Effects of Pringle manoeuvre and ischaemic preconditioning on haemodynamic stability in patients undergoing elective hepatectomy: a randomized trial

A. Choukèr1, T. Schachtner1, R. Schauer2, M. Dugas3, F. Löhe2, A. Martignoni1, B. Pollwein1, M. Niklas1, H. G. Rau2, K. W. Jauch2, K. Peter1 and M. Thiel1,*

1 Clinic of Anaesthesiology and 2 Department of Surgery, 3 Institute for Epidemiology and Biometry, Klinikum Grosshadern, Ludwig-Maximilians-University, D-81377 Munich, Germany

* Corresponding author. E-mail: mthiel{at}med.uni-muenchen.de

Accepted for publication March 1, 2004.


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Background. The Pringle manoeuvre and ischaemic preconditioning are applied to prevent blood loss and ischaemia-reperfusion injury, respectively, during liver surgery. In this prospective clinical trial we report on the intraoperative haemodynamic effects of the Pringle manoeuvre alone or in combination with ischaemic preconditioning.

Methods. Patients (n=68) were assigned randomly to three groups: (i) resection with the Pringle manoeuvre; (ii) with ischaemic preconditioning before the Pringle manoeuvre for resection; (iii) without pedicle clamping.

Results. Following the Pringle manoeuvre the mean arterial pressure increased transiently, but significantly decreased after unclamping as a result of peripheral vasodilation. Ischaemic preconditioning improved cardiovascular stability by lowering the need for catecholamines after liver reperfusion without affecting the blood sparing benefits of the Pringle manoeuvre. In addition, ischaemic preconditioning protected against reperfusion-induced tissue injury.

Conclusions. Ischaemic preconditioning provides both better intraoperative haemodynamic stability and anti-ischaemic effects thereby allowing us to take full advantage of blood loss reduction by the Pringle manoeuvre.

Keywords: arterial pressure ; liver, ischaemia reperfusion ; surgery, liver resection ; surgery, portal triad clamping (Pringle manoeuvre)


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
During hepatic resection, the risk of severe intraoperative bleeding represents a major risk.1 2 To avoid massive blood loss, continuous or intermittent vascular clamping of the hepatic artery and portal vein (‘Pringle manoeuvre’) is an efficient method to reduce haemorrhage.3 4 However, as a consequence, ischaemia and subsequent reperfusion results in complex metabolic,5 6 immunological,7 8 and microvascular911 changes, which together might contribute to hepatocellular damage and dysfunction,5 12 and contribute to haemodynamic instability. Ischaemic preconditioning has been applied successfully to protect against such unwanted effects,3 1214 but its impact in combination with the Pringle manoeuvre is not known.

In the present study, we analysed the intraoperative haemodynamic course in patients who underwent elective liver resection under three defined surgical techniques: portal triad clamping (Pringle manoeuvre) for resection; ischaemic preconditioning before portal triad clamping and resection; or hepatectomy without portal triad clamping. Data were electronically recorded by a PDMS that allowed continuous measurement and documentation of cardiovascular changes, fluid loss, transfusions, infusions, and administration of catecholamines. Our aims were to determine the cardiovascular effects of the Pringle manoeuvre and how these effects are modified by ischaemic preconditioning.


    Methods
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Patients
After approval of the protocol by the local ethics committee and informed written consent, patients undergoing elective partial liver resection were enrolled in the study at the University Hospital of the Ludwig-Maximilians-University in Munich, Germany. Patients were excluded from randomization when their ASA status was 4 or 5, if they were younger than 18 yr, had had a myocardial infarction within 6 months before evaluation or if they suffered from a haematological disorder. Patients were also excluded if they had liver cirrhosis or additional gastroenterological surgery was planned. Between September 1999 and September 2001, 69 eligible patients were assigned randomly to one of three groups: (i) partial hepatectomy following portal triad clamping (‘Pringle’, PR group); (ii) pre-treatment by ischaemic preconditioning by clamping of the portal triad for 10 min followed by 10 min of reperfusion before the Pringle manoeuvre for partial liver resection (ischaemic preconditioning, IPC group); (iii) liver resection without the Pringle manoeuvre (NPR group).

