Management of Hyperosmolar Hyperglycaemic State (HHS) in Adults: An updated guideline from the Joint British Diabetes Societies (JBDS) for Inpatient Care Group.

Hyperosmolar Hyperglycaemic State (HHS) is a medical emergency associated with high mortality. It occurs less frequently than diabetic ketoacidosis (DKA), affects those with pre-existing/new type 2 diabetes mellitus and increasingly affecting children/younger adults. Mixed DKA/HHS may occur. The JBDS HHS care pathway consists of 3 themes (clinical assessment and monitoring, interventions, assessments and prevention of harm) and 5 phases of therapy (0-60 min, 1-6, 6-12, 12-24 and 24-72 h). Clinical features of HHS include marked hypovolaemia, osmolality ≥320 mOsm/kg using [(2×Na+ ) + glucose+urea], marked hyperglycaemia ≥30 mmol/L, without significant ketonaemia (≤3.0 mmol/L), without significant acidosis (pH >7.3) and bicarbonate ≥15 mmol/L. Aims of the therapy are to improve clinical status/replace fluid losses by 24 h, gradual decline in osmolality (3.0-8.0 mOsm/kg/h to minimise the risk of neurological complications), blood glucose 10-15 mmol/L in the first 24 h, prevent hypoglycaemia/hypokalaemia and prevent harm (VTE, osmotic demyelination, fluid overload, foot ulceration). Underlying precipitants must be identified and treated. Interventions include: (1) intravenous (IV) 0.9% sodium chloride to restore circulating volume (fluid losses 100-220 ml/kg, caution in elderly), (2) fixed rate intravenous insulin infusion (FRIII) should be commenced once osmolality stops falling with fluid replacement unless there is ketonaemia (FRIII should be commenced at the same time as IV fluids). (3) glucose infusion (5% or 10%) should be started once glucose <14 mmol/L and (4) potassium replacement according to potassium levels. HHS resolution criteria are: osmolality <300 mOsm/kg, hypovolaemia corrected (urine output ≥0.5 ml/kg/h), cognitive status returned to pre-morbid state and blood glucose <15 mmol/L.

Hyperglycemic Hyperosmolar State During Induction Chemotherapy for Acute Lymphoblastic Leukemia.

We present the case of a 16-year-old boy who presented with fatigue, polyuria, and polydipsia while on chemotherapy for his relapsed acute lymphoblastic leukemia (ALL). Blood gas examination confirmed the diagnosis of hyperosmolar hyperglycemic state. The etiology for his hyperglycemia was most likely a result of oral glucocorticoid therapy combined with asparaginase therapy-both are a cornerstone of induction chemotherapy for ALL. The patient was aggressively rehydrated with saline, and medications were administered to correct his hyperkalemia. He was then slowly brought to euglycemia with a continuous infusion of insulin. Although hyperosmolar hyperglycemic state is rare during the treatment of ALL, frontline providers should be aware of this diagnosis because of the significant risk of hypovolemic shock and death if correction of hyperglycemia occurs prior to complete fluid resuscitation.

Urinary incontinence a first presentation of central pontine myelinolysis: a case report.

An 84-year-old lady was treated for hyperosmolar hyperglycaemia with IV insulin, fluids and catheterisation for fluid balance monitoring. Trial without catheter failed as the patient complained of new-onset urinary incontinence and lack of awareness of bladder filling. In light of her breast cancer history, we excluded cauda equina. Ultrasound KUB showed an enlarged bladder. Whole-body MRI revealed a lesion in the pons which was highly suggestive of central pontine myelinolysis (CPM). Her electrolytes were normal throughout her admission; thus, the rapid fluctuation in osmolality, secondary to her hyperglycaemic state, was the likely cause of CPM. CPM has been reported secondary to hyperglycaemia; however, this is the first reported case of CPM presenting as urinary incontinence and loss of bladder sensation.

