Association of conflicts of interest with the results and conclusions of goal-directed hemodynamic therapy research: a systematic review with meta-analysis
The association between conflicts of interest (COI) and study results or article conclusions in goal-directed hemodynamic therapy (GDHT) research is unknown.
Randomized controlled trials comparing GDHT with usual care were identified. COI were classified as industry sponsorship, author conflict, device loaner, none, or not reported. The association between COI and study results (complications and mortality) was assessed using both stratified meta-analysis and mixed effects meta-regression. The association between COI and an article’s conclusion (graded as GDHT-favorable, neutral, or unfavorable) was investigated using logistic regression.
Of the 82 eligible articles, 43 (53%) had self-reported COI, and 50 (61%) favored GDHT. GDHT significantly reduced complications on the basis of the meta-analysis of studies with any type of COI, studies declaring no COI, industry-sponsored studies, and studies with author conflict but not on studies with a device loaner. However, no significant relationship between COI and the relative risk (GDHT vs. usual care) of developing complications was found on the basis of meta-regression (p = 0.25). No significant effect of GDHT was found on mortality. COI had a significant overall effect (p = 0.016) on the odds of having a GDHT-favorable vs. neutral conclusion based on 81 studies. Eighty-four percent of the industry-sponsored studies had a GDHT-favorable conclusion, while only 27% of the studies with a device loaner had the same conclusion grade.
The available evidence does not suggest a close relationship between COI and study results in GDHT research. However, a potential association may exist between COI and an article’s conclusion in GDHT research.
KeywordsConflicts of interest Goal-directed hemodynamic therapy Study results Article conclusions Association
We thank Dr. Cary P. Gross from the Center for Outcomes Research & Evaluation, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut for his help with manuscript preparation.
Support was provided from institutional and/or departmental sources at Yale University and Central South University, China.
Compliance of ethical standards
Conflicts of interest
L. Meng is a consultant for CAS Medical Systems, Inc. The other authors declare no competing interests.
- 2.Mythen MG, Webb AR (1995) Perioperative plasma volume expansion reduces the incidence of gut mucosal hypoperfusion during cardiac surgery. Arch Surg 130:423–429Google Scholar
- 4.ARISE Investigators, ANZICS Clinical Trials Group, Peake SL, Delaney A, Bailey M, Bellomo R, Cameron PA, Cooper DJ, Higgins AM, Holdgate A, Howe BD, Webb SA, Williams P (2014) Goal-directed resuscitation for patients with early septic shock. N Engl J Med 371:1496–1506Google Scholar
- 6.Pro CI, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, Terndrup T, Wang HE, Hou PC, LoVecchio F, Filbin MR, Shapiro NI, Angus DC (2014) A randomized trial of protocol-based care for early septic shock. N Engl J Med 370:1683–1693Google Scholar
- 7.Meng L, Heerdt PM (2016) Perioperative goal-directed haemodynamic therapy based on flow parameters: a concept in evolution. Br J Anaesth 117:iii3–iii17Google Scholar
- 8.Hamilton MA, Cecconi M, Rhodes A (2011) A systematic review and meta-analysis on the use of preemptive hemodynamic intervention to improve postoperative outcomes in moderate and high-risk surgical patients. Anesth Analg 112:1392–1402Google Scholar