Anaesthesia and surgery
All patients received midazolam (3.75–7.5 mg) orally 2 h before surgery. Before general anaesthesia a thoracic epidural catheter (T10–12) was placed to provide perioperative analgesia. Following i.v. injection of either thiopental (3–5 mg kg–1) or propofol (2–3 mg kg–1), fentanyl (2 µg kg–1), and atracurium (0.5 mg kg) the trachea was intubated and the lungs mechanically ventilated (Dräger CATO, Dräger Werke, Germany) at a ventilatory frequency of 7–8 min–1 and a tidal volume of 10 ml kg–1 with an air/oxygen mixture of 50%. Anaesthesia was maintained with 5–6% end-tidal desflurane, bolus doses of atracurium for neuromuscular block and intermittent injection of bupivacaine 0.5% through the epidural catheter. An SC8000 monitor (Siemens AG, Germany) was used to monitor continuously the electrocardiogram (with ST-segment-analysis), peripheral oxygen saturation, oesophageal temperature, direct arterial pressure, and central venous pressure. In a subset of patients who had given consent, invasive cardiac monitoring (Swan-Ganz-Catheter) was used to calculate the cardiac index (CI), stroke volume index (SVI), and system vascular resistance index (SVRI).

After laparotomy the liver was mobilized and the hilar structures were prepared. The Pringle manoeuvre was performed by placing a clamp on the hepatic artery and portal vein. The Pringle manoeuvre was maintained until the liver resection was finished (PR group). In the IPC group, the Pringle manoeuvre was preceded by a brief period of ischaemia (10 min) and 10 min of reperfusion. Neither in the PR nor the IPC group was additional clamping performed during the resection.

To meet intraoperative fluid demand and to compensate for blood loss, crystalloids (sodium chloride 0.9%, BRAUN, Melsungen, Germany) and colloidal solutions (hydroxyethylstarch 10% 10 ml kg–1, BRAUN, Melsungen, Germany) were infused, respectively. The blood loss was calculated from the volume collected by the continuous autotransfusion system (CATS, Fresenius, Bad Homburg, Germany). Thereafter, erythrocytes were washed and immediately re-transfused after irradiation (30 Gy). Allogeneic packed red blood cell concentrates were transfused if transfusion of autologous blood was not sufficient to return the haemoglobin concentration to ≥7 g dl–1 or higher if electromyocardial signs of ischaemia were present.

A diuresis of more than 100 ml h–1 was maintained throughout by fluid administration, low-dose dopamine infusion (2–3 µg kg–1 min–1) and, if necessary a 5 mg i.v. bolus of furosemide. Crystalloid and colloid solutions were infused to maintain the central venous pressure (CVP) at 9–14 mm Hg. When the mean arterial pressure (MAP) fell below 65 mm Hg despite adequate fluid infusion, vasopressors were administered. Norepinephrine was administered after establishing epidural block and (i) when dopamine concentration had to be further increased (>5 µg kg–1 min–1) or (ii) when the MAP decreased below 65 mm Hg after unclamping and reperfusion of the liver. All surgical procedures and anaesthesia were performed by the same team of three experienced visceral surgeons and anaesthesiologists, ensuring execution of the study protocol in a standardized way. Surgery and anaesthesia were performed by different doctors equally assigned to the three study groups. A blinded allocation of surgeons/ anaesthesists was not feasible.

Patient data management system (PDMS)
For continuous acquisition and storage of data, the monitoring equipment and the ventilator were connected to a patient data management system-PDMS (PICIS®, Barcelona, Spain) that was installed in the operating room. Data (e.g. heat rate, invasive arterial pressure, central venous pressure) were collected continuously, averaged every 10 s, and thereafter automatically saved as ‘per minute’ values. Volumes and amounts of drugs infused were calculated semi-automatically by entering start and end of infusion time, infusion rate, and concentration of drug solutions (e.g. catecholamines). Bolus doses of drugs (e.g. relaxants), the amount of blood loss, urine output, cardiac and other derived indices and all surgical events (e.g. vascular clamping) were entered manually. Six different time intervals (T1–T6) were defined for the analysis of the variables of interest: pre-resection (T1), portal triad clamping (T2) to start, and unclamping (T3) to end ischaemic preconditioning, early (T4) and late (T5) time points during resection with or without the Pringle manoeuvre, and (T6) after the end of the liver resection (Fig. 1). The time intervals reflect the mean values of continuously registered data over a period of 10 (T1, T4, T5, T6) or 7 min (T2, T3). All time intervals do not cover the first and last minutes of clamping and declamping to avoid artifacts in the assessment of the cardiovascular state.



