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Intraoperative monitoring of stroke volume variation versus central venous pressure in laparoscopic liver surgery: a randomized prospective comparative trial
Central venous pressure (CVP) is used as a marker of cardiac preload to control intraoperative blood loss in open hepatectomies, while its reliability in laparoscopy is less certain. The aim of this randomized prospective trial was to evaluate the outcome of laparoscopic resections performed with stroke volume variation (SVV) or CVP monitoring.
Methods
All candidates for laparoscopic liver resection were assigned randomly to SVV or to CVP groups. Outcome was evaluated included conversion rate, cause of conversion, intraoperative blood loss, need for transfusions, length of surgery and postoperative results.
Results
Ninety consecutive patients were enrolled: both SVV and CVP groups included 45 patients each and were comparable in terms of patient and disease characteristics. A reduced rate of conversion was recorded in the SVV compared to the CVP group (6.7% and 17.8% respectively, p = 0.02). Blood loss was lower in the SVV group (150 mL), compared to the CVP group (300 mL, p = 0.04). Morbidity, mortality, length of stay and functional recovery were comparable. On multivariate analysis, lesion location, extent of hepatectomy and type of cardiac preload monitoring were associated significantly to risk of conversion.
Conclusion
SVV monitoring in laparoscopic liver surgery improves intraoperative outcome, thus enhancing the benefits of the minimally-invasive approach and fast-track protocols.
Abbreviations
SVV
stroke volume variation
CVP
central venous pressure
CVC
central venous catheter
LLR
laparoscopic liver resection
Introduction
The minimally-invasive approach for liver resections has experienced a widespread diffusion worldwide,
A correlation between blood loss and clinical outcomes has been demonstrated, with impact on both morbidity and mortality rates as well as disease recurrence and survival rates.
In this setting, any effort to improve bleeding control and to reduce the need for blood transfusions is of key importance. In laparoscopy, the haemostatic effect of the pneumoperitoneum and image magnification contributes to obtain a more accurate haemostasis.
On the other hand, portal triad clamping is an effective method to control intraoperative bleeding and can be adopted even in laparoscopic hepatectomies.
Many reports have shown that the reduction of cardiac preload results in a significant reduction of blood loss, thus decreasing hepatic veins congestion.
Perioperative outcomes of major hepatic resections under low central venous pressure anesthesia: blood loss, blood transfusion, and the risk of postoperative renal dysfunction.
Perioperative outcomes of major hepatic resections under low central venous pressure anesthesia: blood loss, blood transfusion, and the risk of postoperative renal dysfunction.
and pneumoperitoneum influence CVP, may result in unreliable values and may not guide intraoperative fluid management in maintaining patients in an hypovolaemic state, which is still of primary importance in liver surgery, even with laparoscopic approach.
The aim of the present study was to evaluate the role of SVV monitoring in laparoscopic hepatic surgery compared with CVP and to analyse its implications on short-term outcome. The primary endpoint was to assess conversion rate, while secondary endpoints were to record intra- and postoperative outcomes.
Methods
Study design
From April 2012 to October 2014, all candidates for laparoscopic liver resection (LLR) for primary or secondary liver tumours at the Hepatobiliary surgery Division of San Raffaele Hospital, Milano were screened for enrolment in this prospective randomized study. Patients who met one or more of the following criteria were excluded: associated major abdominal procedures (e.g. colorectal and/or pancreatic resections); repeated liver resections; single-port resections; patients under 18 years of age or unable to give their informed consent. Eligible patients were randomly assigned to a treatment arm: patients in the study group (SVV group) underwent intraoperative monitoring of SVV via FloTrac Vigileo system, while patients in the control group (CVP group) underwent intraoperative monitoring of CVP via central venous catheter (CVC). The anaesthetic and surgical teams were the same for all patients. Treatment allocation was open to both the anaesthesiologists (RR, LC, LB) and the surgeons (LA, MP, MC), while it was blinded to principal investigator (FR) who was responsible for data recording. Randomization was performed using the randomization function of Excel (Windows Office package) and block randomization.
The study protocol was designed according to European Ethical Standards and was approved by the medical ethical committee of our institution and all patients provided written informed consent before preoperative assessment.
Anaesthesia and volaemic status monitoring
General anaesthesia was performed in a standardized way, administering for induction intravenous fentanyl (2 mcg/kg) and propofol (2 mg/kg). Muscle relaxation was obtained with a bolus of non-depolarizing curare (cisatracurium or rocuronium at a dose of 0.5 mg/kg or 0.6 mg/kg respectively). All patients were mechanically ventilated with a tidal volume of 8 mL/kg without PEEP. Anaesthesia was maintained with inhaled halogenated gas (sevoflorane or desflorane titrated to minimal alveolar concentration). In all patients ECG (electrocardiogram) and MAP (mean arterial blood pressure) were obtained using a radial or humeral catheterization, pulse oxymetry and diuresis were monitored.
