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Total number of complications comprised five pre-defined clinical endpoints, including acute renal failure ADDIN EN.CITE ADDIN EN.CITE.DATA 1-5, infection (including pneumonia, sepsis, urinary and wound infection) ADDIN EN.CITE ADDIN EN.CITE.DATA 3,5-7, thromboembolic events (TE) ADDIN EN.CITE ADDIN EN.CITE.DATA 1-5,8-10, cardiac events ADDIN EN.CITE ADDIN EN.CITE.DATA 2-5,7, bleeding ADDIN EN.CITE ADDIN EN.CITE.DATA 4,5 (including reoperation because of bleeding, postoperative bleeding, and tamponade) as well as any additionally reported adverse events. Additional complications that were found during the screening process included respiratory (indicated as respiratory complications ADDIN EN.CITE ADDIN EN.CITE.DATA 4, exacerbation of chronic lung disease ADDIN EN.CITE ADDIN EN.CITE.DATA 2, and prolonged ventilation ADDIN EN.CITE ADDIN EN.CITE.DATA 4,5,11), urologic (acute urinary retention and urethral injury ADDIN EN.CITE ADDIN EN.CITE.DATA 2), gastrointestinal (intestinal obstruction ADDIN EN.CITE ADDIN EN.CITE.DATA 11 and clostridium difficile colitis ADDIN EN.CITE ADDIN EN.CITE.DATA 2), medication-related (narcotized from analgesia and adverse drug reaction ADDIN EN.CITE ADDIN EN.CITE.DATA 2), cardiac (arrhythmias and pulmonary edema) ADDIN EN.CITE ADDIN EN.CITE.DATA 11 and other complications (multisystem organ failure and coma >24h ADDIN EN.CITE Moskowitz201066617Moskowitz, D. M.McCullough, J. N.Shander, A.Klein, J. J.Bodian, C. A.Goldweit, R. S.Ergin, M. A.Department of Anesthesiology, Critical Care Medicine, Hyperbaric Medicine and Pain Management, Englewood Hospital and Medical Center, Englewood, NJ 07631, USA. david.moskowitz@ehmc.comThe impact of blood conservation on outcomes in cardiac surgery: is it safe and effective?Ann Thorac SurgThe Annals of thoracic surgeryAnn Thorac SurgThe Annals of thoracic surgeryAnn Thorac SurgThe Annals of thoracic surgery451-89022010/07/30AgedAnemia/therapyBlood Transfusion/*adverse effects*Coronary Artery BypassFemaleHumansMalePostoperative Complications/epidemiology/etiologyTreatment Outcome2010Aug0003-49752066732810.1016/j.athoracsur.2010.04.089NLMeng5, hypotension, acute limb ischemia ADDIN EN.CITE ADDIN EN.CITE.DATA 11, febrile non-hemolytic transfusion reaction and delirium ADDIN EN.CITE ADDIN EN.CITE.DATA 2, intermuscular venous thrombosis ADDIN EN.CITE ADDIN EN.CITE.DATA 9, postoperative haematoma ADDIN EN.CITE ADDIN EN.CITE.DATA 11, prosthesis-related events and allergic events ADDIN EN.CITE ADDIN EN.CITE.DATA 10,11, postoperative confusion ADDIN EN.CITE ADDIN EN.CITE.DATA 11, and readmission within 30 days ADDIN EN.CITE ADDIN EN.CITE.DATA 1,12 or 90 days ADDIN EN.CITE ADDIN EN.CITE.DATA 13 of discharge) (supplemental table content 5). Four studies ADDIN EN.CITE ADDIN EN.CITE.DATA 10-12,14 provided complication rates as a composite endpoint and respective data were also included in the calculation.
