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Cardiopulmonary interventions to decrease blood loss and blood transfusion requirements for liver resection

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References

References to studies included in this review

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El‐Kharboutly 2004 {published data only}

El‐Kharboutly WS, El‐Wahab MA. The role of adoption of low central venous pressure in hepatic resection with pringle manoeuvre in reducing blood loss and improving operative outcome. Egyptian Journal of Anaesthesia 2004;20(4):369‐76.

Hasegawa 2002 {published data only}

Hasegawa K, Takayama T, Orii R, Sano K, Sugawara Y, Imamura H, et al. Effect of hypoventilation on bleeding during hepatic resection: a randomized controlled trial. Archives of Surgery 2002;137(3):311‐5.

Hashimoto 2007 {published data only}

Hashimoto T, Kokudo N, Orii R, Seyama Y, Sano K, Imamura H, et al. Intraoperative blood salvage during liver resection: A randomized controlled trial. Annals of Surgery 2007;245(5):686‐91.

Jarnagin 2008 {published data only}

Jarnagin WR, Gonen M, Maithel SK, Fong Y, D'Angelica MI, Dematteo RP, et al. A prospective randomized trial of acute normovolemic hemodilution compared to standard intraoperative management in patients undergoing major hepatic resection. Annals of Surgery 2008;248(3):360‐9. [PUBMED: 18791356]

Kato 2008 {published data only}

Kato M, Kubota K, Kita J, Shimoda M, Rokkaku K, Sawada T. Effect of infra‐hepatic inferior vena cava clamping on bleeding during hepatic dissection: A prospective, randomized, controlled study. World Journal of Surgery 2008;32(6):1082‐7.

Matot 2002 {published data only}

Matot I, Scheinin O, Jurim O, Eid A. Effectiveness of acute normovolemic hemodilution to minimize allogeneic blood transfusion in major liver resections. Anesthesiology 2002;97(4):794‐800.

Standl 1998 {published data only}

Standl T, Burmeister MA, Horn EP, Wilhelm S, Knoefel WT, Schulte am Esch J. Bovine haemoglobin‐based oxygen carrier for patients undergoing haemodilution before liver resection. British Journal of Anaesthesia 1998;80(2):189‐94.
Standl T, Wilhelm S, Horn EP, Burmeister M, Gundlach M, Schulte am Esch J. [Preoperative hemodilution with bovine hemoglobin. Acute hemodynamic effects in liver surgery patients ]. Der Anaesthesist 1997;46(9):763‐70.

Wang 2006 {published data only}

Wang WD, Liang LJ, Huang XQ, Yin XY. Low central venous pressure reduces blood loss in hepatectomy. World Journal of Gastroenterology 2006;12(6):935‐9.

Yao 2006 {published data only}

Yao XH, Wang B, Xiao ZK, Zhou P, Chen CY, Qing ZH. [Acute normovolemic hemodilution combined with controlled hypotension in patients undergoing liver tumorectomy]. Journal of Southern Medical University 2006;26(6):828‐30.

References to studies excluded from this review

Jump to:

Kostopanagiotou 2007 {published data only}

Kostopanagiotou G, Pandazi A, Matsota P, Arkadopoulos N, Dalamanga N, Politou M, et al. Effect of packed red blood cells transfusion on plasma fibronectin during liver resection. Transfusion Medicine 2007;17(2):115‐8.

Additional references

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Belghiti 1993

Belghiti J, Kabbej M, Sauvanet A, Vilgrain V, Panis Y, Fekete F. Drainage after elective hepatic resection. A randomized trial. Annals of Surgery 1993;218(6):748‐53.

Boutron 2008

Boutron I, Moher D, Altman DG, Schulz KF, Ravaud P. Methods and processes of the CONSORT Group: example of an extension for trials assessing nonpharmacologic treatments. Annals of Internal Medicine 2008;148(4):W60‐W66. [PUBMED: 18283201]

Chouker 2004

Chouker A, Schachtner T, Schauer R, Dugas M, Lohe F, Martignoni A, et al. Effects of Pringle manoeuvre and ischaemic preconditioning on haemodynamic stability in patients undergoing elective hepatectomy: a randomized trial. British Journal of Anaesthesia 2004;93(2):204‐11.

DeMets 1987

DeMets DL. Methods for combining randomized clinical trials: strengths and limitations. Statistics in Medicine 1987;6(3):341‐50.

DerSimonian 1986

DerSimonian R, Laird N. Meta‐analysis in clinical trials. Controlled Clinical Trials 1986;7(3):177‐88.

Egger 1997

Egger M, Davey SG, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphical test. BMJ (Clinical Research Ed) 1997;315(7109):629‐34.

Frilling 2005

Frilling A, Stavrou GA, Mischinger HJ, de Hemptinne B, Rokkjaer M, Klempnauer J, et al. Effectiveness of a new carrier‐bound fibrin sealant versus argon beamer as haemostatic agent during liver resection: a randomised prospective trial. Langenbecks Archives of Surgery 2005;390(2):114‐20.

Gluud 2009

Gluud C, Nikolova D, Klingenberg SL, Whitfield K, Alexakis N, Als‐Nielsen B, et al. Cochrane Hepato‐Biliary Group. About The Cochrane Collaboration (Cochrane Review Groups (CRGs)) 2009, Issue 3. Art. No.: LIVER.

Gomez 2008

Gomez D, Morris‐Stiff G, Wyatt J, Toogood GJ, Lodge JP, Prasad KR. Surgical technique and systemic inflammation influences long‐term disease‐free survival following hepatic resection for colorectal metastasis. Journal of Surgical Oncology 2008;98(5):371‐6. [PUBMED: 18646038]

Gurusamy 2008

Gurusamy KS, Osmani B, Sharma D, Davidson BR. Non‐surgical interventions to decrease blood loss and blood transfusion requirements for liver resection. Cochrane Database of Systematic Reviews 2008, Issue 3. [DOI: 10.1002/14651858.CD007338]

Gurusamy 2009a

Gurusamy KS, Kumar Y, Sharma D, Davidson BR. Vascular occlusion for elective liver resections. Cochrane Database of Systematic Reviews 2009, Issue 1. [DOI: 10.1002/14651858.CD006409.pub2]

Gurusamy 2009b

Gurusamy KS, Pamecha V, Davidson BR. Topical haemostatic agents in liver resection. Cochrane Database of Systematic Reviews Issue under preparation.

Gurusamy 2009c

Gurusamy KS, Li J, Sharma D, Davidson BR. Pharmacological interventions to decrease blood loss and blood transfusion requirements for liver resection. Cochrane Database of Systematic Reviews 2009, Issue 4. [DOI: 10.1002/14651858.CD008085]

HES 2005

Hospital Episode Statistics. Main operations. 3 character: 2004‐05. http://www.hesonline.nhs.uk/Ease/servlet/ContentServer?siteID=1937&categoryID=205 (accessed 19 March 2009).

Higgins 2002

Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta‐analysis. Statistics in Medicine 2002;21(11):1539‐58.

Higgins 2008

Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.0 [updated February 2008]. The Cochrane Collaboration, 2008. Available from www.cochrane‐handbook.org.

Ibrahim 2006

Ibrahim S, Chen CL, Lin CC, Yang CH, Wang CC, Wang SH, et al. Intraoperative blood loss is a risk factor for complications in donors after living donor hepatectomy. Liver Transplantation 2006;12(6):950‐7.

Kitagawa 2001

Kitagawa K, Taniguchi H, Mugitani T, Koh T, Obayashi T, Kunishima S, et al. Safety and advantage of perioperative autologous blood transfusion in hepatic resection for hepatocellular carcinoma. Anticancer Research 2001;21(5):3663‐7.

Kjaergard 2001

Kjaergard LL, Villumsen J, Gluud C. Reported methodologic quality and discrepancies between large and small randomized trials in meta‐analyses. Annals of Internal Medicine 2001;135(11):982‐9.

