Journal of Critical Care 29 (2014) 997–1000
Contents lists available at ScienceDirect
Journal of Critical Care journal homepage: www.jccjournal.org
Goal-directed therapy after cardiac surgery and the incidence of acute kidney injury Rebekah Thomson, Dip HE, BSc (Hons) a,⁎, Hanif Meeran, MBBS, FRCA a, Oswaldo Valencia, MD b, Nawaf Al-Subaie, MBChB, FRCA, EDIC, FFICM a a b
Cardiothoracic Intensive Care Unit, St Georges NHS Hospital Trust, London, United Kingdom Department of Cardiac Surgery, St Georges NHS Hospital Trust, London, United Kingdom
a r t i c l e
i n f o
Keywords: Goal-directed therapy Cardiac surgery Acute kidney injury
a b s t r a c t Objective: The purpose of this study was to assess the effect of goal-directed therapy (GDT), after cardiac surgery, on the incidence of acute kidney injury (AKI). Design: This is a prospective observational study designed to achieve and maintain maximum stroke volume for 8 hours, in patients after cardiac surgery. Setting: This is a single-center study in a 15-bedded cardiothoracic intensive care unit (ICU). Participants: Participants are patients after coronary artery bypass grafting and/or aortic valve surgery. Interventions: Patients in the GDT group received cardiac output monitoring and fluid challenges targeting an increase in stroke volume by at least 10%. Stroke volume maximization was maintained for a period of 8 hours from admission to the ICU. All other aspects of care were dictated by the clinical team. Patients in the standard therapy (ST) group had intravenous fluids in accordance with the routine practice of the unit. Patients were divided into the GDT and ST group dependant on availability of cardiac output monitors and allocation of nursing staff with training in GDT. Patients’ data were collected prospectively in both groups. Measurements and main results: One hundred twenty-three patients received GDT compared with 141 patients in the ST group. Both groups received similar volumes of fluid (GDT, 2905 [1367] mL vs 2704 [1393] mL; P = .09). Incidence of AKI was reduced in the GDT group (n = 8 [6.5%] vs n = 28 [19.9%]; P = .002). The median duration of hospital stay was 6 (4) days in the GDT group vs 7 (8) days in the ST, P = .004. Conclusion: Postoperative GDT in patients after cardiac surgery was associated with reduction in the incidence of AKI and a reduction in ICU and hospital duration of stay. © 2014 Elsevier Inc. All rights reserved.
1. Introduction There are more than 31 000 cardiac surgical procedures performed annually in the United Kingdom [1]. Up to 24% of patients, after cardiac surgery, develop acute kidney injury (AKI) with a subsequent 7-fold increase in mortality [2,3]. The mortality rate can be as high as 80% when renal replacement therapy (RRT) is required [4,5]. Many therapeutic strategies targeting AKI have been studied in the cardiac surgical population. Some of these include diuretics, dopamine, fenoldopam, calcium channel antagonists, atrial natriuretic peptide, N-acetylcysteine, and mannitol. No positive outcome was reported with any of these agents, while some showed deleterious effects on hemodynamics, renal function, and coagulation [6,7]. In the noncardiac surgical population, there are many observational studies that demonstrated an association between reduced cardiac
⁎ Corresponding author at: Cardiothoracic Intensive Care Unit, Atkinson Morley Wing, St Georges Hospital, Blackshaw Road, Tooting, London, SW17 0QT. E-mail address: [email protected] (R. Thomson). http://dx.doi.org/10.1016/j.jcrc.2014.06.011 0883-9441/© 2014 Elsevier Inc. All rights reserved.
