Objective: Chloride is the major plasma anion. There are several methods available for the

determination of serum chloride levels. Unfortunately these methods are sometimes not

available in the urgent setting where values are needed. Here we describe a formula for

estimating plasma chloride levels.

Methods: Fifty-two consecutive patients were enrolled for which serum chloride levels

were estimated using the formula CL-

 = (Na+ + 10 –TBB), and also measured directly through

the colorimetric method. Correlation between the two values was analyzed using Pearson

correlation coefficient and agreement was shown in the Bland-Altman plot.

Results: Comparing the values achieved through estimation and laboratory determination

of plasma chloride revealed a significant correlation (r=0.97). Consistent agreement was

described within -4.8 and +6.6 on the Bland-Altman plot throughout the measurements.

Conclusion: The formula presented here may be a reliable alternative to direct measurement

of serum chloride when direct results are not available

Keywords: Arterial blood gas (ABG), Total buffer base (TBB), Anion gap (AG), Serum chlorid

Reza Hashemi1 , Alireza Majidi2* , Ali Tabatabaey3 , Sadrollah M,

Simorgh Research Repository

Journal of Emergency Practice and TraumaIntroductionChloride is the most important anion associated with so-dium in the extra cellular fluid with a normal concentra-tion ranging from 96 to 106 (1). The complete interpreta-tion of acid-base disorders is impossible without knowing the serum chloride concentration (2). In the process of quantitative acid-base analysis, plasma pH is determined by three independent variables: pCO2, total concentration of nonvolatile weak acids, and the strong ion difference (SID). On the other hand, bicarbonate (HCO3) concentra-tion is considered to be dependent on the SID. It has been suggested that chloride is the major electrolyte determin-ing the SID and thus directly affecting acid-base disorders in the clinical setting (3). Furthermore, the serum chloride level has been associated with rates of mortality in certain groups of patients and has been suggested as a prognostic factor (4,5). Therefore, timely and accurate determination of serum chloride concentration is of great importance for decision-making in the emergency department. Several methods have been described for the measurement of se-rum chloride (6). The coulometric titration method uses electrolysis current to measure ion formation (7), while the ion-selective electrode uses a transducer to convert the activity of the chloride ion into an electrical potential, which can be measured by a voltmeter or pH meter (8). The colorimetric method combines chloride with other elements to form a colored solution and then measures color density to determine chloride concentration (9). A cyclic voltammetry using an Ag electrode has also been described for selective measurement of chloride ions (10). These methods have been described for years and range in their complexity, cost, and accuracy, yet even today mea-surement of serum chloride levels is not available in Ira-nian hospitals as an emergent test 24 hours a day. To over-come this problem here we describe a formula for calcula-tion of serum chloride levels using information available in the emergency setting through analysis of blood gases.MethodsIn this study the authors developed a practical formula based on known acid-base physiology. Then we predicted Cl– concentration in 52 consecutive patients in the emer-gency department for which Cl– concentration had been ordered by the treating physician. For each patient, three simultaneous samples were collected: One complete blood count tube, one clot sample for serum collection, and one arterial blood gas analysis heparinated sample. Serum Hb, electrolytes and blood gas analysis were derived from these samples. The results derived from the formula were compared with the biochemical report of the chlorine Original ArticleVolume 3, Issue 2, 2017, p. 42-45Calculation of plasma chloride levels using blood gas measurements© 2017 The Author(s). Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Reza Hashemi1, Alireza Majidi2*, Ali Tabatabaey3, Sadrollah Mahmoudi41Shohada-e Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran2 Department of Emergency Medicine, Shohada-e Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran3Department of Emergency Medicine, Qom University of Medical Sciences, Qom, Iran4Department of Emergency Medicine, Baqiyatallah University of Medical Sciences, Tehran, IranReceived: 3 June 2016Accepted: 9 July 2016Published online: 22 January 2017*Corresponding author: Alireza Majidi; Tel/Fax:  0098-2122721155, Email: pezeshkmajidy@yahoo.comCompeting interests: None.Funding information: None.Citation: Hashemi R, Majidi  A, Tabatabaey A, Mahmoudi S. Calculation of plasma chloride levels using blood gas measurements. Journal of Emergency Practice and Trauma 2017; 3(2): 42-45. doi: 10.15171/jept.2016.16.AbstractObjective: Chloride is the major plasma anion. There are several methods available for the determination of serum chloride levels. Unfortunately these methods are sometimes not available in the urgent setting where values are needed. Here we describe a formula for estimating plasma chloride levels.Methods: Fifty-two consecutive patients were enrolled for which serum chloride levels were estimated using the formula CL- = (Na+ + 10 –TBB), and also measured directly through the colorimetric method. Correlation between the two values was analyzed using Pearson correlation coefficient and agreement was shown in the Bland-Altman plot. Results: Comparing the values achieved through estimation and laboratory determination of plasma chloride revealed a significant correlation (r = 0.97). Consistent agreement was described within -4.8 and +6.6 on the Bland-Altman plot throughout the measurements.Conclusion: The formula presented here may be a reliable alternative to direct measurement of serum chloride when direct results are not availableKeywords: Arterial blood gas (ABG), Total buffer base (TBB), Anion gap (AG), Serum chlorideJepthttp://jept.irOpen AccessPublish Freedoi 10.15171/jept.2016.16Hashemi et alJournal of Emergency Practice and Trauma, 2017, 3(2), 42-45 43sample from the laboratory. Correlation was analyzed us-ing the Pearson coefficient and agreement described in the Bland-Altman plot.The Stewart physicochemical approach to acid-base inter-pretation takes into account all the cations and anions that play a role in plasma electroneutrality (11). The plasma remains electrically neutral in physiologic and pathologic conditions through the equilibration of total cations with total anions. The concept is summarized in the formula below in which A- represents serum albumin, phospho-rus, and other negatively charged proteins:Strong ion difference (mmol/L) = [Na+] + [K+] + [Ca2+]+[Mg2+] – [Cl−][Strong ion difference] − [A−] = [HCO3−] + [CO3−2] + [(OH−)] – [H+]The equation for SID − [A−] can be reduced to approxi-mately [HCO3−] because [HCO3−] is much greater than [H+], [OH−], and [CO3−2]. In addition, if one replaces the normal values for these concentrations in a physiologic state as shown in Table 1, several conclusions can be made:Since variations in K+, Ca+2 and Mg+2 concentrations are trivial and their influence in the formula adds up to a to-tal of approximately 10 meq/L we replace them with this value. Also we refer to the accumulative concentration of (Co3H- + Po4H-2 +Alb +Hb + others) as total buffer base (TBB). Then the following formula can be rewritten: (Na+ +10) = (Cl– +TBB) and finallyCl-= (Na++10)-TBBBox 1 summarizes these formulas.Chloride was measured in a simultaneously collected se-rum sample. Care was taken for the serum to be extracted immediately after sample collection to limit alterations caused by cell metabolism. An automated colorimetric method was used. Chlorine was measured using colori-metric method by Randex kit, UK with Cl- 5526 ×100 mc, Reagent G×100 mc 2STd 11×5 mg 3ST, 1×5 mg. The chemical reaction led to the creation of ferric thiocyanate, a brown colored complex. The mixture was left to sit at 37°C for 270 seconds. The density of this substance was then measured using spectrophotometry at 505 nm wave-length compared to a standard sample which revealed the concentration of chloride. Although relatively simple, when available, the test was usually reported over 2-hours after sample collection in the emergency setting. For practical purposes we chose a sample size according to the following formula:2 2 21 2 1 22( ) (6 6 ) 48z zNd+ += =which a =0.05, d=3 , 61 = 4, and 62=4.Fifty-two sequential patients were enrolled, 33 male and 19 female. There was no limitation on the condition for which the test was ordered. In our study, patients suffered from varying disorders such as diabetic ketoacidosis, acute renal failure, chronic kidney disease, intoxication, gastro-enteritis, suspected electrolyte or acid-base disturbances. Results Overall 52 patients were included in the study. For every case two chloride values were available: one through calcu-lation and the other through direct biochemical measure-ment using the automated colorimetric method. Figure 1 shows the agreement between these two methods using the Bland-Altman plot. This diagram plots the difference between the values achieved through