Macaskill 2001

Macaskill P, Walter SD, Irwig L. A comparison of methods to detect publication bias in meta‐analysis. Statistics in Medicine 2001;20(4):641‐54.

Moher 1998

Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, et al. Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta‐analyses?. Lancet 1998;352(9128):609‐13.

Moher 2001

Moher D, Schulz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel‐group randomised trials. Lancet 2001;357(9263):1191‐4. [PUBMED: 11323066]

Newell 1992

Newell DJ. Intention‐to‐treat analysis: implications for quantitative and qualitative research. International Journal of Epidemiology 1992;21(5):837‐41.

Poon 2001

Poon RT, Fan ST, Lo CM, Ng IO, Liu CL, Lam CM, et al. Improving survival results after resection of hepatocellular carcinoma: a prospective study of 377 patients over 10 years. Annals of Surgery 2001;234(1):63‐70. [PUBMED: 11420484]

RevMan 2008 [Computer program]

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Royle 2003

Royle P, Milne R. Literature searching for randomized controlled trials used in Cochrane reviews: rapid versus exhaustive searches. International Journal of Technology Assessment in Health Care 2003;19(4):591‐603.

Schulz 1995

Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273(5):408‐12.

Shimada 1998

Shimada M, Takenaka K, Fujiwara Y, Gion T, Shirabe K, Yanaga K, et al. Risk factors linked to postoperative morbidity in patients with hepatocellular carcinoma. The British Journal of Surgery 1998;85(2):195‐8.

Shinozuka 2000

Shinozuka N, Koyama I, Arai T, Numajiri Y, Watanabe T, Nagashima N, et al. Autologous blood transfusion in patients with hepatocellular carcinoma undergoing hepatectomy. American Journal of Surgery 2000;179(1):42‐5.

StatsDirect 2.7 [Computer program]

StatsDirect Ltd. StatsDirect Statistical software Version 2.7.2. StatsDirect Ltd, 2008.

Strasberg 2000

Strasberg SM, Belghiti J, Clavien PA, Gadzijev E, Garden JO, Lau WY, et al. The Brisbane 2000 terminology of liver anatomy and resections. HPB Surgery 2000;2(3):333‐9.

Sweeting 2004

Sweeting MJ, Sutton AJ, Lambert PC. What to add to nothing? Use and avoidance of continuity corrections in meta‐analysis of sparse data. Statistics in Medicine 2004;23(9):1351‐75.

Wang 2006

Wang WD, Liang LJ, Huang XQ, Yin XY. Low central venous pressure reduces blood loss in hepatectomy. World Journal of Gastroenterology 2006;12(6):935‐9.

Wood 2008

Wood L, Egger M, Gluud LL, Schulz KF, Juni P, Altman DG, et al. Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta‐epidemiological study. BMJ (Clinical Research Ed.) 2008;336(7644):601‐5. [PUBMED: 18316340]

Yoshimura 2004

Yoshimura Y, Kubo S, Shirata K, Hirohashi K, Tanaka H, Shuto T, et al. Risk factors for postoperative delirium after liver resection for hepatocellular carcinoma. World Journal of Surgery 2004;28(10):982‐6.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

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El‐Kharboutly 2004

Methods

Randomised clinical trial

Sequence generation: unclear.
Allocation concealment: unclear.
Blinding: inadequate.
Incomplete outcome data addressed: unclear.
Free of selective reporting: inadequate.
Free of other bias: unclear.

Participants

Country: Egypt.
Number randomised: 40.
Post‐randomisation drop‐out: not stated.
Mean age: 51.1 years.
Females: 17 (42.5%).
Major liver resections: 25 (62.5%).
Cirrhotic livers: 40 (100%).

Inclusion criteria:
Elective liver resection.

Exclusion criteria:

  1. Cardiopulmonary diseases.

  2. Diabetes mellitus.

  3. Hypertension.

  4. Child‐Pugh class B or C.

  5. MEGX < 50 ng/ml

Interventions

Participants were randomly assigned to two groups.

Group 1: low CVP (n = 20).
Group 2: control (n = 20).

Further details of intervention:
CVP maintained at 0 to 4 mm Hg using nitroglycerine infusion.
Sytemic hypotension was avoided.
Urine output was maintained at > 0.5 ml/Kg

Other details:
Vascular occlusion: intermittent PTC.
Method of parenchymal transection: not stated.
Management of raw surface: sutures, argon beam and infra‐red heating.
Other co‐interventions to decrease blood loss: none reported.

Outcomes

The outcome measures were mortality, transfusion requirements, peri‐operative morbidity, operating time, blood loss, and liver function tests.

Notes

Attempts to contact the authors in November 2008 were unsuccessful.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Unclear.

Allocation concealment?

Unclear risk

Quote: "Patients were randomly (closed envelop method) divided into two groups...."

Comment: It is not clear whether the authors used opaque envelopes.

Blinding?
All outcomes

High risk

No.

Incomplete outcome data addressed?
All outcomes

Unclear risk

Unclear.

Free of selective reporting?

High risk

Comment: Important outcomes such as liver failure were not reported.

Free of baseline imbalance?

Low risk

Comment: The patients were well matched for important baseline characteristics.

Free of early stopping bias?

Low risk

Comment: The trialists recruited the intended number of patients.

Free of academic bias?

Low risk

Comment: There were no previously published trials of same comparisons by the author.

Free of sponsor bias?

Unclear risk

Unclear.
Hasegawa 2002

Methods

Randomised clinical trial

Sequence generation: unclear.
Allocation concealment: unclear.
Blinding: inadequate.
Incomplete outcome data addressed: adequate.
Free of selective reporting: inadequate.
Free of other bias: unclear.

Participants

Country: Japan.
Number randomised: 80.
Post‐randomisation drop‐out: 1 (1.3%) (see notes).
Mean age: 65 years.
Females: not stated.
Major liver resections: 26 (32.9%).
Cirrhotic livers: 35 (44.3%).

Inclusion criteria:
Liver resection for the removal of tumours.

Exclusion criteria:
Severe pulmonary dysfunction (< 70% vital capacity or FEV1/FVC < 60%).

Interventions

Participants were randomly assigned to two groups.

Group 1: hypoventilation (n = 40) (see notes).
Group 2: control (n = 40).

Further details of intervention and control:
Intervention: hypoventilation (4 ml/kg tidal volume; respiratory rate 15/min) only during clamping.
Control:
ventilation at 10 ml/kg tidal volume; respiratory rate 10/min.

Other details
Vascular occlusion: intermittent PTC.
Method of parenchymal transection: clamp crush or CUSA.
Management of raw surface: not stated.
Other co‐interventions to decrease blood loss: none reported.

Outcomes

The outcome measures were mortality, transfusion requirements, peri‐operative morbidity, hospital stay, blood loss, and liver function tests.

Notes

One patient from intervention group who did not undergo liver resection was excluded from analysis.

Attempts to contact the authors in November 2008 were unsuccessful.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Unclear.

Allocation concealment?

Unclear risk

Unclear.

Blinding?
All outcomes

High risk

No.

Incomplete outcome data addressed?
All outcomes

Low risk

Comment: There was one post‐randomisation drop‐out. This patient did not undergo liver resection. This was not due to the treatment effect.

Free of selective reporting?

High risk

Comment: Important outcomes such as liver failure were not reported.

Free of baseline imbalance?

Low risk

Comment: The patients were well matched for important baseline characteristics.

Free of early stopping bias?

Unclear risk

Unclear.

Free of academic bias?

Low risk

Comment: There were no previously published trials of same comparisons by the author.

Free of sponsor bias?

Unclear risk

Unclear.
Hashimoto 2007

Methods

Randomised clinical trial

Sequence generation: adequate.
Allocation concealment: adequate.
Blinding: inadequate.
Incomplete outcome data addressed: adequate.
Free of selective reporting: inadequate.
Free of other bias: adequate.

