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Fluid therapy and acute kidney injury in cardiogenic shock after cardiac arrest
Resuscitation 84 (2013) 194–199
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Clinical Paper
Fluid therapy and acute kidney injury in cardiogenic shock after cardiac arrest夽 Christoph Adler a,c , Hannes Reuter a,c , Catherine Seck a , Martin Hellmich b , Carsten Zobel a,∗ a b
Department of Internal Medicine III, University of Cologne, Cologne, Germany Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany
a r t i c l e
i n f o
Article history: Received 3 March 2012 Received in revised form 12 June 2012 Accepted 19 June 2012
Keywords: Cardiogenic shock Acute kidney injury Hemodynamic monitoring Volumetric monitoring
a b s t r a c t Aim of the study: It has recently been suggested that acute kidney injury (AKI) may strongly be influenced by post-resuscitation disease and cardiogenic shock (CS), and may not just be a consequence of cardiac arrest and time without spontaneous circulation. AKI also has been suggested as a strong independent predictor of in-hospital mortality. Therefore the present study aimed at investigating the effect of fluid management on the incidence of AKI in patients with cardiogenic shock after cardiac arrest treated by mild therapeutic hypothermia. Methods: Fluid therapy and the incidence of acute kidney injury (AKI) was retrospectively reviewed in 51 patients with cardiogenic shock after cardiac arrest comparing patients with and without hemodynamic (PPV, SVV) and volumetric (ELWI, GEDI) monitoring. Results: There was no significant difference in baseline or cardiac arrest characteristics between hemodynamic monitored patients and conventional monitored patients. 28 patients were monitored by standard monitoring, in 23 patients monitoring was complemented by a PICCO system. In the first 24 h of treatment the total amount of fluid was significantly higher in patients under PICCO monitoring compared to conventional monitoring (4375 ± 1285 ml vs. 5449 ± 1438 ml, p = 0.007). This was associated with a significant reduction in the incidence of AKI (RIFLE ‘I’/‘F’: PICCO-group: 1 (4.3%) vs. conventional group 8 (28.6%), p = 0.03). Conclusion: The presented data suggest that volume therapy guided by volumetric (ELWI, GEDI) and arterial waveform derived variables (PPV, SVV) can reduce the incidence of AKI in patients with cardiogenic shock after cardiac arrest treated with mild therapeutic hypothermia. © 2012 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Acute kidney injury, which is part of the post-resuscitation syndrome after cardiac arrest contributes to the persistent high mortality of cardiogenic shock (CS). In these patients the classic paradigm of ischemia-reperfusion injury and CS represented
Abbreviations: AKI, acute kidney injury; CI, cardiac index; CS, cardiogenic shock; CVP, central venous pressure; ELWI, extravascular lung water index; FiO2 , fraction of inspired oxygen; GCS, glasgow coma scale; GEDI, global end diastolic volume index; ICU, intensive care unit; LV, left ventricle; MTH, mild therapeutic hypothermia; NOS, nitric oxide synthase; OHCA, out-of-hospital cardiac arrest; PaO2 , partial pressure of arterial oxygen; PCI, percutaneous coronary intervention; PEEP, positive end-expiratory pressure; PICCO, pulse indicator continuous cardiac output system; ROSC, return of spontaneous circulation; PPV, pulse pressure variation; PVPI, pulmonary vascularpermeability index; RV, right ventricle; SIRS, systemic inflammatory response syndrome; SVV, stroke volume variation. 夽 A Spanish translated version of the abstract of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2012.06.013. ∗ Corresponding author at: Department of Internal Medicine III, University of Cologne, 50924 Cologne, Germany. Tel.: +49 22147832401. E-mail address: [email protected] (C. Zobel). c These authors contributed equally to this work. 0300-9572/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.resuscitation.2012.06.013
by the vicious cycle of low cardiac output, low blood pressure, and compensatory high systemic vascular resistance with consecutive multiple organ failure has been challenged in recent years. The so called post resuscitation disease and CS are multifactorial and beside myocardial dysfunction may include a systemic inflammatory response (SIRS) mediated by cytokine release and expression of inducible nitric oxide synthase (NOS) among others.1,2 Excessive NOS results in high levels of nitric oxide that, in turn, lead to inappropriate systemic vasodilatation, progressive systemic and coronary hypoperfusion, and myocardial depression.1,3 Despite recognition of the clinical relevance of CS-related SIRS,2,4,5 pharmacologic attempts to influence these negative sequelae have been disappointing so far.6 It has recently been suggested that acute kidney injury (AKI) may strongly be influenced by post-resuscitation disease and CS, and may not just be a consequence of cardiac arrest and time without spontaneous circulation.7 Furthermore, patients with myocardial infarction undergoing primary PCI have an additional risk for AKI associated with the exposure to contrast agents or other medications and a higher incidence of bleeding complications. In the SHOCK trial, 13% of patients treated with early revascularization and 24% of those treated with initial medical therapy developed AKI
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defined by an increase in serum creatinine exceeding 3 mg/dl.8 More recently Marenzi and coworkers9 reported a 55% incidence of AKI (defined as a rise in creatinine >25%) in CS-patients with acute ST-elevation myocardial infarction. However, there is limited information on the epidemiology of AKI after cardiac arrest in adult human survivors, with a reported incidence ranging widely from 12–40%.10–12 Mild therapeutic hypothermia (MTH) is the only therapy applied in the post-cardiac arrest setting that has been shown to significantly improve survival.13,14 Unexpectedly, during induction of MTH high volume load by rapid infusion of crystalloids was well tolerated by CS-patients with ROSC after out-of-hospital cardiac arrest (OHCA).15 Since maintenance of adequate circulating blood volume is an essential goal in the proper management of critically ill patients and preserves renal function, the present study investigated the effect of fluid management on the incidence of AKI in CS-patients with ROSC after OHCA. In a retrospective analysis we compared the incidence of AKI in patients with either conventional fluid therapy or optimized to the upper limit of preload values derived from transpulmonary thermodilution and arterial waveform derived variables. 2. Patients and methods In this study, we retrospectively reviewed the fluid therapy of patients in cardiogenic shock after OHCA comparing patients with and without hemodynamic and volumetric monitoring. All patients were treated with MTH for 24 h in the intensive care unit (ICU) of the Heart Centre of the University of Cologne between November 2007 and October 2010. Patients were enrolled in the study if they fulfilled the inclusion criteria (OHCA, ROSC, ≥18 years, GCS ≤ 8 and cardiogenic shock) and all relevant data during the observation period was documented. Criteria for cardiogenic shock were adopted in a modified version from the SHOCK-Trial.8 Patients were included if they showed hypotension with systolic blood pressure <90 mm Hg for at least 30 min. Patients with systolic blood pressure higher than 90 mm Hg supported by catecholamines and typical clinical signs of end-organ hypoperfusion like cool extremities and cyanosis were also included.16,17 After June 2009 invasive hemodynamic monitoring by means of a pulse indicator continuous cardiac output system (PICCO, Pulsion Medical Systems AG, Munich, Germany) was introduced as standard therapy for all patients with cardiogenic shock. The investigation was approved by the Ethics Committee of the University of Cologne and conforms to the principles outlined in the Declaration of Helsinki. Patients consent was gained after they regained consciousness. The Ethics Committee approved this procedure since only routinely collected clinical data were used. 2.1. Treatment protocol All patients received standard intensive care treatment and therapeutic hypothermia according to the current recommendations.18 MTH was initiated by the emergency team in the ambulance by means of infusion of 2 l ice cold saline (4 ◦ C) in combination with ice packs. The controlled cooling to target temperature of 33 ◦ C was continued in ICU by using an endovascular cooling device (Coolgard 3000/ICY® catheter, Zoll Medical Corp., Chelmsford, MA) and maintained for 24 h. MTH was terminated by rewarming through the same endovascular device at a controlled rate of 0.3 ◦ C/h until the physiologic body temperature of 37 ◦ C was reached. To determine a myocardial ischemia as the suspected cause for cardiac arrest, all patients were transferred to the catheter lab for coronary angiography and revascularization when indicated prior to admission at the
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Fig. 1. Volumetric treatment algorithm. CI: cardiac index; GEDI: global end diastolic volume index; ELWI: extravascular lung water index; SVV: stroke volume variation; PPV: pulse pressure variation; V+ = volume loading; V− = volume reduction; Cat = catecholamine.