the formula and laboratory to the average of these two values and demon-strates the proximity of the two methods throughout the range of measurements obtained. Furthermore, Pearson coefficient was used to measure the statistical correla-tion between the two values and a correlation coefficient of r = 0.94 was reached, indicating excellent correlation of the two methods.DiscussionChloride is an important extracellular anion with proven impact on the acid-base status of the body (1-3). Although the best method for determining Cl- concentration is through direct measurement, sometimes this is not an op-tion in the emergency setting. Here we have described a formula which predicts serum Cl- levels with strong cor-Table 1. Normal values of serum electrolytesNa+ 142 meq/L Cl– 103 meq/L K+ 4.3 meq/L Co3H- 25 meq/L Ca++ 4 meq/L Po4 H—2 meq/L Mg++ 2 meq/L Proteins 16 meq/L Others (So4H--, Lactate) 6 meq/L Total: 152 meq/L Total: 152 meq/L Box 1. Formula summaryNa+K+Ca+Mg=Cl+CO3+Protein+Hb+PO4K+Ca+Mg=Unmeasurable cation  ≈10 mmolProtein+Hb+PO4 = Unmeasurable anionHCO3+Protein+Hb+PO4 =TBBNa+10 = Cl+TBBCL= Na+10-TBBAnion gap=UA-UC=Na-(Cl+CO3)Anion gap=UA-UC=Na-(Na+10-TBB+CO3)Aniongap=TBB-(CO3+10)Figure 1. Blad-Altman plot showing agreement between calculated and measured serum chloride levels Blad-Altman plot showing agreement between calculated and measured serum chloride levels80 90 100 110 120 130 140-10-505101520Mean of Calculated and MeasuredCalculated - MeasuredMean0.9-1.96 SD-4.8+1.96 SD6.6Difference between calculated and measuredHashemi et alJournal of Emergency Practice and Trauma, 2017, 3(2), 42-4544relation with the colorimetric method used as the refer-ence value. There are several methods available for mea-surement of chloride levels in the laboratory including the autoanalyzer (colorimetric method), a coulometric method, a mercurimetric method, and a chloride-specific ion electrode method (1). Among these, the colorimet-ric method is considered to be simpler (12) and can be performed using automated apparatus. Here we used the colorimetric method as the reference value since this was the method available at our center. Unfortunately despite the importance of chloride concentration determination, this test is not available during off hours at our center and the use of an alternative formula for this purpose is welcomed. This is not the first time calculated formulas are turned to in hope of replacing direct measurement of plasma concentrations. Rees et al have described a com-puterized formula in order to estimate arterial O2 pres-sures using the data gained through venous sample blood gas analysis (13). Another example of using formulas to estimate values that are difficult to obtain is the estima-tion of glomerular filtration rate (14,15). These formulas help make quick decisions when waiting for a direct re-sult is not an option. Chloride measurement is essential not only for etiologic evaluation of the acid-base status, but also for classification of the condition and choosing an often urgent path for treatment (i.e., saline-responsive or saline-resistant metabolic alkalosis or normal and high anion gap [AG] metabolic acidosis) (2,11). Therefore, in instances when the direct measurement of chloride is not performed urgently, our formula is a well correlated al-ternative which may help guide urgent management of patients. As seen on the Bland-Altman plot, almost all of the cases included in this study are plotted within a lim-ited range of difference between negative and positive 5 mg/dL of one another. This means that the measurements usually differed less than 5 mg/dL which is considered ac-ceptable in the clinical setting. Moreover, this agreement is consistent throughout the range of measurements made with no increased tendency towards bias at either end of the plot. The impressive Pearson coefficient further em-phasizes the correlation between the values obtained from both methods. Our formula may further be developed to estimate the AG when Chloride levels are not available. For this purpose for AG we have:AG=Na+-(Cl-+Co3H-)After substitution for chloride we have:AG=Na+-(Na++10–TBB+Co3H-) orAG=TBB–(Co3H-+10Through the same steps the Δ/Δ ratio can also be obtain-able as follows: Δ/Δ Ratio = (AG–12) / (25-Co3H-) or Δ/Δ Ratio= [TBB–(Co3H-+22)] / (25–Co3H-)ConclusionThe formulas presented in this paper are an accurate and acceptable alternative to direct measurement of serum chloride level in situations when direct analysis is not available.LimitationsLimitations are an inherent part of clinical research. In our study we recognize that a larger patient sample could allow us to test the accuracy of our formula in a wider