History

Fact Explanation
Symptoms can occur over several days in first presentation or rapid onset of symptoms in a diagnosed patient with diabetes. Diabetic ketoacidosis stands for an acute state of uncontrolled severe diabetes associated with ketoacidosis requiring emergency management. Biochemically it is a disordered metabolic condition of hyperglycemia, dehydration and ketoacidosis. Diabetic ketoacidosis occurs as a result of hepatic gluconeogenesis, glycogenolysis and lipolysis due to absolute or relative insulin deficiency. This can be the first presentation or can be a complication of a diagnosed patient due to failure to comply with insulin therapy. Diabetic ketoacidosis predominantly occur in children with type 1 diabetes. [1],[2],[3],[4],[5],
Polyuria. Polyuria results due to the osmotic diuresis that results when blood glucose levels exceed the renal threshold. [1],[2],[3],[4],[5]
Increased thirst (Polydipsia). Due to hyperglycaemia and osmotic diuresis serum osmolality increases. High serum osmolality shifts water from intracellular to extracellular space. By stimulating the osmo receptors thirst mechanism is activated in the hypothalamus. [1],[2],[3],[4],[5]
Weight loss. Their is a history of weight loss despite good appetite. This occur due to the fluid depletion and the accelerated break down of fat and muscles secondary to insulin deficiency. [1],[2],[3],[4],[5]
Nausea and vomiting. Ketone bodys specially beta hydroxy butrate induce nausea and vomiting. [1],[2],[3],[4],[5]
Abdominal pain. Due to dehydration and acidosis diffuse abdominal pain occurs. The severity range from mild to very severe pain. [1],[2],[3],[4],[5]
Malaise and fatigability. Muscle pain may occur as a result of electrolyte imbalance. It can also present as a symptom of hyperglycemia. [1],[2],[3],[4],[5]
Deep sighing respiration. Metabolic acidosis condition occurs due to accumulation of acidic organic substance in the blood. Respiratory compensation results in deep sighing breathing. [1],[2],[3],[4],[5]
Altered consciousness Increased osmolality of brain cells occur due to serum hyperosmolality, dehydration and acidosis. It cause cerebral edema resulting alteration of level of consciousness. [1],[2],[3],[4],[5]
History of inter current infection. History of inter current infection ( Eg:- urinary or respiratory tract infection) may be present. They predispose to increase the activity of anti insulin hormones such as cortisol causing relative insulin deficiency. Usually ill children have poor diabetic control which predispose to diabetic ketoacidosis.[1],[2],[3],[4],[5]
History of other auto immune disorders. Diabetic ketoacidosis predominantly occur in children with type 1 diabetes. Type 1 diabetes is commonly associated with other auto immune diseases such as thyroid diseases and vitiligo. [1],[2]
History of secondary causes of diabetes mellitus type-1. Their may be positive secondary causes of diabetes mellitus in the history. Diabetes in thalassaemia is thought to be caused mainly by iron overload, from repeated blood transfusions, damaging the pancreas. There is also evidence in some people with thalassaemia for an autoimmune reaction against ß-cells. Insulin resistance may occur in thalassaemia, caused by liver disease from iron overload or hepatitis C virus infection. [1],[2],[4]
References
  1. LISSAUER, TOM and CLAYDEN, GRAHAM. Illustrated Textbook of Paediatrics. 4th Ed. ELESVIER, 2012,433-441.
  2. ONYIRIUKA ALPHONSUS N, IFEBI EMEKA. Ketoacidosis at diagnosis of type 1 diabetes in children and adolescents: frequency and clinical characteristics. Array [online] 2013 December [viewed 09 June 2014] Available from: doi:10.1186/2251-6581-12-47
  3. WESTERBERG DP. Diabetic ketoacidosis: evaluation and treatment. Am Fam Physician [online] 2013 Mar 1, 87(5):337-46 [viewed 09 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/23547550
  4. USHER-SMITH J. A., THOMPSON M., ERCOLE A., WALTER F. M.. Variation between countries in the frequency of diabetic ketoacidosis at first presentation of type 1 diabetes in children: a systematic review. Diabetologia [online] December, 55(11):2878-2894 [viewed 09 June 2014] Available from: doi:10.1007/s00125-012-2690-2
  5. ASL AS, MALEKNEJAD S, KELACHAYE ME. Diabetic ketoacidosis and its complications among children. Acta Med Iran [online] 2011, 49(2):113-4 [viewed 09 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/21598221