Participants

Country: Japan.
Number randomised: 80.
Post‐randomisation drop‐outs: 1 (1.3%) (see notes).
Median age: 30 and 37 years in the two groups.
Females: 30 (38.0%).
Major liver resections: 77 (97.5%).
Cirrhotic livers: 0 (0%).

Inclusion criteria:

  1. Living donor liver transplantation (donor retrieval).

  2. Normal livers.

  3. Age 18 to 65 years.

Exclusion criteria

  1. Hypertension or hypotension.

  2. Hemoglobin <11 g/dL within a week prior to the operation.

  3. INR > 1.5.

  4. Bleeding time > 5 minutes.

  5. Unstable haemodynamics during surgery.

Interventions

Participants were randomly assigned to two groups.

Group 1: autologous blood donation (n = 40).
Group 2: control (n = 39 ‐ see notes).

Further details of intervention:
Whole blood equal to 0.7% of body weight was withdrawn before start of hepatic parenchymal division and stored for re‐transfusion after graft procurement.

Other details:
Vascular occlusion: intermittent PTC.
Method of parenchymal transection: CUSA.
Management of raw surface: not stated.
Other co‐interventions to decrease blood loss: none reported.

Outcomes

The outcome measures were mortality, transfusion requirements, peri‐operative morbidity, hospital stay, blood loss and liver function tests.

Notes

One patient from control group in whom the surgery was cancelled because of asthmatic attack was excluded from analysis.

Authors replied to questions related to mortality and transfusion requirements in November 2008.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Quote: "The participants were randomly assigned in the operating room to either the blood salvage group (BS group) or a control group using a minimization method with 3 stratifying factors: age....."

Allocation concealment?

Low risk

Quote: "The participants were randomly assigned in the operating room to either the blood salvage group (BS group) or a control group using a minimization method with 3 stratifying factors: age....."

Blinding?
All outcomes

High risk

Quote: "the surgical team and participants were blinded to the data throughout the study period."

Comment: The anaesthetists were not blinded to the groups. This could have resulted in different managements for the two groups.

Incomplete outcome data addressed?
All outcomes

Low risk

Comment: There was one post‐randomisation drop‐out. This patient did not undergo surgery and none of the outcomes could be measured or reported. This was not due to the treatment effect.

Free of selective reporting?

High risk

Comment: Important outcomes such as liver failure were not reported.

Free of baseline imbalance?

Low risk

Comment: The patients were well matched for important baseline characteristics.

Free of early stopping bias?

Low risk

Comment: The trialists recruited the intended number of patients.

Free of academic bias?

Low risk

Comment: There were no previously published trials of same comparisons by the author.

Free of sponsor bias?

Low risk

Quote: "Supported by a grant from the Kanae Foundation for Life & Socio‐medical Science, a grant from the Public Trust Surgery Research Fund, a grant from the Japanese Clinical Oncology Fund, a grant from the Public Trust Haraguchi Memorial Cancer Research Fund in Japan, and a Grant‐in‐Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. 18790955)."

Jarnagin 2008

Methods

Randomised clinical trial

Sequence generation: adequate.
Allocation concealment: unclear.
Blinding: inadequate.
Incomplete outcome data addressed: inadequate.
Free of selective reporting: inadequate.
Free of other bias: unclear.

Participants

Country: USA.
Number randomised: 135.
Post‐randomisation drop‐outs: 5 (3.7%).
Mean age: 53.5 years.
Females: 61 (46.9%).
Major liver resections: 111 (85.4%).
Cirrhotic livers: not stated.

Inclusion criteria:

  1. Adult patients older than 18 years of age.

  2. Preoperative haemoglobin at least 11 g/dL for men and 10 g/dL for women within 14 days of registration.

Exclusion criteria:

  1. Active coronary artery disease (exceptions for cardiac stress study showing no reversible ischaemia)

  2. History of cerebrovascular disease.

  3. History of congestive heart failure.

  4. Uncontrolled hypertension.

  5. Restrictive or obstructive pulmonary disease (COPD).

  6. Renal dysfunction (creatinine  > 1.8 mg/dL).

  7. Abnormal coagulation parameters (INR > 1.5 not on warfarin and/or platelet count < 100,000).

  8. Presence of active infection.

  9. Evidence of hepatic metabolic disorder (bilirubin > 2 mg/dL or ALT > 75 U/L).

  10. Preoperative autologous blood donation.

Interventions

Participants were randomly assigned to two groups.

Group 1: haemodilution (n = 63).
Group 2: control (n = 67).

Further details of intervention:
haemodilution by withdrawing blood and replacing it with colloids to a target haemoglobin of 8 gm/dl.

Other details:
Vascular occlusion: intermittent PTC.
Method of parenchymal transection:not stated.
Management of raw surface: not stated.
Other co‐interventions to decrease blood loss: low CVP in both groups.

Outcomes

The outcomes reported were mortality, transfusion requirements, peri‐operative morbidity, operating time, and hospital stay.

Notes

There were 3 dropouts in ANH group and 2 in standard.  The reason for dropouts were resection not performed in 2, resection smaller than required by the study in 2 and inability to accurately determine blood loss in 1 (author replies).

Authors replied to questions related to methodological quality in November 2008.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Quote: "The random sequence was computer generated" (author replies).

Allocation concealment?

Unclear risk

Quote: "Allocation was concealed by sealed envelopes" (author replies).

Comment: It is not clear whether the authors used opaque envelopes.

Blinding?
All outcomes

High risk

No.

Incomplete outcome data addressed?
All outcomes

High risk

Comment: There were 5 post‐randomisation drop‐outs.

Free of selective reporting?

High risk

Comment: Important outcomes such as liver failure were not reported.

Free of baseline imbalance?

Unclear risk

Unclear.

Free of early stopping bias?

Low risk

Comment: The trialists recruited the intended number of patients.

Free of academic bias?

Low risk

Comment: There were no previously published trials of same comparisons by the author.

Free of sponsor bias?

Low risk

Quote: "The authors thank ... Robert Wittes, MD, Physician‐in‐Chief, Memorial Hospital, for providing financial support."

Kato 2008

Methods

Randomised clinical trial

Sequence generation: adequate.
Allocation concealment: adequate.
Blinding: inadequate.
Incomplete outcome data addressed: adequate.
Free of selective reporting: inadequate.
Free of other bias: unclear.

Participants

Country: Japan.
Number randomised: 85.
Post‐randomisation drop‐outs: 0.
Mean age: 66 years.
Females: not stated.
Major liver resections: not stated.
Cirrhotic livers: not stated.

Inclusion criteria:
Liver resection.

Interventions

Participants were randomly assigned to two groups.

Group 1: low CVP (n = 20).
Group 2: control (n = 20).

Further details of intervention:
CVP was lowered by clamping the infra‐hepatic inferior vena cava.

Other details:
Vascular occlusion: intermittent PTC.
Method of parenchymal transection: CUSA.
Management of raw surface: diathermy, sutures, fibrin glue.
Other co‐interventions to decrease blood loss: none reported.

Outcomes

The outcomes reported were mortality, transfusion requirements, and hospital stay.

Notes

Attempts to contact the authors in November 2008 were unsuccessful.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Quote: "Eighty‐five patients who underwent hepatic resection....randomly assigned to an IVC clamping or an IVC non‐clamping group by the minimization method with stratified factors of age, .."

Allocation concealment?

Low risk

Quote: "Eighty‐five patients who underwent hepatic resection....randomly assigned to an IVC clamping or an IVC non‐clamping group by the minimization method with stratified factors of age, .."

Blinding?
All outcomes

High risk

No.

Incomplete outcome data addressed?
All outcomes

Low risk

Comment: There were no post‐randomisation drop‐outs.

Free of selective reporting?

