during moderate physical activity, lactate levels remain stable. However, when the rate of production exceeds the capacity for clearance—whether through increased metabolic demand, impaired organ function, or mitochondrial dysfunction—hyperlactatemia ensues, potentially progressing to life-threatening lactic acidosis.[4, 6, 7]

Lactate's role is no longer viewed as purely deleterious. It is now recognized as a vital mobile fuel and signaling molecule. During periods of severe metabolic stress, the heart can derive up to

60%

of its energy from lactate, and the brain may utilize it for up to

25%

of its metabolic requirements.[1] Furthermore, emerging evidence suggests lactate functions in wound healing and immune modulation, potentially acting as a chemoattractant for immune cells at sites of tissue damage.[8] This dual nature—both a marker of distress and a component of the adaptive response—requires clinicians to interpret lactate levels with high degrees of nuance rather than viewing them through a binary lens of "good" or "bad".[3, 9]

Normal Physiological Values and Laboratory Thresholds	Value / Definition	Source
Normal Reference Range	$0.5 - 1.5 mmol/L$	[4, 5]
Definition of Hyperlactatemia	Serum Lactate $> 2.0 mmol/L$	[1, 6, 10]
Lactic Acidosis (Standard Definition)	Lactate $> 5.0 mmol/L$ and $p H < 7.35$	[4, 11, 12]
Severe Hyperlactatemia	$\geq 10.0 mmol/L$	[10, 13]
Basal Daily Production Rate	$15 - 20 mmol/kg/day$	[1, 5, 6]
Optimal ED Prognostic Cutoff (Relative Hyperlactatemia)	$1.33 mmol/L$	[14, 15, 16]

Biochemical Mechanisms and the Intracellular Redox State

The production of lactate occurs in the cytosol and is catalysed by the enzyme lactate dehydrogenase (LDH). This reaction is the terminal step of glycolysis when the mitochondrial oxidative pathways are bypassed or overwhelmed. Pyruvate, the end product of glucose breakdown, is converted into lactate while simultaneously converting reduced nicotinamide adenine dinucleotide (NADH) back into its oxidized form (

N A D^{+}

).[6, 16] This regeneration of

N A D^{+}

is essential for glycolysis to continue in the absence of oxygen, as it provides the necessary electron acceptor for the earlier steps of the pathway.[6]

The cellular redox state, often expressed as the

N A D^{+} / N A DH

ratio, is a primary determinant of lactate production. In states of tissue hypoxia, the mitochondrial electron transport chain fails, leading to an accumulation of NADH and a shift in the LDH equilibrium toward lactate.[6, 16, 17] This shift is not merely a consequence of oxygen lack; it can also be driven by a "metabolic bottleneck" where the rate of pyruvate production via glycolysis simply outpaces the capacity of the pyruvate dehydrogenase (PDH) complex to transport it into the mitochondria.[3, 6] This phenomenon, known as aerobic glycolysis, is frequently observed in states of high catecholamine stress (such as sepsis or severe trauma), where

β_{2}

-adrenergic stimulation accelerates glycolytic flux beyond the limits of mitochondrial oxidation.[3, 18]

Lactate exists as two stereoisomers:

L

-lactate and

D

-lactate. Human metabolism is almost entirely specific for the

L

-isomer. Most clinical laboratory tests only measure

L

-lactate, meaning that

D

-lactate—often a product of bacterial fermentation—will be missed on standard panels, potentially leading to diagnostic confusion in patients with high anion gap metabolic acidosis but "normal" lactate levels.[1, 11, 19] The accumulation of lactate also has profound implications for acid-base homeostasis. Lactate is a strong anion that is virtually fully dissociated at physiological

p H

. Its accumulation reduces the strong ion difference (SID) in the blood, exerting a direct acidifying effect that typically manifests as a high anion gap metabolic acidosis.[18, 20, 21]

Classification of Lactic Acidosis: The Cohen and Woods Framework

The differential diagnosis of hyperlactatemia in the emergency department is traditionally organized using the Cohen and Woods classification, which distinguishes between hypoxic and non-hypoxic mechanisms.[6, 22, 23] This framework is essential for guiding clinical management, as the treatment for a high lactate level varies radically depending on whether the underlying cause is a lack of oxygen delivery or a biochemical derangement.[3, 22, 24]

