Paracetamol: a review with specific focus on the haemodynamic effects of intravenous administration

Paracetamol is one of the most commonly used drugs worldwide with non-prescription sales exceeding 25 thousand million doses per year in the United States of America. The haemodynamic effects of the intravenous paracetamol formulations are largely understudied. There is an emerging body of evidence suggesting that intravenous paracetamol may cause iatrogenic hypotension. Little is known as to the mechanisms of this phenomenon or if intravenous paracetamol indeed does cause hypotension. As paracetamol has negligible solubility in aqueous solutions, many of the commercially available intravenous formulations contain mannitol (up to 3.91 g/100 mL paracetamol) as a stabilising ingredient. It is unknown if mannitol is a contributing factor in the observed hypotension. In this review, we outline the development of paracetamol's current intravenous formulations, describe the composition of these formulations, and overview the literature pertaining to the proposed phenomenon of paracetamol-induced altered hypotension. Understanding the pharmacokinetic and pharmacodymanic properties of intravenous paracetamol may have important clinical implications for vulnerable patients in subgroups where haemodynamic stability is at risk such as those undergoing elective and emergency surgery.