After the first infusion of normal saline, the second step is to continue to give normal saline or change to semi-normal saline according to the blood sodium concentration. The latter should be added to the same amount of physiological saline as distilled water for injection, and then it can be changed to 1/3 tablets or sugar-free continuous solution. Potassium salt can be added 3 ~ 6 mmol/kg when urinating by infusion.
After blood transfusion and insulin administration, ketone bodies can be metabolized to produce HCO3-. When the blood pH is above 7.2, it is generally unnecessary to inject sodium bicarbonate to correct acidosis, nor should sodium lactate be used to correct acidosis. When the blood pH is less than 7.2, the acidosis must be corrected with isotonic (1.4%) sodium bicarbonate, and the required amount of sodium bicarbonate is calculated by the following formula:
HCO3 supplement =( 15- measured HCO3-)×kg (body weight )× 0.6.
At first, give half of the calculated amount, 1 ~ 2 hours. The more serious the acidosis is, the slower the input speed of alkali solution should be. When the blood pH is still below 7.2, an allowance will be given. Generally, the input speed of NaHCO3 should not exceed 2 ~ 3 mmol/kg every 2 hours. For example, too fast or too much NaHCO3 input can cause hypernatremia and alkalosis, because NaHCO3 passes through the blood-brain barrier slowly, while CO2 permeates quickly. If acidosis is corrected too quickly, alkalosis, hypokalemia and central nervous system acidosis will make the reaction more serious or cause death.
(2) In the application of insulin in diabetic ketoacidosis, it is best to use low-dose insulin for continuous intravenous drip, and calculate the dosage for 3-4 hours according to the insulin amount of 0. 1u/kg/ hour, add it into 180-240 ml physiological saline, and use another infusion bottle for even intravenous infusion. The infusion speed can be controlled by the infusion pump, so it can be kept at 65438 0 ml per minute or controlled at an hourly rate. Infants under 4 years old are sensitive to insulin, and the dosage of insulin can be reduced to 0.05u/kg per hour. If the blood sugar is more than 28 mmol/L (more than 500 mg/DL), the dosage can be 0. 15u/kg per hour. Or when the blood sugar can't drop to more than 20% of the blood sugar before treatment after 2 hours of insulin infusion, the dosage of insulin can be increased to 0. 15u/kg per hour, and the blood sugar can be rechecked after 1 hour. Generally speaking, after intravenous injection of insulin, blood sugar tends to drop at a quiet slope, but everyone drops at a different speed. Blood sugar should be monitored every 1 ~ 2 hours when insulin is injected intravenously. When the blood sugar is greater than 14 mmol/L (250 mg/DL), sugary liquid should not be infused, but when the blood sugar is less than or equal to 14 mmol/L (250 mg/DL), grape liquid should be added, and at the same time, 2u insulin should be infused from two infusion bottles at a fixed ratio every 5g of glucose, so that the blood sugar can be maintained at 8. Use 2.5 ~ 5% glucose, and give insulin 1.5 ~ 2.5U per 5g glucose, so as to keep the blood sugar at least above 5.6 ~ 8.4mmol/l (100 ~150mg/dl). With the decrease of blood sugar, the speed of intravenous insulin infusion should be slowed down to 0.02 ~ 0.06 U/kg per hour. At the same time, sugar-containing liquid should continue to be infused until ketoacidosis is completely corrected. Check blood sugar first, and then inject insulin subcutaneously 0.25u/ time. After half an hour, stop all infusion, eating or drinking.
After the acute stage of ketoacidosis, patients began to eat. On the first day, the amount of insulin injected subcutaneously was calculated as1u/(kg d), and it was injected in four times, at morning, noon, evening and before going to bed. At the same time, the dosage of insulin can be determined according to the blood sugar level produced by stopping intravenous injection of insulin. See Table 3 120 for the calculated dosage. The first subcutaneous injection of insulin can also be calculated by weight according to clinical experience, 20 ~ 30kg4u, ~ ~40kg6u, ~ ~50kg8u, ~ ~60kg 10u. Adjust the dosage of the next day according to blood sugar or urine sugar after injection. Routine insulin can be injected 3 ~ 4 times a day or RI+NPH2 twice.