In the SVV group, arterial access was connected to the FloTrac sensor of the Vigileo monitor system (Edwards Lifesciences) to measure SVV. In this group SV (stroke volume), CO (cardiac output) and CI (cardiac index) were monitored; VO2 (oxygen consumption) and DO2 (oxygen delivery) were calculated on the basis of blood gas analysis which was repeated during surgery in both groups to check either the onset of acidosis or the level of haemoglobin.
In the SVV group, the goal was to maintain SVV over 12% (at least among 12–15%) during resection. In the CVP group, CVP was measured through a CVC inserted in the internal jugular vein after the induction of general anaesthesia. In this group SvO2 (oxygen venous saturation) was monitored as well. The goal was to maintain CVP under or equal to 5 cm H20. Hence, fluid therapy with crystalloids was guided by SVV or CVP values to achieve an hypovolaemic state. Whenever the simply restriction of fluid administration was not sufficient to guarantee hypovolaemia, a diuretic (furosemide 5–10 mg i.v.) was administered. Low MAP (<50 mmHg) was an indication for fluids administration, while tachycardia was not. No patient received vasopressors to maintain mean arterial pressure above 50 mmHg or to correct any oxygen debt due to cardiac failure.
Perioperative management of patients was conducted following the principles of fast-track protocol in liver surgery.
For laparoscopic resections the patient was placed in the “French” position with the first surgeon standing between the patient's legs and assistants on each side. Whenever possible, a four trocar configuration was used. The liver was examined by direct vision and intraoperative ultrasonography and the line of intended resection marked on its surface using diathermy. Hepatic transection was performed using the SonoSurg system (Olympus, Tokyo, Japan), which integrates an ultrasonic coagulating cutter and a conventional ultrasonic dissector.
Vessels were sealed according to their size by using bipolar forceps, clips or staplers. The resected specimen was placed in a retrieval bag and removed, without fragmentation, through an enlargement of one of the port incisions or through a Pfannenstiel incision. Pringle's manoeuver was used as required to control intraoperative bleeding.
Laparoscopic approaches were chosen based on location of tumour within the liver and the estimated possibility of achieving a disease-free margin. Treatment strategies were systematically evaluated at weekly multidisciplinary meetings, where liver surgeons, radiologists and medical oncologists defined the indications for surgical procedures, the type and the resection technique.
Variables
Data were collected on preoperative patient and disease characteristics as well as on intraoperative and histopathological findings. Impact of fluids administration and measurement of volaemia on feasibility of LLR (primary endpoint) was evaluated according to the rate of conversion to laparotomy and reasons of conversion. Outcomes of LLR (secondary endpoint) were evaluated in terms of operative time, blood loss, rate of blood transfusions, postoperative mortality and morbidity and length of postoperative period until discharge.
Complications in the first 90 days were reviewed and assessed retrospectively according to the Dindo–Clavien classification.
Mortality was defined as any death during postoperative hospitalization or within 90 days after resection.
Statistical methods
Based on a retrospective analysis of 170 patients undergoing laparoscopic liver resection at our institution (with CVP monitoring) from 2005 to 2011, the conversion rate was 15.9%. A reduction of 5% in conversion rate seemed therefore feasible. At 90% power and α = 0.05, a sample size of 2 × 40 patients in the randomization arms would be sufficient to detect this difference. Assuming an expected withdrawal rate of ≤5%, a total sample size of 90 (n = 2 × 45) was required.
All variables were compared using the χ2 or Fisher's exact test for categorical data, the Mann–Whitney U test for non-normally distributed continuous data, and Student's t-test for normally distributed continuous variables. All data are expressed as mean plus or minus the standard deviation or median and range. Cox proportional hazards models were developed by using relevant clinicopathological variables to determine the association of each with risk of conversion. Significance was defined as p < 0.05. All analyses were performed using the statistical package SPSS 18.0 (SPSS, Chicago, IL, USA).
Results
Participants
Ninety consecutive patients, out of 128 undergoing LLR in the study period, met inclusion criteria and were therefore enrolled in the prospective study. Each patient was randomly assigned to the study or to the control group, so that both the SVV and the CVP groups included 45 patients each. No patient dropped out once included into the study (Fig. 1). Mean SVV value in the SVV group was 17% ± 4, while mean CVP in the CVP group was 3 ± 2, during transection phase. All resections were performed by the same team of surgeons and anaesthesiologists.
