Studies on Mechanisms of Cerebral Edema in Diabetic Comas. EFFECTS OF HYPERGLYCEMIA AND RAPID LOWERING OF PLASMA GLUCOSE IN NORMAL RABBITS

Arieff, Allen I.; Kleeman, Charles R.

doi:10.1172/jci107218

Cited by 181 publications

(68 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High doses of insulin may also be a risk factor for cerebral oedema, as indicated by animal models [26,27] and supported by our observational studies. Finally, the dangers inherent in using large volumes of relatively dilute fluids have been highlighted by many studies [5,7,17].…”

Section: Discussionsupporting

confidence: 83%

“…Finally, the dangers inherent in using large volumes of relatively dilute fluids have been highlighted by many studies [5,7,17]. It is compatible with the 'idiogenic osmole' hypothesis of cerebral oedema risk, where relatively 'dilute' fluids may cross the blood-brain barrier more easily when the intracerebral osmolality is increased [26,28].…”

Section: Discussionmentioning

confidence: 84%

See 1 more Smart Citation

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

et al. 2006

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 84%

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

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Group I: effects of acute untreated hypernatraemia on brain adaptation In preliminary studies on conscious rabbits, not reported here, it was noted that infusion of hypertonic NaCl (1-7 M) sometimes resulted in slowing of respiration. Therefore, all of these experiments were performed on rabbits that were anaesthetized, paralysed and artificially ventilated (Arieff, Kleeman, Keushkerian & Bagdoyan, 1973). Briefly, twelve control and nine experimental rabbits, which were to be made acutely hypernatraemic (see below), were fasted overnight.…”

Section: Studies In Rabbitsmentioning

confidence: 99%

“…After removing the rabbit from the box, it was placed on a heating blanket (37°C) and tracheostomized. A 20 gauge catheter (Angiocath; Quinton Instrument Company, Bothell, WA, USA) was inserted into the ear artery and attached to a strain gauge transducer (Statham) via a tap so that arterial blood pressure and heart rate could be continuously recorded on a strip chart recorder (Statham) and to allow blood samples to be removed every hour for arterial blood gas analysis (Arieff et al 1973). As previously described (Arieff et al 1974b), paralysis was induced with succinylcholine (20 mg kg-' i.v.)…”

Section: Studies In Rabbitsmentioning

confidence: 99%

Effects of hypernatraemia in the central nervous system and its therapy in rats and rabbits.

Ayus

Armstrong

Arieff

1996

The Journal of Physiology

View full text Add to dashboard Cite

1. We studied the effects of acute (1 or 4 h) and chronic (1 week) hypernatraemia (plasma [Na+], 170-190 mM) on brain histology, and brain water and solute contents in rats and rabbits. 2. In rabbits with acute hypernatraemia, there was significant loss of intracelluar brain water, with increases in brain [Na+ + K+], amino acid concentration, and undetermined solute (idiogenic osmole). After 1 week of recovery, brain intracellular water content had returned to normal. 3. In hypernatraemic rats there was myelinolysis of brain white matter, with karyorrhexis and necrosis of neurons.4. Hypernatraemic rabbits were treated with 77 mm NaCl (i.v.) to normalize plasma [Nae] over 4-24 h intervals. Therapy of either acute or chronic hypernatraemia resulted in significant brain oedema because brain osmolality failed to decrease at the same rate as plasma osmolality. 5. It is concluded that: (a) untreated hypernatraemia results in brain lesions demonstrating myelinolysis and cellular necrosis; (b) normalization of hypernatraemia over 4-24 h results in cerebral oedema, due primarily to failure of brain amino acids and idiogenic osmoles to dissipate as plasma [Na+] is decreased to normal.Hypernatraemia is a common clinical condition which tends to affect individuals at the extremes of age -children and the elderly -and frequently leads to central nervous system damage or death. Plasma Na+ levels associated with brain damage in hypernatraemic patients have been in the range 160-190 mm (Zierler, 1958;Finberg, Kiley & Luttrell, 1963;Morris-Jones, Houston & Evans, 1967; Snyder, Feigal & Arieff, 1987). Previous studies on animals from both our laboratory and others suggest that central nervous system damage or death can occur as a consequence of untreated hypernatraemia (Finberg et al. 1963;Morris-Jones et al. 1967;De Villota, Cavanilles & Stein, 1973; Simmons, Adcock, Bard & Battaglia, 1974;Snyder et al. 1987), but the mechanisms responsible are unclear.Improper therapy of hypernatraemia can also produce brain dysfunction, neurological deterioration and death (Lutrell & Finberg, 1959;Hogan, Dodge & Gill, 1969 METHODS Studies in rabbitsThe experimental protocol was approved by the Animal Studies Subcommittee (Veterans Administration Medical Center, San Francisco, CA, USA). Rabbits were used to study the effects of hypernatraemia on brain water and solute content because in this species grey matter can be readily isolated, and also because of our substantial experience in brain analysis using rabbit models of fluid and electrolyte disorders (Arieff, Doerner, Zelig & Massry, 1974a;Arieff, Kleeman, Keushkerian & Bagdoyan, 1974b). Studies were carried out on New Zealand White rabbits (3-4 kg) of both genders, in which hypernatraemia was induced either acutely for periods of 1 or 4 h, or chronically for 7 days. Hypernatraemic rabbits were then treated over intervals of 4-24 h, to return the plasma [Na+] to normal values (below 150 mM). The following goups of rabbits were studied. Group I: effects of acute untreated hypernatraem...

