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

Riad A Sulimani; Anwar A Jammah; Ibrahim M Ghozzi; Hadil A Alotair; Suleiman A Al-Mohaya; Tarek E Ashour

doi:10.4103/JNSM.JNSM_15_18

BRIEF REPORT

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

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

Riad A Sulimani¹, Anwar A Jammah¹, Ibrahim M Ghozzi², Hadil A Alotair³, Suleiman A Al-Mohaya², Tarek E Ashour⁴
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 Publication

6-Jun-2018

Correspondence Address:
Riad A Sulimani
Department of Medicine, College of Medicine, King Saud University, Riyadh 11323
Saudi Arabia

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JNSM.JNSM_15_18

Abstract

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

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

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 1^st 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 7^th 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

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

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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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