[Neuroprotector therapy of patients with decompensated diabetes mellitus type 1].

The influence of actovegin and reamberin on diabetic ketoacidotic crises has been studied on a group of 128 patients with severe diabetic ketoacidosis on the background of diabetes mellitus type 1 with disorders ranging from consciousness to coma or precoma states. Patients of group 1 received standard intensive therapy of diabetic ketoacidosis. In group 2, an intensive therapy for neuroprotection by actovegin was added. In group 3, patients received reamberin on the background of standard therapy. In group 4, the neuroprotective therapy using actovegin and reamberin was combined. The mental status was estimated upon recovery from coma, on 5th and 28th days from the beginning of treatment, by taking into consideration cognitive functions such as attention, memory, mentality. The results showed that the use of neuroprotective drugs, including the combination of actovegin and reamberin, allowed to the restore the compensatory-adaptive reaction of patients to ketoacidotic crisis, accelerate the restoration of consciousness within 19.2 +/- 3.8 h, restore the cognitive functions with exceeding norm for patients with diabetes mellitus in compensation stage and maintain their high level on 28th day after crisis.

Studies on mechanisms of cerebral edema in diabetic comas. Effects of hyperglycemia and rapid lowering of plasma glucose in normal rabbits.

To investigate the pathophysiology of cerebral edema occurring during treatment of diabetic coma, the effects of hyperglycemia and rapid lowering of plasma glucose were evaluated in normal rabbits. During 2 h of hyperglycemia (plasma glucose=61 mM), both brain (cerebral cortex) and muscle initially lost about 10% of water content. After 4 h of hyperglycemia, skeletal muscle water content remained low but that of brain was normal. Brain osmolality (Osm) (343 mosmol/kg H(2)O) was similar to that of cerebrospinal fluid (CSF) (340 mosmol/kg), but increases in the concentration of Na+, K+, Cl-, glucose, sorbitol, lactate, urea, myoinositol, and amino acids accounted for only about half of this increase. The unidentified solute was designated "idiogenic osmoles". When plasma glucose was rapidly lowered to normal with insulin, there was gross brain edema, increases in brain content of water, Na+, K+, Cl- and idiogenic osmoles, and a significant osmotic gradient from brain (326 mosmol/kg H(2)O) to plasma (287 mosmol/kg). By similarly lowering plasma glucose with peritoneal dialysis, increases in brain Na+, K+, Cl-, and water were significantly less, idiogenic osmoles were not present, and brain and plasma Osm were not different. It is concluded that during sustained hyperglycemia, the cerebral cortex adapts to extracellular hyperosmolality primarily by accumulation of idiogenic osmoles rather than loss of water or gain in solute. When plasma glucose is rapidly lowered with insulin, an osmotic gradient develops from brain to plasma. Despite the brain to plasma osmotic gradient, there is no net movement of water into brain until plasma glucose has fallen to at least 14 mM, at which time cerebral edema occurs.

Red-cell aggregation and red-cell deformability in diabetes.

The anomaly of the viscosity of human blood is more pronounced in diabetics. This is caused by an increase in plasma viscosity, a more pronounced red-cell aggregation, and a reduction of individual cell deformability. The changes in viscosity and in red-cell aggregation both are the consequence of abnormal plasma proteins, the incidence of which is largely independent of the onset and duration of disease, and actual metabolic state. The presence of complicating infectious diseases further aggravates the pathologic red-cell aggregation. The decreased red-cell deformability is largely independent on onset, duration, and complications but depends critically in the incident metabolic control of the diabetics. The possible role of hemorrheologic factors in the development of microangiopathy is discussed.

Profound hypokalemia in diabetic ketoacidosis: a therapeutic challenge.

