Association of Postoperative Anaemia With Patient-centred Outcomes

Primary aim - To investigate the relationship between postoperative anaemia and patient-centred outcomes after major abdominal surgery.

Secondary aim - To determine whether a more liberal perioperative IV fluid strategy increases the risk of postoperative anaemia (haemodilution).

Hypothesis: Adults with anaemia in the immediate postoperative period following major abdominal surgery have a poorer quality of recovery and higher risk of complications, leading to poor disability-free survival when compared with patients without postoperative anaemia.

Study Overview

• Status: Completed
• Conditions: Anemia After Surgery
• Intervention / Treatment: Other: Anemia

Detailed Description

The consequences of postoperative anemia remain unclear. Postoperative anaemia is more likely if there is pre-existing anemia, but also increased perioperative blood loss, frequent blood sampling, excess IV fluids (leading to hemodilution), sepsis, and inadequate nutritional intake after surgery. A nadir in Hb concentration is most often observed within the first 3-4 days after surgery. Postoperative anemia is believed to have deleterious effects on patient outcomes, including prolonged hospital stay, increased postoperative complications, and perhaps poor survival, but there is very little data to support this belief.

A recent consensus statement suggested that all patients recovering from major surgery (defined as blood loss > 500 ml or lasting > 2 h) and either had preoperative anemia or moderate-to-severe blood loss during surgery must be screened for anemia after surgery. Furthermore, this consensus group recommended that patients recovering from uncomplicated major surgery should have their Hb concentration measured for at least 3 days after surgery to detect anemia. As outlined above, this is problematic if there is fluid retention.

The role of IV iron for the treatment of postoperative anemia is unclear, with the most recent systematic review concluding that neither oral nor IV iron had a significant effect on patient quality of life or functional outcomes following surgery. A diagnosis of iron deficiency is very difficult in the postoperative period because the acute phase inflammatory response results in spuriously elevated ferritin levels, and several studies have demonstrated oral iron therapy is ineffective in this setting.

The investigators propose a study to investigate the incidence, extent, and outcomes of patients with anemia after major surgery, including an assessment of the amount of IV fluids administered in the immediate perioperative period.

• Study Type: Observational
• Enrollment (Actual): 3000

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult, elective major abdominal surgery

Description

Inclusion Criteria:

1. Adults (≥18 years) undergoing elective major surgery and providing informed consent
2. All types of open or lap-assisted abdominal or pelvic surgery with an expected duration of at least 2 hours, and an expected hospital stay of at least 3 days

3. At increased risk of postoperative complications, as defined by any of the following criteria:

   1. age ≥70 years
   2. known or documented history of coronary artery disease
   3. known or documented history of heart failure
   4. diabetes currently treated with an oral hypoglycemic agent and/or insulin
   5. preoperative serum creatinine >200 micromol/L (>2.8 mg/dl)
   6. morbid obesity (BMI ≥35 kg/m2)
   7. preoperative serum albumin <30 g/L
   8. anaerobic threshold (if done) <12 mL/kg/min

   9. or two or more of the following risk factors:

      • ASA 3 or 4
      • chronic respiratory disease
      • obesity (BMI 30-35 kg/m2)
      • aortic or peripheral vascular disease
      • preoperative Hb <100 g/L
      • preoperative serum creatinine 150-199 micromol/L (>1.7 mg/dl)
      • anerobic threshold (if done) 12-14 mL/kg/min

Exclusion Criteria:

1. Urgent or time-critical surgery
2. ASA physical status 5 - such patients are not expected to survive with or without surgery, and their underlying illness is expected to have an overwhelming effect on outcome (irrespective of fluid therapy)
3. Chronic renal failure requiring dialysis
4. Pulmonary or cardiac surgery - different pathophysiology, and thoracic surgery typically have strict fluid restrictions
5. Liver resection - most units have strict fluid/CVP limits in place and won't allow randomisation
6. Minor or intermediate surgery, such as laparoscopic cholecystectomy, transurethral resection of the prostate, inguinal hernia repair, splenectomy, closure of colostomy - each of these are typically "minor" surgery with minimal IV fluid requirements, generally low rates of complications and mostly very good survival.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Postoperative anemia; All patients enrolled in the RELIEF trial in which a postoperative Day 1-3 hemoglobin concentration was measured. Anaemia will be defined according to the World Health Organisation definition (males Hb <130 g/L, and female Hb <120 g/L).	Other: Anemia; Depends on Day 3 Hb result; Other Names: Observational
No postoperative anemia; All patients enrolled in the RELIEF trial in which a postoperative Day 1-3 hemoglobin concentration was measured. No anaemia will be defined according to the World Health Organisation definition (males Hb ≥130 g/L, and females Hb ≥120 g/L).	Other: Anemia; Depends on Day 3 Hb result; Other Names: Observational