5. Hypertonic state (MH) is defined as serum osmotic pressure > 3 10 mmol/L, and the blood sugar of many children with IDDM ketoacidosis can be as high as ≥33.6mmol/L(600mg/dl). At this time, hypertonic state may occur, mostly mild osmotic pressure increase.
Pathological hypertonic state (MH) refers to plasma osmotic pressure > 375 mmol/L and blood sugar > 78.4 mmol/L (65 65,438+400 mg/DL), which is life-threatening and has a high mortality rate. Children's morbid hyperosmotic disease is often caused by central nervous system injury, which makes patients easily stimulated, thirsty and drink a lot of fruit juice or soda water. When these patients are considered to have diabetes, they may delay the necessary treatment and die.
When the patient only has a slight increase in plasma osmotic pressure, and the patient has cerebral hyponatremia, the blood sugar is not very high, but there may be brain edema, such patients should also be treated as pathological hyperosmotic. For those who have brain edema but no plasma osmotic pressure increase and hyperglycemia, but have a history of drinking water or hypotonic liquid, they should also be treated as pathological hypertonic as soon as possible. MH in IDDM patients can be ketotic or non-ketotic, and the importance of measuring plasma osmotic pressure can not be ignored.
Pathological hypertonic state has a high mortality rate, which can cause disseminated intravascular coagulation and is extremely difficult to treat. Due to severe dehydration, acute renal failure may occur and peritoneal dialysis is needed. The mortality rate of patients with ketoacidosis and hyperosmotic blood is lower than that of patients without ketoacidosis and hyperosmotic blood.
Monitoring of patients with morbid hypertonic diseases: patients with morbid hypertonic diseases are often in a coma, suggesting that patients have central nervous system damage. When serum osmotic pressure rises, brain cells dehydrate, which can rupture meningeal blood vessels, cause subdural hemorrhage, increase blood viscosity and appear shock. Ignorance can cause arteriovenous embolism, and disseminated intravascular coagulation can cause bleeding. Finally, due to too much hypotonic fluid and insulin input, blood sugar and plasma osmotic pressure may drop too fast, leading to brain edema and increased intracranial pressure. Because the condition of morbid hypertonic state is complex and critical, intracranial pressure should be monitored clinically. If brain edema is diagnosed only from the examination of clinical nervous system, it is the late stage of brain edema. If the pressure outside the intestinal membrane is monitored by computer at the same time of treatment. Although this method is invasive and dangerous, it is extremely useful for MH, because the danger is small when handled carefully.
Evaluation of blood volume: Too fast blood expansion in MH patients will cause brain edema, and too slow will increase renal anuria and aggravate acidosis. When expanding blood volume and reducing shock, monitoring central venous pressure can provide the condition of body fluids and the tension of heart function, indirectly prevent too much or too little body fluids from flowing to the kidneys, and guide doctors to correctly infuse. The measurement of central venous pressure is also useful for monitoring blood pressure, which is very important for treating MH patients.
Treatment of morbid hypertonic;
(1) The purpose of electrolyte and liquid infusion is to make patients wake up from shock and make internal organs have proper liquid perfusion.
(2) Gradually restore the normal plasma osmotic pressure to prevent the occurrence or aggravation of brain edema.
In order to achieve the above goals, it is necessary to monitor arterial blood pressure, hard brain pressure and urine volume, and analyze their interaction. Proper fluid replacement can keep the central venous pressure in the normal range. If the treatment causes the intracranial pressure to increase, it is necessary to take excessive breathing, barbiturate coma and raising the head position to reduce the intracranial pressure.
In the treatment of morbid hypertonic, it is agreed that isotonic solution or hypertonic solution should be used to dilute blood glucose concentration, rather than hypotonic solution, because hypotonic solution can cause severe brain edema when plasma osmotic pressure is low. The osmotic pressure of the input liquid should be only 40mmol/L lower than that of the patient's plasma. If the patient's plasma osmotic pressure is 370mmol/L, the osmotic pressure of the input fluid should be 330 mmol/L. This fluid is prepared by adding 20 ~ 40 mmol/L potassium chloride to physiological saline and adding a small amount of 5%NaHCO4 to the solution, but it should be prevented from alkalosis, and NaHCO3 should not be used when there is no acidosis. The infusion volume should meet the needs of moderate perfusion to prevent the adverse consequences caused by low perfusion, but the infusion volume should not be too large to prevent the irreversible development of brain edema. According to recent research, the total body fluid lost and maintained within 24 hours should be less than 4L/m2 body surface area, and the effect of supplementing body fluid in 48 ~ 72 hours is better than that in 24 hours.