Type A Lactic Acidosis: Impaired Tissue Oxygenation

Type A lactic acidosis is defined by lactate accumulation in the setting of clinical evidence of tissue hypoxia or hypoperfusion.[1, 6, 22] In these scenarios, the delivery of oxygen (

D O_{2}

) is insufficient to meet the cellular oxygen demand (

V O_{2}

). This forced transition to anaerobic metabolism results in a rapid buildup of lactate. Type A is the most common form encountered in the emergency department and typically represents a medical emergency.[4, 6]

The primary drivers of Type A acidosis include global hypoperfusion states such as shock (septic, cardiogenic, hypovolemic, and obstructive) and cardiac arrest.[3, 6, 22] Regional ischemia also falls into this category; localized vascular compromise in the mesenteric, limb, or cerebral territories can generate significant lactate that eventually enters the systemic circulation.[3, 6, 25] Furthermore, conditions that severely limit oxygen-carrying capacity—such as profound anaemia or carbon monoxide poisoning—or those that severely impair gas exchange can induce Type A acidosis even if cardiac output remains high.[3, 26, 27] Finally, excessive muscular activity, such as that seen in generalized tonic-clonic seizures or extreme physical exertion, creates a temporary mismatch between oxygen supply and the massive demand of contracting muscle, leading to transient but often severe hyperlactatemia.[2, 4, 5]

Type B Lactic Acidosis: Non-Hypoxic Mechanisms

Type B lactic acidosis occurs without clinical evidence of tissue hypoxia or hypoperfusion.[1, 6, 22] These elevations are driven by metabolic alterations, mitochondrial toxins, or impaired clearance. Type B is further subdivided into three clinical categories:

1. Type B1: Associated with underlying systemic diseases. This includes liver failure, which directly impairs lactate clearance; malignancies, particularly lymphomas and leukemias, which can produce lactate through the Warburg effect; and thiamine deficiency, which cripples the PDH complex.[11, 22, 23]

2. Type B2: Triggered by drugs and toxins. This is a critical category for emergency physicians and includes commonly used medications like metformin, epinephrine, albuterol, and linezolid, as well as toxic ingestions such as cyanide and toxic alcohols.[3, 6, 26, 28]

3. Type B3: Caused by inborn errors of metabolism. These rare congenital disorders, such as pyruvate dehydrogenase deficiency or mitochondrial myopathies, are typically diagnosed in the pediatric population but may present in the emergency department during acute metabolic decompensation.[11, 22, 23]

Type A Aetiologies: Shock and Regional Ischemia

The detection of hyperlactatemia in the emergency department mandates an immediate search for Type A causes, as these are most frequently associated with reversible mortality if caught early.[3, 7, 9]

The Spectre of Sepsis and Septic Shock

Sepsis remains the most frequent reason for lactate measurement in modern emergency departments.[1, 2, 29] However, the pathophysiology of lactate in sepsis is more complex than simple tissue hypoxia. While microcirculatory dysfunction certainly contributes to Type A production, sepsis also induces a massive adrenergic stress response. This catecholamine surge stimulates the

β_{2}

-receptors on skeletal muscle, activating the

N a^{+} / K^{+}

-ATPase pump and accelerating aerobic glycolysis.[3, 30] Consequently, hyperlactatemia in sepsis is often a hybrid of Type A (hypoperfusion) and Type B (stress-induced aerobic glycolysis).[3, 18]

Despite this complexity, lactate remains the premier biomarker for risk stratification in sepsis. The Surviving Sepsis Campaign (SSC) guidelines utilize a threshold of lactate

\geq 4 mmol/L

to initiate aggressive protocolized fluid resuscitation (

30 mL/kg

).[14, 16, 31] Furthermore, the definition of septic shock requires persistent hypotension needing vasopressors and a lactate

> 2 mmol/L

despite adequate fluid resuscitation.[16, 31] The presence of "cryptic shock"—normal blood pressure with elevated lactate—identifies a cohort of patients with a mortality risk nearly equal to those with overt hypotension, highlighting the danger of relying solely on vital signs.[9, 24, 31]