ICU. All patients were intubated, mechanically ventilated and received midazolam for sedation and sufentanil for analgesia aiming at a Richmond agitation and sedation (RASS) score of −4 until rewarming. The respiration management with a target partial arterial oxygen pressure (PaO2 ) of 100 mm Hg and partial arterial carbon dioxide pressure of 40 mm Hg (PaCO2 ) was controlled by regular blood gas analyses. When indicated the medical treatment with inotropes (dobutamine) and vasopressors (norepinephrine or in individual cases also epinephrine) was used to influence a target mean arterial blood pressure of ≥65 mm Hg. Heart rate, pulse oximetry, invasive blood pressure and central venous pressure were monitored routinely. Core temperature was continuously registered in the bladder through a thermal sensor at the tip of a transurethral urinary catheter. In nearly half of the patients continuous ICU monitoring was complemented by invasive hemodynamic monitoring by the use of pulse indicator continuous cardiac output system (PICCO, Pulsion Medical Systems AG, Munich, Germany). The PICCO system was routinely calibrated by thermodilution with 20 ml ice cold saline (4 ◦ C) every 6 h during hypothermia and regularly during cooling and rewarming. A minimum of three consecutive measurements was obtained and a difference of <10% between the measurements was accepted for data collection. 2.2. Fluid management For fluid therapy crystalloids and colloidal solution were used. In standard ICU monitored patients their application was performed based on conventional ICU monitoring, urine output and fluid requirements at the discretion of the attending physician. In addition, fluid management was controlled by clinical signs of possible volume overload, like peripheral edema, filled jugular veins and lung auscultation at regular intervals. In hemodynamic monitored patients fluid management was assessed by measurements of global end diastolic volume index (GEDI target between 700 and 800 ml/m2 ) as a prediction preload value and extravascular lung water index (ELWI target ≤ 10 ml/kg) as a volume parameter for detecting and quantification of pulmonary edema.19,20 Further on, pulmonary vascular permeability index (PVPI) was measured to specify the difference between hydrostatic lung edema (PVPI ≤ 3) and permeability lung edema (PVPI > 3).21 Decisions regarding volume therapy were also based on arterial waveform derived variables, (PPV target < 10% and SVV target < 10%). The complete treatment algorithm is shown in Fig. 1. Renal function was continuously monitored by urinary excretion and routine determination of serum creatinine. Acute kidney injury (AKI) was defined by the RIFLE criteria.22 On this basis, patients with an increase in serum
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creatinine or a reduced urine secretion were categorized into at risk of AKI, kidney injury or kidney failure. Since only one patient (conventional monitoring) fulfilled the criteria of kidney failure we have combined the categories kidney injury and kidney failure for further analysis. All OHCA and clinic data was reviewed retrospectively by analyzing the documented records of pre-hospital emergency team and the intensive care unit. 2.3. Statistical analysis Distributions of categorical data were summarized by count and percentage, of continuous data by mean ± standard deviation (SD). Since we found indications for non-normality (using the Shapiro–Wilk test) we thoroughly applied non-parametric rankbased methods for comparisons of groups (Mann–Whitney U test) or over time (Wilcoxon signed rank test). Correlations between continuous variables were assessed by linear regression analysis (r2 , explained variation). Categorical data, particularly the occurrence of AKI (RIFLE criteria), were compared between groups by Fisher’s exact test and binary logistic regression adjusted for multivariable propensity score (based on sex, age, diabetes, arterial hypertension, time to ROSC, volume of contrast medium etc.). Missing values were multiple imputed (fully conditional specification). Statistical analysis was done with SPSS Statistics 20 (IBM Co., Armonk, NY, USA). p values < 0.05 were considered statistically significant, albeit not corrected for multiple testing. 3. Results 3.1. Baseline characteristics A total of 51 patients with a mean age of 61 ± 1.9 years were included in the study. Myocardial infarction was the most common cause of cardiac arrest (76%) followed by primary arrhythmia. Almost 80% of patients exhibited ventricular fibrillation or pulseless ventricular tachycardia as the first recorded rhythm. The remaining patients showed initial asystole. Eight patients had a previous history of advanced renal disease. All patients underwent coronary angiography, the amount of contrast agent was not significantly different between treatment groups (conventional monitoring: 169 ± 78 ml vs. picco monitoring: 166 ± 67 ml, p = 0.96). 28 patients (55%) were monitored by standard ICU monitoring. In 23 patients (45%) continuous ICU monitoring was complemented by a PICCO system. There was no significant difference in baseline or cardiac arrest characteristics between hemodynamic monitored patients and conventional monitored patients (Table 1). 3.2. Fluid therapy During the first 6 h on ICU patients under standard ICU monitoring received an average fluid volume of 1075 ± 488 ml. Patients with hemodynamic monitoring by means of the PICCO system were infused with a cumulative volume of 2111 ± 676 ml within the same period (p = <0.001). As shown in Fig. 1, the ratio of the applied fluid volume between the two groups remained almost constant from the 6–24 h. In total the amount of fluid was significantly lower in patients under conventional monitoring compared to PICCO monitoring (4375 ± 1285 ml vs. 5449 ± 1438 ml, p = 0.007). 3.3. Hemodynamic monitoring At the time of presentation on the ICU the average GEDI was 685 ± 114 ml/m2 and ELWI was 9.6 ± 3.2 ml/kg in the PICCO group. Under the infusion regimen the values showed an initial increase and remained then on a similar level during the observation period (Table 2). On admission the average SVV was 14.6 ± 3.6% and
Fig. 2. Cumulative amount of administered fluid in PICCO monitored patients and conventional monitored controls. *p < 0.05 vs. conventional monitoring.
