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Original article

Prognostic value of early hemodynamic improvement in patients with acute kidney injury and hemodynamic instability treated with continuous renal replacement therapy

Zayyat, Ali Al; Selim, Khaled*; Rashad, Rania; Mowafy, Hossam

Author Information
The Egyptian Journal of Critical Care Medicine: August 2018 - Volume 6 - Issue 2 - p 47-51
doi: 10.1016/j.ejccm.2018.06.001
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1. Introduction

Acute kidney injury (AKI) develops in nearly 40% of the patients admitted in intensive care unit (ICU) [1]. For ICU patients, particularly those with hemodynamic instability, continuous renal replacement therapy (CRRT) has emerged as the dialysis modality of choice. In hemodynamically stable patients, the Kidney Disease Improving Global Outcome (KDIGO) guidelines recommend either intermittent or continuous renal replacement therapy (CRRT) [2]. CRRT is the preferred mode of renal replacement therapy (RRT) in patients with hemodynamic instability. The KDIGO guidelines of 2012 also suggest using CRRT in hemodynamically unstable patients. CRRT offers advantages of improved hemodynamic stability, better overall solute clearance, and better fluid balance. Since 1977 Kramer's [3] description of continuous renal replacement therapies (CRRT), it was clear that these therapies provided improvement in hemodynamic parameters while reducing need for vasopressor agents in shock [4]. Different factors have been referred as possible explanation apart from a hypothetical role in immunomodulation, like a slow exchange of fluids providing a better elimination of interstitial fluid and a subsequent improvement in perfusion; a raise in vascular resistance secondary to a decreased temperature or an efficient normalization of acid-base status [5].

Aim of work

To determine whether hemodynamic improvement after 24 h in patients with AKI and hemodynamic instability treated with CRRT is a predictor of short term survival.

2. Patients and methods

  • This is a prospective, observational, single-center study carried out in critical care department, Cairo university in which we enrolled 30 patients admitted with hemodynamic instability and acute kidney injury (AKI). All patients were subjected to continuous renal replacement therapy (CRRT).
  • Patients were considered hemodynamically unstable if their mean arterial pressure (MAP) was lower than 60 mm Hg and/or necessitate norepinephrine (NE) support before CRRT.
  • AKI was defined according to the KDIGO definition of 2012 as an increment of serum creatinine ≥ 0.3 mg/dl within 48 h or an increase ≥ 50% from baseline within 7 days or urine output < 0.5 ml/kg/h for more than 6 h despite fluid resuscitation when applicable [2].
  • All patients enrolled in the study were subjected to the following: full history taking and thorough clinical examination, Acute Physiology and Chronic health evaluation (APACHE II) scoring on admission, daily SOFA scoring assessment, 12- lead ECG, chest x-ray, routine laboratory investigations including renal functions and electrolytes, abdominal ultrasound, echocardiographic assessment of LV function before and after CRRT.

2.1. CRRT data:

Our CRRT protocol consisted of a CVVHD mode with a double-lumen venous access catheter. The initial dosage was 35 ml/kg/hour, and convective treatment (ultrafiltrate) was administered in a dose as high as the vascular access permitted, aiming for a filtration fraction lower than 20%. The rest of the dosage was administered as diffusive therapy. The overall dose remained unchanged for at least the first 24 h and was then increased if metabolic control (serum creatinine below 2 mg/dl and pH normalization) was not acceptable. The anticoagulation regime depended on patient characteristics. Undergoing CVVHD using multifiltrate operating system manufactured by: Fresenius, Medical Care AG, GERMANY. (Fresenius medical care Multifiltrate operation manual). During CVVHD, close monitoring of the following was done: BP, HR, CVP, urine output, fluid balance and bleeding complications.

2.2. Data collection:

Clinical data were recorded, follow up of mean arterial blood pressure (MAP) and norepinephrine (NE) dosage before and 24 h after CRRT, daily follow up of hemodynamics, dosage of vasopressors, arterial blood gases, blood urea, serum creatinine, sodium, potassium and haemoglobin.

2.3. Patient groups:

Based on the hemodynamic response 24 h after CRRT, patients were classified into responders (defined as having a 20% reduction in norepinephrine (NE) dosage or a 20% rise in MAP with no increase in NE), compared with non-responders.

  • All patients were followed up for 15 days after withdrawal of CRRT.
  • Institutional Review Board approval was obtained from the Research Ethics Committee of Cairo university.

Informed consent was obtained from all participants included in the study.

3. Statistical analysis

Data was analyzed using IBM SPSS Advanced Statistics version 20.0 (SPSS Inc., Chicago, IL). Numerical data were expressed as mean and standard deviation or median and range as appropriate. Qualitative data were expressed as frequency and percentage. Chi-square test (Fisher's exact test) was used to examine the relation between qualitative variables. For quantitative data, comparison between two groups was done using Mann-Whitney test. Comparison of repeated measures was done using Wilcoxon signed-ranks test. P-value < 0.05 was considered significant.

