Jump to comment:

• A DKA Summit?
  Timothy Lachlan Chambers
  Published on: 7 January 2003
• Ketoacid levels may alter osmotonicity in diabetic ketoacidosis and precipitate cerebral edema
  Jacob M Puliyel
  Published on: 21 December 2002
• Re: Fluid management in diabetic ketoacidosis
  Tapabrata Chatterjee
  Published on: 2 September 2002
• Physiologic management of DKA
  Glenn D Harris
  Published on: 3 July 2002
• Fluid therapy and diabetic ketoacidosis: the intensive care perspective
  Andrew Durward
  Published on: 18 June 2002

• Published on: 7 January 2003

  A DKA Summit?

  • Timothy Lachlan Chambers, Physician

  Dear Editor

  I thank Dr Edge and other correspondents and am gratified that none dissents from the view of Dr Inward and myself that the assessment and fluid management of DKA in childhood needs multispecialty review. Perhaps this is underway: if not then should our College President - Elect invite his Newcastle colleague Sir George Alberti to convene and chair it?

  TL Chambers

  Conflict of Interest:
  None declared.

  • Back to top
• Published on: 21 December 2002

  Ketoacid levels may alter osmotonicity in diabetic ketoacidosis and precipitate cerebral edema

  • Jacob M Puliyel, Consultant Pediatrician
  • Other Contributors:
    • Vikas Bhambhani

  Dear Editor

  Cerebral Edema During Treatment of Diabetic Ketoacidosis: Fall In Ketoacid Levels and Consequent Fall In Osmolality May Be A Culprit

  Inward and Chambers[1] have called for a rethink of the management of diabetic ketoacidosis. In their article they quote a study by Grove L M and colleagues[2] suggesting that pediatricians overestimated the quantum of dehydration in DKA. Over correction of dehydrat...

  Show More

  Dear Editor

  Cerebral Edema During Treatment of Diabetic Ketoacidosis: Fall In Ketoacid Levels and Consequent Fall In Osmolality May Be A Culprit

  Inward and Chambers[1] have called for a rethink of the management of diabetic ketoacidosis. In their article they quote a study by Grove L M and colleagues[2] suggesting that pediatricians overestimated the quantum of dehydration in DKA. Over correction of dehydration is implicated in precipitating cerebral edema. On the face of it, it seems implausible that pediatricians who are so adapt at estimating dehydration in the context of gastroenteritis, diarrhea, and vomiting should err in estimating the dehydration in DKA, unless the dehydration of DKA has special features. Hypertonicity may be that special feature. We hypothesize that hypertonic dehydration can result in the tongue appearing dry and parched and when this is combined with acidotic respiration of DKA, the treating pediatrician may classify the child as more severely dehydrated than he or she actually is.

  In a study of DKA we found that the mean osmolality at admission was 318 (SD 12.9, Range 291-337).[3] Further we also found that the calculated osmolality {Calculated osmolality=1.86(Na + + K + ) + Urea + Glucose} [4] was only 289 (Range 282 - 304) . This suggests hypertonicity is common in DKA and calculated osmolality underestimates the true osmolality. The mean osmolar gap was 29 (Range 14-48). The osmolar gap between true and the calculated osmolality, is made up of unmeasured substances like ketoacids. The osmolality of ketoacids have been ignored in the past, as they are considered to be osmotically inactive and not contributing to osmotonicity.[5] A study done by us (sent for publication) has demonstrated that ketoacids (acetoacetates) are osmotically active. (Acetoacetate can influence fluid shifts across a semipermeable membranes. This is in contrast to urea, which is not osmotically active) Osmolality, osmolar gap and ketone bodies are not measured routinely during the management of DKA. A rapid fall in ketone body level can result in a fall in osmolality and osmoticity of the serum and lead to cerebral edema. In a recent paper looking at the risk factors for development of cerebral edema in DKA[6] the author noted that since none of the ‘relevant variables’ - serum glucose concentration at presentation, change in serum glucose concentration during therapy, rate of fluid and sodium administration were associated with the risk of cerebral edema, their data did not support the theory that a rapid decrease in extra cellular osmolality during treatment results in osmotic mediated swelling. Osmolality and osmolar gap were not measured, nor was ketone body levels studied (Personal communication Glaser N ). Our studies demonstrates that the ketone level is probably a 'relevant variable ' that needs to be estimated before we can be certain that rapid decrease in extra-cellular osmolality did not occur. In summary we suggest that changes in ketone body levels be considered, as a factor that can be partially responsible for the cerebral edema often seen during treatment of DKA .We will be glad to share our data at any summit of experts convened to study the enigma of cerebral edema in DKA.