the PPV was 11.4 ± 3.7%. PPV was reduced below 10% (9.6 ± 3.6%, p = 0.02) after 6 h. After 24 h both values were under the target value of <10% (PPV 7.8 ± 2.9%, p < 0.01 and SVV 8.8 ± 4.2%, p < 0.01). The detailed hemodynamic parameters are presented in Table 2. No patient developed a PVPI above 3 and the average stayed well below 3 suggesting the absence of acute lung injury in the patients monitored with PiCCO.21,23 In the patients not monitored by a PICCO-system, no patient showed clinical signs of pulmonary edema. 3.4. Respiratory data The respiratory parameters are summarized in Table 3. The increased amount of infused volume in the PICCO group was not associated with a deterioration of respiration parameters. 3.5. Renal function The average serum creatinine of all patients at admission was 1.26 ± 0.35 mg/dl with no difference between the two groups (1.22 ± 0.49 vs. 1.29 ± 0.34, p = 0.55). After 24 h a trend towards an increased serum creatinine emerged in the conventional group which became statistically significant after 48 h (Table 4). Using simple linear regression including all patients a significant negative correlation between the increase in creatinine and the amount of intravenous fluid after 48 h was observed (r2 = 0.09, p = 0.02). Thus, it appears that the increase of serum creatinine is connected with the applied amount of fluid (Fig. 2). Urine output was not significantly different between both groups after 24 h and 48 h (Table 4). Applying the RIFLE criteria 22 22 of 51 patients (43%) developed AKI (conventional monitoring: 19 of 28; PICCO: 3 of 23; univariable odds ratio: 14.1, 95% confidence interval 3.3–60.0, p < 0.001; propensity score adjusted odds ratio: 13.5, 95% confidence interval 2.3–75.4, p = 0.003), 13 (25.5%) had AKI class ‘at riskˇı and 9 patients (17.6%) had a AKI class ‘kidney injury’ or ‘kidney failure’. Patients in the PICCO-group showed a significant lower rate of both AKI classes compared to patients under conventional monitoring (‘at riskˇı 2 (8.7%) vs. 11 (39.3%) p = 0.02 and ‘kidney injury’ or ‘kidney failure’ 1 (4.3%) vs. 8 (28.6%), p = 0.03) (Fig. 3). In 4 patients under conventional monitoring a dialysis became necessary. No patient under PICCO monitoring were treated with dialysis (p = 0.11). As expected, patients with known advanced renal disease had an increased risk to develop an acute kidney injury. Almost 90% (7 from 8) of these patients were affected. Interestingly, no patient under PICCO
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Table 1 Clinical characteristics of the patients included in the investigation. Characteristic Age (years) Mean Range Sex Female – no./total no. (%) Medical history Diabetes mellitus – no./total no. (%) Arterial hypertension – no./total no. (%) Coronary heart disease – no./total no. (%) Advanced renal disease – no./total no. (%) Cause of cardiac arrest Myocardial infarction – no./total no.(%) Primary arrhythmia – no./total no. (%) Pulmonary embolism – no./total no. (%) Time from collapse to emergency-medical-services arrival (min) Basic life support provided by bystander – no./total no. (%) First recorded rhythm Ventricular fibrillation or pulseless ventricular tachycardia – no./total no. (%) Asystolia – no./total no. (%) Number of defibrillations shocks Time from collapse to return of spontaneous circulation (min) Period of ICU hospitalization (days) Mean Range Ventilation time (days) Mean Range Pneumonia – no./total no. (%) Death in hospital – no./total no. (%)
Study population (n = 51)
PICCO monitoring (n = 23)
Conventional monitoring (n = 28)
p value
61 28–89
60 34–89
62 28–80
0.64
8/51 (16)
6/23 (26)
2/28 (7)
0.11
9/51 (18) 23/51 (45) 39/51 (76) 8/51 (16)
5/23 (22) 14/23 (61) 18/23 (78) 4/23 (17)
4/28 (14) 9/28 (32) 21/28 (75) 4%28 (14)
0.71 0.05 1 1
39/51 (76) 11/51 (22) 1/51 (2) 6.3 ± 0.72
18/23 (78) 4/23 (17) 1/23 (4) 7.6 ± 1.60
21/28 (75) 7/28 (25) 0/28 (0) 5.5 ± 0.79
1 0.73 0.45 0.33
17/51 (33)
9/23 (39)
8/28 (29)
0.55
40/51 (78)
19/23 (83)
21/28 (75)
0.73
11/51 (22) 4.5 ± 0.72 25.3 ± 1.91
4/23 (17) 3.7 ± 0.69 22.7 ± 2.08
7/28 (25) 5.0 ± 0.92 27.7 ± 3.06
0.73 0.31 0.20
16 2–56
16 2–56
16 2–35
0.99
12 2–52 22/51 (43) 19/51 (37)
9 2–18 8/23 (35) 5/23 (29)
13 2–52 14/28 (50) 14/28 (50)
0.13 0.39 0.08
Clinical characteristics of included patients.
Table 2 PICCO monitored fluid parameters.
GEDI [ml/m2 ] ELWI [ml/kg] PVPI SVV [%] PPV [%]
Admission to ICU
6h
12 h
18 h
24 h
685 (±114) 9.6 (±3.2) 2.3 (±0.9) 14.6 (±3.6) 11.4 (±3.7)
768 (±228) 9.5 (±3.1) 2.1 (±0.8) 12.8 (±4.7) 9.6 (±3.6)*
799 (±170)* 9.7 (±3.2) 2.1 (±0.7) 12.3 (±4.4)* 9.6 (±4.0)*
800 (±185)* 10.2 (±3.3) 2.0 (±0.6) 10.3 (±2.9)* 8.9 (±4.4)*
783 (±157)* 9.9 (±3.0) 2.1 (±0.6) 8.8 (±4.2)* 7.8 (±2.9)*
PICCO: pulse indicator continuous cardiac output system; GEDI: global end diastolic volume index; ELWI: extravascular lung water index; PVPI: pulmonary vascular permeability index; SVV: stroke volume variation; PPV: pulse pressure variation. * p < 0.05 vs. value on admission.
Table 3 Ventilator parameters during the first 24 h at the intensive care unit.
FiO2
PaO2 [mm Hg]
PaO2/ FiO2
PEEP [mbar]
Treatment group
Admission to ICU
6h
12 h
18 h
24 h
PICCO Conventional p-Value§ PICCO Conventional p-Value§ PICCO Conventional p-Value§ PICCO Conventional p-Value§
0.81 (±0.2) 0.79 (±0.2) 0.711 268 (±110) 245 (±119) 0.482 344 (±142) 321 (±151) 0.672 6.7 (±1.8) 7.0 (±2.5) 0.548
0.48 (±0.1)* 0.45 (±0.2)* 0.348 144 (±30)* 131 (±28)* 0.143 341 (±128) 308 (±141) 0.336 6.9 (±1.8) 6.9 (±2.2) 0.683
0.37 (±0.1)* 0.39 (±0.1)* 0.592 123 (±25)* 128 (±37)* 0.628 331 (±90) 339 (±134) 0.666 7.3 (±2.0) 7.1 (±2.4) 0.833
0.36 (±0.1)* 0.38 (±0.1)* 0.447 120 (±28)* 115 (±22)* 0.485 357 (±109) 310 (±105) 0.406 6.9 (±1.5) 7.1 (±2.1) 0.272
0.34 (±0.1)* 0.42 (±0.2)* 0.06 114 (±20)* 132 (±59)* 0.199 356 (±87) 317 (±104) 0.490 7.1 (±1.5) 7.2 (±2.0) 0.546
Ventilation parameters during the first 48 h. FiO2 : fraction of inspired oxygen; PaO2 : partial pressure of arterial oxygen; PEEP: positive end-expiratory pressure. * p < 0.05 vs. value on admission. § p < 0.5 conventional vs. PICCO.
