Rajiv Gandhi University of Health Sciences



6. BRIEF RESUME OF THE INTENDED WORK

6.1 NEED FOR STUDY

The care of a critically ill patient is very important for a physician. Prediction of outcome of a critically ill patient is as important as patients care because the goal of resuscitation to cure and complete resolution of the underlying illness is not possible in every case and the outcome of treatment may vary from each patient and it’s the duty of the treating physician to answer the questions posed by the patients attendants. At times it is very challenging task for the physician to explain about the disease and its prognosis. Although various clinical parameters, laboratory investigations and imaging modalities help in predicting the outcome of the disease, none of them alone has helped as a prognosticating tool. For this reason various scoring systems (like APACHE II & III ,SAPS II & III) were designed to provide a morbidity score for a patient admitted in medical emergency ward or medical ICU. Calculating a morbidity score of a patient is a complex task and is time consuming or may even require a calculator for a physician. Hence there is need for a simplified approach in predicting the morbidity and mortality of a critically ill patient.

Several studies have convincingly shown that various biochemical changes occur in an acutely ill patients and that includes changes in the blood glucose levels and thyroid hormonal changes. Changes in the blood glucose levels may be in the form of hyperglycaemia or hypoglycaemia and both may have an influence on the disease severity, duration of the hospital stay, in-hospital morbidity and mortality. Transient hyperglycaemia, even without a diagnosis of established diabetes, occurs frequently in critically ill hospitalized patients. Aggressive glycaemic control may reduce mortality in this population. Hyperglycaemia from any cause is associated with worse outcomes in proportion to the elevations in blood glucose (BG) levels.1

Similarly during critical illness, changes in circulating hormone levels are a common phenomenon. These alterations are correlated with the severity of morbidity and the outcomes of patients in ICUs. Thyroid hormones play a key role in the maintenance of body growth and in modulating metabolism and the immune system. Various studies have found that thyroid dysfunction is associated with the mortality of patients admitted to the ICU and medical emergency ward. Subsequent studies confirmed the association between NTIS and adverse outcomes in patients with sepsis, multiple trauma, acute respiratory distress syndrome, respiratory failure and mechanical ventilation, as well as in ICU and medical emergency ward patients admitted for other causes.

Hence, thyroid hormone levels and serial blood glucose estimation in an acutely ill patient admitted in medical emergency ward and ICUs can be used as an important tool in predicting the outcome of a patient.

6.2 REVIEW OF LITERATURE

Non-thyroidal illness syndrome (NTIS or euthyroid sick syndrome) is a complex endocrine condition that may occur in critically ill patients. It is associated with significant deterioration of prognosis. NTIS is characterised by three components that may occur single or in combination: central hypothyroidism (transient thyrotropic insufficiency), impaired protein binding of thyroid hormones and reduced formation of T3 with simultaneously increased conversion to rT3 (low-T3-syndrome).2

Although all cells are exposed to essentially the same circulating concentrations of thyroid hormone, only certain cells express iodothyronine deiodinases, which are enzymes that modulate local thyroid hormone signaling by the removal of specific iodine moieties from T4 or T3. Type I and type II iodothyronine deiodinases (D1 and D2) activate T4 to T3, whereas type III iodothyronine deiodinase (D3) is the main inactivator of both T4 and T3.3

 Low-T3 syndrome (also known as the euthyroid sick syndrome or non-thyroidal illness) includes low serum levels of T3 and high levels of the inactive metabolite reverse T3 (rT3). Life-threatening trauma and critical illness are associated with the low-T3 syndrome. Serum T3 levels fall in proportion to the severity of illness and, in critically ill patients, this is followed by a decrease in serum T4 and serum TSH levels. The low-T3 syndrome is common, with an incidence of up to 75% in hospitalized patients.4

Peeters RP, et al. studied that in 451 critically ill patients who received intensive care for more than 5 days, serum thyroid parameters were determined on day 1, 5, 15, and last day (LD).  On day 1, rT3 was higher and T3/rT3 was lower in non-survivors as compared with survivors. In critically ill patients who required more than 5 d of intensive care, rT3 and T3/rT3 were already prognostic for survival on day 1. On day 5, T4, T3, but also TSH levels are higher in patients who will survive. Serum rT3 and T3/rT3 were correlated with postmortem tissue deiodinase activities.5

