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Meta-Analysis
. 2012 Nov 14;11(11):CD004082.
doi: 10.1002/14651858.CD004082.pub5.

Perioperative increase in global blood flow to explicit defined goals and outcomes following surgery

Michael P W Grocott  1 , Ahilanandan Dushianthan, Mark A Hamilton, Michael G Mythen, David Harrison, Kathy Rowan; Optimisation Systematic Review Steering Group
Affiliations
Meta-Analysis

Perioperative increase in global blood flow to explicit defined goals and outcomes following surgery

Michael P W Grocott et al. Cochrane Database Syst Rev. .

Abstract

Background: Studies have suggested that increasing whole body blood flow and oxygen delivery around the time of surgery reduces mortality, morbidity and the expense of major operations.

Objectives: To describe the effects of increasing perioperative blood flow using fluids with or without inotropes or vasoactive drugs. Outcomes were mortality, morbidity, resource utilization and health status.

Search methods: We searched CENTRAL (The Cochrane Library 2012, Issue 1), MEDLINE (1966 to March 2012) and EMBASE (1982 to March 2012). We manually searched the proceedings of major conferences and personal reference databases up to December 2011. We contacted experts in the field and pharmaceutical companies for published and unpublished data.

Selection criteria: We included randomized controlled trials with or without blinding. We included studies involving adult patients (aged 16 years or older) undergoing surgery (patients having a procedure in an operating room). The intervention met the following criteria. 'Perioperative' was defined as starting up to 24 hours before surgery and stopping up to six hours after surgery. 'Targeted to increase global blood flow' was defined by explicit measured goals that were greater than in controls, specifically one or more of cardiac index, oxygen delivery, oxygen consumption, stroke volume (and the respective derived indices), mixed venous oxygen saturation (SVO(2)), oxygen extraction ratio (0(2)ER) or lactate.

Data collection and analysis: Two authors independently extracted the data. We contacted study authors for additional data. We used Review Manager software.

Main results: We included 31 studies of 5292 participants. There was no difference in mortality: 282/2615 (10.8%) died in the control group and 238/2677 (8.9%) in the treatment group, RR of 0.89 (95% CI 0.76 to 1.05, P = 0.18). However, the results were sensitive to analytical methods and the intervention was better than control when inverse variance or Mantel-Haenszel random-effects models were used, RR of 0.72 (95% CI 0.55 to 0.95, P = 0.02). The results were also sensitive to withdrawal of studies with methodological limitations. The rates of three morbidities were reduced by increasing global blood flow: renal failure, RR of 0.71 (95% CI 0.57 to 0.90); respiratory failure, RR of 0.51 (95% CI 0.28 to 0.93); and wound infections, RR of 0.65 (95% CI 0.51 to 0.84). There were no differences in the rates of nine other morbidities: arrhythmia, pneumonia, sepsis, abdominal infection, urinary tract infection, myocardial infarction, congestive cardiac failure or pulmonary oedema, or venous thrombosis. The number of patients with complications was reduced by the intervention, RR of 0.68 (95% CI 0.58 to 0.80). Hospital length of stay was reduced in the treatment group by a mean of 1.16 days (95% CI 0.43 to 1.89, P = 0.002). There was no difference in critical care length of stay. There were insufficient data to comment on quality of life and cost effectiveness.

Authors' conclusions: It remains uncertain whether increasing blood flow using fluids, with or without inotropes or vasoactive drugs, reduces mortality in adults undergoing surgery. The primary analysis in this review (mortality at longest follow-up) showed no difference between the intervention and control, but this result was sensitive to the method of analysis, the withdrawal of studies with methodological limitations, and is dominated by a single large RCT. Overall, for every 100 patients in whom blood flow is increased perioperatively to defined goals, one can expect 13 in 100 patients (from 40/100 to 27/100) to avoid a complication, 2/100 to avoid renal impairment (from 8/100 to 6/100), 5/100 to avoid respiratory failure (from 10/100 to 5/100), and 4/100 to avoid postoperative wound infection (from 10/100 to 6/100). On average, patients receiving the intervention stay in hospital one day less. It is unlikely that the intervention causes harm. The balance of current evidence does not support widespread implementation of this approach to reduce mortality but does suggest that complications and duration of hospital stay are reduced.

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Conflict of interest statement

Pre‐existing views

None: Emberton M, Langham J, Rowan K, Dushianthan A

Against: no‐one.

