New-onset supraventricular arrhythmia during septic shock: prevalence, risk factors and prognosis

Abstract

Background

The aims of this study were to prospectively assess the prevalence of sustained (lasting more than 30 s) new-onset supraventricular arrhythmia (NOSVA) during septic shock, identify the associated factors (including septic myocardial dysfunction), and evaluate its impact on hemodynamics and prognosis.

Methods

Patients with a diagnosis of septic shock were screened in a medical intensive care unit of a tertiary hospital center in France with a continuous 12-lead EKG for the occurrence of NOSVA. Biological and clinical data (including septic myocardial dysfunction characterized by echocardiography) were collected. We also assessed the hemodynamic tolerance and prognosis of NOSVA.

Results

Among the 71 septic shock episodes assessed during the study, NOSVA occurred in 30 [prevalence of 42 %, 95 % confidence interval (CI) 30-53 %]. Among all recorded factors, only renal failure (as assessed by renal SOFA score at day 1) was associated with NOSVA and this difference persisted by multivariable analysis (odds ratio of 1.29, 95 % CI 1.03-1.62, p = 0.03). There was a significant increase in norepinephrine dosage during the first hour after SVA onset. NOSVA was associated with longer catecholamine use during septic shock as compared with patients in sinus rhythm, whereas ICU mortality was identical between groups.

Conclusions

We found a high prevalence of sustained NOSVA during septic shock. NOSVA was not related to septic myocardial dysfunction, but rather to acute renal failure, raising the hypothesis of an acute renocardiac syndrome.

Seemann et al. Ann. Intensive Care (2015) 5:27 DOI 10.1186/s13613-015-0069-5

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Web End = Aurlien Seemann1,2, Florence Boissier1,3, Keyvan Razazi1,4, Guillaume Carteaux1,4, Nicolas de Prost1,4, Christian BrunBuisson1,4 and Armand Mekontso Dessap1,4,5*

Abstract

Background: The aims of this study were to prospectively assess the prevalence of sustained (lasting more than 30 s) newonset supraventricular arrhythmia (NOSVA) during septic shock, identify the associated factors (including septic myocardial dysfunction), and evaluate its impact on hemodynamics and prognosis.

Methods: Patients with a diagnosis of septic shock were screened in a medical intensive care unit of a tertiary hospi tal center in France with a continuous 12lead EKG for the occurrence of NOSVA. Biological and clinical data (including septic myocardial dysfunction characterized by echocardiography) were collected. We also assessed the hemody namic tolerance and prognosis of NOSVA.

Results: Among the 71 septic shock episodes assessed during the study, NOSVA occurred in 30 [prevalence of 42 %, 95 % condence interval (CI) 3053 %]. Among all recorded factors, only renal failure (as assessed by renal SOFA score at day 1) was associated with NOSVA and this dierence persisted by multivariable analysis (odds ratio of 1.29, 95 % CI 1.031.62, p = 0.03). There was a signicant increase in norepinephrine dosage during the rst hour after SVA onset.

NOSVA was associated with longer catecholamine use during septic shock as compared with patients in sinus rhythm, whereas ICU mortality was identical between groups.

Conclusions: We found a high prevalence of sustained NOSVA during septic shock. NOSVA was not related to septic myocardial dysfunction, but rather to acute renal failure, raising the hypothesis of an acute renocardiac syndrome.

Keywords: Arrhythmia, Sepsis, Shock, Myocardial dysfunction

Background

Supraventricular arrhythmia (SVA) is the most common cardiac rhythm disturbance occurring in intensive care unit (ICU) patients [1]. Sepsis is frequently associated with new-onset SVA (NOSVA), which has been reported in 6% of patients with severe sepsis [2] and in 46% of those with septic shock [3]. Data evaluating risk factors for NOSVA during septic shock are scarce [2, 4].

