European Journal of Cardiovascular Medicine

Central venous catheter (CVC) is commonly inserted in critically ill patients in intensive care unit (ICU) and in major surgeries in operation theatre for multiple purposes like CVP monitoring, infusion of inotropes and irritant drugs and haemodialysis. CVC placement requires training and complication rate varies from 3.6% to 14% depending on expertise of the clinician (1)(2). Ultrasound guided CVC placement can minimize(3) multiple complications like arterial puncture, pneumothorax, hematoma and nerve injury but correct location of the tip of catheter cannot be assured. Ideal position is in superior vena cava (SVC) above its outlet in right atrium (RA). It is very important to place CVC tip at correct site, because misplacement can be very hazardous and sometimes lethal to the patients.

There are multiple methods to confirm the placement of CVC tip like, endo cavitary electrocardiography, trans-oesophageal echocardiography, guide wire localization in IVC or RA with ultrasonography, fluoroscopy and CT scan and chest x ray(4). Chest x ray is considered as gold standard and routinely performed after CVC placement in intensive care unit and in recovery room after completion of surgery(5)(6). Chest radiography exposes the patient to radiation and is time consuming and this delay can be harmful to the critical patient.

Echocardiographic bubble test is recent technique which is non-invasive and without any harmful effect, can be used as alternative to chest x ray to confirm the normal position of CVC tip(7)(8). The rationale of the bubble test is that the right atrium (RA) should be immediately (within 2 sec) and completely filled with micro-bubbles when a bolus of agitated sa-line is administered through the distal lumen of a normally positioned CVC (9)(3). The micro-bubbles can be easily recognized by echocardiography because they appear brighter than the blood. Advantage of bubble test is, it can be easily performed on bed side and immediately after placement of CVC as compared to chest x ray which is more time consuming, particularly in operation theatre where performing chest x ray after CVC placement is not feasible(10). And is more time consuming in odd hours in Intensive care unit also, where patient may need inotropic support and need to start dialysis urgently.

Primary aim of this study was to compare the diagnostic accuracy of “Echocardiographic bubble test” with CXR in confirmation of CVC placement and time required for each test.

This prospective, observational, cross-sectional, analytical study was conducted at our institute, a tertiary care centre. Total 120 CVC placements were done during the study period of 8 months.  After excluding 13 patients, 103 patients were included in the study. This sample size was also confirmed by the Buderers formula, according to which sample size of 103 was adequate. Study was conducted after taking approval from institutional ethics committee. Informed consent was taken from patient and relatives.

Patient more than 18 years of age who undergo internal jugular vein cannulation as a part of intensive care or in operation theatre as a part of anaesthesia management of kidney transplant were included. Patient who undergoes central venous cannulation other than internal jugular vein and who had contraindication for CVC insertion were excluded from study. 

Patient was kept in 15-degree Trendelenburg position Right or left internal Jugular vein is selected Under all aseptic precaution painting and draping done Ultrasonic assessment of selected vein was done with high frequency linear probe for any narrowing or thrombus formation. POLYMED 7 fr. 16 cm double lumen catheter for renal transplant surgery or 12 fr. 16 or 20 cm haemodialysis catheter (depending on right or left IJV) was inserted using Seldinger technique as per indication under ultrasonic guidance.

Chest x ray:

Immediately after central line insertion chest x ray was advised as a gold standard method for detecting malposition of CVC. Time was noted from requisition to the availability of chest x ray to confirm catheter tip position and any other complications of catheter placement. In patients where CVC was done in operation theatre, chest x ray was done in post-operative period in recovery room.

A CVC tip positioned within 2 cm of SVC-RA junction is considered normal position which can be interpreted on CXR as two vertebral bodies below the tracheal bifurcation. A tip of CVC anywhere between tracheal bifurcation to two vertebral bodies below it, is considered normal position for the study purpose. All the misplaced catheter need not to be corrected if tip is endovenous. These catheters can be used for delivering medications in emergency situation. Misplaced catheters were corrected only if indicated (inadequate blood flow or outside the venous systems) under the guidance of the senior faculty.

