Lactic Acidosis from Medications: A Rare but Dangerous Complication

Most people think of medications as safe when taken as prescribed. But some drugs, even common ones, can trigger a silent, life-threatening condition called lactic acidosis. It doesn’t come with a warning sign like a rash or nausea. Instead, it creeps in with fatigue, rapid breathing, and confusion-symptoms easily mistaken for something else. By the time it’s recognized, it’s often too late. This isn’t a theory. It’s a documented danger tied to real drugs people take every day.

What Exactly Is Lactic Acidosis?

Lactic acidosis happens when your blood becomes too acidic because lactate-a natural byproduct of energy production-builds up faster than your body can clear it. Normal lactate levels are between 0.5 and 2.2 mmol/L. When they climb above 4-5 mmol/L and your blood pH drops below 7.35, you’re in danger. This isn’t just a lab number. Severe acidosis weakens your heart, lowers your blood pressure, and makes your body unable to respond to life-saving drugs like epinephrine. In critical care units, it’s one of the top predictors of death.

There are two main types. Type A comes from poor oxygen delivery-like in a heart attack or severe infection. Type B is different. It happens even when your tissues have enough oxygen. That’s where medications come in. They mess with your mitochondria, the power plants inside your cells, forcing them to produce energy the inefficient, lactate-heavy way.

Medications That Can Trigger It

You might be surprised to learn that some of the most commonly prescribed drugs carry this risk. Here’s what actually causes it:

• Metformin: The go-to drug for type 2 diabetes. Used by over 150 million people worldwide. While the risk is low-about 3 to 10 cases per 100,000 patient-years-it’s still the most frequently reported cause. The problem isn’t the drug itself. It’s what happens when you’re dehydrated, have kidney problems, or get sick with an infection. Your body can’t clear metformin or lactate, and the two combine to trigger acidosis. Mortality in these cases hits 22%.
• Linezolid: An antibiotic used for stubborn infections like MRSA. It’s effective, but it shuts down mitochondrial protein production. After 14 days of use, the risk spikes. Studies show 2.5% to 15% of patients on long courses develop elevated lactate. Some never recover.
• Albuterol: The inhaler you use for asthma or COPD flare-ups. It’s supposed to open your airways. But it also tricks your muscles into burning sugar faster and blocks the enzyme that turns pyruvate into energy. That means excess sugar turns into lactate. One documented case saw lactate jump to 11 mmol/L after standard nebulizer treatments-then dropped to 4.5 mmol/L just by reducing the frequency.
• Propofol: The sedative used in ICUs for intubated patients. When given at high doses (over 4 mg/kg/hour) for more than 48 hours, it causes Propofol Infusion Syndrome. Lactic acidosis is one of its hallmarks. Mortality? Over 66%. That’s why guidelines now limit its use in critically ill children and adults.
• NRTIs (like zidovudine or stavudine): Used in HIV treatment. They damage mitochondrial DNA. Risk goes up if you’re female, have low CD4 counts, or poor kidney function. A 2023 study found a specific gene variant (POLG) makes some people 8 times more likely to develop this complication.
• Acetaminophen: Even at normal doses, it can cause lactic acidosis in elderly patients with liver or kidney issues. It’s often missed because the symptoms look like general illness. One case series showed diagnosis delays averaging 36 hours.
• Epinephrine: Used in emergencies like anaphylaxis or shock. It’s life-saving-but it also stimulates lactate production. In ICU settings, it’s often the culprit behind unexplained high lactate levels, especially when combined with other drugs.

Who’s Most at Risk?

This isn’t a random event. Certain people are far more vulnerable:

• People over 65
• Those with kidney disease (eGFR below 60 mL/min)
• Patients with liver cirrhosis
• Anyone with heart failure or sepsis
• Those on multiple high-risk medications at once

In fact, 72% of metformin-related lactic acidosis cases involve patients with kidney impairment. The same goes for linezolid and NRTIs. It’s not the drug alone. It’s the drug plus your body’s inability to handle it.

Why Is It So Often Missed?

Doctors don’t always connect the dots. In the ICU, patients are already sick. High lactate? Must be sepsis. Rapid breathing? Must be pneumonia. But what if the drug is the real problem?

A 2019 review of 286 cases found that in 41% of cases, the medication causing lactic acidosis was never stopped-even when lactate levels were dangerously high. Why? Because the drug was deemed necessary. Epinephrine for shock. Albuterol for breathing. Linezolid for a deadly infection. Stopping it felt riskier than continuing it.

But that’s the trap. The drug might be saving you from one threat, but it’s creating another. And when both are happening at once, the body has no chance to recover.

How Is It Diagnosed and Treated?

There’s no single test. Diagnosis requires three things:

1. Serum lactate above 4-5 mmol/L
2. Arterial pH below 7.35
3. Bicarbonate below 22 mmol/L

But some experts now say: if you’re on a high-risk drug and your lactate hits 3 mmol/L, start looking. Don’t wait for full acidosis.

Here’s what works:

• Stop the drug: Unless it’s absolutely life-saving (like epinephrine in anaphylaxis), discontinue it immediately.
• Fluids: Give 20-30 mL/kg of IV saline. This helps flush out lactate and improves circulation.
• Dialysis: For metformin cases with lactate over 20 mmol/L or pH below 7.1, hemodialysis is the fastest way to remove both metformin and lactate.
• Don’t use bicarbonate: The Surviving Sepsis Campaign says it doesn’t improve survival. It might even make things worse.
• Monitor closely: Check lactate every 2-4 hours. If it drops by 50% within 2 hours of stopping the drug and giving fluids, you’re on the right track.

Recovery is possible-if caught early. Acetaminophen-induced cases often resolve within 24-48 hours after stopping the drug. Albuterol cases improve within hours of reducing the dose.

What’s New in Prevention?

The good news? We’re getting better at catching this before it kills.

In 2023, the FDA approved a new device called Lactate Scout+. It’s a continuous monitor that tracks lactate levels in real time. Early data shows it cuts detection time from over 12 hours to just 2 hours. That’s huge.

New guidelines from the World Federation of Critical Care Societies (2024) now recommend routine lactate checks for anyone on high-dose beta-agonists or continuous epinephrine. Pharmacists are being trained to flag at-risk prescriptions before they’re filled.

And research is moving toward personalized medicine. If you have a certain gene variant (POLG), you’re at higher risk for NRTI-induced lactic acidosis. Future testing could screen for that before starting HIV therapy.

What Should You Do?

If you’re on any of these drugs-especially if you’re older or have kidney, liver, or heart issues-know the signs:

• Unexplained fatigue or weakness
• Rapid, deep breathing (Kussmaul respirations)
• Nausea, vomiting, or stomach pain
• Feeling cold or dizzy

Don’t wait. Tell your doctor. Ask: "Could this drug be raising my lactate levels?" Request a lactate test if you feel off. It’s a simple blood test.

And if you’re a caregiver for someone in the hospital-especially in the ICU-ask the team: "Are we checking lactate? Could any of these meds be causing this?"

Lactic acidosis from medications isn’t common. But when it happens, it’s often fatal. The difference between life and death isn’t always the drug itself-it’s whether someone recognized the warning signs in time.