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Table of Contents
Year : 2018  |  Volume : 1  |  Issue : 2  |  Page : 82-84

Cerebral injury in diabetic ketoacidosis: Is there a room for conservative management?

1 Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
2 Department of Medicine, Security Forces Hospital, Riyadh, Saudi Arabia
3 Department of Critical Care Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
4 Department of Medicine, New Mowasat Hospital, Hawalli, Kuwait

Date of Web Publication6-Jun-2018

Correspondence Address:
Riad A Sulimani
Department of Medicine, College of Medicine, King Saud University, Riyadh 11323
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JNSM.JNSM_15_18

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Diabetic ketoacidosis is a manifestation of decompensated glycemic control. Two cases are outlined, representing severe cerebral edema in one case and multiple cerebral infarcts in the other. Favorable outcome was achieved in both cases with conservative management, excluding the immediate use of mannitol in the first patient and the use of thrombolytic or full anticoagulant therapy in the second.

Keywords: Diabetic ketoacidosis, cerebral edema, mannitol, thrombolysis

How to cite this article:
Sulimani RA, Jammah AA, Ghozzi IM, Alotair HA, Al-Mohaya SA, Ashour TE. Cerebral injury in diabetic ketoacidosis: Is there a room for conservative management?. J Nat Sci Med 2018;1:82-4

How to cite this URL:
Sulimani RA, Jammah AA, Ghozzi IM, Alotair HA, Al-Mohaya SA, Ashour TE. Cerebral injury in diabetic ketoacidosis: Is there a room for conservative management?. J Nat Sci Med [serial online] 2018 [cited 2023 Mar 23];1:82-4. Available from: https://www.jnsmonline.org/text.asp?2018/1/2/82/233812

  Introduction Top

Cerebral crisis during diabetic ketoacidosis (DKA) is a serious complication with significant morbidity and mortality.[1],[2] Cerebral edema (CE) alone is responsible for 50%–80% of diabetes-related deaths.[1],[2] Brain injury with swelling and lateral ventricle compression appears to be common in DKA but often subclinical.[3] In addition to CE, up to 10% of cerebral complications in DKA may be related to hemorrhagic or ischemic strokes.[4] Guidelines and recommendations for the management of CE have been made, including the early use of mannitol during management.[5] In the case of ischemic stroke, there is still some controversy whether thrombolytic treatment should be offered to patients.[6] In this report, two patients with excellent outcomes are reported: one with severe CE with no mannitol given initially and a patient with multiple ischemic lesions with no antithrombolytic or therapeutic anticoagulant therapy were given.

  Case Reports Top

Case 1

A 13-year-old boy (weight = 40 kg) with Type 1 diabetes mellitus was referred to our hospital from another hospital 12 h after presentation. In the previous hospital, he was a conscious state but with severe DKA (pH of 6.93, bicarbonate 7 mmol/l, and sodium of 153 mmol/l). He was given a liter of normal saline in the 1st h and another liter in the next 2 h followed by a maintenance fluid rate of 250 ml/h. Three hours after a presentation, he developed generalized seizures and had cardiac arrest twice requiring cardiorespiratory resuscitation. The patient was intubated and subsequently transferred to our hospital.

On arrival at the Intensive Care Unit (ICU), he had bilateral dilated nonreactive pupils. Magnetic resonance imaging (MRI) showed evidence of severe CE with widespread infarcts in the watershed areas with minimal subarachnoid hemorrhage [Figure 1]. Due to his late referral, he was treated conservatively, and no mannitol was given. On the 7th day after admission, mannitol was given. Four days later, he started to show improvement and was extubated. During the next 2 weeks, he showed progressive improvement in his intellectual and motor function. Eventually, he was discharged in good condition with little memory impairment.
Figure 1: Case 1 severe cerebral edema

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Case 2

A 17-year-old girl presented to the emergency room with severe DKA in a coma. Her initial laboratory workup revealed a pH of 6.79, bicarbonate of 2mmol/l, and serum glucose of 43.6mmol/l. MRI showed multiple acute ischemic foci and in the head of left caudate nucleus [Figure 2].
Figure 2: Case 2 multiple ischemic areas

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The patient was treated for DKA along the usual measures, including 100 mmol/l of bicarbonate. Aspirin (81 mg) was given through a nasogastric tube. No therapeutic anticoagulant or antithrombolytic therapy was given. She stayed comatose for 24 h. Subsequently, she regained consciousness with evidence of left-sided hemiplegia with right-sided parasethesia. Ten days after, she showed progressive improvement in the motor function on the right side and was able to walk in 3 weeks after discharge with mild difficulty.

