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Diabetic Emergencies: Diabetic Ketoacidosis in Childhood and Adolescence, Part 3 of 3

Christina Kanaka-Gantenbein, MD, PhD

Diabetic_Emergencies

Acidosis management 

Severe acidosis is reversible by fluid and insulin replacement. Insulin stops lipolysis and further ketone production and allows ketoacids to be metabolized, generating bicarbonate.4 Moreover, treatment of hypovolemia improves tissue perfusion and renal function, thereby increasing the excretion of organic acids.

Controlled trials have shown no clinical benefit from bicarbonate administration 3,4 and there are well-recognized serious adverse effects, including paradoxical CNS acidosis 28,29 and hypokalemia from rapid acidosis correction. 30,31 Nevertheless, there may be selected patients who may profit from cautious alkali administration, such as patients with severe acidemia (arterial pH < 6.9) in whom decreased cardiac contractility and peripheral vasodilatation can further impair tissue perfusion, and patients with life-threatening hyperkalemia. 4,32….

If bicarbonate is considered necessary, cautiously give 1-2 mmol/kg over 60 minutes. 3,4

Follow-up management — transition to per os fluid intake and SC insulin injections

  • Oral fluids should be introduced only when substantial clinical improvement has occurred and when oral fluids are well tolerated; IV fluid administration should then be reduced.
  • The most convenient time to change to SC insulin is just before a mealtime, provided that ketoacidosis has resolved (venous pH > 7.3 and serum bicarbonate > 18 mmol/L), plasma glucose is < 200 mg/dl (11.1 mmol/L), and oral fluid intake is well tolerated.
  • To prevent rebound hyperglycemia, the first SC insulin injection should be given 15-30 minutes (with rapid-acting insulin analog) or 1-2 hours (with regular insulin) before stopping the insulin infusion to allow sufficient time for the insulin to be absorbed. With intermediate or long-acting insulin the overlap should be longer and the IV insulin gradually lowered. For example, for patients on a basal-bolus insulin regimen, the first dose of basal insulin should be administered in the evening and the insulin infusion should be stopped the next morning.
  • There is no clear advantage of one SC insulin regimen over the other when changing from IV to SC insulin, and the dose and type of insulin should be according to local preferences and circumstances.3,4 One possible insulin regimen for newly diagnosed diabetes after resolution of DKA is to provide two thirds of the total daily insulin requirement in the morning 30 minutes before breakfast, divided as two thirds intermediate-acting insulin and one third rapid-acting insulin, and the remaining one third of the daily requirement in the evening 30 minutes before dinner, again dividing the dose as two-thirds intermediate-acting insulin and one third rapid-acting. When the decision has been made to start an insulin analog regimen, 40-50% of daily insulin requirement is provided before going to bed as a long-acting analog (glargine or detemir), while the remaining insulin requirement is divided into doses of a rapid-acting analog 10-15 minutes before meals. Type 1 diabetic patients who were already on an insulin regimen (for example insulin pump or basal-bolus principle) before the occurrence of DKA can go back on their usual regimen.
  • After transition to SC insulin, frequent blood glucose monitoring is required to avoid marked hyper- or hypoglycemia.

Potential complications — morbidity and mortality

The overall mortality rate from DKA in children is 0.15-0.30%. 3,4,22

Cerebral edema 

The most severe potential complication of DKA management is cerebral edema. It accounts for 60-90% of all DKA deaths. 3,4,16,22 Although rare, when it supervenes it is accompanied by a mortality rate of 21-24%. Moreover, 10-25% of survivors of cerebral edema have significant residual morbidity. Despite considerable efforts to identify the potential cause of cerebral edema, its pathogenesis is incompletely understood and there is evidence that some cerebral edema cases supervene even before the initiation of DKA treatment.16 There is no convincing evidence of an association between the rate of fluid or sodium administration used in the treatment of DKA and the development of cerebral edema. 4,33 Patients more likely to develop cerebral edema are:

  • The young
  • Those with new-onset diabetes
  • Those with a longer duration of symptoms.

The signs and symptoms of cerebral edema are:

  • Headache and slowing of heart rate
  • Change in neurological status (restlessness, irritability, increased drowsiness, incontinence)
  • Specific neurological signs (e.g., cranial nerve palsies)
  • Rising blood pressure
  • Decreased O 2 saturation.