Bubble test:

Philips CX50 ultrasound machine was used to perform bubble test. With echo probe S5-1 subcostal four chamber view was obtained. Agitated saline was used for bubble test. Two 10 ml syringe (filled with 9 ml normal saline and 1 ml air) with 3 ways stop cock was used to make saline agitated. Due to its acoustic property, the microbubble contained in the agitated saline appear brighter than blood and can be seen easily on echocardiography. Agitated saline was injected rapidly from the distal lumen of CVC. Time was noted from injecting agitated saline to complete opacification of RA on echo. Test is positive if bubble appears in RA immediately or in < 2sec suggesting normal position of catheter tip. Delayed A short video was recorded for data collection purpose.

Total 103 patients were taken in to study. Patients’ characteristics are shown in table 1.

Table 1: Patients characteristics

Complications of central venous catheterization: in the whole study cohort no pneumothorax detected by CXR. And there was no inadvertent arterial cannulation occurred.

Chest x ray shows CVC tip at normal position in 92 out of 103 patients and in 11 patients CVC tip was at abnormal position.

Echocardiographic bubble test was positive in 94 of 103 patients which suggest tip of catheter is in correct position and negative in 9 patients suggesting tip is at abnormal position.

In 99 of the 103 patients, there was concordance between the chest radiography and Echocardiographic finding (Both the techniques demonstrated correct placement in 91 patients and incorrect placement in 8 patients)

The characteristic of four patients in whom there was lack of concordance between radiography and echocardiography are shown in table 2.

Table 2. Lack of concordance in both techniques

The mean time:

• Chest radiography is 300 ± 11.844 min
• Echocardiographic bubble test is 106 ± 2.028 min.
• student’s t= 33.96 with 95% confidence interval
• p<0.0001(highly significant)

Table 3: Time taken for both techniques

STATISTICAL ANALYSIS

Sample size was calculated according to the formula described by Buderer⁽¹¹⁾. Considering expected sensitivity and specificity of US to detect catheter malposition to be 98% and 95% respectively with 10% precision (95% confidence interval), 10% prevalence of catheter tip malposition at our institute, we calculated minimum sample size of 95 patient, according to which sample size of 103 was adequate

Collected data was analysed using software SPSS 26 for Windows (SPSS Inc. IBM Corp., Chicago, IL, USA) and medcalc 23.2.1 for windows. The data was not noramally distributed according to shapiro wilk test. Continuous variables were presented as the mean (±SD). Sensitivity, specificity, and predictive values were calculated by comparing ultrasonography results with radiographic findings. For calculating concordance between ultrasound and CXR, the statistic was used. P values of <0.05 were considered statistically significant. Time taken for chest x ray and ultrasound were compared by Wilcoxon signed-rank test as these data were not normally distributed.

Table 4: Result of chest radiography and Echocardiographic bubble test

Bubble test results

POSITIVE PREDICTIVE VALUE = TP/(TP+FP) X 100 = 91/ (91+3) X 100 = 0.9680X100 = 96.808%

NEGATIVE PREDICTIVE VALUE = TN/(TN+FN) X 100= 8/ (8+1) X 100=0.888X100= 88.888%

SENSITIVITY = TP/(TP+FN) X 100 = 91/ (91+1) X100= 0.98X100=98.91%

SPECIFICITY = TN/(TN+FP) X 100= 8/ (8+3) X100=72.72%

Likelihood Ratio: LR+ 3.62 and LR- 0.014

Central venous catheterization is widely performed procedure in intensive care unit and in major surgeries. In this study we have taken patients those admitted in ICU with critical condition who were either in volume overload condition due to CRF requiring urgent dialysis or in shock who require vassopressors and those posted for renal transplant surgery where cvp measurement is required as per institutional protocol.

Central venous catheterization is associates with multiple complication like malposition, inadvertent arterial puncture, pneumothorax, hemothorax, hematoma formation, nerve injury, catheter wire shearing(12)(13). Malposition is defined as catheter position any other than superior vena cava and right atrium junction(14)(15)(1)(16). It is always advisable to confirm the position of CVC tip in right position before using it. Traditionally Chest x ray is commonly done post procedure to confirm CVC in appropriate position. Advantage of chest x ray is, it is easy to perform but it is associated with risk of radiation exposure and time delay to arrive x ray image. Ultrasonography guided catheter insertion can be very useful to reduce incidence of such complications (17).

