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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.

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.

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.

Human cerebral cortical slices preincubated with [3H]GABA, [3H]noradrenaline, or 5-[3H]hydroxytryptamine and superfused with Krebs solution or Mg(2+)-free Krebs solution were used to investigate the influence of increased D-glucose concentrations on the release of these [3H]-neurotransmitters evoked by high K+ content or NMDA receptor activation, respectively. An increase in level of D-glucose (normal content, 11.1 mM) by 32, 60, and/or 100 mM (a range characteristic for hyperosmolar diabetic coma) increased the [3H]GABA release and inhibited the [3H]noradrenaline release evoked by both methods of stimulation. The K(+)-induced 5-[3H]hydroxytryptamine release was also inhibited by high D-glucose content. Blockade of GABAB receptors by p-(3-aminopropyl)-p-diethoxymethylphosphinic acid (CGP 35348) attenuated the inhibitory effect of high D-glucose content on the K(+)-evoked release of [3H]noradrenaline and 5-[3H]hydroxytryptamine, suggesting that the effect on monoamine release is, at least to a major part, the result of the increased GABA release and, as a consequence, of an increased GABA concentration at inhibitory GABAB receptors. The membrane-impermeable sorbitol mimicked the increasing effect of D-glucose on [3H]GABA release and its inhibitory effect on 5-[3H]hydroxytryptamine release. However, dimethyl sulfoxide, which is known to permeate rapidly through biological membranes, had no effect at concentrations equiosmolar to D-glucose. It is concluded that a reduction in brain cell volume caused by increased extracellular, compared with cytoplasmic, osmolarity is crucial for the changes in neuronal function observed at high D-glucose and sorbitol content.(ABSTRACT TRUNCATED AT 250 WORDS)

The reactivity of mesoappendix arterioles to applicated epinephrine application was investigated in 2 models of metabolic coma, hypoglycemic and acetonemic. Hypoglycemic coma (HC) was induced by insulin injection (20 IE/kg) i. m. to rats fasting for 18 hours. Acetonemic coma (AC) was induced by i. v. acetone injection (5.5 mmol). The sensitivity of arterioles to applicated epinephrine did not change in HC and increased twofold in AC vs. the control values (p < 0.01). The reaction of arterioles to injection of double threshold dose of epinephrine in HC developed sooner and the degree of vasoconstriction was 41% higher than in controls. In AC the reaction developed two times sooner and the degree of arterioles constriction was 1.5 times higher vs. the control (p < 0.01).

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.

We studied the effect of hyperosmolality on the tap-induced blink reflex (TBR) in patients with diabetes. The TBR, consisting of R1 and R2 components, was either absent or delayed in patients compared to controls. The abnormalities correlated better with the degree of hyperosmolality than with the level of blood glucose. TBR was usually absent in unconscious patients with greatly elevated serum osmolality. In some patients with similar elevations in serum osmolality the R2' component was absent at a time when consciousness was preserved. Hence, TBR may be useful in monitoring CNS dysfunction in diabetics with hyperosmolality.

The diabetic coma is characterized by fundamental metabolic changes. Apart from the hyperglycaemia, exsiccosis and the disturbed electrolyte metabolism are considerable factors contributing to the coma. The treatment of diabetic coma puts great demands on the doctors, since the prognosis can only be improved by systematic and correct intervention. A fast filling up of the volume and a specific electrolyte (potassium) substitution are very important. In cases of ketoacidotic diabetic coma the acidosis must be carefully balanced, whereby the "rest-acidosis" up to pH 7.1 can be tolerated. The administration of insulin can only begin, when the volume and electrolyte substitution is guaranteed, otherwise dangerous insulin-induced hypokalaemia is unavoidable. By no means may the first treatment for the insulinisation be carried out ambulatory.

Diabetic coma is frequently associated with thromboembolic complications. A prospective study was undertaken of the haemostatic changes occurring in 15 patients (12 with ketoacidosis, three with the hyperosmolar syndrome) during diabetic coma. When compared with the results after stabilization of the diabetes, ketoacidosis was associated with significantly higher levels of factor VIII coagulant activity, factor VIII-related antigen and fibrin degradation products, a shorter partial thromboplastin time and reduced concentrations of antithrombin III. These results suggest that in uncomplicated ketoacidosis, haematological changes occur which may reflect vascular endothelial damage and intravascular fibrin deposition. Out of three deaths, two patients (both with the hyperosmolar syndrome) had evidence of disseminated intravascular coagulation. To reduce further the mortality and morbidity from diabetic coma, controlled clinical trials of anticoagulant and antiplatelet drugs may be indicated.