Supplemental data content 2. Preoperative anemia management (pillar 1)
Iron was administered orally in three ADDIN EN.CITE ADDIN EN.CITE.DATA 4,9,10 and intravenously in nine ADDIN EN.CITE ADDIN EN.CITE.DATA 1-3,6,7,14-17 studies, whereas further three studies provided both treatment options on a patient-related basis ADDIN EN.CITE ADDIN EN.CITE.DATA 8,11,13, and one trial did not report information on route ADDIN EN.CITE ADDIN EN.CITE.DATA 12. If further detailed, single IV iron infusion contained 1,000-2,000mg ADDIN EN.CITE ADDIN EN.CITE.DATA 2,7,15,17 or 200mg IV iron weekly ADDIN EN.CITE ADDIN EN.CITE.DATA 14. Oral iron was administrated with a dosage of 200mg iron, three times a day for a period of three weeks ADDIN EN.CITE ADDIN EN.CITE.DATA 10. Iron treatment started 40 ADDIN EN.CITE ADDIN EN.CITE.DATA 14, 28 ADDIN EN.CITE ADDIN EN.CITE.DATA 6,13,17, or 21 ADDIN EN.CITE ADDIN EN.CITE.DATA 10,11 days before surgery. Nine studies reported the subcutaneous administration of EPO ADDIN EN.CITE ADDIN EN.CITE.DATA 1,6,8,10-14,17, using doses of 40,000IU ADDIN EN.CITE ADDIN EN.CITE.DATA 10,14,17, 600IU/kg body weight ADDIN EN.CITE Gross201516161617Gross, I.Seifert, B.Hofmann, A.Spahn, D. R.Patient Blood Management Program, Eastern Maine Medical Center, Bangor, Maine.
Department of Hematology and Oncology, Eastern Maine Medical Center, Bangor, Maine.
Institute of Anesthesiology, University and University Hospital Zurich, Zurich, Switzerland.Patient blood management in cardiac surgery results in fewer transfusions and better outcomeTransfusionTransfusionTransfusionTransfusionTransfusionTransfusion1075-815552015/01/08AgedAlgorithmsBlood TransfusionCardiac Surgical Procedures/*methodsErythrocyte TransfusionFemaleHumansMaleMiddle AgedPlatelet Transfusion2015May0041-11322556530210.1111/trf.12946NLMeng1, or 80,000-90,000IU ADDIN EN.CITE ADDIN EN.CITE.DATA 6, and four studies additionally performed treatment with vitamin B12 and/or folic acid ADDIN EN.CITE ADDIN EN.CITE.DATA 4,8,14,17.
Supplemental data content 3. Minimization of iatrogenic blood loss (pillar 2)
Autologous RBC collection and re-transfusion (e.g. cell salvage) was used in 10 studies ADDIN EN.CITE ADDIN EN.CITE.DATA 1,3-7,10,14,15,17. All studies involving cardiac surgical patients ADDIN EN.CITE ADDIN EN.CITE.DATA 1,3-7,15 and 7 ADDIN EN.CITE ADDIN EN.CITE.DATA 3,6,10,13-15,17 out of 14 studies involving orthopedic surgical patients used cell salvage. Blood-sparing and meticulous surgical techniques were reported in 10 trials ADDIN EN.CITE ADDIN EN.CITE.DATA 1,3-5,7,9,13,15-17. Regarding cardiac surgery, specified techniques such as minimized extracorporeal circuits ADDIN EN.CITE ADDIN EN.CITE.DATA 1,3-5,15, retrograde autologous priming ADDIN EN.CITE ADDIN EN.CITE.DATA 1,3-5, and bloodless saphenous vein graft removal with immediate wound closure ADDIN EN.CITE ADDIN EN.CITE.DATA 4 were used to minimize blood loss. Sixteen trials ADDIN EN.CITE ADDIN EN.CITE.DATA ADDIN EN.CITE.DATA 1-9,11-17 applied antifibrinolytic drugs during surgery. Tranexamic acid (TXA) was administered with dosage of 10mg/kg ADDIN EN.CITE ADDIN EN.CITE.DATA 14, 15mg/kg ADDIN EN.CITE ADDIN EN.CITE.DATA 2,9,16 , 20mg/kg ADDIN EN.CITE ADDIN EN.CITE.DATA 8 or 1,000mg ADDIN EN.CITE ADDIN EN.CITE.DATA 11,13. Aminocaproic acid was used in 3 cardiac surgery studies ADDIN EN.CITE ADDIN EN.CITE.DATA 1,4,5. Six studies provided no specific information on antifibrinolytic pharmacological agents used ADDIN EN.CITE ADDIN EN.CITE.DATA 3,6,7,12,15,17. Hemostasis management including point-of-care testing for coagulopathy (viscoelastic and aggregometric methods) was applied in five studies ADDIN EN.CITE ADDIN EN.CITE.DATA 1,3,5,7,15.
