Acid-base disturbance in cirrhosis – a clinical study

Cirrhosis of the liver is associated with increased respiration (hyperventilation) and consequent hypocapnic respiratory alkalosis. The severity of this acid-base disturbance correlates with severity of cirrhosis as well as severity of the abnormal hyperdynamic systemic circulation that characterizes this irreversible chronic liver disease. 

These are the headline findings of a recently published study conducted at Hvidovre hospital Denmark by researchers with a long-standing research interest in the pathophysiology of cirrhosis. The study population comprised 66 patients with cirrhosis, but no other major disease, who had been referred for hemodynamic investigation to diagnose and quantify portal hypertension, a central feature of cirrhosis. 

Forty-four apparently healthy individuals served as controls. A well-validated cirrhosis severity scoring system was used to assign each study patient to one of three groups A, B or C (A being least severe and C being most severe). Of the 66 patients 10 were assigned to group A, 32 to group B, and 24 to group C.

In addition to the invasive hemodynamic investigations, which involved insertion of a catheter via femoral artery and measurement of arterial and hepatic vein blood pressure, all study and control subjects had blood sampled for routine biochemistry (U&E, liver function). 

Blood was also sampled from artery and hepatic vein for blood gas analysis. Compared with controls, cirrhosis study patients had increased respiratory rate (16.5 ±4.0 breaths/min vs. 12.9 ±2.4 breaths/min), increased arterial blood pH (7.44 ±0.033 vs. 7.41 ±0.03) decreased arterial pCO₂ (4.56 ±0.57 kPa vs. 5.51 ±0.77 kPa) and decreased bicarbonate (22.8 ±2.8 mmol/L vs. 25.6 ±3.1). 

The combination of increased respiration, increased pH, decreased pCO₂ and decreased bicarbonate indicates chronic respiratory alkalosis with some degree of metabolic compensation. Subgroup analysis revealed that the severity of this respiratory alkalosis is related to severity of cirrhosis. 

So for example, the pH of group A patients (7.41 ±0.027) was significantly less than that of group B patients (7.43 ±0.026), which was significantly less than that of group C patients (7.46 ±0.028). Similarly, there was statistically significant difference between the three groups with regard to pCO₂, so that group C patients on average were more hypocapnic than group B patients who were more hypocapnic than group A patients. 

At 50 months after entry to the study 35 of the 66 study patients had died. Kaplan-Meier survival curve demonstrated marked reduction in survival associated with reduced pCO₂ (<4.5 kPa) compared with normal pCO₂ (4.6-6.2 kPa), further demonstrating the link between severity of acid-base disturbance and severity of cirrhosis.

The authors demonstrated a correlation between acid-base measures (pH, pCO₂) and measures used to assess severity of hyperdynamic systemic circulation (indocyanine green clearance, cardiac index, systemic vascular resistance). This allowed the authors to conjecture that the hyperventilatory state and hemodynamic derangement evident in cirrhosis may have a common cause, a notion that they expand on in discussion of their study.