Cecchi, E.

Chiostri, Marco

Gensini, Gian Franco

Giglioli, C.

Landi, D.

Mattesini, A.

Romano, Salvatore

Spini, V.

Valente, S.

English

Florence Research

Continuous renal replacement therapy: Should the cardiologist be able tomanage it outof intensive care units?Cristina Giglioli ⁎, Valentina Spini, Daniele Landi, Alessio Mattesini, Serafina Valente, Marco Chiostri,Salvatore Mario Romano, Gian Franco Gensini, Emanuele CecchiDepartment of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italya r t i c l e i n f oArticle history:Received 8 April 2011Accepted 13 May 2011Available online 11 June 2011Keywords:Continuous renal replacement therapyCongestive Heart failureContrast induced nephropathyAcute kidney injuryCardiac step down unitContinuous renal replacement therapy (CRRT) has receivedincreasing attention in recent years parallel to the publication ofseveral favourable data regarding the use of this technique in differentclinical conditions such as congestive heart failure (CHF) [1,2] andcontrast induced nephropathy (CIN) [3,4]. Moreover, the improve-ment in technology has led to the diffusion of devices easier to use,that can be managed in Cardiology Units also out of the intensive caresetting, overcoming logistic and practical problems.CRRT can be performed in cardiac patients with three differentmain techniques:a) Slow Continuous Ultrafiltration (SCUF): removes plasma waterthank to a transmembrane pressure gradient (diffusion); solutesare passively removed accompanying the plasma water flow(convection);b) Continuous Veno-Venous Hemofiltration (CVVHF): removes solutesbymeans of convection but fluid loss determined by ultrafiltration iscompensated by a reinfusion solution;c) Continuous Veno-Venous Hemo-Diafiltration (CVVHDF): removesliquids and solutes with the implementation of both dialysis andhemofiltration.From January 2005 to December 2010 132 patients were consecu-tively treated with CRRT in the Cardiac Step Down Unit (CSDU) of theUniversity of Florence, consisting of eight monitored beds with anurse/patients ratio of 1:4. In the present letter we report ourexperience with CRRT and, in particular, in-hospital outcomes ofpatients submitted to this procedure and data regarding safety of CRRTin a non-intensive environment.Themain indications to CRRT in our populationwere: decompensatedCHF in 63patients (47.7%), prevention or treatment of CIN in 42patients(31.8%) and acute kidney injury (AKI) for several causes in 27 criticalcardiac patients (20.5%).CHF patients were treated with CRRT if they showed at admissionsigns of fluid overloadwith peripheral edema N2+ and at least one ofthe following: 1) pulmonary rales or crackling; 2) dyspnea; 3) thirdheart sound; 4) jugular venous distension; 5) positive epato-jugularreflux; 6)maximal systolic arterial pulmonary pressure above 50 mmHg at echocardiogram; 7) radiographic pleural effusion. A clinicalscore was used to objectivate the severity of clinical status of ourpatients assigning one point for each sign or symptom mentionedabove (minimum value 2, maximum 8). CHF patients submitted toCRRT were those unresponsive to diuretic therapy despite theincreased doses. They were divided in two subgroups: a) thosewith serum creatinine N3 mg/dl or glomerular filtration rate (GFR)MDRD b30 ml/min/m2 were treated with CVVHDF; b) those withserum creatinine b3 mg/dl or GFRMDRDbetween 30 and 60 ml/min/m2treated with SCUF. Diuretic therapy was withdrawn during CRRT.CIN was defined as an absolute increase in serum creatinine≥0.5 mg/dl from baseline or as a relative increase≥25% from baselinewithin 48–72 hours after contrast medium administration after the⁎ Corresponding author at: Dipartimento del Cuore e dei Vasi, Azienda Ospedaliero-Universitaria