|Year : 2021 | Volume
| Issue : 2 | Page : 76-81
Efficacy of C-Reactive protein as a marker in patients with odontogenic fascial space infection: A prospective analytical study
Centina Rose John1, Sumir Gandhi2, Inderjot Singh2, Tittu Thomas James3
1 Department of Plastic and Reconstructive Surgery, Saveetha Medical College, Chennai, Tamil Nadu, India
2 Department of Oral and Maxillofacial Surgery, Christian Dental College, Ludhiana, Punjab, India
3 Physiotherapist, National Institute for Mental Health and Neuro Sciences (NIMHANS), Bengaluru, Karnataka, India
|Date of Submission||06-Oct-2020|
|Date of Decision||23-Jun-2021|
|Date of Acceptance||16-Aug-2021|
|Date of Web Publication||20-Dec-2021|
Mr. Tittu Thomas James
Physiotherapist, Physiotherapy Centre, NIMHANS Hospital Campus, Bengaluru - 560 029, Karnataka
Source of Support: None, Conflict of Interest: None
Purpose: Odontogenic fascial space infections are often unpredictable in their course of spread due to the anatomical connectivity of potential spaces. C-reactive protein (CRP) has been widely studied and accepted as a marker in monitoring acute phase of infection. The purpose of this prospective analytical study was to identify the efficacy of CRP in fascial space infections by analyzing the correlation of CRP levels with other parameters of inflammation.
Methods: About 30 patients with fascial space infection who required incision and drainage (I&D) were included in the study. The clinical parameters of infection such as pain, temperature, swelling, and pus discharge were measured. Laboratory parameters such as serum levels of CRP, Erythrocyte Sedimentation Rate (ESR), and Total Leukocyte Count (TLC) were also estimated. The measures were analyzed prior to I&D on day 1, as well as on third, seventh, eleventh, and fifteenth day of I&D. The mean values at different time frames were analyzed statistically and spearman's correlation was performed to identify the relation of CRP with other parameters.
Results: The mean CRP values dropped from 149.4 ± 81.8 ml/dl on the first day to 3.39 ± 0.9 mg/dl on the final day of assessment (P < 0.001). The CRP values demonstrated a significant positive correlation with ESR and TLC values and clinical parameters of infection.
Conclusion: The results of this study suggest that CRP can be used as an effective marker and should be incorporated as a monitoring tool in the diagnosis and prognosis in patients with fascial space infections.
Keywords: C-reactive protein, erythrocyte sedimentation rate, fascial space infections, incision and drainage, total leukocyte count
|How to cite this article:|
John CR, Gandhi S, Singh I, James TT. Efficacy of C-Reactive protein as a marker in patients with odontogenic fascial space infection: A prospective analytical study. J NTR Univ Health Sci 2021;10:76-81
|How to cite this URL:|
John CR, Gandhi S, Singh I, James TT. Efficacy of C-Reactive protein as a marker in patients with odontogenic fascial space infection: A prospective analytical study. J NTR Univ Health Sci [serial online] 2021 [cited 2023 Jan 27];10:76-81. Available from: https://www.jdrntruhs.org/text.asp?2021/10/2/76/332850
| Introduction|| |
Orofacial and neck infections of odontogenic or non-odontogenic origin are often unpredictable in their course of spread due to the anatomical connectivity of potential spaces. These spaces act as pathways of least resistance to the spread of infection. The advent of modern imaging and diagnostic techniques along with the widespread availability of antimicrobials has immensely reduced the morbidity and mortality associated with fascial space infections. The most commonly encountered portals of entry are the infections of odontogenic origin. The pathogenic spectrum includes both aerobic and anaerobic bacteria. The classical clinical presentation includes the history of progressively increased swelling, fever, trismus and pain associated with dysphagia, dyspnea and change in voice, which evolves rapidly from localized to deep neck-space infection compromising the airway. Toxicity and life-threatening situations like impaired vision, respiratory distress, decreased level of consciousness, meningitis, and cavernous sinus thrombosis can be the sequelae of odontogenic infection.,, Appropriate antibiotic therapy is the first line of treatment for the resolution of fascial space infection. Infections of fascial spaces are further managed surgically by decompressing the tissues and allowing good perfusion and increased oxygenation by incision and drainage (I&D).,,
Infection sparks off inflammatory processes, the mediators of which may prove reliable in quantifying the intensity of the reaction thereby aiding in the decision-making for the need of drug administration. Thus, inflammatory markers can act as a tool for guiding antibiotic therapy. Among various acute phase proteins such as haptoglobulin, ceruloplasmin, fibrinogen, and C-reactive protein (CRP), the latter has been widely studied and accepted as a marker in monitoring acute phase of infection because of its higher concentration when compared to others in the initial stage, and is very consistent in response. Therefore, it is the most satisfactory single screening test for an acute phase reaction and a useful marker for the amount of tissue injury and inflammation. The serum concentration reaches its peak within 48 hours, initially rising above 5 mg/l in 6 hours. The plasma half-life of CRP is about 19 hours irrespective of health or disease conditions. Therefore, the intensity of stimulus that triggers the secretion directly reflects the intensity of the pathological process, which defines the plasma CRP concentration. When the stimulus has been removed, the production process comes to a halt, causing a rapid decline in circulating CRP concentration. In this way, the severity of pathological process and plasma CRP concentration are related. CRP is also a marker of general tissue damage in addition to inflammation.