Haemorrhagic and Cardiogenic Shock

In trauma and acute cardiac events, lactate serves as a direct proxy for the depth of the oxygen debt. In haemorrhagic shock, initial lactate levels correlate more closely with the extent of blood loss than serial haematocrit measurements, which can be misleadingly normal in the early phases of acute bleeding.[31] For trauma patients, a lactate level of

> 4.0 mmol/L

is associated with a nearly four-fold increase in mortality compared to those with levels

< 2.5 mmol/L

.[32]

Similarly, in cardiogenic shock, whether from acute myocardial infarction or acute-on-chronic heart failure, elevated lactate reflects the failure of the pump to maintain systemic perfusion.[6, 27, 33] In the setting of acute cardiogenic pulmonary edema (ACPO), lactate clearance has been shown to be a powerful prognostic factor; a clearance of less than

14.29%

over six hours is significantly associated with increased mortality.[33]

The Diagnostic Challenge of Mesenteric Ischemia

Acute mesenteric ischemia (AMI) represents one of the most lethal and diagnostically difficult causes of Type A hyperlactatemia.[34, 35, 36] The "classic" presentation—abdominal pain disproportionate to the physical exam—is often accompanied by metabolic acidosis and elevated lactate, but these are late findings representing bowel infarction.[25, 35, 36]

Biomarker Utility in Acute Mesenteric Ischemia	Sensitivity	Specificity	Negative Likelihood Ratio	Source
Serum L-Lactate (Early)	$33% - 52%$	Low	$0.6 - 0.9$	[34, 35, 37]
Serum L-Lactate (Infarction)	$\approx 100%$	Low	$\approx 0$	[36]
D-Dimer	$89% - 96%$	$40%$	$0.12$	[34, 35]
WBC Count	$80%$	$50%$	$0.41$	[35, 36]
CT Angiography (Gold Standard)	$82.8% - 97.6%$	$91.2% - 98.2%$	N/A	[25, 36]

The clinical implication is clear: a normal lactate level cannot be used to rule out mesenteric ischemia in the early, potentially salvageable stages.[34, 36, 37] The liver's ability to clear lactate from the portal circulation may mask the systemic rise until transmural necrosis occurs.[35, 37] Therefore, if the clinical suspicion for AMI is high, the physician must proceed directly to CT angiography regardless of the lactate value.[25, 31]

Type B Aetiologies: Medical Diseases and Metabolic Bottlenecks

When hyperlactatemia occurs without overt signs of shock, the focus shifts to Type B mechanisms, where the primary problem is biochemical rather than circulatory.[3, 24]

Hepatic Failure and Clearance Saturation

The liver is the central hub for lactate metabolism. Consequently, any degree of hepatic dysfunction—whether acute liver failure or end-stage cirrhosis—profoundly affects lactate kinetics.[4, 8, 23] In cirrhosis, the combination of reduced hepatocyte mass and portosystemic shunting limits the organ's ability to extract lactate from the blood.[8] This creates a fragile state where even minor increases in production (e.g., from a localized infection or mild exercise) can result in significant hyperlactatemia.[4, 23] Furthermore, in critically ill cirrhotic patients, lactate and "unmeasured ions" are independent predictors of 28-day mortality, reflecting the failure of the body's primary metabolic buffer system.[8]

Malignancy and the Warburg Effect

The phenomenon of malignancy-associated lactic acidosis, primarily seen in high-grade lymphomas and leukemias, is a classic example of Type B1 acidosis.[11, 23, 38] Tumor cells often undergo metabolic reprogramming to favor anaerobic glycolysis even in well-oxygenated environments—the Warburg effect.[28, 38] This allows rapid synthesis of the building blocks required for cell division but leads to massive lactate production.[38] Clinically, these patients may present with stable hemodynamics but persistently high and rising lactate levels that do not respond to fluid resuscitation.[38] This "refractory" hyperlactatemia in a cancer patient should prompt a search for disease progression or "over-production" rather than occult shock.[28, 38]