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Table 4 Urine output and course of serum creatinine. Characteristic Serum creatinine [mg/dl] At admission 24 h 48 h Urine output [ml] After 24 h After 48 h
Study population (n = 51)
PICCO monitoring (n = 23)
Conventional monitoring (n = 28)
p value
1.26 ± 0.35 0.16 ± 0.34 0.56 ± 0.47
1.22 ± 0.49 0.06 ± 0.37 0.18 ± 0.18
1.29 ± 0.34 0.24 ± 0.41 0.87 ± 0.78
0.55 0.10 0.0005
2541 ± 752 4729 ± 1057
2717 ± 765 4866 ± 1360
2417 ± 754 4300 ± 1106
0.64 0.11
Urine output and course of serum creatinine. 24 h: change in serum creatinine in the first 24 h; 48 h: change in serum creatinine in the first 48 h.
monitoring without a history of chronic renal insufficiency developed an acute renal failure (Fig. 4). 4. Discussion We have investigated the influence of volume therapy guided by volumetric (ELWI, GEDI) and arterial waveform derived variables (PPV, SVV) on AKI in patients with cardiogenic shock after cardiac arrest treated with mild therapeutic hypothermia. We found that, compared to conventionally monitored patients, the resulting increase in volume therapy correlated with a significantly reduced rate of AKI. Fluid management in cardiogenic shock has not been adequately studied.24 Traditionally the central venous pressure (CVP) has been used to guide fluid management. However, due to the changes in venous tone, intrathoracic pressures, LV and RV compliance and geometry that occur in critically ill patients, there is a poor relationship between the central venous pressure and RV end-diastolic volume. More than 100 studies have been published to date that have demonstrated no relationship between the CVP (or change in CVP) and fluid responsiveness in various clinical settings.25 In contrast to this, parameters derived from transpulmonary thermodilution like the extra vascular lung water index (ELWI) or the global enddiastolic volume index (GEDI) have been shown to reliable allow the assessment of the volume status of a patient.19,26 A recent meta analysis also found that dynamic changes in arterial waveformderived parameters like PPV and SVV measured during mechanical ventilation can predict with a high of accuracy patients who are likely to respond to a fluid challenge.27 The present study demonstrates that in patients with cardiogenic shock after cardiac arrest treated with mild therapeutic hypothermia an increase in volume therapy driven by volumetric (ELWI, GEDI) and arterial waveform
Fig. 3. Linear correlation between the increase in serum creatinine after 48 h and the amount of intravenous administered fluid. r2 = 0.09; p = 0.02.
derived variables (PPV, SVV) results in a significant reduction of AKI compared to patients treated without invasive monitoring. Of the limited number of studies on AKI in patients with cardiogenic shock after cardiac arrest only two reported the incidence of AKI based on modern consensus definitions. Hasper et al.28 used the AKIN criteria29 and found that 22.7% of the included patients had AKI stage 2 or 3. Based on the RIFLE criteria22 the incidence of AKI class I/F was 31.4% in a recent publication by Chua et al.7 In contrast to our patients only 57% of the patients were treated with mild therapeutic hypothermia by Hasper et al., while none of the patients were cooled in the study of Chua et al. Despite these differences regarding hypothermia we observed similar rates of AKI (28.6%) in the group with conventional monitoring. In addition to that, a recent meta analysis found no evidence that mild therapeutic hypothermia influences the occurrence of AKI.30 The authors are not aware of a study specifically addressing the issue of AKI and fluid management in patients with cardiogenic shock after cardiac arrest. Rivers et al.31 demonstrated that early, protocol directed resuscitation including crystalloid, colloid and blood administration was associated with improved survival and less organ dysfunction in septic shock. In another single center study, protocolized resuscitation for septic shock initiated in the ICU within 4 h of diagnosis resulted in improved survival and lower incidence of renal dysfunction.32 However there is emerging evidence that timing and amount of fluid therapy are important issues and that liberal fluid administration might have detrimental effects.24,33
Fig. 4. Frequency of acute kidney injury stages ‘at risk’ or ‘injury’ and ‘failure’ in PICCO monitored patients and conventional monitored patients defined by the RIFLE criteria.
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5. Limitations The present study has certain limitations that need to be taken into account for the interpretation of the results. Patients with preexisting renal disease have been included into the study. To be completely methodologically completely correct, the basis for the investigation of a treatment preventing kidney disease should be normal kidney function. However, since in clinical reality patients with post-resuscitation syndrome are often affected by renal disease it seemed reasonable to also include such patients into the analysis. The number of patients with preexisting renal disease was not significantly different between the groups, therefore a bias is not likely (PICCO monitoring 17% vs. conventional monitoring 14%, p = 1). Due the retrospective nature, the relatively small sample size and the fact that the two groups compared in the study are not contemporary but differ for the time of enrolment further evaluation is warranted before routinely recommending the suggested fluid regime in patients with CS after OHCA”. 6. Conclusion The presented data suggest that volume therapy guided by volumetric (ELWI, GEDI) and arterial waveform derived variables (PPV, SVV) can reduce the incidence of AKI in patients with cardiogenic shock after cardiac arrest treated with mild therapeutic hypothermia. Conflict of interest statement None. Acknowledgment The study was not sponsored. References 1. Hochman JS. Cardiogenic shock complicating acute myocardial infarction: expanding the paradigm. Circulation 2003;107:2998–3002. 2. Adrie C, Laurent I, Monchi M, Cariou A, Dhainaou JF, Spaulding C. Postresuscitation disease after cardiac arrest: a sepsis-like syndrome? Curr Opin Crit Care 2004;10:208–12. 3. Akiyama K, Kimura A, Suzuki H, et al. Production of oxidative products of nitric oxide in infarcted human heart. J Am Coll Cardiol 1998;32:373–9. 4. Laurent I, Monchi M, Chiche JD, et al. Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest. J Am Coll Cardiol 2002;40:2110–6. 5. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization and long-term survival in cardiogenic shock complicating acute myocardial infarction. J Am Med Asoc 2006;295:2511–5. 6. Alexander JH, Reynolds HR, Stebbins AL, et al. Effect of tilarginine acetate in patients with acute myocardial infarction and cardiogenic shock: the TRIUMPH randomized controlled trial. J Am Med Assoc 2007;297:1657–66. 7. Chua HR, Glassford N, Bellomo R. Acute kidney injury after cardiac arrest. Resuscitation 2011. 8. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK investigators. Should we emergently revascularize occluded coronaries for cardiogenic shock. N Engl J Med 1999;341:625–34.
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9. Marenzi G, Assanelli E, Campodonico JAL>. Acute kidney injury in ST-segment elevation acute myocardial infarction complicated by cardiogenic shock at admission. Crit Care Med 2010;38:438–44. 10. Mattana J, Singhal PC. Prevalence and determinants of acute renal failure following cardiopulmonary resuscitation. Arch Intern Med 1993;153:235–9. 11. Domanovits H, Schillinger M, Mullner M, et al. Acute renal failure after successful cardiopulmonary resuscitation. Intensive Care Med 2001;27:1194–9. 12. Domanovits H, Mullner M, Sterz F, et al. Impairment of renal function in patients resuscitated from cardiac arrest: frequency, determinants and impact on outcome. Wien Klin Wochenschr 2000;112:157–61. 13. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;3468:549–56. 14. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557–63. 15. Kim F, Olsufka M, Longstreth Jr WT, et al. Pilot randomized clinical trial of prehospital induction of mild hypothermia in out-of-hospital cardiac arrest patients with a rapid infusion of 4 degrees C normal saline. Circulation 2007;115:3064–70. 16. Hasdai D, Topol EJ, Califf RM, Berger PB, Holmes Jr DR. Cardiogenic shock complicating acute coronary syndromes. Lancet 2000;356:749–56. 17. Menon V, White H, LeJemtel T, Webb JG, Sleeper LA, Hochman JS. The clinical profile of patients with suspected cardiogenic shock due to predominant left ventricular failure: a report from the SHOCK Trial Registry. Should we emergently revascularize occluded coronaries in cardiogenic shocK? J Am Coll Cardiol 2000;36:1071–6. 18. Nolan JP, Soar J, Zideman DA, et al. European Resuscitation Council Guidelines for Resuscitation 2010 Section 1. Executive summary. Resuscitation 2010;81:1219–76. 19. Della RG, Costa MG, Pietropaoli P. How to measure and interpret volumetric measures of preload. Curr Opin Crit Care 2007;13:297–302. 20. Fernandez-Mondejar E, Rivera-Fernandez R, Garcia-Delgado M, Touma A, Machado J, Chavero J. Small increases in extravascular lung water are accurately detected by transpulmonary thermodilution. J Trauma 2005;59:1420–3. 21. Monnet X, Anguel N, Osman D, Hamzaoui O, Richard C, Teboul JL. Assessing pulmonary permeability by transpulmonary thermodilution allows differentiation of hydrostatic pulmonary edema from ALI/ARDS. Intensive Care Med 2007;33:448–53. 22. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004;8:R204–12. 23. Groeneveld AB, Verheij J. Extravascular lung water to blood volume ratios as measures of permeability in sepsis-induced ALI/ARDS. Intensive Care Med 2006;32:1315–21. 24. Bagshaw SM, Bellomo R. The influence of volume management on outcome. Curr Opin Crit Care 2007;13:541–8. 25. Marik PE, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest 2008;134:172–8. 26. Khan S, Trof RJ, Groeneveld AB. Transpulmonary dilution-derived extravascular lung water as a measure of lung edema. Curr Opin Crit Care 2007;13:303–7. 27. Marik PE, Cavallazzi R, Vasu T, Hirani A. Dynamic changes in arterial waveform derived variables and fluid responsiveness in mechanically ventilated patients: a systematic review of the literature. Crit Care Med 2009;37:2642–7. 28. Hasper D, von HS, Storm C, Jorres A, Schefold JC. Changes in serum creatinine in the first 24 h after cardiac arrest indicate prognosis: an observational cohort study. Crit Care 2009;13:R168. 29. Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007;11:R31. 30. Susantitaphong P, Alfayez M, Cohen-Bucay A, Balk EM, Jaber BL. Therapeutic hypothermia and prevention of acute kidney injury: a meta-analysis of randomized controlled trials. Resuscitation 2011. 31. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368–77. 32. Lin SM, Huang CD, Lin HC, Liu CY, Wang CH, Kuo HP. A modified goal-directed protocol improves clinical outcomes in intensive care unit patients with septic shock: a randomized controlled trial. Shock 2006;26:551–7. 33. Prowle JR, Bellomo R. Fluid administration and the kidney. Curr Opin Crit Care 2010;16:332–6.