This prospective study was conducted to correlate the variation of CRP with laboratory parameters such as Erythrocyte Sedimentation Rate (ESR) and Total Leukocyte Count (TLC) along with other clinical parameters in patients with fascial space infections, thus evaluating the efficacy of CRP as a marker for determining the severity of infection in this population.
| Materials and Methods|| |
Thirty patients with fascial space infections irrespective of caste, sex, or socioeconomic status, who required I&D, were selected for the study. The duration of the study was from December 2015 to September 2017. Ethical clearance was obtained from the institution review board and informed consent was signed by the participants prior to any data collection procedures. Pregnant women, patients who were on steroids and contraceptive medications, chronic alcoholics, patients with malnutrition, immunological ailments, hepatocellular or cardiovascular system damage, neoplasm, and inflammatory conditions like Rheumatoid arthritis were excluded from the study. Patients were also excluded if they had developed complications after I&D. Informed consent was taken and collected from all the patients after they were explained about the study and had expressed their willingness to participate in it.
Clinical parameters of infection such as body temperature, pain, pus discharge and facial swelling, and serum levels of CRP, WBC, and ESR were measured on the first day of admission prior to I&D (T0). Clinical signs and serum marker levels were also documented on the following days after I&D as follows; T1 on the third day after I&D, T2 on the seventh day of I&D, T3 4 days after T2, and T4 4 days after T3. Body temperature was measured using digital thermometer in degree Fahrenheit. Pain scores were evaluated on a basis of 10 point Visual Analog Scale (VAS). Presence or absence of pus discharge (both extra-oral and intra-oral) was documented as 'Yes' or 'No,' respectively. Facial swelling measurements were taken as the distance between the symphysis and mastoid (A), distance between the angle of mandible to lateral canthus of eye (B), and distance between the angle of mandible to ala of nose (C). I&D was performed under strict aseptic condition and empirical intravenous or oral antibiotics (Amoxicillin and Clavulanate Potassium, and Metronidazole) were initiated. Pus drained was sent for aerobic and anaerobic culture, and antibiotic sensitivity. Antibiotics were administered based on culture and sensitivity, and later terminated as per surgeon's order till the inflammatory parameters reached normal values. Ethical approval obtained - Date: 24 November 2015.
The normality of the collected data was analyzed using Kolmogorov–Smirnov test. Measures of central tendency and distribution were analyzed for demographic details and continuous variables. Friedman test followed by post hoc analysis using Wilcoxon signed-rank test was performed for comparing laboratory and clinical parameters of infection (P value set at 0.01 for post hoc analysis). Spearman's correlation analysis was also performed to analyze the relationship of CRP with other parameters. To analyze the data, SPSS (IBM SPSS Statistics for Windows, Version 22.0, Armonk, NY: IBM Corp. Released 2013) was used.
| Results|| |
Thirty patients consisting of 17 (56.7%) males and 13 (43.3%) females within the age group of 20–65 with a mean age of 41.77 ± 11.5 years (Mean age of males = 39.88 ± 11, females = 44.23 ± 12 years), who were undergoing I&D were selected for the study. The spaces involved in the patients were submental, submandibular, buccal, canine, infratemporal, submasseteric, parotid, temporal, pharyngeal, pterygomandibular, and sublingual spaces. The number of spaces affected within an individual ranged from one (N = 8) to a maximum of four (N = 4). Twenty-four patients (80%) were prescribed antibiotics prior to I&D, whereas six patients (20%) were not given any prior antibiotics. [Table 1] shows the mean value of the progression of the laboratory and clinical parameters measured within the individuals during the course of time.
