kitabchi terapie come diabetice

8/12/2019 Kitabchi Terapie Come Diabetice

http://slidepdf.com/reader/full/kitabchi-terapie-come-diabetice 1/51

Official reprint from UpToDate® www.uptodate.com

©2012 UpToDate® Print | Back

Treatment of diabetic ketoacidosis andhyperosmolar hyperglycemic state in adultsAuthors Abbas E Kitabchi, PhD, MD, FACP, FACE Burton D Rose, MD Section Editor David M Nathan, MD Deputy Editor Jean E Mulder, MD Disclosures

All topics are updated as new evidence becomes available and our peer review process is

complete.Literature review current through: Feb 2012. | This topic last updated: Feb 16, 2011.

INTRODUCTION — Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state

(HHS, also called nonketotic hyperglycemia) are two of the most serious acute

complications of diabetes. They are part of the spectrum of hyperglycemia and each

represents an extreme in the spectrum.

The treatment of DKA and HHS in adults will be reviewed here. The epidemiology,

pathogenesis, clinical features, and diagnosis of these disorders are discussed separately.

(See "Epidemiology and pathogenesis of diabetic ketoacidosis and hyperosmolar

hyperglycemic state" and "Clinical features and diagnosis of diabetic ketoacidosis and

hyperosmolar hyperglycemic state in adults".)

DEFINITIONS — DKA and HHS differ clinically according to the presence of ketoacidosis

and the degree of hyperglycemia [1-3]. The definitions proposed by the American Diabetes

Association for DKA and HHS are shown in the table (table 1) [1].

In DKA, metabolic acidosis is often the major finding, while the serum glucose

concentration is generally below 800 mg/dL (44 mmol/L) [1-3]. However, serum

glucose concentrations may exceed 900 mg/dL (50 mmol/L) in patients with DKA

who are comatose [3,4].

In HHS, there is little or no ketoacid accumulation, the serum glucose concentration

frequently exceeds 1000 mg/dL (56 mmol/L), the serum osmolality may reach 380

mosmol/kg, and neurologic abnormalities are frequently present (including coma in

25 to 50 percent of cases) [1,2,5,6].

http://www.uptodate.com/



http://www.uptodate.com/contents/treatment-of-diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults?view=print





http://www.uptodate.com/contents/treatment-of-diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults/contributors














http://www.uptodate.com/contents/treatment-of-diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults/contributor-disclosure


http://www.uptodate.com/home/about/policies/editorial_policy.html



http://www.uptodate.com/contents/epidemiology-and-pathogenesis-of-diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state?source=see_link




http://www.uptodate.com/contents/clinical-features-and-diagnosis-of-diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults?source=see_link




http://www.uptodate.com/contents/treatment-of-diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults/abstract/1-3


http://www.uptodate.com/contents/image?imageKey=ENDO%2F72111&topicKey=ENDO%2F1795&source=see_link



http://www.uptodate.com/contents/treatment-of-diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults/abstract/1






http://www.uptodate.com/contents/treatment-of-diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults/abstract/3,4



http://www.uptodate.com/contents/treatment-of-diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults/abstract/1,2,5,6



























Significant overlap between DKA and HHS occurs in more than one-third of patients [7]. The

typical total body deficits of water and electrolytes in DKA and HHS are compared in Table 2

(table 2). (See "Clinical features and diagnosis of diabetic ketoacidosis and hyperosmolar

hyperglycemic state in adults", section on 'Definitions'.)

TREATMENT

Treatment overview and protocols — The treatment of DKA and HHS is similar,

including the administration of insulin and correction of the fluid and electrolyte

abnormalities that are typically present, including hyperglycemia and hyperosmolality,

hypovolemia, metabolic acidosis (in DKA), and potassium depletion (table 3) [1,8-10]. The

factors responsible for these metabolic abnormalities are discussed separately. (See "Clinical

features and diagnosis of diabetic ketoacidosis and hyperosmolar hyperglycemic state in

adults".)

Therapy also requires frequent patient monitoring and identification and treatment of

precipitating events. Infection (most commonly pneumonia and urinary tract infection) is a

common precipitating event. Thus, cultures should be obtained if there are suggestive

clinical findings, recognizing that infection may be present in the absence of fever [1,9,10].

An algorithmic approach developed for the ADA is shown in the flow diagrams for treating

DKA (algorithm 1) and HHS (algorithm 2) [1,3].

Initial evaluation — Both DKA and HHS are medical emergencies that require prompt

recognition and management. An initial history and rapid but careful physical examination

should focus on:

Airway, breathing, and circulation (ABC) status

Mental status

Possible precipitating events (eg, source of infection, myocardial infarction)

Volume status

The initial laboratory evaluation of a patient with suspected DKA or HHS should include

determination of:

Serum glucose

Serum electrolytes (with calculation of the anion gap), BUN, and plasma creatinine

Complete blood count with differential

Urinalysis and urine ketones by dipstick

Plasma osmolality

Serum ketones (if urine ketones are present)







http://www.uptodate.com/contents/clinical-features-and-diagnosis-of-diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults?source=see_link&anchor=H2#H2




http://www.uptodate.com/contents/image?imageKey=EM%2F57723&topicKey=ENDO%2F1795&source=see_link



http://www.uptodate.com/contents/treatment-of-diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults/abstract/1,8-10








http://www.uptodate.com/contents/treatment-of-diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults/abstract/1,9,10


























Arterial blood gas if the serum bicarbonate is substantially reduced

Electrocardiogram

Additional testing, such as cultures of urine, sputum, and blood, serum lipase and amylase,

and chest x-ray, should be performed on a case-by-case basis.

Monitoring — The serum glucose should initially be measured every hour until stable, while

serum electrolytes, blood urea nitrogen, creatinine, osmolality, and venous pH (for DKA)

should be measured every two to four hours, depending upon disease severity and the

clinical response [1,10].

Repeat arterial blood gases are unnecessary during the treatment of DKA; venous pH, which

is about 0.03 units lower than arterial pH [11], is adequate to assess the response to

therapy and avoids the pain and potential complications associated with repeated arterial

punctures (figure 1). Monitoring serum bicarbonate is another alternative if blood

chemistries can be returned in a timely fashion.

Acidosis in DKA — Direct measurement of beta-hydroxybutyrate in the blood is the

preferred method for monitoring the degree of ketonemia and has become more convenient

with the development of bedside meters capable of measuring whole blood beta-

hydroxybutyrate [12]. However, this approach is not available in many hospitals.

Nitroprusside tablets or reagent sticks react with acetoacetate and acetone (produced by

the decarboxylation of acetoacetic acid), but do not identify beta-hydroxybutyrate. (See

"Clinical features and diagnosis of diabetic ketoacidosis and hyperosmolar hyperglycemic

state in adults", section on 'Serum ketones'.)

During insulin therapy, beta-hydroxybutyrate is converted to acetoacetate. Thus, if the

nitroprusside method is used for monitoring of ketones in the blood or urine, an increasingly

positive test due to this conversion may erroneously lead the clinician to believe that ketosis

has worsened (figure 2) [13]. As a result, assessments of urinary or serum ketone levels by

the nitroprusside method should not be used as an indicator of response to therapy.

If the results of blood chemistries can be returned in a timely fashion, an alternative to

monitoring venous pH and serum beta-hydroxybutyrate is monitoring the serumbicarbonate concentration (to assess correction of the metabolic acidosis) and the serum

anion gap (to assess correction of the ketoacidemia).

The serum anion gap provides an estimate of the quantity of unmeasured anions in the

plasma, such as albumin and, in DKA, ketoacid anions. It is calculated by subtracting the











http://www.uptodate.com/contents/nitroprusside-drug-information?source=see_link
























major measured anions (chloride and bicarbonate) from the major measured cation

(sodium):

Serum anion gap = Serum sodium - (serum chloride + bicarbonate)

(See "Approach to the adult with metabolic acidosis", section on 'Serum anion gap anddifferential diagnosis'.)