index in the perioperative period and poor postoperative outcome [8–10]. Interventional studies where cardiac output and oxygen delivery were measured and artificially manipulated to achieve predefined hemodynamic goals showed a reduction in morbidity and, in some patient groups, improved survival [11–14]. Further work using minimally invasive cardiac output monitoring to achieve maximum stroke volume (SVmax) with intravenous fluid therapy resulted in a significant reduction in the rate of complications and duration of hospital stay [15–21]. The beneficial effect is likely to be attributed to the prevention of tissue hypoxia [22,23]. There are currently limited data in relation to the role of GDT in cardiac surgery specifically in relation to AKI, but it is thought that maintaining renal perfusion in the postoperative period may have a beneficial impact. Studies in this group of patients are hindered by the differing hemodynamic goals targeted and the heterogeneity in assessing postoperative outcome. However, 2 recent meta-analyses showed a beneficial impact of GDT on postcardiac surgery complications [24,25]. A GDT protocol (Fig. 1.) was recently introduced in a 15-bed cardiac intensive care unit (ICU) with the therapeutic target of SV maximization for the first 8 postoperative hours. The aim of this
998
R. Thomson et al. / Journal of Critical Care 29 (2014) 997–1000
Fig. 1. Algorithm for SV maximization.
clinical evaluation is to assess the safety of this regimen in patients after cardiac surgery and its impact on renal dysfunction.
2. Materials and methods This was a prospective, single-center, observational study of GDT, in patients after cardiac surgery and the effect on renal dysfunction. The GDT protocol was based on SV maximization implemented by the intensive care nursing team (Fig. 1). This work was part of a clinical evaluation of GDT in the cardiac surgery setting with the aim to improve fluid administration on the ICU. Therefore, formal ethical approval and informed consent were not required in accordance with the UK National Health Service research authority [26]. Data collection was performed prospectively between December 2011 and August 2012. The primary outcome measure was AKI as defined by the AKI Network based on changes in serum creatinine concentrations [27] Urine output was not used to identify AKI in this study to exclude the effect of diuretic administration [28]. The serum creatinine measured on the third postoperative day, compared with the most recent preoperative measurement, was used to identify AKI to minimize the dilutional effects in relation to cardiopulmonary bypass [29]. Secondary outcome measures were total fluids administered in the
first 8 postoperative hours, commencement of RRT, duration of ICU stay, readmission rate to ICU, and duration of hospital stay. There were patients who did not receive GDT either because of the lack of nurses trained to deliver this therapy or the unavailability of cardiac output monitors. Those patients established the “standard therapy” (ST) group for the purpose of this data analysis. 2.1. Participants Adult patients undergoing on- and off-pump coronary artery bypass grafts (CABGs), aortic valve replacement (AVR), or combined CABG and AVR admitted to the ICU after surgery were included. These patients were selected due to the lower risk of right ventricular dysfunction. 2.2. Protocol The GDT protocol is based on achieving and maintaining SVmax in the first 8 hours after admission to the ICU. The patients were connected to a continuous arterial pressure-derived cardiac output monitor (LiDCOplus; LiDCO Group plc, London, United Kingdom) and a fluid challenge of 250 mL administered within 30 minutes of arrival
R. Thomson et al. / Journal of Critical Care 29 (2014) 997–1000
(SD) or median interquartile range (IQR), for parametric and nonparametric data, respectively. Categorical data were presented as ratios or percentages. The Kolmogorov-Smirnov test was used to determine whether data were normally distributed. A 2-tailed Student t test or Mann-Whitney U test were used to determine statistical significance for parametric and non-parametric data, respectively. χ2 or Fisher exact tests was used for categorical variables. A P b .05 was regarded as statistically significant.
Table 1 Characteristics
Age Sex Surgery (Off pump) (MIDCAB)
Height Weight BMI Ethnicity
Euroscore Baseline creatinine Creatinine clearance (Cockroft-Gault) median (IQR)
Mean (SD)
Years F:M
CABG total
AVR CABG & AVR Mean (SD) cm Mean (SD) kg Mean (SD) kg/m−2 White British Asian White other Afro-Caribbean Other median (IQR) median (IQR) μmol/L−1 mL/min−1
ST, n = 141
GDT, n = 123
P
69.8 (9.8) 1: 3.03 99 (2) (2) 18 24 169 (9) 80 (18) 27.77 (4.98) 95 (67.4%) 19 (13.5%) 21 (14.9%) 2 (1.4%) 4 (2.8%) 4.78 [5.87] 85 [29] 73 [40]
69 (10.9) 1:3.24 90 (2) (2) 15 18 171 (9) 84 (16) 28.84 (4.80) 99 (80.5%) 15 (12.2%) 4 (3.3%) 3 (2.4%) 2 (1.6%) 4.83 [5.98] 91 [29] 76 [49]
.51 .81 .85
999
.23 .05 .08 .01
3. Results
.57 .32 .50
BMI indicates body mass index; MIDCAB, minimally invasive direct coronary artery bypass.
