I. Definition of stress hyperglycemia in critically ill patients Clement et al. classified hyperglycemia in critically ill patients into stress hyperglycemia, hyperglycemia in patients with a history of diabetes mellitus, and hyperglycemia in new-onset diabetes mellitus.WHO classified a person with typical diabetes mellitus symptoms (polydipsia, polydipsia, and unexplained weight loss) with an arbitrary glucose of ≥11.1 mmol/L or fasting blood glucose (FPG) ≥7.0 mmol/ L, a diagnosis of diabetic hyperglycemia was made. In fact, there is no clear limit to the level of stress hyperglycemia, and it is generally believed that it can be diagnosed with reference to the diagnostic index of diabetes mellitus.Van den et al. even believe that stress hyperglycemia can be diagnosed when blood glucose >6.1mmol/L. Mechanism of stress hyperglycemia 1. Neural regulation mechanism: trauma, burns, major surgery, severe infections and other physiological stress can occur in a series of neuroendocrine changes, the main changes in the hypothalamic-pituitary-adrenocortical axis (HPA) and the blueprint -noradrenergic neurons, sympathetic-adrenomedullary neurons, sympathetic-adrenomedullary neurons, and the adrenocortical neurons. , and strong excitation of the sympathetic-adrenomedullary axis. Pro-catabolic hormones such as glucocorticoids, glucagon, growth hormone, catecholamines and other secretions increase, directly or indirectly antagonize the role of insulin, so that insulin secretion is inhibited and insulin resistance occurs. 2, insulin resistance: any type of disease or injury-induced stress can lead to insulin resistance, glucose intolerance and hyperglycemia. Elevated levels of cytokines, growth hormone, glucagon, and hydrocortisone may play a role in gluconeogenesis. The effects of these hormones counteract normal insulin activity, resulting in enhanced lipolysis and protein hydrolysis to provide enzymatic degradation for gluconeogenesis. Acute injury results in the release of catecholamines that enhance hepatic glycogenolysis and inhibit gluconeogenesis. Stimulation of glucose uptake in skeletal muscle by activity is attenuated or absent due to activity limitation in critically ill patients. In addition, insulin stimulates glucose uptake during stress and activates damaged glycogen synthase, resulting in decreased glucose uptake in the heart, skeletal muscle and adipose tissue, leading to elevated blood glucose. 3.Inflammatory mediator release: In critical disease states, the body releases a variety of cytokines that play a very important role in the production of stress hyperglycemia. The main cytokines involved are tumor necrosis factor-a (tumor necrosis factor-alpha, TNF- a), interleukin (interleukin, IL)-1, IL-6 and so on. Cytokines act as systemic inflammatory mediators and produce hyperglycemic effects by stimulating the secretion of counter-regulatory hormones and causing insulin resistance. It is now known that the mechanism of insulin resistance and hyperglycemia induced by TNF- a may be related to the indirect stimulation of reverse-regulated hormone secretion or direct action on the insulin receptor signaling pathway and/or influence the function of glucose transporters. 4, insulin receptor defects: traumatic stress can lead to insulin receptor or receptor complex invagination, causing a decrease in the number of receptors, a decrease in receptor binding, and a decrease in receptor tyrosine protein kinase activity, resulting in hyperglycemia. Third, the harm of stress hyperglycemia on the body Hyperglycemia can cause fluid imbalance, decreased immune function, and increased chances of infection.Capes et al. found that non-diabetic ischemic stroke (AIS) patients, when blood glucose more than 6.0~8.0mmol/L when the hospitalization mortality rate increased 3 times, while the disability rate also increased.Leigh et al. reported 201 cases of acute ischemic stroke patients at the onset of the disease. Leigh et al. reported that 201 patients with acute ischemic stroke who received thrombolytic therapy within 6 h of the onset of the stroke had 13% deterioration, 39% improvement, and 48% no significant change in outcome; factors associated with deterioration were combined intracranial hemorrhage, failure of recanalization, and elevated glucose >8.3 mmol/L. This suggests that hyperglycemia has a detrimental effect on ischemic cerebrovascular disease. Some researchers have found that myocardial infarction patients with a mean blood glucose level of (7.8±3.0) mmol/L are significantly more likely to have nonfatal reinfarction, heart failure, and serious cardiovascular accidents, and that glucose is predictive of risk.Capes et al. found that non-diabetic patients with AMI had a 3.9-fold increase in the rate of death in the presence of combined stress hyperglycemia (>8.3 to 10 mmol/L). This suggests that stress hyperglycemia is an important risk factor for AMI. This suggests that stress hyperglycemia has a significant impact on the prognosis of myocardial infarction. In a study of trauma patients, Laird et al. found that early (day 1-2 of admission) blood glucose ≥11.1 mmol/L became an independent influence associated with late infection and morbidity and mortality after multifactorial logistic analysis. Other authors retrospectively analyzed 1826 critically ill patients in specialized ICUs and found that the level of elevated blood glucose was strongly associated with ICU morbidity and mortality in all types of critically ill patients, with the mean glucose level in the surviving group being lower than that in the non-surviving group. Blood glucose levels were positively correlated with APACHE II scores, and the higher the blood glucose concentration, the