A Randomised Controlled Trial

Liver surgery is still associated with a high rate of morbidity and mortality. We aimed to compare different haemodynamic treatments in liver surgery. In a prospective, blinded, randomised, controlled pilot trial patients undergoing liver resection were randomised to receive haemodynamic management guided by conventional haemodynamic parameters or by oesophageal Doppler monitor (ODM, CardioQ-ODM) or by pulse power wave analysis (PPA, LiDCOrapid) within a goal- directed algorithm adapted for liver surgery. The primary endpoint was stroke volume index before intra-operative start of liver resection. Secondary endpoints were the haemodynamic course during surgery and postoperative pain levels. Due to an unbalance in the extension of the surgical procedures with a high rate of only minor procedures the conventional group was dropped from the analysis. Eleven patients in the ODM group and 10 patients in the PPA group were eligible for statistical analysis. Stroke volume index before start of liver resection was 49 (37; 53) ml/m2 and 48 (41; 56) ml/m2 in the ODM and PPA group, respectively (p=0.397). The ODM guided group was haemodynamically stable as shown by ODM and PPA measurements. However, the PPA guided group showed a significant increase of pulse-pressure-variability (p=0.002) that was not accompanied by a decline of stroke volume index displayed by the PPA (p=0.556) but indicated by a decline of stroke volume index by the ODM (p<0.001). The PPA group had significantly higher postoperative pain levels than the ODM group (p=0.036). In conclusion, goal-directed optimization by ODM and PPA showed differences in intraoperative cardiovascular parameters indicating that haemodynamic optimization is not consistent between the two monitors

Influence of a flow-directed restrictive volume protocol on intraoperative haemodynamic during liver resection

