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Ketoacidosis: Treatment, Prevention & Complications

Written by Carlos Tello, PhD (Molecular Biology) | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Puya Yazdi
Medically reviewed by
Puya Yazdi, MD | Written by Carlos Tello, PhD (Molecular Biology) | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:

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Characterized by high glucose, ketone, and acid levels in the blood, ketoacidosis is a life-threatening condition that mainly occurs as a complication of poorly managed diabetes. Fortunately, it can be effectively treated with fluids, insulin, and ion therapy. Keep on reading to learn more about this condition, how to prevent and treat it, and what complications may arise.

What Is Ketoacidosis?

Ketoacidosis is a medical condition that is mainly characterized by the 3 following abnormalities [1]:

  • High blood concentration of glucose
  • High blood and urine concentration of ketone bodies
  • High blood acid levels

The most common type of ketoacidosis occurs as a complication of diabetes. In diabetic ketoacidosis, the low level of insulin and the excess of its opposing hormones cause the buildup of glucose in the blood and the breakdown of fatty molecules into ketone bodies in the liver [2].

Standard Treatment

Contact your doctor immediately if you have high blood ketone levels or experience ketoacidosis symptoms. Follow your treatment plan and never change or discontinue it without consulting your doctor beforehand.

The successful treatment of ketoacidosis depends on adequately [3]:

  • Providing fluids to restore blood circulation and correct dehydration
  • Giving insulin to stop the generation of ketone bodies
  • Replacing electrolytes
  • Treating any causes
  • Monitoring complications during therapy

1) Fluid Therapy & Electrolyte Replacement

All people with ketoacidosis have water and sodium deficits [4, 5].

Fluid therapy has the following positive effects [6]:

  • It increases the amount of fluids inside and outside the vessels, increasing volume, which improves blood circulation into the kidneys
  • It increases glucose elimination in the urine
  • It reduces the concentration of insulin-opposing hormones

The goal of this therapy is to replace 50% of the total water loss during the first 8 hours and the rest over the next 16 to 24 hours [7].

Fluid replacement is carried out by infusing a salt water solution containing both fluids and electrolytes to restore hydration and electrolyte balance [8, 9].

Sodium Electrolytes

In people with diabetic ketoacidosis, blood sodium deficits can occur. High blood glucose levels cause a decrease in sodium levels, and sodium therapy can be considered if it gets too low [10].

Potassium Electrolytes

People with ketoacidosis may have low blood potassium levels, especially if they have been vomiting or taking diuretics [11].

Generally, potassium is infused to ensure that its blood concentration is within the normal range (4-5 mmol/l) [12].

In people with severe potassium deficits, it is important to monitor heart function [13].

One of the first steps to treating ketoacidosis is to reverse dehydration by administering fluids. This should be done under careful medical surpervision.

2) Insulin Therapy

Ketoacidosis was fatal before the discovery of insulin in the 1920s. Thanks to insulin therapy, its death rate has been reduced to less than 1% in developed countries [14].

Some people with diabetic ketoacidosis have potassium deficits. Because insulin therapy may further decrease the blood levels of this ion, it is important to make sure that its concentration is not too low (at least 3.3 mmol/l) before starting the treatment [1].

In an old trial on 48 people with diabetic ketoacidosis, low doses of insulin were as efficient as high-dose therapies at reducing blood glucose levels. The low-dose treatment showed a lower risk of glucose and potassium deficits [15].

Another trial on 40 people found that insulin injections into the veins and muscles are equally safe, but the former acts faster to reduce glucose and ketone levels [16].

Insulin (initial dose of 0.1 U per kg and hour) is infused during the treatment until the blood glucose concentration reaches a normal level (250 mg/dl) [17].

At this point, the insulin dose may be reduced by half and supplemented with glucose (5%). The treatment is continued until acidosis is resolved (blood bicarbonate level over 18 mmol/l and pH exceeding 7.3) [1].

Low insulin is a major part of the mechanism of development of ketoacidosis. Insulin treatment is therefore an important part of recovering from this condition.

3) Treatment of Causes

Work with your doctor to immediately identify and appropriately treat any underlying conditions that may be causing you ketoacidosis to facilitate the management process [6].