Septic myocardial dysfunction is characterized by an acute, reversible depression of left ventricle (LV)

contractility with normal or low lling pressures [5]. Its mechanisms are not fully understood, though circulating cytokines or cellular respiration alteration resulting from mitochondrial dysfunction may play a crucial role [6]. Septic cardiomyopathy may also involve diastolic dys-function [7] and right ventricle dysfunction [8]. Whether septic cardiomyopathy may constitute an arrythmogenic condition is unknown to date. In addition, whether ino-tropic drugs used to correct LV systolic dysfunction in septic shock patients [8] may increase the risk of NOSVA remains unclear.

SVA has been associated with increased morbidity related to circulatory compromise, cardio-embolic events or hemorrhagic complications of anticoagulant

*Correspondence: [email protected]

1 APHP, CHU Henri Mondor, DHU ATVB, Service de Ranimation Mdicale, 51, avenue du Mal de Lattre de Tassigny, 94 010 Crteil Cedex, FranceFull list of author information is available at the end of the article

2015 Seemann et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License

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Seemann et al. Ann. Intensive Care (2015) 5:27

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treatments. Little is known about the prognostic impact of NOSVA in the context of septic shock [2].

The aim of our study was to prospectively assess the prevalence of NOSVA during septic shock, to identify the associated factors (including the role of septic myocardial dysfunction), and to evaluate its impact on hemodynamics and outcome of patients.

Patients andmethods

Patients

Patients who met septic shock criteria (as dened according to the ACCP/SCCM Consensus Conference [9]) were prospectively included at the medical ICU of Henri Mondor University Hospital (Crteil, France) between October 2011 and December 2012. Non-inclusion criteria were cardiac surgery within the preceding month, chronic heart failure (dened by a baseline left ventricular ejection fraction below 45%) or a history of persistent SVA. The study was approved by the institutional ethics committee (Comit de Protection de Personnes Ile de France IX) as a component of standard care and patients consent was waived. Written and oral information about the study was given to the families. Patients severity was evaluated by the McCabe and Jackson score for underlying diseases [10], the SAPS II score for acute illness at ICU admission [11] and the SOFA (sequential organ failure assessment) score for organ dysfunction during septic shock [12]. Chronic renal failure was dened as a glomerular ltration rate below 30 ml/min/1.73 m2 according to MDRD formula [13]. Acute renal failure and other organ failures were dened using the SOFA score [12]. Acute respiratory distress syndrome (ARDS) was dened according to the Berlin criteria [14]. Blood concentration of thyroid stimulating hormone, NT-pro BNP and cardiac troponin T were assessed using an immuno-assay on a COBAS 6000 analyzer (Roche Diagnostics, Boulogne-Billancourt, France). Follow-up for the study was at least until ICU discharge.

NOSVA

All patients were continuously monitored with a reconstructed 12-lead EKG (using a continuous 6-lead cardiac monitoring, Drger Innity Acute Care System, Antony, France). EKG data were automatically recorded, digitally stored and checked daily for occurrence of NOSVA during the entire course of septic shock. SVA episodes lasting more than 30 s were assessed by two cardiologists (any discrepancy being solved by consensus) and classied as atrial brillation, atrial utter or atypical utter, using standard denitions [15].

Septic myocardial dysfunction

To evaluate cardiac function, we used transthoracic echocardiography (TTE) or multiplane transesophageal

echocardiography (TEE), when TTE did not allow accurate measurements because of poor acoustic windows. Echocardiograms were performed by trained operators (competence in advanced critical care echocardiography) [16] using an iE33 system (Philips Ultrasound, Bothell, WA, USA) with a standard procedure [17]. Briey, the following echocardiographic views were examined: four-chamber and two-chamber long-axis views to assess left ventricle (LV) ejection fraction (computed from LV volumes using the bi-plane Simpson method [18] when image quality was good, or visually estimated when poor image quality did not allow sufficient identication of the endocardium [19]), right and left atrium size [18], right ventricle size (a dilated RV was dened by an end-diastolic RV/LV area ratio >0.6) [20]), right ventricle function (using the tricuspid annular plane systolic excursion and tissue Doppler peak systolic wave at the tricuspid valve annulus [21]); long-axis M-mode view of the superior (TEE) or inferior (TTE) vena cava to assess their respiratory variability [22]; and the presence of pericardial eusion. Pulsed-wave Doppler aortic ow was obtained at the level of the aortic annulus and the velocitytime integral was automatically processed by tracing the envelope of aortic ow for cardiac index calculation. Echocardiographic images were digitally stored, and a computer-assisted evaluation was performed o-line by two trained operators. Septic cardiac dysfunction was dened as an LVEF <45% or the need for an inotrope infusion in order to achieve an LVEF 45%.