High risk

Comment: Important outcomes such as liver failure were not reported.

Free of baseline imbalance?

Unclear risk

Unclear.

Free of early stopping bias?

Low risk

Comment: The trialists recruited the intended number of patients.

Free of academic bias?

Low risk

Comment: There were no previously published trials of same comparisons by the author.

Free of sponsor bias?

Unclear risk

Unclear.
Matot 2002

Methods

Randomised clinical trial

Sequence generation: adequate.
Allocation concealment: unclear.
Blinding: inadequate.
Incomplete outcome data addressed: unclear.
Free of selective reporting: inadequate.
Free of other bias: unclear.

Participants

Country: Israel.
Number randomised: 78.
Post‐randomisation drop‐outs: not stated.
Mean age: 56.5 years.
Females: 47 (60.3%).
Major liver resections: 78 (100%).
Cirrhotic livers: not stated

Inclusion criteria:

  1. > 18 years.

  2. Elective major liver resection.

  3. ASA I or II.

  4. Pre‐operative haematocrit > 36%.

  5. No cardiovascular or pulmonary disease.

Exclusion criteria:
Severe liver dysfunction.

Interventions

Participants were randomly assigned to two groups.

Group 1: haemodilution (n = 39).
Group 2: control (n = 39).

Further details of intervention:
haemodilution by withdrawing blood and replacing it with colloids to a target hematocrit of 24%.

Other details:
Vascular occlusion: not stated.
Method of parenchymal transection: not stated.
Management of raw surface: not stated.
Other co‐interventions to decrease blood loss: none reported.

Outcomes

The outcome measures were transfusion requirements, peri‐operative morbidity, operating time, blood loss, and liver function tests.

Notes

Attempts to contact the authors in November 2008 were unsuccessful.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Quote: "On admission to the operating room, patients who met inclusion criteria were randomly assigned (random numbers) to one of two groups..."

Allocation concealment?

Unclear risk

Unclear.

Blinding?
All outcomes

High risk

Quote: "The anaesthesiologist making decisions regarding transfusion was not blinded to patient group assignment."

Incomplete outcome data addressed?
All outcomes

Unclear risk

Unclear.

Free of selective reporting?

High risk

Comment: Important outcomes such as liver failure were not reported.

Free of baseline imbalance?

Unclear risk

Unclear.

Free of early stopping bias?

Low risk

Comment: The trialists recruited the intended number of patients.

Free of academic bias?

Low risk

Comment: There were no previously published trials of same comparisons by the author.

Free of sponsor bias?

Unclear risk

Unclear.
Standl 1998

Methods

Randomised clinical trial

Sequence generation: unclear.
Allocation concealment: unclear.
Blinding: inadequate.
Incomplete outcome data addressed: unclear.
Free of selective reporting: inadequate.
Free of other bias: unclear.

Participants

Country: Germany.
Number randomised: 12.
Post‐randomisation drop‐outs: not stated.
Mean age: 59 years.
Females: 6 (50.0%).
Major liver resections: 5 (41.7%).
Cirrhotic livers: 0 (0%).

Inclusion criteria:
Elective liver resection.

Exclusion criteria

  1. Severe cardiovascular disease (uncontrolled hypertension > 180/100 mm Hg, recent myocardial infarction <6 months, unstable angina, congestive heart failure).

  2. Decompensated pulmonary disease.

  3. Porphyria.

  4. Acute or chronical hepatic infections (eg, hepatitis B and C).

  5. Liver cirrhosis.

  6. Anaemia (preoperative packed cell volume < 30% or haemoglobin <10 g/ dl).

  7. Allergic reactions to beef products.

Interventions

Participants were randomly assigned to two groups.

Group 1: HBOC‐201 (n = 6).
Group 2: control (n = 6).

Further details of intervention and control:
Pre‐operative haemodilution was performed after induction of anaesthesia (1 litre autologous blood donation followed by 2 litres of RL) followed by intervention or control within 30 minutes.

Other details:
Vascular occlusion: not stated.
Method of parenchymal transection: not stated.
Management of raw surface: not stated.
Other co‐interventions to decrease blood loss: none reported.

Outcomes

The outcome measures were mortality, transfusion requirements, peri‐operative morbidity, operating time, hospital stay, blood loss, and liver function tests.

Notes

Attempts to contact the authors in November 2008 were unsuccessful.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Unclear.

Allocation concealment?

Unclear risk

Unclear.

Blinding?
All outcomes

High risk

No.

Incomplete outcome data addressed?
All outcomes

Unclear risk

Unclear.

Free of selective reporting?

High risk

Comment: Important outcomes such as liver failure were not reported.

Free of baseline imbalance?

Low risk

Yes.

Free of early stopping bias?

Unclear risk

Unclear.

Free of academic bias?

Low risk

Comment: There were no previously published trials of same comparisons by the author.

Free of sponsor bias?

Unclear risk

Unclear.
Wang 2006

Methods

Randomised clinical trial

Sequence generation: unclear.
Allocation concealment: unclear.
Blinding: inadequate.
Incomplete outcome data addressed: inadequate.
Free of selective reporting: inadequate.
Free of other bias: unclear.

Participants

Country: China.
Number randomised: 52
Post‐randomisation drop‐outs: 2 (3.8%) (see notes).
Mean age: 45.7 years.
Females: 10 (20%).
Major liver resections: 17 (34%).
Cirrhotic livers: 29 (58%).

Inclusion criteria:
Liver resection.

Interventions

Participants were randomly assigned to two groups.

Group 1: low CVP (n = 25).
Group 2: control (n = 27).

Further details of intervention:
CVP maintained at 2 to 4 mm Hg using nitroglycerine infusion, furosemide and by limiting volume of infusion.
Systolic blood pressure was maintained at > 90 mm Hg using dopamine infusion.
Trendelenburg's position (15 degree tilt) was used to avoid the risk of air embolism.

Other details:
Vascular occlusion: no vascular occlusion for cirrhotic livers; PTC or selective vascular occlusion for non‐cirrhotic livers.
Method of parenchymal transection: blunt division.
Management of raw surface: ligatures and fibrin glue.
Other co‐interventions to decrease blood loss: none reported.

Outcomes

The outcome measures were mortality, transfusion requirements, peri‐operative morbidity, operating time, hospital stay, blood loss, and liver function tests.

Notes

Two patients from control group in whom per‐operative death occurred (n = 1) and in whom the procedure was abandoned because of unclear tumour demarcation (n = 1) were excluded from analysis.

Attempts to contact the authors in November 2008 were unsuccessful.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Unclear.

Allocation concealment?

Unclear risk

Quote: "By the sealed envelope method, the patients were blindly randomised into LCVP group....".

Comment: It is not clear whether the authors used opaque envelopes.

Blinding?
All outcomes

High risk

No.

Incomplete outcome data addressed?
All outcomes

High risk

Comment: 2 patients were excluded post‐randomisation. This could be related to the treatment effect.

Free of selective reporting?

High risk

Comment: Important outcomes such as liver failure were not reported.

Free of baseline imbalance?

Low risk

Yes.

Free of early stopping bias?

Unclear risk

Unclear.

Free of academic bias?

Low risk

Comment: There were no previously published trials of same comparisons by the author.

Free of sponsor bias?

Unclear risk

Unclear.
Yao 2006

Methods

Randomised clinical trial

Sequence generation: unclear.
Allocation concealment: unclear.
Blinding: inadequate.
Incomplete outcome data addressed: unclear.
Free of selective reporting: inadequate.
Free of other bias: unclear.

Participants

Country: China.
Number randomised: 30.
Post‐randomisation drop‐outs: not stated.
Mean age: not stated.
Females: 14 (46.7%).
Major liver resections: not stated.
Cirrhotic livers: not stated.

