Stress hyperglycaemia following trauma - a survival benefit or an outcome detriment?

PURPOSE OF REVIEW: Stress hyperglycaemia occur often in critically injured patients. To gain new consideration about it, this review compile current as well as known immunological and biochemical findings about causes and emergence. RECENT FINDINGS: Glucose is the preferred energy substrate for fending immune cells, reparative tissue and the cardiovascular system following trauma. To fulfil these energy needs, the liver is metabolically reprogrammed to rebuild glucose from lactate and glucogenic amino acids (hepatic insulin resistance) at the expenses of muscles mass and - to a less extent - fat tissue (proteolysis, lipolysis, peripheral insulin resistance). This inevitably leads to stress hyperglycaemia, which is evolutionary preserved and seems to be an essential and beneficial survival response. It is initiated by damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), intensified by immune cells itself and mainly ruled by tumour necrosis factor (TNF)α and catecholamines with lactate and hypoxia inducible factor (HIF)-1α as intracellular signals and lactate as an energy shuttle. Important biochemical mechanisms involved in this response are the Warburg effect as an efficient metabolic shortcut and the extended Cori cycle. SUMMARY: Stress hyperglycaemia is beneficial in an acute life-threatening situation, but further research is necessary, to prevent trauma patients from the detrimental effects of persisting hyperglycaemia.

Catabolism highly influences ICU-acquired hypernatremia in a mainly trauma and surgical cohort.

PURPOSE: To further analyse causes and effects of ICU-acquired hypernatremia. METHODS: This retrospective, single-centre study, analysed 994 patients regarding ICU-acquired hypernatremia. Non-hypernatremic patients (n = 617) were compared to early-hypernatremic (only before ICU-day 4; n = 87), prolonged-hypernatremic (before and after ICU-day 4; n = 169) and late-hypernatremic patients (only after ICU-day 4; n = 121). Trends in glomerular filtration rate (eGFR), urea-to-creatinine ratio (UCR), fraction of urea in total urine osmolality and urine sodium were compared. Risk factors for i) the development of hypernatremia and ii) mortality were determined. RESULTS: Thirty-eight percent (n = 377) developed ICU-acquired hypernatremia. Specifically in the prolonged- and late-group, decreased eGFRs and urine sodium but increased UCR and fractions of urea in urine osmolality were present. Decreased eGFR was a risk factor for the development of hypernatremia in all groups; disease severity and increased catabolism particularly in the prolonged- and late-hypernatremic group. Increased age, SAPS-III and signs of catabolism but not the development of hypernatremia itself was identified as significant risk factor for mortality. CONCLUSIONS: Late- and prolonged-hypernatremia is highly related to an increased protein metabolism. Besides excessive catabolism, initial disease severity and a decrease in renal function must be considered when confronted with ICU-acquired hypernatremia.

[Volatile anesthetics for prehospital analgesia by paramedics-An overview]. / Volatile Anästhetika zur präklinischen Analgesie durch Rettungssanitäter ­ Eine Übersicht.

