Trends in diabetic ketoacidosis in childhood and adolescence: a 15-yr experience

Abstract: The number of episodes of diabetic ketoacidosis (DKA) is a significant outcome measure for diabetes care. We ascertained patterns of admission due to DKA over 15 yr to determine whether this indicator of diabetes care had improved in parallel with clinical practices. Between 1 January 1985 and 31 December 1999, 630 admissions were reviewed. We subanalyzed these admissions according to whether the patient was newly diagnosed, had infrequent episodes of DKA (non-relapsers) or had frequent (≥ 2/yr) episodes of DKA (relapsers). Overall there was a slight downward trend in the incidence of DKA admissions over the study period. There was a proportionate increase in the incidence of DKA amongst newly diagnosed patients, with a proportionate decrease in the incidence of DKA seen in relapsers. DKA occurring in non-relapsers remained relatively stable. Adverse clinical events during the admission were relatively uncommon and occurred in all three subgroups. There was no significant difference in HbA1C prior to admission between the relapser and non-relapser groups and there was similarity in the degree of acidosis between all three subgroups. The frequency of significant complications associated with DKA remained unchanged over the study period. Slower rehydration policies were not associated with decreases in either cerebral edema or death rates. DKA remains a significant complication of type 1 diabetes associated with a variety of significant adverse events. Our experience indicates that further efforts to reduce the occurrence of DKA must be focused upon earlier diagnosis and intervention in newly diagnosed patients.     

Current understanding and management of paediatric diabetic ketoacidosis

Diabetic Ketoacidosis (DKA) is a serious complication of insulin deficiency. It is typically seen in children and young people with Type 1 Diabetes Mellitus, either at first presentation, or in established disease, for instance due to poor compliance, equipment failure, or concurrent illness. Insulin deficiency leads to hyperglycaemia causing osmotic fluid loss, dehydration and electrolyte derangement. Osmotic symptoms of polyuria and polydipsia due to hyperglycaemia may give way to oliguria or anuria as circulatory insufficiency develops. Unable to utilise glucose, cells default to alternative mechanisms of energy production resulting in the accumulation of ketone bodies. Kussmaul breathing may compensate partially for the worsening acidosis. Untreated, DKA results in progressively worsening acidosis, development of shock, coma and ultimately death. Clear guidelines for the management of DKA in children and young people exist once a diagnosis is made. However, evidence for these guidelines is limited and remains the subject of ongoing debate. Diligence is required to ensure that fluid and insulin is delivered appropriately, and to identify early the complications of both DKA and its treatment, such as cerebral oedema. In this article we review the current state of DKA management with key practice points.     

Acute renal failure complicating diabetic ketoacidosis

Two previously healthy children, aged 13 and 14 years, respectively, presented with diabetic ketoacidosis. Both children developed acute renal failure, a rare complication of diabetic ketoacidosis and required dialysis.     

Factors predicting cerebral edema in young children with diabetic ketoacidosis and new onset type I diabetes

We have attempted to identify any characteristics which could be used to predict the development of cerebral edema in four children under 5 years of age with new onset insulin-dependent diabetes mellitus and diabetic ketoacidosis. We retrospectively analysed and compared the concentration of serum sodium (corrected for serum glucose value) and effective serum osmolality of these 4 children with values of 10 age-matched controls with new onset insulin-dependent diabetes mellitus who did not develop cerebral edema during treatment of diabetic ketoacidosis. The initial serum sodium values of the two groups were not statistically different. Patients who developed cerebral edema had lower initial serum glucose values and effective serum osmolality. During treatment, patients who developed cerebral edema had consistently lower mean serum sodium and osmolality than controls at each 4-h interval after the first 4 h of therapy. Serum sodium and osmolality declined progressively after the initiation of therapy in cerebral edema patients, while remaining stable in controls. These data suggest that children who develop cerebral edema during treatment for diabetic ketoacidosis initially may have a relatively normal serum osmolality and subsequently develop progressive hyponatremia and/or a trend of declining serum sodium before developing cerebral edema.     

Current concepts in the pathophysiology and management of diabetic ketoacidosis

Recent studies indicate that for the development of diabetic ketoacidosis glucagon excess is essential in addition to a deficiency of insulin. Glucagon activates the carnitine acyl transferase I leading to ketonemia. Low dose continuous infusion of insulin appears to be the ideal mode of therapy for the correction of hyperglycemia. The use of sodium bicarbonate and phosphate as adjuvants in management is discussed in the light of recent observations.     

