Saline Compared to Balanced Crystalloid in Patients With Diabetic Ketoacidosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Alghamdi, Naif Ali; Major, Paityn; Chaudhuri, Dipayan; Tsui, Janice; Brown, Brent; Self, Wesley H.; Semler, Matthew W.; Ramanan, Mahesh; Rochwerg, Bram

doi:10.1097/cce.0000000000000613

Cited by 16 publications

(19 citation statements)

References 41 publications

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“…Based on these data, balanced crystalloid versus NS trials going forward need to carefully consider the exclusion of patients with acute brain injury from different causes as well as different severity of injuries. In addition, recent evidence generated from systematic reviews of small trials and subgroup analyses of large trials suggest balanced crystalloids as compared with NS may reduce death from sepsis and time to resolution of diabetic ketoacidosis27 38 and represent important subgroups to examine in the future large FLUID trial.…”

Section: Discussionmentioning

confidence: 99%

FLUID trial: a hospital-wide open-label cluster cross-over pragmatic comparative effectiveness randomised pilot trial comparing normal saline to Ringer’s lactate

et al. 2023

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ObjectivesNormal saline (NS) and Ringer’s lactate (RL) are the most common crystalloids used for fluid therapy. Despite evidence of possible harm associated with NS (eg, hyperchloremic metabolic acidosis, impaired kidney function and death), few large multi-centre randomised trials have evaluated the effect of these fluids on clinically important outcomes. We conducted a pilot trial to explore the feasibility of a large trial powered for clinically important outcomes.DesignFLUID was a pragmatic pilot cluster randomised cross-over trial.SettingFour hospitals in the province of Ontario, CanadaParticipantsAll hospitalised adult and paediatric patients with an incident admission to the hospital over the course of each study period.InterventionsA hospital wide policy/strategy which stocked either NS or RL throughout the hospital for 12 weeks before crossing over to the alternate fluid for the subsequent 12 weeks.Primary and secondary outcome measuresThe primary feasibility outcome was study fluid protocol adherence. Secondary feasibility outcomes included time to Research Ethics Board (REB) approval and trial initiation. Primary (composite of death or re-admission to hospital in first 90 days of index hospitalisation) and secondary clinical outcomes were analysed descriptively.ResultsAmong 24 905 included patients, mean age 59.1 (SD 20.5); 13 977 (56.1%) were female and 21 150 (85.0%) had medical or surgical admitting diagnoses. Overall, 96 821 L were administered in the NS arm, and 78 348 L in the RL arm. Study fluid adherence to NS and RL was 93.7% (site range: 91.6%–98.0%) and 79.8% (site range: 72.5%–83.9%), respectively. Time to REB approval ranged from 2 to 48 days and readiness for trial initiation from 51 to 331 days. 5544 (22.3%) patients died or required hospital re-admission in the first 90 days.ConclusionsThe future large trial is feasible. Anticipating and addressing logistical challenges during the planning stages will be imperative.Trial registration numberNCT02721485.

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Section: Discussionmentioning

confidence: 99%

FLUID trial: a hospital-wide open-label cluster cross-over pragmatic comparative effectiveness randomised pilot trial comparing normal saline to Ringer’s lactate

et al. 2023

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“…Two randomized trials comparing saline with Plasma-Lyte 148 in 45 and 90 patients showed faster normalization of acidosis [1,12]. These findings, as well as a reduced length of stay in patients treated with Plasma-Lyte 148, were recently confirmed in a meta-analysis [13]. Unfortunately, specific data on the course of the Na-Cl gap are lacking in these reports, and a larger trial is needed to establish whether Plasma-Lyte 148 is beneficial in DKA.…”

Section: Literaturementioning

confidence: 91%

Plasma volume expansion reveals hidden metabolic acidosis in patients with diabetic ketoacidosis

Svensson

Hahn²,

Zdolsek³

et al. 2022

ICMx

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Background Hyperchloremic metabolic acidosis that develops during the treatment of diabetic ketoacidosis is usually attributed to the chloride content of resuscitation fluids. We explored an alternative explanation, namely that fluid-induced plasma volume expansion alters the absolute differences in the concentrations of sodium and chloride (the Na–Cl gap) enough to affect the acid–base balance. We analyzed data from a prospective single-center cohort study of 14 patients treated for diabetic ketoacidosis. All patients received 1 L of 0.9% saline over 30 min on two consecutive days. Blood gases were sampled before and after the infusions. Results The initial plasma volume was estimated to be 25 ± 13% (mean ± SD) below normal on admission to the intensive care unit. At that time, most patients had an increased actual Na–Cl gap, which counteracts acidosis. However, the correction of the plasma volume deficit revealed that these patients would have had a decreased Na–Cl gap upon admission if they had been normovolemic at that time; the estimated “virtual Na–Cl gap” of 29 ± 5 mmol/L was significantly lower than the uncorrected value, which was 39 ± 5 mmol/L (P < 0.001). On Day 2, most patients had a decreased actual Na–Cl gap (33 ± 5 mmol/L), approaching the corrected value on Day 1. Conclusions The hyperchloremic acidosis commonly seen in diabetic ketoacidosis may not be primarily caused by the chloride content of resuscitation fluids but, rather, by the restoration of plasma volume, which reveals the hidden metabolic acidosis caused by a decreased Na–Cl gap. Trial registration Clinical Trials Identifier NCT02172092, registered June 24, 2014, https://www.clinicaltrials.gov/NCT02172092

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“…A 2016 systematic review of four prospective cohort studies and one case-control study (N5711) compared percent change of bone mineral density (BMD) over time for premenopausal adolescent females using depot medroxyprogesterone acetate (DMPA) with those not receiving DMPA or using another hormonal treatment. 1 Change in BMD in adolescents was one of many outcomes of concern of this broad-based systematic review. BMD was measured at the lumber spine, femoral neck, hip, and distal forearm.…”

Section: Does Long-term Use Of Depot Medroxyprogesterone Acetate Incr...mentioning

confidence: 97%

“…A systematic review and meta-analysis of eight randomized controlled trials (N5482) compared time to DKA resolution and hospital length of stay with balanced crystalloids for fluid resuscitation compared with normal saline. 1 The studies included children and adults who were hospitalized or critically ill with variable severity of DKA. The studies used several different balanced crystalloids, such as Ringer's lactate, Plas-maLyte, Ringerfundin, and Hartmann's solution.…”

mentioning

confidence: 99%

In patients with diabetes, is fluid replacement with balanced crystalloids more effective than normal saline when correcting electrolyte imbalances in diabetic ketoacidosis?

Brynne Estoesta,

Sheth-Dutt

2023

EBPR

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Saline Compared to Balanced Crystalloid in Patients With Diabetic Ketoacidosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract: Supplemental Digital Content is available in the text.

Cited by 16 publications

References 41 publications

FLUID trial: a hospital-wide open-label cluster cross-over pragmatic comparative effectiveness randomised pilot trial comparing normal saline to Ringer’s lactate

FLUID trial: a hospital-wide open-label cluster cross-over pragmatic comparative effectiveness randomised pilot trial comparing normal saline to Ringer’s lactate

Plasma volume expansion reveals hidden metabolic acidosis in patients with diabetic ketoacidosis

In patients with diabetes, is fluid replacement with balanced crystalloids more effective than normal saline when correcting electrolyte imbalances in diabetic ketoacidosis?

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