to ICU via a large bore cannula. A positive response was defined as a at least 10% rise in stroke volume (SV) as in per previous GDT studies [16,19–21]. Fluid challenges were administered, until the patient was no longer fluid responsive as evident by a SV response of less than 10% after a fluid challenge (Fig. 1). Fluid challenges included gelatin-based colloids (Volplex, 4%; Beacon Pharmaceuticals, Kent, United Kingdom), crystalloids, and blood products when necessary. The central venous pressure, measured from the superior vena cava using an internal jugular venous catheter, was used as a safety trigger during the administration of a fluid challenge. A rise in central venous pressure of at least 5 mm Hg was the cut-off for further fluid administration and triggered an assessment of right ventricular function and cardiac tamponade. Maintaining SVmax can be difficult after cardiac surgery due to rewarming and changes in sedation/analgesia, which affect the SV by altering systemic vascular resistance. The contractility of the myocardium can also change, as the effect of any cardioplegic solution used is wearing off. Therefore, other indicators of intravascular volume depletion were considered such as a rise in arterial lactate concentration, oliguria, and hypotension (systemic mean arterial pressure of b60 mm Hg). A medical review was sought, when a patient was in circulatory shock refractory to fluid therapy. The patients in the control group did not receive cardiac output monitoring, and the intravenous fluids therapy was based on the perceived clinical need. These were guided by systemic arterial and venous pressures, serum lactate concentrations, urine output, and base deficit. 2.3. Statistical analysis Data were analyzed using IBM SPSS statistics for Windows version 20.0 (IBM Corp, Armonk, NY). Continuous data were presented as mean
A total of 264 patients were included with 123 patients in the GDT group and 141 in the control. There were 20 patients excluded from the analysis due to interruption of GDT, and implementation was incomplete. Patients in the GDT and ST groups had similar baseline characteristics with no difference in the number of off-pump or valve surgery in the 2 groups (Table 1). The preoperative creatinine was also similar in both groups (GDT 91 [29] μmol/L −1 vs ST, 85 [29] μmol/L −1; P = .32). There was no statistically significant difference in the volume of intravenous fluid administered in both groups during the first 8 hours in the intensive care (2704 [1393] mL in the ST vs 2905 [1367] mL in the GDT; P = .09). The incidence of AKI, on the third postoperative day, was significantly different between the 2 groups (19.9% vs 6.5% in the ST and GDT, respectively; P = .002) (Table 2). The rate of RRT was 10.6% in the ST vs 3.3% in the GDT (P = .021). The median ICU duration of stay in the control group was 24 hours in ST and 20 hours in the GDT (P≤ .001). The total duration of hospital stay was also reduced by 1 day (7 [8] in the ST vs 6 [4] in GDT; P = .04). The rate of readmissions to the intensive care was reduced in the GDT group (9.2% vs 3.3%; P = .049; see Electronic supplementary material for the indications of readmission). 4. Discussion A nurse-delivered GDT protocol targeting SVmax for the first 8 hours after cardiac surgery was associated with reduction in the incidence of AKI and a reduction in the number of patients requiring RRT. There was a reduction in the duration of ICU and hospital stay with a reduced incidence of readmissions to the ICU associated with GDT. The volume of intravenous fluids administered to patients in both groups was similar. Although the GDT group received fluids early on before hemodynamic, compromise was observed unlike the ST group, which received fluids based on hemodynamic observations. The impact of GDT on the incidence of renal dysfunction, as a primary outcome, was not assessed in any previous studies. However a metaanalysis, including noncardiac and cardiac surgery studies, identified an associated reduction in renal dysfunction with GDT [30]. The generalizability of these findings are limited by the varying criteria used to identify renal dysfunction and the heterogeneity in the studies included. The overall incidence of AKI requiring RRT in this clinical evaluation was higher than described in the literature with approximately half of the patients who developed AKI went on to receive RRT. This was applicable to both the ST and the GDT groups, which