A successfully treated case of hypopituitarism complicated with hyperosmolar hyperglycaemic state and rhabdomyolysis.

INTRODUCTION: This study aimed to report a rare case of hypopituitarism complicated with hyperosmolar hyperglycaemic state and rhabdomyolysis. CASE PRESENTATION: Hypopituitarism is a clinical syndrome in which there is a deficiency in hormone production by the pituitary gland. It often leads to hypoglycaemia, but in this case the patient was complicated with hyperosmolar hyperglycaemic state. The patient received prompt medical treatment, which effectively prevented the occurrence of possible acute kidney failure and other complications. CONCLUSION: This is a complicated and rare case. Our report provides some indications for the timely diagnosis and the standardised treatments for a patient who has hypopituitarism complicated with hyperosmolar hyperglycaemic state and rhabdomyolysis.

Hyperosmolar hyperglycemic state secondary to neuroleptic malignant syndrome.

Neuroleptic malignant syndrome (NMS) is often considered to be a precipitating factor for diabetic coma, such as a hyperosmolar hyperglycemic state (HHS). The combination of NMS and a systemic illness such as HHS can be difficult to diagnose because NMS may mask the coexisting condition. Although this coexistence is rare, it may be fatal if not detected early. We report a case of HHS in a 47-year-old male patient that developed after the distinguishing features of NMS had subsided. After the diagnosis of HHS, his recovery was a result of intravenous administration of soluble human insulin and fluid supplementation. Physicians caring for patients with diabetes who are also treated with neuroleptic agents should be aware that NMS may precipitate the development of secondary hyperglycemia despite a history of well-controlled blood glucose levels.

[In-hospital cardiac arrest due to unobserved steroid-induced hyperglycaemic hyperosmolar syndrome]. / Manglende diagnostik af hyperosmolært hyperglykæmisk syndrom førte til hjertestop.

The merging of hospital wards into highly specialized units facilitates targeted diagnostics and treatment. Often the result is favourable for the patient, but in some cases the basic conditions are overlooked. We describe a patient with inoperable oesophageal cancer who had unexplained mental confusion for three days due to an unobserved corticosteroid-induced hyperglycaemic hyperosmolar syndrome. The main differential diagnosis was cerebral metastases and a cerebral computed tomography was performed before cardiac arrest led to the right diagnosis. It is crucial to remember that unexplained deterioration in a patient with inoperable cancer can have a reversible cause.

Coexistence of neuroleptic malignant syndrome and a hyperosmolar hyperglycemic state.

Neuroleptic malignant syndrome (NMS) is a rare idiosyncratic disorder characterized by muscle rigidity, hyperthermia, autonomic dysfunction, and altered consciousness. Although the incidence of NMS is low, it may be fatal if early recognition is delayed. There are a variety of precipitating factors for NMS including systemic illness and dehydration. The combination of NMS with systemic illness can be difficult to diagnose because the systemic illness may mask the coexistence of NMS. We report a patient with hyperosmolar hyperglycemic state with coexistent NMS to remind physicians that hyperosmolar hyperglycemic state may precipitate the development of NMS in patients receiving neuroleptics.

Coma hiperosmolar / Hyperosmolar coma

El coma hiperosmolar, hiperglicémico, no cetoacidótico, o más conocido como hiperosmolar, es un grave trastorno metabólico que puede verse en determinados pacientes diabéticos cuando, a expensas, sobre todo de una hiperglicemia severa, mayor de 500 mg/dL, y en menor grado, de una hipernatremia absoluta. Se origina por el aumento de la osmolaridad plasmática, estableciéndose con un cuadro de deshidratación intensa, tanto intracelular como extracelular, con toma de la conciencia (que puede llegar hasta el coma). En el coma hiperosmolar se destaca la escasa existencia o la ausencia total de la cetoacidosis acompañante. Es característica su elevada mortalidad, cuando el referido coma no es diagnosticado a tiempo o no se aplican las medidas terapéuticas adecuadas(AU)