Monitoring the anion gap will give a good estimate of serum ketoacid anion levels in DKA.

Normalization of the anion gap reflects disappearance of ketoacid anions in the serum and

correction of the ketoacidosis. However, ketonemia and ketonuria may persist for more than

36 hours due to the slower removal of acetone, in part via the lungs [14,15]. Since acetone

is biochemically neutral, such patients do not have persistent ketoacidosis.

The factors that can affect the anion gap during the treatment of DKA are reviewed below.

(See 'Anion gap' below.)

Fluid replacement — Initial fluid therapy in DKA and HHS is directed toward expansion of

the intravascular volume and restoration of renal perfusion [16]. Adequate rehydration with

subsequent correction of the hyperosmolar state may result in a more robust response to

low dose insulin therapy [17,18].

The average fluid loss is 3 to 6 liters in DKA and up to 8 to 10 liters in HHS, due largely to

the glucose osmotic diuresis (table 2) [1,2,8,10]. In addition to inducing water loss,

glucosuria results in the loss of approximately 70 meq of sodium and potassium for each

liter of fluid lost. The aim of therapy is to replete the extracellular fluid volume withoutinducing cerebral edema due to too rapid reduction in the plasma osmolality. (See 'Cerebral

edema' below and "Treatment and complications of diabetic ketoacidosis in children",

section on 'Cerebral edema'.)

Fluid repletion is usually initiated with isotonic saline (0.9 percent sodium chloride). This

solution will replace the fluid deficit, correct the extracellular volume depletion more rapidly

than one-half isotonic saline, lower the plasma osmolality (since it is still hypoosmotic to the

patient), and reduce the serum glucose concentration both by dilution and by increasing

urinary losses as renal perfusion is increased [16,19].

The optimal rate at which isotonic saline is given is dependent upon the clinical state of the

patient. Isotonic saline should be infused as quickly as possible in patients who are in shock.

In the absence of cardiac compromise, isotonic saline is infused at a rate of 10 to 15 mL/kg

lean body weight per hour (about 1000 mL/h in an average-sized person) during the first

few hours, with a maximum of <50 mL/kg in the first four hours (algorithm 1 and algorithm

2) [1].

http://www.uptodate.com/contents/approach-to-the-adult-with-metabolic-acidosis?source=see_link&anchor=H8#H8







http://www.uptodate.com/contents/treatment-of-diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults?view=print#H18



















http://www.uptodate.com/contents/treatment-and-complications-of-diabetic-ketoacidosis-in-children?source=see_link&anchor=H17#H17



































The subsequent choice for fluid replacement depends upon the state of hydration, serum

electrolyte levels, and the urine output. Most patients are switched at some point to one-

half isotonic saline to replace the free water loss induced by the glucose osmotic diuresis.

When this should occur is uncertain, because of concern about the possible development of

cerebral edema if the plasma osmolality is reduced too rapidly. (See 'Cerebral

edema' below.)

In general, one-half isotonic saline infused at 4 to 14 mL/kg per hour is appropriate if the

corrected serum sodium is normal or elevated; isotonic saline at a similar rate is appropriate

if the corrected serum sodium is low [1]. Concurrent potassium replacement may be

another indication for the use of one-half isotonic saline. (See 'Serum sodium' below and

'Effect of potassium supplementation' below.)

Successful progress with fluid replacement is judged by frequent hemodynamic and

laboratory monitoring. Fluid replacement should correct estimated deficits within the first 24hours. In patients with renal or cardiac compromise, more frequent monitoring must be

performed during fluid resuscitation to avoid iatrogenic fluid overload [9,10,16,18-21].

Effective volume repletion will raise the glomerular filtration rate, resulting in reductions in

the blood urea nitrogen (BUN) and serum creatinine concentration. The serum creatinine is

initially elevated out of proportion to the fall in glomerular filtration rate, because

acetoacetate artifactually raises measured creatinine in the standard colorimetric assay

[22]. Metabolism of the acetoacetate following the administration of insulin will lower the

measured serum creatinine concentration toward its true value.

Effect of potassium supplementation — The timing of one-half isotonic saline therapy

may be influenced by potassium balance. Almost all patients with DKA or HHS have a

substantial potassium deficit due to urinary, and in some cases gastrointestinal, losses.

However, because of a shift of potassium out of the cells due primarily to insulin deficiency

and hyperosmolality, the serum potassium is often elevated at presentation. In such

patients, potassium repletion is not begun until the serum potassium concentration falls

below 5.3 meq/L. (See 'Potassium depletion' below.)

Potassium repletion affects the saline solution that is given since potassium is as osmotically

active as sodium. If 40 meq of potassium is added to each liter, one-half isotonic saline

should be used if the patient is hemodynamically stable since this solution contains 117 meq

of cation (77 meq of sodium and 40 meq of potassium) and is therefore equivalent to

approximately three-quarters isotonic saline. In contrast, the addition of potassium to

isotonic saline results in the generation of a hypertonic fluid that will not correct the













http://www.uptodate.com/contents/treatment-of-diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults/abstract/9,10,16,18-21


















hyperosmolality. (See "Overview of the treatment of hyponatremia", section on 'Effect of

potassium'.)

Insulin — Insulin therapy lowers the serum glucose concentration (primarily by decreasing

hepatic glucose production rather than enhancing peripheral utilization [23]), diminishes

ketone production (by reducing both lipolysis and glucagon secretion), and may augment

ketone utilization. The antilipolytic action of insulin requires a much lower dose than that

required to reduce the serum glucose concentration. As a result, any dose of insulin that

corrects the hyperglycemia will also normalize ketone metabolism [9,13,23]. (See

"Epidemiology and pathogenesis of diabetic ketoacidosis and hyperosmolar hyperglycemic

state", section on 'Pathogenesis'.)

Intravenous regular insulin — After an initial infusion of isotonic saline to increase insulin

responsiveness by lowering the plasma osmolality [17,18], the only indication for delaying

insulin therapy is a serum potassium below 3.3 meq/L, since insulin will worsen thehypokalemia by driving potassium into the cells. (See 'Potassium depletion' below.)

A continuous intravenous infusion of regular insulin is the treatment of choice, unless the

episode of DKA is uncomplicated and mild. In the past, a bolus dose of insulin was given

before the low dose insulin infusion to more rapidly activate insulin receptors [9,24-27].

However, a randomized trial showed that a bolus dose was not necessary if intravenous

insulin was infused at a rate of 0.14 U/kg per h, which is equivalent to 10 U/h in a 70 kg

patient [28]. Based upon this trial, DKA can be treated either with an IV bolus (0.1 U/kg

body weight), followed by a continuous infusion of regular insulin at a dose of 0.1 U/kg per

h or with an intravenous infusion alone at a rate of at least 0.14 U/kg per h.

The insulin dosing is the same in DKA and HHS (algorithm 1 and algorithm 2). The possible

role of other insulin preparations is discussed below. (See 'Intravenous insulin

analogs' below and 'Alternatives to intravenous insulin' below.)

The low dose of regular insulin usually decreases the serum glucose concentration by 50 to

70 mg/dL (2.8 to 3.9 mmol/L) per hour or more [23,25-27]. Higher doses do not generally

produce a more prominent hypoglycemic effect, possibly because the insulin receptors are

already saturated [24]. If the serum glucose does not fall by 50 to 70 mg/dL (2.8 to 3.9

mmol/L) from the initial value in the first hour, the insulin infusion rate should be doubled

every hour until a steady decline in serum glucose is achieved. If the serum glucose levels

fail to fall, the intravenous access should be checked to make certain that the insulin is

being delivered and that no filters are interposed that may bind insulin.