Einleitung: Ein restriktives Flüssigkeitsmanagement, mit dem Ziel intraoperativ den zentral-venösen Druck unter fünf mmHg zu halten, kann die perioperative Morbidität und Mortalität nach großen Leberteilresektionen senken. Eine intraoperative, flussorientierte Volumen-therapie zur Optimierung der Vorlast reduziert postoperative Komplikationen und die Krankenhausverweildauer. In dieser Arbeit wurden Patienten mit Leberteilresektionen verglichen, deren hämodynamisches Management mittels konventioneller Parameter (Kontrolle), sowie mittels zweier unterschiedlicher Monitoringverfahren (Intervention) (LiDCOrapid® [PPA] und CardioQ-ODM® [ODM] im Rahmen eines neu entwickelten, flussorientierten, aber restriktiven hämodynamischen Algorithmus) erfolgte. Methoden: Es handelt sich um eine prospektive, kontrollierte, randomisierte, verblindete, drei-armige Pilotstudie bei Patienten mit Leberteilresektionen. Der Studienalgorithmus beginnt mit einer initialen Optimierung des Schlagvolumenindex (SVI), gefolgt von intravenösen Volumengaben erst nach Abfall des SVI um 25% oder unter 40ml/kg/m2 und einer erneuten SVI-Optimierung nach Leberresektionsende. Die Steuerung des Algorithmus wurde in der ODM-Gruppe mit dem CardioQ-ODM®, in der PPA-Gruppe mit dem LiDCOrapid® durchgeführt. Primäres Ziel der Studie war der Schlagvolumenindex [SVI] im Vergleich der drei Gruppen, insbesondere vor dem Leberresektionsbeginn. Sekundäres Ziel war das Outcome der Patienten, speziell die Intensivstation- und Krankenhausverweildauer sowie das Auftretens von postoperativen Komplikationen. Aufgrund der Imbalance bezüglich des Ausmaßes der Leberresektionen mit einer hohen Rate an kleinen Eingriffen sowie einer (nicht-randomisierten) Nachrekrutierung in der Kontrollgruppe, wurden nur die beiden Interventionsgruppen statistisch ausgewertet und die Kontrolle lediglich deskriptiv dargestellt. Die Studie reduzierte sich damit praktisch auf ein zweiarmiges Design. Ergebnisse: Für die statistische Analyse wurden in der ODM-Gruppe elf Patienten und in der PPA-Gruppe zehn Patienten eingeschlossen. Zum Leberresektionsbeginn gab es keinen gruppenspezifischen Unterschied im SVI (p=0,397). Innerhalb des Algorithmus blieben in der ODM- Gruppe die hämodynamischen Parameter, gemessen mit beiden Monitoren über die gesamte Operationsdauer stabil. In der PPA-Gruppe gab es bis zum Leberresektionsende einen signifikanten Abfall im SVI, der jedoch durch den CardioQ-ODM® (p<0,001) und nicht durch den LiDCOrapid® (p=0,556) dargestellt wurde. Die Pulsdruckvariation (PPV) in der PPA-Gruppe war über die gleiche Zeit signifikant angestiegen (p=0,002). Postoperativ wiesen die Patienten aus der PPA-Gruppe stärkere postoperative Schmerzen (p=0,036) und einen höheren Opiatverbrauch (p=0,002) auf. Es fanden sich keine Unterschiede in der Intensivstations- und Krankenhausverweildauer. Schlussfolgerung: Die Optimierung des SVI innerhalb des flussorientierten, restriktiven Studienalgorithmus während einer Leberteilresektion unterscheidet sich zwischen dem CardioQ-ODM® und dem LIDCOrapid®. In der ODM-Gruppe gelang, trotz zeitbegrenzter restriktiver Volumentherapie, die Aufrechterhaltung des Schlagvolumenindex während der gesamten Operation sowie das gleichzeitige Erzielen eines niedrigen zentral-venösen Druckes während der Leberparenchymresektion. Es ist ein Einfluss des hämodynamischen Algorithmus auf die postoperativen Schmerzen festzustellen.Introduction: A restrictive fluid management maintaining intraoperatively the central venous pressure below five mmHg can reduce perioperative morbidity and mortality after major liver resection. Perioperative, flow-directed volume therapy to optimize preload reduces postoperative complications and hospital length of stay. In this work we compared patients undergoing liver resection, whose haemodynamic management guided by conventional haemodynamic parameters (control) or by oesophageal Doppler monitor (intervention) (ODM, CardioQ-ODM®) or by pulse power wave analysis (PPA, LiDCOrapid® within a goal-directed algorithm adapted for liver surgery). Methods: This was a prospective, controlled, randomized, blinded, three-arm pilot study of patients undergoing a liver resection. The study algorithm started with an initial optimization of stroke volume index (SVI), followed by fluid challenges if SVI decreased by more than 25% or if SVI has fallen below 40ml/kg/m2. After sealing the liver resection area optimization of SVI was restarted. The algorithm was guided by CardioQ-ODM® in the ODM group and by LiDCOrapid® in the PPA group. Primary aim of the study was the comparison of the three groups with respect to SVI, particular before the start of the liver resection. Secondary aim of the study was postoperative outcome, based on length of stay in the ICU and in the hospital as well as the occurrence of postoperative complications. Due to an unbalance in the extension of the surgical procedures with a high rate of only minor procedures and a (non-randomised) further recruitment of patients in the conventional group, the statistical analysis was only performed with the intervention groups, and the controls were solely descriptive represented. The study was therefore reduced to a two-armed design. Results: 11 patients in the ODM group and 10 patients in the PPA group have been included in the statistical analysis. At the beginning of the liver incision there was no difference in SVI between the groups (p = 0.397). The haemodynamic parameters in the ODM group remained stable over the course of surgery as shown by both monitors. In the PPA group there was a significant decline of SVI at the beginning of the liver incision measured by the CardioQ-ODM® (p<0.001) but not by the LiDCOrapid® (p=0.556). At the same time there was a significant increase of pulse pressure variation in the PPA group (p=0.002). The patients in the PPA group had higher postoperative pain scores (p=0.036) although higher amount of opiates were administered (p=0.002). There were no differences in length of stay in the ICU or in the hospital. Conclusion: The optimization of SVI within the flow-directed, restrictive study algorithm during liver surgery differed between CardioQ-ODM® and LIDCOrapid®. In the ODM group it was possible to maintain the SVI during the entire surgery as well as the simultaneous low central-venous pressure during the liver incision, despite time-limited, restrictive volume therapy. An influence of the algorithm on the postoperative pain has been shown

Goal-directed haemodynamic algorithm for liver surgery.