Echocardiographic bubble test is a newer method to confirm the catheter tip position using agitated saline(7)(8). In this method, with the use of echocardiographic probe, subcostal four chamber cardiac view is obtained and agitated saline injected from the distal most lumen of central venous catheter(8)(16). Agitated saline will appear as shiny bright image in right atrium in echo screen immediately after injecting. If there is delay in appearing agitated saline in right atrium more than 2 seconds, it will consider as malposition.

In our study, time of bubble test was defined by, (time taken from preparation of agitated saline till appearance of bubbles in RA on echocardiography) time interval between echocardiographic screening and appearance of bubble in right atrium. It was 8.106 ± 2.028 minutes (mean). And time for chest x ray was defined by interval between advising chest x ray till x ray image comes for review. It was 60.300 ±11.84 minutes (mean). P value for that is <0.0001, that was highly significant. in our study we found that echocardiographic bubble test has sensitivity of 98.91% and excellent positive predictive value of 96.808% whereas specificity of 72.72% and moderate negative predictive value for detection of CVC malposition. These findings suggest that the bubble test is an excellent test to detect correct position of CVC tip. Thus, it can be a good screening test for evaluating the normal position of CVC, however, the negative bubble test should be further evaluated by CXR.

The time taken to visualize the bubbles in the RA is probably an arbitrary value which depends on many factors like pressure difference, fluid viscosity, length and diameter of the catheter. In high cardiac output states also, saline will reach the RA more rapidly and produce false negative results. Choosing a cut of value of less than 2 sec can lead to better specificity but reduces sensitivity therefore reducing its utility as a screening test.  In past many studies done to investigate the accuracy and time taken for CVC tip position confirmation by bubble test and chest x ray. Many of them describe ultrasonographic bubble test as accurate and less time-consuming method. Also, it is associated with lesser life-threatening complication like pneumothorax (18). 

Kamalipour H et al. (19) had compared chest radiography with contrast enhanced ultrasonography with 93% concordance in both the technique. They derived sensitivity of 98%, specificity of 69% and Positive and negative predictive values were 95% and 85% respectively. They concluded that ultrasonographic confirmation of CVC tip can be used as a triage method in operating room on real time basis, but not suitable alternative of standard chest radiography. Results of our study coincides with their results.

M. MEGGIOLARO et al. (20) found that qualitative bubble test has sensitivity of 50% and specificity of 100 % where as quantitative bubble test with 500ms cut off time will have sensitivity of 100% and specificity of 99%. They have done two consecutive bubble tests and considered the mean of the two values for push to bubble time. We have taken the cut off time as 2 sec as it is easy to observe and don’t require much preparation. This gives 99% sensitivity but low specificity 70% and thus can be used as screening test but the negative results should be ruled out with CXR. Reducing the cut off time to <0.5 sec and doing second test will lead to increased specificity of the test but at the same time it will increases the true negative rate causing unnecessary exposure to CXR. This will again lead to delay in catheter utilization. The time taken in both the technique coinside with our syudy.

Khalid I. Khatib et al. (21) done a study in 2015 for Confirmation of endo venous placement of central catheter using the ultrasonographic “bubble test” on 25 patients. In their study they found that mean time taken for performing bubble test was 45 seconds and time taken for chest x ray confirmation was from 20 minutes to more than 1 hour. From their study they concluded that bubble test is easy to perform without consuming too much extra time for confirming endo venous placement of CVC.

Anthony J Weekes et  al (22) (2013) found that PTX and CVC tip malposition were rare after US-guided CVC placement. In contrast to our study, they derived sensitivity of 75% and specificity of 100%. Higher Specificity might be because of repeat saline flush test was done when first test result was uncertain. We had not done 2nd test and directly did chest x ray as a confirmatory test. Repeating the saline flush test will increase the chances of getting positive test but at the same time false positive result can also increase which may lead to avoidance of the confirmatory test in case of malpositioned CVC. They haven’t compared time required for CXR and bubble test in same study. Same author in their other study in 2016 derived mean time taken for CXR and Saline flush test was 20 min and 1.1 min respectively.

A recent study done by De Man L et al.(23)(2022) confirms the usefulness of ultrasonograhic bubble test to confirm the position of CVC. They concluded 85% sensitivity and 50% specificity of bubble test

Peter K et al. (2018) (24) concluded in their study that the overall sensitivity of the RASS was 100% and specificity was 94.32% where as positive and negative predictive value were 70.59% and 100% respectively.