show abstract

“…The brain generates intracellular osmolytes as a protective mechanism (8). Osmolytes are organic solutes that are essential for cell-volume homeostasis and they may also function as general protectors for brain cells.…”

Section: Discussionmentioning

confidence: 99%

Changes of the Cerebral Metabolite Patterns in Patients Undergoing Hemodialysis due to Chronic Renal Failure: Evaluation with Proton Magnetic Resonance Spectroscopy

Baik

et al. 2007

J Korean Radiol Soc

View full text Add to dashboard Cite

Purpose:We wanted to evaluate the cerebral metabolites in patients with chronic renal failure (CRF) and who were undergoing hemodialysis by performing proton MR spectroscopy and we wanted to evaluate the correlation between the changes in the cerebral metabolite ratios and the duration after starting the initial hemodialysis. Materials and Methods: Proton MR spectroscopy was performed in 15 patients with CRF and who were undergoing hemodialysis and in ten healthy volunteers. The changes in N-acetylaspartate (NAA), choline-containing compounds (Cho), myo-inositol (Myo), glutamine/glutamate complex (Glx), and creatine (Cr) were analyzed. MR spectroscopy was performed before and after hemodialysis. Results: For the patients with CRF before hemodialysis, the Cho/Cr ratio in the gray matter (p<0.001) and the Myo/Cr ratio in both the gray and white matter (p<0.01) were significantly elevated compared with those in the control subjects. For the patients with CRF after hemodialysis, their Cho/Cr ratios were significantly reduced in both the gray and white matter compared with that before hemodialysis (p<0.05). There was a significant positive correlation between the Cho/Cr ratio and serum Cr in the gray matter of CRF patients after hemodialysis (r=0.54, p<0.05). The cerebral metabolite ratios were not significantly correlated with the duration after starting the initial hemodialysis. Conclusion: The cerebral metabolite patterns are significantly different between the patients with CRF and who are undergoing hemodialysis and the normal controls. The cerebral metabolite ratios are not significantly correlated with the duration after starting the initial hemodialysis.

show abstract

Studies on Mechanisms of Cerebral Edema in Diabetic Comas. EFFECTS OF HYPERGLYCEMIA AND RAPID LOWERING OF PLASMA GLUCOSE IN NORMAL RABBITS

Cited by 181 publications

References 39 publications

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

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

Effects of hypernatraemia in the central nervous system and its therapy in rats and rabbits.

Changes of the Cerebral Metabolite Patterns in Patients Undergoing Hemodialysis due to Chronic Renal Failure: Evaluation with Proton Magnetic Resonance Spectroscopy

Contact Info

Product

Resources

About