Strong Ion Gap as Prognostic Indicator for Adult Patients Admitted With Shock to the Intensive Care Units
Condition: Shock
MeSH terms: Shock
Study type: Observational

Summary: 
      This study evaluates if strong ion gap on admission or 24 hours after admission to critical
      care unit can predict 28 day outcome in patients admitted with shock due to any cause
    

Detailed description: 
      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)
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patient with any form of shock on admission to ICU defined by those who require
        vasopressors or inotropes to maintain MAP > 65mmHg on admission