Supplemental Parental Nutrition and Abdominal Surgery

Effect of Early vs Late Supplemental Parenteral Nutrition
in Patients Undergoing Abdominal Surgery:
A Randomized Clinical Trial

Gao. JAMA Surg. 2022; 157: 384 – 393. doi:10.1001/jamasurg.2022.0269

Clinical Question

  • In patients undergoing major abdominal surgery who are at high nutritional risk and have poor tolerance to enteral nutrition (EN) does the early use of supplemental parental nutrition (E-SPN), compared with late supplemental parental nutrition (L-SPN), reduce the risk of nosocomial infection?

Background

  • EN should be implemented as soon as possible following major abdominal surgery, however in many cases the energy delivery by EN is less than the estimated requirements
  • A 2022 meta-analysis showed that a combination of EN with PN “improved nutrition intake in the acute phase of critical illness in adults and was not inferior regarding the patients’ outcomes”
  • The 2017 ESPEN guidelines for clinical nutrition in surgery suggest “that if the energy and nutrient requirements cannot be met by oral and enteral intake alone (<50% of caloric requirement) for more than seven days, a combination of enteral and parenteral nutrition is recommended (Good Practice Point)”
  • For context, the evidence and recommendations vary for SPN in ICU:
    • The EPaNIC study in 2011 showed potential harm with early SPN, however the 2017 TOP-UP study showed no increased risk of infection with SPN
    • The 2016 SCCM and ASPEN guidelines recommend the “use of supplemental PN be considered after 7–10 days if unable to meet >60% of energy and protein requirements by the enteral route alone. Initiating supplemental PN prior to this 7- to 10-day period in critically ill patients on some EN does not improve outcomes and may be detrimental to the patient. [Quality of Evidence: Moderate]”
    • There is some suggestion that the infectious complications seen with PN may have related to early caloric overfeeding, as when calories administered by EN and PN were similar there was no difference in ICU infections

Design

  • Investigator initiated, multi-centre, randomised trial
  • Open label
  • Randomised in 1:1 ratio
    • Stratified by different centres
    • Sequentially numbered, sealed opaque envelopes used for randomisation
  • Clinicians involved in follow up blinded, alongside statisticians
  • Sample size calculations based on incidence of nosocomial infection of 25% in those receiving PN
    • Based on meta-analysis
    • E-SPN hypothesised to reduce this by 15%
    • Power 80%, two-tailed type 1 error rate of 5% required 110 in each group, increased to 230 in total to allow for withdrawal and loss to follow up
  • Energy targets verified every 24 hours
  • Daily nutritional information collected for 12 days or until normal diet/discharge
  • Monitored for post-operative complications by clinicians not associated with surgical teams
  • Pre-defined subgroups
  • Clear definitions for infections provided in the supplemental appendix
  • Missing data not imputed
  • Appropriate ethical approval
  • Registered at ClinicalTrials.gov

Setting

  • China, 11 hospitals
  • April 2017 – December 2018

Population

  • Inclusion:
    • Adult patients aged 18 – 80 years
    • Elective gastric, colorectal, hepatic and pancreatic resections for non-traumatic reasons
    • At risk of malnutrition (NRS2002 ≥ 3)
      • Ranges from 0-7 and a score ≥ 3 indicates at nutritional risk
    • ≤ 30% of energy target on day 2 of surgery
    • Expected post-operative hospital stay > 7 days
  • Exclusion:
    • Extensive, included:
      • Pre-operative severe malnutrition
      • Unstable haemodynamics or refractory shock
        • Wide definition used: SBP < 90 not responsive to 500ml fluid bolus, 50% increase in vasoactive support in prior hour, or high levels of vasoactive support [adrenaline or noradrenaline > 30 mcg/min, vasopressin > 0.04U/min]
      • Hepatic or renal insufficiency (creatinine, bilirubin or AST/ALT > 200% ULN)
      • Metabolic disorders including T1DM and T2DM (with intensive medical treatment or insulin treatment)
      • Nutritional support prior to enrolment
  • 1560 screened –> 230 randomised (115 in each arm)
    • 1330 excluded primarily for not meeting inclusion criteria
  • Comparing baseline characteristics of E-SPN vs. L-SPN
    • Age: 60.3 vs 59.8
    • Male: 61.7% vs 60.5%
    • BMI: 23 vs 22.8
    • NRS
      • 3: 80% vs 79.8%
      • 4: 18.3% vs 17.5%
    • Diagnosis:
      • Gastric Cancer: 33.9% vs 31.6%
      • Colorectal Cancer: 34.8% vs 40.4%
      • Pancreatic Cancer: 10.4% vs 14.9%
      • Benign diagnosis: 7.0% vs 3.5%
    • Biochemistry:
      • Albumin (g/dL): 4.11 vs 4.06
      • ALT (U/L): 26.7 vs 20.5
      • ALP (U/L): 100.4 vs 104/9
      • Creatinine (mg/dL): 0.83 vs 0.81
      • Median Glucose (mg/dL): 93.69 vs 91.89
      • CRP (mg/dL): 0.93 vs 0.72
    • Operative:
      • Laparotomy: 52.2% vs 45.6%
      • No Intraoperative Contamination: 93.9% vs 91.2%
      • Operative Time
        • < 2 hrs: 8.7% vs 7.9%
        • > 5 hrs: 17.4% vs 13.2%
      • Blood Loss > 500mls: 13.9% vs 12.3%
      • Blood Transfusion: 14.8% vs 11.4%

