Strong Ion Gap as Prognostic Indicator for Adult Patients Admitted With Shock to the Intensive Care Units

Metabolic acidosis is frequently found in patients with shock. Traditional methods of evaluating acid-base status can underestimate and even miss complex acid-base disorders particularly in the setting of hypoalbuminemia, hypo/hypernatraemia and hypo/hyperchloraemia .An alternative approach to acid-base balance, based on chemical and physical principles, and was proposed by Peter Stewart more than 30 years ago. Later in 1992 Figge and Fencl modified the strong ion difference, which corresponds with the net charge balance of all strong ions present in a given solution (the ''Fencl-Stewart'' approach). The strong ion gap (SIG) which corresponds with the difference between the apparent strong ion difference and the effective strong ion difference was proposed by Kellum. Compared to the Fencl- Stewart approach SIG has more accuracy and bedside practicality.

As the SIG is calculated from all known charged components of blood, it is considered the gold standard for the quantification of unmeasured anions. In contrast, the traditional anion gap calculation only factors in sodium, potassium, chloride and bicarbonate. In healthy humans, the SIG equals zero. In critically ill patients, a high SIG, defined as >2mEq/L, indicates the accumulation of unmeasured anions in blood as a cause of acidosis. The unmeasured anions include lactate, ketoacids, uraemic acids and toxins like ethylene glycol and methanol. Studies found that a higher SIG on admission to intensive care unit is associated with poorer outcomes, and has a role in prediction of outcome in septic patients. However this finding is not consistent.

In addition it was found that there is a significant difference in the threshold for SIG value associated with higher mortality. The abnormal SIG value in American studies are described around 5 mEq/l . However studies from Europe and Australia reported higher values in the range of 8-13 mEq/l. It is speculated that this difference is due to exogenous sources of unmeasured ions from gelatin based intravenous fluids used for resuscitation. Interestingly studies using gelatine- based fluids also failed to show a correlation between SIG and mortality. SIG values have not been published in critically ill Asian adult patients admitted to the Intensive Care Units (ICU) as yet. We aim to find the SIG for these patients in the hope that it will be useful for predicting outcome. Our hypothesis is that SIG is an independent predictor of outcomes in adult patient with shock.

We propose to conduct this prospective observational study in the surgical and medical ICUs of 2 hospitals in Singapore. (Singapore General Hospital and Changi General Hospital) We aim to enrol 112 of you admitted to the ICU with shock of any etiology. Shock is defined as persistence of arterial hypotension despite adequate volume resuscitation. Hypotension is defined as systolic pressure \<90mmHg, Mean arterial pressure (MAP)\<70 mmHg or drop in SBP >40 mmHg from baseline. 30ml/kg of fluid is considered as the threshold for adequate volume resuscitation.

The methodology of this observational study was approved by Sing health Institutional review Board, Singapore. We will include you if you have persistent hypotension despite adequate fluid resuscitation as defined above or if you require vasopressors or inotropes to maintain MAP above 65mmHg on admission.

We will exclude the conditions with acid base disturbance which are not amenable to using standard supportive care such as pre-existing chronic kidney disease stage 3 and above ( defined as estimated GFR\<60 ml/min/1.73m2 ) and chronic liver failure.

Blood samples will be taken from indwelling intra-arterial catheters on admission and 24 hours after admission. Blood samples will be analyzed in the respective hospital laboratory for Arterial Blood Gas(ABG) analysis, electrolytes albumin and lactate levels in order to calculate the SIG.

All of you included in the study will be managed by the same group of critical care physician in accordance with pre-existing protocols in both ICUs to ensure that there will not be any major discrepancies among patients in terms of organ support and therapy. Haemodynamic support will be applied to reverse the hypotension and to correct peripheral perfusion abnormalities after optimal resuscitation. IV noradrenaline is the vasopressor of first choice followed by vasopressin and adrenaline.

Data collection-

Fluid resuscitation before ICU admission, SOFA and APACHE II score 24 hours after the admission, requirement for vasopressors, mechanical ventilation renal replacement therapy(RRT) ,duration of ICU stay, number of ventilator days, duration of vasopressor support, number of vasopressors used and the duration of RRT, 28 day outcome will be collected.

Calculation of SIG-

SIG will be calculated according to the following formulae;

1. SIG= SIDapp - SIDeff

   (SIDapp -Strong ion difference apparent; SIDeff - Strong ion difference effective)

2. SIDapp = ( Na++K++Ca2++Mg2+) - (Cl-+Lactate-)

   ( all concentrations in mEq/l)

3. SIDeff = 2.46 x 10-8 x Pco2/ 10-pH + [albumin] x ( 0.123xpH - 0.631) +[PO43-] x (0.309xpH -0.469)

(PCO2 is measured in mm Hg, albumin in g/L, and phosphate in mmol/L)