LOW‐DOSE PROPOFOL AMELIORATES HAEMORRHAGIC SHOCK‐INDUCED ORGAN DAMAGE IN CONSCIOUS RATS

Abstract

1. Propofol is an anti-inflammatory agent commonly used for general anaesthesia and sedation in intensive care unit patients. Haemorrhagic shock (HS) followed by resuscitation can induce the production of several inflammatory mediators, such as tumour necrosis factor (TNF)-a and interleukin (IL)-10, leading to multiple organ dysfunction and death. 2. In the present study, we investigated the effects of treatment with high-dose (10 mg/kg per h) and low-dose (1 mg/kg per h) propofol after HS on the physiopathology and cytokine levels in conscious rats. 3. The experiments were designed to induce HS by withdrawing 40% of total blood volume from a femoral artery catheter (6 mL/100 g bodyweight) over 30 min. Mean arterial pressure (MAP) and heart rate (HR) were monitored continuously for 48 h after the start of blood withdrawal. Levels of biochemical parameters, including glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine, creatine phosphokinase (CPK) and lactate dehydrogenase (LDH), were measured 30 min before and 0, 1, 3, 6, 9, 12, 18, 24 and 48 h after the end of the 30 min blood withdrawal period. Serum cytokine levels, including TNF-a and IL-10, were measured at 1, 6, 12, 24 and 48 h after HS. The kidneys, liver, lungs and small intestine were removed for pathological assessment 48 h after HS. 4. In the present study, HS significantly increased blood GOT, GPT, BUN, LDH, CPK, TNF-a and IL-10 levels in conscious rats. Post-treatment with high-dose propofol accentuated systemic hypotension, increased serum TNF-a and IL-10 levels and increased the severity of organ damage after HS. In contrast, post-treatment with low-dose propofol did not affect MAP, but did suppress increased serum levels of the inflammatory cytokines and improved the survival rate after HS, thus protecting rats against HS-induced organ damage. 5. In conclusion, post-treatment with low-dose propofol ameliorated HS-induced markers of organ injury, suppressed the release of TNF-a and IL-10 and protected against HS-induced liver, kidney, lung and small intestine damage in conscious rats. These findings suggest the need to investigate whether low-dose propofol may be beneficial for patients with HS-induced organ damage.