Examination

Fact Explanation
Ill looking child. As a combined effect of dehydration, hyperglycemia and electrolyte imbalance child looks ill. [1],[2],[3],[4]
Low BMI. Severe loss of weight can identify with low BMI. This occur due to the fluid depletion and the accelerated breakdown of fat and muscles secondary to insulin deficiency. [1],[2],[3],[4]
Signs of dehydration. Due to the dehydration signs such as dry mucous membranes, reduced skin turgor, weak rapid pulse, sunken eyes, hypo tension and increased capillary refilling time can be elicited. Identifying the degree of dehydration as mild (3%), moderate (5%) or severe (8%) is very important in pediatric management. [1],[2],[3],[4]
Kussmaul's breathing Deep sighing respiration occurs as a respiratory compensation to metabolic acidosis condition in the body. [1],[2],[3],[4]
Ketotic breath. Ketotic breath with characteristic fruity odor occur due to acetone. [1],[2],[3],[4]
Abdominal tenderness. Diffuse abdominal tenderness can be elicited due to dehydration and acidosis. The severity range from mild to very severe pain mimicking a surgical emergency. [1],[2],[3],[4]
Altered level of conciseness Assess the level of conciseness with Glasgow coma scale. Alteration of conciseness can range from drowsiness to coma. Coma condition occurs in approximately 10% of patients. [1],[2],[3],[4]
Insulin injection sites in the body. Common complications of subcutaneous insulin injection include lipoatrophy and lipohypertrophy. The development of lipoatrophy may have an immunological basis, predisposed by lipolytic components of certain insulins. With time, patients learn that these areas are relatively pain free and continue to use them. However, the absorption of insulin from lipoatrophic areas is erratic leading to frequent difficulties in achieving ideal blood glucose control. Lipohypertrophy is the most common cutaneous complication of insulin therapy. Newer insulins have also reduced its prevalence considerably, although its adverse effect on diabetic control is similar to lipoatrophy through impaired absorption of insulin into the systemic circulation. [1],[2],[3],[4]
Signs of intercurrent infection. Fever, signs of respiratory tract infection or urinary tract infection may be positive in examination. Fever is not part of diabetic ketoacidosis. [1],[2],[3],[4]
References
  1. LISSAUER, TOM and CLAYDEN, GRAHAM. Illustrated Textbook of Paediatrics. 4th Ed. ELESVIER, 2012,433-441.
  2. ONYIRIUKA ALPHONSUS N, IFEBI EMEKA. Ketoacidosis at diagnosis of type 1 diabetes in children and adolescents: frequency and clinical characteristics. Array [online] 2013 December [viewed 09 June 2014] Available from: doi:10.1186/2251-6581-12-47
  3. USHER-SMITH J. A., THOMPSON M., ERCOLE A., WALTER F. M.. Variation between countries in the frequency of diabetic ketoacidosis at first presentation of type 1 diabetes in children: a systematic review. Diabetologia [online] December, 55(11):2878-2894 [viewed 09 June 2014] Available from: doi:10.1007/s00125-012-2690-2
  4. ASL AS, MALEKNEJAD S, KELACHAYE ME. Diabetic ketoacidosis and its complications among children. Acta Med Iran [online] 2011, 49(2):113-4 [viewed 09 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/2159822