View larger version (10K):
[in this window]
[in a new window]
 
Fig 1 Intraoperative data and time intervals for blood collection: before start of resection/portal triad clamping (T1, baseline values), after onset (T4) or before end of resection (T5) and after end of resection (T6). When patients were randomly assigned to ischaemic preconditioning (10 min of portal clamping followed by 10 min of reperfusion) before the Pringle manoeuvre for resection, additional time intervals during (T2) and after ischaemic preconditioning (T3) were included. The time intervals T1, T4, T5, and T6 each reflect 10 min, T2 and T3 7 min of observation, respectively.

 
Statistics
Based on an alpha-error of 0.05 and 90% power to detect a difference of 1 SD between the three study groups, 23 patients (cases) per group were recruited to the study. Intraoperative data were extracted from the PDMS database into EXCEL 8.0 (Microsoft USA) and statistical analyses were performed using SPSS 10.0 (SPSS Inc., Chicago, IL, USA). Data are calculated as mean values (SD). When the hypothesis of normal distribution was not rejected (by one-sample Kolmogorov–Smirnov test), comparison of intra-group changes was performed by paired t-test. For comparison between test-groups (PR/IPC/NPR), ANOVA and post-hoc unpaired t-test were calculated. The {chi}2-test was used for comparison of categorical variables. Parameter free tests were applied when variables were not normally distributed. Multiple comparisons within groups were performed using the Friedman test and post-hoc Wilcoxon test. Comparison of data between groups was carried out using Kruskal–Wallis test and post-hoc Mann–Whitney U-test. P-values below 0.05 are considered statistically significant.


    Results
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Patients
The analysis of data was based on the criteria of the CONSORT group.15 One patient was recruited but subsequently excluded from randomization because their ASA status was more than 3. Of the remaining 68 patients, 23 were allocated randomly by lot to the PR group, 22 patients to the IPC group and 23 patients to the NPR group. Further patients were excluded as follows: violation of the anaesthetic protocol, that is no epidural catheter for perioperative analgesia (n=3); intraoperative cardiovascular instability before resection for surgical reasons (blood loss >2l) (n=2); technical failure of the continuous electronic data acquisition by the PDMS with a subsequent partial or total loss of data (n=3); changes in the anaesthetic management before resection (n=5); portal clamping less than 20 min (n=5); cirrhotic liver disease, which was not diagnosed preoperatively or intraoperatively but became evident by pathological analysis of the liver tissue samples taken intraoperatively (n=2).

For surgical reasons, the initial allocation had to be changed in a few patients: three NPR patients and one IPC patient were cross allocated to the PR group. The final number of patients eligible for analyses was 19, 14, and 15 patients in the PR, IPC, and NPR groups, respectively.

Patient details are shown in Table 1. No significant differences between the study groups were observed either for the time of surgical preparation (before resection: from skin-incision to start of resection) or post-resection period (after resection: from the end of resection to skin-closure) or for the total duration of surgery (from skin-incision to closure). The mean duration of resection was not different between PR (35 min) and IPC groups (32 min) but was significantly shorter than in the NPR group (53 min).


View this table:
[in this window]
[in a new window]
 
Table 1 Patients and surgery.