Table 2 Results
Surgical drain loss median (IQR) Total fluids received Creatinine clearance (day 3) median (IQR) AKI (day 3) RRT Readmission Time to readiness to discharge from ICU Duration of hospital stay Mortality
Median (IQR)
Median (IQR) Median (IQR)
mL mLs mL/min−1 n n n Hours Days n
ST, n = 141
GDT, n = 123
P
500 [440] 2704 [1393] 73 [49] 28 (19.9%) 15 (10.6%) 13 (9.2%) 24 [25] 7 [8] 2 (1.4%)
520 [360] 2905 [1367] 79 [51] 8 (6.5%) 4 (3.3%) 4 (3.3%) 20 [6] 6 [4] 2 (1.6%)
.48 .09 .048 .002 .021 .049 b.001 .004 .89
1000
R. Thomson et al. / Journal of Critical Care 29 (2014) 997–1000
indicate the ICU unit practice of early initiation of RRT at the time of data collection. The findings of this clinical evaluation with regards to the duration of hospital stay are in line with previous GDT work both in noncardiac and cardiac surgery patients [15,20,31]. The reported hospital duration of stay is the number of days spent in the hospital with the clinical team on the ward having no knowledge of the type of fluid therapy patients had received in the ICU. However, fitness for discharge from the hospital was not based on a preset criteria, and a number of factors unrelated to patient’s well being may have played a role in determining the duration of hospital stay. The work presented is limited by its observational nature, where a causal relationship between GDT and the reduction in the incidence of renal dysfunction observed cannot be ascertained. A potential source of bias may be related to delivery of GDT by a group of self-selected proactive nurses who have shown an interest in adopting this change in practice. Other aspects of patients’ care provided by those nurses may have been different, which may have influenced outcome. The primary outcome of the study was AKI, as defined by the Acute Kidney Injury Network criteria, based on change in creatinine concentration and not including urine output. The latter was thought to be affected by a multitude of factors including physiologic adaptation to stress and the use of diuretics [28], but this may have led to underdiagnosis of the incidence of AKI [32]. The number of patients included was not based on formal sample size calculations, and there were 20 patients excluded from analysis due to lack of adherence to GDT or missing data. The original purpose of this work was to evaluate the clinical impact of maximizing SV on patients after cardiac surgery. Although the surgical procedures included may seem varied, it was thought that CABG, AVR, or combined CABG and AVR are similar in many respects. Patients undergoing these procedures have a similar complication profile based on local hospital data. Those patients are less likely to develop right ventricular dysfunction, compared with other cardiac surgical procedures, where any improvement in cardiac output must be weighed against the risk of right ventricular failure. The inclusion of off-pump surgery was in light of lack of definitive evidence to suggest a lower risk of postoperative AKI compared with on-pump surgery [33]. The delivery of this protocol was by the nursing staff routinely caring for patients. The intensive care nurses were competent in protocol implementation after a short period of training. The lack of difference in the volume of intravenous fluids given, in the first 8 postoperative hours, is reassuring and consistent with a previous GDT study [21]. The significant reduction in the incidence of AKI has both short- and long-term implication on overall morbidity in addition to the financial impact as result of reducing duration of ICU and hospital stay [2]. The association shown in this study between GDT, in the postoperative period after cardiac surgery, and the reduction in renal dysfunction forms a foundation for a randomized controlled trial in this group of patients. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.jcrc.2014.06.011.