When insulin is used in MH, it is necessary to reduce the glucose pressure, but the speed should not be too fast, so that blood sugar can quickly enter the muscle and adipose tissue with insulin injection, which will change the inflation pressure gradient. The effect of osmotic pressure reduction is mainly in extracellular fluid space. Hypotonia can cause cells to absorb water, leading to edema of the central nervous system. Because children with MH are often insulin dependent, insulin must be used, but the dose must be small, 0.05u/kg per hour, and 0.02 U/kg； per hour for children under 4 years old; If you use this amount, you can also reduce the amount of insulin when the blood sugar rate is still falling rapidly. Some people even advocate giving insulin later to reduce the risk of brain edema. When the blood sugar drops sharply to < < 250mgdl due to the use of insulin, brain edema will occur. After the blood sugar gradually drops slowly, if appropriate insulin is used to maintain this level, the possibility of brain edema is less. Whether insulin is used in non-ketotic hypertonic state is controversial, while ketotic hypertonic state agrees to use dose insulin for treatment.
etiology
At present, it is generally believed that IDDM leads to the damage and destruction of B cells on the basis of genetic susceptibility genes, and eventually leads to the failure of islet B cells. However, there are still many problems in the above factors that cannot be completely explained. According to the current research results, it is summarized as follows:
1. Genetic factors IDDM and NIDDM have different heritability. According to the study of identical twins, it is proved that the consistency of NIDDM is 100%, while the consistency of IDDM is only 50%, which shows that IDDM is a polygenic genetic disease with both environmental and genetic factors.
2. Environmental factors For many years, it has been reported that the incidence of IDDM is related to the infection of many viruses, such as rubella virus, adenovirus disease, coxsackie virus and brain myocardial virus. There is not enough evidence in animal experiments to prove that virus infection or chemical toxins such as streptozotocin and alloxan can directly destroy islet B cells and produce diabetes. Genetically sensitive animals can develop diabetes only by feeding. In a word, environmental factors, including virus infection, chemical poisons in the environment and some components in nutrition, may produce B cell toxicity to people with susceptible genes, stimulate changes in immune function in vivo, and eventually lead to IDDM. The complexity of environmental factors may play an important role in the difference of IDDM incidence among different ethnic groups in different regions. In addition, severe mental and physical stress, infection and stress may play an important role in the difference of IDDM incidence. In addition, severe mental and physical stress, infection and stress can obviously worsen the metabolism of IDDM. Stress can produce insulin resistance, increase blood sugar and make some susceptible people suffer from ketoacidosis.
3. Immunological factors first found that patients with newly diagnosed IDDM had acute lymphocytic and chronic lymphocytic infiltrative insulitis, and then found that there were many autoantibodies such as anti-islet cell antibody (ICA), anti-islet cell surface antibody (ICSA) and anti-insulin antibody in the blood of patients with IDDM, and now they tend to think that ICA antibody is the result of islet cell destruction. It is also found that lymphocytes of patients can inhibit insulin release from islet B cells. The ratio of helper T cells to inhibitory T cells increased, and K killer cells increased. In addition, it is also proved that there are a series of functional receptors on the surface of patients' T lymphocytes, and the immune function changes such as the increase of Ia antigen T lymphocytes. Different theories have been put forward about the mechanism of immune function change. In a word, the change of immune function in IDDM patients is an important link in its pathogenesis.
According to different causes, childhood diabetes can be divided into the following categories:
1. Insulin-dependent diabetes (IDDM) is called type I diabetes. It is divided into two subtypes: type ia and type IB. Type ia refers to the onset due to genetic factors, immune factors and environmental factors, represented by IDDM. Type IB refers to IDDM in familial autoimmune diseases and belongs to a part of autoimmune diseases. This paper mainly studies type ia IDDM (hereinafter referred to as IDDM).
2. Non-insulin dependent diabetes mellitus (NIDDM), also known as type II diabetes mellitus, can be divided into obesity type and obesity type. In the past, when NIDDM occurred in childhood, it was called youny's mature diabetes (MODY), and the word MODY was not completely abandoned. This is autosomal dominant inheritance. However, there are also sporadic cases of type II diabetes in children.