 
Cardiovascular changes
Figure 2A shows a significant (P<0.05) increase of the MAP by up to 6% when the blood vessels of the portal triad were clamped either once for resection (PR: P<0.05 T4 vs T1) or twice for ischaemic preconditioning and resection thereafter (IPC: P<0.05, T2 vs T1 and T4 vs T3). In the absence of major blood loss during the phase of ischaemic preconditioning, the haemodynamic effects of the brief period of vascular clamping were characterized by an increase in MAP, and SVRI and a decrease in the indices of cardiac output (CI, SVI) (Table 3). Removal of the clamp was followed by the opposite haemodynamic changes. When vascular clamping was performed again for resection, the MAP increased once more (T4) but returned to baseline values (T5) in both the PR and IPC group despite the clamp being left in place. Following reperfusion (T6), a significant decrease of the MAP and the systemic vascular resistance occurred but there was no effect on CI (Table 3). To treat arterial hypotension after reperfusion, the average infusion rate of norepinephrine was almost 250-fold higher in the PR group than in patients pre-treated with IPC in order to maintain MAP>65mm Hg (Fig. 2E). In other words, four out of 19 patients in the Pringle group were in need of noradrenaline infusion rates that were even higher than the maximum infusion rate observed in the IPC group (P=0.0359), {chi}2-test, two-tailed comparison between PR and IPC for frequency of patients with noradrenaline infusion rates above IPC maximum rate). This result indicates a statistically significant reduction of high noradrenaline infusion rates after Pringle by prior ischaemic preconditioning (Fig. 2E).



View larger version (21K):
[in this window]
[in a new window]
 
Fig 2 Changes in (A) MAP, (B) central venous pressure, (C) heart rate (HR), (D) dopamine, and (E) norepinephrine infusion rates during liver resection with Pringle manoeuvre (PR), Pringle manoeuvre preceded by ischaemic preconditioning of the liver (IPC), or without vascular control (NPR). Data are expressed as mean (SD) on a linear (AC) or on a logarithmic scale (D and E); PR group, n=19, IPC group, n=14, NPR group, n=15. Intragroup comparisons: *P<0.05 (*) P=0.055 vs mean baseline values T1, #P<0.05 vs T4, $P<0.05 vs T5 (paired t-test, Bonferoni corrected). §P<0.05 vs NPR, +P<0.05 vs PR/IPC (unpaired t-test). For description of time points see Figure 1.

 

View this table:
[in this window]
[in a new window]
 
Table 3 Swan–Ganz catheter monitoring.

 
Monitoring of the CVP revealed an inverse time course as compared with that of the MAP (Fig. 2B). Accordingly, CVP values decreased, while MAP values increased upon portal triad clamping (T2 and T4) followed by opposite changes of both variables when clamping was released (T3 and T6). These changes reflect pre-portal congestion of venous blood during clamping in the PR or IPC groups. Splanchnic sequestration of blood did, however, not reduce MAP, because systemic vascular resistance increased spontaneously after vascular occlusion (T2 and T4; Table 3).

Most importantly, the Pringle manoeuvre significantly reduced the cumulative blood loss during (T5) and after liver resection (T6) by up to approximately 65% (Table 2). The amounts of blood lost during liver transection were 350, 400, and 1020 ml in the PR, IPC, and NPR groups, respectively. The number of patients who received intraoperatively heterologous blood (transfused patients/all patients) was only one out of 19 (PR) or zero out of 14 (IPC) but six out of 15 in the NPR group. As blood loss was significantly higher in the NPR group than in the groups with vascular control (Table 2), MAP and CVP values continuously decreased throughout surgery (Fig. 2A and B) and hence NPR patients required more dopamine and norepinephrine especially during resection (P<0.05, T5 vs T4). As a result, there was also a significantly greater need for intravascular volume therapy with greater amounts of crystalloids and colloids used in patients of the NPR group (Table 2).


View this table:
[in this window]
[in a new window]
 
Table 2 Blood loss and fluid management. .

 
Fluid management appeared to be adequate, because urine output was high in all patients with mean rates exceeding 290 ml h–1. Furosemide boluses were not routinely applied and no significant differences between the study groups were observed for the rate or the mean concentration of furosemide given (PR 3/19 mean 5.8 mg; IPC 1/14 1x5 mg; NPR 6/15 mean 6.6 mg). There were also no differences between the groups with respect to the haemoglobin concentration, which decreased slowly, thereby explaining the continuous and compensatory increase in the heart rate in all groups (Fig. 2C). Further support for adequate haemodynamic therapy is provided by the lack of any differences in acid–base status until liver resetion was terminted (Table 4, T1–T5). Lactate concentrations after resection were higher when the liver was ischaemic (PR>IPC>NPR; Table 5, T6).