Zarger, et al studied the prevalence and pattern of alterations in thyroid hormone levels in various non-thyroidal illnesses in Soura, Srinagar. They analyzed circulating T3, T4, TSH in 382 patients with non-thyroidal illness (285 acute and 97 acute on chronic) and correlated the alterations with severity and outcome of the non-thyroidal disorder. T3 (mean +/- SEM) was significantly reduced at the onset of illness, in both acute and chronic patient groups (1.61 +/- 0.05 nmol/l) compared to that in the controls (3.17 +/- 0.06 nmol/l). In spite of clinical improvement in most instances, T3 continued to remain low in the 3rd week (1.49 +/- 0.11 nmol/ l) but increased (2.14 +/- 0.09 nmol/l) in 24th week. Low T3 was found in 93 (32.6%) cases with acute illness in 20 (20.6%) cases with chronic illness. A combination of low T3 and T4 was found in 35 (12.3%) of cases with acute and 15 (15.5%) with chronic illness. Severity of illness correlated with decrease in T3 (r=0.58) and T4 (r=0.38). A low T3 and T4 with low or undetectable TSH were associated with increased mortality.6

Feilong Wang, et al screened a total of 480 consecutive patients without known thyroid diseases for eligibility and followed up during their ICU stay and collected each patient's baseline characteristics, including the Acute Physiology and Chronic Health Evaluation II (APACHE II) score and thyroid hormone, N-terminal pro-brain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) levels. The primary outcome was ICU mortality. Potential predictors were analyzed for possible association with outcomes. They also evaluated the ability of thyroid hormones together with APACHE II score to predict ICU mortality by calculation of net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indices. In this large-scale study of unselected ICU patients, they found that FT3 was the most powerful and only independent predictor of ICU mortality among the complete thyroid hormone indicators. FT3 had greater ability than NT-proBNP or CRP to predict primary outcomes. Addition of FT3 levels to APACHE II scores significantly improved the ability to predict ICU mortality, as demonstrated by IDI and NRI. The FT3 levels were negatively correlated with CRP and NT-proBNP levels.7

In hospitalized patients, hyperglycaemia may occur because of a combination of increased production of catabolic hormones, increased hepatic gluconeogenesis, and resistance to the peripheral and hepatic actions of insulin. Excessive administration of glucose can also give rise to hyperglycaemia. Stress hyperglycaemia, compared with the hyperglycaemia of diabetes, appears to confer a higher risk of mortality, possibly because of differences in the pathophysiology and the natural history of these two states of hyperglycaemia. In a retrospective observational study for a high A1C cohort, however, survivors showed a trend toward higher glycaemia; whereas in a lower A1C cohort, survivors showed a trend toward lower glycaemia. This study generated a hypothesis that glucose levels that are considered safe and desirable in patients without diabetes might be undesirable and too low for patients with diabetes who have chronic hyperglycemia.8

Finney SJ, et al conducted a single-centre, prospective, observational study of 531 patients (median age, 64 years) newly admitted over the first 6 months of 2002 to an adult intensive care unit (ICU) in a UK national referral centre for cardio-respiratory surgery and medicine. The primary end point was intensive care unit (ICU) mortality. Secondary end points were hospital mortality, ICU and hospital length of stay, and predicted threshold glucose level associated with risk of death. Increased insulin administration is positively associated with death in the ICU regardless of the prevailing blood glucose level. Thus, control of glucose levels rather than of absolute levels of exogenous insulin appears to account for the mortality benefit associated with intensive insulin therapy demonstrated by others.9

Al-Tarifi A, et al. carried out a study in a single centre to assess the effect of intensive insulin therapy [IIT; target BG 4.4-6.1 mmol/L (80-110 mg/dL)] versus conventional insulin therapy [CIT; target BG 10-11.1 mmol/L (180-200 mg/dL)] in a medical/surgical ICU. All patients were divided into six groups based on the mean daily BG levels. A logistic regression model was used to determine the association of BG and ICU mortality. Among six groups, the ICU mortality was least in patients with BG ................
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