Statistical analysis

The data were analyzed using SPSS Base 13.0 (SPSS Inc, Chicago, IL, USA) and R 2.15.2 (The R Foundation for Statistical Computing, Vienna, Austria) statistical software packages. Continuous data were expressed as median [25th75th percentiles], unless otherwise specied and were compared using the MannWhitney test for independent samples and the Friedman test for related samples. Categorical variables, expressed as percentages, were evaluated using the Chi-square test or Fisher exact test. To evaluate independent factors associated with NOSVA (time-dependent variable), signicant or marginally signicant univariate risk factors (p<0.10) recorded prior or at the time of the rst episode of NOSVA, were examined using backward stepwise multivariate Cox proportional-hazards regression model; septic myocardial dysfunction and patient severity as assessed by SAPS II score at ICU admission were also included in the model; thus, the ve variables included in the model were SAPS II score at ICU admission, age, septic myocardial dysfunction, renal and non-renal SOFA scores at day 1 of septic shock. Coefficients

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Table 1 Patients baseline characteristics, according tothe occurrence ofnew-onset supraventricular arrhythmia duringat least one septic shock episode

were computed by the method of maximum likelihood. Two-tailed p values lower than 0.05 were considered signicant.

Results

Patients characteristics andNOSVA

Eighty-six patients were admitted in our unit with a diagnosis of septic shock during the study period. Among them, 21 patients were excluded because of cardiac surgery within the preceding month (n=8), chronic heart failure (n = 6), history of permanent atrial brillation (n=4) or logistic difficulties impeding proper data collection (n=3). Thus, a total of 65 patients were included in the study, with 71 episodes of septic shock (six patients exhibited two distinct episodes of septic shock during the study period). Baseline characteristics of included patients are displayed in Table1. SAPS II at ICU admission was 51 [3968], and SOFA score at onset of septic shock was 10 [714]. NOSVA occurred during 30 septic shock episodes (in 27 patients), dening a prevalence of 42% (95% CI 3054%). In the six patients with two distinct episodes of septic shock (more than 1week apart), three experienced a paroxysmal NOSVA during the rst episode with a relapse during the second episode, one experienced NOSVA during the rst episode only, and two remained in sinus rhythm during both episodes. NOSVA subtypes were atrial brillation (n=23), atypical utter (n=4) and atrial utter (n=3). The median time from septic shock onset to NOSVA was 2 [14]

days, with 15 (50.0%) episodes occurring on the rst day of septic shock. NOSVA occurred only once during 19 septic shock episodes and occurred two or more times during 11 septic shock episodes. The median cumulative length of NOSVA was 19.5 [357] h.

Factors associated withNOSVA occurrence

There was no signicant dierence in baseline characteristics between patients with or without NOSVA, including cardiovascular risk factors, cardiac medications, chronic renal failure, thyroid dysfunction, and SAPS II score at ICU admission (Table1). Organ dysfunction and treatments administered during septic shock according to the occurrence of NOSVA are displayed in Table2. Renal SOFA score at day 1 of septic shock was signicantly higher in patients with NOSVA. Among the 11 patients with a NOSVA episode who needed dialysis during shock, arrhythmia occurred before dialysis initiation in six patients. Other organ dysfunctions (neurological, cardiovascular, hematological, respiratory, coagulation and hepatic) had similar rates between groups. Daily uid balance was not associated with the occurrence of NOSVA. Maximal doses of catecholamines infused did not differ between patients with NOSVA and others. Biological

data, including blood potassium, thyroid stimulating hormone, cardiac Troponin T and NT-pro-BNP levels were similar between groups. Respiratory variables and the use of superior vena cava central line were similar between groups. Overall, steroid use for septic shock was signicantly higher among patients with NOSVA as compared to those without, but this dierence disappeared when considering only steroids administered before SVA onset.

