**1. Introduction**

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Diabetic ketoacidosis (DKA) is considered a predominantly acute type 1 diabetic complica‐ tion, although it may occur in type 2 diabetes as well, particularly in patients who already have a decreased insulin secretion capacity. Stress –induced burst in catecholamine and ACTH secretion in acute myocardial infarction (AMI) promotes release of free fatty acids and their hepatic and muscular tissue utilization. The impairment in insulin-mediated intra‐ cellular glucose influx owing to the absent or insufficient pancreatic insulin secretion is the prerequisite for the occurrence of diabetic ketoacidosis.

The results of the analysis of acid – base disturbances from our previous study [26] per‐ formed in the intensive-care unit in diabetics and non-diabetics suffering acute myocardial infarction are shown in Fig. 1.

Cardiovascular accidents have a marked place among the possible causes of diabetic ketoa‐ cidosis. Cardiovascular morbidity influences the severity and duration of diabetic ketoaci‐ dosis and limits the first and most important step in its treatment- the fluid resuscitation. The resulting hyperosmolarity of body fluids precipitates a pro-thrombotic state, thus aggra‐ vating prognosis in patients with myocardial infarction. The clinical features of hyperglyce‐ mic/hyperosmolar state and diabetic ketoacidosis may overlap and are observed simultaneously (overlap cases) [44].

© 2013 Jovanovic et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Hyperosmolar state and circulatory impairment with decreased oxygen tissue delivery may stimulate lactate production. Although true lactic acidosis occurs rarely, the increased lac‐ tate load may further contribute to the degree of acidosis. In our study, bicarbonate levels was lower (p<0.05) and base deficit were significantly (p<0.01) higher in patients with diabe‐ tes mellitus and acute myocardial infarction comparing to patients with acute myocardial infarction only. Serum lactate was moderately high (Fig.2), but true lactic acidosis defined as serum lactate > 5 mmol/l was registered only in one case with lethal outcome. Moreover, it seems that rise in the serum lactate level between diabetics and non-diabetics with AMI was not accounted for the differences in oxygen delivery, since hemoglobin saturation was much the same in both groups. Therefore, it seems that DKA itself caused further tissue hypo-per‐ fusion and contributed to serum lactate rise. These findings are compatible with the results

Distinctive Characteristics and Specific Management of Diabetic Ketoacidosis in Patients with Acute Myocardial

Infarction, Stroke and Renal Failure http://dx.doi.org/10.5772/ 52390 315

**Figure 2.** Serum lactate in diabetics and non-diabetics suffering AMIThe lactate level in diabetic / AMI patients was higher (4.143 +- 0.914 vs. 3.156 +- 1.12 mmol/L, p<0.01) comparing to patients with acute myocardial infarction only

Finally, the intensive care unit mortality reached 15% among DM/AMI patients comparing

The excess in-hospital mortality of diabetic patients results primarily from an increased inci‐ dence of congestive heart failure, severe coronary artery disease, decreased vasodilatory re‐ serve of epicardial artery resistance, abnormal metabolism of myocardial substrate, diffuse nature of the atherosclerotic disease and hyper-coagulable state. Autonomic neuropathy predisposes patients to ventricular arrhythmia [5]. Also, inhibition of myocardial protective mechanisms against ischaemia / reperfusion injury may contribute to the increased mortali‐ ty rate [46, 58]. The similar mechanisms are operative in developing cerebrovascular injury

of the recent study performed by Cox et al. [14]

to 5% in patients with AMI only.

in diabetics [18].

**Figure 1.** Acid-base disturbances in diabetics and non-diabetics suffering acute myocardial infarction: Almost onethird of diabetic patients with acute myocardial infarction had un-compensated metabolic acidosis defined as pH< 35, HCO3- < 22mmol/L. Although acidosis was mild in most of the cases at least third of these patients had criteria for true diabetic ketoacidosis (pH<30, HCO3- <15mmol/L). Additional 30% had a compensated metabolic acidosis with normal pH and mild to moderately decreased bicarbonate level. The pH was normalized at a price of the increased respiratory effort to lower the PaCO2 which may lead to respiratory muscle fatigue.

Additional risk factors for development of hyperosmolarity include the presence of conges‐ tive heart failure, impaired thirst, limited access to water (especially in patients with demen‐ tia or who are bed bound), older age, and poor kidney function. Table 1 depicts the significant correlations of pH values and certain clinical and biochemical parameters in dia‐ betics suffering AMI.