Profound hypokalemia associated with severe diabetic ketoacidosis

Hypokalemia is common during the treatment of diabetic ketoacidosis (DKA); however, severe hypokalemia at presentation prior to insulin treatment is exceedingly uncommon. A previously healthy 8‐yr‐old female presented with new onset type 1 diabetes mellitus, severe DKA (pH = 6.98), and profound hypokalemia (serum K = 1.3 mmol/L) accompanied by cardiac dysrhythmia. Insulin therapy was delayed for 9 h to allow replenishment of potassium to safe serum levels. Meticulous intensive care management resulted in complete recovery. This case highlights the importance of measuring serum potassium levels prior to initiating insulin therapy in DKA, judicious fluid and electrolyte management, as well as delaying and/or reducing insulin infusion rates in the setting of severe hypokalemia.     

胰岛素泵治疗儿童1型糖尿病酮症酸中毒32例临床分析

目的 观察胰岛素泵持续皮下注射胰岛素对儿童1型糖尿病酮症酸中毒(DKA)的疗效.方法 将2005-2008年收治的1型DKA患儿64例分为治疗组32例和对照组32例.治疗组予胰岛素泵治疗,对照组予小剂量胰岛素持续静脉滴注治疗.比较两组患儿血精变化、DKA纠正时间及住院时间.结果 治疗组血糖下降相对稳定,酸中毒纠正时间治疗组[(16.91±4.223)h]短于对照组[(23.31±3.797)h](P<0.001),且无反复.治疗过程中治疗组未出现低血糖,对照组出现1例.住院时间治疗组[(15.63±2.458)d]短于对照组[(20.88±3.348)d](P<0.001).结论 胰岛素泵持续皮下注射胰岛索治疗儿童1型糖尿病酮症酸中毒安全有效.     

Posterior reversible encephalopathy syndrome complicating diabetic ketoacidosis; an important treatable complication

Development of acute neurological symptoms secondary to cerebral oedema is well described in diabetic ketoacidosis (DKA) and often has a poor prognosis. We present the clinical and radiological data of a 17‐yr‐old girl who developed cortical blindness, progressive encephalopathy, and seizures caused by posterior reversible encephalopathy syndrome (PRES) that developed after her DKA had resolved. Vasogenic oedema in PRES resolves if the underlying trigger is identified and eliminated. In this case, hypertension was identified as the likely precipitating factor and following treatment her vision and neurological symptoms rapidly improved. We suggest how recent DKA may have contributed to the development of PRES in this patient.     

New-onset diabetes mellitus presenting with diabetic ketoacidosis after pediatric liver transplantation

Abstract:  The development of NODM is a common metabolic complication after liver transplantation. Presentation of post-liver transplant diabetes mellitus with DKA is rare especially among pediatric patients. We reported three pediatric patients who presented with DKA after liver transplantation. The underlying diseases leading to transplantation were cryptogenic liver cirrhosis, Wilson disease, and congenital hepatic fibrosis. None of the three patients had a history of diabetes prior to transplantation and all of them were cases of NODM after transplantation. All three patients presented with severe hyperglycemia, significant ketosis, and metabolic acidosis of variable severity. All of them received tacrolimus as one of the immunosuppressant agents. The patients received a liver transplant from a DD. The patients were treated with intravenous insulin injection (0.1 U/kg/h) and recovered from DKA, but one case expired in the intensive care unit because of bacterial sepsis after recovery from DKA. Our experience suggests that PTDM may result in ketoacidosis, and we emphasize the importance of paying more attention to glucose metabolism and risk of diabetes mellitus in patients with immunosuppressive therapy, especially tacrolimus.     

Predicting diabetic ketoacidosis in children by measuring end-tidal CO2 via non-invasive nasal capnography

AIM: To determine if nasal capnography can be used as a screening tool to predict diabetic ketoacidosis (DKA) in children with Type 1 diabetes mellitus (T1DM) presenting to the emergency department. METHODS: Cross-sectional, prospective, observational study of children with T1DM who presented to the Emergency Department of Princess Margaret Hospital for Children, Western Australia, over a 12-month period from June 2003 to June 2004. Information on demographic data and T1DM was recorded. Nasal capnography, venous blood gases and urinary analysis were performed on patients. Data were analysed using chi(2) tests and receiver operating characteristic curve analysis. Sensitivities and specificities were calculated at different end-tidal carbon dioxide (ETCO(2)) levels to predict presence of DKA. RESULTS: Fifty-eight patients aged 1-18 years (mean 10.7, SD 4.7) were analysed. Thirty-three (57%) were male and 30 (52%) presented with new onset of T1DM. Of the 58 cases, 15 (26%) had DKA, and 11 of these were new T1DM patients. No patients with an ETCO(2) > 30 mmHg had DKA (sensitivity 1.0, specificity 0.86). Six patients with an ETCO(2) < 30 mmHg did not have DKA. CONCLUSIONS: Nasal capnography in conjunction with clinical assessment is predictive of DKA. Further research into this area with larger numbers could help validate ETCO(2) as a screening tool for DKA in the emergency department.     