Temperature and biological data at the time of the rst occurrence of SVA are displayed in Table3. Overall, these variables were within the normal range in the majority of patients experiencing the rst SVA episode, except for elevated serum urea and creatinine which were common in this group.

Table 4 shows echocardiographic parameters in patients with and without NOSVA. As expected,

NOSVA duringseptic shock episode p value

Never (n=38) Ever (n=27)

Age, years 55.5 [48.568.5] 66 [5675.0] 0.071 Weight, kg 73.0 [57.085.0] 72.0 [64.089.0] 0.464 Height, cm 171 [164178] 170.0 [162.55173.5] 0.468 Female sex 15 (39.5) 14 (51.9) 0.323 History of cardiac

disease

15 (39.5) 6 (22.2) 0.143

Coronary artery disease

7 (18.4) 4 (14.8) 0.751

Paroxysmal SVA 3 (7.9) 5 (18.5) 0.260 Valvular heart disease 3 (7.9) 1 (3.7) 0.636 PM or ICD 2 (5.3) 1 (3.7) >0.99 Chronic renal failure 3 (8.1) 2 (7.4) >0.99 Chronic dialysis 2 (5.3) 2 (7.4) >0.99 History of stroke 3 (7.9) 3 (11.1) 0.686 History of thyroid

dysfunction

2 (5.3) 1 (3.7) >0.99

Diabetes 8 (21.1) 5 (18.5) 0.801 Smoker 11 (28.9) 8 (29.6) 0.952 History of dyslipidemia 5 (13.2) 5 (18.5) 0.729 History of hypertension 15 (39.5) 8 (29.6) 0.413 Betablocker use 13 (34.2) 7 (25.9) 0.589 Amiodarone use 4 (10.5) 2 (7.4) >0.99 McCabe score 1.0 [0.02.0] 1.0 [0.02.0] 0.321 SAPS II score at ICUadmission

48.5 [33.262.2] 56 [4071] 0.136

Data are n (%) or median [25th75th percentile] unless otherwise specied Chronic renal failure was dened as a glomerular ltration rate below 30ml/

min/1.73m2 according to simplied MDRD formula [13]

NOSVA new-onset supraventricular arrhythmia, PM pacemaker, ICD intra-cardiac debrillator, SAPS Simplied Acute Physiologic Score, ICU intensive care unit, LVEF left ventricular ejection fraction

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Table 2 Organ dysfunction, biological data andtreatments duringseptic shock according tosupraventricular arrhythmia occurrence

Sinus rhythm (n=41) SVA (n=30) p

SOFA day 1

Global (024) 10.0 [7.012.5] 10 [816] 0.369 Neurological (04) 1.0 [0.04.0] 1.0 [0.04.0] 0.869 Respiratory (04) 2.0 [0.04.0] 2.0 [0.83.0] 0.976 Cardiovascular (04) 4.0 [4.04.0] 4.0 [4.04.0] 0.709 Renal (04) 1.0 [0.02.5] 2.0 [1.04.0] 0.034 Coagulation (04) 0.0 [0.01.5] 1.0 [0.02.0] 0.573 Hepatic (04) 0.0 [0.02.0] 0.0 [0.01.25] 0.875 Day 1 blood gasespH 7.33 [7.217.41] 7.32 [7.247.40] 0.802 PCO2, mmHg 37.0 [29.044.5] 36.0 [30.747.5] 0.692

PO2, mmHg 123.0 [84.5185.5] 102.0 [76.0215.2] 0.802 Bicarbonates, mmol/L 19.0 [15.925.2] 20.5 [17.025.0] 0.518

Lactate, mmol/L 2.90 [1.434.30] 2.10 [1.403.60] 0.514 FIO2, % 100 [55100] 100 [70100] 0.910

PEEP, cmH2O 5 [5] 5 [5] 0.759 Thyroid stimulating hormone, UI/L 0.94 [0.353.12] 1.04 [0.342.26] 0.694

