Immunonutrition in Total Hip Arthroplasty
Condition: Arthroplasty, Hip Replacement; Perioperative Care; Nutritional Support
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The aim of this pilot study was to investigate whether the use of a multimodal protocol of
      preoperative care plus preoperative immune nutrition would decrease the length of stay and
      acute phase inflammation in patients submitted to total hip arthroplasty (THA). The study was
      designed to be randomized and controlled, but not double blind. The patients were randomized
      to receive either preoperative care based on evidence plus immune nutrition for 5 days prior
      to surgery (Acerto group) or traditional preoperative care (control group). Main endpoints
      were length of stay and acute-phase postoperative response
    

Detailed description: 
      A large broad of evidence has shown that traditional perioperative care have a weak
      scientific basis and needs to be changed. Multimodal or fast-track protocols of perioperative
      care for abdominal surgery have been associated with lower morbidity, lower costs and faster
      postoperative recovery when compared to traditional care . Similarly the prescription of
      perioperative immune nutrition for 5-7 days before major abdominal surgery may decrease the
      risk of infections and reduce postoperative length of stay (LOS). Interestingly there is lack
      of studies on multimodal protocols of enhanced recovery and on immune nutrition in elective
      total hip arthroplasty (THA). In Brazil, the ACERTO (an acronym in Portuguese for
      acceleration of postoperative recovery) protocol is a multimodal protocol of perioperative
      care that includes: shortening of preoperative fasting with carbohydrates (CHO)-rich drinks
      up to 2h before surgery, restriction of intravenous fluids and early postoperative re-feeding
      and mobilization. Recently as a dynamic protocol the Acerto protocol included the
      recommendation of perioperative immune nutrition. All the elements of the protocol are based
      on evidence and are recommended by various international guidelines and consensus. Thus, the
      aim of this pilot study was to investigate whether the use of the Acerto multimodal protocol
      plus preoperative immune nutrition would decrease the length of stay and acute phase
      inflammation in patients submitted to THA.

      METHODS This was a prospective randomized pilot study. All procedures were performed at São
      Mateus Hospital (Cuiabá, Brazil) from May 2012 to February 2013. The study was approved by
      the Research Ethics Committee of the Júlio Müller University Hospital (Federal University of
      Mato Grosso) and all patients signed a term of informed consent.

      Inclusion and exclusion criteria. The investigators included adult patients of both sex
      having a hip osteoarthrosis and candidates of elective THA. Patients were excluded if they
      had fasting glycemia greater than 200mg/dl; acquired immunodeficiency (AIDS); renal failure
      (creatinin above 2 mg/dl); cirrhosis; moderate or serious Alzheimer's disease (clinical
      dementia rating score between 2 and 3); an American Society of Anesthesiologists (ASA) score
      higher than 2; previous spinal surgery (arthrodesis) or THA (reviewing or changing the
      prosthetic); and severe malnutrition (history of loss of 10% of body weight over the last 6
      months). The investigators also excluded patients who did not have their blood samples taken
      at the scheduled time and those who broke perioperative protocol, e.g. the non-intake of the
      immune supplement in the Acerto group.

      Design of the study. Patients were consecutively included and randomized into two groups:
      Group Control and ACERTO group with the aid of electronic software of random numbers
      available at www.graphpad.com. All patients were assessed by a multidisciplinary team, who
      carried out a nutrition assessment, preoperative education, and collected the relevant
      anthropometric, biochemical and clinical data.

      Anesthesia and operative technique. Antibiotic prophylaxis was done with 2g of intravenous
      kefazolin at the time of anesthetic induction. Measures were taken against postoperative
      nausea and vomiting (PONV) according to the protocol applied by the anesthesia team and will
      be discussed in this paper. Preoperative sedation was done with intravenous midazolam (0.03
      to 0.1mg/kg) and propofol (30 to 60 mcg/kg/min) No general anesthetic was applied in both
      groups. All subjects received epidural neuro-axis blockage at L3-L4 space with ropivacain
      7.5% to 10% (150-200mg) and morphine chlorate 2mg (30 to 50 micrograms/kg). The surgical
      access of the hip was done by anterior-lateral approach. The investigators used in all cases
      hybrid type total arthroplasty (cementation of the femoral component and fixation of the
      acetabular component by means of pressure fitting of the implant to the bone and the addition
      of screws to the acetabular cup when necessary).

      Carbohydrate drink Patients belonging to the Acerto group received a drink (200 mL)
      containing water plus 12% maltodextrin 2h before the induction of anesthesia.

      Immune supplementation therapy. The patients in the ACERTO group received an immune
      supplement containing arginine, w-3 fatty acids, nucleotides, and vitamins (Impact; Nestlé;
      Sao Paulo, Brazil. Formula: proteins: 23% (77% calcium caseinate, 23% arginine);
      carbohydrates: 52% (100% maltodextrin); lipids: 25% (68% fish oil; 20% medium-chain
      triglycerides and 12% corn oil), vitamins and electrolytes) for five days prior to surgery,
      with a daily dosage of thress units (600ml per day in total).

      Blood samples. Blood samples were collected preoperatively and at the 2nd PO day and assayed
      for CRP assay.

      Criteria for hospital discharge.

      Discharge was signed by an orthopedic surgeon if all of these five parameters were fulfilled:

        1. patient is confident and willing to go home,

        2. no pain or pain controlled by oral analgesics,

        3. walking alone or with minimal help,

        4. no fever or signs of postoperative infection, and

        5. accepting normal oral diet

      Outcome variables The main outcome variable was the postoperative length of stay. As
      secondary outcome variables it was compared the evolution of serum C-reactive protein (CRP)
      overtime.

      Statistical analysis. The calculation of the sample was based on the premise that the
      intervention with the Acerto Project protocol would reduce the hospital stay length by 50%.
      For a β error (type II) of 20% and an α error (type I) of 5%, it was calculated that 15
      patients in each group would be sufficient for this study. Investigators used paired and
      unpaired t-test when samples were homogeneous or the Mann-Whitney test or the Wilcoxon test
      if samples were heterogeneous. Categorical variables were compared by the chi square test or
      Fisher exact test. Statistical analyses were made using the Minitab 14 and the null
      hypothesis rejection was fixed at 0.05 (α=5%).
    

Intervention name(s): Impact
Intervention type(s): Dietary Supplement
Intervention description(s): 600 ml of Impact, Nestle for 5 days prior to surgery
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Prevention