Rhabdomyolysis in diabetic ketoacidosis

Rhabdomyolysis is a potentially lethal disorder, characterized by elevated serum concentrations of creatine kinase (CK) due to skeletal muscle injury. In this paper a patient with diabetic ketoacidosis (DKA) is reported who developed rhabdomyolysis (maximum CK level, 37,700 U/L; normal, < 170 U/L), anemia (6.2 g/dL) and thrombocytopenia (16,000/microL). This combination of rhabdomyolysis with anemia and thrombocytopenia has not yet been reported in DKA. The pathogenic mechanism leading to rhabdomyolysis in DKA remains unsettled. From the literature it seems that those patients who develop rhabdomyolysis have very high glucose levels and a high osmolality on admission. Low phosphate levels can play a role as well. The etiology of anemia and thrombocytopenia in our patient remains obscure. Intravascular hemolysis could not be demonstrated but intramedullar hemolysis, due to osmolar shift or hypophosphatemia, cannot be excluded. A review of the literature data revealed that rhabdomyolysis is not so uncommon in DKA. However, to obtain incidence data in children, prospective studies are necessary.     

Use of hypertonic saline in the treatment of cerebral edema in diabetic ketoacidosis (DKA)

Abstract: Cerebral edema is the primary cause of morbidity and mortality in children and adolescents with diabetic ketoacidosis (DKA). We report a case of an adolescent female with life-threatening DKA-related cerebral edema who responded to a combination of mannitol and hypertonic saline. This is the first report of the use of hypertonic saline in the treatment of cerebral edema due to DKA.     

Continuous non-invasive end-tidal CO2 monitoring in pediatric inpatients with diabetic ketoacidosis

INTRODUCTION: Pediatric inpatients with diabetic ketoacidosis (DKA) are routinely subjected to frequent blood draws in order to closely monitor degree of acidosis and response to therapy. The typical level of acidosis monitoring is less than ideal, however, because of the high cost and invasiveness of frequent blood labs. Previous studies have validated end-tidal carbon dioxide (EtCO2) monitoring in the emergency department (ED) for varying periods of time. We extend these findings to the inpatient portion of the hospitalization during which the majority of blood tests are sent. METHODS: All patients admitted to an intermediate care unit in (InCU) a large children's hospital were fitted with an appropriately sized oral/nasal cannula capable of sensing EtCO2. Laboratory studies were obtained according to hospital clinical practice guidelines. In a retrospective analysis, EtCO2 values were correlated with serum total CO2 (stCO2), venous pH (vpH), venous pCO2 (vpCO2), and calculated bicarbonate from venous blood gas (vHCO3-). RESULTS: A total of 78 consecutive episodes of DKA in 72 patients aged 1-21 yr were monitored for 3-38 h with both capnography and laboratory testing, producing 334 comparisons. Initial values were as follows, reported as median (range): stCO2, 11 (4-22) mmol/L; vpH, 7.281 (6.998-7.441); vpCO2, 28.85 (9.3-43.3) mmHg; and vHCO3-, 14 (3-25) mmol/L. EtCO2 was correlated well with stCO2 (r = 0.84, p < 0.001), vHCO3- (r = 0.84, p < 0.001), and vpCO2 (r = 0.79, p < 0.001). CONCLUSIONS: These data support the findings of previous studies limited to ED populations and suggest that non-invasive EtCO2 monitoring is a valuable and reliable tool to continuously follow acidosis in the setting of the acutely ill pediatric patient with DKA. Continuous EtCO2 monitoring offers the practitioner an early warning system for unexpected changes in acidosis that augments the utility of intermittent blood gas determinations.     

Sub-clinical cerebral oedema does not occur regularly during treatment for diabetic ketoacidosis

Fulminant cerebral oedema is an uncommon, fatal complication of diabetic ketoacidosis (DKA) in children. This study aimed to find out whether the sub-clinical compression of the brain ventricles found by an earlier study, is a general phenomenon during intravenous treatment for DKA. Four boys and four girls were examined. Blood glucose values ranged from 40 to 24. 6mmol/l, base excess -34. 6 to - 13. 6 and capillary blood pH 6. 89–7. 22. The patients received fluids containing both glucose and electrolytes, and insulin intravenously. After about lOh, blood glucose was 8. 7–21. 8mmol/l and base excess had decreased substantially (-9. 5 to -2. 9) in seven of the eight cases. Computerized tomography of the brain was then performed, and again after full recovery. Only two of the patients had an initial decrease in intercaudate distance, which exceeded the variability found in a reference group. Compression of the cerebral ventricles does not occur regularly during treatment for DKA.