Contents lists available at SciVerse ScienceDirect
Resuscitation journal homepage: www.elsevier.com/locate/resuscitation
Clinical Paper
Fluid therapy and acute kidney injury in cardiogenic shock after cardiac arrest夽 Christoph Adler a,c , Hannes Reuter a,c , Catherine Seck a , Martin Hellmich b , Carsten Zobel a,∗ a b
Department of Internal Medicine III, University of Cologne, Cologne, Germany Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany
a r t i c l e
i n f o
Article history: Received 3 March 2012 Received in revised form 12 June 2012 Accepted 19 June 2012
Keywords: Cardiogenic shock Acute kidney injury Hemodynamic monitoring Volumetric monitoring
a b s t r a c t Aim of the study: It has recently been suggested that acute kidney injury (AKI) may strongly be influenced by post-resuscitation disease and cardiogenic shock (CS), and may not just be a consequence of cardiac arrest and time without spontaneous circulation. AKI also has been suggested as a strong independent predictor of in-hospital mortality. Therefore the present study aimed at investigating the effect of fluid management on the incidence of AKI in patients with cardiogenic shock after cardiac arrest treated by mild therapeutic hypothermia. Methods: Fluid therapy and the incidence of acute kidney injury (AKI) was retrospectively reviewed in 51 patients with cardiogenic shock after cardiac arrest comparing patients with and without hemodynamic (PPV, SVV) and volumetric (ELWI, GEDI) monitoring. Results: There was no significant difference in baseline or cardiac arrest characteristics between hemodynamic monitored patients and conventional monitored patients. 28 patients were monitored by standard monitoring, in 23 patients monitoring was complemented by a PICCO system. In the first 24 h of treatment the total amount of fluid was significantly higher in patients under PICCO monitoring compared to conventional monitoring (4375 ± 1285 ml vs. 5449 ± 1438 ml, p = 0.007). This was associated with a significant reduction in the incidence of AKI (RIFLE ‘I’/‘F’: PICCO-group: 1 (4.3%) vs. conventional group 8 (28.6%), p = 0.03). Conclusion: The presented data suggest that volume therapy guided by volumetric (ELWI, GEDI) and arterial waveform derived variables (PPV, SVV) can reduce the incidence of AKI in patients with cardiogenic shock after cardiac arrest treated with mild therapeutic hypothermia. © 2012 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Acute kidney injury, which is part of the post-resuscitation syndrome after cardiac arrest contributes to the persistent high mortality of cardiogenic shock (CS). In these patients the classic paradigm of ischemia-reperfusion injury and CS represented
Abbreviations: AKI, acute kidney injury; CI, cardiac index; CS, cardiogenic shock; CVP, central venous pressure; ELWI, extravascular lung water index; FiO2 , fraction of inspired oxygen; GCS, glasgow coma scale; GEDI, global end diastolic volume index; ICU, intensive care unit; LV, left ventricle; MTH, mild therapeutic hypothermia; NOS, nitric oxide synthase; OHCA, out-of-hospital cardiac arrest; PaO2 , partial pressure of arterial oxygen; PCI, percutaneous coronary intervention; PEEP, positive end-expiratory pressure; PICCO, pulse indicator continuous cardiac output system; ROSC, return of spontaneous circulation; PPV, pulse pressure variation; PVPI, pulmonary vascularpermeability index; RV, right ventricle; SIRS, systemic inflammatory response syndrome; SVV, stroke volume variation. 夽 A Spanish translated version of the abstract of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2012.06.013. ∗ Corresponding author at: Department of Internal Medicine III, University of Cologne, 50924 Cologne, Germany. Tel.: +49 22147832401. E-mail address: [email protected] (C. Zobel). c These authors contributed equally to this work. 0300-9572/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.resuscitation.2012.06.013
by the vicious cycle of low cardiac output, low blood pressure, and compensatory high systemic vascular resistance with consecutive multiple organ failure has been challenged in recent years. The so called post resuscitation disease and CS are multifactorial and beside myocardial dysfunction may include a systemic inflammatory response (SIRS) mediated by cytokine release and expression of inducible nitric oxide synthase (NOS) among others.1,2 Excessive NOS results in high levels of nitric oxide that, in turn, lead to inappropriate systemic vasodilatation, progressive systemic and coronary hypoperfusion, and myocardial depression.1,3 Despite recognition of the clinical relevance of CS-related SIRS,2,4,5 pharmacologic attempts to influence these negative sequelae have been disappointing so far.6 It has recently been suggested that acute kidney injury (AKI) may strongly be influenced by post-resuscitation disease and CS, and may not just be a consequence of cardiac arrest and time without spontaneous circulation.7 Furthermore, patients with myocardial infarction undergoing primary PCI have an additional risk for AKI associated with the exposure to contrast agents or other medications and a higher incidence of bleeding complications. In the SHOCK trial, 13% of patients treated with early revascularization and 24% of those treated with initial medical therapy developed AKI
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defined by an increase in serum creatinine exceeding 3 mg/dl.8 More recently Marenzi and coworkers9 reported a 55% incidence of AKI (defined as a rise in creatinine >25%) in CS-patients with acute ST-elevation myocardial infarction. However, there is limited information on the epidemiology of AKI after cardiac arrest in adult human survivors, with a reported incidence ranging widely from 12–40%.10–12 Mild therapeutic hypothermia (MTH) is the only therapy applied in the post-cardiac arrest setting that has been shown to significantly improve survival.13,14 Unexpectedly, during induction of MTH high volume load by rapid infusion of crystalloids was well tolerated by CS-patients with ROSC after out-of-hospital cardiac arrest (OHCA).15 Since maintenance of adequate circulating blood volume is an essential goal in the proper management of critically ill patients and preserves renal function, the present study investigated the effect of fluid management on the incidence of AKI in CS-patients with ROSC after OHCA. In a retrospective analysis we compared the incidence of AKI in patients with either conventional fluid therapy or optimized to the upper limit of preload values derived from transpulmonary thermodilution and arterial waveform derived variables. 2. Patients and methods In this study, we retrospectively reviewed the fluid therapy of patients in cardiogenic shock after OHCA comparing patients with and without hemodynamic and volumetric monitoring. All patients were treated with MTH for 24 h in the intensive care unit (ICU) of the Heart Centre of the University of Cologne between November 2007 and October 2010. Patients were enrolled in the study if they fulfilled the inclusion criteria (OHCA, ROSC, ≥18 years, GCS ≤ 8 and cardiogenic shock) and all relevant data during the observation period was documented. Criteria for cardiogenic shock were adopted in a modified version from the SHOCK-Trial.8 Patients were included if they showed hypotension with systolic blood pressure <90 mm Hg for at least 30 min. Patients with systolic blood pressure higher than 90 mm Hg supported by catecholamines and typical clinical signs of end-organ hypoperfusion like cool extremities and cyanosis were also included.16,17 After June 2009 invasive hemodynamic monitoring by means of a pulse indicator continuous cardiac output system (PICCO, Pulsion Medical Systems AG, Munich, Germany) was introduced as standard therapy for all patients with cardiogenic shock. The investigation