higher the case fatality rate for the same level of severity.Srinivasan et al. retrospectively analyzed 152 pediatric ICU patients and found that 69% of the patients were admitted with combined hyperglycemia (>8.0 mmol/L), and case fatality was strongly correlated with the highest blood glucose concentration (>11.1 mmol/L) and the duration of ICU stay (>10 d). The case fatality rate was closely related to the maximum blood glucose concentration (>11.1 mmol/L) and the duration of ICU stay (>10 d). A large amount of data confirms that stress hyperglycemia brings extensive and serious harm to critically ill patients. Fourth, the impact of strict glycemic control on the prognosis of critically ill patients In 2001, Van den Berghe et al. conducted a large sample randomized controlled study on surgical ICU patients, and divided the enrolled 1548 patients into two groups, of which the conventional treatment group had blood glucose more than 11.93 mmol/L when the intravenous insulin was applied to maintain the blood glucose in the range of 9.99~11.10 mmol/L; intensive In the conventional treatment group, intravenous insulin was applied when blood glucose exceeded 11.93 mmol/L, and blood glucose was maintained at 9.99~11.10 mmol/L; in the intensive insulin treatment group, intravenous insulin was applied when blood glucose exceeded 6.10 mmol/L. The results of the study showed that controlling blood glucose could relatively reduce the mortality rate of ICU patients by 42% (8.0% in the control group and 4.6% in the intensive treatment group, P<0.05), and the hospitalization mortality rate by 34% (10.9% in the control group and 7.2% in the intensive treatment group, P=0.01). In addition to reducing mortality, intensive insulin therapy also reduced complications associated with critically ill patients, such as a 46% reduction in the incidence of blood-borne infections, a 41% reduction in the proportion of acute renal failure requiring dialysis or hemofiltration, a 50% reduction in the proportion of red blood cell transfusions, a 44% reduction in the incidence of polyneuropathy in critically ill patients, and a reduction in the duration of mechanical ventilation and the length of stay in the ICU. The publication of the results of this study has led to a new understanding of glycemic control in ICU patients. V. The organ-protective role of insulin Although the prognostic impact of strict glycemic control strategies on critically ill patients is still more controversial, it is undeniable that the advantageous results of intensive insulin therapy on the reduction and control of complications in critically ill patients still dominate. Whether this superior outcome is a result of lower blood glucose or an effect of insulin, then, is unclear. Several clinical studies have found that insulin has an organ-protective effect, especially in single-disease specialty studies.The results of a prospective, randomized, controlled, large-sample study published by Schetz et al. showed that intensive insulin therapy had a positive protective effect on renal function in critically ill patients. This renoprotective effect was seen with glycemic control in the normal range. Intensive insulin therapy reduces the incidence of renal dysfunction and failure in non-diabetic patients in the perioperative cardiac surgery setting and reduces the rate of renal replacement therapy and 30-day mortality. In two new randomized clinical studies from Lueven, an intensive insulin therapy strategy reduced the incidence of critically ill polyneuromyelitis optica and the duration of mechanical ventilation in this group of patients.Otto and colleagues explored the effects of intensive insulin therapy in critically ill patients with hyperglycemia in terms of molecular immunological mechanisms and found that hyperosmolality associated with hyperglycemia in a hyperphysiological state enhances the production of cytokines, and also reduces the phagocytosis of human monocytes. They found that the hyperosmolality associated with hyperglycemia in the supraphysiological state enhances cytokine production and reduces phagocytosis and oxidative burst in human monocytes, and that intensive insulin therapy improves this hyperosmolality phenomenon more than anything else. studied the effect of intensive insulin therapy and found that intensive insulin therapy improved insulin sensitivity, and this improved sensitivity had a positive effect on organ protection. Sixth, the goal of glycemic control Van den Berghe et al. showed that compared with conventional treatment to control blood glucose at 9.99~11.10 mmol/L, intensive insulin therapy to control blood glucose at 4.44~6.10 mmol/L, the intensive treatment group can improve the prognosis. However, the results of recent studies have questioned. the NICE-SUGAR study and the Glucontrol study compared the difference between applying insulin to control blood glucose at 4.44-6.10 mmol/L and 7.77-9.99 mmol/L. The Glucontrol study was forced to be terminated prematurely, and enrolled more than 1,100 patients, with the incidence of hypoglycemia and the occurrence of at least 1 severe hypoglycemia in the intensive treatment group. In the intensive treatment group, the incidence of hypoglycemia and the rate of death due to at least one severe hypoglycemic event were significantly higher; there was no significant difference between the two groups in terms of important prognostic indicators, and glycemic control of 7.77-9.99 mmol/L was safer than that of 4.44-6.10 mmol/L. The results of the NICE-SUGAR study confirmed that the rate of severe hypoglycemia increased significantly with glycemic control of 4.50-5.99 mmol/L, and that glycemic control ≤4.50-5.99 mmol/L was significantly