Differential Diagnoses

Fact Explanation
Metabolic acidosis Their are causative factors for metabolic acidosis other than diabetic ketoacidosis. In children metabolic acidosis commonly occur due to diarrhea. It is a normal anion gap metabolic acidosis. Metabolic acidosis with a elevated anion gap occur in conditions such as uremia, ethanol poisoning and lactic acidosis. [1],[2],[3],[4]
Respiratory acidosis Respiratory acidosis occur in conditions such as neuromuscular diseases, chest wall disorders, obstructive sleep apnea, neurological disorders, central nervous system depressant overdose and severe asthma. [1],[2],[3],[4]
Pneumonia Pneumonia commonly presents with productive cough, fever accompanied by shaking chills, shortness of breath, pluritic type chest pain and an increased respiratory rate. But can present with atypical symptoms such as abdominal pain and confusion. [1],[2],[3],[4]
Hypokalemia Hypokalemia usually occur with excessive loss usually accompanied by a history of vomiting or diarrhea. Clinically presents with acute intermittent episodes of paralysis. [1],[2],[3],[4]
Acute appendicitis The typical history is periumbilical pain followed by nausea, right hypochondrial pain and vomiting. On examination rebound tenderness, rigidity and guarding suggest the diagnosis. [1],[2],[3],[4]
Septic shock Usually presents with non specific symptoms such as fever with chills and rigors, malaise, nausea, vomiting, difficulty in breathing and confusion. Identifying septic focus by localizing symptoms helps to the management. [1],[2],[3],[4]
Salicylate toxicity Salicylate toxicity causes metabolic acidosis. It usually presents with hyperventilation, tinnitus and epigastric pain. [1],[2],[3],[4]
Hyperosmolar hyperglycemic nonketotic coma Most patients with hyperosmolar hyperglycemic are diagnosed patients with diabetes mellitus-type 2. Usually develops over a course of days to weeks. But diabetic ketoacidosis, rapidly develops , over few days. Patient present with increasing thirst, polydipsia, polyuria, weight loss, and weakness. But do not complain of abdominal pain. [1],[2],[3],[4]
References
  1. LISSAUER, TOM and CLAYDEN, GRAHAM. Illustrated Textbook of Paediatrics. 4th Ed. ELESVIER, 2012,433-441.
  2. ONYIRIUKA ALPHONSUS N, IFEBI EMEKA. Ketoacidosis at diagnosis of type 1 diabetes in children and adolescents: frequency and clinical characteristics. Array [online] 2013 December [viewed 09 June 2014] Available from: doi:10.1186/2251-6581-12-47
  3. USHER-SMITH J. A., THOMPSON M., ERCOLE A., WALTER F. M.. Variation between countries in the frequency of diabetic ketoacidosis at first presentation of type 1 diabetes in children: a systematic review. Diabetologia [online] December, 55(11):2878-2894 [viewed 09 June 2014] Available from: doi:10.1007/s00125-012-2690-2
  4. KUMAR, Parveen and CLARK, Michael. KUMAR & CLARK'S Clinical Medicine. 8th Ed. ELSEVIER.2012.

Investigations - for Diagnosis

Fact Explanation
Blood glucose level In diabetic ketoacidosis serum glucose concentration is usually higher than 200mg/dl (>11.1mmol/l) Capillary blood sugar level check as a bedside test, while venous blood sample is sent to the lab for the confirmation. Monitor capillary blood glucose level hourly in initial hours of management. Serum glucose level check 2 hours after start of IV fluid therapy, there after monitor it 4 hourly. [1],[2],[3],[4],
Urine analysis. Urine dipstick is useful to identify glycosurea and ketonuria. For urine sugar Benedict's test and for urine ketones Rothera's test can be done in the ward. [1],[2],[3],[4],
Serum ketone level In diabetic ketoacidosis serum ketone concentration is usually higher than 5 mEq/L. [1],[2],[3],[4],
Serum electrolytes Their is a shift of potassium from intracellular to extracellular space in exchange with hydrogen ions. Most of the extracellular potassium loss in urine. Due to the dilutional effect of hyperglycemia sodium values are likely to be low than actual values. Therefore corrected sodium value calculation done. Serum electrolyte level check 2 hours after start of IV fluid therapy, there after monitor it 4 hourly. [1],[2],[3],[4],
ECG Electrocardiographic monitoring, may be required in the initial hours of therapy due to hypokalemia. [1],[2],[3],[4],
Arterial blood gas analysis This assess the degree of acidosis. Usually in diabetic ketoacidosis pH <7.3. The report shows features of metabolic acidosis. Venous blood sample is adequate in children due to difficulty in arterial blood sample collection. [1],[2],[3],[4],
Serum bicarbonate level This is useful to assess the degree of acidosis and to calculate the anion gap.Characteristically serum bicarbonate level is <15mmol/l. [1],[2],[3],[4],
Blood urea and creatinine level. Blood urea level is increased due to dehydration. Some times show falsely elevated creatinine value due to ketone bodies. [1],[2],[3],[4],
Full blood count In diabetic ketoacidosis neutrophil leukocytosis can occur in absence of infection. Heamoglobin level and pack cell volume must assessed because dehydration predispose thrombosis. [1],[2],[3],[4],
Septic screen urine culture, blood culture, chest x-ray perform to identify any intercurrent infection. [1],[2],[3],[4],
Serum amylase level High levels can be seen in diabetic ketoacidosis. But this is less than values in acute pancreatitis. [1],[2],[3],[4],
CT brain To detect early cerebral edema. This is performed in children with altered consciousness level with features of diabetic ketoacidosis. [1],[2],[3],[4],
MRI brain To detect early cerebral edema. To perform this child should show altered consciousness level . [1],[2],[3],[4],
References
  1. LISSAUER, TOM and CLAYDEN, GRAHAM. Illustrated Textbook of Paediatrics. 4th Ed. ELESVIER, 2012,433-441.
  2. ONYIRIUKA ALPHONSUS N, IFEBI EMEKA. Ketoacidosis at diagnosis of type 1 diabetes in children and adolescents: frequency and clinical characteristics. Array [online] 2013 December [viewed 09 June 2014] Available from: doi:10.1186/2251-6581-12-47
  3. WESTERBERG DP. Diabetic ketoacidosis: evaluation and treatment. Am Fam Physician [online] 2013 Mar 1, 87(5):337-46 [viewed 09 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/23547550
  4. KUMAR, Parveen and CLARK, Michael. KUMAR & CLARK'S Clinical Medicine. 8th Ed. ELSEVIER.2012.