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Haemodynamic goal-directed therapy in cardiac and vascular surgery. A systematic review and meta-analysis. Interact Cardiovasc Thorac Surg 2012;15(5):878–87. Aya HD, Cecconi M, Hamilton M, Rhodes A. Goal-directed therapy in cardiac surgery: a systematic review and meta-analysis. Br J Anaesth 2013;110(4):510–7. NHS Health Research Authority. http://www.hra.nhs.uk//research-community/ before-you-apply/determine-whether-your-study-is-research/; 2014. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute Kidney Injury N. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007;11(2):R31. Legrand M, Payen D. Understanding urine output in critically ill patients. Ann Intensive Care 2011;1(1):13. Ho J, Reslerova M, Gali B, Nickerson PW, Rush DN, Sood MM, et al. Serum creatinine measurement immediately after cardiac surgery and prediction of acute kidney injury. Am J Kidney Dis 2012;59(2):196–201. 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Contents lists available at ScienceDirect
Journal of Critical Care journal homepage: www.jccjournal.org
Goal-directed therapy after cardiac surgery and the incidence of acute kidney injury Rebekah Thomson, Dip HE, BSc (Hons) a,⁎, Hanif Meeran, MBBS, FRCA a, Oswaldo Valencia, MD b, Nawaf Al-Subaie, MBChB, FRCA, EDIC, FFICM a a b
Cardiothoracic Intensive Care Unit, St Georges NHS Hospital Trust, London, United Kingdom Department of Cardiac Surgery, St Georges NHS Hospital Trust, London, United Kingdom
a r t i c l e
i n f o
Keywords: Goal-directed therapy Cardiac surgery Acute kidney injury
a b s t r a c t Objective: The purpose of this study was to assess the effect of goal-directed therapy (GDT), after cardiac surgery, on the incidence of acute kidney injury (AKI). Design: This is a prospective observational study designed to achieve and maintain maximum stroke volume for 8 hours, in patients after cardiac surgery. Setting: This is a single-center study in a 15-bedded cardiothoracic intensive care unit (ICU). Participants: Participants are patients after coronary artery bypass grafting and/or aortic valve surgery. Interventions: Patients in the GDT group received cardiac output monitoring and fluid challenges targeting an increase in stroke volume by at least 10%. Stroke volume maximization was maintained for a period of 8 hours from admission to the ICU. All other aspects of care were dictated by the clinical team. Patients in the standard therapy (ST) group had intravenous fluids in accordance with the routine practice of the unit. Patients were divided into the GDT and ST group dependant on availability of cardiac output monitors and allocation of nursing staff with training in GDT. Patients’ data were collected prospectively in both groups. Measurements and main results: One hundred twenty-three patients received GDT compared with 141 patients in the ST group. Both groups received similar volumes of fluid (GDT, 2905 [1367] mL vs 2704 [1393] mL; P = .09). Incidence of AKI was reduced in the GDT group (n = 8 [6.5%] vs n = 28 [19.9%]; P = .002). The median duration of hospital stay was 6 (4) days in the GDT group vs 7 (8) days in the ST, P = .004. Conclusion: Postoperative GDT in patients after cardiac surgery was associated with reduction in the incidence of AKI and a reduction in ICU and hospital duration of stay. © 2014 Elsevier Inc. All rights reserved.
1. Introduction There are more than 31 000 cardiac surgical procedures performed annually in the United Kingdom [1]. Up to 24% of patients, after cardiac surgery, develop acute kidney injury (AKI) with a subsequent 7-fold increase in mortality [2,3]. The mortality rate can be as high as 80% when renal replacement therapy (RRT) is required [4,5]. Many therapeutic strategies targeting AKI have been studied in the cardiac surgical population. Some of these include diuretics, dopamine, fenoldopam, calcium channel antagonists, atrial natriuretic peptide, N-acetylcysteine, and mannitol. No positive outcome was reported with any of these agents, while some showed deleterious effects on hemodynamics, renal function, and coagulation [6,7]. In the noncardiac surgical population, there are many observational studies that demonstrated an association between reduced cardiac
⁎ Corresponding author at: Cardiothoracic Intensive Care Unit, Atkinson Morley Wing, St Georges Hospital, Blackshaw Road, Tooting, London, SW17 0QT. E-mail address: [email protected] (R. Thomson). http://dx.doi.org/10.1016/j.jcrc.2014.06.011 0883-9441/© 2014 Elsevier Inc. All rights reserved.