  Discussion Top

The two cases presented were major cerebral insults secondary to severe DKA. The outcome for both was favorable despite initial catastrophic presentations and lack of recommended treatment such as the early use of mannitol in the first case and possible antithrombolytic therapy in the second case.

The first case is a classic severe case of CE with multiple ischemic areas causing two cardiac arrests in which mannitol were not used initially. The second case displays a pattern of diffuse ischemia and multiple infarcts with reversible hemiplegia.

CE, in the first case, was diagnosed on clinical and radiological evidence. In the second case, the presentation was that of ischemic brain injury but with no clinical or radiological findings suggestive of CE.

In general, the pathogenesis of brain insult in DKA is not well understood. Three proposed mechanisms were suggested: vasogenic edema,[7] osmotic edema from aggressive fluid therapy,[8] and ischemia with cytotoxic edema.[9] It is likely that individual pathologic mechanism, or all three, could be operating to different degrees in the affected patient. Use of overzealous fluid replacement therapy, especially in the first few hours of therapy (as in our first patient) and early use of insulin therapy could be blamed for the resulting osmotic edema in this patient.[10] The issue of careful rehydration, particularly in children with severe DKA, prolonged hyperglycemia and severe dehydration has been emphasized in previous guidelines and reviews.[11],[12] When the patient is aggressively rehydrated, water will flow into the brain excessively with resultant increased intracranial pressure.[13] Treatment with an early large bolus of insulin could aggravate the situation by metabolizing glucose to water, could further aggravate the situation.[13]

The issue for the use of mannitol in the management of CE in DKA, which was not administered immediately in this patient due to his late arrival to our hospital has been well emphasized.[14],[15] However, in a report by Marcin et al., it was revealed that the use of mannitol was not particularly associated with better outcome, neither was it associated with a worse effect. It was suggested in this study that the majority of patients had severe CE which may not be applicable to many other patients with milder degrees of CE.[16] The second case displays a pattern of diffuse ischemia and multiple such as cerebral infarcts but with no CE. A decrease in N-acetylaspartate (which is a marker of neuronal integrity) was documented, especially in areas such as basal ganglia, occipital, and gray matter in these patients.[9]

It has been emphasized that DKA is an inflammatory condition characterized by elevated levels of inflammatory markers caused by oxidative stress accompanied by diffuse endothelial injury.[17] Such a proinflammatory state may be chronic in Type 1 diabetic patients,[18] and it gets exaggerated under the oxidative stress caused by hyperglycemia and ketosis. In addition, there is evidence of a procoagulant state in these patients, and such coagulation defects are multiple including low protein C, low protein S, elevated factor VIII and factor V, and changes and increased platelet aggregation.[19]

In our patient, only aspirin and prophylactic subcutaneous heparin were given. Although guidelines for management of stroke in young patients are not well established, the use of thrombolytic therapy has been well documented in case reports with favorable outcome.[20] Otherwise, use of alteplase (tPA) is not approved in the United States Food and Drug Administration for use in children <18 years of age. Until evidence-based guidelines for the use of thrombolytic therapy are available, we suggest that general good care along with aspirin may be sufficient in some of these patients. In addition, our patient did not receive full therapeutic anticoagulant therapy – whether acutely or for a long-term.