Hyperosmolar, hyperglycemic, non-ketoacidotic coma, or better known as hyperosmolar, is a serious metabolic disorder that can be seen in certain diabetic patients when, at the expense, especially of severe hyperglycemia, greater than 500 mg / dL, and to a lesser degree , of an absolute hypernatremia. It originates from the increase in plasma osmolarity, establishing itself with a picture of intense dehydration, both intracellular and extracellular, with awareness (which can lead to coma). In hyperosmolar coma, the scarce existence or total absence of the accompanying ketoacidosis stands out. Its high mortality is characteristic, when the referred coma is not diagnosed in time or the appropriate therapeutic measures are not applied(AU)

Approach to management of malignant hyperthermia-like syndrome in pediatric diabetes mellitus.

BACKGROUND: Hyperglycemic hyperosmolar nonketotic syndrome (HHNS) is usually associated with type 2 diabetes mellitus and is rare in children. However, a fatal malignant hyperthermia-like syndrome (MHLS) with rhabdomyolysis associated with new-onset diabetes mellitus and HHNS in adolescents has been described. DESIGN/METHODS: Case series. RESULTS: A 16-yr-old obese male (case A) and a 10-yr-old mid-pubertal nonobese female (case B) presented within a 6-month period with emesis, altered mental status, blood glucose >1600 mg/dL, and laboratory evidence of rhabdomyolysis. Case A developed fever after initiation of insulin therapy, along with refractory hypotension and multiorgan failure. He died 14 hrs after admission. Case B developed fever before insulin therapy, was treated with dantrolene, and made a full recovery. Metabolic workup showed evidence of short-chain acyl-CoA dehydrogenase (SCAD) deficiency. CONCLUSIONS: We report two cases of malignant hyperthermia-like syndrome associated with HHNS in adolescents. Their respective fluid management and clinical courses are described. Dantrolene therapy should be initiated immediately after this syndrome is recognized. We believe it is unlikely insulin is the sole trigger for MHLS. Case B is unique in that there was evidence of SCAD deficiency, a metabolic defect that we propose could lead to MHLS. We recommend that all patients with HHNS and MHLS be evaluated for an underlying metabolic disorder.

Hyperglycemic hyperosmolar nonketotic syndrome.

Hyperglycemic hyperosmolar nonketotic syndrome (HHNS) was infrequently diagnosed till recently. Now it is being diagnosed with increasing frequency in obese children with type 2 diabetes mellitus (T2 DM) and its incidence is likely to go up, given global increase in incidence of childhood obesity, increased insulin resistance, and T2 DM. The syndrome is characterized by severe hyperglycemia, a marked increase in serum osmolality and dehydration without accumulation of beta -hydroxybutyric or acetoacetic ketoacids. Significant ketogenesis is restrained by the ability of the pancreas to secrete small amount of insulin. Prolonged phase of osmotic diuresis leads to severe depletion of body water, which excees that of sodium, resulting in hypertonic dehydration. These children, usually obese adolescents with T2 DM, present with signs of severe dehydration and depressed mental status but continue to have increased rather than decreased urine output and are at increased risk of developing rhabdomyolysis and malignant hyperthermia. Emergency treatment is directed at restoration of the intravascular volume, followed by correction of deficits of fluid and electrolyte (Na+, K+, Ca++, Mg++, PO4++), hyperglycemia and serum hyperosmolarity, and a thorough search for conditions that may lead to this metabolic decompensation and their treatment. Use of iso-osomolar isotonic fluid (0.9% saline) until hemodynamic stabilization initially, followed by 0.45% saline with insulin infusion at the rate of 0.1 units/kg/hour, addition of 5% dextrose in fluids and reduction of insulin infusion once the blood glucose is 250 to 300 mg/dl is generally recommended. However, evidence-based guidelines about composition and tonicity of fluids and electrolyte solutions for early resuscitation and rehydration, the rate of infusion-rapid vs slow, and insulin dose-low vs normal, in treatment of HHNS in children are awaited. Careful monitoring of glucose levels and ensuring adequate hydration in patients 'at risk' of HHNS, including those receiving medications that interfere with the secretion or effectiveness of insulin should decrease the risk of HHNS.

