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Hyperglycemic hyperosmolar state (HHS) is rare in the paediatric population. The diagnosis and management of HHS presents a challenge in paediatric patients who may present with a mixed picture of HHS and diabetic ketoacidosis (DKA).
A 15-year-old obese African American male was brought to the emergency department following a two-day history of feeling unwell. The patient was obtunded, hypotensive and tachypneic. Initial investigations revealed the following: pH 6.97 (normal 7.35 to 7.41), HCO3− 5 mEq/L (normal 20 mEq/L to 25 mEq/L), glucose 90.9 mmol/L (normal 3.4 mmol/L to 6.3 mmol/L), serum osmolality 454 mOsm/kg (normal 275 mOsm/kg to 295 mOsm/kg), Na+ 141 mEq/L (normal 135 mEq/L to 145 mEq/L), corrected Na+ 165 mEq/L, K+ 8.4 mEq/L (normal 3.5 mEq/L to 5.0 mEq/L), urinalysis revealed 1+ ketones and 4+ glucose. The patient’s clinical course was complicated by severe hyperkalemia, acute renal failure, refractory status epilepticus, rhabdomyolysis, pancreatitis and hypertension.
The present case emphasizes the complexity of managing patients with a mixed DKA/HHS presentation and associated morbidities. It is very important to disseminate and implement screening guidelines for type 2 diabetes mellitus, so as to prevent this potentially devastating complication.
Le syndrome d’hyperosmolarité hyperglycémique (SHH) est rare au sein des populations pédiatriques. Son diagnostic et sa prise en charge posent un défi auprès des patients pédiatriques qui peuvent présenter un bilan mixte de SHH et d’acidocétose diabétique (ACD).
Un adolescent afro-américain obèse de 15 ans est arrivé à l’urgence parce qu’il ne se sentait pas bien depuis deux jours. Ses sens étaient émoussés, et il faisait de l’hypotension et de la tachypnée. Les premiers examens ont donné lieu aux constatations suivantes : pH de 6,97 (normal : 7,35 à 7,41), HCO3 de 5 mEq/L (normal : 20 mEq/L à 25 mEq/L), glycémie de 90,9 mmol/L (normal : 3,4 mmol/L à 6,3 mmol/L), osmolalité sérique de 454 mOsm/kg (normal : 275 mOsm/kg à 295 mOsm/kg), Na+ de 141 mEq/L (normal : 135 mEq/L à 145 mEq/L), Na+ corrigée de 165 mEq/L, et K+ de 8,4 mEq/L (normal : 3,5 mEq/L à 5,0 mEq/L), et l’urinalyse a révélé des cétones de 1+ et une glycémie de 4+. L’évolution clinique du patient était compliquée par une grave hyperkaliémie, une insuffisance rénale aiguë, un état de mal épileptique réfractaire, une rhabdomyolyse, une pancréatite et une hypertension.
Ce cas fait ressortir la complexité de prise en charge d’une présentation mixte d’ACD et de SHH et de ses morbidités connexes. Il est très important de diffuser et d’adopter des lignes directrices de dépistage du diabète de type 2 afin de prévenir cette complication au potentiel dévastateur.
Hyperglycemic hyperosmolar state (HHS) is rare in the paediatric population; however, this is changing as the incidence of type 2 diabetes mellitus (T2D) increases among children and youth. HHS has a high mortality and morbidity rate. Furthermore, the diagnosis and management of HHS presents a unique challenge in paediatric patients who may present with a mixed picture of HHS and diabetic ketoacidosis (DKA). Males, African-Americans and patients with developmental delay have been reported to be at highest risk of presenting with HHS. Evidence for optimal treatment of HHS in the paediatric population is sparse.
A 15-year-old African American male was brought to the emergency department by ambulance in an obtunded state. The patient presented with a two-day history of vomiting, diarrhea, abdominal pain, general malaise and emotional distress. Before presentation, the patient experienced a recent history of polyuria and polydipsia of unknown duration. The patient did not have a primary care physician and this was his initial presentation to medical care. On arrival in the emergency room, the patient had a Glasgow Coma Scale score of 9. On examination, the patient was obese, with a body mass index (BMI) of 33 kg/m2. His blood pressure was 112/57 mmHg, with a heart rate of 146 beats/min (normal 60 beats/min to 100 beats/min), a respiratory rate of 60 breaths/min (normal 12 breaths/min to 16 breaths/min) with Kussmaul respirations and a temperature of 38.4°C. The patient’s pupillary response was sluggish and the patient was noted to have dry mucous membranes. Skin examination of the patient revealed acanthosis nigricans along the nape of his neck. The patient’s abdomen was slightly distended but soft.