Inclusion criteria:

  1. Hepatic resection.

  2. Hb above 12 mg/dl.

  3. Hct above 35%.

  4. Albumin over 35 g/l.

  5. ASA I‐II.

Interventions

Participants were randomly assigned to three groups.

Group 1: acute normovolemic haemodilution with hypotension (n = 10).
Group 2: acute normovolemic haemodilution without hypotension (n = 10).
Group 3: control (n = 10).

Further details of intervention:

Group 1: dilution with crystalloid solution (10ml/kg), autologous blood donation (replaced with 6% HES), and reduced the MAP to 70% with 0.01% sodium nitroprusside (1 mcg/kg/min).
Group 2: dilution with crystalloid solution (10ml/kg) and autologous blood donation (replaced with 6% HES).
Group 3: control.

Other details:
Vascular occlusion: not stated.
Method of parenchymal transection: not stated.
Management of raw surface: not stated.
Other co‐interventions to decrease blood loss: none reported.

Outcomes

The outcomes reported were mortality, transfusion requirements, and operative blood loss.

Notes

Attempts to contact the authors in December 2008 were unsuccessful.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Unclear.

Allocation concealment?

Unclear risk

Unclear.

Blinding?
All outcomes

High risk

No.

Incomplete outcome data addressed?
All outcomes

Unclear risk

Unclear.

Free of selective reporting?

High risk

Comment: Important outcomes such as liver failure were not reported.

Free of baseline imbalance?

Unclear risk

Unclear.

Free of early stopping bias?

Unclear risk

Unclear.

Free of academic bias?

Low risk

Comment: There were no previously published trials of same comparisons by the author.

Free of sponsor bias?

Unclear risk

Unclear.

CUSA = cavitron ultrasonic surgical aspirator
CVP = central venous pressure
MAP = mean arterial pressure
PTC = portal triad clamping

Characteristics of excluded studies [ordered by study ID]

Jump to:

Study

Reason for exclusion

Kostopanagiotou 2007

This trial compared plasma fibronectin levels in patients who underwent pre‐operative autologous blood donation and controls. Patients who required allogenic blood transfusion and who did not require any transfusion were excluded from analysis. As we consider the allogenic blood transfusion requirements and the morbidity directly or indirectly related to this as the important outcomes in this comparison, we have excluded this trial.

Data and analyses

Open in table viewer
Comparison 1. Intervention versus control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality Show forest plot

8

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 1.1
Comparison 1 Intervention versus control, Outcome 1 Mortality.

Comparison 1 Intervention versus control, Outcome 1 Mortality.

1.1 Low CVP versus control

3

177

Risk Ratio (M‐H, Fixed, 95% CI)

0.36 [0.02, 8.43]

1.2 Autologous blood donation versus control

1

79

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.3 Haemodilution versus control

2

150

Risk Ratio (M‐H, Fixed, 95% CI)

0.35 [0.04, 3.32]

1.4 Haemodilution with controlled hypotension versus control

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.5 Haemodilution with bovine haemoglobin (HBOC‐201) versus haemodilution with hydroxy ethyl starch (HES)

1

12

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.15, 61.74]

1.6 Hypoventilation versus control

1

79

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2 Peri‐operative morbidity

Other data

No numeric data

2.1 See analysis 2

Other data

No numeric data

3 Number requiring allogeneic blood transfusion Show forest plot

8

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 1.3
Comparison 1 Intervention versus control, Outcome 3 Number requiring allogeneic blood transfusion.

Comparison 1 Intervention versus control, Outcome 3 Number requiring allogeneic blood transfusion.

3.1 Low CVP versus control

3

177

Risk Ratio (M‐H, Fixed, 95% CI)

0.66 [0.42, 1.03]

3.2 Autologous blood donation versus control

1

79

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.3 Hemodilution versus control

3

233

Risk Ratio (M‐H, Fixed, 95% CI)

0.41 [0.25, 0.66]

3.4 Hemodilution with controlled hypotension versus control

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.05 [0.00, 0.72]

3.5 Hypoventilation versus control

1

79

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.18, 3.22]

4 Red cell transfusion Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 1.4
Comparison 1 Intervention versus control, Outcome 4 Red cell transfusion.

Comparison 1 Intervention versus control, Outcome 4 Red cell transfusion.

4.1 Low CVP versus control

2

135

Mean Difference (IV, Fixed, 95% CI)

‐0.00 [‐0.00, 0.00]

4.2 Haemodilution versus control

2

150

Mean Difference (IV, Fixed, 95% CI)

‐0.09 [‐0.48, 0.29]

4.3 Haemodilution with controlled hypotension versus control

1

20

Mean Difference (IV, Fixed, 95% CI)

‐665.0 [‐818.71, ‐511.29]

4.4 Haemodilution with bovine haemoglobin (HBOC‐201) versus haemodilution with hydroxy ethyl starch (HES)

1

12

Mean Difference (IV, Fixed, 95% CI)

167.0 [‐606.55, 940.55]

4.5 Hypoventilation versus control

1

79

Mean Difference (IV, Fixed, 95% CI)

‐56.00 [‐155.73, 39.73]

5 Fresh frozen plasma Show forest plot

1

Std. Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 1.5
Comparison 1 Intervention versus control, Outcome 5 Fresh frozen plasma.

Comparison 1 Intervention versus control, Outcome 5 Fresh frozen plasma.

5.1 Low CVP versus control

1

50

Std. Mean Difference (IV, Fixed, 95% CI)

‐1.22 [‐1.83, ‐0.62]

6 Operating time (minutes) Show forest plot

5

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 1.6
Comparison 1 Intervention versus control, Outcome 6 Operating time (minutes).

Comparison 1 Intervention versus control, Outcome 6 Operating time (minutes).

6.1 Low CVP versus control

2

90

Mean Difference (IV, Fixed, 95% CI)

‐24.69 [‐44.28, ‐5.09]

6.2 Hemodilution versus control

2

208

Mean Difference (IV, Fixed, 95% CI)

‐28.86 [‐57.37, ‐0.35]

6.3 Hemodilution with bovine haemoglobin (HBOC‐201) versus hemodilution with hydroxy ethyl starch (HES)

1

12

Mean Difference (IV, Fixed, 95% CI)

23.0 [‐83.60, 129.60]

7 Hospital stay (days) Show forest plot

4

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 1.7
Comparison 1 Intervention versus control, Outcome 7 Hospital stay (days).

Comparison 1 Intervention versus control, Outcome 7 Hospital stay (days).

7.1 Low CVP versus control

2

135

Mean Difference (IV, Fixed, 95% CI)

‐4.53 [‐7.38, ‐1.68]

7.2 Hemodilution versus control

1

130

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐2.66, 2.66]

7.3 Haemodilution with bovine haemoglobin (HBOC‐201) versus hemodilution with hydroxy ethyl starch (HES)

1

12

Mean Difference (IV, Fixed, 95% CI)

2.30 [‐7.52, 12.12]

8 Transection blood loss (ml) Show forest plot

4

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 1.8
Comparison 1 Intervention versus control, Outcome 8 Transection blood loss (ml).

Comparison 1 Intervention versus control, Outcome 8 Transection blood loss (ml).

8.1 Low CVP versus control

2

135

Mean Difference (IV, Fixed, 95% CI)

‐81.71 [‐219.79, 56.37]

8.2 Autologous blood donation versus control

1

79

Mean Difference (IV, Fixed, 95% CI)

‐90.0 [‐171.60, ‐8.40]

8.3 Hypoventilation versus control

1

79

Mean Difference (IV, Fixed, 95% CI)

95.0 [‐186.40, 376.40]

9 Operative blood loss (ml) Show forest plot

7

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 1.9
Comparison 1 Intervention versus control, Outcome 9 Operative blood loss (ml).

Comparison 1 Intervention versus control, Outcome 9 Operative blood loss (ml).