OBJECTIVE: To describe profound hypokalemia in a comatose patient with diabetic ketoacidosis. METHODS: We present a case report, review the mechanisms for the occurrence of hypokalemia in diabetic ketoacidosis, and discuss its management in the setting of hyperglycemia and hyperosmolality. RESULTS: A 22-year-old woman with a history of type 1 diabetes mellitus was admitted in a comatose state. Laboratory tests revealed a blood glucose level of 747 mg/dL, serum potassium of 1.9 mEq/L, pH of 6.8, and calculated effective serum osmolality of 320 mOsm/kg. She was intubated and resuscitated with intravenously administered fluids. Intravenous administration of vasopressors was necessary for stabilization of the blood pressure. Intravenous infusion of insulin was initiated to control the hyperglycemia, and repletion of total body potassium stores was undertaken. A total of 660 mEq of potassium was administered intravenously during the first 12.5 hours. Despite such aggressive initial repletion of potassium, the patient required 40 to 80 mEq of potassium daily for the next 8 days to increase the serum potassium concentration to normal. CONCLUSION: Profound hypokalemia, an uncommon initial manifestation in patients with diabetic ketoacidosis, is indicative of severe total body potassium deficiency. Under such circumstances, aggressive potassium repletion in a comatose patient must be undertaken during correction of other metabolic abnormalities, including hyperglycemia and hyperosmolality. Intravenously administered insulin should be withheld until the serum potassium concentration is (3)3.3 mEq/L.

Hyperosmolar nonketotic coma in the elderly diabetic.

The gravity of this syndrome of severe diabetic stupor without ketosis may not be recognized because patients are usually middle-aged or elderly with mild diabetes. A lack of urgency in treating these patients is probably the cause of the widely reported mortality of 40 to 70 per cent.

Diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic coma.

Diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic coma are two of the most common acute complications of diabetes. The pathophysiologic changes that occur in both disease states represent an extreme example of the super-fasted state. The physiology of the fed and fasted state, evaluation, therapeutic issues, recommendations for therapy, immediate follow up care, and complications of therapy are reviewed for both syndromes.

A review of hypersomolar hyperglycemic nonketotic dehydration (HHND): etiology, pathophysiology and prevention during intravenous hyperalimentation.

The records of 200 patients, nutritionally supported by synthetic means, were reviewed for evidence of clinical hyperosmolar hyperglycemic nonketotic dehydration (HHND). There was a 3% incidence of morbidity, with a single mortality. Laboratory values demonstrated a positive correlation between persistent glucosuria and HHND. The pathophysiology of HHND demonstrated a relative insulin lack with sufficient insulin to prevent lipolysis, but insufficient to prevent hyperglycemia, glucosuria and osmotic diuresis. The mechanism and management of the pseudodiabetes of stress is reviewed. It is concluded that HHND is an avoidable iatrogenic morbidity. Prevention of osmotic diuresis secondary to glucosuria and, therefore, prevention of HHND is achieved by providing exogenous insulin sufficient to prevent glucosuria.

Hyperosmolar nonketotic diabetic coma: diagnosis and management.

Hyperosmolar nonketotic diabetic coma (HHNC) is a syndrome of acute decompensation of diabetes mellitus, occurring mainly in the elderly and characterized by marked hyperglycemia, hyperosmolarity, severe dehydration, occasional neurological signs, obtunded sensorium, and absence of ketonemia or acidosis. The mortality is high. Early aggressive therapy with large amounts of normal or half normal saline, insulin, and potassium is of prime importance. Since associated diseases cause most fatalities the importance of managing these problems effectively cannot be overemphasized. Complications of therapy can be congestive heart failure secondary to excessive fluid administration, hypoglycemia if too much insulin is given, and hypokalemia if potassium is inadequately replaced.

[Hyperosmolar diabetic coma. Case reports and review of the literature]. / Coma diabetico iperosmolare. Contributo casistico e revisione della letteratura.

The physiopathology and clinical picture of hyperosmolar diabetic coma are described, and four personal cases are presented. This form of coma is a rare, but particularly serious complication of diabetes mellitus. Since its prognosis is poor, even when suitable treatment is provided, the greatest possible care should be devoted to preventing its main cause, namely dehydration.

Hyperosmolar syndrome and diffuse CNS dysfunction with clinical implications.

In an electrophysiological study, hyperosmolality damaged the central nervous system including the cerebral cortex, hippocampus, midbrain reticular formation, pyramidal pathway, extrapyramidal pathway and anterior horn cells, and peripheral nervous system. In the experimental model in which acute changes were made, sodium ion concentration was related to the dysfunction of reticular formation. In the clinical setting, hyperosmolality with hyperglycemia is related to the individual's level of consciousness. In the clinical management of hyperosmolar syndromes, plasma osmolality should be kept below 320 mOsm/L.