**Table 1.** Significant (p<0.05 and less) correlations between serum pH and clinical and biochemical parameters in diabetics suffering AMIAs expected, serum pH correlated with glycemic control, but also with clinical and biochemical parameters that were related to tissue hypo-perfusion (incidence of heart failure and rhythm/conduction disturbances, haemoglobin oxygen saturation, serum lactate) and to infarct size and stress-hormone release (e.g. serum creatinine – kinase and plasma noradrenaline values)

Hyperosmolar state and circulatory impairment with decreased oxygen tissue delivery may stimulate lactate production. Although true lactic acidosis occurs rarely, the increased lac‐ tate load may further contribute to the degree of acidosis. In our study, bicarbonate levels was lower (p<0.05) and base deficit were significantly (p<0.01) higher in patients with diabe‐ tes mellitus and acute myocardial infarction comparing to patients with acute myocardial infarction only. Serum lactate was moderately high (Fig.2), but true lactic acidosis defined as serum lactate > 5 mmol/l was registered only in one case with lethal outcome. Moreover, it seems that rise in the serum lactate level between diabetics and non-diabetics with AMI was not accounted for the differences in oxygen delivery, since hemoglobin saturation was much the same in both groups. Therefore, it seems that DKA itself caused further tissue hypo-per‐ fusion and contributed to serum lactate rise. These findings are compatible with the results of the recent study performed by Cox et al. [14]

**Figure 1.** Acid-base disturbances in diabetics and non-diabetics suffering acute myocardial infarction: Almost onethird of diabetic patients with acute myocardial infarction had un-compensated metabolic acidosis defined as pH< 35, HCO3- < 22mmol/L. Although acidosis was mild in most of the cases at least third of these patients had criteria for true diabetic ketoacidosis (pH<30, HCO3- <15mmol/L). Additional 30% had a compensated metabolic acidosis with normal pH and mild to moderately decreased bicarbonate level. The pH was normalized at a price of the increased

Additional risk factors for development of hyperosmolarity include the presence of conges‐ tive heart failure, impaired thirst, limited access to water (especially in patients with demen‐ tia or who are bed bound), older age, and poor kidney function. Table 1 depicts the significant correlations of pH values and certain clinical and biochemical parameters in dia‐

**Table 1.** Significant (p<0.05 and less) correlations between serum pH and clinical and biochemical parameters in diabetics suffering AMIAs expected, serum pH correlated with glycemic control, but also with clinical and biochemical

parameters that were related to tissue hypo-perfusion (incidence of heart failure and rhythm/conduction disturbances, haemoglobin oxygen saturation, serum lactate) and to infarct size and stress-hormone release (e.g.

serum creatinine – kinase and plasma noradrenaline values)

**Spearman's correlation coefficients ρ**

pH

respiratory effort to lower the PaCO2 which may lead to respiratory muscle fatigue.

**Blood glucose** -0.71 **Blood ketones** -0.72 **Anion gap** -0.77 **Noradrenaline** -0.54 **Heart failure** -0.41 **Rhythm / Conduction disturbances** -0.5 **SaO2** 0.68 **CK** -0.62 **Serum lactate** -0.54

betics suffering AMI.

314 Type 1 Diabetes

**Figure 2.** Serum lactate in diabetics and non-diabetics suffering AMIThe lactate level in diabetic / AMI patients was higher (4.143 +- 0.914 vs. 3.156 +- 1.12 mmol/L, p<0.01) comparing to patients with acute myocardial infarction only

Finally, the intensive care unit mortality reached 15% among DM/AMI patients comparing to 5% in patients with AMI only.

The excess in-hospital mortality of diabetic patients results primarily from an increased inci‐ dence of congestive heart failure, severe coronary artery disease, decreased vasodilatory re‐ serve of epicardial artery resistance, abnormal metabolism of myocardial substrate, diffuse nature of the atherosclerotic disease and hyper-coagulable state. Autonomic neuropathy predisposes patients to ventricular arrhythmia [5]. Also, inhibition of myocardial protective mechanisms against ischaemia / reperfusion injury may contribute to the increased mortali‐ ty rate [46, 58]. The similar mechanisms are operative in developing cerebrovascular injury in diabetics [18].

Since volume repletion must be done cautiously and gradually, its therapeutic reach in dia‐ betic ketoacidosis is limited. Intravenous insulin remains the keystone in treatment of dia‐

Distinctive Characteristics and Specific Management of Diabetic Ketoacidosis in Patients with Acute Myocardial

Infarction, Stroke and Renal Failure http://dx.doi.org/10.5772/ 52390 317

Potassium levels must be monitored continuously and corrected as need occurs. If the potas‐ sium level is less than 3.3 mEq per L (3.3 mmol per L), potassium replacement should be given immediately and insulin should be started only after the potassium level is above 3.3

Bicarbonate therapy is not recommended unless pH falls to critically low levels (<7.0). Even

Phosphate replacement is done only if the patient's serum phosphate level is below normal.

