Correspondence / American Journal of Emergency Medicine 34 (2016) 2029-2049 2043

(P = .03) greater percentage of adverse events in the CIN (16.7%) com- pared to non-CIN (2.4%) groups. The authors concluded that, “…CIN was…found to be responsible for increased mortality and adverse clinical events.”

I question the central tenet of the causal relationship of contrast ex- posure with Acute kidney injury . Most Toxic exposures such as CIN are defined solely upon observational studies such as this one by Yazici et al [1] showing an association between contrast exposure and AKI. Ob- servational studies for causal relationships are especially prone to con- founding bias where a hidden variable(s) explains the causal link between predictor and outcomes better than the observed temporal as- sociation. Without a prospective randomized controlled trial of suffi- cient sample size with appropriate safeguards against biases, a definitive causal relationship between contrast exposure and AKI can- not be accepted without some doubt.

Lipsitch et al [2] stated that noncausal associations between outcomes and exposures in observations studies are the result of mismeasurement (recall bias), confounding, or selection bias. To prevent confounding, Lipsitch et al [2] suggests a counterfactual test by designing a negative con- trol experiment where the observation is repeated under conditions not expected to produce the outcome of interest. If the outcome is encoun- tered without the exposure, then a confounding bias may exist.

A counterfactual methodology for testing the causal link between contrast and AKI would compare the incidence of AKI between patients’ exposed and unexposed to contrast. Such a counterfactual methodology of studying CIN from intravenous contrast was reported in systematic reviews of CIN by Rao and Newhouse [3] in 2006 and McDonald et al

[4] in 2013. These 2 systematic reviews found no statistically significant difference in the incidence of AKI in contrast-exposed compared to un- exposed patients. Most of the studies reviewed in these 2 systematic re- views mixed inpatients with emergency department (ED) patients, with and without chronic kidney disease. Sinert et al [5] studied ED pa- tients with normal baseline renal function (serum creatinine, b1.5 mg/ dL) comparing 773 contrast-exposed to 2956 unexposed. Using the con- ventional definition of CIN, unexposed compared to contrast-exposed patients had a significantly (P = .003) higher incidence of AKI 8.96% vs 5.69%, respectively. From these data, it would appear that intrave- nous contrast was not a risk for AKI but protected against hospital- acquired AKI. The patients in the contrast-exposed and unexposed Contrast-induced nephropathy related to “>groups that developed AKI by the CIN criteria had similar outcomes with respect for dialysis requirements and mortality rates.

The PROSPERO [6] study is a planned systematic review of CIN after in- travenous contrast will use a similar counterfactual methodology, includ- ing more recent studies by Davenport et al [7] and McDonald et al [8] that used propensity-matching analysis to reduce confounding bias of observa- tional studies [9]. Both the studies of Davenport et al [7] and McDonald et al [8] of patients with normal kidney function (serum creatinine, b1.5 mg/dL) also failed to find a higher rate of CIN in contrast-exposed com- pared to unexposed patients receiving Computed tomographic scans.

The study by Yazici et al [1] now goes one step further than linking contrast exposure with AKI, by attempting to assign a cause and effect relationship between CIN and a series of adverse events in APE patients. Because by definition CIN only occurs in patients with a preexisting in- dication for contrast, it is possible that other etiologies beside contrast exposure are in part or wholly responsible for AKI. Confounding the risk of contrast causing AKI includes not only the primary disease that prompted the contrast administration but also preexisting (chronic kid- ney disease or diabetes) or intercurrent complications such (arrhyth- mias or hypotension) common in APE patients. Acute pulmonary embolism patients are more likely to be critically ill than the typical pa- tient administered contrast, which may explain higher CIN rates (12% [10] to 13% [11]) in APE patients compared to CIN (4% [3] to 6.4% [4]) in all contrast-exposed patients.

Applying Occam’s razor, it would seem more plausible to assign AKI and any other untoward outcomes directly to the patients’ pulmonary embolism than postulating how a small change in kidney function

results in such divergent adverse events as nonrenal death, hemor- rhage, and respiratory failure. The findings of this study by Yazici et al

[1] pose a significant risk of a confounding bias conflating adverse

events from CIN with those complications (including AKI) primarily from APE. I would suggest that future studies of CIN and AKI compare the adverse events and incidence of AKI between APE patients random- ized to computed tomography angiography vs ventilation perfusion scans, not requiring iodinated contrast administration.