  References

  (1) Inward CD, Chambers TL. Fluid management in diabetic ketoacidosis. Arch Dis Child 2002;86:443-5.

  (2) Grove LM, Nobel-Jamieson CM, Barnes ND et al. Assessment of dehydration, fluid balance and insulin requirement in diabetic ketoacidosis. Proc Br Paediatr Assoc Annual Meet 1995; 67:26.

  (3) Puliyel J, Puliyel M, Hincliffe R. Hypertonicity in diabetic ketoacidosis. Proceedings of International Symposium on Diabetes. Chaing Mai Thailand Jan 26 - 29 1997.

  (4) Varley H, Gowenlock AH, Bell M. Practical Clinical Biochemistry. 5 Th ed. London, William Heinemann Medical Books Ltd, 1980: 776-777.

  (5) Van der Meulen JA, Klip A, Grinstein S. Possible mechanism for cerebral edema in diabetic ketoacidosis. Lancet 1987; ii 306-8.

  (6) Glaser N, Bernett P, McCaslin I, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. N Engl J Med 2001; 344: 264- 9.

  Show Less

  Conflict of Interest:
  None declared.

  • Back to top
• Published on: 2 September 2002

  Re: Fluid management in diabetic ketoacidosis

  • Tapabrata Chatterjee, Dr

  Dear Editor

  I read with interest "Fluid Management in Diabetic Ketoacidosis" published in June 2002.[1] I appreciate that duration of fluid therapy for correction of dehydration is of profound importance. I also feel that the issue of giving potassium in form of potassium phosphate is inadequately addressed in most of the guidelines for management of DKA in this country.

  It is almost inevitable that...

  Show More

  Dear Editor

  I read with interest "Fluid Management in Diabetic Ketoacidosis" published in June 2002.[1] I appreciate that duration of fluid therapy for correction of dehydration is of profound importance. I also feel that the issue of giving potassium in form of potassium phosphate is inadequately addressed in most of the guidelines for management of DKA in this country.

  It is almost inevitable that patients with DKA receive an excess of chloride which aggrevates acidosis. Chloride administration, however, can be reduced by substitution of phosphate, which is also significantly depleted in DKA. Moreover, phosphate in conjuncture with glycolysis is essential of formation of 2,3-DPG, which governs the oxygen dissociation curve. During deficiency of 2,3-DPG the oxygen dissociation curve is shifted to the left, i.e. more oxygen is retained by haemoglobin and less is available to the tissues, a situation that predisposes to lactic acidosis. Acidosis per se tends to shift the oxygen dissociation curve towards the right and thus partially compensates for 2,3-DPG deficiency. As acidosis resulting from accumulation of ketones is corrected by provision of insulin with or without administration of bicarbonate, the effect of 2,3-DPG deficiency may no longer be compensated and release of oxygen to the tissues may again be impaired. Exogenous phosphate, by contributing to the formation of 2,3-DPG shifts the oxygen dissociation curve to the right and thus facilitates release of oxygen to the tissues and thus aids in the correction of acidosis.

  Furthermore, resistance to insulin action is associated with hypophosphataemia, hence potassium phosphate use as a means of potassium supplementation, is increasingly receiving popularity. However, most of the hospital, protocols for management of DKA, that I have seen in this country, does not include use of potassium phosphate, therefore, I think it is a issue that needs to be addressed.

  Reference

  (1) Inward CD, Chambers TL, and EdgeFluid L. Management in diabetic ketoacidosis. Arch Dis Child 2002;86:443-444.

  Show Less

  Conflict of Interest:
  None declared.

  • Back to top
• Published on: 3 July 2002

  Physiologic management of DKA

  • Glenn D Harris, Physician - Associate Professor of Pediatrics
  • Other Contributors:
    • Irma Fiordalisi, MD

  Dear Editor

  Inward and Chambers provide a provocative description and discussion of the continued confusion regarding the issues surrounding rehydration and treatment of the pediatric patient with DKA.[1] They review some of the key issues that link fluid therapy to complications from brain swelling, and question the appropriateness of using a volume of fluid calculated by 'maintenance plus deficit', calling for...