- 11.Una Orejon R, Huercio Martinez I, Mateo Torres E, Jofre Escudero C, Gomez Rivas J, Diez Sebastian J, Ureta Tolsada MP (2017) Impact of a goal directed therapy in the implementation of an ERAS (enhanced recovery after surgery) protocol in laparoscopic radical cystectomy. Arch Esp Urol 70:707–714PubMedGoogle Scholar
- 22.Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535Google Scholar
- 25.Chong MA, Wang Y, Berbenetz NM, McConachie I (2018) Does goal-directed haemodynamic and fluid therapy improve peri-operative outcomes? A systematic review and meta-analysis. Eur J Anaesthesiol 35:469–483Google Scholar
- 26.Jorgensen L, Paludan-Muller AS, Laursen DR, Savovic J, Boutron I, Sterne JA, Higgins JP, Hrobjartsson A (2016) Evaluation of the Cochrane tool for assessing risk of bias in randomized clinical trials: overview of published comments and analysis of user practice in Cochrane and non-Cochrane reviews. Syst Rev 5:80PubMedPubMedCentralGoogle Scholar
- 28.Viechtbauer W (2010) Conducting meta-analyses in R with the metafor package. J Stat Softw 36:48Google Scholar
- 31.Bonazzi M, Gentile F, Biasi GM, Migliavacca S, Esposti D, Cipolla M, Marsicano M, Prampolini F, Ornaghi M, Sternjakob S, Tshomba Y (2002) Impact of perioperative haemodynamic monitoring on cardiac morbidity after major vascular surgery in low risk patients. A randomised pilot trial. Eur J Vasc Endovasc Surg 23:445–451PubMedGoogle Scholar
- 32.Gan TJ, Soppitt A, Maroof M, el-Moalem H, Robertson KM, Moretti E, Dwane P, Glass PS (2002) Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery. Anesthesiology 97:820–826Google Scholar
- 33.Conway DH, Mayall R, Abdul-Latif MS, Gilligan S, Tackaberry C (2002) Randomised controlled trial investigating the influence of intravenous fluid titration using oesophageal Doppler monitoring during bowel surgery. Anaesthesia 57:845–849Google Scholar
- 34.Venn R, Steele A, Richardson P, Poloniecki J, Grounds M, Newman P (2002) Randomized controlled trial to investigate influence of the fluid challenge on duration of hospital stay and perioperative morbidity in patients with hip fractures. Br J Anaesth 88:65–71Google Scholar
- 35.Sandham JD, Hull RD, Brant RF, Knox L, Pineo GF, Doig CJ, Laporta DP, Viner S, Passerini L, Devitt H, Kirby A, Jacka M (2003) A randomized, controlled trial of the use of pulmonary-artery catheters in high-risk surgical patients. N Engl J Med 348:5–14Google Scholar
- 36.Wakeling HG, McFall MR, Jenkins CS, Woods WG, Miles WF, Barclay GR, Fleming SC (2005) Intraoperative oesophageal Doppler guided fluid management shortens postoperative hospital stay after major bowel surgery. Br J Anaesth 95:634–642Google Scholar
- 38.Noblett SE, Snowden CP, Shenton BK, Horgan AF (2006) Randomized clinical trial assessing the effect of Doppler-optimized fluid management on outcome after elective colorectal resection. Br J Surg 93:1069–1076Google Scholar
- 49.Pillai P, McEleavy I, Gaughan M, Snowden C, Nesbitt I, Durkan G, Johnson M, Cosgrove J, Thorpe A (2011) A double-blind randomized controlled clinical trial to assess the effect of Doppler optimized intraoperative fluid management on outcome following radical cystectomy. J Urol 186:2201–2206PubMedGoogle Scholar
- 51.Brandstrup B, Svendsen PE, Rasmussen M, Belhage B, Rodt SA, Hansen B, Moller DR, Lundbech LB, Andersen N, Berg V, Thomassen N, Andersen ST, Simonsen L (2012) Which goal for fluid therapy during colorectal surgery is followed by the best outcome: near-maximal stroke volume or zero fluid balance? Br J Anaesth 109:191–199PubMedGoogle Scholar