Investigations - Followup

Fact Explanation
Follow up clinic visits. Arrange monthly follow up clinic visits. During clinic visits check home blood sugar monitoring chart and Benedict's test results and assess the diabetic control. [1],[2]
Periodic assessment. Ensure optimal growth and development. Assess for microvascular and macrovascular complications of diabetes. Arrange annual screening for retinopathy after 10years of age and annual screening for nephropathy after 5 years 0f onset but not before puberty.[1],[2]
References
  1. LISSAUER, TOM and CLAYDEN, GRAHAM. Illustrated Textbook of Paediatrics. 4th Ed. ELESVIER, 2012,433-441.
  2. ONYIRIUKA ALPHONSUS N, IFEBI EMEKA. Ketoacidosis at diagnosis of type 1 diabetes in children and adolescents: frequency and clinical characteristics. Array [online] 2013 December [viewed 09 June 2014] Available from: doi:10.1186/2251-6581-12-47

Management - General Measures

Fact Explanation
Child need HDU admission Diabetic Ketoacidosis is a pediatric emergency. Assess airway, give 100% oxygen via face mask. Insert 2 IV cannulae, one in each arm and start fluid replacement. If child in shock 10ml/kg bolus of 0.9% saline up to 30ml/kg.[1],[2],[3]
Nil by mouth. Gastroparesis is common in these patients. Therefore keep nil by mouth for at least 6 hours. [1],[2],[3]
Insert urinary catheter. If oliguria is present or serum creatinine level is high insert a urinary catheter. [1],[2],[3]
Insert NG tube. If their is impaired conscious level insert a NG tube to prevent aspiration. [1],[2],[3]
Insert an arterial line. Considering the severity insert an arterial line to monitor ABG and potassium. [1],[2],[3]
Insert CVP line Insert CVP line if child is in shock. [1],[2],[3]
Close observation. Cerebral oedema, hypoglycaemia and hypokalaemia are possible complications which should be identified early. Therefore monitor blood glucose level, neurological state, fluid input and output hourly. Serum electrolytes and serum glucose level check 2 hours after start of IV therapy, then do it 4 hourly. [1],[2],[3]
Educate the patient and family. If this is the first presentation, when patient is stable, educate the patient and family that Diabetes is a chronic illness requiring lifelong insulin injections. Educate family that child can lead a normal life and try not to treat differently. Refer child to the diabetic team. [1],[2],[3]
Correct the underlying cause. Assess the insulin compliance, dose, technique, injecting sites, storage method. Advise to rotate the injecting site. Advise them to seek medical advise at vtime of infection. Try to identify the underlying cause and correct it to prevent further episodes. [1],[2],[3],[4]
References
  1. LISSAUER, TOM and CLAYDEN, GRAHAM. Illustrated Textbook of Paediatrics. 4th Ed. ELESVIER, 2012,433-441.
  2. ROSENBLOOM ARLAN L.. The management of diabetic ketoacidosis in children. Diab Ther [online] December, 1(2):103-120 [viewed 09 June 2014] Available from: doi:10.1007/s13300-010-0008-2
  3. SAVAş ERDEVE ŞENAY, BERBEROğLU MERIH, OYGAR PEMBE, ŞıKLA ZEYNEP, KENDIRLI TANıL, HACıHAMDIOğLU BüLENT, BILIR PELIN, ÖçAL GöNüL. Efficiency of Fluid Treatments with Different Sodium Concentration in Children with Type 1 Diabetic Ketoacidosis. JCRPE [online] 2011 September, 3(3):149-153 [viewed 09 June 2014] Available from: doi:10.4274/jcrpe.v3i3.29
  4. CARDELLA F. Insulin therapy during diabetic ketoacidosis in children. Acta Biomed [online] 2005:49-54 [viewed 10 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/16915797