  Conclusion Top

Select patients with DKA presenting with brain injury may have a good outcome from conservative management. In the case of CE, adherence to the available guidelines in terms of mannitol use is still necessary if the patient is managed within the proper time window. However, good recovery may still be achieved with good ICU care while there is still room for mannitol to be given during the subsequent course of illness if deemed necessary. By the same token, DKA associated cerebral ischemic event may be successfully managed with aspirin with no need for thrombolytic treatment and in the absence of a definite indication for anticoagulation, for example, atrial fibrillation.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Glaser N, Barnett P, McCaslin I, Nelson D, Trainor J, Louie J, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. The pediatric emergency medicine collaborative research committee of the American academy of pediatrics. N Engl J Med 2001;344:264-9.  Back to cited text no. 1
Edge JA, Hawkins MM, Winter DL, Dunger DB. The risk and outcome of cerebral oedema developing during diabetic ketoacidosis. Arch Dis Child 2001;85:16-22.  Back to cited text no. 2
Wootton-Gorges SL, Glaser NS. Imaging of the brain in children with type I diabetes mellitus. Pediatr Radiol 2007;37:863-9.  Back to cited text no. 3
Foster JR, Morrison G, Fraser DD. Diabetic ketoacidosis-associated stroke in children and youth. Stroke Res Treat 2011;2011:219706.  Back to cited text no. 4
Wolfsdorf J, Craig ME, Daneman D, Dunger D, Edge J, Lee W, et al. Diabetic ketoacidosis in children and adolescents with diabetes. Pediatr Diabetes 2009;10 Suppl 12:118-33.  Back to cited text no. 5
Eleftheriou D, Ganesan V. Controversies in childhood arterial ischemic stroke and cerebral venous sinus thrombosis. Expert Rev Cardiovasc Ther 2009;7:853-61.  Back to cited text no. 6
Jeha George S, Haymond MW. Cerebral edema in children with diabetic ketoacidosis. In: Wolfsdorf JI, Hoppin AG, editors. Up to Date Endocrinology. Waltham, MA: Up To Date; 2011.  Back to cited text no. 7
Silver SM, Clark EC, Schroeder BM, Sterns RH. Pathogenesis of cerebral edema after treatment of diabetic ketoacidosis. Kidney Int 1997;51:1237-44.  Back to cited text no. 8
Wootton-Gorges SL, Buonocore MH, Kuppermann N, Marcin J, Dicarlo J, Neely EK, et al. Detection of cerebral {beta}-hydroxy butyrate, acetoacetate, and lactate on proton MR spectroscopy in children with diabetic ketoacidosis. AJNR Am J Neuroradiol 2005;26:1286-91.  Back to cited text no. 9
Edge JA, Jakes RW, Roy Y, Hawkins M, Winter D, Ford-Adams ME, et al. The UK case-control study of cerebral oedema complicating diabetic ketoacidosis in children. Diabetologia 2006;49:2002-9.  Back to cited text no. 10
Fiordalisi IG, Harris RM. Pediatric DKA: fluids and Insulin, How Much and When? Practical Summaries in Acute Care. Atlanta: Perkin; 2008.  Back to cited text no. 11
Rosenbloom AL. Cerebral edema in diabetic ketoacidosis. J Clin Endocrinol Metab 2000;85:507-9.  Back to cited text no. 12
Finberg L. Appropriate therapy can prevent cerebral swelling in diabetic ketoacidosis. J Clin Endocrinol Metab 2000;86:508-9.  Back to cited text no. 13
Muir AB, Quisling RG, Yang MC, Rosenbloom AL. Cerebral edema in childhood diabetic ketoacidosis: Natural history, radiographic findings, and early identification. Diabetes Care 2004;27:1541-6.  Back to cited text no. 14
Dunger DB, Sperling MA, Acerini CL, Bohn DJ, Daneman D, Danne TP, et al. European society for paediatric endocrinology/Lawson wilkins pediatric endocrine society consensus statement on diabetic ketoacidosis in children and adolescents. Pediatrics 2004;113:e133-40.  Back to cited text no. 15
Marcin JP, Glaser N, Barnett P, McCaslin I, Nelson D, Trainor J, et al. Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema. J Pediatr 2002;141:793-7.  Back to cited text no. 16
Romano M, Pomilio M, Vigneri S, Falco A, Chiesa PL, Chiarelli F, et al. Endothelial perturbation in children and adolescents with type 1 diabetes: Association with markers of the inflammatory reaction. Diabetes Care 2001;24:1674-8.  Back to cited text no. 17
Doğruel N, Kirel B, Akgün Y, Us T. Serum soluble endothelial-cell specific adhesion molecules in children with insulin-dependent diabetes mellitus. J Pediatr Endocrinol Metab 2001;14:287-93.  Back to cited text no. 18
Carr ME. Diabetes mellitus: A hypercoagulable state. J Diabetes Complications 2001;15:44-54.  Back to cited text no. 19
Benedict SL, Ni OK, Schloesser P, White KS, Bale JF Jr. Intra-arterial thrombolysis in a 2-year-old with cardioembolic stroke. J Child Neurol 2007;22:225-7.  Back to cited text no. 20


  [Figure 1], [Figure 2]


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