Control Design Considerations

Hyperglycaemia or high blood sugar (glucose) is prevalent in critical care (Capes et al., 2000, McCowen et al., 2001, Mizock, 2001, van den Berghe et al., 2001) which increases the risks of further complications and mortality (Capes et al., 2000, van den Berghe et al., 2001, Krinsley, 2003) . An analysis summary of OHCA patient, treated with hypothermia shown in this chapter suggests that the main intention of glycaemic control on these cohort during cool and warm is solely to maintain blood glucose level within normal range (4.4 to 6.1 mmol/L) (Plank et al., 2006b), even though the metabolic and physiological conditions are still unstable. This is obvious since consistent insulin dosage is given to the patients throughout the first 2 days of treatment, while modulating nutrient ensures patients glucose needs to support metabolic activities. As a results, majority of blood glucose levels (Table 8.3) are recorded at moderate level (6.1 to 8.0 mmol/L), except for block 1 (0-6 hours).

The success in maintaining blood glucose level within 6.1 to 8.0 mmol/L at this stage is important since the patients had highly insulin resistant and variable during the first 2 days of cool and warm. The difficulties in dealing with these metabolic and physiological backgrounds paid off by maintaining blood glucose at these levels before further decrease to within normal range. Hence, exogenous insulin and nutrition administration approach for this cohort is the key for successful glycemic control. However, the ability of insulin and nutrition modulation method to reduce BG level for this cohort does not reflect the mortality statistics as shown in the Table 3.4. There are about 45.6% OHCA patient who were not survived after undergo the same therapies as mention above. This fact is supported by a study of survival rates from OHCA found that 14.6% of those who had received resuscitation by ambulance staff survived as far as admission to hospital. Of these, 54% died during admission, half of these within the first 24 hours, while 46% survived until discharge from hospital. Of those who were discharged from hospital, 70% were still alive 4 years (Cobbe et al., 1996). This shows that mortality rate is still high even though glycaemia control is implemented and successfully maintaining blood glucose level within 6.1 to 8.0 mmol/L at this stage. The question is, besides hyperglycemia what else causing a cardiac arrest patient to increase its mortality rate?

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Referring to the summary results in the Table 8.1-8.3, it shows that glycaemic variability (%∆BG) decrease is not significant, implying that there is not much different in glycaemic variability between cool or warm for the first 48 hours of treatment (p > 0.05). Since there are about 45.6% OHCA patient who were not survived after undergo the same therapies, the inability of glycemic control to reduce glycemic variability significantly from cool to warm might be the possible cause of cardiac arrest patient’s high mortality rate. This fact is consistent with similar studies by Krinsley (Krinsley, 2009), who have showed that increased glycaemic variability is associated with mortality in critically ill patients. Additionally, the event of hypoglycaemia (BG < 2.22 mmol/L) is potentially increased during rewarming (Lee et al., 2013), which is also contributed to higher risk of death (Finfer et al., 2012).

Thus, even though the glycaemic control scheme implemented on these cohort has shown successful in maintaining blood glucose level within 6.1 to 8.0 mmol/L throughout the treatment from cool to warm, but the fact that only 54.4% survive from this method has ruined its reputation. This method is unable to decrease glycemic variability significantly as mentioned above. Hence, different glycemic control approach and settings should be proposed in order to overcome the problems posed by this cohort.

In order to develop suitable glycaemic controller for OHCA patients, treated with hypothermia, the design should consider several problems identified from the above analysis:

i) Very low metabolic activities, but high glycaemic level at initial (cool period),

which demand too much insulin given during cool period

It is not surprised that an OHCA patient, treated with hypothermia will have a very high blood glucose level at the initial of cool period. Hyperglycaemia is dangerous and demand more insulin externally. However, an overdose insulin infusion might increase metabolic variability, which will influence higher glycaemic variability, which may cause hypoglycaemia and associated with mortality. Thus, controller design should consider higher BG target (Moghissi et al., 2009), and gradually BG decrease from cool to warm rather than drastic change. This consideration will affect insulin and nutrition administration to ensure safe and reliable glycaemic control.

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ii) High glycaemic variability due to metabolic variability, which may cause

hypoglycaemia episode and associated with mortality.

The event of hypothermia and the first 24 hours of rewarming is critical for an OHCA patient since metabolic conditions is unstable and highly variable especially at transition period between cool and warm. This may cause hypoglycemia, which is associated with mortality (Egi et al., 2006, Bagshaw et al., 2009, Krinsley, 2009). It was notable that modulating both insulin and nutrition inputs may achieve good control with lesser insulin and reduces hypoglycemic risk. Thus, controllers with the ability to adapt patient-specific metabolic conditions and forecast possible future parameter values such as blood glucose should be able to provide better modulation of insulin and nutrition inputs.

However, the unique metabolic evolution and variability found in OHCA cohort during the cool-warm transition period between 18 – 30 hours (Sah Pri et al., 2014) suggested that either higher BG targets (Moghissi et al., 2009) , and/or adding nutritional intake (Suhaimi et al., 2010) must be considered, in addition to patient-specific adaptive glycaemia control.

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