The actual fall in serum glucose is greater than that produced by insulin alone. Fluid

repletion can initially reduce the serum glucose by 35 to 70 mg/dL (1.9 to 3.9 mmol/L) per

http://www.uptodate.com/contents/overview-of-the-treatment-of-hyponatremia?source=see_link&anchor=H8#H8









http://www.uptodate.com/contents/epidemiology-and-pathogenesis-of-diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state?source=see_link&anchor=H3#H3









http://www.uptodate.com/contents/insulin-regular-drug-information?source=see_link



















































hour due to both hemodilution and increased urinary losses as renal perfusion is enhanced

[19,26]. The rate of fall in serum glucose may be more pronounced in patients with HHS

who are typically more volume depleted.

When the serum glucose reaches 200 mg/dL (11.1 mmol/L) in DKA or 250 to 300 mg/dL

(13.9 to 16.7 mmol/L) in HHS, the intravenous saline solution is switched to dextrose in

saline, and it may be possible to decrease the insulin infusion rate to 0.02 to 0.05 U/kg per

hour [10,18,24]. Reducing the serum glucose at this time below 200 mg/dL (11.1 mmol/L)

in DKA or 250 to 300 mg/dL (13.9 to 16.7 mmol/L) in HHS may promote the development

of cerebral edema. (See 'Cerebral edema' below and "Cerebral edema in children with

diabetic ketoacidosis".)

Intravenous insulin analogs — The possible role of other intravenous insulin preparations

was evaluated in a trial of 74 patients with DKA who were randomly assigned to intravenous

regular or glulisine insulin [29]. The initial dosing was the same (0.1 unit/kg IV bolus,followed by an infusion at 0.1 unit/kg per h). Patients were otherwise treated similarly,

according to ADA guidelines. After resolution of DKA, patients treated with regular

insulin received subcutaneous NPH and regular insulin twice daily, whereas patients treated

with IV glulisine insulin received glargine once daily and glulisine before meals.

There were no differences between the two groups in the mean duration of treatment,

amount of insulin administered, or total duration of insulin infusion until resolution of DKA.

After transition to subcutaneous insulin, glycemic control was also similar. However,

patients treated with NPH and regular insulin had a higher incidence of hypoglycemia. Thus,

intravenous regular and glulisine insulins were equally effective in treating DKA. Choice of

intravenous insulin should be based upon institutional preferences, clinician experience, and

cost concerns. (See "General principles of insulin therapy in diabetes mellitus", section on

'Human versus analogs'.)

DKA or HHS resolution — The hyperglycemic crisis is considered to be resolved when the

following goals are reached:

The ketoacidosis has resolved, as evidenced by normalization of the serum anion gap

(less than 12 meq/L). As mentioned above, ketonemia and ketonuria may persist for

more than 36 hours due to the slower removal of acetone, in part via the lungs

[14,15]. Since acetone is biochemically neutral, such patients do not have persistent

ketoacidosis.

Patients with HHS are mentally alert and the plasma effective osmolality is below

315 mosmol/kg.

The patient is able to eat.










http://www.uptodate.com/contents/cerebral-edema-in-children-with-diabetic-ketoacidosis?source=see_link














http://www.uptodate.com/contents/general-principles-of-insulin-therapy-in-diabetes-mellitus?source=see_link&anchor=H4#H4





















The ADA guidelines and one author (AK) suggest that the intravenous insulin infusion can

be tapered, and a multiple-dose subcutaneous (SC) insulin schedule started, in patients who

meet the following goals (the last three apply only to DKA):

Serum glucose below 200 mg/dL (11.1 mmol/L) in DKA or 250 to 300 mg/dL (13.9

to 16.7 mmol/L) in HHS

Serum anion gap <12 meq/L (or less than the upper limit of normal for the local

laboratory)

Serum bicarbonate ≥18 meq/L

Venous pH >7.30

A second author (BR) notes that, in the absence of end-stage renal disease, all patients

develop a normal anion gap acidosis ("non-gap acidosis") with resolution of the

ketoacidosis. (See 'Anion gap' below.) In this setting, insulin therapy will have no further

effect on the acidosis. Thus, the intravenous insulin may be tapered and a multiple-dose

subcutaneous insulin schedule started when the ketoacidosis is corrected (as evidenced by a

normal anion gap or the absence of beta-hydroxybutyric acid with direct testing) and the

serum glucose meets the above target.

Regardless of when rapid or short-acting subcutaneous insulin is started, intravenous insulin

infusion should be continued for an overlap of one to two hours. Abrupt discontinuation of

intravenous insulin can lead to an acute fall in insulin levels, possibly resulting in recurrence

of hyperglycemia and/or ketoacidosis. If the patient is unable to take oral nutrition, it is

preferable to continue the intravenous insulin infusion.

Patients with known diabetes who were previously treated with insulin may be given insulin

at the dose they were receiving before the onset of DKA or HHS. In insulin-naive patients, a

multi-dose insulin regimen should be started at a dose of 0.5 to 0.8 U/kg per day, including

bolus and basal insulin until an optimal dose is established. However, good clinical judgment

and frequent glucose assessment is vital in initiating a new insulin regimen in insulin-naive

patients. (See "General principles of insulin therapy in diabetes mellitus" and "Insulin

therapy in adults with type 1 diabetes mellitus" and "Insulin therapy in type 2 diabetes

mellitus".)

Alternatives to intravenous insulin — Both intramuscular and subcutaneous insulin

therapy, although less often used, appear to be as effective as intravenous therapy if the

patient is not in shock [30-32]. The efficacy and cost effectiveness of subcutaneous rapid-

acting insulin analogs (insulin lispro and aspart) in the management of uncomplicated DKA

have been demonstrated in two randomized trials in adults [31,32]. In one trial, for

example, 40 patients were assigned to one of two regimens [31]:




http://www.uptodate.com/contents/general-principles-of-insulin-therapy-in-diabetes-mellitus?source=see_link



http://www.uptodate.com/contents/insulin-therapy-in-adults-with-type-1-diabetes-mellitus?source=see_link




http://www.uptodate.com/contents/insulin-therapy-in-type-2-diabetes-mellitus?source=see_link






http://www.uptodate.com/contents/insulin-lispro-drug-information?source=see_link




















To prevent hypokalemia, potassium chloride (20 to 30 meq/L) is generally added to the

replacement fluid once the serum potassium concentration falls below 5.3 meq/L, assuming

an adequate urine output (>50 mL/h). If the patient is hemodynamically stable, one-half

isotonic saline is preferred since the addition of potassium to isotonic saline will result in a

hypertonic solution that will delay correction of the hyperosmolality. The serum potassium

should be maintained between 4.0 and 5.0 meq/L. (See 'Effect of potassium

supplementation' above.)

Potassium repletion is more urgent in patients with massive potassium deficits who are

hypokalemic prior to therapy [34,35]. Such patients require aggressive potassium

replacement (20 to 30 meq/hour), which usually requires 40 to 60 meq/L added to one-half

isotonic saline. Since insulin will worsen the hypokalemia, insulin therapy should be delayed

until the serum potassium is above 3.3 meq/L to avoid possible arrhythmias, cardiac arrest,

and respiratory muscle weakness [1,34,35].

Serum sodium — Hyperglycemia in uncontrolled diabetes mellitus has a variable effect on

the serum sodium concentration, as factors are present that can both lower and raise the

measured value [36]:

By raising the serum osmolality, hyperglycemia results in osmotic water movement

out of the cells, thereby lowering the serum sodium concentration by dilution.

The direct effect of hyperglycemia is counteracted by the glucosuria-induced osmotic

diuresis. The diuresis results in water loss in excess of sodium and potassium, which

will tend to raise the serum sodium concentration and plasma osmolality unless there

is a comparable increase in water intake.

The serum sodium concentration at presentation varies with the balance of these

mechanisms. (See "Clinical features and diagnosis of diabetic ketoacidosis and

hyperosmolar hyperglycemic state in adults", section on 'Serum sodium'.)