9.1 Low CVP versus control

3

175

Mean Difference (IV, Fixed, 95% CI)

‐419.35 [‐575.06, ‐263.63]

9.2 Autologous blood donation versus control

1

79

Mean Difference (IV, Fixed, 95% CI)

‐37.0 [‐100.51, 26.51]

9.3 Hemodilution versus control

2

98

Mean Difference (IV, Fixed, 95% CI)

1.53 [‐102.37, 105.44]

9.4 Hemodilution with controlled hypotension versus control

1

20

Mean Difference (IV, Fixed, 95% CI)

‐245.00 [‐357.80, ‐136.20]

9.5 Hemodilution with bovine haemoglobin (HBOC‐201) versus haemodilution with hydroxy ethyl starch (HES)

1

12

Mean Difference (IV, Fixed, 95% CI)

370.0 [‐1103.59, 1843.59]

10 Bilirubin (micromol/litre)

Other data

No numeric data

10.1 See analysis 3

Other data

No numeric data

11 Prothrombin activity

Other data

No numeric data

11.1 See analysis 4

Other data

No numeric data

12 AST (IU/L)

Other data

No numeric data

12.1 See analysis 5

Other data

No numeric data

13 ALT (IU/L)

Other data

No numeric data

13.1 See analysis 6

Other data

No numeric data
Open in table viewer
Comparison 2. Peri‐operative morbidity

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Low CVP versus control Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 2.1
Comparison 2 Peri‐operative morbidity, Outcome 1 Low CVP versus control.

Comparison 2 Peri‐operative morbidity, Outcome 1 Low CVP versus control.

1.1 All peri‐operative morbidities

2

90

Risk Ratio (M‐H, Fixed, 95% CI)

0.62 [0.28, 1.34]

1.2 Intra‐abdominal collections

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.12, 3.57]

1.3 Upper gastro‐intestinal bleed

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

0.2 [0.01, 3.92]

1.4 Wound infection

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.07, 14.90]

2 Autologous blood donation versus control Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 2.2
Comparison 2 Peri‐operative morbidity, Outcome 2 Autologous blood donation versus control.

Comparison 2 Peri‐operative morbidity, Outcome 2 Autologous blood donation versus control.

2.1 Bile leak

1

79

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 7.75]

2.2 Intra‐abdominal bleeding

1

79

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 7.75]

3 Haemodilution versus control Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 2.3
Comparison 2 Peri‐operative morbidity, Outcome 3 Haemodilution versus control.

Comparison 2 Peri‐operative morbidity, Outcome 3 Haemodilution versus control.

3.1 Bile leak

1

78

Risk Ratio (M‐H, Fixed, 95% CI)

1.5 [0.27, 8.49]

3.2 Intra‐abdominal bleeding

2

208

Risk Ratio (M‐H, Fixed, 95% CI)

1.87 [0.40, 8.67]

3.3 Intra‐abdominal infection

1

78

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.04, 3.07]

3.4 Intra‐abdominal collection requiring drainage

1

130

Risk Ratio (M‐H, Fixed, 95% CI)

1.26 [0.61, 2.60]

3.5 Wound infection

2

208

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.34, 2.03]

3.6 Chest infection

1

78

Risk Ratio (M‐H, Fixed, 95% CI)

1.5 [0.27, 8.49]

4 Haemodilution with bovine haemoglobin (HBOC‐201) versus haemodilution with hydroxy ethyl starch (HES) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 2.4
Comparison 2 Peri‐operative morbidity, Outcome 4 Haemodilution with bovine haemoglobin (HBOC‐201) versus haemodilution with hydroxy ethyl starch (HES).

Comparison 2 Peri‐operative morbidity, Outcome 4 Haemodilution with bovine haemoglobin (HBOC‐201) versus haemodilution with hydroxy ethyl starch (HES).

4.1 Liver failure

1

12

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.15, 61.74]

4.2 Re‐operation

1

12

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.02, 6.86]

4.3 Hyperamylasemia

1

12

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.15, 61.74]

4.4 Atelectasis

1

12

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.15, 61.74]

5 Hypoventilation versus control Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 2.5
Comparison 2 Peri‐operative morbidity, Outcome 5 Hypoventilation versus control.

Comparison 2 Peri‐operative morbidity, Outcome 5 Hypoventilation versus control.

5.1 Bile leak

1

79

Risk Ratio (M‐H, Fixed, 95% CI)

4.10 [0.48, 35.10]

5.2 Cholangitis

1

79

Risk Ratio (M‐H, Fixed, 95% CI)

3.08 [0.13, 73.27]

5.3 Thrombosis

1

79

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.07, 15.83]
Open in table viewer
Comparison 3. Bilirubin (micromol/litre)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Low CVP versus control Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 3.1
Comparison 3 Bilirubin (micromol/litre), Outcome 1 Low CVP versus control.

Comparison 3 Bilirubin (micromol/litre), Outcome 1 Low CVP versus control.

1.1 POD 1

2

90

Mean Difference (IV, Fixed, 95% CI)

0.22 [‐10.31, 10.75]

1.2 POD 3

2

90

Mean Difference (IV, Fixed, 95% CI)

2.02 [‐9.90, 13.94]

1.3 POD 7

2

90

Mean Difference (IV, Fixed, 95% CI)

5.02 [‐5.05, 15.09]
Open in table viewer
Comparison 4. Prothrombin activity

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Low CVP versus control Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 4.1
Comparison 4 Prothrombin activity, Outcome 1 Low CVP versus control.

Comparison 4 Prothrombin activity, Outcome 1 Low CVP versus control.

1.1 POD 1

1

40

Mean Difference (IV, Fixed, 95% CI)

‐2.0 [‐10.00, 6.00]

1.2 POD 3

1

40

Mean Difference (IV, Fixed, 95% CI)

2.0 [‐5.17, 9.17]

1.3 POD 7

1

40

Mean Difference (IV, Fixed, 95% CI)

‐9.0 [‐33.48, 15.48]

2 Haemodilution with bovine haemoglobin (HBOC‐201) versus haemodilution with hydroxy ethyl starch (HES) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 4.2
Comparison 4 Prothrombin activity, Outcome 2 Haemodilution with bovine haemoglobin (HBOC‐201) versus haemodilution with hydroxy ethyl starch (HES).

Comparison 4 Prothrombin activity, Outcome 2 Haemodilution with bovine haemoglobin (HBOC‐201) versus haemodilution with hydroxy ethyl starch (HES).

2.1 POD 1

1

12

Mean Difference (IV, Fixed, 95% CI)

6.0 [‐9.29, 21.29]

2.2 POD 3

1

12

Mean Difference (IV, Fixed, 95% CI)

8.0 [‐24.26, 40.26]

2.3 POD 7

1

12

Mean Difference (IV, Fixed, 95% CI)

24.0 [‐5.38, 53.38]
Open in table viewer
Comparison 5. Aspartate transaminase (international units/litre)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Low CVP versus control Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 5.1
Comparison 5 Aspartate transaminase (international units/litre), Outcome 1 Low CVP versus control.

Comparison 5 Aspartate transaminase (international units/litre), Outcome 1 Low CVP versus control.

1.1 POD 1

1

40

Mean Difference (IV, Fixed, 95% CI)

50.0 [‐18.40, 118.40]

1.2 POD 3

1

40

Mean Difference (IV, Fixed, 95% CI)

14.0 [‐47.39, 75.39]

1.3 POD 7

1

40

Mean Difference (IV, Fixed, 95% CI)

9.0 [‐15.48, 33.48]

2 Hypoventilation versus control Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 5.2
Comparison 5 Aspartate transaminase (international units/litre), Outcome 2 Hypoventilation versus control.

Comparison 5 Aspartate transaminase (international units/litre), Outcome 2 Hypoventilation versus control.

2.1 POD 1

1

79

Mean Difference (IV, Fixed, 95% CI)

‐5.00 [‐31.26, 17.26]
Open in table viewer
Comparison 6. Alanine transaminase (international units/litre)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Low CVP versus control Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 6.1
Comparison 6 Alanine transaminase (international units/litre), Outcome 1 Low CVP versus control.