Supplemental data content 4. Harnessing the tolerance of anemia (pillar 3)
Low to medium risk pa t i e n t s w e r e t r a n s f u s e d i f h e m o g l o b i n l e v e l w a s d" 6 g / d L A D D I N E N . C I T E A D D I N E N . C I T E . D A T A 3 , 5 , 1 0 , d" 7 g / d L A D D I N E N . C I T E A D D I N E N . C I T E . D A T A 1 , 7 - 9 , 1 1 - 1 3 , 1 5 , d" 7 . 5 g / d L A D D I N E N . C I T E A D D I N E N . C I T E . D A T A 6 , 1 8 o r d" 8 g / d L A D D I N E N . C I T E A D D I N E N . C I T E . D A T A 2 , 1 4 , 1 6 , 1 7 . H i g h r i s k p a t i e n t s r e c e i v e d R B C t r a n s f u s i o n s i f h e m o g l o b i n w a s 6 - 8 g / d L A D D I N E N . C I T E A D D I N E N . C I T E . D A T A 3 , d" 7 g / d L A D D I N E N . C I T E A D D I N E N . C I T E . D A T A 5 , 1 2 , d" 8 g / d L A D D I N E N . C I T E A D D I N E N . C I T E . D A T A 8 , 9 , 1 1 , 1 6 , 1 7 , d" 9 g / d L A D D I N E N . C I T E A D D I N E N . C I T E . D A T A 1 3 , 1 4 , 1 6 , d" 9 . 7 g / d L A D D I N E N . C I T E A D D I N E N . C I T E . D A T A 1 0 , u p t o 1 0 g / d L A D D I N E N . C I T E A D D I N E N . C I T E . D A T A 9 , 1 1 o r i n t h e p r e s e n c e o f p h y s i o l o g i c a l t r a n s f u s i o n t r i g g e r s w i t h o u t d e t e r m i nation of a hemoglobin value ADDIN EN.CITE ADDIN EN.CITE.DATA 4,15.
Supplemental data content 5. Subgroup characteristics
Fourteen studies ADDIN EN.CITE ADDIN EN.CITE.DATA ADDIN EN.CITE.DATA 2,3,6-17 included procedures in orthopedic surgery and more women underwent orthopedic interventions (64.7%). However, the gender distribution was equal between the relevant groups (pre-PBM: 65% vs PBM: 64.5% females). Six studies ADDIN EN.CITE ADDIN EN.CITE.DATA 6,7,10,12,15,17 investigated knee and hip interventions including re-surgery. Another six studies ADDIN EN.CITE ADDIN EN.CITE.DATA 2,8,9,11,13,16 focused on primary arthroplasty. One study ADDIN EN.CITE ADDIN EN.CITE.DATA 17 additionally included spine surgery and one study ADDIN EN.CITE ADDIN EN.CITE.DATA 3 combined all orthopedic and trauma interventions.
