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.

Risk Factors for Hyperosmolar Hyperglycemic State in Pediatric Type 2 Diabetes.

Background: There is a paucity of data on the risk factors for the hyperosmolar hyperglycemic state (HHS) compared with diabetic ketoacidosis (DKA) in pediatric type 2 diabetes (T2D). Methods: We used the national Kids' Inpatient Database to identify pediatric admissions for DKA and HHS among those with T2D in the years 2006, 2009, 2012, and 2019. Admissions were identified using ICD codes. Those aged <9yo were excluded. We used descriptive statistics to summarize baseline characteristics and Chi-squared test and logistic regression to evaluate factors associated with admission for HHS compared with DKA in unadjusted and adjusted models. Results: We found 8,961 admissions for hyperglycemic emergencies in youth with T2D, of which 6% were due to HHS and 94% were for DKA. These admissions occurred mostly in youth 17-20 years old (64%) who were non-White (Black 31%, Hispanic 20%), with public insurance (49%) and from the lowest income quartile (42%). In adjusted models, there were increased odds for HHS compared to DKA in males (OR 1.77, 95% CI 1.42-2.21) and those of Black race compared to those of White race (OR 1.81, 95% CI 1.34-2.44). Admissions for HHS had 11.3-fold higher odds for major or extreme severity of illness and 5.0-fold higher odds for mortality. Conclusion: While DKA represents the most admissions for hyperglycemic emergencies among pediatric T2D, those admitted for HHS had higher severity of illness and mortality. Male gender and Black race were associated with HHS admission compared to DKA. Additional studies are needed to understand the drivers of these risk factors.

DKA/HHS insulin infusion protocol adherence and patient outcomes in Shellharbour Hospital.

BACKGROUND: Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS) are medical emergencies requiring prompt assessment and management to avoid complications. AIMS: To examine adherence to the hospital DKA/HHS insulin infusion protocol, assess outcomes in patients admitted with DKA or HHS, and determine if improvements have been observed from a similar audit in 2016. METHODS: An audit was conducted on 40 patients admitted to Shellharbour Hospital with DKA or HHS. Protocol adherence was assessed in the domains of fluid replacement, potassium replacement, use of the correct insulin infusion schedule, timing of commencement of dextrose infusion and appropriate transition to subcutaneous insulin. The outcomes assessed included length of hospital stay, duration of insulin infusion, time to euglycaemia, intensive care unit (ICU) transfer, overlap between insulin infusion and subcutaneous insulin, diabetes team review and incidence and management of hypoglycaemia. RESULTS: The proportion of cases that adhered to the components of the insulin infusion protocol is as follows: fluid replacement (40%), potassium replacement (72.5%), correct insulin schedule (82.5%), appropriate commencement of intravenous dextrose (80%) and appropriate transition to subcutaneous insulin (87.5%). Appropriate overlap between insulin infusion and subcutaneous insulin occurred in 62.5% of patients. Eighty-five per cent of patients were reviewed by the diabetes team. Three per 40 patients experienced hypoglycaemia, and none of the three patients was treated as per protocol. Compared to the 2016 audit, there was a significant improvement in potassium replacement but a decrease in appropriate fluid replacement. CONCLUSION: This audit highlights areas in DKA/HHS management requiring improvement. These include fluid and potassium replacement and appropriate overlap between subcutaneous insulin and insulin infusion.

What Is the Optimal Speed of correction of the Hyperosmolar Hyperglycemic State in Diabetic Ketoacidosis? An Observational Cohort Study of U.S. Intensive Care Patients.