Careggi, VialeMorgagni, 85 I - 50134 Firenze, Italy. Tel.:+39 0557949577; fax:+39 0557947617.E-mail address: cristinagiglioli@yahoo.it (C. Giglioli).Table 1Clinical and biohumoral parameters variations, modality of CRRT and its relatedcomplications in congestive heart failure patients.Congestive heart failure patients, n=63 (47.6%)Demographic featuresAge, years (mean±SD) 71.6±13.6Male gender, n (%) 43 (68.2)Hypertension, n (%) 33 (52.4)Diabetes mellitus, n (%) 30 (47.5)Dyslipidemia, n (%) 20 (15.1)Chronic kidney injury, n (%) 37 (58.7)Ischemic cardiomyopathy, n (%) 33 (25.0)Primitive cardiomyopathy, n (%) 22 (16.7)Valvulopathy, n (%) 8 (6.1)Ejection fraction pre-CRRT (mean±SD) 31.5±14.9In-hospital mortality, n (%) 8 (7.9)Modality of CRRTSCUF, n (%) 33 (52.4)CVVHDF, n (%) 30 (47.6)Treatment length, hours [median (IR)] 48 (72–96)Clinical andlaboratoryfeaturesAdmission(pre-CRRT)Discharge(post-CRRT)p ValueSerum creatinine,mg/dl(mean±SD)2.6±1.5 2.6±1.5 0.091Clinical score[median (IR)]5 (3.5 - 7) 1 (0–2.5) b0.001NT-proBNP[median (IR)]16878 (8914–34015) 5114 (1648–12808) b0.001Patients in NYHAclass I-II, n (%)4 (6.3) 29 (46.0) b0.001Patients in NYHAclassesIII–IV, n (%)59 (93.7) 34 (54.7) b0.001CRRT-relatedcomplicationsAnemia, n (%) 1 (0.8)Thrombocytopenia,n (%)1 (0.8)Infection, n (%) 1 (0.8)SCUF, Slow Continuous Ultrafiltration; CVVHDF Continuous Veno-Venous Hemodiafiltration;CRRT, Continuous Renal ReplacementTherapy., Slow Continuous Ultrafiltration; CVVHDF Continuous Veno-Venous Hemodiafil-tration; CRRT, Conti uous Renal ReplacementTherapy.233Letters to the Editorexclusion of alternative causes. CIN prevention with CRRT wasperformed with CVVHF in patients with severe chronic renal dysfunc-tion (GFR ≤30 ml/min/1.73 m2) following Marenzi's protocol [3,4] andaccording to recent guidelines on myocardial revascularization [5].Treatment of CIN with CRRT was performed with CVVHDF in patientswith an increase in creatinine values ≥3 mg/dl associated with oliguria48–72 hours after contrast medium administration.AKI was defined as an increase in serum creatinine N0.3 mg/dl(≥24 μmol/l) or increase ≥150% (N1.5 fold) respect to baselineassociated with a urine output b0.5 ml/kg/h for almost 6 hours [6]. Inthis group of patients treatment consisted in CVVHDF.CRRT was usually performed with a double-lumen catheter placedin the femoral vein and connected to the PRISMA™ System (HOSPAL-GAMBRO DASCO, Medolla, Italy) or Aquadex Flex Flow S-100 (CHFSolutions, Inc., Brooklyn Park, MN 55428, USA) when only SCUF wasindicated. Pre-dilution modality of treatment was preferred to post-dilution modality for its minor risk of filter clotting. Unfractionedheparin was used in all patients to prevent filter clotting maintainingaPTT between 40 and 60 s. In patients at high hemorrhagic risk aPTTwas maintained under 40 s, optimizing blood flow and maintainingfiltration fraction between 10% and 20%.Anemia was defined according to TIMI minor bleeding classifica-tion and thrombocytopenia as a platelet reductionN50% respect tobaseline.Tables 1 and 2 show demographic and clinical characteristics ofpatients who underwent CRRT for CHF, CIN prevention/treatment or AKI,respectively, as well as variations in some parameters determined byCRRT.CRRT was initially introduced in clinical practice in intensive careunits for the treatment of AKI associated with critical conditions suchas cardiogenic and septic shock. However, in the last few years the useof CRRT has been also extended to other conditions such as CHF andprevention or treatment of CIN, two conditions for which an intensiveenvironment is not always required. Parallel to this, new technologieshave become available offering devices that are easier to use,contributing to the diffusion