acute kidney injury after hepatic surgery with goal...

Original Article J. St. Marianna Univ.Vol. 6, pp. 47–54, 2015

1 Department of Anesthesiology, St. Marianna University School of Medicine2 Department of Surgery, Division of Gastroenterological and General Surgery

Acute Kidney Injury after Hepatic Surgery

with Goal Directed Fluid Therapy

Miki Sakamoto1, Yuki Kobayashi1, Saori Tanigawa1, Hidetoshi Miyakawa1, Takehito Otsubo2, and Takeshi Tateda1

(Received for Publication: February 26, 2015)

AbstractBackground: Goal-directed therapy (GDT) has been shown to reduce perioperative complications. However,whether the restriction of fluid volume in goal-directed therapy causes acute kidney injury (AKI) remains to bedetermined. The aim of this study was to determine intraoperative risk factors for AKI after hepatic surgery withgoal-directed therapy using restricted fluid volume.Methods: Anesthesia and medical records of 67 patients who underwent hepatic resection were analyzed. Cen‐tral venous pressure (CVP) and stroke volume variation (SVV) were monitored continuously by arterial contouranalysis using a FloTrack sensorTM (Edwards life sciences LLC, CA, USA) for restrictive fluid management dur‐ing portal triad clamping (PTC) with inferior vena cava (IVC) clamping. Low CVP (<5 cmH2O) and high SVV(>12%) were achieved by restrictive fluid management during PTC. AKI was assessed using the AKI networkdefinition.Results: Eight patients developed stage-1 AKI (12%) after hepatic resection, but none of the patients requiredrenal replacement therapy. The durations of anesthesia and PTC were longer in the AKI group than in the non-AKI group (P=0.006 and P=0.004). The IVC was clamped more frequently in the AKI group than in the non-AKI group (P=0.004). The amount of blood loss was larger and the necessity for blood transfusion was higherin the AKI group than in the non-AKI group (P=0.02 and P=0.001).Conclusion: The duration of PTC with IVC clamping and blood loss affects the incidence of AKI after hepaticsurgery using GDT with restrictive fluid volume management. We suggest that unstable hemodynamics duringPTC with IVC clamping and blood loss contribute to AKI after hepatic surgery.

Key wordsgoal directed therapy (GDT), acute kidney injury (AKI), hepatic resection

Introduction

Perioperative renal failure has a large influenceon postoperative complications and mortality. Whenan acute kidney injury (AKI) occurs, the risk of mor‐tality rises after an operation. Impaired renal func‐tion, an existing disease (diabetes and heart disease),or advanced age are known as factors distinctive tothe patients, while cardiovascular surgery, the use ofcontrast media, or massive bleeding and transfusion

are considered as intraoperative factors12). Severalstudies showed AKI in about 30% of cases after car‐diovascular surgery3). On the other hand, the occur‐rence of AKI was estimated at less than 10% afterliver resection4). Recently, Spolverato et al demon‐strated that acute renal failure occurred in 4.2% of ca‐ses after hepatic surgery5).

During hepatic resection, lowering the centralvenous pressure is effective in reducing blood loss6).Thus, intraoperative restrictive fluids and clamping of

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the portal triad (PTC) and inferior vena cava (IVC)are required to decrease central venous pressure7).However, both restriction of the volume of fluids andPTC with clamping of IVC may decrease cardiac out‐put, resulting in reduction of renal blood flow as wellas causing postoperative AKI8). Restricted fluids vol‐ume therapy during surgery has been advocated forthe last decade9)and has shown better outcomes thanconventional therapy10). Furthermore, volume over‐load during fluid resuscitation worsens organ perfu‐sion during AKI11). Goal-directed therapy (GDT) is astrategy for administering fluids and cardiovasculardrugs to help guide physicians with monitoring tech‐niques12). However, whether goal-directed and/or re‐stricted volume therapy causes AKI has not been de‐termined13).

The aim of this retrospective study was to evalu‐ate the intraoperative risk factors for AKI after hep‐atic surgery with goal-directed therapy using restric‐ted volumes.

Methods

The ethical approval for this study (No. 2331)was provided by the Ethical Committee of St. Ma‐rianna University School of Medicine.

Patients with significant renal dysfunction (pre‐operative eGFR <60ml/min) and patients who re‐ceived hemodialysis or emergency operation were ex‐cluded.

1. Study DesignAnesthesia and medical records of patients who

underwent hepatic resection for liver tumors at St.Marianna University Hospital between August 2009and July 2010 were studied.