OBJECTIVE: The international guidelines for the treatment of diabetic ketoacidosis (DKA) advise against rapid changes in osmolarity and glucose; however, the optimal rates of correction are unknown. We aimed to evaluate the rates of change in tonicity and glucose level in intensive care patients with DKA and their relationship with mortality and altered mental status. METHODS: This is an observational cohort study using 2 publicly available databases of U.S. intensive care patients (Medical Information Mart for Intensive Care-IV and Electronic Intensive Care Unit), evaluating adults with DKA and associated hyperosmolarity (baseline Osm ≥300 mOsm/L). The primary outcome was hospital mortality. The secondary neurologic outcome used a composite of diagnosed cerebral edema or Glasgow Coma Scale score of ≤12. Multivariable regression models were used to control for confounding factors. RESULTS: On adjusted analysis, patients who underwent the most rapid correction of up to approximately 3 mmol/L/hour in tonicity had reduced mortality (n = 2307; odds ratio [OR], 0.21; overall P < .001) and adverse neurologic outcomes (OR, 0.44; P < .001). Faster correction of glucose levels up to 5 mmol/L/hour (90 mg/dL/hour) was associated with improvements in mortality (n = 2361; OR, 0.24; P = .020) and adverse neurologic events (OR, 0.52; P = .046). The number of patients corrected significantly faster than these rates was low. A maximal hourly rate of correction between 2 and 5 mmol/L for tonicity was associated with the lowest mortality rate on adjusted analysis. CONCLUSION: Based on large-volume observational data, relatively rapid correction of tonicity and glucose level was associated with lower mortality and more favorable neurologic outcomes. Avoiding a maximum hourly rate of correction of tonicity >5 mmol/L may be advisable.

Acute stroke-like deficits associated with nonketotic hyperglycemic hyperosmolar state: an illustrative case and systematic review of literature.

INTRODUCTION: Nonketotic hyperglycemic hyperosmolar state (NKHHS) is associated with a wide spectrum of neurological syndromes including acute stroke-like deficits. Clinical features and etiology have not been established yet. METHODS: Here we provide a case illustration and systematic review on non-epileptic acute neurological deficits in NKHSS. The systematic literature search followed PRISMA guidelines and a predefined protocol, including cases of NKHSS with acute stroke-like presentation. RESULTS: The database search yielded 18 cases. Hemianopia was the most common clinical presentation (73%), followed by partial or total anterior circulation syndrome (26%). Patients with symptoms of acute anterior circulation infarct were significantly older (69.5 ± 5.1 vs. 52.2 ± 13.9 years; p = 0.03) and showed higher mean glucose levels at the admission vs. those with hemianopia (674.8 ± 197.2 vs. 529.4 ± 190.8 mg/dL; p = 0.16). Brain MRI was performed in 89% of patients, resulting abnormal in 71% of them, especially hemianopic (91%). Subcortical hypointensities in T2-FLAIR MR sequences were present in all the analyzed cases. Cortical DWI hyperintensities were also common (64%). EEG showed diffuse or focal slow wave activity in 68% of patients, especially with visual hallucinations (85%). Neurological symptoms completely resolved in 78% of patients within 6 (IQR 3-10) days, following aggressive treatment and glucose normalization. CONCLUSIONS: Our results suggest neuronal dysfunction on a metabolic basis as the leading cause of acute neurological deficits in NKHHS. Despite the generally favorable prognosis, prompt identification and aggressive treatment are crucial to avoid irreversible damage. Larger cohort studies are needed to confirm our findings.

A case of hyperglycemic hyperosmolar syndrome in a pug dog.

An 8-year-old spayed female pug dog that had recently been diagnosed with pancreatitis was brought to a veterinary clinic with polyuria, polydipsia, and seizures. The dog was diagnosed with hyperglycemic hyperosmolar syndrome, a rare complication of diabetes mellitus. The dog was hospitalized and was administered intravenous fluids and insulin therapy, and clinical signs improved.

Un cas de syndrome hyperosmolaire hyperglycémique chez une chienne carlin. La chienne carlin femelle stérilisée âgée de 8 ans qui avait récemment reçu un diagnostic de pancréatite a été amenée dans une clinique vétérinaire avec une polyurie, une polydipsie et des convulsions. La chienne a été diagnostiquée avec le syndrome hyperosmolaire hyperglycémique, une complication rare du diabète sucré. La chienne a été hospitalisée et a reçu des fluides intraveineux et une insulinothérapie, et les signes cliniques se sont améliorés.(Traduit par Dr Serge Messier).

Diagnosis and Management of the Critically Ill Adult Patient with Hyperglycemic Hyperosmolar State.