Seven studies ADDIN EN.CITE ADDIN EN.CITE.DATA 1,3-7,15 examined patients undergoing cardiac surgery. Gender distribution was unequal in favor of males (25.5% females), however, similar between the two groups (pre-PBM: 27.7% vs PBM: 23.3% females). Specified types of cardiac procedures were isolated CABG (coronary artery bypass grafting) ADDIN EN.CITE ADDIN EN.CITE.DATA 1,3-6, isolated valve surgery ADDIN EN.CITE ADDIN EN.CITE.DATA 1,4,5, combined CABG, and valve replacements and non-CABG surgery ADDIN EN.CITE ADDIN EN.CITE.DATA 1,4,5. One multicenter study ADDIN EN.CITE ADDIN EN.CITE.DATA 3 additionally included patients undergoing pericardium and heart rhythm surgery as well as septum and aortic surgery.
Four studies ADDIN EN.CITE ADDIN EN.CITE.DATA 3,6,7,15 included patients undergoing vascular surgery. Gender distribution was unequal in favor of males (16.4% females), however, similar between the two groups (pre-PBM: 14.6% vs PBM: 18.1% females). Specified types of vascular procedures were AAA (abdominal aortic aneurysm surgery) ADDIN EN.CITE ADDIN EN.CITE.DATA 6, major peripheral vascular surgery ADDIN EN.CITE ADDIN EN.CITE.DATA 3, and open aortic surgery ADDIN EN.CITE ADDIN EN.CITE.DATA 3.
Three studies ADDIN EN.CITE ADDIN EN.CITE.DATA 3,7,15 examined patients undergoing general surgery, of which one study ADDIN EN.CITE ADDIN EN.CITE.DATA 3 defined surgeries of the esophagus, stomach, small and large bowels, appendix, rectum and anus, liver, gall bladder and biliary tract, pancreas, hernia, thyroid gland, and other glands were included. One study ADDIN EN.CITE ADDIN EN.CITE.DATA 3 included patients undergoing surgery in other fields. Gender distribution was equal (48.4% females) and similar between the two groups (pre-PBM: 48.5% vs PBM: 48.3% females) (supplemental table content 4).
Supplemental data content 6. Between-study-variance
Tests for subgroup differences showed high I2 values for the outcomes mortality, transfusion rate, and RBC units per patient (I>80%), indicating that the model of subgroups by type of surgery had an impact on observed heterogeneity. Moderate degrees of heterogeneity (I>50%) were detected for LOS, mortality, acute renal failure, and infection. We focused on orthopedic and cardiac surgery due to corresponding variation in sample sizes among relevant studies. Within these subgroups in the field of orthopedic surgery, studies were homogenous regarding the outcomes mortality (I2=0%, p=0.75), acute renal failure (I2=0%, p=0.40), and TE (I2=0%, p=0.95). However, moderate to high heterogeneity (I2>50%) was observed for transfusion rate, RBC units per patient, LOS, total number of complications, infection, and cardiac events. Here, further tests for subgroup differences suggest that variations in sample sizes had an impact on between-study variance for infection (I2=72.5%, p=0.06), but were not related to heterogeneity regarding the outcomes transfusion rate (I2=47.1%, p=0.15), RBC units per patient (I2=0%, p=0.64), LOS (I2=0%, p=0.42), total number of complications (I2=49.5%, p=0.14), and cardiac events (I2=4.7%, p=0.31). Overall, a statistically significant reduction in transfusion rate, transfused RBC units per patient, LOS, total number of complication, acute renal failure, and mortality could be observed in orthopedic surgery (supplemental table content 6). Within the subgroups of cardiac surgery, studies were homogenous regarding the outcomes mortality (I2=26%, p=0.24) and cardiac events (I2=24%, p=0.27). We observed moderate to high heterogeneity (I2>50%) for transfusion rate, RBC units per patient, LOS, total number of complications, acute renal failure, TE, and infection. Tests for subgroup differences indicate that sample sizes had an impact on between study-variance of transfusion rate (I2=84.9%, p=0.001), RBC units per patient (I2=70.7%, p=0.03), LOS (I2=80.6%, p=0.006), total number of complications (I2=70.5%, p=0.03), and infection (I2=64.3%, p=0.06). Overall, transfusion rate, number of RBC units transfused per patient, LOS, total number of complications, and bleeding events decreased in patients undergoing cardiac surgery after implementation of multimodal PBM measures (supplemental table content 6).