Cardiac Troponin peak between day 1 and day 3, ng/L 44 [12.5295] 157.5 [22.7545.8] 0.222 NT proBNP peak between day 1 and day 3, pg/mL 8092 [242432,410] 15,522 [598746209] 0.229 Minimal potassium level during septic shock, mmol/L 3.3 [2.83.7] 3.2 [2.93.4] 0.571 Maximal potassium level during septic shock, mmol/L 4.6 [4.35.2] 4.5 [4.25.1] 0.771 Hemodynamic treatmentsCumulative uid balance during shock, mL 5358 [24019965] 4233 [32419682] 0.979 Daily uid balance during shock, mL/day 2285 [15543825] 1387 [10801859] 0.106 Dobutamine use during shock 8.0 (19.5) 5 (16.7) 0.759 Dobutamine maximal dose, g/kg/mina 5.0 [5.013.8] 10.0 [5.012.5] 0.622 Dobutamine maximal dose, g/kg/min, mean (SD)a 7.8 (4.9) 9.0 (4.2)

Norepinephrine use during shock 40 (97.6) 29 (96.7) >0.99 Norepinephrine maximal dose, mg/ha 2.9 [1.28.0] 3.3 [2.010.0] 0.210 Norepinephrine maximal dose, mg/h, mean (SD)a 5.1 (5.5) 6.7 (6.4)

Epinephrine use during shock 3 (7.3) 3 (10.0) 0.692 Dual catecholamine use during shock 10 (24.4) 6 (20.0) 0.662 Length of catecholamine use during shock, days 3 [25] 4 [37] 0.035 Length of vasopressor use during shock, days 3 [25] 4 [37.0] 0.021 Respiratory treatmentsInvasive mechanical ventilation 33 (80.5) 27 (90.0) 0.335 Mild ARDS 7 (17.9) 7 (24.1) 0.532 Moderate to severe ARDS 17 (41.5) 11 (36.7) 0.683 Other treatmentsDialysis during shock 7 (17.1) 11 (36.7) 0.061 Steroid use during shock 25 (61.0) 25 (83.3) 0.041 Steroid use before SVA onset 25 (61.0) 14 (46.7) 0.231 Superior vena cava central line in place during shock 13 (31.7) 10 (33.3) 0.885

Data are n (%) or median [25th75th percentile] unless otherwise specied

SVA supraventricular arrhythmia, SOFA sepsis-related organ failure assessment, PEEP positive end-expiratory pressure, ARDS acute respiratory distress syndrome

a Only patients receiving the drug during septic shock were considered

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Table 3 Body temperature andbiological variables stratied according to their reference limits, at time of rst occurrence of supraventricular arrhythmia during septic shock

Variables SVA (n=30)

Temperature, C 37.3 [36.038.2] Temperature >38.3 C 7 (21.9) Temperature <36.0 C 4 (12.5) Potassium level, mmol/L 3.7 [3.44.2] Potassium level <3.5 mmol/L 8 (25.0) Potassium level >5 mmol/L 2 (6.3) Glycemia, mmol/L 6.5 [5.58.4] Glycemia <4 mmol/L 3 (9.7) Glycemia >10 mmol/L 6 (19.4)pH 7.39 [7.297.44] pH <7.38 14 (43.8) PaCO2, mmHg 34.0 [30.040.2]

PaO2, mmHg 100 [85164] PaO2 <60 mmHg 1 (3.1 %)

SaO2 (%) 98 [96100] Bicarbonates, mmol/L 21.2 [18.024.8]

Lactates, mmol/L 1.6 [1.33.3] Serum creatinine, mol/L 157 [90272] Serum creatinine >130 mol/L 20 (62.5) Serum urea, mmol/L 12.9 [7.921.1] Serum urea >7 mmol/L 26 (81.3) PaO2/FiO2 ratio 228 [175340]

echocardiograms were performed less often in sinus rhythm in the NOSVA group. Cardiac chamber sizes, presence of pericardial eusion as well as median LVEF were similar between the two groups. The presence of septic myocardial dysfunction was similar between groups (p=0.303 and p=0.329 for Chi-square test and log-rank test, respectively).