3. Malnutrition-related diabetes mellitus (MRDM), accompanied by pancreatic fiber calcification or islet calcification and a history of protein deficiency.
4. Other types include pancreatic diseases, endocrine diseases, diabetes directly caused by drugs or chemicals, and sugar diseases caused by some genetic syndromes and abnormal insulin receptors.
5. Most diabetes in childhood (more than 90%) is insulin-dependent diabetes 1A (IDDM, 1A). Ia dependence means that patients must receive insulin injection to prevent coma and death from diabetic ketoacidosis.
pathogenesis
The destruction of islet B cells in IDDM leads to metabolic disorder. Tryptophan has a wide range of effects on energy metabolism, activating surface receptors of target cells, promoting intracellular glucose transport, directly converting glucose into glycogen, promoting fat synthesis and inhibiting fat members. Tryptophan can also enhance the synthesis of protein and promote the growth and differentiation of cells. Promote glycolysis and inhibit gluconeogenesis. There is a lack of tryptophan in IDDM patients, and the secretion of tryptophan after meals does not increase. After the postprandial blood sugar rises, it cannot be lowered. When the blood sugar exceeds the renal sugar threshold, urine sugar appears, energy in the body is lost, the mobilization of fat catabolism increases, and ketone body production increases. Because the lack of tryptophan can damage growth, the weight has dropped before symptoms such as polyuria and excessive drinking appear.
In addition, the increase of anti-regulatory hormones such as glucagon, adrenaline and cortisol envelope growth hormone in diabetes aggravated metabolic disorder and made diabetes develop into a state of decompensation. Anti-regulatory hormones promote glycogen decomposition, gluconeogenesis increases, fat decomposition is vigorous, and various fat intermediates and ketone bodies are produced. Hyperglycemia, hyperlipidemia and hyperketonemia cause osmotic diuresis, which leads to polyuria, dehydration and acidosis. Due to the increase of plasma osmotic pressure, thirst and excessive drinking are produced, and the weight is obviously reduced.
When ketosis is caused by ketosis, brain function is damaged, oxygen utilization rate is reduced, drowsiness and consciousness disorder gradually appear, and gradually enter a coma. When acidosis is severe, CO2 is stored. In order to expel more CO2, the respiratory center is excited and irregular deep breathing (Kussmause breathing) occurs. Acetone in the breath will produce a special smell (rotten fruit smell).
epidemiology
Due to regional and ethnic factors, the incidence of IDDM varies greatly. The highest prevalence rate in Europe and America can reach 100 ~ 200/65438+ 10,000 people. In China, the prevalence of diabetes in children under 4 years old in 1980 is 5/ 140000. IDDM can occur at any age before the age of 30, and the youngest confirmed case we have ever seen is a baby of 10 month. There is no farewell between men and women. In recent years, cases of children diagnosed with NIDDM can be seen occasionally, and the number of obese children in China is increasing. Patients with impaired glucose tolerance should be followed up for early diagnosis of NIDDM.
clinical picture
IDDM usually begins with acute symptoms. Most patients may have symptoms such as excessive drinking, excessive urination, excessive eating and weight loss due to infection, emotional excitement or improper diet. These symptoms are called "three more and four less symptoms" of IDDM. However, the baby is not easy to be found because of excessive urination and drinking, and dehydration and ketoacidosis will soon occur. Due to the increase of nocturia, infants may suffer from enuresis. Overeating is not an inevitable symptom of patients, and some children have normal or decreased appetite. Weight loss or emaciation is rapid, and fatigue and listlessness are also common. If you have polydipsia, polyuria, vomiting, nausea, anorexia or abdominal pain, diarrhea and leg pain, you should consider diabetic ketoacidosis. Fever, cough and other respiratory infections or skin infections, vaginal itching and tuberculosis can coexist with diabetes.
There are generally no positive signs except weight loss and emaciation during physical examination. When ketoacidosis occurs, deep breathing, ketone body odor, dehydration and mental changes may occur. If the course of disease is long, poor control of diabetes will lead to growth retardation, short stature and mental retardation, and the liver is called diabetic dwarf syndrome. Cataracts, visual impairment, retinopathy and even blindness may occur in the late stage. Diabetic nephropathy such as proteinuria and hypertension can also occur, which eventually leads to renal failure.