Reversing the hyperglycemia with insulin will lower the plasma osmolality, which will cause

water to move from the extracellular fluid into the cells, thereby raising the serum sodium

concentration [1,5,10,36,37]. Thus, a patient with a normal initial serum sodium

concentration will usually become hypernatremic during therapy with insulin and isotonicsaline. The degree to which this is likely to occur can be estimated at presentation by

calculation of the "corrected" serum sodium concentration, that is, the serum sodium

concentration that should be present if the serum glucose concentration were lowered to

normal with insulin alone [36]:

Corrected serum Na = Measured serum Na + [ΔSG ÷ 42]

http://www.uptodate.com/contents/potassium-chloride-drug-information?source=see_link




















http://www.uptodate.com/contents/treatment-of-diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults/abstract/1,5,10,36,37


















where ΔSG is the increment above normal in the serum glucose concentration (in mg/dL).

The ΔSG should be divided by 2.3 if measured in mmol/L.

Bicarbonate and metabolic acidosis — The indications for bicarbonate therapy in DKA

are controversial [38] and evidence of benefit is lacking [39-41]. In a randomized trial of 21

DKA patients with an admission arterial pH between 6.90 and 7.14 (mean 7.01),

bicarbonate therapy did not change morbidity or mortality [39]. However, the study was

small, limited to patients with an arterial pH 6.90 and above, and there was no difference in

the rate of rise in the arterial pH and serum bicarbonate between the bicarbonate and

placebo groups. No prospective randomized trials have been performed concerning the use

of bicarbonate in DKA with pH values less than 6.90.

The specific indications for bicarbonate administration are important because there are

three potential concerns with such therapy:

Overzealous use of alkali can lead to a rise in pCO2 (since there is less of an

acidemic stimulus to hyperventilation), resulting in a paradoxical fall in cerebral pH

as the lipid-soluble CO2 rapidly crosses the blood-brain barrier. Neurologic

deterioration has been reported in this setting, but is probably a rare event [42].

The administration of alkali may slow the rate of recovery of the ketosis [43,44]. In a

study of seven patients, the three patients who were treated with bicarbonate had a

rise in serum ketoacid levels during bicarbonate infusion, resulting in a six-hour

delay in improvement of ketosis [43]. Animal studies suggest that bicarbonate

therapy increases hepatic ketogenesis. However, in the randomized trial cited above,

bicarbonate therapy had no effect on the rate of decline in serum ketone levels [39].

Alkali administration can lead to a posttreatment metabolic alkalosis, since

metabolism of ketoacid anions with insulin results in the generation of bicarbonate

and spontaneous correction of most of the metabolic acidosis. (See 'Anion

gap' below.)

There are, however, selected patients who may benefit from cautious alkali therapy [42].

These include:

Patients with an arterial pH less than 7.00 in whom decreased cardiac contractility

and vasodilatation can further impair tissue perfusion. At an arterial pH above 7.00,

most experts agree that bicarbonate therapy is not necessary, since insulin therapy

alone will result in resolution of most of the metabolic acidosis [45].

Patients with potentially life-threatening hyperkalemia, since bicarbonate

administration in acidemic patients drives potassium into cells, thereby lowering the










































serum potassium concentration [46]. (See "Treatment and prevention of

hyperkalemia".)

We recommend administering bicarbonate if the arterial pH is less than 6.90. We give 100

meq of sodium bicarbonate in 400 mL sterile water with 20 meq of potassium chloride, if

the serum potassium is less than 5.3 meq/L, administered over two hours.

The venous pH should be monitored every two hours, and bicarbonate dosed as above, until

the pH rises above 7.00.

Anion gap — There is a variable relationship between the elevation in serum anion gap and

the fall in serum bicarbonate concentration because of the excretion of ketoacid anions in

the urine [47,48]. (See "The Δanion gap/ΔHCO3 ratio in patients with a high anion gap

metabolic acidosis".)

Ketoacid anions have been called "potential bicarbonate," since their metabolism following

the administration of insulin results in the generation of bicarbonate and reversal of the

acidosis. The effect of ketoacid anion excretion on the course of ketoacidosis varies with the

accompanying cation:

The excretion of ketoacid anions with hydrogen or ammonium is associated with an

equivalent loss of protons, correcting both the anion gap and the acidemia. It has

been estimated that approximately 30 percent of the ketoacids produced in DKA are

excreted in the urine in patients with relatively normal renal function; the conversion

of acetoacetic acid to acetone can neutralize another 15 to 25 percent of the acidload [49].

The excretion of ketoacid anions with sodium or potassium represents the loss of

bicarbonate precursors (ie, "potential bicarbonate") and is therefore equivalent to

bicarbonate loss. The net effect is that the anion gap is reduced but the acidosis

persists.

As a result of the urinary loss of "potential bicarbonate," almost all patients with DKA

(except those with advanced renal failure) develop a normal anion gap acidosis (also known

as a "non-gap acidosis") during treatment [47,50,51]. Suppose, for example, that a patienthas a serum bicarbonate of 8 meq/L and an anion gap of 24 meq/L (approximately 16

meq/L above normal). Insulin therapy promotes correction of the ketoacidosis by inhibiting

lipolysis, which decreases the supply of free fatty acids to the liver for ketogenesis, by

inhibiting ketogenesis in the liver, and by promoting peripheral ketone metabolism. (See

"Insulin action", section on 'Insulin and ketone body metabolism'.)




http://www.uptodate.com/contents/treatment-and-prevention-of-hyperkalemia?source=see_link




http://www.uptodate.com/contents/sodium-bicarbonate-drug-information?source=see_link









http://www.uptodate.com/contents/the-anion-gap-hco3-ratio-in-patients-with-a-high-anion-gap-metabolic-acidosis?source=see_link










http://www.uptodate.com/contents/insulin-action?source=see_link&anchor=H8#H8















The net effect is that the 16 meq/L of ketoacid anion will be metabolized, which will

regenerate some of the HCO3 lost in the initial buffering reaction. However, the plasma

HCO3 may only rise by about 8 meq/L (to 16 meq/L), with the rest of the HCO3

replenishing the cell and bone buffer stores. At this point, the patient will have metabolic

acidosis with a normal AG, due to the combination of the previous production of the intact

ketoacid and the subsequent loss of the ketoacid anion in the urine. If no ketoacid anions

had been excreted in the urine (as in a dialysis patient), then insulin therapy would have

returned both the anion gap and serum bicarbonate concentration to baseline. (See "The

Δanion gap/ΔHCO3 ratio in patients with a high anion gap metabolic acidosis", section on

'Ketoacidosis'.)

Phosphate depletion — Whole body phosphate depletion is common in uncontrolled

diabetes mellitus, although the serum phosphate concentration may initially be normal or

elevated due to movement of phosphate out of the cells [8,52]. As with potassium balance,

phosphate depletion is rapidly unmasked following the institution of insulin therapy,

frequently leading to hypophosphatemia that is usually asymptomatic.

The fall in serum phosphate concentration during the treatment of DKA is acute, self-

limited, and usually not associated with marked phosphate depletion or adverse effects.

Clinically evident hemolysis as well as rhabdomyolysis with myoglobinuria are rare

complications of the hypophosphatemia [53-55]. (See "Signs and symptoms of

hypophosphatemia".)

Prospective randomized trials of patients with DKA have failed to show a beneficial effect of

phosphate replacement on the duration of ketoacidosis, dose of insulin required, rate of fall

of serum glucose, or morbidity and mortality [56-58]. In addition, phosphate replacement

may have adverse effects such as hypocalcemia and hypomagnesemia [56,59-61].

Based upon these observations, we do NOT recommend the routine use of phosphate in the

treatment of DKA or HHS. However, to avoid cardiac and skeletal muscle weakness and

respiratory depression due to hypophosphatemia, careful phosphate replacement may be

indicated in patients who develop cardiac dysfunction, hemolytic anemia, or respiratory

depression, and in those with a serum phosphate concentration below 1.0 mg/dL (0.32

mmol/L) [62]. When needed, 20 to 30 meq/L of potassium phosphate can be added toreplacement fluids.