Risk factors for the development of cerebral edema at diagnosis or during treatment of DKA have been reported to be: 4,16

  • Greater hypocapnea at presentation after adjusting for the degree of acidosis 16,34
  • Increased serum urea nitrogen at presentation 16,34
  • More severe acidosis at presentation 22,35
  • Bicarbonate treatment for correction of acidosis 16
  • An attenuated rise in measured serum sodium concentration during therapy 36
  • Greater volumes of fluid given in the first 4 hours 4,22
  • Administration of insulin during the first hour of fluid treatment. 22

In recent studies, the degree of edema formation during DKA in children correlated with the degree of dehydration and hyperventilation at presentation, but not with factors related to initial osmolality or osmotic changes during treatment. 4 These data have been interpreted as supporting the hypothesis that cerebral edema is related to cerebral hypoperfusion during DKA and that osmotic fluctuations during DKA treatment do not play a primary causal role. 4,34

Clinically significant cerebral edema usually occurs 4-12 hours after treatment has started, but can even occur before treatment initiation, 4,16 or, rarely, may develop as late as 24-48 hours after initiation of treatment.

 

Box 2.3 Criteria used for the diagnosis of cerebral edema

Diagnostic criteria
  • Abnormal motor or verbal response to pain
  • Decorticate or decerebrate posture
  • Cranial nerve palsy (especially III, IV, and VI)
  • Abnormal neurogenic respiratory pattern (e.g. grunting, tachypnea, Cheyne-Stokes respiration, apneusis)
Major criteria
  • Altered mentation/fluctuating level of consciousness
  • Sustained heart rate deceleration (decrease more than 20 beats per minute) not attributable to improved intravascular volume or sleep state
  • Age-inappropriate incontinence
Minor criteria
  • Vomiting
  • Headache
  • Lethargic or not easily arousable
  • Diastolic blood pressure > 90 mmHg
  • Age < 5 years

The criteria used for the diagnosis of cerebral edema are categorized as major or minor (Box 2.3).4,37 Thus, one diagnostic criterion, two major criteria, or one major and two minor criteria have a sensitivity of 92% to diagnose cerebral edema and a false positive rate of only 4%.

Treatment of cerebral edema

  • Initiate treatment as soon as the condition is suspected.
  • Mannitol or hypertonic saline should be available at the bedside.
  • Reduce the rate of fluid administration by one third.
  • Give mannitol 0.5-1 g/kg IV over 20 minutes and repeat if there is no initial response in 30 minutes to 2 hours. 4,38 Note, however, that mannitol may result in rebound cerebral edema!
  • Hypertonic saline (3%) 5-10 ml/kg over 30 minutes may be an alternative to mannitol or a second-line therapy if there is no initial response to mannitol. 4,39
  • Elevate the head of the bed.
  • Intubation may be necessary for the patient with impending respiratory failure, but aggressive hyperventilation (to a PCO2 < 2.9 kPa [22 mmHg]) has been associated with poor outcome and is not recommended.
  • After treatment for cerebral edema has been started, a cranial CT scan should be obtained to rule out other possible intracerebral causes of neurological deterioration (about 10% of cases), especially thrombosis or hemorrhage, which may benefit from specific therapy. 40,41

 

Box 2.4 summarizes all possible complications and causes of morbidity and mortality after DKA in children.

Box 2.4 Potential complications — causes of important morbidity and mortality in DKA

  • Cerebral edema
  • Hypokalemia
  • Hyperkalemia
  • Severe hypophosphatemia
  • Severe hypoglycemia
  • Other CNS complications (disseminated intravascular coagulation, dural sinus thrombosis, basilar artery thrombosis)
  • Peripheral venous thrombosis
  • Sepsis
  • Rhinocerebral or pulmonary mucormycosis
  • Aspiration pneumonia
  • Pulmonary edema
  • Acute respiratory distress syndrome (ARDS)
  • Pneumothorax, pneumomediastinum, subcutaneous emphysema
  • Rhabdomyolysis
  • Acute renal failure
  • Acute pancreatitis

Prevention of recurrent DKA

It is important to clarify the causes of an episode of DKA, especially in patients known to have diabetes, in order to avoid a subsequent episode.

