Clinical trial NCT04978285: Association of Postoperative Anaemia With Patient-centred Outcomes
Official title: Association of Postoperative Anaemia With Patient-centred Outcomes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Anemia After Surgery
Keywords: anemia
complications
hemoglobin
iron
patient-centered outcome
surgery
Lead sponsor: Bayside Health
Sponsor class: OTHER_GOV
Collaborators: name: Monash University
First posted: 2021-07-27
Enrollment: 3000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult, elective major abdominal surgery

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Persistent disability or death by 90 days
timeFrame: 90 days after surgery
Secondary outcomes:
measure: Death: all-cause mortality at 90 days, then up to 12 months after surgery
timeFrame: 1 year
measure: A composite (pooled) and individual septic complications: sepsis, surgical site infection, anastomotic leak, and pneumonia
timeFrame: 30 days
measure: Sepsis: using Centers for Disease Control and Prevention (CDC) with National Healthcare Safety Network (NHSN) criteria
timeFrame: 30 days
measure: Surgical site infection
timeFrame: 30 days
measure: Pneumonia
timeFrame: 30 days
measure: Anastomotic leak
timeFrame: 30 days
measure: Acute kidney injury
timeFrame: 30 days
measure: Unplanned admission to ICU within 30 days of surgery
timeFrame: 30 days
measure: ICU stay
timeFrame: 30 days
measure: Hospital stay
timeFrame: 30 days
measure: Quality of recovery
timeFrame: Postoperative Days 3 and 30
measure: Hospital re-admission
timeFrame: At 3, 6 and 12 months.
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
Study officials:
References:
citation: 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.
citation: 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.