  Show More

  Dear Editor

  Inward and Chambers provide a provocative description and discussion of the continued confusion regarding the issues surrounding rehydration and treatment of the pediatric patient with DKA.[1] They review some of the key issues that link fluid therapy to complications from brain swelling, and question the appropriateness of using a volume of fluid calculated by 'maintenance plus deficit', calling for a second revolution in the management of DKA. In the accompanying commentary, Edge makes several statements concerning fluid therapy in DKA, including that 'DKA is associated with severe fluid losses', that 'any guidelines for fluid and electrolyte management must be simple to calculate', that administration of base is a risk factor for intracranial complications, and that despite published data and 'changes in protocols', there is no evidence that the 'incidence of cerebral oedema has changed over the past 20 years'.[1] It is our opinion that the problem in the rehydration of the pediatric patient with DKA does not lie in assigning a maintenance fluid allotment. Rather, the source of error lies largely with failure to accurately estimate the volume of deficit and the tendency to automatically assume a severe degree of dehydration. From our experience with over 450 consecutive episodes of moderate and severe DKA, and our weight gain data,[2] severe DKA (i.e. severe ketoacidemia) does not necessarily mean severe dehydration; the converse is also true.[2,3] The degree of dehydration ranges from negligible (<_1 _="_" to="to" extreme="extreme"/>20 %).[3] Severe ketoacidemia, however, does cause vasoconstriction which may be manifested peripherally by cool, mottled skin, and Kussmaul breathing which leads to very dry oral mucosa. The striking appearance of a parched mouth and the presence of cool, even mottled skin without a critical assessment of vital signs and examination of distal (foot) pulses often results in an erroneous impression of shock and 'severe dehydration':[3] A method for estimation of the volume of deficit was described in 1990 [2] and we continue to use this approach successfully. Successful therapy requires not only gradual deficit replacement (evenly over 48 hours) but an accurate estimation of the volume of deficit along with critical monitoring of the clinical and biochemical response.[3] If the deficit is assumed to be 10-15 % but is actually only 3 %, that patient will receive excess water independent of the more gradual timeframe and independent of the type of fluid given. Guidelines that have proposed 'safe' limits to fluid volumes administered such as 4 liters/m²/day [4] or 50 ml/kg body wt./4 hrs. [5] violate the concept of the individualised assessment of the degree of dehydration and will invariably overhydrate the mild to moderately dehydrated child; the problem is compounded when actual body weight is used instead of ideal body weight in fluid calculations for the obese patient. On the other hand, certain patients, particularly those with complicating illness e.g. septic shock, pancreatitis, may require more than 20 ml/kg of fluid resuscitation in the first treatment hour and more than 50 ml/kg in the first four hours. Setting arbitrary fluid volume limits per hour or per day endanger particularly those patients at the mild and severe end of the dehydration spectrum. Although the insult would be greater with hypotonic fluid, overhydration occurs readily with isotonic fluid as well when water requirements are overestimated.

  DKA represents the effects of a complex disruption of normal metabolism, which leads to metabolic death if left untreated. Shock (decreased peripheral pulses, with or without hypotension), if present, should be corrected rapidly. Insulin should be given preferably by continuous, low dose, intravenous infusion, as soon as possible to begin correction of ketoacidemia/ketoacidosis. Regardless of the serum concentration of glucose, insulin is required to inhibit the hepatic fatty acyl carnitine cycle leading to ketoacid formation.[6] A delay in insulin administration only serves to enhance and prolong ketoacidemia thereby extending the period of time during which the patient remains vulnerable to central nervous system and other complications.

  Our proposed management strategy may not satisfy the call for simplicity but it is an easily learned approach. It requires an understanding of relevant, known pathophysiology, the monitoring of serial physical examinations and laboratory studies with special attention to correction of acidemia and osmolality, and the anticipatory care that is inherent in the care of the critically ill.[2,3,6-10,12]

  Physiologic management was first described between 1988 [10] and 1990,[2] and set forth with additional detail and data in 1994. [3] It is rarely described in its complete form when referenced in texts; mere portions of our recommendations do not constitute what we have called physiologic management. Not only is it unlikely that large numbers of patients outside our own institution have been managed using our guidelines in their entirety, but the recommendations simply are not old enough to be reflected in data over the past 20 years. We suspect that physiologic management is significantly underrepresented in the multicenter studies conducted thus far, all of which compare variations of traditional therapy (empiric volume resuscitation whether or not shock is present, assumption of a large volume of deficit, planned rehydration in less than 48 hours with either 0.45 % or 0.9 % NaCl, with or without urinary output replacement). In a retrospective portion of our study in 1990 [2] we compared these same therapies and also found that no form of traditional therapy minimized the risk of brain herniation during treatment.