index in the perioperative period and poor postoperative outcome [8–10]. Interventional studies where cardiac output and oxygen delivery were measured and artificially manipulated to achieve predefined hemodynamic goals showed a reduction in morbidity and, in some patient groups, improved survival [11–14]. Further work using minimally invasive cardiac output monitoring to achieve maximum stroke volume (SVmax) with intravenous fluid therapy resulted in a significant reduction in the rate of complications and duration of hospital stay [15–21]. The beneficial effect is likely to be attributed to the prevention of tissue hypoxia [22,23]. There are currently limited data in relation to the role of GDT in cardiac surgery specifically in relation to AKI, but it is thought that maintaining renal perfusion in the postoperative period may have a beneficial impact. Studies in this group of patients are hindered by the differing hemodynamic goals targeted and the heterogeneity in assessing postoperative outcome. However, 2 recent meta-analyses showed a beneficial impact of GDT on postcardiac surgery complications [24,25]. A GDT protocol (Fig. 1.) was recently introduced in a 15-bed cardiac intensive care unit (ICU) with the therapeutic target of SV maximization for the first 8 postoperative hours. The aim of this
998
R. Thomson et al. / Journal of Critical Care 29 (2014) 997–1000
Fig. 1. Algorithm for SV maximization.
clinical evaluation is to assess the safety of this regimen in patients after cardiac surgery and its impact on renal dysfunction.
2. Materials and methods This was a prospective, single-center, observational study of GDT, in patients after cardiac surgery and the effect on renal dysfunction. The GDT protocol was based on SV maximization implemented by the intensive care nursing team (Fig. 1). This work was part of a clinical evaluation of GDT in the cardiac surgery setting with the aim to improve fluid administration on the ICU. Therefore, formal ethical approval and informed consent were not required in accordance with the UK National Health Service research authority [26]. Data collection was performed prospectively between December 2011 and August 2012. The primary outcome measure was AKI as defined by the AKI Network based on changes in serum creatinine concentrations [27] Urine output was not used to identify AKI in this study to exclude the effect of diuretic administration [28]. The serum creatinine measured on the third postoperative day, compared with the most recent preoperative measurement, was used to identify AKI to minimize the dilutional effects in relation to cardiopulmonary bypass [29]. Secondary outcome measures were total fluids administered in the
first 8 postoperative hours, commencement of RRT, duration of ICU stay, readmission rate to ICU, and duration of hospital stay. There were patients who did not receive GDT either because of the lack of nurses trained to deliver this therapy or the unavailability of cardiac output monitors. Those patients established the “standard therapy” (ST) group for the purpose of this data analysis. 2.1. Participants Adult patients undergoing on- and off-pump coronary artery bypass grafts (CABGs), aortic valve replacement (AVR), or combined CABG and AVR admitted to the ICU after surgery were included. These patients were selected due to the lower risk of right ventricular dysfunction. 2.2. Protocol The GDT protocol is based on achieving and maintaining SVmax in the first 8 hours after admission to the ICU. The patients were connected to a continuous arterial pressure-derived cardiac output monitor (LiDCOplus; LiDCO Group plc, London, United Kingdom) and a fluid challenge of 250 mL administered within 30 minutes of arrival
R. Thomson et al. / Journal of Critical Care 29 (2014) 997–1000
(SD) or median interquartile range (IQR), for parametric and nonparametric data, respectively. Categorical data were presented as ratios or percentages. The Kolmogorov-Smirnov test was used to determine whether data were normally distributed. A 2-tailed Student t test or Mann-Whitney U test were used to determine statistical significance for parametric and non-parametric data, respectively. χ2 or Fisher exact tests was used for categorical variables. A P b .05 was regarded as statistically significant.