It’s important to recognize other factors that might be masked by the symptoms of diabetic ketoacidosis, such as [18]:

  • Heart attack
  • Stomach and bowel bleeding
  • Pancreatic inflammation
  • Stroke
  • Blockage of lung vessels
  • Trauma

Experimental Treatment

The following therapies are currently undergoing clinical study and are not part of most standard treatments, except at the occasional discretion of the doctor or emergency nurse treating the patient. Do not under any circumstances attempt to treat yourself with these techniques. If you believe that you have or are developing ketoacidosis, seek medical attention immediately.

4) Bicarbonate Therapy

The use of bicarbonate to correct acidosis remains controversial. Several studies have failed to demonstrate any benefits of its use except in extreme acidosis (pH below 6.9) [13].

In 2 clinical trials on 60 people with severe diabetic ketoacidosis, bicarbonate treatment failed to resolve the symptoms of blood acidosis and excessive glucose levels [19, 20].

In 2 additional trials on 33 people, bicarbonate therapy took longer to reduce blood ketone bodies and lactate [21, 22].

A systematic review of 44 articles did not find any effects of bicarbonate therapy on ketoacidosis symptoms. Plus, its intake was associated with an increased risk of fluid buildup in the brain [23].

However, it’s important to note that none of these studies included people with a blood pH below 6.9. In this situation, patients may be given bicarbonate to prevent the negative impacts of severe acidosis on the heart, brain, and liver [24].

In extreme acidosis, some researchers have argued for the use of bicarbonate to restore normal pH in the blood. However, some studies have found no benefit to this therapy.

5) Phosphate Therapy

During insulin therapy, the entry of phosphate into the cells decreases its concentration in the blood. Although it occurs very rarely, phosphate deficit in the blood can cause the following complications [25]:

  • Muscle weakness
  • Anemia
  • Poor heart performance
  • Limited oxygen delivery into tissues

A clinical trial on 44 people with diabetic ketoacidosis did not find any beneficial effects of phosphate therapy on treatment duration, insulin dose required, muscle function, glucose levels, health status, or death risk [26].

Additionally, another trial on 30 people found an increased risk of calcium deficit in those treated with phosphate [27].

Therefore, it is only recommended to apply phosphate therapy to patients with very low blood phosphate levels (below 1 mg/dl), or suffering from conditions such as heart failure, anemia, or breathing abnormality [28].

Some patients may develop a phosphate deficit during insulin therapy and may benefit from receiving phosphate therapy. However, clinical studies have found mixed results as to the benefit of such therapy.

6) Magnesium Therapy

Blood magnesium deficits usually occur in people with diabetic ketoacidosis. Symptoms of magnesium deficiency include [10]:

  • Pins and needles
  • Muscle contractions
  • Cramps
  • Agitation
  • Seizures
  • Irregular heart rate

Treatment with magnesium sulfate is an option if the blood magnesium concentration is below normal (0.74 mmol/l) and symptoms are present [18].

Complications

1) Fluid Buildup in the Brain

During the first 24 hours of therapy, 0.5 to 2% of patients experience fluid buildup in the brain. This complication is most frequent in children [29].

The main early signs of this complication are [10]:

  • Headache
  • Confusion
  • Sleepiness
  • Behavioral changes

Other, less frequent symptoms include [10]:

  • Eye swelling
  • High blood pressure
  • High body temperature
  • Increased thirst and diluted urine (diabetes insipidus)

In severe cases, the patient can experience [10]:

  • Seizures
  • Changes in pupils
  • Breathing cessation
  • Slow heart rate

Fluid buildup in the brain is the main cause of death in children with ketoacidosis, accounting for 31% of the deaths associated with this condition and 20% of the overall deaths in diabetic children [30].

Possible causes of fluid buildup as a result of the treatment include [9]:

  • Increased water entry into brain tissues due to ion therapy
  • Entry of electrolytes into brain tissues due to insulin therapy
  • Restoring sodium levels too quickly

The complication can be prevented by [31, 6]:

  • Gradually correcting water and sodium deficits
  • Minimizing glucose loss
  • Adding glucose to therapy fluids once the blood concentration of this sugar has reached normal values (250 mg/dl)
  • Avoiding bicarbonate therapy unless absolutely necessary

Once developed, this complication can be treated with mannitol and hyperventilation [32, 33].

One of the most dangerous potential complications of ketoacidosis is fluid buildup in the brain. This complication accounts for 31% of the deaths associated with ketoacidosis in children.