Management - Specific Treatments

Fact Explanation
Correct dehydration If dehydration is <5% correct dehydration with oral fluid, If dehydration is >5% correct dehydration with IV fluid. Initial resuscitation is performed with 0.9% saline. If do IV fluid replacement, correct over 48 hours. Rapid re hydration should be avoided as it may lead to cerebral edema. Initial rehydration fluids need to be taken in to account in calculating fluid requirements. When the blood glucose level <12mmol/l fluid replacement do with 0.45% saline + 5% dextrose. If cerebral edema developed restrict IV fluids and consider IV mannitol. [1],[2],[3],[4]
Potassium replacement To prevent hypokalemia add KCL 20mmol to every 500ml of IV fluid. [1],[2],[3],[4]
Insulin therapy Select IV route if dehydration is >5%. Soluble insulin 0.1unit/kg/hour is given. When the blood glucose level <12mmol/l insulin dose reduce to 0.05units/kg/hour if pH >7.3. Once child clinically improved and blood ketones less than 1.0mmol/l commence subcutaneous insulin. To prevent hyperglycaemia commence subcutaneous insulin 1 hour before stopping soluble insulin infusion. Total daily dose of subcutaneous insulin 0.75-1.0 u/kg in prepubertal child and 1-1.2 u/kg on pubertal group. [1],[2],[4],[5],[6],[7]
Sodium bicarbonate Sodium bicarbonate need to be given only if pH < 6.9. [1],[2][5],[6]
Treat underlying cause If infection is suspected start broad spectrum antibiotics empirically after taking samples for culture. [1],[2],[5],[6]
References
  1. LISSAUER, TOM and CLAYDEN, GRAHAM. Illustrated Textbook of Paediatrics. 4th Ed. ELESVIER, 2012,433-441.
  2. ROSENBLOOM ARLAN L.. The management of diabetic ketoacidosis in children. Diab Ther [online] December, 1(2):103-120 [viewed 09 June 2014] Available from: doi:10.1007/s13300-010-0008-2
  3. SAVAş ERDEVE ŞENAY, BERBEROğLU MERIH, OYGAR PEMBE, ŞıKLA ZEYNEP, KENDIRLI TANıL, HACıHAMDIOğLU BüLENT, BILIR PELIN, ÖçAL GöNüL. Efficiency of Fluid Treatments with Different Sodium Concentration in Children with Type 1 Diabetic Ketoacidosis. JCRPE [online] 2011 September, 3(3):149-153 [viewed 09 June 2014] Available from: doi:10.4274/jcrpe.v3i3.29
  4. NATIONAL COLLABORATING CENTRE FOR WOMEN'S AND CHILDREN'S HEALTH (UK). [online] 2004 Sep [viewed 09 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/21938860
  5. BENNET, P.N. and BROWN, M.J. CLINICAL PHARMACOLOGY. 9th Ed. CHURCHILL LIVINGSTONE. 2003.
  6. KATZUNG, Bertram G. MASTERS, Susan B. and TREVOR, Anthony J. Basic and Clinical Pharmacology. 12th Ed. Tata McGraw-Hill. 2012.
  7. CARDELLA F. Insulin therapy during diabetic ketoacidosis in children. Acta Biomed [online] 2005:49-54 [viewed 10 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/16915797