4. Results

Baseline demographic and clinical characteristics are summarized in Table 1. The mean age of the entire population was 67.4 ± 10 years, 16 (53.3%) were males.18 patients (60%) were diagnosed with septic shock, 9 (30%) with cardiogenic shock, and 3 (10%) with hemorrhagic shock. The most prevalent co morbidities in the study population were hypertension (60%), diabetes (56.7%), IHD (40%), CKD (33.3%), and malignancy (33.3%). On admission, the mean APACHE II score was 27.13 ± 8 and the mean SOFA score was 7.9 ± 3.12. Out of the 30 patients enrolled in the study, 26 (86.7%) were mechanically ventilated prior to initiation of CRRT. Based on the hemodynamic response 24 h after CRRT, patients were classified into responders (defined as having a 20% reduction in norepinephrine (NE) dosage or a 20% rise in MAP with no increase in NE, compared with non-responders. Out of the 30 patients studied, 12 (40%) were responders and 18 (60%) were non-responders. The demographic data were not significantly different between responders and non-responders. There were no significant differences between both groups regarding the etiology of shock and the associated co morbidities apart from diabetes and end stage liver disease (ESLD) which were remarkably higher in non-responders compared with responders (13 versus 4, P = 0.03 and 8 versus 0, P = 0.01; respectively). The assessment scores at admission were not significantly different between the responders group and non-responders group (APACHE II score: 28 ± 7 versus 27 ± 9; P = 0.78). However, SOFA score tended to increase significantly in non-responders on day 3 (SOFA3) and day 4 (SOFA4) compared to responders (P = 0.01, P = 0.001; respectively). Furthermore, non-responders had higher incidence of mechanical ventilation prior to CRRT compared with responders (18 versus 8; P = 0.01).

Table 1
Table 1:
Baseline demographic and clinical characteristics of the study population.
Table 2
Table 2:
Baseline biochemical characteristics of responders and non responders.
Table 3
Table 3:
Comparison between responders and non-responders regarding hemodynamics and vasopressors during CRRT.
Table 4
Table 4:
Biochemical data of responders pre and post CRRT.
Table 5
Table 5:
Biochemical data of non-responders pre and post CRRT.

Echocardiographic data showed no significant differences between both groups before and after CRRT (Table 6).

Table 6
Table 6:
Comparison of echocardiographic data between responders and non-responders.

During a 15 days follow-up period, the mortality rate among the non responders group was 100%, compared to 25% among the responders group (18 versus 3; P = 0.001) (Fig. 1).

Fig. 1.
Fig. 1.:
Comparison between responders and non-responders regarding survival.

5. Discussion

Examining the factors that contribute to the occurrence of AKI in critically ill patients found that direct circulation dysfunction (including hypovolemia and cardiogenic shock)-induced AKI accounts for 47.3% of all cases of AKI [6]. In addition, Poukkanen et al, [7] showed that time-adjusted mean arterial pressure (MAP) below 73 mmHg, the use of dobutamine within the first 24 h in the ICU, and the highest lactate value during the first 24 h can accelerate the progression of AKI in patients with severe sepsis. These findings clearly demonstrated that renal injury is closely associated with hemodynamics, and the use of CRRT for accurate quantitative volume management can therefore provide prompt improvement in renal perfusion [8]. Since CRRT reduces further deterioration of renal function, and consequently the dependence on dialysis through maintenance of hemodynamic stability, the application of CRRT is highly recommended in severe AKI patients, especially for those with hemodynamic instability [9].

One of the most common complications with shock is acute kidney injury (AKI). Acute Kidney Injury (AKI) is a common complication in critically ill adult patients in critical care units [10]. The concerns about hemodynamic stability during hemodialysis, nephron injury, and the inability to adequately remove excess water and solutes have led to the development of a slower, less aggressive renal replacement therapy: continuous renal replacement therapy (CRRT). In our study we examined 30 patients admitted with hemodynamic instability and acute kidney injury. All patients were subjected to continuous renal replacement therapy (CRRT). Two groups of patients were defined after 24 h of treatment with CVVHD: responders; those with a 20% increase in MAP or 20% decrease in norepinephrine (NE) dosage and non-responders; those who did not develop a 20% decrease in (NE) dosage or a 20% increase in MAP without increase in NE dosage. Out of the 30 patient enrolled in this study, 12 (40%) were responders and 18 (60%) were nonresponders. Several possible mechanisms have been proposed to explain the improved hemodynamics after treatment with CVVHD. The improvement of hemodynamics has been detected in animal studies and, later, in different clinical studies and has been partly explained by a positive effect in the elimination of inflammatory mediators. Another explanation could be an immunomodulatory effect of CRRT which would also help to explain the possible benefit obtained when instituting these therapies early in the course of the inflammatory process [11].