Comparison 6 Alanine transaminase (international units/litre), Outcome 1 Low CVP versus control.

1.1 POD 1

2

90

Mean Difference (IV, Fixed, 95% CI)

54.72 [7.89, 101.56]

1.2 POD 3

2

90

Mean Difference (IV, Fixed, 95% CI)

22.05 [‐31.05, 75.14]

1.3 POD 7

2

90

Mean Difference (IV, Fixed, 95% CI)

‐8.95 [‐49.61, 31.71]

Reference flow chart
Figures and Tables -
Figure 1

Reference flow chart

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Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
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Figure 2

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

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Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
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Figure 3

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Comparison 1 Intervention versus control, Outcome 1 Mortality.
Figures and Tables -
Analysis 1.1

Comparison 1 Intervention versus control, Outcome 1 Mortality.

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Comparison 1 Intervention versus control, Outcome 3 Number requiring allogeneic blood transfusion.
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Analysis 1.3

Comparison 1 Intervention versus control, Outcome 3 Number requiring allogeneic blood transfusion.

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Comparison 1 Intervention versus control, Outcome 4 Red cell transfusion.
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Analysis 1.4

Comparison 1 Intervention versus control, Outcome 4 Red cell transfusion.

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Comparison 1 Intervention versus control, Outcome 5 Fresh frozen plasma.
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Analysis 1.5

Comparison 1 Intervention versus control, Outcome 5 Fresh frozen plasma.

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Comparison 1 Intervention versus control, Outcome 6 Operating time (minutes).
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Analysis 1.6

Comparison 1 Intervention versus control, Outcome 6 Operating time (minutes).

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Comparison 1 Intervention versus control, Outcome 7 Hospital stay (days).
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Analysis 1.7

Comparison 1 Intervention versus control, Outcome 7 Hospital stay (days).

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Comparison 1 Intervention versus control, Outcome 8 Transection blood loss (ml).
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Analysis 1.8

Comparison 1 Intervention versus control, Outcome 8 Transection blood loss (ml).

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Comparison 1 Intervention versus control, Outcome 9 Operative blood loss (ml).
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Analysis 1.9

Comparison 1 Intervention versus control, Outcome 9 Operative blood loss (ml).

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Comparison 2 Peri‐operative morbidity, Outcome 1 Low CVP versus control.
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Analysis 2.1

Comparison 2 Peri‐operative morbidity, Outcome 1 Low CVP versus control.

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Comparison 2 Peri‐operative morbidity, Outcome 2 Autologous blood donation versus control.
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Analysis 2.2

Comparison 2 Peri‐operative morbidity, Outcome 2 Autologous blood donation versus control.

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Comparison 2 Peri‐operative morbidity, Outcome 3 Haemodilution versus control.
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Analysis 2.3

Comparison 2 Peri‐operative morbidity, Outcome 3 Haemodilution versus control.

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Comparison 2 Peri‐operative morbidity, Outcome 4 Haemodilution with bovine haemoglobin (HBOC‐201) versus haemodilution with hydroxy ethyl starch (HES).
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Analysis 2.4

Comparison 2 Peri‐operative morbidity, Outcome 4 Haemodilution with bovine haemoglobin (HBOC‐201) versus haemodilution with hydroxy ethyl starch (HES).

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Comparison 2 Peri‐operative morbidity, Outcome 5 Hypoventilation versus control.
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Analysis 2.5

Comparison 2 Peri‐operative morbidity, Outcome 5 Hypoventilation versus control.

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Comparison 3 Bilirubin (micromol/litre), Outcome 1 Low CVP versus control.
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Analysis 3.1

Comparison 3 Bilirubin (micromol/litre), Outcome 1 Low CVP versus control.

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Comparison 4 Prothrombin activity, Outcome 1 Low CVP versus control.
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Analysis 4.1

Comparison 4 Prothrombin activity, Outcome 1 Low CVP versus control.

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Comparison 4 Prothrombin activity, Outcome 2 Haemodilution with bovine haemoglobin (HBOC‐201) versus haemodilution with hydroxy ethyl starch (HES).
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Analysis 4.2

Comparison 4 Prothrombin activity, Outcome 2 Haemodilution with bovine haemoglobin (HBOC‐201) versus haemodilution with hydroxy ethyl starch (HES).

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Comparison 5 Aspartate transaminase (international units/litre), Outcome 1 Low CVP versus control.
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Analysis 5.1

Comparison 5 Aspartate transaminase (international units/litre), Outcome 1 Low CVP versus control.

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Comparison 5 Aspartate transaminase (international units/litre), Outcome 2 Hypoventilation versus control.
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Analysis 5.2

Comparison 5 Aspartate transaminase (international units/litre), Outcome 2 Hypoventilation versus control.

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Comparison 6 Alanine transaminase (international units/litre), Outcome 1 Low CVP versus control.
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Analysis 6.1

Comparison 6 Alanine transaminase (international units/litre), Outcome 1 Low CVP versus control.

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Comparison 1. Intervention versus control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality Show forest plot

8

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 Low CVP versus control

3

177

Risk Ratio (M‐H, Fixed, 95% CI)

0.36 [0.02, 8.43]

1.2 Autologous blood donation versus control

1

79

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.3 Haemodilution versus control

2

150

Risk Ratio (M‐H, Fixed, 95% CI)

0.35 [0.04, 3.32]

1.4 Haemodilution with controlled hypotension versus control

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.5 Haemodilution with bovine haemoglobin (HBOC‐201) versus haemodilution with hydroxy ethyl starch (HES)

1

12

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.15, 61.74]

1.6 Hypoventilation versus control

1

79

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2 Peri‐operative morbidity

Other data

No numeric data

2.1 See analysis 2

Other data

No numeric data

3 Number requiring allogeneic blood transfusion Show forest plot

8

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 Low CVP versus control

3

177

Risk Ratio (M‐H, Fixed, 95% CI)

0.66 [0.42, 1.03]

3.2 Autologous blood donation versus control

1

79

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.3 Hemodilution versus control

3

233

Risk Ratio (M‐H, Fixed, 95% CI)

0.41 [0.25, 0.66]

3.4 Hemodilution with controlled hypotension versus control

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.05 [0.00, 0.72]

3.5 Hypoventilation versus control

1

79

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.18, 3.22]

4 Red cell transfusion Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

4.1 Low CVP versus control

2

135

Mean Difference (IV, Fixed, 95% CI)

‐0.00 [‐0.00, 0.00]

4.2 Haemodilution versus control

2

150

Mean Difference (IV, Fixed, 95% CI)

‐0.09 [‐0.48, 0.29]

4.3 Haemodilution with controlled hypotension versus control

1

20

Mean Difference (IV, Fixed, 95% CI)

‐665.0 [‐818.71, ‐511.29]

4.4 Haemodilution with bovine haemoglobin (HBOC‐201) versus haemodilution with hydroxy ethyl starch (HES)

1

12

Mean Difference (IV, Fixed, 95% CI)

167.0 [‐606.55, 940.55]

4.5 Hypoventilation versus control

1

79

Mean Difference (IV, Fixed, 95% CI)

‐56.00 [‐155.73, 39.73]

5 Fresh frozen plasma Show forest plot

1

Std. Mean Difference (IV, Fixed, 95% CI)

Subtotals only

5.1 Low CVP versus control

1

50

Std. Mean Difference (IV, Fixed, 95% CI)

‐1.22 [‐1.83, ‐0.62]

6 Operating time (minutes) Show forest plot

5

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

6.1 Low CVP versus control

2

90

Mean Difference (IV, Fixed, 95% CI)

‐24.69 [‐44.28, ‐5.09]