BACKGROUND: Hyperglycemic hyperosmolar state is a life-threatening complication of diabetes mellitus. Therefore, it is important for emergency physicians to be aware of this unique diagnosis and treatment considerations. OBJECTIVE: This manuscript reviews the emergency department evaluation and management of the adult patient with hyperglycemic hyperosmolar state. DISCUSSION: Hyperglycemic hyperosmolar state is diagnosed by an elevated glucose, elevated serum osmolality, minimal or absent ketones, and a neurologic abnormality, most commonly altered mental status. Treatment involves fluid resuscitation and correction of electrolyte abnormalities. It is important to monitor these patients closely to avoid overcorrection of osmolality, sodium, and other electrolytes. These patients are critically ill and generally require admission to an intensive care unit. CONCLUSIONS: Hyperglycemic hyperosmolar state is associated with significant morbidity and mortality. It is important for clinicians to be aware of the current evidence regarding the diagnosis, management, and disposition of these patients.

Diabetes at the front door. A guideline for dealing with glucose related emergencies at the time of acute hospital admission from the Joint British Diabetes Society (JBDS) for Inpatient Care Group.

People with diabetes account for nearly one-fifth of all inpatients in English and Welsh hospitals; of these, up to 90% are admitted as an emergency. Most are admitted for a reason other than diabetes with only 8% requiring admission for a diabetes-specific cause. Healthcare professionals working in emergency departments experience numerous clinical challenges, notwithstanding the need to know whether each individual with diabetes requires urgent admission. This document has been developed and written by experts in the field, and reviewed by the parent organizations of the Joint British Diabetes Societies for Inpatient Care-Diabetes UK, the Diabetes Inpatient Specialist Nurse Group and the Association of British Clinical Diabetologists. The document aims to support staff working in emergency departments and elsewhere by offering practical advice and tools for effective, appropriate and safe triage. Each section relates to the commonest diabetic specific emergencies and algorithms can be printed off to enable ease of access and use.

Clinical profiles, outcomes and risk factors among type 2 diabetic inpatients with diabetic ketoacidosis and hyperglycemic hyperosmolar state: a hospital-based analysis over a 6-year period.

OBJECTIVE: Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the two most common hyperglycemic emergencies (HEs) associated with diabetes mellitus. Individuals with HEs can present with combined features of DKA and HHS. The objective of this study is to assess the clinical characteristics, therapeutic outcomes, and associated predisposing factors of type 2 diabetic patients with isolated or combined HEs in China. METHODS: We performed a retrospective analysis of 158 patients with type 2 diabetes (T2DM), complicated with DKA, HHS, or DKA combined with HHS (DKA-HHS) in Shanghai Tongji Hospital, China from 2010 to 2015. Admission clinical features, therapeutic approaches and treatment outcomes of those patients were extracted and analyzed. RESULTS: Of the 158 patients with T2DM, 65 (41.1%) patients were DKA, 74 (46.8%) were HHS, and 19 (12.0%) were DKA-HHS. The most common precipitants were infections (111, 70.3%), newly diagnosed diabetes (28,17.7%) and non-compliance to medications (9, 5.7%). DKA patients were divided into mild, moderate and severe group, based on arterial blood gas. Spearman correlation analysis revealed that C-reaction protein (CRP) was positively correlated with severity of DKA, whereas age and fasting C peptide were inversely correlated with severity of DKA (P < 0.05). The mortality was 10.8% (17/158) in total and 21.6% (16/74) in the HHS group, 5.9% (1/17) in DKA-HHS. Spearman correlation analysis indicated that death in patients with HHS was positively correlated to effective plasma osmolality (EPO), renal function indicators and hepatic enzymes, while inversely associated with the continuous subcutaneous insulin infusion (CSII) therapy. Logistic regression analysis suggested that elevated blood urea nitrogen (BUN) on admission was an independent predisposing factor of mortality in HHS, while CSII might be a protective factor for patients with HHS. Furthermore, the receiver-operating characteristic (ROC) curve analysis indicated that BUN had the largest area under the ROC curves for predicting death in patients with HHS. CONCLUSIONS: Our findings showed elevated CRP and decreased fasting C-peptide might serve as indicator for severe DKA. Elevated BUN might be an independent predictor of mortality in patients with HHS, whereas CSII might be a protective factor against death in HHS.

Care of Children and Adolescents with Diabetes Mellitus and Hyperglycemia in the Inpatient Setting.