Thiamine Deficiency and the PDH Blockade

Thiamine (Vitamin

B_{1}

) is an indispensable cofactor for the pyruvate dehydrogenase complex, which converts pyruvate to acetyl-CoA for entry into the Krebs cycle.[3, 11, 22] In the absence of thiamine, pyruvate cannot enter the mitochondria and is diverted to lactate via LDH.[6, 28] This condition, often termed "shoshin beriberi" when presenting as fulminant lactic acidosis and cardiovascular collapse, should be suspected in any malnourished patient, those with chronic alcohol use disorder, or patients on long-term TPN.[11, 22, 28] Empiric high-dose intravenous thiamine is both diagnostic and therapeutic in these cases.[3, 26, 39]

Drug and Toxin-Induced Hyperlactatemia (Type B2)

The emergency department is a frequent site for drug-induced hyperlactatemia, both through iatrogenic administration and toxic ingestions. These cases require a high index of suspicion, as the management involves stopping the offending agent rather than aggressive fluid loading.[3, 26, 30]

Biguanides: Metformin-Associated Lactic Acidosis (MALA)

Metformin is the most common pharmaceutical cause of severe Type B lactic acidosis.[3, 6, 26] Metformin's primary mechanism involves inhibiting mitochondrial complex I of the electron transport chain, which blocks oxidative phosphorylation and hepatic gluconeogenesis.[3, 6, 12] While MALA is rare (

< 10 cases per 100,000 patient-years

), it is highly lethal.[6, 40] It typically occurs when metformin accumulates due to acute kidney injury (AKI) or in the setting of a secondary "insult" like sepsis.[6, 12, 26] These patients present with profound acidosis (

p H

often

< 7.0

) and extremely high lactate levels, necessitating urgent renal replacement therapy to remove the drug and stabilize the blood

p H

.[6, 40, 41]

Adrenergic Stimulants: Epinephrine and Albuterol

Iatrogenic hyperlactatemia is frequently caused by the administration of

β_{2}

-adrenergic agonists.[12, 28] Epinephrine and high-dose albuterol (used in status asthmaticus) stimulate muscle glycolysis, leading to a rise in lactate that is often "benign"—meaning it does not represent tissue hypoxia.[3, 18, 30] In a classic clinical scenario, a patient with anaphylaxis treated with an epinephrine infusion may develop a rising lactate despite stabilizing hemodynamics; recognizing this as a metabolic effect of the drug prevents unnecessary and potentially harmful diagnostic workups.[3, 12, 30]

Mitochondrial Toxins: Cyanide and Carbon Monoxide

Cyanide and carbon monoxide are classic mitochondrial poisons often encountered in smoke inhalation or industrial accidents.[3, 20, 26] Cyanide binds to cytochrome c oxidase (complex IV), completely halting the mitochondrial use of oxygen.[3, 40] In these patients, the lactate level is a direct marker of the severity of the poisoning; a lactate level

> 10 mmol/L

in a smoke inhalation victim is highly suggestive of cyanide toxicity and mandates immediate antidote administration (e.g., hydroxocobalamin).[3, 40]

Drug/Toxin	Mechanism of Lactate Elevation	ED Pearl	Source
Metformin	Complex I Inhibition	Suspect in AKI; needs dialysis	[3, 6, 40]
Epinephrine	$β_{2}$ -stimulation; Aerobic glycolysis	Benign if vitals are stable	[3, 18, 30]
Cyanide	Complex IV Inhibition	Lactate $> 10$ in smoke = Cyanide	[3, 40]
Linezolid	Mitophagy / Protein Synthesis Inhibition	Occurs with long-term use	[12, 26, 40]
NRTIs (e.g., AZT)	Mitochondrial DNA Polymerase Inhibition	Chronic HIV therapy complication	[12, 26, 40]
Propofol	Impairment of Fatty Acid Oxidation	"PRIS"; monitor in ICU infusions	[3, 6, 26]
Acetaminophen	Mitochondrial Damage (Acute Overdose)	Early acidosis before ALT rise	[40, 42]

Isomeric and Metabolic Mimics: D-Lactate and 5-Oxoproline

Perhaps the most challenging cases in the emergency department are those with high anion gap metabolic acidosis (HAGMA) where the standard