Intervention

  • E-SPN
    • Commenced on day 3 post surgery

Control

  • L-SPN
    • Commenced on day 8 post surgery

Management common to both groups

  • Oral diet or EN via tube started within 24 hours
    • Energy requirements calculated based on IBW [30 kcal/kg for men and 25 kcal/kg for women]
    • Protein 1.2g/kg IBW
    • EN contained 1kcal/ml
  • ESPEN guidelines used
  • Trained clinicians developed personalised plans to reach target, initially with EN
  • Energy provision of EN and SPN was 100% of requirements
  • SPN could be provided centrally or peripherally
  • Both groups received nutritional support for a minimum of 5 days, until EN comprised 80% of requirements or hospital discharge

Outcome

  • Primary outcome:
  • Occurrence of nosocomial infections between day 3 and discharge
    • E-SPN 8.7% vs L-SPN 18.4%
    • Absolute difference of 9.7% (95% CI 0.9 – 18.5%) p = 0.04
  • Secondary outcomes:
  • Comparing E-SPN vs. L-SPN group
    • No significant difference in
      • Non-infectious complications
        • 27.0 vs 33.3%
        • Absolute difference 6.4% (95% CI -5.5 – 18.2%)
      • Total Adverse Events
        • 65.2% vs 71.9%
        • Absolute difference 6.7% (95% CI -5.3 – 18.7%)
      • Parental Nutrition related complications
        • 7.8% vs 3.5%
      • Hospital LOS
        • 16.6 days vs 17.6 days
      • Mechanical ventilatory support
        • 3.5% vs 6.1%
      • ICU admission
        • 6.1% vs 7.9%
      • No difference in mean energy intake or protein intake between days 8 – 12
    • Significantly more in E-SPN group
      • Mean daily energy intake between days 3 – 8
        • 26.5 kcal/kg/day vs 15.1 kcal/kg/day
        • p < 0.001
      • Mean protein intake between days 3 – 8
        • 1.02 g/kg/day vs 0.48 g/kg/day
        • p < 0.001
    • Significantly less in E-SPN group
      • Mean Therapeutic Antibiotic Days
        • 6 vs 7 days
        • Absolute difference 1.0 (95% CI 0.2 – 1.9)
    • No mortality in either group
  • Subgroups
    • All point estimates favoured E-SPN but no 95% CI fully favour E-SPN
    • Subgroups included age, sex, NRS2002 score, Cancer, Laparotomy vs Laparoscopy, operative time, blood loss

Authors’ Conclusions

  • E-SPN associated with reduced nosocomial infections in patients undergoing abdominal surgery

Strengths

  • Randomised trial
  • No loss to follow up
  • Analysed on intention to treat basis
  • Balanced baseline characteristics
  • Clear separation in energy and protein intake during the intervention period (between days 3 and 8)
  • Results consistent with similar previous studies
  • Although this paper has a low rate of critical care patients this is still an important trial for critical care practitioners as this cohort of patients will be admitted to ICU; additionally in some countries ICU physicians will look after PN patients on the wards

Weaknesses

  • Single country may reduce external generalisability
    • ~2/3 of patients came from 4 of the sites
  • Small trial, with a calculated Fragility Index of 1
  • Not a truly patient orientated primary outcome
  • Significant exclusion criteria:
    • Diabetics may be an important group to study with risk of hyperglycaemia
    • Did not include emergency surgical patients
    • Difficult to extrapolate these results to all ICU patients however every patient in ICU > 48 hours should be considered at risk of malnutrition so likely that ICU patients may meet the malnutrition risk criteria
      • ICU admission is a scoring point on NRS2002 score
  • No record of numbers in L-SPN group that actually received PN
    • Did all patients in the L-SPN group receive PN? If so, was it needed?
      • It’s possible that by day 8 EN would be sufficient (>80% requirements) and therefore PN was not required for those randomised to L-SPN
  • Unable to blind bedside clinicians and patients
  • Time lag bias
    • Data collection finished in 2018, and wasn’t analysed until 2020 with publication this year

The Bottom Line

  • For patients in ICU post abdominal surgery with poor enteral intake I will now consider, alongside the ICU dieticians, the early implementation of SPN
  • Although a large proportion of patients were not critically unwell in this study, it seems critical illness increases nutritional risk and early (>3 days) SPN may reduce risk of nosocomial infections in a cohort of patients at high nutritional risk

External Links

Metadata

Summary author: @hgmwalker89
Summary date: 16th May 2022
Peer-review editor: David Slessor

Picture by: Pexels/cottonbro

 

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