From above study we concluded that the bubble test is as good as chest x ray in confirmation of CVC tip position and can be used as alternative to chest x ray as a screening test in emergency situation when waiting for chest x ray to come can delay the emergency interventions which can lead to hazardous consequences at patient’s end. In operation theatre also, where doing chest x ray after placement of CVC is not feasible. Doing bubble test takes very less time compare to chest x ray and easy to interpret.

1.       Pikwer A, Baath L, Davidson B, Perstoft I, Akeson J. The incidence and risk of central venous catheter malpositioning: A prospective cohort study in 1619 patients. Anaesth Intensive Care 2008;36:30‑7.

2.       Venugopal AN, Koshy RC, Koshy SM. Role of chest X-ray in citing central venous catheter tip: A few case reports with a brief review of the literature. J Anaesthesiol Clin Pharmacol. 2013 Jul;29(3):397-400. doi: 10.4103/0970-9185.117114. PMID: 24106371; PMCID: PMC3788245.

3.       Tawk S, Barakat E, Hammer F. A Proposed Simple and Accurate Technique for Optimal Long-Term Hemodialysis Catheter Tip Placement. J Belg Soc Radiol. 2018 Jan 31;102(1):21. doi: 10.5334/jbsr.1474. PMID: 30039035; PMCID: PMC6032382.

4.       Practice Guidelines for Central Venous Access 2020: An Updated Report by the American Society of Anesthesiologists Task Force on Central Venous Access. Anesthesiology. 2020 Jan;132(1):8-43. doi: 10.1097/ALN.0000000000002864. PMID: 31821240.

5.       Gibson F, Bodenham A. Misplaced central venous catheters: applied anatomy and practical management. Br J Anaesth. 2013 Mar;110(3):333-46. doi: 10.1093/bja/aes497. Epub 2013 Feb 5. PMID: 23384735.

6.       Hade AD, Beckmann LA, Basappa BK. A checklist to improve the quality of central venous catheter tip positioning. Anaesthesia. 2019 Jul;74(7):896-903. doi: 10.1111/anae.14679. Epub 2019 May 6. PMID: 31062348.

7.       Cortellaro F, Mellace L, Paglia S, Costantino G, Sher S, Coen D. Contrast enhanced ultrasound vs chest x-ray to determine correct central venous catheter position. Am J Emerg Med. 2014 Jan;32(1):78-81. doi: 10.1016/j.ajem.2013.10.001. Epub 2013 Oct 9. PMID: 24184012.

8.       Bou Chebl R, Kiblawi S, El Khuri C, El Hajj N, Bachir R, Aoun R, Abou Dagher G. Use of Contrast-Enhanced Ultrasound for Confirmation of Central Venous Catheter Placement: Systematic Review and Meta-analysis. J Ultrasound Med. 2017 Dec;36(12):2503-2510. doi: 10.1002/jum.14296. Epub 2017 Jun 29. PMID: 28660688.

9.       Saul, T, Doctor, M, Kaban, NL, Avitabile, NC, Siadecki, SD and Lewiss, RE. The Ultrasound‐Only Central Venous Catheter Placement and Confirma¬tion Procedure. J Ultras Med. 2015; 34(7): 1301–6. DOI: https://doi.org/10.7863/ultra.34.7.1301

10.    Meggiolaro, Marco Antônio, Alessio Scatto, Andrea de Zorzi, Erik Roman-Pognuz, Alessandro Lauro, Christian Passarella and Giuseppina Bonaccorso. “Confirmation of correct central venous catheter position in the preoperative setting by echocardiographic "bubble-test".” Minerva anestesiologica 81 9 (2015): 989-1000 .

11.    Buderer, N.M.F. (1996), Statistical Methodology: I. Incorporating the Prevalence of Disease into the Sample Size Calculation for Sensitivity and Specificity. Academic Emergency Medicine, 3: 895-900.

12.    Torres-Millán J, Torres-López M, Benjumea-Serna M. Ubicación de la punta del catéter venoso central en aurícula derecha: descripción en 2.348 pacientes críticos [Location of the central venous catheter tip in the right atrium: description in 2348 critical patients]. Med Intensiva. 2010 Dec;34(9):595-9. Spanish. doi: 10.1016/j.medin.2010.07.003. Epub 2010 Aug 10. PMID: 20702000.

