Interstitial Pulmonary Edema in Children and Adolescents with Diabetic Ketoacidosis

Hoffman, William H.; Locksmith, John P.; Burton, Edward M.; Hobbs, Elgin; Passmore, Gregory G.; Pearson-Shaver, Anthony L.; Deane, Daniel A.; Beaudreau, Margaret; Bassali, Reda

doi:10.1016/s1056-8727(98)00012-9

Cited by 56 publications

(27 citation statements)

References 35 publications

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“…The numerous physiologic (Emerich et al, 2005) and immunologic (Chodobski et al, 2001) functions of the CP make it a candidate to play a role in the fatal BE of DKA. While we have no information on the onset or extent of the initial insult to the CP or the sequence of progression, we hypothesize that these neuroinflammatory factors are not involved in the initiation or early progression of subclinical BE (Hoffman et al, 1988;Durr et al, 1992), but rather during the clinical BE of DKA and may be the critical factor in a progressively edematous brain. This later insult would be in keeping with: 1) the direct perturbation of cerebral capillary endothelial cells by the ketone bodies serving as the initiating factor of subclinical BE (Isales et al, 1999;Hoffman et al 2002); 2) a pattern of inflammation is similar to the accentuated SIR which follows the initiation of treatment of DKA Jerath et al, 2005); and 3) the relatively infrequent occurrence of fatal clinical BE in DKA in comparison to the frequency of subclinical BE (Hoffman et al, 1988;Durr et al, 1992;Edge et al, 2001).…”

Section: Discussionmentioning

confidence: 89%

“…Since we did not find any signs of necrosis in the DKA brains is possible that C5b-9 could result in a sublethal attack and a protective effect on CPE. The potential protective effect of sublethal attacks by C5b-9, may explain the infrequent occurrence of clinical BE in DKA (Edge et al, 2001) despite the significant prevalence of subclinical BE (Hoffman et al, 1988;Durr et al, 1992;Glaser et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

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Neuroinflammatory response of the choroid plexus epithelium in fatal diabetic ketoacidosis

Hoffman

Casanova

Cudrici

et al. 2007

Experimental and Molecular Pathology

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A systemic inflammatory response (SIR) occurs prior to and during the treatment of severe diabetic ketoacidosis (DKA). IL-1β, TNF-α and C5b-9 are components of SIR and have been speculated to be involved in the clinical brain edema (BE) of DKA. We studied IL-1β, TNF-α, C5b-9, inducible nitric oxide (iNOS), ICAM-1, IL-10 and Hsp70 expression in the brains of two patients who died as the result of clinical BE during the treatment of DKA. IL-1β was strongly expressed in the choroid plexus epithelium (CPE) and ependyma, and to a lesser extent in the hippocampus, caudate, white matter radiation of the pons, molecular layer of the cerebellum and neurons of the cortical gray matter. TNF-α was expressed to a lesser extent than IL-1 β, and only in the CP. C5b-9, previously shown to be deposited on neurons and oligodendrocytes, was found on CPE and ependymal cells. iNOS and ICAM-1 had increased expression in the CPE and ependyma. Hsp70 and IL-10 were also expressed in the CPE of the case with the shorter duration of treatment. Our data demonstrates the presence of a multifaceted neuroinflammatory cytotoxic insult of the CPE, which may play a role in the pathophysiology of the fatal brain edema of DKA.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Neuroinflammatory response of the choroid plexus epithelium in fatal diabetic ketoacidosis

Hoffman

Casanova

Cudrici

et al. 2007

Experimental and Molecular Pathology

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“…It may be that these effects are greater if they occur during the first phase of rapid rehydration when membrane electrolyte transport may be at its most active. Furthermore, it has recently been suggested that the subclinical cerebral oedema seen in most children with DKA [21,22], may be consistent with a vasogenic (rather than cytotoxic) mechanism, possibly representing reperfusion of previously hypoperfused tissues with the administration of fluid during treatment [23]. The administration of larger volumes of fluid as a risk factor would also be compatible with this theory, and the effects of insulin on electrolyte transport may be additive.…”