Uncertain: Beale R, Roberts I, Thompson J.

In favour: Boyd O, Mythen M, Grocott M, Hamilton MA.

Professor Mike Grocott has received unrestricted grant funding (paid to his institution) not related to this review from John Caudwell, British Oxygen Company (Linde Gas Therapeutics), Smiths Medical Ltd., Ely‐Lilly Critical Care Ltd., Deltex Medical Ltd., The London Clinic, UCL Business, Rolex Ltd., Association of Anaesthetists of Great Britain and Ireland, The Intensive Care Foundation, National Institute of Health Research, National Institute of Academic Anaesthesia, The Sir Halley‐Stuart Trust, The Frances and Augustus Newman Trust and The Down Syndrome Trust. Mike Grocott has also received fees for lecturing, unrelated to this review, from Fresenius Kabi, Edwards Lifesciences and Cortex GmBH.

Professor Mythen has received honoraria for speaking/consultation and/or travel expenses from Baxter, BBraun, Covidien, Fresenius‐Kabi, Hospira, LidCo and as a consultant to AQIX (start up company with a novel crystalloid solution – pre‐clinical). He is a director of Medical Defence Technologies LLC (“Gastrostim” patented) and a co‐Inventor of “QUENCH” IP being exploited by UCL Business. Professor Mythen's chair at UCL is endowed by Smiths Medical Ltd and this company provide charitable donations to the department on an annual basis. Deltex Medical also provide unrestricted grant funds to Prof Mythen's Department. Professor Mythen is a member of the IV Fluids Guideline Development Group for the National Institute of Clinical Excellence (NICE) and he is a co‐Author of the GIFTASUP fluid guidelines.

Mark Hamiltion has received lecture fees from Edwards Life Sciences for two lectures related to optimization.

Professor Kathy Rowan is ICNARC CTU Director and the ICNARC CTU is managing a trial (evaluating the effectiveness of perioperative goal directed haemodynamic therapy in high‐risk patients undergoing major abdominal surgery involving the gastrointestinal tract) part‐funded via a National Institute for Health Research (NIHR) Clinician Scientist Award given to Dr Rupert Pearse.