Other possible factors affecting improvement have also been suggested; for example, vascular resistance and venous tone, as well as arterial blood pressure, are significantly higher during cold hemofiltration, and a decreased temperature could explain the improvement in some patients. Use of bicarbonate buffer, even with inconclusive evidence, has been shown in some reports to have a better hemodynamic profile than lactate-based solutions [11]. Our study showed that most of the diabetic patients included in the study were non-responders. It showed also that all patients with end stage liver disease included in the study were non responders.

Our results regarding end stage liver disease is similar to that of Allegretti et al, 2013[12], that showed increased in-hospital mortality in patients with co morbid liver disease. The association between end stage liver disease and poor outcome may reflect the high mortality associated with hepatorenal syndrome. However, Allegretti study showed that advanced age (age over 60) was a predictor for mortality in patients with AKI in contrast of our study. Daily SOFA scores were summarized to average SOFA scores before CRRT (SOFA 1 and SOFA 2) and average SOFA scores after CRRT (SOFA 3 and SOFA 4). It was found that there was no statistically significant differences between both groups regarding the APACHE II score. However, there was statistically significant higher SOFA scores post CRRT in the non-responders group.

Results regarding APACHE II score is different than that showed in the study of Brown et al, [13] that showed increased mortality with increasing APACHE II score in patients with AKI treated with CRRT. In contrast to our results, Shiao CC et al, showed that pre-CRRT SOFA score was a strong predictor for in-hospital mortality [14]. There was also a significant difference between responders and non-responders regarding the norepinephrine dose that was used to support hemodynamics before and during CRRT. Our study revealed statistically significant differences between responders and non responders regarding the short-term survival, the in-hospital mortality was significantly higher in non-responders (100%) compared to 25% among the responders. This results go with that of Manuel E et al., [11] that revealed significant differences in mortality rates between responders and non-responders in all patients included (30% mortality rate in responders vs. 74.7% in non-responders).

In conclusion, early hemodynamic improvement post-CRRT in patients with AKI and hemodynamic instability could be used as a predictor of short term survival.

6. Limitations

Because of the limited number of patients enrolled in the study, our results need to be confirmed by a larger multicenter studies. Our study is an observational study so no cause-effect relationship can be made.


[1] Liaño F, Junco E, Pascual J, et al. The spectrum of acute renal failure in the Intensive Care Unit compared with that seen in other settings. The Madrid Acute Renal Failure Study Group. Kidney Int Suppl 1998;66:S16-S24.
[2] Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;1:1-138.
[3] Kramer P, Wigger W, Rieger J, et al. Arteriovenous haemofiltration: a new and simple method for treatment of over-hydrated patients resistant to diuretics. Klin Wochenschr 1977;55:1121-1122.
[4] Barzilay E, Kessler D, Berlot G, et al. Use of extracorporeal supportive techniques as additional treatment for septic-induced multiple organ failure patients. Crit Care Med 1989;17:634-637.
[5] Van Kuijk WH, Hillion D, Savoiu C, et al. Critical role of the extracorporeal blood temperature in the hemodynamic response during hemofiltration. J Am Soc Nephrol 1997;8:949-955.
[6] Hoste EA, Bagshaw SM, Bellomo R, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med 2015;41:1411-1423.
[7] Poukkanen M, Wilkman E, Vaara ST, et al. Hemodynamic variables and progression of acute kidney injury in critically ill patients with severe sepsis: data from the prospective observational FINNAKI study. Crit Care 2013;17:R295.
[8] Obi Y, Kim T, Kovesdy CP, et al. Current and potential therapeutic strategies for hemodynamic cardiorenal syndrome. Cardiorenal Med 2016;6:83-98.
[9] Prowle JR, Bellomo R. Continuous renal replacement therapy: Recent advances and future research. Nat Rev Nephrol 2010;6:521-529.
[10] Palevsky PM, Baldwin I, Davenport A, et al. Renal replacement therapy and the kidney: minimizing the impact of renal replacement therapy on recovery of acute renal failure. Curr Opin Crit Care 2005;11:548-554.
[11] ASAIO Journal 2006, Dr. Manuel E. Herrera Gutiérrez, UCI, Hospital Carlos Haya, Av. Carlos Haya s/n, 29018 Málaga Spain.
[12] Allegretti AS, Steele DJ, David-Kasdan JA, et al. Continuous renal replacement therapy outcomes in acute kidney injury and end-stage renal disease: a cohort study. Crit Care 2013;17(3):R109.
[13] Brown K, Challis M, Mikhail A. Continuous renal replacement therapy (CVVHD) for acute kidney injury in critical care: incidence and outcome across South West Wales. Crit Care 2014;18(Suppl 1):P391.
[14] Shiao CC, Wu VC, Li WY, et al. Late initiation of renal replacement therapy is associated with worse outcomes in acute kidney injury after major abdominal surgery. Crit Care 2009;13(5):R171.

Hemodynamic; Acute kidney injury; Continuous renal replacement therapy

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