2) Adult Respiratory Distress Syndrome (ARDS)

Adult respiratory distress syndrome (ARDS) is the buildup of fluid in the lung tissues. ARDS reduces lung function and dramatically decreases oxygen levels in the blood. The mechanisms and treatment of this condition are similar to those for fluid buildup in the brain [34].

3) Hyperchloremic Acidosis

This complication consists of blood acidosis with high chloride and low bicarbonate concentrations [35].

The main mechanisms of hyperchloremic acidosis during ketoacidosis treatment are [36, 37]:

  • Loss of ketone bodies, which are necessary to regenerate bicarbonate
  • Infusion of fluid therapy with high concentrations of chloride
  • Infusion of bicarbonate-free solutions during fluid therapy
  • Sodium bicarbonate entry into the cells during fluid therapy

The acidosis is normally temporary and is not a health concern, except in people with kidney failure [6].

4) Glucose and Potassium Deficits

These complications are the most common ones due to [6]:

  • Excessive insulin intake (glucose deficit)
  • Insulin intake combined with treatment against acidosis (potassium deficit)

Fluid therapy must correct the potassium deficit and 5% glucose must be added as soon as blood glucose levels reach normal values (250 mg/dl) to prevent deficits in this sugar [9].

It is also important not to interrupt insulin therapy too soon to prevent blood sugar levels from rising again [6].

Risk Factors

1) Individual Factors

Two studies on almost 5,000 children associated low birth weight with a higher incidence of diabetic ketoacidosis [38, 39].

In two studies on over 250 people, the second member of the family affected by type 1 diabetes was less likely to present diabetic ketoacidosis due to the increased awareness of this condition by their families [40, 41].

2) Socioeconomic Factors

The frequency of diabetic ketoacidosis is higher in ethnic minority groups. This is usually due to socioeconomic factors like wealth, language barriers, and difficulties in accessing healthcare [42, 43, 44, 45].

In 3 population-based studies on almost 1,700 children, those of parents with lower educational levels had a higher incidence of diabetic ketoacidosis, and vice versa [46, 47, 48].

In 2 studies conducted in the US, the lack of private healthcare insurance increased the risk of children to present diabetic ketoacidosis, since their parents tended to avoid seeking medical care until the condition was severe [43, 49].

Two studies failed to find a negative correlation between family income and ketoacidosis incidence. However, another study on over 700 people showed that children from families with a very low income had an almost 2-fold risk of developing this condition [48, 50, 51].

A study on almost 700 Swedish and Lithuanian children assessed the correlation between the work status of the parents and the child incidence of diabetic ketoacidosis. While this factor was irrelevant in Lithuania, Swedish children with unemployed mothers had an almost 5-fold risk of developing this condition [46].

Diabetic ketoacidosis is more common in people with economic and language barriers to accessing healthcare.

3) Medical Factors

Poor control of blood sugar among diabetic patients is the most important risk factor for the development of ketoacidosis and can be due to [52, 53]:

  • Undetected defects in the insulin pump
  • Lack of education
  • Eating disorders (especially frequent in adolescent girls)
  • Not adhering to diabetes management guidelines (especially frequent in adolescent and elderly patients)
  • Lack of adequate healthcare insurance (in adolescents and adults)
  • Psychological or psychiatric disorders (in adolescents and adults)

Two out of four studies found an association between a delayed diagnosis of type 1 diabetes and an increased risk of the children to develop diabetic ketoacidosis [44, 49, 54, 50].

In turn, 4 studies found a 3-fold increased risk of diabetic ketoacidosis in children who were initially given a wrong diagnosis [49, 50, 55, 56].

Diabetic ketoacidosis was also more frequent if there was a delay of more than 24 hours between diabetes diagnosis and treatment start or if the hospital did not have a structured diabetic team [54, 57].

In 2 out of 3 studies, the incidence of previous infectious illnesses increased the risk of developing diabetic ketoacidosis [58, 59, 60].

In children under 13 years old, high hemoglobin (A1c) levels and high insulin doses were associated with recurrent diabetic ketoacidosis episodes [53].

Poor control of blood sugar is the most common cause of ketoacidosis. This may result from defects in the insulin pump, poor adherence to management guidelines, and lack of adequate healthcare or health insurance.

4) High-Risk Patients

Diabetic ketoacidosis is 3 times more frequent in children under 2 years old, since [61, 62, 48, 49]:

  • Diabetes may remain undiagnosed
  • They are more prone to infections that mask the symptoms
  • Ketosis and acidosis develop faster

Children below this age are also more prone to complications such as fluid buildup in the brain [32].