Initial laboratory investigations confirmed a diagnosis of diabetes (Table 1). Of note, the patient’s blood glucose level was markedly elevated at 90.9 mmol/L (normal 3.4 mmol/L to 6.3 mmol/L), serum osmolality 454 mOsm/kg (normal 275 mOsm/kg to 295 mOsm/kg), pH 6.97 (normal 7.35 to 7.41), PCO2 23 mmHg (normal 38 mmHg to 50 mmHg), HCO3−5 mEq/L (normal 20 mEq/L to 25 mEq/L), Na+ 141 mEq/L (normal 135 mEq/L to 145 mEq/L with ‘corrected’ Na+ for hyperglycemia 165 mEq/L), K+ 8.4 mEq/L (normal 3.5 mEq/L to 5.0 mEq/L), and 1+ urine ketones. Hemoglobin A1C was elevated at 13.4% (normal 4.0% to 6.0%), indicating longstanding hyperglycemia.
Other than some learning difficulties in school, the patient’s medical history was noncontributory. The patient had a sedentary lifestyle and had been obese for several years. There was a strong family history of T2D in maternal relatives.
The patient was admitted to the paediatric intensive care unit for further investigation and treatment. He was given a 6 mL/kg bolus for the first hour of intravenous (IV) treatment initially, which was reduced to 250 mL/h of 0.9% saline as per the institution’s DKA protocol. The initial fluid bolus was below current recommendations for HHS because the patient’s weight was initially underestimated by approximately 30 kg. Furthermore, due to his normal blood pressure and obesity, his level of dehydration was also initially underestimated. The patient’s lack of hypotension at presentation was likely due to pre-existing hypertension, which was unmasked and sustained after appropriate rehydration. The patient developed cardiac arrhythmia secondary to hyperkalemia 3 h after IV fluids were initiated. Insulin infusion was started to treat hyperkalemia at 0.03 units/kg/h with dextrose added to the IV fluids. Within the first 12 h of treatment, he developed status epilipticus and required intubation and ventilation. Additional acute complications within the first two days of treatment included severe hypernatremia (peak level 181 mEq/L), acute renal failure, rhabdomyolysis, hypertension and pancreatitis. Computed tomography and magnetic resonance imaging of the patient’s brain were normal, with no indication of cerebral edema or thrombosis. IV fluids and insulin infusion were titrated to slowly bring serum glucose and sodium levels into the normal range.
The patient’s seizures resolved on the second day of admission, he was then extubated on the fourth day of admission and transferred out of the intensive care unit. The patient was significantly deconditioned and required 35 days of rehabilitation before discharge from hospital. Initially, he was not able to ambulate without assistance, but was able to do so independently at discharge. His current medications include subcutaneous insulin, metformin and fosinopril. In follow-up, the patient has returned to his previous level of cognitive functioning. To date, he has been nonadherent to his diabetes management and remains hypertensive.
HHS is a preventable and potentially fatal complication of undiagnosed or inadequately treated T2D, and rarely, type 1 diabetes (T1D). Literature regarding the incidence, management and prognosis of HHS in the paediatric population is sparse. A critical review by Rosenbloom (1) identified 97 published cases of paediatric HHS, with 74% of these cases being published after 2000. A recent prospective national surveillance study of diabetes in Canadian children revealed the observed minimum incidence of T2D to be 1.54 per 100 000 children <18 years of age per year, and that the incidence is increasing compared with historical data (2). A case series estimated that up to 4.2% of children and adolescents have HHS at diagnosis of T2D (3). Appropriate screening in children is essential to preventing complications of T2D, including HHS.
HHS is characterized by serum glucose levels >33.3 mmol/L and osmolality >320 mOsm/kg in the absence of significant acidosis and ketosis (4). Although HHS is a distinct clinical entity from DKA, the two conditions may occur simultaneously, which can present both diagnostic and therapeutic dilemmas, particularly in children for whom the risk of cerebral edema is a factor in the management of DKA in T1D. A recent critical review of all published cases to date revealed that approximately 28% of patients with HHS also had evidence of DKA (1), which is consistent with HHS reported in the adult literature (5).
The mortality rate of HHS in children is high. Rosenbloom (1) reported that 32 of 97 published cases (32.9%) did not survive, with multiple organ failure being the most common cause of death. In addition, obese patients experienced a significantly higher mortality rate than nonobese patients. Accurate estimation of the degree of dehydration can be challenging in obese patients (6), which could result in insufficient rehydration, as was seen in our case. Patients with HHS are vulnerable to a number of serious complications including severe electrolyte imbalances, thrombosis, cerebral edema, malignant hyperthermia, rhabdomyolysis, renal failure and pancreatitis.