In the Cox proportional-hazards regression analysis adjusted for septic myocardial dysfunction, SAPS II score and renal and non-renal SOFA scores at day 1 of septic shock, the only factor signicantly associated with NOSVA was the renal SOFA score at day 1 of septic shock (hazard ratio of 1.29, 95% CI 1.031.62, p=0.03;

Table5).

Treatment ofNOSVA

A treatment for cardioversion was administered in 21 of 30 episodes of NOSVA, including magnesium sul-fate (n=6), amiodarone (n=19), and/or electric shock (n=3). Cardioversion was eective in 18 (86%) cases.

Curative anticoagulant treatment with heparin was used in eight (27%) patients with NOSVA; in the other cases, the attending physician considered that the benet/risk ratio of curative anticoagulation was unfavorable. No stroke was diagnosed among patients with NOSVA up to ICU discharge.

Outcome ofNOSVA

Table6 shows hemodynamic changes induced by the rst recorded episode of NOSVA. There was a trend towards

Data are n (%) or median [25th75th percentile] unless otherwise specied SVA supraventricular arrhythmia

Table 4 Echocardiographic data duringseptic shock

Sinus rhythm (n=41) SVA (n=30) p

Echocardiogram on sinus rhythm 40 (97.6)a 23 (76.7) 0.006 Echocardiogram under inotropes 2 (4.9) 4 (13.3) 0.233 LVEF, % 60 [4460] 59 [4460] 0.587 Septic myocardial dysfunction (n = 69)b 11 (28.2) 12 (40.0) 0.303

Cardiac index, L/min/m2 2.8 [2.23.6] 3.4 [2.53.8] 0.131 E/e ratio 8.5 [6.911.5] 8.3 [5.310.8] 0.547 RV/LV ratio 0.6 [0.40.7] 0.5 [0.40.7] 0.818 RV dilatation 20 (51.3) 12 (42.9) 0.496 RA size, cm2 12.1 [11.017.5] 15.6 [11.019.7] 0.422 LA size, cm2 17.0 [14.221.0] 18.0 [14.019.5] 0.879 TAPSE, mm 20.0 [17.022.0] 17.0 [13.825.0] 0.150 Tricuspid tissue Doppler s wave, cm/s 13 [1014] 13 [815] 0.812 Pericardial eusion 3 (7.3) 4 (13.3) 0.446

Data are n (%) or median [25th75th percentile]

SVA supraventricular arrhythmia; E/e ratio ratio of transmitral Doppler early (E) lling velocity to tissue Doppler early diastolic mitral annular velocity; RA right atria; LA

left atria; LV left ventricle; RV right ventricle, RV dilatation was dened as end-diastolic area ratio >0.6; TAPSE tricuspid annular plane systolic excursion

a One patient had internal pacing

b Two patients were excluded from this analysis because of a poor echogenicity

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Table 5 Factors associated withnew-onset supraventricular arrhythmia occurrence byCox analysis

Variable Hazard ratio (95% CI), p value

Univariate Multivariable

SAPS II score at ICU admission

1.02 (1.001.03), p = 0.05 I/NR

Age 1.02 (0.991.05), p = 0.23 I/NR

Septic myocardial dysfunction

1.40 (0.682.92), p = 0.36 I/NR

Renal SOFA 1.28 (1.021.60), p = 0.03 1.29 (1.03 1.62), p = 0.03

Nonrenal SOFA 0.99 (0.901.11), p = 0.97 I/NR

SAPS Simplied Acute Physiologic Score; SOFA sepsis-related organ failure assessment; ICU intensive care unit; I/NR included, but not retained in the nal model

a decrease in mean, systolic and pulse arterial pressure despite a signicant increase in norepinephrine dosage during the rst hour after SVA onset. NOSVA was associated with longer catecholamine use and longer vasopressor use during septic shock (Table2). ICU mortality was identical between patients with NOSVA and those without [16 (42.1%) vs. 13 (48.1%), p=0.63], whereas there was a trend towards prolonged ICU length of stay in ICU survivors in the former group (16.0 [10.532.0] days vs. 8.5 [4.024.5] days, p=0.08).