  • In most cases, insulin omission, either inadvertent or deliberate, is the cause of DKA.
  • There is usually an important psychosocial reason for insulin omission:
    • in an adolescent girl an attempt to lose weight
    • a means of escaping an intolerable home situation
    • the result of clinical depression and trial of a multisystematic psychotherapeutic approach may lead to reduction of new episodes of DKA in poorly controlled type 1 diabetic adolescents (Figure 2.3). 42
  • Specifically in insulin pump users, the most common cause of DKA is the failure to take extra insulin using a pen or a syringe when hyperglycemia and hyperketonemia or ketonuria occur due to technical problems with the pump such as catheter occlusion, etc.
  • An infection that is not associated with vomiting or diarrhea is seldom the cause of DKA when the patient and the whole family are well educated in diabetes management and there is a 24-hour telephone helpline available. 43

DCMS148CG 

Figure 2.3 The impact of a multisystematic approach in diminishing the incidence of episodes of diabetic ketoacidosis in adolescents with poorly controlled Type 1 diabetes mellitus. Cumulative number of DKA admissions during five 6-month intervals for MST and control participants. The baseline interval (T1) started 6 months before trial entry; the subsequent intervals were from T1 to treatment termination (T2), from treatment termination to 12-month follow-up (T3), from 12-month to 18-month follow-up (T4), and from 18-month to 24-month follow-up (T5). Error bars are } 1 SE. Copyright 2008 American Diabetes Association. From Diabetes Care, Vol. 31, 2008; 1746-1747. Reproduced by permission of The American Diabetes Association.

Summary box
  • It is important that children and adolescents with DKA should be managed in centers experienced in treating DKA
  • It is important that general practitioners and all health professionals have a high level of suspicion to recognize and diagnose a case of DKA early in order to prevent severe metabolic deterioration and loss of consciousness
  • It is important to begin fluid replacement therapy 1 – 2 hours before starting insulin therapy
  • Volume expansion is required only if needed to restore peripheral circulation, and subsequent fluid administration (including oral fluids) should rehydrate evenly over 48 hours at a rate rarely in excess of 1.5 – 2 times the usual daily maintenance requirement
  • If the blood glucose concentration decreases too quickly or becomes too low before DKA has resolved, increase the amount of glucose administered. Do not decrease the insulin infusion
  • Even with normal or high levels of serum potassium at presentation, there is always a total body deficit of potassium
  • There is no evidence that bicarbonate is either necessary or safe in DKA
  • All cases of recurrent DKA are preventable
  • Abdominal pain mimicking acute abdomen in childhood may be a symptom of DKA and not necessarily of appendicitis
 
Patient advice
  • Always check your blood glucose levels, especially when you are ill.
  • Besides blood glucose measurements, check for the presence of ketones in urine, or even better in plasma, when you are sick and have high blood glucose readings. The presence of ketones in combination with high blood glucose readings suggests that you are at risk for decompensation, i.e. for diabetic ketoacidosis.
  • Always have a pen of rapid-acting and long-acting insulin analog available, even if you wear an insulin pump, since technical problems with the insulin pump or the catheter may lead to diabetic ketoacidosis if they are not quickly reversed and treated.
  • Remember that all cases of recurrent DKA are preventable and it is up to you to avoid a subsequent episode.
Next Excerpt: Case Studies
 
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Nikolaos Katsilambros, MD, PhD, FACP

SCOPE Founding Fellow
Professor of Internal Medicine
Athens University Medical School
Evgenideion Hospital and Research Laboratory ‘Christeas Hall’
Athens, Greece
Christina Kanaka-Gantenbein, MD, PhD
Associate Professor of Pediatric Endocrinology and Diabetology
First Department of Pediatrics, University of Athens
Agia Sofia Children’s Hospital
Athens, Greece
Stavros Liatis, MD
Consultant in Internal Medicine and Diabetology
Laiko General Hospital
Konstantinos Makrilakis, MD, MPH, PhD
Assistant Professor of Internal Medicine and Diabetology
Athens University Medical School
Laiko General Hospital
Athens, Greece
Nikolaos Tentolouris, MD, PhD
Assistant Professor of Internal Medicine and Diabetology
University of Athens
Laiko General Hospital
Athens, Greece
 
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Diabetic Emergencies: Diagnosis and Clinical Management provides emergency room staff, diabetes specialists and endocrinologists with highly practical, clear-cut clinical guidance on both the presentation of serious diabetic emergencies like ketoacidosis, hyperosmolar coma and severe hyper- and hypoglycemia, and the best methods of both managing the emergencies and administering appropriate follow-up care.
 
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