L

-lactate is normal. This suggests the presence of an "unmeasured" anion, which may be a lactate isomer or a different organic acid entirely.[19, 42, 43]

D-Lactic Acidosis: The Enigmatic Isomer

D

-lactic acidosis, or

D

-lactic encephalopathy, is a rare but critical syndrome seen in patients with short bowel syndrome (SBS), gastric bypass, or intestinal malabsorption.[6, 44, 45] When simple carbohydrates reach the colon, specific bacteria (e.g., Lactobacillus) ferment them into

D

-lactate, which is then absorbed into the systemic circulation.[19, 39, 44]

The clinical hallmark is the "drunk-like" state: ataxia, slurred speech, and confusion that worsens after a high-carbohydrate meal.[39, 45] Because

D

-lactate is not recognized by human LDH, it cannot be cleared effectively, and standard lab tests will return a "normal" lactate value.[19, 43, 45] Clinicians must specifically order a

D

-lactate assay when HAGMA and neurological symptoms occur in a patient with gut pathology.[19, 39]

5-Oxoproline (Pyroglutamic Acid)

5-oxoproline is an organic acid that accumulates when the

γ

-glutamyl cycle (responsible for glutathione production) is disrupted.[42, 46, 47] This occurs primarily in malnourished patients, chronic alcohol users, or pregnant women who take regular, "therapeutic" doses of acetaminophen.[42, 46, 48] The depletion of glutathione causes a buildup of 5-oxoproline, resulting in a severe HAGMA.[42, 47]

This diagnosis is often missed because acetaminophen levels in these patients are usually low or undetectable.[42, 47] Suspicion should be high in an elderly, malnourished woman with an unexplained HAGMA.[46, 48] Treatment involves stopping acetaminophen and administering N-acetylcysteine (NAC) to replenish glutathione levels.[42, 46, 47]

Diagnostic Approach in the Emergency Department

The systematic evaluation of elevated lactate in the emergency department requires integrating physiological principles with practical triage and laboratory tools.

Sampling Considerations: Venous vs. Arterial

While arterial blood gas (ABG) analysis is often considered the gold standard for metabolic evaluation, peripheral venous lactate is acceptable for initial screening.[1, 4, 49] However, several caveats apply:

• Correlation: Venous and arterial values correlate well when lactate is within the normal range, but discrepancies arise at higher levels.[1, 2, 5]

• Local Milieu: Venous lactate reflects the metabolism of the limb it was drawn from, whereas arterial or central venous samples represent systemically circulated levels.[1, 2]

• Technique: Prolonged tourniquet use or vigorous fist-clenching during the draw can falsely elevate the venous lactate.[2, 4]

The Role of Triage and Automated Ordering

Early identification of high-risk patients is facilitated by automated triage protocols. The Rapid Emergency Triage and Treatment System (RETTS) and similar protocols integrate vital signs with early point-of-care (POC) lactate testing.[50, 51] Implementation of computerized lactate orders for any patient with suspected infection or SIRS criteria has been shown to reduce the time to treatment room placement and the time to clinical intervention.[50, 51]

Acid-Base Analysis: Anion Gap and Delta Gap

For a clinician presented with hyperlactatemia, the acid-base profile provides clues to the aetiology. Lactic acidosis typically presents as a high anion gap metabolic acidosis (HAGMA). The anion gap must be corrected for hypoalbuminemia, as a low albumin can "mask" the severity of the anion gap.[6, 20, 21]

Anion Gap (AG) = [N a^{+}] - ([C l^{-}] + [H C O_{3}^{-}])

Corrected AG = Measured AG + 2.5 \times (4.0 - Albumin)

An anion gap

> 25 mEq/L

is highly specific for lactic acidosis, ketoacidosis, or toxic ingestions.[21] Furthermore, calculating the "Delta Gap" (

Δ A G /Δ H C O_{3}^{-}

) can identify mixed acid-base disorders, such as a concomitant non-anion gap metabolic acidosis (NAGMA) or metabolic alkalosis.[20, 21]

Point-of-Care Ultrasound (POCUS) as a Bedside Extension

POCUS has transformed the initial management of hyperlactatemia by allowing real-time hemodynamic assessment, helping the physician differentiate between shock types and identify occult sources of infection or ischemia.[41, 52, 53]