COMPLICATIONS — The most common complications of the treatment of DKA and HHS,

hypoglycemia and hypokalemia, have been reduced significantly since the administration of

low dose insulin and careful monitoring of serum potassium [63]. Hyperglycemia may result

http://www.uptodate.com/contents/the-anion-gap-hco3-ratio-in-patients-with-a-high-anion-gap-metabolic-acidosis?source=see_link&anchor=H6#H6










http://www.uptodate.com/contents/signs-and-symptoms-of-hypophosphatemia?source=see_link









http://www.uptodate.com/contents/potassium-phosphate-drug-information?source=see_link




















from interruption or discontinuation of intravenous insulin without prior coverage with

subcutaneous insulin.

Cerebral edema — Cerebral edema in uncontrolled diabetes mellitus (usually DKA, with

occasional reports in HHS) is primarily a disease of children and almost all affected patients

are below the age of 20 years [64]. Symptoms typically emerge with 12 to 24 hours of the

initiation of treatment for DKA, but may be present prior to the onset of therapy. Issues

related to cerebral edema in DKA, including pathogenesis, are discussed in detail separately

in the pediatric section but will be briefly reviewed here. (See "Cerebral edema in children

with diabetic ketoacidosis".)

Headache is the earliest clinical manifestation, followed by lethargy, and decreased arousal.

Neurologic deterioration may be rapid, with seizures, incontinence, pupillary changes,

bradycardia, and respiratory arrest. These symptoms progress if brainstem herniation

occurs, and the rate of progression may be so rapid that papilledema is not seen.

Cerebral edema is associated with a mortality rate of 20 to 40 percent [1]. Thus, an

essential part of therapy in DKA is careful monitoring for changes in mental or neurologic

status that would permit early identification and therapy of cerebral edema.

The 2009 ADA guidelines on hyperglycemic crises in diabetes in adults suggested that the

following preventive measures may reduce the risk of cerebral edema in high-risk patients

[1]:

Gradual replacement of sodium and water deficits in patients who are hyperosmolar.

The usual regimen for the first few hours is isotonic saline at a rate of 10 to 15

mL/kg lean body weight per hour (about 1000 mL/h in an average-sized person)

with a maximum of <50 mL/kg in the first four hours (algorithm 1 and algorithm 2).

The addition of dextrose to the saline solution once the serum glucose levels reach

200 mg/dL (11.1 mmol/L) in DKA or 250 to 300 mg/dL (13.9 to 16.7 mmol/L) in

HHS. In HHS, the serum glucose should be maintained at 250 to 300 mg/dL (13.9 to

16.7 mmol/L) until the hyperosmolality and mental status improve and the patient is

clinically stable.

Data evaluating the outcome and treatment of cerebral edema in adults are not available.

Recommendations for treatment are based upon clinical judgment in the absence of

scientific evidence. Case reports and small series in children suggest benefit from prompt

administration of mannitol (0.25 to 1.0 g/kg) and perhaps from hypertonic (3 percent)

saline (5 to 10 mL/kg over 30 min) [64]. These approaches raise the plasma osmolality,

resulting in osmotic movement of water out of the brain and a reduction in cerebral edema.



















http://www.uptodate.com/contents/mannitol-drug-information?source=see_link

















Noncardiogenic pulmonary edema — Hypoxemia and rarely noncardiogenic pulmonary

edema can complicate the treatment of DKA [65-67]. Hypoxemia is attributed to a reduction

in colloid osmotic pressure that results in increased lung water content and decreased lung

compliance [68]. Patients with DKA who have a widened alveolar-arterial oxygen gradient

noted on initial blood gas measurement or rales on physical examination appear to be at

higher risk for the development of pulmonary edema.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education

materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are

written in plain language, at the 5th to 6th grade reading level, and they answer the four or

five key questions a patient might have about a given condition. These articles are best for

patients who want a general overview and who prefer short, easy-to-read materials. Beyond

the Basics patient education pieces are longer, more sophisticated, and more detailed.

These articles are written at the 10th to 12th grade reading level and are best for patients

who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to

print or e-mail these topics to your patients. (You can also locate patient education articles

on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

Basics topics (see "Patient information: Diabetic ketoacidosis (The Basics)")

SUMMARY AND RECOMMENDATIONS

Therapy for both diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state

(HHS) includes fluid replacement to correct both hypovolemia and hyperosmolality,

insulin administration to correct hyperglycemia and, in DKA, metabolic acidosis,

potassium repletion, and, in selected patients with DKA, sodium bicarbonate.

Frequent monitoring is essential and underlying precipitating events should be

identified and corrected. A table outlining the emergency management of DKA in

adults is provided (table 3).

Treatment algorithms for the management of DKA and HHS were included in the

2009 American Diabetes Association guidelines on hyperglycemic crises in adults

(algorithm 1 and algorithm 2) [1]. (See 'Treatment overview and protocols' above.)

Monitoring involves hourly glucose measurement until stable, and basic chemistry

profile, plasma osmolality, and venous pH every two to four hours. The course of

ketoacidemia can be assessed by direct measurement of beta-hydroxybutyrate, the

major circulating ketoacid, and/or measurement of the serum anion gap. In contrast,






http://www.uptodate.com/contents/patient-information-diabetic-ketoacidosis-the-basics?source=see_link
































nitroprusside tablets or reagent sticks should not be used because they react with

acetoacetate and acetone, but not with beta-hydroxybutyrate. Acetone is

biochemically neutral and does not contribute to the ketoacidosis. (See

'Monitoring' above.)

We recommend vigorous intravenous fluid replacement to correct both hypovolemia

and hyperosmolality (Grade 1A). Fluid replacement should correct estimated deficits

within the first 24 hours, with care to avoid an overly rapid reduction in the serum

osmolality.

We begin with isotonic (0.9 percent) saline infused at a rate of 15 to 20 mL/kg per

hour, in the absence of cardiac compromise, for the first few hours. This is followed

by one-half isotonic (0.45 percent) saline at 4 to 14 mL/kg per hour if the serum

sodium is normal or elevated; isotonic saline is continued if hyponatremia is present

[1]. We add dextrose to the saline solution when the serum glucose reaches 200

mg/dL (11.1 mmol/L) in DKA or 250 to 300 mg/dL (13.9 to 16.7 mmol/L) in HHS.

(See 'Fluid replacement' above.)

The need for potassium repletion may influence the timing of one-half isotonic saline

therapy, since the addition of potassium to isotonic saline creates a hypertonic

solution that can worsen the underlying hyperosmolality. (See 'Effect of potassium

supplementation' above.)

We recommend initial treatment with low-dose intravenous insulin in all patients with

moderate to severe DKA who have a serum potassium ≥3.3 meq/L (Grade 1B).

Patients with an initial serum potassium below 3.3 meq/L should receive aggressive

fluid and potassium replacement PRIOR to treatment with insulin. (See 'Potassium

depletion' above.)

The insulin regimen is the same in DKA and HHS. If the serum potassium is ≥3.3

meq/L, we give a continuous intravenous infusion of regular insulin at 0.14 U/kg per

h; at this dose, an initial intravenous bolus is not necessary. An alternative option is

to administer an IV bolus (0.1 U/kg body weight) of regular insulin, followed by a

continuous infusion at a dose of 0.1 U/kg per hour. The dose is doubled if the

glucose does not fall by 50 to 70 mg/dL (2.8 to 3.9 mmol/L) in the first hour. (See

'Insulin' above.)

A cost-effective alternative to intravenous insulin in the initial treatment of

uncomplicated DKA is the use of subcutaneous rapid-acting insulin analogs (insulin





http://www.uptodate.com/contents/grade/1?title=Grade%201A&topicKey=ENDO/1795













http://www.uptodate.com/contents/grade/2?title=Grade%201B&topicKey=ENDO/1795




























lispro and aspart) in selected patients in settings in which adequate monitoring can

be assured. (See 'Alternatives to intravenous insulin' above.)