Richard Sinert, DO Department of Emergency Medicine SUNY-Downstate Medical Center

Kings county hospital Center, New York, NY

Tel.: +1 646 645 1086 (Mobile), +1 718 245 2973 (Office)

E-mail addresses: [email protected] [email protected]

http://dx.doi.org/10.1016/j.ajem.2016.07.049

References

1. Yazici S, Kiris T, Emre A, Ceylan A, Akyuz US, Uzun S, O A, et al. Relation of contrast nephropathy to adverse events in pulmonary emboli patients diagnosed with con- trast CT. Am J Emerg Med 2016;34:1247-50.
2. Lipsitch M, Tchetgen Tchetgen E, Cohen T. Negative controls: a tool for detecting confounding and bias in observational studies. Epidemiology 2010;21:383-8.
3. Rao QA, Newhouse JH. Risk of nephropathy after intravenous administration of con- trast material: a critical literature analysis. Radiology 2006;239:392-7.
4. McDonald JS, McDonald RJ, Comin J, Williamson EE, Katzberg RW, Murad MH, et al. Frequency of acute kidney injury following intravenous contrast medium adminis- tration: a systematic review and meta-analysis. Radiology 2013;267:119-28.
5. Sinert R, Brandler E, Subramanian RA, Miller AC. Does the current definition of contrast-induced acute kidney injury reflect a true clinical entity? Acad Emerg Med 2012;19:1261-7.
6. Kayibanda JF, Hiremath S, Knoll GA, Fergusson D, Chow BJ, Shabana W, et al. Does intravenous contrast-enhanced computed tomography cause acute kidney injury? Protocol of a systematic review of the evidence. Syst Rev 2014;3:94.
7. Davenport MS, Khalatbari S, Dillman JR, Cohan RH, Caoili EM, Ellis JH. Contrast material-induced nephrotoxicity and intravenous low-osmolality iodinated contrast material. Radiology 2013;267:94-105.
8. McDonald RJ, McDonald JS, Bida JP, Carter RE, Fleming CJ, Misra S, et al. Intravenous

   Contrast material-induced nephropathy: causal or coincident phenomenon? Radiol- ogy 2013;267:106-18.

   Luo Z, Gardiner JC, Bradley CJ. Applying propensity score methods in medical re- search: pitfalls and prospects. Med Care Res Rev 2010;67:528-54.

9. Mitchell AM, Jones AE, Tumlin JA, Kline JA. Prospective study of the incidence of contrast-induced nephropathy among patients evaluated for pulmonary embolism by contrast-enhanced computed tomography. Acad Emerg Med 2012;19(6):618-25.
10. Doganay S, Oguz AK, Ergun I. Increased of contrast-induced acute kidney injury in patients with pulmonary thromboembolism. Ren Fail 2015;37(7):1138-44.

    Contrast-induced nephropathy related to adverse events in pulmonary embolism patients: causation or conflation? Reply

    

    We would like to thank Dr Sinert for his interest in our article [1]. As stated in his letter, we found that contrast-induced nephropathy (CIN) was associated with mortality in patients with acute pulmonary embolism.

    The CIN which occurs after use of Contrast agents is associated with mortality in many clinical settings [2,3]. In addition, CIN is considered to be the third most common cause of inhospital Acute Kidney Injury [4]. In recent studies, AKI frequency has been shown to be similar in pa- tients receiving a contrast agent and those not receiving [5,6]. In these studies, there is an increase in serum creatinine without the use of con- trast agent, which meet the definition of AKI, and this situation is de- fined as hospital-acquired AKI. These studies brought to mind the

    2044 Correspondence / American Journal of Emergency Medicine 34 (2016) 2029-2049

    question whether CIN is actually the false identification of AKI (or “con-

    flation” as Dr Sinert stated in a better way).

    However, there are some issues to be considered here. First, we must remember that CIN is a diagnosis of exclusion, and all the other possible causes of AKI (eg, hemodynamic instability, bleeding, and usage of nephrotoxic drugs) should be excluded. We did not include the patients presenting in shock and using nephrotoxic drugs in our study [1].

    Another important issue is that most of the studies which com- pared the increase of serum creatinine in patients exposed to a con- trast agent and those did not are retrospective and the criteria used in selection of patients bring to mind some questions [5-7]. For ex- ample, the patients in these studies must have had the repeated cre- atinine measurement. Generally, this measurement is performed in high-risk patients for AKI. Therefore, high-risk patients for AKI may be chosen more often in these studies.

    In the aforementioned studies, patients who received contrast agent and those who did not may have different degrees of risk for AKI. Clini- cians will avoid using contrast agents in patients at risk for AKI. The use of contrast agent was independently associated with AKI in patients having baseline Creatinine levels greater than 1.5 mg/dL in a study by Davenport et al [8], where risk factors for AKI were similar between the groups. Our results are also in agreement with their results. In our analysis, a baseline estimated glomerular filtration rate less than 60 mL/min per 1.73m² was independently related to CIN [8].

    We agree that it would be useful to compare the adverse events and incidence of AKI between acute pulmonary embolism patients random- ized to contrast-enhanced computed tomography vs ventilation perfu- sion scans in large and randomized studies.

    Selcuk Yazici, MD

    Dr Siyami Ersek Thoracic and Cardiovascular Surgery Center

    Cardiology Clinic, Istanbul, Turkey Corresponding author at: Cihadiye Street, No: 61/10 A-Blok Altintepe, Maltepe, Istanbul 34840, Turkey

    Tel.: +90 50547482588; fax: +90 216 444 52 57

    E-mail address: [email protected]

    Tuncay Kiris, MD Ataturk Training and Research Hospital, Cardiology Clinic

    Katip Celebi University, Izmir, Turkey http://dx.doi.org/10.1016/j.ajem.2016.07.048

    References

    Yazici S, Kiris T, Emre A, Ceylan US, Akyuz S, Uzun AO, et al. Relation of contrast ne- phropathy to adverse events in pulmonary emboli patients diagnosed with contrast CT. Am J Emerg Med 2016;34:1247-50.