was approved by the Ethics Committee of the University of Cologne and conforms to the principles outlined in the Declaration of Helsinki. Patients consent was gained after they regained consciousness. The Ethics Committee approved this procedure since only routinely collected clinical data were used. 2.1. Treatment protocol All patients received standard intensive care treatment and therapeutic hypothermia according to the current recommendations.18 MTH was initiated by the emergency team in the ambulance by means of infusion of 2 l ice cold saline (4 ◦ C) in combination with ice packs. The controlled cooling to target temperature of 33 ◦ C was continued in ICU by using an endovascular cooling device (Coolgard 3000/ICY® catheter, Zoll Medical Corp., Chelmsford, MA) and maintained for 24 h. MTH was terminated by rewarming through the same endovascular device at a controlled rate of 0.3 ◦ C/h until the physiologic body temperature of 37 ◦ C was reached. To determine a myocardial ischemia as the suspected cause for cardiac arrest, all patients were transferred to the catheter lab for coronary angiography and revascularization when indicated prior to admission at the
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Fig. 1. Volumetric treatment algorithm. CI: cardiac index; GEDI: global end diastolic volume index; ELWI: extravascular lung water index; SVV: stroke volume variation; PPV: pulse pressure variation; V+ = volume loading; V− = volume reduction; Cat = catecholamine.
ICU. All patients were intubated, mechanically ventilated and received midazolam for sedation and sufentanil for analgesia aiming at a Richmond agitation and sedation (RASS) score of −4 until rewarming. The respiration management with a target partial arterial oxygen pressure (PaO2 ) of 100 mm Hg and partial arterial carbon dioxide pressure of 40 mm Hg (PaCO2 ) was controlled by regular blood gas analyses. When indicated the medical treatment with inotropes (dobutamine) and vasopressors (norepinephrine or in individual cases also epinephrine) was used to influence a target mean arterial blood pressure of ≥65 mm Hg. Heart rate, pulse oximetry, invasive blood pressure and central venous pressure were monitored routinely. Core temperature was continuously registered in the bladder through a thermal sensor at the tip of a transurethral urinary catheter. In nearly half of the patients continuous ICU monitoring was complemented by invasive hemodynamic monitoring by the use of pulse indicator continuous cardiac output system (PICCO, Pulsion Medical Systems AG, Munich, Germany). The PICCO system was routinely calibrated by thermodilution with 20 ml ice cold saline (4 ◦ C) every 6 h during hypothermia and regularly during cooling and rewarming. A minimum of three consecutive measurements was obtained and a difference of <10% between the measurements was accepted for data collection. 2.2. Fluid management For fluid therapy crystalloids and colloidal solution were used. In standard ICU monitored patients their application was performed based on conventional ICU monitoring, urine output and fluid requirements at the discretion of the attending physician. In addition, fluid management was controlled by clinical signs of possible volume overload, like peripheral edema, filled jugular veins and lung auscultation at regular intervals. In hemodynamic monitored patients fluid management was assessed by measurements of global end diastolic volume index (GEDI target between 700 and 800 ml/m2 ) as a prediction preload value and extravascular lung water index (ELWI target ≤ 10 ml/kg) as a volume parameter for detecting and quantification of pulmonary edema.19,20 Further on, pulmonary vascular permeability index (PVPI) was measured to specify the difference between hydrostatic lung edema (PVPI ≤ 3) and permeability lung edema (PVPI > 3).21 Decisions regarding volume therapy were also based on arterial waveform derived variables, (PPV target < 10% and SVV target < 10%). The complete treatment algorithm is shown in Fig. 1. Renal function was continuously monitored by urinary excretion and routine determination of serum creatinine. Acute kidney injury (AKI) was defined by the RIFLE criteria.22 On this basis, patients with an increase in serum
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creatinine or a reduced urine secretion were categorized into at risk of AKI, kidney injury or kidney failure. Since only one patient (conventional monitoring) fulfilled the criteria of kidney failure we have combined the categories kidney injury and kidney failure for further analysis. All OHCA and clinic data was reviewed retrospectively by analyzing the documented records of pre-hospital emergency team and the intensive care unit. 2.3. Statistical analysis Distributions of categorical data were summarized by count and percentage, of continuous data by mean ± standard deviation (SD). Since we found indications for non-normality (using the Shapiro–Wilk test) we thoroughly applied non-parametric rankbased methods for comparisons of groups (Mann–Whitney U test) or over time (Wilcoxon signed rank test). Correlations between continuous variables were assessed by linear regression analysis (r2 , explained variation). Categorical data, particularly the occurrence of AKI (RIFLE criteria), were compared between groups by Fisher’s exact test and binary logistic regression adjusted for multivariable propensity score (based on sex, age, diabetes, arterial hypertension, time to ROSC, volume of contrast medium etc.). Missing values were multiple imputed (fully conditional specification). Statistical analysis was done with SPSS Statistics 20 (IBM Co., Armonk, NY, USA). p values < 0.05 were considered statistically significant, albeit not corrected for multiple testing. 3. Results 3.1. Baseline characteristics A total of 51 patients with a mean age of 61 ± 1.9 years were included in the study. Myocardial infarction was the most common cause of cardiac arrest (76%) followed by primary arrhythmia. Almost 80% of patients exhibited ventricular fibrillation or pulseless ventricular tachycardia as the first recorded rhythm. The remaining patients showed initial asystole. Eight patients had a previous history of advanced renal disease. All patients underwent coronary angiography, the amount of contrast agent was not significantly different between treatment groups (conventional monitoring: 169 ± 78 ml vs. picco monitoring: 166 ± 67 ml, p = 0.96). 28 patients (55%) were monitored by standard ICU monitoring. In 23 patients (45%) continuous ICU monitoring was complemented by a PICCO system. There was no significant difference in baseline or cardiac arrest characteristics between hemodynamic monitored patients and conventional monitored patients (Table 1). 3.2. Fluid therapy During the first 6 h on ICU patients under standard ICU monitoring received an average fluid volume of 1075 ± 488 ml. Patients with hemodynamic monitoring by means of the PICCO system were infused with a cumulative volume of 2111 ± 676 ml within the same period (p = <0.001). As shown in Fig. 1, the ratio of the applied fluid volume between the two groups remained almost constant from the 6–24 h. In total the amount of fluid was significantly lower in patients under conventional monitoring compared to PICCO monitoring (4375 ± 1285 ml vs. 5449 ± 1438 ml, p = 0.007). 3.3. Hemodynamic monitoring At the time of presentation on the ICU the average GEDI was 685 ± 114 ml/m2 and ELWI was 9.6 ± 3.2 ml/kg in the PICCO group. Under the infusion regimen the values showed an initial increase and remained then on a similar level during the observation period (Table 2). On admission the average SVV was 14.6 ± 3.6% and
Fig. 2. Cumulative amount of administered fluid in PICCO monitored patients and conventional monitored controls. *p < 0.05 vs. conventional monitoring.
