Intraoperative Insulin Administration at Cardiac Surgery for Diabetic Patients
Condition: Diabetes Mellitus; Cardiac Event
MeSH terms: Cardiovascular Diseases; Diabetes Mellitus
Study type: Interventional
Phase: Phase 4

Summary: 
      The primary objective of the study was to explore which insulin-based regimen is better,
      infusion or bolus regimen, for intraoperative management of glucose level for the diabetic
      patient at cardiac surgery. Secondary objectives include: comparing the relative amounts of
      insulin needed during the operation and subsequent cost impact and comparing potassium levels
      between groups.

      Ethical approval for the study was obtained from the Office for Research Ethics Committees at
      Hashemite University - Prince Hamza hospital.

      This study was a parallel-group, randomized, controlled trial with 1:1 allocation ratio.

      Participants: Adult diabetic patients, type 2, who were admitted to hospital for cardiac
      surgery.

      The intervention: Both patients in the infusion or bolus group received their dose of
      insulin, fast-acting human insulin (Actrapid®) was used.

      Setting: Patients were recruited at Prince Hamza hospital, Amman, Jordan. A tertiary care
      center specialized unit in cardiac surgery for diabetic patients.

      Outcomes monitoring: It was monitored six times as follows: preoperative induction measure,
      then glucose post heparin, and after that for 2 hours, glucose levels were monitored every 30
      minutes. Insulin quantities were recorded as well to be used in secondary outcomes analysis.

      Randomization, allocation, and blinding During patient enrolment, concealed allocation to
      either infusion group or bolus group was guaranteed through the use of a closed envelope
      system prepared by an independent investigator. Block randomization with random block sizes,
      ensured allocation balance, and avoided selection bias by preventing allocation prediction.
      Researchers and physicians were blind to the block size sequence and randomization. Envelopes
      were unopened until completion of patient registration. Hospital staff who monitor glucose
      and those who administered insulin were blinded to the primary and secondary outcomes'
      measure.
    

Detailed description: 
      The primary objective of the study was to explore which insulin-based regimen is better,
      infusion or bolus regimen, for intraoperative management of glucose level for the diabetic
      patient at cardiac surgery. Secondary objectives include: comparing the relative amounts of
      insulin needed during the operation and subsequent cost impact and comparing potassium levels
      between groups.

      Ethical approval and study registration Ethical approval for the study was obtained from the
      Office for Research Ethics Committees at Hashemite University - Prince Hamza hospital with
      reference number 2/1/2019/2020.

      Methods and Materials This study was a parallel-group, randomized, controlled trial with 1:1
      allocation ratio.

      Participants Adult diabetic patients, type 2, who were admitted to hospital for cardiac
      surgery. In addition to signing the consent form, patients were recruited when they met the
      following criteria: >40 years old, patients who need the usual insulin according to insulin
      dosing guidelines, patients with pre-operation glucose level > 200 mg/dL and < 300 mg/dL.

      The following patients were excluded: Insulin sensitive patents (Age >70 years, Glomerular
      Filtration Rate (GFR) <45 ml/min, No history of Diabetes, Insulin resistance patients (Body
      Mass Index > 35 kg/m2, total daily insulin dose >80 units, Steroids > 20 mg prednisone daily,
      patients who at high risk of complications and or (those whom their operation was differed to
      be supervised by a specialized team). Patients who were unable to give written informed
      consent, who had ≥4 emergency admissions during the six months prior to the index admission.

      The intervention Both patients in the infusion or bolus group received their dose of insulin,
      fast-acting human insulin (Actrapid®) was used. The protocol of the insulin regimen and its
      related details were carried out according to the standard recommendations.

      Setting Patients were recruited at Prince Hamza Hospital, Amman, Jordan. A tertiary care
      center specialized unit in cardiac surgery for diabetic patients.

      Diabetic patients who had booked cardiac surgery and met the criteria were invited to the
      study. Patients who accepted participation and signed the consent were recruited by
      well-trained research assistance, who was trained on an ethical standard and patient-centered
      approach.

      Primary and secondary outcomes In the present study, the primary outcome was the
      intraoperative level of glucose. It was monitored six times as follows: preoperative
      induction measure, then glucose post heparin, and after that for 2 hours, glucose levels were
      monitored every 30 minutes. Insulin quantities were recorded as well to be used in secondary
      outcomes analysis.

      Sample size To detect a difference of at least 25mg/dL between infusion and bolus groups (the
      standard deviation of the two groups is expected to be 35 mg/dL, i.e., the variance is 1225
      mg/dL), the study will need to recruit and record full data for at least 31 patients in each
      group. Providing that significant level of confidence 95% and the power of 80%.

      n = (Zα/2+Zβ)2 *2*σ2 / d2. where Zα/2 is the critical value of the Normal distribution at α/2
      (for a confidence level of 95%, α is 0.05, and the critical value is 1.96), Zβ is the
      critical value of the Normal distribution at β (for a power of 80%, β is 0.2, and the
      critical value is 0.84), σ2 is the population variance, and d is the difference needed to be
      detected.

      Statistical methods Standard independent-samples t-test or separate variances t-test (Welch
      t-test) was used to compare the results between the two arms of the study. General Linear
      Model, one-way repeated measures ANOVA was conducted to determine whether there was a
      statistically significant difference within groups. Cost analysis and cost-effectiveness were
      used for the pharmacoeconomic analysis. Incremental cost-effectiveness ratio (ICER) was
      calculated as the cost of insulin in the Infusion protocol minus the cost of insulin in the
      bolus protocol divided by drop-in glucose level by infusion - drop in glucose level by
      bolus).

      Randomization, allocation, and blinding During patient enrolment, concealed allocation to
      either infusion group or bolus group was guaranteed through the use of a closed envelope
      system prepared by an independent investigator. Block randomization with random block sizes,
      ensured allocation balance, and avoided selection bias by preventing allocation prediction.
      Researchers and physicians were blind to the block size sequence and randomization. Envelopes
      were unopened until completion of patient registration. Hospital staff who monitor glucose
      and those who administered insulin were blinded to the primary and secondary outcomes'
      measure.
    

Intervention name(s): Fast-acting human insulin
Intervention type(s): Drug
Intervention description(s): Both patients in the infusion or bolus group received their dose of insulin. The protocol of the insulin regimen and its related details were carried out according to the standard recommendations in a hospital where the trial done.
Other intervention name(s): Actrapid®
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This study was a parallel-group, randomized, controlled trial with 1:1 allocation ratio.
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Type II diabetes mellitus; Cardiac surgery; Insulin; Insulin infusion regimen; Insulin bolus regimen