Furthermore, we performed a sensitivity analysis by omitting data from Meybohm et al. ADDIN EN.CITE ADDIN EN.CITE.DATA 3, as this was the largest study population included in this meta-analysis. With the exception of acute renal failure (RR 1.19, 95% CI 0.58 to 2.45, p=0.649), results were similar between meta-analysis including respectively excluding Meybohm et al28 for transfusion rate (RR 0.50, 95% CI 0.41 to 0.6, p<0.0001), transfused RBC units per patient (MD -0.35, 95% CI -0.48 to -0.22, p<0.0001), LOS (MD -0.61, 95% CI -0.92 to -0.3, p<0.0001), total number of complications (RR 0.75, 95% CI 0.67 to 0.83, p<0.00001), and mortality (RR 0.77, 95% CI 0.65 to 0.9, p=0.001) (supplemental table content 7).
Reference
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Supplemental figure content 1. Risk of bias summary
Review authors judgments about each methodological quality item for each included study.
Supplemental figure content 2. Risk of bias graph
Review authors judgments about each risk of bias items presented as percentages across all included studies. 17 studies are included in this meta-analysis.
Supplemental figure content 3. Funnel plots of investigated outcomes
RBC=red blood cells; LOS=length of hospital stay
Supplemental table content 1: Included PBM measures in meta-analysis
Study
1st Pillar2nd Pillar3rd PillarTotal number of included measures
RefTreatment of hematinic deficienciesBlood-sparing techniquesUse of perioperative autologous RBC re-transfusionPharmacological/ hemostatic agentsHemostasis management (POC)Restrictive transfusion thresholds Albinarrate et al((((419Brevig et al(((((520Freedman et al((((421Frew et al(((((522Gross et al((((((623
3Holt et al(((324Kopanidis et al(((325Leahy et al((((((626
33Leahy et al((((((627Loftus et al(((328Ma et al((((429Meybohm et al((((((630Morais et al((((431Moskowitz et al((((((632Rineau et al(((333So-Osmann et al(((334Theusinger et al((((535 POC=Point-of-care
Supplemental table content 2: Overview of questions for assessment using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS)
BiasQuestions to support authors' judgmentSelection of participantsWere the key characteristics of patients in different cohorts similar?
Were the patients in different cohorts recruited from the same population (e.g. from the same hospital)?
Were study subjects in different cohorts recruited and examined at the same time point?Intervention measurementWere there any differences in intervention measurement between groups?
Can we be confident in the assessment of exposure (secure records such as medical record, pharmacy record, radiological record)?Blinding of outcome assessment Were methods of blinding used to avoid detection bias?
In case of knowledge of the allocated interventions by outcome assessors:
Was the outcome measurement objective?
Is it likely that non-blinding has influenced results? Incomplete outcome dataWere both statistically significant and insignificant outcome data fully reported?
Were data presented to be included in a meta-analysis?
Were there indications for loss to follow-up?Selective reportingWere primary and secondary endpoints pre-specified and reported in the pre-specified way?
Was the follow-up time long enough to reliably measure respective outcomes?Confounding variablesCan we be confident in the adherence to the PBM protocol?
Were there any differences in treatment apart from PBM interventions (e.g. physiotherapy, surgical team, additional surgical techniques)?
Were there any indications for changes to the study protocol based on findings?
Did the authors report adjustment for confounding in the analysis?
Did the authors declare any conflicts of interest?