Hemodynamic Profiles in the Hyperlactatemic Patient

Using standardized protocols like the RUSH exam (Rapid Ultrasound for Shock and Hypotension), clinicians can categorize the cause of lactate elevation:

• Pump (Cardiac): Poor LV contractility or right heart strain suggests cardiogenic or obstructive shock.[41, 52, 53]

• Tank (Volume): A collapsible inferior vena cava (

I V C > 50%

) or "LV kissing" indicates a need for fluids (hypovolemia).[52, 54]

• Pipes (Vessels): Checking for an abdominal aortic aneurysm (AAA) or pleural effusions can identify sources of haemorrhage.[52, 53]

In non-hypotensive sepsis patients, POCUS parameters such as a low left ventricular end-diastolic diameter (

L V E DD < 25 mm

) have a high sensitivity for predicting an elevated lactate

\geq 4 mmol/L

, serving as an "early warning" system for occult hypoperfusion.[54]

Prognosis and Resuscitation Targets

Serum lactate is perhaps the most validated prognostic marker in acute care. The severity of hyperlactatemia at presentation and its kinetics during treatment provide essential data on the likelihood of survival.[7, 10, 31]

Severe Hyperlactatemia (

\geq 10 mmol/L

)

Patients presenting with severe hyperlactatemia have an extremely high mortality rate, ranging from

65%

92%

depending on the population.[10, 24] However, the aetiology matters immensely:

• High-Risk Aetiologies: Trauma, non-septic shock, and neurological disasters carry the worst prognosis (

50% - 60%

mortality).[10, 13]

• Low-Risk Aetiologies: Seizures or fainting can produce a lactate

> 10 mmol/L

with a

0%

mortality rate, as the elevation is purely exertional and transient.[10, 13]

The Utility of Lactate Clearance

Monitoring the "trend" of lactate—lactate clearance—is more valuable than any single measurement.[6, 7, 24] Clearance of lactate within 24 hours is a hallmark of successful resuscitation.[9, 31]

Clinical Condition	Clearance Target / Prognostic Meaning	Source
Sepsis / Septic Shock	$\geq 10%$ clearance in first 6 hours is as good as $S c v O_{2}$	[24, 31]
Trauma	Normalization within 24h = $100%$ survival	[31]
Trauma	Persistent elevation $> 48 h = 13.6%$ survival	[31]
Cardiac Arrest (Post-ROSC)	Clearance is a strong predictor of survival	[24, 31]
ACPO	Clearance $< 14.29%$ at 6h = high mortality	[33]

Conclusion: The Integrated Approach to the Hyperlactatemic Patient

The approach to elevated lactate in the emergency department must be systematic, moving from the most life-threatening to the more subtle biochemical causes.

1. Immediate Stabilization: If the lactate is elevated, first assume Type A. Assess for shock and hypoperfusion using vital signs and POCUS. If shock is present, initiate protocolized resuscitation (fluids, vasopressors) while searching for the source (sepsis, haemorrhage, cardiac).[3, 41, 49]

2. Evaluate for Regional Ischemia: If the patient is stable but has abdominal pain, consider mesenteric ischemia. proceed to CTA; do not wait for the lactate to rise further.[25, 34]

3. Screen for Toxins and Medications: Review the drug list for metformin,

β

-agonists, and linezolid. In smoke inhalation, treat empirically for cyanide if lactate is

> 10

.[3, 26, 28]

4. Identify Metabolic Mimics: If the patient has a history of gut surgery and HAGMA, test for

D

-lactate. If the patient is malnourished and uses acetaminophen, consider 5-oxoproline and treat with NAC.[19, 42, 45]

5. Monitor Kinetics: Always repeat the lactate. Failure to clear lactate by

\geq 10%

within a few hours of treatment should trigger a complete reassessment for unrecognized sources of ischemia or a failure of the current resuscitation strategy.[3, 24, 31]

Lactate is not a diagnosis but a signal. In the fast-paced environment of the emergency department, correctly interpreting this signal is the difference between identifying a critical illness in its earliest, most treatable phase and a catastrophic diagnostic delay.[3, 9]

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