Treatment of acute pain is a central task in emergency medicine. Yet, prehospital pain relief is often insufficient or delayed since the administration of potent intravenous analgesic drugs (such as opioids) is mostly limited to physicians due to legal restrictions or training deficiencies in Germany and Austria. Frequently, prehospitally operating emergency physicians have to be demanded later for anguished patients limiting disposability of physicians for patients who are in a potentially life-threatening condition. Thus, inhaled analgesics could represent an interesting alternative.A mixture of 50% nitrous oxide and 50% oxygen (N2O, Livopan®) has been available in Germany and Austria for several years; however, prehospital use of Livopan has been merely realized and only one trial has been published. In addition, methoxyflurane (Penthrop®), a volatile anesthetic from the group of the dialkyl esters (2-dichloro-1:1-difluoroethyl-methyl-ester) was approved for the treatment of moderate to severe pain following trauma in adults in many European countries in recent years and was brought onto the market in Austria in 2018. Several in-hospital trials demonstrated high effectiveness in this setting.This article discusses the effects and prehospital areas of application of both substances in the light of the existing literature. We provide a narrative overview of the current study situation and report on a recently performed prehospital application study of methoxyflurane (Penthrop®) from Austria.The need for pressurized gas cylinders for the use of N2O represents a certain limitation in prehospital use. Furthermore, in certain injuries such as of the inner ear or a pneumothorax N2O should not be used and the risk of diffusion hypoxemia has to be addressed. Users should be particularly careful and limit the use in alcohol addicts and vegans. The advances of N2O are that it is odorless, has a fast onset of action, the usability in patients over 1 month old and has stabilizing effects on the circulation. Plenty of literature regarding prehospital as well as in-hospital use of nitrous oxide in emergency, obstetric and pediatric settings show its effectiveness as a single drug as well as in combination with other analgesics, such as paracetamol or various opioids. Its long tradition in Anglo-American countries is also based on its safety and low rate of side effects.Methoxyflurane is easier to store and handle and may be slightly more effective in severe pain after trauma; however, its approval is restricted to adults, where it works significantly better with increasing age, based on the declining minimal alveolar concentration (MAC) of all inhaled anesthetics with increasing age. Furthermore, decades of use of inhaled methoxyflurane in Australia have shown the drug is effective, safe and low in side effects and has a broad spectrum of applications. The use of methoxyflurane is limited in patients with severe hepatic or renal insufficiency and the characteristic odor has been described as unpleasant by some patients. In Europe, three large in-hospital trials showed strong pain relief in trauma patients, even comparable to opioids.Overall, based on the current evidence, the use of nitrous oxide and even more of methoxyflurane may be recommended also for prehospital use by skilled paramedics.

ICU-Admission Hyperphosphataemia Is Related to Shock and Tissue Damage, Indicating Injury Severity and Mortality in Polytrauma Patients.

Hyperphosphataemia can originate from tissue ischaemia and damage and may be associated with injury severity in polytrauma patients. In this retrospective, single-centre study, 166 polytrauma patients (injury severity score (ISS) ≥ 16) primarily requiring intensive care unit (ICU) treatment were analysed within a five-year timeframe. ICU-admission phosphate levels defined a hyperphosphataemic (>1.45 mmol/L; n = 56) opposed to a non-hyperphosphataemic group (n = 110). In the hyperphosphataemic group, injury severity was increased (ISS median and IQR: 38 (30-44) vs. 26 (22-34); p < 0.001), as were signs of shock (lactate, resuscitation requirements), tissue damage (ASAT, ALAT, creatinine) and lastly in-hospital mortality (35.7% vs. 5.5%; p < 0.001). Hyperphosphataemia at ICU admission was shown to be a risk factor for mortality (1.46-2.10 mmol/L: odds ratio (OR) 3.96 (95% confidence interval (CI) 1.03-15.16); p = 0.045; >2.10 mmol/L: OR 12.81 (CI 3.45-47.48); p < 0.001) and admission phosphate levels alone performed as good as injury severity score (ISS) in predicting in-hospital mortality (area under the ROC curve: 0.811 vs. 0.770; p = 0.389). Hyperphosphataemia at ICU admission is related to tissue damage and shock and indicates injury severity and subsequent mortality in polytrauma patients. Admission phosphate levels represent an easily feasible yet strong predictor for in-hospital mortality.

Absence of Stress Hyperglycemia Indicates the Most Severe Form of Blunt Liver Trauma.

BACKGROUND: Stress hyperglycemia is common in trauma patients. Increasing injury severity and hemorrhage trigger hepatic gluconeogenesis, glycogenolysis, peripheral and hepatic insulin resistance. Consequently, we expect glucose levels to rise with injury severity in liver, kidney and spleen injuries. In contrast, we hypothesized that in the most severe form of blunt liver injury, stress hyperglycemia may be absent despite critical injury and hemorrhage. METHODS: All patients with documented liver, kidney or spleen injuries, treated at a university hospital between 2000 and 2020 were charted. Demographic, laboratory, radiological, surgical and other data were analyzed. RESULTS: A total of 772 patients were included. In liver (n = 456), spleen (n = 375) and kidney (n = 152) trauma, an increase in injury severity past moderate to severe (according to the American Association for the Surgery of Trauma, AAST III-IV) was associated with a concomitant rise in blood glucose levels independent of the affected organ. While stress-induced hyperglycemia was even more pronounced in the most severe forms (AAST V) of spleen (median 10.7 mmol/L, p < 0.0001) and kidney injuries (median 10.6 mmol/L, p = 0.004), it was absent in AAST V liver injuries, where median blood glucose level even fell (5.6 mmol/L, p < 0.0001). CONCLUSIONS: Absence of stress hyperglycemia on hospital admission could be a sign of most severe liver injury (AAST V). Blood glucose should be considered an additional diagnostic criterion for grading liver injury.