of this treatment also out of the intensivecare units.These recent advances have led cardiologists to deal increasinglywith this technique and nurses to be specifically trained to manageCRRT devices.In agreement with this trend and with new evidences in this field,since 2005 we progressively introduced CRRT in our clinical practice;data reported in this letter suggest the safety and feasibility of thistechnique also in a CSDU.In our CHF patients CRRT has been able to improve clinical status anddetermine a significant reduction in clinical score, NYHA class and pro-BNP plasma levels with low rate of complications. In our populationCRRT was also used and resulted as effective in four patients in NYHAclass II at variance with previous studies demonstrating its efficacy inpatients with more advanced NYHA class [1,2].Moreover, according to the studies by Marenzi et al. [3,4] and torecent guidelines on myocardial revascularization [5] we used CRRTalso for CIN prevention in patients at high risk for this complication.Our experience confirmed the efficacy of these techniques since nopatient developed this complication and stable values of creatinineand higher urinary output after the procedure were observed.PatientswithAKI fromother causes have been shown tobenefit fromCRRT even though they have, also in our population, a higher mortality,confirming data from the literature according to which renal dysfunc-tion is one of the main determinant of in-hospital mortality [7–11].In conclusion, our data suggest that cardiologists should be able tomanage CRRT even out of an intensive care setting for almost thesethree subgroups of patients.The authors of this manuscript have certified that they complywith the Principles of Ethical Publishing in the International Journal ofCardiology [12].References[1] Costanzo MR, Guglin ME, Saltzberg MT, et al. Ultrafiltration versus intravenousdiuretics for patients hospitalized for acute decompensated heart failure. J Am CollCardiol 2007;49:675–83.[2] Costanzo MR, Saltzberg MT, Jessup M, Teerlink JR. Ultrafiltration versus intravenousdiuretics for patients hospitalized for acute decompensated heart failure (UNLOAD)investigators. Ultrafiltration is associated with fewer rehospitalizations thancontinuous diuretic infusion in patients with decompensated heart failure: resultsfrom UNLOAD. J Card Fail 2010;16:277–84.[3] Marenzi G, Marana I, Lauri G, et al. The prevention of radiocontrast-agent-inducednephropathy by hemofiltration. N Engl J Med 2003;349:1333–40.[4] Marenzi G, Lauri G, Campodonico J, et al. Comparison of two hemofiltrationprotocols for prevention of contrast-induced nephropathy in high-risk patients.Am J Med 2006;119:155–62.[5] Wijns W, Kolh P, Danchin N, et al. Guidelines on myocardial revascularization. ESCClinical Practice Guidelines. Eur Heart J 2010;31:2501–55.[6] Cuhaci B. More data on epidemiology and outcome of acute kidney injury withAKIN criteria: benefits of standardized definitions, AKIN and RIFLE classifications.Crit Care Med 2009;37:2659–61.[7] Waikar SS, Liu KD, Chertow GM. Diagnosis, epidemiology and outcomes of acutekidney injury. Clin J Am Soc Nephrol 2008;3:844–61.[8] Lameire N, Van Biesen W, Vanholder R. Acute renal failure. Lancet2005;365:417–30.