View this table:
[in this window]
[in a new window]
 
Table 4 Blood gas-analyses.

 

View this table:
[in this window]
[in a new window]
 
Table 5 ALT, AST.

 
After liver resection amino alanine and aspartate amino transferase (ALT, AST) activities were significantly increased in all groups but the highest values were in the PR group at the first and second postoperative day (1. POD, P<0.05 vs NPR; Table 5). This increase was prevented by ischaemic pre-conditioning (ALT 1. POD, P=0.05, IPC vs PR).


    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Pringle manoeuvre reduces blood loss
Almost 100 yr ago, Pringle described a new technique to reduce blood loss during liver surgery.16 Since that time, the Pringle manoeuvre has become a routine procedure17 18 and a preferred method to avoid massive haemorrhage during partial liver resection for a large spectrum of non-malignant and malignant diseases. In the present study blood loss was significantly reduced by the Pringle manoeuvre during resection (Table 2, T5) and hence for the whole period of surgery (Table 2, T6). As a result, the need for infusion of colloids and, even more importantly, the frequency of patients transfused with red blood cells was reduced.

Ischaemia-reperfusion associated haemodynamic effects
The reduction in transfusion needs by the Pringle manoeuvre, however, has to be weighed against the adverse effects of vascular clamping, for example warm ischaemia-reperfusion and haemodynamic changes. When the blood vessels of the portal triad were clamped for ischaemic preconditioning, the CVP decreased because of a reduction in venous return from the splanchnic organs, including the liver and the intestine. In general, one would expect that an acute decrease in CVP would also cause a decrease in MAP, but this was not the case. In contrast, the MAP increased by 6% above pre-clamping values as a result of an increase in systemic vascular resistance of 20% causing cardiac output to decrease by 10%. All these changes were reversed by the release of the vascular clamps. Although these changes could be studied only in a small number of patients with invasive haemodynamic monitoring using a pulmonary artery catheter, the effects observed are similar to previously published data. Delva and co-workers19 postulated a role for sympatho-adrenergic stimulation and the endogenous release of epinephrine and norepinephrine. Subsequently block of these neuro-humoral pathways by direct injection of lidocaine into the hepatic pedicle before vascular occlusion was shown to reduce systemic levels of these catecholamines and abolish the increase of the MAP after portal triad clamping.20 All our patients received epidural anaesthesia, but presumably this was ineffective in blocking such sympathetic reflex mechanisms.

When the portal triad was clamped for periods longer than 10 min, that is for institution of the Pringle manoeuvre, the clamping-induced cardiovascular effects were the same, but removal of the vascular clamps was associated with haemodynamic changes typical of reperfusion. Post-reperfusion arterial hypotension is thought to result from the release of vasoactive substances such as prostaglandins (e.g. 6ketoPGF1-alpha/thromboxane)21 or adenosine.22 Arterial hypotension may further exacerbate reperfusion injuries, because it will reduce blood flow to the liver10 and thereby adversely affect the hepatic microcirculation. Reduced sinusoidal perfusion can exacerbate11 the negative metabolic, and pro-inflammatory6 23 24 consequences of ischaemia-reperfusion, which enhances the development of organ dysfunction. Although vasopressors are used in such situations to ensure arterial pressure-dependent perfusion of other vital organ systems, a cross over study (dopamine vs norepinephrine and vice versa) in 14 patients undergoing visceral surgery showed that norepinephrine (60 ng kg–1 min–1) significantly reduced blood flow of the hepatic artery and the portal vein, whereas dopamine (7 µg kg–1 min–1) induced a significant increase in portal vein blood-flow without affecting the flow in the hepatic artery.25 Similar results were obtained in another group of patients in which norepinephrine (60 ng kg–1 min–1) given for 5 min only decreased hepatic artery blood flow, while with dopamine minor changes were observed in the portal vein.25

Thus, correction of reperfusion induced arterial hypotension by the use of noradrenaline may further compromise liver tissue perfusion.