  Comments regarding the administration of base should be better defined. Rapid administration or 'pushes' of hypertonic sodium bicarbonate should not be given. On the other hand, there is no evidence that administration of physiologic concentrations of base in the rehydration solution are either harmful or undesirable. In our experience, this practice mitigates the development of hyperchloremic acidosis during treatment.

  Since ours is a referral center, most of our patients have some form of therapy initiated in outlying hospitals, sometimes in keeping with our recommended approach, and sometimes with our recommendations instituted only after initial telephone contact. In this setting, we have managed certain patients with severe DKA who received resuscitation fluids in excess of what their physical examination and laboratory data would dictate. It is not unusual for such patients to require as little as a typical maintenance allotment (without a deficit replacement component) for the remainder of therapy; some patients required fluid restriction to as little as two-thirds the usual maintenance volume.

  Our approach has been criticized because of the incidence of mannitol administration in our series. [1] In our mannitol recipients, several of whom did not receive their initial management by us, there was no central nervous system morbidity or mortality. In another large series of patients there was a 50 % failure rate of mannitol to reverse a deteriorating neurologic status even when mannitol was given prior to respiratory arrest, with a near 100 % failure rate when mannitol was given after respiratory arrest. [11] It is possible that not all of our mannitol recipients actually had raised intracranial pressure. We believe, however, that the key to our good outcome is that the fluid and electrolyte therapy on which mannitol is superimposed is relevant to its success. It is erroneous to assume that the 100 % success rate among our mannitol recipients would be reproducible in the setting of a therapy that violates the fundamental principles of rehydrating the hypertonic state of DKA.

  Drs Inward and Chambers ask 'do we have it right yet?' and convey concern that certain recommendations do not, as of yet, 'have it right.' We agree.

  Our work regarding the management of the pediatric patient in moderate to severe DKA has spanned 14 years [1,12] and nearly 500 consecutive prospectively managed episodes. We remain available to participate in any endeavor to continue to improve the care of the pediatric patient in DKA.

  References

  (1) Inward CD, TL Chambers, Edge J. Fluid management in diabetic ketoacidosis. Arch Dis Child2002;86(6):443-5.

  (2) Harris GD, et al.: Minimizing the risk of brain herniation during treatment of diabetic ketoacidemia: a retrospective and prospective study. J Pediatr 1990;117:22-4.

  (3) Harris GD, Fiordalisi I. Physiologic management of diabetic ketoacidemia. A 5 year prospective pediatric experience in 231 episodes. Arch Pediatr Adolesc Med 1994;148:1046-52.

  (4) Duck SC, Wyatt DT. Factors associated with brain herniation in the treatment of diabetic ketoacidosis. J Pediatr 1988;113:10-4.

  (5) Mahoney CP, Vleck BW, DelAguila M. Risk factors for developing brain herniation during diabetic ketoacidosis. Pediatr Neurol 1999;21:721-7.

  (6) Fiordalisi I, Harris GD. Diabetic Ketoacidemia. In: Finberg L, Kleinman RE (Eds) Saunders Manual of Pediatric Practice, 2nd ed. Philadelphia: WB Saunders Co., 938-46.

  (7) Harris GD, Fiordalisi I, Yu C. Maintaining normal intracranial pressure in a rabbit model during treatment of severe diabetic ketoacidemia. Life Sci 1996;59:1695-702.

  (8) Harris GD, Lohr JW, Fiordalisi I, Acara M. Brain osmoregulation during extreme and moderate dehydration in a rat model of severe DKA. Life Sci 1993;53:185-91.

  (9) Bohn D, Daneman D. Diabetic ketoacidosis and cerebral edema. Curr Opin Pediatr 2002;14(3):287-91.

  (10) Harris GD, Fiordalisi I, Finberg L. Safe management of diabetic ketoacidemia. J Pediatr 1988;13:65-7.

  (11) Rosenbloom A. Intracranial crises during treatment of diabetic ketoacidosis. Diabetes Care 1990;13:22-33.

  (12) Fiordalisi I, Harris GD, Gilliland MGF. Prehospital cardiac arrest in diabetic ketoacidemia. Why brain swelling may lead to death before treatment. J Diabet Compl 2002;16:214-9.

  Show Less

  Conflict of Interest:
  None declared.

  • Back to top
• Published on: 18 June 2002

  Fluid therapy and diabetic ketoacidosis: the intensive care perspective

  • Andrew Durward, Consultant PICU
  • Other Contributors:
    • Shane M. Tibby, Shymala Moganasundrum, and Ian A. Murdoch

  Dear Editor

  We read with interest the article by Inward and Chambers proposing a review on the current fluid management of DKA in the United Kingdom.[1] The authors correctly state the importance of avoiding “rapid rates of fluid infusion” and the need to “maintain serum sodium concentrations” in order to reduce the administration of free water and hence reduce the risk of cerebral oedema.