Table 1 Characteristics
Age Sex Surgery (Off pump) (MIDCAB)
Height Weight BMI Ethnicity
Euroscore Baseline creatinine Creatinine clearance (Cockroft-Gault) median (IQR)
Mean (SD)
Years F:M
CABG total
AVR CABG & AVR Mean (SD) cm Mean (SD) kg Mean (SD) kg/m−2 White British Asian White other Afro-Caribbean Other median (IQR) median (IQR) μmol/L−1 mL/min−1
ST, n = 141
GDT, n = 123
P
69.8 (9.8) 1: 3.03 99 (2) (2) 18 24 169 (9) 80 (18) 27.77 (4.98) 95 (67.4%) 19 (13.5%) 21 (14.9%) 2 (1.4%) 4 (2.8%) 4.78 [5.87] 85 [29] 73 [40]
69 (10.9) 1:3.24 90 (2) (2) 15 18 171 (9) 84 (16) 28.84 (4.80) 99 (80.5%) 15 (12.2%) 4 (3.3%) 3 (2.4%) 2 (1.6%) 4.83 [5.98] 91 [29] 76 [49]
.51 .81 .85
999
.23 .05 .08 .01
3. Results
.57 .32 .50
BMI indicates body mass index; MIDCAB, minimally invasive direct coronary artery bypass.
to ICU via a large bore cannula. A positive response was defined as a at least 10% rise in stroke volume (SV) as in per previous GDT studies [16,19–21]. Fluid challenges were administered, until the patient was no longer fluid responsive as evident by a SV response of less than 10% after a fluid challenge (Fig. 1). Fluid challenges included gelatin-based colloids (Volplex, 4%; Beacon Pharmaceuticals, Kent, United Kingdom), crystalloids, and blood products when necessary. The central venous pressure, measured from the superior vena cava using an internal jugular venous catheter, was used as a safety trigger during the administration of a fluid challenge. A rise in central venous pressure of at least 5 mm Hg was the cut-off for further fluid administration and triggered an assessment of right ventricular function and cardiac tamponade. Maintaining SVmax can be difficult after cardiac surgery due to rewarming and changes in sedation/analgesia, which affect the SV by altering systemic vascular resistance. The contractility of the myocardium can also change, as the effect of any cardioplegic solution used is wearing off. Therefore, other indicators of intravascular volume depletion were considered such as a rise in arterial lactate concentration, oliguria, and hypotension (systemic mean arterial pressure of b60 mm Hg). A medical review was sought, when a patient was in circulatory shock refractory to fluid therapy. The patients in the control group did not receive cardiac output monitoring, and the intravenous fluids therapy was based on the perceived clinical need. These were guided by systemic arterial and venous pressures, serum lactate concentrations, urine output, and base deficit. 2.3. Statistical analysis Data were analyzed using IBM SPSS statistics for Windows version 20.0 (IBM Corp, Armonk, NY). Continuous data were presented as mean
A total of 264 patients were included with 123 patients in the GDT group and 141 in the control. There were 20 patients excluded from the analysis due to interruption of GDT, and implementation was incomplete. Patients in the GDT and ST groups had similar baseline characteristics with no difference in the number of off-pump or valve surgery in the 2 groups (Table 1). The preoperative creatinine was also similar in both groups (GDT 91 [29] μmol/L −1 vs ST, 85 [29] μmol/L −1; P = .32). There was no statistically significant difference in the volume of intravenous fluid administered in both groups during the first 8 hours in the intensive care (2704 [1393] mL in the ST vs 2905 [1367] mL in the GDT; P = .09). The incidence of AKI, on the third postoperative day, was significantly different between the 2 groups (19.9% vs 6.5% in the ST and GDT, respectively; P = .002) (Table 2). The rate of RRT was 10.6% in the ST vs 3.3% in the GDT (P = .021). The median ICU duration of stay in the control group was 24 hours in ST and 20 hours in the GDT (P≤ .001). The total duration of hospital stay was also reduced by 1 day (7 [8] in the ST vs 6 [4] in GDT; P = .04). The rate of readmissions to the intensive care was reduced in the GDT group (9.2% vs 3.3%; P = .049; see Electronic supplementary material for the indications of readmission). 4. Discussion A nurse-delivered GDT protocol targeting SVmax for the first 8 hours after cardiac surgery was associated with reduction in the incidence of AKI and a reduction in the number of patients requiring RRT. There was a reduction in the duration of ICU and hospital stay with a reduced incidence of readmissions to the ICU associated with GDT. The volume of intravenous fluids administered to patients in both groups was similar. Although the GDT group received fluids early on before hemodynamic, compromise was observed unlike the ST group, which received fluids based on hemodynamic observations. The impact of GDT on the incidence of renal dysfunction, as a primary outcome, was not assessed in any previous studies. However a metaanalysis, including noncardiac and cardiac surgery studies, identified an associated reduction in renal dysfunction with GDT [30]. The generalizability of these findings are limited by the varying criteria used to identify renal dysfunction and the heterogeneity in the studies included. The overall incidence of AKI requiring RRT in this clinical evaluation was higher than described in the literature with approximately half of the patients who developed AKI went on to receive RRT. This was applicable to both the ST and the GDT groups, which