Ischaemic preconditioning attenuates haemodynamic side effects of the Pringle manoeuvre and reduces the need for vasopressor therapy
Against this background of ischaemia-reperfusion related haemodynamic problems and the knowledge that ischaemic preconditioning is able to attenuate ischaemia-reperfusion induced tissue damage, we asked whether ischaemic preconditioning might also prevent post-reperfusional arterial hypotension. In contrast to our concern that the haemodynamic instability could be worsened by an additional short ischaemic period, ischaemic preconditioning did not further aggravate the Pringle manoeuvre-induced haemodynamic changes. Indeed, ischaemic preconditioning substantially decreased the need for vasopressor therapy during the reperfusion phase with a reduction of the norepinephrine infusion rate by as much as 250-fold. This reduced need for norepinephrine in the IPC group as compared with the PR group was not a result of any differences in blood loss, or transfusion, or infusion requirements, because the blood saving effect of the PR manoeuvre was well preserved by previous ischaemic preconditioning. Given the improvements of postoperative liver function and the better intraoperative haemodynamic stability produced by ischaemic pre-treatment, one is tempted to speculate that ischaemic preconditioning may also protect by stabilization at the macrocirculatory level besides its suggested beneficial effects in the microcirculation and on cellular metabolism.

Taken together, the results presented here indicate that the Pringle manoeuvre for liver resection reduces blood loss during liver surgery. This positive effect, however, is at the expense of post-reperfusion arterial hypotension as a result of vasodilation. Pre-treatment of the liver by ischaemic preconditioning attenuates these responses without influencing the blood saving effects of the Pringle manoeuvre and protects the liver from warm ischaemia-reperfusion injury.


    Acknowledgments
 
The authors thank Peter Conzen, MD, and Manfred Nuscheler, MD, Madeleine Sachs, MD, Youssuf Summa, Maria Niederschweiberer and Gerhard Teichert for their assistance and help during the study. Some of the research was conducted by Thomas Schachtner in partial fulfilment of his doctorial thesis from the medical faculty of the Ludwig-Maximilians-University of Munich, Germany. This study was supported by a research Grant of the ‘Stiftung der Münchner Medizinschen Wochenschrift (MMW)’ Munich, Germany.


    References
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
1 Delva E, Camus Y, Nordlinger B, et al. Vascular occlusions for liver resections. Operative management and tolerance to hepatic ischemia: 142 cases. Ann Surgy 1989; 209: 211–18

2 Stephenson KR, Steinberg SM, Hughes KS, et al. Perioperative blood transfusions are associated with decreased time to recurrence and decreased survival after resection of colorectal liver metastases. Ann Surg 1988; 208: 679–87[ISI][Medline]

3 Rudiger HA, Kang KJ, Sindram D, Riehle HM, Clavien PA. Comparison of ischemic preconditioning and intermittent and continuous inflow occlusion in the murine liver. Ann Surg 2002; 235: 400–7[CrossRef][ISI][Medline]

4 Torzilli G, Makuuchi M, Inoue K. The vascular control in liver resection: revisitation of a controversial issue. Hepatogastroenterology 2002; 49: 28–31[ISI][Medline]

5 Jaeschke H. Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning. Am J Physiol Gastrointest Liver Physiol 2003; 284: G15–G26[Abstract/Free Full Text]

6 Peralta C, Bartrons R, Riera L, et al. Hepatic preconditioning preserves energy metabolism during sustained ischemia. Am J Physiol Gastrointest Liver Physiol 2000; 279: G163–G171[Abstract/Free Full Text]

7 Grace PA. Ischaemia-reperfusion injury. Br J Surg 1994; 81: 637–47[ISI][Medline]

8 Serracino-Inglott F, Habib NA, Mathie RT. Hepatic ischemia-reperfusion injury. Am J Surg 2001; 181: 160–66[CrossRef][ISI][Medline]