the PPV was 11.4 ± 3.7%. PPV was reduced below 10% (9.6 ± 3.6%, p = 0.02) after 6 h. After 24 h both values were under the target value of <10% (PPV 7.8 ± 2.9%, p < 0.01 and SVV 8.8 ± 4.2%, p < 0.01). The detailed hemodynamic parameters are presented in Table 2. No patient developed a PVPI above 3 and the average stayed well below 3 suggesting the absence of acute lung injury in the patients monitored with PiCCO.21,23 In the patients not monitored by a PICCO-system, no patient showed clinical signs of pulmonary edema. 3.4. Respiratory data The respiratory parameters are summarized in Table 3. The increased amount of infused volume in the PICCO group was not associated with a deterioration of respiration parameters. 3.5. Renal function The average serum creatinine of all patients at admission was 1.26 ± 0.35 mg/dl with no difference between the two groups (1.22 ± 0.49 vs. 1.29 ± 0.34, p = 0.55). After 24 h a trend towards an increased serum creatinine emerged in the conventional group which became statistically significant after 48 h (Table 4). Using simple linear regression including all patients a significant negative correlation between the increase in creatinine and the amount of intravenous fluid after 48 h was observed (r2 = 0.09, p = 0.02). Thus, it appears that the increase of serum creatinine is connected with the applied amount of fluid (Fig. 2). Urine output was not significantly different between both groups after 24 h and 48 h (Table 4). Applying the RIFLE criteria 22 22 of 51 patients (43%) developed AKI (conventional monitoring: 19 of 28; PICCO: 3 of 23; univariable odds ratio: 14.1, 95% confidence interval 3.3–60.0, p < 0.001; propensity score adjusted odds ratio: 13.5, 95% confidence interval 2.3–75.4, p = 0.003), 13 (25.5%) had AKI class ‘at riskˇı and 9 patients (17.6%) had a AKI class ‘kidney injury’ or ‘kidney failure’. Patients in the PICCO-group showed a significant lower rate of both AKI classes compared to patients under conventional monitoring (‘at riskˇı 2 (8.7%) vs. 11 (39.3%) p = 0.02 and ‘kidney injury’ or ‘kidney failure’ 1 (4.3%) vs. 8 (28.6%), p = 0.03) (Fig. 3). In 4 patients under conventional monitoring a dialysis became necessary. No patient under PICCO monitoring were treated with dialysis (p = 0.11). As expected, patients with known advanced renal disease had an increased risk to develop an acute kidney injury. Almost 90% (7 from 8) of these patients were affected. Interestingly, no patient under PICCO
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Table 1 Clinical characteristics of the patients included in the investigation. Characteristic Age (years) Mean Range Sex Female – no./total no. (%) Medical history Diabetes mellitus – no./total no. (%) Arterial hypertension – no./total no. (%) Coronary heart disease – no./total no. (%) Advanced renal disease – no./total no. (%) Cause of cardiac arrest Myocardial infarction – no./total no.(%) Primary arrhythmia – no./total no. (%) Pulmonary embolism – no./total no. (%) Time from collapse to emergency-medical-services arrival (min) Basic life support provided by bystander – no./total no. (%) First recorded rhythm Ventricular fibrillation or pulseless ventricular tachycardia – no./total no. (%) Asystolia – no./total no. (%) Number of defibrillations shocks Time from collapse to return of spontaneous circulation (min) Period of ICU hospitalization (days) Mean Range Ventilation time (days) Mean Range Pneumonia – no./total no. (%) Death in hospital – no./total no. (%)
Study population (n = 51)
PICCO monitoring (n = 23)
Conventional monitoring (n = 28)
p value
61 28–89
60 34–89
62 28–80
0.64
8/51 (16)
6/23 (26)
2/28 (7)
0.11
9/51 (18) 23/51 (45) 39/51 (76) 8/51 (16)
5/23 (22) 14/23 (61) 18/23 (78) 4/23 (17)
4/28 (14) 9/28 (32) 21/28 (75) 4%28 (14)
0.71 0.05 1 1
39/51 (76) 11/51 (22) 1/51 (2) 6.3 ± 0.72
18/23 (78) 4/23 (17) 1/23 (4) 7.6 ± 1.60
21/28 (75) 7/28 (25) 0/28 (0) 5.5 ± 0.79
1 0.73 0.45 0.33
17/51 (33)
9/23 (39)
8/28 (29)
0.55
40/51 (78)
19/23 (83)
21/28 (75)
0.73
11/51 (22) 4.5 ± 0.72 25.3 ± 1.91
4/23 (17) 3.7 ± 0.69 22.7 ± 2.08
7/28 (25) 5.0 ± 0.92 27.7 ± 3.06
0.73 0.31 0.20
16 2–56
16 2–56
16 2–35
0.99
12 2–52 22/51 (43) 19/51 (37)
9 2–18 8/23 (35) 5/23 (29)
13 2–52 14/28 (50) 14/28 (50)
0.13 0.39 0.08
Clinical characteristics of included patients.
Table 2 PICCO monitored fluid parameters.
GEDI [ml/m2 ] ELWI [ml/kg] PVPI SVV [%] PPV [%]
Admission to ICU
6h
12 h
18 h
24 h
685 (±114) 9.6 (±3.2) 2.3 (±0.9) 14.6 (±3.6) 11.4 (±3.7)
768 (±228) 9.5 (±3.1) 2.1 (±0.8) 12.8 (±4.7) 9.6 (±3.6)*
799 (±170)* 9.7 (±3.2) 2.1 (±0.7) 12.3 (±4.4)* 9.6 (±4.0)*
800 (±185)* 10.2 (±3.3) 2.0 (±0.6) 10.3 (±2.9)* 8.9 (±4.4)*
783 (±157)* 9.9 (±3.0) 2.1 (±0.6) 8.8 (±4.2)* 7.8 (±2.9)*
PICCO: pulse indicator continuous cardiac output system; GEDI: global end diastolic volume index; ELWI: extravascular lung water index; PVPI: pulmonary vascular permeability index; SVV: stroke volume variation; PPV: pulse pressure variation. * p < 0.05 vs. value on admission.
Table 3 Ventilator parameters during the first 24 h at the intensive care unit.