higher. NICE-SUGAR study results confirmed that the incidence of severe hypoglycemia increased significantly when the blood glucose control was 4.50~5.99 mmol/L, and the death rate of ICU patients could be reduced when the blood glucose was ≤9.99 mmol/L. Therefore, in 2009, the American Association of Clinical Endocrinologists (AACE) and the American Diabetes Association (ADA) jointly issued a consensus statement on diabetes and glycemic control in hospitalized patients, recommending that most critically ill patients should have their blood glucose controlled between 7.8 and 10 mmol/L, depending on the patient's specific condition, but patients with blood glucose <6.1 mmol/L or >10 mmol/L are are unacceptable. Therefore, clinicians have adopted this range as the glycemic control goal for critically ill patients. Diabetes mellitus has a “protective” effect on critically ill patients It was previously believed that diabetes mellitus was closely related to the increase in the mortality rate of patients in the intensive care unit (ICU), especially for surgical intensive care patients, diabetes mellitus is one of the risk factors for poor prognosis, which is important because of the multiple chronic complications of diabetes mellitus will seriously affect the normal metabolism and stress function of the organism. stress function. However, in recent years, more and more evidence has shown that diabetes is not an independent risk factor for mortality in patients with critical illnesses, and some studies have even suggested that hyperglycemia may increase the risk of mortality in critical illnesses only in patients without a history of diabetes mellitus, so that the relationship between diabetes mellitus and prognosis of critical illnesses has been reexamined, and diabetes mellitus does not necessarily increase the rate of mortality in patients with ICU, and diabetic status may even be a a predictor of decreased morbidity and mortality in ICU patients. Possible mechanisms for the potential “protective” effect of diabetes against acute stress in critical illness include: adaptive response of diabetes to chronic oxidative stress; decreased incidence of critical illness complications in diabetic patients; and non-biological protective factors. However, the pathophysiology of the “protective” mechanism of diabetes against critical illnesses is still being explored, so we only believe that diabetes may enhance the body’s ability to fight against the acute shock through some kind of “protective” effect. However, the balance between the chronic cumulative damage caused by diabetes and this potential “protection” when critical illness occurs still deserves further analysis and exploration. As pointed out in the study by Graham et al, the increased mortality rate of diabetic patients with acute myocardial infarction compared with those without a history of diabetes may be due to the chronic damage caused by diabetes to the coronary arteries. This may be due to the fact that the chronic damaging effects of diabetes on the coronary arteries outweigh the potential “protection” during acute stress. We believe that patients without a history of diabetes need stricter glycemic control, and it is more reasonable to control their blood glucose target between 6.1 and 7.8 mmol/L, while the glycemic target for diabetic patients is still 7.8-10 mmol/L. VIII. The effect of the magnitude of change in blood glucose concentration Egi et al. retrospectively analyzed the data on 7,049 critically ill patients, and found that the magnitude of change in glucose was significantly lower in survivors than in those who died, and that the magnitude of change in glucose was significantly lower in patients who died. significantly lower than those who died, and the results of statistical analysis suggest that the magnitude of blood glucose changes is closely related to the survival rate. In diabetic patients, the magnitude of change in blood glucose level is a better predictor of ICU mortality than absolute blood glucose values. In previous studies conducted on critically ill patients, the effect of the magnitude of blood glucose variation on patients was not analyzed. In the Glucontrol study, the range of blood glucose fluctuations was essentially the same in both treatment groups. Nine, the impact of blood glucose testing methods In the ICU, capillary blood glucose values measured by fingertip blood collection are most often used to monitor blood glucose and regulate insulin dosage. However, the measured blood glucose value is not very reliable, especially for patients in shock. Shock-induced microcirculatory disorders, whether low perfusion or no re-flow state, can lead to stagnation of blood flow, so that the tissue uptake of glucose increased, causing a decrease in peripheral whole blood glucose, especially in infectious toxic shock, the phenomenon of high catabolism is particularly prominent. Although hemorrhagic shock can cause a decrease in erythrocyte pressure volume and an increase in whole blood glucose values, this is insignificant compared to the large peripheral glucose uptake. In addition, capillary leakage is present in many patients during shock, and the subcutaneous blood component of the patient is significantly lower than the blood component of the blood vessels, and the tissue fluid component is significantly higher than the tissue fluid component of the blood, so that the glucose value measured by rapid glucose meter is significantly lower than that measured in the laboratory. Therefore, under the state of shock, the monitoring of blood glucose prioritizes arterial blood, followed by venous blood, and tries to avoid peripheral microcirculation blood glucose monitoring.