A new and simple form of insulin therapy for diabetic hyperglycaemia and ketoacidosis has been developed using a continuous intravenous infusion of insulin at a rate of 2.4 U/hr to maintain serum insulin concentration at physiological levels. This rate raises the mean serum insulin to 83 muU/ml and has a therapeutic effect which is not augmented by higher infusion rates. The response to such low doses of insulin indicates a need for a reappraisal of currently held theories about insulin resistance in diabetic ketoacidosis. In 11 diabetic patients with a mean plasma glucose of 514 mg/100 ml this therapy produced continuous falls in plasma glucose at a mean rate of 75 mg/100 ml/hr, and 10 out of 11 patients recovered within eight hours. This form of therapy is simple to institute, not complicated by hypoglycaemia, and avoids the confusion and empiricism of previously described forms of therapy.

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 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.

Diabetic emergencies continue to be a significant cause of premature death in patients with diabetes. They include the diabetic comas (hypoglycaemia, severe diabetic ketoacidosis, hyperosmolar hyperglycaemic non-ketotic coma, lactic acidosis), emergency surgery and myocardial infarction. There is still considerable avoidable morbidity and mortality during treatment, and as a result of misdiagnosis. Simple guidelines are thus needed for the general practitioner and admitting physician to improve management. Hypoglycaemia is far the commonest diabetic emergency, and is relatively easy to diagnose and treat. Delays in treatment are potentially damaging and largely unnecessary. Diabetic ketoacidosis is still relatively common but is often preventable. Initial treatment for this and hyperosmolar nonketotic coma is rehydration. This is followed by IM or IV infusion of moderate amounts of insulin, early potassium replacement, and alkali only if the acidaemia is severe. Lactic acidosis requires mainly rigorous alkalinisation but is very rare. The metabolic derangements in emergency surgery and myocardial infarction are best treated by combined glucose, potassium and insulin infusions. In all cases treatment is easiest and probably more successful if consistent simple guidelines are provided.

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.

Continuous intravenous infusion of small amounts of insulin has been used in the management of a series of patients with diabetic ketoacidosis. In 13 patients with a plasma glucose level on admission of 725 mg/100 ml (+/- 80 S.E. of mean) and an arterial pH of 7.07 +/- 0.05 a mean loading dose of 6.5 +/- 0.82 units of soluble insulin was administered intravenously, and thereafter a sustaining infusion of 6.5 +/- 0.82 U/hr was continued until ketosis was corrected and the plasma glucose fell below 300 mg/100 ml. The total insulin dose needed to achieve this was 39.2 +/- 6.6 units given over a 3 to 10-hour period. Plasma insulin was measured in patients who had not previously received insulin and the mean level at an infusion rate of 4 U/hr was 75.6 +/- 8.0 muU/ml. Plasma glucose fell at a regular rate of 101 +/- 11 mg/100 ml/hr, and ketosis improved in parallel. Plasma potassium was well maintained throughout treatment. This regimen of treatment was clinically effective and simple to follow.

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.

Two groups of diabetic patients in poor metabolic control were followed prospectively for platelet function in the course of adequate insulin therapy. All 8 ketoacidotic and 38 nonacidotic, but markedly hyperglycemic, patients showed decreased platelet aggregation at the time of entering the hospital in comparison to subsequent controls. Platelet adenylate cyclase activity rose during the observation periods significantly. Changes of beta-thromboglobulin plasma levels were not uniform. These data give evidence for a metabolic factor which modifies platelet functions to a considerable degree.

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.

Hyperosmolar nonketotic coma occurs most frequently in the elderly patient with underlying renal impairment. It often has an insidious onset, and may be precipitated by an identifiable illness, medication or procedure. Various neurologic manifestations may occur and obscure the diagnosis. Rapid recognition and appropriate treatment can greatly reduce the high mortality rate.

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.

Hyperosmolar diabetic coma is characterised by extreme hyperglycaemia and dehydration. Hypernatremia often contributes additionally to plasma hyperosmolarity. The pathogenesis of these component abnormalities is considered. The explanation of the absence of hyperketonaemia is examined in the light of recent experimental and clinical data. At the beginning of the development of the syndrome, high peripheral plasma insulin probably explains the lack of ketosis via inhibition of lipolysis. Later, when hyperosmolar coma is established, peripheral insulinopenia but an "insulinised" liver may coexist. This would favour metabolism of free fatty acids along nonketogenic pathways.

Pulmonary capillary wedge pressure (PCWP), serum albumin concentrations, and arterial oxygenation (PaO2) were monitored during crystalloid loading in 10 patients with severe decompensated diabetic states (SDDS). Rapid infusion of crystalloid induced marked rises in PCWP (median 6 mmHg, range 1-21 mmHg) and falls in albumin concentrations (median 5 g/l, range 0.8-15 g/l) over the first few hours of treatment. PaO2 was significantly related (r(s) = -0.25, p less than 0.05) to the calculated hydrostatic forces across the pulmonary capillary bed. However, hypoxaemia was found at initiation of therapy in 2 patients where calculated COP greatly exceeded PCWP. Hypoxaemia developing during crystalloid loading for SDDS may imply the formation of sub-clinical pulmonary oedema and the subsequent fluid replacement regimen should then be appropriately reviewed.