What can cause acidosis in a patient after a Therapeutic Plasma Exchange (TPE) session?

Causes of Acidosis After Therapeutic Plasma Exchange (TPE)

Primary Mechanism: Hyperchloremic Metabolic Acidosis from Albumin Replacement Fluid

The most common cause of acidosis after TPE is hyperchloremic metabolic acidosis resulting from the high chloride content (132-145 mmol/L) in albumin replacement solutions, particularly in patients with impaired renal function who cannot adequately excrete the chloride load. 1, 2, 3

Pathophysiology

• Albumin solutions used as replacement fluid contain supraphysiologic chloride concentrations of 132-145 mmol/L, significantly higher than normal plasma chloride (98-106 mmol/L) 1, 3
• Large volumes of albumin infused during TPE (typically 1-1.5 plasma volumes per session) deliver massive chloride loads that overwhelm the kidney's excretory capacity 1, 2
• The resulting hyperchloremic acidosis manifests as decreased serum pH (Δ pH = -0.06 ± 0.04), decreased bicarbonate (Δ bicarbonate = -4.03 ± 2.29 mmol/L), and decreased base excess (Δ base excess = -2.54 ± 3.82 mmol/L) 2
• This mechanism is distinct from citrate-induced metabolic alkalosis, which occurs when fresh-frozen plasma (FFP) is used as replacement fluid 2

Risk Factors for Severe Acidosis

• Impaired renal function is the most critical risk factor, as the kidneys cannot adequately excrete the chloride load 1, 3
• Multiple consecutive TPE sessions compound the chloride burden before renal clearance can occur 1, 2
• Renal transplant patients are particularly vulnerable due to baseline impaired kidney function 1
• Patients with chronic kidney disease stages 3-5 have reduced capacity to maintain acid-base homeostasis 4

Clinical Presentation and Diagnosis

Symptoms

• Gastrointestinal complaints (nausea, vomiting) are common presenting symptoms 1
• Muscle weakness develops as acidosis worsens 1
• Symptoms typically appear after 3-4 TPE sessions when using albumin replacement 1, 2

Laboratory Findings

• Low serum bicarbonate (<22 mmol/L, often <15 mmol/L in severe cases) 1, 2
• Elevated serum chloride (>106 mmol/L, typically 111-115 mmol/L) 1, 3
• Normal anion gap (distinguishing this from lactic acidosis or ketoacidosis) 1, 3
• Normal total-to-ionized calcium ratio (ruling out citrate accumulation) 1
• Arterial pH <7.35 with PaCO2 showing compensatory hyperventilation 4, 2

Differential Diagnosis: Other Causes of Post-TPE Acidosis

Citrate-Related Alkalosis (Not Acidosis)

• When FFP is used as replacement fluid, citrate metabolism produces bicarbonate, causing metabolic alkalosis rather than acidosis 2
• This manifests as increased pH (Δ pH = +0.04 ± 0.05) and increased bicarbonate (Δ bicarbonate = +3.6 ± 3.68 mmol/L) 2
• An elevated total-to-ionized calcium ratio indicates citrate accumulation 1

Pseudo-Hypobicarbonatemia

• Severe hypertriglyceridemia (>1000 mg/dL) can cause falsely low bicarbonate measurements on enzymatic assays 5
• This creates an apparent anion gap metabolic acidosis that doesn't actually exist 5
• Blood gas analysis shows normal calculated bicarbonate, distinguishing this from true acidosis 5
• Lipemic serum is visually apparent and should prompt blood gas confirmation 5

Underlying Disease-Related Acidosis

• Patients with chronic kidney disease may have baseline metabolic acidosis that worsens with TPE 4, 1
• Diabetic patients may develop ketoacidosis if insulin is held perioperatively 4
• Sepsis or tissue hypoperfusion can cause lactic acidosis independent of TPE 6