Sensitivity analyses

When repeating the analyses while considering only the rst episode of septic shock in patients with multiple episodes, we found concordant results: (1) in the Cox proportional-hazards regression analysis, the only factor associated with NOSVA was the renal SOFA score at day 1 of septic shock [hazard ratio of 1.26 (95% CI 0.991.60), with a marginally signicant p value (p = 0.06]; (2) NOSVA was associated with longer catecholamine

use (4 [37] vs. 3 [26], p=0.049), and vasopressor use (4 [37] vs. 3 [25], p=0.03) during septic shock, and a trend towards longer ICU length of stay in survivors (16.0 [10.032.0] days vs. 8.5 [4.024.0] days, p=0.067).

Discussion

We report a high prevalence of NOSVA (42%; 95% CI [3054%]) during septic shock. NOSVA was not associated with septic myocardial dysfunction, but with renal failure by multivariable analysis. Patients with NOSVA exhibited longer durations of shock and a trend towards longer ICU stay.

The prevalence of NOSVA in our study is higher than reported in the general ICU population [1, 2, 23], but comparable to the 46 % atrial brillation rate reported by Meierhenrich et al. [3] in a cohort of patients with septic shock. The higher prevalence of SVA in septic shock patients might be related to their higher severity of illness. The use of inotropes in septic shock patients is unlikely to fully explain such a dierence, since many of our patients presented NOSVA before initiating catecholamine support.

We were unable to demonstrate an association between the occurrence of NOSVA and septic myocardial dys-function, as assessed by LVEF. Several explanations are possible. First, LVEF may not be the ideal criterion to assess septic cardiomyopathy, notably because of its load-dependency. However, evaluation of cardiac function in our patients was done after uid loading and while receiving vasoconstrictors. Whether echocardiographic parameters less dependent on afterload, such as speckle tracking derived strain-rate, may better characterize septic cardiomyopathy warrants further research. Second, the mechanisms of septic myocardial dysfunction and substrates/ triggers of SVA may dier. Septic cardiomyopathy mainly aects heart ventricles, with depressed contractility and

Table 6 Hemodynamic data immediately beforeand duringthe rst hour ofthe rst episode ofsupraventricular arrhythmia

Data are n (%) or median [25th75th percentile] unless otherwise specied SVA supraventricular arrhythmia

a Only patients receiving the drug before or after SVA onset were considered

Before SVA onset (n=30) After SVA onset (n=30) p

Systolic arterial pressure, mmHg 114 [97127] 97 [86118] 0.076 Diastolic arterial pressure, mmHg 58 [5163] 58 [4764] 0.513 Mean arterial pressure, mmHg 77.0 [70.087.0] 73.0 [58.580.5] 0.056 Arterial pulse pressure, mmHg 54 [3970] 42 [3157] 0.081 Heart rate, beats/min 99 [87118] 140 [123165] <0.001 Dobutamine dose, g/kg/mina 7.5 [5.010.0] 7.5 [5.010.0] >0.99 Norepinephrine dose, mg/ha 1.7 [0.33.0] 1.8 [0.54.5] 0.010 Epinephrine dose, mg/ha 1.3 [0.52.0] 1.5 [0.03.0] 0.655

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low or normal lling pressures [6], whereas SVA is an atrial disorder that is mainly inuenced by atrial pressure and autonomous nervous system tone. Cardiac biomarkers (B-type natriuretic peptides and troponins), which are mainly released from the ventricular myocytes and mostly inuenced by left ventricle function and mass, were not signicantly associated with SVA in our series despite a trend towards higher values in the NOSVA group.