Comparison of laboratory parameters using Friedman test revealed that the mean values of the progression of CRP, ESR, and TLC at different time frames are statistically highly significant (P = 0.00). Wilcoxon signed-rank test for post hoc analysis showed that all time frames are significantly different (P < 0.01) from each other (T0vsT1, T0vsT2, T0vsT3, T0vsT4, T1vsT2, T1vsT3, T1vsT4, T2vsT3, T2vsT4, T3vsT4) for CRP, ESR, and TLC except for T0vsT1, T0vsT2, T1vsT2, and T2vsT3 of ESR as well as T1vsT2 and T3vsT4 of TLC. Friedman test also revealed significant difference between mean values of clinical parameters. Post hoc analysis between different time frames also showed significant difference except for T1vsT3, T2vsT3, T2vsT4, and T3vsT4 for temperature, T3vsT4 for pain, T0vsT1 for Swelling A, B, and C.
Frequency of the presence and absence of pus discharge at various time frames has been depicted in [Table 2]. By T3, 83.3% of study population did not show pus discharge, and by T4, none of the patients showed discharge.
Correlation between CRP and other laboratory and clinical parameters are depicted in [Table 3]. Spearman's correlation performed to identify the relation between the mean values of the three laboratory outcome measures over the course of infection showed a significant positive correlation of CRP with ESR (ρ = 0.356, P = 0.000) as well as with TLC (ρ = 0.460, P = 0.000). CRP demonstrates significant positive correlation with all other clinical parameters (P < 0.01), particularly with Spearman's ρ of 0.834 with pain, which is the highest. [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5] provide the pictorial representation of correlation between variables.
|Figure 5: Correlation analysis CRP vs. Swelling A (SA), Swelling B (SB), and Swelling C (SC)|
Click here to view
| Discussion|| |
The serum CRP values demonstrated significantly higher levels in all the patients with fascial space infections and thereafter declined significantly after I&D in the present study. The mean value of CRP on the initial day of assessment before I&D was 149.4 ± 81.8 mg/dl, which subsequently reduced to 3.4 ± 0.9 mg/dl over a period of 15 days during follow-up. Alotaibi et al. advocated that elevated CRP should be considered as criteria for admission to high-risk deep neck-space infection.
The drastic reduction in the mean value of CRP between T1 and T2 were noted when compared to other time frames of assessment. Progression of CRP was found to be gradual after T2, reaching the normal values by T3. Although it is impossible to identify normal CRP levels of an individual prior to fascial space infection, substantial reduction of CRP was seen during the course of disease.
ESR and TLC are used as markers of infection in various studies and have significantly represented the changes within an individual during the course of infection.,,,,, Our study also supports this fact that ESR and TLC have the capacity to identify infections and also to identify the changes in accordance with the course of infection. Post hoc analysis revealed that the TLC values dropped with the progression of days of treatment, whereas ESR remained elevated. Few other studies have demonstrated elevated ESR levels for a longer period than CRP.,
The severity of infection was correlated with raised TLC, ESR, and clinical parameters like pain, swelling, rise in the temperature, and constant pus discharge. Thus it shows that as the clinical signs of infection are evident in an individual, CRP values also tend to be in the higher levels. Therefore, CRP was found to be sensitive to the changes during a fascial space infection and thus can act as a marker in this particular patient population. The direct linear relationship of CRP with the severity of the infection was also explained in the studies of Dražić R and Singh WT, et al. The latter demonstrated a significant mean decrease in the swelling size and CRP values with time (P < 0.01). The study detected no complications or re-infection during the follow-up of the patients.
Infection, tissue damage, inflammation, and malignancies evoke various local, systemic, and metabolic changes, which are physiological and biochemical in nature indicative of acute phase responses. Acute phase proteins (APP) are defined as plasma proteins whose concentration increases at least by 25% (positive APP) during acute phase responses and maximal change varies to over 1000 folds for CRP. Among the various APP, CRP and ESR have been widely used in clinical practice for the various conditions due to their high serum levels. The major site of synthesis of CRP is the hepatocyte, and stimuli that induce CRP synthesis include Interleukin (IL)-6 and IL-1. In the resting state, CRP is retained in the endoplasmic reticulum of hepatocytes by binding to carboxylesterases. During the acute phase response, stimulated synthesis and enhanced secretion from endoplasmic reticulum elevate the levels of CRP, which can be seen rapidly in the blood. After the resolution of infection or removal of stimulus, CRP level shows drastic reduction as it has a half-life of 19 hours. If the underlying cause of elevation persists, CRP may remain elevated for longer periods., Due to the long half-life of plasma protein, ESR normalizes slower than other acute phase reactants. ESR is also affected by the size/shape of red blood cells, plasma composition, fluid status, temperature, drugs, and so on.