[9] Cruz DN, Bolgan I, Perazella MA, et al. North East Italian Prospective Hospital RenalOutcome Survey on Acute Kidney Injury (NEiPHROS-AKI) Investigators. North EastItalian Prospective Hospital Renal Outcome Survey on Acute Kidney InjuryTable 2Clinical characteristics, complications and variation of creatininemia and urinary output in patients requiring CRRT for prevention or treatment of CIN and AKI.Demographic features Prevention of CIN, n=22 (16.7%) Treatment of CIN, n=20 (15.2%) Treatment of AKI, n=27 (20.5%)Age, years (mean±SD) 71.0±12.4 77.0±8.5 75.2±10.5Male gender, n (%) 16 (72.7) 14 (70.0) 14 (51.9)Chronic kidney injury, n (%) 22 (100) 13 (65.0) 20 (74.1)Diabetes mellitus, n (%) 9 (40.9) 9 (45.0) 14 (51.9)Contrast medium volume, ml (mean±SD) 275 (250–400) 300 (250–400) n.a.CRRT duration, hours [median (IR)] 32 (18–32) 36 (36–72) 42 (21–84)In-hospital mortality 0 1 (5.0) 5 (18.5)CRRT-related complicationsAnemia 1 (4.5) 1 (5.0) 1 (3.7)Thrombocytopenia 0 0 1 (3.7)Bleeding at the insertion site 0 1 (5.0) 0Clinical and laboratory featuresAdm. Dis. P Adm. Dis. P Adm. Dis. PSerum creatinine mg/dl (mean±SD) 2.8±1.0 2.1±1.0 b0.001 4.0±1.5 2.6±1.4 b0.001 4.5±2.3 2.9±1.9 b0.001Urine output ml/kg/h (mean±SD) 1.71±0.39 2.30±0.59 b0.001 0.39±0.10 1.87±0.61 b0.001 0.29±0.12 1.22±0.44 b0.001CIN, contrast induced nephropathy; AKI, acute kidney injury; CRRT, Continuous Renal Replacement Therapy; Adm., admission; Dis., discharge.I, c t kidney injury; CRRT, Continuous Renal Replacement Therapy; Adm., admi sion; Dis., discharge.234 Letters to the Editor(NEiPHROS-AKI): targeting the problem with the RIFLE Criteria. Clin J Am SocNephrol 2007;2:418–25.[10] Uchino S, Kellum JA, Bellomo R, et al. Beginning and Ending Supportive Therapy forthe Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients:a multinational, multicenter study. JAMA 2005;294:813–8.[11] Prowle JR, Bellomo R. Continuous renal replacement therapy: recent advances andfuture research. R Nat Rev Nephrol 2010;6:521–9.[12] Shewan LG, Coats AJ. Ethics in the authorship and publishing of scientific articles.Int J Cardiol 2010;144:1–2.0167-5273/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved.doi:10.1016/j.ijcard.2011.05.023Contrast transthoracic echocardiography versus transcranial Doppler for patentforamen ovale detectionGiovanni Corrado a,⁎, Laura Massironi b, Daniela Torta b, Fausto Rigo c, Sandro Beretta d, Dario Sansalone b,Eleonora Zenoni b, Antonio Mantero ba Department of Cardiology, Ospedale Valduce, Como, Italyb Department of Cardiology, Ospedale San Paolo, Milano, Italyc Department of Cardiology, Ospedale dell'Angelo, Mestre, Italyd Department of Neurology, Ospedale Civile, Vimercate, Italya r t i c l e i n f oArticle history:Received 10 April 2011Accepted 13 May 2011Available online 2 June 2011Keywords:Right-to-left shuntContrast microbubblesDiagnostic imaging toolsEchocardiographyEmbolism paradoxicalPatent foramen ovaleContrast transthoracic echocardiography (c-TTE)[1,2] and contrasttranscranial Doppler (c-TCD) [3,4] are widely used for noninvasivediagnosis of patent foramen ovale (PFO). We thought to evaluate in alarge series of patients the concordance between c-TTE and c-TCD inright-to-left shunt (RLS) diagnosis and in quantification. From June2006 to July 2009 RLS was looked for in two hundred thirty twoconsecutive patients (160 females, aged 42.6±15.3 years) whounderwent on succession c-TCD and c-TTE at echocardiographylaboratories of San Paolo and Dell'Angelo Hospitals (Milano andMestre-Venezia, Italy). All patients gave their informed consent. Thereason for RLS search was migraine in 167 patients (72%), stroke in 23patients (9.9%), TIA in 29 patients (12.5%) and other causes in 13patients (5.6%). Contrast TTE and TCD tests were performed using anagitated saline solution mixed with air [4]. Given that the Valsalvamaneuver (VM) increases the sensitivity of RLS detection all patientswere trained in VM execution. In all cases the study begunwith c-TCD.In case of no or little microbubbles (MB) detection at the MCA the testwas repeated with VM. Results were classified in a four-levelcategorization according to MB appearance in the TCD spectrum asfollows: 0 indicates no occurrence of MB (test negative),1 indicates 