2. AnesthesiaPremedication was not administered to all pa‐

tients. However, all patients received epidural anes‐thesia before surgery. An epidural catheter was inser‐ted in the vertebral interspace via either Th9/10 orTh10/11. General anesthesia was induced with pro‐pofol 1–2 mg/kg and remifentanil 0.5 mcg/kg/min.Tracheal intubation was facilitated with rocuronium0.9 mg/kg. Anesthesia was maintained with 1–1.5%sevoflurane and oxygen-air mixture and remifentanil.Levobupivacaine 0.125% or 0.25% was administeredvia epidural catheter during and after surgery for per‐ioperative analgesia.

All patients underwent controlled mechanicalventilation with oxygen and air.

After the induction of anesthesia, either the leftor right radial artery was cannulated.

Then central venous catheter was introduced viathe right internal jugular vein.

3. Goal-directed and Fluid Management DuringSurgery

Radial arterial pressure and central venous pres‐sure catheter were connected to a hemodynamicmonitor, recording arterial pressure and CVP.

CVP and stroke volume variation (SVV) weremonitored continuously by arterial contour analysisusing the FloTrac sensorTM and the Vigileo TM moni‐tor (Edwards lifesciences LLC, CA, USA) for restric‐tive fluid management during PTC.

PTC with inferior vena cava clamping was per‐formed for 15 minutes followed by several periods ofunclamping for 5 minutes each.

Both low CVP (5 cm H2O) and high SVV (12%)during PTC were achieved by restricting fluid vol‐ume. Fluid management was achieved with standardapproach for liver resection14). Restricting fluid vol‐ume management (less than 5ml/kg/h) was appliedfrom the start of operation to completion of hepaticresection. After hepatic resection, maintenance fluidswere infused to achieve the assumed fluid require‐ment (over 10ml/kg/h). After this fluid therapy, if ei‐ther systolic blood pressure was <80 mmHg or SVVwas <12%, additional fluid boluses either colloid orcrystalloid were given. Packed blood cells were in‐cluded in resuscitation if the hemoglobin level was<7 g/dl.

4. Definition of AKI and Group ClassificationAKI was assessed using the AKI network defini‐

tion15).The AKI and non-AKI groups were differenti‐

ated by the level of serum creatinine (SCr) after sur‐gery.

Group AKI: Patients who showed a post-opera‐tive SCr of more than or equal to 0.3 mg/dl or an in‐crease of more than or equal to 150% to 200% fromthe baseline with in a 48 hour postoperative period(stage 1), or patients who showed that a post-opera‐tive SCr increase to more than 200 to 300% from thebaseline (stage 2), or patients who showed a post-op‐erative SCr increase of more than 300% from thebaseline or equal to 4.0 mg/dl with an acute increaseof at least 0.5 mg/dl (stage3).

Group non-AKI: Patients who showed a post-operative SCr of less than 0.3 mg/dl with in a 48 hour

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Sakamoto M Kobayashi Y et al48

postoperative period.

5. Data AnalysisThe patients’ demographic data, duration of sur‐

gery, anesthesia, and PTC, intraoperative fluid vol‐ume, amount of blood loss and blood transfusion uri‐nary output and frequency of IVC clamping wereinvestigated.

The preoperative and postoperative SCr valuesfor the AKI and non-AKI groups were also studied.Finally, the relationship between the increase of SCrand duration of surgery, anesthesia and PTC was ana‐lyzed.

6. Statistical AnalysisContinuous variables were presented as medians

(IQR: interquartile range). Categorical variables werepresented as persentages (%). All data were analyzedwith SPSS Statistics software, version 18.0 (IBM,Chicago, IL, USA).

Statistical analyses included Mann-Whitney U-test, Fisher’s exact test, Pearson correlation, and mul‐tiple logistic regression analysis. P<0.05 was consid‐ered significant.

Results

Between August 2009 and July 2010, hepatic re‐section for liver tumor was performed on 67 consecu‐tive patients. Eight patients developed stage-1 AKI(12%) after surgery, but none required renal replace‐ment therapy.

There were no differences in preoperative SCrbetween the AKI and non-AKI groups (median; 0.79vs 0.73 mg/dl, IQR; 0.67–0.84 vs 0.56–0.84). Postop‐eratively , SCr in the AKI group was larger (median;1.25 mg/dl, IQR; 1.04–1.34) than in the non-AKIgroup (median; 0.80 mg/dl, IQR; 0.65–0.93)(P=0.001, Figure 1).

