None listed
Conditions
Brief summary
Background: Intravenous paracetamol is ubiquitously used in hospitals as an antipyretic and analgesic worldwide. It is administered to a wide array of patients including those undergoing major surgeries due to its minimal side effect profile. Previous studies have suggested that 4g/day paracetamol is safe in patients undergoing liver resection surgery, however other authorities recommend that administration be kept at a maximum of 2g/day in patients with hepatic impairment. There is now a growing body of evidence that supports the safety of paracetamol use even in patients with liver disease. However, there are no studies to date that have investigated the haemodynamic effects of paracetamol in patients with chronic liver disease. Recent studies have provided evidence that paracetamol may cause hypotension in critically ill patients, which may have important clinical implications for patients undergoing major surgery. The mechanism for this hypotension is unknown but may be attributable to one the stabilizing compounds found in the formulation, mannitol. Mannitol is a known diuretic and even in small quantities can cause episodes of transient hypotension. There is insufficient evidence evaluating the use of paracetamol in the setting of liver transplantation, and importantly there are no pharmacokinetic studies that evaluate safety and efficacy in this setting. Hypothesis: A single dose of paracetamol (1g IV) has adverse effects on blood pressure in patients with chronic liver disease undergoing liver transplantation surgery. Study aims: To determine whether paracetamol has any adverse haemodynamic effects in patients with chronic liver disease who are undegoing liver transplantation.
Interventions
Intravenous paracetamol (Actavis, North Adelaide, SA)
Paracetamol is one of the most commonly used medications in the world. The intravenous format is the preferred method of administration in the intraoperative and immediate postoperative periods.
In 100mL of solution for infusion, intravenous paracetamol contains the following:
Paracetamol = 1g
Mannitol = 3.91g
Cysteine hydrochloride monohydrate
Dibasic dihydrate sodium phosphate
Sodium hydroxide
Hydrochloric acid
Water for injections
For
Intravenous paracetamol (Actavis, North Adelaide, SA) Paracetamol is one of the most commonly used medications in the world. The intravenous format is the preferred method of administration in the intraoperative and immediate postoperative periods. In 100mL of solution for infusion, intravenous paracetamol contains the following: Paracetamol = 1g Mannitol = 3.91g Cysteine hydrochloride monohydrate Dibasic dihydrate sodium phosphate Sodium hydroxide Hydrochloric acid Water for injections For this clinical trial, intravenous paracetamol will be used once intraoperatively only. The insertion of a pulmonary artery catheter (PAC) is required for routine anaesthesia treatment during liver surgery. Haemodynamic measurements will be monitored via the PAC. After insertion of the PAC, 100mL paracetamol (containing 1g paracetamol and 3.91g mannitol) will be administered intravenously. Volume of paracetamol to be administered: Actavis (North Adelaide, SA) recommends 1g of paracetamol per administration with a maximum of 4g of paracetamol per day. The minimum dose interval is 4 hours. The duration of infusion is 15 minutes. In this trial, one dose of 1g/100mL IV paracetamol will be administered over 15 minutes. This will be administered post arrival to the operating room, prior to induction of anaesthesia, but after the insertion of the pulmonary artery catheter. The administration of this trial drug will be electronically logged as per hospital protocol. This will be done regardless of whether the trial drug contains paracetamol as the trial is double-blinded and all research staff will be unaware of the contents of the trial drug until the end of the study. This additional safety measure will be in place to ensure there will be no overdose of paracetamol should the trial drug contain paracetamol. Additional postoperative pain treatment will be administered to patients via patient controlled analgesia as per routine clinical care.
Sponsors
Austin Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult surgery patients (age >18 years) 2. Patients with chronic liver disease requiring liver transplantation
Exclusion criteria
Paracetamol use 24 hours prior to surgery (in paracetamol only or in combination therapy) Pregnancy Chronic renal impairment (creatinine >250 umol/L) Chronic liver disease (ALT >200IU/L) Morbid obesity (BMI >35kg/m2) Known allergic reaction to IV paracetamol Consumption of caffeine (e.g. coffee or energy drinks) <10 hours prior to surgery
Outcome results
None listed