Hemorrhagic pituitary apoplexy in an 18 year-old male presenting as non-ketotic hyperglycemic coma (NKHC).

Pituitary apoplexy is an acute clinical event usually caused by hemorrhage or infarction in a pituitary adenoma. We report the unusual case of hemorrhagic pituitary apoplexy in an 18 year-old male with previously undiagnosed type 2 diabetes mellitus who presented with unexplained hyperglycemia (glucose 49.2 mmol/l [887 mg/dl]) and obtundation and in whom an initial diagnosis of non-ketotic hyperglycemic coma (NKHC) was made. MRI revealed a heterogeneous mass arising from an expanded sella turcica into the suprasellar cistern. Despite well-controlled glucose levels on continuous insulin infusion, dexamethasone, and initiation of bromoergocriptine (parlodel) therapy, the patient's vision and pupillary responses deteriorated acutely. Following emergency transphenoidal surgery, the patient's vision and mental status improved. Data confirmed preoperative panhypopituitarism; serum prolactin was 396 ng/ml (microg/l). Immunostudies demonstrated tumoral labeling for prolactin, but not for ACTH, GH, TSH, LH, FSH, or P53.

Hyperglycemic hyperosmolar nonketotic syndrome in a child with acute lymphoblastic leukemia undergoing induction chemotherapy: case report.

Hyperglycemic hyperosmolar nonketotic syndrome, a life-threatening complication commonly associated with uncontrolled type 2 diabetes mellitus in adults, is characterized by severe hyperglycemia, a marked increase in serum osmolality, and clinical evidence of dehydration without the accumulation of beta-hydroxybutyric or acetoacetic ketoacids. There is a variable alteration in sensorium. The syndrome has been rarely reported in children with leukemia undergoing induction therapy. The authors' aim is to sensitize physicians to this life-threatening illness, which can be treated effectively if diagnosed early.

Fatal malignant hyperthermia-like syndrome with rhabdomyolysis complicating the presentation of diabetes mellitus in adolescent males.

OBJECTIVE: This report describes a new fatal syndrome observed in adolescent males at the initial presentation of diabetes mellitus. The features include hyperglycemic hyperosmolar coma complicated by a malignant hyperthermia-like picture with fever, rhabdomyolysis, and severe cardiovascular instability. DESIGN: Case series. SETTING: Pediatric intensive care units of 3 tertiary care facilities in the United States. PATIENTS: Six adolescent males, 5/6 obese with acanthosis nigricans, 4/6 black. RESULTS: Four of 6 patients died. Four of 6 patients did not have significant ketosis. Six of 6 patients had increased temperature after the administration of insulin. CONCLUSIONS: The underlying etiology of this syndrome remains unclear. Possibilities include an underlying metabolic disorder such as a fatty acid oxidation defect, an unrecognized infection, exposure to an unknown toxin, or a genetic predisposition to malignant hyperthermia. Evaluation for all these possibilities and empiric treatment with dantrolene should be considered for this type of patient until this syndrome is better characterized.

Acute postoperative metabolic complications of diabetes.