Prevention Strategies

Prophylactic Sodium Bicarbonate Administration

• Prophylactic sodium bicarbonate should be administered during TPE sessions when albumin is used as replacement fluid, particularly in patients with impaired renal function. 2
• Prophylactic bicarbonate partially corrects the pH decrease (Δ pH = -0.04 ± 0.04 vs -0.06 ± 0.04 without prophylaxis) and bicarbonate decrease (Δ bicarbonate = -3.1 ± 2.47 vs -4.03 ± 2.29 mmol/L) 2
• This approach reduces adverse events from 4.8% to 2.0% (p < 0.001) 2

Fluid Selection Strategies

• Consider using FFP instead of albumin when feasible, as FFP causes metabolic alkalosis rather than acidosis 2
• If albumin must be used, limit the number of consecutive sessions before allowing renal recovery 1, 2
• Use balanced crystalloid solutions (Ringer's lactate or Plasma-Lyte) for any additional fluid resuscitation rather than normal saline 7
• Avoid normal saline entirely in acidotic patients, as it contains 154 mmol/L chloride and will worsen hyperchloremic acidosis 8, 7

Monitoring Requirements

• Measure serum bicarbonate, chloride, and arterial blood gases before each TPE session and 2-4 hours after completion 4, 2
• Monitor for clinical symptoms (muscle weakness, GI complaints) that indicate developing acidosis 1
• Check total-to-ionized calcium ratio if citrate toxicity is suspected 1
• In patients with severe hypertriglyceridemia, obtain blood gas analysis rather than relying on serum bicarbonate measurements 5

Treatment of Established Acidosis

Immediate Management

• Administer intravenous sodium bicarbonate for symptomatic hyperchloremic acidosis or bicarbonate <18 mmol/L. 4, 1, 2
• Initial dose: 1-2 mEq/kg IV given slowly over several minutes, using 4.2% concentration (dilute 8.4% solution 1:1 with normal saline) 6
• Target pH of 7.2-7.3, not complete normalization 6
• Ensure adequate ventilation before administering bicarbonate, as it produces CO2 that must be eliminated 6

Ongoing Management

• Continue oral sodium bicarbonate supplementation (2-4 g/day or 25-50 mEq/day) between TPE sessions 4, 6
• Maintain serum bicarbonate ≥22 mmol/L to prevent complications of chronic metabolic acidosis 4
• Monitor serum potassium closely, as bicarbonate therapy shifts potassium intracellularly and may cause hypokalemia 6
• Add 20-30 mEq/L potassium to IV fluids (2/3 KCl and 1/3 KPO4) to prevent hypokalemia 7

Adjusting TPE Protocol

• Temporarily discontinue TPE if bicarbonate falls below 15 mmol/L despite treatment 4
• Switch to FFP as replacement fluid if albumin-induced acidosis is severe 2
• Reduce the plasma volume exchanged per session (e.g., from 1.5 to 1.0 plasma volumes) 1
• Increase the interval between TPE sessions to allow renal recovery 1

Critical Pitfalls to Avoid

• Do not ignore mild acidosis (bicarbonate 18-22 mmol/L) in patients with impaired renal function, as it will worsen with repeated TPE sessions 4, 1
• Do not use normal saline for volume resuscitation in acidotic patients, as it contains 154 mmol/L chloride and will exacerbate hyperchloremic acidosis 8, 7
• Do not rely solely on serum bicarbonate measurements in patients with severe hypertriglyceridemia; obtain arterial blood gas analysis to confirm true acid-base status 5
• Do not administer bicarbonate without ensuring adequate ventilation, as paradoxical intracellular acidosis can occur if CO2 cannot be eliminated 6
• Do not mix sodium bicarbonate with calcium-containing solutions or vasoactive amines, as precipitation or inactivation will occur 6

Special Populations

Renal Transplant Patients

• These patients are at highest risk due to impaired baseline kidney function 1
• Prophylactic bicarbonate should be standard practice in this population 1, 2
• Consider using FFP instead of albumin when possible 2

Patients with Chronic Kidney Disease

• Baseline metabolic acidosis (bicarbonate <22 mmol/L) is common and will worsen with albumin-based TPE 4, 1
• Maintain bicarbonate ≥22 mmol/L to prevent protein catabolism, bone disease, and CKD progression 4
• Monitor bicarbonate before and after each TPE session 4