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Sodium chloride or Plasmalyte-148 evaluation in severe diabetic ketoacidosis (SCOPE-DKA): a cluster, crossover, randomized, controlled trial

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An Editorial to this article was published on 05 October 2021

Abstract

Purpose

To determine whether treatment with Plasmalyte-148 (PL) compared to sodium chloride 0.9% (SC) results in faster resolution of diabetic ketoacidosis (DKA) and whether the acetate in PL potentiates ketosis.

Methods

We conducted a cluster, crossover, open-label, randomized, controlled Phase 2 trial at seven hospitals in adults admitted to intensive care unit (ICU) with severe DKA with hospital randomised to PL or SC as fluid therapy. The primary outcome, DKA resolution, was defined as a change in base excess to ≥ − 3 mEq/L at 48 h.

Results

Ninety-three patients were enrolled with 90 patients included in the modified-intention-to-treat population (PL n = 48, SC n = 42). At 48 h, mean fluid administration was 6798 ± 4850 ml vs 6574 ± 3123 ml, median anion gap 6 mEq/L (IQR 5–7) vs 7 mEq/L (IQR 5–7) and median blood ketones 0.3 mmol/L (IQR 0.1–0.5) vs 0.3 (IQR 0.1–0.5) in the PL and SC groups. DKA resolution at 48 h occurred in 96% (PL) and 86% (SC) of patients; odds ratio 3.93 (95% CI 0.73–21.16, p = 0.111). At 24 h, DKA resolution occurred in 69% (PL) and 36% (SC) of patients; odds ratio 4.24 (95% CI 1.68–10.72, p = 0.002). The median ICU and hospital lengths of stay were 49 h (IQR 23–72) vs 55 h (IQR 41–80) and 81 h (IQR 58–137) vs 98 h (IQR 65–195) in the PL and SC groups.

Conclusion

Plasmalyte-148, compared to sodium chloride 0.9%, may lead to faster resolution of metabolic acidosis in patients with DKA without an increase in ketosis. These findings need confirmation in a large, Phase 3 trial.

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Availability of data and material

Deidentified data are available for sharing. To request data, please contact the corresponding author with a request. This will be reviewed by the trial management committee. Applications from investigators with the suitable academic capability to conduct the proposed work will be given consideration. Any proposal will require approval from the ethics committee which approved the conduct of this trial prior to sharing of any patient data. If a proposal is approved, a signed data transfer agreement will be required before data sharing.

Code availability

Not applicable.

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Acknowledgements

The authors would like to thank and acknowledge the Queensland Critical Care Research Network (QCCRN) for providing a forum to plan, discuss and refine the SCOPE-DKA trial, and to the individual member sites for their participation.

SCOPE-DKA Collaborators and Sites: Mark Scott: Staff Specialist, Emergency Department, Caboolture Hospital, Brisbane, Queensland, Australia; Stacey Watts: Research Coordinator, Emergency Department, Caboolture Hospital and Kilcoy and Woodford Correctional Health, Brisbane, Queensland, Australia; Timothy Harding: Staff Specialist, Emergency Department, Ipswich Hospital, Ipswich, Queensland, Australia; Senior Lecturer, School of Medicine, University of Queensland, Brisbane, Queensland, Australia; Steven Tyler: Clinical and Research Nurse, Intensive Care Unit, Ipswich Hospital, Ipswich, Queensland, Australia; Bauke Hovinga: Assistant Clinical Director, Department Emergency Medicine, Mackay Base Hospital, Mackay, Queensland. Australia; Tracy Joy Hess: Clinical Trials Nurse, Mackay Institution of Research and Innovation, Mackay, Queensland. Australia; School-Based Immunisation Nurse (Endorsed), Queensland Health; Rajbir Sing Sandha: Staff Specialist- ED, Rockhampton Hospital, Canning Street, The Range, QLD , Australia 4700; David Austin: Director—Intensive Care Services, Central Queensland Health Service, Rockhampton, QLD, Australia 4700; Syed Giasuddin Khadri: Clinical Director—Emergency Department Rockhampton Hospital, Canning Street, The Range, QLD, Australia 4700; Salomon Jacobus Poggenpoel: Deputy Director ICU, Rockhampton Hospital, Canning Street, The Range, QLD, Australia 4700; Helen Miles: Staff Specialist, Intensive Care Unit, Rockhampton Hospital, Canning Street, The Range, QLD , Australia 4700; Associate Lecturer, University of Queensland; Jane Brailsford: Intensive Care Unit, Sunshine Coast University Hospital, Birtinya, Australia; Teena Maguire: Intensive Care Unit, Sunshine Coast University Hospital, Birtinya, Australia; Kym Roberts: Department of Emergency Medicine, Sunshine Coast University Hospital, Birtinya, Australia; Ogilvie Thom: Department of Emergency Medicine, Sunshine Coast University Hospital; Isuru Seneviratne: Staff Specialist, Intensive Care Unit, Queen Elizabeth-2 Jubilee Hospital, Brisbane, Queensland, Australia; David Stewart: Staff Specialist, Intensive Care Unit, Queen Elizabeth-2 Jubilee Hospital, Brisbane, Queensland, Australia.