9 Glanemann M, Vollmar B, Nussler AK, Schaefer T, Neuhaus P, Menger MD. Ischemic preconditioning protects from hepatic ischemia/reperfusion-injury by preservation of microcirculation and mitochondrial redox-state. J Hepatol 2003; 38: 59–66[Medline]

10 Pannen BH. New insights into the regulation of hepatic blood flow after ischemia and reperfusion. Anesth Analg 2002; 94: 1448–57[Free Full Text]

11 Vollmar B, Glasz J, Leiderer R, Post S, Menger MD. Hepatic microcirculatory perfusion failure is a determinant of liver dysfunction in warm ischemia-reperfusion. Am J Pathol 1994; 145: 1421–31[Abstract]

12 Clavien PA, Yadav S, Sindram D, Bentley RC. Protective effects of ischemic preconditioning for liver resection performed under inflow occlusion in humans [see comments]. Ann Surg 2000; 232: 155–62[CrossRef][ISI][Medline]

13 Pagliaro P, Gattullo D, Rastaldo R, Losano G. Ischemic preconditioning: from the first to the second window of protection. Life Sci 2001; 69: 1–15[CrossRef][ISI][Medline]

14 Clavien PA, Selzner M, Rudger HA, et al. A prospective randomized study in 100 consecutive patients undergoing major liver resection with versus without ischemic preconditioning. Ann Surg 2003; 238: 843–50[ISI][Medline]

15 Moher D, Schulz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. Ann Intern Med 2001; 134: 657–62[Abstract/Free Full Text]

16 Pringle JH. Notes on the arrest of hepatic hemorrhage due to trauma. Ann Surg 1908; 48: 541–9

17 Arnoletti JP, Brodsky J. Reduction of transfusion requirements during major hepatic resection for metastatic disease. Surgery 1999; 125: 166–71[CrossRef][ISI][Medline]

18 Bismuth H, Majno PE. Hepatobiliary surgery. J Hepatol 2000; 32 (Suppl 1): 208–24[Medline]

19 Delva E, Camus Y, Paugam C, Parc R, Huguet C, Lienhart A. Hemodynamic effects of portal triad clamping in humans. Anesth Analg 1987; 66: 864–8[Abstract]

20 Lentschener C, Franco D, Bouaziz H, et al. Haemodynamic changes associated with portal triad clamping are suppressed by prior hepatic pedicle infiltration with lidocaine in humans. Br J Anaesth 1999; 82: 691–7[Abstract/Free Full Text]

21 Aggarwal S, Kang Y, Freeman J, DeWolf AM, Begliomini B. Is there a post-reperfusion syndrome? Transplant Proc 1989; 21: 3497–9[ISI][Medline]

22 Chouker A, Martignoni A, Schauer R., Dugas M, Rau HG, Thiel M. Zentralvenöse und portalvenöse Purinspiegel während ischämischer Präkonditionierung der Leber. Z Gastroenterol 2001; 6: 484

23 Jaeschke H, Farhood A, Smith CW. Neutrophils contribute to ischemia/reperfusion injury in rat liver in vivo. FASEB J 1990; 4: 3355–9[Abstract/Free Full Text]

24 Martinez-Mier G, Toledo-Pereyra LH, McDuffie JE, Warner RL, Ward PA. Neutrophil depletion and chemokine response after liver ischemia and reperfusion. J Invest Surg 2001; 14: 99–107[CrossRef][ISI][Medline]

25 Fischer S, Conzen PF, Nuscheler M, Schauer R, Peter K. Influence of norepinephrine and dopamine on splanchnic blood flow and oxygen delivery during abdominal surgery: a randomized, single-blind, comparative study. ASA Meeting Abstracts 2002; A–153





This Article
Abstract
Full Text (PDF)
All Versions of this Article:
93/2/204    most recent
aeh195v1
E-Letters: Submit a response to the article
Alert me when this article is cited
Alert me when E-letters are posted
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Search for citing articles in:
ISI Web of Science (4)
Disclaimer
Request Permissions
Google Scholar
Articles by Choukèr, A.
Articles by Thiel, M.
PubMed
PubMed Citation
Articles by Choukèr, A.
Articles by Thiel, M.