11. Mehran R, Nikolsky E. Contrast-induced nephropathy: definition, epidemiology, and

    patients at risk. Kidney Int Suppl 2006;100:S11-5.

    McCullough PA, Wolyn R, Rocher LL, Levin RN, O’Neill WW. Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. Am J Med 1997;103:368-75.

12. Hou SH, Bushinsky DA, Wish JB, Cohen JJ, Harrington JT. Hospital-acquired renal insuf-

    ficiency: a prospective study. Am J Med 1983;74:243-8.

    Newhouse JH, Kho D, Rao QA, Starren J. Frequency of serum creatinine changes in the absence of iodinated contrast material: implications for studies of contrast nephro- toxicity. Am J Roentgenol 2008;191(2):376-82.

13. McDonald RJ, McDonald JS, Bida JP, Carter RE, Fleming CJ, Misra S, et al. Intravenous contrast material-induced nephropathy: causal or coincident phenomenon? Radiolo- gy 2013;267(1):106-18.
14. Bruce RJ, Djamali A, Shinki K, Michel SJ, Fine JP, Pozniak MA. Background fluctu- ation of kidney function versus contrast-induced nephrotoxicity. Am J Roentgenol 2009;192(3):711-8.
15. Davenport MS, Khalatbari S, Dillman JR, Cohan RH, Caoili EM, Ellis JH. Contrast material-induced nephrotoxicity and intravenous low-osmolality iodinated contrast

    Should nurses use mechanical Chest compression devices during CPR??

    To the Editor,

    

    High-quality chest compressions are a key element in cardiopulmo- nary resuscitation, affecting the patients’ survival. This is pointed at by both the European Resuscitation Council (ERC) [1] and the American Heart Association [2] guidelines. To minimize interruptions in chest compressions, the guidelines recommend procedures such as intuba- tion or obtaining intravascular access to be performed without chest compression breaks. (See Figure.)

    According to the ERC guidelines, chest compressions in an adult should be performed with the frequency of 100 to 120 per minute, the depth of 5 to 6 cm, and the ratio of chest compressions to relaxation of 1:1. As shown by numerous studies, the effectiveness of chest compressions is insufficient in many cases, including resuscitation performed by medical personnel or prolonged resuscitation [3-5]. When the quality of manual chest compressions is low, ERC recom- mends the usage of Mechanical chest compression devices as a reason- able alternative [1].

    The aim of the study was to compare the parameters of chest com- pressions with and without the Lifeline ARM chest compression device (ARM; Defibtech, Guilford, CT) during simulated cardiopulmonary re- suscitation performed by nurses.

    The study was designed as a randomized crossover manikin trial and was accepted by the international review board of the International In- stitute of Rescue Research and Education. A total of 40 nurses with min- imum of 5 years experience in anesthesiology and intensive care or emergency medicine nursing participated in the study, conducted in July 2016. Before the trial, the participants received a 20-minute train- ing on Basic Life Support and the use of mechanical chest compression systems, including ARM (Figure). Then the nurses took part in a 10- minute practical training focused on the application of ARM. During the target study, each participant performed a single-rescuer 2-minute cycle of asynchronous resuscitation (without interruptions in chest compressions) with and without ARM.

    The participants were divided into 2 groups with the use of the Re- search Randomizer software (www.randomizer.org). The first group per- formed uninterrupted chest compressions without ARM (with the standard manual method), and the second using ARM, for 2 minutes. After a 30-minute break, each participant performed chest compressions with the other method. The cardiopulmonary resuscitation was carried out on a Resusci Anne training manikin (Laerdal Medical, Stavanger, Norway). The trial manikin was connected to a computer that allowed the chest compression and Ventilation parameters to be collected with the Skill Reporting software, version 2.0.0.14 (Resusci Anne SkillReporter; Laerdal Medical). While performing the resuscitation, the participants were not provided any information recorded by the manikin monitoring system and were guided only by their own experience.

    The effective compression rate during resuscitation with the ARM and during manual resuscitation varied and amounted to 96% (inter- quartile range, 94%-98%) vs 33% (interquartile range, 30%-37%), respec- tively (P b .001). The median rate of correct depth chest compressions was significantly different between the trials with the ARM and manual resuscitation (97% vs 35%, respectively; P b .001). Also, the median chest compression rate varied significantly between the trials (100 min^-1 with ARM vs 141 min^-1 without ARM; P b .001).

    Summing up, the nurses participating in the study performed chest compressions of poor quality. Therefore, continuous training is neces- sary to improve the Quality of chest compressions by this professional

    material. Radiology 2013;267(1):94-105. ? Source of support: No sources of financial and material support to be declared.