Accuracy of training blood volume quantification using a visual estimation tool.

BACKGROUND: We investigated whether the use of a specially designed visual estimation tool may improve accuracy in quantifying blood volumes related to surface spreading. METHODS: A prospective, paired-control, single-blinded experimental study was performed at a medical university. Anesthesiologists and emergency medical personnel estimated various blood volumes on surfaces with varying absorptivity (carpet, towel, polyvinyl chloride, wooden flooring) in an experimental setting. We assessed the sensitivity of training blood volume quantification using a self-designed visual estimation tool by comparing the accuracy of visual blood volume estimations before and after practical training with the tool. RESULTS: A total of 352 estimations by 44 participants were evaluated. Accurate estimations improved significantly from pre-training to post-training (P<0.05). The sensitivity of blood volume quantification was 33.0% after training with the visual estimation tool. Estimations did not depend on age, profession, gender or years of the estimator's professional experience. CONCLUSIONS: Training with a visual estimation tool by professional rescuers can improve the estimation accuracy of blood volumes spread on surfaces with varying absorptivity.

Early ICU-acquired hypernatraemia is associated with injury severity and preceded by reduced renal sodium and chloride excretion in polytrauma patients.

PURPOSE: To further elucidate the origin of early ICU-acquired hypernatraemia. MATERIAL AND METHODS: In this retrospective single-centre study, polytrauma patients requiring ICU treatment were analysed. RESULTS: Forty-eight (47.5%) of 101 included polytrauma patients developed hypernatraemia within the first 7 days on ICU. They were more severely ill as described by higher SAPS III, ISS, daily SOFA scores and initial norepinephrine requirements as well as longer requirements of mechanical ventilation and ICU treatment in general. The development of hypernatraemia was neither attributable to fluid- or sodium-balances nor renal impairment. Although lower in the hypernatraemic group from day 4 onwards, median creatinine clearances were sufficiently high throughout the observation period. However, in the hypernatraemic group, urine sodium and chloride concentrations prior to the evolvement of hypernatraemia (56 (27-87) mmol/l and 39 (23-77) mmol/l) were significantly decreased when compared to i) the time after developing hypernatraemia (94 (58-134) mmol/l and 78 (36-115) mmol/l; p < 0.001) and ii) the non-hypernatraemic group in general (101 (66-143) mmol/l and 75 (47-109) mmol/l; p < 0.001). CONCLUSIONS: Early ICU-acquired hypernatraemia is associated with injury severity and preceded by reduced renal sodium and chloride excretion in polytrauma patients.

ICU-Acquired Hypernatremia Is Associated with Persistent Inflammation, Immunosuppression and Catabolism Syndrome.

Developing hypernatremia while on intensive care unit (ICU) is a common problem with various undesirable effects. A link to persistent inflammation, immunosuppression and catabolism syndrome (PICS) can be established in two ways. On the one hand, hypernatremia can lead to inflammation and catabolism via hyperosmolar cell stress, and on the other, profound catabolism can lead to hypernatremia via urea-induced osmotic diuresis. In this retrospective single-center study, we examined 115 patients with prolonged ICU stays (≥14 days) and sufficient renal function. Depending on their serum sodium concentrations between ICU day 7 and 21, allocation to a hypernatremic (high) and a nonhypernatremic group (low) took place. Distinct signs of PICS were detectable within the complete cohort. Thirty-three of them (28.7%) suffered from ICU-acquired hypernatremia, which was associated with explicitly higher signs of inflammation and ongoing catabolism as well as a prolonged ICU length of stay. Catabolism was discriminated better by the urea generation rate and the urea-to-creatinine ratio than by serum albumin concentration. An assignable cause for hypernatremia was the urea-induced osmotic diuresis. When dealing with ICU patients requiring prolonged treatment, hypernatremia should at least trigger thoughts on PICS as a contributing factor. In this regard, the urea-to-creatinine ratio is an easily accessible biomarker for catabolism.