Data Safety Monitoring Committee: Anthony Russell FRACP Director of Endocrinology, Princess Alexandra Hospital, Brisbane, Queensland, Australia Associate Professor, School of Medicine, University of Queensland, Brisbane, Queensland, Australia. Michael D’Emden FRACP Director of Endocrinology, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia. Kunwarjit Sangla FRACP Staff Specialist, Endocrinology, Rural Hospital Services Group, Queensland Health, Queensland, Australia.

Queensland Critical Care Research Network (QCCRN): The QCCRN was formed in June 2017 with a mission “to foster a state-wide collaborative approach to critical care research with the goals of increasing research capacity in Queensland’s Intensive Care Units and support high quality research output from local investigators with a focus on improving patient outcomes”. QCCRN is not open to commercial enterprise and access is restricted to individuals working non-commercially in the field of critical care research. Mahesh Ramanan is currently the Chair of QCCRN (term July 2019-June2021).

Funding

This study did not receive any funding or financial support.

Author information

Authors and Affiliations

  1. Intensive Care Unit, Caboolture Hospital, McKean Street, Caboolture, QLD, 4510, Australia

    Mahesh Ramanan & Melissa Petty

  2. Adult Intensive Care Services, The Prince Charles Hospital, Rode Road, Chermside, QLD, 4032, Australia

    Mahesh Ramanan

  3. The George Institute for Global Health, University of New South Wales, Level 5/1 King Street, Newtown, NSW, 2042, Australia

    Mahesh Ramanan, Laurent Billot & Balasubramanian Venkatesh

  4. School of Medicine, University of Queensland, Sir Fred Schonell Drive, St Lucia, QLD, 4072, Australia

    Mahesh Ramanan

  5. Intensive Care Unit, Rockhampton Hospital, Canning Street, Rockhampton, QLD, 4700, Australia

    Antony Attokaran

  6. Intensive Care Unit, Sunshine Coast University Hospital, Doherty Street, Birtinya, QLD, 4575, Australia

    Lauren Murray & Peter Garrett

  7. Intensive Care Unit, Ipswich Hospital, Chelmsford Avenue, Ipswich, QLD, 4305, Australia

    Neeraj Bhadange

  8. Intensive Care Unit, Queen Elizabeth-2 Jubilee Hospital, Kessels Road, Coopers Plains, QLD, 4108, Australia

    David Stewart

  9. Intensive Care Unit, Mackay Base Hospital, Bridge Road, Mackay, QLD, 4741, Australia

    Gokulnath Rajendran

  10. Intensive Care Unit, Hervey Bay Hospital, Urraween Road, Pialba, QLD, 4655, Australia

    Raju Pusapati

  11. Intensive Care Unit, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, QLD, 4102, Australia

    Peter Kruger

  12. Department of Intensive Care Medicine, The Queen Elizabeth Hospital, Woodville Road, Woodville South, South Australia, 5011, Australia

    Sandra Peake

  13. Intensive Care Unit, Wesley and Princess Alexandra Hospitals, Woolloongabba, QLD, Australia

    Balasubramanian Venkatesh

Authors
  1. Mahesh Ramanan
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  2. Antony Attokaran
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  3. Lauren Murray
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  4. Neeraj Bhadange
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  5. David Stewart
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  6. Gokulnath Rajendran
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  7. Raju Pusapati
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  8. Melissa Petty
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  9. Peter Garrett
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  10. Peter Kruger
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  11. Sandra Peake
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  12. Laurent Billot
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  13. Balasubramanian Venkatesh
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Consortia

the SCOPE-DKA Collaborators and Queensland Critical Care Research Network (QCCRN)

  • Mark Scott
  • , Stacey Watts
  • , Timothy Harding
  • , Steven Tyler
  • , Bauke Hovinga
  • , Tracy Joy Hess
  • , Rajbir Sing Sandha
  • , David Austin
  • , Syed Giasuddin Khadri
  • , Salomon Jacobus Poggenpoel
  • , Helen Miles
  • , Jane Brailsford
  • , Teena Maguire
  • , Kym Roberts
  • , Ogilvie Thom
  • , Isuru Seneviratne
  •  & David Stewart

Contributions

Conceptualisation: MR, PK, SP, LB and BV. Data curation: MR, AA. Formal analysis: MR, LB. Investigation: MR, AA, LM, NB, DS, GR, RP, MP, PG. Methodology: MR, LM, PK, SP, LB and BV. Project administration: MR, BV. Resources: MR, AA. Validation: MR, BV. Writing—original draft: MR. Writing—review and editing: All authors. Supervision: BV, SP.

Corresponding author

Correspondence to Mahesh Ramanan.

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Conflicts of interest

The authors do not have any conflicts of interest or competing interests to declare.

Ethics approval (include appropriate approvals or waivers)

Ethics approval was granted by the Royal Brisbane and Women’s Hospital Human Research Ethics Committee (HREC/2018/QRBW/43868) for this trial to be conducted at all participating sites with a full consent waiver.

Consent to participate

Full consent waiver was approved by the Ethics Committee.

Consent for publication

Not applicable.

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SCOPE-DKA Collaborators and Queensland Critical Care Research Network (QCCRN) are listed in the Acknowledgements section.

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Ramanan, M., Attokaran, A., Murray, L. et al. Sodium chloride or Plasmalyte-148 evaluation in severe diabetic ketoacidosis (SCOPE-DKA): a cluster, crossover, randomized, controlled trial. Intensive Care Med 47, 1248–1257 (2021). https://doi.org/10.1007/s00134-021-06480-5

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