All other authors': none known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Contour‐enhanced funnel plot: mortality.
5
5
Galbraith plot, Harbord analysis, mortality. The regression slope is ‐0.72 (‐0.08 to ‐1.39).
6
6
Contour‐enhanced funnel plot for rate of complications.
7
7
Galbraith plot of Harbord analysis for rate of complications.
1.1
1.1. Analysis
Comparison 1 Mortality, Outcome 1 All studies (longest follow‐up).
1.2
1.2. Analysis
Comparison 1 Mortality, Outcome 2 All studies (hospital or 28 day).
1.3
1.3. Analysis
Comparison 1 Mortality, Outcome 3 Participant numbers.
1.4
1.4. Analysis
Comparison 1 Mortality, Outcome 4 Time intervention started.
1.5
1.5. Analysis
Comparison 1 Mortality, Outcome 5 Type of intervention.
1.6
1.6. Analysis
Comparison 1 Mortality, Outcome 6 Goals of intervention.
1.7
1.7. Analysis
Comparison 1 Mortality, Outcome 7 Mode of surgery.
1.8
1.8. Analysis
Comparison 1 Mortality, Outcome 8 Type of surgery.
2.1
2.1. Analysis
Comparison 2 Complications, Outcome 1 Renal impairment.
2.2
2.2. Analysis
Comparison 2 Complications, Outcome 2 Arrhythmia.
2.3
2.3. Analysis
Comparison 2 Complications, Outcome 3 Infection: numbers.
2.4
2.4. Analysis
Comparison 2 Complications, Outcome 4 Infections: types.
2.5
2.5. Analysis
Comparison 2 Complications, Outcome 5 Respiratory failure / ARDS.
2.6
2.6. Analysis
Comparison 2 Complications, Outcome 6 Myocardial infarction.
2.7
2.7. Analysis
Comparison 2 Complications, Outcome 7 Congestive heart failure / pulmonary oedema.
2.8
2.8. Analysis
Comparison 2 Complications, Outcome 8 Venous thrombosis.
2.9
2.9. Analysis
Comparison 2 Complications, Outcome 9 Number of participants with complications.
3.1
3.1. Analysis
Comparison 3 Resource utilization, Outcome 1 Length of hospital stay.
3.2
3.2. Analysis
Comparison 3 Resource utilization, Outcome 2 Length of critical care stay.
4.1
4.1. Analysis
Comparison 4 Sensitivity analysis: excluding studies with active controls, Outcome 1 Mortality (Longest follow‐up).
4.2
4.2. Analysis
Comparison 4 Sensitivity analysis: excluding studies with active controls, Outcome 2 Mortality (Hospital or 28 days).
4.3
4.3. Analysis
Comparison 4 Sensitivity analysis: excluding studies with active controls, Outcome 3 Renal Impairment.
4.4
4.4. Analysis
Comparison 4 Sensitivity analysis: excluding studies with active controls, Outcome 4 Arrhythmia.
4.5
4.5. Analysis
Comparison 4 Sensitivity analysis: excluding studies with active controls, Outcome 5 Infection (Number of patients with infections).
4.6
4.6. Analysis
Comparison 4 Sensitivity analysis: excluding studies with active controls, Outcome 6 Respiratory Failure/ ARDS.
4.7
4.7. Analysis
Comparison 4 Sensitivity analysis: excluding studies with active controls, Outcome 7 Myocardial Infarction.
4.8
4.8. Analysis
Comparison 4 Sensitivity analysis: excluding studies with active controls, Outcome 8 Congestive Heart Failure/ Pulmonary oedema.
4.9
4.9. Analysis
Comparison 4 Sensitivity analysis: excluding studies with active controls, Outcome 9 Venous Thrombosis.
4.10
4.10. Analysis
Comparison 4 Sensitivity analysis: excluding studies with active controls, Outcome 10 Number of patients with complications.
4.11
4.11. Analysis
Comparison 4 Sensitivity analysis: excluding studies with active controls, Outcome 11 Length of Hospital Stay [Days].
4.12
4.12. Analysis
Comparison 4 Sensitivity analysis: excluding studies with active controls, Outcome 12 Length of Critical Care Stay [Days].
5.1
5.1. Analysis
Comparison 5 Sensitivity analysis: excluding poorly‐controlled studies, Outcome 1 Mortality (Longest follow‐up).
5.2
5.2. Analysis
Comparison 5 Sensitivity analysis: excluding poorly‐controlled studies, Outcome 2 Mortality (Hospital or 28 day).
5.3
5.3. Analysis
Comparison 5 Sensitivity analysis: excluding poorly‐controlled studies, Outcome 3 Renal Impairment.
5.4
5.4. Analysis
Comparison 5 Sensitivity analysis: excluding poorly‐controlled studies, Outcome 4 Arrhythmia.
5.5
5.5. Analysis
Comparison 5 Sensitivity analysis: excluding poorly‐controlled studies, Outcome 5 Infection (Number of patients with infections).
5.6
5.6. Analysis
Comparison 5 Sensitivity analysis: excluding poorly‐controlled studies, Outcome 6 Respiratory Failure/ ARDS.
5.7
5.7. Analysis
Comparison 5 Sensitivity analysis: excluding poorly‐controlled studies, Outcome 7 Myocardial Infarction.
5.8
5.8. Analysis
Comparison 5 Sensitivity analysis: excluding poorly‐controlled studies, Outcome 8 Congestive Heart Failure/ Pulmonary oedema.
5.9
5.9. Analysis
Comparison 5 Sensitivity analysis: excluding poorly‐controlled studies, Outcome 9 Venous Thrombosis.
5.10
5.10. Analysis
Comparison 5 Sensitivity analysis: excluding poorly‐controlled studies, Outcome 10 Number of patients with complications.
5.11
5.11. Analysis
Comparison 5 Sensitivity analysis: excluding poorly‐controlled studies, Outcome 11 Length of Hospital Stay [Days].
5.12
5.12. Analysis
Comparison 5 Sensitivity analysis: excluding poorly‐controlled studies, Outcome 12 Length of Critical Care Stay [Days].
6.1
6.1. Analysis
Comparison 6 Sensitivity analysis: Sandham 2003, Outcome 1 Mortality (Longest Follow‐up)‐ excluding patients lost follow‐up.
6.2
6.2. Analysis
Comparison 6 Sensitivity analysis: Sandham 2003, Outcome 2 Mortality (Longest Follow‐up)‐ if all patients lost follow‐up have died.
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References

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Pearse 2009 {unpublished data only}
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References to other published versions of this review

Grocott 2013
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