Patient demographics including underlying diagnoses are reported in Table 1. The two groups were comparable.
Table 1Patients and disease characteristics according to randomization group
SVV group (n = 45)
CVP group (n = 45)
p
Age (years)
Mean ± SD
58 ± 11
61 ± 9
ns
Male sex, n (%)
21 (46.7)
24 (53.3)
ns
ASA score, n (%)
ns
1
8 (17.8)
6 (13.3)
2
32 (71.1)
35 (77.8)
3
5 (11.1)
4 (8.9)
BMI
Mean ± SD
22.8 ± 1.5
23.1 ± 1.7
ns
Underlying liver disease, n (%)
ns
None
25 (55.6)
22 (48.9)
Steatosis/mild impairment
13 (28.9)
15 (33.3)
Cirrhosis
7 (15.6)
8 (17.8)
Previous abdominal surgery, n (%)
10 (22.2)
11 (24.4)
ns
Indication, n (%)
n (%)
ns
Malignant
39 (86.7)
40 (88.9)
Colorectal Cancer Metastases
10 (22.2)
8 (17.8)
Non Colorectal Cancer Metastases
3 (6.7)
4 (8.9)
Hepatocellular Carcinoma
22 (48.9)
25 (55.6)
Cholangiocarcinoma
4 (8.9)
3 (6.7)
Benign
6 (13.3)
5 (11.1)
Focal Nodular Hyperplasia
2 (4.4)
3 (6.7)
Adenoma
2 (4.4)
0
Haemangioma
2 (4.4)
1 (2.2)
Extent of hepatectomy, n (%)
ns
Minor
39 (86.7)
41 (91.1)
Major
6 (13.3)
4 (8.9)
Abbreviations: SVV, stroke volume variation; CVP, central venous pressure; ASA, America Society of Anesthesiology; BMI, body mass index; ns, not significant.
Within the SVV group, 3 of 45 patients (6.7%) required conversion to open surgery (Table 2). In the CVP group, 8 of 45 patients were converted (17.8%, p = 0.02).
Table 2Conversions according to randomization group
SVV group (n = 45)
CVP group (n = 45)
p
Conversion, n (%)
3 (6.7)
8 (17.8)
0.02
Reason for conversion, n (%)
Haemorrhage
0 (0)
4 (8.9)
0.05
Oncologic inadequacy
1 (2.2)
2 (4.4)
ns
Anaesthesiological problems
0 (0)
1 (2.2)
ns
Damage to the liver
1 (2.2)
0 (0)
ns
Inadequate biliostasis
1 (2.2)
0 (0)
ns
Abbreviations: SVV, stroke volume variation; CVP, central venous pressure.
Conversion was performed due to concerns about the oncological adequacy of the procedure, inadequate biliostasis and damage to liver parenchyma during mobilization in the SVV Group but no patient was converted to open due to intraoperative bleeding. Haemorrhage from the hepatic surface was the most frequent cause of conversion in the CVP Group with only one case of bleeding from an intrahepatic branch of one hepatic vein. No statistically significant differences were recorded concerning the other reasons of conversion. Although not reaching statistical significance, patients in the CVP group who required conversion due to bleeding had a higher intraoperative blood loss compared to patients in the same group who were not converted to open surgery (450 ± 250 mL and 250 ± 250 mL, respectively). Blood loss in converted patients from the CVP group were significantly higher compared to converted patients from the SVV group (400 ± 250 mL and 150 ± 150 mL, respectively; p = 0.04).
On univariate analysis, 7 of 14 factors significantly affected the risk of conversion (Table 3). Multivariate analysis revealed that location in non-laparoscopic segments (risk ratio 1.38; P = 0.032), major extent of hepatectomy (risk ratio 1.35; p = 0.043) and intraoperative preload monitoring with CVP (risk ratio 1.75; p = 0.031) were independent prognostic factors.