Misdiagnosis or inappropriate treatment of HHS has been highlighted in a number of case series (7–9), and has prompted the development of proposed HHS guidelines for children (6). According to the proposed guidelines, there are several distinct differences in the management of HHS compared with DKA. Dehydration is profound in HHS, and should be assumed to be 12% to 15% of body weight. As such, children with HHS should undergo more vigorous fluid replacement than that recommended for DKA, specifically, a minimum initial bolus of 20 mL/kg isotonic saline (0.9% NaCl) with repeated boluses until peripheral perfusion is restored. After the initial boluses, the fluid deficit should be replaced over 24 h to 48 h, with a goal of slowly reducing serum osmolality and sodium levels. The fluid choice should be individualized based on serum electrolytes, serum glucose and fluid status. In contrast to DKA, in which early insulin administration is necessary to reduce ketosis, insulin administration should be delayed in the treatment of HHS. Fluid administration alone will result in a significant decline of serum glucose levels, and exogenous insulin should only be considered when glucose is no longer declining with fluid alone. Earlier insulin administration should be considered in children who have more severe ketosis and acidosis (ie, moderate to large urine ketones and serum bicarbonate <10 mmol/L to 12 mmol/L). In our patient, IV insulin was started early due to a potentially fatal hyperkalemia-related cardiac arrhythmia. The recommended dosage of insulin in HHS is 0.025 units/kg/h to 0.05 units/kg/h initially, compared with 0.1 unit/kg/h that is generally used in DKA. As with DKA, serum glucose levels should be monitored hourly initially, and the IV insulin rate should be titrated according to blood glucose concentration. As with DKA, insulin boluses are not recommended in patients with HHS.
In adults, HHS occurs more commonly in elderly patients with established T2D (10,11). In contrast, only one of 97 published paediatric cases identified in Rosenbloom’s critical review had previously diagnosed T2D (1). Most paediatric patients presenting with HHS have not had a documented previous diagnosis of T2D; therefore, the index of suspicion must be high in patients with severe hyperglycemia, metabolic acidosis, hyperosmolality and known risk factors.
Several case series have shown that patients with T2D who are obese, African American and developmentally delayed are at greatest risk for HHS (3,7,9). Most paediatric patients who develop HHS have a family history of T2D. Rosenbloom’s critical case review found that, among those in whom family history was documented, 85% of patients with HHS had a positive family history of diabetes (1).
The Canadian Diabetes Association has established screening criteria for T2D in children. Children who are 10 years of age, or younger if pubertal, should be screened for T2D every two years with a fasting plasma glucose test if they have ≥2 of the following risk factors: obesity (BMI >95th percentile for age and sex); member of a high-risk ethnic group and/or family history of T2D and/or exposure to diabetes in utero; signs or symptoms of insulin resistance (acanthosis nigricans, hypertension, dyslipidemia, nonalcoholic fatty liver disease); impaired glucose tolerance (IGT); or use of antipsychotic medications/atypical neuroleptics. Children who are severely obese (BMI > 99th percentile for age and sex) and who meet the above criteria should undergo yearly screening with an oral glucose tolerance test (12). However, as seen in our patient, screening is difficult and not performed in those who do not have regular interactions with the health care system, underscoring the importance of public awareness campaigns on diabetes prevention, its risk factors and its clinical manifestations. Public health initiatives, such as poster campaigns directed at teachers, students, parents and paediatricians, have been shown to prevent DKA (13). Similarly, public health strategies that could be implemented to increase awareness about T2D in youth include school-based education programs for students and school personnel, as well as education programs for the workplace.
In Canada, the incidence of T2D in children is particularly high in the Aboriginal population (23.3 cases per 100,000 per year), followed by Asian children (7.7 cases per 100,000 per year), and African/Caribbean children (1.9 cases per 100,000 per year) (2). The prospective national surveillance study by Amed et al (2) found that 95% of children with T2D were obese, and 37% had at least one comorbidity at diagnosis.
Our patient developed several serious complications secondary to HHS; however, he was able to make a full recovery, unlike many published cases. He had a BMI >95th percentile for age and sex, was from a high-risk ethnic group, had a family history of T2D, acanthosis nigricans and hypertension. He met the criteria for screening and thus, HHS could have been prevented with appropriate screening. Our case demonstrates the importance of following the recommended screening guidelines in high-risk paediatric patients, and educating the general public regarding the signs and symptoms of diabetes, particularly for patients with little or no interaction with the health care system.
HHS is a distinct clinical entity from DKA, although the two may coexist, making the diagnosis and treatment challenging. If HHS is suspected in a child, they should be treated in consultation with paediatric endocrinology in an intensive care setting. Close monitoring for acute complications and long-term sequelae is important to ensure the best possible outcomes for patients with HHS.