FiO2
PaO2 [mm Hg]
PaO2/ FiO2
PEEP [mbar]
Treatment group
Admission to ICU
6h
12 h
18 h
24 h
PICCO Conventional p-Value§ PICCO Conventional p-Value§ PICCO Conventional p-Value§ PICCO Conventional p-Value§
0.81 (±0.2) 0.79 (±0.2) 0.711 268 (±110) 245 (±119) 0.482 344 (±142) 321 (±151) 0.672 6.7 (±1.8) 7.0 (±2.5) 0.548
0.48 (±0.1)* 0.45 (±0.2)* 0.348 144 (±30)* 131 (±28)* 0.143 341 (±128) 308 (±141) 0.336 6.9 (±1.8) 6.9 (±2.2) 0.683
0.37 (±0.1)* 0.39 (±0.1)* 0.592 123 (±25)* 128 (±37)* 0.628 331 (±90) 339 (±134) 0.666 7.3 (±2.0) 7.1 (±2.4) 0.833
0.36 (±0.1)* 0.38 (±0.1)* 0.447 120 (±28)* 115 (±22)* 0.485 357 (±109) 310 (±105) 0.406 6.9 (±1.5) 7.1 (±2.1) 0.272
0.34 (±0.1)* 0.42 (±0.2)* 0.06 114 (±20)* 132 (±59)* 0.199 356 (±87) 317 (±104) 0.490 7.1 (±1.5) 7.2 (±2.0) 0.546
Ventilation parameters during the first 48 h. FiO2 : fraction of inspired oxygen; PaO2 : partial pressure of arterial oxygen; PEEP: positive end-expiratory pressure. * p < 0.05 vs. value on admission. § p < 0.5 conventional vs. PICCO.
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Table 4 Urine output and course of serum creatinine. Characteristic Serum creatinine [mg/dl] At admission 24 h 48 h Urine output [ml] After 24 h After 48 h
Study population (n = 51)
PICCO monitoring (n = 23)
Conventional monitoring (n = 28)
p value
1.26 ± 0.35 0.16 ± 0.34 0.56 ± 0.47
1.22 ± 0.49 0.06 ± 0.37 0.18 ± 0.18
1.29 ± 0.34 0.24 ± 0.41 0.87 ± 0.78
0.55 0.10 0.0005
2541 ± 752 4729 ± 1057
2717 ± 765 4866 ± 1360
2417 ± 754 4300 ± 1106
0.64 0.11
Urine output and course of serum creatinine. 24 h: change in serum creatinine in the first 24 h; 48 h: change in serum creatinine in the first 48 h.
monitoring without a history of chronic renal insufficiency developed an acute renal failure (Fig. 4). 4. Discussion We have investigated the influence of volume therapy guided by volumetric (ELWI, GEDI) and arterial waveform derived variables (PPV, SVV) on AKI in patients with cardiogenic shock after cardiac arrest treated with mild therapeutic hypothermia. We found that, compared to conventionally monitored patients, the resulting increase in volume therapy correlated with a significantly reduced rate of AKI. Fluid management in cardiogenic shock has not been adequately studied.24 Traditionally the central venous pressure (CVP) has been used to guide fluid management. However, due to the changes in venous tone, intrathoracic pressures, LV and RV compliance and geometry that occur in critically ill patients, there is a poor relationship between the central venous pressure and RV end-diastolic volume. More than 100 studies have been published to date that have demonstrated no relationship between the CVP (or change in CVP) and fluid responsiveness in various clinical settings.25 In contrast to this, parameters derived from transpulmonary thermodilution like the extra vascular lung water index (ELWI) or the global enddiastolic volume index (GEDI) have been shown to reliable allow the assessment of the volume status of a patient.19,26 A recent meta analysis also found that dynamic changes in arterial waveformderived parameters like PPV and SVV measured during mechanical ventilation can predict with a high of accuracy patients who are likely to respond to a fluid challenge.27 The present study demonstrates that in patients with cardiogenic shock after cardiac arrest treated with mild therapeutic hypothermia an increase in volume therapy driven by volumetric (ELWI, GEDI) and arterial waveform
Fig. 3. Linear correlation between the increase in serum creatinine after 48 h and the amount of intravenous administered fluid. r2 = 0.09; p = 0.02.
derived variables (PPV, SVV) results in a significant reduction of AKI compared to patients treated without invasive monitoring. Of the limited number of studies on AKI in patients with cardiogenic shock after cardiac arrest only two reported the incidence of AKI based on modern consensus definitions. Hasper et al.28 used the AKIN criteria29 and found that 22.7% of the included patients had AKI stage 2 or 3. Based on the RIFLE criteria22 the incidence of AKI class I/F was 31.4% in a recent publication by Chua et al.7 In contrast to our patients only 57% of the patients were treated with mild therapeutic hypothermia by Hasper et al., while none of the patients were cooled in the study of Chua et al. Despite these differences regarding hypothermia we observed similar rates of AKI (28.6%) in the group with conventional monitoring. In addition to that, a recent meta analysis found no evidence that mild therapeutic hypothermia influences the occurrence of AKI.30 The authors are not aware of a study specifically addressing the issue of AKI and fluid management in patients with cardiogenic shock after cardiac arrest. Rivers et al.31 demonstrated that early, protocol directed resuscitation including crystalloid, colloid and blood administration was associated with improved survival and less organ dysfunction in septic shock. In another single center study, protocolized resuscitation for septic shock initiated in the ICU within 4 h of diagnosis resulted in improved survival and lower incidence of renal dysfunction.32 However there is emerging evidence that timing and amount of fluid therapy are important issues and that liberal fluid administration might have detrimental effects.24,33
Fig. 4. Frequency of acute kidney injury stages ‘at risk’ or ‘injury’ and ‘failure’ in PICCO monitored patients and conventional monitored patients defined by the RIFLE criteria.
C. Adler et al. / Resuscitation 84 (2013) 194–199
5. Limitations The present study has certain limitations that need to be taken into account for the interpretation of the results. Patients with preexisting renal disease have been included into the study. To be completely methodologically completely correct, the basis for the investigation of a treatment preventing kidney disease should be normal kidney function. However, since in clinical reality patients with post-resuscitation syndrome are often affected by renal disease it seemed reasonable to also include such patients into the analysis. The number of patients with preexisting renal disease was not significantly different between the groups, therefore a bias is not likely (PICCO monitoring 17% vs. conventional monitoring 14%, p = 1). Due the retrospective nature, the relatively small sample size and the fact that the two groups compared in the study are not contemporary but differ for the time of enrolment further evaluation is warranted before routinely recommending the suggested fluid regime in patients with CS after OHCA”. 6. Conclusion The presented data suggest that volume therapy guided by volumetric (ELWI, GEDI) and arterial waveform derived variables (PPV, SVV) can reduce the incidence of AKI in patients with cardiogenic shock after cardiac arrest treated with mild therapeutic hypothermia. Conflict of interest statement None. Acknowledgment The study was not sponsored. References 1. Hochman JS. Cardiogenic shock complicating acute myocardial infarction: expanding the paradigm. Circulation 2003;107:2998–3002. 2. Adrie C, Laurent I, Monchi M, Cariou A, Dhainaou JF, Spaulding C. Postresuscitation disease after cardiac arrest: a sepsis-like syndrome? Curr Opin Crit Care 2004;10:208–12. 3. Akiyama K, Kimura A, Suzuki H, et al. Production of oxidative products of nitric oxide in infarcted human heart. J Am Coll Cardiol 1998;32:373–9. 4. Laurent I, Monchi M, Chiche JD, et al. Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest. J Am Coll Cardiol 2002;40:2110–6. 5. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization and long-term survival in cardiogenic shock complicating acute myocardial infarction. J Am Med Asoc 2006;295:2511–5. 6. Alexander JH, Reynolds HR, Stebbins AL, et al. Effect of tilarginine acetate in patients with acute myocardial infarction and cardiogenic shock: the TRIUMPH randomized controlled trial. J Am Med Assoc 2007;297:1657–66. 7. Chua HR, Glassford N, Bellomo R. Acute kidney injury after cardiac arrest. Resuscitation 2011. 8. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK investigators. Should we emergently revascularize occluded coronaries for cardiogenic shock. N Engl J Med 1999;341:625–34.
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