1–10 MB (small shunt), 2 indicatesN10 MB without “curtain” effect(medium shunt) and finally 3 indicates “curtain” effect, whereas MBare so numerous that a single MB cannot be discriminated within theDoppler spectrum (large shunt) [4]. Subsequently patients underwentc-TTE. Once again results were classified in a four-level categorizationaccording to MB appearance in the left hear after completeopacification of the right atrium [2]: 0 indicates no occurrence ofMB (test negative), 1 indicatesb10 MB passed through the PFO (smallshunt), 2 indicates a cloud ofN10 MB documented in the left atrium(medium shunt) and 3 indicates opacification of the left heart (largeshunt)[5]. Quantitative data were expressed as mean±standarddeviation. Inter observer agreement in the diagnosis and grading ofRLS both on c-TCD and c-TTE was assessed by calculating the Kappa-statistic. Odds Ratios and 95% Confidence Intervals were calculated.The concordance between c-TCD and c-TTE scores was estimatedusing the Lin's concordance correlation coefficient and the Spearman'srho rank correlation coefficient. Finally, the optimal trade-off betweensensitivity and specificity of c-TTEwas estimated bymeans of ReceiverOperating Characteristic (ROC) curve analysis. All calculations wererepeated on split subgroups with homogeneous diagnostic question.Overall, we noticed an excellent interobserver agreement both in c-TCD RLS scoring (K=0.962, 95%CI 0.93–0.99) and in c-TTE RLS scoring(K=0.985, 95%CI 0.96–1.00). Subsequently, we compared the c-TCDand c-TTE RLS gradations. In the overall study population theconcordance correlation coefficient (CCC) between c-TCD and c-TTERLS scores was CCC=0.68 (95%CI 0.60–0.74), indicating a moderatecorrelation between c-TTE and c-TCD. The Spearman's coefficient ofrank correlation (rho) was 0.68 (95%CI 0.60–0.74) confirming amoderate correlation between the two diagnostic procedures.Correlation and concordance between c-TCD and c-TTE RLS gradationswere then analyzed in two subgroups of patients with homogeneousdiagnostic question. The CCC between c-TCD and c-TTE RLS scores wasmoderate in patients with migraine (CCC=0.63, 95%CI 0.53–0.71),and was good in patients referred for cerebrovascular diseases (CVD)(CCC=0.87, 95%CI 0.79–0.92). The Spearman's coefficient of rankcorrelationwas 0.63 (95% CI 0.52 – 0.71) in patientswithmigraine and0.88 (95%CI 0.80–0.93) in patients with CVD, confirming the goodcorrelation between the two diagnostic procedures in this subgroup ofpatients. The diagnostic performance of c-TTE compared with thepresence of MB on c-TCD is exhibited by the Receiver OperatingCharacteristic (ROC) curve (Fig. 1). RLS score≥1 on c-TTE can predictthe presence of MB on c-TCD with the highest trade-off betweensensitivity and specificity both in CVD and in migraine. Nevertheless,in CVD patients c-TTE had a higher sensitivity (100.0; 95% CI 88.1–100.0) and specificity (73.9; 95% CI 51.6–89.8) than in patients with⁎ Corresponding author at: Unità Operativa di Cardiologia, Ospedale GeneraleValduce, Via Dante 11 22100 Como Italy. Fax: +39 031 308 047.E-mail addresses: gcorr@iol.it (G. Corrado), laura.massironi@tiscali.it (L. Massironi),danielatorta@hotmail.com (D. Torta), faustorigo@alice.it (F. Rigo), alberetta@tin.it(S. Beretta), mr_sansa@yahoo.it (D. Sansalone), eleonorazenoni@libero.it (E. Zenoni),antonio.mantero@ao-sanpaolo.it (A. Mantero).235Letters to the Editor

Continuous renal replacement therapy: should the cardiologist be able to manage it out of intensive care units?

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Continuous renal replacement therapy: should the cardiologist be able to manage it out of intensive care units?

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