In the AKI group, there were fewer female thanmale patients (P=0.002). More patients were compro‐mised with hypertension and diabetes mellitus in theAKI group than in the non-AKI group (P=0.02, Ta‐ble 1). The range of hepatic resections performedwas larger in the AKI group than in the non-AKIgroup (P=0.001, Table 1).

The durations of anesthesia and PTC were moreprolonged in the AKI group than in the non-AKIgroup (P=0.006 and P= 0.004, Table 2). The clamp‐ing of IVC was performed more frequently in theAKI group than in the non-AKI group (P= 0.004).The amount of blood loss was larger in the AKI

group than in the non-AKI group (P=0.02). Hence,there was a higher necessity for blood transfusion inthe AKI group than in the non-AKI group (P=0.001,Table 2).

There were no differences in fluids infusion rateand urinary output between the two groups.

Although the increase of SCr correlated weaklywith the duration of anesthesia and PTC(r=0.33,P=0.008 and r=0.30, P=0.013, Figure 2A and 2B),the correlation with the duration of surgery was notstatistically significant.

Finally, multiple logistic regression analysis forthe duration of anesthesia, and PTC and, volume ofblood loss and total fluids showed no differences be‐tween the AKI and non-AKI groups (Table 3).

Discussion

The incidence of AKI after hepatic surgery inthe present study was 12%. This agrees with the re‐sults of Slankamenac et al16) who reported an inci‐dence of 15.1% which was highly associated withmortality (23.2%). In our study, the degree of renaldysfunction was less than in the study of Slankama‐naec et al. All of the AKI patients in our study werestage-1 and no patients received renal replacementtherapy or passed away. This discrepancy may bepartly explained by the difference of pre-existing co‐morbidity. Although any patients with renal dysfunc‐tion was excluded in our study, patient with preexist‐ing chronic renal failure (32.6%) were included in thestudy of Slankamanaec et al.

Our findings are congruent with those reportedby Correa-Gallego17). They reported that low centralvenous pressure-assisted hepatectomy was associatedwith AKI (17%). They also reported that 13% of pa‐tients had been at risk, 2% experienced injury and 1%experienced failure in RIFLE (risk-injury-failure-loss-end-stage) criteria18).

Fluids management during abdominal surgeryhas changed in the last decade. Traditional ap‐proaches to perioperative fluid therapy are based onhistorical estimates of fluid requirements during fast‐ing and during episodes of excess loss. In this ap‐proach, the large volume of fluids must be adminis‐tered during the perioperative period and isassociated with increased postoperative morbidity19).Fluid overload can cause edema formation in severalorgans. Edema can leads to myocardial dysfunctionand heart failure. Pulmonary edema impairs gas ex‐change in the lungs. Interstitial edema also affects re‐covery of gastrointestinal function and wound heal‐

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AKI after hepatic surgery 49

Figure 1. Changes of serum creatinine (SCr) in AKI and non-AKI group.

Boxes represent median and interquartile range.

Pre: preoperative level of SCr,.Post: postoperative level of SCr

Right: change of SCr in non-AKI group. Left: change of SCr in AKI group

There were no differences between preoperative level and postoperative level in non-

AKI group. Preoperative SCr: 0.73mg/dl (0.56–0.84), postoperative SCr: 0.80mg/dl

(0.65–0.93). Values are median (IQR).

As a result, SCr increased significantly after hepatic resection in AKI group (P=0.012).

Preoperative SCr: 0.79 mg/dl (0.67–0.84), postoperative SCr: 1.25 mg/dl (1.04–1.34).

Values are median (IQR).

Table 1. Patient Demographic

ing. Furthermore, edema of the kidney increasesinterstitial pressure, decreases renal blood flow, andmay cause AKI11).

On the other hand, restrictive fluid therapy maycause hypovolemia and also disturbs hemodynamicstability during anesthesia. Both hypovolemia andhypotension during anesthesia reduce cardiac output,hence reducing renal blood flow. Restrictive fluid

therapy may contribute to the progress of AKI. How‐ever, there are no reports that restrictive fluid therapyduring anesthesia causes AKI. Many studies have hadbetter outcomes with restrictive fluid managementthan liberal fluid management9).

Several studies have shown that goal-directedtherapy (GDT) has a benefit in reducing perioperativerisk20). On the other hand, Pearse et al. showed that

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Table 2. Operative Parameters

Figure 2. Relationship between increase of SCr and duration of PTC or anesthesia.