Were there any indications for other confounding factors that may have affected the results? Supplemental table content 3: Outcome measures provided by studies included in meta-analysis
AuthorBleedingCardiac eventsAcute renal failureInfectionTELOSTotal complicationMortalityTransfusion rateRBC units per patientRefAlbinarrate et al(((19Brevig et al(((((((20Freedman et al ((((((21Frew et al((22Gross et al((((((23Holt et al(((24Kopanidis et al(((((((25Leahy et al((((((26
Leahy et al (27Loftus et al((((28Ma et al(((((29Meybohm et al (((((((((30Morais et al(31Moskowitz et al(((((((32Rineau et al((((33So-Osmann et al(((((34Theusinger et al((35TE= Thromboembolic events; LOS= Length of hospital stay, RBC= Red blood cell
Supplemental table content 4: Subgroup characteristics
Surgical disciplineAge
(mean SD)Pre-PBM groupPBM groupN (=)Female rate (%)N (=)Female rate (%)Orthopedic surgery67.4 11.435,7706545,03164.5Cardiac surgery65.3 10.58,50327.712,95023.2Vascular surgery71.0 86,42414.67,92518.1General surgeryn.a.13,676n.a.19,131n.a.Other fields55.7 0.836,51348.549,85648.3n.a.= not available
Supplemental table content 5: Detailed outcome measure provided by studies included in meta-analysis
AuthorEndpointRefAcute renal failureBrevig et alNew hemodialysis20Gross et alKidney injury: increase in serum creatinine to >2.0 mg/dL23Kopanidis et alAcute kidney injury25Meybohm et alAcute renal failure30Moskowitz et alRenal complications: patients creatinine >2.0 mg/dL or doubled from most recent preoperative creatinine level or experienced renal failure requiring dialysis postoperatively.32Rineau et al*Acute kidney injury (increase of creatinine > 25% from baseline)33Cardiac eventsBrevig et alPostoperative myocardial infarction20Kopanidis et alAcute coronary syndrome, exacerbation of heart failure25Leahy et alAcute myocardial infarction-stroke26Meybohm et alMyocardial infarction30Moskowitz et alMyocardial infarction, cardiac arrest32Rineau et al*Acute coronary syndrome, arrhythmias, cardiac arrest, pulmonary oedema33So-Osmann et al*Myocardial infarction34Thromboembolic eventsBrevig et alPostoperative cerebrovascular accident20Gross et alCerebrovascular accident23Holt et alPostoperative stroke, deep vein thrombosis/pulmonary embolism24Kopanidis et aldeep vein thrombosis, pulmonary embolism25Ma et aldeep vein thrombosis29Meybohm et alIschemic stroke (cerebral infarction, non-bleeding, non-infarct stroke)30Moskowitz et alPermanent Stroke32Rineau et al*Venous thrombosis, pulmonary embolism, stroke33So-Osmann et al*Thromboembolic events, pulmonary embolism, stroke/transient ischemic attack34InfectionFreedman et alRelevant symptoms and positive culture21Leahy et alHospital-acquired infection26Meybohm et alPneumonia, sepsis30Moskowitz et alPneumonia, sternal wound infection, septicaemia, urinary tract infection32Rineau et al*Pneumonia, wound infections, urinary tract infections33BleedingBrevig et alReoperation for bleeding20Moskowitz et alTamponade, postoperative bleeding32Respiratory complicationsBrevig et alRespiratory complications, prolonged ventilation20Kopanidis et alExacerbation of chronic lung