A serum deficit of about 1 mmol per L of magnesium usually exists. Severe magnesium defi‐ ciency may lead to cardiac dysrhythmias. Magnesium level should be monitored, especially in patients who receive diuretics and low levels should be corrected in order to avoid this

In summary, acute myocardial infarction may precipitate diabetic ketoacidosis. Heart failure following infarction reduces patients' capacity for volume resuscitation, so clinical features of hyperglycemic hyperosmolar state and diabetic ketoacidosis may overlap and are ob‐ served simultaneously. Additional risk factors for development of hyperosmolarity include the presence of congestive heart failure, impaired thirst, limited access to water, older age,

When acidosis is severe, i.e. pH is less than 7.2, the H+ ions have a direct cardiac depres‐ sant action. Another consequence of tissue hypoperfusion resulting both from impaired myocardial output and increased osmolality as well as counter-regulatory hormone meta‐ bolic effects is increased lactate production. Increased lactate production may aggravate

Diabetic acidosis itself may be the precipitating event for the occurrence of a true myocar‐ dial necrosis. Also, the ECG changes in hyperkalemia in DKA can mimic acute anteroseptal myocardial infarction. Moreover, a bio-marker elevation was also noted, without further evidence of a true myocardial infarction. Knowing that "silent" myocardial infarction occurs with higher incidence among diabetics, the differential diagnosis between myocardial ne‐

Since volume repletion must be done cautiously and gradually, its therapeutic reach in dia‐ betic ketoacidosis is limited. Intravenous insulin remains the keystone in treatment of dia‐ betics with AMI, yet their recovery from ketoacidosis may be prolonged. Potassium levels must be monitored continuously and corrected as need occurs. Phosphate replacement is needed occasionally. Bicarbonate therapy is not recommended unless pH falls to critically

betics with AMI, yet their recovery from ketoacidosis may be prolonged.

mEq per L. Phosphate replacement is needed occasionally.

Excessive replacement can lead to hypocalcemia.

and other complications of hypomagnesaemia.

crosis and hypokalemic disturbances may be difficult.

and poor kidney function.

existing acidosis.

low levels (<7.0).

then, positive effects of bicarbonate therapy remain questionable.

**Figure 3.** Haemoglobin saturation (SaO2) in diabetics and non-diabetics suffering AMI and in control groupAlthough SaO2 was significantly depressed in all patients suffering AMI comparing to control group subjects, there was no sig‐ nificant difference between diabetics and non-diabetics with AMI.

Diabetic acidosis itself may be the precipitating event for the occurrence of serious arrhyth‐ mia, pulmonary edema or even acute myocardial infraction [22]. When acidosis is severe, i.e. pH is less than 7.2 the H+ ions have a direct cardiac depressant action. They cause negative inotropy, bradycardia, reduced cardiac output, peripheral vasodilatation and severe shock. Sometimes, a bio-marker elevation is also noted, without further evidence of a true myocar‐ dial infarction [42].

Potassium deficit is one of the most important of electrolyte imbalances seen in DKA, as it can lead to fatal arrhythmia, especially when the serum potassium level is < 3 mmol/L. On the other hand iatrogenic or spontaneously occurring hyperkalemia may lead to ventricular tachycardia or fibrillation, intra-ventricular conduction defects, sine wave, slow ventricular escape rhythm or ventricular stand. Hyperkalemia can also induce a current of injury called 'dialyzable current of injury', which can cause ST-segment elevation and thus be mistaken for acute infarction. [7, 6)].

Pseudo-infarction presents a unique danger for the clinician treating these critically ill pa‐ tients. While the mechanism of these and other temporary electrocardiographic changes in diabetic ketoacidosis remains unclear, appreciation of their transient nature is essential if misdiagnosis of myocardial infarction and possible inappropriate delay in intravenous fluid administration are to be avoided [21]. However a true myocardial necrosis was also report‐ ed with the DKA as the precipitating factor [50], which further complicates the management and the outcome of these patients.

A pulmonary edema in the absence of left ventricular failure has also been reported in DKA and may be a variant of adult respiratory distress syndrome (ARDS). The aetiology may be pulmonary vascular microangiopathy seen in diabetics. Vigorous fluid therapy can precipi‐ tate this condition.

Since volume repletion must be done cautiously and gradually, its therapeutic reach in dia‐ betic ketoacidosis is limited. Intravenous insulin remains the keystone in treatment of dia‐ betics with AMI, yet their recovery from ketoacidosis may be prolonged.