We initiate a multiple-dose subcutaneous insulin schedule when the ketoacidosis has

resolved and the patient is able to eat. The intravenous insulin infusion should be

continued for one to two hours after initiating the subcutaneous insulin, to avoid

recurrence of hyperglycemia. (See 'DKA or HHS resolution' above.)

Patients with DKA or HHS typically have a marked degree of potassium depletion due

to both renal and, in some patients, gastrointestinal losses. However, because of

potassium redistribution from the cells into the extracellular fluid, the initial serum

potassium concentration is often normal or elevated, an effect that will be reversed

by insulin therapy.

We recommend that replacement with intravenous potassium chloride (Grade

1A) be initiated when the serum potassium concentration is ≤5.3 meq/L. Patients

with an initial serum potassium below 3.3 meq/L should receive aggressive fluid and

potassium replacement PRIOR to treatment with insulin to prevent initial worsening

of the hypokalemia. (See 'Potassium depletion' above.)

Indications for sodium bicarbonate therapy to help correct the metabolic acidosis are

controversial. We suggest treatment with intravenous sodium bicarbonate in patients

with an arterial pH less than 6.9 (Grade 2B). (See 'Bicarbonate and metabolic

acidosis' above.)

Although whole body phosphate depletion is usually present, we recommend NOT

administering phosphate routinely (Grade 1A). We suggest phosphate replacement

for patients with severe hypophosphatemia (<1.0 mg/dL [0.32 mmol/L]), respiratory

or cardiac failure, or severe anemia (Grade 2C). (See 'Phosphate depletion' above.)

Cerebral edema is rare in adults, but is associated with high rates of morbidity and

mortality. Possible preventive measures in high-risk patients include gradual rather

than rapid correction of fluid and sodium deficits (maximum reduction in plasma

osmolality of 3 mosmol/kg per hour), and maintenance of a slightly elevated serum

glucose until the patient is stable. (See 'Cerebral edema' above.)

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

1. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients withdiabetes. Diabetes Care 2009; 32:1335.






























http://www.uptodate.com/contents/grade/6?title=Grade%202C&topicKey=ENDO/1795









http://www.uptodate.com/contents/license

























2. Arieff AI, Carroll HJ. Nonketotic hyperosmolar coma with hyperglycemia: clinical features,pathophysiology, renal function, acid-base balance, plasma-cerebrospinal fluid equilibria andthe effects of therapy in 37 cases. Medicine (Baltimore) 1972; 51:73.

3. Kitabchi AE, Umpierrez GE, Fisher JN, et al. Thirty years of personal experience inhyperglycemic crises: diabetic ketoacidosis and hyperglycemic hyperosmolar state. J ClinEndocrinol Metab 2008; 93:1541.

4. Morris LR, Kitabchi AE. Efficacy of low-dose insulin therapy for severely obtunded patients indiabetic ketoacidosis. Diabetes Care 1980; 3:53.

5. Daugirdas JT, Kronfol NO, Tzamaloukas AH, Ing TS. Hyperosmolar coma: cellulardehydration and the serum sodium concentration. Ann Intern Med 1989; 110:855.

6. Fulop M, Tannenbaum H, Dreyer N. Ketotic hyperosmolar coma. Lancet 1973; 2:635. 7. Kitabchi, AE, Fisher, JN. Insulin therapy of diabetic ketoacidosis: physiologic versus

pharmacologic doses of insulin and their routes of administration. In: Handbook of DiabetesMellitus Brownlee, M (Ed), Garland ATPM Press, New York 1981. p. 95.

8. Rose, BD, Post, TW, Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed,McGraw-Hill, New York, 2001, pp. 809-815.

9. Barrett EJ, DeFronzo RA. Diabetic ketoacidosis: diagnosis and treatment. Hosp Pract (OffEd) 1984; 19:89.

10. Kitabchi AE, Umpierrez GE, Murphy MB, et al. Management of hyperglycemic crises in

patients with diabetes. Diabetes Care 2001; 24:131. 11. Middleton P, Kelly AM, Brown J, Robertson M. Agreement between arterial and central

venous values for pH, bicarbonate, base excess, and lactate. Emerg Med J 2006; 23:622. 12. Wiggam MI, O'Kane MJ, Harper R, et al. Treatment of diabetic ketoacidosis using

normalization of blood 3-hydroxybutyrate concentration as the endpoint of emergencymanagement. A randomized controlled study. Diabetes Care 1997; 20:1347.

13. Kitabchi, AE, Fisher, JN, Murphy, MB, Rumbak, MJ. Diabetic ketoacidosis and thehyperglycemic hyperosmolar nonketotic state. In: Joslin's Diabetes Mellitus. 13th ed. Kahn,CR, Weir, GC (Eds), Lea & Febiger, Philadelphia 1994. p. 738.

14. Sulway MJ, Malins JM. Acetone in diabetic ketoacidosis. Lancet 1970; 2:736. 15. Reichard GA Jr, Skutches CL, Hoeldtke RD, Owen OE. Acetone metabolism in humans during

diabetic ketoacidosis. Diabetes 1986; 35:668.

16. Hillman K. Fluid resuscitation in diabetic emergencies--a reappraisal. Intensive Care Med1987; 13:4. 17. Bratusch-Marrain, PR, Komajati, M, Waldhausal, W. The effect of hyperosmolarity on

glucose metabolism. Pract Cardiol 1985; 11:153. 18. Kitabchi, AE, Umpierrez, GE, Murphy, MB. Diabetic ketoacidosis and hyperglycemic

hyperosmolar state. In: International Textbook of Diabetes Mellitus, 3rd edition. DeFronzo,RA, Ferrannini, E, Keen, H, Zimmet, P (Eds), John Wiley & Sons, Ltd, Chichester, UK 2004.p.1101.

19. Waldhäusl W, Kleinberger G, Korn A, et al. Severe hyperglycemia: effects of rehydration onendocrine derangements and blood glucose concentration. Diabetes 1979; 28:577.

20. Ennis, ED, Stahl, EJ, Kreisberg, RA. The hyperosmolar hyperglycemic syndrome. DiabetesRev 1994; 2:115.

21. Wachtel TJ. The diabetic hyperosmolar state. Clin Geriatr Med 1990; 6:797.

22. Molitch ME, Rodman E, Hirsch CA, Dubinsky E. Spurious serum creatinine elevations inketoacidosis. Ann Intern Med 1980; 93:280.

23. Luzi L, Barrett EJ, Groop LC, et al. Metabolic effects of low-dose insulin therapy on glucosemetabolism in diabetic ketoacidosis. Diabetes 1988; 37:1470.

24. Brown PM, Tompkins CV, Juul S, Sönksen PH. Mechanism of action of insulin in diabeticpatients: a dose-related effect on glucose production and utilisation. Br Med J 1978;1:1239.

25. Rosenthal NR, Barrett EJ. An assessment of insulin action in hyperosmolar hyperglycemicnonketotic diabetic patients. J Clin Endocrinol Metab 1985; 60:607.























































































































26. Page MM, Alberti KG, Greenwood R, et al. Treatment of diabetic coma with continuous low-dose infusion of insulin. Br Med J 1974; 2:687.

27. Padilla AJ, Loeb JN. "Low-dose" versus "high-dose" insulin regimens in the management ofuncontrolled diabetes. A survey. Am J Med 1977; 63:843.

28. Kitabchi AE, Murphy MB, Spencer J, et al. Is a priming dose of insulin necessary in a low-dose insulin protocol for the treatment of diabetic ketoacidosis? Diabetes Care 2008;

31:2081. 29. Umpierrez GE, Jones S, Smiley D, et al. Insulin analogs versus human insulin in the

treatment of patients with diabetic ketoacidosis: a randomized controlled trial. DiabetesCare 2009; 32:1164.