disease25Moskowitz et alProlonged ventilation32Rineau et al*Need for re-intubation, prolonged ventilation33Urinary complicationsKopanidis et alAcute urinary retention, ureteral injury25Gastrointestinal complicationsKopanidis et alClostridium difficile colitis25Rineau et al*Intestinal obstruction33Readmission rateFrew et alReadmitted within 90 days of discharge22Gross et al30-day readmission rate23Loftus et al30-day readmission28Medication-relatedKopanidis et alNarcotised from analgesia, adverse drug reaction25OthersKopanidis et alHypotension, delirium, febrile non-haemolytic transfusion reaction25Ma et alIntermuscular venous thrombosis29Moskowitz et alMultisystem organ failure, coma >24 hours32Rineau et al*Acute limb ischemia, postoperative confusion, allergies, postoperative hematoma33* Indicate studies that provided composite endpoint
Supplemental table content 6: Risk ratios of meta-analysis for infection rate, acute renal failure, cardiac events, thromboembolic events, and bleeding between pre-PBM and PBM
Surgical disciplineRR95% CIP-valueRefInfection rateOrthopedic surgery0.790.61, 1.03=0.0821, 26, 30 Cardiac surgery0.630.38, 1.07=0.0921, 26, 30, 32Vascular surgery0.910.82, 1.00=0.0621, 28, 30General surgery0.970.89, 1.04=0.3926, 30Other fields0.980.93, 1.04=0.5730Total0.910.84, 0.99=0.03Acute renal failureOrthopedic surgery0.720.61, 0.86=0.000225, 30Cardiac surgery0.960.62, 1.49=0.8620, 23, 30, 32Vascular surgery0.590.51, 0.68<0.0000130General surgery0.710.63, 0.80<0.0000130Other fields0.760.70, 0.83<0.0000130Total0.740.66, 0.83<0.00001Cardiac eventsOrthopedic surgery0.690.22, 2.12=0.5225, 26, 30Cardiac surgery1.010.67, 1.52=0.9622, 26, 30, 32Vascular surgery0.990.69, 1.42=0.9426, 30General surgery0.920.70, 1.21=0.5426, 30Other fields1.190.98, 1.44=0.0830Total0.930.74, 1.17=0.56Thromboembolic eventsOrthopedic surgery0.790.56, 1.11=0.1724, 25, 29, 30, 34 Cardiac surgery0.860.67, 1.12=0.2620, 23, 30, 32Vascular surgery0.750.58, 0.96=0.0230General surgery0.580.41, 0.81=0.00130Other fields0.680.56, 0.84=0.000430Total0.750.67, 0.84<0.00001BleedingOrthopedic surgeryn.a.n.a.n.a.Cardiac surgery0.300.15, 0.64=0.00220, 32Vascular surgeryn.a.n.a.n.a.General surgeryn.a.n.a.n.a.Other fieldsn.a.n.a.n.a.Total0.300.15, 0.64=0.002RR= Relative risk ratio; CI= Confidence interval; TE=Thromboembolic events; n.a.= not available
Supplemental table content 7: Subgroup analysis with subgroups of <1,000, 1,000-5,000 and >5,000 patients for orthopedic and cardiac surgery
Type of surgeryOutcome<1,000 patients1,000-5,000 patients>5,000 patientsRR/WDM*95% CIP-valueRR/WDM*95% CIP-valueRR/WDM*95% CIP-valueOrtho-Transfusion rate0.390.23, 0.650.0030.210.03, 1.230.080.660.46, 0.940.02pedicRBC unit0.10*-0.85, -1.040.84-0.17*-0.25, -0.09<0.0001-0.22*-0.31, -0.12<0.00001LOS-0.61*-1.19, -0.030.04-0.91*-2.06, 0.240.12-0.33*-0.48, -0.18<0.0001Total number of complication10.67, 1.490.990.620.47, 0.820.00090.7910.63, 0.990.04Mortality0.340.01, 8.170.501..930.18, 21.280.580.730.64, 0.83<0.00001Cardiac events0.330.04, 3.150.34n.a.n.a.n.a.0.790.23, 2.760.71Acute renal failure20.18, 21.710.57n.a.n.a.n.a.0.720.61, 0.850.0002TE0.640.04, 