Table 3Univariate and multivariate analysis of factors potentially affecting the risk of conversion
Variable
n
Conversion, n (%)
Univariate, p
Risk ratio (95% confidence interval)
Multivariate, p
Age
ns
<70
69
8 (11.6)
>70
21
2 (9.5)
Sex
ns
Male
45
6 (13.3)
Female
45
4 (8.9)
BMI
0.048
<25
72
7 (9.7)
>25
18
3 (16.7)
ASA Score
ns
1–2
81
9 (11.1)
3
9
1 (11.1)
Previous abdominal surgery
0.05
Yes
21
3 (14.3)
No
69
7 (10.1)
Indication
ns
Malignant
79
9 (11.4)
Benign
11
1 (9.1)
Extent of hepatectomy
0.034
0.043
Minor
80
7 (8.8)
1
Major
10
3 (30)
1.35 (1.01–1.85)
Lesion location
0.031
0.032
Laparoscopic segment
67
6 (9)
1
Non-laparoscopic segment
23
4 (17.4)
1.38 (1.19–1.99)
Number of lesions
ns
Single
73
8 (11)
Multiple
17
2 (11.8)
Lesion diameter
0.048
<5 cm
59
5 (8.5)
>5 cm
31
5 (16.1)
Underlying liver impairment
0.046
Yes
43
6 (14)
No
47
4 (8.5)
Length of surgery
ns
<180 min
50
5 (10)
>180 min
40
5 (12.5)
Pringle manoeuver
ns
Yes
47
6 (12.8)
No
43
4 (9.3)
Intraoperative preload monitoring
0.026
0.031
CVP
45
8 (17.8)
1.75 (1.39–2.14)
SVV
45
3 (6.7)
1
Abbreviations: ASA, America Society of Anesthesiology; SVV, stroke volume variation; CVP, central venous pressure.
Secondary endpoint: intra- and postoperative outcomes
To avoid any underestimation of data on perioperative outcomes, the SVV and the CVP groups were analysed and compared including all patients, even those who required conversion to an open approach. The mean operative time was 220 ± 50 min (mean ± SD) in the SVV group and 210 ± 60 min in the control group (p = ns). In spite of comparable intraoperative use of the Pringle manoeuver in the two groups, there was less intraoperative blood loss (150 ± 100 mL, mean ± SD) in the SVV than the CVP group (300 ± 250 mL, p = 0.04).
Blood transfusions needs, achievement of negative resection margins, and depth of surgical margins on liver parenchyma were comparable between the two groups. Postoperative morbidity and mortality is reported in Table 4.
Table 4Intra- and postoperative details according to randomization group
SVV group (n = 45)
CVP group (n = 45)
p
Pringle manoeuvre, n (%)
ns
Not performed
19 (42.2)
24 (53.3)
Performed
26 (57.8)
21 (46.7)
Length of surgery (min)
Mean ± SD
220 ± 50
210 ± 60
ns
Blood Loss (mL)
Mean ± SD
150 ± 100
300 ± 250
0.04
Associated procedures, n (%)
ns
None
39 (86.7)
41 (91.1)
Colecistectomy
6 (13.3)
4 (8.9)
Surgical margin, n (%)
ns
R0
44 (97.8)
45 (100)
R1
1 (2.2)
0 (0)
Surgical margin (mm)
Mean ± SD
8 ± 4
9 ± 6
ns
Intraoperative blood transfusions, n (%)
ns
No
43 (95.6)
43 (95.6)
Yes
2 (4.4)
2 (4.4)
Total blood transfusions, n (%)
ns
No
43 (95.6)
41 (91.1)
Yes
2 (4.4)
4 (8.9)
Morbidity, n (%)
5 (11.1)
6 (13.3)
ns
Grade of complications, n (%)
Minor
I grade
1 (2.2)
1 (2.2)
ns
II grade
2 (4.4)
3 (6.7)
ns
Major
IIIa grade
1 (2.2)
1 (2.2)
ns
Mortality, n (%)
0 (0)
0 (0)
ns
Functional recovery (days)
Median (range)
3 (1–6)
3 (1–7)
ns
Length of stay (days)
Median (range)
4 (2–10)
5 (3–13)
ns
Abbreviations: R0, negative resection margin; R1, positive resection margin; ns, not significant; SVV, stroke volume variation; CVP, central venous pressure.
The results of this study have shown that intraoperative monitoring of cardiac preload through SVV improved outcome of laparoscopic liver surgery, as compared to conventional CVP use. Furthermore, a reduction in conversion rate and intraoperative blood losses were recorded. Moreover, among all the well-known factors that potentially influence the risk of conversion even the technique used to monitor intraoperatively volaemia and to guide fluid therapy was statistically significant on multivariate analysis.
SVV indicates patient's fluid responsiveness during mechanical ventilation and it is calculated every 20 s through the system FloTrac/Vigileo as the variation of the beat-to-beat stroke volume divided by the mean stroke volume.