Table 2 Results
Surgical drain loss median (IQR) Total fluids received Creatinine clearance (day 3) median (IQR) AKI (day 3) RRT Readmission Time to readiness to discharge from ICU Duration of hospital stay Mortality
Median (IQR)
Median (IQR) Median (IQR)
mL mLs mL/min−1 n n n Hours Days n
ST, n = 141
GDT, n = 123
P
500 [440] 2704 [1393] 73 [49] 28 (19.9%) 15 (10.6%) 13 (9.2%) 24 [25] 7 [8] 2 (1.4%)
520 [360] 2905 [1367] 79 [51] 8 (6.5%) 4 (3.3%) 4 (3.3%) 20 [6] 6 [4] 2 (1.6%)
.48 .09 .048 .002 .021 .049 b.001 .004 .89
1000
R. Thomson et al. / Journal of Critical Care 29 (2014) 997–1000
indicate the ICU unit practice of early initiation of RRT at the time of data collection. The findings of this clinical evaluation with regards to the duration of hospital stay are in line with previous GDT work both in noncardiac and cardiac surgery patients [15,20,31]. The reported hospital duration of stay is the number of days spent in the hospital with the clinical team on the ward having no knowledge of the type of fluid therapy patients had received in the ICU. However, fitness for discharge from the hospital was not based on a preset criteria, and a number of factors unrelated to patient’s well being may have played a role in determining the duration of hospital stay. The work presented is limited by its observational nature, where a causal relationship between GDT and the reduction in the incidence of renal dysfunction observed cannot be ascertained. A potential source of bias may be related to delivery of GDT by a group of self-selected proactive nurses who have shown an interest in adopting this change in practice. Other aspects of patients’ care provided by those nurses may have been different, which may have influenced outcome. The primary outcome of the study was AKI, as defined by the Acute Kidney Injury Network criteria, based on change in creatinine concentration and not including urine output. The latter was thought to be affected by a multitude of factors including physiologic adaptation to stress and the use of diuretics [28], but this may have led to underdiagnosis of the incidence of AKI [32]. The number of patients included was not based on formal sample size calculations, and there were 20 patients excluded from analysis due to lack of adherence to GDT or missing data. The original purpose of this work was to evaluate the clinical impact of maximizing SV on patients after cardiac surgery. Although the surgical procedures included may seem varied, it was thought that CABG, AVR, or combined CABG and AVR are similar in many respects. Patients undergoing these procedures have a similar complication profile based on local hospital data. Those patients are less likely to develop right ventricular dysfunction, compared with other cardiac surgical procedures, where any improvement in cardiac output must be weighed against the risk of right ventricular failure. The inclusion of off-pump surgery was in light of lack of definitive evidence to suggest a lower risk of postoperative AKI compared with on-pump surgery [33]. The delivery of this protocol was by the nursing staff routinely caring for patients. The intensive care nurses were competent in protocol implementation after a short period of training. The lack of difference in the volume of intravenous fluids given, in the first 8 postoperative hours, is reassuring and consistent with a previous GDT study [21]. The significant reduction in the incidence of AKI has both short- and long-term implication on overall morbidity in addition to the financial impact as result of reducing duration of ICU and hospital stay [2]. The association shown in this study between GDT, in the postoperative period after cardiac surgery, and the reduction in renal dysfunction forms a foundation for a randomized controlled trial in this group of patients. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.jcrc.2014.06.011.
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