Figure A: relationship between increase of SCR and duration of PTC

Figure B: relationship between increase and duration of anesthesia

SCr: serum creatinine,PTC: portal triad clamping

Increase of SCr correlated weakly duration of PTC (Figure A, r=0.331, P=0.008) or

anesthesia (Figure B, r=0.300, P=0.013)

Table 3. Multiple logistic analysis

there was no difference between GDT and usual careby meta-analysis21). Thus the issue of whether or notGDT reduces postoperative complication is still un‐

solved. However, Prowle et al.showed a meta-analy‐sis that the incidence of AKI on GDT -based fluid re‐suscitation decreases AKI in surgical patients10). In

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hepatic surgery, intraoperative hemorrhage is a cru‐cial complication. The massive bleeding and bloodtransfusion affect the patients’ prognosis. ControlCVP during PTC is well accepted to reduce bloodloss during liver resection and has been shown tohave no side effect on renal function by meta-analy‐sis6).

In a previous report, we showed that PTC withIVC clamping causes significant reduction of cardiacoutput during hepatic resection22). In the presentstudy, we found that PTC combined with IVC clamp‐ing deteriorates renal function. Renal injury on PTCwith IVC clamping can be caused by three differentmechanisms. First, PTC with IVC clamping reducescardiac output by a decrease of venous return andthen reduces renal blood flow. The second mecha‐nism is a hormonal change by PTC with IVC clamp‐ing. PTC and IVC clamping activates arginine vaso‐pressin and the sympathetic system23)24). Theseendocrine substances strongly decreases renal bloodflow. Third, although IVC clamping decreases hep‐atic venous pressure, it increases CVP at the distalclamping site. The increased renal venous pressuredecreases renal perfusion pressure and also reducesrenal blood flow. These three mechanisms may con‐tribute to AKI.

In this study we also demonstrated that theamount of blood loss was greater in the AKI groupthan in the non-AKI group, resulting in a greater ne‐cessity for blood transfusion in the former. This indi‐cated that anemia and blood transfusion affects renalinjury during surgery.

Anemia appears to have a crucial role in AKI. Incardiac surgery with cardiopulmonary bypass, severalstudies suggest that perioperative blood transfusion isindependently associated with a 10–20% increase inthe risk of AKI after surgery25). In hepatic surgery,anemia ensues when oxygen delivery is compromisedby hemodynamic change due to PTC with IVCclamping.

In this study, the total fluid volume in the AKIgroup was larger than that in the non-AKI group. Thereason may have been that the operative procedure inAKI group was more difficult than that in the non-AKI group, prolonging the duration of anesthesia andrequiring more fluid volume. It was not clear whetherthe increase in fluid volume affected kidney injury inour study.

There are several limitations in this study. Wecould not determine intraoperative risk factors withmultiple logistic analyses. Because the present study

was a retrospective analysis, the result may have beenaffected by unknown factors.

Furthermore, the sample size was too small todetect significant differences between the AKI andnon-AKI groups on logistic regression analysis.Strictly speaking, GDT with restrictive fluid manage‐ment in the present study was different from standardGDT. Many studies have used the stroke volume in‐dex or cardiac index as the goal of fluid managementthroughout surgery. We used SVV and CVP as thegoal of fluid management during PTC, as opposedduring surgery. As a result, the total fluid volume wasthe same in both the AKI and non-AKI groups. Still,SVV is a good predictor of fluid responsiveness inhypovolemic patients, so continuing to measure bySVV may help to evaluate the volume status duringrestrictive fluid management26)27). However, we didnot compare GDT with restrictive fluid managementand with liberal fluid management. Therefore, noconclusion can be made regarding whether GDT withrestrictive fluid management or liberal fluid manage‐ment is better for postoperative AKI after hepatic sur‐gery. Further study and a larger investigation are nee‐ded to define the intraoperative risk factors for AKIafter hepatic surgery with goal directed and restrictedvolume therapy.

We conclude that the duration of PTC with IVCclamping and blood loss affect the incidence of AKIafter hepatic surgery using GDT with restrictive fluidvolume management. The unstable hemodynamicduring PTC with IVC clamping and blood loss ap‐pears to be involved in AKI after hepatic surgery.We recommend that early inotropic support andblood transfusion are essential for preventing AKIduring hepatic resection with goal directed and re‐stricted volume therapy.

Conflict of Interests

The authors declare that they have no conflictinginterests.

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