range of clinical settings and chloride levels. Also, due to the limited number of patients included and the variety of conditions for which serum chloride level measurement is desired, stratification of patients based on underlying condition was not an option. Larger studies may be able to test the accuracy of the formula in different settings such as toxicology, shock, respiratory disorders, etc. Lastly, in our study we used the colorimetric method as the refer-ence value for serum chloride levels. This was due to the lack of availability of other measurement methods at our hospital. A comparison with the results obtained through different methods of measurement would have been more desirable.Ethical issues There were no ethical concerns since no extra blood was drawn from the patients and all interventions were based on the measured rather than the calculated chlorine concentration. Authors’ contributions RH contributed to concept development, data gathering, and statistical analysis of the data. AM contributed to concept development and data gathering. AT contributed to statistical analysis and manuscript preparation of the paper. References1. Morisson G. Serum chloride. In: Walker HK, Hall WD, Hurst JW, eds. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd ed. Boston: Butterworths; 1990.2. Seifter JL. Integration of acid–base and electrolyte disorders. N Engl J Med 2014; 371(19): 1821-31. doi: 10.1056/NEJMra1215672.3. Funk GC, Doberer D, Heinze G, Madl C, Holzinger U, Schneeweiss B. Changes of serum chloride and metabolic acid-base state in critical illness. Anaesthesia 2004; 59(11): 1111-5. doi: 10.1111/j.1365-2044.2004.03901.x.4. Kimura S, Matsumoto S, Muto N, Yamanoi T, Higashi T, Nakamura K, et al. Association of serum chloride concentration with outcomes in postoperative critically ill patients: a retrospective observational study. J Intensive Care 2014; 2(1): 39. doi: 10.1186/2052-0492-2-39.5. McCallum L, Jeemon P, Hastie CE, Patel RK, Williamson C, Redzuan AM, et al. Serum chloride is an independent predictor of mortality in hypertensive patients. Hypertension 2013; 62(5): 836-43. doi: 10.1161/HYPERTENSIONAHA.113.01793.6. Panteghini M, Bonora R, Malchiodi A, Calarco M. Evaluation of the direct potentiometric method for serum chloride determination--comparison with the most commonly employed methodologies. Clin Biochem 1986; 19(1): 20-5. doi: 10.1016/s0009-9120(86)80066-2.7. Parham H, Zargar B. Simultaneous coulometric determination of iodide, bromide and chloride in a Hashemi et alJournal of Emergency Practice and Trauma, 2017, 3(2), 42-45 45mixture by automated coupling of constant current chronopotentiometry and square wave voltammetry. Analytica Chimica Acta 2002; 464(1): 115-22. doi: 10.1016/s0003-2670(02)00379-3.8. Sekerka I, Lechner JF. Ion selective electrode for determination of chloride ion in biological materials, food products, soils and waste water. J Assoc Off Anal Chem 1978; 61(6): 1493-5.9. Tavallali H, Deilamy Rad G, Parhami A, Abbasiyan E. Colorimetric detection of copper and chloride in DMSO/H2O media using bromopyrogallol red as a chemosensor with analytical applications. Spectrochim Acta A Mol Biomol Spectrosc 2012; 97: 60-5. doi: 10.1016/j.saa.2012.05.071.10. Arai K, Kusu F, Noguchi N, Takamura K, Osawa H. Selective determination of chloride and bromide ions in serum by cyclic voltammetry. Anal Biochem 1996; 240(1): 109-13. doi: 10.1006/abio.1996.0336.11. Stewart PA. Modern quantitative acid-base chemistry. Can J Physiol Pharmacol 1983; 61(12): 1444-61. doi: 10.1139/y83-207.12. Schoenfeld RG, Lewellen CJ. A colorimetric method for determination of serum chloride. Clin Chem 1964; 10: 533-9.13. Rees SE, Toftegaard M, Andreassen S. A method for calculation of arterial acid-base and blood gas status from measurements in the peripheral venous blood. Comput Methods Programs Biomed 2006; 81(1): 18-25.14. Rink N, Zappitelli M. Estimation of glomerular filtration rate with and without height: effect of age and renal function level. Pediatr Nephrol 2015; 30(8): 1327-36. doi: 10.1007/s00467-015-3063-0.15. Casado Cerrada J, Carrasco Sanchez FJ, Perez-Calvo JI, Manzano L, Formiga F, Aramburu Bodas O, et al. Prognostic value of glomerular filtration rate estimation equations in acute heart failure with preserved versus reduced ejection fraction. Int J Clin Pract 2015; 69(8): 829-39. doi: 10.1111/ijcp.12616.

Calculation of plasma chloride levels using blood gas

measurements

http://eprints.kmu.ac.ir/27510/1/JEPT_Volume%203_Issue%202_Pages%2042-45.pdf

Calculation of plasma chloride levels using blood gas measurements

Abstract

Similar works

Full text

Available Versions

Simorgh Research Repository