<p><b>Haemodynamic algorithm-abbreviations:</b> SVI: stroke volume index [ml/m²], MAP: mean arterial pressure [mmHg], SBP: systolic blood pressure [mmHg], CVP: central venous pressure [mmHg]. <b>Guidelines on the use of the algorithm:</b> After induction of anaesthesia and implementation of advanced haemodynamic monitoring a fluid challenge with 200ml of a colloid solution is performed. If stroke SVI increases by more than 10% a further fluid challenge is performed up to the point SVI is not increasing anymore. The value of SVI after the last fluid challenge is defined as Starting-SVI. After determining the Starting-SVI the second time period of the haemodynamic algorithm starts up to the point the liver resection area is surgically sealed. During that period arterial blood pressure is maintained by titration of continuous administration of norepinephrine to reach a systolic blood pressure (SBP) of more than 100mmHg and a mean arterial blood pressure (MAP) of more than 65mmHg. If SVI falls by more than 25% in relation to the Starting-SVI (#) or SVI drops below 40ml/m² a fluid challenge with 200ml of a colloid solution is performed. The performance of a fluid challenge is not followed up to SVI is not increasing anymore as in published algorithm for preload optimization. Instead the volume administration is stopped if the SVI is higher than 40ml/m² and not lower than 25% of the Starting-SVI (#). If there is still central venous congestion measured by an increased central venous pressure (CVP) and the clinical judgment of venous bleeding during incision of the liver by the surgeon administration of either enoximone or nitroglycerine could be performed (^X). After sealing the liver resection area volume administration can once again be guided to optimize SVI according to the previously published algorithms up to the end of surgery[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132715#pone.0132715.ref020" target="_blank">20</a>].</p

Haemodynamic Optimization by Oesophageal Doppler and Pulse Power Wave Analysis in Liver Surgery: A Randomised Controlled Trial

<div><p>Liver surgery is still associated with a high rate of morbidity and mortality. We aimed to compare different haemodynamic treatments in liver surgery. In a prospective, blinded, randomised, controlled pilot trial patients undergoing liver resection were randomised to receive haemodynamic management guided by conventional haemodynamic parameters or by oesophageal Doppler monitor (ODM, CardioQ-ODM) or by pulse power wave analysis (PPA, LiDCOrapid) within a goal-directed algorithm adapted for liver surgery. The primary endpoint was stroke volume index before intra-operative start of liver resection. Secondary endpoints were the haemodynamic course during surgery and postoperative pain levels. Due to an unbalance in the extension of the surgical procedures with a high rate of only minor procedures the conventional group was dropped from the analysis. Eleven patients in the ODM group and 10 patients in the PPA group were eligible for statistical analysis. Stroke volume index before start of liver resection was 49 (37; 53) ml/m² and 48 (41; 56) ml/m² in the ODM and PPA group, respectively (p=0.397). The ODM guided group was haemodynamically stable as shown by ODM and PPA measurements. However, the PPA guided group showed a significant increase of pulse-pressure-variability (p=0.002) that was not accompanied by a decline of stroke volume index displayed by the PPA (p=0.556) but indicated by a decline of stroke volume index by the ODM (p<0.001). The PPA group had significantly higher postoperative pain levels than the ODM group (p=0.036). In conclusion, goal-directed optimization by ODM and PPA showed differences in intraoperative cardiovascular parameters indicating that haemodynamic optimization is not consistent between the two monitors.</p><p>Trial Registration</p><p>ISRCTN.com <a href="http://www.isrctn.com/ISRCTN64578872?q=ISRCTN64578872&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search" target="_blank">ISRCTN64578872</a></p></div

CONSORT Flow Diagram of the study.

<p>CONSORT Flow Diagram of the study.</p

Time course of intraoperative haemodynamic parameters.

<p>Time course of stroke volume index (SVI) of the two intervention groups displayed by ODM (A1) and PPA (A2); time course of pulse pressure variation (PPV) of the two intervention groups displayed by PPA (B) and systemic vascular resistance index (SVRI) of the two intervention groups displayed by ODM (C). Data are shown as median (25%; 75%) quartiles over the time course of surgery and the nonparametric analysis for the parameters that are outlined with corresponding p values. Statistical significances: # for comparisons with respect to time points within the group (exact Wilcoxon tests); #1: p<0.05 vs. T1, #2: p<0.05 vs. T2, #3: p<0.05 vs. T3 and * for comparisons between the ODM and PPA group (Mann-Whitney tests) with p<0.05 at the time point ODM group vs. PPA group.</p

General patient characteristics.

<p>Data are shown as median (25%; 75%) quartiles or as number n of patients (%). p-values calculated for the ODM versus the PPA group using the exact Wilcoxon-Mann-Whitney test #, the exact Mantel-Haenszel test (ordered categories)</p><p>§ or the exact Chi-square test</p><p>$ as appropriate.</p><p>Abreviations: ACEI: angiotensin converting enzyme inhibitor, LOS: length of stay, PACU: postanaesthesia care unit, HDU: high dependency care unit.</p><p>General patient characteristics.</p