Background: The increasingly recognized prognostic impact of the strong ion gap in critical illness is in contrast to its largely unknown chemical nature. Experimental and clinical evidence suggest that acute phase proteins might account for elevation of the strong ion gap. The hypothesis of this investigation was that acute phase proteins account for strong ion gap in critically ill patients.
Materials and methods: The charges of the two acute phase proteins C-reactive protein and fibrinogen were estimated by a computer model. Additionally, 142 patients admitted to a medical intensive care unit of a university hospital were studied prospectively during a six month period. Serial daily observations were recorded and classified according to the systemic inflammatory state. The acute phase proteins C-reactive protein and fibrinogen were measured and the strong ion gap was calculated from the measured acid-base variables.
Results: The approximated mean charges of C-reactive protein and fibrinogen at a pH of 7.4 are -4.0 and -13.6 per molecule, respectively. Therefore, their negative charge is too small to explain the elevated strong ion gap even during a substantial increase of C-reactive protein and fibrinogen due to an acute-phase reaction. Moreover, C-reactive protein did not correlate with the strong ion gap when partialized for creatinine (R = 0.02, P = 0.567). Fibrinogen did not correlate with the strong ion gap. Creatinine correlated with the strong ion gap (R = 0.42, P < 0.001). Neither systemic inflammatory state nor increasing C-reactive protein levels were associated with an increasing strong ion gap.
Conclusion: Acute phase proteins do not account for an elevated strong ion gap in critically ill patients.