10.220.760.690.25, 1.930.480.80.56, 1.160.24Infectionn.a.n.a.n.a.0.540.33, 0.900.020.860.67, 1.090.21CardiacTransfusion rate0.60.39, 0.920.020.380.25, 0.59<0.00010.810.78, 0.83<0.00001RBC unit-0.85*-1.25, -0.45<0.0001-0.77*-0.92, -0.62<0.00001-0.97*-0.99, -0.95<0.00001LOS-2.97*-4.49, -1.450.0001-1.29*-2.24, -0.340.008-0.35*-1.02, 0.320.31Total number of complication0.530.30, 0.950.030.700.52, 0.940.020.940.85, 1.030.20Mortality0.330.07, 1.630.170.900.60, 1.350.600.960.84, 1.100.54Cardiac eventsn.a.n.a.n.a.0.710.41, 1.250.231.340.91, 1.960.14Acute renal failuren.a.n.a.n.a.1.140.52, 2.520.740.750.66, 0.85<0.0001TEn.a.n.a.n.a.0.660.42, 1.030.071.490.29, 7.710.63Infection0.530.3, 0.950.030.450.08, 2.460.361.020.93, 1.120.72RR= Relative risk ratio; WDM*= Weighted mean difference; CI= Confidence interval; RBC= Red blood cells; LOS= Length of hospital stay; TE=Thromboembolic events
Supplemental table content 8: Meta-analysis of subgroup analysis without Meybohm et al
Surgical disciplineRR/WDM*95% CIP-valueTransfusion rateOrthopedic surgery0.430.33, 0.55<0.00001Cardiac surgery0.450.32, 0.64<0.00001Vascular surgery0.910.77, 1.09=0.32General surgery1.330.93, 1.90=0.11Other fieldsn.a.n.a.n.a.Total0.500.41, 0.60<0.00001RBC units per patientOrthopedic surgery-0.13*-0.29, 0.03=0.10Cardiac surgery-0.79*-0.93, -0.65<0.00001Vascular surgery-0.39*-0.51, -0.68<0.00001General surgery-0.18*-0.26, -0.10<0.00001Other fieldsn.a.n.a.n.a.Total-0.35*-0.48, -0.22<0.00001LOSOrthopedic surgery-0.47*-0.69, -0.24<0.0001Cardiac surgery-1.74*-2.86, -0.62=0.002Vascular surgery-2.20*-6.05, -1.65=0.26General surgery0.48*0.11, 0.85=0.01Other fieldsn.a.n.a.n.a.Total-0.61*-0.92, -0.30=0.0001Total number of complicationsOrthopedic surgery0.720.65, 0.79<0.00001Cardiac surgery0.680.52, 0.88=0.004Vascular surgery0.880.64, 1.21=0.42General surgery0.990.83, 1.19=0.95Other fieldsn.a.n.a.n.a.Total0.750.67, 0.83<0.00001MortalityOrthopedic surgery0.670.50, 0.90=0.008Cardiac surgery0.840.56, 1.27=0.41Vascular surgery0.820.55, 1.22=0.34General surgery0.710.51, 1.00=0.71Other fieldsn.a.n.a.n.a.Total0.770.65, 0.90=0.001Infection rateOrthopedic surgery0.690.53, 0.90=0.006Cardiac surgery0.490.19, 1.27=0.14Vascular surgery1.030.76, 1.40=0.84General surgery1.010.84, 1.23=0.88Other fieldsn.a.n.a.n.a.Total0.750.57, 0.98=0.03Acute renal failureOrthopedic surgery2.000.18, 21.71=0.57Cardiac surgery1.140.52, 2.52=0.74Vascular surgeryn.a.n.a.n.a.General surgeryn.a.n.a.n.a.Other fieldsn.a.n.a.n.a.Total1.190.58, 2.45=0.64Cardiac eventsOrthopedic surgery0.410.27, 0.62<0.0001Cardiac surgery0.710.41, 1.25=0.23Vascular surgery0.750.42, 1.33=0.32General surgery0.820.45, 1.50=0.52Other fieldsn.a.n.a.n.a.Total0.600.46, 0.77=0.0001Thromboembolic eventsOrthopedic surgery0.690.26, 1.80=0.44Cardiac surgery0.660.42, 1.03=0.07Vascular surgeryn.a.n.a.n.a.General surgeryn.a.n.a.n.a.Other fieldsn.a.n.a.n.a.Total0.660.44, 1.00=0.05RR= Relative risk ratio; WDM*= Weighted mean difference; CI= Confidence interval; RBC= Red blood cells; LOS= Length of hospital stay; TE=Thromboembolic events; n.a.= not available
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