Hyperlactataemia with acute kidney injury following community assault: cause or effect?

BACKGROUND: Crush injury is a common presenting clinical problem in South African trauma patients, causing acute kidney injury (AKI). It has been theorised previously that the AKI was not due to an anaerobic phenomenon. A previous local study noted the presence of a mild hyperlactataemia among patients with crush syndrome, but the significance and causes of this was not fully explored. This study aimed to examine the incidence of hyperlactataemia in patients with crush syndrome presenting to a busy emergency department (ED) in rural South Africa. METHOD: The study was conducted at Edendale Hospital in KwaZulu-Natal province in South Africa from 1 June 2016 to 31 December 2017. All patients from the ED who had sustained a crush injury secondary to a mob assault were included in the study. Patients with GCS on arrival of < 13 or polytrauma were excluded from analysis. The primary outcome of interest was the presence of hyperlactataemia (> 2.0mmol/L) on presentation. The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used to diagnose and stage AKI as a secondary outcome. RESULTS: A total of 84 patients were eligible for analysis. Sixty-nine (82%) patients presented with hyperlactataemia. The median serum lactate was 4.9mmol/L (IQR 2.3-7.2mmol/L). Fifteen (18%) patients were diagnosed with AKI on presentation according to serum creatinine. Ten patients were diagnosed as Stage 1, three were Stage 2 and two Stage 3 AKI respectively. There was no difference in the incidence of AKI in patients with or without hyperlactataemia (p = 0.428). Time from injury to presentation was a median 365 minutes (IQR 180-750 minutes). Six (7%) patients were admitted to high care unit and nine (11%) were admitted to the intensive care unit (ICU). No patients died within 48 hours of admission. Two patients received renal replacement therapy during the first 48 hours of admission to hospital. CONCLUSION: Hyperlactataemia is a common feature of patients presenting to the ED following crush syndrome secondary to beatings received during interpersonal violence. The origin of this hyperlactataemia is currently unknown. Further research needs to be conducted into the origin of the hyperlactataemia and its clinical significance. In this cohort, the utilisation of RRT was low but the incidence of AKI was high and developed rapidly following the injury. The utilisation of RRT also needs to be further studied in larger patient populations in South Africa to make local clinical recommendations for use.

Systemic Inflammatory Response and Multiple Organ Dysfunctions Following Crush Injury: a New Experimental Model in Rabbits.

In this study, we aim to develop a new, reproducible crush injury (CI) model in rabbits. Anesthetized rabbits were compressed on both hind limbs using a special instrument for 6 h followed by 3 h of reperfusion. Blood samples and injured muscles were collected for biochemical analysis and morphological evaluation. Survival observation lasted for 72 h. Bilateral compressions with 10 kg/kg body weight (BW), but not with 5 kg/kg BW, reduced serious systemic impairment. Bilateral compressions with 10 kg/kg BW resulted in severe lactic acidosis; increased serum K+, creatine phosphokinase, aspartate transaminase, alanine transaminase, blood urea nitrogen, and creatinine levels; and a sharply decreased mean arterial blood pressure after compression release. Serious tissue edema and inflammation were observed in the damaged muscles. The mortality rates in compression groups were 20% (5 kg/kg BW) and 60% (10 kg/kg BW). There was a significant increase in plasma concentrations of TNF-α and IL-1ß after compression. Plasma IL-1ß levels returned to control levels at 6 h after compression release, whereas TNF-α peaked at 12 h following reperfusion. Furthermore, antiinflammatory cytokines, including IL-4 and IL-10, were also increased after compression, and these two cytokines peaked at 12 h after compression release. Our data suggested that bilateral compression with 10 kg/kg BW on rabbits' hind limbs is a reproducible CI model, and we also reported the CI-induced systemic inflammatory responses and changes of cytokines over time.

Hemorrhagic shock and tissue injury drive distinct plasma metabolome derangements in swine.

BACKGROUND: Tissue injury and hemorrhagic shock induce significant systemic metabolic reprogramming in animal models and critically injured patients. Recent expansions of the classic concepts of metabolomic aberrations in tissue injury and hemorrhage opened the way for novel resuscitative interventions based on the observed abnormal metabolic demands. We hypothesize that metabolic demands and resulting metabolic signatures in pig plasma will vary in response to isolated or combined tissue injury and hemorrhagic shock. METHODS: A total of 20 pigs underwent either isolated tissue injury, hemorrhagic shock, or combined tissue injury and hemorrhagic shock referenced to a sham protocol (n = 5/group). Plasma samples were analyzed by UHPLC-MS. RESULTS: Hemorrhagic shock promoted a hypermetabolic state. Tissue injury alone dampened metabolic responses in comparison to sham and hemorrhagic shock, and attenuated the hypermetabolic state triggered by shock with respect to energy metabolism (glycolysis, glutaminolysis, and Krebs cycle). Tissue injury and hemorrhagic shock had a more pronounced effect on nitrogen metabolism (arginine, polyamines, and purine metabolism) than hemorrhagic shock alone. CONCLUSION: Isolated or combined tissue injury and hemorrhagic shock result in distinct plasma metabolic signatures. These findings indicate that optimized resuscitative interventions in critically ill patients are possible based on identifying the severity of tissue injury and hemorrhage.

Sciatic nerve regeneration in rats subjected to ketogenic diet.

OBJECTIVES: Ketogenic diet (KD) is a high-fat-content diet with insufficiency of carbohydrates that induces ketogenesis. Besides its anticonvulsant properties, many studies have shown its neuroprotective effect in central nervous system, but its influence on peripheral nervous system has not been studied yet. We examined the influence of KD on regeneration of peripheral nerves in adult rats. METHODS: Fifty one rats were divided into three experimental (n = 15) and one control (n = 6) groups. Right sciatic nerve was crushed and animals were kept on standard (ST group) or ketogenic diet, the latter was introduced 3 weeks before (KDB group) or on the day of surgery (KDA group). Functional (CatWalk) tests were performed once a week, and morphometric (fiber density, axon diameter, and myelin thickness) analysis of the nerves was made after 6 weeks. Body weight and blood ketone bodies level were estimated at the beginning and the end of experiment. RESULTS: Functional analysis showed no differences between groups. Morphometric evaluation showed most similarities to the healthy (uncrushed) nerves in KDB group. Nerves in ST group differed mostly from all other groups. Ketone bodies were elevated in both KD groups, while post-surgery animals' body weight was lower as compared to ST group. DISCUSSION: Regeneration of sciatic nerves was improved in KD - preconditioned rats. These results suggest a neuroprotective effect of KD on peripheral nerves.