Because of several factors, including a change in the hormonal behavior, the postoperative period is at high risk for the diabetic patient to present a metabolic complication. On the other hand, a diabetic metabolic disorder may be secondary and reveal a severe underlying complication (sepsis...). Ketoacidosis is the consequence of an absolute or relative lack of insulin and occurs mainly in insulin dependent diabetic patients. Its incidence should be very low during the postoperative period since insulin protocols are systematically used. The main clinical and biological signs are a polypnea, signs of dehydration, an hyperglycemia associated with a high anion gap metabolic acidosis and the presence of ketoacids in the urine. Its treatment is mainly based on an active rehydration and an insulin and potassium supply. Sodium bicarbonate should not be used systematically any more, even during severe acidosis. Hyperosmolar non ketotic states affects insulin nondependent and older diabetic patients for the most part and occurs under similar conditions than ketoacidosis, revealing most of the time a severe underlying complication. Clinical and biological manifestations include a severe dehydration, alterations in consciousness and a major hyperglycemia associated to a moderate or mild metabolic acidosis. Its main treatment is an active rehydration and insulin plus potassium in a second time. Hypoglycemia is usually the consequence of a mistake in the diabetes care and in the insulin management. Every sickness or consciousness disorder occurring in a diabetic patient treated with insulin should lead to perform a blood glucose measurement. In case of severe manifestations, glucose should be administered in emergency, orally if the patient is conscious or intravenously if he is not. Lactic acidosis occurring during the postoperative period in a diabetic patient is usually non specific of diabetic disease and reflects the existence of an underlying complication (sepsis, hemorrhage, hypoxia,...), as it would in an non diabetic patient. Lactic acidosis due to a treatment with metformin is now very rare and occurs almost only in patients having a contraindication to the use of metformin.

Glycemic crises in patients with hematologic malignancies.

Persons with hematologic malignancies such as leukemia, lymphoma, or myeloma often have coexisting medical conditions. Among these may be diabetes mellitus. The physiologic and psychologic stress of diagnosis and treatment may precipitate the life-threatening complications of DKA or HHNS in this group of patients. People with personal risk factors may develop diabetes mellitus secondary to diagnosis and treatment and present with either DKA or HHNS. It is essential that the health care team have a heightened awareness of potential complications. These are complex syndromes involving severe hyperglycemia, metabolic acidosis, fluid and electrolyte imbalances, and neurologic and cardiovascular collapse. Working collaboratively with the critical care team to provide optimal care, nurses play an essential role in the management of these challenging complications of diabetes mellitus.

Coma hiperosmolar / Hyperosmolar coma

Se conoce que el coma hiperosmolar o estado hiperglucémico no cetótico (EHNC), es una grave complicación de la diabetes mellitus que constituye aún en nuestros días un reto para el emergencista, por lo difícil de su manejo y las consecuencias tan graves que se derivan del diagnóstico tardío o errado, por lo que constituye una de las urgencias más graves del diabético. En esta revisión se presentaron los aspectos más importantes de su diagnóstico, tratamiento y complicaciones. Se hizo especial énfasis en los 3 pilares fundamentales del tratamiento, a saber, la administración de líquido, la administración de insulina y el aporte de potasio. Nos proponemos que este trabajo pueda servir de guía para el abordaje de esta grave afección

Coma hiperglicémico, hiperosmolar, no cetósico: realidad del servicio de medicina adultos del hospital Gustavo Fricke de Viña de Mar 1984-1993 / Hyperglycemic, hyperosmolar, nonketotic coma: reality of the adult medicine service at Gustavo Fricke Hospital in Viña del Mar

Se revisaron retrospectivamente las fichas clínicas de 16 pacientes egresados del Hospital "Gustavo Fricke", entre 1984 y 1993, con el diagnóstico de coma hiperglicémico hiperosmolar no cetósico; a fin de explotar y describir la experiencia del centro asistencial en dicha patología. Se observó una mayor prevalencia en pacientes del sexo femenino y añosos. El antecedente diabético estuvo presente en aproximadamente dos tercios de la muestra. Dentro de los factores precipitantes destacan los cuadros infecciosos (81,2 por ciento). Resalta una hiperglicemia promedio de 723 mgr por ciento y una osmolaridad plasmática promedio de 369,4 mOsm/lt. En el período estudiado de nueve años, sólo logró detectarse 16 casos de esta complicación diabética; sobresaliendo su mortalidad (50 por ciento), mayor que lo expuesto en la literatura