The role of CRP in the field of maxillofacial infection was evaluated in few studies, but less established as a marker in clinical practice. Monitoring the course of maxillofacial space infection is the mainstay in the management, as it is characterized by constant pus discharge, raised WBC counts, persistent rise in temperature, continued airway distress, and septicemia. Confronted with acute life-threatening condition and immediate spread beyond the boundaries of the maxillofacial region, fascial space infection required proper monitoring, expeditious I&D, and judicious antimicrobial coverage. The clinical and biochemical variables like CRP, which predict the severity and outcome, would thus help in monitoring the severity as well as the resolution of infections. As the half-life of CRP is shorter and constant, it reflects the severity of the precipitating factor faster than WBC and ESR. Our study thus identified the effectiveness of CRP as a marker in space infections, and also proved its role in the guidance of antibiotic therapy in this population.
CRP is an excellent marker in patients with fascial space infection. Elevated CRP levels accurately reflected the severity of the infection and correlated well with the serum ESR and TLC values, and with the clinical parameters. We recommend that CRP should be incorporated as a monitoring tool for the diagnosis of fascial space infection as well as in monitoring the response to therapy.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Topazian RG, Goldberg MH, Hupp JR. Oral and Maxillofacial Infections. 4th
ed. Philadelphia (PA): W.B. Saunders; 2002. p. 192-3.
Ylijoki S, Suuronen R, Somer HJ, Meurman JH, Lindqvist C. Differences between patients with or without the for intensive care due to severe odontogenic infections. J Oral Maxillofac Surg 2001;59:867-72.
Krishnan V, Johnson JV, Helfrick JF. Management of maxillofacial infections: A review of 50 cases. J Oral Maxillofac Surg 1993;51:868-73.
Husain TM, Kim DH. C-reactive protein and erythrocyte sedimentation rate in orthopaedics. Univ Pennsylvania Orthopaedic J 2002;15:13-6.
DuClos TW, Mold C. C-reactive protein: An activator of innate immunity and a modulator of adaptive immunity. Immunol Res 2004;30:261-77.
Pepys MB, Hirschfield GM. C-reactive protein: A critical update. J Clin Invest 2003;111:1805-12.
Alotaibi N, Cloutier L, Khaldoun E, Bois E, Chirat M, Salvan D. Criteria for admission of odontogenic infections at high risk of deep neck space infection. Eur Ann Otorhinolaryngol Head Neck Dis 2015;132:261-4.
Shetty JN, Shah PD. A comparative biochemical evaluation of serum C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR) in healthy individuals and patients having odontogenic infections. Int J Sci Res 2013;2:460-1.
Singh WT, Singh WR, Devi WM, Devi NA. C-reactive protein as a monitoring tool for facial space infections of odontogenic origin: A prospective study. Int J Contemporary Dent 2012;3:18-22.
Sharma A, Gokkulakrishnan S, Shahi AK, Kumar V. Efficacy of serum CRP levels as monitoring tools for patients with fascial space infections of odontogenic origin: A clinicobiochemical study. Natl J Maxillofac Surg 2012;3:148-51.
Bagul R, Chandan S, Sane VD, Patil S, Yadav D. Comparative evaluation of C-reactive protein and WBC count in fascial space infections of odontogenic origin. J Maxillofac Oral Surg 2017;16:238-42.
Stathopoulos P, Igoumenakis D, Shuttleworth J, Smith W, Ameerally P. Predictive factors of hospital stay in patients with odontogenic maxillofacial infections: The role of C-reactive protein. Br J Oral Maxillofac Surg 2017;55:367-70.
Ellitsgaard N, Andersson AP, Jensen KV, Jorgensen M. Changes in C-reactive protein and erythrocyte sedimentation rate after hip fractures. Int Orthop 1991;15:311-4.
Dražić R, Jurišić M, Marković A, Colić S, Gačić B, Stojčev-Stačić L. C-reactive protein as an inflammatory marker in monitoring therapy effectiveness of acute odontogenic infections. Srp Arh Celok Lek 2011;139:446-51.
Kilicarslan A, Uysal A, Roach EC. Acute phase reactants. Acta Medica 2013;2:2-7.
Pepys MB, Baltz ML. Acute phase proteins with special reference to C-reactive protein and related proteins (pentaxins) and serum amyloid a protein. Adv Immunol 1983;34:141-212.
Vigushin DM, Pepys MB, Hawkins PN. Metabolic and scintigraphic studies of radioiodinated human C-reactive protein in health and disease. J Clin Invest 1993;91:1351-7.
Rega AJ, Aziz SR, Ziccardi VB. Microbiology and antibiotic sensitivities of head and neck space infections of odontogenic origin. J Oral Maxillofac Surg 2006;64:1377-80.
Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Eng J Med 1999;340:448-54.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3]