We found an association between NOSVA and renal failure by univariate and multivariable analysis. Patients with NOSVA exhibited higher values of serum urea and creatinine, and a higher renal SOFA score as compared to patients in sinus rhythm, whereas the prevalence of chronic renal failure and chronic dialysis was similar between groups. Cardiorenal syndrome (CRS) is a complex pathophysiological disorder of the heart and kidneys in which acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ [24]. The association we observed between acute renal failure and NOSVA may correspond to either a type 1 CRS (acute cardiorenal syndrome, i.e., an acute deterioration in cardiac function that leads to acute kidney injury), a type 3 CRS (acute renocardiac syndrome, i.e., an acute kidney injury that leads to acute cardiac injury), or a type 5 CRS (secondary cardiorenal syndrome, i.e., a systemic disorder causing cardiac and renal dysfunction) [25, 26]. Hemodynamic alteration during SVA episodes might have impeded renal perfusion, thus leading to an acute cardiorenal syndrome. However, the renal SOFA score was signicantly dierent between the NOSVA group and the sinus rhythm group from the very start of septic shock (day 1), favoring the hypothesis of an acute renocardiac syndrome. The mechanisms underlying acute renocardiac syndrome are not clearly understood, but may involve direct (e.g., cytokines, sympathetic tonus and reninangiotensinaldosterone system) or indirect (e.g., uid and electrolyte imbalances) eects of acute kidney injury on the heart [27, 28]. However, in our study, the potential role of dyskalemia and uid balance on the occurrence of NOSVA did not seem pivotal. Further studies are needed to better scrutinize the spectrum of acute renocardiac syndrome in septic shock patients.

As expected, the occurrence of NOSVA during septic shock was associated with a poor acute hemodynamic tolerance, with a fall in arterial pressure and increased doses of catecholamines. Indeed, the loss of auricular systole and tachycardia-related shortening of ventricular diastole may both contribute to ventricular lling impairment. NOSVA was also associated with longer use of drugs and vasopressors, and a trend towards longer ICU stay. Whether NOSVA is a direct cause of prolonged catecholamine use and longer ICU stay or merely an

indicator of severity of illness remains to be determined. The absence of clinical ischemic stroke in our study despite a low curative anticoagulation rate underscores the need to weight the benet/risk ratio of this treatment for each patient with NOSVA in the ICU setting.

Our study has several limitations. First, the study power was limited by the inclusion of only 71 episodes of septic shock. We cannot formally exclude a possible relationship between septic myocardial dysfunction and NOSVA in a larger sample size. In view of the 30 events observed, we did not strictly follow the classical rule of a minimum of 10 outcome events per predictor variable in the multivariable analysis [29], but our analysis fullled the minimum of 5 events per predictor variable proposed by recent simulation studies [30]. Second, we included some patients with multiple septic shock episodes (more than 1 week apart). Our sensitivity analysis considering only the rst episode yielded nearly similar results despite a reduced power. However, we cannot exclude a role for personal susceptibility in the occurrence of NOSVA. Third, we could not perform consecutive echocardiograms during sinus rhythm and at the onset of SVA to better scrutinize hemodynamic changes induced by SVA.

Conclusions

In conclusion, our study showed that sustained NOSVA is frequent during septic shock, poorly tolerated, and is associated with longer catecholamine use. Renal failure, but not myocardial dysfunction, was signicantly associated with occurrence of NOSVA during septic shock, raising the hypothesis of an acute renocardiac syndrome.

Authors contributions

AS, AMD and CBB designed the study, interpreted the data and drafted the manuscript. AS, FB, KR, GC, and NdP collected and interpreted data. All authors read and approved the nal manuscript.

Author details

1 APHP, CHU Henri Mondor, DHU ATVB, Service de Ranimation Mdicale, 51, avenue du Mal de Lattre de Tassigny, 94 010 Crteil Cedex, France. 2 APHP, CHU Henri Mondor, DHU ATVB, Service de Cardiologie, 94010 Crteil, France.

3 APHP, Hpital Europen Georges Pompidou, Service de Ranimation Mdi cale, 75015 Paris, France. 4 Universit Paris Est Crteil, Facult de Mdecine, Groupe de recherche clinique CARMAS, 94010 Crteil, France. 5 INSERM U955, IMRB, Facult de Mdecine de Crteil, 94010 Crteil, France.

Acknowledgements

None.

Compliance with ethical guidelines

Competing interests

The authors declare that they have no competing interests.

Financial support

None.

Received: 17 July 2015 Accepted: 13 September 2015

Seemann et al. Ann. Intensive Care (2015) 5:27

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