6.2 Hemodilution versus control

2

208

Mean Difference (IV, Fixed, 95% CI)

‐28.86 [‐57.37, ‐0.35]

6.3 Hemodilution with bovine haemoglobin (HBOC‐201) versus hemodilution with hydroxy ethyl starch (HES)

1

12

Mean Difference (IV, Fixed, 95% CI)

23.0 [‐83.60, 129.60]

7 Hospital stay (days) Show forest plot

4

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

7.1 Low CVP versus control

2

135

Mean Difference (IV, Fixed, 95% CI)

‐4.53 [‐7.38, ‐1.68]

7.2 Hemodilution versus control

1

130

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐2.66, 2.66]

7.3 Haemodilution with bovine haemoglobin (HBOC‐201) versus hemodilution with hydroxy ethyl starch (HES)

1

12

Mean Difference (IV, Fixed, 95% CI)

2.30 [‐7.52, 12.12]

8 Transection blood loss (ml) Show forest plot

4

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

8.1 Low CVP versus control

2

135

Mean Difference (IV, Fixed, 95% CI)

‐81.71 [‐219.79, 56.37]

8.2 Autologous blood donation versus control

1

79

Mean Difference (IV, Fixed, 95% CI)

‐90.0 [‐171.60, ‐8.40]

8.3 Hypoventilation versus control

1

79

Mean Difference (IV, Fixed, 95% CI)

95.0 [‐186.40, 376.40]

9 Operative blood loss (ml) Show forest plot

7

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

9.1 Low CVP versus control

3

175

Mean Difference (IV, Fixed, 95% CI)

‐419.35 [‐575.06, ‐263.63]

9.2 Autologous blood donation versus control

1

79

Mean Difference (IV, Fixed, 95% CI)

‐37.0 [‐100.51, 26.51]

9.3 Hemodilution versus control

2

98

Mean Difference (IV, Fixed, 95% CI)

1.53 [‐102.37, 105.44]

9.4 Hemodilution with controlled hypotension versus control

1

20

Mean Difference (IV, Fixed, 95% CI)

‐245.00 [‐357.80, ‐136.20]

9.5 Hemodilution with bovine haemoglobin (HBOC‐201) versus haemodilution with hydroxy ethyl starch (HES)

1

12

Mean Difference (IV, Fixed, 95% CI)

370.0 [‐1103.59, 1843.59]

10 Bilirubin (micromol/litre)

Other data

No numeric data

10.1 See analysis 3

Other data

No numeric data

11 Prothrombin activity

Other data

No numeric data

11.1 See analysis 4

Other data

No numeric data

12 AST (IU/L)

Other data

No numeric data

12.1 See analysis 5

Other data

No numeric data

13 ALT (IU/L)

Other data

No numeric data

13.1 See analysis 6

Other data

No numeric data
Figures and Tables -
Comparison 1. Intervention versus control
Navigate to table in Review
Comparison 2. Peri‐operative morbidity

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Low CVP versus control Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 All peri‐operative morbidities

2

90

Risk Ratio (M‐H, Fixed, 95% CI)

0.62 [0.28, 1.34]

1.2 Intra‐abdominal collections

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.12, 3.57]

1.3 Upper gastro‐intestinal bleed

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

0.2 [0.01, 3.92]

1.4 Wound infection

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.07, 14.90]

2 Autologous blood donation versus control Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 Bile leak

1

79

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 7.75]

2.2 Intra‐abdominal bleeding

1

79

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 7.75]

3 Haemodilution versus control Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 Bile leak

1

78

Risk Ratio (M‐H, Fixed, 95% CI)

1.5 [0.27, 8.49]

3.2 Intra‐abdominal bleeding

2

208

Risk Ratio (M‐H, Fixed, 95% CI)

1.87 [0.40, 8.67]

3.3 Intra‐abdominal infection

1

78

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.04, 3.07]

3.4 Intra‐abdominal collection requiring drainage

1

130

Risk Ratio (M‐H, Fixed, 95% CI)

1.26 [0.61, 2.60]

3.5 Wound infection

2

208

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.34, 2.03]

3.6 Chest infection

1

78

Risk Ratio (M‐H, Fixed, 95% CI)

1.5 [0.27, 8.49]

4 Haemodilution with bovine haemoglobin (HBOC‐201) versus haemodilution with hydroxy ethyl starch (HES) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 Liver failure

1

12

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.15, 61.74]

4.2 Re‐operation

1

12

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.02, 6.86]

4.3 Hyperamylasemia

1

12

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.15, 61.74]

4.4 Atelectasis

1

12

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.15, 61.74]

5 Hypoventilation versus control Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 Bile leak

1

79

Risk Ratio (M‐H, Fixed, 95% CI)

4.10 [0.48, 35.10]

5.2 Cholangitis

1

79

Risk Ratio (M‐H, Fixed, 95% CI)

3.08 [0.13, 73.27]

5.3 Thrombosis

1

79

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.07, 15.83]
Figures and Tables -
Comparison 2. Peri‐operative morbidity
Navigate to table in Review
Comparison 3. Bilirubin (micromol/litre)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Low CVP versus control Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 POD 1

2

90

Mean Difference (IV, Fixed, 95% CI)

0.22 [‐10.31, 10.75]

1.2 POD 3

2

90

Mean Difference (IV, Fixed, 95% CI)

2.02 [‐9.90, 13.94]

1.3 POD 7

2

90

Mean Difference (IV, Fixed, 95% CI)

5.02 [‐5.05, 15.09]
Figures and Tables -
Comparison 3. Bilirubin (micromol/litre)
Navigate to table in Review
Comparison 4. Prothrombin activity

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Low CVP versus control Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 POD 1

1

40

Mean Difference (IV, Fixed, 95% CI)

‐2.0 [‐10.00, 6.00]

1.2 POD 3

1

40

Mean Difference (IV, Fixed, 95% CI)

2.0 [‐5.17, 9.17]

1.3 POD 7

1

40

Mean Difference (IV, Fixed, 95% CI)

‐9.0 [‐33.48, 15.48]

2 Haemodilution with bovine haemoglobin (HBOC‐201) versus haemodilution with hydroxy ethyl starch (HES) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 POD 1

1

12

Mean Difference (IV, Fixed, 95% CI)

6.0 [‐9.29, 21.29]

2.2 POD 3

1

12

Mean Difference (IV, Fixed, 95% CI)

8.0 [‐24.26, 40.26]

2.3 POD 7

1

12

Mean Difference (IV, Fixed, 95% CI)

24.0 [‐5.38, 53.38]
Figures and Tables -
Comparison 4. Prothrombin activity
Navigate to table in Review
Comparison 5. Aspartate transaminase (international units/litre)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Low CVP versus control Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 POD 1

1

40

Mean Difference (IV, Fixed, 95% CI)

50.0 [‐18.40, 118.40]

1.2 POD 3

1

40

Mean Difference (IV, Fixed, 95% CI)

14.0 [‐47.39, 75.39]

1.3 POD 7

1

40

Mean Difference (IV, Fixed, 95% CI)

9.0 [‐15.48, 33.48]

2 Hypoventilation versus control Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 POD 1

1

79

Mean Difference (IV, Fixed, 95% CI)

‐5.00 [‐31.26, 17.26]
Figures and Tables -
Comparison 5. Aspartate transaminase (international units/litre)
Navigate to table in Review
Comparison 6. Alanine transaminase (international units/litre)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Low CVP versus control Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 POD 1

2

90

Mean Difference (IV, Fixed, 95% CI)

54.72 [7.89, 101.56]

1.2 POD 3

2

90

Mean Difference (IV, Fixed, 95% CI)

22.05 [‐31.05, 75.14]

1.3 POD 7

2

90

Mean Difference (IV, Fixed, 95% CI)

‐8.95 [‐49.61, 31.71]
Figures and Tables -
Comparison 6. Alanine transaminase (international units/litre)
Navigate to table in Review