Comparative study of pressure- and volume-controlled ventilation on stroke volume variation as a predictor of fluid responsiveness in patients undergoing major abdominal surgery.
it is evident that the importance of every surgical or anaesthesiological manoeuver affecting the risk of bleeding is key. A reduced blood loss and transfusion requirement as compared to open approach,
More recently, the introduction of fast-track management protocols to enhance functional recovery of patients have stressed the role of intraoperative volaemic control.
In particular, maintenance of patient's hypovolaemia and avoidance of water overload seem to favourably affect the intraoperative outcome of candidates to hepatic resection.
Perioperative outcomes of major hepatic resections under low central venous pressure anesthesia: blood loss, blood transfusion, and the risk of postoperative renal dysfunction.
In laparoscopic liver surgery, the positive effect of hypovolaemia is increased since it reduces bleeding from hepatic veins which cannot be controlled by portal triad clamping and is frequently responsible for conversion to an open approach.
Perioperative outcomes of major hepatic resections under low central venous pressure anesthesia: blood loss, blood transfusion, and the risk of postoperative renal dysfunction.
the correlation between CVP and SVV in the setting of liver surgery was demonstrated and the Vigileo system was proposed as a valuable non-invasive alternative to CVC insertion, avoiding its risk of vascular and infectious complications. In the same study,
a proportion of patients were submitted to laparoscopic liver resection, with results similar to those of patients undergoing open surgery in terms of concordance between CVP and SVV.
To our knowledge, the present study is the first to address the issue of cardiac preload monitoring in laparoscopic liver surgery. The importance of this topic relies in the undeniable unreliability of the CVP measurement in laparoscopic surgery, because of the effects of the pneumoperitoneum and patient's position.
In laparoscopy, even when measures of CVP suggest hypovolaemia, the real haemodynamic state of the patient is different. However, when monitored with Vigileo, values of SVV > 12% better correlate to an effective low preload. Avoidance of CVC placement reduces time for catheter placement and potential complications, which is reported in 5–20% of patients.
In laparoscopic liver surgery, SVV monitoring seems to increase the safety profile of parenchymal transection, thereby reducing the need of conversion and blood loss.
Although beyond the aims of the present study, it was the surgeons' perception that SVV monitoring allowed underfilling of the inferior vena cava and suprahepatic veins. This facilitates parenchymal transection and direct, precise visualization of intrahepatic structures that can be preserved or divided. Secondly, the phases of hepatic mobilization and inferior vena cava dissection are improved during major hepatectomies or resections of non-laparoscopic segments, as shown in Fig. 2a and b.
Figure 2(a & b) Right liver mobilization. a. Effective and safe dissection of right ligaments without risk of injury of liver parenchyma by retraction instruments. b. Low preload allows the creation of a real dissection space between the liver and the anterior aspect of the inferior vena cava to facilitate the liver-hanging manoeuver
In the present study, management of hypovolaemia was standard and was applied in the same way in both groups. The difference in blood loss therefore cannot be considered to result from different anaesthesiological management, but instead it can be interpreted as the result of the different reliability of volaemic status. It is vital to have strict cooperation between surgeons and anaesthesiologists with a dedicated team standardizing management protocols to obtain clinical benefit. CVC placement still deserves to be taken into consideration in some cases of planned laparoscopic liver resection, such as when peripheral accesses is not available due to obesity, massive oedema or prolonged previous chemotherapy, total parenteral nutrition during the postoperative course or when severe cardiac comorbidities are diagnosed.
Despite some limits of the present study, such as sample size and unavailability of correlation in each patient of CVP and SVV measures, we still argue that this study constitutes a valuable demonstration of the intraoperative effects of the availability of a reliable system to measure haemodynamic changes.
Author contribution
Study design: Ratti, Aldrighetti.
Acquisition of data: Reineke, Comotti, Cipriani.
Analysis and interpretation: Catena, Paganelli.
Manuscript drafted by: Ratti.
Revision: Aldrighetti, Beretta.
Statistical advice: Ratti.
Disclosure
The material has not been previously published or submitted elsewhere for publication. All listed authors have participated in the study and have approved the final manuscript. There is no personal conflicts of interest or financial disclosure for any of the authors.
References
Nguyen K.T.
Gamblin T.C.
Geller D.A.
World review of laparoscopic liver resection-2,804 patients.
Perioperative outcomes of major hepatic resections under low central venous pressure anesthesia: blood loss, blood transfusion, and the risk of postoperative renal dysfunction.
Comparative study of pressure- and volume-controlled ventilation on stroke volume variation as a predictor of fluid responsiveness in patients undergoing major abdominal surgery.
☆Disclosure: The authors of this manuscript have no conflicts of interest to disclose and further disclose any commercial interest that they may have in the subject of study and the source of any financial or material support.
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