30. Fisher JN, Shahshahani MN, Kitabchi AE. Diabetic ketoacidosis: low-dose insulin therapy byvarious routes. N Engl J Med 1977; 297:238.

31. Umpierrez GE, Latif K, Stoever J, et al. Efficacy of subcutaneous insulin lispro versuscontinuous intravenous regular insulin for the treatment of patients with diabeticketoacidosis. Am J Med 2004; 117:291.

32. Umpierrez GE, Cuervo R, Karabell A, et al. Treatment of diabetic ketoacidosis withsubcutaneous insulin aspart. Diabetes Care 2004; 27:1873.

33. Adrogué HJ, Lederer ED, Suki WN, Eknoyan G. Determinants of plasma potassium levels indiabetic ketoacidosis. Medicine (Baltimore) 1986; 65:163.

34. Abramson E, Arky R. Diabetic acidosis with initial hypokalemia. Therapeutic implications.JAMA 1966; 196:401.

35. Beigelman PM. Potassium in severe diabetic ketoacidosis. Am J Med 1973; 54:419. 36. Hillier TA, Abbott RD, Barrett EJ. Hyponatremia: evaluating the correction factor for

hyperglycemia. Am J Med 1999; 106:399. 37. Kreisberg RA. Diabetic ketoacidosis: new concepts and trends in pathogenesis and

treatment. Ann Intern Med 1978; 88:681. 38. Viallon A, Zeni F, Lafond P, et al. Does bicarbonate therapy improve the management of

severe diabetic ketoacidosis? Crit Care Med 1999; 27:2690. 39. Morris LR, Murphy MB, Kitabchi AE. Bicarbonate therapy in severe diabetic ketoacidosis. Ann

Intern Med 1986; 105:836. 40. Lever E, Jaspan JB. Sodium bicarbonate therapy in severe diabetic ketoacidosis. Am J Med

1983; 75:263. 41. Latif KA, Freire AX, Kitabchi AE, et al. The use of alkali therapy in severe diabeticketoacidosis. Diabetes Care 2002; 25:2113.

42. Narins RG, Cohen JJ. Bicarbonate therapy for organic acidosis: the case for its continueduse. Ann Intern Med 1987; 106:615.

43. Okuda Y, Adrogue HJ, Field JB, et al. Counterproductive effects of sodium bicarbonate indiabetic ketoacidosis. J Clin Endocrinol Metab 1996; 81:314.

44. Hale PJ, Crase J, Nattrass M. Metabolic effects of bicarbonate in the treatment of diabeticketoacidosis. Br Med J (Clin Res Ed) 1984; 289:1035.

45. DeFronzo, RA, Matzuda, M, Barret, E. Diabetic ketoacidosis: a combined metabolic-nephrologic approach to therapy. Diabetes Rev 1994; 2:209.

46. Fraley DS, Adler S. Correction of hyperkalemia by bicarbonate despite constant blood pH.Kidney Int 1977; 12:354.

47. Adrogué HJ, Eknoyan G, Suki WK. Diabetic ketoacidosis: role of the kidney in the acid-basehomeostasis re-evaluated. Kidney Int 1984; 25:591.

48. Adrogué, HJ, Wilson, H, Boyd, AE III, et al. Plasma acid-base patterns in diabeticketoacidosis. N Engl J Med 1982; 307:1603.

49. Owen OE, Licht JH, Sapir DG. Renal function and effects of partial rehydration duringdiabetic ketoacidosis. Diabetes 1981; 30:510.

50. Oh MS, Carroll HJ, Goldstein DA, Fein IA. Hyperchloremic acidosis during the recovery phaseof diabetic ketosis. Ann Intern Med 1978; 89:925.





























































































































































51. Oh MS, Carroll HJ, Uribarri J. Mechanism of normochloremic and hyperchloremic acidosis indiabetic ketoacidosis. Nephron 1990; 54:1.

52. Kebler R, McDonald FD, Cadnapaphornchai P. Dynamic changes in serum phosphorus levelsin diabetic ketoacidosis. Am J Med 1985; 79:571.

53. RAINEY RL, ESTES PW, NEELY CL, AMICK LD. Myoglobinuria following diabetic acidosis withelectromyographic evaluation. Arch Intern Med 1963; 111:564.

54. Casteels K, Beckers D, Wouters C, Van Geet C. Rhabdomyolysis in diabetic ketoacidosis.Pediatr Diabetes 2003; 4:29.

55. Shilo S, Werner D, Hershko C. Acute hemolytic anemia caused by severe hypophosphatemiain diabetic ketoacidosis. Acta Haematol 1985; 73:55.

56. Fisher JN, Kitabchi AE. A randomized study of phosphate therapy in the treatment ofdiabetic ketoacidosis. J Clin Endocrinol Metab 1983; 57:177.

57. Keller U, Berger W. Prevention of hypophosphatemia by phosphate infusion duringtreatment of diabetic ketoacidosis and hyperosmolar coma. Diabetes 1980; 29:87.

58. Wilson HK, Keuer SP, Lea AS, et al. Phosphate therapy in diabetic ketoacidosis. Arch InternMed 1982; 142:517.

59. Barsotti MM. Potassium phosphate and potassium chloride in the treatment of DKA.Diabetes Care 1980; 3:569.

60. Winter RJ, Harris CJ, Phillips LS, Green OC. Diabetic ketoacidosis. Induction of hypocalcemia

and hypomagnesemia by phosphate therapy. Am J Med 1979; 67:897. 61. Zipf WB, Bacon GE, Spencer ML, et al. Hypocalcemia, hypomagnesemia, and transient

hypoparathyroidism during therapy with potassium phosphate in diabetic ketoacidosis.Diabetes Care 1979; 2:265.

62. Kreisberg RA. Phosphorus deficiency and hypophosphatemia. Hosp Pract 1977; 12:121. 63. Kitabchi AE, Ayyagari V, Guerra SM. The efficacy of low-dose versus conventional therapy of

insulin for treatment of diabetic ketoacidosis. Ann Intern Med 1976; 84:633. 64. Wolfsdorf J, Glaser N, Sperling MA, American Diabetes Association. Diabetic ketoacidosis in

infants, children, and adolescents: A consensus statement from the American DiabetesAssociation. Diabetes Care 2006; 29:1150.

65. Sprung CL, Rackow EC, Fein IA. Pulmonary edema; a complication of diabetic ketoacidosis.Chest 1980; 77:687.

66. Powner D, Snyder JV, Grenvik A. Altered pulmonary capillary permeability complicatingrecovery from diabetic ketoacidosis. Chest 1975; 68:253. 67. Brun-Buisson CJ, Bonnet F, Bergeret S, et al. Recurrent high-permeability pulmonary edema

associated with diabetic ketoacidosis. Crit Care Med 1985; 13:55. 68. Kitabchi, AE, Umpierrez, GE, Murphy, MB. Diabetic ketoacidosis and hyperglycemic

hyperosmolar state. In: International Textbook of Diabetes Mellitus, 3rd ed, DeFronzo, RA,Ferrannini, E, Keen, H, Zimmet, P (Eds), John Wiley & Sons, Ltd, Chichester, UK 2004, p.1101.

Topic 1795 Version 5.0











































































































GRAPHICS



Diagnostic criteria for diabetic ketoacidosis (DKA) and hyperosmolarhyperglycemic state (HHS)

DKAHHS

Mild Moderate Severe

Plasma glucose (mg/dL) >250 >250 >250 >600

Arterial pH 7.25-7.30

7.00-7.24 <7.00 >7.30

Serum bicarbonate (mEq/L) 15-18 10 to <15 <10 >18

Urine ketones* Positive Positive Positive Small

Serum ketones* Positive Positive Positive Small

Effective serum osmolality(mOsm/kg)• Variable Variable Variable >320

Anion gapΔ >10 >12 >12 Variable

Alteration in sensoria or mentalobtundation

Alert Alert/drowsy Stupor/coma Stupor/coma



* Nitroprusside reaction method.