- 53.Scheeren TW, Wiesenack C, Gerlach H, Marx G (2013) Goal-directed intraoperative fluid therapy guided by stroke volume and its variation in high-risk surgical patients: a prospective randomized multicentre study. J Clin Monit Comput 27:225–233Google Scholar
- 54.Salzwedel C, Puig J, Carstens A, Bein B, Molnar Z, Kiss K, Hussain A, Belda J, Kirov MY, Sakka SG, Reuter DA (2013) Perioperative goal-directed hemodynamic therapy based on radial arterial pulse pressure variation and continuous cardiac index trending reduces postoperative complications after major abdominal surgery: a multi-center, prospective, randomized study. Crit Care 17:R191PubMedPubMedCentralGoogle Scholar
- 63.Goepfert MS, Richter HP, Zu Eulenburg C, Gruetzmacher J, Rafflenbeul E, Roeher K, von Sandersleben A, Diedrichs S, Reichenspurner H, Goetz AE, Reuter DA (2013) Individually optimized hemodynamic therapy reduces complications and length of stay in the intensive care unit: a prospective, randomized controlled trial. Anesthesiology 119:824–836PubMedGoogle Scholar
- 65.Phan TD, D’Souza B, Rattray MJ, Johnston MJ, Cowie BS (2014) A randomised controlled trial of fluid restriction compared to oesophageal Doppler-guided goal-directed fluid therapy in elective major colorectal surgery within an enhanced recovery after surgery program. Anaesth Intensive Care 42:752–760PubMedGoogle Scholar
- 66.Pearse RM, Harrison DA, MacDonald N, Gillies MA, Blunt M, Ackland G, Grocott MP, Ahern A, Griggs K, Scott R, Hinds C, Rowan K, Group OS (2014) Effect of a perioperative, cardiac output-guided hemodynamic therapy algorithm on outcomes following major gastrointestinal surgery: a randomized clinical trial and systematic review. JAMA 311:2181–2190PubMedGoogle Scholar
- 68.Pestana D, Espinosa E, Eden A, Najera D, Collar L, Aldecoa C, Higuera E, Escribano S, Bystritski D, Pascual J, Fernandez-Garijo P, de Prada B, Muriel A, Pizov R (2014) Perioperative goal-directed hemodynamic optimization using noninvasive cardiac output monitoring in major abdominal surgery: a prospective, randomized, multicenter, pragmatic trial: POEMAS Study (PeriOperative goal-directed thErapy in Major Abdominal Surgery). Anesth Analg 119:579–587Google Scholar
- 71.Mikor A, Trasy D, Nemeth MF, Osztroluczki A, Kocsi S, Kovacs I, Demeter G, Molnar Z (2015) Continuous central venous oxygen saturation assisted intraoperative hemodynamic management during major abdominal surgery: a randomized, controlled trial. BMC Anesthesiol 15:82PubMedPubMedCentralGoogle Scholar
- 75.Ackland GL, Iqbal S, Paredes LG, Toner A, Lyness C, Jenkins N, Bodger P, Karmali S, Whittle J, Reyes A, Singer M, Hamilton M, Cecconi M, Pearse RM, Mallett SV, Omar RZ (2015) Individualised oxygen delivery targeted haemodynamic therapy in high-risk surgical patients: a multicentre, randomised, double-blind, controlled, mechanistic trial. Lancet Respir Med 3:33–41PubMedGoogle Scholar
- 76.Correa-Gallego C, Tan KS, Arslan-Carlon V, Gonen M, Denis SC, Langdon-Embry L, Grant F, Kingham TP, DeMatteo RP, Allen PJ, D’Angelica MI, Jarnagin WR, Fischer M (2015) Goal-directed fluid therapy using stroke volume variation for resuscitation after low central venous pressure-assisted liver resection: a randomized clinical trial. J Am Coll Surg 221:591–601PubMedPubMedCentralGoogle Scholar
- 83.Osawa EA, Rhodes A, Landoni G, Galas FR, Fukushima JT, Park CH, Almeida JP, Nakamura RE, Strabelli TM, Pileggi B, Leme AC, Fominskiy E, Sakr Y, Lima M, Franco RA, Chan RP, Piccioni MA, Mendes P, Menezes SR, Bruno T, Gaiotto FA, Lisboa LA, Dallan LA, Hueb AC, Pomerantzeff PM, Kalil Filho R, Jatene FB, Auler Junior JO, Hajjar LA (2016) Effect of perioperative goal-directed hemodynamic resuscitation therapy on outcomes following cardiac surgery: a randomized clinical trial and systematic review. Crit Care Med 44:724–733Google Scholar