Natural process: the process of IDDM has a certain development law. The time from symptoms to clinical diagnosis is mostly within 3 months. There are various symptoms in this period, which is called acute metabolic disorder period. About 20% of them are diabetic ketoacidosis, 20 ~ 40% are diabetic ketoacidosis, and there is no acidosis. All that's left is hyperglycemia and polyuria. All patients need insulin treatment. After treatment, symptoms disappear, blood sugar drops, urine sugar decreases "+"and becomes "-",that is, it enters remission period, when insulin demand decreases for several weeks to several years. The remission period of a few patients is not obvious. After remission, patients will gradually enter the intensive period of diabetes, and the insulin dosage is relatively stable, which is called permanent diabetes. In adolescence, due to the increase of sex hormones and the antagonism to insulin, the dosage of insulin increased again, and the condition was unstable. After puberty, the demand for insulin decreases and the condition tends to be stable. Whenever there is infection or stress, the condition will deteriorate rapidly.
complication
Acute complications The most common acute complications of IDDM are diabetic ketoacidosis (DKA) and hypoglycemia. The former is insulin deficiency and the latter is insulin excess. There are also various infections that may occur at any time.
Patients with 1.IDDM may develop ketoacidosis due to acute infection, delayed diagnosis, overeating or interruption of insulin therapy, and their clinical manifestations are as described above. The younger the age, the higher the incidence of ketosis. Patients with new IDDM ketoacidosis can be misdiagnosed as pneumonia, asthma, septicemia, acute abdomen and meningitis, and should be differentiated. In ketoacidosis, blood sugar can be increased by > 28.0 mmol/L (500 mg/dl), and blood ketone body can be increased by > 65,438+00 mmol/L (200 mg/DL). There are not only acetoacetic acid, β -hydroxybutyric acid and acetone in blood ketone bodies, but also many ketone bodies as intermediates of fatty acid metabolism, such as α -pentanone and 3- pentene 2. The disorder of fat metabolism in patients with diabetic ketoacidosis is more complicated. When ketoacidosis occurs, the blood pH value decreases, HCO3- decreases, and the blood sodium, potassium and chlorine are also lower than normal. Some blood potassium is not low before treatment, and potassium quickly enters potassium after insulin treatment. Qualitative test of urine ketone body All ketone body powders are nitrohydrocyanic acid, which should react with acetoacetic acid, but not with ketone bodies and fatty acids such as β -hydroxybutyric acid. The positive reaction of urine ketone body test can be weak positive or (-). After preliminary treatment, the production of acetoacetic acid increased, but the reaction of urine ketone body increased.
2. Hypoglycemia diabetes occurs after insulin therapy, because the dosage of insulin is too large or you can't eat on time after insulin injection, which leads to palpitation, sweating, hunger, dizziness and tremor. In severe cases, hypoglycemia coma and even convulsions may occur; Failure to rescue in time will lead to death. Repeated hypoglycemia attacks can cause brain dysfunction or epilepsy.
3.IDDM infection is a lifelong disease, and various infections may occur at any time, including acute and chronic infections such as respiratory tract, urinary system and limbs. Whenever there is a mild cold, the condition can be aggravated, and toxic shock can occur when there is a serious infection. If we only pay attention to the treatment of infection and ignore the diagnosis and treatment of diabetes, we should be vigilant.
4.IDDM is rare in children with diabetic hyperosmolar nonketotic coma, and most patients have nervous system diseases first. When diagnosed as diabetic hyperosmotic nonketotic coma, diabetic patients must have hyperglycemic nonketotic coma, which should be distinguished from iatrogenic hyperglycemic osmotic coma caused by hypertonic glucose saline injection. In diabetic osmotic coma, blood sugar is often > 28 ~ 54 mmol/L (500 mg ~1000 mg/DL), blood sodium is > 145 mmol/L, and plasma osmotic pressure is > 3 10 mmol/L, sometimes reaching > 370 mmol/L. There is no need for acidosis, isotonic solution or hypertonic solution lower than plasma osmotic pressure of 40mmol/L(20mosm/L), such as hypertonic solution > 330 mmol/L when plasma osmotic pressure is > 370 mmol/L (370 mosm/ng). The dosage of insulin should be small, and the speed of lowering blood sugar should be slow to prevent brain edema caused by rapid drop of blood sugar and rapid drop of plasma osmotic pressure. The mortality rate of this disease is very high.