Pregnant women have an increased risk of developing ketoacidosis since they have [63]:

  • Decreased sensitivity to insulin
  • Increased sensitivity to starvation (accelerated starvation)
  • Frequent nausea and vomiting
  • Increased levels of insulin-opposing hormones
  • Lower bicarbonate levels

Ketoacidosis can severely damage the fetus and must be carefully managed in pregnant women [64].

Older people typically require more insulin to treat ketoacidosis, have a longer length of hospital stay, and higher death rates [65].

In people suffering from a stroke, fluid replenishment is slower. As a result, the effect of insulin may be reduced [66].

People with kidney failure are less efficient at eliminating excess glucose and ketone bodies as well as maintaining their water and ion balances. When treating them against ketoacidosis, it is important to note that these patients are more prone to:

  • Extremely high sugar and ketone levels [67]
  • Excessive potassium levels [68]
  • Fluid overload [69]
  • Changes in blood acid level [70]
  • Blood acidosis with high chloride and low bicarbonate concentrations (hyperchloremic acidosis) [71]

People with a history of heart failure must be carefully monitored because the ion imbalance resulting from ketoacidosis can reduce heart function [72].

Additionally, heart failure stimulates the production of ketone bodies, which can make the ketoacidosis worse [73].

Babies, pregnant women, the elderly, and people with a history of kidney failure, stroke, or heart failure are most likely to develop ketoacidosis.

Prevention & Management

People with diagnosed type 1 diabetes and their social environment (parents, spouses, colleagues) must receive proper education on all the aspects of diabetes care, such as [11]:

  • Importance of adhering to insulin therapy
  • Frequency of insulin use
  • Insulin pump functioning
  • Monitoring of main parameters (blood glucose, urine ketones)
  • Blood glucose goals
  • Sick-day management
  • Use of a liquid diet containing sugars and salts when sick
  • Guidelines for high-risk patients
  • Early symptoms of ketoacidosis
  • When to contact their healthcare providers

Young people with recurrent ketoacidosis episodes must undergo a psychological evaluation to identify disorders that may contribute to it, such as [6]:

  • Depression
  • Eating disorders
  • Sexual or physical abuse

SGLT2 blockers are medications for diabetic patients that lower blood glucose levels. They also reduce insulin blood levels and increase those of glucagon, which can worsen ketoacidosis. High-risk patients should avoid these types of drugs [74, 75].

Because poor adherence to insulin therapy is associated with the active use of drugs such as cocaine and cannabis, rehabilitation might help prevent recurrent diabetic ketoacidosis episodes [76].

In people with type 2 diabetes, a healthy lifestyle (appropriate diet, regular exercise) and weight maintenance help reduce the incidence of ketoacidosis [13].

People with type 1 diabetes can prevent ketoacidosis by carefully following their healthcare provider’s instructions on controlling their blood sugar. Managing other underlying conditions like type 2 diabetes, depression, and eating disorders is also important.

Takeaway

Ketoacidosis is a dangerous condition characterized by high blood sugar, ketone bodies in the blood and urine, and high blood acidity. It is most often caused by diabetes, though infections, alcohol abuse, starvation, salicylate toxicity, or lactation can also cause the condition.

Emergency nurses and doctors treat ketoacidosis by giving fluids to rehydrate and insulin to lower blood sugar, and then treating any underlying conditions that may have caused ketoacidosis to develop. If you think that you have or are developing ketoacidosis, seek medical attention immediately.

Individual health, socioeconomic factors (such as access to healthcare and health insurance), and other factors may contribute to the development of ketoacidosis and to rates of death from this condition. Type 1 diabetes patients are advised to carefully follow their doctor’s instructions to control their blood sugar and prevent ketoacidosis.

Further Reading

About the Author

Carlos Tello

Carlos Tello

PhD (Molecular Biology)
Carlos received his PhD and MS from the Universidad de Sevilla.
Carlos spent 9 years in the laboratory investigating mineral transport in plants. He then started working as a freelancer, mainly in science writing, editing, and consulting. Carlos is passionate about learning the mechanisms behind biological processes and communicating science to both academic and non-academic audiences. He strongly believes that scientific literacy is crucial to maintain a healthy lifestyle and avoid falling for scams.

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