13.    Wang L, Liu ZS, Wang CA. Malposition of Central Venous Catheter: Presentation and Management. Chin Med J (Engl). 2016 Jan 20;129(2):227-34. doi: 10.4103/0366-6999.173525. PMID: 26830995; PMCID: PMC4799551.

14.    Stonelake PA, Bodenham AR. The carina as a radiological landmark for central venous catheter tip position. Br J Anaesth. 2006 Mar;96(3):335-40. doi: 10.1093/bja/aei310. Epub 2006 Jan 16. PMID: 16415318.

15.    Lok CE, Huber TS, Lee T, Shenoy S, Yevzlin AS, Abreo K, Allon M, Asif A, Astor BC, Glickman MH, Graham J, Moist LM, Rajan DK, Roberts C, Vachharajani TJ, Valentini RP; National Kidney Foundation. KDOQI Clinical Practice Guideline for Vascular Access: 2019 Update. Am J Kidney Dis. 2020 Apr;75(4 Suppl 2):S1-S164. doi: 10.1053/j.ajkd.2019.12.001. Epub 2020 Mar 12. Erratum in: Am J Kidney Dis. 2021 Apr;77(4):551. doi: 10.1053/j.ajkd.2021.02.002. PMID: 32778223.

16.    Maury E, Guglielminotti J, Alzieu M, Guidet B, Offenstadt G. Ultrasonic examination: an alternative to chest radiography after central venous catheter insertion? Am J Respir Crit Care Med. 2001 Aug 1;164(3):403-5. doi: 10.1164/ajrccm.164.3.2009042. PMID: 11500340.

17.    Leung J, Duffy M, Finckh A. Real-time ultrasonographically-guided internal jugular vein catheterization in the emergency department increases success rates and reduces complications: a randomized, prospective study. Ann Emerg Med. 2006; 48:540–7.

18.    Vezzani A, Brusasco C, Palermo S, Launo C, Mergoni M, Corradi F. Ultrasound localization of central vein catheter and detection of postprocedural pneumothorax: an alternative to chest radiography. Crit Care Med. 2010 Feb;38(2):533-8. doi: 10.1097/CCM.0b013e3181c0328f. PMID: 19829102.

19.    Kamalipour H, Ahmadi S, Kamali K, Moaref A, Shafa M, Kamalipour P. Ultrasound for Localization of Central Venous Catheter: A Good Alternative to Chest X-Ray? Anesth Pain Med. 2016 Aug 10;6(5):e38834. doi: 10.5812/aapm.38834. PMID: 27847699; PMCID: PMC5101724.

20.    Pictorial essay: central venous catheters on chest radiographs, Krishnan Melarkode and M Y Latoo BJMP 2009:2(2) 55-56

21.    Baviskar, Ajitsubhash & Khatib, Khalid & Bhoi, Sanjeev & Galwankar, Sagar & Dongare, Harshad. (2015). Confirmation of endovenous placement of central catheter using the ultrasonographic "bubble test". Indian Journal of Critical Care Medicine. 19. 38-41. 10.4103/0972-5229.148642

22.    Weekes AJ, Johnson DA, Keller SM, Efune B, Carey C, Rozario NL, Norton HJ. Central vascular catheter placement evaluation using saline flush and bedside echocardiography. Acad Emerg Med. 2014 Jan;21(1):65-72. doi: 10.1111/acem.12283. PMID: 24552526.

23.    de Man L, Wentzel M, van Rooyen C, Turton E. Comparison between ultrasound and chest X-ray to confirm central venous catheter tip position. SA J Radiol. 2023 Jun 29;27(1):2587. doi: 10.4102/sajr.v27i1.2587. PMID: 37416693; PMCID: PMC10319935

24.    Korsten P, Mavropoulou E, Wienbeck S, Ellenberger D, Patschan D, Zeisberg M, Vasko R, Tampe B, Müller GA. The "rapid atrial swirl sign" for assessing central venous catheters: Performance by medical residents after limited training. PLoS One. 2018 Jul 16;13(7):e0199345. doi: 10.1371/journal.pone.0199345. PMID: 30011285; PMCID: PMC6047781.