accessory examination
1. Urine sugar is usually positive. In recent years, urine sugar test paper has been used to compare urine sugar with standard color. When there is no test paper, still use 9 drops of ketone sulfate reducing reagent (Banteay's solution) to add fresh urine 1, and do not boil urine sugar. Results Blue is (-), green is (+), yellow is (++), orange is (++), and brick color is (++). At the beginning of treatment, urine sugar was left four times a day in the morning, at noon, at night and before going to bed, and the bladder was emptied 30 minutes before each urine leave, and then urine test was carried out. Urine sugar can indicate blood sugar during the second urine leave. During the acute disorder period, urine sugar should be left for four periods, that is, after breakfast to before meals, after lunch to before dinner, after dinner to before bed, after sleep to before breakfast the next day. Leave urine for four periods, record urine volume, check urine sugar and urine ketone body. The results of the four-level urine test are 24-hour urine volume and urine sugar, which can help us to know the basis of insulin in detail. We should also regularly (2 ~ 4 weeks) determine the 24-hour urine glucose quantification.
In diabetic ketosis or ketoacidosis, urine ketone body is positive, and sometimes urine protein is positive.
2. Blood routine examination is normal, and the total number of white blood cells in ketoacidosis is increased. Blood sugar test showed that the blood sugar of untreated IDDM was greater than11mmol/l (> 200mg/dl), and the fasting blood sugar of mild IDDM was greater than 6.7 mmol/L (120 mg/DL). When blood sugar is out of control, various fat components in the blood increase.
3. Those with positive urine glucose and high fasting blood glucose in glucose tolerance test can definitely diagnose diabetes, and glucose tolerance test is not needed. This test is used for patients whose fasting blood sugar is normal or higher than the normal limit, postprandial blood sugar is higher than normal or occasionally urine sugar is positive, and can not be diagnosed. Methods: After fasting for 8 ~ 16 hours, fasting blood glucose was measured first, and then oral glucose was taken (1.75g/kg). The maximum amount of glucose is 75g, 2.5ml of water is added to each gram, and it is taken orally within 3 minutes (sugar-free juice can be added for tolerance). Blood sugar was measured 1/2, 1, 2, 3 hours after glucose, and urine was taken before each blood collection. Results: The normal fasting blood glucose was 4.4 ~ 6.7 mmol/L (80 ~120 mg/dl), and the blood glucose after taking sugar was 8.4 ~10.08 mmol/L (150 ~ 6550). Impaired glucose tolerance (IGT) (called diabetes curve in the past) is that fasting blood glucose is > 6.7 mmol/L (120 mg/DL), 1 hour ≥10.08 mmol/L (180 mg/DL), and 2 hours ≥ 7. Sugar should not be less than 150g every day for 3 days before the test. Avoid strenuous exercise and mental stress before the exam, and stop using drugs that affect glucose metabolism, such as dihydrothiazide and salicylic acid.
4. Glycosylated hemoglobin (HbA 1) is formed by non-enzymatic combination of hemoglobin with blood sugar or phosphorylated glucose in red blood cells. Its main component is HbA 1c, which is mainly combined with glucose. The HbA 1c of normal people is 4 ~ 6%. Before treatment, the number of diabetic patients doubled, often exceeding 12%. After treatment, it is better for IDDM patients to be below 9%, and the highest should be below 10%.
prevent
Because of the characteristics of immune changes in IDDM, such as the relationship between the onset and HLA susceptibility, the cellular infiltration of insulin and the appearance of anti-islet cell antibodies in the early stage of onset, and the abnormal proportion of T cell subtypes, frog IDDM is an autoimmune disease. For these reasons, it is urgent to take immunotherapy for newly diagnosed patients, especially those who have just started hyperglycemia. Studies on mice can be infected by viruses injected into the body, and mice can have an immune process similar to human IDDM's insulitis. If we can provide some protection for these virus infections, animals can avoid chronic infections and are expected to be used in humans in the future.
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