PURPOSE OF REVIEW: Children and adolescents with acute hyperglycemia and diabetes mellitus frequently have acute, potentially life-threatening presentations which require high-acuity care in an inpatient and often intensive care setting. This review discusses the evaluation and care of hyperglycemia and diabetes mellitus in hospitalized children in both critical and non-critical care settings, highlighting important differences in their care relative to adults. RECENT FINDINGS: Diabetic ketoacidosis remains highly prevalent at diagnosis among children with type 1 diabetes, and hyperglycemic hyperosmolar state is increasingly prevalent among children with type 2 diabetes. Recent clinical trials have investigated the potential benefits of various types of intravenous fluids and their rates of administration as well as the risks and benefits of intensive glucose control in critically ill children. The Endocrine Society has developed guidelines focused on managing hyperglycemic hyperosmolar state, outlining important aspects of care shown to decrease morbidity and mortality. In the non-critical illness setting, intensive therapy on newly diagnosed diabetes is increasingly recommended at the outset. With the increasing incidence of diabetes mellitus in children and adolescents, recent studies addressing acute diabetes emergencies help inform best practices for care of hospitalized children with hyperglycemia and diabetes.

Treatment of Diabetic Ketoacidosis (DKA)/Hyperglycemic Hyperosmolar State (HHS): Novel Advances in the Management of Hyperglycemic Crises (UK Versus USA).

PURPOSE OF REVIEW: Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are diabetic emergencies that cause high morbidity and mortality. Their treatment differs in the UK and USA. This review delineates the differences in diagnosis and treatment between the two countries. RECENT FINDINGS: Large-scale studies to determine optimal management of DKA and HHS are lacking. The diagnosis of DKA is based on disease severity in the USA, which differs from the UK. The diagnosis of HHS in the USA is based on total rather than effective osmolality. Unlike the USA, the UK has separate guidelines for DKA and HHS. Treatment of DKA and HHS also differs with respect to timing of fluid and insulin initiation. There is considerable overlap but important differences between the UK and USA guidelines for the management of DKA and HHS. Further research needs to be done to delineate a unifying diagnostic and treatment protocol.

Hyperosmolar Hyperglycemic State.

Hyperosmolar hyperglycemic state is a life-threatening emergency manifested by marked elevation of blood glucose and hyperosmolarity with little or no ketosis. Although there are multiple precipitating causes, underlying infections are the most common. Other causes include certain medications, nonadherence to therapy, undiagnosed diabetes mellitus, substance abuse, and coexisting disease. In children and adolescents, hyperosmolar hyperglycemic state is often present when type 2 diabetes is diagnosed. Physical findings include profound dehydration and neurologic symptoms ranging from lethargy to coma. Treatment begins with intensive monitoring of the patient and laboratory values, especially glucose, sodium, and potassium levels. Vigorous correction of dehydration is critical, requiring an average of 9 L of 0.9% saline over 48 hours in adults. After urine output is established, potassium replacement should begin. Once dehydration is partially corrected, adults should receive an initial bolus of 0.1 units of intravenous insulin per kg of body weight, followed by a continuous infusion of 0.1 units per kg per hour (or a continuous infusion of 0.14 units per kg per hour without an initial bolus) until the blood glucose level decreases below 300 mg per dL. In children and adolescents, dehydration should be corrected at a rate of no more than 3 mOsm per hour to avoid cerebral edema. Identification and treatment of underlying and precipitating causes are necessary.

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.

[Diabetic emergencies : Hypoglycemia, ketoacidotic and hyperglycemic hyperosmolar nonketotic coma]. / Diabetologische Notfälle : Hypoglykämie, ketoazidotisches und hyperglykämisches Koma.

The diabetic emergencies diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HHS) and hypoglycemia represent severe and potentially life-threatening complications of diabetes mellitus that require prompt diagnostics and treatment. Absolute or relative insulin insufficiency is characteristic of DKA und HHS along with severe dehydration. They differ by the prevalence of ketone bodies and the severity of acidosis; however, the treatment regimens are similar. In contrast, hypoglycemia is the limiting factor for achieving ambitious glucose targets. This article decribes the clinical presentation, diagnostics and emergency management of these metabolic derangements.

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.

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.

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.