  It has been ou...

  Show More

  Dear Editor

  We read with interest the article by Inward and Chambers proposing a review on the current fluid management of DKA in the United Kingdom.[1] The authors correctly state the importance of avoiding “rapid rates of fluid infusion” and the need to “maintain serum sodium concentrations” in order to reduce the administration of free water and hence reduce the risk of cerebral oedema.

  It has been our experience over the last few years that children with severe DKA admitted to our paediatric intensive care unit have, as suggested by Inward and Chambers, received excessive amounts of intravenous fluid, a factor which may potentiate the development of cerebral oedema. Over the last 2 years, ten patients with severe DKA (median pH 6.9, median pCO2 1.8 kPa) were admitted our PICU of which four developed cerebral oedema. All four patients received between 50 and 85 ml/kg resuscitation within the first 5 hours of treatment. Two of the patients with signs of brainstem herniation were receiving 0.45 % saline maintenance fluid therapy. No patient had a corrected sodium value recorded at any stage.

  These excessive volumes of fluid are placing these children at an unnecessary risk for brainstem herniation for the following reasons. First, the initial fluid resuscitation volumes (first four hours) often exceed the “50 ml/kg” threshold value identified by Mahoney as an important risk factor for cerebral oedema.[2] As hypotension in DKA is both unusual and uncommon, the indication for fluid boluses is often poor capillary refill or failure of rapid improvement in acidosis. Only one of the ten patients admitted to our PICU had hypotension which was effectively treated with inotropes. Adopting the “maintenance plus rehydration” strategy currently advocated by the British Society for Paediatric Endocrinology,[3] in addition to the large volumes of resuscitation fluid, commonly leads to the administration of fluid volumes above the threshold value proposed by Duck of 4 L/m²/day as a risk factor for cerebral oedema as dehydration is often corrected within 24 hours.[4] In addition, the administration of free water in the form of 0.45 % saline as maintenance fluid (half of which will distribute to the tissues as electrolyte free water) may potentiate hyponatraemia, a known risk factor in the development of cerebral oedema.

  Prevention of rapid osmotic shifts in DKA and the defence of plasma tonicity are important goals to minimise the risk of cerebral oedema. Hyponatraemia or a fall in the glucose corrected plasma sodium are indicators of excessive free water retention and in the DKA patient with a depressed level of consciousness, mandates treatment. Mannitol, although effective at reducing cerebral oedema, may cause a large osmotic diuresis that may complicate the fluid rehydration regime without correcting the plasma sodium. In contrast to mannitol, hypertonic saline will increase the plasma sodium (and hence tonicity) and simultaneously expand the plasma volume which is itself an important target in maintaining adequate cerebral perfusion pressure.[5] Hypertonic saline may also be required for the treatment of cerebral salt wasting which has been proposed as a mechanism of hyponatraemia in patients with DKA. It is our experience that the use of 3 % saline in patients with DKA is increasing as clinicians continue to prescribe large amounts of fluids for both initial fluid resuscitation and ongoing maintenance which is often 0.45 % saline.

  Although the final solution on how and why cerebral oedema develops in DKA remains unsolved, a number of factors concerning current fluid management place these children at unnecessary risk. We strongly support the proposal of Inward and Chambers for review of the current guidelines and as Intensive Care Specialists would especially like to see and be involved in the development of guidelines for the ongoing management of patients unfortunate enough to develop the most catastrophic complication of DKA, cerebral oedema.

  References

  (1) CD Inward, TL Chambers, J Edge. Fluid management in diabetic ketoacidosis. Arch Dis Child 2002;86:443-4.

  (2) Mahoney CP, Vleck BW, DelAguila M. Risk factors for developing brain herniation during diabetic ketoacidosis. Pedaitr Neurol 1999;21:721-7.

  (3) British Society of Paediatric Endocrinology and Diabetis, Recommended DKA guidelines. http://bspe.shef.ac.uk/dka.html, 2001.

  (4) Duck SC, Wyatt DT. Factors associated with brain herniation in the treatment of diabetic ketoacidosis. J Paediatrics 1988;113:10-4.

  (5) Curtis JR, Bohn D, Daneman D. Use of hypertonic saline in the treatment of cerebral edema in diabetic ketoacidosis Pediatric Diabetes 2001; 2:191-4.

  Show Less

  Conflict of Interest:
  None declared.

  • Back to top