Potassium levels must be monitored continuously and corrected as need occurs. If the potas‐ sium level is less than 3.3 mEq per L (3.3 mmol per L), potassium replacement should be given immediately and insulin should be started only after the potassium level is above 3.3 mEq per L. Phosphate replacement is needed occasionally.

Bicarbonate therapy is not recommended unless pH falls to critically low levels (<7.0). Even then, positive effects of bicarbonate therapy remain questionable.

Phosphate replacement is done only if the patient's serum phosphate level is below normal. Excessive replacement can lead to hypocalcemia.

A serum deficit of about 1 mmol per L of magnesium usually exists. Severe magnesium defi‐ ciency may lead to cardiac dysrhythmias. Magnesium level should be monitored, especially in patients who receive diuretics and low levels should be corrected in order to avoid this and other complications of hypomagnesaemia.

**Figure 3.** Haemoglobin saturation (SaO2) in diabetics and non-diabetics suffering AMI and in control groupAlthough SaO2 was significantly depressed in all patients suffering AMI comparing to control group subjects, there was no sig‐

Diabetic acidosis itself may be the precipitating event for the occurrence of serious arrhyth‐ mia, pulmonary edema or even acute myocardial infraction [22]. When acidosis is severe, i.e. pH is less than 7.2 the H+ ions have a direct cardiac depressant action. They cause negative inotropy, bradycardia, reduced cardiac output, peripheral vasodilatation and severe shock. Sometimes, a bio-marker elevation is also noted, without further evidence of a true myocar‐

Potassium deficit is one of the most important of electrolyte imbalances seen in DKA, as it can lead to fatal arrhythmia, especially when the serum potassium level is < 3 mmol/L. On the other hand iatrogenic or spontaneously occurring hyperkalemia may lead to ventricular tachycardia or fibrillation, intra-ventricular conduction defects, sine wave, slow ventricular escape rhythm or ventricular stand. Hyperkalemia can also induce a current of injury called 'dialyzable current of injury', which can cause ST-segment elevation and thus be mistaken

Pseudo-infarction presents a unique danger for the clinician treating these critically ill pa‐ tients. While the mechanism of these and other temporary electrocardiographic changes in diabetic ketoacidosis remains unclear, appreciation of their transient nature is essential if misdiagnosis of myocardial infarction and possible inappropriate delay in intravenous fluid administration are to be avoided [21]. However a true myocardial necrosis was also report‐ ed with the DKA as the precipitating factor [50], which further complicates the management

A pulmonary edema in the absence of left ventricular failure has also been reported in DKA and may be a variant of adult respiratory distress syndrome (ARDS). The aetiology may be pulmonary vascular microangiopathy seen in diabetics. Vigorous fluid therapy can precipi‐

nificant difference between diabetics and non-diabetics with AMI.

dial infarction [42].

316 Type 1 Diabetes

for acute infarction. [7, 6)].

and the outcome of these patients.

tate this condition.

In summary, acute myocardial infarction may precipitate diabetic ketoacidosis. Heart failure following infarction reduces patients' capacity for volume resuscitation, so clinical features of hyperglycemic hyperosmolar state and diabetic ketoacidosis may overlap and are ob‐ served simultaneously. Additional risk factors for development of hyperosmolarity include the presence of congestive heart failure, impaired thirst, limited access to water, older age, and poor kidney function.

When acidosis is severe, i.e. pH is less than 7.2, the H+ ions have a direct cardiac depres‐ sant action. Another consequence of tissue hypoperfusion resulting both from impaired myocardial output and increased osmolality as well as counter-regulatory hormone meta‐ bolic effects is increased lactate production. Increased lactate production may aggravate existing acidosis.

Diabetic acidosis itself may be the precipitating event for the occurrence of a true myocar‐ dial necrosis. Also, the ECG changes in hyperkalemia in DKA can mimic acute anteroseptal myocardial infarction. Moreover, a bio-marker elevation was also noted, without further evidence of a true myocardial infarction. Knowing that "silent" myocardial infarction occurs with higher incidence among diabetics, the differential diagnosis between myocardial ne‐ crosis and hypokalemic disturbances may be difficult.

Since volume repletion must be done cautiously and gradually, its therapeutic reach in dia‐ betic ketoacidosis is limited. Intravenous insulin remains the keystone in treatment of dia‐ betics with AMI, yet their recovery from ketoacidosis may be prolonged. Potassium levels must be monitored continuously and corrected as need occurs. Phosphate replacement is needed occasionally. Bicarbonate therapy is not recommended unless pH falls to critically low levels (<7.0).