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistent disability or death by 90 days	Defined as a World Health Organization Disability Assessment Schedule 2.0 (WHODAS) score of at least 24 points (on the 48-point scale) at both 30 and 90 days postoperatively, reflecting a disability level of at least 25% and being the threshold point between "disabled" and "not disabled" as per WHO guidelines. Disability was assessed by the participant, but if unable then we used the proxy's report.	90 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death: all-cause mortality at 90 days, then up to 12 months after surgery		1 year
A composite (pooled) and individual septic complications: sepsis, surgical site infection, anastomotic leak, and pneumonia		30 days
Sepsis: using Centers for Disease Control and Prevention (CDC) with National Healthcare Safety Network (NHSN) criteria		30 days
Surgical site infection	CDC criteria	30 days
Pneumonia	The presence of new and/or progressive pulmonary infiltrates on chest radiograph plus two or more of the following: i. Fever ≥ 38.5°C or postoperative hypothermia <36°C ii. Leucocytosis ≥ 12,000 WBC/mm3 or leucopenia < 4,000 WBC/mm3 iii. Purulent sputum and/or iv. New onset or worsening cough or dyspnea.	30 days
Anastomotic leak	A defect of the intestinal wall at the anastomotic site (including suture and staple lines of neorectal reservoirs) leading to a communication between the intra- an extra luminal compartments.	30 days
Acute kidney injury	According to The Kidney Disease: Improving Global Outcomes (KDIGO) group criteria, but not urine output - for Stage 2 or worse AKI defined as at least 2-fold increase in creatinine, or estimated GFR decrease >50%	30 days
Unplanned admission to ICU within 30 days of surgery		30 days
ICU stay	Total days - additive, including initial ICU admission and readmission times up to Day 30	30 days
Hospital stay	Total -additive, from the start (date, time) of surgery until actual hospital discharge , plus readmission(s) up to Day 30	30 days
Quality of recovery	QoR-15 scale score	Postoperative Days 3 and 30
Hospital re-admission		At 3, 6 and 12 months.

Collaborators and Investigators

• Sponsor: Bayside Health
• Collaborators: Monash University

Publications and helpful links

General Publications

• Myles PS, Bellomo R, Corcoran T, Forbes A, Peyton P, Story D, Christophi C, Leslie K, McGuinness S, Parke R, Serpell J, Chan MTV, Painter T, McCluskey S, Minto G, Wallace S; Australian and New Zealand College of Anaesthetists Clinical Trials Network and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery. N Engl J Med. 2018 Jun 14;378(24):2263-2274. doi: 10.1056/NEJMoa1801601. Epub 2018 May 9.
• Myles PS, Richards T, Klein A, Wood EM, Wallace S, Shulman MA, Martin C, Bellomo R, Corcoran TB, Peyton PJ, Story DA, Leslie K, Forbes A; RELIEF Trial Investigators. Postoperative anaemia and patient-centred outcomes after major abdominal surgery: a retrospective cohort study. Br J Anaesth. 2022 Sep;129(3):346-354. doi: 10.1016/j.bja.2022.06.014. Epub 2022 Jul 15.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 16, 2021
• Primary Completion (ACTUAL): October 31, 2021
• Study Completion (ACTUAL): November 30, 2021

Study Registration Dates

• First Submitted: July 16, 2021
• First Submitted That Met QC Criteria: July 16, 2021
• First Posted (ACTUAL): July 27, 2021

Study Record Updates

• Last Update Posted (ACTUAL): July 13, 2022
• Last Update Submitted That Met QC Criteria: July 11, 2022
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: hemoglobin; surgery; complications; anemia; iron; patient-centered outcome
• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia
• Other Study ID Numbers: 544/12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Consider, on request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No