- 84.Schmid S, Kapfer B, Heim M, Bogdanski R, Anetsberger A, Blobner M, Jungwirth B (2016) Algorithm-guided goal-directed haemodynamic therapy does not improve renal function after major abdominal surgery compared to good standard clinical care: a prospective randomised trial. Crit Care 20:50PubMedPubMedCentralGoogle Scholar
- 86.Stens J, Hering JP, van der Hoeven CWP, Boom A, Traast HS, Garmers LE, Loer SA, Boer C (2017) The added value of cardiac index and pulse pressure variation monitoring to mean arterial pressure-guided volume therapy in moderate-risk abdominal surgery (COGUIDE): a pragmatic multicentre randomised controlled trial. Anaesthesia 72:1078–1087PubMedGoogle Scholar
- 87.Weinberg L, Ianno D, Churilov L, Chao I, Scurrah N, Rachbuch C, Banting J, Muralidharan V, Story D, Bellomo R, Christophi C, Nikfarjam M (2017) Restrictive intraoperative fluid optimisation algorithm improves outcomes in patients undergoing pancreaticoduodenectomy: A prospective multicentre randomized controlled trial. PLoS One 12:e0183313PubMedPubMedCentralGoogle Scholar
- 88.Kaufmann KB, Stein L, Bogatyreva L, Ulbrich F, Kaifi JT, Hauschke D, Loop T, Goebel U (2017) Oesophageal Doppler guided goal-directed haemodynamic therapy in thoracic surgery—a single centre randomized parallel-arm trial. Br J Anaesth 118:852–861Google Scholar
- 89.Elgendy MA, Esmat IM, Kassim DY (2017) Outcome of intraoperative goal-directed therapy using Vigileo/FloTrac in high-risk patients scheduled for major abdominal surgeries: A prospective randomized trial. Egypt J Anaesth 33:263–269Google Scholar
- 92.Gomez-Izquierdo JC, Trainito A, Mirzakandov D, Stein BL, Liberman S, Charlebois P, Pecorelli N, Feldman LS, Carli F, Baldini G (2017) Goal-directed fluid therapy does not reduce primary postoperative ileus after elective laparoscopic colorectal surgery: a randomized controlled trial. Anesthesiology 127:36–49Google Scholar
- 94.Szturz P, Folwarczny P, Kula R, Neiser J, Sevcik P, Benes J (2018) Multi-parametric functional hemodynamic optimization improves postsurgical outcome after intermediate risk open gastrointestinal surgery, a randomized controlled trial. Minerva Anestesiol. https://doi.org/10.23736/S0375-9393.18.12467-9 CrossRefPubMedGoogle Scholar
- 95.Gerent ARM, Almeida JP, Fominskiy E, Landoni G, de Oliveira GQ, Rizk SI, Fukushima JT, Simoes CM, Ribeiro U Jr, Park CL, Nakamura RE, Franco RA, Candido PI, Tavares CR, Camara L, Dos Santos Rocha Ferreira G, de Almeida EPM, Filho RK, Galas F, Hajjar LA (2018) Effect of postoperative goal-directed therapy in cancer patients undergoing high-risk surgery: a randomized clinical trial and meta-analysis. Crit Care 22:133PubMedPubMedCentralGoogle Scholar
- 97.Calvo-Vecino JM, Ripolles-Melchor J, Mythen MG, Casans-Frances R, Balik A, Artacho JP, Martinez-Hurtado E, Serrano Romero A, Fernandez Perez C, Asuero de Lis S, Group FTI (2018) Effect of goal-directed haemodynamic therapy on postoperative complications in low-moderate risk surgical patients: a multicentre randomised controlled trial (FEDORA trial). Br J Anaesth 120:734–744Google Scholar
- 109.Viswanathan M, Carey T, Belinson S, Berliner E, Chang S, Graham E, Guise J, Ip S, Maglione M, McCrory D, McPheeters M, Newberry S, Sista P, White C (2014) A proposed approach may help systematic reviews retain needed expertise while minimizing bias from nonfinancial conflicts of interest. J Clin Epidemiol 67:1229–1238PubMedGoogle Scholar