[Pathophysiology and therapy of diabetic ketoacidosis and of non-ketoacidotic hyperosmolar diabetic coma]. / Pathophysiológie und Therapie der diabetischen Ketoazidose und des nicht-ketoazidotischen hyperosmolaren Coma diabeticum.

Metabolic derangements in diabetic coma are the sequelae of insulin deficiency. These defects are aggravated by the actions of insulin counteracting ("diabetogenic") hormones and hypertonic dehydration, which both impair insulin action. Conversely, it has been shown that hypo-osmolar rehydration of a hyperosmolar, severely hyperglycaemic diabetic patient reduces insulin resistance and restores biological responsiveness of previously dehydrated insulin-dependent tissues towards insulin. Thus treatment of diabetic coma requires appropriate fluid and electrolyte replacement as a life-saving emergency action alongside insulin replacement. The use of proper rehydration during the past decade might also explain the reported fall in the insulin requirement for the treatment of diabetic coma from approximately 1,000 units per coma to low-dose insulin therapy. In order to guarantee proper treatment of severe hyperglycaemia and normalization of the hyperosmolar state, we feel that hypo-osmolar rehydration has to be initiated in parallel with low-dose insulin therapy (5 to 6 U/h) to restore the physiological response of the respective target tissues to insulin action and to ameliorate glucose utilization. This approach probably avoids a too rapid fall in plasma osmolarity, minimizes the risk of cerebral oedema and hypokalaemia, and improves survival. The development of severe diabetic ketoacidosis or of hyperosmolar non-ketotic diabetic coma should be prevented by advice to patients on the importance of metabolic monitoring, which can be done by proper self-monitoring of blood glucose. In addition, information should be provided on the detrimental metabolic effects of both dehydration and stress.

[Critical illness polyneuropathy: clinical aspects and long-term outcome]. / Critical Illness Polyneuropathie: Klinik und Langzeitergebnisse.

Patients treated in intensive care units may develop a primary axonal form of polyneuropathy complicating sepsis and multiple organ failure more frequently than previously assumed. This critical illness polyneuropathy causes difficulty in weaning patients from the ventilator and delays further recovery and mobilisation. Over a period of two years we have treated five patients with flaccid tetra- or paraparesis. Recovery of motor function was largely satisfactory, but a long rehabilitation process was necessary. If attention were paid to detecting this disease in the early stages of intensive care neurorehabilitation might be facilitated. Hence, electrophysiological tests should be performed as soon as possible. The clinical outcome was markedly influenced by long-lasting neuropsychological disturbances in three of the five patients as well as by other complications such as joint contractures.

Fluid and electrolyte disorders associated with diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic coma.

DKA and HHNK are emergency conditions requiring quick medical care and nursing intervention. DKA can develop at any age and is most likely to occur in the insulin-dependent patient. The hallmark signs of DKA are a relative or absolute lack of insulin along with acidosis, ketosis, and hyperglycemia. Insulin and fluid and electrolyte therapy are initiated to control the hyperglycemia and prevent shock and further complications. The patient in HHNK presents with a very high serum glucose level (higher than in DKA), a high serum osmolarity, and usually no ketosis or acidosis. The patient may also experience more severe and sudden neurologic changes than those in DKA. Most patients who experience HHNK are older and may also have some other underlying disease process present. The nursing process should be used to correct the fluid and electrolyte imbalances and to prevent further complications in both DKA and HHNK. The patient needs to understand the reasons for his or her hyperglycemic crisis and how to prevent it from occurring in the future. Assessment of the patient's knowledge about diabetes is essential so that proper education can be incorporated into his or her plan of care.

[Mechanisms of acute respiratory insufficiency in patients with hyperglycemic coma]. / O mekhanizmakh ostroi dykhatel'noi nedostatochnosti u bol'nykh s giperglikemicheskimimi komami.

Basic parameters of pulmonary gas exchange, central and pulmonary hemodynamics, and colloid osmotic pressure were investigated in 31 patients in diabetic hyperglycemic coma over the course of intensive care. Pulmonary gas exchange disorders were observed in all patients in the presence of increased shunting of the blood in the lungs and disorders of transcapillary liquid exchange. On the other hand, we failed to obtain data indicative of an increase in the volume of extravascular water in the lungs. However, it does not rule out the possibility of iatrogenic disorders of gas exchange during noncontrolled rehydration.