• Calculation: 2[measured Na (mEq/L)] + glucose (mg/dL)/18.



Δ Calculation: (Na+) - (Cl- + HCO3-) (mEq/L). See text for details. Copyright © 2006 American Diabetes Association From Diabetes Care Vol 29, Issue 12, 2006. Information updated from Kitabchi, AE, Umpierrez,GE, Miles, JM, Fisher, JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care 2009;32:1335.



Reprinted with permission from the American Diabetes Association.



Typical total body deficits of water and electrolytes in DKA and HHS*

DKA HHS

Total water (L) 6 9

Water (ml/kg•) 100 100-200

Na+ (mEq/kg) 7-10 5-13

Cl- (mEq/kg) 3-5 5-15

K+ (mEq/kg) 3-5 4-6

PO4 (mmol/kg) 5-7 3-7

Mg++ (mEq/kg) 1-2 1-2

Ca++ (mEq/kg) 1-2 1-2



* Data are from Ennis et al (1994) and Kreisberg (1978).



Emergent DKA management in adults: rapid overview

Clinical features

DKA usually evolves rapidly over a 24-hour period.

Common, early signs of ketoacidosis include nausea, vomiting, abdominal pain, andhyperventilation. The earliest symptoms of marked hyperglycemia are polyuria, polydipsia, andweight loss.

As hyperglycemia worsens, neurologic symptoms appear, and may progress to include lethargy,focal deficits, obtundation, seizure, and coma.

Common causes of DKA include: infection; noncompliance, inappropriate adjustment, or cessation ofinsulin; new onset diabetes mellitus; and myocardial ischemia.

Evaluation and laboratory findings

Assess vital signs, cardiorespiratory status, and mental status.

Assess volume status: vital signs, skin turgor, mucosa, urine output.

Obtain the following studies: serum glucose, urinalysis and urine ketones, serum electrolytes, BUNand creatinine, plasma osmolality, mixed venous blood gas, electrocardiogram; add serum ketonesif urine ketones present.

Diabetic ketoacidosis (DKA) is characterized by hyperglycemia, an elevated anion gap metabolicacidosis, and ketonemia. Dehydration and potassium deficits are often severe.

Serum glucose is usually greater than 250 mg/dL (13.9 mmol/L) and less than 800 mg/dL (44.4mmol/L). In certain instances (eg, insulin given prior to ED arrival), the glucose may be only mildlyelevated.

Additional testing is obtained based on clinical circumstances and may include: blood or urinecultures, lipase, chest x-ray.

Management

Stabilize the patient's airway, breathing, and circulation.

Obtain large bore IV (≥16 gauge) access; monitor using a cardiac monitor, capnography, and pulseoximetry.

Monitor serum glucose hourly, and basic electrolytes, plasma osmolality, and venous pH every twoto four hours until the patient is stable.

Determine and treat any underlying cause of DKA (eg, pneumonia or urinary infection, myocardialischemia).

Replete fluid deficits:

• Give several liters of isotonic (0.9 percent) saline as rapidly as possible to patients with signs ofshock.



• Give isotonic saline at 15 to 20 mL/kg per hour, in the absence of cardiac compromise, for thefirst few hours to hypovolemic patients without shock.

• After intravascular volume is restored, give one-half isotonic (0.45 percent) saline at 4 to 14mL/kg per hour if the corrected serum sodium is normal or elevated; isotonic saline is continued ifthe corrected serum sodium is reduced.

• Add dextrose to the saline solution when the serum glucose reaches 200 mg/dL (11.1 mmol/L).

Replete potassium (K+) deficits:

• Regardless of the initial measured serum potassium, patients with DKA have a large total bodypotassium deficit.

• If initial serum K+ is below 3.3 mEq/L, hold insulin and give K+ 20 to 30 mEq/hour IV until K+concentration is above 3.3 mEq/L.

• If initial serum K+ is between 3.3 and 5.3 mEq/L, give K+ 20 to 30 mEq per liter IV fluid;maintain K+ between 4 to 5 mEq/L.

• If initial serum K+ is above 5.3 mEq/L do not give K+; check K+ every 2 hours.

Give insulin:

• Do not give insulin if initial serum K+ is below 3.3 mEq/L; replete K+ first.

• Give all patients without a serum K+ below 3.3 mEq/L regular insulin. Either of two regimenscan be used: 0.1 units/kg IV bolus, then start a continuous IV infusion 0.1 units/kg per hour; ORdo not give bolus and start a continuous IV infusion at a rate of 0.14 units/kg per hour.

• Continue insulin infusion until ketoacidosis is resolved, serum glucose is below 200 mg/dL (11.1mmol/L), and subcutaneous insulin is begun.

Give sodium bicarbonate to patients with pH below 7.00:

• If the arterial pH is between 6.90 and 7.00, give 50 meq of sodium bicarbonate plus 10 meq ofpotassium chloride in 200 mL of sterile water over two hours.

• If the arterial pH is below 6.90, give 100 meq of sodium bicarbonate plus 20 meq of potassiumchloride in 400 mL sterile water over two hours.



Protocol for the management of adult patients with DKA



DKA diagnostic criteria: serum glucose >250 mg/dl, arterial pH <7.3, serum bicarbonate<18 mEq/l, and moderate ketonuria or ketonemia. Normal laboratory values vary; checklocal lab normal ranges for all electrolytes. IV: intravenous; SC: subcutaneous.



* After history and physical exam, obtain capillary glucose and serum or urine ketones (nitroprussidemethod). Begin one liter of 0.9 percent NaCl over one hour and draw arterial blood gases, complete bloodcount with differential, urinalysis, serum glucose, BUN, electrolytes, chemistry profile, and creatinine levelsSTAT. Obtain electrocardiogram, chest X-ray, and specimens for bacterial cultures, as needed.



• Serum Na+ should be corrected for hyperglycemia (for each 100 mg/dl glucose >100 mg/dl, add 1.6 mEqto sodium value for corrected serum sodium value).



Δ An alternative IV insulin regimen is to give a continuous intravenous infusion of regular insulin at 0.14units/kg/hour; at this dose, an initial intravenous bolus is not necessary. Copyright ©2006 AmericanDiabetes Association From Diabetes Care Vol 29, Issue 12, 2006. Modifications from Diabetes Care, Vol 32,Issue 7, 2009. Reprinted with permission from the American Diabetes Association.



Protocol for the management of adult patients with HHS



HHS diagnostic criteria: serum glucose >600 mg/dl, arterial pH >7.3, serum bicarbonate>15 mEq/l, and minimal ketonuria and ketonemia. Normal laboratory values vary; checklocal lab normal ranges for all electrolytes. IV: intravenous; SC: subcutaneous.



* After history and physical exam, obtain capillary glucose and serum or urine ketones (nitroprussidemethod). Begin one liter of 0.9 percent NaCl over one hour and draw arterial blood gases, complete bloodcount with differential, urinalysis, serum glucose, BUN, electrolytes, chemistry profile and creatinine levelsSTAT. Obtain electrocardiogram, chest X-ray, and specimens for bacterial cultures, as needed.



Δ An alternative IV insulin regimen is to give a continuous intravenous infusion of regular insulin at 0.14

units/kg per hour; at this dose, an initial intravenous bolus is not necessary. Copyright © 2006 AmericanDiabetes Association From Diabetes Care Vol 29, Issue 12, 2006. Modifications from Diabetes Care Vol 32,Issue 7, 2009. Reprinted with permission from the American Diabetes Association.



Patient data flow sheet



* A: Alert; D: Drowsy; S: Stuporous; C: Comatose.



• D: Deep; S: Shallow; N: Normal.



Δ [2 x Na (meq/L)] + [glucose (mg/dL) ÷ 18].

kitabchi terapie come diabetice

Documents