Section: Discussionmentioning

confidence: 96%

The UK case–control study of cerebral oedema complicating diabetic ketoacidosis in children

et al. 2006

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Aims/hypothesis Cerebral oedema complicating diabetic ketoacidosis (DKA) remains the major cause of morbidity and mortality in children with type 1 diabetes, but its aetiology remains unknown. Our objective was to determine the impact of baseline biochemical factors and of treatment-related variables on risk of the development of cerebral oedema in children with DKA. Materials and methods This was a national UK casecontrol study. Through the British Paediatric Surveillance Unit we identified 43 cases of cerebral oedema. Through a parallel reporting system, we also identified 2,940 episodes of DKA and selected 169 control subjects on the basis of comparable age, sex, numbers of new or known cases of diabetes and date of admission. Baseline biochemical data and treatment-related variables were extracted from the clinical notes of cases and control subjects. Results Allowing for differences in age, sex and new or known diabetes, cases were more acidotic at diagnosis of DKA (odds ratio [OR] for events in the least acidotic compared with the most acidotic tertile=0.02 [95% CI: 0.002-0.15], p<0.001). In addition, cases had higher potassium and urea levels at baseline. Calculated osmolality and baseline glucose were not significantly different. After allowing for severity of acidosis, insulin administration in the first hour .5], p=0.02) and volume of fluid administered over the first 4 h .97], p=0.01) were associated with risk. Low baseline plasma sodium and an elevated p a CO 2 also contributed to risk in the final regression model. Bicarbonate administration was not associated with increased risk of an event when corrected for acidosis. Conclusions/interpretation In this case-control study of DKA, baseline acidosis and abnormalities of sodium, potassium and urea concentrations were important predictors of risk of cerebral oedema. Additional risk factors identified were early administration of insulin and high volumes of fluid. These observations should be taken into account when designing treatment protocols.

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“…The observation that cerebral oedema usually occurs within a few hours of initiation of treatment has led to the speculation that it is iatrogenic [42]. However, there is evidence that subclinical cerebral oedema may be present before treatment is started [43]. The exact cause of this phenomenon is unknown; recent studies suggest that cerebral hypoperfusion with subsequent re-perfusion may be the mechanism operating [38,44,45].…”

Section: Cerebral Oedemamentioning

confidence: 99%

Joint British Diabetes Societies guideline for the management of diabetic ketoacidosis

Savage

Dhatariya²,

Kilvert³

et al. 2011

Diabetic Medicine

291

297

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The Joint British Diabetes Societies guidelines for the management of diabetic ketoacidosis (these do not cover Hyperosmolar Hyperglycaemic Syndrome) are available in full at: This article summarizes the main changes from previous guidelines and discusses the rationale for the new recommendations. The key points are: Monitoring of the response to treatment (i) The method of choice for monitoring the response to treatment is bedside measurement of capillary blood ketones using a ketone meter.(ii) If blood ketone measurement is not available, venous pH and bicarbonate should be used in conjunction with bedside blood glucose monitoring to assess treatment response.(iii) Venous blood should be used rather than arterial (unless respiratory problems dictate otherwise) in blood gas analysers.(iv) Intermittent laboratory confirmation of pH, bicarbonate and electrolytes only.Insulin administration (i) Insulin should be infused intravenously at a weight-based fixed rate until the ketosis has resolved.(ii) When the blood glucose falls below 14 mmol ⁄ l, 10% glucose should be added to allow the fixed-rate insulin to be continued.(iii) If already taking, long-acting insulin analogues such as insulin glargine (Lantus Ò

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Interstitial Pulmonary Edema in Children and Adolescents with Diabetic Ketoacidosis

Cited by 56 publications

References 35 publications

Neuroinflammatory response of the choroid plexus epithelium in fatal diabetic ketoacidosis

Neuroinflammatory response of the choroid plexus epithelium in fatal diabetic ketoacidosis

The UK case–control study of cerebral oedema complicating diabetic ketoacidosis in children

Joint British Diabetes Societies guideline for the management of diabetic ketoacidosis

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